Correlates of self-rated health in people with diabetic peripheral neuropathy: a longitudinal study.

AIM: Self-rated health, a measure of self-reported general health, is a robust predictor of morbidity and mortality in various populations, including persons with diabetes. This study examines correlates of self-rated health in adults with diabetic peripheral neuropathy (DPN). METHODS: Participants recruited from the UK and USA (n = 295; mean (± sd) age: 61.5 ± 10.7 years; 69% male; 71% type 2 diabetes) rated their health at baseline and 18 months. DPN severity was assessed using the neuropathy disability score and the vibration perception threshold. Validated self-report measures assessed neuroticism, DPN-symptoms of pain, unsteadiness and reduced sensation in feet, DPN-related limitations in daily activities, DPN-specific emotional distress and symptoms of depression. RESULTS: In the fully adjusted baseline model, younger age, presence of cardiovascular disease and higher depression symptom scores showed likely clinically meaningful independent associations with worse health ratings. Being at the UK study site and presence of nephropathy indicated potentially meaningful independent associations with lower baseline health ratings. These predictors were largely consistent in their association with health ratings at 18 months. CONCLUSION: Results identify independent correlates of health ratings among adults with DPN. Future research should investigate the clinical implications of associations and examine changes in these variables over time and potential effects on changes in health perceptions. If these associations reflect causal pathways, our results may guide interventions to target issues that are likely to have an impact on subjectively experienced health as an important patient-reported outcome in DPN care.

Trajectories of PTSD risk and resilience in World Trade Center responders: an 8-year prospective cohort study.

BACKGROUND: Longitudinal symptoms of post-traumatic stress disorder (PTSD) are often characterized by heterogeneous trajectories, which may have unique pre-, peri- and post-trauma risk and protective factors. To date, however, no study has evaluated the nature and determinants of predominant trajectories of PTSD symptoms in World Trade Center (WTC) responders. METHOD: A total of 10835 WTC responders, including 4035 professional police responders and 6800 non-traditional responders (e.g. construction workers) who participated in the WTC Health Program (WTC-HP), were evaluated an average of 3, 6 and 8 years after the WTC attacks. RESULTS: Among police responders, longitudinal PTSD symptoms were best characterized by four classes, with the majority (77.8%) in a resistant/resilient trajectory and the remainder exhibiting chronic (5.3%), recovering (8.4%) or delayed-onset (8.5%) symptom trajectories. Among non-traditional responders, a six-class solution was optimal, with fewer responders in a resistant/resilient trajectory (58.0%) and the remainder exhibiting recovering (12.3%), severe chronic (9.5%), subsyndromal increasing (7.3%), delayed-onset (6.7%) and moderate chronic (6.2%) trajectories. Prior psychiatric history, Hispanic ethnicity, severity of WTC exposure and WTC-related medical conditions were most strongly associated with symptomatic trajectories of PTSD symptoms in both groups of responders, whereas greater education and family and work support while working at the WTC site were protective against several of these trajectories. CONCLUSIONS: Trajectories of PTSD symptoms in WTC responders are heterogeneous and associated uniquely with pre-, peri- and post-trauma risk and protective factors. Police responders were more likely than non-traditional responders to exhibit a resistant/resilient trajectory. These results underscore the importance of prevention, screening and treatment efforts that target high-risk disaster responders, particularly those with prior psychiatric history, high levels of trauma exposure and work-related medical morbidities.

Dimensional structure and course of post-traumatic stress symptomatology in World Trade Center responders.

BACKGROUND: Post-traumatic stress disorder (PTSD) in response to the World Trade Center (WTC) disaster of 11 September 2001 (9/11) is one of the most prevalent and persistent health conditions among both professional (e.g. police) and non-traditional (e.g. construction worker) WTC responders, even several years after 9/11. However, little is known about the dimensionality and natural course of WTC-related PTSD symptomatology in these populations. METHOD: Data were analysed from 10 835 WTC responders, including 4035 police and 6800 non-traditional responders who were evaluated as part of the WTC Health Program, a clinic network in the New York area established by the National Institute for Occupational Safety and Health. Confirmatory factor analyses (CFAs) were used to evaluate structural models of PTSD symptom dimensionality; and autoregressive cross-lagged (ARCL) panel regressions were used to examine the prospective interrelationships among PTSD symptom clusters at 3, 6 and 8 years after 9/11. RESULTS: CFAs suggested that five stable symptom clusters best represent PTSD symptom dimensionality in both police and non-traditional WTC responders. This five-factor model was also invariant over time with respect to factor loadings and structural parameters, thereby demonstrating its longitudinal stability. ARCL panel regression analyses revealed that hyperarousal symptoms had a prominent role in predicting other symptom clusters of PTSD, with anxious arousal symptoms primarily driving re-experiencing symptoms, and dysphoric arousal symptoms primarily driving emotional numbing symptoms over time. CONCLUSIONS: Results of this study suggest that disaster-related PTSD symptomatology in WTC responders is best represented by five symptom dimensions. Anxious arousal symptoms, which are characterized by hypervigilance and exaggerated startle, may primarily drive re-experiencing symptoms, while dysphoric arousal symptoms, which are characterized by sleep disturbance, irritability/anger and concentration difficulties, may primarily drive emotional numbing symptoms over time. These results underscore the importance of assessment, monitoring and early intervention of hyperarousal symptoms in WTC and other disaster responders.

Exposure, probable PTSD and lower respiratory illness among World Trade Center rescue, recovery and clean-up workers.

BACKGROUND: Thousands of rescue and recovery workers descended on the World Trade Center (WTC) in the wake of the terrorist attack of September 11, 2001 (9/11). Recent studies show that respiratory illness and post-traumatic stress disorder (PTSD) are the hallmark health problems, but relationships between them are poorly understood. The current study examined this link and evaluated contributions of WTC exposures. METHOD: Participants were 8508 police and 12 333 non-traditional responders examined at the WTC Medical Monitoring and Treatment Program (WTC-MMTP), a clinic network in the New York area established by the National Institute for Occupational Safety and Health (NIOSH). We used structural equation modeling (SEM) to explore patterns of association among exposures, other risk factors, probable WTC-related PTSD [based on the PTSD Checklist (PCL)], physician-assessed respiratory symptoms arising after 9/11 and present at examination, and abnormal pulmonary functioning defined by low forced vital capacity (FVC). RESULTS: Fewer police than non-traditional responders had probable PTSD (5.9% v. 23.0%) and respiratory symptoms (22.5% v. 28.4%), whereas pulmonary function was similar. PTSD and respiratory symptoms were moderately correlated (r=0.28 for police and 0.27 for non-traditional responders). Exposure was more strongly associated with respiratory symptoms than with PTSD or lung function. The SEM model that best fit the data in both groups suggested that PTSD statistically mediated the association of exposure with respiratory symptoms. CONCLUSIONS: Although longitudinal data are needed to confirm the mediation hypothesis, the link between PTSD and respiratory symptoms is noteworthy and calls for further investigation. The findings also support the value of integrated medical and psychiatric treatment for disaster responders.

Atherosclerotic aortic component quantification by noninvasive magnetic resonance imaging: an in vivo study in rabbits.

OBJECTIVES: We sought to demonstrate the ability that noninvasive in vivo magnetic resonance imaging (MRI) has to quantify the different components within atherosclerotic plaque. BACKGROUND: Atherosclerotic plaque composition plays a critical role in both lesion stability and subsequent thrombogenicity. Noninvasive MRI is a promising tool for the characterization of plaque composition. METHOD: Thoracic and abdominal aortic atherosclerotic lesions were induced in rabbits (n = 5). Nine months later, MRI was performed in a 1.5T system. Fast spin-echo sequences (proton density-weighted and T2-weighted [T2W] images) were obtained (in-plane resolution: 350 x 350 microns, slice thickness: 3 mm). Magnetic resonance images were correlated with matched histopathological sections (n = 108). RESULTS: A significant correlation (p < 0.001) was observed for mean wall thickness and vessel wall area between MRI and histopathology (r = 0.87 and r = 0.85, respectively). The correlation was also present on subanalysis of the thoracic and upper part of the abdominal aorta, susceptible to respiratory motion artifacts. There was a significant correlation for plaque composition (p < 0.05) between MRI and histopathology for the analysis of lipidic (low signal on T2W, r = 0.81) and fibrous (high signal on T2W, r = 0.86) areas with Oil Red O staining. T2-weighted images showed greater contrast than proton density-weighted between these different components of the plaques as assessed by signal intensity ratio analysis with the mean difference in signal ratios of 0.47 (S.E. 0.012, adjusted for clustering of observations within lesions) being significantly different from 0 (t1 = 39.1, p = 0.016). CONCLUSIONS: In vivo noninvasive high resolution MRI accurately quantifies fibrotic and lipidic components of atherosclerosis in this model. This may permit the serial analysis of therapeutic strategies on atherosclerotic plaque stabilization.

Effect of a bicultural community health worker on completion of diabetes education in a Hispanic population.

OBJECTIVE: To determine the effect of a bicultural community health worker (CHW) on completion of diabetes education in an inner-city Hispanic patient population and to evaluate the impact of completion of the education program on patient knowledge, self-care behaviors, and glycemic control. RESEARCH DESIGN AND METHODS: Patients were randomized into CHW intervention and non-CHW intervention groups. All patients received individualized, comprehensive diabetes education from a certified diabetes nurse educator after baseline demographic information, diabetes knowledge, diabetes self-care practices, and glycohemoglobin levels were assessed. Rates of education program completion were determined. Diabetes knowledge, self-care practices, and glycohemoglobin levels were reassessed at program completion and at a later postprogram follow-up medical appointment and compared to baseline. Logistic regression analysis and the Mantel-Haenszel chi 2 statistic were used to determine the effect of the CHW assignment on program completion. Analyses of covariance were performed with end-of-treatment behavior scores, knowledge scores, and glycohemoglobin levels as outcome variables, controlling for baseline values and testing for the effect of CHW assignment. RESULTS: Of 64 patients enrolled in the study, 40 (63%) completed and 24 (37%) dropped out before completing the diabetes education program. Of the patients having CHW intervention, 80% completed the education program, compared with 47% of patients without CHW intervention (P = 0.01). "Dropouts" were younger (age 47.5 +/- 12.5 years [mean +/- SD]) compared with patients who completed the program (55.9 +/- 9.9 years) (P = 0.004). Dropout status showed no significant relationship to educational level achieved or literacy level. For the program "completers," knowledge levels and selected self-care practices significantly improved, and glycohemoglobin levels improved from a baseline level of 11.7% to 9.9% at program completion (P = 0.004) and 9.5% at the postprogram follow-up (P < 0.001). The effect of the CHW assignment on program completion, controlling for financial status and language spoken, was extremely robust (P = 0.007). The effect of the CHW on knowledge, self-care behavior, or glycohemoglobin outcome variables was not statistically significant. CONCLUSIONS: These findings suggest that intervention with a bicultural CHW improved rates of completion of a diabetes education program in an inner-city Hispanic patient population irrespective of literacy or educational levels attained. Our data further suggests that completion of individualized diabetes educational strategies leads to improved patient knowledge, self-care behaviors, and glycemic control.

Influenza and pneumococcal vaccination of HIV-infected patients: a policy analysis.

OBJECTIVE: To analyze the policy of vaccinating human immunodeficiency virus (HIV)-infected young adults against influenza and pneumococcal infections. METHODS: Transition state model of clinical immune deterioration of HIV infection, published data, and experts' estimates for the uncertain variables. Outcome measures are the number of influenza and pneumococcal infection hospitalizations and deaths prevented over 10 years and cost-effectiveness ratios. PATIENTS: Hypothetical cohort of HIV-infected 30-year-old patients. RESULTS: Although pneumococcal vaccine effectiveness diminishes with advanced HIV disease, the risks of pneumococcal infection rise substantially. Pneumococcal vaccination was therefore found to be a reasonable prevention strategy at all HIV disease stages: few vaccinations are needed to prevent hospitalizations and deaths, and the vaccination strategy is cost-effective. By contrast, influenza incidence is low among young adults, and HIV-related immunodeficiency increases influenza risks only minimally. Because the vaccine is administered yearly, many more vaccinations must be administered and fewer hospitalizations and deaths are prevented than with pneumococcal vaccination. The costs to extend life expectancy are high, and beyond the costs of other prevention strategies for persons with moderate to severe immunodeficiency. CONCLUSIONS: Pneumococcal vaccination is a reasonable prevention strategy for HIV-infected patients at all stages of immunodeficiency. Fewer hospitalizations and deaths are prevented by influenza vaccination, making it a far less cost-effective prevention strategy than pneumococcal vaccination.

Outpatient treatment of deep venous thrombosis in diverse inner-city patients.

PURPOSE: We sought to describe the development and outcomes of a hospital-based program designed to provide safe and effective outpatient treatment to a diverse group of patients with acute deep venous thrombosis. METHODS: Patients enrolled in the program were usually discharged on the day of or the day after presentation. Low- molecular-weight heparin was administered for a minimum of 5 days and warfarin was given for a minimum of 3 months. The hospital provided low-molecular-weight heparin free of charge to patients. Patients received daily home nursing visits to monitor the prothrombin time, assess compliance, and detect complications. The inpatient and outpatient records of the first 89 consecutive patients enrolled in the program were reviewed. Patients were observed for a 3-month period after enrollment. RESULTS: The median length of stay was 1 day. Low-molecular-weight heparin was administered for a mean (+/- standard deviation [SD]) of 4.7 +/- 2.4 days at home. Recurrent thromboembolism was noted in 1 patient (1%), major bleeding in 2 patients (2%), and minor bleeding in 2 patients (2%). No patients died or developed thrombocytopenia. Assuming that patients would have been hospitalized for the duration of treatment with low-molecular-weight heparin, the program eliminated a mean of 4.7 days of hospitalization, with an estimated reduction of $1,645 in total health care costs per patient. CONCLUSION: This hospital-based program to provide outpatient treatment of deep venous thrombosis to a diverse group of inner-city patients achieved a low incidence of adverse events and substantial health care cost savings. Specific strategies, including providing low-molecular-weight heparin free of charge and daily home nursing visits, can be utilized to facilitate access to outpatient treatment and ensure high-quality care.

The utility of an in-hospital observation period after discontinuing intravenous antibiotics.

PURPOSE: To determine whether observing patients overnight in the hospital after intravenous antibiotics have been discontinued is a useful way to identify important clinical events. SUBJECTS AND METHODS: We performed a retrospective chart review of patients admitted during a 6-month period to a tertiary care teaching hospital with a primary diagnosis of either pneumonia, urinary tract infection, or cellulitis who were treated with intravenous antibiotics. Charts were abstracted for patient characteristics, including comorbid illnesses and laboratory values, as well as for evidence of recurrent infection or other adverse events. RESULTS: Of the 374 patients in the study, 63 (17%) were discharged on the day intravenous antibiotics were discontinued. These patients were 10 years younger (P = 0.0009) and had fewer comorbid illnesses (P = 0.02) than those who were observed in the hospital. Recurrent infection was noted in 3 (1%; 95% confidence interval 0.2% to 3%) of the 308 patients who were observed. A mild adverse antibiotic reaction was also noted in three observed patients. The readmission rate to the same institution for recurrent infection was 3% for patients with an observation period and 2% for patients without an observation period (P = 0.70). CONCLUSIONS: Observing patients overnight in the hospital after discontinuing intravenous antibiotics is a common clinical practice. There was an extremely low incidence of adverse events during the observation period, and the events that did occur would have been discovered in an outpatient setting. In-hospital observation after discontinuing intravenous antibiotics is unnecessary for most patients with pneumonia, urinary tract infection, or cellulitis and greatly increases health-care costs.

Effects of practice setting on quality of lipid-lowering management in patients with coronary artery disease.

We undertook a study to determine whether there were differences in the quality of lipid management in patients with coronary artery disease (CAD) in 2 different practice settings (which represent different socioeconomic classes), and to determine the level of compliance with the National Cholesterol Education Program guidelines by academic physicians in managing patients with CAD. A retrospective cross-sectional study was performed using a systematic chart review of 270 medical records (131 from the cardiology clinic, 139 from the cardiology private practice) of patients with known CAD at an academic tertiary care center in New York City. The total proportion of patients with CAD having a lipid profile ordered in the clinic and private suite was 43%. Of these people, 22% had a low-density lipoprotein cholesterol (LDL) < or = 100 mg/dl and 54% had an LDL < or = 130 mg/dl (10% and 23% of the total population, respectively). The total proportion of patients taking lipid-lowering medications was 29%. When comparing the quality of treatment between the 2 settings, there were no statistically significant differences in the percentages of patients who had lipid profiles measured (40% clinic vs 47% private suite, p >0.10), in the percentage of patients with LDL < or = 130 mg/dl (50% clinic vs 57% private suite, p >0.10) or in the weighted percentage of patients taking lipid-lowering medications (29% clinic vs 48% private suite, p = 0.099). The performances of individual physicians, however, varied widely. The percentages of patients with lipid profiles measured by individual physicians ranged from 0% to 83%, while the percentages of patients on drug treatment by a physician ranged between 10% and 88%. These findings indicate that socioeconomic differences, represented by different practice settings, do not account for differences in the screening for, control of, or use of medications in managing hyperlipidemia. Rather, individual physicians are accountable for differences in lipid management.

In vitro glycolysis of whole blood can detect primed neutrophils in septic ICU patients.

The purpose of this study was to develop a bedside assay based on the in vitro glycolysis of a whole blood sample that could detect primed neutrophils (PMNs). A mathematical index of the PMN response to exogenous stimulation with phorbol myristate 13-acetate (PMA), called the Delta value, was derived by comparing the increase in glycolysis for paired blood samples with and without PMA to that expected from normal subjects. Delta values for systemic inflammatory response syndrome/sepsis patients (9.09 +/- 7.61) (N = 36) were significantly higher than normal controls (2.02 +/- 1.76) (N = 51), nonsepsis ICU patients (3.81 +/- 2.80) (N = 14) and patients in septic shock (2.33 +/- 3.04) (N = 10) (p < .05). Delta values were consistently reflected in parallel measurements of increased reactive oxygen species production by neutrophils detected cytofluorometrically. PMN priming can be simply and rapidly detected by an assay based on the numbers of PMNs and erythrocytes and the measured rates of in vitro glycolysis of paired whole blood samples with and without PMA.

Decreased efficacy of inhaled pentamidine in the prevention of Pneumocystis carinii pneumonia among HIV-infected patients with severe immunodeficiency.

STUDY OBJECTIVE: To determine the relationship between the degree of immune deficiency and the risk of Pneumocystis carinii pneumonia (PCP) among HIV-infected patients receiving inhaled pentamidine prophylaxis. DESIGN: Retrospective chart review. SETTING: AIDS clinic of inner-city hospital. PATIENTS: Patients attending inhaled pentamidine clinic between 1989 and 1991. INTERVENTION: Review of medical records of patients receiving inhaled pentamidine, 300 mg/month, via nebulizer (Respirgard II) as primary or secondary prophylaxis of PCP. Statistical analysis of lymphocyte subset results and selected clinical data. RESULTS: Ten of 57 patients developed PCP during the period of analysis. Patients with CD4 counts less than 60/mm3 were significantly more likely to develop PCP (p = 0.01; Fisher's exact test) with a relative risk of 7.55 compared to patients with CD4 lymphocyte counts greater than 60/mm3. CONCLUSION: Failure of inhaled pentamidine prophylaxis is seen almost exclusively among patients with CD4 lymphocyte counts below 60/mm3.

Study of a needleless intermittent intravenous-access system for peripheral infusions: analysis of staff, patient, and institutional outcomes.

OBJECTIVE: To assess the effect on staff- and patient-related complications of a needleless intermittent intravenous access system with a reflux valve for peripheral infusions. DESIGN: A 6-month cross-over clinical trial (phase I, 13 weeks; phase II, 12 weeks) of a needleless intermittent intravenous access system (NL; study device) compared to a conventional heparin-lock system (CHL, control device) was performed during 1991 on 16 medical and surgical units. A random selection of patients was assessed for local intravenous-site complications; all patients were assessed for the development of nosocomial bacteremia and device-related complications. Staff were assessed for percutaneous injuries and participated in completion of product evaluations. A cost analysis of the study compared to the control device was performed. SETTING: A 1,100-bed, teaching, referral medical center. PATIENTS AND STAFF PARTICIPANTS: 594 patients during 602 patient admissions, comprising a random sample of all patients with a study or control device inserted within a previous 24-hour period on study and control units, were assessed for local complications. The 16 units included adult inpatient general medicine, surgical, and subspecialty units. Pediatrics, obstetrics-gynecology, and intensive-care units were excluded. All patients on study and control units were assessed for development of nosocomial bacteremia and device-related complications. All staff who utilized, manipulated, or may have been exposed to sharps on study and control units were assessed for percutaneous injuries. Nursing staff completed product evaluations. INTERVENTION: The study device, a needleless intermittent intravenous access system with a reflux valve, was compared to the control device, a conventional heparin lock, for peripheral infusions. RESULTS: During the study, 35 percutaneous injuries were reported. Eight injuries were CHL-related; no NL-related injuries were reported (P=.007). An evaluation of 602 patient admissions, 1,134 intermittent access devices, and 2,268 observed indwelling device days demonstrated more pain at the insertion site for CHL than NL; however, no differences in objective signs of phlebitis were noted. Of 773 episodes of positive blood cultures on study and control units, 6 (0.8%) were device-related (assessed by blinded investigator), with no difference between NL and CHL. Complications, including difficulty with infusion (P<.001) and disconnection of intravenous tubing from device (P<.001), were reported more frequently with CHL than with NL. Of nursing staff responding to a product evaluation survey, 95.2% preferred the study over control device. The projected annual incremental cost to our institution for hospitalwide implementation of NL for intermittent access for peripheral infusions was estimated at $82,845, or $230 per 1,000 patient days. CONCLUSIONS: A needleless intermittent intravenous access system with a reflux valve for peripheral infusions is effective in reducing percutaneous injuries to staff and is not associated with an increase in either insertion-site complications or nosocomial bacteremia. Institutions should consider these data, available institutional resources, and institution-specific data regarding the frequency and risk of intermittent access-device-related injuries and other types of sharps injuries in their staff when selecting the above or other safety devices.

Beliefs, social normative influences, and compliance with antihypertensive medication.

We explored the relationship between beliefs and social normative influences and self-reported hypertension medication compliance using questionnaire items based on the belief intention model of Ajzen and Fishbein. Persons for whom antihypertensive medication had been prescribed were asked to agree or disagree with statements about taking their medicine. Respondents were a subset of participants in a 1980 survey of risk factors for heart disease in two Pennsylvania counties. Highly significant differences between compliant and noncompliant individuals were observed for all items except one referring to cost. A stepwise multiple logistic regression analysis was performed with age, sex, and the belief and social normative items as independent variables, and reported compliance as the dependent variable. Three variables, age, "taking my blood pressure medicine as the doctor told me would not be necessary when my blood pressure is normal," and "your family wants you to take your blood pressure medicine as the doctor told you," entering into the equation in that order, significantly improved discrimination between compliant and noncompliant persons. The questionnaire's success may have resulted from moving beyond assessing participant's knowledge or beliefs about hypertension in the abstract to ascertaining the direct relevance of these beliefs to their taking their medicine.

Tuberculosis prevention: cost-effectiveness analysis of isoniazid chemoprophylaxis.

Isoniazid chemoprophylaxis is not recommended for all persons infected with tubercle bacilli. Because of the small but significant risk of isoniazid hepatotoxicity, chemoprophylaxis is reserved for only those at the highest risk of tuberculosis activation. To evaluate this policy, we performed a cost-effectiveness analysis of isoniazid chemoprophylaxis for two populations with positive tuberculin skin tests: recent tuberculin converters, who are at high risk for activation, and older tuberculin reactors, who have a low risk for activation and for whom chemoprophylaxis is not now recommended. The cost-effectiveness ratios found were stable, despite wide variations in model assumptions and probability estimates. For high-risk tuberculin reactors, chemoprophylaxis resulted in net medical care monetary savings, extended life expectancy, and fewer fatal illnesses. For low-risk tuberculin reactors, chemoprophylaxis resulted in positive, but small, health effects. Because the cost to gain these positive effects were also small, the resulting cost-effectiveness ratios were reasonable and in the realm of accepted prevention strategies: $12,625 to gain one year of life and $35,011 to avert one death. These findings suggest that the current policy is too restrictive and that many in the large population of low-risk tuberculin reactors should be considered for isoniazid chemoprophylaxis.

Tuberculin screening: cost-effectiveness analysis of various testing schedules.

Because there is no tuberculin screening schedule currently recommended for adults, we used a Markov process in a cost-effectiveness analysis to determine an optimal strategy. We simulated the prognosis of a cohort of black 20-year-olds to evaluate the effects of various screening schedules with intradermal tuberculin and administration of isoniazid prophylaxis to those with positive results. The schedule with the lowest cost-effectiveness ratio is a single screening at 50 years of age, which costs $41,672 per quality-adjusted life year (QALY) gained. The cost-effectiveness ratio is nearly the same for all schedules involving a single screening between 30 and 70 years of age. Repeated screening strategies are less cost effective. Sensitivity analysis shows that the range of acceptable screening strategies changes significantly under alternate assumptions about the mortality from isoniazid hepatitis. However, screening at 50 years of age remains nearly optimal under the alternatives considered. Altering the values of other parameters generally produced only small changes. Tuberculin screening at 50 years of age should be added to primary care preventive practices because the strategy is as cost effective as standard health interventions and is robust to alternative assumptions. If further research confirms the base case assumptions about isoniazid toxicity, consideration should be given to increasing screening to every 10 years, which would produce a larger health benefit, albeit at substantially higher cost.

Contingency valuation and preferences of health states associated with side effects of antipsychotic medications in schizophrenia.

The purpose of this study was to investigate the construct validity and the test-retest reliability of the willingness to pay (WTP) method for estimating health state preferences associated with side effects of antipsychotic medication. Ninety-six schizophrenia patients on antipsychotics were asked (1) how much they would be willing to pay to get rid of side effects with 100 percent probability, (2) a standard gamble (SG) question measuring utilities of patient's health state associated with side effects, and (3) their WTP to get rid of side effects based on the utility found with SG. Patients were divided into three groups based on severity of side effects. There was a significant difference between side effect severity groups for (1) the utility associated with side effects (Kruskal-Wallis [K-W] chi-square = 8.48, p = 0.014), and (2) their WTP to get rid of side effects with either 100 percent probability (K-W chi-square = 14.32,p = 0.001) or based on the utility associated with side effects (K-W chi-square = 5.96, p = 0.051). There was a significant correlation between utility and the WTP based on utility (Spearman r = -0.42, p = 0.003). Because of a wide variation in side effects at the 1-month interval, we were unable to assess the test-retest reliability of SG and WTP. Our results suggest that WTP has some construct validity in valuating and measuring preferences of health states associated with side effects of antipsychotics in schizophrenia.

Decision analysis in formulary decision making.

Although decision making about what drugs to include in an institutional formulary appears to lend itself readily to quantitative techniques such as decision analysis and cost-benefit analysis, a review of the literature reveals that very little has been published in this area. Several of the published decision analyses use non-standard techniques that are, at best, of unproved validity, and may seriously distort the underlying issues through covert under-counting or double-counting of various drug attributes. Well executed decision analyses have contributed to establishing that drug acquisition costs are not an adequate measure of the total economic impact of formulary decisions and that costs of labour and materials associated with drug administration must be calculated on an institution-specific basis to reflect unique staffing patterns, bulk purchasing practices, and the availability of surplus capacity within the institution which might be mobilised at little marginal cost. Clinical studies of newly introduced drugs frequently fail to answer the questions that weigh most heavily on the structuring of a formal assessment of a proposed formulary acquisition. Studies comparing a full spectrum of therapeutically equivalent drugs are rarely done, and individual studies of particular pairs of drugs can rarely be used together because of differences in methodology or patient populations studied. Gathering of institution-specific economic and clinical data is a daunting, labour-intensive task. In many institutions, incentive and reward structures discourage behaviour that takes the broad institutional perspective that is intrinsic to a good decision analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Sequential decision making with continuous disease states and measurements: I. Theory.

The question of whether to perform a continuous valued test to assess a continuous valued health state such as blood pressure or serum cholesterol is explored by decision analysis. Principal assumptions are that the underlying health state and measurement variability are both normally distributed, and that the impact of treatment on the utility of outcomes varies linearly with the underlying health state. Using Bayes' theorem, an expression for the expected utility of performing the test is derived and compared with immediate treatment or decision to withhold treatment. The calculations can be carried out with a pocket calculator and a table of the normal distribution. Iterating the analysis, a sequential decision making process is developed, leading to a series of no treat/test again and test again/treat thresholds with which a running average of independently obtained measurements can be compared to produce stepwise optimal results. The thresholds are readily calculated on a microcomputer. Finally, the conjugate-normal-linear model is extended to encompass the correlated observations that may be made on a single visit. This paper concentrates on the mathematics of decision making with continuous variables. The companion paper illustrates its application to diastolic blood pressure.

Sequential decision making with continuous disease states and measurements: II. Application to diastolic blood pressure.

The model and strategy for sequential decision making using normally distributed measurements proposed in a companion paper are applied to the problem of diagnosing diastolic hypertension. The assumptions of the model are discussed and justified clinically. Methods for assigning values to the model's parameters are explained and illustrated in the context of a hypothetical "generic" patient. Although current national recommendations and the sequential strategy both lead to an average of 1.89 measurements per patient prior to diagnosis, the sequential strategy applies a sequence of four or more measurements to 12% of patients. Fewer than 1% of patients would require ten or more measurements under this strategy. The sequential strategy leads to fewer patients' receiving unnecessary treatment and substantially higher expected utility for the patient. The role of multiple blood pressure determinations per visit is explored in the absence of appropriate estimates. Even under "best-case" assumptions, however, it is shown that obtaining more than one observation per visit is called for only in about 15% of visits. While the exact role of multiple determinations cannot be specified from existing data, it is likely to be much more limited than current recommendations suggest.