Pharmacogenetics and the Future of Perzonalized Medications

Clinical genetic testing has grown across the globe over the past 30 decades as the causative mutations for Mendelian diseases have been pointed out, especially helped in part by the recent advances in molecular technologies. Substantially, the use of up to date tests and other strategies such as diagnostic confirmation, testing prenatally, and population-based carrier screening is offered with caution and careful consideration before implementing clinically. This may facilitate the appropriate use of brand new genetic tests available. It helps clinicians to judge and prescribe drugs more wisely. Nowadays, most of the health organizations and drug safety commissions provide revisions that include pharmacogenetic information leaflets for selected drugs. However, regardless of some pharmacogenetic associations with adverse results, rest of the proposals has been proven successfully. When compared with testing for the Mendelian diseases, pharmacogenetic testing for other manifestations may have only a negligible positive predictive value, which is one rationale for underutilization. A number of other barriers remain with implementing clinical pharmacogenetics, including lack of clinical utility, professional education, and regulatory and reimbursement issues, among others. Through this review we put forward some of the challenges and barriers faced in executing a clinical pharmacogenetic test

FUSOGENIC LIPOSOME FOR THE TREATMENT OF FUNGAL MENINGITIS: AN OVERVIEW

Fungal meningitis is an infection which is caused by fungus which spreads through the blood to the spinal cord. People with weakened immunity get this disease easily like persons with AIDs, etc. To make sure the disease is fungal meningitis, a sample is taken from the cerebrospinal fluid and it is sent to the laboratory. Usually, fungal meningitis is not mediated from person to person, but it is caused when a fungi are inhaled from the surrounding and spread into the blood to the central nervous system. Normally medications such as vaccines, IV, and oral suspensions are given to the people for curing fungal meningitis. Commonly used drugs are Amphotericin B and fluconazole oral suspension. Amphotericin B is an antifungal, antiprotozoal, and hydrophobic drug. However, these drugs cannot give a directly as medication therapy for the patients, because it offers toxic effect and side effects, absorption rate is slower, and crossing the blood–brain barrier (BBB) is getting difficult. Adverse effects can be minimized with the application of nanotechnology. Therefore, in human medical services, the availability of molecular nanotechnology will provide rapid progress. Nanoparticle (NP) systems help to improve the solubility of poorly water-soluble drugs which has been explained using Noyes–Whitney equations. Nanoparticles offers several advantages as a drug delivery system, such as better drug bioavailability, reduction of dosing frequency enables them for the betterment of diseases, can cross the BBB, and it is very cost-effective. Types of NP include polymeric NP, carbon nanotubes, metallic structures, nanocrystals, and fusogenic liposomes. Fusogenic liposomes are a peculiar class of phospholipid vesicles. The fusogenic liposomes can deliver encapsulated NP into the targeted sites and also can cross the BBB. On comparing with cationic liposomes, fusogenic liposomes are more effective as well as rapid in the drug delivery

Awareness of cervical cancer and practice of Papanicolou smears among adult women availing health services or visiting a rural maternity hospital, Ramnagara District, Karnataka, India

Background: Cervical cancer is a leading cause of cancer-related deaths among women worldwide. Almost 87% of cervical cancer deaths occur in low and middle-income countries. The study was conducted to assess the awareness of cervical cancer and practice of Papanicolou (Pap) smears among women availing health services or visiting a rural maternity hospital, Karnataka.Methods: A hospital-based cross-sectional study was conducted using a 50-item interview schedule. The interview was administered to women >18 years of age who availed services at the hospital and their caretakers.Results: Mean age of the 158 women interviewed was 32.68±13.7 years. Only 21% of women had heard about cervical cancer. Only 11.4% knew at least one symptom and 1.9% knew one risk factor of cervical cancer. Most of the women (99%) were not aware about prevention of cervical cancer. Only 4% of the women had heard about Pap smears and 3% of the women had undergone a Pap smear test.Conclusions: Women in our study had very poor awareness of cervical cancer and practice of Pap smears. Gainfully employed women (OR=32; 8.8-111.2) and women who reported cervical cancer among family members or friends (OR=116; 20.2-665.4).  were more likely to have heard about cervical cancer. This study indicates a need to increase the awareness on cervical cancer and its prevention especially regarding Pap smears among rural women in Karnataka

Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017:a systematic analysis for the Global Burden of Disease Study 2017

Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk outcome pairs, and new data on risk exposure levels and risk outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017. Findings In 2017,34.1 million (95% uncertainty interval [UI] 33.3-35.0) deaths and 121 billion (144-1.28) DALYs were attributable to GBD risk factors. Globally, 61.0% (59.6-62.4) of deaths and 48.3% (46.3-50.2) of DALYs were attributed to the GBD 2017 risk factors. When ranked by risk-attributable DALYs, high systolic blood pressure (SBP) was the leading risk factor, accounting for 10.4 million (9.39-11.5) deaths and 218 million (198-237) DALYs, followed by smoking (7.10 million [6.83-7.37] deaths and 182 million [173-193] DALYs), high fasting plasma glucose (6.53 million [5.23-8.23] deaths and 171 million [144-201] DALYs), high body-mass index (BMI; 4.72 million [2.99-6.70] deaths and 148 million [98.6-202] DALYs), and short gestation for birthweight (1.43 million [1.36-1.51] deaths and 139 million [131-147] DALYs). In total, risk-attributable DALYs declined by 4.9% (3.3-6.5) between 2007 and 2017. In the absence of demographic changes (ie, population growth and ageing), changes in risk exposure and risk-deleted DALYs would have led to a 23.5% decline in DALYs during that period. Conversely, in the absence of changes in risk exposure and risk-deleted DALYs, demographic changes would have led to an 18.6% increase in DALYs during that period. The ratios of observed risk exposure levels to exposure levels expected based on SDI (O/E ratios) increased globally for unsafe drinking water and household air pollution between 1990 and 2017. This result suggests that development is occurring more rapidly than are changes in the underlying risk structure in a population. Conversely, nearly universal declines in O/E ratios for smoking and alcohol use indicate that, for a given SDI, exposure to these risks is declining. In 2017, the leading Level 4 risk factor for age-standardised DALY rates was high SBP in four super-regions: central Europe, eastern Europe, and central Asia; north Africa and Middle East; south Asia; and southeast Asia, east Asia, and Oceania. The leading risk factor in the high-income super-region was smoking, in Latin America and Caribbean was high BMI, and in sub-Saharan Africa was unsafe sex. O/E ratios for unsafe sex in sub-Saharan Africa were notably high, and those for alcohol use in north Africa and the Middle East were notably low. Interpretation By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning. Copyright (C) 2018 The Author(s). Published by Elsevier Ltd

Proceedings of Patient Reported Outcome Measure’s (PROMs) Conference Oxford 2017: Advances in Patient Reported Outcomes Research

A33-Effects of Out-of-Pocket (OOP) Payments and Financial Distress on Quality of Life (QoL) of People with Parkinson’s (PwP) and their Carer

The use of plants in the traditional management of diabetes in Nigeria: Pharmacological and toxicological considerations

Ethnopharmacological relevance: The prevalence of diabetes is on a steady increase worldwide and it is now identified as one of the main threats to human health in the 21st century. In Nigeria, the use of herbal medicine alone or alongside prescription drugs for its management is quite common. We hereby carry out a review of medicinal plants traditionally used for diabetes management in Nigeria. Based on the available evidence on the species׳ pharmacology and safety, we highlight ways in which their therapeutic potential can be properly harnessed for possible integration into the country׳s healthcare system. Materials and methods: Ethnobotanical information was obtained from a literature search of electronic databases such as Google Scholar, Pubmed and Scopus up to 2013 for publications on medicinal plants used in diabetes management, in which the place of use and/or sample collection was identified as Nigeria. ‘Diabetes’ and ‘Nigeria’ were used as keywords for the primary searches; and then ‘Plant name – accepted or synonyms’, ‘Constituents’, ‘Drug interaction’ and/or ‘Toxicity’ for the secondary searches. Results: The hypoglycemic effect of over a hundred out of the 115 plants reviewed in this paper is backed by preclinical experimental evidence, either in vivo or in vitro. One-third of the plants have been studied for their mechanism of action, while isolation of the bioactive constituent(s) has been accomplished for twenty three plants. Some plants showed specific organ toxicity, mostly nephrotoxic or hepatotoxic, with direct effects on the levels of some liver function enzymes. Twenty eight plants have been identified as in vitro modulators of P-glycoprotein and/or one or more of the cytochrome P450 enzymes, while eleven plants altered the levels of phase 2 metabolic enzymes, chiefly glutathione, with the potential to alter the pharmacokinetics of co-administered drugs. Conclusion: This review, therefore, provides a useful resource to enable a thorough assessment of the profile of plants used in diabetes management so as to ensure a more rational use. By anticipating potential toxicities or possible herb–drug interactions, significant risks which would otherwise represent a burden on the country׳s healthcare system can be avoided

Production of He-4 and (4) in Pb-Pb collisions at root(NN)-N-S=2.76 TeV at the LHC

Results on the production of He-4 and (4) nuclei in Pb-Pb collisions at root(NN)-N-S = 2.76 TeV in the rapidity range vertical bar y vertical bar <1, using the ALICE detector, are presented in this paper. The rapidity densities corresponding to 0-10% central events are found to be dN/dy4(He) = (0.8 +/- 0.4 (stat) +/- 0.3 (syst)) x 10(-6) and dN/dy4 = (1.1 +/- 0.4 (stat) +/- 0.2 (syst)) x 10(-6), respectively. This is in agreement with the statistical thermal model expectation assuming the same chemical freeze-out temperature (T-chem = 156 MeV) as for light hadrons. The measured ratio of (4)/He-4 is 1.4 +/- 0.8 (stat) +/- 0.5 (syst). (C) 2018 Published by Elsevier B.V.Peer reviewe

Azimuthal anisotropy of charged jet production in root s(NN)=2.76 TeV Pb-Pb collisions

We present measurements of the azimuthal dependence of charged jet production in central and semi-central root s(NN) = 2.76 TeV Pb-Pb collisions with respect to the second harmonic event plane, quantified as nu(ch)(2) (jet). Jet finding is performed employing the anti-k(T) algorithm with a resolution parameter R = 0.2 using charged tracks from the ALICE tracking system. The contribution of the azimuthal anisotropy of the underlying event is taken into account event-by-event. The remaining (statistical) region-to-region fluctuations are removed on an ensemble basis by unfolding the jet spectra for different event plane orientations independently. Significant non-zero nu(ch)(2) (jet) is observed in semi-central collisions (30-50% centrality) for 20 <p(T)(ch) (jet) <90 GeV/c. The azimuthal dependence of the charged jet production is similar to the dependence observed for jets comprising both charged and neutral fragments, and compatible with measurements of the nu(2) of single charged particles at high p(T). Good agreement between the data and predictions from JEWEL, an event generator simulating parton shower evolution in the presence of a dense QCD medium, is found in semi-central collisions. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe