In Vivo Effects of Nonselective, Partially Selective, and Selective Non Steroidal Anti-Inflammatory Drugs on Lipid Peroxidation and Antioxidant Enzymes in Patients with Rheumatoid Arthritis: A Clinical Study.

BACKGROUND: The relationship between oxidative stress, decreased antioxidant status, and rheumatoid arthritis (RA) has been widely investigated. To date, few clinical studies have assessed the role of conventional nonsteroidal anti-inflammatory drugs (NSAIDs) in the modulation of oxidative stress in patients with RA. AIM: The aim of this study was to compare the effects of nonselective, partially selective, and selective cyclooxygenase (COX) inhibitors on markers of oxidative stress in patients with RA. MATERIALS AND METHODS: Thirty RA patients were enrolled in this open label, prospective study for 12 weeks and randomly assigned to either group receiving diclofenac 100 mg, meloxicam 15 mg, or celecoxib 200 mg daily (n = 10 in each group). Patients were evaluated for superoxide dismutase (SOD) and serum malondialdehyde (MDA) as oxidative markers at the baseline and at the end of 12 weeks. Various parameters for efficacy were also assessed. RESULTS: The baseline values of the SOD enzyme were significantly lower and MDA values were significantly elevated in patients randomized to the three treatment groups as compared to the control group (P < 0.05). MDA level was significantly decreased in patients across all the treatment groups (P < 0.05) after 12 weeks. There was an improvement in mean SOD enzyme levels at the end of 12 weeks; the difference for SOD was significant as compared to the baseline in the meloxicam group only (P < 0.05) but not in diclofenac- and celecoxib-treated patients. Significant improvement was observed in all the treatment groups as regards patient assessment of pain visual analog scale, tender and swollen joint count, and patient global assessment. CONCLUSIONS: Diclofenac, meloxicam, and celecoxib carry antioxidant effects to a variable extent. NSAID possesses additional mechanism independent of COX inhibition which modulates oxidative stress.

Pattern of Adverse Drug Reactions to Anticancer Drugs: A Quantitative and Qualitative Analysis.

INTRODUCTION: Anticancer drugs contribute significantly to the global burden of adverse drug reactions (ADRs). Any attempt to quantify their magnitude and provide upgraded knowledge would help oncologists in writing safer prescriptions. AIM: This observational follow-up study was conducted on newly diagnosed cancer patients receiving anticancer therapy with an aim to determine the frequency, severity, causality, predictability, and preventability of ADRs. SUBJECTS AND METHODS: The patients were followed up for 6 months for the appearance of adverse events. Data were analyzed using IBM SPSS Statistics for Windows, Version 22.0. (Armonk, NY) and presented in the form of descriptive statistics. RESULTS: Each patient was prescribed approximately 6.85 ± 1.51 (mean ± standard error) drugs on average. All the patients (100%) receiving anticancer chemotherapy had ADRs. Alopecia, nausea and vomiting, burning tingling, and numbness were the most frequently encountered ADRs. The incidence of alopecia (P < 0.0004), nausea (P < 0.03), and oral ulceration (P < 0.02) was higher in females. Maximum reactions were of Grade 2 (69.53%). Most of the reactions (75.80%) appeared within 10 days of receiving the first cycle. 99.58% reactions were not serious. According to the WHO - The Uppsala Monitoring Centre criteria, 99.47% ADRs fell in possible category. According to the Naranjo's algorithm, 100% ADRs fell in probable category. About 94.80% reactions were found to be predictable. About 56.47% reactions were probably preventable, and 43.53% reactions were not preventable. CONCLUSION: Multiple ADRs were seen in newly diagnosed cancer patients. Most of them were predictable, of mild-to-moderate severity, nonserious, and preventable. A majority of the ADRs recovered over time.

Impact of regulatory spin of pioglitazone on prescription of antidiabetic drugs among physicians in India: A multicentre questionnaire-based observational study.

Background & objectives: Pioglitazone was suspended for manufacture and sale by the Indian drug regulator in June 2013 due to its association with urinary bladder carcinoma, which was revoked within a short period (July 2013). The present questionnaire-based nationwide study was conducted to assess its impact on prescribing behaviour of physicians in India. Methods: Between December 2013 and March 2014, a validated questionnaire was administered to physicians practicing diabetes across 25 centres in India. Seven hundred and forty questionnaires fulfilling the minimum quality criteria were included in the final analysis. Results: Four hundred and sixteen (56.2%) physicians prescribed pioglitazone. Of these, 281 used it in less than the recommended dose of 15 mg/day. Most physicians (94.3%) were aware of recent regulatory events. However, only 333 (44.8%) changed their prescribing pattern. Seventeen of the 416 (4.1%) physicians who prescribed pioglitazone admitted having come across at least one type 2 diabetes mellitus patient (T2DM) who had urinary bladder carcinoma, and of these 13 said that it was in patients who took pioglitazone for a duration of more than two years. Only 7.8 per cent of physicians (n=58) categorically advocated banning pioglitazone, and the rest opined for its continuation or generating more evidence before decision could be taken regarding its use in T2DM. Interpretation & conclusions: Majority of the physicians though were aware of the regulatory changes with regard to pioglitazone, but their prescribing patterns were not changed for this drug. However, it was being used at lower than the recommended dose. There is a need for generating more evidence through improved pharmacovigilance activities and large-scale population-based prospective studies regarding the safety issues of pioglitazone, so as to make effectual risk-benefit analysis for its continual use in T2DM.

Role of concept map in teaching general awareness and pharmacotherapy of HIV/AIDS among second professional medical students.

OBJECTIVE: Medical students as future doctors will play an important role in caring for HIV-infected patients. This study assessed and evaluated the existing level of knowledge of MBBS students about HIV/AIDS given through lecture delivery methods and by use of concept map (CM). MATERIALS AND METHODS: This study was carried out on 150 professional MBBS students of tertiary care hospital. A pretest was conducted by giving 10 multiple choice questions (MCQ) of general awareness and 15 questions regarding pharmacotherapy of HIV/AIDS. In between pre- and post-test, a session of 1-week integrated teaching module was organized. After completion of integrated teaching, 2 h session of CM on general awareness and pharmacotherapy of HIV/AIDS was taken. A posttest was conducted using MCQs and problem-based question (PBQ) to assess the effect of integrated teaching and CM on their knowledge about HIV/AIDS. Feedback was also taken from the students to regarding their views about CM. RESULTS: There was a significant increase in student's score in MCQ test after integrated teaching than pretest (P < 0.05). There was also significant improvement in PBQ score after CM than that of after integrated teaching (P < 0.05). Students' perception about the effectiveness of CM was positive. CONCLUSION: CM can make a significant improvement in the knowledge of medical students and were motivated and developed interest in the subject.

Introducing structured viva voce examination in medical undergraduate pharmacology: A pilot study.

OBJECTIVE: Viva voce examination is an important tool of evaluation in medical examinations marred by high subjectivity. Gross subjectivity in viva voce assessment can be reduced by structuring it. MATERIALS AND METHODS: The marks obtained in theory and viva voce (traditional viva voce examination [TVVE]) of I sessional, II MBBS students were compared and a huge disparity was identified. A structured viva voce examination (SVVE) was then proposed and experimented as an objective and standardized alternative. Sets of equitable question cards for SVVE were prepared, each having eight questions with two parts each, arranged successively with increasing difficulty, domains of learning, and appropriate marks. The percentage variation in scoring in viva versus theory marks was calculated for both TVVE and SVVE, and students were grouped as Group I (+100 to +51%); Group II (+50 to -50%); Group III (-51 to -100%); Group IV (-101 to -150%); Group V (-151 to -200%); and Group VI (< -200%) variation, as? inappropriate, appropriate, inappropriate, erroneous, more erroneous and most erroneous respectively. Student's feedback on the SVVE was also obtained. RESULTS: In TVVE (n = 128), the students distributed were:none,17.2%, 23.4%, 22.7%, 11.7% and 25% in Group I, II, III, IV, V, and VI in contrast to SVVE (n = 107) as 7.5%, 57.9%, 19.6%, 6.5%, 5.6%, and 2.8%, respectively. Marked disparity of TVVE was annulled with SVVE. Student's feedback was quite encouraging with 83% overall acceptability and almost 66% preferred SVVE. CONCLUSION: SVVE was more realistic as compared to TVVE. Most of the students favored this approach.

Effect of educational intervention on adverse drug reporting by physicians: a cross-sectional study.

In India, the pharmacovigilance program is still in its infancy. National Pharmacovigilance Program of India was started for facilitating the pharmacovigilance activities. The ADR reporting rate is still below satisfactory in India. This cross-sectional questionnaire based study was carried out in a tertiary care teaching hospital in Uttarakhand, which is a peripheral ADR monitoring centre to assess the level of knowledge, attitude, and the practices of pharmacovigilance among the doctors and to compare it with the group of doctors attending educational CME for improving awareness of pharmacovigilance. The most important revelation of this study was that although adequate knowledge and the right attitude about adverse drug reaction reporting were instigated in the doctors after the educational intervention, the practice was still neglectful in both groups, emphasizing the need to design the strategies to develop adverse drug reaction reporting culture.

Comparative Efficacy and Safety of Various Anti-Microbials in Patients of Acute Rhinosinusitis at Tertiary-Care Hospital in Uttarakhand (UK).

To compare the efficacy of gatifloxacin, azithromycin with amoxicillin as positive control for the treatment of Acute rhinosinusitis (ARS). To monitor adverse drug reaction profile of amoxicillin, azithromycin and gatifloxacin in patient of ARS. An open randomized trial of comparative efficacy and safety of amoxicillin, azithromycin and gatifloxacin in patients with ARS. Patients were randomized into three groups as under: group 1: patients on oral amoxicillin 500 mg TDS for 10 days; group 2: patients on oral azithromycin 500 mg OD for 5 days; group 3: patients on oral gatifloxacin 400 mg OD for 10 days. Patients were evaluated for signs and symptoms at day 1, day 7 (for group 2), on day 12 (for group 1, 3) as primary end points and 28 days after post therapy as secondary end point. All the three antimicrobial drugs i.e., amoxicillin, azithromycin and gatifloxacin were effective in reducing symptoms of acute sinusitis on visual analogue scale scoring. Azithromycin showed significant improvement radiographically on day 7 (P < 0.01) and on day 35 (P < 0.01). Gatifloxacin elicited very highly significant improvement radiographically on day 40 (P < 0.001) and significant improvement on day 12 (P < 0.01) when compared with amoxicillin. Azithromycin, the ketolide was associated with lesser adverse effects as compared to amoxicillin. All the three antimicrobial drugs i.e., amoxicillin, azithromycin and gatifloxacin were effective in reducing symptoms of acute sinusitis on visual analogue scale scoring. Gatifloxacin was found to be most effective drug both in terms of improvement in signs and symptoms on visual analogue scale and radiographic scoring and was associated with least adverse events in comparison to rest of two drugs under study.

Effect of Palliative Drug Therapy on Quality of life in Advanced Head and Neck Cancer Patients.

Advanced cancer patients are managed by palliative care and its main aim is to provide best possible quality of life to the patients by symptom management. Pain is the most agonizing symptom experienced by advanced head and neck cancer patients. Control of pain hence requires more attention by the caregiver in order to improve their quality of life. Recently quality of life issues have emerged as a main focus of cancer treatment as compared to conventional increase in survival rate. This study mainly focuses on the effect of palliative drug therapy on quality of life.

Biological response modifiers: current use and future prospects in cancer therapy.

Over the past few decades, considerable success has been achieved in the field of cancer treatment with biological response modifiers (BRM), which are agents that improve the body's ability to fight cancer by immunostimulation. Biological agents, such as interferons and interleukins, provide nonspecific active immunity, whereas the monoclonal antibodies provide passive immunity. Apart from this, other biological agents, such as antiangiogenic agents, matrix metalloprotease inhibitors, tyrosine kinase inhibitors, and tumor vaccines, are also increasingly being used in cancer treatment. Hematopoietic factors, such as granulocyte colony-stimulating factor, are used to increase the general immunity and prevent opportunistic infection. BRM are basically used alone or as adjuvants to cancer chemotherapeutic agents. This review sheds light on the current use and the future development of cancer immunotherapy. Search strategy included Pubmed, using the terms "Biological response modifiers in cancer" citations relevant to the topic were screened.

Angiogenesis: Future of pharmacological modulation.

Angiogenesis is a fundamental biological process that is regulated by a fine balance between pro- and antiangiogenic molecules, and is deranged in various diseases. Historically, angiogenesis was only implicated in few diseases, such as, cancer, arthritis, and psoriasis. However, in recent years, it has been increasingly evident that excessive, insufficient or abnormal angiogenesis contributes to the pathogenesis of many more disorders. Research in angiogenesis offers a potential to cure a variety of diseases such as Alzheimer's and AIDS. Modulation of angiogenesis may have an impact on diseases in the twenty-first century similar to that which the discovery of antibiotics had in the twentieth century.

Quality of life as an outcome variable in the management of advanced cancer.

BACKGROUND AND OBJECTIVE: Though well recognized in the West, palliative care and quality of life are relatively newer concepts in a developing country like India. The aim of this study was to assess the effect of palliative care on pain and quality of life and to identify the association between the two. STUDY DESIGN: Observational prospective study. MATERIALS AND METHODS: Patients with advanced cancer, receiving palliative drug therapy, were recruited from a tertiary care hospital. City of Hope Medical Center Quality of Life Survey and visual analog scale (VAS) were used to assess the quality of life and cancer pain severity, respectively. RESULTS: A total of 100 patients were included in the study. Palliative drug therapy produced a significant reduction in pain scores expressed as mean ± SD in VAS [7.13 ± 2.2 vs. 2.62 ± 2.1 (P<0.001) after 1 month in 93 patients; 7.06 ± 2.1 vs. 2.47 ± 2.1 (P<0.001) after 1 month and 2.02 ± 1.9 (P<0.001) after 2 months in 51 patients]. Also, significant improvement in the quality of life scores [919.78 ± 271.3 vs. 1280.65 ± 306.8 (P<0.01) after 1 month in 93 patients; 950.39 ± 238.2 vs. 1336.67 ± 291 (P<0.01) after 1 month and 1405.49 ± 368.3 (P<0.01) after 2 months in 51 patients] was obtained. There was a high correlation between the average change of pain intensity and quality of life scores (r= -0.53, P<0.02). Overall, a reduction in pain resulted in significant improvement in the quality of life (P<0.001). CONCLUSION: This study emphasizes the role of palliative care and, more importantly, pain management in improving the quality of life of advanced cancer patients.

Modulation of pain perception by ramipril and losartan in human volunteers.

The angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are a well known entity and have been used in therapeutics for various indications like hypertension, myocardial infarction and CHF. However, there is a renewed interest in these compounds in terms of their effects on pain perception in animals as well as in human beings. They have yielded contradictory results, showing hyperalgesia in some studies but analgesia in others. Hence this study was undertaken to evaluate the effect of Ramipril (an ACE-I) and Losartan (an ARB) on pain perception in human volunteers using cola caps and handcuff of sphygmomanometer. A total of 30 healthy, normotensive individuals with no previous history of intake of analgesics during or 4 weeks prior to the study were selected after an informed consent. The first group received a single dose of placebo, the second group received Ramipril (2.5 mg) & the third group received Losartan (50 mg). Pain perception threshold (the point at which an individual first experiences pain) and the maximum tolerated pain were assessed using the above method. The control group showed no significant changes in pain threshold, but the group receiving either Ramipril or Losartan showed a decline in threshold for maximum tolerated pain. Only Ramipril and not Losartan decreased the pain perception threshold. Our study revealed that single dose treatment of healthy volunteers with Ramipril and Losartan may cause algesia as early as after ingestion of the first dose and further studies are needed to study their long term effects on pain perception.

Pharmacokinetics of aspirin in aged Indians.

The pharmacokinetics of aspirin (ASA) has been studied in elderly Indians (greater than 60 y) of either sex, composing, apparently healthy subjects controlled hypertensives and NIDDM diabetics, in comparison with healthy young subjects. Serum salicylate levels were estimated a 0, 0.5, 1, 2, 4 & 8 h after ASA. The pharmacokinetics of serum salicylate were not changed in elderly subjects as compared to the young after the first dose or after one week of ASA therapy, although greater variability was observed in the elderly. Various laboratory investigations were unaltered after one week in all the groups, except that one elderly hypertensive patient gained weight, and a young subject showed an increase in SGOT & SGPT.