The irrational fixed dose combinations in the Indian drug market: an evaluation of prescribing pattern using WHO guidelines

Background: Evaluation of the pattern of fixed dose combinations (FDCs) prescribing amongst the practitioners in a tertiary care hospital in Central India. Methods: Nine hundred and ninety four prescriptions, containing 639 FDCs were scrutinized in the tertiary care hospital. After excluding the total and the interdepartmental repetitions, the numbers of FDCs were 278, which were considered for final analysis. Inclusion criteria were FDCs from the major out-patient department (OPD) of the tertiary care hospital from January 2011 to December 2011. FDCs from the wards, casualty, infectious disease unit, intensive cardiac care unit (ICCU), tuberculosis and chest and HIV unit were excluded from the study. FDCs were analysed for the different pattern of prescribing and rationalism. Results were expressed as percentages. Results: Out of 639 FDCs, the most commonly prescribed FDCs were B complex (12.20%), pantoprazole plus domperidone (9.55%) and amoxicillin plus clavulanic acid (7.35%). Seventy percent of the FDCs were prescribed to the age group of 21-60 years. The FDCs were maximum from the department of medicine (25.59%), followed by surgery (15.47%) and ENT 13.69%. Out of 278 FDCs, only 5.4% were rational, and rest of the FDCs were irrational. Ninety five percent of all FDCs were brand names. The physicians were unaware of the active pharmacological ingredients (APIs) of 20.86% FDCs. Ninety two percent FDCs were available as over the counter (OTCs). Forty eight percent FDCs were costing from Rs. 0-50. There were 2.87% FDCs whose price was above Rs. 500.Conclusions: Irrational FDCs are prescribed by all the departments. Physicians were ignorant about the essential drugs and FDCs. Patients didn’t have access to rational medicines. Therefore, physicians and regulators should be alerted in time. Regulatory actions or government laws should be made mandatory. Availability and access to 348 essential medicines for basic health care should be the priority of the government. Implementation of central drug standard control organisations (CDSCO) guidelines on industries for manufacture of FDCs must be made compulsory

Urine Biomarkers of Risk in the Molecular Etiology of Breast Cancer

Endogenous estrogens can be bio-activated to endogenous carcinogens via formation of estrogen quinones. Estrogen-3,4-quinones react with DNA to form mutagenic depurinating estrogen-DNA adducts. The carcinogenicity of endogenous estrogens is related to unbalanced estrogen metabolism leading to excess estrogen quinones and formation of depurinating DNA adducts. The present studies were initiated to confirm that relatively high levels of depurinating estrogen-DNA adducts are present in women at high risk for breast cancer or diagnosed with the disease. These adducts may be biomarkers for early detection of breast cancer risk. The estrogen metabolites, conjugates and depurinating DNA adducts were identified and quantified by using ultraperformance liquid chromatography/tandem mass spectrometry to analyze urine samples from 40 healthy control women, 40 high-risk women and 40 women with newly diagnosed breast cancer. Estrogen metabolism was shifted from protective methoxylation and conjugation pathways in healthy control women towards activating pathways leading to formation of depurinating DNA adducts in women at high risk or with breast cancer. These results support the hypothesis that breast cancer is initiated by mutations derived from depurination of estrogen-DNA adducts. Therefore, relative levels of depurinating estrogen-DNA adducts could become biomarkers for early detection of breast cancer risk and aid in determining preventive strategies

Effect of Acinetobacter sp on Metalaxyl Degradation and Metabolite Profile of Potato Seedlings (Solanum tuberosum L.) Alpha Variety

One of the most serious diseases in potato cultivars is caused by the pathogen Phytophthora infestans, which affects leaves, stems and tubers. Metalaxyl is a fungicide that protects potato plants from Phytophthora infestans. In Mexico, farmers apply metalaxyl 35 times during the cycle of potato production and the last application is typically 15 days before harvest. There are no records related to the presence of metalaxyl in potato tubers in Mexico. In the present study, we evaluated the effect of Acinetobacter sp on metalaxyl degradation in potato seedlings. The effect of bacteria and metalaxyl on the growth of potato seedlings was also evaluated. A metabolite profile analysis was conducted to determine potential molecular biomarkers produced by potato seedlings in the presence of Acinetobacter sp and metalaxyl. Metalaxyl did not affect the growth of potato seedlings. However, Acinetobacter sp strongly affected the growth of inoculated seedlings, as confirmed by plant length and plant fresh weights which were lower in inoculated potato seedlings (40% and 27%, respectively) compared to the controls. Acinetobacter sp also affected root formation. Inoculated potato seedlings showed a decrease in root formation compared to the controls. LC-MS/MS analysis of metalaxyl residues in potato seedlings suggests that Acinetobacter sp did not degrade metalaxyl. GC–TOF–MS platform was used in metabolic profiling studies. Statistical data analysis and metabolic pathway analysis allowed suggesting the alteration of metabolic pathways by both Acinetobacter sp infection and metalaxyl treatment. Several hundred metabolites were detected, 137 metabolites were identified and 15 metabolic markers were suggested based on statistical change significance found with PLS-DA analysis. These results are important for better understanding the interactions of putative endophytic bacteria and pesticides on plants and their possible effects on plant metabolism

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Development of Orange Grading Machine on Weight Basis

High value fresh agricultural produce such as orange must be carefully handled and graded in order to meet customer demands and quality standards. Manual grading is widely adopted practice which is costly and time consuming. The existing mechanical graders grade fruits on the basis of size, and owing to mechanical nature have limitations of lower capacity and efficiency. The present work describes the development of electronic grading machine on weight basis for oranges. The machine comprised of various elements such as feeding unit, weighing assembly, dropping and collection unit. The machine is capable of individually metering fruits in weighing section and weighing of individual fruits and grading them in four different weight grades

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Not AvailableThe study assesses noise hazards in agri-based industrial workplaces in Punjab state of India. Guidelines of Canadian Centre for Occupational Health and Safety were employed to generate the primary data on noise survey. Potential noise hazardous areas within 40 agri-based industrial units (flour units/wheat milling units) were identified through constructing the contour map. A layout mentioning the locations of various machines and workers in the units were prepared. Data on output capacity, size of power source, maintenance condition of machines and workroom configurations were solicited through the personal interview of the owner of the units. Semi-structured interview schedule was prepared to generate the primary data. Average temperature, relative humidity and air velocity in the working rooms were also recorded. A specific grid (2 m × 2 m) was made on the layout based on the size of unit to get representative data for unit. A sound-level meter was also placed to record the noise levels. It was observed that the normal working hours (h) of flour units were varied from 8 to 12 h. The highest sound level was generated at power transmission unit varying in the range of 92.2 dBA and 98.5 dBA. The average sound intensity was recorded as 95.1 dBA which was the highest noise intensity. For ensuring the safe working environment, noise control devices should be provided to all workers in the units and need to be enforced. The machines should be regularly maintained to reduce warbling of components which increase noise and employers should consider reduction in working period to minimize noise exposure period. Personal protective measures for the safety of workers are also needed.Not Availabl

A PROSPECTIVE, OBSERVATIONAL STUDY OF ADVERSE REACTIONS TO DRUG REGIME FOR MULTI-DRUG RESISTANT PULMONARY TUBERCULOSIS IN CENTRAL INDIA.

Abstract Objective: 1) To assess the adverse drug reactions of second line anti-tubercular drugs used to treat Multi-drug resistant Tuberculosis (MDR TB) in central India on the basis of causality, severity and avoidability scales. 2) To study the relationship of type of MDR TB (primary or secondary) and presence of diabetes mellitus (DM) with mean smear conversion time. Material and Methods: A prospective, observational study was carried out on diagnosed multidrug resistant tuberculosis patients enrolled for DOTS‑Plus regimen at TB and Chest Disease Department from January to December 2012. They were followed for 9 months thereafter and encountered adverse drug reactions (ADRs) were noted along with the time of sputum conversion. The data were analysed by Chi-square or Fisher’s exact test and unpaired student’s‘t’ test. Results: Total 64 ADRs were reported in 55 patients out of total 110 patients (n = 110). As per the Naranjo causality assessment of ADRs, 7 patients had “definite” causal relation, 45 had “probable” causal relation and 3 had “possible” causal relation with drugs of DOTS Plus regime. As per the Hartwig’s severity assessment scale, there were total 7 ADRs in Level 1, 6 in Level 2, 33 in Level 3 and 9 in Level 4. Hallas avoidability assessment scale divided the ADRs as 3 being “Definitely avoidable”, 26 “Possibly avoidable”, 23 “Not avoidable” and 3 “unevaluable”. ). Mean sputum smear conversion time is significantly higher in patients with secondary type than that of primary type of MDR TB (p = 0.0001) and in patients with DM than those without DM (p <0.0001). Conclusion: ADRs were common in patients of MDR TB on DOTs-Plus drug regime. It was due to lack of availability of safer and equally potent drugs in DOTs-Plus drug regime compared to DOTS regime in non-resistant TB. The frequency and severity of ADRs can be reduced by strict vigilance about known and unknown ADRs, monitoring their laboratory and clinical parameters and instituting appropriate measures. Keywords: Adverse drug reactions, Avoidability, Causality, DOTs-Plus, MDR TB, Severity

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Not AvailableThe effect of juice extraction methods (from arils and halved fruits), temperature (70, 80, 90 and 100̊C) and thermal processing time (2, 5 and 10 minutes) on quality of the pomegranate (Punica granatum L.) juice has been studied. The quality parameters studied included biochemical parameters such as ascorbic acid, total anthocyanin content, total phenolic compounds, antioxidant capacity, TSS, and acidity. The color, microbial, and sensory quality was also evaluated. The results revealed that thermal treatment reduces important bioactive compound with increase in temperature and time of processing. The thermal processing at 80 ̊C for 5 min. found to be suitable for reducing microbial load to below detectable limits and maintaining sensory quality up to 7.91 on ten point hedonic scale. The juice extracted from halved fruits was found to be nutritionally rich than juice extracted from arils in terms of antioxidant capacity, ascorbic acid, total phenolic compounds, total anthocyanin and color value a*. The retention of antioxidant capacity, total phenolic compounds,total anthocyanin content, ascorbic acid and color for thermal processing at 80 ̊C for 5 minutes for juice extracted from halved fruits was 22.68 mg/100ml AAE, 2189 mg/l GAE, 3.18 mg/100 ml, 18.33 mg/100 ml and 37.05 respectively.Not Availabl

Association of the CYP1B1*3 allele with survival in patients with prostate cancer receiving docetaxel

Using a single nucleotide polymorphism association study in 52 men with prostate cancer receiving docetaxel, we found that individuals carrying two copies of the CYP1B1*3 polymorphic variant had a poor prognosis after docetaxel-based therapies compared with individuals carrying at least one copy of the CYP1B1*1 allele (30.6 versus 12.8 months; P = 0.0004). The association between CYP1B1*3 and response to therapy was not observed in similar subjects receiving non-taxane-based therapy (P = 0.18). The systemic clearance of docetaxel was also unrelated to CYP1B1 genotype status (P = 0.39), indicating that the association of CYP1B1*3 with clinical response is not due to docetaxel metabolism. To explain these results, we hypothesized that an indirect gene-drug interaction was interfering with the primary mechanism of action of docetaxel, tubulin polymerization. We therefore conducted tubulin polymerization experiments with taxanes in the presence or absence of certain CYP1B1 estrogen metabolites, which are known to bind to nucleophilic sites in proteins and DNA, that revealed the primary estrogen metabolite of CYP1B1, 4-hydroxyestradiol (4-OHE2), when oxidized to estradiol-3,4-quinone strongly inhibits tubulin polymerization. The 4-OHE2 is also formed more readily by the protein encoded by the CYP1B1*3 allele, validating further our data in patients. Furthermore, estradiol-3,4-quinone reacted in vitro with docetaxel to form the 4-OHE2-docetaxel adduct. This pilot study provides evidence that CYP1B1*3 may be an important marker for estimating docetaxel efficacy in patients with prostate cancer. This link is likely associated with CYP1B1*3 genotype-dependent estrogen metabolism. Copyrigh