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In spite of the long-standing def erence toward patient autonomy in genetics,100 professionals have begun to consider some limits on patient choice. Others argue that, to protect reproductive autonomy, parents should be the ultimate arbiters. Even if professionals agree in theory on the principles that would set the lines, it may be quite difcult in practice to sort out what is in and what is out, particularly at the margins. The tyranny of choice r 285 At the heart of these debates are questions of the clinical utility of genomic infor mation in the reproductive context. Genetic variants largely pre dictive of serious diseases clearly have clinical utility under either defnition. Whether highly penetrant variants associated with non-medical traits also have clinical utility in the reproductive context is more complicated. Under the broader defnition, some non-medical traits might have clinical utility because of their potential social impact on parents. Such information has not, however, been treated as having clinical utility thus far. Concerns about information overload, comprehension challenges, and limited resources (too few counselors and insufcient time), however, could lead professional societies to limit the scope of clin ical utility. By limiting disclosure to information with clinical utility under the nar row defnition, providers could beter educate patients about, and patients could beter comprehend, the limited information they receive. While professional considerations about the use of limited and scarce resources argue against unlimitedpatientautonomy,thepossibilityofobtainingbroadamountsofnon-medical information will force the medical profession and society to think hard about the appro priate scope of patient autonomy in this context. In short, this remedy pits professional autonomy and integrity against patient autonomy. While the coverage of sex chromosomes analysis might seem to contradict that principle, the decision is based on theclinicalutilityofrulingoutsex-linkedconditions,notonanotionofclinicalutilitythatconsiderssatisfying parental curiosity. If professional guidelines limited disclosure only to genomic variants associated with serious conditions, some fertility clinics might fll the void by oferingtoprovideinformationaboutvariantsassociatedwithlesserhealthrisksornon medical traits. Although commercial labs would do the sequencing, the clinics might request more expansive analysis when sending samples to the labs. One could imagine advocates of patient autonomy urging clinics to ofer more expansive disclosure, much as they have pushed for broader access to genetic informa tionthroughdirect-to-consumertesting. Finally, depending on their coverage decisions, insur ers could potentially infuence the scope of information disclosure and, ultimately, equality. The tyranny of choice r 287 assessments of clinical utility to decide the scope of coverage. If such groups concluded that genomic information about non-medical traits or minor medical conditions had no clinical utility,118 insurers would not cover disclosure of these variants. In practice, this would mean that labs would generate the genomic sequence, but insurance would only cover analysis of variants associated with highly penetrant medical conditions. Being able to select on the basis of some non-medical information might merely fulfll parental preferences (eg green eyes over blue). If access to this broader information was infuenced by wealth, those with societal advantages (higher income, beter education, access to health care, etc. In addition, only the wealthiest would be able to take advantage of this technology. B describes the general issues algorithms present for reproductive decision making and the specifc issues they raise, depending on who creates them. Indeed, it might be more costly to try to select out parts of the genome for sequencing than to sequence all of it. One could imagine, however,thatcoveragedecisionsmightdiferentiatebetweenwhatkindofgenomicinformationwasanalysed and disclosed given that the interpretation of the sequence is the more costly part of genome sequencing. Parentsmightidentifythediseaseand/ornon disease traits they wanted to select against or for and the relative weights they would assign these categories, or they could just rank features most important to them and let the algorithm assign relative weights. Some might fnd it too difcult or abstract to assign rankings or relative weights to diferent kinds of genomic informa tion. For example, they could create algorithms that award points for genotypes associated with diseases based on various categories: the potential severity, age of onset, degree of impairment or physical sufering, etc. Diferent weights would be assigned to diferent categories and the scores would be discounted by the probabilistic association between the vari ants and phenotype (penetrance). The resulting scores, based on the genomic profle of each embryo, would be used to se lect embryos for implantation. The outcome of these algorithms would depend as much on the weights assigned to the categories as to the determination of which categories to use. Two algorithms that used the same categories could lead to very diferent out comes if diferent weights were assigned to each category. In other words, the formulas could have signifcant impact on the selection of embryos. Individualized features could be used to modify generic algorithms based on key parental dislikes or predilections regarding medical and non-medical traits. Parents might indicate that a specifc category of disease risk, such as a propensity for conditions that require specialized diets, like Celiac disease, would be a deal breaker. All embryos 121 As noted above, cost may infuence whether clinics are able to ofer more than one algorithm package. To the extent that individuals have the wherewithal to choose among diferent clinics, the type of algorithm the clinic ofered might infuence their choice of clinics. Algorithms might also factor in whether the variant is associated with great variability in expressivity. The former are normally measured on a scale in which 1 represents full health and 0 represents death, therefore higher values correspond to more desirable statesandstatesdeemedworsethandeathcantakenegativevalues. Telateraremeasuredonascaleinwhich 0 represents no disability, therefore lower scores correspond to more desirable states. Conversely, only embryos with a signifcantly increased propensity for a particular trait, such as vari ants associated with intelligence (assuming a meaningful correlation between variant and trait)126 would be selected for ranking according to the generic algorithm. Individualized algorithms could ofer parents the opportunity to decide what kinds of non-medical traits they wanted to include and the weight they would assign those traits. As with variants associ ated with disease, values assigned to traits would have to be discounted based on the probabilities of expression. For example, it is unlikely that providers would let future parents decide whether or not to select embryos based on lethal or debilitating childhood illnesses like Tay Sachs or Lesch Nyhan. Most clinics would likely use algorithms with a baseline selection against such devastating conditions. A more complicated issue is whether providers would be willing to honor other kinds of requests, particularly those that involve the selection for less serious disabilities. Some clinics, however, will implant such embryos,129 125 Of course, one would have to decide what constituted a signifcantly increased propensity. The mosthighlyrankedembryoswouldthenbefurthernarroweddownbasedonparentalinputaboutafewtraits that they particularly valued or considered deal breakers. Even with respect to a particular trait, like height, diferent genetic variants can have signifcantly difer ent impacts. Some might ofer highly individualized algorithms for those who wanted full choice; others might ofer more limited individualized algo rithms.

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See also the study selection flow chart in Appendix E, study evidence table in Appendix G and exclusion list in Appendix F. In all of the studies it was unclear which variables had been inputted into the multivariate analysis. There were no studies that met our inclusion criteria that looked at malnutrition. Bone mineral density was the only dependent variable out of our outcomes that was reported in the 21 studies. None of the other outcomes (epiphyseal fusion, bone age) were reported in the multivariate analyses as a dependent variable (outcome). Cumulative dose of prednisolone and Netherlands, unclear diagnosis related significantly to lumbar setting. Inadequate covariates/events ratio 3 Mainly cross-sectional data, limited information reported for the multivariate analysis, missing data is not described, and some important confounders were not considered 4 Cross-sectional study followed by a prospective cohort, unclear how the patients were recruited(consecutive/ random), no dose/ duration of corticosteroid use, limited information reported for the multivariate analysis, missing data is not described, and some important confounders were not considered. Relative values of different Children and young people outcomes the critical outcomes were the incidence of fractures (validated by medical records/radiological reports), osteoporosis/osteopenia as indicated by bone mineral density Z-score and reduction in bone mineral density score. The important outcomes were epiphyseal fusion (normal, delayed) and bone age (wrist x-ray, delayed, normal or advanced). The incidence of osteoporosis or osteopenia was not included as a dependant variable. Trade off between clinical the identification of risk factors that contribute to poor bone health is benefits and harms important to indicate when to monitor, and then to adjust treatment if necessary, to reduce the risk of fractures and further deterioration of bone health. The review did not evaluate the different methods of assessing bone health and their relative benefits and harms, and as such no one method for monitoring is recommended. Not only would it be unlikely there would be sufficient change over this period the risks of radiation exposure should be considered. The evidence from the review did not demonstrate that any of the risk factors contributed to poor bone health. Benefits include reducing the risk of fractures and preventing further deterioration of bone health. In addition, downstream cost savings could be made if the use of drugs National Clinical Guideline Centre, 2013. Quality of evidence There were four studies, three were rated as low quality and one as very low quality. No other evidence identified these or any of the other potential risk factors as predictors for poor bone health. The rationale for considering these risk factors was that during active disease the production of interleukin 6 may affect bone formation. Steroids are commonly associated with lowering bone density and increasing the incidence of fractures. However, short stature and pubertal delay is thought to occur to a far National Clinical Guideline Centre, 2013. Clinicians must take into account potential reasons for growth failure and pubertal delay. These may be due to intrinsic factors related to disease, such as, disease severity including extent, complications, duration of symptoms prior to achieving disease control and frequency of disease relapse or extrinsic factors, such as duration and frequency of steroid use. Consideration should also be given to identify other co-existing conditions that may predispose to growth failure and pubertal delay such as eating disorders or other causes of primary growth hormone and gonadotropin deficiency secondary to poor nutritional status. The clinician needs to consider the most appropriate assessments in children and young people to identify those at risk of faltering growth and pubertal delay and the optimal frequency of monitoring needed. In clinical practice, weight and height recording (including parental heights with mid parental height estimation), documentation on age and sex appropriate growth chart and Tanner pubertal staging undertaken by trained healthcare professionals are considered important assessments for growth and puberty respectively. Consideration should be given to alternative methods for assessing puberty, including self-assessment, to take into account the sensibilities of children and young people to allow for discreet assessment and to aid compliance. The necessary frequency of assessments will depend on the degree to which growth and puberty are impaired at disease presentation and subsequent disease course and severity. Prompt recognition of cause for growth failure and or pubertal delay is necessary to allow for timely intervention; this is particularly important when active disease including associated steroid use may coincide with the potential vulnerable periods of rapid skeletal growth during pubertal development. The aim of timely intervention is to maximise adult height potential and complete pubertal development. The use of self-monitoring compared to medical monitoring will also be considered, and whether there needs to be special measures taken over the transitional period. There were no limitations on the settings for the studies, and no trial duration or sample size restrictions. See the study selection flow chart in Appendix E and exclusion list in Appendix F. Studies were identified that looked at the use of corticosteroids but not in relation to how frequent the monitoring should take place. They only demonstrated that the use of corticosteroids depending on the dose and duration of treatment could affect growth in children and young people. Some studies commented on the fact that growth should be monitored within their conclusions, but the frequency in which it should be carried out was not evidenced. There were also some guidelines 77,96 and clinical recommendations found in the search but they were consensus and lacked a referenced clinical evidence base. If the young person prefers self-assessment for monitoring pubertal development, this should be facilitated where possible and they should be instructed on how to do this. Ensure that relevant information about monitoring of growth and pubertal development and about disease activity is shared across services (for example, community, primary, secondary and specialist services). Relative values of different Growth outcomes the critical outcomes were deviation from normal/baseline height (growth velocity) as measured on the centile chart trajectory and bone age (wrist x rays) in pre-pubertal children. The important outcome was deviation from normal weight as measured by the weight centiles. Pubertal development the critical outcomes were delayed puberty (as indicated by assessment on the Tanner staging) and quality of life. Trade off between clinical Growth and pubertal delay are important markers of wellbeing in children and benefits and harms young people with ulcerative colitis. Poor growth may be an indicator of poor disease control and delayed growth and puberty can result in feelings of isolation from peers. The benefits of measuring growth and pubertal development are clear but the frequency of measurement is not. However, if monitoring occurs when patients make their routine clinic visits, costs may not be substantially higher than in usual care. Quality of evidence No studies were identified that indicated any optimal timing strategies for monitoring growth or pubertal development. High risk times, from clinical experience, are defined as during disease relapse, persistent disease, approaching puberty and when taking corticosteroids. The recording of Z-scores is considered to be more accurate as they represent all values which sit between the centile lines. Radiologic determination of bone age by wrist x-ray compared to chronological age can help inform discussion with children and young people about their remaining growth potential.

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Patients who cannot or will not adhere to recommendations for diagnostic testing should be treated on the basis of history, physical exam, and measured office peak flow compared to predicted peak flow. Chest X-ray A chest X-ray may be desirable to evaluate for other pathologies since many people experiencing homelessness have not previously had access to these diagnostic tests because of lack of health insurance and financial resources, lack of transportation, and priorities that do not include diagnostic testing. Be alert to common infectious respiratory diseases in your region and in regions where the patient has lived, such as histoplasmosis in the Midwest and coccidioidomycosis in the Southwest and California. People experiencing homelessness may travel from region to region and may have recently come from an area of endemic disease. The high rate of asthma in individuals experiencing homelessness is thought to be related, in part, to the presence of mold, animal dander, dust, cockroaches, and cigarette smoke in shelters or other living situations. Patients with unexplained, severe, or difficult-to-control asthma symptoms should be referred for allergy testing. Asthma Action Plans Work with the patient to develop an appropriate treatment plan. Patient-centered care is a shared endeavor, and cultural humility must be displayed. Use appropriate language, and reinforce with written action plans containing pictures, etc. For persistent asthmatics, make sure the patient understands how to distinguish the different types of inhalers and how each should be used. Consider applying a sticker or other visual reminder to differentiate rescue inhalers from controller inhalers. An educational chart or poster of the respiratory inhalers is useful to help patients correctly identify the type of inhaler they use. Ask the patient to demonstrate inhaler use at every visit; if incorrect, demonstrate correct use. A plastic water bottle with a hole cut in the bottom may be used as a spacer; clients can discard these and make new ones as needed (Duarte & Camargos, 2002; Zar Asmus, & Weinberg, 2002). Nebulizers If used properly, inhalers can provide medication delivery equivalent to nebulizers. Due to the cost, health insurance coverage is generally necessary to obtain a nebulizer. If critically necessary, work with shelter staff and other service providers to provide a place for nebulizers to be used and stored. Consider giving daily or twice-daily nebulizer medication treatments in the clinic, especially if the patient is unable to obtain his or her own nebulizer and the clinic is readily accessible, as in a shelter-based clinic. Nebulizers and spacers should be disassembled, rinsed in solution, and dried rather than left on the floor. Give the patient a bottle of vinegar or make it available in shelters, since people experiencing homelessness may not be able to obtain vinegar. Living Conditions Explain to the patient how environmental conditions, like exposure to cigarette smoke, can worsen asthma symptoms. Insecticidal baits are readily available and are the most effective strategy for eliminating infestations. You may also be able to assist by writing a letter to the shelter requesting pest management when needed. Eliminating reservoirs of house dust mites is generally ineffective at reducing symptoms and does not need to be recommended. Smoking Do not assume that patients experiencing homelessness are not interested in smoking cessation, although it may be a lower priority than meeting survival needs. Studies show that smoking cessation interventions can be successful and do not increase relapse risk for recovering substance users. If the patient is not ready to quit smoking, promote harm reduction by encouraging the patient to reduce the number of cigarettes smoked daily. Symptoms Educate the patient about signs and symptoms of asthma exacerbations, such as night-time/early morning cough, post-tussive emesis, shortness of breath (only able to talk in short sentences), and wheezing. Teach the patient to recognize his or her own symptoms, to implement the asthma action plan, and to contact you or their primary care provider early on, instead of waiting until they have a full-blown attack. To facilitate this, ensure that the patient has a number to reach for on-call support. The practice of cultural humility is critical to improving compliance with treatment. Symptom-based action plans have been demonstrated to be comparable to peak flow-based action plans. Ask the patient what he or she would do if an asthma attack did not respond to a rescue short-acting beta agonist. Good asthma control should allow patients to comfortably exercise and participate in activities. The ability to engage in regular exercise may be a challenge because of space or safety in or around shelters. Help patients to plan and to incorporate physical activity into their routines, as possible. Educational Materials Make sure the patient can read and understand any written materials you provide (Klass, 2007). In general, written patient education materials should be at the fourth-grade reading level or lower. Prevention Make the patient aware of increased risks when exposed to people with respiratory infections (colds, flu). Strongly encourage an annual flu shot and explain the difference between a cold and the flu. Having the patient repeat back what you discussed can be a way to assess understanding and reinforce the plan. Education of service providers Encourage improvements in places where patients experiencing homelessness live. Identify partners in your community to help families experiencing housing instability with medical, legal, and housing issues. Educate shelter staff about controlling environmental conditions that exacerbate asthma by: o Prohibiting smoking in shelters. Choice of Rx Use the simplest medical regimen possible to facilitate adherence to treatment. Use whatever medications are appropriate and available to the patient, considering medication expense (including co-pay) and duration of treatment. Nevertheless, these anti-inflammatory medications are frequently under-prescribed by practitioners and underused by patients. Educate the patient about the importance of preventive rather than crisis management of asthma. Although this is frustrating for the clinician, repeated explanation, encouragement, and support may promote adherence. Short-acting Beta-agonists Because of their immediate effect, patients usually like short-acting beta-agonists.

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As an example, I had hoped to submit one of the manuscripts to a relevant clinical journal with a short word count. One of my supervisors advocated for this piece by contacting the journal editor to ask if there was flexibility with the word count, considering that my qualitative manuscript would include the data in the body of the text, rather than in tables or figures. We received a response that stated that while this particular journal was not opposed to qualitative research, they preferred that quotations be omitted, or paraphrased and summarized. Since the exclusion of participant data would compromise the credibility of the work (Charmaz, 2006), we chose to submit that paper to another journal. While a wide range of interdisciplinary literature allowed me intellectual flexibility and the ability to respond to my study data in a unique way, it was a challenge to keep a sufficiently tight focus on the research questions. Throughout the doctorate, but especially in the beginning, I was constantly reading new ideas and expanding my research proposal to encompass these new ideas. While I knew that I had to rein in this tendency so that the research did not become too diffuse, it was a constant challenge to put aside interesting, valuable, and invigorating ideas, especially when I could see the ways in which these ideas could be made relevant to the project. This task became easier after I started collecting data; I began to identify a theme of informed decision-making in the data and this became the touchstone for keeping my research focused. Engagement with a wide variety of interdisciplinary literature also presents the challenge of choosing what definitions and theories to represent as authoritative. Disciplinary knowledge presents a range of possibilities to choose from, and a foundation of what combinations are acceptable. Working in an interdisciplinary way, I was challenged to find and 310 evaluate ideas from many different sources, reconciling tensions where I could find them. While I understand that it is impossible for any scholar, disciplinary or interdisciplinary, to conduct a literature review that is absolutely exhaustive, I think this is an additional challenge for those who engage with literature from a wide variety of disciplines. While some may conceptualize the purpose of doctoral research to be the production of knowledge, I firmly believe that the purpose of doctoral research is also to learn, practice, and demonstrate proficiency in the research process (Franke & Arvidsson, 2011). This tension is often echoed in the language used to describe quality criteria (Reynolds et al. I have engaged with the idea of the doctorate as a process rather than a product throughout the entire program, choosing methods, theories, and methodologies I wanted to learn and practice; incorporating as many ideas as possible; becoming actively involved in many other research projects in order to learn new ideas, work with different scholars, practice my existing skills, and expand my list of accomplishments. As I was writing my dissertation, I have used many ideas gathered from these extra research projects, the knowledge and experience I gained throughout the whole doctoral program has influenced not just the research product that I have produced, but the way I think of research, academia, and the world. An examination of data from patient education materials, policy documents, and pregnant women currently experiencing this process has generated four integrated articles which comment on various aspects of informed decision-making. An examination of the literature on autonomy, normalization, medicalization, and governmentality has revealed a tension around an individualized way of considering informed decision-making: the choice to participate in prenatal screening is deeply embedded within the particular societal context in which it is made. It becomes clear that promoting informed choice about prenatal screening is not just a matter of providing clear and comprehensive information, but includes broader considerations of how choices are constructed and the ways in which particular courses of action are enabled and constrained. Comparison of selected outcomes of CenteringPregnancy versus traditional prenatal care. Proceedings of the Tenth Conference on Australasian Computing Education, Wollongong, Australia, 78. Assessing expert interdisciplinary work at the frontier: An empirical exploration. GenetiKit: A randomized controlled trial to enhance delivery of genetics services by family physicians. Decision-making in the physician-patient encounter: Revisiting the shared treatment decision-making model. The foundations of social research: Meaning and perspective in the research process. The elephant in the living room: Or extending the conversation about the politics of evidence. Proceedings of the National Academy of Sciences of the United States of America, 105(42), 16266-71. The challenges of conducting interdisciplinary research in traditional doctoral programs. Assessment of an interactive computer-based patient prenatal genetic screening and testing education tool. Genetics in Medicine: Official Journal of the American College of Medical Genetics, 9(5), 259-267. The quest for effective interdisciplinary graduate supervision: A critical narrative analysis. Moving from information transfer to information exchange in health and health care. A model of information practices in accounts of everyday-life information seeking. Gauging the transdisciplinary qualities and outcomes of doctoral training programs. Confidence of primary care physicians in their ability to carry out basic medical genetic tasks: A European survey in five countries. Negotiating academicity: Postgraduate research supervision as category boundary work. Barriers to the provision of genetic services by primary care physicians: A systematic review of the literature. The public life of the fetal sonogram: Technology, consumption, and the politics of reproduction. Failure to identify women at risk of hereditary breast cancer in southwestern Ontario: Missed opportunities for genetic counseling and cancer prevention strategies. Interestingly, she has been the only one not to know the meaning of "positive result"/"negative result" so far. She said her doctor was pushing the test and when I asked why she thought he was pushing it, she compared it to a flu shot, a precaution. I think I need to search out women with lower education levels to round out some categories which I can already see emerging. I struggled with that throughout this interview Post-Transcription Memo for Lucy: Transcribing this I remember how difficult this interview was, how I kept trying to pull answers out of her. For all the questions re: any more investigation or what could your doctor have done better, she would always answer "somebody else might. This might be the majority viewpoint and it might be what I am missing in my sample. I wonder if as we begin if you could tell me a bit about your understanding of what prenatal screening is Can you give me some background about why you think your doctor offered prenatal screening to you Have your views about prenatal screening changed, since talking to your doctor about the option to participate in screening Was there anything you were confused about, or wished you had more time to discuss during the prenatal screening visit Did your doctor give you any written material, or direct you to other resources to learn more about prenatal screening Would this be best coming from a doctor, or written in a pamphlet, or communicated in another way Kinsella, PhD, Faculty of Health Sciences, University of Western Ontario (519)661-2111 x81396, akinsel@uwo. McKenzie, PhD, Faculty of Information and Media Studies, University of Western Ontario (519)661-2111 x88497, pmckenzi@uwo. Please take your time to make a decision and discuss this proposal with family members, friends, or your doctor, as you feel inclined. The purpose of this letter is to provide you with the information you require to make an informed decision about participating in this research. It is important for you to understand why the study is being conducted and what it will involve. Please take the time to read this carefully and feel free to ask questions if anything is unclear. Once you have read and understand the information, you will be asked to sign this form if you wish to participate in the study.

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An Assessment of Prednisone, Salazopyrin, and Topical Hydrocortisone Hemisuccinate Used As Out-Patient Treatment for Ulcerative Colitis. Effect of budesonide enema on remission and relapse rate in distal ulcerative colitis and proctitis. Early predictors of glucocorticosteroid treatment failure in severe and moderately severe attacks of ulcerative colitis. Budesonide versus prednisolone retention enemas in active distal ulcerative colitis. Clinical epidemiology of inflammatory bowel disease: Incidence, prevalence, and environmental influences. A two-stage decision analysis to assess the cost of 5-aminosalicylic acid failure and the economics of balsalazide versus mesalamine in the treatment of ulcerative colitis. Intermittent therapy with high-dose 5-aminosalicylic acid enemas maintains remission in ulcerative proctitis and proctosigmoiditis. A prospective randomized observer-blind 2-year trial of azathioprine monotherapy versus azathioprine and olsalazine for the maintenance of remission of steroid-dependent ulcerative colitis. A double-blind dose escalating trial comparing novel mesalazine pellets with mesalazine tablets in active ulcerative colitis. Use of mesalazine slow release suppositories 1 g three times per week to maintain remission of ulcerative proctitis: a randomised double blind placebo controlled multicentre study. Combined oral and enema treatment with Pentasa (mesalazine) is superior to oral therapy alone in patients with extensive mild/moderate active ulcerative colitis: a randomised, double blind, placebo controlled study. Olsalazine sodium in the treatment of ulcerative colitis among patients intolerant of sulfasalazine. A prospective, randomized, placebo-controlled, double-blind, dose-ranging clinical trial. Safety and efficacy of controlled-release mesalamine for maintenance of remission in ulcerative colitis. Double-blind comparison of slow-release 5-aminosalicylate and sulfasalazine in remission maintenance in ulcerative colitis. National Institute for Health and Clinical Excellence, 2011 Available from: guidance. Olsalazine versus sulphasalazine for relapse prevention in ulcerative colitis: a multicenter study. Birth outcome in women exposed to 5-aminosalicylic acid during pregnancy: a Danish cohort study. Methotrexate in chronic active ulcerative colitis: a double-blind, randomized, Israeli multicenter trial. Inflammation is the main determinant of low bone mineral density in pediatric inflammatory bowel disease. Long-term intermittent treatment with low-dose 5-Aminosalicylic enemas for remission maintenance in ulcerative colitis. Efficacy and tolerability of mesalazine foam enema (Salofalk foam) for distal ulcerative colitis: A double-blind, randomized, placebo-controlled study. Comparative trial of methylprednisolone and budesonide enemas in active distal ulcerative colitis. A comparison of oral prednisolone given as single or multiple daily doses for active proctocolitis. A Defense of the Small Clinical-Trial Evaluation of 3 Gastroenterological Studies. Cost effectiveness of ulcerative colitis treatment in Germany: a comparison of two oral formulations of mesalazine. Balsalazide is superior to mesalamine in the time to improvement of signs and symptoms of acute mild-to-moderate ulcerative colitis. Mesalazine (5-aminosalicylic acid) micropellets show similar efficacy and tolerability to mesalazine tablets in patients with ulcerative colitis-results from a randomized-controlled trial. Relapses of inflammatory bowel disease during pregnancy: In-hospital management and birth outcomes. The prophylactic effect of salazosulphapyridine in ulcerative colitis during long-term treatment. The efficacy and safety of sulphasalazine and olsalazine in patients with active ulcerative colitis. Relapse-preventing effect and safety of sulfasalazine and olsalazine in patients with ulcerative colitis in remission: A prospective, double-blind, randomized multicenter study. Comparison of delayed-release 5 aminosalicylic acid (mesalazine) and sulfasalazine as maintenance treatment for patients with ulcerative colitis. Oral beclometasone dipropionate in the treatment of active ulcerative colitis: a double-blind placebo controlled study. Oral beclomethasone dipropionate in patients with mild to moderate ulcerative colitis: a dose-finding study. Analysis of fat and muscle mass in patients with inflammatory bowel disease during remission and active phase. Oral beclomethasone dipropionate in pediatric active ulcerative colitis: a comparison trial with mesalazine. Inflammatory bowel disease: epidemiology and management in an English general practice population. High incidence of inflammatory bowel disease in the Netherlands: results of a prospective study. Cost utility of inflammation-targeted therapy for patients with ulcerative colitis. Once-daily dosing of delayed-release oral mesalamine (400-mg tablet) is as effective as twice-daily dosing for maintenance of remission of ulcerative colitis. Low bone mineral density in children and adolescents with inflammatory bowel disease: A population-based study from western Sweden. Longitudinal assessment of bone mineral density in children and adolescents with inflammatory bowel disease. Coated Oral 5-Aminosalicylic Acid Therapy for Mildly to Moderately Active Ulcerative-Colitis A Randomized Study. Evaluation of the clinical course of acute attacks in patients with ulcerative colitis through the use of an activity index. Incidence of inflammatory bowel disease across Europe: is there a difference between north and south Oral Mesalamine (Asacol) for Mildly to Moderately Active Ulcerative-Colitis A Multicenter Study. The beneficial effect of azathioprine on maintenance of remission in severe ulcerative colitis. Azathioprine versus sulfasalazine in maintenance of remission in severe ulcerative colitis. Role of azathioprine in severe ulcerative colitis: one-year, placebo-controlled, randomized trial. Methylprednisolone acetate versus oral prednisolone in moderately active ulcerative colitis. Budesonide enema in active haemorrhagic proctitis-a controlled trial against hydrocortisone foam enema. Azathioprine and 6-mercaptopurine for maintenance of remission in ulcerative colitis. Predicting the need for colectomy in severe ulcerative colitis: a critical appraisal of clinical parameters and currently available biomarkers. 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Specific emotions, including anger, laughter, and sadness can trigger some patients. Inhaled substances: Ask the patient to specify any inhaled or smoked substances, such as tobacco, vaping, electronic cigarettes, marijuana, crack cocaine, methamphetamines, or volatile inhalants (glue, paint, Freon, etc. Weather, including changes in temperature and storms, can trigger symptoms It is often unclear why certain work or housing environments trigger symptoms. If serum testing for allergies is conducted, use a region-specific aeroallergen panel. Do not include food allergy testing because this has high rates of false-positive results that will confuse the picture. Explore the differences in what a patient has been prescribed and what they have been able to access. Patients may not offer this information before the establishment of a trusting relationship with the provider. Pharmacies can provide information about the frequency of refills dispensed, but medications may also be dispensed directly by providers at outreach sites. Inquire where the patient receives their asthma medication and whether they can access it when needed. Inquire about adherence to prior treatment and what the patient does to relieve symptoms if a quick-relief inhaler is not available. Patients may also be rationing their medication, sharing with friends or family members, or lacking it altogether. Comorbid Conditions There are some medical conditions that make asthma management more difficult because of their direct effect on asthma or by mimicking symptoms in patients who have both conditions. Vocal cord dysfunction is commonly present in patients with asthma, but patients can learn to differentiate by locating symptoms in the throat versus the chest. Access to sleep studies can be challenging, but if risk factors are present, treatment with nasal steroid can be initiated. Allergic rhinitis makes asthma more difficult to control; intranasal steroids are often helpful to improve rhinitis and asthma. Diagnosis of asthma is best made using spirometry when symptoms are present to document airways obstruction with reversibility after a bronchodilator is administered. If there is concern that symptoms are entirely from a comorbid condition, referral for spirometry should be made. Inquire about the immunization history, especially Pneumovax and annual influenza immunization. Many people experiencing homelessness live in environments with asthma triggers, such as mold, dust mites, cockroach feces, animal dander, tobacco smoke, and air pollution. If the patient is living in a shelter, ask for a description of the living conditions at the shelter. If the patient has been seen before, ascertain whether environmental conditions have improved or deteriorated. Many patients may not know their triggers, so this part of the assessment will be a good opportunity for education and to help them learn more about the association with their asthma control. Activities such as sweeping, cleaning, and exposure to cleaning solvents, insecticides, herbicides, and fumes can be triggering. If living at a shelter, inquire about chores the patient does that may trigger or exacerbate symptoms. Continuity of care is associated with improved outcomes in patients with chronic medical conditions. Inquire about health care providers the patient has seen and whether he or she is currently receiving care from the shelter or other outreach sites. Federally funded health centers are medical homes that accept patients regardless of ability to pay. In some states, adults experiencing homelessness are eligible for certain benefits if they are U. If possible, have the patient sign a release of information to obtain prior health records. Inquire whether the patient has Medicaid/Medicare; if not, inquire whether he or she would like to receive assistance enrolling in it. Medication Affordability Inquire where the patient obtains medications; explicitly ask if there are multiple sites. Many adults experiencing homelessness are uninsured or have insurance that does not adequately pay for medications. Ask whether the patient has health insurance that adequately covers prescriptions. Federally funded health centers have access to 340B pharmacy pricing to reduce costs. Assess for survival sex activities (prostitution or trading sex for goods or protection), history of being a victim of human sex trafficking, other high-risk behaviors, and trauma. Family Health/Stress Understand that the individual may have experienced significant access barriers to care or have an incomplete understanding of the health condition or treatment needs. Discuss social supports, patient strengths, and small or large successes that may be built upon and encouraged. He or she may live in a neighborhood with minimal access to healthy, affordable food. Patients who live on the streets may be primarily living off scavenged food items that others have discarded. Treatment During Incarceration Some people experiencing homelessness have a history of incarceration, which may be a factor in their asthma control or treatment needs. Discuss barriers to asthma treatment and maintenance during and after incarceration. Inquire whether current medications were those stored/released after incarceration. The physical examination may be your only contact with the patient; many people experiencing homelessness rarely see a primary care provider because of housing instability and limited access to health care. Take sufficient time for observation to ensure accuracy and reproducibility of the exam. Signs of Pulmonary Disease Look for clubbed fingers and barrel chest as clues to pulmonary disease other than asthma. Nasal Findings Inspect the nasal mucosa; chronic sinusitis or nasal inflammation/irritation because of drug inhalation may contribute to symptoms and complicate asthma control. Control of allergic rhinitis also improves asthma symptoms in patients who have both. Mental Health Status Assess for cognitive deficits secondary to substance abuse, mental illness, trauma or developmental delay that may compromise understanding and treatment adherence. Spirometry Spirometry is the recommended tool for diagnosis and is very important to assess reversible airway obstruction. Clinics should adopt the use of spirometry only when there is sufficient volume to maintain the skills of the individual performing the test. If your clinic cannot afford a spirometer, explore collaboration with another facility that has one, consider writing a grant to purchase a spirometer or seek donated equipment. If spirometry is not available, do not delay treatment; treat on empirically based on the history and physical exam.

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The calcific deposits in these areas are visible as retain normal architecture and staining quality of cells and nodular yellow-white or grey-white masses, which often ulcer interstitial tissues (57). Microscopically, calcifi Nonstructural dysfunction cation predominates in the spongiosa of the valve cusps (56). Paravalvular leaks the calcific deposits occur in relation to connective tissue Paravalvular leaks are most often caused by infective endo cells or collagen in the valve cusps (27,57). However, a paravalvular leak may also occur as a Prosthesis failure in general, and that due to calcification result of suture knot failure, inadequate placement of sutures, specifically, is influenced by the age of the patient at the time separation of sutures from an annulus that is heavily calcified of implantation (16,27,57-61). Calcification and prosthesis or myxomatous, or healing-induced tissue retraction (5,16). Young adults, partic cause significant hemolysis and, when severe, can cause heart ularly those aged less than 40 years, also show accelerated rates failure (5,16). Importantly, paravalvular leaks also increase the of calcification and failure (8,58,59). Hemolysis Cuspal tears or perforations unrelated to calcification (or Hemolysis was common with earlier generation heart valve endocarditis) are likely the result of direct mechanical damage prostheses, especially with mechanical valves (5,8,16). Hemolysis was severe enough in certain cases to cause Degeneration of collagen has been observed using high resolu hemolytic anemia. In general, normally functioning tissue tion imaging methodologies such as scanning electron valves and contemporary mechanical valves rarely cause clini microscopy (63). Severe hemolysis leading to anemia time postimplantation and appear more frequently in valves in can occur in prosthetic valves as a result of a paravalvular leak, the mitral than in the aortic site (54). Detachment of one or more Prosthesis disproportion commissural regions from their respective stent posts has also As large a prosthetic heart valve as possible is used to minimize been described as a form of prosthesis failure. Occasionally, howev typically occurs in second generation Carpentier-Edwards er, a prosthetic heart valve is used that is too large for the porcine bioprostheses in the mitral location and may occur in anatomic site of implantation, a situation referred to as pros the absence of significant calcification or infection (64). Such overly large valves may not function Stentless bioprosthetic porcine aortic valves, designed for use effectively, may lead to damage to surrounding structures or in the aortic site, have only been used for a relatively short peri may even result in obstruction (22). At the current time, these prosthetic valves have shown minimal cuspal calcification or tissue degen Prosthetic valve dysfunction due to fibrous tissue eration for periods up to eight years following implantation. However, the second gener may prevent complete excursion of valve occluder(s) or cusps ation of bovine pericaridal prostheses, such as the Carpentier to cause valvular stenosis or regurgitation. Valve occluder or Edwards pericardial valve, have increased durability compared cuspal motion may be interfered with by a variety of extrinsic with first generation pericardial valves (3,44). In fact, these factors other than fibrous tissue overgrowth, including a large bioprostheses appear to give results comparable with, and pos mitral annular calcific mass, septal hypertrophy, large rem sibly better than, porcine bioprostheses (73). Sutures Can J Cardiol Vol 20 Suppl E October 2004 77E Jamieson et al looped around stent posts may also restrict cuspal motion in critical if progress in valve prosthesis technology is to be main tissue valves (46). It is equally, if not even more, important that explant prosthetic valve cusps causing incompetence of tissue valves ed heart valve prostheses be examined in detail by individuals (46,86,87). In any patho Detailed analysis of surgically explanted prostheses and those logical examination of cardiovascular tissue, an established seen at autopsy is critical if progress is to be maintained in the protocol is important, so critical items in the analysis are not improvement of existing prostheses and the development of missed. One such protocol for the pathological analysis of pros newer prosthetic heart valves. Similar proto autopsies performed on cardiovascular patients who die is cols developed by others have been published in the past (5,8). Clin Exp Pharmacol Rupture of the posterior wall of the left ventricle after mitral valve Physiol 2002;29:735-8. Pathologic considerations in the surgery of adult heart New York: Springer-Verlag, 1985:209-38. Pathologic analysis of the cardiovascular system and New York: McGraw Hill, 1997:85-144. Guide to Prosthetic isolated replacement of the aortic or mitral valve with the Starr Cardiac Valves. J Am Coll Cardiol aortic valve replacement and myocardial revascularization: Results in 1988;11:1130-7. Klepetko W, Moritz A, Mlczoch J, Schurawitzki H, Domanig E, 78E Can J Cardiol Vol 20 Suppl E October 2004 Surgical management of valvular heart disease Wolner E. Semin Thorac Cardiovasc Surg embolization of a St Jude prosthetic mitral valve leaflet. Mechanical Eight-year results of aortic root replacement with the freestyle failure of a St Jude Medical prosthesis. J Heart Valve failure and pathologic findings in surgically removed Ionescu-Shiley Dis 2002;11:424-30. Thromboembolic risk and durability of the Hancock causes of failure in 24 explanted Ionescu-Shiley low-profile bioprosthetic cardiac valve. J Thorac Cardiovasc Surg echocardiographic and clinical follow-up of aortic Carpentier 1985;89:499-507. Anatomic analysis of removed prosthetic cryopreserved homograft valved conduits in the pulmonary heart valves: Causes of failure of 33 mechanical valves and circulation. Bioprosthetic cryopreserved allograft heart valves: Comparison with aortic valves valve failure. Calcific deposits in porcine bioprostheses: Structure A complication of cardiac valve replacement. Carpentier-Edwards overgrowth on Hancock mitral xenografts: A cause of late supraannular porcine bioprosthesis evaluation over 15 years. Early dehiscence from the stent post of Carpentier-Edwards bioprosthetic leaflet perforation as a cause of bioprosthetic dysfunction. Cuspal perforations bioprosthesis: Review of morphological findings in eight valves. Echocardiography dimensional measurement difficult, especially when assessment is an important adjuvant to the clinical evaluation of the of the effective valve area is more important. Epicardial echocar patient by providing more specific and quantitative informa diography may also be used in the operating room to evaluate the tion. In such cases, it is recommended that the examination be severity of valvular lesions. Similar considerations apply to the performed by an experienced cardiologist or anesthesiologist, electrocardiogram and chest radiograph which, in addition to trained in echocardiography, familiar with the evaluation of orienting towards hypertrophy or prior infarction, may provide valvular heart disease by Doppler echocardiography. Accurate and precise description of valve dient and valve area may be determined by Doppler interroga morphology is essential. The peak instantaneous pressure of leaflet thickness, mobility, calcification, annular character gradient between the left ventricle and the aorta can be meas istics and subvalvular disease for the atrioventricular valves. Echocardiographic and Doppler techniques dynamic muscular subaortic obstruction, the modified are needed to assess the severity of valvular regurgitation and Bernoulli equation cannot be applied to the aortic velocity jet remodelling of the cardiac chambers in response to the volume because the proximal velocity is not laminar. Another important aspect to consider is the com However, the severity of aortic stenosis, in many patients, may parison with previous examinations, to determine if the be incorrectly estimated by transthoracic two-dimensional situation is stable or has deteriorated. Interventions to normalize cardiac output echocardiography or cardiac catheterization as mild, moderate with dobutamine may distinguish the two entities (28-31). If the cardiac output does not However, it is important to recognize that transvalvular pres change and the mean pressure gradient is less than 30 mmHg, sure gradients are proportional to the square of transvalvular there is diminished myocardial reserve. Thus, transvalvular pressure gradients may overestimate the role of exercise testing in patients with aortic stenosis the severity of aortic stenosis in the presence of hyperdynamic has evolved and may become an important method for risk states or aortic regurgitation, and underestimate the severity of assessment in asymptomatic adult patients with significant aor aortic stenosis in low flow states as with significant dysfunction tic stenosis (32-35). The normal valve area in small exercise decrease in stroke volume or cardiac output (26). With this orifice reduction, Exercise testing can be included in the decision-making small incremental changes in orifice area lead to large incre process for surgery and during clinical follow-up. It is important to recognize that the absolute time method, two-dimensional orifice planimetry or the conti valve area may not be an ideal index of aortic stenosis severity nuity equation (37,38). In this regard, mild aortic tral flow (eg, exercise, emotional stress, infection, pregnancy) stenosis is defined as a valve area greater than 1. The morphological appearance of the mitral valve appa premature diastolic closure of the mitral valve, which may be ratus is assessed by two-dimensional echocardiography, includ detected on M-mode recordings of the mitral valve. Fluttering ing leaflet thickness and mobility, commissural calcification of the anterior mitral valve leaflet confirms the presence of and degree of subvalvular fusion (42). Each of these parameters aortic regurgitation but does not provide any assessment of is subjectively scored from one (least severe) to four (most severity. The presence of holodiastolic flow reversal in the severe) and a total score out of 16 is reported.

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In general, 10% of clefts were accompanied by a chromosomal abnormality and 27% had associated anomalies [26,29,30]. Syndromes associated with craniofacial abnormalities abnormalities and molecular analysis in some syndromes, such as Other Syndromes Apert, Crouzon, Pfeiffer, and Jackson-Weiss syndromes, and Saethre abnormalities Chotzen syndrome when the family history is informative [38 Facial cleft Hands Ectrodactyly, ectodermal dysplasia, 40]. If the prognosis is Chotzen syndrome, Muenke syndrome, Jackson-Weiss syndrome, poor, as in cases of multiple anomalies or associated aneuploidies, Antley-Bixtler syndrome, Wolf the option of termination of pregnancy can be offered depending on Hirschhorn (4p) syndrome the gestational age and local regulations. Alternatively, continuation of pregnancy with prenatal counseling is appropriate for mild and isolated abnormalities such as cleft lip. Craniosynostosis is associated When fetal cataract, microphthalmia or anophthalmia, or with a higher unplanned cesarean delivery rate, birth trauma, microcephaly is found, maternal blood can be taken to screen perinatal complications, and airway obstructions [43]. Isolated cleft Inquiring about exposure to some medications, such as valproic acid, lip/palate or cleft palate alone carry an increased recurrence risk. Many facial Conclusion abnormalities, including median cleft lip, hypertelorism/hypotelorism, microphthalmia/anophthalmia, and cataract, are associated with the prenatal diagnosis of craniofacial abnormalities remains diffcult, chromosomal abnormalities, some of which are common and some especially in the frst trimester. For example, hypertelorism is associated with skull and face can increase the detection rate. When an abnormality deletion 4p (Wolf-Hirschhorn syndrome) or tetrasomy 12p (Pallister is found, it is important to perform a detailed scan to determine its Killian syndrome). The prenatal diagnosis of craniosynostosis severity and to search for additional abnormalities. The use of 3D/4D depends on the ultrasonographic findings of craniofacial ultrasound may be useful in the assessment of cleft palate and 22 Ultrasonography 38(1), January 2019 e-ultrasonography. Family series with report of neurodevelopmental outcome and review of the literature. The accuracy of antenatal ultrasound prenatal diagnosis by 2D/3D ultrasound, magnetic resonance in the detection of facial clefts in a low-risk screening population. Leibovitz Z, Daniel-Spiegel E, Malinger G, Haratz K, Tamarkin M, Structural fetal abnormalities: the total picture. Prenatal fndings in children with early postnatal diagnosis of third trimester study and a review. Second-trimester molecular prenatal diagnosis of chromosomal abnormalities, associated anomalies and postnatal sporadic Apert syndrome following suspicious ultrasound fndings. In that context, it should not be assumed that those women who really do not wish to know will be recognised as having a protective right. The Plausibility of a Claimed Right to Know and Right Not to Know With rapid developments in human genetics, while some humans might wish to know more about their own genetic profile, other humans might prefer not to inquire and not to be 6 Generally, see R. Shickle (eds), the Right to Know and the Right Not to Know, Cambridge, Cambridge University Press, 2014. After all, the whole point of recognising a right to informational privacy and confidentiality is to deny that there is a general right to know. Similarly, simply because A would prefer not to know something about B, it surely does not follow (absent special circumstances) that A has a claim-right against B, or against others, that they should not disclose the information to A. If we concede that there is no general right to know, we might nevertheless argue that, in some particular contexts (such as insurance and employment) or special circumstances (such as B making the equivalent of an easy rescue by passing on potentially 11 life-saving information to A), there is a reasonable expectation that certain information will be disclosed (and, thus, a prima facie right to know). Scheingold, the Politics of Rights: Lawyers, Public Policy, and Political Change, Ann Arbor, University of Michigan Press, 1974. Laurie (eds), Inspiring a Medico Legal Revolution (Essays in Honour of Sheila McLean), Farnham, Ashgate, 2015, 173. This is not a case of A seeking information about B or, conversely, resisting the disclosure of information about B; the information in respect of which A claims a right to know, or not to know, is about herself or her baby. If anyone has a 12 right to know, or not to know, about herself or her baby, it is surely A. The mother and the foetus were two distinct organisms living symbiotically, not a 17 single organism with two aspects. The circumstances, however, might be otherwise; possibly, this is a mother who does not wish to know because, quite simply, she has decided to continue with the pregnancy regardless of the test results. At this stage, it is enough to say that, while a general right to know or a general right not to know is implausible, there are reasons for thinking that, in the context of pregnancy screening, the claimed rights have a sufficient plausibility to put the burden on to those who would deny them. While, as we have seen already, the precise scope of each claimed right is somewhat unclear, this is just one of a number of potentially contentious points. In principle, there are a number of responses open to B and counter-responses open to A. Rather, the justification for proposed public health interventions or practices is that they promise to promote the general utility; and, in clinical settings, medical professionals strive to avoid doing any harm as well as trying to do some good for patients. It follows that, if the default position in relation to current practice is that individuals have a right not to be conscripted, then this undermines any claim that screening is a rights-free zone. The particular rights are not recognised Even if it is conceded that pregnant women who are screened have some rights, B might object that the claimed rights are simply not recognised. Mieth (eds), Cambridge Handbook of Human Dignity, Cambridge, Cambridge University Press, 2014, 1. More ambitiously, A might argue that the claimed rights are immanent within our existing understanding of such concepts as agency, property, and privacy (and our understanding of their associated rights).


  • https://www.interscienceinstitute.com/docs/Neuroendocrine-Tumors-4th-Edition.pdf
  • https://www.cartercenter.org/resources/pdfs/health/ephti/library/lecture_notes/nursing_students/LN_Pediatrics_final.pdf
  • https://www.velocityhc.com/wp-content/uploads/2019/09/Dorlands-Dictionary-of-Medical-Acronyms-and-Abbreviations-2016.pdf
  • https://promundoglobal.org/wp-content/uploads/2018/04/Masculine-Norms-and-Violence-Making-the-Connection-20180424.pdf

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