Measurement of health-related quality of life in patients with amyotrophic lateral sclerosis in clinical trials of new therapies.

OBJECTIVES: Recent trials of amyotrophic lateral sclerosis (ALS) therapies have included the Sickness Impact Profile (SIP) to evaluate health-related quality of life (HQL). The purpose of this study was to assess the feasibility, psychometric properties, and interpretation of the Sickness Impact Profile in this setting. METHODS: The Sickness Impact Profile was administered at baseline, 3, 6, and 9 months during a double-blind, placebo-controlled study of recombinant human insulin-like growth factor I. The frequency of missing Sickness Impact Profile data and administration time were recorded. Patients' scores on the Appel ALS (AALS) Rating Scale were used to identify a stable subgroup for reliability testing and clinically distinct groups for validity testing. Internal consistency reliability and reproducibility were evaluated using Cronbach's alpha and intraclass correlation coefficients, respectively. Analysis of variance (ANOVA) models and t tests were used to assess validity. Effect sizes and the responsiveness index were used to assess responsiveness. RESULTS: At baseline, 259 (97%) patients completed a 30-minute Sickness Impact Profile interview. At subsequent assessments, response rates ranged from 92% to 97% and mean administration times ranged from 25 to 27 minutes. The overall Sickness Impact Profile score demonstrated alpha reliability and 3-month stability coefficients of 0.94 and 0.80, respectively. Baseline overall Sickness Impact Profile scores discriminated between patients in the two AALS-defined groups with a mean of 13.0+/-7.8 and 24.0+/-11.7 in the better and worse AALS groups, respectively. Similarly, mean overall SIP change scores discriminated patients progressing at different rates (slow to moderate = 4.00+/-7.97; rapid = 10.74+/-8.76). With few exceptions, dimension and category scores met similar criteria. Responsiveness statistics for the physical and overall Sickness Impact Profile scores were lower at 3 months and higher at 6 and 9 months. CONCLUSIONS: The feasibility, psychometric, and interpretive findings support the validity of the Sickness Impact Profile for assessing outcomes of amyotrophic lateral sclerosis and its treatment. Based on these findings, we recommend including the Sickness Impact Profile in future amyotrophic lateral sclerosis clinical trials.

Cost effectiveness of recombinant human insulin-like growth factor I therapy in patients with ALS.

OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a fatal, degenerative neuromuscular disease characterised by a progressive loss of voluntary motor activity. Recombinant human insulin-like growth factor I (rhIGF-I) has been shown to be useful in treating ALS. The purpose of this study was to examine the cost effectiveness of rhIGF-I therapy in patients who have ALS. DESIGN: We performed a cost-effectiveness analysis from the societal perspective on 177 patients who received treatment with rhIGF-I or placebo in a North American randomised clinical trial. We estimated the incremental cost-effectiveness ratio of rhIGF-I using resource utilisation and functional status measurements from the clinical trial. Costs were estimated from 1996 US Medicare reimbursement schedules. Utility weights were elicited from ALS healthcare providers using the standard gamble technique. MAIN OUTCOME MEASURES AND RESULTS: The overall cost per quality-adjusted life-year (QALY) gained for rhIGF-I therapy compared with placebo was $US67,440. For the subgroups of patients who were progressing rapidly or were in earlier stages of disease at enrolment, rhIGF-I cost $US52,823 and $US43,197 per QALY gained, respectively. CONCLUSIONS: Treatment with rhIGF-I is most cost effective in ALS patients who are either in earlier stages of the disease or progressing rapidly. The cost effectiveness of rhIGF-I therapy compares favourably with treatments for other chronic progressive diseases.

Effect of recombinant human insulin-like growth factor-I on progression of ALS. A placebo-controlled study. The North America ALS/IGF-I Study Group.

The objective of this study was to investigate the safety and efficacy of recombinant human insulinlike growth factor-I (rhIGF-I) in the treatment of sporadic ALS. A double-blind, placebo-controlled, randomized study of 266 patients was conducted at eight centers in North America. Placebo or rhIGF-I (0.05 mg/kg/day or 0.10 mg/kg/day) was administered for 9 months. The primary outcome measure was disease symptom progression, assessed by the rate of change (per patient slope) in the Appel ALS rating scale total score. The Sickness Impact Profile (SIP), a patient-perceived, health-related quality of life assessment, was a secondary outcome variable. Progression of functional impairment in patients receiving high-dose (0.10 mg/kg/day) rhIGF-I was 26% slower than in patients receiving placebo (p = 0.01). The high-dose treatment group was less likely to terminate the study due to protocol-defined markers of disease symptom progression, and members in this group exhibited a slower decline in quality of life, as assessed by the SIP. Patients receiving 0.05 mg/kg/day of rhIGF-I exhibited trends similar to those associated with high-dose treatment, suggesting a dose-dependent response. The incidence of clinically significant adverse experiences was comparable among the three treatment groups. Recombinant human insulin-like growth factor-I slowed the progression of functional impairment and the decline in health-related quality of life in patients with ALS with no medically important adverse effects.

Post-anesthesia uncal herniation secondary to a previously unsuspected temporal glioma.

We report the case of a 21-year-old male who sustained an uncal herniation and subsequent brain death following general anesthesia, for a minor orthopedic procedure, owing to the presence of a large, unsuspected temporal glioma. The possible factors responsible for the precipitation of this event are appraised.

Incidence of cavum septum pellucidum in adults: a sign of boxer's encephalopathy.

We studied the relative frequency of cavum septum pellucidum (CSP) by CT. Six of 9 men with CSP were boxers or had head trauma. We conclude that some cases of CSP are not congenital variants, but rather may serve as an indicator of prior head trauma, especially in boxers. In such instances, CSP may be a CT sign of traumatic encephalopathy.

Malignant hyperthermia susceptibility in X-linked muscle dystrophies.

To evaluate malignant hyperthermia (MH) susceptibility in X-linked muscular dystrophies, halothane and caffeine contracture tests were performed on muscle fiber bundles from five patients with Duchenne muscular dystrophy (DMD) and two patients with Becker muscular dystrophy (BMD). Two DMD patients and one BMD patient had positive contracture tests. Since a positive contracture test is currently the best indicator of anesthetic susceptibility in the MH population, and episodes of MH in dystrophic patients have been reported, patients with DMD and BMD may be at risk for developing similar anesthetic complications. Awareness of this potential anesthetic risk is of importance because orthopedic interventions are increasingly more common in these patients.