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By Y. Innostian. The Naval Postgraduate School.

It then slowly distributes back into the plasma compartment at subtherapeutic concentrations with a long terminal elimination half- life generic seroflo 250 mcg. Therefore trusted 250mcg seroflo, single doses of diazepam can be used as a short-term preanesthesia med- ication buy 250 mcg seroflo, whereas daily dosing will result in accumulation during the terminal elimination phase and provide long-acting therapy. Drug Interactions with Benzodiazepines 7 Table 3 Uses of Benzodiazepines Listed in Martindale Half-Life Route(s) of Usual Generic Name (h)a Administration Dose (mg) Usesb Adinazolam short — — 1, 8 Alprazolam 11–15 oral 0. The benzodiazepines are well absorbed from the gastrointestinal tract, which allows for oral dosing of benzodiazepines (Table 3). The plasma concentration benzodiazepines, or their primary phar- macodynamically active metabolites, correlates well with the dose of benzodiazepine administered (Fig. There are structural differ- ences between them, and these differences will affect the manner in which the benzo- diazepine is metabolized, and thereby have an impact on their individual susceptibility to drug interactions. In all but two of the commercially avail- able benzodiazepines, the nitrogens in the diazepine ring are in the 1,4 position. Cloba- zam has nitrogens in the 1,5 position of the diazepine ring; tofisopam has nitrogens in the 2,3 position of the diazepine ring (Fig. The range of (A) therapeutic doses and (B) plasma concentrations of selected ben- zodiazepines. Therefore, with the exception of clobazam and tofisopam, these are 5-aryl-1,4- benzodiazepines. Following the initial synthesis of chlordiazepoxide by Sternbach in 1957, and its introduction as a therapeutic agent in 1961, a number of benzodiazepines have been introduced onto the market. The initial modifications involved changes in the substit- uents on the diazepine ring. Modifications along this line first led to the development of diazepam, flurazepam, and oxazepam. Substitution of the benzene with a thieno group produced the 1,4-thienodiazepines (Figs. While most benzodiazepines have a phenyl substituent at the 5 position of the diazepine ring, bromazepam has a 2- pyridinyl substituent, and tetrazepam has a 1-cyclohexen-1-yl substituent at this posi- tion (Fig. Bentazepam, with a benzylthieno group fused to the diazepine ring, and brotizolam with both the thieno and triazolo groups are unique 1,4-thieno- diazepines (Fig. An electron-withdrawing group is required at the 7 position of the benzene (or thieno) group (R10 for oxazolo and R8 for triazolo or imidazo). These are generally the halides chloride, and occasionally bromide, or a nitroso group. Basic Metabolism of Benzodiazepines Most of the 5-aryl-1,4-benzodiazepines are metabolized by N-dealkylation at the N-1 position and hydroxylation at the 3 position (Fig. Structure of “odd” benzodiazepines that could not easily be described in Tables 5 or 6. In many cases the N-dealkyl metabolite is nordiazepam (N-desmethyldiazepam, nordiazam) (Fig. The 3-hydroxyl group is then conjugated, usually with glucuronide, resulting in an inactive metabolite. Clorazepate is nonenzymatically decarboxylated to nordiazepam at the low pH of the stomach. The 4,5-oxazolo-benzodiazepines, such as ketazolam, oxazolam, and mexazolam, have the 4,5-oxazolo cleaved. Adinazolam is successively N-demethylated at the1-dimethylaminomethyl constituent to N-desmethyladinazolam and didesmethyladinazolam. The first N-demethyl product has a higher area under the curve than the parent drug and higher affinity for the central benzodiazepine receptors. Deamination of N-desmethyladinazolam with eventual 1-hydroxylation to 1-hydroxy- alprazolam or side chain cleavage to estazoalm have been described in the mouse, but does not appear important in humans (10,11). Although both metabolites have minor activity, they are not formed in sufficient amounts to contribute to the pharmacologic activity of estazolam. The 7-nitroso-benzodiazepines, clonazepam, flunitrazepam, and nitrazepam, are metabolized by successive reduction of the nitroso-group to the amine and subsequent N-acetylation of the amine to the corresponding acetamido-group (Fig. N-Dealkylation at the 1 position of the diazo-ring is also a prominent route of metabolism for flunitrazepam. Clonazepam and flunitrazepam can also be hydroxylated at the 3 position of the diazoring. With nitrazepam, oxidative metab- olism at the diazo ring results in ring cleavage; this can be followed by hydroxylation of the phenyl (B) ring (Fig. The routes of metabolism of other benzodiazepines, bromazepam (ring cleavage and 3-hydroxylation), clobazam (N-dealkylation and c-ring hydroxylation), clotiazepam (N-dealkylation and side chain hydroxylation), and loprazolam (N-dealkylation and spontaneous hydrolysis to polar compounds) have been described (Fig. This appears to block hydroxy- lation at the 3 position, with N- and O-demethylations forming the primary metabolites (Fig. Successive hydroxylations of the methyl groups followed by N-hydroxymethy- 14 Moody Fig. From (401); reproduced from the Jour- nal of Analytical Toxicology by permission of Preston Publications, a division of Preston Industries, Inc. Tofisopam (tofizopam) is an unusual 2,3-diazepine with hydroxymethyl groups at four positions. O-Demethylation at the R1 and R4 positions has been described as the major routes of tofisopam’s metabolism (Fig. Based upon the principles discussed above, however, one can speculate on putative pathways of their metabolism (Table 7). Metabolism of the 4,5-oxazolone ring as postulated for mexazolam by Ishigami et al. Methods Used to Determine Enzyme Involvement in the Metabolic Pathway The methods for determination of the role of a specific enzyme in the pathway of a drug’s metabolism have been developed most thoroughly for the cytochrome P450s 16 Moody Fig. From (401); repro- duced from the Journal of Analytical Toxicology by permission of Preston Publications, a division of Preston Industries, Inc. Studies are done using human liver tissue that is now usually procured from donor tissue that is deemed unsuitable for transplantation.

Among 248 pregnancies exposed to oxcarbazepine monotherapy during pregnancy purchase seroflo 250 mcg with mastercard, there were six congenital anomalies (2 generic seroflo 250mcg. Among 61 infants whose mothers were given polytherapy that included oxcarbazepine order seroflo 250mcg with visa, four birth defects (6. Among 35 infants born to epileptic women treated with oxcarbazepine monotherapy in one series, no congenital anomalies were found (Meischenguiser et al. Among 20 infants born to women who took polytherapy anticonvulsant regimen that included 176 Anticonvulsant drugs during pregnancy oxcarbazepine, one baby was born with a major cardiac congenital anomaly. One of nine infants born to epileptic women treated in the first trimester with oxcarbazepine monotherapy had multiple major birth defects involving the genitourinary tract (Kaaja et al. Isolated case reports involving polytherapy (including oxcarbazepine) of single infants with spina bifida, short spine, hypospadias, or limb reduction defects have been published (Lindhout et al. Tiagabine Among nine infants whose mothers took tiagabine during pregnancy, one infant had a congenital anomaly, but this was not similar to any of the anomalies in the ‘fetal anti- convulsant syndrome’ (Morrell, 1996). In unpublished experimental animal studies (rats, rabbits) employing doses much higher than the human dose, and at doses toxic to the mother, there were increased fre- quencies of congenital anomalies in rats but not rabbits. None of this information is rel- evant to the assessment of human risk of birth defects following exposure to tiagabine during embryogenesis. Topiramate In a case series three normal infants were reported whose mothers were treated with top- iramate sometime during gestation (Morrell, 1996). In another case report, a pattern of minor anomalies similar to the ‘fetal anticonvulsant syndrome’ were observed in an infant whose mother took topiramate monotherapy throughout pregnancy (Hoyme et al. The relevance of these anecdotal reports, if any, to human risks following exposure to topiramate during embryogenesis is unknown. The results of studies of rats, mice, and rabbits exposed to topiramate during embryo- genesis are conflicting. Rats had limb defects at the highest doses, mice had craniofacial defects, and rabbits had vertebral anomalies. The inconsistent findings and the lack of peer review of these unpublished studies confound any possible interpretation of these data. Vigabatrin Among 47 infants born to women who took vigabatrin during the first trimester two (4. In several studies, major anomalies were increased among mice exposed to vigabatrin during embryogenesis, and cleft palate occurred among rabbits exposed to maternally and fetotoxic doses. No increased frequency of congenital anomalies was found among rats exposed to vigabatrin during embryogenesis. Zonisamide Zonisamide is an anticonvulsant used either in monotherapy or polytherapy to treat a broad spectrum of epileptic conditions (Oguni et al. In one Special considerations 177 small prospective case series of 26 infants born to women treated throughout pregnancy with zonisamide as part of a polytherapy anticonvulsant regimen, two infants (7. A child whose mother took zonisamide, carbamazepine, pheny- toin, sodium valproate, and a barbiturate during pregnancy was reported with features of anticonvulsant embryopathy (Noda et al. Increased frequencies of congenital anomalies were found in animal studies of terato- genicity of zonisamide in rats (cardiac), mice (visceral, skeletal), dogs (cardiac), and monkeys (pregnancy wastage) (Terada et al. If a pregnant woman presents on anticonvulsant therapy, she should be given counseling regarding the two- to three-fold increased risk of malformations. She should also be offered high-resolution ultrasound and alpha-fetoprotein screening at appropriate gestational intervals. It should be emphasized that these techniques, although helpful, may not rule out anticonvulsant embryopathy. It may be possible to discontinue medications in certain patients who have been seizure-free for protracted periods of time, especially in patients who have had petit mal seizures. Trimethadione and paramethadione are generally contraindicated during pregnancy, and valproic acid should be avoided if possible. One of the succinimides, etho- suximide, would appear to be a better choice for petit mal seizures in the rare pregnant patient where it is indicated. Monitoring of serum levels of anticonvulsants may be indicated in some pregnant women, especially those with increased seizure activity. A suggested man- agement protocol for pregnant patients with epilepsy is summarized in Box 9. Patients should be counseled that anticonvulsant therapy during pregnancy is associ- ated with risks of serious birth defects. For example, with valproic acid and carba- mazepine, the risk for neural tube defects, spina bifida in particular, is increased with exposure during the first trimester (Table 9. Risks for other congenital anomalies are increased when associated with exposure to other anticonvulsants during embryogene- sis (Table 9. Risk for valproic acid-associated neural tube defects is increased at (1) high doses (> 800 mg/day) and (2) polytherapy. Interestingly, recent analyses indicate that the risk for neural tube defects with exposure to oxcarbazepine or to lamotrigene is not different from the risk with carbamazepine (Perucca, 2005). Pharmacogenetics The metabolism of folic acid is inhibited by many anticonvulsant drugs. This alteration in folate metabolism is presumed to be provoked by hepatic enzyme induction and folate malabsorption (Janz, 1982; Maxwell et al. Phenobarbitone, phenytoin, carba- mazepine, valproic acid, and primidone have been implicated in these metabolic alter- ations (Donaldson, 1991). Human and animal studies support the finding that folic acid supplementation decreases the rate of congenital malformations in infants of epileptic mothers who are receiving anticonvulsants during pregnancy (Biale and Lewenthal, 1984; Dansky et al. Epileptic mothers with a positive history of neural tube defects or orofacial clefts in previous children, or paternal or maternal family history should be supplemented preconceptually and through the first trimester with 4–5 mg per day of folic acid, especially women taking valproic acid or carbamazepine (Perucca, 2005). In addition, mothers receiving the above anticonvulsants should be given 20 mg of vitamin K1 in the final month of pregnancy (Delblay et al. Umbilical cord prothrombin, par- tial thromboplastin values, and vitamin-K-dependent clotting factors should be evalu- ated shortly after delivery (Bleyer and Skinner, 1976, Srinivasan et al. Folic acid and vitamin D supplements should be considered for pregnant women on phenytoin and other similar anticonvulsants, in addition to vitamin K supplementation in the third trimester (Yerby, 2003). Further, it is not pos- sible to unravel the relationship of the disease being treated, the treatment for the dis- ease, and the genetic complement of the mother and fetus in assessing the risk for birth defects in epileptic pregnancies. The management of pregnancy in women with epilepsy requires the coordinated efforts of the patient’s primary treating physician and her neurologist. With proper man- agement, 90 percent of women with epilepsy can anticipate uneventful pregnancies and normal children. Association of prenatal phenobarbital and phenytoin exposure with small head size at birth and with learning problems.

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While the normal pains are increased discount seroflo 250 mcg with visa, all erratic cheap 250 mcg seroflo amex, rheumatic cheap 250 mcg seroflo with mastercard, irregular and nagging pains are relieved. Knox observed the action of this remedy as a partus preparator in a hundred and sixty cases. His observations, summed up, are that the remedy has a positive sedative influence upon the parturient women, quieting reflex irritability, nausea, pruritis and insomnia. It has a positive anti-spasmodic effect, correcting neuralgic cramps, and irregular pains of the first stage of labor, sometimes terminating the labor precipitately, if given in too large doses, often without prodomic symptoms. Ellingwood’s American Materia Medica, Therapeutics and Pharmacognosy - Page 124 It relieves undue irritation of the uterine muscular fiber, relaxes the soft parts of the parturient canal, and thus facilitates labor and diminishes the risks of laceration by controlling undue irritability of the muscular fiber. It maintains a better contraction of the uterus after delivery, but for this purpose he administers a special dose of thirty minims of the fluid extract after the birth of the fetal head. It was his habit in using this remedy for its preparatory effects, to give fifteen minims, at the time of retiring each night, for six weeks prior to confinement. Coffin used this remedy for the above purpose, there was postpartem hemorrhage, and this caused the doctor to question whether or not the agent had such a relaxing influence, as he was not in the habit of giving either this or any other remedy to anticipate such hemorrhage. Webster claims to have observed a case of epilepsy, attended with amenorrhea which was kept under control with Cimicifuga in conjunction with the bromides, when the bromides alone had previously failed. The elder Adolphus, treated ophthalmia with this remedy, especially when there was severe pain. In the severe cases, he applied it externally, as well as administering it internally. In those cases where there was much nervous irritability, he combined it with gelsemium, which he was confident enhanced its influence. One of the old writers claimed that he used it persistently through an entire epidemic, and the results caused him to entertain the highest confidence in this remedy. If given with the appearance of the premonitory symptoms, the disease was so abridged, that no eruptions appeared. He usually gave it in the form of a decoction, in conjunction with equal parts of asclepias, and a small quantity of ginger. He gave enough of the remedy, to induce the physiological influence, such as aching in the muscles and pain in the head. The agent should have a further trial in this disease, as others have claimed to obtain results similar to those quoted above, and the influence of the remedy should be confirmed or disproved. Ellingwood’s American Materia Medica, Therapeutics and Pharmacognosy - Page 125 In the male it is valuable in gonorrhea, with aching, in the bladder and across the kidneys. It soothes the nervous irritability and materially assists in relieving the active inflammation. We usually find indications for aconite in the acute cases, or gelsemium where there is irritation with a tendency to spasmodic stricture, or hydrangea where there are sharp, cutting pains in urination; and these properly combined have been our “sure cure” treatment for many years, with mild injections of zinc sulphate, hydrastine, or hydrogen peroxide, all warm, or of warm water alone. In spermatorrhea with irritability and considerable sexual weakness and plethora, it will cure when other agents fail, if given in half-dram doses after meals. The pure alkaloids of cinchona are not employed in medicine, but their salts, formed from acid and basic combinations, are in common use. In the consideration of the therapeutic properties of the various alkaloids of cinchona there is but little difference observed in their action. There is almost no influence exercised by any one of them that is not exercised to an equal extent by quinine, and except where otherwise specified, the Sulphate. Ellingwood’s American Materia Medica, Therapeutics and Pharmacognosy - Page 126 Quinine Sulphate. Physiological Action—In doses of five grains three or four times a day for a few days, it produces fullness of the capillary circulation of the brain, throbbing in the head, suffusion of the face, ringing in the ears, with dullness of hearing, headache, mental confusion and nervous excitement. If the above doses be given every three hours continuously there is muscular feebleness, with general impairment of motility, increasing debility, great restlessness, with wakefulness, dilated pupils and partial loss of sight. A single dose of sixty grains of quinine sulphate, given to an adult male caused extreme depression, with feeble circulation, coldness of the surface and extremities, respiration slow and sighing; pulse slow and almost imperceptible, pupils widely dilated, sight and hearing almost extinct, voice very feeble; thirst great, tongue pale and moist, breath cold. While in some cases blindness from quinine has continued for some time in no case has it been permanent. In some cases death has followed the administration of the remedy in disease, a result fairly attributed to the drug. In small doses it is tonic, in large doses stimulant, and in still larger doses sedative, acting on the cerebro-spinal nervous system and through the ganglionic nervous system on the heart. Besides the above named effects, large and repeated doses may cause gastric irritation, eructations, chill and fever paroxysms headache, perspiration, vertigo, staggering and delirium— the condition known as cinchonism. Specific Symptomatology—Quinine will act favorably upon the system if the skin be soft, if the mucous membranes of the mouth are moist, and if the tongue is moist and inclined to clean, if the pulse is full and soft and the temperature declining or at normal. In other words, when the secretory functions of the body are in a working condition, quinine will produce no unpleasant results. It will overcome malarial periodicity, especially if the above named conditions are present when the agent is administered. It is profoundly tonic; under limited conditions it is antipyretic and also antiseptic. Ellingwood’s American Materia Medica, Therapeutics and Pharmacognosy - Page 127 Quinine destroys the plasmodium malariae readily, even in the minute quantity of one part to twenty thousand of water. Therapy—In the administration of quinine as an antiperiodic, the beneficial influences are not altogether in proportion to the size of the dose. Enormous doses may abort a chill if given during its course, or during the course of the fever. They are very likely, however, to increase the nervous erethism and the temperature; whereas, if proper doses be given during the intermission, from one to three hours preceding the anticipated attack, or at the time when the temperature has reached its lowest point, small doses will accomplish positive results. In continued fever, with a sufficiently marked remission occurring at a given time each day, or on each alternate day, the agent should be given during the remission, provided the temperature declines to a point sufficiently low to admit of a temporary restoration of the suspended secretions. As a result the temperature does not run quite as high as on the previous day, and the next remission is more marked and of longer duration. The fever is still lower and the remission so marked by the third day that the agent, in reasonable doses, may be continued through the exacerbation, the temperature at no time, probably, rising above 101 degrees and not increasing above normal after the third day. The writer has adopted this course for so many years, with perfectly satisfactory results, that the method is confirmed in his mind as the proper one in all cases where malaria is the cause, Where continued fever exists, quinine is of no benefit if there is no marked remission or other evidence of malaria. It is thus of no use during the progress of typhus, typhoid and other protracted fevers. In such cases it causes nerve irritation and increased temperature, especially if there is deficient secretion. When the fever is broken and there is a tendency toward a restoration of secretion, and the temperature is normal or subnormal, then this agent is a vitally important one.

Are they refusing treatment because of a general mistrust of health care ment buy seroflo 250mcg with mastercard, do not vary providers? Or do some decline treatment because of negative experiences in the clinical greatly and cannot encounter or a perception that their doctor is not invested in their care? More research is fully explain racial and needed to fully understand treatment refusal because the reasons for refusal may lead to ethnic disparities in different strategies to help patients make informed treatment decisions order seroflo 250 mcg without a prescription. If minority patients’ attitudes toward healthcare and preferences for treatment are not likely to be a major source of health care disparities discount 250mcg seroflo with visa, what other factors may contribute to these disparities? The first set of factors are those related to the operation of healthcare systems and the legal and regulatory climate in which they operate. Differences, Disparities, and Discrimination: Populations with Equal Access to Healthcare. Three mechanisms might be operative in healthcare disparities from the provider’s side of the exchange: bias (or prejudice) against minorities; greater clinical uncertainty when interacting with minority patients; and beliefs (or stereotypes) held by the provider about the behavior or health of minorities. Patients might also react to providers’ behavior associated with these practices in a way that also contributes to disparities. Research on how patient race or ethnicity may influence physician decision-making and the quality of care for minorities is still developing, and as yet there is no direct evidence to illustrate how prejudice, stereotypes, or bias may influence care. In the absence of such research, the study com- mittee drew upon a mix of theory and relevant research to understand how these proc- esses might operate in the clinical encounter. Clinical Uncertainty Any degree of uncertainty a physician may have relative to the condition of a patient Any degree of uncer- can contribute to disparities in treatment. Doctors must depend on inferences about sever- tainty a physician may ity based on what they can see about the illness and on what else they observe about the have relative to the patient (e. The doctor can therefore be viewed as operating with prior beliefs condition of a patient about the likelihood of patients’ conditions, “priors” that will be different according to can contribute to dis- age, gender, socioeconomic status, and race or ethnicity. Doctors must balance new information gained from the patient (sometimes with vary- ing levels of accuracy) and their prior expectations about the patient to make a diagnosis and determine a course of treatment. If the physician has difficulty accurately understand- ing the symptoms or is less sure of the “signal” – the set of clues and indications that 3 physicians rely upon to make diagnostic decisions – then he or she is likely to place greater weight on “priors. The Implicit Nature of Stereotypes …there is considerable A large body of research in psychology has explored how stereotypes evolve, persist, empirical evidence that shape expectations, and affect interpersonal interactions. Stereotyping can be defined as even well-intentioned the process by which people use social categories (e. The beliefs (stereotypes) and general orienta- overtly biased and who tions (attitudes) that people bring to their interactions help organize and simplify complex do not believe that or uncertain situations and give perceivers greater confidence in their ability to under- stand a situation and respond in efficient and effective ways. These biases may exist in overt, explicit forms, as represented by traditional big- negative racial atti- otry. However, because their origins arise from virtually universal social categorization tudes and stereotypes. In the United States, because of shared socialization influences, there is considerable empirical evidence that even well-intentioned whites who are not overtly biased and who do not believe that they are prejudiced typically demonstrate unconscious implicit negative racial attitudes and stereotypes. Both implicit and explicit stereotypes significantly shape interpersonal inter- actions, influencing how information is recalled and guiding expectations and inferences in systematic ways. They can also produce self-fulfilling prophecies in social interaction, in that the stereotypes of the perceiver influence the interaction with others in ways that conform to stereotypical expectations. Healthcare Provider Prejudice or Bias Prejudice is defined in psychology as an unjustified negative attitude based on a per- son’s group membership. Survey research suggests that among white Americans, prejudi- cial attitudes toward minorities remain more common than not, as over half to three- quarters believe that relative to whites, minorities – particularly African Americans – are less intelligent, more prone to violence, and prefer to live off of welfare. It is reasonable to assume, however, that the vast majority of healthcare providers find prejudice morally abhorrent and at odds with their professional values. But healthcare providers, like other members of society, may not recognize manifestations of prejudice in their own behavior. While there is no direct evidence that provider biases affect the quality of care for But healthcare pro- minority patients, research suggests that healthcare providers’ diagnostic and treatment viders, like other decisions, as well as their feelings about patients, are influenced by patients’ race or eth- members of nicity. In another experimental design, Abreu (1999) found that mental health professionals sub- liminally “primed” with African American stereotype-laden words were more likely to evaluate the same hypothetical patient (whose race was not identified) more negatively than when primed with neutral words. Further, in a study based on actual clinical encoun- ters, van Ryn and Burke (2000) found that doctors rated black patients as less intelligent, less educated, more likely to abuse drugs and alcohol, more likely to fail to comply with 4 medical advice, more likely to lack social support, and less likely to participate in cardiac rehabilitation than white patients, even after patients’ income, education, and personality characteristics were taken into account. These findings suggest that while the relationship between race or ethnicity and treatment decisions is complex and may also be influenced by gender, providers’ perceptions and attitudes toward patients are influenced by patient race or ethnicity, often in subtle ways. Medical Decisions Under Time Pressure with Limited Information Indeed, studies suggest that several characteristics of the clinical encounter increase In the process of the likelihood that stereotypes, prejudice, or uncertainty may influence the quality of care care, health profes- for minorities. In the process of care, health professionals must come to judgments about sionals must come to patients’ conditions and make decisions about treatment, often without complete and ac- judgments about pa- curate information. In most cases, they must do so under severe time pressure and re- tients’ conditions source constraints. The assembly and use of these data are affected by many influences, and make decisions including various “gestalts” or cognitive shortcuts. In fact, physicians are commonly about treatment, of- trained to rely on clusters of information that functionally resemble the application of ten without complete “prototypic” or stereotypic constellations. These conditions of time pressure, resource and accurate infor- constraints, and the need to rely on gestalts map closely onto those factors identified by mation. Patient Response: Mistrust and Refusal As noted above, the responses of racial and ethnic minority patients to healthcare providers are also a potential source of disparities. Little research has been conducted as to how patients may influence the clinical encounter. It is reasonable to speculate, how- ever, that if patients convey mistrust, refuse treatment, or comply poorly with treatment, providers may become less engaged in the treatment process, and patients are less likely to be provided with more vigorous treatments and services. But these kinds of reactions from minority patients may be understandable as a response to negative racial experi- ences in other contexts, or to real or perceived mistreatment by providers. Survey re- Little research has search, for example, indicates that minority patients perceive higher levels of racial dis- been conducted as to crimination in healthcare than non-minorities. Patients’ and providers’ behavior and atti- how patients may in- tudes may therefore influence each other reciprocally, but reflect the attitudes, expecta- fluence the clinical en- tions, and perceptions that each has developed in a context where race and ethnicity are counter. Given that stereotypes, bias, and clinical uncertainty may influence clinicians’ diag- nostic and treatment decisions, education may be one of the most important tools as part of an overall strategy to eliminate healthcare disparities.

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