Samir Malhotra

Drug related medical emergencies in the elderly: role of adverse drug reactions and non-compliance

BACKGROUND Adverse drug reactions and non-compliance are important causes of admissions in the elderly to medical clinics. The contribution of adverse drug reactions and non-compliance to admission by the medical emergency department was analysed. METHODS A total of 578 consecutive elderly patients admitted to the medical emergency department were interviewed to determine the percentage of admissions due to adverse drug reactions or non-compliance with medication regimens, their causes, consequences, and predictors. RESULTS Eighty three (14.4%) of the 578 admissions were drug related: 39 (6.7%) caused by adverse drug reactions and 44 (7.6%) caused by non-compliance with medication. One hundred ninety two (33.2%) patients had a history of non-compliance. Factors associated with an increased risk of admission because of an adverse drug reaction were patients with diabetes or neoplasms, and patients using numerous different medications. Factors associated with a higher risk of hospitalisation because of non-compliance were poor recall of the medication regimen, seeing numerous physicians, female sex, polypharmacy, drug costs, and switching over to non-conventional forms of treatment. CONCLUSION Many elderly admissions are drug related, with non-compliance accounting for a substantial fraction of these. Elderly people at high risk of suffering a drug related medical emergency are identified and suitable interventions may be planned by the healthcare policymakers to target them.

Probiotic VSL#3 Reduces Liver Disease Severity and Hospitalization in Patients With Cirrhosis: A Randomized, Controlled Trial

BACKGROUND & AIMS Little is known about whether probiotics can affect outcomes of patients with cirrhosis and hepatic encephalopathy (HE). We assessed the efficacy of a probiotic preparation in preventing the recurrence of HE (primary outcome) and reducing the number of hospitalizations and severity of liver disease in patients with cirrhosis. METHODS We performed a double-blind trial at a tertiary care hospital in India. Patients with cirrhosis who had recovered from an episode of HE during the previous month were assigned randomly (using computer-generated allocation) to groups given a probiotic preparation (VSL#3, 9 × 10(11) bacteria; CD Pharma India Private Limited, New Delhi, India) (n = 66) or placebo (n = 64) daily for 6 months. RESULTS There was a trend toward a reduction in the development of breakthrough HE among patients receiving the probiotic (34.8% in the probiotic group vs 51.6% in the placebo group; hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.38-1.11; P = .12). Fewer patients in the probiotic group were hospitalized for HE (19.7% vs 42.2%, respectively; HR, 0.45; 95% CI, 0.23-0.87; P = .02) or for complications of cirrhosis (24.2%) than in the placebo group (45.3%) (HR, 0.52; 95% CI, 0.28-0.95; P = .034). Child-Turcotte-Pugh and model for end-stage liver disease scores improved significantly from baseline to 6 months in the probiotic group, but not in the placebo group. There were no adverse events related to VSL#3. CONCLUSIONS Over a 6-month period, daily intake of VSL#3 significantly reduced the risk of hospitalization for HE, as well as Child-Turcotte-Pugh and model for end-stage liver disease scores, in patients with cirrhosis. ClinicalTrials.gov number: NCT01110447.

Pilot trial: Pioglitazone versus placebo in patients with plaque psoriasis (the P6).

Background  Disordered differentiation and hyperproliferation of keratinocytes with inflammation are the hallmarks of psoriasis. Ligand activation of peroxisome proliferator receptor‐γ (a class of nuclear receptors) by thiazolidinediones can normalize the histologic features of psoriasis.

A Preliminary Study of Melatonin in Irritable Bowel Syndrome

Background and Aims Melatonin is involved in the regulation of gut motility and sensation. We aimed to determine if melatonin was effective in improving bowel symptoms, extracolonic symptoms, and quality of life (QOL) in irritable bowel syndrome (IBS) patients. Methods Eighteen patients (aged 18 to 65 y; 6 females) were randomly assigned to receive either melatonin 3 mg (n=9) or matching placebo (n=9) at bed time for 8 weeks. The overall IBS scores, extracolonic IBS scores, QOL scores were assessed at 2, 4, 6, and 8 weeks during treatment and at 16, 24, and 48 weeks during follow up. Results Compared with placebo, melatonin taken for 8 weeks significantly improved overall IBS score (45% vs. 16.66%, P<0.05). The posttreatment overall extracolonic IBS score was significantly lower (49.16% to 13.88%, P<0.05) when compared with placebo group. The overall improvement in QOL score was 43.63% in melatonin group and 14.64% in placebo group that is statistically significant. Conclusions The result of this study showed that melatonin has some beneficial role in IBS. Further studies using large number of patients may provide a definite answer.

Efficacy and Safety of Combination Acitretin and Pioglitazone Therapy in Patients With Moderate to Severe Chronic Plaque-Type Psoriasis: A Randomized, Double-blind, Placebo-Controlled Clinical Trial

OBJECTIVE To evaluate the efficacy and safety of combination therapy with acitretin and pioglitazone hydrochloride in patients with moderate to severe chronic plaque-type psoriasis. DESIGN Randomized, double-blind, placebo-controlled clinical trial. SETTING A tertiary care referral hospital. Patients The study included patients of either sex (age range, 18-65 years) with moderate to severe chronic plaque-type psoriasis. Patients were excluded if they were of child-bearing potential or if they had impaired liver or renal function, hyperlipidemia, diabetes mellitus, coronary artery disease, or a body mass index greater than 30 (calculated as weight in kilograms divided by height in meters squared). Of the 62 patients screened, 41 were randomly assigned to 2 groups: 22 to an acitretin (25 mg) plus placebo group and 19 to an acitretin (25 mg) plus pioglitazone hydrochloride (15 mg) group. Main Outcome Measure Change in Psoriasis Area and Severity Index score between the 2 groups from baseline to 12 weeks. RESULTS After 12 weeks of therapy, the percentage of reduction in the Psoriasis Area and Severity Index score was 64.2% in the acitretin plus pioglitazone group and 51.7% in the acitretin plus placebo group. The majority of the adverse events were mild to moderate except for 1 possibly unrelated episode of acute myocardial infarction in a 49-year-old woman in the acitretin plus placebo group. CONCLUSIONS Pioglitazone has a potential beneficial antipsoriatic effect and may provide a convenient, efficacious, and relatively safe option to combine with acitretin, although further studies are needed. Trial Registration clinicaltrials.gov Identifier: NCT00395941.

Effects of pioglitazone and metformin on plasma adiponectin in newly detected type 2 diabetes mellitus

Objective  This prospective study evaluates the effect of insulin sensitizers, pioglitazone (PGZ) and metformin (MET) on plasma adiponectin and leptin levels in subjects newly diagnosed with type 2 diabetes mellitus (T2DM).

Melatonin treatment is beneficial in pancreatic repair process after experimental acute pancreatitis.

Current treatment options for acute pancreatitis are supportive and symptomatic. Due to lack of agents targeting the underlying pathophysiology a large amount of experimental work is going on to identify novel therapeutic agents. The present study was carried out to explore if melatonin can modulate the spontaneous regeneration process of the pancreas after experimentally induced acute pancreatitis. Rats were given two i.p. injections of l-arginine in a dose of 200mg/100g at an interval of 1h for induction of pancreatitis. After this rats were randomly divided into three groups i.e. saline, CCK-8 and melatonin. Drug treatment was started 2h after the last l-arginine injection and continued till the day of sacrifice. An additional only saline treated control group was included for comparison. Animals in each group were sacrificed at 24h, days 3, 14 and 28 after pancreatitis induction for determination of biochemical parameters (serum amylase, lipase and IL-10 and pancreatic amylase, total proteins and nucleic acid content) and histological examination. For rate of DNA synthesis and immunohistochemical studies animals were sacrificed at day 3 and day 7. Melatonin treatment was found to be beneficial in acute pancreatitis. Severity of acute pancreatitis was significantly reduced in melatonin group. Nucleic acid content, rate of DNA synthesis, pancreatic proteins and pancreatic amylase content were significantly improved. Histopathological examination showed significantly lower total scores in melatonin group. Results of melatonin group were comparable to that of positive control, CCK-8 group. Thus melatonin treatment was found to promote the spontaneous regeneration process of pancreatic tissue.

Clinical Profile of Idiopathic Chronic Pancreatitis in North India

BACKGROUND & AIMS Tropical pancreatitis, a form of idiopathic chronic pancreatitis (ICP) with unique features, has been described in South and North India. We investigated the clinical profile of ICP patients in North India. METHODS Detailed demographic data were recorded; hematological and biochemical analyses were performed on samples from 155 patients (mostly from North India) who had been diagnosed with chronic pancreatitis. Ultrasonography and computed tomography were performed on all patients. Magnetic resonance cholangiopancreatography, endoscopic retrograde cholangiopancreatography, glucose tolerance tests, and fecal fat studies were performed on some patients. Patients were divided into groups based on early- or late-onset ICP (before or after 35 years of age). RESULTS ICP was reported in 41.3% of patients and alcoholic chronic pancreatitis in 38.1%. The mean age of ICP patients was 33.0 +/- 13.0 years and the mean duration of symptoms at the time of presentation was 40.2 +/- 34.4 months. Pain was the dominant symptom in patients with early- (95.1%) and late-onset (100%) ICP; pseudocyst was the most common local complication. Diabetes was observed in 17.1% of patients with early-onset ICP and 34.8% with late-onset ICP. Pancreatic calcification was noted in 46.3% of patients with early-onset and 47.8% with late-onset ICP. Pseudocyst and segmental portal hypertension occurred more frequently in non-calcific ICP, whereas diabetes mellitus and abnormal fecal fat excretion occurred more frequently in patients with calcific ICP. CONCLUSIONS In North India, ICP differs from the classical tropical pancreatitis described in the literature. It is associated with a higher prevalence of pain and lower frequencies of diabetes, calcification, and intraductal calculi.

Safety and efficacy of vitamin-based antioxidant therapy in patients with severe acute pancreatitis: a randomized controlled trial.

Background/Aim: Oxidative stress plays a major role in the pathogenesis of pancreatitis. Antioxidant therapy in the form of high-dose vitamin has been used for the treatment of severe acute pancreatitis with equivocal results. We wished to evaluate the efficacy and safety of antioxidant (vitamin A, vitamin C, vitamin E) therapy in patients with severe acute pancreatitis. Setting and design: This was a single-center, prospective, randomized, open-label with blinded endpoint assessment study of antioxidant therapy, conducted in the emergency department attached to our hospital. Materials and Methods: Thirty-nine patients with severe acute pancreatitis were randomly assigned to antioxidant treatment group (n=19) or a control group (n=20) within 96 hours of developing symptoms. Patients in the antioxidant group received antioxidants (vitamin A, vitamin E, vitamin C) in addition to the standard treatment provided to both the groups for a period of 14 days. The primary outcome variable was presence of organ dysfunction at day 7. The secondary outcome variables were length of hospital stay, multiorgan dysfunction (MODS) at day 7, recovery at the end of 4 weeks, complications, and mortality. The change in markers of oxidative stress from baseline was also measured. Results: We demonstrated no significant difference in organ dysfunction (P=1.0), MODS (P=0.8), and length of hospital stay (P=0.29) between the two groups. All the patients survived in the antioxidant-treated group, whereas two patients died in the control group. The change in the levels of malondialdehyde, superoxide dismutase, and reduced glutathione were not significantly different in the two groups at day 7. Univariate analysis showed marginal benefit with antioxidant treatment (P=0.034) in patients with severe acute pancreatitis. Conclusions: This randomized study demonstrates that there is no significant benefit from antioxidant therapy in patients with established severe acute pancreatitis.

PHARMACOKINETICS AND TISSUE DISTRIBUTION STUDIES OF ORALLY ADMINISTERED NANOPARTICLES ENCAPSULATED ETHIONAMIDE USED AS POTENTIAL DRUG DELIVERY SYSTEM IN MANAGEMENT OF MULTI-DRUG RESISTANT TUBERCULOSIS

Sustained release nanoformulations of second line anti-tubercular drugs can help in reducing their dosing frequency and improve patient’s compliance in multi-drug resistant tuberculosis (MDR TB). The objective of the current study was to investigate the pharmacokinetics and tissues distribution of ethionamide encapsulated in poly (DL-lactide-co-glycolide) (PLGA) nanoparticles. The drug loaded nanoparticles were 286 ± 26 nm in size with narrow size distribution, and zeta-potential was −13 ± 2.5 mV. The drug encapsulation efficiency and loading capacity were 35.2 ± 3.1%w/w and 38.6 ± 2.3%w/w, respectively. Ethionamide-loaded nanoparticles were administered orally to mice at two different doses and the control group received free (unencapsulated) ethionamide. Ethionamide-loaded PLGA nanoparticles produced sustained release of ethionamide for 6 days in plasma against 6 h for free ethionamide. The Ethionamide was detected in organs (lung, liver, and spleen) for up to 5–7 days in the case of encapsulated ethionamide, whereas free ethionamide was cleared within 12 h. Ethionamide-loaded PLGA nanoparticles exhibited significant improvement in pharmacokinetic parameters, i.e. Cmax, tmax, AUC0–∞, AUMC0–∞, and MRT of encapsulated ethionamide as compared with free ethionamide. Drug in nanoparticles also exhibited a dose proportional increase in the AUC0–∞ values. The pharmacodynamic parameters such as AUC0–24/MIC, Cmax/MIC, and Time > MIC were also improved. PLGA nanoparticles of ethionamide have great potential in reducing dosing frequency of ethionamide in treatment of MDR TB.