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The sections and chapters researched in this manner are noted throughout the guideline and the source of the information noted. The issues raised in these submissions were considered carefully and consulted about internally and externally by the guideline developers. The evidence base included only high-risk populations (but with differences in definitions), who represent only 10% of people who develop type 1 diabetes. Applicability A the studies included one from Australia; the remainder were from countries with well- established health-care systems. Evidence statement There is no evidence to support the use of any intervention to delay or prevent the onset of type 1 diabetes. Consistency A All studies reporting diabetes as an outcome were consistent (excluding the one poor- quality study). Details For full systematic review, see Chapter 3 of the accompanying technical report Recommendation R3. Level I evidence shows that there is increased prevalence of bulimia nervosa in adults and adolescents with type 1 diabetes compared to the general population. Generalisability A Paediatric, adolescent and adult populations were delineated in most studies. Applicability B Studies were from North America and Europe; thus, they were from countries with well- established health-care systems. Details For full systematic review, see Chapter 4 of the accompanying technical report Recommendation R4. The magnitude of this effect is greatest in children with early onset type 1 diabetes. Adults demonstrated a small-to-moderate effect on several cognitive domains, again with no effect on learning and memory. In relation to metabolic control, a higher HbA1c is associated with a negative impact on cognitive function (reported in two studies including children >9 years, adolescents and adults). In early-onset diabetes, a negative association was reported in one prospective study and one meta-analysis. Exclusions included diabetes complications, history of head trauma and depression. There is no evidence from the older adult or the elderly population (especially with respect to dementia). Applicability A One study was in Australian children, two were from the United States. There was a nonsignificant advantage to real-time monitoring, with the direction fairly consistent across studies. Clinical impact D Generalisability C Studies included children and adolescents, or adults, but some had a small sample size. Other factors Continuous real-time monitoring is not used routinely in Australia, but is a rapidly developing technology. The clinical role of real-time blood glucose monitoring is expected to increase with time; therefore, the current evidence statement may become outdated. Evidence statement There is insufficient evidence to support routine use of continuous real-time monitoring to improve HbA1c and reduce severe hypoglycaemia. Clinical impact D Generalisability C Applicability B Other factors None identified. Evidence statement There is insufficient evidence to support routine use of continuous retrospective blood glucose monitoring systems to improve HbA1c and reduce severe hypoglycaemia. A sensitivity analysis of the high- quality studies reduced the magnitude of the effect. A subgroup analysis of the paediatric group found a significant effect, but results in adults were conflicting. Generalisability B Applicability B the studies included one Australian study in children. Evidence base A Consistency C There were no reports of severe hypoglycaemia; there was insufficient evidence on this outcome, because studies lacked power due to low event rates.
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The incidence of nodal metastases varies widely Neck management of supraglottic cancer requires a different from 10% to 50%, depending on the choices of clinical, imag- philosophy than that of glottic cancer because in the former, the ing, and histopathological methods [207,261,262]. The propriate cervical lymph node treatment is an important aspect morbidity associated with selective neck dissection is very low. The presence of clini- served difference in the development of postoperative regional cally palpable cervical lymph node metastasis is associated with metastases in a prospective case-control study, with rates of an approximately 50% reduction in overall survival [252-256]. These authors demonstrated patients with supraglottic cancer who underwent comprehensive that 38 of 39 recurrences among 202 patients with supraglottic neck dissection. An analysis of the lymph node metastasis distri- cancer had developed in non-surgically treated necks. In their study, occult metas- 20 Clinical and Experimental Otorhinolaryngology Vol. Some authors suggested considering involved in cases of metastatic disease, and may be left in place elective neck dissection only when the tumor had spread into during neck dissection in patients with N0 necks [215,279-281]. Approximately 15% of the lymphatic circulation crosses the Recommendation 20 laryngeal midline and may lead to bilateral and contralateral Preoperative assessment and management of factors that metastases . The contralateral undissected neck is the most predispose a patient to postoperative complications are nec- common site of failure in cases of supraglottic cancer . However, other authors pre- edema of the skin flaps, fever, foul odor, and an elevated leuko- ferred to perform ipsilateral neck dissection under the assump- cyte count imply wound infection. Many investigators ing or extending up to the midline had a higher risk of contra- have reported factors that predispose patients to pharyngocuta- lateral metastases when compared with well-lateralized tumors. Routine bilateral neck dissection cal factors such as the tumor location and stage, persistent dis- for the treatment of early-stage lateral supraglottic cancer with a ease, pre- or postoperative radiotherapy, preoperative tracheos- clinically N0 neck might not be necessary because no significant tomy, extent of neck dissection, method of pharyngeal closure, improvements in regional control and survival have been ob- and early nasogastric tube removal are considered predisposing served with this technique relative to the use of ipsilateral neck factors for pharyngocutaneous fistula [282-289]. Usually, the incidence and severity of this clinically N0 patients with supraglottic and transglottic carcino- condition are related to the extent of resection. Laryngeal Cancer Surgical Guidelines 21 surgical closure or cicatricial scar formation. This study found that the chemoradiotherapy presence of a tube that induces local inflammation and fibrosis, group had a higher locoregional control rate (82% vs. Radiation therapy, thy- verse features and found that the chemoradiotherapy group, roid gland invasion, nodal metastasis, and postoperative fistula when compared with the radiotherapy group, had better 5-year were found to correlate significantly with the development of progression-free survival (47% vs. Adjuvant treatment apy, data from the two studies were subjected to a combined analysis . However, there were no additional gains in locoregion- or extracapsular nodal extension (strong recommenda- al control and disease-specific survival in the chemoradiotherapy tion, high-quality evidence). Postoperatively, what types of rehabilitation and/or mained the standard treatment. Generally, a total dose of 60 to psychiatric support are required for patients with laryngeal 66 Gy of conventional postoperative radiation is administered cancerfi However, local recurrence and distant failure rates are as high as 30% and Recommendation 22 25% and the 5-year survival rate is as low as 40% after radical (A) Swallowing rehabilitation can be recommended for pa- surgery with postoperative radiotherapy. In general, patients who undergo hemilaryngectomy have a Among the various methods, the supraglottic swallow and su- relatively lower rate of aspiration and a more rapid return to a per-supraglottic swallow maneuvers are especially effective not normal diet, compared to patients who undergo supraglottic lar- only for reducing aspirations in supraglottic laryngectomy pa- yngectomy [304,305]. However, a broader dissection site, which tients but also in patients who have received a full course of ra- may include arytenoid cartilage, increases the risk of developing diotherapy for head and neck [308,328]. A brief change in swallowing, particularly Surgical excision of laryngeal cancer may have a significant liquids, will occur after surgery; within 1 to 2 weeks; however, impact on the swallowing function because of the following fac- recovery begins as the normal side of the larynx compensates tors: tumor site, resected structures, and subsequent reconstruc- for the damaged side . Therefore, di- Up to 74% of patients who underwent supraglottic laryngec- agnostic imaging procedures such as the modified barium swal- tomy reported postoperative aspiration, and approximately 4 to low with videofluorography should be used along with various 6 weeks were required for these patients to achieve a safe and rehabilitation methods for successful swallowing rehabilitation. However, a longer period might be needed to recover normal swallowing once a large tongue E2-2. Voice rehabilitation methods after total laryngectomy base resection has been performed .
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In a study in Sweden, a trend towards an association was found with duration of residence in areas endemic for goitre (Galanti et al. The odds ratio was significantly increased for women who were currently using oral contraceptives (odds ratio, 1. The few studies available generally did not address the specific compounds included in this volume. These reports are reviewed in each of the four monographs dealing with these drugs (methimazole, methylthiouracil, propylthiouracil and thiouracil). Exposure to non-radioactive chemicals has not been shown to result in the development of thyroid carcinoma in humans. Pathogenesis of thyroid neoplasms in humans Studies on the pathogenesis of thyroid neoplasms in humans have tended to focus on structural changes in cancer-related genes in thyroid tumours, rather than on hormonal factors. Chromosomal abnormalities have been identified in follicular and papillary thyroid adenomas and carcinomas and in medullary thyroid neoplasms (Gillenwater & Weber, 1997; Kroll et al. These chromosomal changes are associated with alterations in both oncogenes and tumour suppressor genes. Such agents often also produce hepatocellular tumours, particularly in mice (see McClain & Rice, 1999). The lack of evidence for a role of chemicals in the causation of human thyroid neoplasms, in contrast to the frequent observation of thyroid tumours in bioassays for carcinogenicity in experimental animals, raises the question of whether, and in what way, thyroid tumours in laboratory animals predict a cancer hazard for humans (Capen, 1997). Simply feeding an iodine- deficient diet to rats is sufficient to cause not only goitre but thyroid follicular cell adenoma and carcinoma as well (Ohshima & Ward, 1986). After iodine is taken up in the follicular cell, it is oxidized by thyroid peroxidase and bound to tyrosyl residues of the thyroid-specific protein thyroglobulin. More T4 than T3 is released from the thyroid, but T4 is deiodinated by 5fi-monodeiodinase type I peripherally to produce T3 locally. These agents can be assumed not to be carcinogenic in humans at concentrations that do not lead to alterations in thyroid hormone homeostasis. The Working Group considered that some clarification of these criteria was desirable. Animals used in hormonal assays should be treated by the same route and dose as animals in which tumours developed in bio- assays for carcinogenicity. General statement regarding the determination of genotoxicity or non- genotoxicity of a substance There is no general agreement about the numbers or types of tests that are needed to determine the genotoxicity or non-genotoxicity of a substance. It is generally agreed, however, that tests for gene mutation and for chromosomal damage are required (McGregor et al. The tests for gene mutation most widely used involve bacteria (usually Salmonella) and mammalian cells in vitro, with and without exogenous metabolic activation. As a rule, a substance that reproducibly induces gene mutation or chromo- somal damage (measured as aberrations or micronuclei) is to be considered a geno- toxic agent. It should be specified whether the evidence of genotoxicity is based on the results of in-vitro tests, in-vivo tests or both. It is more difficult to find agreement on the tests and patterns of test results necessary to declare a substance non-genotoxic. In order to do so, a consistent pattern of negative results should have been found in bacteria and mammalian cells in vitro and in mammals in vivo. For most of the agents reviewed in this Monographs volume, few data were available from adequate tests of genetic toxicity. Trade names for methimazole include Basolan, Danantizol, Favistan, Frentirox, Mercazole, Metazole, Metibasol, Metothyrine, Strumazol, Tapazole, Thacapzol, Thia- methazole, Thycapzol, Thyrozol and Tirodril (Budavari, 2000; Royal Pharmaceutical Society of Great Britain, 2000; Swiss Pharmaceutical Society, 2000). Methods have been reported for the analysis of methimazole in biological fluids (blood, milk, serum, urine), tissues, incubation material and dried animal feed. Studies have shown better compliance with methimazole than with propylthiouracil (see monograph in this volume), most likely due to the single daily dose of the former (Nicholas et al. Carbimazole, the 3-carbethoxy derivative of methimazole, is converted to methi- mazole in vivo.
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African Grey Parrots appear to be with a bird progressively damaging all or part of the particularly prone to feather picking, perhaps as a accessible plumage, leading to abnormalities in nor- result of their sensitive natures or need for a highly mal feather development and molt. Spoiled, improperly social- characterized by over-preening and subsequent dam- ized, hand-raised birds of any species may also be age to the skin or muscle. Cockatoos and conures fre- cause, or occur secondary to, chronic ulcerative der- quently develop feather-picking behavior for which matitis. By Many feather-picking or self-mutilating birds are comparison, idiopathic feather picking in budgeri- considered to be pruritic, which is difficult to docu- gars and cockatiels is rare. Over-preening and scratching an area with the picking associated with ulcerative dermatitis of the nails is suggestive. Chronic feather picking can result in sufficient damage to the follicles to prevent any future feather growth (Figure 24. Therapy for self-mutila- tion of undetermined etiology should be considered effective if the destructive behavior can be reduced. In a retrospective study of 106 feather-picking cases, 31 had no change on follow-up examination; resolu- tion of the problem occurred in 20 cases; 21 showed some improvement; and 34 were lost to follow-up. Some of these birds will stop mu- with behavior modification, drugs may be necessary. Assuming that idi- sants and antihistamines (hydroxyzine hydrochlo- opathic self-mutilation is a result of some undetect- ride,c 2 mg/kg oral). These therapeutic agents are able neurosis, it would be considered unwise for frequently discussed but are rarely effective. Hormo- these birds to be added to a breeding collection where nal therapies including thyroxine, testosterone and they may pass on genes that will predispose their medroxyprogesterone have also been suggested for progeny to the same problem. Any underlying medical problems should be stopping some sexually related behavioral disorders identified and corrected. Various foul-tasting sub- including feather picking, aggressiveness and mas- stances are frequently applied to the feathers in an turbation; however, the drug can have severe side-ef- unsuccessful attempt to modify the picking behavior. Treatment for feather picking should include the correction of organopa- Ongoing studies suggest that haloperidold may be thies, specific therapies for folliculitis (bacterial or effective in some feather-picking cases. It takes two days to stabilize the photoperiod that varies naturally with the seasons, dose. Side-effects include loss of appetite, incoordina- and behavioral modification (see Chapter 4). If there are no side-effects and a therapies are determined to be ineffective over a bird is still picking, the dose can be increased in 0. Dosed at 1-2 mg/kg, the patients unliked child, an abusive adult) can guide the clinician respond for up to 14 to 21 days. Both administration in making specific recommendations to correct the be- forms have to be used continually unless the initiat- havior and resolve the problem (see Chapter 4). With Feather damage can be prevented by beak trimming or, some birds, the addition of new toys or moving an as a last resort, by applying restrictive collars (Figure enclosure to a different location will be a stress factor 24. These procedures only suppress the clinical that induces feather-picking, while with other birds signs and do not address the underlying problem. A bird that is properly social- Endocrine-related Feather Disorders ized and adapted early in life to changes in daily routine is less likely to develop emotional problems In poultry, hypothyroidism causes black, brown and due to separation anxiety when changes occur later yellow feathers to become red, longer and more in life. Hyperestrogenism has been asso- ciated with proliferation of endosteal bone in birds, but has not been associated with feather lesions (see Chapter 23). Up to 60% of the male canaries in some flocks may develop baldness that is responsive to a change in the level of nutrition provided. Persistent generalized inactivity of the feather folli- cles should be considered abnormal. Although no feather measurements were obtained, photographs of this bird suggest that con- Polyfolliculitis tour feathers lacked width and were shorter than normal. This bird responded favorably to treatment Pruritic polyfolliculitis and dermatitis that may be with 0.
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