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Kanchan Tyagi,1 Nidhi Bharal Agarwal,2 Prem Kapur,3 Sunil Kohli,3 Rajinder K Jalali4 1Department of Pharmaceutical Medicine, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, 110062, India; 2Centre for Translational and Clinical Research, School of Chemical & Life Sciences, Jamia Hamdard, New Delhi, 110062, India; 3Hamdard Institute of Medical Sciences and, Research, HAH Centenary Hospital, New Delhi, 110062, India; 4Physician and Healthcare Consultant. Formerly, Sun Pharmaceuticals Industries Limited, Gurgaon, 122015, IndiaCorrespondence: Nidhi Bharal AgarwalCentre for Translational and Clinical Research, School of Chemical & Life Sciences, Jamia Hamdard, New Delhi, 110062, IndiaTel +91 9818334770Email nidhi.bharal@gmail.comPurpose: Type 2 diabetes mellitus (T2DM), a metabolic disorder, remains associated with a physiological impairment affecting large populations worldwide. Onset of T2DM is multifactorial where obesity and abnormal basal metabolic rate are considered most critical. Of people diagnosed with T2DM, about 80% are also obese. It is also reported that obese individuals have an increased odds of developing depression, whereas T2DM is estimated to increase the incidence by two-fold. The preponderance of research data demonstrates that T2DM alters the serum level of cortisol and adiponectin which are known to be associated with neuronal physiology. The study explored, how a metabolic disorder like T2DM is linked with the altered plasma level of cortisol and adiponectin, the risk factors for stress and depression.Patients and Methods: A cross-sectional population study was conducted in T2DM patients using a bimodal approach. First approach used questionnaires, (1) Patient Health Questionnaire (PHQ-9) and (2) Stress Coping Inventory Questionnaire (SCQ) to assess signs and symptoms of depression and stress, respectively, in T2DM patients. In the second approach, robust biochemical analysis was conducted for serum adiponectin and cortisol levels.Results: An association of T2DM in stress and depression was evaluated in 158 subjects (105 T2DM obese patients and 53 healthy controls). A lower PHQ-9 score and adiponectin levels were seen in T2DM obese patients compared to healthy controls (p< 0.05). Further, results also depicted a lower adiponectin levels in T2DM obese patients with depression compared to T2DM obese patients without depression (p< 0.05). The study did not find a significant difference in cortisol serum levels among the T2DM and control groups. However, a higher level of serum cortisol was reported in T2DM obese patients with depression over those T2DM obese patients who lacked depression (p< 0.05).Conclusion: The findings suggest that T2DM obese patients might have a higher risk of developing stress and depression. Further, biochemical parameters, adiponectin and cortisol, might be the potential biomarkers for T2DM and may help in early diagnosis of these comorbid conditions.Keywords: type 2 diabetes mellitus, depression, stress, PHQ-9, SCQ, adiponectin, cortisol

Himanshu Sharma,1 Prem Kapur,2 Rajinder K Jalali,3 Kiran Dubey11Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India; 2Department of Medicine, Hamdard Institute of Medical Sciences and Research (HIMSR) and HAH-Centenary Hospital, Jamia Hamdard, New Delhi, India; 3Sushant Lok Phase-1, Gurgaon, Haryana 122001, IndiaCorrespondence: Kiran DubeyDepartment of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, IndiaTel +91 981 059 0843Email kirandubey@gmail.comPurpose: Chronic Obstructive Pulmonary Disease (COPD) is considered as a risk factor for atherosclerosis and a leading cause of mortality due to cardiovascular disease (CVD). The study assessed the association of COPD with atherosclerotic risk factors and compared the predictor role of various cardiovascular (CV) risk score calculators in Indian subjects with COPD.Patients and methods: Forty subjects with stable COPD and forty age, gender and body mass index (BMI)-matched healthy controls were included in the case-control study conducted in a tertiary care hospital. Atherogenic indices were calculated by using the values of lipid parameters. CV risk calculators were utilized to assess the 10-year CV risk for the COPD group.Results: The study subjects had a mean age of 60.83±12.40 years in COPD group and 57.73±9.49 years in control group (p=0.213). Gender distribution was similar in both the groups. The mean High sensitivity C-reactive protein (hs-CRP) levels were 3.70±2.37 mg/L in COPD group and 2.39±2.23 mg/L in control group. The hs-CRP levels were significantly higher in COPD than in control subjects (p=0.012). Using bivariate correlations, we found significant positive correlations between hs-CRP and atherogenesis indices-atherogenic index of plasma, cardiogenic risk ratio, atherogenic coefficient in COPD patients [(r=0.4265, p

Neelam Kaushal,1 Divya Vohora,1 Rajinder K Jalali,2 Sujeet Jha3 1Pharmaceutical Medicine, Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, 2Medical Affairs and Clinical Research, Sun Pharmaceutical Industries Limited, Gurgaon, 3Institute of Endocrinology, Diabetes and Metabolism, Max Healthcare Inst. Ltd, New Delhi, India Purpose: Oxidative stress has been implicated as a fundamental mechanism in the decline of bone mass. Reactive oxygen species are reported to suppress osteoblast generation and differentiation and enhance osteoclast development and activity. Increasing evidence suggests favorable effect of serum uric acid (UA) on bone metabolism due to its antioxidant properties. Therefore, we investigated the association between serum UA levels and bone mineral density (BMD) in healthy adult Indian subjects.Materials and methods: We reviewed the medical records of 524 subjects who had undergone preventive health check-ups in a tertiary care hospital that included UA and BMD measurements at femur neck, total femur, and lumbar spine. Subjects concomitantly taking drugs or having a medical condition that would affect the bone metabolism or UA levels were excluded.Results: The final analysis included 310 subjects (mean age: 47.2±12.2 years; females: 43.5%; males: 56.5%). Study population was categorized into two groups based on the group median value for UA (ie, 5.4 mg/dL). BMD was significantly higher at all skeletal sites in subjects with UA >5.4 mg/dL compared to subjects with UA ≤5.4 mg/dL (p

Ankur Arora,1,2 Rajinder K Jalali,1,2 Divya Vohora1 1School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India; 2Medical Affairs and Clinical Research, Sun Pharmaceutical Industries Limited, Gurgaon, Haryana, India Background: Numerous reporting biases have been known to affect spontaneous reporting databases. The Weber effect, which constitutes a peak in adverse event (AE) reporting of a drug at the end of second year after regulatory approval followed by a continuous decline thereafter, has been considered an important bias for a long time. The existence of this bias in AE reporting of oncology drugs remains an underevaluated area, prompting a targeted examination.Methods: The US Food and Drug Administration (USFDA) Adverse Event Reporting System (FAERS) was studied for AE reporting patterns of 5 years of 15 new molecular entities (NMEs) and biologics used in oncology. This 5-year period started from the USFDA date of approval for the NMEs and biologics. The number of AEs reported for each of the drugs was plotted against time (years). The AE reporting patterns were specifically examined for the existence of the Weber effect. In addition, AE reporting rate patterns of 5 years of seven NMEs and biologics used in oncology were examined.Results: A total of 50,630 AE reports were logged in to the FAERS for all 15 drugs examined for AE reporting patterns. We observed five distinct AE reporting patterns for 15 drugs; however, none of the AE patterns were identical to the Weber effect. We did not observe a consistent AE reporting rate pattern for the seven drugs examined for AE reporting rates. With the exception of one drug (cetuximab), none of the drugs exhibited a second-year peak in AE reporting rates. This peak was not followed by continuous decline in AE reporting rate thereafter.Conclusion: This study does not support the existence of the Weber effect in AE reporting of oncology drugs. The contemporary AE reporting of oncology drugs does not exhibit a consistent pattern. Keywords: Weber effect, adverse event reporting patterns, oncology drugs, USFDA, FAERS

Background & Objectives: In India, the burden of Plasmodium vivax malaria has been projected to be highest in some areas. This study investigated the efficacy and safety of fixed dose combination (FDC) of arterolane maleate (AM) 37.5 mg and piperaquine phosphate 187.5 mg (PQP) dispersible tablets and (not with) chloroquine in the treatment of uncomplicated vivax malaria in pediatric patients., Methods: This multicentric, open-label trial was carried out at 12 sites in India. A total of 164 patients aged 6 months to 12 years with P. vivax malaria were randomized in a ratio of 2:1 to AM-PQP (111 patients) or chloroquine (53 patients) arms. The duration of follow up was 42 days., Results: At 72 hours, the proportion of a parasitaemic and afebrile patients was 100% in both treatment arms in per protocol (PP) population, and 98.2% and 100% [95% CI: -1.8 (-6.33 to 5.08)] in AM-PQP and chloroquine arms, respectively, in intent to treat (ITT) population. The efficacy and safety of AM-PQP was found to be comparable to chloroquine in the treatment of uncomplicated P. vivax malaria in pediatric patients. Overall, the cure rate at Day 28 and 42 was >95% for both AM-PQP or CQ. The commonly reported clinical adverse event was vomiting. No patient was discontinued for any QTc abnormality., Interpretation & Conclusion: The efficacy and safety of FDC of arterolane maleate and piperaquine phosphate was found to be comparable to chloroquine for treatment of uncomplicated P. vivax malaria in pediatric patients., Competing Interests: None

Objectives: An understanding of bone mineral density (BMD) pattern in a population is crucial for prevention and diagnosis of osteoporosis and management of its complications in later life. This study aimed to screen the bone health status and factors associated with osteoporosis in an apparently healthy Indian population., Methods: A retrospective review of medical records was done in a tertiary-care hospital for the subjects who had undergone preventive health-check-ups that included BMD measurements at femur-neck, total-femur, and lumbar-spine., Results: We evaluated 524 subjects (age, 50.0 ± 12.4 years) including 41.2% female and 58.8% male subjects. Osteoporosis was present in 6.9% subjects (female, 11.1%; male, 4.2%) and osteopenia in 34% subjects (female, 40.3%; male, 29.9%). Absolute BMD was higher in male subjects (P < 0.001) compared to female subjects at all bone sites. Prevalence of osteoporosis increased with age in female subjects, but not in male subjects. Osteoporosis rates in the age-groups of 30-39, 40-49, 50-59, 60-69, and ≥70 years were 3%, 3.4%, 14.3%, 18.6%, and 36.4%, respectively in female subjects while prevalence in male subjects was 0%, 4%, 6.5%, 4.3%, and 5.6%, respectively, at lumbar spine. Height (r = 0.234-0.358), weight (r = 0.305-0.388), body mass index (r = 0.143-0.285) and physical activity (r = 0.136-0.153) were positively; and alkaline phosphatase (r = -0.133 to -0.203) was negatively correlated with BMD (all P < 0.01) at all sites. These parameters retained significant correlation after controlling for age and sex. No correlation of serum 25-hydroxy-vitamin-D and calcium was noted with BMD (P > 0.05) at any site., Conclusions: Further data on absolute BMD, T scores, and prevalence rates of osteoporosis/osteopenia on multiple bone sites have been presented in this article.

Background: Chloroquine has been the treatment of choice for acute vivax malaria for more than 60 years. Malaria caused by Plasmodium vivax has recently shown resistance to chloroquine in some places. This study compared the efficacy and safety of fixed dose combination (FDC) of arterolane maleate and piperaquine phosphate (PQP) with chloroquine in the treatment of uncomplicated vivax malaria., Methods: Patients aged 13-65 years with confirmed mono-infection of P. vivax along with fever or fever in the previous 48 h were included. The 317 eligible patients were randomly assigned to receive FDC of arterolane maleate and PQP (n = 159) or chloroquine (n = 158) for 3 days. Primaquine was given as an anti-relapse measure on day 3 and continued for 14 consecutive days. Primary efficacy analysis included assessment of the proportion of aparasitaemic and afebrile patients at 72 h. Safety endpoints were analysis of adverse events, vital signs, laboratory data, and abnormalities on electrocardiograph. Patients participated in the study for at least 42 days., Results: In per protocol population, the proportion of aparasitaemic and afebrile patients at 72 h was 100% (140/140) in the FDC of arterolane maleate and PQP group, and 99.3% (145/146) in the chloroquine group (Fisher, p > 0.9999). In intent to treat population, the corresponding value was reported to be 96.9% (154/159) in the FDC of arterolane maleate and PQP group and 98.7 % (156/158) in the chloroquine group (Fisher, p = 0.4479). The median parasite clearance time was 24 h in FDC of arterolane maleate and PQP group and 26 h in chloroquine group (Log-rank, p = 0.2264). Similarly, median fever clearance time was 24 h in both the groups (Log-rank, p = 0.7750). In PP population, day 28 cure rates were 100 % in both the groups (95% CI (96.52, 100.0 for FDC of arterolane maleate and PQP and 96.73, 100.0 in chloroquine group)). Incidence of adverse events was 82.4% in the FDC of arterolane maleate and PQP group and 85.4% in the chloroquine group. Most of the adverse events were mild to moderate in intensity. The commonly reported clinical adverse events in the FDC of arterolane maleate and PQP versus chloroquine group were vomiting (5.0 vs 5.1%), headache (1.3 vs 3.2%) and prolonged QT (1.9 vs 3.2%). No deaths were reported. The pharmacokinetic analysis indicates that arterolane maleate is well absorbed and has a relatively short t1/2 of 3.2 h. Piperaquine is also well absorbed after oral administration with a t1/2 of about 228.33 h., Conclusions: The study showed that FDC of arterolane maleate and PQP effectively cured vivax malaria and attained acceptable level of cure up to day 28. Both the groups showed similar safety profile. Trial Registration Clinical Trial Registry India: CTRI/2011/11/002129.

Background: The World Health Organization (WHO) recommends artemisinin combination therapy (ACT) for the treatment of uncomplicated Plasmodium falciparum malaria. The present study investigated the efficacy and safety of fixed dose combination (FDC) of arterolane maleate 37.5 mg and piperaquine phosphate (PQP) 187.5 mg dispersible tablets in paediatric patients aged 6 months to 12 years., Methods: Male and female patients aged 6 months to 12 years who were confirmed cases of P. falciparum mono-infection with fever or documented history of fever in the previous 24 h were included. The patients were administered FDC of arterolane maleate and PQP as single daily doses for three consecutive days based on their age. The primary efficacy outcome was proportion of patients with polymerase chain reaction (PCR)-corrected adequate clinical and parasitological response (ACPR) on day 28. Safety was analysed based on adverse events (AE), laboratory abnormalities and abnormalities on electrocardiograph., Results: A total of 141 eligible paediatric patients received FDC of arterolane maleate and PQP in a 42-day follow-up study. All the enrolled patients (141) were included in intention to treat (ITT) and safety analyses, and 126 patients were considered in per protocol (PP) population. The PCR-corrected ACPR on day 28 was achieved in all patients (100 %; 95 % CI 97.11-100) included in PP population. The median parasite clearance time (PCT) and fever clearance time (FCT) were 24 h (95 % CI 18.0-24.0) and 10 h (95 % CI 4.0-18.0), respectively. The most frequently reported clinical AE was vomiting. Majority of the AEs were mild to moderate in severity and resolved without sequelae. No patient was discontinued for any QTc (corrected QT interval) prolongation. No deaths or serious AEs were reported during the study., Conclusion: The findings from this study showed that FDC of arterolane maleate and PQP effectively cures P. falciparum malaria and attains acceptable level of cure by day 28 in paediatric patients. The efficacy and safety results observed in children warrants further studies on FDC of arterolane maleate and PQP dispersible tablets., Trial Registration: Clinical Trial Registry India: CTRI/2009/091/000531.

Objective: The purpose of this study was to investigate the efficacy and safety of Fixed Dose Combination (FDC) of olanzapine 5 mg and fluoxetine 20 mg in Indian patients with severe or treatment resistant depression., Design: This was an open, non-comparative study of seven weeks duration with an initial placebo run in period of one week., Method: One hundred and fifty three patients were enrolled. One hundred and forty-four patients completed the study as per protocol and 151 patients were safety evaluable. One hundred and eleven patients (77%) received one tablet of FDC of olanzapine 5 mg / fluoxetine 20 mg once daily for 6 weeks, in patients (14%), the dose was stepped up at the end of 2 weeks to 2 tablets of FDC of olanzapine 5 mg/ fluoxetine 20 mg once daily for a further 4 weeks and 13 patients (9%) required dose to be stepped up at the end of 4 weeks to 3 tablets of FDC of olanzapine 5 mg and fluoxetine 20 mg once daily for last 2 weeks., Results: One hundred and thirty four patients (93%) responded to FDC of olanzapine and fluoxetine therapy (a responder was defined as a patient with 50 % reduction over baseline in HDRS total score at the end of therapy).Statistically significant (p < 0.0001) reductions in HDRS total score, MADRS total score and CGI severity scores were seen with olanzapine/ fluoxetine combination. One hundred and four patients (72%) were remitters (HDRS total score of <7) after 6 weeks of therapy. Adverse experiences were reported by thirty one patients (20.5%). Majority of them were mild in intensity. No serious adverse event was recorded with study therapy. Three patients were withdrawn from the therapy due to adverse event., Conclusion: Treatment with FDC of olanzapine 5 mg / fluoxetine 20 mg was highly effective and well tolerated in Indian patients with severe or treatment resistant depression.

Sparfloxacin, a new quinolone antibacterial was used to treat one hundred and thirty two patients with acute purulent sinusitis, at a dosage of 400 mg on the first day followed by 200 mg once daily for a further four days. A clinically successful outcome (defined as disappearance of nasal discharge, fever, pain, tenderness over the sinuses and headache) was recorded in 122 ( 95.3%) patients. Sparfloxacin was well tolerated. Fourteen adverse experiences were reported in 7 patients ( 5.3%); they were mainly gastrointestinal and mild. No phototoxic or cardiological adverse events occurred. An unusual feature was that Staphylococcus aureus and Pseudomonas spp. were the most common bacterial species isolated from middle meatal was of patients in this study.

Conventional antipsychotic agents are not effective against negative symptoms of schizophrenia and are also noted for their extrapyramidal side effects. Risperidone is a noval antipsychotic agent whose dual antagonism of dopamine and serotonin receptors is believed to underlie its efficacy against negative symptoms and the low incidence of extrapyramidal side effects. An open, non-comparative study of seven weeks duration was performed to evaluate risperidone in the treatment of schizophrenia in Indian patients. Previous antipsychotic therapy was discontinued for a week before risperidone therapy was initiated. At the end of six weeks of risperidone therapy, clinical improvement (≥ 20% reduction in total score on positive and negative syndrome scale for schizophrenia (PANSS;; was shown by 128 (87.7%) of the 146 evaluable patients. Statistically significant reduction (p < 0.05) occurred in the total score of this scale and in the subscale scores for positive, negative and general psychopathology symptoms and in the clinical global impression severity score. The number of patients with adverse experiences were 108 (65.5%) at baseline and 120 (72.7%) at the end of risperidone therapy. Extrapyramidal symptoms, seen in 65 (39.4%) patients compared to 22 (13.3%) patients at baseline, were largely mild to moderate in intensity.

A young female with pure red cell aplasia with brisk response to prednisolone therapy is described. The patient has remained in remission on a small dose of prednisolone for 10 months.