Safety and tolerability of controlled-release oxycodone on postoperative pain in patients submitted to the oncologic head and neck surgery

Objective: To evaluate the safety and tolerability of controlled-release oxycodone in the treatment of postoperative pain of head and neck oncologic resections.Methods: We conducted a prospective, observational and open study, with 83 patients with moderate to severe pain after head and neck oncological operations. All patients received general anesthesia with propofol, fentanyl and sevoflurane. Postoperatively, should they have moderate or severe pain, we began controlled-release oxycodone 20 mg 12/12 b.i.d on the first day and 10 mg b.i.d. on the second. We assessed the frequency and intensity of adverse effects, the intensity of postoperative pain by a verbal numeric scale and the use of rescue analgesia from 12 hours after administration of the drug and between 7 and 13 days after the last oxycodone dose.Results: The most common adverse events were nausea, vomiting, dizziness, pruritus, insomnia, constipation and urinary retention, most mild. No serious adverse events occurred. In less than 12 hours after the use of oxycodone, there was a significant decrease in the intensity of postoperative pain, which remained until the end of the study. The rescue medication was requested at a higher frequency when the opioid dose was reduced, or after its suspension.Conclusion: Controlled release oxycodone showed to be safe and well tolerated and caused a significant decrease in post-operative pain.

Establishment of a health and safety management system according to the OHSAS 18001 standard

The thesis develops guidelines for the implementation of the health and safety management system according to the OHSAS 18001 standard, as well as the feasible threat analysis, project proposal schedule, future system quality improvements and organizational change evaluation. The theoretical part clarifies determination of occupational health and safety, its management system, the OHSAS 18001 standard and integrated management system compounded of triple ISO 14001, ISO 9001 and OHSAS 18001 standards. The literature includes such important aspects as human factor, organizational policies, possible benefits, threats, organizational safety culture, Deming’s quality improvement cycle, system implementation, maintenance and cost matters. The empirical part demonstrates real-life situation by using Andritz Pulp & Paper Oy as a case study. Prior the thesis proposal, Andritz Group is analysed including separate business areas, acquisition and integration strategies, current status of the health and safety management and parallel experiences of the largest business area Andritz Hydro. The proposal is aimed at improving the current health and safety system for the permanent and sub-contracted employees at Andritz Pulp & Paper both in Finland and in various projects globally.

Field evaluation of safety during gestation and horizontal spread of a recombinant differential bovine herpesvirus 1 (BoHV-1) vaccine

Bovine herpesvirus type 1 (BoHV-1) is recognized as a major cause of respiratory, reproductive disease and abortion in cattle. Vaccination is widely applied to minimize losses induced by BoHV-1 infections; however, vaccination of dams during pregnancy with modified live virus (MLV) vaccines has been occasionally associated to abortions. We have previously reported the development of a BoHV-1 recombinant virus, constructed with basis on a Brazilian BoHV-1 (Franco et al. 2002a) from which the gene coding for glycoprotein E (gE) was deleted (gE-) by genetic manipulation. Such recombinant has been previously evaluated in its potential as a differential vaccine (gE- vaccine) that allows differentiation between vaccinated and infected animals. Here, in the first part of the present study, the safety of the gE- vaccine during pregnancy was evaluated by the intramuscular inoculation of 10(7.4) tissue culture 50 % infective doses (TCID50) of the virus into 22 pregnant dams (14 BoHV-1 seronegative; 8 seropositive), at different stages of gestation. Other 15 pregnant dams were kept as non-vaccinated controls. No abortions, stillbirths or fetal abnormalities were seen after vaccination. Seroconversion was observed in both groups of previously seronegative vaccinated animals. In the second part of the study, the potential of the gE- vaccine virus to spread among beef cattle under field conditions was examined. Four heifers were inoculated intranasally with a larger amount (10(7,6) TCID50) of the gE- vaccine (to increase chances of transmission) and mixed with other sixteen animals at the same age and body condition, in the same grazing area, at a population density equal to the average cattle farming density within the region (one cattle head per 10,000 m²), for 180 days. All animals were monitored daily for clinical signs. Serum samples were collected on days 0, 30, 60 and 180 post-vaccination. Seroconversion was observed only in vaccinated heifers. These results indicate that, under the conditions of the present study, the gE- vaccine virus did not cause any noticeable harmful effect on pregnant dams and on its offspring and did not spread horizontally among cattle.

Safety study of hydrogen peroxide direct synthesis

Kandidaatintyön johdantokappaleessa esitellään vetyperoksidi ja mihin sitä käytetään teollisuudessa. Työssä vertaillaan antrakinoniprosessia ja suoraa prosessia sekä selvitetään nykyisin enemmän vetyperoksidituotantoon käytetyn antrakinoniprosessin ongelmakohdat ja osoitetaan, miksi suora synteesi vetyperoksidin tuotannossa olisi parempi vaihtoehto. Kandidaatintyön käsittelee suurilta osin turvallisuusongelmia, joita esiintyy suoran synteesin yhteydessä. Kirjallisuudesta on etsitty ratkaisuja näihin ongelmiin, kuten membraaniprosessin käyttöä räjähdysvaaran välttämiseksi. Pienemmän reaktorin eli ns. mikroreaktorin käyttö tuo mukanaan monia etuja vetyperoksidin tuotantoon. Tällöin prosessi on turvallisempi ja sitä on helpompi hallita. Mikroreaktorissa voidaan käyttää korkeampia lämpötiloja ja paineita kuin makroreaktorilla ilman, että räjähdysvaara prosessissa kasvaisi. Mikroreaktorin sisällä olevat mikrokanavat luovat turvallisen ympäristön synteesille. Aspen plus – simulointiohjelmalla mallinnettiin ja simulointiin suoran prosessin kriittisiä virtoja mikroreaktorissa. Tarkoituksena oli löytää virrat, joissa kulkee mahdollisesti räjähtävä kaasuseos. Kaasumaiset prosessivirrat ovat kriittisimmät vetyperoksidin suorassa synteesissä, koska ne aiheuttavat todennäköisemmin räjähdyksen kuin nestemäiset prosessivirrat. Kaikkein eniten prosessiturvallisuutta uhkaavat ainevirrat ennen ja jälkeen mikroreaktoria.

Productivity and Services – Safety Telephone Services for the Elderly

Previous research on productivity is often associated with manufacturing or uses manufacturing definitions of productivity. Marketing research on services has not been satisfied with the manufacturing definitions. No universal definition for service productivity exists. The lack of a universal definition highlights the complexity entailed in the concept of productivity. The objective of this study was to investigate service productivity in situations, where traditional ways are in some cases even not possible or are not enough. In one definition of the productivity of service organisations there is the efficiency of the organisation on the input side and on the output side the customers’ perceived quality or value-in-use. To learn about value-in-use, many methods have been developed. A common practice is to make customer opinion surveys in the form of customer questionnaires and interviews. However, customers cannot always be asked directly, for example, because of impaired cognitive abilities. Such cases include the elderly and children. Furthermore, customer opinion surveys are time consuming. In addition, customers do not always know what kind of services they would benefit from. For the empirical part of the study, a business area was identified where traditional ways of measuring value-in-use are difficult or in some cases even not possible. This business area is safety telephone services. These services are most often used by the elderly. The way to define value-in-use here was to assess how well the services offered met customer expectations. Comparing the services customers asked for and the services provided to them indicated whether customer expectations were met. This study showed that customers had their ideas concerning the contents of the services but many times the services provided did not meet these expectations. Organisational efficiency aspirations can decrease customers’ value-in-use. This study found a solution, in which increasing organisational efficiency would go hand-in-hand with increasing customers’ value-in-use; the result being that the organisations’ needs and the service users’ expectations were in line. Value creation for customers produced organisational efficiency and thus increased productivity. In this study, customer expectations were observed by means of wellness technology. With the help of modern technology, customer expectations can be followed quickly and easily and customers can co-create with the organisation. This type of an approach could be useful even in the development of other services for other ages and in different contexts. If a service organisation decreases the number of personnel and, at the same time, tries to offer services to the same or a larger clientele, customers easily notice the change, which is often negative. To avoid harmful decrease in value-in-use, limitations to the aspiration of efficiency should be implemented – one of such is that the organisation is required to meet certain quality standards defined by experts. The aim is to secure that, as a result of efficiency aspirations in the organisation, the quality of the service offerings does not diminish below mutually agreed standards. Traditionally, when productivity in services has been estimated, organisational efficiency has not been combined with both customer expectations and an expert assessment of quality. This study contributes with novel thinking entitled ‘Relationship Management of the Elderly’. This study handles productivity, expert defined quality and value-in-use in an organisational context, which is practically untouched in previous research studies.

Overview on the Cost-effectiveness of Maritime Safety Policy Instruments

Maritime safety is an issue that has gained a lot of attention in the Baltic Sea area due to the dense maritime traffic and transportation of oil in the area. Lots of effort has been paid to enhance maritime safety in the area. The risk exists that excessive legislation and other requirements mean more costs for limited benefit. In order to utilize both public and private resources efficiently, awareness is required of what kind of costs maritime safety policy instruments cause and whether the costs are in relation to benefits. The aim of this report is to present an overview of the cost-effectiveness of maritime safety policy instruments focusing on the cost aspect: what kind of costs maritime safety policy causes, to whom, what affects the cost-effectiveness and how cost-effectiveness is studied. The study is based on a literature review and on the interviews of Finnish maritime experts. The results of this study imply that cost-effectiveness is a complicated issue to evaluate. There are no uniform practices for which costs and benefits should be included in the evaluation and how they should be valued. One of the challenges is how to measure costs and benefits during the course of a longer time period. Often a lack of data erodes the reliability of evaluation. In the prevention of maritime accidents, costs typically include investments in ship structures or equipment, as well as maintenance and labor costs. Also large investments may be justifiable if they respectively provide significant improvements to maritime safety. Measures are cost-effective only if they are implemented properly. Costeffectiveness is decreased if a measure causes overlapping or repetitious work. Costeffectiveness is also decreased if the technology isn’t user-friendly or if it is soon replaced with a new technology or another new appliance. In future studies on the cost-effectiveness of maritime safety policy, it is important to acknowledge the dependency between different policy instruments and the uncertainty of the factors affecting cost-effectiveness. The costs of a single measure are rarely relatively significant and the effect of each measure on safety tends to be positive. The challenge is to rank the measures and to find the most effective combination of different policy instruments. The greatest potential offered for the analysis of cost-effectiveness of individual measures is their implementation in clearly defined risk situations, in which different measures are truly alternative to each other. Overall, maritime safety measures do not seem to be considered burdening for the shipping industry in Finland at the moment. Generally actors in the Finnish shipping industry seem to find maintaining a high safety level important and act accordingly.

Maritime safety in the Gulf of Finland. Evaluation of the regulatory system

Growing traffic is believed to increase the risk of an accident in the Gulf of Finland. As the consequences of a large oil accident would be devastating in the vulnerable sea area, accident prevention is performed at the international, regional and national levels. Activities of shipping companies are governed with maritime safety policy instruments, which can be categorised into regulatory, economic and information instruments. The maritime regulatory system has been criticised for being inefficient because it has not been able to eliminate the violations that enable accidents. This report aims to discover how maritime governance systems or maritime safety policy instruments could be made more efficient in the future, in order to improve the maritime safety level. The results of the research are based on a literature review and nine expert interviews, with participants from shipping companies, interest groups and authorities. Based on the literature and the interviews, a suggestion can be made that in the future, instead of implementing new policy instruments, maritime safety risks should be eliminated by making the existing system more efficient and by influencing shipping companies’ safety culture and seafarers’ safety related attitudes. Based on this research, it can be stated that the development of maritime safety policy instruments should concentrate on harmonisation, automation and increasing national and cross-border cooperation. These three tasks could be primarily accomplished by developing the existing technology. Human error plays a role in a significant number of maritime accidents. Because of this, improving companies’ safety culture and voluntary activities that go beyond laws are acknowledged as potential ways of improving maritime safety. In the future, maritime regulatory system should be developed into a direction where the private sector has better possibilities to take part in decision-making.

Dam safety guide

A new Dam Safety Act (494/2009) came into force on 1st October 2009 and a Government Decree on Dam Safety (319/2010) on 5th May 2010. This Dam Safety Guide replaces the Dam Safety Code of Practice (Publication of the Ministry of Agriculture and Forestry 7/1997), removed from circulation on 1st October 2009. The Dam Safety Guide is not binding on the dam owner; the purpose is to complement and elucidate the relevant law and and decree through examples and descriptions. The Guide takes up questions concerning dam design, for instance hydrological dimensioning and technical safety requirements, dam construction and use, the dam break hazard analysis and the dam owner’s emergency action plan, maintenance, use, monitoring as well as the annual and periodic inspections. Dams are classified according to the hazard they pose into class 1, 2 or 3 dams. The classification is not needed, if, according to the dam safety authority, the dam poses no danger. The owner of a classified dam must prepare a monitoring programme, to be approved by decision of the dam safety authority. To establish the hazard caused by a dam, the owner of a class 1 dam must prepare an analysis of the dam hazard to humans and property as well as to the environment. The dam safety authority may also require a dam break hazard analysis for a dam other than class 1 dam if deemed necessary for classification. The owner of a class 1 dam must prepare a plan of measures in case of emergency or operational failure. The plan shall present the dam owner’s state of preparedness to act on their own initiative in the situations described above. In each case, the rescue authorities make a separate assessment for the need to prepare a plan as set out in the Rescue Act. The dam owner must provide the information specified in the Dam Safety Decree to be entered into the dam safety information system. The dam safety authority and the owner of the dam must keep up-to-date printouts in their own dam safety files from the information system for each dam as well as other important documents connected with dam safety to ensure that these are readily available in case of disturbance.

Efficacy, safety, quality control, marketing and regulatory guidelines for herbal medicines (phytotherapeutic agents)

This review highlights the current advances in knowledge about the safety, efficacy, quality control, marketing and regulatory aspects of botanical medicines. Phytotherapeutic agents are standardized herbal preparations consisting of complex mixtures of one or more plants which contain as active ingredients plant parts or plant material in the crude or processed state. A marked growth in the worldwide phytotherapeutic market has occurred over the last 15 years. For the European and USA markets alone, this will reach about $7 billion and $5 billion per annum, respectively, in 1999, and has thus attracted the interest of most large pharmaceutical companies. Insufficient data exist for most plants to guarantee their quality, efficacy and safety. The idea that herbal drugs are safe and free from side effects is false. Plants contain hundreds of constituents and some of them are very toxic, such as the most cytotoxic anti-cancer plant-derived drugs, digitalis and the pyrrolizidine alkaloids, etc. However, the adverse effects of phytotherapeutic agents are less frequent compared with synthetic drugs, but well-controlled clinical trials have now confirmed that such effects really exist. Several regulatory models for herbal medicines are currently available including prescription drugs, over-the-counter substances, traditional medicines and dietary supplements. Harmonization and improvement in the processes of regulation is needed, and the general tendency is to perpetuate the German Commission E experience, which combines scientific studies and traditional knowledge (monographs). Finally, the trend in the domestication, production and biotechnological studies and genetic improvement of medicinal plants, instead of the use of plants harvested in the wild, will offer great advantages, since it will be possible to obtain uniform and high quality raw materials which are fundamental to the efficacy and safety of herbal drugs.

Rigorous development of safety-critical systems

Nowadays, computer-based systems tend to become more complex and control increasingly critical functions affecting different areas of human activities. Failures of such systems might result in loss of human lives as well as significant damage to the environment. Therefore, their safety needs to be ensured. However, the development of safety-critical systems is not a trivial exercise. Hence, to preclude design faults and guarantee the desired behaviour, different industrial standards prescribe the use of rigorous techniques for development and verification of such systems. The more critical the system is, the more rigorous approach should be undertaken. To ensure safety of a critical computer-based system, satisfaction of the safety requirements imposed on this system should be demonstrated. This task involves a number of activities. In particular, a set of the safety requirements is usually derived by conducting various safety analysis techniques. Strong assurance that the system satisfies the safety requirements can be provided by formal methods, i.e., mathematically-based techniques. At the same time, the evidence that the system under consideration meets the imposed safety requirements might be demonstrated by constructing safety cases. However, the overall safety assurance process of critical computerbased systems remains insufficiently defined due to the following reasons. Firstly, there are semantic differences between safety requirements and formal models. Informally represented safety requirements should be translated into the underlying formal language to enable further veri cation. Secondly, the development of formal models of complex systems can be labour-intensive and time consuming. Thirdly, there are only a few well-defined methods for integration of formal verification results into safety cases. This thesis proposes an integrated approach to the rigorous development and verification of safety-critical systems that (1) facilitates elicitation of safety requirements and their incorporation into formal models, (2) simplifies formal modelling and verification by proposing specification and refinement patterns, and (3) assists in the construction of safety cases from the artefacts generated by formal reasoning. Our chosen formal framework is Event-B. It allows us to tackle the complexity of safety-critical systems as well as to structure safety requirements by applying abstraction and stepwise refinement. The Rodin platform, a tool supporting Event-B, assists in automatic model transformations and proof-based verification of the desired system properties. The proposed approach has been validated by several case studies from different application domains.

Sleep disorders, sleepiness and traffic safety: a public health menace

Sleep disorders are not uncommon and have been widely reported throughout the world. They have a profound impact on industrialized 24-h societies. Consequences of these problems include impaired social and recreational activities, increased human errors, loss of productivity, and elevated risk of accidents. Conditions such as acute and chronic insomnia, sleep loss, excessive sleepiness, shift-work, jet lag, narcolepsy, and sleep apnea warrant public health attention, since residual sleepiness during the day may affect performance of daily activities such as driving a car. Benzodiazepine hypnotics and zopiclone promote sleep, both having residual effects the following day including sleepiness and reduced alertness. In contrast, the non-benzodiazepine hypnotics zolpidem and zaleplon have no significant next-day residual effects when taken as recommended. Research on the effects of wakefulness-promoting drugs on driving ability is limited. Countermeasures for excessive daytime sleepiness have a limited effect. There is a need for a social awareness program to educate the public about the potential consequences of various sleep disorders such as narcolepsy, sleep apnea, shift-work-related sleep loss, and excessive daytime sleepiness in order to reduce the number of sleep-related traffic accidents.

Efficacy and safety of combined piroxicam, dexamethasone, orphenadrine, and cyanocobalamin treatment in mandibular molar surgery

Third molar extraction is a common procedure frequently accompanied by moderate or severe pain, and involves sufficient numbers of patients to make studies relatively easy to perform. The aim of the present study was to determine the efficacy and safety of the therapeutic combination of 10 mg piroxicam, 1 mg dexamethasone, 35 mg orphenadrine citrate, and 2.5 mg cyanocobalamin (Rheumazin®) when compared with 20 mg piroxicam alone (Feldene®) in mandibular third molar surgery. Eighty patients scheduled for removal of the third molar were included in this randomized and double-blind study. They received (vo) Rheumazin or Feldene 30 min after tooth extraction and once daily for 4 consecutive days. Pain was determined by a visual analogue scale and by the need for escape analgesia (paracetamol). Facial swelling was evaluated with a measuring tape and adverse effects and patient satisfaction were recorded. There was no statistically significant difference in facial swelling between Rheumazin and Feldene (control group). Both drugs were equally effective in the control of pain, with Rheumazin displaying less adverse effects than Feldene. Therefore, Rheumazin appears to provide a better risk/benefit ratio in the mandibular molar surgery. Since the side effects resulting from nonsteroidal anti-inflammatory drug administration are a severe limitation to the routine use of these drugs in clinical practice, our results suggest that Rheumazin can be a good choice for third molar removal treatment.

A safety and feasibility study of cell therapy in dilated cardiomyopathy

The aim of this study was to determine if bone marrow mononuclear cell (BMMC) transplantation is safe for moderate to severe idiopathic dilated cardiomyopathy (IDC). Clinical trials have shown that this procedure is safe and effective for ischemic patients, but little information is available regarding non-ischemic patients. Twenty-four patients with IDC, optimized therapy, age 46 ± 11.6 years, 17 males, NYHA classes II-IV, and left ventricular ejection fraction <35% were enrolled in the study. Clinical evaluation at baseline and 6 months after stem cell therapy to assess heart function included echocardiogram, magnetic resonance imaging, cardiopulmonary test, Minnesota Quality of Life Questionnaire, and NYHA classification. After cell transplantation 1 patient showed a transient increase in enzyme levels and 2 patients presented arrhythmias that were reversed within 72 h. Four patients died during follow-up, between 6 and 12 weeks after therapy. Clinical evaluation showed improvement in most patients as reflected by statistically significant decreases in Minnesota Quality of Life Questionnaire (63 ± 17.9 baseline vs 28.8 ± 16.75 at 6 months) and in class III-IV NYHA patients (18/24 baseline vs 2/20 at 6 months). Cardiopulmonary exercise tests demonstrated increased peak oxygen consumption (12.2 ± 2.4 at baseline vs 15.8 ± 7.1 mL·kg-1·min-1 at 6 months) and walked distance (377.2 ± 85.4 vs 444.1 ± 77.9 m at 6 months) in the 6-min walk test, which was not accompanied by increased left ventricular ejection fraction. Our findings indicate that BMMC therapy in IDC patients with severe ventricular dysfunction is feasible and that larger, randomized and placebo-controlled trials are warranted.