Cost-effectiveness analysis of a placebo-controlled randomized trial evaluating the effectiveness of arthroscopic subacromial decompression in patients with subacromial shoulder pain.

AIMS: The aims of this study were to compare the use of resources, costs, and quality of life outcomes associated with subacromial decompression, arthroscopy only (placebo surgery), and no treatment for subacromial pain in the United Kingdom National Health Service (NHS), and to estimate their cost-effectiveness. PATIENTS AND METHODS: The use of resources, costs, and quality-adjusted life-years (QALYs) were assessed in the trial at six months and one year. Results were extrapolated to two years after randomization. Differences between treatment arms, based on the intention-to-treat principle, were adjusted for covariates and missing data were handled using multiple imputation. Incremental cost-effectiveness ratios were calculated, with uncertainty around the values estimated using bootstrapping. RESULTS: Cumulative mean QALYs/mean costs of health care service use and surgery per patient from baseline to 12 months were estimated as 0.640 (standard error (se) 0.024)/£3147 (se 166) in the decompression arm, 0.656 (se 0.020)/£2830 (se 183) in the arthroscopy only arm and 0.522 (se 0.029)/£1451 (se 151) in the no treatment arm. Statistically significant differences in cumulative QALYs and costs were found at six and 12 months for the decompression versus no treatment comparison only. The probabilities of decompression being cost-effective compared with no treatment at a willingness-to-pay threshold of £20 000 per QALY were close to 0% at six months and approximately 50% at one year, with this probability potentially increasing for the extrapolation to two years. DISCUSSION: The evidence for cost-effectiveness at 12 months was inconclusive. Decompression could be cost-effective in the longer-term, but results of this analysis are sensitive to the assumptions made about how costs and QALYs are extrapolated beyond the follow-up of the trial.

Macular translocation with radial scleral ouffolding: experimental studies and initial human results.

PURPOSE: Different techniques have been proposed for translocating the macula in patients with subfoveal neovascularization secondary to age-related macular degeneration. A new approach utilizing radial outfolding of the sclera was investigated. MATERIALS AND METHODS: Surgical techniques and retinal displacement were evaluated in animal trials using metal scleral clips. Successful translocation and reattachment of the retina was achieved in eight rabbits (eight eyes). We conducted a retrospective review of macular translocation surgery, performed with radial scleral outfolding, in a series of five consecutive human patients (five eyes) using full-thickness transscleral mattress sutures. RESULTS: After surgery, vision improved in two of five patients, with one patient achieving a visual acuity of 20/50. The mean angle of rotation was 11.5 deg (range 8.6 -15.1). The mean amount of foveal displacement was 1,276 pm (range 852-1,620). Complications included one case of retinal detachment, one of diplopia, and one of subretinal hemorrhage. CONCLUSIONS: Limited macular translocation by radial scleral outfolding can improve vision in selected patients. Radial evagination appears to be as effective as circumferential infolding.

Active Fe-containing superoxide dismutase and abundant sodF mRNA in Nostoc commune (Cyanobacteria) after years of desiccation.

Active Fe-superoxide dismutase (SodF) was the third most abundant soluble protein in cells of Nostoc commune CHEN/1986 after prolonged (13 years) storage in the desiccated state. Upon rehydration, Fe-containing superoxide disumutase (Fe-SOD) was released and the activity was distributed between rehydrating cells and the extracellular fluid. The 21-kDa Fe-SOD polypeptide was purified, the N terminus was sequenced, and the data were used to isolate sodF from the clonal isolate N. commune DRH1. sodF encodes an open reading frame of 200 codons and is expressed as a monocistronic transcript (of approximately 750 bases) from a region of the genome which includes genes involved in nucleic acid synthesis and repair, including dipyrimidine photolyase (phr) and cytidylate monophosphate kinase (panC). sodF mRNA was abundant and stable in cells after long-term desiccation. Upon rehydration of desiccated cells, there was a turnover of sodF mRNA within 15 min and then a rise in the mRNA pool to control levels (quantity of sodF mRNA in cells in late logarithmic phase of growth) over approximately 24 h. The extensive extracellular polysaccharide (glycan) of N. commune DRH1 generated superoxide radicals upon exposure to UV-A or -B irradiation, and these were scavenged by SOD. Despite demonstrated roles for the glycan in the desiccation tolerance of N. commune, it may in fact be a significant source of damaging free radicals in vivo. It is proposed that the high levels of SodF in N. commune, and release of the enzyme from dried cells upon rehydration, counter the effects of oxidative stress imposed by multiple cycles of desiccation and rehydration during UV-A or -B irradiation in situ.

Immunomodulatory effects of linomide in animals immunized with immunopathogenic retinal antigens: dissociation between different immune functions.

Linomide (LS-2616, quinoline-3-carboxamide) has been reported to exert a diverse range of effects on the immune system. On one hand, this drug was found to stimulate the immune system and to enhance activities such as DTH or allograft rejection. On the other hand, linomide was shown to inhibit the induction of experimental autoimmune encephalomyelitis and myasthenia gravis, as well as the development of diabetes in non-obese diabetic (NOD) mice. Here we report the effects of linomide in animals immunized with uveitogenic retinal antigens. Treatment with linomide completely inhibited the development of experimental autoimmune uveoretinitis (EAU) in mice immunized with interphotoreceptor retinoid-binding protein and markedly suppressed EAU in rats immunized with S-antigen (S-Ag). In addition, linomide-treated rats exhibited reduced antibody production and lymphocyte proliferative response to S-Ag. In contrast to these suppressive activities, linomide treatment did not affect the development of adoptively transferred EAU in rats and moderately enhanced the DTH reactions to S-Ag in immunized rats in which EAU and other immune responses to this antigen were suppressed.

T-lymphocyte subsets in nephrotic syndrome.

T-lymphocyte subsets when measured in steroid responsive nephrotic syndrome (SRNS) have demonstrated significant variance from normal values. T-cell subsets were studied by using two-color flow cytometric analysis in 32 children (9.2 +/- 5 years of age) with SRNS. The children were divided into four groups: a) SRNS in acute relapse, on prednisone; b) SRNS in acute relapse, off prednisone; c) SRNS in long-term remission, off prednisone (nephrotic controls); d) patients in remission on long-term prednisone therapy; and e) 15 age-matched normal controls. Children suffering an acute relapse of SRNS showed an increase in Leu2a+/DR+ (CD8) activated lymphocytes (P less than 0.05), a decrease in Leu4a+ total T-lymphocytes (P = 0.01) and a decrease in Leu3a+ (CD4) helper T-cells (P less than 0.05) when compared to normal controls and nephrotic controls. Though some subset changes may represent a prednisone effect and the functional role of these lymphocytes in the disease process is unknown, this study provides additional evidence to support a role for abnormal T-cell subsets in the etiology of SRNS.

Effect of growth hormone on kidney growth and glomerular structure.

The effect of growth hormones (GH) on renal growth was measured in growing uremic rats using a five-sixths nephrectomy model and GH, 5 mg/kg per day. At the end of 8 weeks, somatic size was significantly smaller in the untreated uremic rats. The uremic rats given GH were the same size as the non-uremic control animals. Organ size (heart, liver and kidney) differed in that only untreated uremic animals had a significantly smaller kidney weight. Despite a five-sixths nephrectomy, the uremic animals receiving GH had kidneys the same size as sham-operated control animals. Renal function was not changed by GH therapy in either control or uremic animals. DNA content expressed as milligrams per kilogram kidney tissue was low only in the untreated uremic rats. Glomerular volume and proximal tubular area were elevated in both groups of uremic animals but were elevated to a significantly greater degree in those receiving GH. GH given in large doses to growing animals appears to induce both somatic and renal growth.