Padmaja A Marathe

Awareness about medical research among resident doctors in a tertiary care hospital: A cross-sectional survey

Context: Every medical practitioner should strive to contribute to the generation of evidence by conducting research. For carrying out research, adequate knowledge, practical skills, and development of the right attitude are crucial. A literature review shows that data regarding knowledge, attitude, and practices toward medical research, among resident doctors in India, is lacking. Aims: This study was conducted to assess research-related knowledge, attitude, and practices among resident doctors. Settings and Design: A cross-sectional survey was conducted using a pretested, structured, and pre-validated questionnaire. Materials and Methods: With approval of the Institutional Ethics Committee and a verbal consent, a cross-sectional survey among 100 resident doctors pursuing their second and third years in the MD and MS courses was conducted using a structured and pre-validated questionnaire. Statistical Analysis: Descriptive statistics were used to analyze the results. Results: The concept of research hypothesis was known to 58% of the residents. Ninety-eight percent of the residents were aware of the procedure to obtain informed consent. Seventy-six percent agreed that research training should be mandatory. Although 88% of the residents were interested in conducting research in future, 50% had participated in research other than a dissertation project, 28% had made scientific presentations, and only 4% had publications. Lack of time (74%), lack of research curriculum (42%), and inadequate facilities (38%) were stated as major obstacles for pursuing research. Conclusions: Although resident doctors demonstrated a fairly good knowledge and positive attitude toward research, it did not translate into practice for most of them. There is a need to improve the existing medical education system to foster research culture among resident doctors

A split dose regimen of streptozotocin to induce diabetes in a neonatal rat model

Th is PD F is av ail ab le for fr ee d ow nlo ad fr om of the beta cells in neonates are destroyed by STZ, but they gradually regenerate to about half the original mass. The animals exhibiting blood glucose levels above 100 mg% are considered as diabetic. By varying the administration time of STZ, one can obtain hyperglycemia of differing severity depending upon the extent of beta-cell damage and regeneration. 5] Susceptibility of rats to STZ varies with species, strain, sex, age and nutritional state of the animals, and all the STZ-treated animals do not develop hyperglycemia. Variations in blood glucose levels, high mortality (30-50%) due to STZ toxicity and lack of response to oral hypoglycemic drugs are the drawbacks of n0 and n5 models. 5, 7] In addition, there is no documentation of the number of excluded animals which failed to show desired hyperglycemia. A study by Portha et al, in 1974 has shown that a split dose of STZ injected over two consecutive days (day 0 and 1) after birth induces hyperglycemia and decreases pancreatic insulin stores by day 5 as compared to a single dose injection. In this study the authors did not investigate the blood glucose and insulin levels beyond 3 weeks. Such a split dose regimen has not been used by any other researcher. Hence, we decided to test the efficacy of a split dose regimen of STZ to develop a neonatal diabetes model. After obtaining the permission of the Animal Ethics Committee, seven batches of newborn, Wistar rat pups (n=54) consisting of six to eight per batch were taken up. STZ was administered to 46 neonates on the 2nd and 3rd postnatal day in the dose of 50 mg/kg/day intraperitoneally, and 0.3 ml of vehicle (citrated buffer) was administered to eight neonates. After 28 days, the neonates were weaned. Fasting blood glucose one animal died in the 1st week and the other in the 4th week). Thirty-five out of 39 rats (89.74%) developed hyperglycemia in the range of 100-160 mg%. The average FBG was 119.94±17.93 mg%. Out of the six batches that were administered STZ, five showed uniform levels of hyperglycemia (102-130 mg%). However, only one batch showed a higher level of 153.04±9.21 mg%. The FBG of the vehicle treated group was found to be 75.33±8.91. Twelve hyperglycemic rats from the STZ treated group and six from the vehicle group were observed for a further period of 8 weeks. Six of these 12 STZ treated rats were administered glibenclamide in a dose of 0.5 mg/kg orally once daily, to evaluate the effect of the oral hypoglycemic agent on FBG and OGTT. In all these rats, FBG and OGTT were reassessed at the end of the 12th and the 16th week. The hyperglycemia in the STZ group sustained even at the 12th week and the 16th week. All the six animals survived upto the 16th week. However, in rats treated with glibenclamide, significantly lower FBG levels were seen (P<0.001). [Figure 1] The STZ and vehicle groups exhibited significant difference with respect to OGTT (P<0.01). All the

Effect of combination of Phyllanthus emblica, Tinospora cordifolia, and Ocimum sanctum on spatial learning and memory in rats

Background: There has been a steady rise in number of patients suffering from dementia including dementia associated with Alzheimer′s disease. Effective treatment of Alzheimer′s disease dementia is an unmet medical need. Objective: To evaluate effects of formulation containing combination of Phyllanthus emblica (Pe) and Tinospora cordifolia (Tc) with and without Ocimum sanctum (Os) on learning and memory performance of normal and memory impaired rats in complex maze and compare with effects of Tinospora cordifolia and Phyllanthus emblica alone. Materials and Methods: Wistar rats; either sex (100-150 g) were divided in seven groups Control, Piracetam, Rivastigmine, Tc, Pe, Formulation 1 (Tc + Pe), and Formulation 2 (Tc + Pe + Os).The study was divided in four parts: In part 1 memory enhancement was tested in normal rats. In part 2, 3, and 4 the effects of drugs were tested in Scopolamine-, Diazepam-, and Cyclosporine-induced amnesia. Hebb-Williams maze was used to test for learning and memory. Time required to trace food and number of errors in maze were noted. Results: In normal rats, all test drugs showed significant reduction in time required to trace the food and number of errors after 24 h compared with vehicle control. Formulations 1 and 2 reduced the time required to trace food and number of errors and the results were comparable with positive control groups and comparators Tc and Pe. Formulations 1 and 2 reversed amnesia produced by Scopolamine, Diazepam, and Cyclosporine when compared with vehicle control and showed comparable results with those of positive control groups and comparators Tc and Pe. Conclusion: Formulations 1 and 2 demonstrated nootropic activity and both the formulations showed comparable nootropic activity with that of Tc and Pe alone.

Introduction of case based teaching to impart rational pharmacotherapy skills in undergraduate medical students

Objective: The aim of this study is to assess the impact of case based teaching (CBT) on learning rational prescribing and to compare CBT with the traditional method of teaching (TRD). Materials and Methods: Second year Bachelor of Medicine and Bachelor of Surgery (MBBS) students (n = 179) were administered a pre-test and randomly divided into groups to receive CBT (n = 96) and TRD (n = 83). CBT group was further sub-divided into CBT1 and CBT2. Both these groups were taught two topics each by CBT and TRD during tutorials; however, the topics were switched with respect to method of teaching. The post-test comprised of three therapeutic problems of which two were related, and one was not related to the tutorial topics. Marks obtained in the post-test were graded and analysed using Fischers exact test. Results: In the post-test, the therapeutic problems on diabetes mellitus and peptic ulcer were attempted by 85.41% students from CBT and 73.49% from TRD group. CBT group obtained more marks for these problems (4.23 ± 0.94; P < 0.001) than the TRD (3.32 ± 0.92) group. Also, more students in the CBT obtained grade 3 (P < 0.001) and fewer obtained grade 1 (P < 0.01), compared to the TRD group. When the grades of the two CBT groups were compared, it was found that fewer students in CBT 2 had obtained grade 1 and those scoring higher grades were comparable between the two groups. For the therapeutic problem on malaria, 7.29% students from CBT and 18.07% from TRD received 0 grade (P < 0.05). More students received ≥ 2 grade in CBT group (P < 0.05). Conclusion: Use of CBT during tutorials is better than TRD and facilitates learning of rational pharmacotherapy.

Experimental evaluation of analgesic, anti-inflammatory and anti-platelet potential of Dashamoola

Background: Dashamoola, in the form of arishta and kwath, is a commonly used classical Ayurvedic multi-ingredient formulation for management of pain, arthritis and inflammatory disorders. Objective: To study analgesic, anti-inflammatory and anti-platelet activity of Dashamoola and its combination with aspirin. Materials and Methods: Wistar albino rats (180-200 g) and Swiss albino mice (20-25 g) of either sex were divided randomly into five groups: Distilled water, aspirin (500mg/kg in rats; 722.2 mg/kg in mice), Dashamoolarishta (1.8 mL/kg in rats; 2.5 mL/kg in mice) and Dashamoolarishta with aspirin. Anti-inflammatory activity was measured by change in paw volume in carrageenan-induced inflammation, protein content in model of peritonitis and granuloma weight in cotton pellet granuloma. Analgesic effect was evaluated by counting number of writhes in writhing model. Maximum platelet aggregation and percentage inhibition of ADP and collagen-induced platelet aggregation were estimated in vitro. Statistical analysis was done using one way ANOVA (post hoc Tukey′s test) and P < 0.05 was considered significant. Results: Dashamoolarishta and its combination with aspirin showed significantly (P < 0.01) less number of writhes. It showed significant (P < 0.001) anti-inflammatory activity by paw edema reduction in rats, decrease in proteins in peritoneal fluid (P < 0.001) and decrease in granuloma weight (P < 0.05) as compared to respective vehicle control groups. Dashamoola kwath alone and in combination with aspirin inhibited maximum platelet aggregation and percent inhibition of platelets as compared to vehicle (P < 0.001). Conclusion: Dashamoola formulation alone and its combination with aspirin showed comparable anti-inflammatory, analgesic and anti-platelet effects to aspirin.

An Audit of Protocol Deviations Submitted to an Institutional Ethics Committee of a Tertiary Care Hospital

Protocol deviations (PDs) may jeopardize safety, rights, and welfare of subjects and data integrity. There is scarce literature and no guidelines for Institutional Ethics Committees (IECs) to process PD reports. The PD reports submitted to IECs from Jan 2011 to August 2014 were analyzed retrospectively. Types of studies reporting PDs, category and type of PDs, PD rate per participant, time of reporting PD since its occurrence and corrective actions stated by principal investigator (PI) for major deviations were noted. Out of 447 PDs from 73/1387 total studies received during study period, 402 were from 126 pharma studies. Investigator initiated studies and dissertations reported negligible PDs. Median number of PDs was 4 per protocol. Out of 447 PDs, 304 were related to study procedure, 87, 47 and 9 were from safety, informed consent document (ICD) and eligibility category respectively. The most common reason for PDs was incomplete ICD (22/47). Maximum study procedure related PDs were due to patient visiting outside window period (126/304). Thirty five of 87 PDs were due to missed safety assessment. The overall PD reporting rate per participant was 0.08. In 90% of reports, date of occurrence of PD was not specified. The median delay for reporting PDs after occurrence was 94 days. PDs classified as Major were 73% (323/447). The most common corrective actions stated by PI were participant counseling (85/323) and caution in future (70/323). The study findings emphasize the need for GCP training at regular interval of study team members. IEC have to be vigilant and visit sites frequently, take initiative and formulate guidelines regarding PD reporting.

Effect of Jyotiṣmatī seed oil on spatial and fear memory using scopolamine induced amnesia in mice

Background: Treatment of memory impairment associated with dementia such as Alzheimer′s disease is still inadequate and requires development of new drugs. Objective: The objective was to evaluate the memory enhancing effect of Celastrus paniculatus seed oil. Materials and Methods: C. paniculatus seed oil was mixed with equal amount of pure ghee and administered orally to mice in the dose of 200 mg/kg/day. Piracetam was used as a standard nootropic. Elevated plus maze and passive avoidance tests were used as a models to test spatial and fear memory respectively. Scopolamine (3 mg/kg, i.p.), was used as an amnestic agent. Results: Mice receiving C. paniculatus showed significant memory enhancement as compared to scopolamine group. The effect of C. paniculatus and combination of C. paniculatus with piracetam was comparable to that with piracetam alone. Conclusion: The present study demonstrates that C. paniculatus seed oil has memory enhancing effect and hence can be developed as a potential drug in the treatment of dementia.

Effect of Saraswatarishta in animal models of behavior despair

Background: Saraswatarishta (SA) is a herbo-mineral formulation consisting of 18 plants some of which are Medhyarasayanas. It has been claimed to be useful in treating central nervous system disorders. Objective: To evaluate antidepressant effect of ′Saraswatarishta′(SA) alone and in combination with imipramine and fluoxetine in animal models of depression. Materials and Methods: After obtaining IAEC permission, 144 rats (n = 36/part) were randomized into 6 groups- Group 1: Distilled water (1 mL), Group 2: Imipramine (30 mg/kg), Group 3: Fluoxetine (10 mg/kg), Group 4: SA (1.8 mL/kg), Group 5: Imipramine + SA, Group 6: Fluoxetine + SA. Effects of study drugs were evaluated in forced swim test (FST) with single exposure to FST (Part 1) and repeated exposure for 14 days (Part 2). In Part 3, reserpine was used with FST and effects of study drugs were evaluated against single exposure to FST. Same model was used with repeated exposures to FST (Part 4). In each part, rats were subjected to open field test (OFT) for 5 min prior to final FST. The variables measured: Immobility time in FST; line crossing, rearing and defecation in the OFT. Results: In all four parts, individual drugs and combinations thereof produced significant decrease in immobility time as compared to control, and extent of decrease was comparable amongst these groups. However, values for combination of fluoxetine with SA group were found to be lesser than that for individual agents in Parts 2 and 3. Combination of SA with imipramine did not enhance its anti-depressant effect in any of the parts. OFT findings did not vary significantly amongst the study groups. Conclusion: Decreased immobility in FST and absence of generalized stimulation or depression of motor activity in OFT point towards potential antidepressant effect of Saraswatarishta. Its co-administration with fluoxetine showed more promising effects.

A study to assess completeness of project application forms submitted to Institutional Ethics Committees (IEC) of a tertiary care hospital

Objectives: To review Ethics Committee (EC) application forms and to find out similarities and differences in content of five ECs forms in India. Materials and Methods: The completeness of EC application forms was assessed on the following themes: title, study team, sponsor responsibility, scientific aspects, patient safety, regulatory permissions, Informed consent process from 2008-2009. Application forms (available online) of 5 ECs were studied and compared. Results: A total of 445 application forms were analyzed, 382 were academic, 63 were sponsored. The common deficiencies in academic studies were inappropriate titles (25.13%), lack of budget details (90%). More than 95% studies had not mentioned the method of recruitment. The issue of vulnerability was not marked in more than 50% of studies. Compensation for participation/injury was poorly stated in academic (99%) studies. Among industry sponsored studies, 98% were compliant with regulatory permissions and 41% were CTRI registered. The information pertaining to Informed Consent was mentioned in all forms. Comparative analysis of application forms of 5 ECs showed that the requirements for submission were similar except 1-2 ECs asked for additional information like percentage of time allotted by investigator for studies, GCP training of study team, certification by investigator regarding accuracy of local versions of Informed consent. Conclusion: Our study recommends that increased awareness and vigilance by investigators of academic studies regarding submission of applications to EC will increase efficiency and speed of review process. A common application form for all ECs across India would be an important step to achieve uniformity in functioning of ethics committees.

Payment for participation in clinical research: Review of proposals submitted to the ethics committees

Objective: In view of dearth of information in national and international guidelines on payment practices in research, the present study was done to find out payments for participation allowed by 3 Ethics committees (ECs) and reasons for payment. Method: This was a retrospective observational study which analysed research proposals reviewed by 2 institutional and 1 non-institutional ECs over a period of 2 years. The permission of ECs was obtained and confidentiality of data was maintained. Results: Of the 73 studies requiring payment, 89.04% were interventional and 10.96% observational. Reimbursement of travel expenses (60%) was the major reason for payment followed by inconvenience due to participation, loss of wages and time spent. The queries raised by EC in more than 50 % of studies were related to informing patients about the payment in the informed consent document. The investigators complied with the EC requirements regarding payment (15/21) and the remaining provided explanations. The median amount of payment in pharmaceutical sponsored studies was higher compared to investigator initiated studies. Higher payments were approved by ECs on case to case basis in a few studies. The ECs did not have any policy/ standard operating procedure for payment practices. Conclusion: The present study first of its kind in India, demonstrated that quantum of payment was not uniform for pharmaceutical sponsored and investigator initiated studies and payments were not considered for majority of observational studies. Travel reimbursement was the most common reason for payment. There is a need to develop guidelines for determining appropriate payment/incentives to participants for specific types of research related activities.