Assessing completion reports for compliance with institutional ethics committee-approved protocols: An observational study.

BACKGROUND: Protocol non-compliance in clinical research studies is common and can affect both patient safety and data integrity. There are no published studies which actively looked for non-compliance. The present study was carried out, against this background, with the objective of assessing the proportion of protocol non-compliance and evaluating those aspects of protocol where there was non-compliance. METHODS: The study completion reports that were submitted to the institutional ethics committee for the period January 2017 to December 2017 were compared with the approved protocol. A checklist for recording protocol non-compliance was developed, which was validated by five experts and consisted of a 12-point checklist with responses such as yes, no, not applicable, and insufficient information. RESULTS: Out of 193 studies, prospective observational studies were n = 120 (62.17 %), retrospective studies were n = 39 (20.21%), interventional studies n = 28 (14.51 %), and observational studies with both prospective and retrospective study design were n = 6 (3.11%). The study objective was modified in n=18 (9.32%) studies. Only n = 14 (7.24%) satisfied the selection criteria. Six studies (3.10%) did not collect the data as mentioned in the protocol. Fifty-eight studies (30.05%) did not achieve the calculated sample size, whereas n = 78 (40.41%) did not complete the study as per the stipulated study duration. Contrary to 180 protocol deviations found in this study, only 14 protocol deviations were reported by the principal investigator. Aspects like blinding and randomisation, which are relevant to interventional studies (n = 28), showed 100 % compliance. CONCLUSION: The research protocol is not adhered to in all aspects. Adequate training to investigators will help prevent non-compliance and enable us to conduct studies with higher ethical and scientific integrity.

Perception of postgraduate students in pharmacology toward animal simulation model.

OBJECTIVE: The objective of the study is to evaluate the perception of postgraduate pharmacology students toward computer-simulated method (CSM) in comparison to the prevalent isolated live tissue-based bioassay method. MATERIALS AND METHODS: A questionnaire-based survey was conducted in 30 postgraduate pharmacology students who had used the animal simulation software and had completed at least five isolated tissue experiments. Students' opinions on the usage, logistics, advantages, disadvantages, and usefulness of CSM compared to live animal experiments (LAE) were analyzed. RESULTS: Four tissues were used for LAE, whereas with CSM, students could perform experiments using 11 different tissues. Of the total nine bioassay methods, students had performed six assay methods using both LAE and CSM. Majority of the students (23/30) agreed that CSM reduces anxiety, technical errors and is less time consuming when used before LAE. Most of the students agreed that CSM can be used for difficult, lengthy experiments (19/30), and for UG/PG teaching (19/30). However, opinions regarding replacing LAE with CSM in PG teaching were divided (agree: 7, neutral: 12, and disagree: 12). CONCLUSION: CSM should be integrated alongside LAE to complement, reinforce, and enhance learning from other techniques.

Minocycline in Alcohol Withdrawal Induced Anxiety and Alcohol Relapse in Rats.

INTRODUCTION: Anxiety and negative sensations due to alcohol withdrawal are factors leading to alcohol relapse and addiction. Minocycline, an antibiotic, can decrease alcohol consumption in rats, however, its effects on alcohol withdrawal anxiety and relapse have not been studied. MATERIAL AND METHODS: Part 1: Forced alcohol drinking in gradually increasing concentration was administered till day 22 in rats. Effect of drugs on anxiety was assessed using elevated plus maze (EPM) and two-chambered box apparatus, after removal of alcohol. Part 2: For relapse, an alcohol deprivation effect model was used, rats were continuously offered alcohol and water for 4 consecutive weeks in a two-bottle choice paradigm, followed by 2 weeks of alcohol deprivation. Effect of drugs on alcohol consumption during the first hour of alcohol reintroduction was assessed. Animals were sacrificed and whole brain Tumor Necrosis Factor (TNF) α was estimated. RESULTS: Part 1: Anxiety at 3 hours was significantly lower following minocycline (20 mg/kg i.p.) or diazepam compared to vehicle control. Part 2: Acute administration of minocycline (5,10 and 20 mg/kg, i.p.) suppressed alcohol consumption significantly (p value<0.05) as compared to vehicle control. A significant decrease in whole brain TNF α was observed in animals treated with minocycline compared to untreated animals. CONCLUSION: Minocycline attenuates alcohol withdrawal anxiety and disrupts alcohol relapse.

Evaluation of effect of minocycline on rewarding potential and alcohol relapse in place preference model in mice.

INTRODUCTION: Medical management for alcohol abuse has limitations. Alcohol consumption activates N-methyl-d-aspartate receptors and release of nitric oxide which can be inhibited by minocycline as it readily crosses blood brain barrier and may have effect on alcohol consumption. Thus, study objective is to evaluate the effect of minocycline on rewarding property, extinction and the reinstatement phenomenon induced by alcohol in a model of conditioned place preference (CPP) in mice. METHODOLOGY: To evaluate rewarding effects of alcohol, CPP procedure consisted of 4 parts, including adaptation (day 1), pre-conditioning test (day 2), conditionings with alcohol (days 3, 5, 7 and 9) or saline (days 4, 6, 8 and 10) and postconditioning test (day 11) conducted on 11 consecutive days. The groups included were saline treated group (alcohol control), naltrexone - 1mg/kg (positive control), and minocycline in the doses of 10, 30 and 50mg/kg. To evaluate the effect of minocycline on alcohol relapse, CPP procedure consisted 6 parts, the first 4 were the same as enumerated above followed by extinction (days 12-16) and reinstatement phase (day 17). RESULTS: The time spent in alcohol paired compartment by different groups, revealed that minocycline and naltrexone significantly attenuated alcohol-induced place preference compared to alcohol control (p<0.05). Pretreatment with minocycline and naltrexone blocked reinstatement of extinguished CPP. CONCLUSION: Minocycline may have a role in attenuating the rewarding property of alcohol and prevent alcohol relapse.

Evaluation of antiepileptic effect of S-adenosyl methionine and its role in memory impairment in pentylenetetrazole-induced kindling model in rats.

BACKGROUND: Epilepsy is the third most common cause of neurological disability worldwide. Despite the introduction of antiepileptic drugs (AEDs) in the past 20years, the seizures of around 30% of patients with epilepsy remain refractory to available treatment. Also, available AEDs and the disease itself have the potential to exert detrimental effects on cognitive function and therefore compromise patient wellbeing. S-adenosyl methionine has potential antiepileptic and memory-enhancing properties because of its involvement in the transmethylation reaction. OBJECTIVES: The present study was designed to evaluate the antiepileptic effect of S-adenosyl methionine and its role in memory impairment in the pentylenetetrazole (PTZ)-induced kindling model in rats. MATERIALS AND METHODS: The antiepileptic effect of 2 doses of SAM (50 and 100mg/kg) was tested by evaluating seizure severity score and seizure latency in the pentylenetetrazole-induced kindling model in rats. At the end of the study, spatial memory was evaluated in an elevated plus maze (EPM) test, and animals were sacrificed for estimation of oxidative stress markers in brain tissue homogenate. RESULTS: A higher dose of SAM (100mg/kg) exhibited an increase in seizure latency and a decrease in seizure severity score, suggesting its antiepileptic activity in the PTZ-induced kindling model. Also, the administration of SAM (50 and 100mg/kg) showed a decrease in transfer latency in the EPM test compared to the disease control group (p<0.0001). Biochemical analysis of rat brain tissue revealed significantly decreased malondialdehyde (p<0.0001) and increased glutathione (GSH) (p<0.0001) in the SAM 100-mg/kg group compared with that in the disease control group. CONCLUSION: The results demonstrated that S-adenosyl methionine exerts antiepileptic, memory-enhancing, and antioxidant properties in a pentylenetetrazole-induced kindling model of epilepsy.

Drug utilisation and off-label use of medications in anaesthesia in surgical wards of a teaching hospital.

BACKGROUND AND AIMS: When a drug is used in a way that is different from that described in regulatory body approved drug label, it is said to be 'off label use'. Perioperative phase is sensitive from the point of view of patient safety and off-label drug use in this setup can prove to be hazardous to patient. Hence, it was planned to assess the pattern of drug utilisation and off-label use of perioperative medication during anaesthesia. METHODS: Preoperatively, demographic details and adverse events check list were filled from a total of 400 patients from general surgery, paediatric surgery and orthopaedics departments scheduled to undergo surgery. The perioperative assessment form was assessed to record all prescriptions followed by refilling of adverse events checklist in case record form. World Health Organization (WHO) prescribing indicators were used for analysis of drug utilisation data. National Formulary of India 2011 was used as reference material to decide off-label drug use in majority instances along with package insert. RESULTS: A total of 3705 drugs were prescribed to the 400 participants and average number of drugs per patient was 9.26 ± 3.33. Prescriptions by generic name were 68.07% whereas 85.3% drugs were prescribed from hospital schedule. Off-label drugs overall formed 20.19% of the drugs prescribed. At least one off-label drug was prescribed to 82.5% of patients. Inappropriate dose was the most common form of off-label use. There was 1.6 times greater risk of occurrence of adverse events associated with the use of off-label drugs. CONCLUSION: Prescription indicators were WHO compliant. Off-label drug use was practiced in anaesthesia department with questionable clinical justification in some instances.