M. Marcus. Northwest Christian College.
Memory aids generic 400 mg skelaxin amex, use of concrete communications cheap skelaxin 400 mg on line, and short psychotherapeutic sessions may help cheap 400mg skelaxin free shipping. The patient should be taught skills that assist coping, relaxation, and stress management. Problem-solving skills and breaking down goals into achievable ones will assist progress. Mittenberg ea (1996) reported that participating in education programs aimed at normalising reactions can improve post-concussional symptoms. They will need to learn the middle road between excessive protection and risk-taking if the patient is to achieve optimal independence and competence. Headache3118 Childhood headache, which is associated with psychosocial adversity, may be a risk factor for adult headache and psychiatric symptoms in adulthood. Structures above the tentorium are innervated by the ophthalmic division of the V cranial nerve, whilst structures below the tentorium are innervated by C2 and C3. Cerebellar lesions usually cause pain posteriorly, and pain from occipital lobe lesions is felt anteriorly. However, because of a contribution from the caudal nucleus of V nerve, pain from upper cervical spine or posterior fossa can also be referred to the front of the head. Chronic renal failure may be associated with headache, emesis, and left ventricular failure. Many cases of bacterial meningitis suffer headache for months after the initial illness. It tends to be symmetrical, have a particular distribution (bifrontal, bioccipital, and nuchal), be of mild to moderate intensity, to have a stable intensity, to get worse as the day progresses, to lack features of migraine, and is often of high frequency (sometimes daily). It responds to reduction in stress, psychotherapy, environmental manipulation, alcohol, tranquillisers, etc. Sufferers (migraineurs) have been characterised as ‘anxious and neurotic’, but, whilst they do suffer an excess of anxiety and depression (probably more than other headache sufferers: Fleminger, 2009b, p. Rasmussen (1992) found that people with tension headache rather than migraine had high neuroticism scores on the Eysenck Personality Inventory. Indeed, previous descriptions of migraineurs as being particularly ‘neurotic’ may have been due to confinement of studies to clinic samples. Migraine with aura is more likely to be familial than is migraine without aura, but the likelihood of a latter case having a similarly affected close relative is increased nonetheless. The risk of a child developing migraine is, respectively, 45% and 70% if one or both parents have the disorder. Being pregnant may relieve migraine and two-thirds of cases improve with physiological menopause, the opposite number worsening with surgical menopause. The same phenomenon can be induced in animal studies by applying a strong solution of potassium. The wave may be preceded by a brief hyperaemic phase, possibly the cause of the lights that occur during an aura. Digitolingual paraesthesias (cheiro-oral syndrome) are a common part of the aura – numbness and pins and needles start in the fingers of one hand and extend into the arm and face, especially the nose and mouth area ipsilaterally; this usually follows the visual disturbance but uncommonly occurs without it. Teichopsia consists of visual hallucinations, especially of battlements, and is characteristic of migraine. Delirium may complicate an attack: there may be different combinations of dysphasia, agnosia, apraxia, amnesia, temporal lobe phenomena (e. Disturbed body image may occur at any stage of an attack – bodily components seem bigger (e. Pain is severe and throbbing or non-throbbing, and often arises early in the morning. Most attacks last less than a day and those lasting more than 72 hours are referred to as migraine status. The patient tends to lie down in a dark room (photophobia), may vomit, or faint if standing. The resolution phase is associated with fatigue, irritability, scalp tenderness, depression or euphoria. Pain may be felt in the face and is then often misdiagnosed as being due to sinus problems. Migraine attacks may be accompanied by psychiatric symptoms and sufferers may have increased rates of affective and anxiety disorders, nicotine dependence, and alcohol or illicit drug abuse or dependence. The lifetime prevalence of anxiety disorder and major depression has been estimated at 54% and 34% respectively in migraine patients (27% and 10% in controls respectively). Migraine with aura is associated with an increased risk of ischaemic stroke, migraine angina, as well as other ischaemic vascular events such as myocardial infarction, the risk varying by vascular risk factors. However, the same individual may experience attacks of either of these types and even an aura without headache (migraine equivalent or acephalgic migraine). In older cases without headache the term late-life migraine accompaniment may be used. Seizure activity may be precipitated by the aura of migraine, in which case valproate may be useful as an anticonvulsant and migraine prophylaxis. If the migraine sufferer is depressed, amoxapine or trazodone may be useful because of their high affinity for serotonin receptors. Botulinum toxin has also been used for this purpose (when attacks last for at least 15 days in every month): injections are given in forehead, sides of neck, and back of neck. Telcagepant, a new calcitonin gene-related peptide receptor blocking drug, does not (unlike triptans) cause vasoconstriction, is probably as effective as the triptans for migraine prophylaxis. Persistence of signs lasting over 1 week or evidence on a scan of cerebrovascular accident is termed migrainous infarction: to make the diagnosis, the infarction must occur during a typical attack of migraine with aura; the usual infarct involves a wedge of posterior occipital lobe; and risk factors include young, female, smoking, and anovulant use. Chronic migraine (transformed migraine) is the term used for attacks that increase quickly in frequency over at least a three-month period. Some, but not all, may be due to over-treatment (rebound headache) and such cases need to be detoxified very slowly. Familial hemiplegic migraine (rare, heterogeneous, autosomal dominant, chromosomes 19p13, 2q24) is associated with transient hemiparesis (with sensory, visual, or language dysfunction) preceding headache. Other types of ‘migraine’ are ophthalmoplegic (headache plus diplopia) and retinal (attacks of monocular scintillations, 3130 scotomata, blindness, and headaches) migraine. There is often a migraine history and one-quarter experience a virus-like illness in the weeks before onset. There are a variable number of episodes of varying fleeting neurological deficits (incl. Cluster headache (migrainous neuralgia): This may be due to a disorder of the hypothalamus. It usually affects above one eye , though sometimes it may affect a cheek or even occur close to an ear. A partial Horner’s syndrome (minor degree of ptosis and meiosis), transient or permanent, may persist between attacks. If the condition is expected to last for a few weeks, corticosteroids can be used. Treatment of an attack may involve oxygen (100%, 7-12 litres/minute: vasoconstrictive effect and reduces release of calcitonin gene-related peptide), sumatriptan (subcutaneous [6 mg] or nasal), zolmitriptan (nasal or oral), dihydroergotamine, nasal lidocaine, corticosteroids, and various other procedures, e. Percutaneous radiofrequency trigeminal rhizotomy may be useful for chronic intractable cluster headache.
Accreditation generally is required by federal law to obtain certification considered a higher standard of oversight than from the U generic skelaxin 400mg with amex. While adopting these standards maintenance programs found that voluntary 156 accreditation was strongly related to adoption of largely is voluntary cheap skelaxin 400 mg overnight delivery, some states grant licenses 157 these practices; however skelaxin 400 mg with amex, after accreditation to programs that have been accredited, such that the program is deemed to have met the state became mandatory in 2000, this relationship licensure requirements because it has been disappeared. The authors speculated that † 158 programs that voluntarily seek accreditation tend approved by a national accrediting body. By granting “deemed status” licenses to accredited to be resource-rich (in funds, staff and training) programs, the state essentially delegates to the and more motivated to improve their quality of accrediting body its responsibility for ensuring care, and therefore more likely to adopt 165 that the facility or program meets state licensure evidence-based practices. Accreditation standards are more detailed than state licensing requirements The five organizations that accredit addiction and while some require facilities and programs treatment programs and facilities in the United to use evidence-based practices or to analyze States are: 160 patient outcomes, not all do. Similarly, facilities voluntarily responding to a national federal requirements stipulate that some types of † survey: care must be provided under the supervision of a physician, while services such as “rehabilitation 56. The categories are Dentists and other health professionals may be not mutually exclusive, as programs and facilities responsible for services they are qualified to perform may have multiple accreditations. Among the 21 medical services are defined as detoxification, states that specify the minimum educational/ opioid replacement therapy or the assessment, training requirements for this position, few have diagnosis and treatment of co-occurring medical particularly high standards: or mental health conditions, not as addiction 181 Eight states require a minimum of a master’s treatment itself. Few states require non-hospital- based programs that do not provide opioid One state requires an associate’s degree; and maintenance therapy to have a physician serving as medical director or on staff; 10 states require One state simply requires the person to residential treatment programs to have a demonstrate competence to perform certain physician either as a medical director or on staff services. Without a physician as A national survey of treatment professionals medical director or on staff, addiction treatment conducted in 1998 found that 60. Organizations that seek percent had some college or an associate’s elective accreditation for assertive community ‡ degree and 1. In states that The Joint Commission allows programs to provide addiction treatment using Medicaid define the qualifications required for staff to funding, hospital and clinic services must be perform their job and requires staff who provide 187 provided under the direction of a physician, care to be licensed, certified or registered “in but if states choose to provide services under the accordance with the law. If physician on staff; this person must have services are required to be provided under the experience in addiction medicine, including 193 direction of a physician, the facility physician is medication-assisted treatment. Licensed health care facilities must deliver care The facility and the staff providing care also are that meets standards of medical practice; state required to hold appropriate state licenses, regulations tend to defer to health care 189 certifications or registrations. In contrast, those who providers, including addiction counselors, provide addiction treatment often have minimal comply with the credentialing requirements of 190 † their respective profession. A While most states regulate addiction treatment survey conducted in 2006 found that three services, they treat these services as completely states--Oregon, North Carolina and Alaska-- * 196 separate and distinct from medical care, and have enacted legislation that mandate or state regulations regarding addiction treatment encourage the use of evidence-based practices in service requirements vary considerably and tend addiction treatment programs; only Oregon to be vague. Accreditors specify required mandates programs to implement evidence- services in greater detail than state licensing based practices under penalty of fiscal 201 regulations, as do the federal requirements for sanctions. The federal regulate the content of addiction services by regulations for opioid maintenance therapy requiring adherence to specific guidelines, but programs include specific admission criteria, † the extent of the regulation varies considerably. In addition to listing the types of required Admission is limited to patients who meet services, the frequency and timing of services clinical diagnostic criteria for opioid § are specified in some cases; for example, dependence and the person must currently have patients receiving detoxification must receive a addiction and must have become addicted within ** psychosocial assessment within 72 hours of one year before treatment admission. A 197 admission or patients in intensive outpatient physician must perform a full medical programs must receive individual or group examination before admission. Opioid therapy for a minimum of six hours over at least maintenance therapy programs must provide 198 two days a week. State regulations related to addiction treatment ‡ The Department of Corrections, the Oregon Youth services tend to specify the categories of Authority, the State Commission on Children and services that addiction facilities and programs Families and the part of the Oregon Health Authority must offer--such as individual, family and group that deals with mental health and addiction issues. The standards * medication use and control, discharge and do not specify what kind of psychosocial or 204 follow up. Standards or other accepted clinical criteria to diagnose for the core program areas are very detailed and addiction; perform an initial toxicology test and cover which services must be provided, by a comprehensive screening of patients’ medical § 205 whom and how often. Such requirements focus on § For example, day treatment must be provided at assuring specific organizational structures, least three hours a day, four days a week; must include three interventions from a designated list of interventions (e. Patient outcomes may be affected Federal quality assurance requirements vary by by factors independent of the quality of a program. Federal Medicare/Medicaid conditions specific health care service delivered, including of participation address quality assurance issues co-occurring conditions, patient compliance and by requiring utilization review committees to lifestyle. Outcome data also are subjective and assure compliance with written procedures for vary according to the setting and the particular evaluating admissions, continued care and instruments used to measure them. Given these discharges; linking treatment plans to barriers, quality assurance efforts tend to focus established goals; clinical record keeping; and on the process of care, which examines the requiring that the group of professionals within frequency with which interventions known to the program or facility that develops patient care correlate with positive outcomes are policies review and act upon recommendations 209 210 performed. State The federal regulations for opioid maintenance quality assurance requirements for addiction therapy programs require continual quality treatment programs and facilities are highly assurance measures which must include ongoing variable and focus mainly on process. For assessment of patient outcomes (not specified) example, a program that is run efficiently and and annual review of program policies and 211 maintains good records would be considered a procedures. In although this may take the form of simply order to fulfill their requirements under the Act, requiring the establishment of a quality each federal agency must develop a strategic improvement plan. Fewer than half of these plan (including annual performance targets) states (21 states) have explicit requirements that covering each of their programs, conduct patient outcome data be collected but, even for evaluations to assess how well a program is those that do, the types of data required rarely working and why particular outcomes have (or are specified. Four of the states that require the have not) been achieved and produce program collection of patient outcome data have performance reports based on analyses of 212 explicitly-defined categories of such data, but program effectiveness. The absence of funds state prevention, treatment, recovery other indicators linked to improved health and -196- * 213 supports and other services. Programs must analyze patient outcomes--including abstinence; reduction in relapse, criminal activity and hospitalizations; improved psychological function; housing situation; employment status-- 216 to determine the effectiveness of services. Joint Commission standards for addiction treatment facilities and programs focus more on performance improvement measures by requiring programs to conduct data collection and data analysis and to identify any opportunities for improving performance (e. Only opioid maintenance therapy programs are required specifically to collect outcome data, which include measures of the use of illicit opioids, criminal involvement, health status, 217 retention in treatment and abstinence. Providing quality care to identify and reduce risky use and diagnose, treat and manage addiction requires a critical shift to science- based interventions and treatment by medical professionals--both primary care providers and specialists. Significant barriers stand in the way of making this critical shift, including an addiction treatment workforce that is largely unqualified to implement evidence-based practices; a health professional that should be responsible for providing addiction screening, interventions, treatment and management but does not implement evidence-based addiction care practices; inadequate oversight and quality assurance of treatment providers and intervention practices; limited advances in the development of pharmaceutical treatments; and a lack of adequate insurance coverage. Recent efforts by government agencies and professional associations have begun to tackle these challenges to closing the evidence-practice gap, but are insufficient. Instead, Patient Education, Screening, Brief risky users of addictive substances are in most Interventions and Treatment Referrals cases sanctioned in terms of the consequences that result--such as accidents, crimes, domestic Despite the documented benefits of screening violence, child neglect or abuse--while effective * and early intervention practices, medical and interventions to reduce risky use rarely are other health professionals’ considerable provided. Those with addiction frequently are potential to influence patients’ substance use referred to support services, often provided by decisions, and the long list of professional health similarly-diagnosed peers who struggle with organizations that endorse the use of such limited resources and no medical training, to activities, most health professionals do not assist them in abstaining from using addictive educate their patients about the dangers of risky substances. While social support approaches are substance use or the disease of addiction, screen helpful and even lifesaving to many--and can be for risky substance use, conduct brief important supplements to medically-supervised, interventions when indicated, treat the condition evidence-based interventions--they do not or refer their patients to specialty care if qualify as treatment for a medical disease. Based on those principles, risky current approaches is required to bring practice substance use and signs of addiction are highly in line with the evidence and with the standard conducive to screening by general health of care for other public health and medical practitioners: they are significant health conditions. Unfortunately, there is a addictive substances and provide brief considerable gap between what current science interventions, physicians should be essential suggests constitutes risky substance use and the providers of the full range of addiction treatment thresholds set in some of the most common services. There are many venues where health identify, intervene and treat it, continued failure professionals can conduct patient education, to do so signals widespread system failure in screening and brief interventions with relative health care service delivery, financing, ease and most patients would be receptive to professional education and quality assurance. These include primary care This gap between evidence and practice is medical offices, dental offices, pharmacies, particularly acute for adolescents because of the school-based health clinics, mental health critical importance of prevention and early centers and clinics, emergency departments and intervention in this population. Screening and trauma centers, hospitals or encounters with the intervention services by health professionals for justice system due to substance-involved adolescents rarely is part of routine practice 7 crimes.
However cheap skelaxin 400 mg line, when using the traditional model of motherhood to justify the non-traditional goal of obtaining an abortion discount 400mg skelaxin free shipping, it turns out that the pro-choice utility calculation can indicate that the best way to help the most people is to sacriWce the fetus by aborting it order skelaxin 400 mg online. From a political vantage point, this is a strategic way to ‘have your cake and eat it too’, since such a justiWcation leaves in place traditional cultural assumptions about women as care-givers, even while expanding the non- traditional options open to women in the form of the right to an abortion as an instrument of care-giving not to the fetus, of course, but to others. What is signiWcant about Kate Michelman, therefore, is that when she tells her story about why she obtained an abortion, that story reveals a premise that the best way to present the abortion issue is to embed it within a traditional model of motherhood. To put it another way, Michelman’s justiWcation for abortion exempliWes the political power of obtaining non- traditional goals for women by infusing those goals with the most traditional imagery associated with women. Michelman’s story employs a traditional view of a woman whose identity is deWned in terms of her childbearing goals, child care responsibilities and economic dependency on a husband. The killing of the fetus by means of an abortion, therefore, is justiWed as a sacriWce necessary for the survival, if not the good, of the greater whole. Lifeboat ethics and justification for killing Michelman’s story not only illustrates a traditional view of motherhood in the context of obtaining a non-traditional goal for women – abortion rights – it also corresponds to a speciWc ethical model that justiWes killing – lifeboat ethics. The Model Penal Code (Philadelphia: American Law Institute), pre- pared and published by the highly respected American Law Institute, analyses the lifeboat model in terms of a justiWed choice of evils. The context of the lifeboat model involves a situation in which the homicidal actions of an individual that ordinarily would be criminal are nevertheless defensible because these acts are the only way to save other lives. As stated in the Code, ‘conduct that results in taking life may promote the very value [life] sought to be protected by the law of homicide’ in the Wrst place. The example provided by the Model Penal Code is: [Suppose someone] makes a breach in a dike, knowing that this will inundate a farm, but taking the only course available to save a whole town. If he is charged with homicide of the inhabitants of the farm house, he can rightly point out that the object of the law of homicide is to save life, and that by his conduct he has eVected a net saving of innocent lives. The life of every individual must be taken in such a case to be of equal value and the numerical preponderance in the lives saved compared to those sacriWced surely should establish legal justiWcation. As Dame Mary Warnock asserts, when faced with a choice of two people dying, or one person dying at the expense of another, the decision is easy – though it is the lesser of two evils, the latter is preferable to the former. As the journalist Polly Toynbee (2000) notes, the ethicist Professor Bernard Williams oVers these hypotheticals in support of the view that it is preferable to sacriWce the lives of a few if necessary to save the lives of many. For example, if ice cave explorers Wnd themselves trapped and the only way to escape is to kill one of their members so that the rest may live, then it is ethical to do so because this is a situation that is ‘an unavoidable emergency. Similarly, if a rail trolley is speeding toward a man pinned to the tracks, it is imperative to change onto another track to avoid killing him; however, if the other track in question had Wve men pinned to it, then it would be Models of motherhood in the abortion debate 219 preferable, and thus permissible, to stay on the original track in order to save the Wve men at the expense of one. Their separation absolutely entailed the death of one, but failure to separate most likely would have entailed the death of both within six months, due to the strain of supporting two lives on only one set of heart and lungs. The law of some nations, however, does allow for the separation of conjoined twins, even when the operation necessarily entails the loss of life of one of them. However, doctors believed that both twins would die unless this operation was conduc- ted, so with the permission of the parents of the twins, they separated them; one died as a result of the operation, and the other one lived for ten months after the operation. This justiWcation legally and culturally maps onto a traditional model of motherhood, because the nurturing aspect of the woman seeking an abortion is not the issue. As Michelman puts it, she was a 30-year-old mother of three, pregnant with her fourth child, planning to have a total of six children, who had assumed the economic support of a husband. More broadly, we can characterize this type of justiWcation as a sacriWce model having four main components: (1) It applies to a situation where there is a group – more than one person – 220 E. Thus, the lifeboat model can be an environment of harmony and love, but it is also a tragic one because there are not enough resources for everyone to survive. Thus, in order for the greater number to survive, there has to be some sort of sacriWce that will make it possible for more rather than fewer to continue their existence. Hence, one of the most strategically powerful characteristics of the lifeboat model as a justiWca- tion for abortion rights is that it involves no role change for women. The problem with the sacrifice model The problem with the sacriWce model of motherhood, however, is that it cannot be used to argue for the need for abortion funding. If the state could provide a conjoined twin with a needed heart and lungs, for example, that would obviate the question of sacriWcing the life of one twin for the sake of the other; such a solution, obviously, is inWnitely preferable to deciding the ethical and legal issues implied in killing the one twin who lacks those vital organs in order to save the other twin who has them. Similarly, if the state could arrive in time to save all ice cave explorers, thereby obliterating the need to sacriWce the life of one in order to save the lives of the others, that would solve the ethical and legal complications of the sacriWce model; there would be no longer a justiWcation for killing one of the ice cave explorers because there would no longer be a context lacking resources for all. If by a miracle, or by state action, the lifeboat context can be eliminated and there can be enough resources to provide for all in the lifeboat, then the rationale for sacriWcing a member of the group disappears, and with that disappearance, the language of justiWca- tion for the killing of anyone or anything no longer applies. This is because the key principle in a lifeboat context is that there is no initial or inherent conXict among the parties, only a contextual lack of resources. Abortion and the traditional model of motherhood The use by pro-choice advocates of the sacriWcial, lifeboat model for abortion rights, therefore, is a double-edged sword. On the one hand, its strength is that it can justify abortion in a context of scarcity that employs a model of motherhood involving no role change for women. She does not have the time, money or educational requisites, so the fetus is sacriWced in order that she and others for whom she is responsible can survive. It allows pro-choice advocates to meet pro-life advocates on the same footing, by arguing that pro-choice women are dedicated to being good mothers, and that obtaining an abortion is a necessary means a woman must sometimes use in order to be a good mother. Invoking traditional role norms for women in the context of justifying the right to an abortion has been an eVective use of traditional roles to gain non-traditional goals. Most signiWcant is that such a justiWcation contains no principle that can be used to claim the right to state assistance in providing an abortion, that is, killing the fetus. In contrast, the lifeboat model argues just the opposite; the purpose of state assistance is to provide resources so that it is not necessary for anyone or anything to be sacriWced in a lifeboat scenario; the state’s job is to solve the problem of scarce resources so that all may survive. Thus, to Wnd a solution to the problem of access to abortion, including abortion funding, we must turn to a diVerent model of motherhood, one that employs non-traditional roles for women and one that activates the other major justiWcation for killing – self-defence. McDonagh The non-traditional model of motherhood and abortion rights The non-traditional model of motherhood The key issue in redeWning the problem of abortion is to recognize that medically and legally pregnancy is a condition in a woman’s body ‘resulting from the presence of the fetus’. SpeciWc hor- mones and proteins in a woman’s body, for example, are elevated to hun- dreds of times their base level, thereby indicating that a fertilized ovum is present and aVecting her body. While most of the changes resulting from the fetus’s eVects on a woman’s body subside about a month after birth, a ‘few minor alterations persist throughout life’. In a medically normal pregnancy: some hormones in a woman’s body rise to 400 times their base level; a new organ, the placenta, grows in her body; all of her blood is rerouted to be available to the growing fetus; her blood plasma and cardiac volume increase 40 per cent; and her heart rate increases 15 per cent. From choice to consent In Roe, the Court established that the fetus was a separate entity from the woman and that it was constitutional for the state to protect the fetus. With this in mind, the key issue in redeWning abortion rights is to recognize that it follows that a woman not only has a right to choose what to do with her own body, but also a right to consent to the transformations of her body and her liberty resulting from the fetus as a separate, state-protected entity. If we accept that the fetus is indeed a separate entity, a move which pro-choice advocates have more typically resisted, we can actually derive a novel pro- choice argument. The traditional common-law position, still the dominant one in English law, is that the fetus has no separate legal personality: ‘until born alive, a foetus is not a legal person’ (Montgomery, 1997: p. In American constitutional law, the Supreme Court has refused to rule on whether the fetus is a person, stating only that even if the fetus were a person, it would not be included in the protections of the Constitution because the Fourteenth Amendment refers to ‘born’ persons. Yet it is constitutional for the state to protect the fetus, which means that the fetus is in a category with other entities that are not legally people but are nevertheless under state protection, such as endangered wildlife species. What the consent argument does is to hoist anti-abortion campaigners with their own petard by focusing not merely on what the fetus ‘is’, but on what the fetus ‘does’. If a physician, for example, performs life-saving surgery without consent, that physician legally is deemed to have harmed the patient, even if the surgery saved the patient’s life.
In other cases order 400mg skelaxin with amex, are poor metabolizers of mephenytoin generic skelaxin 400mg visa, compared such as antihypertensive agents skelaxin 400mg overnight delivery, the clinical effect to 15±20% of Chinese and Japanese populations of genetic differences may not be seen, because the (Kupfer et al 1988). The lack of digestive enzyme lactase in many Hispanics, especially Mexican-Americans and Af- Prescribing Differences rican-Americans, causes lactose intolerance, with nausea, diarrhea, and occasionally vomiting. Dinsdale et al (1995) tion and clearance), as well as the fact that the confirmed a similar pattern in prescriptions issued metabolism of some benzodiazepines appears to for analgesics for postoperative pain to be self-ad- be slower in Asians than in Caucasians (Kumana ministered by the patient, with Caucasians receiving et al 1987). One study (Zhang et al 1990) showed prescriptions significantly more frequently than mi- that Chinese subjects who were either poor or ex- norities ( p 0:01). There are individual excep- lations, due either to a sizeable representation of tions amongst patients and among drugs, even poor metabolizers present or to a genetic or ethnic- within these classes; e. Clozapine is associated with a- and b-blockers, can be equally effective in both the development of agranulocytosis in 20% of Ash- African-Americans and Caucasians and, as men- kenazi Jews, compared to 1% of the general popu- tioned previously, the Chinese appear twice as sen- lation treated for schizophrenia. This was found to sitive as Caucasians to propranolol (Oster et al be highly associated with specific linked genes, 1987; Zhou et al 1990) agranulocystosis and especially those of Ashkenazi Jewish origin (100%) (Leiberman et al 1990). It Another example of pharmacodynamic differ- has been postulated that Asians have fewer benzo- ences is that of reports on lithium in the manic diazepine and b-blocker receptors than Cauca- phase of bipolar depression. Downregulation of these receptors with age ing Japanese, are reported to have therapeutic (Salzman 1982) has been described and postulated blood levels at 0. If the Chinese are (Jefferson et al 1987; Yang 1987; Takahashi 1979); more sensitive to propranolol in spite of their high these findings, however, are disputed by Chang et catabolic rate, it might be linked to adrenergic al (1985). The use of By direct appeal to manufacturers through an in- appropriate therapy in Black patients has been dependent third party, compliance information be- best studied. Data from 21 com- in reports of efficacy and incidence of adverse reac- pounds developed since 1985 in the West and tions, are much greater than can be accounted for Japan, and covering a wide range of therapeutic by ethnic variations of pharmacokinetics and phar- categories, were analysed. One compound is known to be eliminated by an enzyme Alcohol which is polymorphic, but there was no evidence of altered phenotype or subset population within Even modest amounts of alcohol may induce any ethnic group. All the regional variations were attributable and part of the daily diet, might enhance, to different pharmaceutical formulations, reduc- albeit slightly, a higher metabolism of some tion of initial doses, and alteration in sampling drugs, thus requiring higher dosages to achieve times and techniques, and none of these differences efficacy. This reduction quency of adverse reactions observed during clin- or absence of enzyme occurs in Japanese (44%), ical trials was generally lower in Japanese subjects, Eskimos (43%) or South American Indians although there was no correlation between reduced (41±43%) and to a much lesser degree in other adverse reactions and lower doses. Initially, this re- tudes relating to the use of preferred terms, differ- duced enzyme might exaggerate possible adverse ent assessment methods and reporting differences events with drugs competing for the same meta- were provided as explanations for the lower inci- bolic pathway. More West- ern subjects were included in trials for a given Some curiosities, such as prolongation of ductus indication than Japanese subjects, and Japanese arteriosus closure in the neonate at high altitudes dose-ranging trials were frequently of an open and its resistance to indomethacin closure, are design. Heterozygous sickle cell anemia gene smallest normal males in terms of height and confers immunity against falciparum malaria to Af- weight, there is a 70% difference (Metropolitan ricans (Medawar 1961), but in African-Americans Life Insurance Tables, 1999). Lin et al (1986) function of organs such as kidney and liver and Henry et al (1987) report that antipyrine me- and the metabolism and excretion of drugs. Japan tabolism was different in rural Asian Indians than and Sweden have a greater proportion of their in Asian Indian immigrants resident in England for population over 80years compared to the some years. Dietary environmental differences may other regions and this segment, while generally also account for the findings of Gould et al (1972) increasing worldwide, is increasing faster in and Kato et al (1973) of a gradation of heart and Japan. The next group of factors to showed that enhanced bioavailability of felodipine be discussed are largely subjective, but still have an can be more than doubled, and to a lesser extent, even more profound effect on protocol design, exe- nifedipine, with concurrent consumption with cution, measurement, outcome, recording and grapefruit juice compared to water (an effect not interpretation of the data collected. This reflects in a difference in blood/ section came from the experiences of the author tissue volume which alone probably accounts for or from the literature of anthropology and social more real drug differences than pharmacogenetics biology. In Europe, the aim is to achieve effectiveness made in Japan to share the responsibility with the with some minimal side effects, often by titrating patient for mutual benefit. Defensive medi- are free, to a certain extent, from suspicion of cine is only part of the story; the need for an monetary influence because of extensive socialized aggressive approach, with the need to cure as op- or government-backed health schemes. In Japan, concurrent prescribing of different Again, the reporting, anticipation, or recognition drugs of the same class in small doses is not un- of adverse effects may be diminished. There is great emphasis and concern in Ger- icians often focus on extensive data gathering in an many over the heart and diet; in France, over the attempt to achieve diagnostic certainty. In the different regions, the physicians and inves- tigators are held in varying degrees of esteem by Ethnic Effects on European Adverse their patients. Pro- help patients (Eisenberg 1973); this is also applic- fessor Naito reported for the Japanese delegation able to the interpretation of clinical results. Within this narrow sample, equacy of safety data (E1 and E2), studies in elderly only one drug had genetic polymorphism, but even (E7), reports (E3), clinical trials (E8) and statistics this did not translate to ethnic variations. If the drug is variation (ethnically sensitive) are the converse of ethnically sensitive and clinical data are derived the above, with the addition of low potential for from dissimilar ethnic populations, provided that protein binding and non-systemic use. If pharmacokinetics were also undertaken in the This consists of information from the complete same study, dynamic effects may be directly re- clinical data package selected for its relevance to flected by the blood levels. That is especially so if at needed, this may be a pharmacokinetic study, or that new dose (range) a similar safety and efficacy pharmacodynamic demonstration of efficiency or a profile has been demonstrated. This might utilize shorter duration do pharmacokinetic and pharmacodynamic dose± surrogate end-points, rather than the clinical end- response studies on Japanese patients in Japan. In addition, even if not needed, they conduct a controlled local comparison clinical study to expand the database, and for sound marketing Bridging Safety Studies reasons. This can be used to enroll minority trial, given an expected dropout rate of 15±30%, and cultural ethnic groups, because they tend to dependent on disease and severity of efficacy congregate in regional clusters, e. A small safety study might be done initially to investigator of different ethnic origin can enhance assure the sponsor and the region that a high inci- the enrollment, for frequently they will attract pa- dence of serious events is unlikely to be seen in the tients of that group. Such and combine them with confidence into their drugs, if not useful, are soon discarded (Benet own more extensive clinical data package for for- 1992). Generally, where dosages are the same, the in- Fed Reg (1999) Ethnic factors in the acceptability of foreign cidence of serious adverse events tends to be the clinical data. The chapters flicts that arise between ebullience in the marketing cover the specific areas of knowledge and capabil- department and conservatism in pharmacovigi- ity that those working in such departments should lance matters. If the company must defend itself possess, but perhaps a few words on less concrete in litigation, then it is the responsibility of the aspects of this type of role could be added here. This can sometimes be a lonely role, implications at all, and that is not strictly related and the medical affairs specialist must be acutely to the development of an investigational drug, is aware how properly to take and defend a position likely to end up in medical affairs. Postmarketing safety and surveillance By working effectively across intradepartmental groups, the medical affairs professional helps to The interface that often occurs between medical ensure a successful product launch, label expansion affairs personnel and the three previously men- and, ultimately, product sales growth. The sections tioned functional groups (clinical development, of this chapter will outline the core organizational regulatory affairs, and sales and marketing) is functions and basic information important for the depicted in Figure 30. Staff size is a function of corporate size, value by identifying and communicating clinical specific departmental objectives, expectations, and and research issues from practising thought leaders overall responsibilities. The drug information/med- the medical profession with the best available infor- ical writing/medical library specialist is generally mation pertaining to their use. He/she utilizes his/her training and experi- documented, and has been increasing in sophistica- ence to evaluate the clinical relevance of the litera- tion and influence over the past several years. De- ture relative to a given query, and formulates livery of product information occurs via several that information into an understandable, appropri- different mechanisms, including the sales force, ad- ately formated response.
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