Is thrombolysis of lower extremity acute arterial occlusion cost-effective?

BACKGROUND: The TOPAS (thrombolysis or peripheral artery surgery) trial randomized 544 patients with acute lower extremity ischemia to either surgery or thrombolysis. Although statistically equivalent 1-year morbidities and mortalities were demonstrated, the comparative cost-effectiveness of these two interventions has not been explored. MATERIALS AND METHODS: We constructed a Markov decision-analytic model to determine the cost-effectiveness of thrombolysis relative to surgery for a hypothetical cohort of patients with acute lower extremity arterial occlusion. Our measure of outcome was the cost-effectiveness ratio (CER), defined as the incremental lifetime cost per quality-adjusted life year gained. Estimates of 1-year outcomes were based on the TOPAS trial: mortality (lysis, 20%; surgery, 17%), amputation (lysis, 15%; surgery, 13%), the number of additional interventions required following the initial procedure (lysis, 544; surgery, 439). Procedural costs were estimated from the cost accounting system at the New York Presbyterian Hospital as well as from the literature. RESULTS: Operative intervention for acute lower extremity arterial occlusion extended life and was less costly compared to thrombolysis. The projected life expectancy for patients who underwent initial surgery was 5.04 years versus 4.75 years for initial thrombolysis. The lifetime costs were $57,429 for surgery versus $dollar;76,326 for thrombolysis. In performing sensitivity analyses, a threshold CER of $60,000 was considered what society would pay for accepted medical interventions. Thrombolysis became cost-effective if the 1-year mortality rate for lysis was lowered from 20 to 10.7%, if the amputation rate for lysis diminished from 15 to 3.9%, or if the 1-year cost of lysis could be reduced to a level below $13,000. CONCLUSIONS: Initial surgery provides the most efficient and economical utilization of resources for acute lower extremity arterial occlusion. The high cost of thrombolysis is related to the expense of the lytic agents, the need for subsequent interventions in patients treated with initial lysis, and the long-term costs of amputation in patients who fail lytic therapy.     

Characterization of pristane‐induced arthritis,a murine model of chronic disease: Response to antirheumatic agents,expression of joint cytokines,and immunopathology

Objective

To characterize chronic murine pristane‐induced arthritis (PIA) with regard to the response to antirheumatic agents, expression levels of proinflammatory cytokines, and immunopathologic features.

Methods

Male DBA/1 mice were injected intraperitoneally with pristane oil to induce a chronic polyarthritis, which was monitored by visual scoring. Serum antibody and splenocyte responses to a panel of putative joint‐derived autoantigens were measured. Whole paws were evaluated postmortem for changes in the levels of proinflammatory cytokines tumor necrosis factor α (TNFα), interleukin‐1β (IL‐1β), and IL‐6 by enzyme‐linked immunosorbent assay, and standard histopathology techniques were used to determine joint structural changes. Therapeutic studies were performed for up to 8 weeks of dosing with prednisolone, methotrexate, 3 nonsteroidal antiinflammatory drugs (celecoxib, diclofenac, and indomethacin), a p38 MAPK inhibitor, SB242235, and human soluble TNF receptor (sTNFR; etanercept) and murine sTNFR fusion proteins.

Results

Antibody and cellular responses to the putative joint autoantigens revealed a broad extent of autoimmunity in PIA. TNFα, IL‐1β, and IL‐6 were all persistently up‐regulated in PIA joints. Prednisolone, methotrexate, celecoxib, indomethacin, and SB242235 all significantly reduced the arthritis scores. Etanercept was ineffective in reducing the arthritis scores, whereas murine sTNFR produced a significant, but nonsustained, benefit. Only prednisolone significantly reduced the expression of TNFα, IL‐1β, and IL‐6 in the joints. Prednisolone and methotrexate demonstrated the most effective joint protection.

Conclusion

We have markedly extended the characterization of PIA as a murine model of chronic inflammatory arthritis by demonstrating cellular and humoral autoantigenicity, elevation of clinically precedented joint cytokines, and variation in the response to several antirheumatic therapies. PIA offers significant potential for the long‐term study of immunopathologic mechanisms and novel therapies in rheumatoid arthritis.

     

Detection of monosomy 7 and trisomy 8 in myeloid neoplasia: a comparison of banding and fluorescence in situ hybridization

Fluorescence in situ hybridization (FISH) is a powerful tool for detection of numerical and structural chromosomal aberrations. We have compared conventional banding techniques and FISH for the detection of monosomy 7 (-7) and trisomy 8 (+8) in 89 patients with myeloid malignancies. Of these patients, 21 had -7, 30 had +8, four had both, and 34 had no aberrations or aberrations other than -7 or +8 as assessed by banding techniques. Sequential samples were available in 23 patients. Alphoid DNA probes specific for chromosomes no. 7 and 8 were used for FISH. As controls, 10 normal bone marrow (BM) samples were hybridized with the chromosomes no. 7 and 8 probes, and in addition all tumor samples were hybridized with a chromosome no. 1 specific probe. The cut-off value for -7 was 18% one-spot cells, and for +8 was 3% three-spot cells. FISH analysis of 44 samples with -7 or +8, and at least 10 metaphases evaluated, showed that the proportions of aberrant metaphase cells mirrored the interphase clone sizes. Most samples with nonclonal metaphase aberrations, including those with only a few metaphases, had increased numbers of aberrant interphase cells: 20% to 80% for -7, and 3% to 43% for +8. Interphase cytogenetics of the 34 samples without -7 or +8 did not show significant cell populations with -7 or +8. In four patients, -7 or +8 could not be confirmed by FISH due to additional structural aberrations, marker chromosomes, or wrongly interpreted banding results. As FISH will be used more and more in cytogenetic diagnosis, clinical follow-up, and therapy monitoring, it will be necessary to standardize FISH procedures and supplement the Standing Committee on Human Cytogenetic Nomenclature (ISCN) definitions of a clone with criteria specifically for in situ hybridization.     

氨基多糖对RANKL诱导的RAW264.7向破骨细胞样细胞分化的抑制作用观察

目的 探讨氨基多糖(GAGs)对核因子KB受体活化因子配体(RANKL)诱导的RAW264.7向破骨细胞分化的影响.方法 采用RANKL单独诱导RAW264.7细胞(对照组),分别采用不同浓度肝素、高分子量透明质酸(HA)、硫酸软骨素(CS)C联合RANKL诱导RAW264.7分化(分别为肝素组、HA组、CSC组).细胞培养第3、5、7、8天采用抗酒石酸酸性磷酸酶染色法(TRAP)检测破骨细胞样细胞并计数;ELISA法检测第8天各组培养液上清中抗酒石酸酸性磷酸酶5b(TRAP5b)含量.结果 与对照组比较,诱导第3、5、7、8天,破骨样细胞数均明显减少(P＜0.05);其中肝素组随浓度的增大而减少(P＜0.05).第8天培养液中TRAP5b含量与细胞计数结果相符.结论 氨基多糖对RANKL诱导下RAW264.7向破骨细胞样细胞的分化具有抑制作用;肝素的作用具有剂量依赖性.     

Prospective genomically guided identification of “early/evolving” and “undersampled” IDH-wildtype glioblastoma leads to improved clinical outcomes

BackgroundGenomic profiling studies of diffuse gliomas have led to new improved classification schemes that better predict patient outcomes compared to conventional histomorphology alone. One example is the recognition that patients with IDH-wildtype diffuse astrocytic gliomas demonstrating lower-grade histologic features but genomic and/or epigenomic profile characteristic of glioblastoma typically have poor outcomes similar to patients with histologically diagnosed glioblastoma. Here we sought to determine the clinical impact of prospective genomic profiling for these IDH-wildtype diffuse astrocytic gliomas lacking high-grade histologic features but with molecular profile of glioblastoma.MethodsClinical management and outcomes were analyzed for 38 consecutive adult patients with IDH-wildtype diffuse astrocytic gliomas lacking necrosis or microvascular proliferation on histologic examination that were genomically profiled on a prospective clinical basis revealing criteria for an integrated diagnosis of “diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, WHO grade IV” per cIMPACT-NOW criteria.ResultsWe identified that this diagnosis consists of two divergent clinical scenarios based on integration of radiologic, histologic, and genomic features that we term “early/evolving” and “undersampled” glioblastoma, IDH-wildtype. We found that prospective genomically guided identification of early/evolving and undersampled IDH-wildtype glioblastoma resulted in more aggressive patient management and improved clinical outcomes compared to a biologically matched historical control patient cohort receiving standard-of-care therapy based on histomorphologic diagnosis alone.ConclusionsThese results support routine use of genomic and/or epigenomic profiling to accurately classify glial neoplasms, as these assays not only improve diagnostic classification but critically lead to more appropriate patient management that can improve clinical outcomes.     

Changes in health among 45–64-year-old Dutch persons before,during and after becoming unemployed or employed: a seven year follow-up study

ObjectivesThis study aimed to evaluate the extent to which physical and mental health and body mass index (BMI) changed before, during and after becoming unemployed or employed, and whether these associations differ across psychosocial and physical working conditions.MethodsParticipants from seven waves (2010–2017) of the Dutch longitudinal Study on Transitions in Employment, Ability, and Motivation (STREAM) aged 45–64 years were included. STREAM provides information on physical and mental health, BMI and working conditions, and was enriched with monthly information on income components from Statistics Netherlands to define employment status during 2010–2017. Annual changes in physical and mental health (0–100 scales), and BMI (kg/m²) before, during and after becoming unemployed (N=13 279) and employed (N=1902) were estimated with generalized linear mixed-effect models.ResultsBefore employed persons became unemployed they had poorer health than continuously employed persons, which worsened in the period before becoming unemployed. During the year of becoming unemployed, physical [b=1.45, 95% confidence interval (CI) 0.89–2.01] and mental health (b=1.46, 95% CI 0.85–2.07) improved, in particular among persons with unfavorable working conditions. After becoming unemployed physical health deteriorated (b=-0.52, 95% CI -0.80– -0.24) and BMI (b=0.11, 95% CI 0.03–0.19) increased, but mental health improved (b=0.33, 95% CI 0.02–0.63). Unemployed persons had better health before entering employment than continuously unemployed persons. The health of persons who entered employment did not statistically significantly change before or during the year of the transition. After entering employment, physical health deteriorated and BMI increased.ConclusionsMaintaining a healthy workforce and limiting unfavorable working conditions may contribute to the prevention of unemployment and the promotion of re-integration.     

Stability of therapeutic drugs in serum collected in vacutainer serum separator tubes containing a new gel (SST II)

The stability of therapeutic drugs in sera collected in Becton-Dickinson Vacutainer serum separator SST tubes has been well studied. Although most therapeutic drugs are stable, certain drugs such as phenytoin, carbamazepine, and phenobarbital decrease in concentrations over a long storage time. To circumvent this problem, Becton-Dickinson devised a new gel formulation. The authors studied the stability of 14 commonly monitored drugs in sera when stored on the new gel of the SST II tubes and compared the concentrations of drugs in sera stored in plain tubes (no gel), those stored in the old SST tubes, and those stored in the SST II tubes containing a new serum separator gel. The concentrations of most drugs studied did not decline even after 24 hours of storage in SST II tubes. After storage for 7 days in SST II tubes, the concentration of carbamazepine declined by 10% and that of phenytoin decreased by 4%. This is a significant improvement over the existing tube, where concentrations of several drugs declined with prolonged storage. The authors conclude that new SST II tubes are effective in collecting blood for therapeutic drug monitoring.