An evaluation of certain aspects of an occupational health service

This thesis has been concerned with obtaining evidence to explore the proposition that the provision of occupational health services as arranged at the present time represents a misallocation of resources. The research has been undertaken within the occupational health service of a large Midlands food factory. As the research progressed it became evident that questions were being raised about the nature and scope of occupational health as well as the contribution, in combating danger at work, that occupational health services can make to the health and safety team. These questions have been scrutinized in depth, as they are clearly important, and a resolution of the problem of the definition of occupational health has been proposed. I have taken the approach of attempting to identify specific objectives or benefits of occupational health activities so that it is possible to assess how far these objectives are being achieved. I have looked at three aspects of occupational health; audiometry, physiotherapy and pre-employment medical examinations as these activities embody crucial concepts which are common to all activities in an occupational health programme. A three category classification of occupational health activities is proposed such that the three activities provide examples within each category. These are called personnel therapy, personnel input screening and personnel throughput screening. I conclude that I have not shown audiometry to be cost-effective. My observations of the physiotherapy service lead me to support the suggestion that there is a decline in sickness absence rates due to physiotherapy in industry. With pre-employment medical examinations I have shown that the service is product safety oriented and that benefits are extremely difficult to identify. In regard to the three services studied, in the one factory investigated, and because of the immeasurability of certain activities, I find support for the proposition that the mix of occupational health services as provided at the present time represents a misallocation of resources.

Comparative efficacy and safety of biosimilar infliximab and other biological treatments in ankylosing spondylitis: systematic literature review and meta-analysis.

OBJECTIVES: To compare the efficacy and safety of infliximab-biosimilar with other biological drugs for the treatment of active ankylosing spondylitis (AS). METHODS: Systematic literature review for randomized controlled trials (RCTs) with adalimumab, etanercept, golimumab, infliximab and infliximab-biosimilar in AS was performed and indirect meta-analysis (Bayesian mixed treatment comparison) was carried out. The proportion of patients reaching 20 % improvement by the assessment of Spondyloarthritis International Society response criteria (ASAS20) at weeks 12 and 24 was used as efficacy endpoints, and the occurrence of serious adverse events at week 24 was applied to compare the safety of the biologicals. RESULTS: Altogether, 13 RCTs, identified by the systematic literature search, were included in the analysis. Results on the ASAS20 efficacy endpoint were reported for week 12 in 12 RCTs involving 2,395 patients, and for week 24 in 5 RCTs comprising 1,337 patients. All the five biological agents proved to be significantly superior to placebo. Infliximab showed the highest odds ratio (OR) of 7.2 (95 % CI 3.68-13.19) compared to placebo, followed by infliximab-biosimilar with OR 6.25 (95 % CI 2.55-13.14), both assessed at week 24. No significant difference was found between infliximab-biosimilar and other biological treatments regarding their efficacy and safety. CONCLUSIONS: This is the first study which includes a biosimilar drug in the meta-analysis of biological treatments in AS. The results have proven the similar efficacy and safety profile of infliximab-biosimilar treatment compared to other biologicals.

Efficacy and safety of infliximab-biosimilar compared to other biological drugs in rheumatoid arthritis: a mixed treatment comparison.

OBJECTIVE: The aim of this meta-analysis was to compare the efficacy and safety of infliximab-biosimilar and other available biologicals for the treatment of rheumatoid arthritis (RA), namely abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, rituximab and tocilizumab. METHODS: A systematic literature review of MEDLINE database until August 2013 was carried out to identify relevant randomized controlled trials (RCTs). Bayesian mixed treatment comparison method was applied for the pairwise comparison of treatments. Improvement rates by the American College of Rheumatology criteria (ACR20 and ACR50) at week 24 were used as efficacy endpoints, and the occurrence of serious adverse events was considered to assess the safety of the biologicals. RESULTS: Thirty-six RCTs were included in the meta-analysis. All the biological agents proved to be superior to placebo. For ACR20 response, certolizumab pegol showed the highest odds ratio (OR) compared to placebo, OR 7.69 [95 % CI 3.69-14.26], followed by abatacept OR 3.7 [95 % CI 2.17-6.06], tocilizumab OR 3.69 [95 % CI 1.87-6.62] and infliximab-biosimilar OR 3.47 [95 % CI 0.85-9.7]. For ACR50 response, certolizumab pegol showed the highest OR compared to placebo OR 8.46 [3.74-16.82], followed by tocilizumab OR 5.57 [95 % CI 2.77-10.09], and infliximab-biosimilar OR 4.06 [95 % CI 1.01-11.54]. Regarding the occurrence of serious adverse events, the results show no statistically significant difference between infliximab-biosimilar and placebo, OR 1.87 [95 % CI 0.74-3.84]. No significant difference regarding efficacy and safety was found between infliximab-biosimilar and the other biological treatments. CONCLUSION: This is the first indirect meta-analysis in RA that compares the efficacy and safety of biosimilar-infliximab to the other biologicals indicated in RA. We found no significant difference between infliximab-biosimilar and other biological agents in terms of clinical efficacy and safety.

Data compilation on the biological response to ocean acidification: environmental and experimental context of data sets and related literature

The exponential growth of studies on the biological response to ocean acidification over the last few decades has generated a large amount of data. To facilitate data comparison, a data compilation hosted at the data publisher PANGAEA was initiated in 2008 and is updated on a regular basis (doi:10.1594/PANGAEA.149999). By January 2015, a total of 581 data sets (over 4 000 000 data points) from 539 papers had been archived. Here we present the developments of this data compilation five years since its first description by Nisumaa et al. (2010). Most of study sites from which data archived are still in the Northern Hemisphere and the number of archived data from studies from the Southern Hemisphere and polar oceans are still relatively low. Data from 60 studies that investigated the response of a mix of organisms or natural communities were all added after 2010, indicating a welcomed shift from the study of individual organisms to communities and ecosystems. The initial imbalance of considerably more data archived on calcification and primary production than on other processes has improved. There is also a clear tendency towards more data archived from multifactorial studies after 2010. For easier and more effective access to ocean acidification data, the ocean acidification community is strongly encouraged to contribute to the data archiving effort, and help develop standard vocabularies describing the variables and define best practices for archiving ocean acidification data.

Analytical strategies for the early quality and safety assurance in the global feed chain. Approaches for nitrogen adulterants in soybean meal and mineral and transformer oils in vegetable oils.

In the past decade, several major food safety crises originated from problems with feed. Consequently, there is an urgent need for early detection of fraudulent adulteration and contamination in the feed chain. Strategies are presented for two specific cases, viz. adulterations of (i) soybean meal with melamine and other types of adulterants/contaminants and (ii) vegetable oils with mineral oil, transformer oil or other oils. These strategies comprise screening at the feed mill or port of entry with non-destructive spectroscopic methods (NIRS and Raman), followed by post-screening and confirmation in the laboratory with MS-based methods. The spectroscopic techniques are suitable for on-site and on-line applications. Currently they are suited to detect fraudulent adulteration at relatively high levels but not to detect low level contamination. The potential use of the strategies for non-targeted analysis is demonstrated.

Efficacy and Safety of Radium-223 Dichloride in Symptomatic Castration-resistant Prostate Cancer Patients With or Without Baseline Opioid Use From the Phase 3 ALSYMPCA Trial

Background: The phase 3 ALSYMPCA trial enrolled metastatic castration-resistant prostate cancer patients with or without baseline opioid use.

Objective: To assess the efficacy and safety of radium-223 dichloride (radium-223) versus placebo in ALSYMPCA patients by baseline opioid use.

Design, setting, and participants: Nine hundred and twenty one patients enrolled at 136 centers globally.

Intervention: Radium-223 (50 kBq/kg, intravenous injection) every 4 wk for six cycles or matching placebo, each plus best standard of care.

Outcome measurements and statistical analysis: Primary endpoint (overall survival [OS]), main secondary efficacy endpoints, and safety were evaluated by baseline opioid use. Additional analyses included time to first opioid use, time to first external beam radiation therapy for bone pain, and safety of concomitant external beam radiation therapy.

Results and limitations: At baseline, 408 (44%) patients had no pain and no analgesic use or mild pain with nonopioid therapy (World Health Organization ladder pain score 0–1 [nonopioid subgroup]), and 513 (56%) had moderate pain with occasional opioids or severe pain with regular daily opioids (World Health Organization ladder pain score 2–3 [opioid subgroup]). Radium-223 significantly prolonged OS versus placebo in nonopioid (hazard ratio [HR] = 0.70; 95% confidence interval [CI]: 0.52–0.93; p = 0.013) and opioid (HR = 0.68; 95% CI: 0.54–0.86; p = 0.001) subgroups, and significantly reduced risk of symptomatic skeletal events versus placebo, regardless of baseline opioid use (nonopioid subgroup: HR = 0.56, 95% CI: 0.39–0.82, p = 0.002; opioid subgroup: HR = 0.72, 95% CI: 0.53–0.98, p = 0.038). Time to first opioid use for bone pain was significantly delayed with radium-223 versus placebo (HR = 0.62, 95% CI: 0.46–0.85,p = 0.002). Adverse event incidences were similar between opioid subgroups.

Conclusions: Radium-223 versus placebo significantly prolonged OS and reduced symptomatic skeletal event risk with a favorable safety profile in castration-resistant prostate cancer patients with symptomatic bone metastases, regardless of baseline opioid use.

Patient summary: In this ALSYMPCA opioid subgroup analysis, baseline symptom levels did not appear to impact radium-223 dichloride efficacy or safety.

Transportation of Children in Ground Ambulances: Professionals' Knowledge and Safety Measures

Background: The transport of children in ground ambulances is a rarely studied topic worldwide. The ambulance vehicle is a unique and complex environment with particular challenges for the safe, correct and effective transportation of patients. Unlike the well developed and readily available guidelines on the safe transportation of a child in motor vehicles, there is a lack on consistent specifications for transporting children in ambulances. Nurses are called daily to transfer children to hospitals or other care centers, so safe transport practices should be a major concern. Purpose: to know which are the safety precautions and specific measures used in the transport of children in ground ambulances by nurses and firefighters and to identify what knowledge these professionals had about safe modes of children transportation in ground ambulances. Methods: In this context, an exploratory - descriptive study and quantitative analysis was conducted. A questionnaire was completed by 135 nurses and firefighters / ambulance crew based on 4 possible children transport scenarios proposed by the NHTSA (National Highway Traffic Safety Administration) and covered 5 different children´s age groups (new born children, 1 to 12 months; 1 to 3 years old; 4 to 7 years old and 8 to 12 years old). Results: The main results showed a variety of safety measures used by the professionals and a significant difference between their actual mode of transportation and the mode they consider to be the ideal considering security goals. In addition, findings showed that achieved scores related to what ambulance crews do in the considered scenarios reflect mostly satisfactory levels of transportation rather than optimum levels of safety, according to NHTSA recommendations. Variables as gender, educational qualifications, occupational group and local where professionals work seem to influence the transport options. Female professionals and nurses from pediatric units appear to do a safer transportation of children in ground ambulances than other professionals. Conclusion: Several professionals refereed unawareness of the safest transportation options for children in ambulances and did not to know the existence of specific recommendations for this type of transportation. The dispersion of the results suggests the need for investment in professional training and further regulation for this type of transportation.

The impact of cooking methods on the nutritional quality and safety of chicken breaded nuggets

The impact of cooking methods (industrial pre-frying, deep-fat frying and baking) on the nutritional quality and safety of chicken breaded nugget samples from supermarket and commercial brands was evaluated. The changes in the quality characteristics (nutritional composition, fatty acids profile, cholesterol and salt) of the fried food and frying oil, after ten consecutive frying operations, were evaluated. The total fat content of nuggets varied between 10.9 and 22.7 g per 100 g of edible portion and the salt content ranged from 0.873 to 1.63 g per 100 g. Taking into account one portion of nuggets, the daily intake of salt can reach 49%, which can have a significant impact on the health of those who regularly consume this type of food, especially considering the prevalence of hypertension around the world. The analysed chicken breaded nuggets are rich in unsaturated fatty acids, which have been related with potential health benefits, namely regarding cardiovascular diseases. The cholesterol content of baked samples was two times higher when compared with the fried ones. The trans fatty acids and polar compounds contents of the frying oil used for frying significantly increased, but the values were still away from the maximum recommended by legal entities for its rejection. From a nutritional point of view, it is possible to conclude that the applied cooking methods can significantly influence the nutritional quality and safety of the analysed chicken breaded nuggets. This study will contribute to important knowledge on how the applied cooking methods can change the nutritional quality and safety of foods, namely of chicken nuggets, and can be very useful for dietary recommendations and nutritional assessment.

Utility and safety of invasive (fractional flow reserve) and non-invasive (cardiac magnetic resonance imaging) diagnostic tests in patients with NSTEMI

A prospective randomised controlled clinical trial of treatment decisions informed by invasive functional testing of coronary artery disease severity compared with standard angiography-guided management was implemented in 350 patients with a recent non-ST elevation myocardial infarction (NSTEMI) admitted to 6 hospitals in the National Health Service. The main aims of this study were to examine the utility of both invasive fractional flow reserve (FFR) and non-invasive cardiac magnetic resonance imaging (MRI) amongst patients with a recent diagnosis of NSTEMI. In summary, the findings of this thesis are: (1) the use of FFR combined with intravenous adenosine was feasible and safe amongst patients with NSTEMI and has clinical utility; (2) there was discordance between the visual, angiographic estimation of lesion significance and FFR; (3). The use of FFR led to changes in treatment strategy and an increase in prescription of medical therapy in the short term compared with an angiographically guided strategy; (4) in the incidence of major adverse cardiac events (MACE) at 12 months follow up was similar in the two groups. Cardiac MRI was used in a subset of patients enrolled in two hospitals in the West of Scotland. T1 and T2 mapping methods were used to delineate territories of acute myocardial injury. T1 and T2 mapping were superior when compared with conventional T2-weighted dark blood imaging for estimation of the ischaemic area-at-risk (AAR) with less artifact in NSTEMI. There was poor correlation between the angiographic AAR and MRI methods of AAR estimation in patients with NSTEMI. FFR had a high accuracy at predicting inducible perfusion defects demonstrated on stress perfusion MRI. This thesis describes the largest randomized trial published to date specifically looking at the clinical utility of FFR in the NSTEMI population. We have provided evidence of the diagnostic and clinical utility of FFR in this group of patients and provide evidence to inform larger studies. This thesis also describes the largest ever MRI cohort, including with myocardial stress perfusion assessments, specifically looking at the NSTEMI population. We have demonstrated the diagnostic accuracy of FFR to predict reversible ischaemia as referenced to a non-invasive gold standard with MRI. This thesis has also shown the futility of using dark blood oedema imaging amongst all comer NSTEMI patients when compared to novel T1 and T2 mapping methods.

Transportation of Children in Ground Ambulances: Professionals' Knowledge and Safety Measures

Background: The transport of children in ground ambulances is a rarely studied topic worldwide. The ambulance vehicle is a unique and complex environment with particular challenges for the safe, correct and effective transportation of patients. Unlike the well developed and readily available guidelines on the safe transportation of a child in motor vehicles, there is a lack on consistent specifications for transporting children in ambulances. Nurses are called daily to transfer children to hospitals or other care centers, so safe transport practices should be a major concern. Purpose: to know which are the safety precautions and specific measures used in the transport of children in ground ambulances by nurses and firefighters and to identify what knowledge these professionals had about safe modes of children transportation in ground ambulances. Methods: In this context, an exploratory - descriptive study and quantitative analysis was conducted. A questionnaire was completed by 135 nurses and firefighters / ambulance crew based on 4 possible children transport scenarios proposed by the NHTSA (National Highway Traffic Safety Administration) and covered 5 different children´s age groups (new born children, 1 to 12 months; 1 to 3 years old; 4 to 7 years old and 8 to 12 years old). Results: The main results showed a variety of safety measures used by the professionals and a significant difference between their actual mode of transportation and the mode they consider to be the ideal considering security goals. In addition, findings showed that achieved scores related to what ambulance crews do in the considered scenarios reflect mostly satisfactory levels of transportation rather than optimum levels of safety, according to NHTSA recommendations. Variables as gender, educational qualifications, occupational group and local where professionals work seem to influence the transport options. Female professionals and nurses from pediatric units appear to do a safer transportation of children in ground ambulances than other professionals. Conclusion: Several professionals refereed unawareness of the safest transportation options for children in ambulances and did not to know the existence of specific recommendations for this type of transportation. The dispersion of the results suggests the need for investment in professional training and further regulation for this type of transportation.