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Selective modulation maldevelopmental hypothesis of schizophrenic psychoses purchase cilostazol with mastercard muscle relaxant half-life. J of fibroblast growth factor-2 expression in the rat brain by the Neural Transm 1998;105:85–100 purchase cilostazol 50 mg mastercard muscle relaxant medication. When neurotrophic factors get on your nerves: ther- 434 order 50 mg cilostazol fast delivery infantile spasms 4 months. Iloperidone binding to apy for neurodegenerative disorders discount cilostazol 50mg without prescription muscle relaxant back pain. JClin Psychiatry 1998;59: human and rat dopamine and 5-HT receptors. COVELL ECONOMICS OF MENTAL HEALTH AND economists indicate the range of activities in the field of SCHIZOPHRENIA mental health economics, including the economics of schiz- ophrenia. This chapter focuses on two aspects of the eco- Prior to the 1980s, economists paid scant attention to schiz- nomics of schizophrenia: cost studies and cost-effectiveness ophrenia, or indeed to mental health in general (1). Studies of the cost of mental illnesses appeared be- work in the field included efforts to consider the impact fore other types of work in the economics of mental health, of organization and financing on system efficiency and to and they have continued throughout the past two decades. For example, McGuire (2) reviewed the mar- cost-benefit studies because they identify the range of re- ket for psychotherapy and the insurability of mental health sources that are consumed as a result of an illness. Cost- care, and Frank (3) examined the supply of psychiatrists. The use of diagnosis- brod and colleagues (14) on the cost-benefit of assertive related groupings to pay for care under prospective payment community treatment teams. Collectively, studies of costs was considered by Taube and his colleagues (5). Dickey and cost-effectiveness are perhaps the most important foci and Goldman (6) reviewed the impact of various funding of the economics of schizophrenia. First, the sizable cost to mechanisms in public mental health. Observers of systems change consid- ered major reorganizational efforts, such as those imple- mented through the Robert Wood Johnson Program on Costs Of Schizophrenia Chronic Mental Illness (8) and other types of organizational reforms (9–12). The 1990s also brought analysis of the Early studies of the costs of mental illness (15–17) did not increasing implementation of managed care with behavioral distinguish between the costs of different diagnostic categor- health carve-outs (13). More recent studies have estimated specific costs These examples of the contributions of mental health for schizophrenia and other illnesses. Rice has estimated the cost of schizophrenia in the United States at $32. Goeree and colleagues (21) have calculated costs in Canada in 1996 to Susan M. Essock: Department of Psychiatry, Mount Sinai School of be approximately $2. However, But no study of the cost of schizophrenia can claim to cap- new strategies for improving the employment outcomes for ture all costs. As noted by McGuire (18), even comprehen- persons with serious mental illness, such as Individual Place- sive studies of the cost of schizophrenia often underestimate ment and Support (29), have made employment a realistic two types of costs: the costs to families and the costs of goal of rehabilitation. These new successes suggest that loss publicly owned capital. Economic, or social, costs are the costs of re- Capital Costs sources consumed because of an illness. Cost-effectiveness and cost-benefit analysis should always state the perspective Economic cost studies appropriately study the opportunity from which the study is undertaken. Although a societal costs of all resources, that is, the value of those resources perspective presumably provides the balanced view of the in their best alternative use. In a cost-effectiveness study of neutral scientist, it is also helpful to examine costs from a new residential model for persons with serious mental perspectives of particular stakeholders. For example, in an illness, Cannon and her colleagues (31) carefully considered analysis of the impact of Assertive Community Treatment the value of capital costs of a public hospital, which would in Connecticut, Essock and colleagues (25) present costs have been underestimated if valued through traditional from the perspectives of society, the state, and the Depart- methods of depreciation. Capital costs can be large enough ment of Mental Health. Comparison of the results from to change the most basic findings of a cost study, as shown multiple perspectives may identify areas of cost-shifting that by Rosenheck and colleagues (32). Public administrators results from certain programs and policies. For example, a may not consider the value of buildings and property to be treatment that reduces hospital days may shift costs from part of a cost equation because it is not always part of the state-run inpatient facilities to private nonprofit outpatient operating costs, but the value of the property in alternative settings. Cost Components Other Components Especially where an intervention is expected to have an im- Costs of Treatment and other Services pact on co-occurring substance use disorders, it is important The examples provided by Rice and Knapp are instructive to attend to criminal justice costs (33). Another neglected for those conducting cost-of-illness studies and cost-effec- aspect of cost studies is the costs of administering transfer tiveness studies in the area of schizophrenia. Although disability pay- there are many ways in which the illness is associated with ments themselves do not represent the use of new resources, greater costs. First are the costs of treatment, including med- the cost of administering these payments is a cost that ication. Treatment may be offered by public, private, or should be counted, especially if the intervention could voluntary sector settings, and many persons with schizo- change the rate of receipt of disability payments or other phrenia receive care in multiple places. For example, an intervention that re- services like case management, vocational rehabilitation, turns people to work will not only increase their productiv- and psychosocial clubhouses generate significant costs. The larger the cost per unit, or the more frequently it is used, the more carefully it should be assessed (35). But should cost-effectiveness analyses al- Lost Productivity and Family Burden ways be conducted? As indicated by the range of costs and Mental illnesses, like other disorders, cause people to lose cost perspectives that might be included, these studies can workdays (28) and sometimes even to forfeit aspirations of be expensive to implement. This expense is further increased having any career at all. Although lost productivity is usually because, to detect meaningful differences in a highly variable addressed in comprehensive studies of the costs of schizo- outcome such as cost, significantly more study participants Chapter 57: The Economics of the Treatment of Schizophrenia 811 may be needed than for an effectiveness study alone. Cost studies are critical in nia is funded need information on multiple domains of the analysis of novel antipsychotic agents because of the effectiveness. An example of a cost-utility approach is the use of quality-adjusted life years (QALYs) (38,39). As noted above, different stakeholder groups value different outcomes differ- COST-EFFECTIVENESS ently; hence, approaches such as QALYs create an effective- ness metric representative of at best only one stakeholder The success of interventions in schizophrenia, whether med- group, and at worst the resulting metric is representative of ications or psychosocial rehabilitation programs, is reflected no one. Although elegant in presentation, as with sausages, in multiple domains. An antipsychotic may have an impact observing their creation can reduce enthusiasm for their use. These scheme—deciding, for example, what weight gain is the are all measures of the effectiveness of the agent, some posi- equivalent of what change in extrapyramidal side effects tive and some negative.
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As the use of calcium-containing using a strategy similar to that employed in hemodialysis 100mg cilostazol free shipping muscle relaxant drug test, phosphate binders has increased cheapest generic cilostazol uk muscle relaxant johnny english, hypercalcemia has become a namely order cilostazol visa spasms right side of stomach, lowering the calcium content of the dialysate cheap cilostazol 100 mg overnight delivery quetiapine spasms. This complication has been particularly common in binders and more liberal use of 1,25-dihydroxyvitamin D to patients treated with peritoneal dialysis, since they have a much effect decreases in the circulating level of parathyroid hormone. In fact, the continual positive calcium balance Dialysate Na in Hemodialysis associated with the 3. The low bone turnover state typical of this disorder impairs accrual 2. The drop in serum osm olality as urea is rem oved leads to a shift of water into the intracellular com partm ent that prevents adequate Indications refilling of the intravascular space. This intracellular m ovem ent of Intradialysis hypotension Cramping Initiation of hemodialysis in setting of severe azotemia Hemodynamic instability (eg, intensive care setting) Contraindications Intradialysis development of hypertension Large interdialysis weight gain induced by high-sodium dialysate Hypernatremia Dialysate Buffer in Hemodialysis water, com bined with rem oval of water by ultrafiltration, leads to contraction of the Acid concentrate intravascular space and contributes to the developm ent of hypotension. H igh-sodium NaCl dialysate helps to m inim ize the developm ent of hypo-osm olality. As a result, fluid can be CaCl m obilized from the intracellular and interstitial com partm ents to refill the intravascular KCL M gCl space during volum e rem oval. O ther potential m echanism s whereby low-sodium dialysate Acetic acid contributes to hypotension are indicated. N a— sodium ; BUN — blood urea nitrogen; Dextrose PGE2— prostaglandin E2. Final dialysate FIGURE 2-2 NaHCO3 Na 137 mEq/L There has been interest in varying the concentration of sodium (Na) in the dialysate during concentrate Cl 105 mEq/L the dialysis procedure so as to minimize the potential complications of a high-sodium solution NaHCO Ca 3. The concentration of sodi- um can be reduced in a linear, exponential, or step pattern. This M ECHANISM S BY W HICH ACETATE BUFFER method of sodium control allows for a diffusive sodium influx early CONTRIBUTES TO HEM ODYNAM IC INSTABILITY in the session to prevent a rapid decline in plasm a osm olality sec- ondary to efflux of urea and other sm all-m olecular weight solutes. During the rem ainder of the procedure, when the reduction in Directly decreases peripheral vascular resistance in approximately 10% of patients osm olality accom panying urea rem oval is less abrupt, the dialysate Stimulates release of the vasodilator compound interleukin 1 is sodium level is set lower, thus m inim izing the developm ent of Induces metabolic acidosis via bicarbonate loss through the dialyzer Produces arterial hypoxemia and increased oxygen consumption? Decreased myocardial contractility Dialysate Composition in Hemodialysis and Peritoneal Dialysis 2. In som e but not all studies, sodi- um m odeling has been shown to be effective in treating intradialysis hypotension and cram ps [5-11]. Use of a sodium modeling program is not indi- cated in all patients. As a result the physician needs to be aware of the benefits as well as the dangers of sodium remodeling. The generation of car- -adrenergic receptor agonists bon dioxide causes the pH of the final solution to fall to approxi- m ately 7. The acidic pH and the lower concentrations in the final m ixture allow the calcium and m agnesium to rem ain in solu- tion. The final concentration of bicarbonate in the dialysate is FIGURE 2-4 approxim ately 33–38 m m ol/L. The current utilization of a bicarbonate dialysate requires a special- ly designed system that m ixes a bicarbonate and an acid concen- trate with purified water. The acid concentrate contains a sm all am ount of lactic or acetic acid and all the calcium and m agnesium. The exclusion of these cations from the bicarbonate concentrate prevents the precipitation of m agnesium and calcium carbonate that would otherwise occur in the setting of a high bicarbonate concentration. During the m ixing procedure the acid in the acid 2. Although bicarbonate is the standard buffer in use phosphate serum calcium secondary today, hem odynam ically stable patients can be dialyzed safely using hyperparathyroidism as acetate-containing dialysis solution. Since m uscle is the prim ary Low-phosphate diet If calcium is still low (800–1000 mg/d) after control of Treat with 1,25(OH) site of m etabolism of acetate, patients with reduced m uscle m ass 2 Phophate binders phosphate, treat with vitamin D tend to be acetate intolerant. Such patients include m alnourished 1,25-(OH)2 vitamin D and elderly patients and wom en. Use calcium-containing phosphate binders Dialysate Potassium in 1. Risk of adynamic bone disease Dialysate Composition in Hemodialysis and Peritoneal Dialysis 2. Since potassium is freely perm eable across the dialysis m em brane, m ovem ent of potassium from the intracellular space to the extracellular space appears to be the limiting factor that accounts for the sm aller fractional decline in potassium concentration at lower plasma potassium concentrations. Presumably, the m ovem ent of potassium out of cells and into the extracellular space is slower than the removal of potassium from the extracellular space into the dialysate, so a COM POSITION OF A disequilibrium is created. The rate of potassium removal is largely a function of its predialysis COM M ERCIALLY AVAILABLE concentration. The higher the initial plasma concentration, the greater is the plasma-dialysate PERITONEAL DIALYSATE gradient and, thus, the m ore potassium is rem oved. After the com pletion of a standard dialysis treatm ent there is an increase in the plasm a concentration of potassium secondary to continued exit of potassium from the intracellular space to the extracellular space in an Solute Dianeal PD-2 attem pt to re-establish the intracellular-extracellular potassium gradient. Sodium, mEq/L 132 FIGURE 2-7 Potassium, mEq/L 0 Chloride , mEq/L 96 Calcium , mEq/L 3. W ithout m echanism s to shift potassium into the cell, sm all potassium loads would lead to severe hyperkalem ia. These m ech- anism s are of particular im portance in patients with end-stage FIGURE 2-8 renal disease since the m ajor route of potassium excretion During a typical dialysis session approxim ately 80 to 100 m Eq/L is elim inated from the body by residual renal clearance and of potassium is rem oved from the body. A, Potassium (K) flux from enhanced gastrointestinal excretion. B, The m ovem ent of potassium between the intra- and extracellular spaces is con- trolled by a num ber of factors that can be m odified during the dial- ysis procedure [17,18]. As com pared with a glucose-free dialysate, a bath that contains glucose is associated with less potassium rem oval. The presence of glucose in the dialysate stim ulates insulin release, which in turn has the effect of shifting potassium into the intracellular space, where it becom es less available for rem oval by dialysis. Dialysis in patients who are acidotic is also associated with less potassium rem oval since potassium is shifted into cells as the serum bicarbonate concentration rises. Finally, patients treated with inhaled stim ulants, as for treatm ent of hyperkalem ia, will have less potassium rem oved during dialysis since stim ulation causes a shift of potassium into the cell. Cheung emodialysis remains the major modality of renal replacement therapy in the United States. Since the 1970s the drive for H shorter dialysis time with high urea clearance rates has led to the development of high-efficiency hemodialysis. In the 1990s, certain biocompatible features and the desire to remove amyloidogenic 2- microglobulin has led to the popularity of high-flux dialysis. During the 1990s, the use of high-efficiency and high-flux membranes has steadily increased and use of conventional membrane has declined. In 1994, a survey by the Centers for Disease Control showed that high-flux dialysis was used in 45% and high-efficiency dialysis in 51% of dialysis centers (Fig. Despite the increasing use of these new hemodialysis modalities the clinical risks and benefits of high-performance therapies are not well- defined.
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