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A study was done in which 156 young children with diarrhea had stool samples taken purchase discount levitra extra dosage on line erectile dysfunction drugs and medicare. All of them were tested for the presence of white blood cells in the stool cheap levitra extra dosage 40mg overnight delivery erectile dysfunction drugs reviews, and a positive test was defined as one in which there were Utility and characteristics of diagnostic tests 259 D+ D− Totals Fig safe levitra extra dosage 40mg erectile dysfunction doctor in nashville tn. There were 27 children who had positive cul- tures and 23 of these had smears that were positive for fecal white blood cells discount 60mg levitra extra dosage free shipping gluten causes erectile dysfunction. Of the 129 who had a negative stool culture, 16 had smears that were positive for fecal white blood cells. This is a test that will increase the likelihood of disease by a lot if the test is positive and decrease the likelihood of disease by a lot if the test is neg- ative. We will talk about applying these numbers in a real clinical situation in a later chapter. It is always necessary to be aware of biases in a study, and this example is no different. It was done on 156 children who presented to an emergency department with severe diarrhea and were entered into the study. This meant that someone, either the resident or attending physician on duty at the time, thought that the child had infectious 260 Essential Evidence-Based Medicine or bacterial diarrhea. Therefore, they were already screened before any testing was done on them and the study is subject to filter or selection bias. This simply means that the population in the study may not be representative of the pop- ulation of all children with diarrhea like the ones being seen in a pediatric or family-practice office. The next chapter will deal with this problem and how to generalize the results of this study to real patients. Albert Einstein (1879–1955) Learning objectives In this chapter you will learn: r how to define predictive values of positive and negative test results and how they differ from sensitivity and specificity r the difference between odds and probability and how to use each correctly r Bayes’ theorem and the use of likelihood ratios to modify the probability of a disease r how to define, calculate, and use interval likelihood ratios for a diagnostic test r how to calculate and use positive and negative predictive values r how to use predictive values to choose the appropriate test for a given diag- nostic dilemma r how to apply basic test characteristics to solve a clinical diagnostic problem r the use of interval likelihood ratios in clinical decision making In this chapter, we will be talking about the application of likelihood ratios, sen- sitivity, and specificity to a patient. Introduction Likelihood ratios, sensitivity, and specificity of a test are derived from studies of patients with and without disease. They are stable and essential characteristics of the test that give us the probabilities of a positive or negative test if the patient 261 262 Essential Evidence-Based Medicine does or does not have disease. This is not the information a clinician needs to know in order to apply the test to a single patient. What the clinician needs to know is: if a patient has a positive test, what is the likelihood that patient has the disease? For a given patient, how will the probability of dis- ease change given a positive or negative test result? Applying likelihood ratios or sensitivity and specificity to a selected pretest probability of disease will give the post-test probability to answer this question. The first uses Bayes’ theorem, while the second calculates the predictive values of a positive and negative test directly from sensitivity, speci- ficity, and prevalence using the 2 × 2 table. If the test comes back positive, it shows the probability that this patient really has the disease. Probabilistically, it is expressed as P[D+|T +], the probability of disease if a positive test occurs. That is the proportion of people with a positive test who do not have disease and will then be falsely alarmed by a positive test result. If the test comes back negative, it shows the probability that this patient really does not have the disease. Prob- abilistically, it is expressed as P[D– | T –], the probability of not having disease if a negative test occurs. That is the proportion of people with a negative test who have disease and will be falsely reassured by a negative test result. In eighteenth-century English, it said: “The probability of an event is the ratio between the value at which an expec- tation depending on the happening of the event ought to be computed and the value of the thing expected upon its happening. In simple language, the theorem was an updated way to predict the odds of an event happening when confronted with new information.

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True buy levitra extra dosage 60 mg mastercard erectile dysfunction treatment london, there should have been quite a few more chapter headings than were actually added order 40mg levitra extra dosage mastercard high cholesterol causes erectile dysfunction. For example buy online levitra extra dosage erectile dysfunction drugs in homeopathy, in the Treatments for Women section 40 mg levitra extra dosage with visa non prescription erectile dysfunction drugs, the chapter on cancer of the nose is followed immediately by one on provoking the menses (¶¶ and ), with no chapter division to signal the separation of two such obviously distinct topics. Still, the addition of the regularized rubrics undoubtedly increased the utility of the text for ref- erence purposes. Perhaps the most important of these rubrics was the open- ing one: ‘‘On the Diseases of Women According to Trotula’’ (De passionibus mulierum secundum Trotulam), yet another reinforcement of the attribution of this wide-ranging collection of texts on women’s medicine to the single author ‘‘Trotula. Many of the changes that the texts underwent between their com- position and the mid-thirteenth century were subtle and insignificant for the works’ actual theoretical or therapeutic content. Some changes might be con- sidered real improvements: the transposition of several of Treatments for Women’s cosmetic chapters into the Women’s Cosmetics section rendered them more accessible, while additions like the precise instructions for the prepara- tion of starch (¶) must have been genuinely helpful. But some changes were not calculated emendments but accidental errors that crept into the texts. The loss of the negative in the opening sentence of ¶ in Treatments for Women, for example, had the result of encouraging treatment of old women suffer- ing from a sanious flux, whereas the original text had said it was pointless to treat them because they were already incapable of bearing children. Many errors or corruptions, of course, would not have been obvious to readers without multiple copies of the texts at hand. Yet the failure of later scribes or readers to correct some of the more glaring errors must give us pause when imagining how actively the standardized ensemble in particular might  Introduction have been used in any kind of clinical setting. Not a single reader of the extant standardized ensemble manuscripts seems to have noticed, for example, the obvious logical inconsistency within a recipe in Women’s Cosmetics for redden- ing the skin and lips, where an accidental misreading changed a prescription to use a violet dye into one for a green dye (¶). And one wonders how even the most dedicated occultist could have made sense of the garbled magical passages in ¶¶ and . It is likely, however, that the standardized ensemble became the preferred version of the Trotula texts, not because it was scrutinized in de- tail for every possible remedy for women’s conditions (there are, after all, over three hundred different prescribed therapies), but because it could serve a more general function as a basic referencework on fertility—a subject on which there was increasing concern from the thirteenth century on. L D The standardized ensemble is today found in twenty-nine manuscripts from all parts of Latinate Europe. In the fifteenth century, even though other forms of the texts were still being tran- scribed in many parts of Europe, the standardized ensemble seems to have been rarely copied in Italy, England, or even in France, where the text had earlier achieved its greatest popularity. Most of the extant fifteenth-century manu- scripts come from central and eastern Europe. The standardized ensemble seems always to have been closely associated with university circles and in this context manuscripts preserved their utilityas reference texts for years after their initial composition. At his death (sometime between  and ), the theo- logian Gérard of Utrecht left his copy to the College of the Sorbonne in Paris, where it was to remain until the modern period. Caillau then gave the manuscript to his patron the duke in exchange for another book. A final indication of the standardized ensemble’s utility was its translation in the fifteenth century into the vernacular, once into Dutch, once, perhaps twice into French, and twice into German. Copy after copy reproduced the text with hardly any variation, in stark contrast to earlier versions, which copyists often felt free to abridge or emend as they liked. One scribe re- interpreted the title as ‘‘The Good TreatiseWhich Is Entitled ‘The Old Woman on the Sufferings [of Women]. Kraut’s major editorial innova- tion was to reorganize all the material from the ensemble into one smoothly ordered summa, rearranging the ensemble’s disparate parts into sixty-one chap- ters. Gone, too, of course, were any remaining hints that the Trotula was a concretion of a variety of sources from a variety of differ- ent authors. While in general Kraut seems to have been concerned to preserve most of the material he found in the standardized ensemble, humanist that he was he could not refrain entirely from tidying up the text. He suppressed the two references to magical practices to aid birth in Conditions of Women (¶¶ and ), he clarified that the contraceptives were to be used only if out of fear of death the woman did not dare conceive,221 and he apologized for the in- clusion of mechanisms to ‘‘restore’’ virginity, saying that he would not have included them were they not necessary to aid in conception. Kraut was apparently motivated by the desire to make both the femininity and the originalityof ‘‘Trotula’’ more apparent. Whereas neither the original Condi- tions of Women nor the standardized ensemble had offered any direct hint of the author’s gender, Kraut, presuming the whole of his newly unified text to be the work of a single feminine author, altered the preface to stress her gender.

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Thyroxine dosing is titrated come hypothyroid requiring treatment with thyroxine according to thyroid function tests buy 40mg levitra extra dosage erectile dysfunction pump rings. Hashimoto’s disease (autoimmune Myxoedema coma thyroiditis) Definition Definition This is the end-stage of untreated hypothyroidism buy cheapest levitra extra dosage erectile dysfunction doctor orlando, lead- Organ-specific autoimmune disease causing thyroiditis ing to progressive weakness buy levitra extra dosage in united states online zma erectile dysfunction, hypothermia purchase levitra extra dosage online testosterone associations with erectile dysfunction diabetes and the metabolic syndrome, respiratory and later hypothyroidism. Myxoedema coma may be precipitated by inter- Malignant tumours of the thyroid current illness or disorder, such as heart failure, perhaps Papillary adenocarcinoma following a myocardial infarction, stroke, pneumonia; iatrogenic causes include water overload and sedative or Definition opiate drugs. A slow-growing, well-differentiated primary thyroid tu- mour arising from the thyroid epithelium. Pathophysiology Thyroid hormones maintain many metabolic processes Incidence/prevalence in the body. Severe and chronic lack of these hormones 50% of malignant tumours of the thyroid. F > M Clinical features Clinical features There may be a history of previous thyroid disease, Presentsasasolitaryormultifocalswellingofthethyroid. The patient appears obese with may be the only sign when there is a microscopic pri- hypothermia,yellowishdryskin,thinnedhair,puffyeyes mary. Papillary tumours spread via lymphatics within and has a slow pulse, respiration and reduced reflexes. Investigations Management Patients may be identified during investigation for a soli- Myxoedema coma requires admission to intensive care. Definitive diagnosis r Respiratory failure requires support and may necessi- is by histology, although cytology from fine needle aspi- tate ventilation. Management r Corticosteroids must be given if adrenal insufficiency Total thyroidectomy with excision of involved neck is present. Radioactive iodine therapy may Chapter 11: Thyroid axis 435 be used prophylactically or as treatment for metastases. A postoperative radioisotope scan of the Prognosis skeleton and neck detects metastases as ‘hot spots’, and Tenyear survival rates of almost 90%. Plasma thyroglob- Follicular adenocarcinoma ulin levels can be monitored for recurrence. Definition Aprimary malignancy of the thyroid gland arising from Medullary carcinoma the thyroid epithelium. Definition Incidence/prevalence Tumour of the thyroid that arises from the parafollicular Approximately 20% of cases of thyroid malignancies. F > M Pathophysiology Clinical features The parafollicular cells originate from neural crest tis- Typically presents as a solitary thyroid nodule in middle- sue during embryonic life, but merge with the embry- aged patients. Parafollicular cells normally secrete calcitonin, a Investigations polypeptide, in response to small increases in calcium. Patients are investigated as for a solitary thyroid nodule The tumour cells secrete calcitonin and carcinoembry- (see page 430). Twenty per cent lymph nodes are palpable in about half of cases, but of patients have metastases in the lungs, bone or liver. Resembles a benign solitary thyroid nodule, a round encapsulated mass, but less colloid and more solid in Microscopy appearance. Histology reveals invasion of the capsule, The tumour is composed of sheets of small cells blood vessels and surrounding gland. Investigations Thyroidectomy Calcitonin levels are raised, although serum calcium lev- Hyperthyroid patients must be made euthyroid before els are normal. Calcitonin is also used for follow-up and thyroid surgery using antithyroid drugs and β-blockers for screening of relatives. The thyroid is exposed via a transverse skin-crease Management incision above the sternal notch. The lobes of the thy- Total thyroidectomy and dissection of lymph nodes in roid are supplied by the superior and inferior artery, the central neck compartment. These are dissected out, ligated and divided removing the desired amount of thyroid tissue. Surrounding struc- Anaplastic carcinoma tures that require identification and protection include Definition the parathyroid glands and the recurrent laryngeal This is a highly malignant tumour of the thyroid. Neuropraxia (temporary damage) of the recurrent laryngeal nerve occurs in Pathophysiology 5% of operations.

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