Cost-effectiveness analysis of additional docetaxel for metastatic hormone-sensitive prostate cancer treated with androgen-deprivation therapy from a Chinese perspective.

The E3805 (CHAARTED) study found that docetaxel combined with androgen-deprivation therapy (ADT) significantly improved overall survival of patients with metastatic hormone-sensitive prostate cancer. This study aims to determine whether docetaxel combined with ADT is a cost-effective strategy for advanced prostate cancer in China. According to the E3805 study, two groups (docetaxel + ADT and ADT alone) and three health states [progression-free survival (PFS), progressive disease (PD) and death] were analysed in a Markov model. All medical costs were calculated from the Chinese societal perspective. Quality-adjusted life year (QALY) and incremental cost-effectiveness ratios (ICERs) were applied as the primary outcome. Overall, the addition of docetaxel was estimated to increase the cost by $12 816.93, with a gain of 0.48 QALY. Additionally, for patients with high-volume disease, the increased cost and effectiveness were $14 627.75 and 0.69 QALYs in docetaxel + ADT group versus the ADT alone group, and the ICER was $21 199.63 per QALY. These ICERs are far more than the commonly accepted willingness-to-pay (WTP) threshold of $20 301 per QALY in China. In spite of longer survival time, docetaxel combined with ADT is not a recommended cost-effective treatment for metastatic hormone-sensitive prostate cancer in the Chinese setting.

Molecular and cellular effects of chemicals disrupting steroidogenesis during early ovarian development of brown trout (Salmo trutta fario).

A range of chemicals found in the aquatic environment have the potential to influence endocrine function and affect sexual development by mimicking or antagonizing the effects of hormones, or by altering the synthesis and metabolism of hormones. The aim of this study was to evaluate whether the effects of chemicals interfering with sex hormone synthesis may affect the regulation of early ovarian development via the modulation of sex steroid and insulin-like growth factor (IGF) systems. To this end, ex vivo ovary cultures of juvenile brown trout (Salmo trutta fario) were exposed for 2 days to either 1,4,6-androstatriene-3,17-dione (ATD, a specific aromatase inhibitor), prochloraz (an imidazole fungicide), or tributyltin (TBT, a persistent organic pollutant). Further, juvenile female brown trout were exposed in vivo for 2 days to prochloraz or TBT. The ex vivo and in vivo ovarian gene expression of the aromatase (CYP19), responsible for estrogen production, and of IGF1 and 2 were compared. Moreover, 17ß-estradiol (E2) and testosterone (T) production from ex vivo ovary cultures was assessed. Ex vivo exposure to ATD inhibited ovarian E2 synthesis, while T levels accumulated. However, ATD did not affect ex vivo expression of cyp19, igf1, or igf2. Ex vivo exposure to prochloraz inhibited ovarian E2 production, but did not affect T levels. Further prochloraz up-regulated igf1 expression in both ex vivo and in vivo exposures. TBT exposure did not modify ex vivo synthesis of either E2 or T. However, in vivo exposure to TBT down-regulated igf2 expression. The results indicate that ovarian inhibition of E2 production in juvenile brown trout might not directly affect cyp19 and igf gene expression. Thus, we suggest that the test chemicals may interfere with both sex steroid and IGF systems in an independent manner, and based on published literature, potentially lead to endocrine dysfunction and altered sexual development.

Ecotoxicology of synthetic pyrethroids.

In this chapter we review the ecotoxicology of the synthetic pyrethroids (SPs). SPs are potent, broad-spectrum insecticides. Their effects on a wide range of nontarget species have been broadly studied, and there is an extensive database available to evaluate their effects. SPs are highly toxic to fish and aquatic invertebrates in the laboratory, but effects in the field are mitigated by rapid dissipation and degradation. Due to their highly lipophilic nature, SPs partition extensively into sediments. Recent studies have shown that toxicity in sediment can be predicted on the basis of equilibrium partitioning, and whilst other factors can influence this, organic carbon content is a key determining variable. At present for SPs, there is no clear evidence for adverse population-relevant effects with an underlying endocrine mode of action. SPs have been studied intensively in aquatic field studies, and their effects under field conditions are mitigated from those measured in the laboratory by their rapid dissipation and degradation. Studies with a range of test systems have shown consistent aquatic field endpoints across a variety of geographies and trophic states. SPs are also highly toxic to bees and other nontarget arthropods in the laboratory. These effects are mitigated in the field through repellency and dissipation of residues, and recovery from any adverse effects tends to be rapid.

Extent and sources of geographic variation in Medicare end-stage renal disease expenditures.

Geographic variations in practices and expenditures have been widely documented, leading to concerns that care in some regions is clinically suboptimal and/or economically inefficient. Our objectives are to determine the extent and sources of geographic variation in Medicare expenditures per patient with end-stage renal disease (ESRD) per year. The study population included all patients with ESRD with Medicare as primary payer during 1997 (n = 284,670). Medicare expenditures were summarized at the hospital referral region (HRR) level. Using regression analysis, we estimated the relationship between expenditures and demographics, case mix, dialysis provider characteristics, distribution of patients across renal replacement therapy modalities, standardized hospitalization ratios, and healthcare wages. Spending per patient-year varied threefold across HRRs, ranging from $17,791 to $59,025 (mean, $38,966 +/- $6,774 [SD]). The regression equation explained 80% of this variation. Although several demographic and case-mix indicators that have been related to spending at the individual level were statistically significant predictors of spending at the HRR level, they did not show enough geographic variation to explain a large fraction of spending variation. Rather, patient distributions across renal replacement modalities, hospitalization patterns, and healthcare wages were the most powerful predictors of spending. Compared with Medicare generally, both the mean and SD of ESRD expenditures were approximately seven times larger. The substantial geographic variability in expenditures for patients with ESRD indicates the potential for improving efficiency and quality of care. Interventions designed to increase transplantation rates, ensure access to peritoneal dialysis, and reduce hospitalization appear most promising.

A comparison of charges for continuous ambulatory peritoneal dialysis and center hemodialysis.

Use of continuous ambulatory peritoneal dialysis (CAPD) is increasing, and it is being promoted as a less expensive alternative to center hemodialysis (CHD). The debate over the relative charges for CAPD and CHD cannot generally be answered without considering the relationship between modality selection and patient characteristics. When selection and patient characteristics are accounted for, the difference between annual charges for CAPD and CHD patients is insignificant, in part because of the current payment system. The analysis suggests that patients using CHD may have lower charges than if they were using CAPD; similarly, patients using CAPD may have lower charges than if they were using CHD. Charges during CAPD training are lower than CHD or CAPD charges. Charges during the transition between CHD and CAPD tend to be higher than either CHD or CAPD due to additional hospitalizations. Estimated results suggest that encouraging current CHD patients to transfer to CAPD (or vice versa) may not have the desired effect of reducing charges.

Autogenous graft replacement of infected prosthetic grafts in the femoral position.

Infected prosthetic grafts in the femoral position remain among the most challenging problems in vascular surgery. Over the past 2 years, 11 patients with this critical condition have undergone graft reconstruction with autogenous tissue as described by Ehrenfeld. All infected prosthetic material was removed and replaced by an autogenous graft. The autogenous grafts were constructed with endarterectomized superficial femoral, iliac, and aortic segments as well as portions of saphenous and cephalic veins. This procedure has proven successful, resulting in only one amputation (undertaken with a still functioning autogenous graft) in the series. There was one postoperative death. Six grafts failed in long-term follow-up, due in all cases to inadequate flow because of stenosis of the saphenous vein portion of the autogenous reconstruction. However, the patients were usually free of infection by this time and underwent successful prosthetic reconstruction.

Freshly harvested cadaveric venous homografts as arterial conduits in infected fields.

Six patients with patent multilevel prosthetic grafts (three axillofemoral-femoral grafts, an aortobifemoral graft, an axillofemoral and femoral-anterior tibial graft, and an axillofemoral and femoral-popliteal graft) that demonstrated overt infection involving both the proximal inflow (one infrarenal aorta, five axillary arteries) and groin anastomoses required complete graft excision. Cadaveric inferior vena cava, common and external iliac, common and superficial femoral, and greater saphenous veins were harvested in conjunction with multiple organ donor procedures. Identical anatomic reconstruction within the infected fields was accomplished, with patency and distal perfusion maintained for intervals sufficient to achieve complete resolution of infection in all cases. This interval of revascularization with a venous homograft has served as a temporizing maneuver, which permitted eradication of infection and allowed subsequent reimplantation of prosthetic graft material without associated reinfection in the two instances in which it was required. Use of freshly harvested large-caliber caval, iliac, and femoral homograft veins as arterial substitutes in infected fields has not been previously reported. Case histories and a review of the venous homografting literature are included.

Optimal techniques for harvesting and preparation of reversed autogenous vein grafts for use as arterial substitutes: a review.

Since the first successful use of an autogenous vein graft for arterial reconstruction by Gluck in 1898 and the establishment of the scientific basis for the use of veins as arterial substitutes by Carrell and Guthrie in the early 1900s, reversed autogenous veins have been used extensively in arterial reconstructive operations. Despite being the preferred material for reconstruction, reversed autogenous vein is not an ideal graft material. The primary problem is structural alterations in the implanted vein predisposing to graft failure. Most of these failures occur within the first few months after graft implantation and are though to be due, in part, to endothelial damage incurred during harvesting and preparation of the vein. This review focuses on technical aspects of vein graft harvesting associated with alterations in endothelial morphology including dissection technique, types of irrigation and storage solutions used, temperature of these solutions, distension pressures, and pharmacologic agents. An optimal technique incorporating subcutaneous and perivenous infiltration with papaverine, atraumatic dissection, controlled gradual distension, and storage of the distended vein in cold heparinized blood containing papaverine should produce grafts with improved endothelial preservation and patency rates compared with grafts harvested by techniques in widespread use at present. The importance of morphologically and functionally intact endothelium in reversed vein grafts, a comparison to that produced by in situ vein grafting, and its possible clinical implications are discussed.

Hospital management contracts: institutional and community perspectives.

Previous studies have shown that external management by contract can improve the performance of managed hospitals. This article presents a conceptual framework which develops specific hypotheses concerning improved hospital operating efficiency, increased ability to meet hospital objectives, and increased ability to meet community objectives. Next, changes in the process and structure of management under contractual arrangements, based on observations from two not-for-profit hospital systems, are described. Finally, the effects of these management changes over time on hospital and community objectives are presented. These effects suggest progressive stages in the development of management contracts. The first stage focuses on stabilizing hospital financial performance. Stage two involves recruitment and retention efforts to secure necessary personnel. In the third stage, attention shifts to strategic planning and marketing.

Philanthropy and hospital financing.

OBJECTIVE: This study explores the relationships among donations to not-for-profit hospitals, the returns provided by these hospitals, and fund-raising efforts. It tests a model of hospital behavior and addresses an earlier debate regarding the supply price of donations. DATA SOURCES: The main data source is the California Office of Statewide Health Planning data tapes of hospital financial disclosure reports for fiscal years 1980/1981 through 1986/1987. Complete data were available for 160 hospitals. STUDY DESIGN: Three structural equations (donations, returns, and fund-raising) are estimated as a system using a fixed-effects, pooled cross-section, time-series least squares regression. PRINCIPAL FINDINGS: Estimation results reveal the expected positive relation between donations and returns. The reverse relation between returns and donations is insignificant. The estimated effect of fund-raising on donations is insignificantly different from zero, and the effect of donations on fund-raising is negative. Fund-raising and returns are negatively associated with one another. CONCLUSION: The empirical results presented here suggest a positive donations-returns relations and are consistent with a positive supply price for donations. Hospitals appear to view a trade-off between providing returns and soliciting donations, but donors do not respond equally to these two activities. Attempts to increase free cash flow through expansion of community returns or fund-raising activity, at least in the short run, are not likely to be highly successful financing strategies for many hospitals.

Financial and organizational determinants of hospital diversification into subacute care.

OBJECTIVE: To examine the financial, market, and organizational determinants of hospital diversification into subacute inpatient care by acute care hospitals in order to guide hospital managers in undertaking such diversification efforts. STUDY SETTING: All nongovernment, general, acute care, community hospitals that were operating during the years 1985 through 1991 (3,986 hospitals in total). DATA SOURCES: Cross-sectional, time-series data were drawn from the American Hospital Association's (AHA) Annual Survey of Hospitals, the Health Care Financing Administration's (HCFA) Medicare Cost Reports, a latitude and longitude listing for all community hospital addresses, and the Area Resource File (ARF) published in 1992, which provides county level environmental variables. STUDY DESIGN: The study is longitudinal, enabling the specification of temporal patterns in conversion, causal inferences, and the treatment of right-censoring problems. The unit of analysis is the individual hospital. KEY FINDINGS: Significant differences were found in the average level of subacute care offered by investor-owned versus tax-exempt hospitals. After controlling for selection bias, financial performance, risk, size, occupancy, and other variables, IO hospitals offered 31.3 percent less subacute care than did NFP hospitals. Financial performance and risk are predictors of IO hospitals' diversification into subacute care, but not of NFP hospitals' activities in this market. Resource availability appears to expedite expansion into subacute care for both types of hospitals. CONCLUSIONS: Investment criteria and strategy differ between investor-owned and tax-exempt hospitals.

"Soft" angled bulldog clamp for carotid control.

A bulldog vascular clamp was modified to reduce both weight and clamping force, and to permit easy use in the control of delicate vessels such as the internal carotid artery during carotid endarterectomy. The final instrument (Codman and Shurtleff, Inc, Randolph, MA) retains a simple design.

Initial results and subsequent outcome of laser thermal-assisted balloon angioplasty of 56 consecutive femoropopliteal lesions.

Laser thermal-assisted balloon angioplasty (LABA) was prospectively applied in the treatment of 56 atherosclerotic femoropopliteal occlusive lesions in 51 consecutive patients. All procedures were performed in the operating room using a neodynium:yttrium-aluminum-garnet (Nd:YAG) laser source, and patients were evaluated for immediate and long-term hemodynamic and clinical improvement. Technically successful recanalization was achieved in 82% of cases, with 57% of all patients (32 of 56) obtaining early hemodynamic and clinical improvement. Long-term clinical success (by life-table analysis) was obtained by only 22.5% at 6 months, and only 13.5% at 12 months. Patients presenting with intermittent claudication did significantly better than those presenting for limb salvage (p = 0.01), and trends toward improved outcome were noted for short versus long lesions as well as for patients with "good" versus "poor" distal runoff (NS). Procedure-related morbidity occurred in 14%, and there was one peri-procedural mortality (1.8%). We conclude that the use of LABA is associated with long-term clinical success in only a small proportion of patients, and that widespread clinical application of this technique is not indicated at the present time.

A comparison of surgery for neurogenic thoracic outlet syndrome between laborers and nonlaborers.

OBJECTIVE: To determine factors of outcome following surgical intervention for neurologic thoracic outlet syndrome (NTOS). METHODS: In a retrospective study of patients surgically treated for NTOS, outcome was evaluated by postoperative symptoms and the ability of patients to return to work. RESULTS: Good, fair, and poor results were obtained in 26 (48%), 21 (39%), and 7 (13%) patients, respectively. The best predictor of a good outcome was occupation. Nonlaborers were more likely to have good outcome (21 of 32, 66%) when compared with laborers (5 of 22, 23%; P = 0.0025). Only 6 of 20 (30%) laborers were able to return to their original occupation compared with 17 of 26 (65%) nonlaborers (P = 0.036). CONCLUSIONS: Laborers with NTOS are less likely to have a good result from surgical intervention, are unlikely to return to their original occupation, and may require retraining for a non-labor-intensive occupation if they cannot return to their original work.

Chylomicrons or their remnants penetrate rabbit thoracic aorta as efficiently as do smaller macromolecules, including low-density lipoprotein, high-density lipoprotein, and albumin.

BACKGROUND: The aortic accumulation of chylomicrons, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and albumin were compared in normal New Zealand White rabbits. METHODS: Lipoproteins and albumin were labelled with radioiodinated tyramine cellobiose (TC) to avoid potential oxidative modification of lipoproteins and as a marker of intracellular degradation. In preliminary experiments it was established that TC labelling did not alter the kinetic properties of lipoproteins in vivo. Importantly, radiolabelled apolipoproteins did not transfer significantly between plasma lipoproteins. Therefore, aortic radioactivity following infusion of TC-radiolabelled lipoproteins was considered to be indicative of lipoprotein accumulation. RESULTS: In conscious rabbits, net aortic accumulation of chylomicrons or their remnants was similar to those of LDL, HDL and albumin up to 2 h after infusion, despite rapid clearance from plasma. When accumulation was calculated on the basis of mean arterial exposure to allow for the differences in plasma clearance, the accumulation of aortic chylomicrons/remnants was substantially greater than that of LDL, HDL or albumin. Qualitatively similar results were obtained in rabbits that were functionally eviscerated to slow clearance of chylomicron remnants. Chylomicrons/remnants did not appear to efflux from aortic tissue as rapidly as did LDL or other plasma lipoproteins. Autoradiographic analysis showed that the primary site of lipoprotein accumulation was within medial smooth muscle cells. CONCLUSION: Our data demonstrate that chylomicrons/remnants accumulate in arterial blood vessels more rapidly than does LDL, suggesting that dietary lipoproteins may be directly involved in the pathogenesis of atherosclerosis.

Intraoperative iliac artery stents: combination with infra-inguinal revascularization procedures.

Iliac artery percutaneous transluminal angioplasty (PTA) can effectively provide in-flow for subsequent distal vascular reconstruction. Iliac artery stents may improve the initial hemodynamics and long term patency of PTA, and thus may be well-suited for combined proximal PTA with distal bypass procedures. This report reviews our preliminary experience with iliac artery stenting in combination with infra-inguinal vascular reconstruction. Thirteen iliac artery stent procedures combined with simultaneous distal revascularization were performed in 11 patients. Ten procedures were performed for limb salvage, two for disabling claudication, and one before planned orthopedic surgery. Distal revascularization procedures included seven femoropopliteal, four femorotibial bypasses, one common femoral endarterectomy, and one thrombectomy of a femoropopliteal bypass. Stent placement was technically successful in all patients. Mean pre-operative ankle-brachial index (ABI) was 0.41 (+/- 0.28), which improved to 0.91 (+/- 0.18) post-operatively (P < 0.0001). Mean systolic iliac artery gradients across the lesions improved from 27.1 (+/- 9.8) mm Hg to 2.7 (+/- 3.4) mm Hg after stent placement (P < 0.0001). Mean follow-up is 5.8 months (range 1-12 months). Two femoropopliteal bypass grafts occluded in the follow-up period. One occlusion was caused by a mid-vein graft stenosis that was repaired with subsequent graft patency. The other graft occlusion occurred in a patient with rest pain who did not require a second bypass procedure, as the ABI increased from 0.3 to 0.7 following stent placement with resolution of symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Coexistent abdominal aortic aneurysm and renal carcinoma: management options.

Renal carcinoma (RCA) presenting in association with abdominal aortic aneurysm (AAA) is extremely rare, with only sporadic case reports previously described. The management of six cases of AAA and concomitant RCA presenting to a single institution from March, 1991 through December, 1993 was reviewed and management options considered. AAAs ranged in size from 4.5-7.0 cm (mean, 5.6 cm). Three left renal carcinomas were resected via a retroperitoneal approach simultaneous to repair of the AAA. One right renal carcinoma was resected in combination with repair of an AAA through a transperitoneal approach. The fifth case was managed by left nephrectomy, followed by interval aneurysmectomy, and the sixth case was managed by nonsurgical methods because of the presence of widely metastatic disease. Renal malignancies included five renal cell carcinomas and one transitional cell carcinoma. Three patients remain free of disease 8-11 months postoperatively, and one patient had metastatic disease detected 19 months postoperatively. Two deaths have occurred; one due to a massive CVA 1 month following a combined aneurysmectomy and left nephrectomy, and a second due to unknown etiology in the patient managed non-surgically. No peripheral vascular or aortic graft related complications have occurred. The treatment of AAA and RCA should be governed by the size of the AAA, the location of the cancer, and the extent of malignant disease. Simultaneous resection is safe and effective in patients with coexistent AAA and renal cancer. Left sided tumors should be resected via a retroperitoneal approach that also provides excellent exposure for simultaneous AAA resection.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in functional health status of older women with heart disease: evaluation of a program based on self-regulation.

OBJECTIVES: This study involving 570 women aged 60 years or older with heart disease, assessed the effects of a disease management program on physical functioning, symptom experience, and psychosocial status. METHODS: Women were randomly assigned to control or program groups. Six to eight women met weekly with a health educator and peer leader over 4 weeks to learn self-regulation skills with physical activity as the focus. Evaluative data were collected through telephone interviews, physical assessments, and medical records at baseline and 4 and 12 months post baseline. RESULTS: At 12 months, compared with controls, program women were less symptomatic (p < .01), scored better on the physical dimension of the Sickness Impact Profile (SIP; p < 0.05), had improved ambulation as measured by the 6-minute walk (p < 0.01), and lost more body weight (p < .001). No differences related to psychosocial factors as measured by the SIP were noted. CONCLUSION: A self-regulation-based program that was provided to older women with heart disease and that focused on physical activity and disease management problems salient to them, improved their physical functioning and symptom experience. Psychosocial benefit was not evident and may be a result of measurement error or due to insufficient program time spent on psychosocial aspects of functioning.

The comparison of rapid bioassays for the assessment of urban groundwater quality.

Groundwater is a complex mixture of chemicals that is naturally variable. Current legislation in the UK requires that groundwater quality and the degree of contamination are assessed using chemical methods. Such methods do not consider the synergistic or antagonistic interactions that may affect the bioavailability and toxicity of pollutants in the environment. Bioassays are a method for assessing the toxic impact of whole groundwater samples on the environment. Three rapid bioassays, Eclox, Microtox and ToxAlert, and a Daphnia magna 48-h immobilisation test were used to assess groundwater quality from sites with a wide range of historical uses. Eclox responses indicated that the test was very sensitive to changes in groundwater chemistry; 77% of the results had a percentage inhibition greater than 90%. ToxAlert, although suitable for monitoring changes in water quality under laboratory conditions, produced highly variable results due to fluctuations in temperature and the chemical composition of the samples. Microtox produced replicable results that correlated with those from D. magna tests.

A posterior tunnel for the jugular venous catheter in newborns.

A modified technique of tunnelling for jugular venous catheters in the newborn is described. The technique eliminates cannula-kinking and offers a more convenient position for the catheter.