Low Fuel Convergence Path to Direct-Drive Fusion Ignition.

A new class of inertial fusion capsules is presented that combines multishell targets with laser direct drive at low intensity (2.8×10^{14} W/cm^{2}) to achieve robust ignition. The targets consist of three concentric, heavy, metal shells, enclosing a volume of tens of µg of liquid deuterium-tritium fuel. Ignition is designed to occur well "upstream" from stagnation, with minimal pusher deceleration to mitigate interface Rayleigh-Taylor growth. Laser intensities below thresholds for laser plasma instability and cross beam energy transfer facilitate high hydrodynamic efficiency (∼10%).

Patterns of blood product use among patients with myelodysplastic syndrome.

BACKGROUND AND OBJECTIVES: Most patients with myelodysplastic syndrome (MDS) require blood product support to manage the severe anaemias, which frequently accompany MDS. Our objective was to show the feasibility of linking the Surveillance, Epidemiology and End Results (SEER) database with records from Puget Sound Blood Center (PSBC) to characterize blood product use over time in successive cohorts of patients with MDS. MATERIALS AND METHODS: We identified patients with MDS in the SEER registry. The cohort was then linked to PSBC records to discern blood product use. RESULTS: Included in the analysis were 783 patients with MDS entered in the SEER database from 2001 to 2007 for whom data were also available in the PSBC database. Among patients with MDS who received transfusions, 97% received packed red blood cells; 52% received platelets. The proportion of patients with MDS receiving blood products declined from 2001 to 2007. CONCLUSION: These data show a recent decline in blood product use for patients with MDS. Future studies are needed to further evaluate the reasons for this finding, specifically exploring the impact of newer medications on blood product use in patients with MDS.

A comparison of approaches for association studies of polymorphisms and colorectal cancer risk.

AIM: Meta-analyses have been used to evaluate associations between polymorphisms and colorectal cancer risk, but the quality of individual studies used to inform them may vary substantially. Our aim was to apply well-established quality-control criteria to individual association studies and then compare the results of meta-analyses that included or excluded studies that did not meet these criteria. METHOD: We used meta-analyses of studies reporting a relationship between polymorphisms and colorectal cancer published between 1996 and 2008. Polymorphism-cancer associations were derived in separate meta-analyses including only those meeting the quality-control criteria. RESULTS: Relative ORs varied substantially between the open and restricted group meta-analyses for all variants except MTHFR 677 CT. However, the associations were modest and the direction of relative risk did not change after applying criteria. Publication bias was detected for all associations, except the restricted set of studies for GSTP1 GG. CONCLUSION: We observed variation in calculated relative risk and changes in tests for publication bias that were dependent on the inclusion criteria used for association studies of polymorphisms and colorectal cancer. Standardizing study inclusion criteria may reduce the variation in findings for meta-analyses of gene-association studies of common diseases such as colorectal cancer.

Randomized phase III trial of paclitaxel plus carboplatin versus vinorelbine plus cisplatin in the treatment of patients with advanced non--small-cell lung cancer: a Southwest Oncology Group trial.

PURPOSE: This randomized trial was designed to determine whether paclitaxel plus carboplatin (PC) offered a survival advantage over vinorelbine plus cisplatin (VC) for patients with advanced non--small-cell lung cancer. Secondary objectives were to compare toxicity, tolerability, quality of life (QOL), and resource utilization. PATIENTS AND METHODS: Two hundred two patients received VC (vinorelbine 25 mg/m(2)/wk and cisplatin 100 mg/m(2)/d, day 1 every 28 days) and 206 patients received PC (paclitaxel 225 mg/m(2) over 3 hours with carboplatin area under the curve of 6, day 1 every 21 days). Patients completed QOL questionnaires at baseline, 13 weeks, and 25 weeks. Resource utilization forms were completed at five time points through 24 months. RESULTS: Patient characteristics were similar between the groups. The objective response rate was 28% in the VC arm and 25% in the PC arm. Median survival was 8 months in both arms, with 1-year survival rates of 36% and 38%, respectively. Grade 3 and 4 leukopenia (P =.002) and neutropenia (P =.008) occurred more frequently on the VC arm. Grade 3 nausea and vomiting were higher on the VC arm (P =.001, P =.007), and grade 3 peripheral neuropathy was higher on the PC arm (P <.001). More patients on the VC arm discontinued therapy because of toxicity (P =.001). No difference in QOL was observed. Overall costs on the PC arm were higher than on the VC arm because of drug costs. CONCLUSION: PC is equally efficacious as VC for the treatment of advanced non--small-cell lung cancer. PC is less toxic and better tolerated but more expensive than VC. New treatment strategies should be pursued.

The role of hospital volume in coronary artery bypass grafting: is more always better?

OBJECTIVES: The goal of this study was to determine whether outcomes of nonemergent coronary artery bypass grafting (CABG) differed between low- and high-volume hospitals in patients at different levels of surgical risk. BACKGROUND: Regionalizing all CABG surgeries from low- to high-volume hospitals could improve surgical outcomes but reduce patient access and choice. "Targeted" regionalization could be a reasonable alternative, however, if subgroups of patients that would clearly benefit from care at high-volume hospitals could be identified. METHODS: We assessed outcomes of CABG at 56 U.S. hospitals using 1997 administrative and clinical data from Solucient EXPLORE, a national outcomes benchmarking database. Predicted in-hospital mortality rates for subjects were calculated using a logistic regression model, and subjects were classified into five groups based on surgical risk: minimal (< 0.5%), low (0.5% to 2%), moderate (2% to 5%), high (5% to 20%), and severe (> or =20%). We assessed differences in in-hospital mortality, hospital costs and length of stay between low- and high-volume facilities (defined as > or =200 annual cases) in each of the five risk groups. RESULTS: A total of 2,029 subjects who underwent CABG at 25 low-volume hospitals and 11,615 subjects who underwent CABG at 31 high-volume hospitals were identified. Significant differences in in-hospital mortality were seen between low- and high-volume facilities in subjects at moderate (5.3% vs. 2.2%; p = 0.007) and high risk (22.6% vs. 11.9%; p = 0.0026) but not in those at minimal, low or severe risk. Hospital costs and lengths of stay were similar across each of the five risk groups. Based on these results, targeted regionalization of subjects at moderate risk or higher to high-volume hospitals would have resulted in an estimated 370 transfers and avoided 16 deaths; in contrast, full regionalization would have led to 2,029 transfers and avoided 20 deaths. CONCLUSIONS: Targeted regionalization might be a feasible strategy for balancing the clinical benefits of regionalization with patients' desires for choice and access.

Incidence, outcomes, and cost of foot ulcers in patients with diabetes.

OBJECTIVE: To determine the incidence of foot ulcers in a large cohort of patients with diabetes, the risk of developing serious complications after diagnosis, and the attributable cost of care compared with that in patients without foot ulcers. RESEARCH DESIGN AND METHODS: Retrospective cohort study of patients with diabetes in a large staff-model health maintenance organization from 1993 to 1995. Patients with diabetes were identified by algorithm using administrative, laboratory, and pharmacy records. The data were used to calculate incidence of foot ulcers, risk of osteomyelitis, amputation, and death after diagnosis of foot ulcer, and attributable costs in foot ulcer patients compared with patients without foot ulcers. RESULTS: Among 8,905 patients identified with type 1 or type 2 diabetes, 514 developed a foot ulcer over 3 years of observation (cumulative incidence 5.8%). On or after the time of diagnosis, 77 (15%) patients developed osteomyelitis and 80 (15.6%) required amputation. Survival at 3 years was 72% for the foot ulcer patients versus 87% for a group of age- and sex-matched diabetic patients without foot ulcers (P < 0.001). The attributable cost for a 40- to 65-year-old male with a new foot ulcer was $27,987 for the 2 years after diagnosis. CONCLUSIONS: The incidence of foot ulcers in this cohort of patients with diabetes was nearly 2.0% per year. For those who developed ulcers, morbidity, mortality, and excess care costs were substantial compared with those for patients without foot ulcers. The results appear to support the value of foot-ulcer prevention programs for patients with diabetes.

The use of automated data to identify complications and comorbidities of diabetes: a validation study.

We evaluated the accuracy of administrative data for identifying complications and comorbidities of diabetes using International Classification of Diseases, 9th edition, Clinical Modification and Current Procedural Terminology codes. The records of 471 randomly selected diabetic patients were reviewed for complications from January 1, 1993 to December 31, 1995; chart data served to validate automated data. The complications with the highest sensitivity determined by a diagnosis in the medical records identified within +/-60 days of the database date were myocardial infarction (95.2%); amputation (94.4%); ischemic heart disease (90.3%); stroke (91.2%); osteomyelitis (79.2%); and retinal detachment, vitreous hemorrhage, and vitrectomy (73.5%). With the exception of amputation (82.9%), positive predictive value was low when based on a diagnosis identified within +/-60 days of the database date but increased with relaxation of the time constraints to include confirmation of the condition at any time during 1993-1995: ulcers (88.5%); amputation (85.4%); and retinal detachment, vitreous hemorrhage and vitrectomy (79.8%). Automated data are useful for ascertaining potential cases of some diabetic complications but require confirmatory evidence when they are to be used for research purposes.

Suboptimal medical therapy in COPD: exploring the causes and consequences.

Effective outpatient management of COPD requires prescription of and adherence to appropriate therapies. Although practice guidelines for outpatient management of COPD are widely available, evidence suggests that these guidelines are not being implemented widely in clinical practice. Furthermore, several studies have shown that patient compliance with recommended therapy is poor. This paper discusses several reasons why implementation of practice guidelines and adherence with prescribed therapies may be poor. Potential clinical and economic consequences of suboptimal management are reviewed. Although the evidence suggests that improved compliance with guideline-recommended practice will improve symptoms and disease-specific quality of life, further work needs to be done to establish the cost-effectiveness of chronic therapies for COPD relative to other chronic conditions. Without such data, managed care organizations will be reluctant to allocate scarce resources toward expensive guideline implementation programs for individuals with this condition.

The economic burden of COPD.

COPD is one of the leading causes of morbidity and mortality worldwide and imparts a substantial economic burden on individuals and society. Despite the intense interest in COPD among clinicians and researchers, there is a paucity of data on health-care utilization, costs, and social burden in this population. The total economic costs of COPD morbidity and mortality in the United States were estimated at $23.9 billion in 1993. Direct treatments for COPD-related illness accounted for $14.7 billion, and the remaining $9.2 billion were indirect morbidity and premature mortality estimated as lost future earnings. Similar data from another US study suggest that 10% of persons with COPD account for > 70% of all medical care costs. International studies of trends in COPD-related hospitalization indicate that although the average length of stay has decreased since 1972, admissions per 1,000 persons per year for COPD have increased in all age groups > 45 years of age. These trends reflect population aging, smoking patterns, institutional factors, and treatment practices.

Estimated growth of lung volume reduction surgery among Medicare enrollees: 1994 to 1996.

OBJECTIVE: To estimate the number of lung volume reduction surgery procedures performed on Medicare enrollees from 1994 to 1996. DESIGN: Statistical analysis of national Medicare claims data. PATIENTS: All Medicare enrollees with emphysema hating claims records for pulmonary resection procedures from January 1, 1993, through December 31, 1996. MAIN OUTCOME MEASURE: Estimated number of lung volume reduction procedures performed per month from July 1994 through December 1996. RESULTS: An estimated 1,212 lung volume reduction procedures were performed on Medicare enrollees between July 1994 and December 1995 (95% confidence interval, 1,012 to 1,408). Nearly one half of these procedures were performed in the last 3 months of 1995. At the time Health Care Financing Administration announced that it would suspend reimbursement for the procedure (December 1995), lung volume reduction surgery was being performed in 37 states. The number of claims per month decreased from a peak of 169 in December 1995, to 11 in March 1996. Average Medicare reimbursement per procedure was $31,398. CONCLUSIONS: Lung volume reduction surgery for patients increased rapidly following its reintroduction in 1994. The growth of lung volume reduction surgery demonstrates that widespread adoption and utilization of a surgical procedure can occur in the absence of data from controlled clinical trials. Medicare expenditures for lung volume reduction surgery were an estimated $30 million to $50 million. Performing the surgery for all current Medicare patients who meet the appropriate clinical criteria would cost an estimated $1 billion.

The cost-effectiveness of lung transplantation. A pilot study. University of Washington Medical Center Lung Transplant Study Group.

OBJECTIVE: Lung transplantation is one of the fastest-growing solid organ transplant procedures in the world, yet its cost-effectiveness is unknown. We compared the costs and outcomes of the first 25 patients who received lung transplants at the University of Washington with 24 patients currently on the lung transplant waiting list. DESIGN: Inpatient and outpatient charges were obtained from the hospital billing service and home health agencies. Quality-adjusted life year scores (QALYs) were computed from the following: (1) utility scores obtained through standard gamble interviews, and (2) published survival data from an international lung transplant registry and from studies of patients on lung transplant waiting lists. RESULTS: Transplantation charges averaged $164,989 (median, $152,071). Average monthly charges posttransplant were $11,917 in year 1 and $4,525 thereafter, vs $3,395 for waiting-list patients. Posttransplant utility scores were significantly higher than waiting-list scores (0.80 vs 0.68; p < 0.001). Life expectancy was not greater for lung transplant vs waiting-list patients (5.89 vs 5.32 years; p > 0.05), although quality-adjusted life expectancy did improve significantly. After converting charges to costs, the incremental cost per QALY gained for posttransplant compared with waiting-list patients was $176,817. CONCLUSIONS: Lung transplantation is very expensive, although it can substantially improve quality of life. Two-thirds of care costs are incurred after transplantation. The principal barriers to cost-effectiveness at present are the high cost of postrecovery care and marginal gains in life expectancy compared with conservative care.

Improvement in quality of life after lung transplantation: a preliminary study. The University of Washington Medical Center Lung Transplant Study Group.

BACKGROUND: Lung transplantation is an expensive therapeutic option for a number of endstage conditions. Improving health-related quality of life is an important objective of transplantation. METHODS: We report quality of life measurements in 21 waiting list patients and 23 patients after transplantation with seven different pulmonary conditions using two standardized instruments: the Sickness Impact Profile and the standard gamble. RESULTS AND CONCLUSIONS: This cross-sectional study indicates the following: (1) overall quality of life improves significantly after transplantation; (2) although most dimensions of functional disability improve after transplantation, some aspects may suffer; (3) quality of life gains after transplantation may not be equal for all pretransplantation conditions.

Economic analysis of lung volume reduction surgery as part of the National Emphysema Treatment Trial. NETT Research Group.

BACKGROUND: In today's cost-conscious health care environment, obtaining timely and accurate economic information regarding new medical technologies has become extremely important. The National Emphysema Treatment Trial, a multicenter, randomized controlled trial of lung volume reduction surgery (LVRS) plus medical therapy, versus medical therapy for patients with severe emphysema, includes a parallel cost-effectiveness analysis. METHODS: The analysis is designed to determine the cost-effectiveness of LVRS versus medical therapy for those who are eligible for the procedure. After describing theoretical foundations of cost-effectiveness analysis as they apply to this study, we describe the economic and quality of life data that are being collected alongside the clinical trial, methods of analysis, and approach to presenting the results. RESULTS: The cost-effectiveness of LVRS relative to medical therapy will be presented as costs per quality-adjusted life years gained. CONCLUSIONS: This analysis will provide timely economic data that can be considered alongside the clinical results of the National Emphysema Treatment Trial. As one of the largest clinical trials to include a parallel, prospective cost-effectiveness analyses, this study will also provide valuable practical information about conducting an economic analysis alongside a multicenter clinical trial.

Simulation modeling of outcomes and cost effectiveness.

Modeling will continue to be used to address important issues in clinical practice and health policy issues that have not been adequately studied with high-quality clinical trials. The apparent ad hoc nature of models belies the methodologic rigor that is applied to create the best models in cancer prevention and care. Models have progressed from simple decision trees to extremely complex microsimulation analyses, yet all are built using a logical process based on objective evaluation of the path between intervention and outcome. The best modelers take great care to justify both the structure and content of the model and then test their assumptions using a comprehensive process of sensitivity analysis and model validation. Like clinical trials, models sometimes produce results that are later found to be invalid as other data become available. When weighing the value of models in health care decision making, it is reasonable to consider the alternatives. In the absence of data, clinical policy decisions are often based on the recommendations of expert opinion panels or on poorly defined notions of the standard of care or medical necessity. Because such decision making rarely entails the rigorous process of data collection, synthesis, and testing that is the core of well-conducted modeling, it is usually not possible for external audiences to examine the assumptions and data that were used to derive the decisions. One of the modeler's most challenging tasks is to make the structure and content of the model transparent to the intended audience. The purpose of this article is to clarify the process of modeling, so that readers of models are more knowledgeable about their uses, strengths, and limitations.

Methods for reviewing economic evaluations of community preventive services: a cart without a horse?

PIP: In a health care system with ever-rising demand and limited resources, economic assessment of medical technologies is important for those who make resource allocation decisions that affect the health of populations. Cost-effectiveness analysis (CEA) is the best developed tool available for comparing the relative health benefits for expenditure among a myriad of available health interventions. Although guidelines for systematic reviews of economic evaluations in community prevention presented in the American Journal of Preventive Medicine address the issue of facilitating comparison of programs, other issues that limit usefulness of CEA to decision-makers in the field arise. The issues include availability of studies, poorly developed and inconsistent evaluations, omission of key resources from the CEA in community prevention, and shifts in public awareness, social norms, and technologic improvements. Extensive discussion of these issues is provided in the article. In conclusion, the methods for systematic review of economic evaluations in the American Journal of Preventive Medicine are important steps. However, it is advisable to use caution in applying them.^ieng

Would you like suspenders to go with that belt? An analysis of optimal combinations of cost sharing and managed care.

When and why would it be efficient for a managed care insurance plan using managerial limits to add patient cost sharing? This paper uses a diagrammatic model to indicate that the use of patient point-of-service cost sharing can cause the managerial limits or guidelines to be less restrictive in limiting high value care for cases of severe illness. The model shows that cost-sharing is more likely to improve efficiency the greater the variation in illness severity and the smaller the degree of moral hazard. The model is extended to the case in which provider cost sharing is also used.

On the use of survival analysis techniques to estimate medical care costs.

Measurement of treatment costs is important in the evaluation of medical interventions. Accurate cost estimation is problematic, when cost records are incomplete. Methods from the survival analysis literature have been proposed for estimating costs using available data. In this article, we clarify assumptions necessary for validity of these techniques. We demonstrate how assumptions needed for valid survival analysis may be violated when these methods are applied to cost estimation. Our observations are confirmed through simulations and empirical data analysis. We conclude that survival analysis approaches are not generally appropriate for the analysis of medical costs and review several valid alternatives.

A controlled time-series trial of clinical reminders: using computerized firm systems to make quality improvement research a routine part of mainstream practice.

OBJECTIVE: To explore the feasibility of conducting unobtrusive interventional research in community practice settings by integrating firm-system techniques with time-series analysis of relational-repository data. STUDY SETTING: A satellite teaching clinic divided into two similar, but geographically separated, primary care group practices called firms. One firm was selected by chance to receive the study intervention. Forty-two providers and 2,655 patients participated. STUDY DESIGN: A nonrandomized controlled trial of computer-generated preventive reminders. Net effects were determined by quantitatively combining population-level data from parallel experimental and control interrupted time series extending over two-month baseline and intervention periods. DATA COLLECTION: Mean rates at which mammography, colorectal cancer screening, and cholesterol testing were performed on patients due to receive each maneuver at clinic visits were the trial's outcome measures. PRINCIPAL FINDINGS: Mammography performance increased on the experimental firm by 154 percent (0.24 versus 0.61, p = .03). No effect on fecal occult blood testing was observed. Cholesterol ordering decreased on both the experimental (0.18 versus 0.1 1, p = .02) and control firms (0.13 versus 0.07, p = .03) coincident with national guidelines retreating from recommending screening for young adults. A traditional uncontrolled interrupted time-series design would have incorrectly attributed the experimental-firm decrease to the introduction of reminders. The combined analysis properly indicated that no net prompting effect had occurred, as the difference between firms in cholesterol testing remained stochastically stable over time (0.05 versus 0.04, p = .75). A logistic-regression analysis applied to individual-level data produced equivalent findings. The trial incurred no supplementary data collection costs. CONCLUSIONS: The apparent validity and practicability of our reminder implementation study should encourage others to develop computerized firm systems capable of conducting controlled time-series trials.

A review of quality-of-life evaluations in prostate cancer.

Prostate cancer is a highly prevalent malignancy in older men. Because the disease and its treatments have the potential to cause substantial morbidity in affected individuals, prostate cancer has been the subject of great interest for quality-of-life (QOL) researchers. In this article, we review published QOL studies that have focused on individuals with prostate cancer. Generic survey instruments have generally been found to be insensitive to changes in health-related quality of life (HR-QOL) related to prostate cancer and its treatments. Domain-specific survey instruments (such as those focusing on sexual function) have been more sensitive, but fail to capture all relevant impacts. At least 9 disease-specific instruments have been developed to measure the HR-QOL impact of prostate cancer. These instruments generally focus on specific symptoms related to the disease and its treatment--urinary function, bowel function, sexual function, physical function, psychological function and pain--however, the domains covered are not consistent from instrument to instrument, and the domains of emphasis within each instrument are rarely the same. In addition, no single instrument has been applied to all major therapies for prostate cancer across men at different ages and stages of disease. Finally, HR-QOL evaluations in some patient groups, such as those with advanced disease, have received relatively little attention to date. As a result of the proliferation of prostate cancer-specific survey instruments and inconsistencies in their design and application, decision-makers face great difficulties evaluating HR-QOL across disease stages and comparing the HR-QOL impacts of alternative therapies, including conservative management ('watchful waiting'). In order for these tools to be useful for patient management and policy-making, coordination of instrument development efforts with the goal of consolidating the number of measures used is urgently needed.

Patient-level estimates of the cost of complications in diabetes in a managed-care population.

OBJECTIVE: To develop incidence-based estimates of the cost of several diabetes-related complications. DESIGN AND SETTING: This was a retrospective cohort study in a large health maintenance organisation. A total of 8905 patients with type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes mellitus and 36,520 age- and gender-matched controls without diabetes were observed from 1992 to 1995. Incidence rates of 6 major diabetes-related complications were computed for both populations. Annual health expenditures in the first and second year following diagnosis were computed for each complication. For comparison, annual costs were derived for individuals without diabetes or the complication of interest. MAIN OUTCOME MEASURES AND RESULTS: Over 3 years of observation, incidence rates for the groups with and without diabetes were as follows: myocardial infarction 9.0 versus 3.2%; stroke 8.7 versus 3.8%; hypertension 26.2 versus 16.9%; end-stage renal disease 5.9 versus 1.4%; foot ulcer 7.9 versus 1.1%; and eye disease 44.3 versus 2.8%. Expressed as a multiple of the average annual cost of care for those without diabetes [$US3400/year (1995 dollars) for those over 65 years of age] and the related complication of interest, excess expenditures for those with diabetes were as follows for the first year following diagnosis: no complications 1.59; myocardial infarction 4.1; stroke 3.5; hypertension 2.56; end-stage renal disease 4.32; foot ulcer 4.0; and eye disease 2.46. For younger cohorts (less prevalent in the sample), incremental costs for each complication were generally greater than in the older group. CONCLUSIONS: The high incidences and costs may support the value of aggressive early intervention for patients with diabetes. These data will be useful for pharmacoeconomic modelling of the cost effectiveness of new and existing therapies for this condition.