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Short- and long-term effects of physical activity on glucose tolerance purchase tetracycline 500 mg line, insulin action generic 250mg tetracycline otc, and muscle glucose uptake show that contracting muscle has an “insulin-like” effect on promoting glucose uptake and metabolism (Bergman et al. Further, by increasing muscle mass, decreasing total and abdominal obesity (Björntorp et al. Physical activity can reduce the risk of type 2 diabetes (Diabetes Prevention Program Research Group, 2002; Tuomilehto et al. Dietary Fat The available data on whether diets high in total fat increase the risk for obesity are conflicting and are complicated by underreporting of food intake, notably fat intake (Bray and Popkin, 1998; Lissner and Heitmann, 1995; Lissner et al. Intervention studies have shown that high-fat diets, as compared with low-fat diets with equivalent energy intake, are not intrinsically fattening (Davy et al. Other studies have shown that as the proportion of fat in the diet increases, so does energy intake (Kendall et al. Because energy density was not kept separate from fat content in these studies, recent investigators have questioned the conclusions of these studies and have found differing results. Further studies have shown that fat content does not affect energy intake (Saltzman et al. Increased added sugars intakes have been shown to result in increased energy intakes of children and adults (see Chapter 6) (Bowman, 1999; Gibson, 1996a, 1997; Lewis et al. In spite of this, a negative correlation between added sugars intake and body mass index has been observed in children (Bolton-Smith and Woodward, 1994; Gibson, 1996a; Lewis et al. Published reports disagree about whether a direct link exists between the trend toward higher intakes of sugars and increased rates of obesity. Any association between added sugars intake and body mass index is, in all likelihood, masked by the pervasive and serious problem of underreporting, which is more prevalent and severe among the obese population. In addi- tion, foods and beverages high in added sugars are more likely to be underreported compared to other foods that may be perceived as “healthy” (Johnson, 2000). Dietary Fiber Consumption of soluble fibers, which are low in energy, delays gastric emptying (Roberfroid, 1993), which in turn can cause an extended feeling of fullness and therefore satiety (Bergmann et al. A number of intervention studies suggest that diets high in fiber may assist in weight loss (Birketvedt et al. Thus, the evi- dence to support a role of fiber in the prevention of obesity is unclear at this time. Physical Activity Energy expenditure by physical activity (see Chapters 5 and 12) varies considerably between individuals, affecting the energy balance and the body composition by which energy balance and weight maintenance are achieved (Ballor and Keesey, 1991; Williamson et al. Indeed, physi- cal inactivity is a major risk factor for development of obesity in children and adults (Astrup, 1999; Goran, 2001). In one study, increasing the level of physical activity in obese individuals appeared to have no effect on food intake, whereas in normal-weight individuals an increase in activity was coupled with an increase in food intake (Pi-Sunyer and Woo, 1985). Physical activity increases bone mass in children and adolescents and maintains bone mass in adults (French et al. In elderly individuals, bone mineral density has been found to be higher in those who exercise than in those who do not (Hurley and Roth, 2000). Physical activity results in muscle strength, coordination, and flex- ibility that may benefit elderly individuals by preventing falls and fractures. When the diet is modified for one energy-yielding nutrient, it invariably changes the intake of other nutrients, which makes it extremely difficult to have adequate substantiating evidence for providing clear and specific nutritional guidance. Acceptable Macronutrient Distribution Ranges can be estimated, however, by considering risk of chronic disease, as well as in the context of consuming adequate amounts of essential macronutrients and micronutrients. Lack of effect of a high-fiber cereal supplement on the recurrence of colorectal adenomas. The important role of physical activity in skeletal develop- ment: How exercise may counter low calcium intake. Energy, nutrient intake and prostate cancer risk: A population- based case-control study in Sweden. Effect of omega-3 fatty acids on rectal mucosal cell proliferation in subjects at risk for colon cancer. Influence of moderate physical exercise on insulin-mediated and non-insulin-mediated glucose uptake in healthy subjects. Environmental factors and cancer incidence and mor- tality in different countries, with special reference to dietary practices. Risk assessment of physical activity and physical fitness in the Canada Health Survey Mortality Follow-up Study. Dietary intake of marine n-3 fatty acids, fish intake, and the risk of coronary disease among men. Dietary fat and risk of coronary heart disease in men: Cohort follow up study in the United States. Dietary fibre added to very low calorie diet reduces hunger and alleviates constipation. The role of low-fat diets and fat substitutes in body weight management: What have we learned from clinical studies? Low-density lipoprotein particle size, triglycerides, and high-density lipoprotein cholesterol as risk factors for coronary heart disease in older Japanese-American men.

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For some medical issues order 250 mg tetracycline with amex, gender buy generic tetracycline 500 mg on-line, ethnicity, or cultural background has a huge influence while for other medical issues the influence is very little. To determine which areas fall into each category, more studies of gender and other differences for medical interventions are required. Coherence of the evidence over time In order to have strong evidence, there should be consistency of the evidence over varying types of studies. The results of a cohort study should be similar to those of case–control or cross-sectional studies done on the same cause-and- effect relationship. Studies that show consistency with previously known epi- demiological data are said to evidence epidemiological consistency. Also, results should agree with previously discovered relationships between the presumed cause and effect in studies done on other populations around the world. An 196 Essential Evidence-Based Medicine association of high cholesterol with increased deaths due to myocardial infarc- tion was noted in several epidemiological studies in Scandinavian countries. Analogy Reasoning by analogy is one of the weakest criteria allowing generalization. Knowing that a certain vitamin deficiency predisposes women to deliver babies with certain birth defects will marginally strengthen the evidence that another vitamin or nutritional factor has a similar effect. When using analogy, the pro- posed cause-and-effect relationship is supported by findings from studies using the same methods but different variables. From this, one could infer that a potent anticoagulant like warfarin ought to have the same effect. However, warfarin may increase mortality because of the side effect of causing increased bleeding. Again, although it is suggested by an initial study, the proposed new intervention may not prove beneficial when studied alone. Common sense Finally, in order to consider applying a study result to a patient, the association should make sense and competing explanations associating risk and outcome should be ruled out. For instance, very sick patients are likely to have a poor out- come even if given a very good drug, thus making the drug look less efficacious than it truly is. Conversely, if most patients with a disease do well without any therapy, it may be very difficult to prove that one drug is better than another for that disease. When dealing with this effect, an inordinately large number of patients would be necessary to prove a beneficial effect of a medication. It may lead to the overselling of potent drugs, and may result in clinical researchers neglecting more common, cheaper, and better forms of therapy. Similarly, patients thinking that a new wonder drug will cure them may delay seeking care at a time when a potentially serious problem is easily treated and complications averted. Finally, it is up to the individual physician to determine how a particular piece of evidence should be used in a particular patient. As stated earlier, this is the art Applicability and strength of evidence 197 Fig. We must learn to use the best evi- dence in the most appropriate situations and communicate this effectively to our patients. There is a real need for more high-quality evidence for the practice of medicine, however, we must treat our patients now with the highest-quality evidence available. Pathman’s Pipeline The Pathman ‘leaky’ pipeline is a model of knowledge transfer, taking the best evidence from the research arena into everyday practice. This model considers the ways that evidence will be lost in the process of diffusion into the everyday practice of medicine. Pathman, a family physician in the 1970s, to model the reasons why physicians did not vaccinate children with routine vaccinations. It has been expanded to model the reasons that physicians don’t use the best evidence (Fig. They must then accept the evidence as being legitimate 198 Essential Evidence-Based Medicine and useful. This follows a bell-shaped curve with the innovators followed by the early adopters, early majority, late majority, and finally the laggards. Providers must believe that the evidence is applicable to their patients, specifically the one in their clinic at that time. However, it is still up to the patient to agree to accept the evidence and finally be com- pliant and adhere to the evidence. The next chapter will discuss the process of communication of the best evidence to patients. William Butler Yeats (1865–1939) Learning objectives In this chapter you will learn: r when to communicate evidence with a patient r five steps to communicating evidence r how health literacy affects the communication of evidence r common pitfalls to communicating evidence and their solutions When a patient asks a question, the health-care provider may need to review evidence or evidence-based recommendations to best answer that question.

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Theterm‘‘flower’’(flos) had been used systematically throughout the Trea- tise on the Diseases of Women (the ‘‘rough draft’’ of Conditions of Women buy 500mg tetracycline otc, which had employed frequent colloquialisms) cheap tetracycline 250mg otc, and at least fourteen of the twenty- two different vernacular translations of the Trotula (including Dutch, English, French, German, Hebrew, and Italian) employ the equivalent of ‘‘flowers’’ when translating the Latin menses. But just as a tree which lacks viridity is said to be unfruitful, so, too, the woman who does not have the viridity of her flowering at the proper age is called infertile. Menstrual blood is like the flower: it must emerge before the fruit—the baby—can be born. In the Hippocratic writings themselves, although there is discussion of suffocation caused by the womb, the actual term ‘‘uterine suffocation’’ (in Greek, hysterike pnix) is never used. It was only out of loose elements of Hip- pocratic disease concepts (which were always very vaguely defined and iden- tified) that the etiological entity of uterine suffocation was created, probably sometime before the second century . Such movement was thought to be caused by retention of the menses, excessive fatigue, lack of food, lack of (hetero)sexual activity, and dryness or lightness of the womb (particu- larly in older women). When these conditions obtain, the womb ‘‘hits the liver and they go together and strike against the abdomen—for the womb rushes and goes upward towards the moisture. When the womb hits the liver, it produces sudden suffocation as it occupies the breathing passage around the belly. For example, when the womb strikes the liver or abdomen, ‘‘the woman turns up the whites of her eyes and becomes chilled; some women are livid. If the womb lingers near the liver and the abdomen, the woman dies of the suffocation. Multiple means of treat- ment were employed, including the recommendation that, when the womb moves to the hypochondria (the upper abdomen or perhaps the diaphragm), young widows or virgins be urged to marry (and preferably become preg- nant). This was premised, apparently,on the belief that thewombwas capable of sensing odors. Fetid odors (such as pitch, burnt hair, or castoreum) were applied to the nos- trils to repel the womb from the higher places to which it had strayed, while sweet-smelling substances were applied to the genitalia to coax the uterus back into its proper position. Not all the symptoms were listed every time uterine movement was men- tioned by the Hippocratic writers, nor did all cases of pnix involve uterine movement. Whenanattack occurs, sufferers from the disease collapse, show aphonia, labored breathing, a seizure of the senses, clenching of the teeth, stridor, convulsive contraction of the extremities (but sometimes only weakness), upper abdominal distention, retraction of the uterus, swelling of the thorax, bulging of the network of ves- sels of the face. The whole body is cool, covered with perspiration, the pulse stops or is very small. Critical to his views, and to all contemporary criticisms of the ‘‘wandering womb’’ (in- cluding Galen’s, as we shall see in a moment) were the anatomical discover- ies made at Alexandria in the third century . The womb ‘‘does not issue forth like a wild animal from the lair’’ but is instead ‘‘drawn together because of the stricture caused by the inflammation’’ of these uterine ligaments. Soranus also adamantly rejected the Hippocratic odoriferous therapy, or at least the part of it that employed foul- smelling substances. Yet for all his modifi- cations, Soranus never questioned the disease category itself. On the contrary, his thorough engagement with it was to help render it canonical in almost all later gynecological texts up through the Renaissance. Galen, active only a generation after Soranus, was more accommodating of traditional Hippocratic perspectives. Himself a highly experienced anato- mist,103 Galen no more than Soranus could accept the possibility that the womb actually wandered to various parts of the body since the diaphragm, if nothing else, absolutely prohibited movement to the thorax. He did not, however, question the by now traditional litany of symptoms, let alone the existence of the disease category. He, like Soranus, thought the womb could appear to be drawn up slightly because of inflammation of the ligaments. Yet to explain apnoia hysterike (difficulty of breathing caused by the uterus), Galen offered something of a compromise that would explain how the uterus, with- out moving to the upper parts, could still affect them. He posited a sympa- thetic poisonous reaction caused by either the menses or the woman’s own semen being retained in her uterus. Notable here is Galen’s shift in ideas about how semen and sexuality played into this dis- ease: for Galen, it was not her lack of semen provided by a man that made the widow susceptible, but the buildup of her own seed. Despite these dis- agreements,Galen maintained elements of the traditional odoriferous therapy, though he complemented this with bloodletting, massage, and a host of other treatments. Both Soranus and Galen represented the very highest theoretical tradi- tions of Greek medicine, catering as they did to the elite, Hellenized urban classes of Rome. Their views never eradicated what were apparently deeply rooted popular beliefs that the womb did indeed wander. Even Muscio, in the fifth or sixth century when hewas rendering Soranus into Latin, slipped in the more than suggestive phrase ‘‘when the womb moves upwards toward the chest’’ when referring to uterine suffocation; as he repeated this several times, it seems that he, too, thought the womb capable of more than ‘‘distension caused by the ligaments. One is written into a blank space of a late-ninth-century medical volume by a tenth-century Introduction  hand. Having invoked the aid of the Holy Trinity, the nine orders of the an- gels, the patriarchs, prophets, apostles, martyrs, confessors, virgins, and ‘‘all the saints of God,’’ the priest is to command the womb to cease tormenting the afflicted woman: I conjure you, womb, by our lord Jesus Christ, who walked on the water with dry feet, who cured the infirm, shunned the demons, resuscitated the dead, by whose blood we are redeemed, by whose wounds we are cured, by whose bruise[s] we are healed, by him I conjure you not to harm this maidservant of God, [her name is then to be filled in], nor to hold on to her head, neck, throat, chest, ears, teeth, eyes, nostrils, shoulders, arms, hands, heart, stomach, liver, spleen, kidneys, back, sides, joints, navel, viscera, bladder, thighs, shins, ankles, feet,or toes, but to quietly remain in the placewhich God delegated to you, so that this handmaiden of God, [her name], might be cured. The chief vehicle for Galen’s views in the twelfth century was, of course, Ibn al-Jazzār’s Viaticum. In discussing uterine suffo- cation in book , Ibn al-Jazzār had echoed Galen in asserting that ‘‘the sperm increases, corrupts, and becomes like a poison. Ibn al-Jazzār postulated that the putrefying menses and/or semen in the uterus produced ‘‘a cold vapor’’ that rose to the diaphragm.

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Testing a new drug against one that is never used in current practice is not going to help the practitioner generic tetracycline 250mg fast delivery. This refers to disease markers that ought to cause changes in the disease process buy 500mg tetracycline mastercard. Studies of heart-attack patients done in the 1960s showed that some died suddenly from irregular heart rhythms. Physicians thought this would reduce deaths in all patients with heart attacks, but a large study found that the death rate actually increased when all patients were given these drugs. However, it may be considered when deciding if the study was carried out for a sufficient amount of time. It has been only slightly more than 50 years since statistics was first felt to be an important part of the medical curriculum. In a 1947 commentary in the British Medical Journal entitled “Statistics in the medical curriculum? We recognize the need for physicians to be able to understand the nature of statistical processes and to be able to interpret these for their patients. The science is in the medical literature and in the ability of the clinician to interpret that literature. Students learn the clinical and basic sciences that are the foundation of medicine during the first 2 years of medical school. The art of medicine is in determining to which patients the literature will apply and then communicating the results to the patients. Students learn to perform an adequate history and physical examination of patients to extract the maximum amount of evidence to use for good medical decision making. Students must also learn to give patients information about their illnesses and empower them to act appropriately to effect a cure or control and moderate the illness. Finally, as pracitioners, physicians must be able to know when to apply the results of the most current literature to patients, and when other approaches should be used for their patients. Evidence- based medicine can be viewed as an attempt to standardize the practice of medicine, but at the same time, it is not “cookbook” medicine. However, it is still up to the clinician to determine whether the individual patient will benefit from that approach. If your patient is very different from those for whom there is evidence, you may be justified in taking another approach to solve the prob- lem. These decisions ought to be based upon sound clinical evidence, scientific knowledge, and pathophysiological information. Evidence-based medicine is not a way for managed care (or anyone else) to simply save money. Evidence- based practices can be more or less expensive than current practices, but they should be better. Evidence-based medicine is the application of good science to the practice of health care, leading to reproducibility and transparency in the science support- ing health-care practice. Evidence-based medicine is the way to maximize the benefits of science in the practice of health care. Lord Kelvin, President of the Royal Society, 1895 Learning objectives In this chapter you will learn: r cause-and-effect relationships r Koch’s principles r the concept of contributory cause r the relationship of the clinical question to the type of study The ultimate goal of medical research is to increase our knowledge about the interaction between a particular agent (cause) and the health or disease in our patient (effect). Causation is the relationship between an exposure or cause and an outcome or effect such that the exposure resulted in the outcome. However, a strong association between an exposure and outcome may not be equivalent to proving a cause-and-effect relationship. By the end of this chapter, you will be able to determine the type of causation in a study. Cause-and-effect relationships Most biomedical research studies try to prove a relationship between a partic- ular cause and a specified effect. The cause may be a risk factor resulting in a disease, an exposure, a diagnostic test, or a treatment helping alleviate suffer- ing. The stronger the design of a study, the more likely it is to prove a relationship between cause and effect. Not all study designs are capable of proving a cause-and-effect relation- ship, and these study designs will be discussed in a later chapter. In some studies relating to the prognosis of disease, time is the independent variable. It can be an outcome such as death or survival, the degree of improvement on a clinical score or the detection of disease by a diagnostic test. You ought to be able to identify the cause and effect easily in the study you are evaluating if the structure of the study is of good quality. Types of causation It’s not always easy to establish a link between a disease and its suspected cause. For example, we think that hyperlipidemia (elevated levels of lipids or fats in the blood) is a cause of cardiovascular disease. Perhaps hyperlipidemia is caused by inac- tivity or a sedentary lifestyle and the lack of exercise actually causes both cardio- vascular disease and hyperlipidemia.

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