心血管病患者住院治疗期间潜在的药物相互作用研究

目的:明确住院治疗的心脏病患者中潜在的药物-药物相互作用(drug-drug interaction,DDI),并对DDI相关危险因素进行评估。方法:选择2013年5月至2013年12月入院治疗的至少服用2种药物且入院不少于24小时的心脏病患者为研究对象,应用"标准药物相互作用数据库Micromedex-2(Thomson Reuters)×2.0"对这些患者可能发生的药物相互作用进行分析。结果:共入选150例患者,其中32例患者被确认出现了至少一种药物组合的DDI,发生率为21.3%;明确了48个有潜在危险因素的药物相互作用。阿托伐他汀/阿奇霉素(10.4%)、依那普利/二甲双胍(10.4%)、依那普利/氯化钾(10.4%)、阿托伐他汀/克拉霉素(8.3%)、呋塞米/庆大霉素(6.3%)是最常见的存在相互作用的药物组合,阿托伐他汀、依那普利、地高辛、呋塞米、氯吡格雷、华法林等药物经常参与药物相互作用。大多数药物的相互作用比较温和,但"用药种类增多、住院时间延长、存在合并症"等危险因素与潜在药物-药物相互作用(potential drug-drug interaction,p DDI)密切相关。结论:住院治疗的心脏病患者潜在DDI发生率较高,用药种类增多、住院时间延长、存在合并症均为其发生的危险因素。对那些存在明确危险因素的住院治疗的心脏病患者密切监测是十分必要的,医务人员要尽早发现和预防这些潜在的药物相互作用对人体健康造成的伤害。     

Distribution of heavy metals in the water,sediments, and fishes from Damodar river basin at steel city,India: a probabilistic risk assessment

Abstract

The present study, deals with the estimation of degrees of contamination, ecological and human health risk of heavy metals (As, Cd, Cr, Cu, Mn, Ni, Pb, and Zn) in sediments, surface water and fishes, which were collected from middle stretch of Damodar river and ponds at Asansol, which receives outfall of various coal-based industries. Metal content in the premonsoon season was higher than the postmonsoon, due to influx of rainwater. The heavy metal pollution indices (HPI) at some locations was observed up to 1.45 times than recommended value and the cadmium (Cd) was found dominating metal for high HPI value. The Cd concentration in surface water and pore water varied from 2.8 to 14.9?µg/L and 15.3–57.0?µg/L, respectively, which was up to 6 times higher than the permissible limit. Ecological risk assessment for sediments illustrates ‘moderate to considerable ecological risk’, especially because of Cd. Hazard index (HI) calculated to identify potential human health risk by dermal exposure of surface water was <0.1, indicating ‘negligible non-cancer risk’ for all age group of people. However, HI varied from 0.73 to 1.49 for adult and 1.37–2.78 by consumption of fishes indicates children have higher ‘non-cancer risk’ than adult.     

Assessment of heavy metal toxicity related with human health risk in the surface water of an industrialized area by a novel technique

This study innovates an assessment technique to evaluate heavy metal toxic load (HMTL). Assessment of surface water in Durgapur industrial area, West Bengal India illustrates that heavy metals in majority of sampling locations exceed the drinking water quality standards. Therefore, pollution status and health impact were predicted by heavy metal pollution index (HPI) and hazard index (HI). More than 50% of sampling locations were marked as polluted. Moreover, 5% and 90% of sampling locations near the industries have health risk to adult and child on ingestion. The study of specific exposure-time and exposure-duration affirms the suitability of water for fishing and regular activities. However, HPI or HI does not quantify heavy metal concentrations that pose threat to human health. Therefore, the proposed assessment technique, HMTL, determines the concentration of heavy metals responsible for health hazard. HMTL identifies Mn, Pb, and Co as toxic metals and estimates 85%, 63%, and 70% removal of these metals from surface water to limit pollution. Origins of metals were also investigated through statistical techniques, which revealed that Fe has geogenic and anthropogenic source, while other metals originate by anthropogenic activities solely. This study demonstrates that HMTL will help the planning authority to document effective water quality management plan.     

Predicting Drug-Target Interactions Using Drug-Drug Interactions

Computational methods for predicting drug-target interactions have become important in drug research because they can help to reduce the time, cost, and failure rates for developing new drugs. Recently, with the accumulation of drug-related data sets related to drug side effects and pharmacological data, it has became possible to predict potential drug-target interactions. In this study, we focus on drug-drug interactions (DDI), their adverse effects () and pharmacological information (), and investigate the relationship among chemical structures, side effects, and DDIs from several data sources. In this study, data from the STITCH database, from drugs.com, and drug-target pairs from ChEMBL and SIDER were first collected. Then, by applying two machine learning approaches, a support vector machine (SVM) and a kernel-based L1-norm regularized logistic regression (KL1LR), we showed that DDI is a promising feature in predicting drug-target interactions. Next, the accuracies of predicting drug-target interactions using DDI were compared to those obtained using the chemical structure and side effects based on the SVM and KL1LR approaches, showing that DDI was the data source contributing the most for predicting drug-target interactions.     

Human health risk assessment and source diagnosis of polycyclic aromatic hydrocarbons (PAHs) in the corn and agricultural soils along main roadside in Changchun,China

This work was to investigate distribution characteristics, human health risk assessment, and possible sources of 16 priority polycyclic aromatic hydrocarbons (PAHs) in corn and surface soils of farmlands along main roadside in Changchun City, Jilin Province, China. Total concentrations of 16 PAHs ranged from 1572.4 to 4390.2 µg/kg with a mean value of 2954.9 µg/kg in soils and from 219.9 to 627 µg/kg with a mean value of 362µg/kg in corn. Light-molecular-weight PAHs (2–3 rings) concentration was dominant in soils, accounting for 51%, whereas high-molecular-weight PAHs (5–6 rings) concentration was highest in corn, accounting for 48%. The results of plant concentration factor indicated that high-molecular-weight PAHs have greater mobility. To evaluate potential risk to human health, hazard index (HI) and risk index (RI) were employed. The values of HI for corn and soils were both smaller than 1, indicating that exposure of PAHs posed no or little potential risk to local residents. The fact that values of RI for corn and soils were smaller than 1 × 10^–4 suggested that exposure of PAHs posed no or little cancer risk to local residents. The possible sources of PAHs in corn and soils were both identified as mixture patterns of pyrogenic and petrogenic sources.     

A Comparative Screening-Level Ecological and Human Health Risk Assessment for Dredged Material Management Alternatives in New York/New Jersey Harbor

Managers of New York and New Jersey Harbor dredging projects are developing strategies to dispose and manage the large volumes of sediment that must be dredged to maintain passable waterways. The various management alternatives include aquatic containment facilities, upland containment, and treatment with beneficial reuse. An important consideration in the selection of an appropriate alternative is the evaluation of potential risks to ecological and human receptors. This study presents a framework for a screening-level ecological and human health risk assessment that compares risks associated with management alternatives for contaminated dredged materials. The major objectives of the work were to identify exposure routes that show the potential for risk and develop a framework that can be used to compare relative potential risks among eight management alternatives. Managers can use this framework to: ? identify characteristics of the placement/treatment alternatives that contribute to potential risk, ? choose one alternative over another for sediments with high concentrations of contaminants, ? implement controls that mitigate risk, or ? identify the need for a more comprehensive site-specific risk assessment.     

A Risk Assessment Approach for Policy Evaluation: New Jersey Case Studies

Monitoring environmental policy progress often focuses on contaminant concentrations while policy goals address health. To bridge this gap, we developed policy evaluation case studies applying risk assessment methods to explore population health risks of chemical exposures before and after policy implementation. Beginning in the 1970s the New Jersey Department of Environmental Protection provided some of the United States' first data on contaminants including trichloroethylene in drinking water and polychlorinated biphenyls (PCBs) in fish. These data provide a unique opportunity to evaluate environmental policies. The 1979 PCB manufacturing ban succeeded in reducing exposure and risk, but the persistence of these compounds in local fish requires continued state and local consumption advisories. The positive impact of drinking water standards for trichloroethylene was reflected in declining detection in public water supplies from the late 1970s to 2005, although maximum concentrations in a small percentage of supplies remain above standards. Our case studies show success and progress, and the need for multiple policies in combination when conditions warrant. Tracking specific policies and contaminants using risk assessment methods can be a valuable tool for policy evaluation and can foster population-based environmental health research. Pollution prevention policies are warranted for chemicals that persist in the environment.     

Antimicrobial Residues and Antimicrobial-Resistant Bacteria: Impact on the Microbial Environment and Risk to Human Health—A Review

Water quality has become a major environmental concern due to the presence of potentially harmful bacteria, protozoa, and chemicals. In particular, pharmaceuticals have recently gained prominence due to their potential negative effects on both the aquatic environment and on human health. The antimicrobial classes of penicillins, cephalosporins, macrolides, and fluoroquinolones are among the most frequent pharmaceuticals detected in the environment in Europe. The common route of entry of these antimicrobials into the environment is thought to be through wastewater treatment plant (WWTP) effluent. The main concern with regard to antimicrobial agents is the potential formation of antimicrobial resistance. Evidence suggests WWTPs may promote development of antimicrobial resistance. This study reviews antimicrobial residues typically found in treated water, their sources, process barriers, entry into the environment, and consequent human health concerns. The effects of WWTP on residues and the formation of antimicrobial-resistant bacteria are also discussed in addition to current risk assessment approaches for evaluating human health concerns, including development of antimicrobial resistance and resultant therapeutic failure. The uncertainty surrounding the fate and impact of different classes of antimicrobials in the environment is highlighted in addition to the lack of standardised methods to detect antimicrobials and to assess selective pressures.     

Risk of Gastrointestinal Disease Associated with Exposure to Pathogens in the Sediments of the Lower Passaic River

High levels of pathogenic microorganisms have been documented previously in waters of the Lower Passaic River in northern New Jersey. The purpose of this study was to characterize the microbial contamination of river sediments near combined sewer overflows (CSOs), a known source of pathogens. Concentrations of fecal coliform, total coliform, fecal Streptococcus, fecal Enterococcus, Pseudomonas aeruginosa, Staphylococcus aureus, Giardia lamblia, and Cryptosporidium parvum organisms were measured in 16 samples from three mudflat locations along the Lower Passaic River, as well as from an upstream location. Selected samples were also analyzed for antibiotic resistance. All of the samples contained high concentrations of total coliform, fecal coliform, fecal Streptococcus, and fecal Enterococcus organisms. Analysis of isolates of Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli from several samples indicated that each strain was resistant to at least one antibiotic typically used in clinical settings. Eight of 16 samples contained Giardia, and one sample contained Cryptosporidium. With these sampling data, a quantitative microbial risk assessment was conducted to evaluate the probability of infection or illness resulting from incidental ingestion of contaminated sediments over a 1-year period. Three potential exposure scenarios were considered: visitor, recreator, and homeless person. Single-event risk was first evaluated for the three individual exposure scenarios; overall risk was then determined over a 1-year period using Monte Carlo techniques to characterize uncertainty. For fecal Streptococcus and Enterococcus, annualized risk estimates for gastrointestinal illness ranged from approximately 0.42 to 0.53 for recreators, 0.07 to 0.10 for visitors, and 0.62 to 0.72 for homeless individuals across the three sampling locations. Annualized risk of Giardia infection ranged from 0.14 to 0.64 for recreators, 0.01 to 0.1 for visitors, and 0.30 to 0.87 for homeless individuals, across all locations where detected. Cryptosporidium was detected at one location, and the corresponding annualized risk of infection was 0.32, 0.05, and 0.51 for recreators, visitors, and homeless individuals, respectively. This risk assessment suggests that pathogen-contaminated sediments near areas of CSO discharge in the Lower Passaic River could pose a health risk to individuals coming into contact with sediments in the mudflat areas.     

Detection of Drug-Drug Interactions by Modeling Interaction Profile Fingerprints

Drug-drug interactions (DDIs) constitute an important problem in postmarketing pharmacovigilance and in the development of new drugs. The effectiveness or toxicity of a medication could be affected by the co-administration of other drugs that share pharmacokinetic or pharmacodynamic pathways. For this reason, a great effort is being made to develop new methodologies to detect and assess DDIs. In this article, we present a novel method based on drug interaction profile fingerprints (IPFs) with successful application to DDI detection. IPFs were generated based on the DrugBank database, which provided 9,454 well-established DDIs as a primary source of interaction data. The model uses IPFs to measure the similarity of pairs of drugs and generates new putative DDIs from the non-intersecting interactions of a pair. We described as part of our analysis the pharmacological and biological effects associated with the putative interactions; for example, the interaction between haloperidol and dicyclomine can cause increased risk of psychosis and tardive dyskinesia. First, we evaluated the method through hold-out validation and then by using four independent test sets that did not overlap with DrugBank. Precision for the test sets ranged from 0.4–0.5 with more than two fold enrichment factor enhancement. In conclusion, we demonstrated the usefulness of the method in pharmacovigilance as a DDI predictor, and created a dataset of potential DDIs, highlighting the etiology or pharmacological effect of the DDI, and providing an exploratory tool to facilitate decision support in DDI detection and patient safety.     

Distinguishing potential sources of genotoxic exposure via HPRT mutations

We utilize T-cell HPRT mutations to monitor exposure to environmental mutagens in siblings of children who have developed cancer at a persistently high rate in Toms River, New Jersey, U.S.A. A preliminary epidemiological study has found a statistically-significant association between drinking public water (by pregnant mother or infant) and subsequent risk for childhood cancer. Three potential sources of mutagenic exposures in Toms River may have increased the rate of carcinogenic initiation significantly in children: 1. Benzidine-based, other azo dye and anthraquinone dye wastes released by Ciba-Geigy, 2. Styrene-acrylonitrile (SAN) trimer and other plastic wastes of Union Carbide, and 3. Radium-224, present in unusually high concentrations in the Cohansey aquifer. Specific patterns of HPRT mutations are utilized to distinguish these various potential sources of carcinogenic exposures in the drinking water of families with childhood cancer and to differentiate chemically or radiologically induced cancers from those which occur spontaneously.     

Spatial distribution,exposure, and potential health risk assessment from nitrate in drinking water from semi-arid region of South India

Abstract

Elevated nitrate concentration in groundwater is a worldwide problem. Continuous exposure to high levels of nitrate in groundwater may cause adverse health effects among residents who use groundwater for consumption. Therefore, this study was conducted to identify the nitrate distribution and its potential health risk assessment from semi-arid region of Peddavagu in Central Telangana (PCT), South India. Groundwater samples were collected from thirty five locations and analyzed for nitrate and other water quality parameters. Nitrate (NO₃^-) in groundwater was observed to vary from 17 to 120?mg/L, with a mean of 58.74?mg/L. About 57% of samples exceeded the maximum acceptable limit of Indian drinking water standard. About, 40% of groundwater samples drinking water quality index (DWQI) is good, while 60% of groundwater falls in poor quality for drinking purposes. Health risk maps were created based on hazard quotient to quantify the potential health risk of the residents using US Environmental Protection Agency (US EPA) health risk assessment model. Health risk assessment revealed that mean total hazard index (HI_total) for men, women, and children were found as 1.42E?+?00, 1.67E?+?00, and 1.95E?+?00, respectively. Results exhibited that children are at high health risk than men and women in the PCT. Further, the human exposure to the NO₃^- contaminated water was above the critical limit of non-carcinogenic risk.     

Integrating Comparative Risk Assessment with Multi-Criteria Decision Analysis to Manage Contaminated Sediments: An Example for the New York/New Jersey Harbor

Current environmental challenges involve complex assessment and analysis of tradeoffs among differing criteria, expectations, and levels of certainty. Using multi-criteria decision analysis in combination with comparative risk assessment, a systematic and transparent framework can be created to integrate different types and sources of decision-relevant information. Although examples of decision analysis abound in the literature and academic efforts, its use within the practice of risk assessment and environmental management is still being established. This article provides an example of the use of decision analysis study that builds on a previous screening-level, comparative risk assessment of contaminated sediment from the New York/New Jersey harbor area. Using multi-criteria decision analysis, we explored the effect of different criteria weights, utility functions, and cost estimates on the ranking of seven contaminated sediment management alternatives. Values used in weighting decision criteria were surveyed from two interaction sessions with sediment management professionals.     

Fish larval supply to and within a lagoonal estuary: multiple sources for Barnegat Bay,New Jersey

We evaluated spatial variation in fish larval supply to a temperate, lagoon type estuary (Barnegat Bay, New Jersey) by determining species composition, size, and stage into inlets (n = 2), thoroughfares between adjacent estuaries (n = 3), and within the estuary (n = 4) in seasonal, synoptic sampling on night time flood tides during 2010–2014. Larval supply, as sampled with identical plankton nets (1 m diameter, 1 mm mesh) was dominated by post-flexion stage individuals (most 5–10 but reaching 70+ mm) from species spawned in the Atlantic Ocean from a variety of sources (e.g., Sargasso Sea, outer and inner continental shelf) and in the bay. While abundance for individual species varied among locations and years, in general, the larval composition was similar across inlets, thoroughfares, and within the bay within the same seasons. Homogenization across locations was likely the result of the tidal exchanges between the ocean, the estuary, and the adjacent locations. These exchanges provide numerous, redundant sources of larvae to this estuarine nursery. The similarity in larval supply among inlets, thoroughfares, and within the estuary indicates that the longer term study location behind Little Egg Inlet is representative for this, and probably other, estuaries along the New Jersey shore.     

Literature based drug interaction prediction with clinical assessment using electronic medical records: novel myopathy associated drug interactions

Drug-drug interactions (DDIs) are a common cause of adverse drug events. In this paper, we combined a literature discovery approach with analysis of a large electronic medical record database method to predict and evaluate novel DDIs. We predicted an initial set of 13197 potential DDIs based on substrates and inhibitors of cytochrome P450 (CYP) metabolism enzymes identified from published in vitro pharmacology experiments. Using a clinical repository of over 800,000 patients, we narrowed this theoretical set of DDIs to 3670 drug pairs actually taken by patients. Finally, we sought to identify novel combinations that synergistically increased the risk of myopathy. Five pairs were identified with their p-values less than 1E-06: loratadine and simvastatin (relative risk or RR = 1.69); loratadine and alprazolam (RR = 1.86); loratadine and duloxetine (RR = 1.94); loratadine and ropinirole (RR = 3.21); and promethazine and tegaserod (RR = 3.00). When taken together, each drug pair showed a significantly increased risk of myopathy when compared to the expected additive myopathy risk from taking either of the drugs alone. Based on additional literature data on in vitro drug metabolism and inhibition potency, loratadine and simvastatin and tegaserod and promethazine were predicted to have a strong DDI through the CYP3A4 and CYP2D6 enzymes, respectively. This new translational biomedical informatics approach supports not only detection of new clinically significant DDI signals, but also evaluation of their potential molecular mechanisms.     

Satellite monitoring of cyanobacterial harmful algal bloom frequency in recreational waters and drinking water sources

Cyanobacterial harmful algal blooms (cyanoHAB) cause extensive problems in lakes worldwide, including human and ecological health risks, anoxia and fish kills, and taste and odor problems. CyanoHABs are a particular concern in both recreational waters and drinking water sources because of their dense biomass and the risk of exposure to toxins. Successful cyanoHAB assessment using satellites may provide an indicator for human and ecological health protection. In this study, methods were developed to assess the utility of satellite technology for detecting cyanoHAB frequency of occurrence at locations of potential management interest. The European Space Agency's MEdium Resolution Imaging Spectrometer (MERIS) was evaluated to prepare for the equivalent series of Sentinel-3 Ocean and Land Colour Imagers (OLCI) launched in 2016 as part of the Copernicus program. Based on the 2012 National Lakes Assessment site evaluation guidelines and National Hydrography Dataset, the continental United States contains 275,897 lakes and reservoirs >1 ha in area. Results from this study show that 5.6% of waterbodies were resolvable by satellites with 300 m single-pixel resolution and 0.7% of waterbodies were resolvable when a three by three pixel (3 × 3-pixel) array was applied based on minimum Euclidian distance from shore. Satellite data were spatially joined to U.S. public water surface intake (PWSI) locations, where single-pixel resolution resolved 57% of the PWSI locations and a 3 × 3-pixel array resolved 33% of the PWSI locations. Recreational and drinking water sources in Florida and Ohio were ranked from 2008 through 2011 by cyanoHAB frequency above the World Health Organization’s (WHO) high threshold for risk of 100,000 cells mL⁻¹. The ranking identified waterbodies with values above the WHO high threshold, where Lake Apopka, FL (99.1%) and Grand Lake St. Marys, OH (83%) had the highest observed bloom frequencies per region. The method presented here may indicate locations with high exposure to cyanoHABs and therefore can be used to assist in prioritizing management resources and actions for recreational and drinking water sources.     

Assessing Risks of Plant-Based Pharmaceuticals: II. Non-Target Organism Exposure

Plant-based pharmaceuticals potentially offer a cleaner method of producing a protein for drug manufacturing than traditional methods because plants are free of mammalian infectious agents. However, in the open environment they have the potential for intra-and inter-species gene flow, protein exposure to the public and non-target organisms, and they also have the potential to contaminate livestock feed. This study used probabilistic approaches to quantify the non-target organism risks associated with three pharmaceutical proteins produced in field-grown maize. The risk assessment for plant-based pharmaceuticals was conducted for four receptor species used as surrogates for a wider range of species. Body weights and maize consumption rates for each species were modeled from currently available information and used to calculate the exposure based on expression levels of three proteins. The acute dietary exposure for the receptor species was a single-day event in which the total maize consumption came from the recombinant maize. The non-target organism risk assessment demonstrated that risks will vary between species and between proteins, based primarily on differences in toxic endpoint and consumption rates. It also shows the utility of probabilistic, quantitative risk assessment methodologies and the importance of assessing risks from plant-based pharmaceuticals on a case-by-case basis.     

Human Health Risk Assessment of Soils Contaminated with Metal(loid)s by Using DGT Uptake: A Case Study of a Former Korean Metal Refinery Site

The human health risk of soils contaminated with As, Pb, Cu, and Zn was evaluated based on pseudo-total concentrations of metal(loid)s, the physiologically based extraction test (PBET), and diffusive gradients in thin films (DGT). Non-carcinogenic (NCR) and carcinogenic (CR) risks exceeded the U.S. Environmental Protection Agency criteria under both the residential and non-residential scenarios. Human bioavailable concentrations (PBET) were much lower than pseudo-total concentrations. The Hazardous Index of NCR (HI (NCR)) for the PBET in the studied soils was 67% and 94% less than that for pseudo-total concentration, respectively, under the non-residential and residential scenarios. Similarly, CR for the PBET was also 65% and 93% less for the two soils. The concentration of metal(loid)s accumulated in the DGT resin was highly correlated with the PBET-extractable concentration (R² > 0.649). Therefore, for both the CR and HI (NCR), the DGT-calculated risk was linearly related to the PBET-calculated risk for the studied soils under both scenarios. The results suggest that DGT uptake and PBET-extracted concentrations are good surrogates for risk estimation and that both J1 and J2 soils require remediation before their use for residential or non-residential purposes.     

Health Risk Assessment of Heavy Metals in Urban Soil of Karachi,Pakistan

The potential health risk due to lifetime exposure to copper, lead, chromium, zinc, and iron in urban soil of Karachi, Pakistan, was evaluated. Mean concentrations of Cu, Pb, Cr, Zn, and Fe in topsoil samples were 33.3 ± 12.8, 42.1 ± 55.8, 9.6 ± 4.2, 99.5 ± 37.3, and 908.4 ± 57.8 mg kg^?1, respectively. A U.S. Environmental Protection Agency model was adopted for the carcinogenic and non-carcinogenic risk assessment from different exposure pathways. Risk assessment indicated that the overall results for the carcinogenic risk were insignificant. However, the carcinogenic risk from Pb due to oral ingestion of soil exceeded the value of 1 × 10^?6, in some areas of the city. It indicates that the exposure to Pb-contaminated soil may cause adverse health effects in humans, especially in children. The Hazard Quotient (HQ) for different metals through ingestion and dermal pathways was also found to be less than 1. The combined Hazard Index (HI) for children through different routes of exposure was 8.9 times greater than for adults. It indicates that the children are more susceptible to non-carcinogenic health effects of trace metals compared to adults. Particularly, non-carcinogenic risk of Pb to children via oral ingestion needs special attention.