Search results for: drug safety
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 5123

Search results for: drug safety

4643 Framework for Implementation of National Electrical Safety Grounding Standards for Communication Infrastructure

Authors: Atif Mahmood, Mohammad Inayatullah Khan Babar

Abstract:

Communication infrastructure has been installed, operated, and maintained all over the world according to defined electrical safety standards for separate or joint structures. These safety standards have been set for the safeguard of public, utility workers (employees and contractors), utility facilities, electrical communication equipment’s connected to the utility facilities and other facilities or premise adjacent to utility facilities. Different communication utilities in Pakistan use standards of different countries due to the absence of Common National Electrical Safety Standards of Pakistan. It is really important to devise a framework for implementation of a uniform standard for strict compliance. In this context, it is important to explore the compliance of safety standards for communication conductors and equipment for separate or joint structures for which NESC standards are taken as reference. Specific reference to grounding techniques including grounding AC/DC systems and its frames, leaving Fences, Messenger wires and special circuits used for the protection for lightning etc, ungrounded so recommendations are also given after in-depth analysis of current technical practices for the installation and maintenance of communication infrastructure.

Keywords: utility facilities, grounding electrodes, special circuits, grounding conductor

Procedia PDF Downloads 338
4642 Nurse-Reported Perceptions of Medication Safety in Private Hospitals in Gauteng Province.

Authors: Madre Paarlber, Alwiena Blignaut

Abstract:

Background: Medication administration errors remains a global patient safety problem targeted by the WHO (World Health Organization), yet research on this matter is sparce within the South African context. Objective: The aim was to explore and describe nurses’ (medication administrators) perceptions regarding medication administration safety-related culture, incidence, causes, and reporting in the Gauteng Province of South Africa, and to determine any relationships between perceived variables concerned with medication safety (safety culture, incidences, causes, reporting of incidences, and reasons for non-reporting). Method: A quantitative research design was used through which self-administered online surveys were sent to 768 nurses (medication administrators) (n=217). The response rate was 28.26%. The survey instrument was synthesised from the Agency of Healthcare Research and Quality (AHRQ) Hospital Survey on Patient Safety Culture, the Registered Nurse Forecasting (RN4CAST) survey, a survey list prepared from a systematic review aimed at generating a comprehensive list of medication administration error causes and the Medication Administration Error Reporting Survey from Wakefield. Exploratory and confirmatory factor analyses were used to determine the validity and reliability of the survey. Descriptive and inferential statistical data analysis were used to analyse quantitative data. Relationships and correlations were identified between items, subscales and biographic data by using Spearmans’ Rank correlations, T-Tests and ANOVAs (Analysis of Variance). Nurses reported on their perceptions of medication administration safety-related culture, incidence, causes, and reporting in the Gauteng Province. Results: Units’ teamwork deemed satisfactory, punitive responses to errors accentuated. “Crisis mode” working, concerns regarding mistake recording and long working hours disclosed as impacting patient safety. Overall medication safety graded mostly positively. Work overload, high patient-nurse ratios, and inadequate staffing implicated as error-inducing. Medication administration errors were reported regularly. Fear and administrative response to errors effected non-report. Non-report of errors’ reasons was affected by non-punitive safety culture. Conclusions: Medication administration safety improvement is contingent on fostering a non-punitive safety culture within units. Anonymous medication error reporting systems and auditing nurses’ workload are recommended in the quest of improved medication safety within Gauteng Province private hospitals.

Keywords: incidence, medication administration errors, medication safety, reporting, safety culture

Procedia PDF Downloads 40
4641 Regular or Irregular: An Investigation of Medicine Consumption Pattern with Poisson Mixture Model

Authors: Lichung Jen, Yi Chun Liu, Kuan-Wei Lee

Abstract:

Fruitful data has been accumulated in database nowadays and is commonly used as support for decision-making. In the healthcare industry, hospital, for instance, ordering pharmacy inventory is one of the key decision. With large drug inventory, the current cost increases and its expiration dates might lead to future issue, such as drug disposal and recycle. In contrast, underestimating demand of the pharmacy inventory, particularly standing drugs, affects the medical treatment and possibly hospital reputation. Prescription behaviour of hospital physicians is one of the critical factor influencing this decision, particularly irregular prescription behaviour. If a drug’s usage amount in the month is irregular and less than the regular usage, it may cause the trend of subsequent stockpiling. On the contrary, if a drug has been prescribed often than expected, it may result in insufficient inventory. We proposed a hierarchical Bayesian mixture model with two components to identify physicians’ regular/irregular prescription patterns with probabilities. Heterogeneity of hospital is considered in our proposed hierarchical Bayes model. The result suggested that modeling the prescription patterns of physician is beneficial for estimating the order quantity of medication and pharmacy inventory management of the hospital. Managerial implication and future research are discussed.

Keywords: hierarchical Bayesian model, poission mixture model, medicines prescription behavior, irregular behavior

Procedia PDF Downloads 119
4640 Efficacy and Safety of Sublingual Sufentanil for the Management of Acute Pain

Authors: Neil Singla, Derek Muse, Karen DiDonato, Pamela Palmer

Abstract:

Introduction: Pain is the most common reason people visit emergency rooms. Studies indicate however, that Emergency Department (ED) physicians often do not provide adequate analgesia to their patients as a result of gender and age bias, opiophobia and insufficient knowledge of and formal training in acute pain management. Novel classes of analgesics have recently been introduced, but many patients suffer from acute pain in settings where the availability of intravenous (IV) access may be limited, so there remains a clinical need for rapid-acting, potent analgesics that do not require an invasive route of delivery. A sublingual sufentanil tablet (SST), dispensed using a single-dose applicator, is in development for treatment of moderate-to-severe acute pain in a medically-supervised setting. Objective: The primary objective of this study was to demonstrate the repeat-dose efficacy, safety and tolerability of sufentanil 20 mcg and 30 mcg sublingual tablets compared to placebo for the management of acute pain as determined by the time-weighted sum of pain intensity differences (SPID) to baseline over the 12-hour study period (SPID12). Key secondary efficacy variables included SPID over the first hour (SPID1), Total pain relief over the 12-hour study period (TOTPAR12), time to perceived pain relief (PR) and time to meaningful PR. Safety variables consisted of adverse events (AE), vital signs, oxygen saturation and early termination. Methods: In this Phase 2, double-blind, dose-finding study, an equal number of male and female patients were randomly assigned in a 2:2:1 ratio to SST 20 mcg, SS 30 mcg or placebo, respectively, following bunionectomy. Study drug was dosed as needed, but not more frequently than hourly. Rescue medication was available as needed. The primary endpoint was the Summed Pain Intensity Difference to baseline over 12h (SPIDI2). Safety was assessed by continuous oxygen saturation monitoring and adverse event reporting. Results: 101 patients (51 Male/50 Female) were randomized, 100 received study treatment (intent-to-treat [ITT] population), and 91 completed the study. Reasons for early discontinuation were lack of efficacy (6), adverse events (2) and drug-dosing error (1). Mean age was 42.5 years. For the ITT population, SST 30 mcg was superior to placebo (p=0.003) for the SPID12. SPID12 scores in the active groups were superior for both male (ANOVA overall p-value =0.038) and female (ANOVA overall p-value=0.005) patients. Statistically significant differences in favour of sublingual sufentanil were also observed between the SST 30mcg and placebo group for SPID1(p<0.001), TOTPAR12(p=0.002), time to perceived PR (p=0.023) and time to meaningful PR (p=0.010). Nausea, vomiting and somnolence were more frequent in the sufentanil groups but there were no significant differences between treatment arms for the proportion of patients who prematurely terminated due to AE or inadequate analgesia. Conclusions: Sufentanil tablets dispensed sublingually using a single-dose applicator is in development for treatment of patients with moderate-to-severe acute pain in a medically-supervised setting where immediate IV access is limited. When administered sublingually, sufentanil’s pharmacokinetic profile and non-invasive delivery makes it a useful alternative to IM or IV dosing.

Keywords: acute pain, pain management, sublingual, sufentanil

Procedia PDF Downloads 348
4639 Enhanced Kinetic Solubility Profile of Epiisopiloturine Solid Solution in Hipromellose Phthalate

Authors: Amanda C. Q. M. Vieira, Cybelly M. Melo, Camila B. M. Figueirêdo, Giovanna C. R. M. Schver, Salvana P. M. Costa, Magaly A. M. de Lyra, Ping I. Lee, José L. Soares-Sobrinho, Pedro J. Rolim-Neto, Mônica F. R. Soares

Abstract:

Epiisopiloturine (EPI) is a drug candidate that is extracted from Pilocarpus microphyllus and isolated from the waste of Pilocarpine. EPI has demonstrated promising schistosomicidal, leishmanicide, anti-inflammatory and antinociceptive activities, according to in vitro studies that have been carried out since 2009. However, this molecule shows poor aqueous solubility, which represents a problem for the release of the drug candidate and its absorption by the organism. The purpose of the present study is to investigate the extent of enhancement of kinetic solubility of a solid solution (SS) of EPI in hipromellose phthalate HP-55 (HPMCP), an enteric polymer carrier. SS was obtained by the solvent evaporation methodology, using acetone/methanol (60:40) as solvent system. Both EPI and polymer (drug loading 10%) were dissolved in this solvent until a clear solution was obtained, and then dried in oven at 60ºC during 12 hours, followed by drying in a vacuum oven for 4 h. The results show a considerable modification in the crystalline structure of the drug candidate. For instance, X-ray diffraction (XRD) shows a crystalline behavior for the EPI, which becomes amorphous for the SS. Polarized light microscopy, a more sensitive technique than XRD, also shows completely absence of crystals in SS sample. Differential Scanning Calorimetric (DSC) curves show no signal of EPI melting point in SS curve, indicating, once more, no presence of crystal in this system. Interaction between the drug candidate and the polymer were found in Infrared microscopy, which shows a carbonyl 43.3 cm-1 band shift, indicating a moderate-strong interaction between them, probably one of the reasons to the SS formation. Under sink conditions (pH 6.8), EPI SS had its dissolution performance increased in 2.8 times when compared with the isolated drug candidate. EPI SS sample provided a release of more than 95% of the drug candidate in 15 min, whereas only 45% of EPI (alone) could be dissolved in 15 min and 70% in 90 min. Thus, HPMCP demonstrates to have a good potential to enhance the kinetic solubility profile of EPI. Future studies to evaluate the stability of SS are required to conclude the benefits of this system.

Keywords: epiisopiloturine, hipromellose phthalate HP-55, pharmaceuticaltechnology, solubility

Procedia PDF Downloads 602
4638 Structural Safety of Biocomposites under Cracking: A Fracture Analytical Approach using the Gғ-Concept

Authors: Brandtner-Hafner Martin

Abstract:

Biocomposites have established themselves as a sustainable material class in the industry. Their advantages include lower density, lower price, and easier recycling compared to conventional materials. Now there are a variety of ways to measure their technical performance. One possibility is mechanical tests, which are widely used and standardized. However, these provide only very limited insights into damage capacity, which is particularly problematic under cracking conditions. To overcome such shortcomings, experimental tests were performed applying the fracture energetically GF-concept to study the structural safety of the interface under crack opening (mode-I loading). Two different types of biocomposites based on extruded henequen-fibers (NFRP) and wood-particles (WPC) in an HDPE matrix were evaluated. The results show that the fracture energy values obtained are higher than those given in the literature. This suggests that alternatives to previous linear elastic testing methods are needed to perform authentic safety evaluations of green plastics.

Keywords: biocomposites, structural safety, Gғ-concept, fracture analysis

Procedia PDF Downloads 148
4637 Patient-Reported Adverse Drug Reactions, Medication Adherence and Clinical Outcomes among major depression disorder Patients in Ethiopia: A Prospective Hospital Based Study.

Authors: Tadesse Melaku Abegaz

Abstract:

Background: there was paucity of data on the self-reported adverse drug reactions (ADRs), level of adherence and clinical outcomes with antidepressants among major depressive disorder (MDD) patients in Ethiopia. Hence, the present study sought to determine the level of adherence for and clinical outcome with antidepressants and the magnitude of ADRs. Methods: A prospective cross-sectional study was employed on MDD patients from September 2016 to January 2017 at Gondar university hospital psychiatry clinic. All patients who were available during the study period were included under the study population. The Naranjo adverse drug reaction probability scale was employed to assess the adverse drug reaction. The rate of medication adherence was determined using morisky medication adherence measurement scale eight. Clinical Outcome of patients was measured by using patient health questionnaire. Multivariable logistic carried out to determine factors for adherence and patient outcome. Results: two hundred seventy patients were participated in the study. More than half of the respondents were males 122(56.2%). The mean age of the participants was 30.94 ± 8.853. More than one-half of the subjects had low adherence to their medications 124(57.1%). About 186(85.7%) of patients encountered ADR. The most common ADR was weight gain 29(13.2). Around 198(92.2%) ADRs were probable and 19(8.8%) were possible. Patients with long standing MDD had high risk of non-adherence COR: 2.458[4.413-4.227], AOR: 2.424[1.185-4.961]. More than one-half 125(57.6) of respondents showed improved outcome. Optimal level of medication adherence was found to be associated with reduced risk of progression of the diseases COR: 0.37[0.110-5.379] and AOR: 0.432[0.201-0.909]. Conclusion: Patient reported adverse drug reactions were more prevalent in major depressive disorder patients. Adherence to medications was very poor in the setup. However, the clinical outcome was relatively higher. Long standing depression was associated with non-adherence. In addition, clinical outcome of patients were affected by non-adherence. Therefore, adherence enhancing interventions should be provided to improve medication adherence and patient outcome.

Keywords: adverse drug reactions, clinical outcomes, Ethiopia, prospective study, medication adherence

Procedia PDF Downloads 237
4636 Preparation and Size Control of Sub-100 Nm Pure Nanodrugs

Authors: Jinfeng Zhang, Chun-Sing Lee

Abstract:

Pure nanodrugs (PNDs) – nanoparticles consisting entirely of drug molecules, have been considered as promising candidates for the next-generation nanodrugs. However, the traditional preparation method via reprecipitation faces critical challenges including low production rates, relatively large particle sizes and batch-to-batch variations. Here, for the first time, we successfully developed a novel, versatile and controllable strategy for preparing PNDs via an anodized aluminium oxide (AAO) template-assisted method. With this approach, we prepared PNDs of an anti-cancer drug (VM-26) with precisely controlled sizes reaching the sub-20 nm range. This template-assisted approach has much higher feasibility for mass production comparing to the conventional reprecipitation method and is beneficial for future clinical translation. The present method is further demonstrated to be easily applicable for a wide range of hydrophobic biomolecules without the need of custom molecular modifications and can be extended for preparing all-in-one nanostructures with different functional agents.

Keywords: drug delivery, pure nanodrugs, size control, template

Procedia PDF Downloads 301
4635 Simultaneous Determination of Proposed Anti-HIV Combination Comprising of Elvitegravir and Quercetin in Rat Plasma Using the HPLC–ESI-MS/MS Method: Drug Interaction Study

Authors: Lubna Azmi, Ila Shukla, Shyam Sundar Gupta, Padam Kant, C. V. Rao

Abstract:

Elvitegravir is the mainstay of anti-HIV combination therapy in most endemic countries presently. However, it cannot be used alone owing to its long onset time of action. 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one (Quercetin: QU) is a polyphenolic compound obtained from Argeria speciosa Linn (Family: Convolvulaceae), an anti-HIV candidate. In the present study, a sensitive, simple and rapid high-performance liquid chromatography coupled with positive ion electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method was developed for the simultaneous determination elvitegravir and Quercetin, in rat plasma. The method was linear over a range of 0.2–500 ng/ml. All validation parameters met the acceptance criteria according to regulatory guidelines. LC–MS/MS method for determination of Elvitegravir and Quercetin was developed and validated. Results show the potential of drug–drug interaction upon co-administration this marketed drugs and plant derived secondary metabolite.

Keywords: anti-HIV resistance, extraction, HPLC-ESI-MS-MS, validation

Procedia PDF Downloads 332
4634 Diversity for Safety and Security of Autonomous Vehicles against Accidental and Deliberate Faults

Authors: Anil Ranjitbhai Patel, Clement John Shaji, Peter Liggesmeyer

Abstract:

Safety and security of autonomous vehicles (AVs) is a growing concern, first, due to the increased number of safety-critical functions taken over by automotive embedded systems; second, due to the increased exposure of the software-intensive systems to potential attackers; third, due to dynamic interaction in an uncertain and unknown environment at runtime which results in changed functional and non-functional properties of the system. Frequently occurring environmental uncertainties, random component failures, and compromise security of the AVs might result in hazardous events, sometimes even in an accident, if left undetected. Beyond these technical issues, we argue that the safety and security of AVs against accidental and deliberate faults are poorly understood and rarely implemented. One possible way to overcome this is through a well-known diversity approach. As an effective approach to increase safety and security, diversity has been widely used in the aviation, railway, and aerospace industries. Thus, the paper proposes fault-tolerance by diversity model takes into consideration the mitigation of accidental and deliberate faults by application of structure and variant redundancy. The model can be used to design the AVs with various types of diversity in hardware and software-based multi-version system. The paper evaluates the presented approach by employing an example from adaptive cruise control, followed by discussing the case study with initial findings.

Keywords: autonomous vehicles, diversity, fault-tolerance, adaptive cruise control, safety, security

Procedia PDF Downloads 118
4633 Apollo Quality Program: The Essential Framework for Implementing Patient Safety

Authors: Anupam Sibal

Abstract:

Apollo Quality Program(AQP) was launched across the Apollo Group of Hospitals to address the four patient safety areas; Safety during Clinical Handovers, Medication Safety, Surgical Safety and the six International Patient Safety Goals(IPSGs) of JCI. A measurable, online, quality dashboard covering 20 process and outcome parameters was devised for monthly monitoring. The expected outcomes were also defined and categorized into green, yellow and red ranges. An audit methodology was also devised to check the processes for the measurable dashboard. Documented clinical handovers were introduced for the first time at many locations for in-house patient transfer, nursing-handover, and physician-handover. Prototype forms using the SBAR format were made. Patient-identifiers, read-back for verbal orders, safety of high-alert medications, site marking and time-outs and falls risk-assessment were introduced for all hospitals irrespective of accreditation status. Measurement of Surgical-Site-Infection (SSI) for 30 days postoperatively, was done. All hospitals now tracked the time of administration of antimicrobial prophylaxis before surgery. Situations with high risk of retention of foreign body were delineated and precautionary measures instituted. Audit of medications prescribed in the discharge summaries was made uniform. Formularies, prescription-audits and other means for reduction of medication errors were implemented. There is a marked increase in the compliance to processes and patient safety outcomes. Compliance to read-back for verbal orders rose from 86.83% in April’11 to 96.95% in June’15, to policy for high alert medications from 87.83% to 98.82%, to use of measures to prevent wrong-site, wrong-patient, wrong procedure surgery from 85.75% to 97.66%, to hand-washing from 69.18% to 92.54%, to antimicrobial prophylaxis within one hour before incision from 79.43% to 93.46%. Percentage of patients excluded from SSI calculation due to lack of follow-up for the requisite time frame decreased from 21.25% to 10.25%. The average AQP scores for all Apollo Hospitals improved from 62 in April’11 to 87.7 in Jun’15.

Keywords: clinical handovers, international patient safety goals, medication safety, surgical safety

Procedia PDF Downloads 250
4632 Evaluation of the Cytotoxicity and Cellular Uptake of a Cyclodextrin-Based Drug Delivery System for Cancer Therapy

Authors: Caroline Mendes, Mary McNamara, Orla Howe

Abstract:

Drug delivery systems are proposed for use in cancer treatment to specifically target cancer cells and deliver a therapeutic dose without affecting normal cells. For that purpose, the use of folate receptors (FR) can be considered a key strategy, since they are commonly over-expressed in cancer cells. In this study, cyclodextrins (CD) have being used as vehicles to target FR and deliver the chemotherapeutic drug, methotrexate (MTX). CDs have the ability to form inclusion complexes, in which molecules of suitable dimensions are included within their cavities. Here, β-CD has been modified using folic acid so as to specifically target the FR. Thus, this drug delivery system consists of β-CD, folic acid and MTX (CDEnFA:MTX). Cellular uptake of folic acid is mediated with high affinity by folate receptors while the cellular uptake of antifolates, such as MTX, is mediated with high affinity by the reduced folate carriers (RFCs). This study addresses the gene (mRNA) and protein expression levels of FRs and RFCs in the cancer cell lines CaCo-2, SKOV-3, HeLa, MCF-7, A549 and the normal cell line BEAS-2B, quantified by real-time polymerase chain reaction (real-time PCR) and flow cytometry, respectively. From that, four cell lines with different levels of FRs, were chosen for cytotoxicity assays of MTX and CDEnFA:MTX using the MTT assay. Real-time PCR and flow cytometry data demonstrated that all cell lines ubiquitously express moderate levels of RFC. These experiments have also shown that levels of FR protein in CaCo-2 cells are high, while levels in SKOV-3, HeLa and MCF-7 cells are moderate. A549 and BEAS-2B cells express low levels of FR protein. FRs are highly expressed in all the cancer cell lines analysed when compared to the normal cell line BEAS-2B. The cell lines CaCo-2, MCF-7, A549 and BEAS-2B were used in the cell viability assays. 48 hours treatment with the free drug and the complex resulted in IC50 values of 93.9 µM ± 15.2 and 56.0 µM ± 4.0 for CaCo-2 for free MTX and CDEnFA:MTX respectively, 118.2 µM ± 16.8 and 97.8 µM ± 12.3 for MCF-7, 36.4 µM ± 6.9 and 75.0 µM ± 10.5 for A549 and 132.6 µM ± 16.1 and 288.1 µM ± 26.3 for BEAS-2B. These results demonstrate that free MTX is more toxic towards cell lines expressing low levels of FR, such as the BEAS-2B. More importantly, these results demonstrate that the inclusion complex CDEnFA:MTX showed greater cytotoxicity than the free drug towards the high FR expressing CaCo-2 cells, indicating that it has potential to target this receptor, enhancing the specificity and the efficiency of the drug. The use of cell imaging by confocal microscopy has allowed visualisation of FR targeting in cancer cells, as well as the identification of the interlisation pathway of the drug. Hence, the cellular uptake and internalisation process of this drug delivery system is being addressed.

Keywords: cancer treatment, cyclodextrins, drug delivery, folate receptors, reduced folate carriers

Procedia PDF Downloads 304
4631 Online Public Transport Safety Awareness System

Authors: Danny Mwangi, Collins Oduor Ondiek

Abstract:

Mass mobility is one of the most important characteristics of every industrialized civilization. Man must travel about in order to fulfill his commitment to putting food on his table. As a result, movement is an important part of human life. Man must travel from one place to another. This is a natural trait of humans, according to elementary science. Variables in human mobility have arisen as a result of technological advancements over time. Public transit is one of these modes of transportation. When it comes to reducing safety-related risks in the public transport system, awareness is crucial. So much so even when it comes to public transportation in Kenya. Having a system that can be able to keep users updated with real-time traffic updates on the route, they are on and also have the ability to rate drivers after a trip could go a long way in improving safety on Kenyan roads. What this proposed system is intended to accomplish is to reduce occurrences of reckless driving and give matatu drivers the feeling that they are accountable to someone and more so have the incentive to be better drivers who are motivated to follow the law and have passenger safety as a priority. The research was conducted, and the findings show that 95.2% of respondents were not satisfied with the current safety measures in the Kenyan public transport sector. This means that the chances for this system to be accepted in the market are high because it addresses a key issue. 98.8% of the respondents were of the opinion that the implementation of the proposed system would significantly increase safety measures in the public transport sector. During the research, it was clear that the main challenge 77.1% of the respondents face when using public transport is that there is no way to monitor driver safety performance, and 68.7% of the respondent believed the widespread use of unroadworthy public transit vehicles contributed to the lack of safety when using public transport. However, 77.1% of the respondents expect the benefit of creating a sense of accountability for the drivers, and 74.7% of the respondents expect the benefit of increased passenger safety. 63.9% believe that with the implementation of the system, there will be the benefit of monitoring driver performance. This shows that with the implementation of the proposed system, it will be possible to make a lot of progress in terms of making Kenyan roads safer when using public transit. According to the findings, it is recommended that this proposed public transportation safety awareness system be implemented as it will be able to address matatu passengers' safety concerns while also encouraging matatu drivers to drive more carefully. As a result, it's a project with a chance of becoming viable, marketable, and feasible.

Keywords: public safety, public transportation, accountable driving, safe transportation

Procedia PDF Downloads 87
4630 Muscle Relaxant Dantrolene Repurposed to Treat Alzheimer's Disease

Authors: Huafeng Wei

Abstract:

Failures of developing new drugs primarily based on the amyloid pathology hypothesis after decades of efforts internationally lead to changes of focus targeting alternative pathways of pathology in Alzheimer’s disease (AD). Disruption of intracellular Ca2+ homeostasis, especially the pathological and excessive Ca2+ release from the endoplasmic reticulum (ER) via ryanodine receptor (RyRs) Ca2+ channels, has been considered an upstream pathology resulting in major AD pathologies, such as amyloid and Tau pathology, mitochondria damage and inflammation, etc. Therefore, dantrolene, an inhibitor of RyRs that reduces the pathological Ca2+ release from ER and a clinically available drug for the treatment of malignant hyperthermia and muscle spasm, is expected to ameliorate AD multiple pathologies synapse and cognitive dysfunction. Our own studies indicated that dantrolene ameliorated impairment of neurogenesis and synaptogenesis in neurons developed from induced pluripotent stem cells (iPSCs) originated from skin fibroblasts of either familiar (FAD) or sporadic (SAD) AD by restoring intracellular Ca2+ homeostasis. Intranasal administration of dantrolene significantly increased its passage across the blood-brain barrier (BBB) and, therefore its brain concentrations and durations. This can render dantrolene a more effective therapeutic drug with fewer side effects for chronic AD treatment. This review summarizes the potential therapeutic and side effects of dantrolene and repurposes intranasal dantrolene as a disease-modifying drug for future AD treatment.

Keywords: Alzheimer's disease, calcium, drug development, dementia, neurodegeneration, neurogenesis

Procedia PDF Downloads 200
4629 Extending the AOP Joinpoint Model for Memory and Type Safety

Authors: Amjad Nusayr

Abstract:

Software security is a general term used to any type of software architecture or model in which security aspects are incorporated in this architecture. These aspects are not part of the main logic of the underlying program. Software security can be achieved using a combination of approaches, including but not limited to secure software designs, third part component validation, and secure coding practices. Memory safety is one feature in software security where we ensure that any object in memory has a valid pointer or a reference with a valid type. Aspect-Oriented Programming (AOP) is a paradigm that is concerned with capturing the cross-cutting concerns in code development. AOP is generally used for common cross-cutting concerns like logging and DB transaction managing. In this paper, we introduce the concepts that enable AOP to be used for the purpose of memory and type safety. We also present ideas for extending AOP in software security practices.

Keywords: aspect oriented programming, programming languages, software security, memory and type safety

Procedia PDF Downloads 118
4628 Design Optimization of the Primary Containment Building of a Pressurized Water Reactor

Authors: M. Hossain, A. H. Khan, M. A. R. Sarkar

Abstract:

Primary containment structure is one of the five safety layers of a nuclear facility which is needed to be designed in such a manner that it can withstand the pressure and excessive radioactivity during accidental situations. It is also necessary to ensure minimization of cost with maximum possible safety in order to make the design economically feasible and attractive. This paper attempts to identify the optimum design conditions for primary containment structure considering both mechanical and radiation safety keeping the economic aspects in mind. This work takes advantage of commercial simulation software to identify the suitable conditions without the requirement of costly experiments. Generated data may be helpful for further studies.

Keywords: PWR, concrete containment, finite element approach, neutron attenuation, Von Mises stress

Procedia PDF Downloads 173
4627 Microscopic Simulation of Toll Plaza Safety and Operations

Authors: Bekir O. Bartin, Kaan Ozbay, Sandeep Mudigonda, Hong Yang

Abstract:

The use of microscopic traffic simulation in evaluating the operational and safety conditions at toll plazas is demonstrated. Two toll plazas in New Jersey are selected as case studies and were developed and validated in Paramics traffic simulation software. In order to simulate drivers’ lane selection behavior in Paramics, a utility-based lane selection approach is implemented in Paramics Application Programming Interface (API). For each vehicle approaching the toll plaza, a utility value is assigned to each toll lane by taking into account the factors that are likely to impact drivers’ lane selection behavior, such as approach lane, exit lane and queue lengths. The results demonstrate that similar operational conditions, such as lane-by-lane toll plaza traffic volume can be attained using this approach. In addition, assessment of safety at toll plazas is conducted via a surrogate safety measure. In particular, the crash index (CI), an improved surrogate measure of time-to-collision (TTC), which reflects the severity of a crash is used in the simulation analyses. The results indicate that the spatial and temporal frequency of observed crashes can be simulated using the proposed methodology. Further analyses can be conducted to evaluate and compare various different operational decisions and safety measures using microscopic simulation models.

Keywords: microscopic simulation, toll plaza, surrogate safety, application programming interface

Procedia PDF Downloads 172
4626 A Study for the Effect of Fire Initiated Location on Evacuation Success Rate

Authors: Jin A Ryu, Hee Sun Kim

Abstract:

As the number of fire accidents is gradually raising, many studies have been reported on evacuation. Previous studies have mostly focused on evaluating the safety of evacuation and the risk of fire in particular buildings. However, studies on effects of various parameters on evacuation have not been nearly done. Therefore, this paper aims at observing evacuation time under the effect of fire initiated location. In this study, evacuation simulations are performed on a 5-floor building located in Seoul, South Korea using the commercial program, Fire Dynamics Simulator with Evacuation (FDS+EVAC). Only the fourth and fifth floors are modeled with an assumption that fire starts in a room located on the fourth floor. The parameter for evacuation simulations is location of fire initiation to observe the evacuation time and safety. Results show that the location of fire initiation is closer to exit, the more time is taken to evacuate. The case having the nearest location of fire initiation to exit has the lowest ratio of successful occupants to the total occupants. In addition, for safety evaluation, the evacuation time calculated from computer simulation model is compared with the tolerable evacuation time according to code in Japan. As a result, all cases are completed within the tolerable evacuation time. This study allows predicting evacuation time under various conditions of fire and can be used to evaluate evacuation appropriateness and fire safety of building.

Keywords: fire simulation, evacuation simulation, temperature, evacuation safety

Procedia PDF Downloads 340
4625 Investigation of Slope Stability in Gravel Soils in Unsaturated State

Authors: Seyyed Abolhasan Naeini, Ehsan Azini

Abstract:

In this paper, we consider the stability of a slope of 10 meters in silty gravel soils with modeling in the Geostudio Software.  we intend to use the parameters of the volumetric water content and suction dependent permeability and provides relationships and graphs using the parameters obtained from gradation tests and Atterberg’s limits. Also, different conditions of the soil will be investigated, including: checking the factor of safety and deformation rates and pore water pressure in drained, non-drained and unsaturated conditions, as well as the effect of reducing the water level on other parameters. For this purpose, it is assumed that the groundwater level is at a depth of 2 meters from the ground.  Then, with decreasing water level, the safety factor of slope stability was investigated and it was observed that with decreasing water level, the safety factor increased.

Keywords: slope stability analysis, factor of safety, matric suction, unsaturated silty gravel soil

Procedia PDF Downloads 162
4624 Detection of Safety Goggles on Humans in Industrial Environment Using Faster-Region Based on Convolutional Neural Network with Rotated Bounding Box

Authors: Ankit Kamboj, Shikha Talwar, Nilesh Powar

Abstract:

To successfully deliver our products in the market, the employees need to be in a safe environment, especially in an industrial and manufacturing environment. The consequences of delinquency in wearing safety glasses while working in industrial plants could be high risk to employees, hence the need to develop a real-time automatic detection system which detects the persons (violators) not wearing safety glasses. In this study a convolutional neural network (CNN) algorithm called faster region based CNN (Faster RCNN) with rotated bounding box has been used for detecting safety glasses on persons; the algorithm has an advantage of detecting safety glasses with different orientation angles on the persons. The proposed method of rotational bounding boxes with a convolutional neural network first detects a person from the images, and then the method detects whether the person is wearing safety glasses or not. The video data is captured at the entrance of restricted zones of the industrial environment (manufacturing plant), which is further converted into images at 2 frames per second. In the first step, the CNN with pre-trained weights on COCO dataset is used for person detection where the detections are cropped as images. Then the safety goggles are labelled on the cropped images using the image labelling tool called roLabelImg, which is used to annotate the ground truth values of rotated objects more accurately, and the annotations obtained are further modified to depict four coordinates of the rectangular bounding box. Next, the faster RCNN with rotated bounding box is used to detect safety goggles, which is then compared with traditional bounding box faster RCNN in terms of detection accuracy (average precision), which shows the effectiveness of the proposed method for detection of rotatory objects. The deep learning benchmarking is done on a Dell workstation with a 16GB Nvidia GPU.

Keywords: CNN, deep learning, faster RCNN, roLabelImg rotated bounding box, safety goggle detection

Procedia PDF Downloads 121
4623 Predicting Success and Failure in Drug Development Using Text Analysis

Authors: Zhi Hao Chow, Cian Mulligan, Jack Walsh, Antonio Garzon Vico, Dimitar Krastev

Abstract:

Drug development is resource-intensive, time-consuming, and increasingly expensive with each developmental stage. The success rates of drug development are also relatively low, and the resources committed are wasted with each failed candidate. As such, a reliable method of predicting the success of drug development is in demand. The hypothesis was that some examples of failed drug candidates are pushed through developmental pipelines based on false confidence and may possess common linguistic features identifiable through sentiment analysis. Here, the concept of using text analysis to discover such features in research publications and investor reports as predictors of success was explored. R studios were used to perform text mining and lexicon-based sentiment analysis to identify affective phrases and determine their frequency in each document, then using SPSS to determine the relationship between our defined variables and the accuracy of predicting outcomes. A total of 161 publications were collected and categorised into 4 groups: (i) Cancer treatment, (ii) Neurodegenerative disease treatment, (iii) Vaccines, and (iv) Others (containing all other drugs that do not fit into the 3 categories). Text analysis was then performed on each document using 2 separate datasets (BING and AFINN) in R within the category of drugs to determine the frequency of positive or negative phrases in each document. A relative positivity and negativity value were then calculated by dividing the frequency of phrases with the word count of each document. Regression analysis was then performed with SPSS statistical software on each dataset (values from using BING or AFINN dataset during text analysis) using a random selection of 61 documents to construct a model. The remaining documents were then used to determine the predictive power of the models. Model constructed from BING predicts the outcome of drug performance in clinical trials with an overall percentage of 65.3%. AFINN model had a lower accuracy at predicting outcomes compared to the BING model at 62.5% but was not effective at predicting the failure of drugs in clinical trials. Overall, the study did not show significant efficacy of the model at predicting outcomes of drugs in development. Many improvements may need to be made to later iterations of the model to sufficiently increase the accuracy.

Keywords: data analysis, drug development, sentiment analysis, text-mining

Procedia PDF Downloads 141
4622 Surface Acoustic Waves Nebulisation of Liposomes Manufactured in situ for Pulmonary Drug Delivery

Authors: X. King, E. Nazarzadeh, J. Reboud, J. Cooper

Abstract:

Pulmonary diseases, such as asthma, are generally treated by the inhalation of aerosols that has the advantage of reducing the off-target (e.g., toxicity) effects associated with systemic delivery in blood. Effective respiratory drug delivery requires a droplet size distribution between 1 and 5 µm. Inhalation of aerosols with wide droplet size distribution, out of this range, results in deposition of drug in not-targeted area of the respiratory tract, introducing undesired side effects on the patient. In order to solely deliver the drug in the lower branches of the lungs and release it in a targeted manner, a control mechanism to produce the aerosolized droplets is required. To regulate the drug release and to facilitate the uptake from cells, drugs are often encapsulated into protective liposomes. However, a multistep process is required for their formation, often performed at the formulation step, therefore limiting the range of available drugs or their shelf life. Using surface acoustic waves (SAWs), a pulmonary drug delivery platform was produced, which enabled the formation of defined size aerosols and the formation of liposomes in situ. SAWs are mechanical waves, propagating along the surface of a piezoelectric substrate. They were generated using an interdigital transducer on lithium niobate with an excitation frequency of 9.6 MHz at a power of 1W. Disposable silicon superstrates were etched using photolithography and dry etch processes to create an array of cylindrical through-holes with different diameters and pitches. Superstrates were coupled with the SAW substrate through water-based gel. As the SAW propagates on the superstrate, it enables nebulisation of a lipid solution deposited onto it. The cylindrical cavities restricted the formation of large drops in the aerosol, while at the same time unilamellar liposomes were created. SAW formed liposomes showed a higher monodispersity compared to the control sample, as well as displayed, a faster production rate. To test the aerosol’s size, dynamic light scattering and laser diffraction methods were used, both showing the size control of the aerosolised particles. The use of silicon superstate with cavity size of 100-200 µm, produced an aerosol with a mean droplet size within the optimum range for pulmonary drug delivery, containing the liposomes in which the medicine could be loaded. Additionally, analysis of liposomes with Cryo-TEM showed formation of vesicles with narrow size distribution between 80-100 nm and optimal morphology in order to be used for drug delivery. Encapsulation of nucleic acids in liposomes through the developed SAW platform was also investigated. In vitro delivery of siRNA and DNA Luciferase were achieved using A549 cell line, lung carcinoma from human. In conclusion, SAW pulmonary drug delivery platform was engineered, in order to combine multiple time consuming steps (formation of liposomes, drug loading, nebulisation) into a unique platform with the aim of specifically delivering the medicament in a targeted area, reducing the drug’s side effects.

Keywords: acoustics, drug delivery, liposomes, surface acoustic waves

Procedia PDF Downloads 116
4621 Nutrition and Food Safety as Strategic Assets

Authors: Daniel C. S. Lim, W. Y. Tan

Abstract:

The world is facing a growing food crisis. The concerns of food nutritional value, food safety and food security are becoming increasingly real. There is also a direct relationship to the risk of diseases, particularly chronic diseases, to the food we consume. So, there are increasing concerns about the modern day food ecosystem creating foods that can provide the nutritional components for organ function sustenance, as well as, taking a serious view on diet-related diseases. This paper addresses some of the above concerns and gives an overview of the current global situation relating to food nutrition and safety. The paper reviews nutritional aspects of food today compared to those of the last century, compares whole foods found in supermarkets versus those organically grown, as well as population behaviour towards food choices. It provides scientific insights into the effects of some of the global trends such as climate change and other changes environmental changes, and presents what individuals and corporations are doing to use the latest nutritional technologies as strategic assets. Finally, it briefly highlights some of the innovative solutions that are being applied to address several of the above concerns.

Keywords: food crisis, food safety, global trends, nutritional aspects

Procedia PDF Downloads 374
4620 Assessment of Implementation of the Health and Safety Contents of the Nigerian Factories Act by Small and Medium Scale Industries in Anambra State, Nigeria

Authors: Vivian Uchechi Okpala

Abstract:

Background: Millions of workers die every year as a result of occupational hazards, accidents and injuries, which are as a result of non- compliance to the laws or legislations guiding the health, safety and welfare of workers in the industries. This and many more lead to the assessment of implementation of the health and safety contents of the Nigerian Factories Act (NFA) by small and medium scale industries in Anambra State. Objectives: The study is aimed at achieving the following specific objectives; to assess the extent of implementation of Part-II Health and Part -III Safety (General Provisions), implementation of Part II Health and Part -III Safety (General Provisions Nigerian Factories Acts based on the age of the industries, locations of the industries and level of education of the workers of the small and medium scale industries Methods: the research design that was used for this study was descriptive survey research design, Area of this study was Anambra state, The population for this study comprised 180 chairmen/presidents of union workers of manufacturing industries in Anambra State, The instrument used for this study was structured questionnaire titled ‘assessment of implementation of NFA health and safety contents by small and medium scale industries, results: From the analysis, the following findings were made: Results: The medium scale industries implemented the Part-II Health and Part III Safety (General provisions) better than the small scale industries in Anambra state, the age of the industries, location of the industries and the level of education of the workers in the industries significantly influenced the implementation of the Part III Safety (General Provisions) of NFA, the location of the industries significantly influenced the implementation of the Part II-Health (General Provisions) of NFA. Conclusion: there was generally a certain level of implementation of the factories Act, there is need for more improvement, strict inspection by the regulatory agencies. Implications of the study were highlighted and several suggestions for further studies were made. Based on the findings, several recommendations were made including that the Ministry of Labour and Productivity and the Ministry of Health should strengthen planned information, strict policies to sanction the offenders. Keywords: Occupational Health and Safety, Nigerian Factories Act

Keywords: occupational health and safety, Nigerian factories act, workers, welfare

Procedia PDF Downloads 131
4619 Exploring the Relationship Between Life Experiences and Early Relapse Among Imprisoned Users of Illegal Drugs in Oman: A Focused Ethnography

Authors: Hamida Hamed Said Al Harthi

Abstract:

Background: Illegal drug use is a rising problem that affects Omani youth. This research aimed to study a group of young Omani men who were imprisoned more than once for illegal drug use, focusing on exploring their lifestyle experiences inside and outside the prison and whether these contributed to their early relapse and re-imprisonment. This is the first study of its kind from Oman conducted in a prison setting. Methods: 19 Omani males aged 18–35 years imprisoned in Oman Central Prison were recruited using purposive sampling. Focused ethnography was conducted over 8 months to explore the drug-related experiences outside the prison and during imprisonment. Face-to-face semi-structured interviews with the participants yielded detailed transcripts and field notes. These were thematically analyzed, and the results were compared with the existing literature. Results: The participants’ voices yielded new insights into the lives of young Omani men imprisoned for illegal drug use, including their sufferings and challenges in prison. These included: entry shock, timing and boredom, drug trafficking in prison, as well as physical and psychological health issues. Overall, imprisonment was reported to have negatively impacted the participants’ health, personality, self-concept, emotions, attitudes, behavior and life expectations. The participants reported how their efforts to reintegrate into the Omani community after release from prison were rebuffed due to stigmatization and rejection from society and family. They also experienced frequent unemployment, police surveillance, accommodation problems and a lack of rehabilitation facilities. The immensity of the accumulated psychophysiological trauma contributed to their early relapse and re-imprisonment. Conclusion: This thesis concludes that imprisonment is largely ineffective in controlling drug use in Oman. Urgent action is required across multiple sectors to improve the lives and prospects of users of illegal drugs within and outside the prison to minimize factors contributing to early relapse. Key Words: illegal drugs, drug users, Oman, addiction, Omani culture, prisoners, relapse, re-imprisonment, qualitative research, ethnography.

Keywords: illigal drugs, Prison, Omani culture lifestyle, post prison life

Procedia PDF Downloads 68
4618 An Assessment of Housing Affordability and Safety Measures in the Varied Residential Area of Lagos, A Case Study of the Amuwo-Odofin Local Government Area in Lagos State

Authors: Jubril Olatunbosun Akinde

Abstract:

Unplanned population growth are mostly attributed to a lack of infrastructural facilities and poor economic condition in the rural dwellings and the incidence of rural-urban migration, which has resulted in severe housing deficiency in the urban centre, with a resultant pressure on housing delivery in the cities. Affordable housing does not only encompass environmental factors that make living acceptable and comfortable, which include good access routes, ventilation, sanitation and access to other basic human needs, which include water and safety. The research assessed the housing affordability and safety measures in the varied residential area of lagos by examining the demographic and socioeconomic attributes of residents; examining the existing residential safety measures; by examining the residential quality in terms of safety; the researcher therefore examined if relationship between housing affordability and safety in the varied residential areas. The research adopted the bartlett, kotrlik and higgins (2001) method of t-test to determine the sample size which specifies different populations at different levels of significance (α). The researcher adopted primary data which was sourced from a field survey where the sample population was simply randomly selected to give a member of the population an equal chance of being selected, therefore, the sample size for the field survey was two hundred (200) respondents, and subjected to necessary testing. The research come to conclusion that housing safety and security is the responsibility of every resident, the landlords/landladies possess a better sense of security in their neighbourhood than renters in the community, therefore they need to be aware of their responsibility of ensuring the safety of lives and property.

Keywords: housing, housing affordability, housing security, residential, residential quality

Procedia PDF Downloads 98
4617 Polymeric Sustained Biodegradable Patch Formulation for Wound Healing

Authors: Abhay Asthana, Gyati Shilakari Asthana

Abstract:

It’s the patient compliance and stability in combination with controlled drug delivery and biocompatibility that forms the core feature in present research and development of sustained biodegradable patch formulation intended for wound healing. The aim was to impart sustained degradation, sterile formulation, significant folding endurance, elasticity, biodegradability, bio-acceptability and strength. The optimized formulation was developed using component including polymers including Hydroxypropyl methyl cellulose, Ethylcellulose, and Gelatin, and Citric Acid PEG Citric acid (CPEGC) triblock dendrimers and active Curcumin. Polymeric mixture dissolved in geometric order in suitable medium through continuous stirring under ambient conditions. With continued stirring Curcumin was added with aid of DCM and Methanol in optimized ratio to get homogenous dispersion. The dispersion was sonicated with optimum frequency and for given time and later casted to form a patch form. All steps were carried out under under strict aseptic conditions. The formulations obtained in the acceptable working range were decided based on thickness, uniformity of drug content, smooth texture and flexibility and brittleness. The patch kept on stability using butter paper in sterile pack displayed folding endurance in range of 20 to 23 times without any evidence of crack in an optimized formulation at room temperature (RT) (24 ± 2°C). The patch displayed acceptable parameters after stability study conducted in refrigerated conditions (8±0.2°C) and at RT (24 ± 2°C) upto 90 days. Further, no significant changes were observed in critical parameters such as elasticity, biodegradability, drug release and drug content during stability study conducted at RT 24±2°C for 45 and 90 days. The drug content was in range 95 to 102%, moisture content didn’t exceeded 19.2% and patch passed the content uniformity test. Percentage cumulative drug release was found to be 80% in 12h and matched the biodegradation rate as drug release with correlation factor R2>0.9. The biodegradable patch based formulation developed shows promising results in terms of stability and release profiles.

Keywords: sustained biodegradation, wound healing, polymers, stability

Procedia PDF Downloads 326
4616 Design and Development of Mucoadhesive Buccal Film Bearing Itraconazole

Authors: Yuvraj Singh Dangi, Kamta Prasad Namdeo, Surendra Bodhake

Abstract:

The purpose of this research was to develop and evaluate mucoadhesive films for buccal administration of itraconazole using film-forming and mucoashesive polymers. Buccal films of chitosan bearing Itraconazole were prepared by solvent casting technique. The films have been evaluated in terms of film weight, thickness, density, surface pH, FTIR, X-ray diffraction analysis, bioadhesion, swelling properties, and in vitro drug release studies. It was found that film formulations of 2 cm2 size having weight in the range of 204 ± 0.76 to 223 ± 2.09 mg and film thickness were in the range of 0.44 ± 0.11 to 0.57 ± 0.19 mm. Density of the films was found to be 0.102 to 0.126 g/ml. Drug content was found to be uniform in the range of 8.23 ± 0.07 to 8.73 ± 0.09 mg/cm2 for formulation A1 to A4. Maximum bioadhesion force was recorded for HPMC buccal films (A2) i.e. 0.57 ± 0.47 as compared to other films. In vitro residence time was in range of 1.7 ± 0.12 to 7.65 ± 0.15 h. The drug release studies show that formulations follow non-fickian diffusion. These mucoadhesive formulations could offer many advantages in comparison to traditional treatments.

Keywords: biovariability, buccal patches, itraconazole, Mucoadhesion

Procedia PDF Downloads 499
4615 Getting It Right Before Implementation: Using Simulation to Optimize Recommendations and Interventions After Adverse Event Review

Authors: Melissa Langevin, Natalie Ward, Colleen Fitzgibbons, Christa Ramsey, Melanie Hogue, Anna Theresa Lobos

Abstract:

Description: Root Cause Analysis (RCA) is used by health care teams to examine adverse events (AEs) to identify causes which then leads to recommendations for prevention Despite widespread use, RCA has limitations. Best practices have not been established for implementing recommendations or tracking the impact of interventions after AEs. During phase 1 of this study, we used simulation to analyze two fictionalized AEs that occurred in hospitalized paediatric patients to identify and understand how the errors occurred and generated recommendations to mitigate and prevent recurrences. Scenario A involved an error of commission (inpatient drug error), and Scenario B involved detecting an error that already occurred (critical care drug infusion error). Recommendations generated were: improved drug labeling, specialized drug kids, alert signs and clinical checklists. Aim: Use simulation to optimize interventions recommended post critical event analysis prior to implementation in the clinical environment. Methods: Suggested interventions from Phase 1 were designed and tested through scenario simulation in the clinical environment (medicine ward or pediatric intensive care unit). Each scenario was simulated 8 times. Recommendations were tested using different, voluntary teams and each scenario was debriefed to understand why the error was repeated despite interventions and how interventions could be improved. Interventions were modified with subsequent simulations until recommendations were felt to have an optimal effect and data saturation was achieved. Along with concrete suggestions for design and process change, qualitative data pertaining to employee communication and hospital standard work was collected and analyzed. Results: Each scenario had a total of three interventions to test. In, scenario 1, the error was reproduced in the initial two iterations and mitigated following key intervention changes. In scenario 2, the error was identified immediately in all cases where the intervention checklist was utilized properly. Independently of intervention changes and improvements, the simulation was beneficial to identify which of these should be prioritized for implementation and highlighted that even the potential solutions most frequently suggested by participants did not always translate into error prevention in the clinical environment. Conclusion: We conclude that interventions that help to change process (epinephrine kit or mandatory checklist) were more successful at preventing errors than passive interventions (signage, change in memory aids). Given that even the most successful interventions needed modifications and subsequent re-testing, simulation is key to optimizing suggested changes. Simulation is a safe, practice changing modality for institutions to use prior to implementing recommendations from RCA following AE reviews.

Keywords: adverse events, patient safety, pediatrics, root cause analysis, simulation

Procedia PDF Downloads 140
4614 Molecular Modeling a Tool for Postulating the Mechanism of Drug Interaction: Glimepiride Alters the Pharmacokinetics of Sildenafil Citrate in Diabetic Nephropathy Animals

Authors: Alok Shiomurti Tripathi, Ajay Kumar Timiri, Papiya Mitra Mazumder, Anil Chandewar

Abstract:

The present study evaluates the possible drug interaction between glimepiride (GLIM) and sildenafil citrate (SIL) in streptozotocin (STZ) induced in diabetic nephropathic (DN) animals and also postulates the possible mechanism of interaction by molecular modeling studies. Diabetic nephropathy was induced by single dose of STZ (60 mg/kg, ip) and confirms it by assessing the blood and urine biochemical parameters on 28th day of its induction. Selected DN animals were used for the drug interaction between GLIM (0.5mg/kg, p.o.) and SIL (2.5 mg/kg, p.o.) after 29th and 70th day of protocol. Drug interaction were assessed by evaluating the plasma drug concentration using HPLC-UV and also determine the change in the biochemical parameter in blood and urine. Mechanism of the interaction was postulated by molecular modeling study using Maestro module of Schrodinger software. DN was confirmed as there was significant alteration in the blood and urine biochemical parameter in STZ treated groups. The concentration of SIL increased significantly (p<0.001) in rat plasma when co administered with GLIM after 70th day of protocol. Molecular modelling study revealed few important interactions with rat serum albumin and CYP2C9.GLIM has strong hydrophobic interaction with binding site residues of rat serum albumin compared to SIL. Whereas, for CYP2C9, GLIM has strong hydrogen bond with polar contacts and hydrophobic interactions than SIL. Present study concludes that bioavailability of SIL increases when co-administered chronically with GLIM in the management of DN animals and mechanism has been supported by molecular modeling studies.

Keywords: diabetic nephropathy, glimepiride, sildenafil citrate, pharmacokinetics, homology modeling, schrodinger

Procedia PDF Downloads 366