Where and how to find data on safety: what do systematic reviews of complementary therapies tell us?

Background: Successfully identifying relevant data for systematic reviews with a focus on safety may require retrieving information from a wider range of sources than for ‘effectiveness’ systematic reviews. Searching for safety data continues to prove a major challenge. Objectives: To examine search methods used in systematic reviews of safety and to investigate indexing. Methods: Systematic reviews focusing on safety of complementary therapies and related interventions were retrieved from comprehensive searches of major databases. Data was extracted on search strategies, sources used and indexing in major databases. Safety related search terms were compared against index terms available on major databases. Data extraction by one researcher using a pre-prepared template was checked for accuracy by a second researcher. Results: Screening of 2563 records resulted in 88 systematic reviews being identified. Information sources used varied with the type of intervention being addressed. Comparison of search terms with available index terms revealed additional potentially relevant terms that could be used in constructing search strategies. Seventy-nine reviews were indexed on PubMed, 84 on EMBASE, 21 on CINAHL, 15 on AMED, 6 on PsycINFO, 2 on BNI and HMIC. The mean number of generic safety-related indexing terms on PubMed records was 2.6. For EMBASE the mean number was 4.8 with at least 61 unique terms being employed. Most frequently used indexing terms and subheadings were adverse effects, side effects, drug interactions and herb-drug interactions. Use of terms specifically referring to safety varied across databases. Conclusions: Investigation of search methods revealed the range of information sources used, a list of which may prove a valuable resource for those planning to conduct systematic reviews of safety. The findings also indicated that there is potential to improve safety-related search strategies. Finally, an insight is provided into indexing of and most effective terms for finding safety studies on major databases.

A generic model for integration of Quality, Environment and Safety Management Systems

Purpose – The purpose of this paper is to propose a generic model of Integrated Management System of Quality, Environment and Safety (IMS-QES) that can be adapted and progressively to assimilate various Management Systems, of which highlights: ISO 9001 for Quality; ISO 14001 for Environment; OHSAS 18001 for Occupational Health and Safety. Design/methodology/approach – The model was designed in the real environment of a Portuguese Organization and 160 employees were surveyed. The rate response was equal to 86 percent. The conceived model was implemented in a first phase for the integration of Quality, Environment and Safety Management Systems. Findings – Among the main findings of the survey the paper highlights: the elimination of conflicts between individual systems with resources optimization; creation of added value to the business by eliminating several types of wastes; the integrated management of sustainability components in a global market; the improvement of partnerships with suppliers of goods and services; reducing the number of internal and external audits. Originality/value – This case study is one of the first Portuguese empirical researches about IMS-QES and the paper believes that it can be useful in the creation of a Portuguese guideline for integration, namely the Quality Management Systems; Environmental Management Systems and Occupational Health and Safety Management Systems among others.

The impact of safety politics in the current globalization context

The globalization is a process of economical, social, cultural and political integration motivated by the needs generated by a consumption-orientated society and a set of factors that have led to its development, such as reducing transport costs, the technological advancement and the development of communication networks. However, the phenomenon of globalization has been accompanied by increasing levels of insecurity as a result of various types of threats and transnational crimes that the International Community seeks to control and minimize. Throughout this work, we examined how the globalization process has been developing and how nations are able to maintain security levels consistent with their economical status and social development, without disturbing the normal course of organizations’ economical activity and the well-being of people. From the investigation developed we concluded that, besides the confirmation that economic integration and the opening of markets have influence on internal consumption, market globalization and migrations have been causing modifications in the consumption habits. We also concluded that the security measures implemented by States or by the International Community affect international trade, but do not imply disproportionate costs or significant delays in transactions. Likewise, we concluded that the control measures implemented in international trade are sufficient to ensure the safety of the people and nations, enabling us to confirm two of the three conjectures raised in this study.

Safety climate and its relationship with furniture companies’ safety performance and workers’ risk acceptance

This study aims to analyse the relationship between safety climate and the level of risk acceptance, as well as its relationship with workplace safety performance. The sample includes 14 companies and 403 workers. The safety climate assessment was performed by the application of a Safety Climate in Wood Industries questionnaire and safety performance was assessed with a checklist. Judgements about risk acceptance were measured through questionnaires together with four other variables: trust, risk perception, benefit perception and emotion. Safety climate was found to be correlated with workgroup safety performance, and it also plays an important role in workers’ risk acceptance levels. Risk acceptance tends to be lower when safety climate scores of workgroups are high, and subsequently, their safety performance is better. These findings seem to be relevant, as they provide Occupational, Safety and Health practitioners with a better understanding of workers’ risk acceptance levels and of the differences among workgroups.

Long-Term Lamivudine Treatment of Children with Chronic Hepatitis B: Durability of Therapeutic Responses and Safety

Lamivudine has been demonstrated safe and efficacious in the short term in a large cohort of children with chronic hepatitis B (CHB), but optimal duration of treatment has not been elucidated and limited data on the safety of long-term lamivudine administration have been reported. In addition, the durability of favourable therapeutic outcomes after lamivudine therapy in children has not been well characterized. The aim of this study was to examine the safety of lamivudine and the durability of clinical responses in a group of children who received up to 3 years of treatment for CHB. One hundred and fifty-one children from centres in nine countries who had previously received lamivudine in a large prospective trial were enrolled. During the first year, children had been randomized to either lamivudine or placebo treatment. Subsequently, in a separate extension study, those who remained hepatitis B e antigen (HBeAg) positive were given lamivudine for up to 2 years and those who were HBeAg negative were observed for additional 2 years. Results of these studies have been previously reported. In this study, these children were followed for 2 additional years. Data gathered from medical record review included weight, height, signs and symptoms of hepatitis, alanine aminotransferase (ALT) levels, serologic markers, hepatitis B virus (HBV) DNA levels and serious adverse events (SAEs). Other pharmacological treatments for CHB were allowed according to the practices of individual investigators and were documented. Subjects were divided into two groups for analysis, those who had achieved virological response (VR), defined as HBeAg negative and undetectable HBV DNA by the bDNA assay by the end of the extension study at 3 years, and those who had not. In those who had achieved VR by the end of the extension study, long-term durability of HBeAg seroconversion was 82% and >90% in those who had received lamivudine for 52 weeks and at least 2 years respectively. This compares to 75% for those who had achieved seroconversion after placebo. In those who had not achieved VR by the end of the extension study, an additional 11% did so by the end of the study; they had all received lamivudine in the previous trial, and none had received further treatment during the study. Eight children lost hepatitis B surface antigen during the study and all had received lamivudine at some point during the previous trials. Evaluation of safety data revealed no SAEs related to lamivudine. There was no effect of treatment on weight or height z scores. Clinically benign ALT flares (>10 times normal) were seen in 2% of children. Favourable outcomes from lamivudine treatment of CHB in children are maintained for at least several years after completion of treatment. Up to 3 years of lamivudine treatment is safe in children.

Development and Characterization of bioactive, edible whey protein films and coatings to improve quality and safety of Food products

Dissertação para a obtenção de grau de doutor em Ciências da Engenharia e Tecnologia

Psychological safety, authentic leadership and social networks : A psycho-structural approach to the study of groups

Tese de Doutoramento em Psicologia na área de especialização de Psicologia das Organizações apresentada ao ISPA - Instituto Universitário

The World Health Organization Multi-Professional Patient Safety Curriculum : implementation of key modules and its impact on patient safety knowledge, skills, and attitudes of medical students at the University of Algarve

ABSTRACT - Objectives: We attempted to show how the implementation of the key elements of the World Health Organization Patient Safety Curriculum Guide Multi-professional Edition in an undergraduate curriculum affected the knowledge, skills, and attitudes towards patient safety in a graduate entry Portuguese Medical School. Methods: After receiving formal recognition by the WHO as a Complementary Test Site and approval of the organizational ethics committee , the validated pre-course questionnaires measuring the knowledge, skills, and attitudes to patient safety were administered to the 2nd and3rd year students pursuing a four-year course (N = 46). The key modules of the curriculum were implemented over the academic year by employing a variety of learning strategies including expert lecturers, small group problem-based teaching sessions, and Simulation Laboratory sessions. The identical questionnaires were then administered and the impact was measured. The Curriculum Guide was evaluated as a health education tool in this context. Results: A significant number of the respondents, 47 % (n = 22), reported having received some form of prior patient safety training. The effect on Patient Safety Knowledge was assessed by using the percentage of correct pre- and post-course answers to construct 2 × 2 contingency tables and by applying Fishers’ test (two-tailed). No significant differences were detected (p < 0.05). To assess the effect of the intervention on Patient Safety skills and attitudes, the mean and standard deviation were calculated for the pre and post-course responses, and independent samples were subjected to Mann-Whitney’s test. The attitudinal survey indicated a very high baseline incidence of desirable attitudes and skills toward patient safety. Significant changes were detected (p < 0.05) regarding what should happen if an error is made (p = 0.016), the role of healthcare organizations in error reporting (p = 0.006), and the extent of medical error (p = 0.005). Conclusions: The implementation of selected modules of the WHO Patient Safety Curriculum was associated with a number of positive changes regarding patient safety skills and attitudes, with a baseline incidence of highly desirable patient safety attitudes, but no measureable change on the patient safety knowledge, at the University of Algarve Medical School. The significance of these results is discussed along with implications and suggestions for future research.

Genetic algorithm for shipping route estimation with long-range tracking data : automatic reconstruction of shipping routes based on the historical ship positions for maritime safety applications

Ship tracking systems allow Maritime Organizations that are concerned with the Safety at Sea to obtain information on the current location and route of merchant vessels. Thanks to Space technology in recent years the geographical coverage of the ship tracking platforms has increased significantly, from radar based near-shore traffic monitoring towards a worldwide picture of the maritime traffic situation. The long-range tracking systems currently in operations allow the storage of ship position data over many years: a valuable source of knowledge about the shipping routes between different ocean regions. The outcome of this Master project is a software prototype for the estimation of the most operated shipping route between any two geographical locations. The analysis is based on the historical ship positions acquired with long-range tracking systems. The proposed approach makes use of a Genetic Algorithm applied on a training set of relevant ship positions extracted from the long-term storage tracking database of the European Maritime Safety Agency (EMSA). The analysis of some representative shipping routes is presented and the quality of the results and their operational applications are assessed by a Maritime Safety expert.

Safety and immunogenicity of the M72/AS01 candidate tuberculosis vaccine in HIV-infected adults on combination antiretroviral therapy: a phase I/II, randomized trial.

OBJECTIVE: Tuberculosis (TB) is highly prevalent among HIV-infected people, including those receiving combination antiretroviral therapy (cART), necessitating a well tolerated and efficacious TB vaccine for these populations. We evaluated the safety and immunogenicity of the candidate TB vaccine M72/AS01 in adults with well controlled HIV infection on cART. DESIGN: A randomized, observer-blind, controlled trial (NCT00707967). METHODS: HIV-infected adults on cART in Switzerland were randomized 3 : 1 : 1 to receive two doses, 1 month apart, of M72/AS01, AS01 or 0.9% physiological saline (N = 22, N = 8 and N = 7, respectively) and were followed up to 6 months postdose 2 (D210). Individuals with CD4⁺ cell counts below 200 cells/μl were excluded. Adverse events (AEs) including HIV-specific and laboratory safety parameters were recorded. Cell-mediated (ICS) and humoral (ELISA) responses were evaluated before vaccination, 1 month after each dose (D30, D60) and D210. RESULTS: Thirty-seven individuals [interquartile range (IQR) CD4⁺ cell counts at screening: 438-872 cells/μl; undetectable HIV-1 viremia] were enrolled; 73% of individuals reported previous BCG vaccination, 97.3% tested negative for the QuantiFERON-TB assay. For M72/AS01 recipients, no vaccine-related serious AEs or cART-regimen adjustments were recorded, and there were no clinically relevant effects on laboratory safety parameters, HIV-1 viral loads or CD4⁺ cell counts. M72/AS01 was immunogenic, inducing persistent and polyfunctional M72-specific CD4⁺ T-cell responses [medians 0.70% (IQR 0.37-1.07) at D60] and 0.42% (0.24-0.61) at D210, predominantly CD40L⁺IL-2⁺TNF-α⁺, CD40L⁺IL-2⁺ and CD40L⁺IL-2⁺TNF-α⁺IFN-γ⁺]. All M72/AS01 vaccines were seropositive for anti-M72 IgG after second vaccination until study end. CONCLUSION: M72/AS01 was clinically well tolerated and immunogenic in this population, supporting further clinical evaluation in HIV-infected individuals in TB-endemic settings.

Pharmacokinetics and safety of panobacumab: specific adjunctive immunotherapy in critical patients with nosocomial Pseudomonas aeruginosa O11 pneumonia.

Objectives Nosocomial Pseudomonas aeruginosa pneumonia remains a major concern in critically ill patients. We explored the potential impact of microorganism-targeted adjunctive immunotherapy in such patients. Patients and methods This multicentre, open pilot Phase 2a clinical trial (NCT00851435) prospectively evaluated the safety, pharmacokinetics and potential efficacy of three doses of 1.2 mg/kg panobacumab, a fully human monoclonal anti-lipopolysaccharide IgM, given every 72 h in 18 patients developing nosocomial P. aeruginosa (serotype O11) pneumonia. Results Seventeen out of 18 patients were included in the pharmacokinetic analysis. In 13 patients receiving three doses, the maximal concentration after the third infusion was 33.9 ± 8.0 μg/mL, total area under the serum concentration-time curve was 5397 ± 1993 μg h/mL and elimination half-life was 102.3 ± 47.8 h. Panobacumab was well tolerated, induced no immunogenicity and was detected in respiratory samples. In contrast to Acute Physiology and Chronic Health Evaluation II (APACHE II) prediction, all 13 patients receiving three doses survived, with a mean clinical resolution in 9.0 ± 2.7 days. Two patients suffered a recurrence at days 17 and 20. Conclusions These data suggest that panobacumab is safe, with a pharmacokinetic profile similar to that in healthy volunteers. It was associated with high clinical cure and survival rates in patients developing nosocomial P. aeruginosa O11 pneumonia. We concluded that these promising results warrant further trials.

Safety and occlusion rates of surgical treatment of unruptured intracranial aneurysms: a systematic review and meta-analysis of the literature from 1990 to 2011.

BACKGROUND AND PURPOSE: Surgical clipping of unruptured intracranial aneurysms (UIAs) has recently been challenged by the emergence of endovascular treatment. We performed an updated systematic review and meta-analysis on the surgical treatment of UIAs, in an attempt to determine the aneurysm occlusion rates and safety of surgery in the modern era. METHODS: A detailed protocol was developed prior to conducting the review according to the Cochrane Collaboration guidelines. Electronic databases spanning January 1990-April 2011 were searched, complemented by hand searching. Heterogeneity was assessed using I(2), and publication bias with funnel plots. Surgical mortality and morbidity were analysed with weighted random effect models. RESULTS: 60 studies with 9845 patients harbouring 10 845 aneurysms were included. Mortality occurred in 157 patients (1.7%; 99% CI 0.9% to 3.0%; I(2)=82%). Unfavourable outcomes, including death, occurred in 692 patients (6.7%; 99% CI 4.9% to 9.0%; I(2)=85%). Morbidity rates were significantly greater in higher quality studies, and with large or posterior circulation aneurysms. Reported morbidity rates decreased over time. Studies were generally of poor quality; funnel plots showed heterogeneous results and publication bias, and data on aneurysm occlusion rates were scant. CONCLUSIONS: In studies published between 1990 and 2011, clipping of UIAs was associated with 1.7% mortality and 6.7% overall morbidity. The reputed durability of clipping has not been rigorously documented. Due to the quality of the included studies, the available literature cannot properly guide clinical decisions.

Efficacy and safety of certolizumab pegol induction therapy in an unselected Crohn's disease population: results of the FACTS survey.

Background: Switzerland was the first country to approve certolizumab pegol (Cimzia, CZP) for the treatment of patients with moderate to severe Crohn's disease (CD) in September 2007. This phase IV study aimed to evaluate the efficacy and safety of CZP in a Swiss multicenter cohort of practice-based patients. Methods: Baseline and Week 6 evaluation questionnaires were sent to all Swiss gastroenterologists in hospitals and private practices. Disease activity was assessed with the Harvey-Bradshaw Index (HBI) and adverse events were evaluated according to WHO guidelines. Results: Fifty patients (31 women, 19 men) were included; 56% had complicated disease (stricture or fistula) and 52% had undergone prior CD-related surgery. All patients. had prior exposure to systemic steroids, 96% to immunomodulators, 78% to infliximab, and 50% to adalimumab. A significant decrease in HBI was observed at Week 6 (versus Week 0) following induction therapy with CZP 400 mg subcutaneously at Weeks 0, 2, and 4 (12.6 +/- 4.7 Week 0 versus 6.2 +/- 4.4 Week 6, P < 0.001). Response and remission rates at Week 6 were 54% and 40%, respectively. We identified 8/11 CD patients undergoing a 50% fistula response (P = 0.021). The frequency of adverse drug reactions attributed to CZP was 6%. CZP was continued in 80% of patients beyond Week 6. Conclusions: In a population of CD patients with complicated disease behavior, CZP induced a response and remission in 54% and 40% of patients, respectively. This series provides the first evidence of the effectiveness of CZP in perianal fistulizing CD.