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Levels of 3-hydroxy-3-methylglutaryl coenzyme A (HM G CoA) reductase inhibitors are substantially higher in patients receiving both drugs discount valsartan 80 mg without prescription prehypertension not overweight. HDL— high density lipoprotein; LDL— low density lipoprotein proven 80mg valsartan blood pressure medication and juice. In these patients it m ay be possible to approach diagnosis and therapy in a fairly Blood pressure ≥140/90 standardized fashion order valsartan 160mg online prehypertension systolic normal diastolic. In transplant recipients with blood pressure readings consistently over 140/90 mm Hg generic valsartan 160mg overnight delivery 4, intervention is warranted. Evaluate allograft function The initial approach includes assessm ent of allograft function, Yes No extracellular fluid volum e (ECF) status, and im m unosuppressive dosing. If these variables are stable, it is reasonable to proceed with Optimal blood levels Reduce dose of antihypertensive therapy. Calcium antagonists (CA) are effective of cyclosporine cyclosporine or or tacrolimus? No tacrolimus agents and m ay offer the added benefit of attenuating cyclosporine- Yes induced changes in renal hem odynam ics. Verapam il, diltiazem , nicardipine, and m ibefradil increase blood levels of cyclosporine ECF volume status Consider salt restriction and tacrolimus and should be used with caution. No and/or diuretic with CAs that m ay lim it their use include cost, refractory edem a, Yes and gingival hyperplasia. Angiotensin antagonists (ACEIs and Administer receptor antagonists) are also effective; their use requires close Intervention fails to antihypertensive agent monitoring of renal function, serum potassium levels, and hematocrit normalize BP (CA, ACEI, or other) levels. Diuretics frequently are useful adjuncts to therapy in recipients owing to the salt retention that often accom panies cyclosporine M ultidrug regimen: Adequate response add agents of different use. O ther antihypertensive m edications offer no particular benefits to therapy? No classes as necessary or drawbacks and can be em ployed as needed. The rationale of Yes m ultidrug therapy is to em ploy agents that block hypertensive responses via interruption of differing pathogenetic pathways. As antihypertensive drugs are added, this consideration should Yes rem ain param ount [31,32]. GFR— glom erular filtration rate; Yes No TRAS— transplanted renal artery stenosis. Continue Re-evaluate allograft antihypertensive therapy function and drug therapy Reassess periodically Consider TRAS FIGURE 13-19 Transplant renal artery stenosis (TRAS). TRAS accounts for less than 5% of cases of hypertension after transplantation. N onetheless, TRAS should always be considered in patients with refractory hypertension who develop renal insufficiency after addition of an ACEI to the therapeutic regim en. Although noninvasive studies (such as a renal scan with captopril) m ay be helpful in diagnosing TRAS, angiography rem ains the gold standard for diagnosis. Revascularization of the allograft by either surgical or angioplastic techniques m ay im prove renal function and am eliorate hypertension [33,34]. Both tacrolim us and m ycophenolate m ofetil (M M F) cause bloating, nausea, vom iting, and diarrhea in a dose-dependent m anner, particularly when used Nausea and in combination [15,16,25]. Some authors have noted that this rather nonspecific GI toxicity occurs m ore com m only with N eoral® than Drug vomiting Diarrhea Other complications with Sandim m une® (both from Sandoz Pharm aceuticals, East Cyclosporine 4 3 Hepatotoxicity, constipation H anover, N J). Tacrolimus 30 32 Hepatotoxicity, constipation MMF 20 31 Constipation, dyspepsia Azathioprine 12 Rare Hepatotoxicity, pancreatitis FIGURE 13-21 (See Color Plate) Endoscopic image of candida esophagitis with diffuse white exudate (panel A) and colitis induced by cytomegalovirus infection with submucosal hemorrhage, ulcers, and diffuse mucosal edema (panel B). The avail- ability and common use of effective prophy- laxis against acid-peptic disease (eg, H2 block- ers, omeprazole, and antacids) have signifi- cantly reduced the frequency of upper gastrointestinal bleeding. However, infectious agents such as cytomegalovirus and candida continue to be problematic, particularly in the setting of the more intense immunosup- pression afforded by drugs such as mycophe- A B nolate mofetil (M M F) and tacrolimus. FIGURE 13-22 H istologic im age of chronic active hepatitis secondary to infection with the hepatitis C virus (H CV). N ote the periportal distribution of the lymphocytic infiltrate. Recent identification of HCV has caused intense reevaluation of the causes, frequency, and natural history of liver disease in renal allograft recipients. As the percentage of patients with end-stage renal disease who are infected with the hepatitis B virus has diminished, HCV has become the most problematic cause of liver disease. In recipients with H CV antibodies, im m unosup- pressive therapy m ay potentiate liver injury from the virus and accelerate the course of tim e over which cirrhosis develops. Nonetheless, in patients who desire transplantation and have well- preserved liver function, little evidence exists of better longevity on dialysis. HCV can be transmitted easily from donor to recipient in solid organ transplantation. Because kidney transplantation is not a life-saving procedure, m ost transplant centers choose not to use kidneys from donors who are infected with H CV. Previously, liver disease was thought to be a com m on cause of death in renal allograft recipients. As blood transfusions have becom e less com m on in the dialysis population and hepatitis B virus less prevalent, the risk of death owing to hepatic disease seems to have diminished. Unfortunately, therapies for HCV-related hepatitis (interferon- ) have proved to be of questionable efficacy and m ay stim ulate rejection of the renal allograft [35–37]. Bone densitom etry M agnetic resonance imaging of osteonecrosis. H ere, a renal transplant fem oral head but can affect any weight- early after transplantation. M etabolic bone recipient dem onstrates m arked osteoporosis, bearing bone. The m ost debilitating com pli- disease in this setting is usually multifactorial. This decrease reflects better have som e degree of renal osteodystrophy, options (including bisphosphonates, estrogens, management of calcium and bone homeostasis exacerbated in som e cases by the im pact of and thiazides) have offered hope of preserving during long-term dialysis and less intense alum inum toxicity or 2-m icroglobulin or even increasing bone m ass [38,39]. Patients with diabetes are BM D— bone m ass density. Administration of corticosteroids lim ited (pain m anagem ent while awaiting and cyclosporine also contributes to bone progression to the need for joint replacement). Although biochemical evidence of M agnetic resonance im aging is a sensitive secondary hyperparathyroidism usually diagnostic m ethod, allowing detection of resolves during the first year after transplan- osteonecrosis at a very early stage. Asterisk— values significantly different from those at the time of transplantation. Gout is the clinical m anifestation of hyperuricem ia. After transplantation, cyclosporine can exacerbate hyperuricem ia, and severe gout can be problematic even in the presence of chronic immunosuppression. M anagement of gouty arthritis usually involves some com bination of colchicine and judicious use of short courses of nonsteroidal anti-inflammatory drugs. Concomitant administration of allopurinol and azathioprine can cause profound bone m arrow suppression and is avoided by m ost physicians who treat transplant recipients. Because the m etabolism of m ycophenolate m ofetil (M M F) is not dependent on xanthine oxidase, use of allopurinol in patients treated with M M F is relatively safe [39,40]. FIGURE 13-27 FIGURE 13-28 Photograph of gingival hyperplasia. Gingival hyperplasia occurs Post-transplantation diabetes m ellitus (PTDM ). PTDM com plicates in approxim ately 10% of transplant recipients treated with the course of treatm ent in 5% to 10% of patients on cyclosporine- cyclosporine. Its severity reflects the interaction of effective dental based im m unosuppressive therapy.

No No No Yes Toxic drug or Discontinue alcohol Elevated Yes No enzymes? Consider biopsy Yes Elevated TIBC No and treatment or ferritin No Elect Yes Severe disease Yes Consider M easure HBsAg biopsy? Patients with cholecystitis should be considered for cholecystectom y order valsartan 40mg with amex blood pressure 34 weeks pregnant. For other patients with signs and sym ptom s of liver disease generic 160mg valsartan free shipping blood pressure medication post stroke, poten- tial hepatic toxins should be considered buy valsartan 40 mg online hypertension lifestyle changes. The incidence of liver dis- ease from iron deposition has declined with the dim inishing use of FIGURE 12-8 blood transfusions in dialysis patients valsartan 40mg with amex hypertension dizziness, but m ay be seen occasionally Viral hepatitis. Patients whose test results are positive for anti- in patients with a high total iron binding capacity (TIBC) or ferritin. A liver biopsy should be considered for all patients with antigen (H BsAg) and hepatitis C virus (H CV) antibodies. Both hepatitis C virus (H CV) antibodies or hepatitis B surface antigen. Patients with severe chronic active hepatitis or cirrhosis on biopsy Fortunately, the incidence of hepatitis B is declining am ong patients generally are not candidates for renal transplantation unless sim ul- with renal disease, largely as a result of the use of effective vaccina- taneous liver transplantation is being considered. Although no statistically significant effect of H CV on graft above (anti–H CV negative) and below (anti–H CV positive) survival was seen, patient survival was significantly dim inished survival curves indicate the num ber of patients at risk during am ong those who tested positive for H CV after transplantation. The relative risk after transplantation associat- N ot all investigators have confirm ed these findings. No No No Yes Smoking High Yes Yes Currently Stress test Imaged coronary smoking? No No Yes No No Risk factor Yes Revascularization Severe lung Yes intervention successful? W ait until adequate disease on resolution with therapy No function tests? No Reconsider Evaluate transplantation for CHF candidacy Proceed with evaluation FIGURE 12-11 FIGURE 12-10 Ischem ic heart disease (IH D). Few studies exist that address the effects of cigarette higher in renal transplantation recipients com pared with the general smoking on outcome after renal transplantation. Patients with IHD before transplantation are at high risk transplantation surgery no doubt are increased by cigarette smoking, to develop IHD events after transplantation. Therefore, angiography candidates for transplantation should be referred to smoking cessa- should be considered in candidates for transplantation who have tion programs. Candidates with currently asymptomatic IHD and those at high risk for IHD should undergo a stress test. Patients with severe coronary artery disease on angiography must be considered for a revascularization procedure before transplantation. Aggressive m anagem ent of risk factors is appropriate for all patients, with or without IH D. In this study, 26 patients with insulin-dependent dia- 70 betes who were found to have over 75% stenoses in one or m ore 60 coronary arteries were random ly allocated to either m edical m an- 50 agem ent or a revascularization procedure before transplantation. These findings suggest that transplantation candidates (2) 10 who have diabetes should be screened for silent coronary artery 0 disease because revascularization decreases m orbidity and m ortality 0 3 6 9 12 15 18 21 24 after transplantation. The num bers in parentheses indicate the num - Follow-up, mo ber of patients being followed at that tim e. M yocardial perform ance has been shown to im prove in som e patients after renal transplanta- Signs and Yes tion. Thus, a low ejection fraction alone does not autom atically Exclude secondary symptoms of causes exclude patients from transplantation. O ccasionally, patients m ay be candidates for sim ultaneous heart and kidney transplantation. Patients m ust not undergo History of Yes Recent Yes surgery within 6 m onths of a stroke or transient ischem ic attack stroke or TIA? Asym ptom atic patients with a carotid bruit should be con- No No sidered for carotid ultrasonography because patients with severe Yes Refer to carotid disease m ay be candidates for prophylactic surgery. Consider carotid ultrasonography neurologist with autosom al dom inant polycystic kidney disease (ADPKD) and either a previous episode or a positive fam ily history of a ruptured No intracranial aneurysm m ust be screened with com puted tom ogra- High-risk Risk factor phy or m agnetic resonance im aging. No Proceed with evaluation Evaluation of Prospective Donors and Recipients 12. Peripheral vascular disease is com m only associated with coronary artery disease, cerebral vascular disease, or both. H owever, PVD itself m ay PVD unresponsive Yes Consider require intervention before transplantation to prevent infection and sepsis after transplan- to conservative invasive tation. In addition, som e patients m ay have aortoiliac disease severe enough to require management? Rarely, vascular disease is severe enough to m ake it difficult to find an artery suitable for the anastom osis of the allograft renal artery. Patients m ust be free of cognitive im pairm ents and able to give Psychosocial inform ed consent. M ost transplantation centers require patients with a history of alcohol evaluation or drug abuse to dem onstrate a period of supervised abstinence, generally 6 m onths or m ore. Sim ilarly, patients with a past history of m edication adherence poor enough to suspect that the im m unosuppressive regim en will be com prom ised m ay need to delay Free of limiting No transplantation until reasonable adherence can be dem onstrated. Yes History of limiting Yes Refer until medication resolved noncompliance? O besity 2 Yes increases the risks of surgery, and a weight reduction program BM I >35 kg/m before transplantation m ust be considered for very obese patients. O lder age is a relative contraindication to transplantation; however, No Consider weight it is difficult to precisely define an upper age lim it for all patients. H ypertension should be controlled before transplantation. Yes W hen control of hypertension is difficult, bilateral nephrectom y Age >65? No Proceed with evaluation 100 100 90 * * 90 * * * * 80 * * 70 80 60 50 70 40 Obese patients 60 30 * Nonobese patients 20 Obese patient grafts 10 50 Nonobese patient grafts 0 40 0 3 6 9 12 15 18 21 24 Age n t1/2 Time, mo 30 0–5 198 15. In this case-control study, 46 obese (body m ass index > 30 kg/m 2) recipients of cadav- 0 eric renal transplantation were com pared with nonobese controls 0 1 2 3 4 5 m atched for the following after transplantation: age, gender, dia- Years after transplantation betes, panel reactive antibody status, graft num ber, cardiovascular disease, date of transplantation, and im m unosuppression. Survival of patients and grafts was significantly less am ong obese patients FIGURE 12-19 com pared with controls (P < 0. Data from the following occurred m ore often in obese versus nonobese patients: United Network for Organ Sharing Scientific Registry indicate that delayed graft function, postoperative com plications, wound com - recipients over the age of 60 have slightly less allograft survival com- plications, and new-onset diabetes. No Proceed with FIGURE 12-21 evaluation Pancreas graft survival in recipients of pancreatic transplantation with simultaneous, no previous, and previous kidney transplantation. Survival rates of pancreatic grafts are best when pancreatic and FIGURE 12-20 kidney transplantations are perform ed at the sam e tim e. Patients with difficult to control the United N etwork for O rgan Sharing Scientific Registry. However, patients with diabetes who have a living donor are generally better off undergoing transplantation with the living donor kidney alone. Patients with symptomatic hyperparathyroidism or uncontrolled hypercalcem ia should be considered for parathy- roidectomy before transplantation. M edications that interfere with the metabolism of immunosuppressive agents such as cyclosporine should be substituted with appropriate alternatives, if possible, before transplantation. Patients without signs and symp- Signs or toms of bladder dysfunction generally do not Yes symptoms of No bladder need additional urologic testing. Such patients can be screened initially with voiding cystourethrography Yes (VCUG). No Consider ureteral Indications for No No diversion or native kidney intermittent nephrectomy? No Yes Severe diverticular Yes Endoscopic or Yes Consider partial radiographic No disease on barium colectomy enema?

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University of Hertfordshire: Department of Health/NHS England; 2015 purchase valsartan 40 mg mastercard blood pressure chart female. Department of Health 80mg valsartan otc blood pressure on forearm, Department for Education and Skills 80 mg valsartan free shipping arrhythmia of the heart. National Service Framework for Children cheap valsartan 80mg otc pulse pressure fitness, Young People and Maternity Services: Children and Young People Who Are Ill. Report on the Pilot of the Expert Patient Programme for Children January 2004– January 2005. The adaptation of written self-management plans for children with asthma. Support for self care for patients with chronic disease. Ecological approaches to self-management: the case of diabetes. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that 53 suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. Transitions in the lives of young people with complex healthcare needs. From child to adult: an exploration of shifting family roles and responsibilities in managing physiotherapy for cystic fibrosis. Adherence-related behavior in adolescents with asthma: results from focus group interviews. Gaining freedom: self-responsibility in adolescents with diabetes. Bruzzese JM, Unikel L, Gallagher R, Evans D, Colland V. Feasibility and impact of a school-based intervention for families of urban adolescents with asthma: results from a randomized pilot trial. A systematic review of internet-based self-management interventions for youth with health conditions. A systematic review of self-management interventions for children and youth with physical disabilities. Cystic fibrosis mortality and survival in the UK: 1947–2003. Attention deficit hyperactivity disorder in pre-school children: current findings, recommended interventions and future directions. Royal College of Paediatrics and Child Health (RCPCH). Growing Up With Diabetes: Children and Young People with Diabetes in England. Cochrane Handbook for Systematic Reviews of Interventions (Version 5. Oslo: Norwegian Knowledge Centre for the Health Services; 2015. Self-management education: history, definition, outcomes, and mechanisms. Tsiligianni I, Kocks J, Tzanakis N, Siafakas N, van der Molen T. Factors that influence disease-specific quality of life or health status in patients with COPD: a review and meta-analysis of Pearson correlations. Evaluating the public health impact of health promotion interventions: the RE-AIM framework. Methods for the Economic Evaluation of Health Care Programmes. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. Pildal J, Hróbjartsson A, Jørgensen KJ, Hilden J, Altman DG, Gøtzsche PC. Impact of allocation concealment on conclusions drawn from meta-analyses of randomized trials. Intensive case management for severe mental illness. Bias in meta-analysis detected by a simple, graphical test. Funnel plots for detecting bias in meta-analysis: guidelines on choice of axis. Bartholomew LK, Gold RS, Parcel GS, Czyzewski DI, Sockrider MM, Fernandez M, et al. Watch, discover, think, and act: evaluation of computer-assisted instruction to improve asthma self-management in inner-city children. Integrated care facilitation model reduces use of hospital resources by patients with pediatric asthma. The influence of health education on family management of childhood asthma. Brown JV, Bakeman R, Celano MP, Demi AS, Kobrynski L, Wilson SR. Home-based asthma education of young low-income children and their families. Browning S, Corrigall R, Garety P, Emsley R, Jolley S. Psychological interventions for adolescent psychosis: a pilot controlled trial in routine care. Bruzzese JM, Sheares BJ, Vincent EJ, Du Y, Sadeghi H, Levison MJ, et al. Effects of a school-based intervention for urban adolescents with asthma. Impact of a household environmental intervention delivered by lay health workers on asthma symptom control in urban, disadvantaged children with asthma. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that 55 suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. Butz A, Pham L, Lewis L, Lewis C, Hill K, Walker J, et al. Rural children with asthma: impact of a parent and child asthma education program. Walker J, Winkelstein M, Land C, Lewis-Boyer L, Quartey R, Pham L, et al. Factors that influence quality of life in rural children with asthma and their parents. Butz A, Kub J, Donithan M, James NT, Thompson RE, Bellin M, et al. Influence of caregiver and provider communication on symptom days and medication use for inner-city children with asthma. Byford S, Harrington R, Torgerson D, Kerfoot M, Dyer E, Harrington V, et al. Cost-effectiveness analysis of a home-based social work intervention for children and adolescents who have deliberately poisoned themselves. Harrington R, Kerfoot M, Dyer E, McNiven F, Gill J, Harrington V, et al. Randomized trial of a home-based family intervention for children who have deliberately poisoned themselves.

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It is incumbent on mental health services re- the cost perspective (total societal cost) and for the effective- searchers to report their findings in ways that speak to fun- ness measure in question (reduction in EPS) buy 160 mg valsartan with mastercard blood pressure form. Such displays ders and service system managers order valsartan 80 mg with mastercard pulse pressure too low, which means providing of information give the reader/policy maker a sense of the estimates of the most likely outcome as well as the likelihood tightness of the point estimate and the risk of falling in a of alternative outcomes discount 40 mg valsartan with visa blood pressure ranges by age and gender. One can use these sampling distributions to create cost- acceptability curves from the viewpoint of particular payers COST OF THE NEWER ANTIPSYCHOTIC for particular outcomes (e generic valsartan 80mg without prescription blood pressure goals chart. These Saul Feldman (53) has held positions as the head of the acquisition costs are reflected in formulary budgets. Thus, he has past decade, and the market share of the newer agents has been in a position to make policy based on research, and risen as they have replaced the less costly conventional to inform policy makers with research. Distribution of (left circle) and total dollars paid (right circle) by Medicaid for antipsychotic medication prescriptions during 1998. Newer antipsychotic medications represented slightly over half of the total prescriptions, and they were responsible for 90% of the total cost. These also showed that clozapine is more effective than the usual data show that the newer agents account for 58% of all care in minimizing days hospitalized, enough so that the antipsychotic prescriptions paid for by Medicaid but for reduction in hospital days more than covers the increased $1. These charts dramatically But, from more narrow perspectives (e. For cost- This price difference between the older and the newer effectiveness studies to influence planning and policy mak- antipsychotic medications, which can be a 100-fold differ- ing, the perspectives of these different payers need to be ence (e. A hospi- than simply the cost of the medication was considered. For tal would have a great incentive to use clozapine for a heavy example, if using new and expensive medication X results user of hospital services if it has a fixed budget (the case in fewer days hospitalized than some alternative, then, all with most state hospitals), but a hospital paid a per diem else being equal, using X will reduce overall costs as long would have no such incentive. By the end of 6 months in the Connecticut study, only 11% of the Clozapine Cost Effectiveness Studies As usual care patients had begun a trial on clozapine, but by Case Examples the end of 24 months in the study, 66% had. In the VA The rub, of course, is that 'all else' is rarely equal in effec- clozapine study, 72% of the patients assigned to masked tiveness or cost-effectiveness studies, and the early cost pro- haloperidol had ceased taking the masked medication by jections concerning the impact of using clozapine often suf- the end of the 1-year study period, with 49 of 157 (31%) fered from faulty assumptions about what was equivalent. Be- amined changes in hospital use and lacked a comparison cause of the biases introduced by what is likely to be highly group (54–60). For example, the study by Meltzer and col- nonrandom discontinuation of the assigned treatment, the leagues (59) of patients with schizophrenia who were taking importance of intent-to-treat analyses and the unspecified clozapine collected retrospective cost data for 2 years before biases of crossovers-excluded analyses are well documented and after these 47 individuals began taking clozapine and (68). Regardless, when crossovers are common, analyses ex- concluded that clozapine was associated with a 23% drop cluding crossovers offer a proxy for the best-case scenarios in treatment costs. Critics focused on the who do well enough on treatment B to stay on it. Figure problem of the regression toward the mean that can be 57. The exclusion of treatment crossovers increases low point in their functioning (such as may have prompted the apparent effectiveness of clozapine (the crossovers- the initiation of clozapine), and on the other potential tem- excluded oval is shifted to the right of the intent-to-treat poral and case-mix confounds associated with mirror-image oval in Fig. For example, of conventional antipsychotics among long-term patients in in the VA study just cited, health care costs in the 6 months state hospitals (41,65,66), and in the 1-year masked trial prior to randomization were approximately $27,000 with comparing clozapine to haloperidol among veterans hospi- a standard deviation of about $17,000 (67). Each trial showed clozapine necticut clozapine study, the 95% confidence interval for to be somewhat more effective than the comparison agents, patients assigned to clozapine was $96,847 to $114,308 for and this increase in effectiveness comes at no additional cost year 2 versus $103,665 to $121,144 for those assigned to when costs are viewed from a societal perspective. With such variability, cost differences are Chapter 57: The Economics of the Treatment of Schizophrenia 815 very difficult to detect, even with the relatively large sample than or the same as the usual care and the effectiveness sizes of the VA and Connecticut trials (N 423 and 227, measures favor clozapine or are neutral). Even for individuals who are heavy service data to such a point estimate belies the broad distribution users at study entry, mounting a trial powered to detect cost of possible outcomes that are likely to occur across patients. If the trial were a study of outpatients who are infre- treating clinicians, need a sense of the range of possible quent users of expensive services like hospitals, it would outcomes and their relative likelihood to inform their deci- require even larger samples to detect cost differences apart sions about what chances they want to take. From a public health perspective, an emphasis on point Costs Associated with Risperidone, estimates of costs and effectiveness is misguided when the Olanzapine, and Quetiapine confidence intervals are so broad. Economists would call clozapine the dominant alternative in these randomized Figure 57. Distribution of (left circles) and total dollars paid (right circles) by Medicaid for antipsychotic medication prescriptions in Cali- fornia, Ohio, and New York during 1998. Because Medicaid formularies allow unrestricted and colleagues (74) and Foster and Goa (75) would not be access to any of these medications independent of location expected among treatment-refractory patients, even though in the country and the same financial incentives apply, one these patients are heavy users of inpatient services. Under would expect to see similar rates of prescribing these medica- other scenarios, these patients are the very ones for whom tions. Indeed, the distributions do appear quite similar to new interventions are associated with cost savings because each other and to the national data (Fig. That these they have higher initial rates of utilization on which to show distributions do not reflect what we know about the relative an impact (25,40). An independent study of risperidone effectiveness of these agents suggests that other factors are compared to conventional antipsychotics among outpa- strong influences on medication choice and that these influ- tients with schizophrenia using a matched comparison ences combine to create similar patterns of antipsychotic group found no difference in total treatment costs or effec- prescribing under Medicaid nationwide. These figures serve as CONCLUSION AND ADDITIONAL reminders that medications are started and discontinued for RESOURCES reasons other than effectiveness. The emphasis has been on illustrating the than dollars and does not label the cost units. Many of these studies have any findings reported as point estimates. It is important to methodologic shortcomings similar to those of the earlier tell patients, prescribers, and payers not just the best esti- cost studies of clozapine described above. Another concern mate of costs and effectiveness, but the likelihood that their is that industry sponsorship of many of these studies means costs and outcomes will fall within their acceptable ranges that they do not meet the criteria for lack of an incentive for what they are willing to pay and/or risk to gain a given for bias set forth by the New England Journal of Medicine outcome. Although their work cannot be quite arbitrary as they are prices (not costs) set by the be summarized here, useful source books include those by manufacturer. Although such studies form good starting points ics and thoughtful analyses of the economic influences on for further investigation, they need follow-up by indepen- the treatment of individuals with schizophrenia. An example of an important follow-up study is that of Conley and col- This research is the product of the collaboration of many leagues (73), who found that, among 84 treatment-refrac- individuals, both within and outside the Connecticut De- tory patients randomly assigned to a double-blind 8-week partment of Mental Health and Addiction Services fixed-dose trial of either olanzapine or chlorpromazine, (DMHAS). In particular, we would like to thank Carlos olanzapine appeared to have limited efficacy, showing only Jackson, Ph. Hence, the reduction in treatment costs assistance with the data extraction and statistical analyses associated with olanzapine noted in the reviews of Palmer of the Medicaid prescription data. The research was funded Chapter 57: The Economics of the Treatment of Schizophrenia 817 in part by U. Economic burden of mental disorders in the United MH-48830 and R01 MH-52872 from the National Insti- States. The economic burden tute of Mental Health (NIMH) to Susan Essock, Ph. Br J Psychiatry 1997;171: tion does not express the views of the Department of Mental 509–518. Health and Addiction Services or the State of Connecticut. Costs of services for schizophrenic patients The views and opinions expressed are those of the authors. Expenditures for treating schizophrenia: a population-based study of Georgia Medicaid recipients. Growth of a field in policy research: the economics tive community treatment teams. Financing psychotherapy: costs, effects, and public offset as an incidental effect of psychotherapy. Inpatient and outpatient psychiatric Health J 1983;19:42–53. Cost sharing and the treatment on psychiatric and medical-surgical hospital days. Public health care for the chronically study of supported employment for people with severe mental mentally ill: financing operating costs.

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