Self-reported health outcomes in patients with psoriasis and psoriatic arthritis randomized to two etanercept regimens.

BACKGROUND: Moderate/severe psoriasis combined with psoriatic arthritis (PsA) impairs health-related quality of life (QoL). Etanercept, a fully human tumour necrosis factor-α receptor fusion protein, is approved for treatment of both diseases. OBJECTIVE: To compare patient-reported health outcomes (PROs) of two etanercept regimens in patients with moderate/severe psoriasis and PsA. METHODS: In this randomized, double-blind, multicenter study, participants received etanercept 50 mg twice weekly (BIW; n = 379) or 50 mg weekly (QW; n = 373) for 12 weeks and open-label etanercept 50 mg QW for 12 additional weeks. PROs included: the EuroQOL-5D (EQ-5D), which measures general health status and consists of the utility index measuring five dimensions of health, and a visual analogue scale (VAS) allowing patients to assess health status; the Dermatology Life Quality Index (DLQI), which measures the impact of skin disease on QoL; the Health Assessment Questionnaire-Disability Index (HAQ-DI), an assessment of physical function; the Hospital Anxiety and Depression Scale (HADS), which screens for anxiety and depression symptoms; and individual questions on general health, disease activity, fatigue, itching, joint pain and morning stiffness. RESULTS: At baseline, patients reported QoL worse than that seen in many chronic medical conditions. Significant within-group improvements in each PRO occurred from baseline to Week 12 (P < 0.001) in both groups and were maintained at Week 24; DLQI, EQ-5D, HAQ-DI and self assessments improved significantly (P < 0.001) from baseline as early as Week 3. At Week 12, but not Week 24, improvement in DLQI, itching and psoriasis activity was greater in the BIW arm (P ≤ 0.004). Improvements in other PROs were always similar between groups. CONCLUSIONS: Greater improvements in PROs specific to skin disorders were seen with etanercept BIW than QW at Week 12, but not at Week 24. Both etanercept regimens led to sustained PRO improvements, starting as early as Week 3.

Model of complications of NIDDM. II. Analysis of the health benefits and cost-effectiveness of treating NIDDM with the goal of normoglycemia.

OBJECTIVE: To analyze the health benefits and economics of treating NIDDM with the goal of normoglycemia. RESEARCH DESIGN AND METHODS: Incidence-based simulation model of NIDDM was used. Hazard rates for complications were adjusted for glycemia using risk gradients from the Diabetes Control and Complications Trial. Treatment costs were estimated from national survey data and clinical trials. Incremental costs and benefits were expressed in present value dollars (3% discount rate). Life-years were adjusted for quality of life, yielding quality-adjusted life-years (QALYs). RESULTS: Comprehensive treatment of NIDDM that maintains an HbA1c value of 7.2% is predicted to reduce the cumulative incidence of blindness, end-stage renal disease, and lower-extremity amputation by 72, 87, and 67%, respectively. Cardiovascular disease risk increased by 3% (no effect of treating glycemia is assumed). Life expectancy increased 1.39 years. The cost of treating hyperglycemia increased by almost twofold, which is partially offset by reductions in the cost of complications. The estimated incremental cost/QALY gained is $16,002. Treatment is more cost-effective for those with longer glycemic exposure (earlier onset of diabetes), minorities, and those with higher HbA1c under standard care. CONCLUSIONS: The incremental effectiveness of treating NIDDM with the goal of normoglycemia is estimated to be approximately $16,000/QALY gained, which is in the range of interventions that are generally considered cost-effective.

Model of complications of NIDDM. I. Model construction and assumptions.

OBJECTIVE: To develop a model of NIDDM for analyzing prevention strategies for NIDDM. RESEARCH DESIGN AND METHODS: A Markov type model with Monte Carlo techniques was used. Age, sex, and ethnicity of cohort was based on U.S. data. Incidence rates of complications were also based on community and population studies. RESULTS: Nonproliferative retinopathy, proliferative retinopathy, and macular edema are predicted in 79, 19, and 52%, respectively, of people with NIDDM; 19% are predicted to develop legal blindness. Microalbuminuria, gross proteinuria, and end-stage renal disease related to diabetes are predicted in 53, 40, and 17%, respectively. Symptomatic sensorimotor neuropathy and lower-extremity amputation are predicted in 31 and 17%, respectively. Cardiovascular disease is predicted in 39%. Higher rates of complications (1.1-3.0x) are predicted in minority populations. Predicted average life expectancy is 17 years after diagnosis. CONCLUSIONS: A probabilistic model of NIDDM predicts the vascular complications of NIDDM in a cohort representative of the incident cases of diabetes in the U.S. before age 75 years. Predictions of complications and mortality are consistent with the known epidemiology of NIDDM. The model is suitable for evaluating the effect of preventive interventions on the natural history of NIDDM.

Effectiveness and costs of digoxin treatment for atrial fibrillation and flutter.

Clinical outcomes and costs associated with the use of digoxin in atrial fibrillation and flutter were evaluated in a prospective, observational study at 18 academic medical centers in the United States. Data were collected on 115 patients (aged > 18 years) with atrial fibrillation or flutter who were treated with digoxin for rapid ventricular rate (> or = 120 beats/min). The median time to ventricular rate control (i.e., resting ventricular rate < 100 beats/min, decrease in ventricular rate of > 20%, or sinus rhythm) was 11.6 hours from the first dose of digoxin for all evaluable patients (n = 105) and 9.5 hours for those only receiving digoxin (n = 64). Before ventricular rate control, the mean +/- SD dose of digoxin administered was 0.80 +/- 0.74 mg, and a mean of 1.4 +/- 1.8 serum digoxin concentrations were ordered per patient. Concomitant beta-blocker or calcium antagonist therapy was instituted in 47 patients (41%); in 19 of these, combination therapy was initiated within 2 hours. Adenosine was administered to 13 patients (11%). Patients spent a median of 4 days (range 1 to 25) in the hospital; 28% spent time in a coronary/intensive care unit and 79% in a telemetry bed. Loss of control (i.e., resting ventricular rate returned to > 120 beats/min) occurred at least once in 50% of patients and was associated with a longer hospital stay (p < 0.05). Based on 1991 data, the estimated mean hospital bed cost for patients with atrial fibrillation or flutter was $3,169 +/- $3,174.(ABSTRACT TRUNCATED AT 250 WORDS)

Predicting 10-year care requirements for older people with suspected Alzheimer's disease.

OBJECTIVE: To describe the types and costs of care received for 10 years after the identification of an older person with suspected Alzheimer's disease (AD) by using data from 3254 patients with suspected AD who participated in the National Long Term Care Survey (NLTCS). METHODS: By using a Markov model derived using grade of membership techniques, the following were determined: survival probabilities at 10 years; years of survival during the 10 years; years in institutions; years with two or more impairments in basic activities of daily living; hours of paid and informal care while the older person lived in the community; and costs of paid community, institutional, and medical care. RESULTS: Greater degrees of cognitive impairment present when AD was identified were associated with reduced predicted probability of surviving 10 years, increased predicted number of years spent in institutions, increased hours of care required while affected individuals remained in the community, and increased costs of paid community, institutional, and medical care. Substantial differences between men and women were seen: severity-adjusted 10-year costs were almost two times higher for women with AD than for men ($75,000 compared with $44,000); according to sensitivity analysis, average 10-year costs might be as high as $109,000 for women and $67,000 for men. CONCLUSIONS: AD imposes a substantial burden on older persons. Interventions that slow the progression of the disease may therefore affect community survival as well as healthcare costs.

Assessing the responsiveness of a quality-of-life instrument and the measurement of symptom severity in essential hypertension.

A pilot study was conducted to compare symptoms elicited with an open-ended question versus a checklist and to measure the responsiveness of quality-of-life measures to symptom severity. The pilot study was part of a multicentre, randomised, double-blind, placebo-controlled study of clentiazem, a calcium channel blocker, in the treatment of essential hypertension. Symptom and quality-of-life data were obtained from 88 patients at baseline and after 10 weeks of therapy by a trained telephone interviewer. Comparison of the symptom checklist and open-ended question method suggests that both methods are necessary to capture severe symptomatology. The 24-item checklist failed to elicit approximately 50% of the severe symptoms reported on the open question list. On the other hand, only 18% of the most severe symptoms subsequently reported on the checklist were first reported by the open question method. The responsiveness of quality-of-life measures to symptom severity was tested using a 20% change in symptom severity obtained from the checklist as the minimal clinically significant difference. Using Guyatt's formula, a minimum sample size of approximately 428 (alpha = 0.05, beta = 0.10) patients per treatment group is required to detect differences in measures of general health perception, anxiety, depression and limitations in social activities. A larger sample is required to show differences in leisure activities. Differences in limitations of the capability to perform house or yard work might be demonstrable with as few as 17 patients per group. This pilot study demonstrated that the severity of symptoms associated with hypertension, and the side effects of its treatment with drugs, are adequately captured by a symptom checklist preceded by an open-ended method of questioning. Responsiveness testing estimated the sample size required to show a statistically significant difference, assuming a 20% change in symptom severity.

The validity and reproducibility of a work productivity and activity impairment instrument.

The construct validity of a quantitative work productivity and activity impairment (WPAI) measure of health outcomes was tested for use in clinical trials, along with its reproducibility when administered by 2 different methods. 106 employed individuals affected by a health problem were randomised to receive either 2 self-administered questionnaires (self administration) or one self-administered questionnaire followed by a telephone interview (interviewer administration). Construct validity of the WPAI measures of time missed from work, impairment of work and regular activities due to overall health and symptoms, were assessed relative to measures of general health perceptions, role (physical), role (emotional), pain, symptom severity and global measures of work and interference with regular activity. Multivariate linear regression models were used to explain the variance in work productivity and regular activity by validation measures. Data generated by interviewer-administration of the WPAI had higher construct validity and fewer omissions than that obtained by self-administration of the instrument. All measures of work productivity and activity impairment were positively correlated with measures which had proven construct validity. These validation measures explained 54 to 64% of variance (p less than 0.0001) in productivity and activity impairment variables of the WPAI. Overall work productivity (health and symptom) was significantly related to general health perceptions and the global measures of interference with regular activity. The self-administered questionnaire had adequate reproducibility but less construct validity than interviewer administration. Both administration methods of the WPAI warrant further evaluation as a measure of morbidity.

Mannitol injections: with or without filter needles? A cost-effectiveness analysis.

A clinical economic evaluation was conducted to assess the cost-effectiveness of filtration of i.v. mannitol injections. Clinical decision analysis was used to model the costs and benefits of using filter needles for undiluted, i.v. push injections of mannitol 25%. Sensitivity analysis conducted by varying all uncertain variables to test best and worst case scenarios revealed that the use of filter needles is a cost-effective measure in all relevant scenarios.

Compatibility and stability of cefazolin sodium, clindamycin phosphate, and gentamicin sulfate in two intravenous solutions.

We studied the compatibility and stability of clindamycin phosphate admixed with gentamicin sulfate and cefazolin sodium in small-volume diluents under specific storage conditions. In two replicate 100 ml dilutions of NaCl 0.9% injection and dextrose 5% (D5W) injection, clindamycin phosphate 900 mg was admixed with gentamicin sulfate 80 mg and cefazolin sodium 1 g. Drug concentrations were determined at the time of preparation and at 1, 4, 8, 12, 24, and 48 hours. Clindamycin and cefazolin were assayed by high-performance liquid chromatography and gentamicin was assayed by fluorescence polarization immunoassay. Visual inspections and pH determinations of each solution were performed at each assay time. Test solutions were maintained at constant room temperature and fluorescent lighting. Concentrations of clindamycin and gentamicin remained greater than 90 percent of the original concentrations throughout the study. Cefazolin concentrations dropped below 90 percent in D5W injection at 4 hours after admixture and at 12 hours after admixture in NaCl 0.9% injection. Visual analyses and pH changes revealed no significant changes. The combination of clindamycin phosphate 900 mg, gentamicin sulfate 80 mg, and cefazolin sodium 1 g in D5W 100 ml was found to be compatible for up to 4 hours. The duration of compatibility for these three drugs in 100 ml of NaCl 0.9% was 12 hours.

Pharmacoeconomic analysis of ondansetron versus metoclopramide for cisplatin-induced nausea and vomiting.

A pharmacoeconomic analysis of ondansetron versus metoclopramide use in patients receiving high-dose cisplatin therapy is reported. A meta-analysis of the literature was performed to synthesize the results of clinical trials of ondansetron and metoclopramide for the prevention of nausea and vomiting in patients receiving high-dose cisplatin therapy. A cost-benefit analysis was performed by constructing a decision tree of the possible outcomes of treatment with ondansetron or metoclopramide. Clinical outcomes were measured by counting the emesis episodes occurring within 24 hours after the antiemetic was given and the extrapyramidal reactions occurring after metoclopramide was given. The improvement in quality of life was transformed to an increase in quality-adjusted life years (QALYs) in order to conduct a cost-utility analysis. Only direct costs of drug, materials, and labor were included in the cost calculations. The meta-analysis, combined with empirical observations, yielded expected emesis rates of 2.03 and 2.69 per patient for ondansetron and metoclopramide, respectively. The rate of extrapyramidal symptoms for metoclopramide recipients was 6.8%. The cost-benefit analysis yielded estimated total costs of $139 ($211) and $116 ($154) per 40-kg (70-kg) patient receiving ondansetron and metoclopramide, respectively. The cost-utility analysis yielded an incremental cost of ondansetron of $168,391 ($407,667) per QALY in 40-kg (70-kg) patients. Sensitivity analysis showed robustness of the expected outcomes except in a best-case scenario. A cost-utility analysis suggested that, compared with metoclopramide, ondansetron provides a small antiemetic benefit at a large additional cost.

Compatibility and stability of clindamycin phosphate-aminoglycoside combinations within polypropylene syringes.

The stability and compatibility of clindamycin phosphate admixed separately with gentamicin sulfate, tobramycin sulfate, and amikacin sulfate in polypropylene syringes under specific storage conditions were studied. In duplicate syringes, clindamycin phosphate 900 mg was admixed with sterile NaCl 0.9% l ml and with either gentamicin sulfate 120 mg, tobramycin sulfate 120 mg, or amikacin sulfate 750 mg. In duplicate polypropylene syringes, control solutions of clindamycin phosphate and each aminoglycoside were prepared separately and stored under the same conditions. The clindamycin control consisted of clindamycin phosphate 900 mg in 6 ml. The gentamicin and tobramycin controls consisted of gentamicin sulfate and tobramycin sulfate 120 mg in 3 ml plus 1 ml of sterile NaCl 0.9%. The amikacin control consisted of amikacin sulfate 750 mg in 3 ml plus 1 ml of sterile NaCl 0.9%. Drug concentrations were determined at the time of preparation and 1, 4, 8, 12, 24, and 48 hours thereafter. Aminoglycosides were assayed by fluorescence polarization immunoassay and clindamycin was assayed by high performance liquid chromatography. Visual inspections and pH determinations of each combination and control solution were performed at each assay time. For the clindamycin, gentamicin, tobramycin, and amikacin control solutions, changes in concentration were within ten percent of the original concentration. Concentrations of clindamycin and gentamicin when admixed together also remained within ten percent of the original concentration. Similar results were found with concentrations of clindamycin and amikacin when admixed together. Tobramycin and clindamycin formed a lasting precipitate upon initial contact when admixed under the study conditions.