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The doctrines of the Methodists have a greater tendency than those of any other sect, to produce the most deplorable effects on the human understanding. The brain is perplexed in the mazes of mystery, and the imagination overpowered by the tremendous description of future torments. But it would be glib to suggest that the notion of the irrational was simply turned into a stick with w hich to beat the masses. It was the done thing, throughout the eighteenth and nineteenth centuries, for certain young ladies to have fits of hysterics and for artists and poets to be m orbidly oversensitive, suffering nervous breakdowns, or, like the com poser Robert Schum ann, going insane. Romanticism glamourized the mad genius, and nineteenth-century Bohem ianism cultivated a dandified degenerateness. In England, the immediate family was expected to shoulder responsi bility for crazy relatives. The insane were generally kept at hom e, locked in a cellar or barn if dangerous, perhaps tended by a servant. Failing the family, the parish generally assumed control, sometimes boarding out the lunatic to a local carer. The earliest specialized lunatic asylums had been established under religious aus pices in fifteenth-century Spain - in Valencia, Zaragoza, Seville, Valladolid, Men tal Illness 287 Toledo, and Barcelona (Islam ic models may have been influ ential). The Netherlandish town o f Geel, w hich had the healing shrine of St Dymphna, grew celebrated as a refuge for the mentally disturbed. Throughout urban Europe and along the Eastern seaboard of North America, the eighteenth and nineteenth centuries brought a proliferation o f schools, prisons, houses of indus try and correction, w orkhouses, and, not least, madhouses to deal with troublesome people. Already by the 1660s some 6, 0 0 0 undesirables - mad people included - were locked away in the Hopital General in Paris alone. Hitherto, by dint of peculiarity, the mad person had possessed fascinating power: holy fools, geniuses, and jesters had uttered deep if obscure truths. O nce institutionalized, however, madness was robbed of all such allure, eerie dignity, and truth. Throughout the ancien regim e, French absolutism continued to exercise a centralizing control over the insane; later, under the later Napoleonic Code, provincial prefects assumed these duties. Fam ilies could have mad relatives legally confined on obtaining a lettre de cachet from royal officials; such warrants deprived the lunatic o f legal rights. But elsewhere the picture is highly varied; policies differed, and often there were no policies at all. In Russia, almost no public receptacles for the insane existed before the second half of the nineteenth century. Van Gogh was one of many artists who ended up in lunatic asylums in the Rom antic era; another was the English painter Richard Dadd. Van Gogh was emotionally intense throughout his life; coupled with financial failure, the result w as growing mental disturbance that led to his being voluntarily committed in 1 8 8 9 to the Asylum of StPaul de-Mausole at St Remy. A year later, after a bout of feverish painting, he cut off his ear; he was moved to another asylum at Auvers near Pontoise, where he shot himself, fearing that his mad ness was incurable. Bethlem developed out of a religious house founded in the thir teenth century by Bishopsgate, beyond the walls of London. Across great swathes of rural Europe Poland, Scandinavia, or the Balkans, for instance - few people were institutional ized before 1850. At the close of the nineteenth century, two lunatic asylums suf ficed for the whole o f Portugal. Figures are necessarily unreliable, but it appears that no m ore than around 5, 0 0 0 people (out of a national population o f some 10 m illion) were being held in specialized lunatic asylums in England around 1800, with perhaps as many again in w ork houses and jails. Mental Illness 289 Indeed, in England, the rise of the lunatic asylum is better seen not as an act of state but as a service industry w ithin a flourishing com m ercial society. As late as 1850, more than half the confined lunatics in England were still housed in private institutions, some good, some bad, som e indifferent. Private madhouses had taken root by the mid-seventeenth century, although evidence is scanty (owners and families alike had a vested interest in secrecy).
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There were some painkillers, such as Vioxx (rofecoxib), but that was withdrawn in 2004. The crux of the revolution in the treatment of pain was the widespread availability of oxycodone, a molecule similar to morphine and heroin in its impact on the brain. Oxycodone was billed as nonaddictive, but this does not seem to be true (Van Zee 2009). People become tolerant to a dose that they are taking, and then find they need to take more to achieve the same impact. The net effect may thus be an increase in the extent to which despair can lead to death in the short term. Indeed, it may even be that some of the deaths caused by opioids would not have occurred without these medications. Temporary despair can lead people to take pain relievers, to which they then become addicted. But this explanation does suggest focusing a little bit more on the supply side than just on the demand side. That is, reducing access to legal and illegal opioid drugs may reduce the extent to which short-term despair leads to both temporary and permanently elevated mortality rates. So far, the market has not been able to provide a stable income and social circumstance that people value highly enough to make them want to strive for a long life. But life expectancy at birth in the United States declined in 2015 for the first time since 1994. Although small declines have been observed before, Anne Case and Angus Deaton document a disturbing set of facts. Mortality rates among middle-aged, white non-Hispanics have been rising since 2000, in sharp contrast to what is happening to the mortality rates of other populations, such as Europeans of the same age. Moreover, pain, disability, and other measures of physical and mental health have been worsening. These increases in mortality and poor health are concentrated among whites without college degrees-in fact, mortality among those with a college education continues to fall. Case and Deaton show some new, remarkable patterns that suggest life expectancy will continue to fall. When plotted by birth cohort, one finds that among white non-Hispanics without a college degree, the age profile of mortality is getting steeper for each successive cohort; for more recent cohorts mortality at a given age is higher, and it rises faster with age. The same is true for measures of disability or disease; health is deteriorating faster with age for younger cohorts. Case and Deaton further hypothesize that the decline in health and longevity could be caused by worsening labor market conditions for cohorts entering the labor market in 1970 or later. I estimate this model for the 1940 cohort, using cohort life tables from the Social Security Administration, and show that it can accurately reproduce lifetime mortality rates and life expectancy. I then investigate whether changes in the baseline parameters can generate patterns of mortality and morbidity similar to those documented by Case and Deaton. Just like Case and Deaton, I conclude that at least two forces could account for their findings. First, lifetime health resources-either their level or the rate of increase-could be falling across successive cohorts. Second, the rate of health depreciation (the rate at which people age) could be increasing. Either of these factors would generate steepening mortality and disability age profiles. It is particularly important that these patterns cannot easily be explained by temporary conditions; in the model, they can only be the result of permanent changes in parameters beginning early in adulthood (or even earlier in life). This is the same conclusion that Case and Deaton reach from their nonparametric analysis. To assess the likelihood of each of these hypotheses, I use evidence from the literature to speculate about the root causes of these changes in mortality. Stalling or falling real lifetime incomes, in combination with increasing costs of health inputs, could rationalize lower health resources. Increases in lifetime exposure to pollutants, or increases in stress (due to, for example, declining intergenerational mobility or greater inequality), could also potentially be linked to increases in the depreciation rate. Although a full evaluation of the empirical validity of these hypotheses is beyond the scope of this comment, the discussion suggests several directions for future research.
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The systems used to collect these data are evolving rapidly and differ from state to state. Depending on the data group, state education agencies may submit aggregate counts for the state as a whole or detailed counts for individual schools or school districts. It is designed to provide data on mathematics and science education, the changing high school environment, and postsecondary education. This study features a new student assessment in algebra skills, reasoning, and problem solving and includes surveys of students, their parents, math and science teachers, and school administrators, as well as a new survey of school counselors. Questionnaires in this study have asked questions of students and parents regarding reasons for selecting specific colleges. It asked respondents about college applications, acceptances, and rejections, as well as their actual college choices. In the fall of 2013 and the spring of 2014, high school transcripts were collected and coded. A full second follow-up was conducted in 2016, when most sample members were 3 years beyond high school graduation. During the 200708 collection year, the Enrollment component was broken into two separate components: 12-Month Enrollment (taking place in the fall collection) and Fall Enrollment (taking place in the spring collection). However, some degrees formerly identified as firstprofessional that take more than 2 full-time-equivalent academic years to complete, such as those in Theology (M. The "Asian" race category is now separate from a "Native Hawaiian or Other Pacific Islander" category, and a new category of "Two or more races" has been added. Prior to 1993, data from technical and vocational institutions were collected through a sample survey. Beginning in 1993, all data are gathered in a census of all postsecondary institutions. The classification of institutions offering college and university education changed as of 1996. Higher education institutions were accredited by an agency or association that was recognized by the U. Department of Education or were recognized directly by the Secretary of Education. Tables that contain any data according to this standard are titled "degree-granting" institutions. Time-series tables may contain data from both series, and they are noted accordingly. For example, tables on faculty salaries and benefits were only affected to a very small extent. In contrast, most of the data on public 4-year colleges were affected to a minimal extent. The impact on enrollment in public 2-year colleges was noticeable in certain states, such as Arizona, Arkansas, Georgia, Louisiana, and Washington, but was relatively small at the national level. Overall, total enrollment for all institutions was about one-half of 1 percent higher in 1996 for degree-granting institutions than for higher education institutions. However, they are subject to nonsampling error, the sources of which varied with the survey instrument. While the new system shortened data processing time and provided better data consistency, it did not address the accuracy of the data provided by institutions. Beginning in 200304 with the Prior Year Data Revision System, prior-year data have been available to institutions entering current data. This allows institutions to make changes to their prior-year entries either by adjusting the data or by providing missing data. When institutions made changes to their data, it was assumed that the revised data were the "true" data. The data were analyzed for the number and type of institutions making changes, the type of changes, the magnitude of the changes, and the impact on published data.
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Desserts other than canned and raw fruit pose a problem for many allergic families. The children may get some pleasure and value out of puddings and pie fillings, but cake and cookies should be kept out of the picture, which is too bad. When a woman is full of pent-up nervous energy nothing seems to relieve her quite so much as making a batch of what are called "brownies, " and they can raise the very devil if any of her children have skin trouble or soft teeth. Rice pudding with raisins and tapioca pudding require baking longer than that and are good healthy desserts. A passable pie crust which will not roll but can be patched together can be made by an artistic cook out of potato flour and ice water and sugar and butter. It might be a good thing for the country if the top crusts on pies were all eliminated. If people could get the idea that the top crust is fattening it would be an advance. Not that top or bottom makes any difference, of course, but it is easier to abandon the bottom crust. Butternut squash, pumpkin, mince, apple, plum, and peach pie filling can be wonderful culinary adventures. But, owing to the commercial bakeries, good pie made without chemicals is fast disappearing from the American cuisine, and that is too bad. An easy fortune awaits anyone who can restore good pie with no top crust to New York City. The temperature of the water should be just below boiling, otherwise an irritating substance called mercaptan will be extracted. In parts of the country there are so many degrees of hardness in the water that it is impossible to make good tea or coffee, in which case distilled water should be used. Many people over the age of sixty-five should not expect to fall asleep readily for hours after drinking a cup of tea or coffee, so they may have to dispense with it for the evening meal. There seems to be little advantage to extracting part of the caffeine in special preparations of coffee. I just want to emphasize that the housewife, with her power of the purse and her way of preparing her purchases, controls our destiny. It seems probable that the eternal economic plight of our farmers has a simple explanation. Little of the grain and milk and chicken and eggs and vegetables raised today can be classed as needed. Two acres of grassland on a hilly New England farm will furnish the same energy for a steer as one hundred and sixty acres of pasture land in certain areas of the West. Private capital could take over a whole county in New England for use as a pilot plant. With a processing plant and a collecting system, every farmer in the county could be put to work raising animals. With most of them going forward to animal husbandry, we could relegate plows to the Smithsonian. And a muddy stream means that we are dissipating our greatest natural resourceв"our topsoil. Postscript Reading over this manuscript has made me realize that my dear wife is right, as usual. When the writing has been a bit on the dull side it is because I have been too weary. They are wonderful people, who fight when it is carefully explained to them what they are fighting for. When completely exhausted he sat down on ground that had been drenched with mustard. Convalescent sergeants and corporals sitting around the ward with nothing to do would take pleasure in worrying little Willy Bell. The cares of the day vanish with the first savage strike of a bluefish in the tide rip. Hooking one knee over the tiller of the little Sheilah, I can head toward home while filleting a couple of fish for dinner. See Sinus trouble Anxiety state, 123, 125-26 Appendicitis, 139, 177 Apprehension, feeling of, 121 Army of Occupation, 28 Arsenic poisoning, 212 Arterial hypertension, 122 Arteries, hardening of.
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He became an expert in hysteria, diagnosing an average of 10 hysterical women each day, transforming them into "iatrogenic monsters" and turning simple "neurosis" into hysteria. Only 100 years ago, male doctors believed that female psychological imbalance originated in the uterus. When surgery to remove the uterus was perfected, it became the "cure" for mental instability, effecting a physical and psychological castration. Women are given potent drugs for disease prevention, which results in disease substitution due to side effects. Approximately 4 million births occur annually, with 24% (960, 000) delivered by cesarean section. Sakala contends that an "uncontrolled pandemic of medically unnecessary cesarean births is occurring. They also used this argument for tobacco, claiming that more studies were needed before they could be certain that tobacco really caused lung cancer. State journals such as the New York State Journal of Medicine also began to run advertisements for Chesterfield cigarettes that claimed cigarettes are "Just as pure as the water you drink. The authors estimated that 106, 000 deaths occur annually due to adverse drug reactions. The safety of new agents cannot be known with certainty until a drug has been on the market for many years. The mortality rate in hospitals for patients with bedsores is between 23% and 37%. Critics will say that it was the disease or advanced age that killed the patient, not the bedsore, but our argument is that an early death, by denying proper care, deserves to be counted. It is only after counting these unnecessary deaths that we can then turn our attention to fixing the problem. The report calls for adequate nursing staff to help feed patients who are not able to manage a food tray by themselves. The Coalition report states that malnourished residents, compared with well-nourished hospitalized nursing home residents, have a fivefold increase in mortality when they are admitted to a hospital. Nosocomial Infections the rate of nosocomial infections per 1, 000 patient days rose from 7. Due to progressively shorter inpatient stays and the increasing number of admissions, however, the number of infections increased. Morbidity and Mortality Report found that nosocomial infections cost $5 billion annually in 1999, (10) representing a $0. At this rate of increase, the current cost of nosocomial infections would be around $5. Barbara Starfield presents well-documented facts that are both shocking and unassailable. Starfield warns that one cause of medical mistakes is overuse of technology, which may create a "cascade effect" leading to still more treatment. Starfield notes that many deaths attributable to medical error today are likely to be coded to indicate some other cause of death. She concludes that against the backdrop of our poor health report card compared to other Westernized countries, we should recognize that the harmful effects of health care interventions account for a substantial proportion of our excess deaths. When doctors bill for services they do not render, advise unnecessary tests, or screen everyone for a rare condition, they are committing insurance fraud. In some cultures, elderly people lives out their lives in extended family settings that enable them to continue participating in family and community affairs. American nursing homes, where millions of our elders go to live out their final days, represent the pinnacle of social isolation and medical abuse. Over 40% (3, 800) of the abuse violations followed the filing of a formal complaint, usually by concerned family members. Incidents of physical abuse causing numerous injuries such as fractured femur, hip, elbow, wrist, and other injuries. Dangerously understaffed nursing homes lead to neglect, abuse, overuse of medications, and physical restraints. In 1990, Congress mandated an exhaustive study of nurse-to-patient ratios in nursing homes. Yet it took the Department of Health and Human Services and Secretary Tommy Thompson only four months to dismiss the report as `insufficient. Because many nursing home patients suffer from chronic debilitating conditions, their assumed cause of death often is unquestioned by physicians.
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Helping adolescents separate truth from hype and recognize all aspects of sexual development encourages them to make informed and healthy decisions about sexual matters. Research actually suggests that young people who are knowledgeable about sexuality and reproductive health are less likely to engage in early sexual activity or unprotected sex. Schools do not necessarily provide complete or accurate information to educate adolescents about sexual health and sexuality. Spirituality centers on the connection to a reality greater than oneself and can include the sacred experience of religious awe and reverence. Religion, on the other hand, is a set of common beliefs and practices D shared by a group of people. It can encompass cultural or ancestral traditions, writings, history, and mythology, as well as personal faith and mystical experience. Spiritual development is shaped both within and outside of religious traditions, beliefs, and practices. In the same study, 85 percent of teens reported being affiliated with a religious denomination or tradition, and 42 percent reported attending religious service at least once a week. Just over half (52 percent) said their religious faith was very or extremely important in shaping their daily life. Adolescence can be a time of intense religious and spiritual questioning for many young people. This might be because the development of more complex cognitive abilities promotes thinking on the existential level as well as the formation of a broader world view. Fowler describes adolescence as the stage during which young people begin to form their own spiritual identity and outlook. Typically, children in early adolescence do not yet have a sufficiently developed sense of reason upon which to construct independent views about religion and spirituality. They are still guided by their parents or other adults as well as influenced by peers. As they grow older, teens develop an understanding of the unknown and Prayer and meditation appear to stimulate those parts of the brain responsible for mental focus and higher thinking and reasoning skills. Cerebral blood flow during meditative prayer: Preliminary findings and methodological issues. Younger Teens In 2006, 42 percent of eighth graders said they attended religious services at least once a week. As teens got older, fewer attended every week (36 percent of 10th graders and 32 percent of 12th graders). Interestingly, older adolescents as a group do not consider themselves to have become less religious, which suggests that for older adolescents, religiosity extends well beyond attendance at religious services. Between 2002 and 2006, the percentage of adolescents who attended religious services at least once a week declined, from 35 percent to 32 percent for 12th graders, from 42 percent to 36 percent for 10th graders, and from 47 percent to 42 percent among eighth graders. This decline reverses a trend of increased religious attendance observed between 1991 and 2002. Some adolescents may want to explore other faiths or spiritual disciplines in a quest to find one that is personally meaningful to them. However, for many cultural groups, religion is intricately intertwined with ethnic and national identity. Adolescents in these cultures typically do not change religions, with no detriment to their development. Young people can become more religious than their parents, and young people who hold deeper religious beliefs than their parents report more positive family relations. The opposite tends to be true when parents are more religious than their adolescent children. Faith participation can shield teens from risky behaviors There has been surprisingly little scientific research on the impact of religion and spirituality on young people, but the research that does exist suggests that faith-based organizations can provide young people with role models, moral direction, spiritual experiences, positive social and organizational ties, and community and leadership skills. Attendance at religious services and ceremonies, public prayer, and participation in group religious activities, including youth groups, is associated with less cigarette, alcohol, and marijuana use; higher self-esteem; and more positive family relationships. Strong religious communities emphasize and reward socially acceptable behavior and encourage young people to keep up their studies. By reaching out to others and trying to right wrongs, a young person can experience a deepening of personal faith. These could be drop-in centers, musical programs and dances, or late-night programs.
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The physician has a triple problem in outlining treatment for the ordinary troubles of life. First of all, the patients need to have some inherited ability to exactly follow orders. Then a good way of life has to be prescribed in words that are clearly understood. Lastly, having given the orders, the physician still has to do ninety per cent of the work. A valiant effort must be made to correct the symptoms that can be corrected, and to check up regularly on patients to see that they continue to live well. In spite of all his efforts, at least twenty-five per cent of his patients can be expected to fall by the wayside. Such patients make one humble and realize what an inestimable privilege it is to be a physician. As for the failing twenty-five per cent, they give up because the prescription of simple living is medicine too strong for them to take. What they really want is to buy some miracle drug that will enable them to live in carefree fashion. The secretary deals with them by dropping them into the wastebasket, so that I shall not be bothered. Time, and bitter experience, have made me completely skeptical of something one gets for nothing. The give-away vitamins, hormones, drugs to wake up by, go to sleep by, not to worry by, prevent blood clotting, prevent anemia, cure constipation, and aid weight lossв"all are pretty much in the wishful-thinking class and usually do far more harm than good. As the years roll by I find myself resorting less and less to drugs in the effort to combat disease processes. We can still practice about all the medicine that is worth while with six standard drugs, plus a few new ones. With wild cherry log flames roaring up the chimney of the Franklin stove, drowsing over the new seed catalogue is the order of the day. Life, which heretofore has gone by for me at headlong pace, has reached a stage quite like Indian summer. With most of the harvest in, a pleasant haze lies just over the horizon, and while the telephone is blessedly silent there is nothing to do but to recharge my batteries. Then the seed catalogue injects a sour note with a picture of those new and supposedly desirable "nearest to white" marigolds. Even the ordinary kind attract too many Japanese beetles, and the whiter they are the more beetles. Why, I find myself wondering, does a penalty always seem to attach to anything that is new? It occurs to me that in medicine we have a great many things comparable to "nearest to white" marigolds. Really important things have the strength of simplicity, and I find myself considering what I have done in my own lifetime to simplify medicine. Thousands of patients come to memory, offering their mute testimony to work done over the years. The only possible contribution I can make to human knowledge is to put on record my own clinical impressions of human disease and carelessness in living. Clinical impressions do not constitute scientific proof, even though they have often been the forerunners of great advances in medicine. Only time, and the work of great research men in many lands, can establish anything as the scientific truth. But the ideas demonstrated at the old City Hospital grand rounds have apparently stood the test of time and I offer them here simply for what they are worth. In any medical teaching it seems desirable to make a point three times in order to drive it home.
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Similarly, cognitive and physical development may be in sync, but social development might be delayed. You will no doubt recognize some of these young people; you might have fit one of these descriptions yourself when you were an adolescent. Having teenagers read the profiles may help them see that their nonlinear development is completely normal and to be expected. How to handle the unique patterns of teen growth Physical, cognitive, and social development typically are not in sync all the way through adolescence. Early and late bloomers in the physical sense are acutely aware of being out of sync with their peers, and reassurance that they will catch up-or that other teens will catch up with them-can be extremely helpful. Also helpful is playing the "mean mom" or "mean dad" role and limiting their exposure to situations they are not ready to handle. It is important for adults to follow the same strategies they use for physical development that is out of sync: reassure both themselves and their teen that it is normal, and put in place strategies to help social and cognitive skills develop. These strategies include allowing an extra 15 minutes in the morning to get organized, spending extra time practicing "what if " scenarios, and putting in place systems of accountability. At the age of 11 she began her menstrual periods, and by her 13th birthday she had the fully developed breasts and rounded hips of a much older teenager. Sara was at first delighted by all the attention, since seemingly overnight she had become the envy of many girls her age, not to mention popular with older boys, who previously thought of her as just a kid. She begged her mother to let her date high school boys, but then became petrified and overwhelmed when they tried to kiss her and touch her body. She has become so embarrassed about her body that she has stopped hanging out with her girlfriends, preferring to hide out in her room. When Sara goes out in public, she wears baggy sweatshirts and jeans and hunches her shoulders in an effort to hide her shape. They are physically quite mature, to the point where people are not recognizing them for who they are-still children. Even though they have the bodies of adults, they are nowhere near emotionally ready to be sexually active. Her mother, or a caring adult, could assist Sara by not allowing her to 80 the teen years explained michael More than six feet tall, handsome, and with six-pack abs, 15year-old Michael looks like the next teen idol. Playing sports means hanging out with juniors and seniors, who invite him to parties where there is drinking and where sometimes drugs are passed around. Yet, he also feels weirded out by the pressure to be sexual, and worried the girls will laugh at his reluctance. Sometimes, Michael wishes people could see the kid he is inside, rather than just the man standing before them. They can also discuss ways in which Michael can say no and gracefully sidestep uncomfortable or dangerous situations. Sara and Michael could also benefit by being encouraged to be friends with more boys and girls their own age, and to get involved in activities that do not put undue emphasis on physical appearance. Most of the other guys his age seem stronger, more muscular, and more attractive- they are 16 going on manly. Big and athletic, they knock him over during football practice and run right by him on the basketball court as if he were invisible. He still has some buddies from middle school, but even they cannot help with the feelings of physical inadequacy he experiences on and off the field. Even though it is difficult not to be as tall and muscular as the other boys, Tomas is clearly on track in other areas and is emotionally ready for more mature relationships. He may be socially reticent at times, but he has the ability to be liked by his peers. Adults can support him by affirming that his physical development is normal and that he will catch up soon enough. Also, cheering on his efforts to shine academically will help to sustain his optimism. Looking at Leslie, people might mistake her for a 12-year-old, but then she opens her mouth and all bets are off. Leslie is bright and studious, a complex thinker who tosses around ideas and concepts as if they are hacky sacks. She has expanded her world view beyond the bathroom mirror and is involved in a variety of causes near and dear to her heart, like the environment and animal rescue. In middle school, Leslie was intimidated by being short and petite and hid her light under a bushel.
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The search was conducted in vari ous ways, some rational, and som etim es more speculative or quite random. Many useful drugs resulted from each kind of approach; luck as well as judgem ent is crucial to success in research. However, among m ajor series of drugs, such as sulphonamides and corticosteroids, the original agents have been com pletely superseded by succes 274 The C ambridge Illustrated H istory of M edicine sors widely regarded as having a better overall performance. It has always been m uch easier to believe optim istically in a remedy than to prove its worth in even a faintly scientific way. Extensive clinical research has been applied to discovering how best to use the powerful new remedies produced by the pharm aceutical laboratories, to discovering w hich of similar drugs is prefer able, and indeed to discovering whether their use is, in the long run and in spite of superficial appearances, beneficial at all. Bedside observation of individual patients under treatm ent has been supplemented by collection of facts about as many as possible of the patients treated in one way or another. Sometim es it then turns out that, however excitingly some sufferers appear to recover, m ost of the patients being treated actually do worse than those who are left alone or receive other treatments. Not only do new remedies need evaluating: many traditional remedies must also be questioned, as the eighteenth-century naval physician, Jam es Lind, observed in the preface to his Treatise on Scurvy (1 7 5 3). Elis wisdom remains all too true but is often forgotten: It appeared to me a subject worthy of the strictest inquiry: and I was led upon this occasion to consult several authors who had treated of the disease; where I perceived mistakes which have been attended in practice, with dangerous and fatal consequences. There appeared to me an evident necessity of rectifying those errors, on account of the pernicious effects they have already visibly pro duced. But as it is no easy matter to root out old prejudices, or to overturn opin ions which have acquired an establishment by time, custom, and great authorities; it became therefore requisite for this purpose, to exhibit a full and impartial view of what has hitherto been published on the scurvy; and that in a chronological order, by which the sources of those mistakes may be detected. Indeed, before this subject could be set in a clear and proper light, it was neces sary to remove a great deal of rubbish. History of the use o f m edicines reveals, over and over again, how m uch trust is Jam es Lind, who pioneered early clinical trials that dem onstrated the efficacy of citrus fruits in combating scurvy, discredited many tra ditional remedies. And yet, years or centuries later the remedies have fallen into disuse, if not positive disrepute, because their lack of good or their positive harm has at last been revealed by careful accum ulation of evidence and refusal to be swayed by casual anecdotes. The principles and value of good clinical trials were shown m ost lucidly when the efficacy of streptom ycin in the treatm ent o f tuberculosis was evaluated ju st after the Second W orld W ar by the British Medical Research Council, advised by Sir Austin Bradford Hill of the London School of Hygiene and Tropical Medicine. D r u g T r e a t m e n t a n d t he R i s e o f P h a r m a c o l o g y 275 Very little of the new drug was available when the trial started in 1946 - ju st enough for a small proportion of the patients who might have benefited. It was therefore considered ethically justifiable to carry out a trial in w hich one group received streptomycin whereas a control group was treated with traditional m eth ods. The randomized controlled clinical trial, the first o f its type, provided clear evidence about w hich treatments were more effective than others and set a model for many subsequent studies of new drugs. It has becom e unacceptable to claim benefit for a new drug w ithout clinical trials. The harm caused by thalidomide in the 1950s was particularly distress ing and aroused powerful demands for safe drugs. Testing drugs for toxicity, however, is an insoluble problem; the num ber o f ways in w hich a drug may be toxic is unlimited, and attempts to detect them all in advance have consistently been defeated, whenever new hazards have been discovered. In recent years, the introduction of life-saving drugs has often been delayed while tests of regrettably uncertain value are done. Gradually, it has been accepted that the most valuable safeguard rests on adequate recording of all uses of new drugs and reporting of all adverse effects. Certainly, the media endlessly draw attention to medicines and drugs and arouse enthusiasm or anxiety often on very slender grounds. W ithering, an Edinburghtrained physician who w orked at Birmingham General Hospital, dem onstrat ed that digitalis (a constituent of foxglove leaves) had a pow erful stim ulant action on the heart, increased urine flow, and w as effective in reducing oedema. It was indeed d iffic u lt to take enough o f thalidomide to cause death, and it was widely used in Europe. In 1961, after the drug had been on the market for 2 years, obstetricians in several parts o f Europe observed that babies were being born unusually often with a rare defor m ity - the failure o f the limbs to develop. It took 2 years of extensive research for the cause to be identified as thalido mide, taken at a particular, brief period in early pregnancy to ease the discomforts o f morning sickness. Nearly 500 babies were born with deformities in Britain alone; worldwide, there were many thousands.
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The integrity of neuronal connectivity through appropriate synapses and myelination determines the efficiency of collaboration of various brain structures and likely determines the growth of intellect. In anemic groups, supplementation improved attention, concentration, and intelligence, but had minimal effect on nonanemic participants and no effect on memory, psychomotor skills, or scholastic achievement in either group. Analyzed continuously, anemia affected reaction time but not performance, while low iron status affected performance but not reaction time in the lowest vs highest quintiles. Women with any significant rise in ferritin had improved scores that bore no relation to the magnitude of their ferritin change. Girls who received iron performed minimally better on a test of verbal learning and memory than girls in the control group. Of reported change, 93% was related to baseline scores and only 7% due to the iron supplementation. No differences were seen in attention or self-reported energy, mood, concentration, or memory. Concern around impairment, even small difficult-to-measure changes, suggests that steps should be taken to prevent iron depletion in persons whose brains are continuing to undergo detectable remodeling and growth. Pica Pica is the continual craving and consumption of nonnutritional substances such as ice, dirt, clay, chalk, starch, coal, or paper. The most common manifestation (and the symptom most closely linked with iron deficiency) is pagophagia, the pathologic consumption of ice. Pica was reported in 11% of donors with iron depletion or iron deficiency vs 4% of iron-replete donors (p<0. Donors with pica experienced complete resolution of the behavior after 14 days of iron supplementation. Neither study showed a significant association between iron status and the incidence of pica in men. These studies suggest that pica-in particular, pagophagia-is common in female blood donors who are iron deficient. The data from Bryant et al54 strongly suggest that pica symptoms in blood donors are reversible with oral iron therapy. Bryant et al54 studied 1236 donors deferred for low hemoglobin and 400 nondeferred donors. Pedrazzini et al56 of the Swiss Red Cross studied 291 women 1 week after donation and reported a prevalence of 6. Safety of Iron Supplementation Study Population and Intervention(s) 526 qualified, regular donors randomly assigned to take vitamins with 40, 20, or 0 mg/day elemental Fe for 6 mos. Outcome Measures Outcome/ Conclusion Ferritin and iron stores fell in placebo arm. Assessed by counting pills at visits, but undefined: "Poor in roughly 1/3 of the male participants" and in "roughly 1/4 of females. Rather than posing a risk of harm to the donor, it is more likely that early attention to iron depletion and deficiency would lead to earlier detection of occult malignancy and a higher chance of cure. Hb and ferritin recovery faster w/ Fe and majority w/o Fe did not recover either by 24 weeks. Outcome Measures Outcome/ Conclusion Adherence Safety Exclusions Observational Fe replacement in Denmark (Magnussen et al61) Donor Hb at every donation, ferritin at index and every 10th thereafter. Among completers, prevalence of low ferritin fell >50% and not different in the 3 "active interventions" (19 mg, 38 mg, and iron status letter). Degree of iron repletion inversely proportional to baseline ferritin level Pill groups deenrolled 39% vs 7 with letters. With 19 and 38 mg, identical increases after first 60day course and maintained subsequently. The costing of each strategy was taken from the health-care system perspective-those costs that accrue to the blood centers as part of implementing a strategy and medical care costs of interventions and adverse events. The preferred approach of the societal perspective, accounting for all costs and consequences that accrue to all members of society, is beyond the scope of the current assessment. The generalized structure for assessment of costs is provided in Figure 1 as a hierarchical model. First is the baseline cost to implement a strategy de novo followed by a second level of costs to run/manage a strategy once implemented. The third level of costs are wider ranging and relate to the cost implications in terms of blood supply availability, assuming the current overall number of units in the national supply is maintained. In other words, any units that are lost because donors are ineligible or do not adhere to the intervention strategy will be made up by recruiting additional donors to restore the lost units in the supply.