Central markers of obesity affect heart rate variability independent of physical activity in young adults.

Introduction: Obesity is considered to be a risk factor for a variety of cardiovascular conditions. Various markers for obesity are used to evaluate effect of obesity on cardiovascular autonomic activity. In light of conflicting reports on effect of obesity on heart rate variability (HRV), use of obesity indices, and the effect of physical activity on HRV, we evaluated autonomic activity in young Indian obese adults using revised Indian and World Health Organization (WHO) body mass index (BMI) guidelines for obesity, waist circumference (WC), and waist-hip ratio (WHR) taking into consideration the level of physical activity. Methods: The study was conducted on 91 young healthy adults. Height, weight, waist, and hip circumference were recorded to determine BMI and WHR. Five-minute electrocardiogram (ECG) was recorded for assessment of HRV. Physical activity was assessed by the WHO Global Physical Activity Questionnaire (GPAQ). Results: Waist circumference showed a negative correlation with the time domain parameters of HRV and high frequency normalized units (HFnu) while a positive correlation with low frequency normalized units (LFnu). In multiple linear regression analysis, time domain indices, HFnu and total power decreased while LFnu increased with an increase in WC. The result was supported by the similar effect of waist-hip ratio categories on HRV in analysis of covariance (ANCOVA). Physical activity had no effect on HRV. Conclusion: Central obesity parameters are better predictors of effect of obesity on HRV independent of the effect of physical activity.

Funding opportunities for health research in India - A technical scan.

Health research plays an integral part in scientific and academic innovation in health care. India, a rapidly developing country, showed a tremendous increase in the number of health research projects and publications in recent years. Given the broad spectrum of health research areas and a vast number of funding agencies that fund specific areas, it is difficult to gain knowledge about them from a single source. Hence, we scanned the various funding opportunities which exist in India for healthcare research. Various agencies fund health-care research on their thrust areas of national importance. Choosing the funding agency depending on the area of interest and following the guidelines given by them ensures a successful proposal for funding. This article enlists various funding agencies and gives overall information about the nature of support and fund provided for health research in India.

Is emotional intelligence related to objective parameters of academic performance in medical, dental, and nursing students: A systematic review.

Background: Current research in medical education is increasingly exploring the relevance of emotional intelligence (EI) in the successful performance of health-care people. As assessments of core domains are markers of actual performance of the student when he or she is not observed, this systematic review was aimed to answer the question "what is the influence of EI on objective parameters of academic performance in undergraduate medical, dental, and nursing students aged 18-30 years?" Methods: Databases were systematically searched for empirical studies which measured EI of medical, nursing, or dental undergraduate students and compared it with academic performance during graduation years from January 1, 2000, to August 30, 2016. Quality appraisal and data abstraction was done by two independent authors. Results: Six hundred and twenty-three articles were retrieved from systematic search. Of these, 25 articles were selected. Quality appraisal further led to exclusion of two studies which did not meet ethical criterion. Medical undergraduates were included in 12, dental in 4, and nursing in 7 studies. Four studies examined the relationship of EI with clinical skills, 8 with communication skills, and 18 with overall academic performance. Discussion: The findings of review show that EI has a greater role in academic success of clinical year medical and dental students. Although the review has addressed different rungs of the health-care profession separately, it preludes that better EI skills of health-care team will have a holistic impact on health-care improvement.

Multistation exercises: a combination of problem-based learning and team-based learning instructional design for large-enrollment classes.

To introduce active learning session for a large group of 250 students, we combined the strengths of problem-based learning and team-based learning to promote a structured active learning strategy with less faculty involvement. For the implementation of this strategy, a case on anemia was selected based on the module already covered in classes. Structured exercises were preplanned on six different concepts that a student should possess for solving the problem. The large group of 250 students was divided into groups of 41 or 42 each. The groups were facilitated by one faculty member for one structured exercise. At the station, the group of 41 or 42 was further broken down into 6 smaller groups comprising 7 students each. After completion of the exercise, students cycled to the next exercise station facilitated by another faculty member. The case was solved in a plenary session. The effectiveness of the method was assessed by comparing the academic performance of the group with other similar groups from the previous year. The intervention group performed significantly better than the nonintervention group on the related item. Quartile subanalysis found that the effect was present in the performance of average and higher quartile groups, but not in the lower quartile group.

Longitudinal predictive validity of emotional intelligence on first year medical students perceived stress.

BACKGROUND: Emotional intelligence has been shown to affect academic performance and perceived stress. But conflicting reports suggest that the relationship between academic performance and emotional intelligence may not be straightforward. Hence, this study explored the relationship between emotional intelligence, perceived stress and academic performance. METHODS: First year medical students were invited to participate in this longitudinal study. At Time 1, before mid-semester examinations, they completed the questionnaires on Schutte's Emotional Intelligence Scale (SEIS) and Perceived Stress Scale (PSS) (n = 213). At Time 2, before pre university examinations, students again completed perceived stress scale questionnaire. (n = 138). Academic performance was reported using summative assessment at both T1 and T2. The relationship between academic performance, emotional intelligence and perceived stress was explored using regression analysis. RESULTS: Neither PSS nor SEIS were related to academic performance. However, perceived stress was significantly predicted by SEIS both at T1 (r = 0.333, ß = 0.149, p < 0.001) as well as T2 (r = 0.240, ß = 0.116, p = 0.028). The results were cross-validated at student level both at T1 and at T2. CONCLUSION: Medical students with higher trait emotional intelligence perceived lesser stress. Therefore, it might be prudent to train medical students to increase their emotional intelligence to promote their well-being.

Autonomic Reactivity Differs in Young Adults Classified using Revised Indian and WHO Guidelines for Obesity.

INTRODUCTION: Many studies have reported alteration in autonomic activity in obesity. However, there is paucity of literature comparing autonomic reactivity using different guidelines of obesity. As Indian guidelines were revised recently and WHO states that countries should use all categories of BMI for reporting purposes, it is prudent to compare physiological state in different categories of BMI. AIM: The aim of the present study was to compare the autonomic alteration in young adults using revised Indian and WHO guidelines for obesity. MATERIALS AND METHODS: A battery of autonomic tests (Valsalva Manoeuvre (VM), Deep Breathing Test (DBT), Lying to Standing Test (LST) and Hand Grip isometric exercise Test (HGT) was conducted on 34 overweight and obese and 30 normal weight volunteers categorised using revised Indian guidelines of body mass index. Same participants were regrouped and analysed using WHO guidelines of BMI and waist hip ratio (WHR). RESULTS: For analysis, participants were grouped into 3 categories of normal, overweight and obese using revised Indian guidelines for obesity. Same participants were regrouped according to WHO guidelines. E:I ratio during DBT, 30:15 ratio during LST, Valsalva ratio during VM and increase in DBP during HGT were compared in different subgroups. There was no difference in sympathetic and parasympathetic activities in participants classified according to revised Indian guidelines. In participants classified using WHO criteria, sympathetic reactivity in overweight subjects was significantly less as compared to normal subjects (p<0.05). CONCLUSION: Autonomic alterations might be more related to body fat percent rather than BMI. Indian guidelines are based on the observation that Asian population has more adipose tissue in WHO range of BMI. As the guidelines of BMI are applicable to all age groups and do not consider physical activity profile, they might still not be a good predictor of body fat.

Pharmacokinetics of zolpidem from sublingual zolpidem tartrate tablets in healthy elderly versus non-elderly subjects.

BACKGROUND: Pharmacokinetic parameters of sedative-hypnotic medications can be influenced by age and gender. OBJECTIVE: This study analyzed pharmacokinetic parameters of zolpidem, formulated as a sublingual zolpidem tartrate tablet (ZST; Intermezzo®), in healthy elderly males and females (mean age 72 years) and in non-elderly males and females (34 years). METHODS: This was a randomized, single-dose, open-label, two-way crossover study evaluating pharmacokinetic parameters of 1.75 and 3.5 mg dosages of ZST in elderly subjects (n = 22), and 3.5 mg dosages of ZST in non-elderly subjects (n = 24). Main outcome measures were pharmacokinetic parameters, including area under the plasma concentration-time curve (AUC), maximum observed concentration (C(max)), time to reach C(max) (T(max)), elimination half-life (T(½)), and apparent oral clearance (CL/F). RESULTS: Dose proportionality in zolpidem exposure was maintained between 1.75 and 3.5 mg doses for both elderly females and males. With administration of the 3.5 mg dose of ZST to elderly and non-elderly subjects, significantly higher systemic exposure was seen in elderly females (C(max) +44.6 %, P < 0.01; AUC +40.4 %) compared with non-elderly females. However, systemic exposure was only modestly higher in elderly males compared with non-elderly males. Greater exposure was seen in elderly females compared to males (C(max) +46.8 %, P < 0.01; AUC +31.4 %). In this study, exposure between non-elderly females and males was equivalent. Changes in T(½) and T(max) values were not observed, with no significant age effect on oral clearance. There were no apparent differences in tolerability among age and gender groups. CONCLUSION: Elderly individuals were found to have higher C(max) and AUC values compared with non-elderly subjects. C(max) and AUC were greater in elderly women compared with elderly men.

Gender influences on efficacy and safety of sublingual zolpidem tartrate for middle-of-the-night awakening in insomnia.

OBJECTIVE: Evaluate potential gender effects on efficacy and safety of a buffered zolpidem sublingual tablet (ZST) formulation. METHODS: Post hoc analysis of the pivotal sleep laboratory and outpatient studies, per gender. RESULTS: In the sleep laboratory study, polysomnography-derived latency to persistent sleep after middle-of-the-night was significantly improved for both genders at both 1.75 mg and 3.5 mg ZST (females: 15.7 and 8.6 min, respectively, vs. 27.7 min [placebo]; males: 19.0 and 12.7 min vs. 29.0 min [placebo]) with no significant gender differences. In the outpatient study, subjective sleep onset latency after middle-of-the-night was significantly shorter for both genders treated with ZST 3.5 mg versus placebo over the 4-week average (females: 37.3 vs. 59.4 min, p < 0.0001; males: 38.6 vs. 55.1 min, p ≤ 0.01). There were no gender differences in subjective sleep onset latency after middle-of-the-night awakening. In the outpatient study, weekly usage of ZST and placebo by both genders declined throughout the study. Morning alertness following dosing nights improved in both genders, although significant only in females. In both studies, there were no gender differences in adverse events. CONCLUSION(S): Time to return to sleep after middle-of-the-night dosing with ZST improved in both genders, with no gender differences in efficacy and safety.

Ondansetron augmentation in patients with obsessive-compulsive disorder who are inadequate responders to serotonin reuptake inhibitors: improvement with treatment and worsening following discontinuation.

OBJECT: The aim of this study was to evaluate low-dose ondansetron as an augmentation strategy in patients with obsessive-compulsive disorder (OCD) who do not adequately respond to serotonin reuptake inhibits (SRIs). METHODS: Twenty-one OCD patients who had not responded adequately to an SRI received 12 weeks of single-blind ondansetron augmentation initiated at 0.25mg BID for 2 weeks, and titrated to 0.5mg BID for an additional 10 weeks. Patients were rated every two weeks using the Yale-Brown Obsessive Compulsive Scale (YBOCS) and Clinical Global Impressions Scale (CGI). Treatment response was defined as an additional 25% reduction in YBOCS score from the score at the initiation of ondansetron augmentation, an end of treatment YBOCS score of ≤ 24 and a CGI-Improvement (CGI-I) score of ≤ 2. Upon completion of treatment course patients were followed for 4 weeks. RESULTS: At week 12, twelve of the 21 (57%) patients were responders. The average reduction in the YBOCS score for the overall group was 27.2%. Responders had an average 44% YBOCS score reduction and 76.9% CGI-I reduction. After discontinuation of ondansetron the YBOCS worsened an average of 15.5% in the entire sample and 38.3% in the responder subsample. No clinically meaningful side effects were reported. CONCLUSION: OCD patients who do not adequately respond to an SRI may benefit from augmentation with a low-dose of ondansetron. This may provide an alternative approach to augmentation with atypical antipsychotic agents, with a more favorable safety profile.

Gender differences in pharmacokinetics and pharmacodynamics of zolpidem following sublingual administration.

The effect of dose and gender on the pharmacokinetics (PK) and pharmacodynamics (PD) of zolpidem after administration of a buffered zolpidem sublingual tablet (ZST; Intermezzo®, Purdue Pharma L.P., Stamford, CT, USA) was evaluated in healthy non-elderly male and female volunteers. Subjects received a single morning dose of ZST (1.0, 1.75, and 3.5 mg) or placebo in a four-way crossover study. In male and female subjects zolpidem PK were linear, with area under the curve (AUC) proportional to dose, and apparent oral clearance and elimination half-life independent of dose. However, AUC averaged 40% to 50% higher in females than in males receiving the same dose. The gender effect was incompletely explained by body weight. In females, ZST produced PD changes consistent with benzodiazepine agonist effects, particularly at the 3.5-mg dose. For several PD variables, PD effects were significantly related to plasma zolpidem concentrations when data were aggregated across subjects. However, there was variability in response among individuals. In males, PD effects of zolpidem seldom differed from placebo regardless of plasma concentration. The findings confirm that zolpidem clearance is lower in females than in males. PD effects of zolpidem from ZST are greater in female subjects, due to a combination of higher plasma concentrations and greater intrinsic sensitivity.

Influence of food on pharmacokinetics of zolpidem from fast dissolving sublingual zolpidem tartrate tablets.

Ingesting food can impact the pharmacokinetics of sedative-hypnotic drugs. A buffered zolpidem sublingual tablet (ZST) recently became available for the treatment of middle-of-the-night awakening. In this randomized, open-label, single-site study, the pharmacokinetic profile of ZST was evaluated when administered while fasting and following a standard high-fat meal (fed state). Healthy adults aged 18-64 years received a single morning dose of 3.5 mg ZST in the fed or fasting state. From 20 min to 3 h post-dose, zolpidem plasma levels were lower in the fed state compared to the fasting state. After 4 h post-dose (corresponding to "morning wake time"), higher zolpidem plasma levels were evident in the fed state. Area under the concentration-time curve (AUC) values for the 0-8 h interval were 160 ng/mL h in the fed state and 203 ng/mL h in the fasting state (P < .001). In the fed versus fasting states, Cmax was 32.0 ng/mL versus 57.3 ng/mL (P < .001), respectively, and Tmax was 3.0 h versus 0.92 h (P < .001), respectively. Together these data suggest that administration of ZST in the fed state is not optimal for maximizing the likelihood of therapeutic benefit and minimizing the probability of residual sedation.

Comparison of pharmacokinetic profiles of zolpidem buffered sublingual tablet and zolpidem oral immediate-release tablet: results from a single-center, single-dose, randomized, open-label crossover study in healthy adults.

BACKGROUND: A zolpidem sublingual tablet (ZST) formulation was recently approved by the US Food and Drug Administration to treat middle-of-the-night (MOTN) awakening with difficulty returning to sleep. OBJECTIVE: The aim of this study was to compare the zolpidem pharmacokinetic profiles of 3.5-mg ZST and 10-mg immediate-release (IR) oral zolpidem in healthy female and male adults. METHODS: This randomized, open-label crossover study compared the pharmacokinetic profile of ZST with that of IR oral zolpidem in healthy adults. RESULTS: The study enrolled 19 males and 14 females. After 3.5-mg ZST and 10-mg IR, respectively, mean zolpidem plasma concentrations at 15 minutes (22 vs 17 ng/mL, respectively, in females and 18 vs 10 ng/mL in males) and AUCs from zero to 15 minutes (2.3 vs 0.8 ng · h/mL in females and 1.6 vs 0.5 ng · h/mL in males) were substantially greater for ZST, despite the larger absolute IR dose. After 3.5-mg ZST and 10-mg IR, respectively, clearance was lower in females, even after correcting for body weight (2.63 vs 2.88 mL/min/kg in females and 3.63 vs 3.91 mL/min/kg in males). The lag time prior to the start of first-order absorption was notably shorter for ZST than IR in both males (8 vs 21 minutes) and females (5 vs 22 minutes). Both zolpidem formulations were generally well tolerated by both genders. CONCLUSIONS: Systemic exposure of zolpidem was higher in females for both formulations. Plasma levels and AUC were higher, and clearance was lower, in females with both zolpidem formulations. The initial rate of absorption was faster, and initial systemic exposure was greater, with ZST compared with oral IR.

Novel sublingual low-dose zolpidem tablet reduces latency to sleep onset following spontaneous middle-of-the-night awakening in insomnia in a randomized, double-blind, placebo-controlled, outpatient study.

STUDY OBJECTIVES: To evaluate efficacy and safety of 3.5-mg zolpidem tartrate sublingual tablets (ZST) on latency to sleep onset after middle-of-the-night (MOTN) awakenings in patients with insomnia characterized by difficulty returning to sleep after MOTN awakenings. DESIGN: Multicenter randomized, double-blind, placebo-controlled, parallel-group. SETTING: Outpatient. PATIENTS: There were 295 adults (median age 43 y; 68.1% female) with primary insomnia and difficulty returning to sleep after MOTN awakenings (three or more MOTN awakenings/wk during screening). INTERVENTIONS: After a 2-wk, single-blind placebo eligibility period, participants were randomized 1:1 to as-needed MOTN dosing with 3.5 mg ZST or placebo for 28 nights. An interactive voice response system determined if the study drug could be taken and recorded sleep/wake efficacy measures. RESULTS: ZST significantly (P < 0.0001) decreased latency to sleep onset over 4 wk (baseline 68.1 min; ZST 38.2 min) compared with placebo (baseline 69.4 min; placebo 56.4 min). Ratings of morning sleepiness/alertness significantly (P = 0.0041) favored the ZST group on nights medication was taken but not on other nights. Participants in the ZST group took the study drug on 62% of nights during the 4 wk; members of the placebo group took study medication on 64% of nights. Adverse events were generally mild and at the same rate (19.3% of participants) in both groups. There were no treatment-related serious adverse events (SAEs), and one adverse event-related study discontinuation from the placebo group. Dosing/week did not increase across the study. CONCLUSIONS: 3.5 mg ZST used as needed significantly reduced latency to return to sleep in comparison with placebo in these patients with insomnia. Sleep quality was improved, and morning sleepiness/alertness scores also improved. ZST was well tolerated. These data demonstrate the utility of a sleep-promoting agent when used as needed in the MOTN. CLINICAL TRIALS REGISTRATION: NCT00466193: "A Study of Zolpidem Tartrate Tablet in Adult Patients with Insomnia" http://www.clinicaltrials.gov/ct2/show/NCT00466193?spons=%22Transcept+Pharmaceuticals%22&spons_ex=Y&rank=2

Ondansetron augmentation in treatment-resistant obsessive-compulsive disorder: a preliminary, single-blind, prospective study.

Serotonin and dopamine neuronal systems have been implicated in the modulation of obsessive-compulsive disorder (OCD) symptoms. About 40% of OCD patients do not respond to first-line selective serotonin reuptake inhibitor (SSRI) treatment; among those, dopamine blocker augmentation has been reported to improve the rate of response by an additional one-third. Given that serotonin 5-HT(3) receptors are indirect inhibitors of cortico-mesolimbic dopamine release, augmentation with the 5-HT(3) receptor antagonist ondansetron in combination with SSRIs and antipsychotics has potential efficacy in treatment-resistant OCD patients. To assess the efficacy and tolerability of ondansetron in combination with SSRIs and antipsychotics in patients with treatment-resistant OCD. In total, 14 patients with a DSM-IV diagnosis of OCD, who were treatment resistant and receiving stable treatment with SSRIs and antipsychotic augmentation, entered a 12-week, single-blind trial of ondansetron. The drug was initiated at a dosage of 0.25 mg twice daily for 6 weeks and was then titrated to 0.5 mg twice daily for 6 weeks. Of the 14 patients, nine (64.3%) experienced a treatment response (> or =25% reduction in the Yale-Brown Obsessive Compulsive Scale [YBOCS] score and a Clinical Global Impressions-Improvement [CGI-I] score of 1 or 2) at 12 weeks. The average reduction in YBOCS-rated symptoms for the whole group was 23.2%. None of the treated patients experienced symptom exacerbation or significant adverse effects. These results suggest that low-dose ondansetron may have promise as an augmentation strategy for some patients with OCD resistant to SSRIs and antipsychotic augmentation, but further controlled trials are required. Trial registration number (ClinicalTrials.gov): NCT00796497.

Daytime pharmacodynamic and pharmacokinetic evaluation of low-dose sublingual transmucosal zolpidem hemitartrate.

OBJECTIVES: Buffered low-dose sublingual transmucosal zolpidem lozenge hemitartrate (ST zolpidem) is being developed for the treatment of middle-of-the-night insomnia. The objective of this double-blind placebo-controlled cross-over study (n = 24) was to evaluate the pharmacokinetics (PK) and daytime-sedative profile of 1.0, 1.75, and 3.5 mg dose of the formulation. METHODS: Daytime sedation was measured pre-dose and up to 5 h post-dose objectively by the Digit Symbol Substitution Test (DSST) and subjectively using the Visual Analog Scale (VAS). Blood samples for PK assessment was collected pre-dose and up to 12 h post-dose. RESULTS: The 1.75 and 3.5 mg, but not the 1 mg, ST zolpidem produced significant sedation versus placebo within 20 min of dosing which lasted for up to 3 h. Zolpidem from the formulation was rapidly absorbed and reached maximum plasma concentrations within 38 min of dosing, however the half-life was independent of the dose and side effects were consistent with the known pharmacology of the drug. CONCLUSIONS: ST zolpidem produced rapid, short duration of sedation and the effect was consistent with its PK profile. This novel low-dose formulation of zolpidem may provide clinicians and patients with a prn option for the management of sleep maintenance insomnia.