Unstable Angina: A Serious Adverse Event following Gemcitabine-Cisplatin Based Chemotherapy.

A 29 year male, with an inoperable adenocarcinoma of gall bladder was initiated on gemcitabine and a platinum compound based chemotherapy. During 4th cycle of chemotherapy, patient complained of chest pain following cisplatin and gemcitabine infusion. ECG was suggestive of acute coronary syndrome, which was successfully managed by antianginal therapy. Fifth cycle of chemotherapy was uneventful. Patient died of cardiovascular collapse before receiving the 6th cycle of chemotherapy. As per Naranjo adverse drug reaction probability scale, causal association of the event with cisplatin and gemcitabine was probable and possible respectively. It is advised to routinely assess the cardiovascular status of patients before and during cisplatin and/or gemcitabine based chemotherapy.

Comparison of aqueous humour concentration after single high dose versus multiple administration of topical moxifloxacin in rabbits.

For the prevention of postoperative ocular infections prophylactic topical antibiotics are routinely used. Studies evaluating comparative difference between single dose versus multiple dose administration on aqueous humour concentration of moxifloxacin are lacking. This study compared the aqueous humour concentration of moxifloxacin following its topical administration in rabbit eyes with two dose regimens. Twelve albino rabbits were divided into two groups. In group-1, two drops were administered thrice (total six drops) at 2 min intervals, in both the eyes; in group-2, two drops of moxifloxacin were administered three times a day for three days and also two h before aqueous humour collection i.e. on fourth day. Mean aqueous humour concentrations were calculated and compared using Student's 't' test and P<0.05 was considered significant. Moxifloxacin concentration in aqueous humour in group-1 was 23.79 µg/ml and in group-2 was 42.08 µg/ml. Both dosing regimens produced substantially higher aqueous concentrations than the known minimum inhibitory concentration for most bacteria. Moxifloxacin concentration in aqueous humour with multiple instillations is significantly higher than single instillation (P<0.05), which is adequate to cover ciprofloxacin-resistant gram-negative bacteria. Repeated topical moxifloxacin administration achieved significantly higher aqueous humour concentrations than single administration.

Role of sucrose in reducing painful response to orogastric tube insertion in preterm neonates.

OBJECTIVES: To study whether orogastric tube (OGT) insertion elicits a painful response in preterm neonates, and the role of oral sucrose in reducing this pain. METHODS: This double blinded, randomized control trial was conducted in the neonatal intensive care units of Kalawati Saran Children's Hospital. Clinically stable preterms within the first 7 postnatal days, who had not received painful stimulus 30 min prior to intervention, and who required routine OGT insertion were included. Lingual 24 % sucrose or distilled water (1 ml) was administered 2 min before OGT insertion. The primary outcome was painful response assessed by Premature Infant Pain Profile scale (PIPP), while the secondary outcomes were heart rate and SpO2 changes. The trial is registered with ClinicalTrials.gov ( REGISTRATION NUMBER: NCT 00949104) RESULTS: Sixty preterms were randomized in each group. Final analysis was carried out on 52 subjects in the placebo group and 53 in the sucrose group. The mean intra-procedure PIPP scores were significantly higher than the mean pre-procedure PIPP scores, in the gestational age groups of more than 34 wk, and 32 wk to 33 wk, 6 d, in both the placebo (7.25 vs. 3, and 8.14 vs. 3.14, respectively) and sucrose arm (8.06 vs. 3.21, and 7.18 vs. 4.18, respectively). The mean PIPP scores assessed at 30 s post procedure in the sucrose group were significantly lower than the placebo group (4.32 vs. 5.6, p = 0.014). No significant adverse events were seen. CONCLUSIONS: OGT insertion causes pain in preterms and single dose lingual 24 % sucrose may alleviate this pain.

Comparison of knowledge, attitude and practices of resident doctors and nurses on adverse drug reaction monitoring and reporting in a tertiary care hospital.

BACKGROUND: Lack of knowledge of pharmacovigilance (PhV) and adverse event (AE) reporting culture among the healthcare providers have been identified as major factors for under reporting of AE in developing countries. Hence, this study was planned to assess and compare the knowledge, attitude, and practices (KAP) of resident doctors and nurses about PhV and AE reporting. MATERIAL AND METHODS: This cross-sectional, questionnaire-based study was conducted to compare KAP of 100 doctors and 100 nurses on PhV and AE reporting. RESULTS: All the respondents felt that AE reporting is necessary and two-thirds were aware of the existing PhV Program of India. Significantly, higher proportion of doctors had correct understanding regarding PhV (P<0.05) and knew what should be reported (P<0.05) but nurses (75%) knew better about where to report (P<0.001). Significantly (P<0.001), more doctors (98%) felt that the patients are benefited by reporting AE. Nurses (96%) felt the need for information on drugs causing AE and their management strategy (P<0.001). Around 60% of all the respondents were in favor of mandatory PhV and feedback on the submitted AE. Doctors (67%) (P<0.05) had a practice of inquiring patients for any untoward outcome of therapy. Higher proportion (P<0.05) of nurses (55%) mentioned that observed AE are recorded in patient's case record, but random screening of 1000 patients' record did not reveal it. Nurses mentioned that they never reported any AE (P<0.05) and witnessed discussions on ADRs during the ward rounds (P<0.001). All the respondents preferred phone as the convenient method for reporting AE followed by drop box kept in the ward/OPD and felt the need of frequent workshops and continuing medical education. CONCLUSION: Resident doctors and nurses had good knowledge and awareness on AE reporting and PhV but their practices need to be improved.

Injection practices of healthcare professionals in a Tertiary Care Hospital.

BACKGROUND: Unsafe injection practices are prevalent worldwide and may result in spread of infection. Thus the present study was planned to observe the injection practices of healthcare professionals (HCP), including aseptic precautions and disposal of used syringes/needle. MATERIALS AND METHODS: Injection practices were observed in the outpatients and inpatients departments. Questionnaire was designed, tested and administered for this purpose. RESULTS: 130 patients receiving injections were observed. Overall injection practices of the HCP were satisfactory. However, unsafe practices with respect to not washing hands (95.4%), not wearing/changing gloves (61.6%), recapping of needles (12.2%), wiping of needle with swab (15.4%) and breaking of ampoule with solid object (44.4%) were observed. CONCLUSION: The problem of unsafe injections can be successfully addressed by organizing continuing medical education/symposium/workshops for improving the knowledge, attitude and practices of the HCP. Periodic monitoring and such interventions may also further improve safe injection practices.

Knowledge, attitude and practices associated with adverse drug reaction reporting amongst doctors in a teaching hospital.

AIM: This study was aimed at investigating the knowledge, attitude and practices associated with adverse drug reaction (ADR) reporting among doctors in a teaching hospital. METHODS: A total of 100 doctors working in a teaching hospital were evaluated with a questionnaire for their knowledge, attitude and practices related to ADR reporting and pharmacovigilance programmes. RESULTS: Nearly two third (66%) of the doctors knew the definition of ADR. Only one third (38%, 40%) could correctly define pharmacovigilance and adverse drug event (ADE) respectively. Although 100% of the doctors felt the need for a National Pharmacovigilance Programme (NPP) only approximately three fourth (73%) were aware of the existing programme in India and nearly half of the them (47%) actually knew the current status of the NPP at their institute. Surprisingly only one tenth of the doctors (10%) knew what should be reported. The majority (74.4%) felt that reactions to new drug should be reported and also those reactions that are serious and unusual. Only one third (30%) knew whom to report to and less than half (30%) had actually ever reported an ADR. CONCLUSION: The knowledge of ADRs and how to report them is inadequate among doctors. More awareness should be created regarding the purpose and usefulness of ADR reporting through Continuous Medical Education, training and integration of ADR reporting into the clinical activities of the doctors.

IFN-α-2a (Interferon) and ribavirin induced suicidal attempt in a patient of chronic HCV: A rare case report.

Interferons (IFNs) are proteins produced by cells, fibroblasts and macrophages, in response to viral invasion, and mediates immune response. IFN-α and ribavirin are the approved treatment for HCV infection, but also carries a risk of neuropsychiatric adverse effects, viz. insomnia, irritability, mood changes, and depression.We present a case report of depression induced by IFN-α and ribavirin, leading to attempted suicide. Following the episode, antidepressant paroxetine (20 mg o.d.) and zolpidem (10 mg h.s) were added with psychotherapy. No significant improvement was observed. Patient was given a drug dechallenge (IFN-α and ribavirin). Dramatic improvement was seen over 1 month. Following rechallenge with combination, patient again experienced depressive symptoms with suicidal ideation. IFN-α and ribavirin were promptly stopped. Naranjo causality assessment scale revealed probable association with IFN-α and ribavirin. The report intends to improve awareness among clinicians to facilitate early diagnosis and intervention of similar cases.

Serum leptin changes with metformin treatment in polycystic ovarian syndrome: correlation with ovulation, insulin and testosterone levels.

The relationship between leptin, insulin resistance and other hormonal parameters in polycystic ovarian syndrome (PCOS) is controversial. We investigated the effect of metformin on leptin levels in women with PCOS. Thirty women with PCOS received metformin 500 mg thrice a day. After two months of metformin treatment the mean leptin levels reduced significantly (p < 0.001). Ovulation was achieved in 28 patients, who also had a significant reduction in leptin levels (p < 0.001). Leptin showed significant positive correlation with weight (p < 0.05) and testosterone (p < 0.01), but no significant correlation with insulin. It is concluded that metformin reduces leptin resistance in PCOS women which induces ovulation. Leptin shows a significant correlation with testosterone and not with insulin.

Neo-regeneration of urinary bladder: a desired metaplasia of autologous membrane from rectosigmoid colon containing stem cells of intestinal crypts.

The current management of diseases of urinary bladder requiring resection is by augmentation cystoplasty or transplantation of ureters. Transplantation of ureters is associated with morbidity and mortality. Ideal management will be by regenerating urinary bladder in vivo. Neo-regeneration of tissues and organs like abdominal wall, aponeurosis etc., has been attempted and patented. After neo-regeneration of mesoderm tissues and organs, regeneration of urinary bladder (developed from endoderm) was. In vivo surgical techniques were developed in dogs. It is known that the embryonic morphogenesis of urinary bladder is from uro-genital sinus of hind gut. A membrane, containing endoderm stem cells in crypts of recto-sigmoid colon, was surgically isolated and colonized with remnant of urinary bladder wall after extensive resection. Experimental study was performed in dogs, for 60 days to one and a half year. Regeneration of all the layers of tissues of the wall of urinary bladder was observed. The neo-regeneration phenomenon has been recognized as "desired metaplasia". The regenerated neo tissue/organ on histological examination and cystometry studies was found compatible with normal urinary bladder. The hypothesis, neo-regeneration and desired metaplasia, is discussed.

Topiramate for prevention of olanzapine associated weight gain and metabolic dysfunction in schizophrenia: a double-blind, placebo-controlled trial.

BACKGROUND: Olanzapine associated weight gain (WG) is a major concern in patients with schizophrenia. The purpose of this study was to assess the efficacy of topiramate to prevent olanzapine induced WG in these cases. We also studied various metabolic parameters. METHODS: In this 12-week, double-blind, parallel group study, seventy-two drug-naïve, first-episode schizophrenia patients were randomized to receive olanzapine+placebo (olanzapine group) or olanzapine+topiramate (100mg/day) (topiramate group). Weight, body mass index, fasting glucose, insulin, insulin resistance (IR), leptin, lipids and blood pressure were assessed at baseline and at 12 weeks. The patients were clinically evaluated using Positive and Negative Syndrome Scale (PANSS) and were monitored for adverse effects. RESULTS: Topiramate resulted in a weight loss of 1.27+/-2.28 kg (p<0.01), decrease in leptin (p<0.001), glucose, cholesterol, triglyceride levels and systolic and diastolic blood pressure. In the olanzapine group, there was a significant WG, hyperglycemia, hyperinsulinemia, increased IR, hyperleptinemia, hypercholesterolemia and hypertriglyceridemia (p<0.001).There was a greater clinical improvement (PANSS scores) (p<0.001) in the topiramate group. The adverse effects were well tolerated. CONCLUSIONS: Topiramate could prevent olanzapine induced weight gain and adverse metabolic effects. It also results in a greater clinical improvement when used with olanzapine in schizophrenia.

Efficacy and safety of a single daily dose of gentamicin in hospitalized Indian children: a quasi-randomized trial.

OBJECTIVES: To compare the clinical efficacy, pharmacokinetic profiles and safety of once-daily dosing (ODD) and multiple daily dosing (MDD) of gentamicin in hospitalized Indian children. PATIENTS AND METHODS: Four hundred children admitted to our hospital were studied prospectively. The patients were randomized to ODD or MDD groups alternately. The primary outcomes were: (i) a good clinical outcome, as defined; and (ii) occurrence of side effects, if any. Clinical efficacy was determined by comparing the proportion of patients with a favourable response between the two groups, while pharmacokinetic profile was assessed by comparing the peak and trough concentrations of the drug in a subgroup of patients. Safety of the two regimens was compared, besides recording any symptoms due to side effects of the drug, with the help of serum creatinine and brainstem-evoked response audiometry (in a subgroup of the patients). RESULTS: We found ODD of gentamicin in hospitalized Indian children to be efficacious and safe. A favourable clinical response was achieved in 167 of the 188 patients (89%) in the ODD group and in 161 of the 212 patients (76%) in the MDD group. Similarly, a higher number of patients in the ODD group showed favourable gentamicin peak concentrations as compared with the MDD group (100% versus 87%). The MDD group showed a higher number of trough concentrations in the undesirable range as compared with the ODD group (17% versus 0%). CONCLUSIONS: The study supports extended-interval (single daily) dosing in hospitalized Indian children due to its efficacy and safety with the added advantage of needing fewer injections.

Comparative efficacy and safety of oxcarbazepine versus divalproex sodium in the treatment of acute mania: a pilot study.

OBJECTIVE: This study compared the efficacy and safety of oxcarbazepine and divalproex sodium in acute mania patients. SUBJECTS AND METHODS: In this 12 week, randomized, double-blind pilot study, 60 patients diagnosed with acute mania (DSM-IV) and a baseline Young Mania Rating Scale (YMRS) score of 20 or more received flexibly dosed oxcarbazepine (1,000-2,400 mg/day) or divalproex (750-2,000 mg/day). The mean decrease in the YMRS score from baseline was used as the main outcome measure of response to treatment. A priori protocol-defined threshold scores were or=15 for relapse. Number of patients showing adequate response and the time taken to achieve improvement was compared. Adverse events were systematically recorded throughout the study. RESULTS: Over 12 weeks, mean improvement in YMRS scores was comparable for both the groups including the mean total scores as well as percentage fall from baseline. There were no significant differences between treatments in the rates of symptomatic mania remission (90% in divalproex and 80% in oxcarbazepine group) and subsequent relapse. Median time taken to symptomatic remission was 56 days in divalproex group while it was 70 days in the oxcarbazepine group (p=0.123). A significantly greater number of patients in divalproex group experienced one or more adverse drug events as compared to patients in the oxcarbazepine group (66.7% versus 30%, p<0.01). CONCLUSION: Oxcarbazepine demonstrated comparable efficacy to divalproex sodium in the management of acute mania. Also the overall adverse event profile was found to be superior for oxcarbazepine.

Physician's guide to pharmacovigilance: terminology and causality assessment.

Adverse drug events can range from mild to life threatening reactions resulting in inconvenience or serious morbidity and mortality besides being a financial burden on the society. However clinicians often do not recognize this drug related harm. The terms used to describe these events with medication use cause much confusion. Moreover manifestations of adverse drug reactions can be non-specific making it difficult to differentiate from current illness. To determine the likelihood of relationship between the drug and the event assessment of causality is done. The purpose of this article is to review and clarify the terms encompassing the discipline of pharmacovigilance and also to outline the steps in causality assessment with the help of an actual case report.

A randomized, double-blind, placebo-controlled study comparing the efficacy and safety of paracetamol, serratiopeptidase, ibuprofen and betamethasone using the dental impaction pain model.

Assessment of postoperative sequelae following the removal of an impacted third molar has been used in clinical pharmacology to evaluate the relative efficacy of various analgesic, anti-inflammatory drugs. This study included 150 patients with impacted lower third molars. They were randomly sorted to receive ibuprofen, paracetamol, betamethasone, serratiopeptidase or placebo. Evaluation of efficacy was made using tape measurement (for swelling), visual analogue scale (for pain evaluation), mouth opening ability and oral temperature. The effect of treatment on hematological parameters, bleeding, wound healing and requirement for rescue medication was also studied. Peak pain scores were observed approximately 5-6 hours after the operation. Betamethasone showed significant analgesic activity from day 1. Ibuprofen and betamethasone were significantly more effective than placebo in reducing swelling. Trismus was least with betamethasone. A significant rise in temperature on the operated side occurred only on day 1 in all the groups. Serratiopeptidase did not showed significant analgesic and anti-inflammatory action. Mild-to-moderate adverse effects were reported.

Changes in quality of life after surgical removal of impacted mandibular third molar teeth.

BACKGROUND: The decision to get impacted teeth removed is not straightforward because of the concerns about its possible outcome. Assessment of quality of life is now regarded as an essential component for assessing outcomes of dental health care. The purpose of this paper is to assess the effect of impacted third molar teeth surgery on a number of health related outcomes. PATIENTS AND METHODS: A total of 72 patients undergoing surgical removal of their unilateral impacted mandibular third molar teeth were recruited to participate in this study. Patients were asked to complete two questionnaires, 14-item Oral Health Impact Profile (OHIP-14) and the 16-item UK Oral Health related Quality of Life measure questionnaire (OHQOLUK-16) daily for one week following surgery. RESULTS: There was significant decrease in the mean OHQOLUK-16 score and OHIP-14 scores for the first five postoperative days. There were no significant differences in changes in the mean OHIP-14 scores or OHQOLUK-16 scores on postoperative day 6 and 7. CONCLUSION: There was a significant deterioration in oral health related quality of life in the immediate postoperative period, which slowly returned to preoperative level by day 6. This information may be useful in creating realistic expectation for patients who are considering third molar surgery.

Pattern of drug utilization in acute tonsillitis in a teaching hospital in Nepal.

OBJECTIVE: A prospective study was undertaken to find out the baseline data on prescribing patten of drugs in acute tonsillitis. METHODS: Prescriptions far acute tonsillitis were collected outside the ENT-OPD over a period of 6 months and were analyzed. RESULTS: The average number of drugs per prescription was 3.24. Ninety five percent of the prescriptions contained antimicrobial agents (AMA with an average of 1.03 AMAs per prescription. AMA was the most commonly prescribed (31.81%) group of drugs followed by analgesics and antipyretics (20.70%). Amoxicillin (38.80%) and azithromycin (20.63%) were the most commonly prescribed AMAs. Erythromyein was prescribed in 11(6.73) patients while penicillin was not at all prescribed. Culture and sensitivity test was advised only in 14.75% of cases. Cough expectorants were the most commonly used fixed dose combination. Of the total drugs used, 96.9% were prescribed by brand names. The duration of therapy was not mentioned for 35.60% of the drugs prescribed. the iatyprtyriate and over use off antimicrobil agents make treatment east effective.

Adverse drug reaction monitoring: knowledge, attitude and practices of medical students and prescribers.

BACKGROUND: Adverse drug reactions (ADRs) contribute to excessive health care costs through increased patient morbidity and mortality. Thus, there is an urgent need to create awareness among physicians towards ADR monitoring. The present study was designed to assess the knowledge, attitude and practices of fifth semester undergraduate students and prescribers (interns, junior residents and senior residents) towards the recording and reporting of ADRs. METHODS: The fifth semester MB,BS undergraduate students (n=107) and prescribers (n=l 17) working in different disciplines of Lady Hardinge Medical College and associated hospitals were given a questionnaire to answer. The responses of the undergraduate students were compared with those of prescribers. RESULTS: Knowledge about definition, classification, objectives and methods of ADR monitoring was found to be comparable in both groups. Spontaneous and intensive methods of ADR monitoring were known to the majority of participants of both groups. Attitude and practices of the prescribers were significantly (p<0.01 ) better with regard to the status of ADR monitoring in the institute. A significantly higher (p<0.001) proportion of prescribers (82%) as compared to the undergraduate students (64.5%), felt that ADRs should be reported both when it causes inconvenience to the patient as well as death. ADRs were encountered by both undergraduates (46%) and prescribers (66%) during their clinical project exercises and patient care, respectively. Commonly encountered ADRs were allergic reactions, symptoms of upper gastrointestinal irritation, extrapyramidal symptoms and hepatitis. The common offending groups of drugs causing these ADRs were non-steroidal anti-inflammatory drugs, antidopaminergics and chemotherapeutic agents. A majority of ADRs were suspected and subsided on their own by either stopping the drug or reducing its dose. CONCLUSIONS: The knowledge, attitude and practices of both undergraduates and prescribers were comparable but need further improvement. This suggests the need for suitable changes in the undergraduate teaching curriculum. Further, the prescribers also need periodic reinforcement regardingADR monitoring.

Study of drug utilization pattern in dental OPD at tertiary care teaching hospital.

Irrational prescribing is a global phenomenon. The objective of the study was to find out the prescribing practices of dental prescribers in a tertiary care teaching hospital with special emphasis on the utilization of antimicrobial agents. A prospective study was conducted in the month of March 2000. A total of 491 prescriptions were collected randomly. Prescribing pattern was analyzed using WHO basic drug indicators. The average number of drugs for prescription was 2.4. 78.8% of all prescriptions contained antimicrobial agents. It was most commonly prescribed (40.37%) group of drugs followed by anti-inflammatory and analgesics (33.8%). Fixed dose combination of ampicillin and cloxacillin was most commonly prescribed antimicrobial agents. Prophylactic use of AMA (78%) was more than therapeutic purpose (21.9%). Prophylactic use of antimicrobial agents was irrational in all the cases as duration for the use of antimicrobial agents was 5.1 +/- 0.5 days. Fixed dose combinations (45%), drugs by brand name (98.5%) were frequently used. Drug prescribed from Essential Drug List was maximum when one drug was prescribed. Results indicate that there is a scope for improving prescribing habits and minimizing the use of antimicrobial agents. This could be facilitated by periodic education to the prescribers.