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By D. Dennis. Central Christian College of the Bible.

Since the purpose of qualitative research is discount phenytoin 100 mg with visa, in large measure generic 100mg phenytoin with mastercard, to describe or understand the phenomena of interest from the perspective of the participants order 100mg phenytoin fast delivery, member-checking is useful buy phenytoin 100 mg on line, because the participants are the only ones who can legitimately judge the credibility of the results. Readers of qualitative articles will encounter a few analytic approaches and principles that are commonly employed and deserve mention by name. A con- tent analysis generally examines words or phrases within a wide range of texts and analyzes them as they are used in context and in relationship with other lan- guage. Using this approach, researchers immerse themselves repeatedly in the collected data, usually in the form of transcripts or audio or video recordings, and through iterative review and interaction in investigator meetings, coupled with reflection and intuitive insight, clear, consistent, and reportable observations emerge and crystallize. Grounded theory is another important qualitative approach that readers will encounter. The self-defined purpose of grounded theory is to develop theory about phenomena of interest, but this theory must be grounded in the reality of observation. Coding involves naming and labeling sentences, phrases, words, or even body language into distinct categories; memoing means that the researchers keep written notes about their observations during data analysis and during the coding process; and integration, in short, involves bringing the coded information and memos together, through reflection and discussion, to form a theory that accounts for all the coded information and researchers’ observa- tions. For grounded theory, as for any other qualitative approach, triangulation, member-checking and other approaches to ensuring validity remain relevant. Judging the validity of qualitative research is no easy task, but determining when and how to apply the results is even murkier. When qualitative research is intended to generate hypotheses for future research or to test the feasibility and acceptability of interventions, then applying the results is relatively straight- forward. Whatever is learned from the qualitative studies can be incorporated in the design of future studies, typically quantitative, to test hypotheses. For exam- ple, if a qualitative research study suggests that patients prefer full and timely disclosure when medical errors occur, survey research can determine whether this preference applies broadly and whether there are subsets of the population for whom it does not apply. Moreover, intervention studies can test whether edu- cating clinicians about disclosure results in greater levels of patient satisfaction or other important outcomes. But when can the results of qualitative research be applied directly to the day- to-day delivery of patient care? The answer to this question is, as for quantitative research, that readers must ask, “Were the study participants similar to those in my own environment? If the study participants were clinicians, were their clinical and professional situations similar to my own? If the answers to these questions are “yes,” or even “maybe,” then the reader can use the results of the study to reflect on his or her own practice situation. If the qualitative research study explored patients’ perceived barriers to obtaining preventive health care, for example, and if the study population seems similar enough to one’s own, then the clinician can justifiably consider these poten- tial barriers among his or her own patients, and ask about them. Considering another example, if a qualitative study exploring patient–doctor interactions at the end of life revealed evidence of physicians distancing themselves from rela- tionships with their patients, clinicians should reflect and ask themselves – and their patients – how they can improve in this area. Qualitative research studies rarely result in landmark findings that, in and of themselves, transform the practice of medicine or the delivery of health care. Nevertheless, qualitative studies increasingly form the foundation for quantita- tive research, intervention studies, and reflection on the humanistic components of health care. Napoleon I (1769–1821) Learning objectives In this chapter you will learn: r how to describe the decision making strategies commonly used in medicine r the process of formulating a differential diagnosis r how to define pretest probability of disease r the common modes of thought that can aid or hinder good decision making r the problem associated with premature closure of the differential diagnosis and some tactics to avoid that problem Chapters 21 to 31 teach the process involved in making a diagnosis and thereby determining the best course of management for one’s patient. First, we will address the principles of how to use diagnostic tests efficiently and effectively. Then, we will present some mathematical techniques that can help the health- care practitioner and the health-care system policy maker come to the most appropriate medical decisions for both individuals and populations of patients. Medical decision making Medical decision making is more complex now than ever before. The way one uses clinical information will affect the accuracy of diagnoses and ultimately the outcome for one’s patient. Incorrect use of data will lead the physician away from the correct diagnosis, may result in pain, suffering, and expense for the patient, and may increase cost and decrease the efficiency of the health-care system. This is a list of plausible diseases from which the patient may be suf- fering, based upon the information gathered in the history and physical exami- nation. Gathering more clinical data, usually obtained by performing diagnostic tests, refines this list. However, using diagnostic tests without paying attention to their reliability and validity can lead to poor decision making and ineffective care of the patient. Overall, we are trying to measure the ability of each element of the history, physical examination, and laboratory testing to accurately distin- guish patients who have a given disease from those without that disease. The quantitative measure of this is expressed mathematically as the likelihood ratios of a positive or negative test. This tells us how much more likely it is that a patient has the disease if the test is positive or how much less likely the disease is if the test is negative.

Prognosis Rosacea is a chronic condition cheap phenytoin 100 mg with mastercard, and topical metronida- zole may be required to maintain remission discount 100 mg phenytoin amex. Rosacea Definition Achronic inflammatory facial dermatosis affecting the Hair and nail disorders central face characterised by vascular dilation generic 100mg phenytoin with visa, erythema and pustules generic 100 mg phenytoin amex. Alopecia is defined as hair loss; it is classified into diffuse and localised, scarring and non-scarring. Sex Aetiology/pathophysiology F > M The growth of hair from follicles passes through a cycle (see Fig. Aetiology/pathophysiology There is dilation of dermal blood vessels, hyperplasia of Clinical features and management sebaceous glands but normal excretion of sebum. The r Androgenic alopecia has a genetic tendency and is cause is unknown but it is more common in individu- androgen-dependent. Some females, starting from late teens increasing in inci- evidence suggests a role for hair follicle mites. In males the hairline recedes initially in the temporal regions before hair loss at the Clinical features Symptoms begin with recurrent flushing of the face, which worsens on exposure to hot drinks, alcohol, stress Table9. Thismayprecede,byyears,erythemaofthe Diffuse non-scarring Androgenic alopecia, metabolic, nose and cheeks. Scarring Discoid lupus, burns, radiation, foreign body in the eye, telangiectasia and inflammation lichen planus. Chapter 9: Hair and nail disorders 397 Anagen, Growth phase lasts two to three years. Catagen, Release of hair shaft involutional phase lasts two to three weeks Telogen, resting phase, lasts three to four months Figure 9. Topical minoxidil produces some response in up Idiopathic Possible steroidogenic abnormality to 30% of cases. Finasteride is also used in androgenic Iatrogenic Danzol, some oral contraceptive pills alopecia in males. Pituitary Hyperprolacinaemia r Telogen effluvium occurs when the normally asyn- Adrenal Congenital adrenal hyperplasia, Cushing’s chronous cycles in follicles synchronises after child- syndrome Ovarian Polycystic ovaries, hyperthecosis, some tumours birth, surgery or severe illness. Hir- develop well-demarcated circular patches of hair loss, sutism is caused by increased androgen production or, which may coalesce causing alopecia totalis. Pathog- more rarely, increased sensitivity of hair follicles to an- nomonic is the presence of exclamation mark hairs, drogens (see Table 9. Women with a normal menstrual cycle are unlikely to Hirsutism have an endocrine cause. Other features may include Definition acne, seborrhoea, androgenic alopecia, deepening of the Hirsutism is the androgen-dependent growth of hair in voice and clitoromegaly. The abdomen should be exam- awoman, which is in the same distribution as in males. Increased incidence Systemic illness Hypothyroidism, anorexia nervosa, of impetigo is seen in conditions damaging the integrity malnutrition, porphyria cutanea of skin such as eczema, and its spread is facilitated by tarda overcrowding and poor hygiene. Paraneoplastic syndrome Clinical features Impetigo appears as erythematous erosions with a char- Investigations acteristic golden brown crusting. There may be associ- Dependent on the level of virilisation and menstrual ated localised lymphadenopathy. Bullous impetigo de- anomaliesfound;hormoneprofileandabdominalimag- scribes punched-out blistering lesions with crusting due ing may be required. Management Management r Any underlying cause for excess androgen production Swabs should be taken. Of- r Physical methods of hair removal include shaving, ten the condition requires treatment with oral penicillin chemical depilatories, bleaching, electrolysis and laser (Streptococcus) and flucloxacillin (Staphylococcus). Cellulitis Hypertrichosis Definition Definition Cellulitis is an acute diffuse spreading infection of the Hypertrichosis is excessive hair in a non-androgenic dis- skin extending into the soft tissues. Clinical features Aetiology/pathophysiology Patients present with fine terminal hair diffusely on the The main causative organisms are β-haemolytic Strep- face, limbs and trunk. The mechanisms of infection are not clearly understood but may involve bacterial exotox- Infections of the skin and ins and cytokine release. There is warmth Impetigo andtendernesstotouch,oftenwithlocallymphadenopa- Definition thy. If untreated, there is spreading of the erythema, Impetigo is a contagious superficial skin infection oc- abscess formation and secondary septicaemia. Chapter 9: Infections of the skin and soft tissue 399 Complications Investigations Abscess formation, septicaemia, toxic shock-like syn- r Imaging may allow detection of gas in muscle too deep drome. Management Management Prevention of clostridial infections involves adequate Initial management with penicillin (Streptococcus) and wound care at the time of original trauma including ex- flucloxacillin(Staphylococcus);erythromycinisusefulfor cision and debridement of necrotic tissue. In vanced or if it fails to respond to oral therapy, parenteral established cases penicillin is the drug of choice. Aggres- penicillin and flucloxacillin are used, and clindamycin, sive surgical intervention with wide excision, opening of if penicillin allergic.

A review of observational studies (380) suggested that the background risk of major gastrointestinal complications is about 1–2 per 1000 per year at age 60 years buy 100mg phenytoin with amex. The excess risks attributable to aspirin are therefore 1–2 per 1000 per year at age 60 purchase phenytoin 100 mg overnight delivery. Among unselected people under 60 years generic phenytoin 100mg otc, therefore order 100 mg phenytoin with visa, the expected benefit in terms of myocardial infarction (2 per 1000 per year avoided) does not exceed the expected risk of a major gastrointestinal bleed. Further observational studies strongly suggested that the risk of bleeding associated with aspirin increases substantially in older people, rising to 7 per1000 per year at age 80; the balance of benefit and risk, therefore, needs to be clearly defined before aspirin can recommended for all elderly people. Estimates of the rate of excess haemorrhagic stroke associated with the use of aspirin in three primary prevention trials were 0. The meta-analysis of these studies (378) also found that aspirin was associated with an increased risk of haemorrhagic stroke (summary odds ratio 1. A similar analysis using the same primary prevention studies estimated comparable effects for haemorrhagic stroke, confirming that the absolute excess risk of haemorrhagic stroke attributable to aspirin is small (around 0. Balance of risks and benefits When considering the use of aspirin, the benefits must be weighed against the possible risks associated with its use, particularly the risk of haemorrhagic stroke but also gastrointestinal bleed- ing In people at high risk, the risk–benefit ratio of aspirin therapy is favourable in some European countries and North America, but may be less favourable in populations with a high incidence of gastrointestinal bleeding or haemorrhagic stroke and a low prevalence of coronary heart disease (382). In clinical practice, physicians should consider the individual’s probable risk–benefit profile before using aspirin for primary prevention. Fixed-dose combinations As many high-risk patients would benefit from treatment with several drugs proven to reduce cardiovascular disease, the notion of a combination pill, using fixed-dose formulations of effective drugs, was originally proposed to overcome two problems: the difficulty of adherence to treatment involving multiple pills; and the inadequate dosages often prescribed in routine clinical practice (384). The polypill was conceived as a means of mass treatment for everyone over 55 years of age, regardless of their risk factor profile or estimated total cardiovascular risk. The risk reduc- tion was estimated to be 88% for coronary heart disease and 80% for stroke. While the efficacy of aspirin in men is established, for example (387), the recently completed women’s health study found no difference in all-cause mortality or fatal and non-fatal myocardial infarction between groups of women given 100 mg of aspirin every other day or placebo (388). In reviewing the evidence supporting the use of combination therapy, a recent working group report commented that: (a) the estimates of effect may have been exaggerated; (b) adherence to treatment may be low in healthy populations; (c) new studies of efficacy, effectiveness and cost- effectiveness are needed; and (d) social and behavioural issues related to population coverage, adoption, and long-term maintenance need to be examined (393). In addition, the potentially damaging effect of a mass-medication approach on population-wide public health measures for tobacco control, healthy diets and physical activity need to be considered. Commentators are gen- erally agreed on the need for further research on the combination pill, and for continued strong engagement with public health programmes for cardiovascular disease prevention (394, 395). Marketing a polypill directly to individuals without testing, thus avoiding the costs of clinical consultation, risk factor measurement and scoring, and individualized prescription of treatments, sounds tempting, but runs the risk of overtreating people who are at low cardiovascular risk and undertreating people at substantial risk. Use of the polypill to treat people who have been classi- fied according to their total cardiovascular risk does have attractions, as it would simplify selec- tion of drugs and ensure predefined doses. In summary, while a combination pill has some promise as a means of targeted treatment, it raises major challenges that would have to be addressed if it is to meet the claims made for it. Hormone therapy Issue Does hormone replacement therapy reduce cardiovascular risk? Evidence On the basis of data from observational studies (400), hormone therapy has been used for pre- vention of cardiovascular disease, osteoporosis and dementia. This practice has been called into question following publication of the results of several randomized clinical trials, which showed no coronary protection, and the Women’s Health Initiative (401), which indicated that long-term use of estrogen plus progestin was associated with increased risks of cancer and cardiovascular disease. A Cochrane systematic review (402) of 15 randomized double-blind trials (involving 35 089 women aged 41 to 91 years) examined the effect of long-term hormone replacement therapy on mortality, heart disease, venous thromboembolism, stroke, transient ischaemic attacks, cancer, gallbladder disease, fractures and quality of life. All were placebo-controlled trials, in which perimenopausal or postmenopausal women were given estrogens, with or without progestogens, for at least one year. The only statistically significant benefits of hormone therapy were decreased incidences of frac- tures and colon cancer with long-term use. In relatively healthy women, combined continuous hormone therapy significantly increased the risk of coronary events and venous thromboembolism (after one year’s use), stroke (after 3 years), breast cancer (after 5 years) and gallbladder disease. Long-term estrogen-only hormone therapy also significantly increased the risk of stroke and gall- bladder disease. In relatively healthy women over 65 years taking continuous combined hormone therapy, there was an increase in the incidence of dementia. Global and regional burden of disease and risk factors, 2001: systematic analysis of popula- tion health data. Prevention of recurrent heart attacks and strokes in low and middle income popula- tions. A race against time: the challenge of cardiovascular disease in developing economies. Secondary prevention of non-communicable diseases in low- and middle-income countries through community-based and health service interventions. Risk factors in early life as predictors of adult heart disease: the Bogalusa Heart Study. Combined effects of systolic blood pressure and total cholesterol on cardiovascular disease risk. Joint effects of systolic blood pressure and serum cholesterol on cardiovascular disease in the Asia Pacific Region. Efficacy and safety of cholesterol- lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins.

Studies in baboons fed breast milk or formulas with or without cholesterol and with varying fat composi- tions found that early cholesterol intake had little effect on serum choles- terol concentrations in young adults up to about 8 years of age (Mott et al phenytoin 100mg sale. These differences were not explained by variations in the saturated and unsaturated fat content of the formulas and milk phenytoin 100mg free shipping. The major metabolic difference associated with the differences in plasma lipoproteins was lower rates of bile acid synthesis and excretion among the baboons that had been breast fed phenytoin 100 mg generic. The possible relations of early breast and bottle feeding with later cholesterol concentrations and other coronary heart disease risk factors were explored in several short-term studies and larger retrospective epide- miological studies purchase phenytoin 100 mg online, but these observations are inconsistent (Fall et al. The disparate findings may be due to confounding factors such as duration of breast feeding, since human-milk feeding for less than 3 months was associated with higher serum cholesterol concentrations in men at 18 to 23 years of age, or the type of formula fed since formula composition, especially quality of fat, which has changed dramatically in the last century (Kolacek et al. The available data do not warrant a recommendation with respect to dietary cholesterol intake for infants who are not fed human milk. How- ever, further research to identify possible mechanisms whereby early nutri- tional experiences affect the atherosclerotic process in adults, as well as the sensitive periods in development when this may occur, would be valuable. High amounts of cholesterol are present in liver (375 mg/3 oz slice) and egg yolk (250 mg/ yolk). Although generally low in total fat, some seafood, including shrimp, lobster, and certain fish, contain moderately high amounts of cholesterol (60 to 100 g/half-cup serving). One cup of whole milk contains approxi- mately 30 mg of cholesterol, whereas the cholesterol contained in 2 per- cent and skim milk is 15 and 7 mg/cup, respectively. One tablespoon of butter contains approximately 12 mg of cholesterol, whereas margarine does not contain cholesterol. Dietary Intake Based on intake data from the Continuing Survey of Food Intakes by Individuals (1994–1996, 1998), the median cholesterol intake ranged from approximately 250 to 325 mg/d for men and 180 to 205 mg/d for women (Appendix Table E-15). The meta-analysis also identified a diminishing increment of serum cholesterol with increasing baseline dietary cholesterol intake. With a baseline cholesterol intake of 0, the estimated increases in serum total cholesterol concentration for intakes from 100 to 400 mg/d of added dietary cholesterol were 0. Other predictive formulas for the effect of 100 mg/d of added dietary cholesterol, which did not consider baseline cholesterol intake and are based on compilations of studies with a variety of experimental conditions, have yielded estimates of 0. Furthermore, pooled analyses of the effects of 100 mg/d of added dietary cholesterol on plasma lipoprotein cholesterol concentrations (Clarke et al. The incremental serum cholesterol response to a given amount of dietary cholesterol appears to diminish as baseline serum cholesterol intake increases (Hopkins, 1992). There is also evidence from a number of studies that increases in serum cholesterol concentration due to dietary choles- terol are blunted by diets low in saturated fat, high in polyunsaturated fat, or both (Fielding et al. There is considerable evidence for interindividual variation in serum cholesterol response to dietary cholesterol, ranging from 0 to greater than 100 percent (Hopkins, 1992). There is increasing evidence that genetic factors underlie a substantial portion of interindividual variation in response to dietary cholesterol. An instructive case is that of the Tarahumara Indians, who in addition to consuming a diet low in cholesterol, have both low intestinal cholesterol absorption and increased transformation of cholesterol to bile acids (McMurry et al. However, with an increase in dietary cholesterol from 0 to 905 mg/d, their average plasma cholesterol concentration increased 0. Variations in several genes have been associated with altered respon- siveness to dietary cholesterol. The common E4 polymorphism of the apoE gene has been associated with increased cholesterol absorption (Kesäniemi et al. The recent finding that apoE is of importance in regulating cholesterol absorption and bile acid formation in apoE knockout mice (Sehayek et al. There are numerous other candidate genes that could modulate plasma lipid and lipoprotein response to dietary cholesterol by affecting cholesterol absorption, cellular cholesterol homeostasis, and plasma lipo- protein metabolism. Studies in animal models have generated data in support of the possibility that variations among these genes may be of importance in influencing dietary cholesterol response in humans, but to date such human data are lacking. Nevertheless, the existence of marked interindividual variability in dietary cholesterol response among and within various animal models points to the likelihood that some of the mecha- nisms underlying this variability will also apply to humans. There is compelling evidence that dietary cholesterol can induce atherosclerosis in several animal species, including rabbits, pigs, nonhuman primates, and transgenic mice (Bocan, 1998; McNamara, 2000; Rudel, 1997). However, given the existence of marked inter- and intraspecies differences in cholesterol metabolism and athero- genic mechanisms, it is not possible to extrapolate these data directly to humans. A significant relative risk was also observed in the Western Electric Study, which remained significant after adjustment for a number of covariates, including dietary fat and serum cholesterol concentration (Stamler and Shekelle, 1988). More recently, in a study of 10,802 health- conscious men and women in the United Kingdom, a univariate relation- ship of cholesterol intake to ischemic heart disease mortality was observed (Mann et al. This finding was corroborated in a European study, but after multivariate analysis adjust- ing for fiber intake, the association was no longer significant (Toeller et al. Measures of atherosclerosis using imaging techniques have also been assessed in relation to diet. Angiographically assessed coronary artery disease progression over 39 months in 50 men was weakly related to cholesterol intake in univariate, but not multivariate, analysis (Watts et al. In 13,148 male and female participants in the Atherosclerosis Risk in Commu- nities Study, carotid artery wall thickness, an index of early atherosclerosis, was significantly related to dietary cholesterol intake by univariate analyses; multivariate analysis was not performed (Tell et al.

However discount phenytoin 100mg mastercard, it may be inappropriate for higher doses cheap 100 mg phenytoin fast delivery, as they may be incurred in medicine discount 100mg phenytoin with visa, because a radiation weighted dose quantity applicable to the high dose range is not available cheap phenytoin 100mg line. Should the doses from the medical procedures be high, this deficiency could cause problems of dose specification. The problem created by the lack of a formal quantity for a radiation weighted dose for high doses is not limited to medicine but is also a real challenge in accidents involving radiation, and remains unsolved. In situations after accidental high dose exposures, health consequences have to be assessed and, potentially, decisions have to be made on treatments. The fundamental quantities to be used for quantifying exposure in such situations are organ and tissue absorbed doses (given in grays). Radiation dose to patients from radiopharmaceuticals Another dosimetric issue of concern is the radiation dose to patients from internal emitters, mainly radiopharmaceuticals. Initially, biokinetic models and best estimates of biokinetic data for some 120 individual radiopharmaceuticals were presented, giving estimated absorbed doses, including the range of variation to be expected in pathological states, for adults, children and the foetus. Absorbed dose estimates are needed in clinical diagnostic work for judging the risk associated with the use of specific radiopharmaceuticals, both for comparison with the possible benefit of the investigation and to help in giving adequate information to the patient. These estimates provide guidance to ethics committees having to decide upon research projects involving the use of radioactive substances in volunteers who receive no individual benefit from the study. It also provides realistic maximum 11 18 models for C and F substances, for which no specific models are available. Managing patient dose in digital radiology Digital techniques have the potential to improve the practice of radiology but they also risk the overuse of radiation. It is very easy to obtain (and delete) images with digital fluoroscopy systems, and there may be a tendency to obtain more images than necessary. In digital radiology, higher patient dose usually means improved image quality, so a tendency to use higher patient doses than necessary could occur. Different medical imaging tasks require different levels of image quality, and doses that have no additional benefit for the clinical purpose should be avoided. Image quality can be compromised by inappropriate levels of data compression and/or post-processing techniques. All of these new challenges should be part of the optimization process and should be included in clinical and technical protocols. Local diagnostic reference levels should be re-evaluated for digital imaging, and patient dose parameters should be displayed at the operator console. Training in the management of image quality and patient dose in digital radiology is necessary. Digital radiology will involve new regulations and invoke new challenges for practitioners. As digital images are easier to obtain and transmit, the justification criteria should be reinforced. Commissioning of digital systems should involve clinical specialists, medical physicists and radiographers to ensure that imaging capability and radiation dose management are integrated. The doses can often approach or exceed levels known with certainty to increase the probability of cancer. Proper justification of examinations, use of the appropriate technical parameters during examinations, proper quality control and application of diagnostic reference levels of dose, as appropriate, would all contribute to this end. All of these issues should be addressed for providing assistance in the successful management of patient dose. If the image quality is appropriately specified by the user, and suited to the clinical task, there will be a reduction in patient dose for most patients. Pregnancy and medical radiation Thousands of pregnant patients are exposed to radiation each year as a result of obstetrics procedures. Lack of knowledge is responsible for great anxiety and probably unnecessary termination of many pregnancies. Dealing with these problems continues to be a challenge primarily for physicians, but also for medical and health physicists, nurses, technologists and administrators. Medical professionals using radiation should be familiar with the effects of radiation on the embryo and foetus, including the risk of childhood cancer, at most diagnostic levels. Doses in excess of 100 ± 200 mGy risk nervous system abnormalities, malformations, growth retardation and fetal death. Justification of medical exposure of pregnant women poses a different benefit/risk situation to most other medical exposures, because in in utero medical exposures there are two different entities (the mother and the foetus) that must be considered. Prior to radiation exposure, female patients of childbearing age should be evaluated and an attempt made to determine who is or could be pregnant. For pregnant patients, the medical procedures should be tailored to reduce fetal dose. After medical procedures involving high doses of radiation have been performed on pregnant patients, fetal dose and potential fetal risk should be estimated. Pregnant medical radiation workers may work in a radiation environment as long as there is reasonable assurance that the fetal dose can be kept below 1 mGy during the course of pregnancy. Termination of pregnancy at fetal doses of less than 100 mGy is deemed to be unjustifiable, but at higher fetal doses, informed decisions should be made based upon individual circumstances.