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By W. Brant. Minnesota State University Mankato.

This section contains much information unknown when the last edition of this book was published discount 30 mg prevacid amex gastritis symptoms relief. Charles Nemeroff: Department of Psychiatry and Behavioral Sciences buy prevacid 30 mg without prescription gastritis en ninos, We can all be heartened by the fact that the next edition Emory University School of Medicine buy 30mg prevacid free shipping gastritis rare symptoms, Atlanta generic prevacid 15mg line gastritis diet řčíý, Georgia. KELLER Long-term naturalistic studies have changed the way we remission, an individual still has more than minimal view depression. Full remission is defined as the point at an episodic disease, the past two decades of research have which an individual no longer meets criteria for the dis- underscored the importance of understanding depression as order and has no more than minimal symptoms. Recovery, defined as a full remission that lasts for a de- An appreciation of this longitudinal data is crucial to fined period of time. Conceptually, it implies the end understanding all aspects of depression. Cross-sectional of an episode of an illness, not of the illness per se. Relapse, defined as a return of symptoms sufficient to nostic information. It occurs in an interval nosis or likely treatment response also requires a longitudi- of time before what is defined as 'recovery. Which patient is likely to recover fully, and tually, this refers to the return of an episode, not a new who will suffer from a chronic mood disorder? Recurrence, defined as a return of full symptomatology Studies within the last decade have helped to shed light occurring after the beginning of the recovery period. This chapter examines some of these Conceptually, this represents the beginning of a new studies, and discusses their implications for our approach episode of an illness. REPRESENTATIVE STUDIES THE CHANGE POINTS OF DEPRESSION A relatively small number of studies have been particularly Considerable confusion has resulted from the use of various influential in shedding light on the course of depression. Similar terms, such as 'relapse' and 'recur- rence' have been used interchangeably and inconsistently The Collaborative Depression Study in different studies. As a result, the MacArthur Foundations (CDS) Research Network on the Psychobiology of Depression (1) The CDS (2) is a prospective long-term naturalistic study recommended using the following terms: of the natural course of depression. Episode, defined as a certain number of symptoms for a from patients with depression seeking psychiatric treatment certain period of time. Remission, defined as a period of time in which an indi- Boston, Chicago, Iowa City, New York, and St. In partial This study included programs in biological and clinical studies. The data presented here are from the clinical studies program; 555 subjects in the clinical studies program had an Robert J. Boland: Department of Psychiatry and Human Behavior, index episode of unipolar major depression. Subjects were Brown University; Department of Psychiatry, Miriam Hospital, Providence, examined at 6-month intervals for 5 years and then annually Rhode Island. Keller: DepartmentofPsychiatryandHumanBehavior,Brown University; Department of Psychiatry, Butler Hospital and Brown Affiliated Mental Health (NIMH) funding will extend the follow-up Hospitals, Providence, Rhode Island. However, for those patients who did not recover in the first year, most still had not recovered within 5 years. Thus Angst (3), in Zurich, has conducted the only other long- by 2 years, about 20% of the original sample were still term prospective study of mood disorders. In that study, depressed—two-thirds of those still depressed at 1 year were 173 hospitalized patients with unipolar depression were still in their index episode of depression at 2 years. This group was then years, 12% of patients had still not recovered (6), by 10 evaluated every 5 years for up to 21 years of follow-up. These data are presented The Medical Outcomes Study(MOS) in Fig. The MOS (4) examined the course of several diseases (myo- The long duration of the CDS allowed the investigators cardial infarction, congestive heart failure, hypertension, di- to observe subsequent episodes of major depression begin- abetes, and depression) in a variety of health care settings, ning during the study. This was particularly useful, as the including large medical group practices, small group prac- onset of symptoms could be identified more accurately than tices, and solo practices, in three cities (Los Angeles, Boston, for the retrospective determination done for an index epi- and Chicago). It was found that, for each new episode of depression, specialties—including psychiatry—was chosen, and all pa- the rates of recovery were similar to that seen during the tients seen from February through October 1986 were asked index episode. Thus, for the second episode (first prospec- to participate in the study. In all, over 20,000 patients par- tively observed episode) approximately 8% of subjects did ticipated, and were evaluated yearly for 3 years. An analysis of subsequent episodes (second, third, and fourth prospectively observed episodes) THE COURSE OF DEPRESSION: CHANGE showed similar findings. By the fifth episode, the rate de- POINTS creases, but not significantly so (8). It appears that for each episode of depression, some individuals—about 10%—re- Traditionally, depression was pictured as an acute illness, main ill for at least 5 years. A number of studies, includ- reasonable concern about this result was that the patient ing those mentioned above, however, show the potential population studied may have been unusually treatment re- for great variation from this traditional model. The study used a convenient sample of patients seek- may take much longer, or not occur at all (i. Furthermore, the risk of relapse and recurrence major medical centers. However, most patients studied re- of illness must be considered. Thus, the CDS cohort does not Recovery seem to be biased in the direction of treatment resistance. In the CDS, approximately 70% of patients recovered from Furthermore, other studies show comparable data. In the the index episode of major depression within the first year Zurich study, Angst et al. Outcome of maintenance therapy for de- pressed patients initially stabilized on imipramine plus lithium. Chapter 69: The Course of Depression 1011 follow-up evaluations, about 13% of patients did not re- MITIGATING FACTORS cover from their episode of major depression. In the MOS, Comorbidity patients were divided by severity: of those with milder depression, about 65% recovered within 2 years, whereas Medical Illness 54% of the more severely depressed group recovered in the There are few longitudinal studies looking at the outcome same period (11). Rounsaville and difficulties inherent in recruiting such an unstable popula- colleagues (12), in a prospective follow-up of 96 patients tion. Studies that exist suggest that comorbid medical illness with major depression, found that 12% of subjects had not predispose individuals to a worse course of depression. Relapse Double Depression For the 141 patients in the CDS who recovered from their Double depression refers to the presence of concurrent dys- index episode of major depression, 22% relapsed within 1 thymia and major depression. In this disorder, the episodes year of follow-up (14). Factors predicting relapse included of major depression are superimposed on a more chronic multiple episodes of major depression, older age, and a his- depressive disorder. It appears to be common—studies sug- tory of nonaffective psychiatric illness. The characteristics gest that between one-fourth and two-thirds of patients with of this relapsed group were also examined, and it was found major depression will also have a comorbid dysthymia. Predictors of prolonged time to tant effect on the course of depression. In the collaborative recovery included a longer length of the index episode, older study, it was found that patients with double depression age, and a lower family income. Relapse is also more frequent in patients with double depression than those with major depression alone—almost twice as likely in one Recurrence study of 32 double-depressed subjects followed for 2 years Angst (15), reporting on a 10-follow of patients in the Zu- (20).

The results for negative food markers were generally similar 15mg prevacid otc xyrem gastritis, with the same variables correlated at baseline and at 12 months cheap prevacid 15 mg fast delivery chronic gastritis juice. Similar to the results for energy-dense snacks discount 15mg prevacid otc gastritis diet on a budget, there were no significant associations between gender and negative food markers (18 months) buy discount prevacid 30 mg gastritis symptoms lap band, between school-level deprivation and negative food markers (18 months) and between peer norms and negative food markers (18 months). However, the association between behaviours and strategies and negative food markers (18 months) was significant (p < 0. Additionally, the direct effect of the intervention on negative food markers (18 months) was not significant (p = 0. Gender BMI SDS baseline Number of Year 5 classes School SES NFM baseline Intervention or control NFM 18 months 0. B&S, behaviours and strategies; C&M, confidence and motivation; EDS, energy-dense snacks; FAB&CA, Family approval/behaviours and child attitudes; NFM, negative food markers; PN, peer norms; SES, socioeconomic status. Overall, the effects of the composite mediating variables on the outcome variables were fairly small. The largest association was between family approval/behaviours and child attitudes at 12 months and the outcome variables. For both paths (between family approval/behaviours and child attitudes and energy-dense snacks and between family approval/behaviours and child attitudes and negative food markers), β was –0. Additionally, the results of the behaviours and strategies variable need to be interpreted with caution. As outlined in Appendix 18,this variable was the least psychometrically robust of MLQ variables. The path between behaviours and strategies at 12 months and energy-dense snacks was not significant, but the path between behaviours and strategies at 12 months and negative food markers resulted in a significant change in the opposite direction to those of the other mediating variables. This counterintuitive result is most likely a result of collinearity; as shown in Table 48, behaviours and strategies was negatively correlated with negative food markers. However, in the context of the other MLQ variables, this association became positive (β was 0. Such seemingly paradoxical cases have been described in the literature134 and are most likely due to collinearity with other predictor variables or the operation of suppressor variables. Table 47 shows that behaviours and strategies and confidence and motivation were correlated to an extent (r = 0. Further exploration of these composite variables could clarify which items are responsible for these effects. Summary We developed and evaluated a self-report tool, the MLQ, which aimed to capture changes in knowledge, cognitions and behaviours that could explain changes in weight gain. The MLQ contains items that are relevant, acceptable and feasible for 9- to 10-year-olds to complete in a timely manner and it has undergone psychometric testing, although future additional evaluation of the MLQ could include further tests for reliability and construct validity. Five composite variables emerged from the evaluation of the MLQ and these were used as the mediating variables in the two longitudinal path analyses. The first analysis was for the number of weekday unhealthy foods consumed per day (weekday negative food markers at 18 months) and showed statistical evidence for full mediation as the previous significant effect of the intervention on this outcome variable was no longer present (p = 0. This result suggests that the composite variables arising from the MLQ could provide a possible explanation of how the intervention generated the observed differences in dietary behaviour. However, further exploration could clarify this explanation. The analysis for the number of weekday energy dense snacks consumed per day at 18 months revealed partial mediation (p = 0. Overall, it is noted that the full and partial mediation effects were both close to the cut-off point for statistical significance (p = 0. The findings arising from our use of composite variables require cautious interpretation; we are able only to conclude that children have changed in a combination of ways for two of the secondary outcomes in the trial. Future work could include more theoretically based modelling work (which would be possible given the theoretical underpinning of many of the items in the MLQ) as well as cluster analyses135 to investigate which specific mediator and which moderator variables might predict healthy outcomes in the whole HeLP cohort. 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 99 provided that 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. PROCESS EVALUATION Conclusions from the process evaluation Data from the process evaluation show that HeLP was delivered as designed in all 16 intervention schools, with high uptake and engagement from schools, children and their families across the socioeconomic spectrum. The mediation analyses show that the intervention effects on the consumption of weekday energy-dense snacks were mediated by knowledge and two composite variables, namely family approval/behaviours and child attitudes and confidence and motivation, whereas the intervention effect on weekday consumption of unhealthy foods (negative food markers) was mediated by the same variables as well as the composite variable behaviours and strategies. We found no evidence of a difference in BMI SDS at 24 months or that participating in HeLP reduced the likelihood that children would be overweight or obese compared to children not receiving the intervention. Similarly, no differences between the intervention and control groups were observed in either anthropometric measures or physical activity objectively assessed using accelerometers at 18 months post baseline. Self-reported weekly average consumption of different types of energy-dense snacks was lower in those attending intervention schools (0. These differences were largely accounted for by reported differences in weekday consumption. The cost of implementing HeLP was estimated at approximately £210 per child. Assumptions are reported regarding the proportions of children needing to move weight category for cost-effectiveness to be achieved using NICE cost-per-QALY methodology. The review identified 139 intervention studies that had weight-related outcomes, of which 115 were located in the primary school. The 37 studies that were purely school-based and did not have a family component showed a low strength of evidence for reducing BMI, BMI SDS, prevalence of obesity and overweight, percentage body fat, waist circumference and skinfold thickness. However, studies that also included a family component provided moderate evidence of effectiveness, with half reporting statistically significant beneficial intervention effects. Other systematic reviews and meta-analyses also suggest that school-based obesity prevention interventions can have a modest effect on BMI SDS and it is unclear whether such effect sizes (typically < 0. We are not aware of any recent, well-conducted, school-based obesity prevention RCTs, using objective outcome measures, for this age group, that have shown a clinically relevant effect on adiposity measures at 2-year follow-up. A very recent school-based trial (Active for Life-year 5)16 involving 60 schools and > 2000 children (aged 9–10 years), which aimed to increase physical activity, reduce sedentary behaviour and increase fruit and vegetable consumption at 2-year follow-up, found no effect of the intervention on any of these primary outcomes or on weight status. Furthermore, the exploratory trial showed changes in diet and physical activity behaviours and weight status; however, these were not replicated in the main trial. In addition, HeLP was delivered as designed in all intervention schools with very high levels of engagement, as was also seen in the exploratory trial. The findings from the process evaluation allow us to be confident that the difference in results between the exploratory and the definitive trial are not due to scale-up issues of delivery. 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 101 provided that 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. DISCUSSION AND CONCLUSIONS differential effect of the intervention between the two cohorts on the primary outcome, indicating that this logistical requirement did not affect the overall findings, and our follow-up rates at 18 and 24 months were similar across both trials. Understanding the lack of effectiveness Conducting health promotion interventions within schools has the obvious potential advantage of being able to reach virtually all children. The behaviours that underlie the development of obesity and overweight in children and adolescents result from a complex interaction of individual, family and social factors. This is particularly relevant for children of primary school age, as their ability to influence their diet and activity is directly limited by decisions made by their parents/carers, as well as being affected by wider social influences. We therefore aimed to develop an intervention that would influence not only the children themselves, but also their parents and the school environment, as we felt that this would have a higher likelihood of being effective. Our review of existing evidence suggested that multifaceted interventions were more likely to be effective when they addressed both diet and exercise, were of significant duration and involved the family, although the strength of these conclusions was limited owing to the paucity of existing high-quality studies. We were also aware that a common reason for failure in health promotion programmes is a failure to persuade the target group to participate and to stay involved, so strategies to achieve engagement by children, parents and schools were fundamental in the design of both the intervention and the trial. In addition, for public health interventions to have an impact, they need to be deliverable without disrupting normal activities and at an affordable cost.

Hypertension Hepatotoxicity (abnormal Glucose intolerance (FK > CyA) Gingival hypertrophy Headache Although slight differences exist in side- Nephrotoxicity transaminase levels) Hyperkalemia (CyA only 15 mg prevacid with amex gastritis in pregnancy, especially Paresthesias effect profiles between the two drugs best prevacid 30 mg gastritis caused by alcohol, their (azotemia) Nausea cheap prevacid 30 mg fast delivery gastritis long term, vomiting best 15mg prevacid gastritis diet x factor, diarrhea Hyperlipidemia (CyA > FK) in combination with Seizures overall im pact is rem arkably sim ilar. In (FK > CyA) calcium antagonists) m any cases, dose reduction m ay am eliorate Hyperuricemia Tremor Hirsutism (CyA > FK) the toxic effect; however, the benefit of dose Hypomagnesemia reduction m ust be weighed against increas- ing the risk of acute rejection in each patient. FIGURE 13-2 COMMON DRUG INTERACTIONS Cyclosporine and tacrolim us are subject to rem arkably sim ilar interactions, owing in part W ITH CYTOKINE INHIBITORS to a com m on pathway of m etabolic degradation, the cytochrom e P-450 enzym e system. Although the drugs listed here predictably alter blood levels of the calcineurin inhibitors, other interactions m ay also occur. Drugs that commonly increase blood levels of cyclosporine and tacrolimus Bromocryptine Cimetidine Clarithromycin Clotrimazole Diltiazem Erythromycin Fluconazole Itraconazole Ketoconazole Mefredil Methylprednisolone Nicardipine Verapamil Drugs that commonly decrease blood levels of cyclosporine and tacrolimus Carbamazepine Phenobarbital Phenytoin Rifampin M edical Complications of Renal Transplantation 13. This graph, derived from the para- metric analysis techniques of Blackstone and coworkers, depicts the risk of acute rejec- 0. Using an im m unosuppressive protocol including cyclosporine, m ycopheno- late m ofetil, and prednisone, the risk of acute rejection is greatest during the first 2 m onths 0. Because the risk of rejection is greatest, im m unosuppressive therapy is m ost intense during this period. The relationship between these variables beyond the first 6 to 12 m onths after transplantation is not well established. In these patients the risk of malignancy is increased approximately fourfold when compared with the general population. M alignancies likely to be encountered in the transplantation recipient differ from those m ost com m on in the general population [9,10]. W om en are at an increased risk for cervical carcinom a, again related to infection (hum an papillom a Other Lymphomas virus). Surprisingly, the solid tum ors m ost com m only seen in the general population (eg, of (36%) (24%) the breast, lung, colon, and prostate) do not occur with significantly greater frequency among transplant recipients. N onetheless, long-term care of these patients should involve standard screening for these m alignancies at appropriate intervals. Cutaneous carcinom as (prim arily Posttransplantation lym phoproliferative disease (PTLD): histologic basal cell and squam ous cell) com prise the greatest percentage appearance of a renal allograft infiltrated by a monoclonal proliferation of tum ors in transplant recipients. In im m unocom petent patients the risks of these polyclonal or m onoclonal B-cell com position, with lym phocytes lesions usually are lim ited; however, in transplant recipients driven to proliferate by infection with the Epstein-Barr virus these lesions can be very aggressive and m etastasize locally or [11–13]. Development of PTLD is strongly linked to the intensity even system ically. The best m anagem ent is aggressive prevention: of im m unosuppression and m ay regress with its reduction. W hen suspicious lesions develop, early recognition m ore aggressive unrelenting course despite withdrawal of im m uno- and rem oval are of utm ost im portance. Hematologic Complications is the range of serum erythropoietin levels in norm al persons with- 200 out anem ia. M any patients leave the dialy- 150 sis population with diminished iron stores and are unable to respond to erythropoietin produced by the successful allograft. Iron replace- 100 m ent therapy successfully restores erythropoiesis in these patients. Another common cause of anem ia after transplantation is bone m arrow suppression owing to drug therapy with azathioprine or 50 m ycophenolate m ofetil (M M F), an effect that is usually dose-relat- 25 ed [15,16]. O ther drugs, notably angiotensin-converting enzym e 0 inhibitors and angiotensin receptor antagonists, m ay also inhibit erythropoiesis. Neutropenia also is a common complication after transplantation. Alternatively, neutropenia FIGURE 13-8 can be a m anifestation of system ic viral, fungal, or tubercular infec- The course of norm al erythropoiesis after renal transplantation tions. The approach to the patient with neutropenia usually involves showing m ean serum erythropoietin levels of 31 recipients. In som e settings of refrac- engraftm ent does not result in erythropoiesis. As excellent graft tory neutropenia, adm inistration of filgrastim (granulocyte colony- function is achieved, a second burst of EPO secretion is norm ally stim ulating factor, N eupogen®) reduces the duration and severity of followed by effective production of erythrocytes. PTE usually 52 50 occurs during the first year after transplantation. Although it m ay 48 resolve spontaneously in som e patients, PTE persists in m any. It has 46 44 been linked to an increased risk of throm boem bolic events; howev- 42 40 er, our own experience is that such events are uncom m on. Previous m anagem ent involved serial phlebotom y to m aintain the hem atocrit PRE 1 2 3 4 5 6 9 12 15 at 0. M ore recently, hem atocrit levels have M onths on enalapril (mean 7±4. The pathogenetic m echanism s underlying PTE and its response to these therapies rem ain poorly understood; although elevated serum erythropoietin levels decrease with ACEI use, other pathways also appear to be involved. Cardiovascular Complications 8 FIGURE 13-10 Diabetic Causes of death in renal allograft recipients. Cardiovascular dis- 7 Nondiabetic eases are the m ost com m on cause of death, largely reflecting the 6 high prevalence of coronary artery disease in this population. Effective m anagem ent of cardiac disease after transplan- 2 tation m andates docum entation of preexisting disease in patients 1 at greatest risk. In DEM OGRAPHIC VARIABLES HIGHLY PREDICTIVE OF CORONARY DISEASE patients with diabetes who have end-stage IN RENAL TRANSPLANTATION CANDIDATES W ITH INSULIN-DEPENDENT renal disease with none of the dem ographic DIABETES M ELLITUS characteristics listed, the risk for coronary disease is low. Conversely, in patients who are insulin-dependent and have any of these Age > 45 y risk factors, the prevalence of coronary disease Electrocardiographic abnormality: nonspecific ST-T wave changes is sufficiently high to justify angiography. History of cigarette smoking A random ized study of m edical therapy Duration of diabetes > 25 y versus revascularization in transplantation candidates who have insulin-dependent diabetes and coronary disease showed superior outcomes with prophylactic revascularization, FIGURE 13-11 even in the absence of overt sym ptom atol- Demographic variables highly predictive of coronary disease in renal transplantation candidates ogy. M ost transplant centers screen potential candi- coworkers. H ypercholesterolem ia and hyper- triglyceridem ia are com m on after kidney 45 30 transplantation. Approxim ately two thirds of transplant recipients have low density 30 20 lipoprotein (LDL) or total cholesterol levels 74% 63% signifying increased cardiac risk; 29% have 15 10 elevated triglyceride levels 2 years after 0 0 transplantation (Kasiske, Unpublished 100 200 300 400 70 130 190 250 310 data). N ot only is hyperlipidem ia a clear risk factor for coronary disease (see Figs. Cholesterol, mg/dL LDL, mg/dL 13-13 and 13-14), but it may also contribute 75 40 to the progressive graft dysfunction associated n=588 n=430 with chronic rejection [21,22]. In The indications for lipid-lowering therapy and its goals are based addition to elevated low density lipoprotein (LDL) cholesterol levels, on the clinical history, risk factor profile (see Fig. About 40% of recipients are CHD— coronary heat disease. Sm oking, hypertension, and hyperlipidem ia are am ong the risk factors m ost am enable to long-term m odification. Although dose reduction can reduce lipid levels, it m ay also CyA increase the risk of acute rejection. As depicted, early experience in a large m ulticenter p<0. FIGURE 13-17 FIGURE 13-16 In the current era of im m unosuppressive therapy, hypertension A recent m eta-analysis of published trials in renal transplant affects roughly two thirds of transplant recipients. Unlike hyperten- recipients dem onstrated these benefits of the various treatm ents. These m ay be grouped dysfunction or rhabdom yolysis. These adverse events m ay occur conveniently into those originating within the allograft (intrinsic) m ore frequently in transplant recipients owing to the effect of and those originating elsewhere (extrinsic). Levels of 3-hydroxy-3-methylglutaryl coenzyme A (HM G CoA) reductase inhibitors are substantially higher in patients receiving both drugs. HDL— high density lipoprotein; LDL— low density lipoprotein.

Goeree and colleagues (21) have calculated costs in Canada in 1996 to Susan M prevacid 15 mg visa gastritis diet öĺíçîđ. Essock: Department of Psychiatry discount prevacid 15 mg amex gastritis symptoms upper right quadrant pain, Mount Sinai School of be approximately $2 buy 15mg prevacid otc gastritis lemon. However buy prevacid 15mg with mastercard gastritis hot flashes, 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. Some, such as hallucinations and (EPSs) and what change in psychotic symptoms. Typically, delusions, may be influenced much more directly by the one does this either by interviewing individuals representa- medication than more distal outcomes such as housing or tive of the population under study (e. Sim- with schizophrenia used weights derived as part of a doctoral ilarly, some people are very troubled by changes in weight dissertation by Kleinman (Johns Hopkins University, 1995) or sexual functioning, whereas such changes mean little to of mainly African-American women, only about half of others. Hence, much as we would like a composite measure whom (55%) were diagnosed with schizophrenia (the rest across all effectiveness domains, this reductionistic approach were diagnosed with major depression, bipolar, and other is fraught with untenable compromises. We were unwilling to take the leap of tion among different patients and different providers, pa- faith needed to generalize from groups this disparate when tients and payers ascribe different values to the same out- presenting cost-effectiveness results from our own work come (e. Nevertheless, Rosenheck and colleagues are to be com- public mental health systems may be more concerned about mended for providing the information necessary to follow decreases in violence and patients may be more concerned back their methods to see what was used. This is not always with increases in quality of life). Another type of utility analysis is the measure of symp- Cost-effectiveness analyses have evolved to deal with the tom-free days (42). Under such analyses, interventions are multiple domains touched by a single treatment. Such anal- compared with respect to the number of symptom-free days yses report the change in a given effectiveness measure asso- they produce. Following the methodology of Lave and col- ciated with a particular cost investment in treatment. A leagues (43), Simon and colleagues (42) credited a study medication may be cost-effective with respect to certain out- participant with having one depression-free day if the study comes, cost-neutral for others, and costly for yet others. Many Lehman (37) reminds us that the current explosion of new people with depression, as well as many researchers, would knowledge about effective treatments and the advent of evi- take issue with saying that someone was symptom free for dence-based quality standards for treating schizophrenia half a year if they reported having 50% of full symptoms come at a time when cost containment is paramount in the for each day of that year. Symptom-free days may be a poor health policy agenda. Policy makers need to know the im- measure within schizophrenia studies simply because, unlike pact of dollars invested in treatment—but not just in a with depression, symptoms and functioning are poorly cor- 812 Neuropsychopharmacology: The Fifth Generation of Progress related, and the likelihood of having a completely symptom- lion in the pharmacy budget for medication X, what can I free day is rather small. What will it equals one lost year of healthy life, can also be used to buy me in terms of reductions in hospital use, improvements express years lost, both to premature death and to disabilities in vocational functioning, reductions in violent episodes, associated with living with schizophrenia (44). In a population my sexual functioning, and in my body movements? DALYs are calculated by adding together the than to others. An analogy is a proposal for a city park number of years between mortality and life expectancy to be funded from multiple sources. Calculating YLDs requires making as- park would impact the value of your property, your safety, sumptions about the relative impact of illness onset, dura- your recreational options, what you are called on to invest), tion, and severity on healthy living (for example, making the park may or may not be a good idea. And, depending an assumption that a first psychotic episode at age 15 is on who is paying for what, and which outcome domains worse than a first episode at age 25). As with QALYs, these are most important to you, you may stand to get a lot or metrics can be derived by surveying individuals with schizo- a little out of the dollars going into the park. The challenge phrenia or their proxies, with the accompanying assump- is to present the data on costs and effects in such a way that tions that how one weights hypothetical events is the same the various payers (the city, private foundations, neighbor- as the trade-offs one would make if one could trade fewer hood organizations, individual contributors) can each look days of healthy life for more days of life with particular from their own perspective, see what the expected gains and disabilities. Because such ratings are inherently untestable losses are in the outcome domains they care about most by rigorous methods, whether reliable or not, their validity (less street noise, more open space, more dogs, more people remains suspect.

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