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Voveran

Mark J. Seamon MD

  • Assistant Professor of Surgery, Division of Trauma and Surgical Critical Care,
  • Department of Surgery, Temple University School of Medicine, Philadelphia,
  • Pennsylvania

Methods for applying strength of evidence assessments are established in the "Grading the Strength of a Body of Evidence When Comparing Medical Interventions" chapter of the Methods Guide59 and are based on consideration of four domains: risk of bias muscle spasms youtube purchase cheap voveran online, consistency in direction of the effect spasms 24 generic 50 mg voveran otc, directness in measuring intended outcomes muscle relaxant japan purchase voveran 50mg visa, and precision of effect (Table 4) spasms around the heart cheap voveran 50mg visa. Domains used to assess strength of evidence Domain Risk of bias Explanation a Degree to which the included studies for a given outcome or comparison have a high likelihood of adequate protection against bias gas spasms purchase voveran 50mg on line. Information for this determination comes from the rating of quality (good/fair/poor) done for individual studies spasms video cheap 50mg voveran otc. Consistency Degree to which reported effect sizes from included studies appear to have the same direction of effect. Directness Relates to whether the evidence links the interventions directly to health outcomes. For a comparison of two treatments, directness implies that head-to-head trials measure the most important health or ultimate outcomes. In this case, one body of evidence links the intervention to intermediate outcomes and another body of evidence links the intermediate to most important (health or ultimate) outcomes. Indirectness always implies that more than one body of evidence is required to link interventions to the most important health outcomes. Precision is the degree of certainty surrounding an effect estimate with respect to a given outcome. If a meta-analysis was performed, this will be the confidence interval around the summary effect size. Further research may change our confidence in the estimate of effect and may change the estimate. Further research is likely to change confidence in the estimate of effect and is also likely to change the estimate. Prior Systematic Reviews One prior systematic review met all of our criteria and was used in its entirety in our review. No well-designed studies-only case studies/case descriptions, or cohort studies/single-subject series with no multiple baselines. Applicability Finally, it is important to consider the ability of the outcomes observed to apply both to other populations and to other settings (especially for those interventions that take place within a clinical/treatment setting but are hoped to change behavior overall). Our assessment of applicability included determining the population, intervention, comparator, outcomes and setting in each study and developing an overview of these elements for each intervention category. Results of Literature Searches and Description of Included Studies Article Selection We conducted a broad search to identify any titles or abstracts that might include relevant data for the review. Of the entire group of 1,055 titles and abstracts, we reviewed the full text of 553 because they either appeared to meet criteria or did not provide enough information in the abstract to determine definitively that they should be excluded (Figure 2). Of the 546 full text articles reviewed, 15 articles (comprising 13 unique studies) met our inclusion criteria. This figure includes 12 unique primary research studies (reported in 14 publications) described in this comparative effectiveness review and one systematic review meeting our inclusion criteria. As indicated in Figure 2, we were unable to obtain the full text of eight studies. Table 6 summarizes characteristics of the primary literature meeting our criteria and not addressed in prior systematic reviews summarized here. Compared with other nonsurgical interventions or no intervention, how effective are behavioral interventions, including positioning, oral appliances, oral stimulation, sensorimotor facilitation, and caregiver training, for improving nutritional state/growth, health outcomes and health care/resource utilization, and quality of life in individuals with cerebral palsy and feeding difficulties Strength of evidence (confidence in the estimate of effect) for these interventions across outcomes therefore ranged from insufficient to low. The small, short-term case series of a caregiver intervention66 reported some pre- to postintervention improvements in oral-motor behaviors (increase in number of children able to perform some self-feeding from 0 to 6), caregiver stress (18 indicated feeling very stressed pre-intervention to 2 post), and number of chest infections (15 pre-intervention vs. We assessed the review as good quality as it reported search procedures, assessed and reported quality of studies, and appropriately synthesized results. Most (13 of 21) studies would have met inclusion criteria for our review as well; those that did not were either case reports, published prior to 1980, or did not address interventions of interest. Included studies were assessed as oral sensorimotor facilitation ("techniques specific to the enhancement of oral-motor control aim[ing] to decrease or increase tone and inhibit abnormal reflexes that interfere with safe feeding"34), food consistency, positioning, oral appliances, or adaptive equipment. We summarize key findings of the studies included in the review below: Sensorimotor Interventions Six studies of sensorimotor interventions were included. The remaining studies all were smaller and of poorer quality and results were mixed. Two studies by the same group as that above appear to provide data on overlapping patients and provided data separately for children with and without a history of aspiration. In a case series of eight children with spastic diplegia, sensorimotor treatment provided four times per day was associated with increased efficiency of chewing and swallowing skills, caloric consumption, and gains in height and weight. Four studies of positioning70,76-78 were included in the Snider review, none of which was a comparative study; thus all studies had a high risk of bias. The largest included 24 participants evaluated before and after use of a thoracic-lumbar-sacral orthosis kept within a nonrigid frame. In one study with five participants, videofluoroscopy was used to visualize the effectiveness of feeding in a 30 percent reclined position. Two participants showed a decrease in oral leakage and ability to consume purees improved. Another case series using videofluoroscopy reported that the best reclining position depended on the phase of feeding in which problems occurred. Positioning Altering Food Consistency the one study on altering food consistency79 in the Snider review would not have met criteria for inclusion in our review on the basis that the study provided no pre-post data and did not include an untreated or differently treated comparison group. Oral Appliances Eight studies of oral appliances were included in the Snider review. Oral-motor skills improved during the stabilization (initial) period in each group, but not in the control period during which standard rehabilitation took place. No significant improvements in weight or feeding skills (our primary outcomes) could be attributed to the treatment; rather these physical changes occurred equally in the two groups and were thus associated with maturation. Two papers69,84 report on participants randomized to immediate versus delayed treatment, followed by cessation of use by one group while the other continued use. At this point in time, no significant differences were observed, suggesting that maturation accounted for improvements in the second year. A small study with seven subjects reported improvements in lip seal, nasal breathing, transport of saliva and speech articulation. Harms noted in the studies include worsening of isolated oral functions (leading to discontinuation of the device in 5 participants)81 and discomfort associated with the device. Electric feeder (Handy 1 Robotic Aid to Eating) 27 Summary of Primary Research In updating the Snider review described above, we identified one case series addressing caregiver training. Pairs received advice and completed a baseline assessment during an initial home session and then participated in four to six sessions focused on improving dietary intake and ease and efficiency of feeding, including introduction of a high calorie diet, adaptation of food consistency, use of appropriate utensils and provision of appropriate postural and physical support. Children had significantly fewer episodes of chest-related illness after 3 months (15 vs. Observed child feeding skills and affect also improved, with a significant decrease in child fussiness and food refusal and improvement in general mood and child feeding skills (p<0. At baseline, nine children always refused food, no children were involved in self-feeding, and six were observed munching or chewing. At 4 to 6 months after the caregiver training, only one child was observed refusing food and six and eight children were involved in self-feeding and demonstrated munching or chewing, respectively. The authors also reported a significant improvement in caregiver self-reported stress and reduction in mealtime length (p=0. Is the effectiveness of behavioral interventions modified by age, race, severity, functional status. One study reported in the Snider review provides data separately for children with and without a history of aspiration. Compared with other nonsurgical interventions or no intervention, how effective are nutritional interventions (food thickeners, caloric supplementation with formulas, vitamin supplementation, and altering food consistency. No studies met criteria to address this question although pureed food was used in conjunction with positioning and sensorimotor interventions described in the review by Snider and colleagues. Is the effectiveness of nutritional interventions modified by age, race, severity, functional status. What is the comparative effectiveness of tube feeding compared with oral feeding or to nutritional and behavioral interventions in individuals with cerebral palsy who present with feeding difficulties, including malnourishment, failure to thrive, aspiration and excessive caregiver burden Case series included <60 participants each and reported improvements in weight gain, most measures of caregiver satisfaction, and hospitalizations due to chest infections. The prospective cohort focused on potential overfeeding compared orally fed and gastrostomy-fed children and reported no significant differences between tube-fed and orally fed groups in normalized weight and skinfold z-scores, energy expenditure, resting metabolic rate, fat mass index, or fat-free mass index, but both groups had higher body fat content than a reference population of age- and sex-matched typically developing children. The case series assessing a low energy feed reported weight gain without a corresponding increase in fat mass. The strength of the evidence was low for measures of growth and harms of gastrotomy and insufficient for all other outcomes (respiratory outcomes including reflux, quality of life, long term morbidity and mortality). Children either had gastrostomy (n=22) or were able to eat orally (n=18) and were evaluated using growth measures and energy expenditure. Across studies, followup typically occurred 6 to 12 months after surgery, with one study following patients for up to 41 months91 and another for a median of 55 days. The prospective cohort study was intended to assess potential harms of treatment and is therefore discussed in detail in that section, below. The one multicenter, prospective case series provides the most detailed outcomes data available. Eighteen children with significant reflux (determined by a reflux index > 10% as proposed by Sullivan 199997) had fundoplication performed at the same time as gastrostomy. None of the children had experienced adequate (not defined) weight gain for at least 12 months prior to surgery. Although there was no active comparison group in this study, standards for typically developing children were used as a reference. Median weight z-scores (relative to standards for typically developing children of the same age and sex) increased from -3 at baseline to -1. Thus, improvements were observed and were statistically significant for every measure of growth (p values ranging from <0. Energy intake as measured by 3-day dietary records maintained by caregivers increased, and the proportion of children experiencing at least one infection requiring hospitalization decreased from 26 to 7 percent (p=0. A separate analysis of chest infections showed a significant decrease in the mean number of infections requiring antibiotics from baseline to 12 month followup (mean at baseline=1. Another prospective case series conducted in Brazil included 16 children (mean age 6. Weight, but not height or skinfold, z-scores significantly increased from baseline across all participants (data presented graphically only). Fifty-six percent (n=32) of participants had Nissen fundoplication as well as gastrostomy, suggesting that at least half had substantial reflux prior to surgery; two of these later required jejunostomy after failed fundoplication. Baseline and followup data were available for 35 participants; among these, roughly 70 percent remained below the 5th percentile for height and weight post-gastrostomy. Roughly half (46%) attained appropriate weight for height standards, 21 percent were overweight, and 33 percent were underweight. In subgroup analyses, at least 50 percent of children with gastrostomy before age 2; those with gastrostomy for more than 2 years; and those with fundoplications reached appropriate weight for height. Caregivers generally reported satisfaction with gastrostomy and noted increased ease of feeding and improvements in child affect. Baseline scores on all measures were lower than those for the population norm at baseline. By 12 months, scores had improved on all measures and improved significantly (p values <0. Ratings on questions related to global health, impact on activities, and impact on feeding improved at 6 months, but improvements were not sustained at the final, 12-month followup. Ratings on questions related to impact on parental time and medications improved significantly at 12 months (p0. Investigators also used a reference population of normally developing children for comparison. Twenty-two children were gastrostomy fed (approximately 2/3 also underwent preoperative nasogastric tube feeding prior to gastrostomy), and 18 were fed orally. At followup, the gastrostomy group had greater fat mass than the orally fed group, and had lower fat-free mass, but the differences were not statistically significant. The investigators note that results may be confounded by preoperative nasogastric tube feeding in the gastrostomy group and ongoing nutritional therapy (caloric supplementation and/or enteral feeds) in the orally fed participants, and the degree to which gastrostomy may be associated with poor outcomes from overfeeding remains unclear. All participants were solely tube-fed, and seven of 14 had undergone fundoplication in addition to gastrostomy. Six month followup data were available for eight of the 14 participants; three participants died of respiratory infections in the study period. Fat mass and body fat percentage increased, but not significantly (fat mass at baseline=3. Fat mass was not significantly different from that of a reference group of children without disability, though these data should be interpreted with caution given the limited comparability of the two groups. Micronutrient levels were largely within normal limits both prior to and after gastrostomy feeding, with levels of zinc, coper, vitamin B1 and chromium elevated beyond recommended ranges at followup. Fiber intake remained below recommended levels, and bowel movement frequency was generally unchanged over the study period.

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The land that was once being desertified became green and the amount of yellow sand blown into Beijing has also been significantly reduced muscle spasms yahoo answers quality voveran 50 mg, helping improve its environment muscle relaxant back pain over counter discount voveran uk. With the aim of contributing to society muscle relaxant baclofen generic voveran 50 mg without prescription, we will work together with organizations engaged in nature conservation around the world by establishing projects to solve issues in the areas of living in harmony with nature and biodiversity muscle relaxant rocuronium order voveran online now. The event received favorable comments from many government officials infantile spasms 4 months purchase voveran 50mg with visa, including a high-ranking officer in the Secretariat of the Convention on Biological Diversity muscle relaxant neck purchase voveran 50mg mastercard. Toyota has been supporting important activities for expanding the Red List and has provided vehicles to the two organizations since 2016. The November 2018 update reported that the number of mountain gorillas, an Endangered species, was beginning to recover as a result of cross-border conservation activities and community involvement. To promote biodiversity conservation under the partnership, Toyota has made annual one million U. And, in November 2018, these organizations successfully rescued a Sumatran rhinoceros on the island of Borneo and immediately transferred it to a safe protective facility. Safely capturing an animal living in a high-risk area was hailed as a very positive event by interested parties. Additionally, continued patrol of the Tesso Nilo National Park has significantly reduced illegal logging of the forest. Toyota Environmental Activities Grant Program In 1999, Toyota was honored with the Global 500 Award from the United Nations Environment Programme. Grants are offered to support projects overseas (up to seven million yen per project) and projects in Japan (up to three million yen or one million yen per project). Over the 19 years since the program was established, we have supported 387 projects in 54 countries and regions worldwide. It is trying to increase the scale of its activities through collaboration with initiatives in other regions inside and outside Japan, as well as mutual learning. Specific initiatives included supporting introduction of sustainable organic farming, and developing teaching materials for building a sustainable community, targeted at elementary and junior high school students. Furthermore, since many similar issues are found throughout Asia, the project is also taking actions to spread the initiative to other regions, for example, holding workshops that cover a wide area in order to develop the human resources necessary for continuing activities and build consensus. The project has helped people deepen their understanding about the value of natural resources and continue to autonomously manage the systems that have been built. Consequently, the Toyota Education for Sustainable Development Project promotes sustainable human resource development suited to local communities. Our corporate training approach is to nurture environmentally conscious employees and leverage their awareness to make it better for business. Additionally, we are connecting our training activities to the future by making the best use of the features of business sites and company-owned fields to provide environmental education for children, who will be responsible for sustainable societies in the future. Toyota Shirakawa-Go Eco-Institute will continue to develop new hands-on nature programs to nurture an awareness of living in harmony with nature among a growing number of adults and children. As a follow-on activity, in July 2018, we held an event in which participants themselves planned and implemented a dragonfly-based environmental education program. Dragonflies are familiar creatures that make use of the waterside environments that people create in their lives. They can be easily adopted as an environmental education theme because their egglaying and hatching behaviors can be observed. An expert provided basic knowledge about dragonflies, including the roles they play in the ecosystem and the current status of marshes they inhabit, and the forest interpreter explained the detailed ecology and key points in planning an observation tour. The participants considered the impact people have on nature and the need for living in harmony with nature. We plan to continue holding environmental programs that will take advantage of familiar creatures to teach people about nature and encourage them to take action. Forest of Toyota Forest of Toyota in Toyota City is a company-owned forest near the urban areas. It has been maintained based on the environment of satoyama, which was once part of our lives, creating a forest where living creatures can naturally inhabit. Forest of Toyota was opened to the public in 1997, and anyone can walk freely through it and take part in various events to experience the satoyama environment and learn about nature through their five senses. Since 2001, we have also provided hands-on learning events for local elementary school children. Although this region has the history of timber industry, a decline in domestic forestry had left much of the forest unmaintained. Over the last 10 years, we have been thinning the forest, and as well as providing other functions which benefit the public, such as soil and water conservation, we have also been extracting and utilizing logs that can be used as lumber. Furthermore, by introducing automobile manufacturing expertise to forest management, we are achieving efficient management. Business plans were widely collected from the public, and participants selected through screening started their projects in April 2018. One of the participants, a woodworking artist, is collaborating with a local, nationally renowned frame maker to develop carefully designed wooden products for daily life. He is also promoting a project that connects items produced from forests with consumers who use those items, while deepening his connection with the local community, for example, by holding a woodworking workshop at local Subaru Gakuen High School, Mie Prefecture. Initiatives at the New Toyota R&D Center Promoting Harmony with Nature and Local Communities Toyota is constructing a new R&D Center in the overlapping area of Toyota City and Okazaki City. This new facility will be a hub for development of sustainable next-generation mobility. The main design concept is a technical center in harmony with nature and local communities. About 60 percent of the total project site will be conserved as areas for the regeneration of forests and management of valley bottom rice fields in collaboration with the local community. In April 2019, work was completed on the central section of the new R&D Center which takes a county road as its primarily feature. Partial operation Woodworking workshop Sustainability Data Book 2019 As one of the new projects, an event to walk with your dog in the forest called "Doggies Playing in the Forest" was held. We are aiming to build a framework that can return the profits from the events to the forests. Through these initiatives, we are hoping to increase the number of people who are involved with forests and trees, and promote new future projects so that our program can become a model for revitalizing local communities and forests. Toyota intends to continue cooperating with experts, local governments, and local residents to conduct environmental conservation activities in the forest and valley bottom rice fields of this valuable satoyama ecosystem. We also plan to actively share information including the status of these activities and findings gained from them. After nesting was confirmed, several protective steps were implemented under the guidance of experts. For example, slopeplanting work and blasting near the nesting site were temporarily halted, and entry by weed-cutting workers was restricted. Hand-carved butter knives of the site as "Toyota Technical Center Shimoyama" is now underway. In addition, the Toyota Global Vision announced in 2011 emphasizes the importance of "Respect for the Planet" and positions the environment as one of three values that Toyota provides to society. Under this structure, Toyota is promoting steadily, the environmental management activities globally, including legal compliance activities, collaboration with business partners, and employee education. These committees consider issues and responses, and all relevant divisions work together to carry out company-wide initiatives. Consolidated subsidiaries Parts manufacturers Consolidated subsidiaries Various other products production companies Companies not subject to consolidated accounting Parts manufacturers Daihatsu Motor Co. These committees steadily promote environmental initiatives and enhance our global responses. Maximize environmental performance Varies according to the nature of business Main Overseas Scope (as of End of March 2019) Europe region 37 subsidiaries European Environment Committee China region 14 subsidiaries China Environment Committee (Established 2007) North America region 18 subsidiaries North America Environment Committee (Established 2004) (as of March 31, 2019) (Established 2002) Group 2 All-Toyota Production Environment Conference Members Production Companies (40 companies) Group 3 Cataler Corporation, Central Motor Wheel Co. Africa region 3 subsidiaries South Africa Environment Committee (Established 2008) Asia region 21 subsidiaries Asia Environment Committee (Established 2007) South America region 3 subsidiaries South America Environment Committee (Established 2006) Group 4 All-Toyota Production Environment Meeting Members Group 5 the Asia Pacific Environment Committee was changed to the Asia Environment Committee in 2019 Logistics Companies (4 companies) Consolidated subsidiaries Completed vehicle distribution Parts distribution All-Toyota Logistics Environment Conference Members (50 companies) Sales Companies Fukuoka Toyopet Corporation, Toyota Corolla Aichi Co. Awards for production and logistics companies to encourage environmental kaizen activities at overseas affiliates for carrying out the Toyota Environmental Challenge 2050 and promote yokoten of the best kaizen practices. The presentations included an example of identification, recovery, and use of "discarded heat" from a painting plant air conditioning floor, and an example of analysis of local regional weather to identify and improve optimal operational patterns for equipment such as refrigerators, booth air conditioning, and ovens. Through the presentations, each affiliate learned the beneficial aspects of other examples, for use in higher-level kaizen activities around the world. Our eco-factory activities are to build and develop a mechanism which surely incorporates environmental measures into each stage from planning to design and operations. These measures will be utilized for projects such as construction of new plants, major renovations of existing plants, and capacity expansions. We will continue to promote eco-factory activities as a means to contribute to regional environmental conservation around the world. Toyota aims to ensure that its production activities pose zero environmental risk to local communities. The foundation of our efforts is preventive measures to avoid non-compliance issues and complaints. Neglecting preventive measures can lead to situations where non-compliance may occur. We consider these situations to be non-compliance near-misses, and we take stringent measures to root out the causes of these near-misses and prevent reoccurrence. For incidents posing significant risk, we share information on reoccurrence prevention measures through environmental affairs meetings at all Group companies. Additionally, we are taking measures to completely eliminate the use of ozone-depleting substances, and no significant releases have been found. However, there were six minor non-compliance issues among the environmental management companies (five in Japan and one overseas). At six of our production plants, we completed groundwater pollution prevention measures in 1997. We continue to conduct pumping aeration and purification to complete purification and ensure that groundwater is purified to levels below standards. The levels of trichloroethylene at production plants are reported to the government and to local councils in the surrounding communities. We are also conducting cooperative atmospheric environment research according to the research levels and needs of each country and region, contributing to improvement of the atmospheric environment around the world. We actively participate in atmospheric enhancement measures conducted by the Japan Automobile Manufacturers Association and conduct joint research with research institutions, universities, and other organizations in countries worldwide. The program enables us to assess environmental risks and opportunities across the supply chain. To properly respond to these regulations, Toyota has built and is operating chemical substance management frameworks in cooperation with its suppliers. After announcing the Toyota Environmental Challenge 2050, we revised guidelines in January 2016, working with suppliers to maintain existing measures including compliance with the laws and regulations of each country and managing substances of concern and undertake an even broader range of environmental initiatives to reduce greenhouse gases, assess water risks and reduce impact on water environments from those risks, encourage resource recycling, and protect ecosystems in support of the Challenge. We request that our tier 1 suppliers to roll out environmental initiatives to their suppliers, and we seek to realize the entire supply chain2 management in the pursuit of a sustainable society. Toyota released the Green Purchasing Guidelines published not only in Japan, but also at overseas purchasing sites. We will continue to request suppliers to promote initiatives in accordance with the guideline. In January 2019, theme-specific research groups of the Kyohokai, which is consisted of more than 200 parts suppliers, commenced activities on environmental topics. The aim is to enhance environmental management of each company by exchanging information among companies and conducting lectures by experts. Promote Environmental Activities in Cooperation with Business Partners (Dealers and Distributors) Sales and Service Toyota has strong bonds of trust with its dealers and distributors built on shared values for products and services, supporting a long history of collaborative initiatives in environmental activities. Given their direct contact with customers, dealers are a critical partner in carrying out environmental initiatives. This program is intended to conduct audits of five fundamental environmental items including the proper management of waste and treatment of water discharge. All 5 requirements were satisfied by 4,325 dealers, 96 percent of all participating dealers (up 1 percent year on year). To raise interest, throughout the year we devised innovations such as "information that can be touched" and "information that enters the eyes. During the Water Week Campaign in August, a special page was created on the intranet to inform employees about water issues and the importance of water resources. Educational stickers were also utilized within the company to convey the importance of water resources. These innovative measures were taken to lower the hurdles to participation and educate participants on the importance of natural water. The posters were also displayed in key stations in Tokyo, Nagoya, and Osaka in March, raising awareness and understanding. In 1991, we changed the name to "Toyota Global Environment Month," and we are expanding activities globally. The instructors for the ninth environmental lecture were Hiroko Ida, a weather forecaster, and Seita Emori, a researcher at the National Institute for Environmental Studies, Japan. They gave a lecture entitled "Weather Forecast for 2050: Take Action Now to Preserve a Beautiful Earth 30 Years in the Future. Phase: Act Similar to the previous year, an Environmental Campaign of Creative Suggestion System was conducted as a main program of Toyota Global Environment Month, and a wide variety of environmental proposals were submitted, raising awareness. In addition, measures were taken during the period from October to December, which includes Eco-Drive Month in November, to raise awareness and increase understanding among employees regarding eco-driving. Specifically, we created posters that create a lasting impression with messages that cite 10 key elements of eco-driving recommendations intertwined with athletes affiliated with Toyota. The training provides an opportunity for employees to consider and be aware of the environment as a personal issue after they are assigned and to acquire Sustainability Data Book 2019 the basis for putting that awareness into practice in their day-to-day activities. The video introducing the Toyota Environmental Challenge 2050 employs pop-style animation. In February 2019, our Environmental Report 2018 won the Grand Prize (Minister of the Environment Prize) in the Environmental Reporting Category at the 22nd Environmental Communication Awards sponsored by Ministry of the Environment of Japan and other organizations.

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In addition to being an important cause of mortality quetiapine muscle relaxer voveran 50 mg discount, the disability burden from stroke and other cerebrovascular diseases is also substantial (Murray et al spasms 1983 cheap voveran 50 mg line. There are large variations in cerebrovascular disease mortality rates across countries (Figure 3 muscle relaxant 2mg order voveran 50mg on-line. The high prevalence of risk factors common to both diseases (such as smoking and high blood pressure) may explain this link muscle relaxant trade names cheap 50mg voveran with mastercard. In Estonia spasms near ribs purchase discount voveran online, Luxembourg and Portugal muscle relaxant herniated disc discount 50mg voveran overnight delivery, the rates have been cut by at least two-thirds, although in Estonia this is partly due to a change in death recording practices with a greater recording of other related causes of death such as hypertension. Definition and comparability Mortality rates are based on numbers of deaths registered in a country in a year divided by the size of the corresponding population. The rising share of deaths due to cancer reflects the fact that mortality from other causes, particularly cardiovascular diseases, has been declining more rapidly than mortality from cancer. There are more than 100 different types of cancers, with most named for the organ in which they start. For a large number of cancer types, the risk of developing the disease rises with age. While genetics is a risk factor, only about 5% to 10% of all cancers are inherited. Modifiable risk factors such as smoking, obesity, lack of exercise and excess sun exposure, as well as environmental exposures, explain up to 90-95% of all cancer cases (Anand et al. Mortality due to cancer was lowest in Mexico, Turkey, Finland, Switzerland and Japan, with rates less than 180 per 100 000 population. Hungary, Slovenia, the Slovak Republic and Denmark bear the highest cancer mortality burden, with rates in excess of 240 per 100 000 population. Mortality due to cancer is consistently higher for men than for women in all countries. The gender gap is particularly wide in Korea, Turkey, Estonia, Spain and Portugal, with rates among men more than twice those for women. This gender gap can be explained partly by the greater prevalence of risk factors among men, notably smoking rates. Among men, lung cancer imposes the highest mortality burden, accounting for 26% of all cancer-related deaths (Figure 3. In many countries, lung cancer mortality rates for men have decreased over the last 20 years. But lung cancer mortality has risen for women in several countries such as France and Spain where it has more than doubled since 1990. These conflicting trends are, to a large degree, explained by the high number of females who started smoking several decades later than males (in the 1980s and 1990s). While there has been an increase in the incidence of breast cancer over the past decade, mortality has declined in most countries due to earlier diagnosis and better treatment. Mortality from breast cancer increased somewhat in Korea and Japan, although the rates there remained the lowest in 2013. Mortality rates from breast cancer in 2013 were highest in Denmark, Hungary, Belgium, Ireland, Slovenia and the Netherlands (see indicator "Screening, survival and mortality for breast cancer" in Chapter 8). Colorectal cancer is a major cause of cancer mortality among both men and women (second-highest cause of cancer mortality in men and third in women). In 2013, colorectal cancer mortality was lowest in Mexico and Turkey, and highest in Hungary and the Slovak Republic (see indicator "Survival and mortality for colorectal cancer" in Chapter 8). Mortality from prostate cancer remains lower than for lung cancer in all countries except in Chile and Mexico, where it is the leading cause of cancer deaths in men, and in some Nordic countries (Iceland, Norway and Sweden) where mortality from prostate and lung cancer are almost equal. Mortality rates from prostate cancer in 2013 were lowest in Japan and Korea, and highest in Estonia and Iceland. Substantial declines in mortality from stomach cancer, colorectal cancer, lung cancer for men, breast, cervical and ovarian cancer for women, as well as prostate cancer for men contributed to this reduction. However, these gains were partially offset by increases in the number of deaths due to cancer of the liver, skin and pancreas for both sexes, as well as lung cancer for women. The international comparability of cancer mortality data can be affected by differences in medical training and practices as well as in death certification across countries. Most fatal traffic injuries occur in passenger vehicles, although other road users also face substantial risks. In Korea, Japan, Israel and Poland, pedestrians account for over one third of all road user fatalities. There is considerable variation between countries with transport accidents claiming more than five times as many lives per 100 000 population in Mexico compared to the United Kingdom and Sweden. Mortality rates from road transport accidents were also relatively high in Korea, Chile and the United States. Road safety for car occupants has increased greatly over the past decades in many countries through improvements of road systems, education and prevention campaigns as well as vehicle design. In addition, the adoption of new laws and regulations and the enforcement of these laws to improve compliance with speed limits, seatbelt use and drink-driving rules have had a major impact on reducing the burden of road transport accidents. As a result, deaths due to transport accidents have decreased in almost all countries over the last few decades. Declines in mortality rates for vulnerable road users such as pedestrians, cyclists and motorcyclists were substantially less than those for car occupants. Reductions in deaths among pedestrians, cyclists and motorcyclists have levelled-off and some increases have been recorded. The economic crisis has contributed to the reduction in road traffic deaths in many countries, by reducing the distance travelled (especially by young men and by trucks). A complex set of reasons may explain why some people choose to attempt or commit suicide. A high proportion of people who have attempted or committed suicide are suffering from psychiatric disorders such as severe depression, bipolar disorder and schizophrenia. Low income, alcohol and drug abuse, unemployment and social isolation are all associated with higher rates of suicide. Korea had the highest suicide rate with nearly 30 deaths per 100 000 population, followed by Japan, Hungary and Slovenia with nearly 20 deaths per 100 000 population. In Poland and the Slovak Republic, men are seven times more likely to commit suicide than women. The gender gap is narrower for attempted suicides, reflecting the fact that women tend to use less fatal methods than men. Suicide is also related to age, with young people aged under 25 and elderly people especially at risk. While suicide rates among the latter have generally declined over the past two decades, less progress has been observed among younger people. In Estonia, after an initial rise in the early 1990s, the rates have also fallen sharply. In Japan, there was a sharp rise in the mid-to-late 1990s, coinciding with the Asian financial crisis, but rates have started to come down in recent years. In Korea, suicide rates rose steadily over the past two decades peaking around 2010, before starting to come down (Lim et al. Suicide is often linked with depression and the abuse of alcohol and other substances. Early detection of these psychosocial problems in high-risk groups by families and health professionals is an important part of suicide prevention campaigns, together with the provision of effective support and treatment. Many countries are developing national strategies for prevention, focusing on at-risk groups. Mental health services in Korea lag behind those of other countries with fragmented support, focused largely around institutions, and insufficient or ineffective support services provided to those who remain in the community. Previous studies have shown a strong link between adverse economic conditions and higher levels of suicide (Van Gool and Pearson, 2014). Suicide rates rose slightly at the start of the economic crisis in 2008-2009 in a number of countries, but this trend did not persist in most. In Greece, suicide rates were stable in 2009 and 2010, but have increased since 2011 (Figure 3. All countries need to continue monitoring developments closely in order to be able to respond quickly, including monitoring high-risk populations such as the unemployed and those with psychiatric disorders (see indicator "Mental health care" in Chapter 8). Definition and comparability the World Health Organization defines suicide as an act deliberately initiated and performed by a person in the full knowledge or expectation of its fatal outcome. Mortality rates are based on numbers of deaths registered in a country in a year divided by the size of the corresponding population. Suicide, 2013 (or nearest year) Men Age-standardised rates per 100 000 population 45 40 35 30 25 20 15 10 5 0 ic o It a ly Is ra Un el i the d Sp a Ki in ng d Po om Lu r t xe u g m al bo u Au rg 1 st ra C li a Ne an th ada er la Ge nds rm a No ny rw ay Ch il e N e Ir e w lan Ze d al De and nm Sl ov ar ak k Re I c p. In some large partner countries (India, South Africa and Indonesia), infant mortality remains above 20 deaths per 1 000 live births. In India, one-in-twenty-five children die before their first birthday, although the rates have fallen sharply over the past few decades. Birth defects, prematurity and other conditions arising during pregnancy are the main factors contributing to neonatal mortality in developed countries. With an increasing number of women deferring childbearing and a rise in multiple births linked with fertility treatments, the number of pre-term births has tended to increase (see indicator "Infant health: low birth weight"). In a number of higher-income countries, this has contributed to a levelling-off of the downward trend in infant mortality over the past few years. One of the explanations that have been given for that the high rate of infant mortality in the United States is that it is based on a more complete registration of very premature and low birth weight babies than in many other countries (Joseph et al. In order to remove the impact of differences in registration practices of very small babies, the figures shown in Figure 3. There are large differences in infant mortality among racial groups in the United States, with Black women more likely to give birth to low birth weight infants, and with infant mortality more than double that for White women (10. Many studies use infant mortality as a health outcome to examine the effect of a variety of medical and non-medical determinants of health. Although most analyses show that higher health spending tends to be associated with lower infant mortality, the fact that some countries with a high level of health expenditure do not exhibit low levels of infant mortality suggests that more health spending is not necessarily required to obtain better results (Retzlaff-Roberts et al. Definition and comparability the infant mortality rate is the number of deaths of children under one year of age, expressed per 1 000 live births. Some of the international variation in infant mortality rates is related to variations in registering practices for very premature infants. While some countries register all live births including very small babies with low odds of survival, several countries apply a minimum threshold of a gestation period of 22 weeks (or a birth weight threshold of 500 grams) for babies to be registered as live births (Euro-Peristat, 2013). References Euro-Peristat (2013), European Perinatal Health Report: the Health and Care of Pregnant Women and their Babies in 2010, Luxembourg. Tu ica rk e Ch y in Br a M a zi C o ex i l l co In o m S o do bi a ut nes h ia Af ric In a di a Note: the data for most countries are based on a minimum threshold of 22 weeks of gestation period (or 500 grams birthweight) to remove the impact of different registration practices of extremely premature babies across countries. There are two categories of low birth weight babies: those occurring as a result of restricted foetal growth and those resulting from pre-term birth. Low birth weight infants have a greater risk of poor health or death, require a longer period of hospitalisation after birth, and are more likely to develop significant disabilities. Risk factors for low birth weight include maternal smoking, excessive alcohol consumption, poor nutrition, low body mass index, lower socio-economic status, and having had in-vitro fertilisation treatment and multiple births. The proportions of low-weight births were lowest in Nordic countries (Iceland, Finland, Sweden, Norway, with the exception of Denmark) and Estonia, with less than 5% of live births defined as low birth weight. Despite the widespread use of a 2 500 grams limit for low birth weight, physiological variations in size occur across different countries and population groups, and these need to be taken into account when interpreting differences (Euro-Peristat, 2013). Some populations may have lower than average birth weights than others because of genetic differences. There are several reasons for this rise, including a growing number of multiple pregnancies mainly as a result of the rise in fertility treatment, and a rise in maternal age (Delnord et al. Another factor which may explain the rise in low birth weight infants is the increased use of delivery management techniques such as induction of labour and caesarean delivery, which have increased the survival rates of low birth weight babies. In Japan, this increase can be explained by changes in obstetric interventions, in particular the greater use of caesarean sections, along with changes in maternal socio-demographic and behavioural factors (Yorifuji et al. In Greece, the rise in the proportion of low birth weight babies started in the mid-1990s, well before the economic crisis, and peaked in 2010. Some researchers have suggested that the high rates of low birth weight babies between 2009 and 2012 were linked to the economic crisis and its impact on unemployment rates and lowering family incomes in Greece (Kentikelenis, 2014). Comparisons of different population groups within countries indicate that the proportion of low birth weight infants may also be influenced by differences in education level, income and associated living conditions. Similar differences have also been observed among the indigenous and nonindigenous populations in Australia, Mexico and New Zealand, often reflecting the disadvantaged living conditions of many of these mothers. The proportion of low birth weight infants is also generally higher among women who smoke than for non-smokers. This threshold is based on epidemiological observations regarding the increased risk of death to the infant and serves for international comparative health statistics. The number of low weight births is expressed as a percentage of total live births. Euro-Peristat (2013), European Perinatal Health Report: the Health and Care of Pregnant Women and their Babies in 2010, Luxembourg. Low birth weight infants, 2013 (or nearest year) % of newborns weighing less than 2 500 g 9. A commonly asked question relates to selfperceived health status, of the type: "How is your health in general For the purpose of international comparisons, cross-country variations in perceived health status are difficult to interpret because responses may be affected by the formulation of survey questions and responses, and by social and cultural factors. In addition, since older people report poor health more often than younger people, countries with a larger proportion of aged persons will also have a lower proportion of people reporting to be in good health. New Zealand, Canada, the United States and Australia are the four leading countries, with more than 85% of people reporting to be in good health. On the other hand, less than half of adults in Japan, Korea and Portugal rate their health as being good. The proportion is also relatively low in Estonia, Hungary, Poland, Chile and the Czech Republic, where less than 60% of adults consider themselves to be in good health.

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Little biological damage is caused by the hydrated electron (eaq; Answer Choice A) muscle relaxant exercises generic voveran 50mg overnight delivery. Pubmed I-3) A On average muscle relaxant gel india discount voveran master card, about 25 eV is required to create an ion pair in water zopiclone muscle relaxant buy cheap voveran 50mg line, although the minimum energy needed to eject an electron is only 12 muscle relaxant homeopathy buy voveran uk. C the photoelectric effect is the predominant interaction responsible for producing high quality diagnostic radiographs spasms of the colon buy discount voveran 50mg online. At relatively low photon energies spasms vs cramps discount generic voveran canada, the photoelectric effect is the most likely photon interaction and is the desirable type of photon/tissue interaction since there is complete photon absorption with no production of secondary photons. The other possible tissue interactions at the photon energies used in diagnostic I-4) 110 radiology are the Compton effect and coherent scattering. For these interactions, a deflected photon traveling in an altered direction is produced at the site of interaction. If these secondary photons are permitted to reach the film, there would be a reduction in image sharpness and loss of spatial resolution. Furthermore, with the photoelectric effect, absorption of photons is dependent on the cube of the atomic number of the material. The resultant differential of absorption in tissue allows for the ability to differentiate between bone, soft tissue, and air. I-5) C the predominant atomic interaction for 100 keV photons is the Compton process. Sources provide different answers on minimum energy for triplet production with some stating 2mC2 (1. The primary radicals produced by the ejection of an electron typically have a lifetime of 10-10 second. D Neutrons are not charged particles and, therefore, cannot ionize atoms directly. They do, however, transfer some of their energy to protons or light nuclei, which then cause ionization. I-6) 1-8) 1-9) 111 1-10) B Fast neutrons with kinetic energy between a few and several tens of MeV are slowed down in biological media mainly by elastic collisions with hydrogen nuclei (protons) of the cellular water. A fraction of energy lost by fast neutrons in elastic collision with oxygen nuclei is less than 10% of that which occurs with hydrogen nuclei. For the beams of neutrons used in radiation therapy, recoil protons from elastic collistions produce a large density of ionizations along their tracks. Neutrons do not interact with atomic electrons but, instead, interact with atomic nuclei. Alpha particles can be produced by neutron capture reactions with isotopes of both carbon and oxygen, but the probability is strongly dependent on the neutron energy and target material. Example: 17 O + n 14C + Neutron absorption in a target nucleus is called activation. It occurs when atomic nuclei capture free neutrons, becoming heavier and entering excited states. The excited nucleus often decays immediately by emitting gamma rays, beta particles, alpha particles, fission products, and/or neutrons (in nuclear fission). Neutron activation is a potential health hazard in therapy with high energy photons because when photons with energy > 10 MeV are utilized, neutrons are generated in linacs via the interaction of photons with nuclei of high atomic number materials within the linac head and the beam collimator systems. Histone variants and their post-translational modifications regulate chromosomal functions; the post-translational modifications include acetylation, methylation, and phosphorylation. It has been shown that the number of phosphorylated sites remaining 24 hours after irradiation directly correlates with intrinsic radiosensitivity. Alkaline elution is used to measure single-strand breaks and some base damages (Answer Choice A) Western blotting is for detection of proteins (Answer Choice B). Frequently, these protein accumulations can be visualized as subnuclear "foci" using immunofluorescence microscopy. Although homologous recombination can take place in G1 phase, using the homologous chromosome as the template for repair, it occurs much more frequently after replication when the template strand is the sister chromatid located in close proximity to the damaged strand. It has been estimated that homologous recombination occurs 1000-fold more frequently in S and G2 than in G1. Normal tissue tolerance doses would likely decrease due to radiosensitization (Answer Choice C). Sublethal damage recovery would be inhibited since this process depends at least in part on the repair of double-strand breaks (Answer Choice E). Ataxia-telangiectasia: from a rare disorder to a paradigm for cell signaling and cancer. The formation of terminal deletions follows a linear dose response since these are single-hit aberrations (Answer Choice A). Translocations can be stable aberrations since they do not necessarily lead to cell death (Answer Choice B). The number of dicentric chromosomes detected in peripheral blood lymphocytes decreases with time after irradiation since these are unstable aberrations that ultimately cause the death of the lymphocyte progenitors and stem cells (Answer Choice C). The minimum dose that can be detected through scoring dicentric chromosomes is roughly 0. Sister chromatid exchanges are reciprocal exchanges between chromatids of the same chromosome that are not readily induced by ionizing radiation (Answer Choice A). Chromatid gaps appear as loss of genetic material from a single chromatid arm and may be caused by incomplete breaks (Answer Choice B). Inversions result when two breaks are produced in a single chromosome and the resulting excised chromosomal fragment reinserts itself back into the chromosome, but with the opposite polarity (Answer Choice C). However, some chromosome aberrations lead to the formation of micronuclei, which develop when a pseudo nuclear membrane forms around acentric chromosome fragments or whole chromosomes that did not segregate properly into daughter cells during the previous mitosis. Micronuclei are observed in peripheral lymphocytes and thus can be seen in interphase cells. A the formation of dicentric chromosomes is linear at low radiation doses but follows a quadratic function at higher doses. Two distinct mechanisms are thought to be responsible for these two components of the linearquadratic dose response curve. The linear portion of the dose response relationship is assumed to result from the simultaneous induction of two chromosome breaks by a single track. The quadratic portion is assumed to result from the two chromosome breaks being produced by two separate radiation tracks. D Terminal deletions are induced as a linear function of dose since they result from a single chromosomal break. A ring chromosome is an example of a chromosome-type aberration, not a chromatid-type aberration (Answer Choice A). A dicentric is an unstable aberration since it results in the formation of an acentric fragment and ultimately causes cell death (Answer Choice B). Breaks in two chromatids, followed by illegitimate rejoining, produce an anaphase bridge (Answer Choice C). Mechanisms of Cell Death V-1) C Apoptotic signals trigger a series of proteolytic events known as the caspase cascade. There are at least 14 human caspases, which fall into two categories: the initiator caspases (caspases-2, -8, -9 and -10), which activate the downstream caspases, and the executioner caspases (caspases-3, -6 and -7), which cleave cellular substrates. The actions of the executioner caspases produce the cellular effects that distinguish apoptosis from other forms of cell death. Radiation acts directly on the plasma membrane, activating acid sphingomyelinase, which generates ceramide by enzymatic hydrolysis of sphingomyelin. Ceramide then acts as a second messenger in initiating an apoptotic response via the mitochondrial system. Mitotic catastrophe, and not apoptosis, is the major mechanism of cell death in epithelial tumors. Inhibition of the G1 checkpoint in irradiated cells may increase the probability of mitotic catastrophe since cells are more likely to enter mitosis with damaged chromosomes. Pubmed V-3) C the term "senescence" refers to the loss of cellular replicative potential leading to a reduced capability to repopulate a tissue after exposure to genotoxic agents, including ionizing radiation. Importantly, senescence is not a type of cell death per se because cells remain morphologically intact and metabolically active when senescent. Depending on the level of tumor suppressor proteins and the oncogenic signal, senescence can be reversible in a small subset of cells though in most cells this process is irreversible. A clinically relevant scenario for radiation-induced senescence is the loss of salivary gland function and xerostomia commonly seen in head and neck cancer patients undergoing radiotherapy. Mitochondrial dysfunction is a hallmark of apoptotic cell death, not senescence (Answer Choice B). Nutrient deprivation can lead to autophagy, and ultimately autophagic death cell distinct from apoptosis (Answer Choice A). Ionizing radiation-induced cellular senescence promotes tissue fibrosis after radiotherapy. The activation of procaspase-8 is thought to occur via an induced proximity model leading to its conversion to the active enzyme, caspase8. Ionizing radiation can elicit activation of the extrinsic pathway leading to apoptosis. The other pathway by which ionizing radiation can elicit an apoptotic response is the intrinsic pathway. In this manner, the extrinsic death signal may be amplified through formation and activation of the apoptosome which contributes to effector caspase activation. In other words, the extrinsic pathway can feed into the intrinsic one and additionally change mitochondrial membrane potential. Cellular Pathways in Response to Ionizing Radiation and Their Targetability for Tumor Radiosensitization. Pubmed V-5) C Apoptosis helps maintain tissue homeostasis because cells that are undergoing an apoptotic response recruit phagocytes that clear the dying cells, also known as "apoptotic corpses", from the tissue without stimulating an inflammatory response. As a result, apoptosis can decrease the expression of interferons and other inflammatory factors. The exposure of phosphatidylserines (phospholipids) on the exterior of the plasma membrane is the signal that initially recruits phagocytes. The process of necrosis, which involves rupture of the cell membrane and the leakage of cellular contents into the surrounding tissue, does elicit an inflammatory response. Pubmed V-6) E the characteristic changes associated with apoptosis are due to activation of a family of intracellular cysteine proteases, known as caspases. Initiator caspases are the first to be activated, and include caspases-2, -8, -9 and 10. Initiator caspases cleave and activate the effector/executioner caspases, including caspases-3, -6, and -7, which then cleave, degrade or activate other cellular proteins. There is no cell swelling, such as occurs in necrosis, but rather cell shrinkage after the apoptotic process begins followed by condensation of chromatin at the periphery of the nucleus. During the apoptotic process, the plasma membrane initially remains intact but later fragments and surrounds the apoptotic bodies. Bystander effects are defined as radiation-like effects observed in cells that are not themselves irradiated, but that are in communication with irradiated cells through their location near these cells or by stimuli transferred from the irradiated cells through the intracellular medium. Pubmed V-10) D Mitotic death in most irradiated cells results primarily from misassortment of genetic material into daughter cells as a result of the formation of asymmetrical chromosome aberrations. This aberrant mitosis triggers mitotic catastrophe, which is characterized by cells exhibiting multiple tubulin spindles and centrosomes as well as the formation of multinucleated giant cells that contain uncondensed chromosomes. Single strand breaks are repaired rapidly and do not appear to play an important role in cell lethality (Answer Choice A). An alteration in cell permeability occurs in cells undergoing necrosis (Answer Choice E). Classification of cell death: recommendations of the Nomenclature Committee on Cell Death. Nonselective, bulk degradation of cytoplasm and organelles by autophagy provides material to support metabolism during periods of cellular stress. For example, autophagy provides internal nutrients, when external ones are unavailable. Selective autophagy of proteins and of organelles such as mitochondria (mitophagy), ribosomes (ribophagy), endoplasmic reticulum (reticulophagy), peroxisomes (pexophagy), and lipids (lipophagy) occurs in specific situations. The whole process is tightly regulated through at least 30 Atg-autophagy related genes that orchestrate initiation, cargo recognition, packaging, vesicle nucleation expansion and fusion and breakdown. In contrast to apoptotic cells, there is little or no association of autophagic cells with cells phagocytes. Skin nodule formation is not a functional endpoint; it is a clonogenic assay measuring survival of individual epidermal cells regrowing in situ. All of the other assays cited represent non-clonogenic, functional endpoints for assaying radiation damage. If one assumes that there is full repair of sublethal damage during the 6 hr irradiation (which is probably an oversimplification), sublethal damage would not contribute to cell killing. A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Multiple doses and cell densities typically are needed for the adequate analysis of cell survival. This is not a short-term growth delay assay, and thus a cell capable of multiple cell divisions is needed. From the equation that describes this model, S = e - D / D0, the dose, D, at which there would be an average of one hit per cell would be equal to D0, the constant of proportionality. E the / ratio represents the dose at which the D component of cell killing, assumed to result from single hit killing, is equal to the lethality produced by the D2 component of cell killing that results from multi hit killing. D D0 is a measurement of radiosensitivity made on the exponential part of the survival curve.

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