Study of pattern and time-reaction sequence for adverse drug reactions reported to antiretroviral drugs

Background: Adverse drug reactions (ADRs) to antiretroviral drugs have a varied pattern and wide spectrum of severity from mild to very serious. The lack of a pre-established time-reaction sequence hampers the causality assessment of ADRs. Recognition of pattern of ADRs to antiretroviral drugs in a particular setup might sensitize the reporters to report ADRs, especially in setups dependent on spontaneous reporting. Aim and Objectives: The study of pattern and time-reaction sequence for ADRs reported to antiretroviral drugs. Materials and Methods: Retrospective study was conducted at a first-line antiretroviral therapy (ART) center after obtaining approval from the Institutional Ethics Committee. Pattern of ADRs associated with ART was done by analyzing the type of ADRs, severity, and outcome of ADRs reported to antiretroviral drugs. Mean duration of time lapse between administration of drug to onset of adverse drug reaction was calculated. Descriptive statistics was used for data analysis. Results: There were 73 adverse reactions reported. Most common type of adverse reaction was cutaneous (53.42%) followed by anemia (31%). Causality assessment of most ADRs was concluded as possible (60.27%). Most ADRs were of moderate severity and 12% were severe reactions. Reactions such as anemia and neuropsychiatric ADRs often occurred late, while maculopapular rash usually occurred within 30 days of drug administration. Conclusions: ADRs to ART include an array of reactions ranging from mild rash to psychosis or severe anemia. Most of these reactions are of moderate severity and have a favorable outcome. Many of these reactions actually occur almost a month after initiating a drug regime suggesting the need for intensive monitoring around this time.

Cost-minimization analysis of drugs used for empirical treatment of urinary tract infection in a tertiary care hospital

Background: Urinary tract infections (UTIs) are one of the commonly encountered infections and a large number of drugs are indicated in UTI ranging from oral conventional drugs to most advanced injectable drugs. Cost-minimization analysis (CMA) is employed to project the least costly drug when two treatments are shown to be therapeutic equivalents. Aims and Objectives: This study aims to perform a CMA at a tertiary care center to determine the least expensive drug for UTI and to project a cheapest alternative from available options based on the results of CMA. Materials and Methods: This was a cross-sectional study conducted over duration of 3 months in the clinical departments on patients diagnosed to have UTI and prescribed empirical antimicrobial treatment. The approval of Institutional Ethics Committee was sought before beginning the study. Pattern of drug prescription and average cost incurred in the treatment of patients with empirical antimicrobial therapy was calculated. CMA included the projection of the least expensive drug based on average cost incurred per patient in outpatients and inpatients respectively. Results: A total of 59 patients of UTI given empirical treatment were included in the study. Fluoroquinolones and cephalosporins were commonly used drugs for empirical treatment of UTI. Nitrofurantoin (average cost of 11–14 Rs. per patient) can be projected as the cheapest drug for empirical treatment of UTI on outpatient basis as well as a drug to supplement injectables in indoor patients. Injectable ciprofloxacin can be projected as the most inexpensive alternative for empirical treatment of UTI in patients of the inpatient department. Conclusion: Nitrofurantoin for oral treatment and ciprofloxacin in injectable form are cheapest among available alternatives for empirical treatment of UTI. To prevent treatment failures and increase in cost of treatment, correlation of results of CMA with local antimicrobial sensitivity pattern is important.

Comparative physiological and histological investigations on resistant and susceptible pomegranate genotypes infected with Xanthomonas axonopodis pv. Punicae

Xanthomonas axonopodis pv. punicae (Xap) is a bacterial pathogen wreaking havoc in pomegranate cultivation. It causes bacterial blight disease dwindling yield and making fruit unfit for consumption. Physiological and histological investigations during host-pathogen interaction are prerequisite to assess the onset of defense mechanism in plants. Therefore, we tried to compare the pomegranate resistant (IC 318734) and highly susceptible (Ruby) genotypes challenged with Xap. The bacterial suspension containing Xap cells of 0.3 OD600 (~106 to 107CFU mL?1) was used for challenge inoculation. Uniformly grown resistant and highly susceptible plants were selected, the surface of leaves was pricked and spray-inoculated with bacterial suspension using native strain IIHR1 (NCBI Gen Bank ID: KT 222897). Simultaneously, the control plants were also sprayed with only distilled water and observed. A total of three replications with five plants per replication were maintained and evaluated under completely randomized design. Physiological investigations were recorded using Portable photosynthesis system (LCpro+, ADC BioScientific limited, UK) for one cycle of disease progression viz., 0, 1, 5, 10, 15 and 20 days after bacterial spray inoculation (DAI). Significant changes in gas exchange parameters were witnessed on pathogen inoculation. Higher reduction in mean percent change of photosynthetic and transpiration rate, instantaneous water use efficiency, internal CO2 content, stomatal conductance and relative water content were noticed in highly susceptible genotype than resistant one. On contrary, an increased percent mean change of intrinsic water use efficiency, carboxylation capacity and lignin was documented in resistant genotype. Relative injury caused due to bacterial infection was found high in highly susceptible genotype than resistant one. Histological investigations in highly susceptible and resistant genotype were studied on 20th day of Xap inoculation using Scanning Electron Microscopy. Highly susceptible genotype exhibited maximum deformed cells, tissues and other visible abnormalities upon Xap inoculation. Thus, this study forms a basis for effective disease management and breeding programmes in pomegranate.

Freeman-sheldon syndrome-prenatal and postnatal diagnosis.

A six-day-old girl, born to normal non-consanguineous parents presented with mask like facies with a small mouth giving a ‘whistling’ appearance. Other dysmorphic features include deep set eyes, broad nasal bridge, long philtrum and ‘H’ shaped cutaneous dimple on the chin. There was congenital windmill vane hand position and severe talipes equinovarus deformity. The above features are characteristic of Freeman-Sheldon syndrome also known as Whistling Face syndrome. Ultrasound scanning during 8th month of the pregnancy showed the fetus to have facial abnormality and bilateral clenched hand and talipes with extension contractures of knees. Provisional diagnosis of FSS was made which was confirmed after the birth. Thus all cases of Arthrogryposis during prenatal scan should be carefully looked for the facial abnormality in the fetus.

Non-pharmacological management of nasal polyp: A case report.

Nasal polyp causes difficulty in breathing due to blockage of nasal passage. The pathogenesis of nasal polyposis is not known. The primary medical therapy available for nasal polyposis is steroid administration. Antihistamines, decongestants and cromolyn sodium provide little benefit. With this background of nasal polyp pathophysiology and the existing management, a case of nasal polyp was treated with the cleansing process of yoga i.e. neti kriya and naturopathy with good result. This isolated case report warrants a need for controlled clinical trial of neti kriya to establish its role in the management of nasal polyposis.

Development of an evaluation criteria for rural water supply and environmental sanitation programme in project and non-project villages--a case study.

The Rural Water Supply and Sanitation (RWSS) in project and non-project villages of Mysore Taluk has been evaluated and discussed in this paper. The study area covered two villages (Yelwala and Kadakola) where Integrated Water Supply Scheme (IRWSS) was implemented under World Bank Project and two non-project villages (Belwadi and Byathahalli) closer to them. Pre and post scenarios of the project and non-project villages were investigated in terms of water quality analysis and also grading of villages has been done on the basis of water supply, sanitation, hygienic awareness and practices. Matrix methodology was used to evaluate the indicators from the survey data gathered from all studied villages. Finally, the villages were graded on the basis of cumulative value obtained for each village. Water quality analysis depicted turbidity, total dissolved solids and hardness being high and iron deficiency was also observed in water samples of all the villages. It was concluded that the present method of evaluation of rural water supply and sanitation project could be effectively applied to different upcoming projects.

Prevalence of known diabetes in Chennai City.

AIM: To determine prevalence of known diabetes in those more than 20 years of age in Chennai city. METHODOLOGY: Urban population was selected for the survey. Assuming the prevalence of known diabetes as 5.0% in those aged > 20 years, the cluster sample size calculated to estimate it with 95% CI and +/- 10% precision, was 25800 individuals of all ages. This population obtained from 200 households in each of 30 randomly selected corporation divisions of the city, was surveyed by social workers by house to house enquiry. General information and health status of every member of the household were recorded on prescribed forms. This survey was conducted during January-July, 1998. RESULTS: Among 26,066 individuals of all ages 779 had known diabetes and 99.4% of them had type 2 diabetes. The prevalence of known diabetes was 2.9% for all ages and both sexes combined. Crude and age-standardized prevalence was 4.9% (95% CI 4.6-5.2) for those aged > 20 years. The standardized prevalence was 10.5% (95% CI 9.8 - 11.2) in those aged > or = 40 years. The prevalence was significantly high (P < 0.05) in females. CONCLUSION: The prevalence of known diabetes was low in total population but increased in those aged > 20 and further increased in those aged > or = 40 years. The causes for high prevalence in > or = 40 year age group needs to be explored in this population.

Lot quality assurance sampling (LQAS) for monitoring leprosy elimination in an endemic district in Tamilnadu.

This paper examines whether the health administration can use lot quality assurance sampling (LQAS) for identifying high prevalence areas for leprosy for initiating necessary corrective measures. The null hypothesis was that leprosy prevalence in the district was at or above ten per 10,000 and the alternative hypothesis was that it was at or below five per 10,000. A total of 25,500 individuals were to be examined with 17 as an acceptable maximum number of cases (critical value). Two-stage cluster sample design was adopted. The sample size need not be escalated as the estimated design effect was 1. During the first phase, the survey covered a population of 4,837 individuals out of whom 4,329 (89.5%) were examined. Thirty-five cases were detected and this number far exceeded the critical value. It was concluded that leprosy prevalence in the district should be regarded as having prevalence of more than ten per 10,000 and further examination of the population in the sample was discontinued. LQAS may be used as a tool by which one can identify high prevalence districts and target them for necessary strengthening of the programme. It may also be considered for certifying elimination achievement for a given area.

Bronchioloalveolar carcinoma mimicking miliary tuberculosis.

A case of bronchioloalveolar carcinoma, with widespread dissemination to both lungs and miliary mottling on chest X-ray is reported in a 40 year old male.

Efficacy of naturopathy and yoga in bronchial asthma--a self controlled matched scientific study.

Asthma is one of the common psychosomatic illness influenced by many factors. Bronchodilators give temporary relief and have side effects. The present study is aimed at finding the efficacy of a non-pharmacological approach of naturopathy and Yoga in bronchial asthma. A total no of 37 patients (19 men, 18 women) with mean age 35.06 yrs (men), 40.74 yrs (women) admitted to INYS, Bangalore, for the period of 21 days. The treatment included 1. Diet therapy 2. Nature cure treatment and 3. Yoga therapy. The various parameters including lung function test were measured on admission and once a week. Results showed the significant improvement in PEFR, VC, FVC, FEV1, FEV/FEC %, MVV, ESR and absolute eosinophil count. The patients reported a feeling of well being, freshness and comfortable breathing. Naturopathy and yoga helps in inducing positive health, alleviating the symptoms of disease by acting at physical and mental levels.

Lot quality assurance sampling for monitoring immunization coverage in Madras City.

OBJECTIVE: To explore the usefulness of Lot Quality Assurance Sampling (LQAS) to identify divisions in a city that had immunization coverage levels of 80% for any of the four EPI vaccines. METHODS: Only 43 divisions were considered for the study, the stratification factor being the death rate. The hypothesis that 80% coverage is 'unacceptable' was stipulated. Critical value (the number of unimmunized children) was chosen as 3. A simple random sample of 36 children in the age-group 12-23 months was taken from each selected division. Since sampling frames of children were not available, a simple random sample of 36 households was selected. Immunization status of each child was assessed by interviewing the child's mother/guardian. If the number of unimmunized children exceeded 3, then the division was regarded having coverage level 80% and rejected. RESULTS: The coverage was classified as unacceptable(i. e., below 80%) in 19 divisions for Polio and DPT vaccines, in 26 divisions for Measles vaccine and in 4 divisions for BCG vaccine. The average time spent for undertaking the LQAS survey was 6 man-days per division. CONCLUSION: This study demonstrated the utility of the LQAS technique in identifying 'unsatisfactory' pockets in Madras City, when the overall coverage was satisfactory. The technique will have greater application with an increase in the number of large units (cities/districts) having an overall coverage of 90% or more.

A concurrent comparison of a WHO-recommended 30-cluster survey and a modified version of it under Indian conditions in the estimation of immunization coverages.

A concurrent comparison of the WHO 30-cluster sample survey method for estimating immunization coverages (DPT, Polio, BCG, Measles) and an Indian modification of (GOI) was undertaken in five districts in South India. The essential difference between the two methods is the manner in which the first household is selected in the chosen clusters. With the WHO method, it is chosen clusters. With the WHO method, it is chosen at random, whereas with the GOI method it is often close to the village centre. Estimates with the required degree of precision, i.e., 95% confidence limits of +/- 10 percentage points, were provided in 18 (90%) of 20 instances by the WHO method and in 19 (95%) by the GOI method, findings which are in accordance with expectation. The estimated coverages were, however, higher by the GOI method than by the WHO method in two districts, lower in one district, and in the remaining two districts there was no clear pattern. On the average, there was a suggestion that the GOI method yielded slightly higher coverages, but the differences were not statistically significant.

A comparison of a 30-cluster survey method used in India and a purposive method in the estimation of immunization coverages in Tamil Nadu.

A 30-cluster survey method that is employed for estimating immunization coverages by the Government of India (GOI) was compared with a Purposive method, to investigate whether the likely omission of SC/ST and backward classes in the former would lead to the reporting of higher coverages. The essential difference between the two methods is in the manner in which the first household is selected in the chosen first stage sampling units (villages). With the GOI method, it is often close to the village centre, whereas with the Purposive method it is always in the periphery or in a pocket consisting of SC/ST or backward classes. A concurrent comparison of the two methods in three districts in Tamil Nadu showed no real differences in the coverage with DPT and BCG vaccines. However, the coverage was consistently higher by the GOI method in the case of the Polio vaccine (by 1.5%, 3.1% and 5.3% in the 3 districts), and the Measles vaccine (by 4.8%, 13.3% and 13.9%); the average difference was 3.3% for Polio vaccine (p = 0.08) and 7.3% for Measles vaccine (p = 0.01).

Keratins as markers in odontogenesis--an immunocytochemical experimental study in rats.

The expression and distribution of keratins within different layers of enamel organs of embryonic and neonatal rats studied by using indirect immunoperoxidase and immunofluorescent techniques in paraffin-embedded tissues employing specific antibodies revealed Keratin positivity in odontoblastic layer, oral epithelium and dental lamina in primitive stages; other odontogenic tissues showed negative reaction.

Estimation of immunisation coverages in children by WHO 30-cluster survey.

A WHO 30-cluster survey for estimating immunisation coverages in infancy was undertaken in each of 5 districts in Tamil Nadu, strictly according to the specifications laid out in the WHO manual. The main aim was to examine whether the technique would provide estimates with the required degree of precision under Indian conditions. Of 60 sample survey estimates, 57 had the targeted degree of precision (i.e., 95% confidence limits of +/- 10 percentage points), which is in excellent agreement with expectation. The proportions of infants on whom immunisation was initiated, were very high for DPT vaccine (88-99%) and polio vaccine (85-99%); however, of those who had received the first dose, 23-39 per cent did not complete the 3-dose schedule. Estimated coverage with measles vaccine ranged from 15 to 54 per cent, while BCG coverage ranged from 53 to 97 per cent. Better health education regarding the need and correct age for immunisation, and more effective motivation at the time of administration of the first dose of DPT/polio vaccine, are recommended.

Confidence intervals in medical research.

The utility of confidence intervals in a wide variety of situations in the medical field is re-emphasized, with examples drawn from controlled clinical trials, disease control programmes, vaccine trials and laboratory studies. It is shown that the confidence interval approach is more informative than a mere test of statistical significance, and should therefore be employed as an useful adjuvant. Since proportions are widely quoted in medical literature and as the determination of the exact confidence limits for a binomial proportion is iterative and time-consuming, an assessment is made of 15 published methods which provide approximate confidence limits; the 'Square root transformation' method is recommended since it is accurate and the computation of limits is relatively easy. In the case of a difference between two proportions, the usual method may be employed if sample sizes exceed 75; for smaller sample sizes (even for sizes of 5), the Jeffreys-Perks method is very satisfactory and is therefore recommended.

Direct estimation of absolute glomerular filtration rate from dynamic renal scintigraphy using gamma camera.

Absolute glomerular filtration rate (GFR), which can serve as a useful parameter of renal function, is not applied in clinical practice due to various technical constraints. We estimated GFR in 20 subjects (10 controls, 10 patients) by two different techniques simultaneously with a single intravenous injection of TC99m DTPA. The GFR results obtained by a conventional plasma clearance technique were compared with that of a simpler, scintigraphic technique which does not require any blood or urine sample, and these were found to correlate significantly (r = 0.75, p less than 0.001). The linear relationship between the fraction of the dose injected taken up by the kidneys during the parenchymal phase of the dynamic imaging study and the overall plasma clearance was also found to be significant (r = 0.932, p less than 0.001) our study shows that reliable estimation of absolute GFR is possible from the routine dynamic renal scinti-scanning procedure using the gamma camera - computer system, and hence might prove applicable in clinical practice.

Characterization of a toxin from Parthenium hysterophorus and its mode of excretion in animals.

Fractionation of methanolic extracts of air dried aerial parts of Parthenium resulted in the isolation of a toxic constituent which was identified as parthenin, the major sesquiterpene lactone from the weed. The LD50 (minimal lethal dose required to cause 50% mortality) for parthenin in rats was 42 mg/kg body weight. When [3H]-parthenin was given orally or by intravenous administration, radioactivity appeared in the milk of lactating laboratory and dairy animals. Tissue distribution of radioactivity revealed that maximum label was detectable in kidneys.