Usage Pattern of Fixed-dose Combinations at ICMR Network of Rational Use of Medicine Centres across India: Recommendations for Policymakers and Prescribers

Aim: Irrational use of medicines is a global problem. In India, one contributing factor is the availability of a large number of fixed-dose combinations (FDCs). To improve rational use and to strengthen policies, it is important to assess the usage patterns and rationality of FDCs. Methods: This study was conducted as part of a 1-year prospective cross-sectional analysis of prescriptions in the outpatient clinics of broad specialities from 13 tertiary care hospitals across India. Five most commonly prescribed FDCs in each center were analyzed. In addition, all the prescribed FDCs were classified as per the Kokate Committee classification and it was noted whether any of the FDCs were irrational or banned as per the reference lists released by regulatory authorities. Results: A total of 4,838 prescriptions were analyzed. Of these, 2,093 (43.3%) prescriptions had at least one FDC. These 2,093 prescriptions had 366 different FDCs. Of the 366 FDCs, 241 were rational; 10 were irrational; 14 required further data generation; and the remaining 96 FDCs could not be categorized into any of the above. Vitamins and minerals/supplements, antibacterial for systemic use, and drugs for gastroesophageal reflux disease (GERD) and peptic ulcer were the most used FDCs. Conclusion: Based on the finding that some prescriptions contained irrational FDCs, it is recommended that a rigorous, regular, and uniform method of evaluation be implemented to approve/ban FDCs and that prescribers be periodically notified about the status of the bans.

Antimicrobial usage and its quantification for neonatal sepsis at a tertiary care hospital neonatal intensive care unit

Background: Antimicrobial therapy for neonatal sepsis is challenging as its judicious use can save neonates while its inappropriate use can lead to rapid emergence of resistant strains. Quantification of consumption of antimicrobial agents (AMA) has not been undertaken in Indian neonatal intensive care units (NICU) setting. This prospective observational study evaluated the antimicrobial prescribing pattern and quantified its consumption in clinically suspected neonatal sepsis (NS) cases.Methods: Clinically suspected NS cases admitted over study period of 18 months in a tertiary care level III NICU were enrolled. Data of antimicrobials prescribed, its consumption, culture sensitivity profile of organisms isolated were collected.Consumption was quantified by computing the days of therapy (DOT) per 1000 patient-days (PD).Results: 150 clinically suspected NS cases were enrolled; 37.33% were culture positive. The most common AMA prescribed were netilmicin (94.67%), piperacillin-tazobactam (88.67%). Only 0.67% cases received reserve antimicrobials like colistin, vancomycin and linezolid. 58% received 2 AMA, 39.33% received ?3 agents. Total antimicrobial consumption was 614.86 DOT/1000 PD and 21.68 DOT/ neonate. Statistically significant difference in total AMA consumption amongst culture positive versus negative cases (p <0.001) was observed but difference was not significant in EOS versus LOS (p=0.95).Conclusion: Usage of antimicrobials for neonatal sepsis was guided by sensitivity pattern of local prevalent flora and clinical response. Usage of reserve antimicrobials were restricted. However, consumption of AB was higher compared to developed countries and we intend to use the study outcome data for antibiotic stewardship program to reduce antibiotic consumption and modify prescribing trends at the study setting.

A study of the free radical scavenging effects of Piper betle leaf extract in patients with vitiligo.

Background: Vitiligo is an idiopathic skin disease manifested by depigmented macules. It is characterised by melanocyte destruction, and redox imbalance is proposed to play a contributory role. Aim: The aim of this study was to analyze the effects of an ethanolic extract of Piper betle leaves on the generation of reactive oxygen species in erythrocytes sourced from vitiligo patients. Methods: The effect of Piper betle on the generation of reactive oxygen species in erythrocytes was measured by fl ow cytometry in patients with active and stable vitiligo versus healthy controls, using 5-(and-6)-chloromethyl-2’-7’-dichlorodihydrofl uorescein diacetate. Results: The generation of reactive oxygen species in erythrocytes was higher in patients with vitiligo (n = 23) compared to healthy controls (n = 18). The geometrical mean fl uorescence channel was 23.05 ± 2.11 in patients versus 17.77 ± 1.79 in controls, P = 0.039. The levels of reactive oxygen species were higher in patients with active vitiligo. Treatment of erythrocytes with Piper betle in concentrations of 0.5 and 1.0 μg/ml signifi cantly decreased the baseline levels of reactive oxygen species by 31.7% in healthy controls, and 47.6% and 44.3% in patients with active vitiligo, respectively. Piper betle effectively scavenged hydrogen peroxide, which was evident by a decrease in the geometrical mean fl uorescence channel by 52.4% and 62.9% in healthy controls, and 45.0% and 57.0% in patients with active vitiligo. Limitations: The study had a small sample size. Future studies should focus on evaluation of the antioxidant role of Piper betle at the lesional site. Conclusion: This pilot study indicates that patients with active vitiligo demonstrate enhanced generation of reactive oxygen species in erythrocytes, which was signifi cantly reduced following ex vivo treatment with Piper betle.

Stress modulating antioxidant effect of Nardostachys jatamansi.

The rhizomes of Nardostachysjatamansi, the plant commonly known as Jatamansi have been described in Ayurveda for their soothing and sedative action on the central nervous system. In the present study, the anti-stress effect of hydroethanolic extract (70%) of N. jatamansi (NJE) was evaluated in reference to its antioxidant property. Wistar rats were divided into four groups: naive, stressed, and T-200 and T-500 stressed with oral pre-treatment of NJE 200 and 500 mg/kg, respectively. Restraint of rats in metallic chambers for 4 h at 4 degreesC was followed by sacrifice and assessment of stress-induced alterations in biochemical parameters, incidence and severity of ulcers. Lipid peroxidation (LPO) and NO levels in stomach and LPO, NO levels and catalase activity in brain, plasma corticosterone level and adrenal ascorbic acid were measured. In vitro antioxidant activity of NJE was studied by measuring the free radical scavenging activity. NJE showed potent antioxidant activity and significantly reversed the stress-induced elevation of LPO and NO levels and decrease in catalase activity in the brain. It inhibited the incidence of gastric ulcerations and reversed the alterations in biochemical parameters/markers of stress-induced gastric ulceration. NJE also significantly altered stress-induced increase in adrenal and spleen weights and decrease in level of ascorbic acid in adrenal gland. Elevation of plasma corticosterone level was negated dose- dependently. The findings suggest that the NJE possesses significant anti-stress activity, which may be due to its antioxidant activity.

Immunogenicity and safety of live attenuated hepatitis A vaccine: a multicentric study.

OBJECTIVE: To evaluate immunogenicity and tolerability of single dose live attenuated injectable hepatitis A vaccine in four metropolitan cities of India. METHODS: Live attenuated hepatitis A vaccine was administered to 505 children aged 18 to 60 months in four centers across India. Immunogenicity of the vaccine was assessed by estimation of anti-HAV antibody titer at 6 weeks and 6 months following administration of the vaccine. Safety evaluation of the vaccine was also done during the visits. RESULTS: At 6 weeks, 480 subjects (95%) came for the follow-up and 411 (81.4%) subjects reported at the end of 6 months. The geometric mean titer (GMT) of anti-HAV antibody of the subjects who did not have the seroprotective titer at the baseline were assessed at 6 weeks and 6 months which was 81.04 mIU/ml and 150.66 mIU/ml respectively. At 6 weeks, 95.1 % seroconverted and at the end of 6 months, 97.9 % had seroconverted. Both solicited and unsolicited vaccine-induced local and systemic adverse events were insignificant at all the centers, except swelling and induration in a few. CONCLUSION: Live attenuated injectable hepatitis A vaccine was immunogenic and tolerable with minimal reactogenecity, in this study of single dose schedule. Safety profile was also satisfactory in the study population.