Cost-effectiveness of diagnostic imaging work-up and treatment for patients with intermittent claudication in The Netherlands.

OBJECTIVE: to determine the societal cost-effectiveness of various management strategies, including both the diagnostic imaging work-up and treatment, for patients with intermittent claudication in The Netherlands. METHODS: a decision-analytic model was used and included probability and quality of life data available from the literature. A cost-analysis was performed in a university setting in The Netherlands. Imaging work-up options included magnetic resonance angiography (MRA), color-guided duplex ultrasound, or intraarterial digital subtraction angiography (DSA) and treatment options were percutaneous transluminal angioplasty with selective stent placement if feasible or bypass surgery. Management strategies were defined as combinations of imaging work-up and treatment options. A conservative strategy with no imaging work-up and walking exercises was considered as reference. Main outcome measures were quality-adjusted life years (QALYs), lifetime costs (euro), and incremental cost-effectiveness (CE) ratios. The base-case analysis evaluated 60-year-old men with severe unilateral intermittent claudication of at least one year duration. RESULTS: the range in QALYs and costs across management strategies that considered angioplasty as only treatment option was small (maximum difference: 0.0033 QALYs and 451 euros). Similarly, the range was small across management strategies that considered angioplasty if feasible otherwise bypass surgery (maximum difference: 0.0033 QALYs and 280 euros). MRA in combination with angioplasty (6.1487 QALYs and 8556 euros) had a CE ratio of 20,000 euros/QALY relative to the conservative strategy. The most effective strategy was DSA in combination with angioplasty if feasible otherwise bypass surgery (6.2254 QALYs and 18,583 euros) which had a CE ratio of 131,000 euros/QALY relative to MRA in combination with angioplasty. CONCLUSION: the results suggest that the imaging work-up with non-invasive imaging modalities can replace DSA for the work-up of patients with intermittent claudication without a substantial loss in effectiveness and a minimal cost-reduction. Management strategies including angioplasty are cost-effective in the Netherlands but although strategies including bypass surgery are more effective, their incremental costs are very high.     

Two amino-acid substitutions in the myelin protein zero gene of a case of Charcot-Marie-Tooth disease associated with light-near dissociation.

Charcot-Marie-Tooth disease caused by mutations of the myelin protein zero gene demonstrates considerable phenotypical variability. We describe a 45-year-old female with a peripheral neuropathy with demyelinating and axonal features, pes cavus and pupillary light-near dissociation. She was heterozygous for two mutations in the myelin protein zero gene (His81Tyr and Val113Phe), both present on the same allele. Our patient shows a less severe phenotype than previously described patients with a His81Arg mutation. Multiple mutations in the myelin protein zero gene, as well as Charcot-Marie-Tooth with pupillary abnormalities have previously been described in rare instances. However, concurrent occurrence of both phenomena is a novel finding.     

Transesophageal echocardiography in pediatric patients: preliminary results

Transesophageal echocardiography was attempted in 59 pediatric patients with congenital heart disease in the operating room (n = 33) or during heart catheterization or in the intensive care unit (n = 26). Six different commercially available transducers were used with diameters ranging from 7 to 15 mm. Age ranged from 1 day to 16 years, and body weight ranged from 3.7 to 65 kg. Objectives of the study were to determine (1) minimum body weight in which transesophageal echocardiography with various probes is possible, (2) additional diagnostic value, and (3) potential applications. In three cases (one surgical and two nonsurgical) the probe could not be inserted. Minimum body weight was 17 to 20 kg for probes with a diameter of greater than or equal to 13 mm and approximately 12 kg for the 11 mm probes. A 7 mm probe, on the other hand, could be inserted easily in all patients (including a neonate) in whom transesophageal echocardiography was attempted. In 11 of 56 patients, additional diagnostic information was obtained. Thus, transesophageal echocardiography is feasible in the pediatric age group provided that special probes are used in small children. Additional diagnostic information can be obtained, and the technique is of value during cardiac surgery or balloon interventions for evaluation of the efficacy of the procedure and for monitoring ventricular function.     

Anterior temporal focal abnormalities in EEG in normal aged subjects; correlations with psychopathological and CT brain scan findings

Normal aged subjects (65-83 years) were examined by EEG and CT brain scan; also a Geriatric Mental Scale (GMS) and Neuropsychologic Assessment Battery were administered. Based on the EEG findings 2 subgroups could be distinguished: one with focal abnormalities in the left fronto-temporal region and one without these focal abnormalities. The focal delta subgroup proved to perform poorly on the Fluency Test, a simple quick bedside, but very sensitive, test for word association productivity. Also this subgroup showed more ventricular dilatation than the non-focal group. Therefore slight left-sided antero-temporal abnormalities in normal aged subjects are not irrelevant but an early (subclinical) sign of temporal lobe pathology as expressed in deterioration of language function.     

Prospect for enzyme therapy in glycogenosis II variants: a study on cultured muscle cells

Summary Impairment of skeletal muscle function is the common feature of distinct clinical forms of glycogenosis type II. In the present study, muscle cultures from different patients were used to investigate the cause of clinical heterogeneity and the feasibility of enzyme replacement therapy. The activity of acid -glucosidase appears to be the primary factor in determining the extent of lysosomal glycogen storage in muscle, and thereby the clinical severity of the disease. Neutral -glucosidases do not seem influencial. Correction of the enzymatic defect was achieved in skeletal muscle cultures from patients by administration of a high-uptake form of acid -glucosidase, purified from human urine. The enzyme reaches the lysosomes, including the glycogen storage vacuoles, and the lysosomal glycogen content is reduced to control level. In normal muscle cells 20% of the total cellular glycogen pool is segregated in lysosomal compartments. This percentage is higher than in fibroblasts, which may partly explain why muscles are more prone to store glycogen. The relevance of this study for enzyme therapy is discussed.     

Construction and performance of a new catheter-tip oxygen electrode

A membrane-covered catheter-tip oxygen-electrode system is described, which gives a linear response in the P_o2 range of 0–350 mm Hg. The system is highly stable, free from drift and mechanically safe for application in man. This is accomplished by using a screw cap for fastening the membrane holder, thus preventing the loss of parts and making the electrolyte chamber really fluidtight. Insulation of the platinum wire with glass precludes the possibility of fluid-bridge contact with the silver anode beyond the measuring site at the tip.     

Managing COPD: no more nihilism!

This special issue of Patient Education and Counseling is long overdue. During most of the last two decades asthma, and notably asthma self-management has been in the spotlight, while COPD has had to endure a nihilistic approach. The first sign that interest was shifting to the treatment of COPD came from a few large randomized trials on the use of inhaled corticosteroids (ICS) in COPD. Although these studies demonstrated a moderate effect of ICS in COPD, it has become clear that true improvements in the management of this chronic disease will have to come from behavioral interventions. This special issue of Patient Education and Counseling is dedicated solely to the non-pharmaceutical management of COPD. It addresses many issues related to behavioral therapy, such as smoking cessation, exercise training, nutritional aspects, and self-management programs, including action plans to self-treat exacerbations. With the availability of all the treatment and management options, described in this special issue, a nihilistic attitude toward the patient with COPD is no longer justified.     

HLA-DQ-associated predisposition to and dominant HLA-DR-associated protection against rheumatoid arthritis

We have recently proposed a new hypothesis to explain the association of Human Leukocyte Antigen (HLA) with rheumatoid arthritis (RA) predisposition. In this model, which challenges the Shared Epitope (SE) hypothesis, HLA-DQ predisposes while HLA-DR protects. In the present study, we have compared these two models in an Early Arthritis Clinic started in 1993 in the Department of Rheumatology at the Leiden University Medical Centre. Out of 524 patients who enrolled this programme in the period 1993-1998 and completed the one year follow-up, 155 have been classified as RA. These patients along with 306 consecutive cadaveric renal organ donors have been typed for HLA-DR and -DQ. The distributions of predisposing DR alleles according to SE, and predisposing DQ and protective DR according to our model were analysed. We found that two doses of predisposing DQ alleles strongly predisposed to RA, even in individuals with a single dose of SE while DRB1 alleles carrying the motif DERAA confered a dominant protection in DQ5-positive individuals. We conclude that the present findings are consistent with our previously described model of HLA and RA association. Using this new model, we have been able to characterise two novel groups of individuals on the basis of their HLA typing: one strongly predisposed to RA and one protected. Knowing the mechanism of HLA-related dominant natural protection may help in designing novel treatment modalities for RA.