Management of nanomaterials safety in research environment

Despite numerous discussions, workshops, reviews and reports about responsible development of nanotechnology, information describing health and environmental risk of engineered nanoparticles or nanomaterials is severely lacking and thus insufficient for completing rigorous risk assessment on their use. However, since preliminary scientific evaluations indicate that there are reasonable suspicions that activities involving nanomaterials might have damaging effects on human health; the precautionary principle must be applied. Public and private institutions as well as industries have the duty to adopt preventive and protective measures proportionate to the risk intensity and the desired level of protection. In this work, we present a practical, 'user-friendly' procedure for a university-wide safety and health management of nanomaterials, developed as a multi-stakeholder effort (government, accident insurance, researchers and experts for occupational safety and health). The process starts using a schematic decision tree that allows classifying the nano laboratory into three hazard classes similar to a control banding approach (from Nano 3 - highest hazard to Nano1 - lowest hazard). Classifying laboratories into risk classes would require considering actual or potential exposure to the nanomaterial as well as statistical data on health effects of exposure. Due to the fact that these data (as well as exposure limits for each individual material) are not available, risk classes could not be determined. For each hazard level we then provide a list of required risk mitigation measures (technical, organizational and personal). The target 'users' of this safety and health methodology are researchers and safety officers. They can rapidly access the precautionary hazard class of their activities and the corresponding adequate safety and health measures. We succeed in convincing scientist dealing with nano-activities that adequate safety measures and management are promoting innovation and discoveries by ensuring them a safe environment even in the case of very novel products. The proposed measures are not considered as constraints but as a support to their research. This methodology is being implemented at the Ecole Polytechnique de Lausanne in over 100 research labs dealing with nanomaterials. It is our opinion that it would be useful to other research and academia institutions as well. [Authors]

Vaccinia immune globulin: current policies, preparedness, and product safety and efficacy.

In 1980 the World Health Organization declared that smallpox was eradicated from the world, and routine smallpox vaccination was discontinued. Nevertheless, samples of the smallpox virus (variola virus) were retained for research purposes, not least because of fears that terrorist groups or rogue states might also have kept samples in order to develop a bioweapon. Variola virus represents an effective bioweapon because it is associated with high morbidity and mortality and is highly contagious. Since September 11, 2001, countries around the world have begun to develop policies and preparedness programs to deal with a bioterror attack, including stockpiling of smallpox vaccine. Smallpox vaccine itself may be associated with a number of serious adverse events, which can often be managed with vaccinia immune globulin (VIG). VIG may also be needed as prophylaxis in patients for whom pre-exposure smallpox vaccine is contraindicated (such as those with eczema or pregnant women), although it is currently not licensed in these cases. Two intravenous formulations of VIG (VIGIV Cangene and VIGIV Dynport) have been licensed by the FDA for the management of patients with progressive vaccinia, eczema vaccinatum, severe generalized vaccinia, and extensive body surface involvement or periocular implantation following inadvertent inoculation.

State-of-the-art of 3D cultures (organs-on-a-chip) in safety testing and pathophysiology.

Integrated approaches using different in vitro methods in combination with bioinformatics can (i) increase the success rate and speed of drug development; (ii) improve the accuracy of toxicological risk assessment; and (iii) increase our understanding of disease. Three-dimensional (3D) cell culture models are important building blocks of this strategy which has emerged during the last years. The majority of these models are organotypic, i.e., they aim to reproduce major functions of an organ or organ system. This implies in many cases that more than one cell type forms the 3D structure, and often matrix elements play an important role. This review summarizes the state of the art concerning commonalities of the different models. For instance, the theory of mass transport/metabolite exchange in 3D systems and the special analytical requirements for test endpoints in organotypic cultures are discussed in detail. In the next part, 3D model systems for selected organs--liver, lung, skin, brain--are presented and characterized in dedicated chapters. Also, 3D approaches to the modeling of tumors are presented and discussed. All chapters give a historical background, illustrate the large variety of approaches, and highlight up- and downsides as well as specific requirements. Moreover, they refer to the application in disease modeling, drug discovery and safety assessment. Finally, consensus recommendations indicate a roadmap for the successful implementation of 3D models in routine screening. It is expected that the use of such models will accelerate progress by reducing error rates and wrong predictions from compound testing.

Roadway Lighting and Safety: Phase II – Monitoring Quality, Durability and Efficiency, November 2011

This Phase II project follows a previous project titled Strategies to Address Nighttime Crashes at Rural, Unsignalized Intersections. Based on the results of the previous study, the Iowa Highway Research Board (IHRB) indicated interest in pursuing further research to address the quality of lighting, rather than just the presence of light, with respect to safety. The research team supplemented the literature review from the previous study, specifically addressing lighting level in terms of measurement, the relationship between light levels and safety, and lamp durability and efficiency. The Center for Transportation Research and Education (CTRE) teamed with a national research leader in roadway lighting, Virginia Tech Transportation Institute (VTTI) to collect the data. An integral instrument to the data collection efforts was the creation of the Roadway Monitoring System (RMS). The RMS allowed the research team to collect lighting data and approach information for each rural intersection identified in the previous phase. After data cleanup, the final data set contained illuminance data for 101 lighted intersections (of 137 lighted intersections in the first study). Data analysis included a robust statistical analysis based on Bayesian techniques. Average illuminance, average glare, and average uniformity ratio values were used to classify quality of lighting at the intersections.

Indicateurs sécurité en obstétrique : une étude Delphi [Patient safety indicators for obstetrics: a Delphi based study]

OBJECTIVE: Clinical indicators are increasingly used to assess safety of patient care. In obstetrics, only a few indicators have been validated to date and none is used across specialties. The purpose of this study was to identify and assess for face and content validity a group of safety indicators that could be used by anaesthetists, obstetricians and neonatologists involved in labour and delivery units. MATERIALS AND METHODS: We first conducted a systematic review of the literature to identify potential measures. Indicators were then validated by a panel of 30 experts representing all specialties working in labour and delivery units. We used the Delphi method, an iterative questionnaire-based consensus seeking technique. Experts determined on a 7-point Likert scale (1=most representative/7=less representative) the soundness of each indicator as a measure of safety and their possible association with errors and complications caused by medical management. RESULTS: We identified 44 potential clinical indicators from the literature. Following the Delphi process, 13 indicators were considered as highly representative of safety during obstetrical care (mean score</=2.3). Experts ranked 6 of these indicators as being strongly associated to potential errors and complications. CONCLUSIONS: We identified and validated for face and content, a group of six clinical indicators to measure potentially preventable iatrogenic complications in labour and delivery units.

Effect of computerisation on the quality and safety of chemotherapy prescription.

BACKGROUND: Chemotherapy is prescribed according to protocols of several cycles. These protocols include not only therapeutic agents but also adjuvant solvents and inherent supportive care measures. Multiple errors can occur during the prescription, the transmission of documents and the drug delivery processes, and lead to potentially serious consequences. OBJECTIVE: To assess the effect of a computerised physician order entry (CPOE) system on the number of errors in prescription recorded by the centralised chemotherapy unit of a pharmacy service in a university hospital. PATIENTS AND METHODS: Existing chemotherapy protocols were standardised by a multidisciplinary team (composed of a doctor, a pharmacist and a nurse) and a CPOE system was developed from a File Maker Pro database. Chemotherapy protocols were progressively introduced into the CPOE system. The effect of the system on prescribing errors was measured over 15 months before and 21 months after starting computerised protocol prescription. Errors were classified as major (dosage and drug name) and minor (volume or type of infusion solution). RESULTS: Before computerisation, 141 errors were recorded for 940 prescribed chemotherapy regimens (15%). After introduction of the CPOE system, 75 errors were recorded for 1505 prescribed chemotherapy regimens (5%). Of these errors, 69 (92%) were recorded in prescriptions that did not use a computerised protocol. A dramatic decrease in the number of errors was noticeable when 50% of the chemotherapy protocols were prescribed through the CPOE system. CONCLUSION: Errors in chemotherapy prescription nearly disappeared after implementation of CPOE. The safety of chemotherapy prescription was markedly improved.

Roadway Lighting and Safety: Phase II – Monitoring Quality, Durability and Efficiency, November 2011

This Phase II project follows a previous project titled Strategies to Address Nighttime Crashes at Rural, Unsignalized Intersections. Based on the results of the previous study, the Iowa Highway Research Board (IHRB) indicated interest in pursuing further research to address the quality of lighting, rather than just the presence of light, with respect to safety. The research team supplemented the literature review from the previous study, specifically addressing lighting level in terms of measurement, the relationship between light levels and safety, and lamp durability and efficiency. The Center for Transportation Research and Education (CTRE) teamed with a national research leader in roadway lighting, Virginia Tech Transportation Institute (VTTI) to collect the data. An integral instrument to the data collection efforts was the creation of the Roadway Monitoring System (RMS). The RMS allowed the research team to collect lighting data and approach information for each rural intersection identified in the previous phase. After data cleanup, the final data set contained illuminance data for 101 lighted intersections (of 137 lighted intersections in the first study). Data analysis included a robust statistical analysis based on Bayesian techniques. Average illuminance, average glare, and average uniformity ratio values were used to classify quality of lighting at the intersections.

Rockfall characterisation and structural protection: A review

Rockfall is an extremely rapid process involving long travel distances. Due to these features, when an event occurs, the ability to take evasive action is practically zero and, thus, the risk of injury or loss of life is high. Damage to buildings and infrastructure is quite likely. In many cases, therefore, suitable protection measures are necessary. This contribution provides an overview of previous and current research on the main topics related to rockfall. It covers the onset of rockfall and runout modelling approaches, as well as hazard zoning and protection measures. It is the aim of this article to provide an in-depth knowledge base for researchers and practitioners involved in projects dealing with the rockfall protection of infrastructures, who may work in the fields of civil or environmental engineering, risk and safety, the earth and natural sciences.

Road Safety Audit for IA 28 from the South Corporate Limits of Norwalk in Warren County through the IA 5 Interchange in Polk County, Iowa, November 2012

In response to local concerns, the Iowa Department of Transportation (DOT) requested a road safety audit (RSA) for the IA Highway 28 corridor through the City of Norwalk in Warren County, Iowa, from the south corporate limits of Norwalk through the IA 5 interchange in Polk County, Iowa. The audit included meeting with City staff to discuss concerns, review crash history and operational issues, observe the route under daylight and nighttime conditions, and analyze available data. This report outlines the findings and recommendations of the audit team for addressing the safety concerns and operational matters along this corridor.

ICD-11 for quality and safety: overview of the who quality and safety topic advisory group.

This paper outlines the approach that the WHO's Family of International Classifications (WHO-FIC) network is undertaking to create ICD-11. We also outline the more focused work of the Quality and Safety Topic Advisory Group, whose activities include the following: (i) cataloguing existing ICD-9 and ICD-10 quality and safety indicators; (ii) reviewing ICD morbidity coding rules for main condition, diagnosis timing, numbers of diagnosis fields and diagnosis clustering; (iii) substantial restructuring of the health-care related injury concepts coded in the ICD-10 chapters 19/20, (iv) mapping of ICD-11 quality and safety concepts to the information model of the WHO's International Classification for Patient Safety and the AHRQ Common Formats; (v) the review of vertical chapter content in all chapters of the ICD-11 beta version and (vi) downstream field testing of ICD-11 prior to its official 2015 release. The transition from ICD-10 to ICD-11 promises to produce an enhanced classification that will have better potential to capture important concepts relevant to measuring health system safety and quality-an important use case for the classification.

Pharmacist interventions to improve cardiovascular disease risk factors in diabetes: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: This systematic review and meta-analysis of randomized controlled trials (RCTs) assesses the effect of pharmacist care on cardiovascular disease (CVD) risk factors among outpatients with diabetes. RESEARCH DESIGN AND METHODS: MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials were searched. Pharmacist interventions were classified, and a meta-analysis of mean changes of blood pressure (BP), total cholesterol (TC), LDL cholesterol, HDL cholesterol, and BMI was performed using random-effects models. RESULTS: The meta-analysis included 15 RCTs (9,111 outpatients) in which interventions were conducted exclusively by pharmacists in 8 studies and in collaboration with physicians, nurses, dietitians, or physical therapists in 7 studies. Pharmacist interventions included medication management, educational interventions, feedback to physicians, measurement of CVD risk factors, or patient-reminder systems. Compared with usual care, pharmacist care was associated with significant reductions for systolic BP (12 studies with 1,894 patients; -6.2 mmHg [95% CI -7.8 to -4.6]); diastolic BP (9 studies with 1,496 patients; -4.5 mmHg [-6.2 to -2.8]); TC (8 studies with 1,280 patients; -15.2 mg/dL [-24.7 to -5.7]); LDL cholesterol (9 studies with 8,084 patients; -11.7 mg/dL [-15.8 to -7.6]); and BMI (5 studies with 751 patients; -0.9 kg/m(2) [-1.7 to -0.1]). Pharmacist care was not associated with a significant change in HDL cholesterol (6 studies with 826 patients; 0.2 mg/dL [-1.9 to 2.4]). CONCLUSIONS: This meta-analysis supports pharmacist interventions-alone or in collaboration with other health care professionals-to improve major CVD risk factors among outpatients with diabetes.

What influence do anticoagulants have on oral implant therapy? A systematic review.

OBJECTIVES: This systematic review aims to assess the risks (both thromboembolic and bleeding) of an oral anticoagulation therapy (OAT) patient undergoing implant therapy and to provide a management protocol to patients under OAT undergoing implant therapy. MATERIAL AND METHODS: Medline, Cochrane Data Base of Systematic Reviews, the Cochrane Central Register of Controlled Trials and EMBASE (from 1980 to December 2008) were searched for English-language articles published between 1966 and 2008. This search was completed by a hand research accessing the references cited in all identified publications. RESULTS: Nineteen studies were identified reporting outcomes after oral surgery procedures (mostly dental extractions in patients on OAT following different management protocols and haemostatic therapies). Five studies were randomized-controlled trials (RCTs), 11 were controlled clinical trials (CCTs) and three were prospective case series. The OAT management strategies as well as the protocols during and after surgery were different. This heterogeneity prevented any possible data aggregation and synthesis. The results from these studies are very homogeneous, reporting minor bleeding in very few patients, without a significant difference between the OAT patients who continue with the vitamin K antagonists vs. the patients who stopped this medication before surgery. These post-operative bleeding events were controlled only with local haemostatic measures: tranexamic acid mouthwashes, gelatine sponges and cellulose gauzes's application were effective. Post-operative bleeding did not correlate with the international normalised ratio (INR) status. In none of the studies was a thromboembolic event reported. CONCLUSIONS: OAT patients (INR 2-4) who do not discontinue the AC medication do not have a significantly higher risk of post-operative bleeding than non-OAT patients and they also do not have a higher risk of post-operative bleeding than OAT patients who discontinue the medication. In patients with OAT (INR 2-4) without discontinuation, topical haemostatic agents were effective in preventing post-operative bleeding. OAT discontinuation is not recommended for minor oral surgery, such as single tooth extraction or implant placement, provided that this does not involve autogenous bone grafts, extensive flaps or osteotomy preparations extending outside the bony envelope. Evidence does not support that dental implant placement in patients on OAT is contraindicated.

Therapeutic drug monitoring and pharmacogenetic tests as tools in pharmacovigilance.

Therapeutic drug monitoring (TDM) and pharmacogenetic tests play a major role in minimising adverse drug reactions and enhancing optimal therapeutic response. The response to medication varies greatly between individuals, according to genetic constitution, age, sex, co-morbidities, environmental factors including diet and lifestyle (e.g. smoking and alcohol intake), and drug-related factors such as pharmacokinetic or pharmacodynamic drug-drug interactions. Most adverse drug reactions are type A reactions, i.e. plasma-level dependent, and represent one of the major causes of hospitalisation, in some cases leading to death. However, they may be avoidable to some extent if pharmacokinetic and pharmacogenetic factors are taken into consideration. This article provides a review of the literature and describes how to apply and interpret TDM and certain pharmacogenetic tests and is illustrated by case reports. An algorithm on the use of TDM and pharmacogenetic tests to help characterise adverse drug reactions is also presented. Although, in the scientific community, differences in drug response are increasingly recognised, there is an urgent need to translate this knowledge into clinical recommendations. Databases on drug-drug interactions and the impact of pharmacogenetic polymorphisms and adverse drug reaction information systems will be helpful to guide clinicians in individualised treatment choices.

Multidisciplinary Safety Team (MDST) Factors of Success, 2014

This project included a literature review and summary that focused on subjects related to team building, team/committee member motivational strategies, and tools for effective and efficient committee meetings. It also completed an online survey of multidisciplinary safety team (MDST) members that focused on methods to increase meeting attendance and the identification of factors that make MDSTs successful. The survey had a response rate of about 15 percent. Finally, three small MDST focus groups were held and the participants discussed information similar to that investigated by the online survey. The results of these three activities were similar and complementary. In general, the outcomes of all three tasks show that a well-designed agenda that has items relevant to the meeting attendees is very important. In addition, the literature, online survey, and focus group results identified other characteristics that define a good team or MDST. Some of these characteristics included effective and consistent leadership, members that are allowed to provide input and have an impact, members that are vested in the activities of the group, and a match between the interests of the members and the focus/mission/purpose of the meetings/group. Meetings that are scheduled well in advance of the meeting date, include time for networking, local safety activity discussions, hands-on activities/tasks, and/or some type of educational or informational presentation or activity also appeared to be the most desirable. Lastly, it was shown that MDSTs can thrive and be successful through various means, but the ability to focus on a specific safety issue when the group is first organized was suggested as a benefit that could be of assistance for long-term sustainability.