Mapping tree density at a global scale.

The global extent and distribution of forest trees is central to our understanding of the terrestrial biosphere. We provide the first spatially continuous map of forest tree density at a global scale. This map reveals that the global number of trees is approximately 3.04 trillion, an order of magnitude higher than the previous estimate. Of these trees, approximately 1.39 trillion exist in tropical and subtropical forests, with 0.74 trillion in boreal regions and 0.61 trillion in temperate regions. Biome-level trends in tree density demonstrate the importance of climate and topography in controlling local tree densities at finer scales, as well as the overwhelming effect of humans across most of the world. Based on our projected tree densities, we estimate that over 15 billion trees are cut down each year, and the global number of trees has fallen by approximately 46% since the start of human civilization.

Re-examining the BMI threshold for bariatric surgery in the USA.

BACKGROUND: The optimal BMI threshold above which gastric bypass surgery should be offered to obese patients is controversial. The objective of this study was to compare the impact of Roux-en-Y gastric bypass (RYGB) vs. diet and exercise (D&E) on life expectancy to find the BMI at which patients experience an improvement in their life expectancy by undergoing surgery. METHODS: A Markov state transition model was designed to implement a decision tree that simulated the lives of obese patients. Life expectancies following RYGB and 2 years of D&E were estimated and compared. Ten thousand patients' lives were simulated in each weight-loss intervention group in the model. In addition to base case analysis (45 kg/m(2) BMI pre-intervention), sensitivity analysis of initial BMI at the start of the study was completed. Markov model parameters were extracted from the literature. RESULTS: The impact of RYGB on survival relative to D&E depended on the patient's initial BMI. Compared to patients who underwent 2 years of "optimal" diet and exercise (7 % total body weight loss/year), RYGB improved long-term survival for patients above a BMI of 31.3 kg/m(2). CONCLUSIONS: Roux-en-Y gastric bypass can improve long-term survival for patients with class I obesity. This study suggests that RYGB should not be reserved solely for patients with class II or III obesity.

Cost-effectiveness of a primary care intervention to treat obesity.

BACKGROUND: Data on the cost-effectiveness of the behavioral treatment of obesity are not conclusive. The cost-effectiveness of treatment in primary care settings is particularly relevant. METHODS: We conducted a within-trial cost-effectiveness analysis of a primary care-based obesity intervention. Study participants were randomized to: Usual Care (UC; quarterly visits with their primary care provider); Brief Lifestyle Counseling (BLC; quarterly provider visits plus monthly weight loss counseling visits) or Enhanced Brief Lifestyle Counseling (EBLC; all above interventions, plus choice of meal replacements or weight loss medication). A health-care payer perspective was used. Intervention costs were estimated from tracking data obtained prospectively. Quality-adjusted life years (QALYs) were estimated with the EuroQol-5D. We estimated cost per kilogram-year of weight loss and cost per QALY. RESULTS: Weight losses after 2 years were 1.7, 2.9 and 4.6 kg for UC, BLC and EBLC, respectively (P=0.003 for comparison of EBLC vs UC). The incremental cost per kilogram-year lost was $292 for EBLC compared with UC (95% confidence interval (CI): $219-$437). The short-term incremental cost per QALY was $115,397, but the 95% CI were undefined. Comparison of short-term cost per kg with published estimates of longer-term cost per QALY suggested that the intervention could be cost-effective over the long term (≥ 10 years). CONCLUSIONS: A primary care intervention that includes monthly counseling visits and a choice of meal replacements or weight loss medication could be a cost-effective treatment for obesity over the long term. However, additional studies are needed on the cost-effectiveness of behavioral treatment of obesity.

Direct medical cost of overweight and obesity in the USA: a quantitative systematic review.

To estimate per-person and aggregate direct medical costs of overweight and obesity and to examine the effect of study design factors. PubMed (1968-2009), EconLit (1969-2009) and Business Source Premier (1995-2009) were searched for original studies. Results were standardized to compute the incremental cost per overweight person and per obese person, and to compute the national aggregate cost. A total of 33 US studies met review criteria. Among the four highest-quality studies, the 2008 per-person direct medical cost of overweight was $266 and of obesity was $1723. The aggregate national cost of overweight and obesity combined was $113.9 billion. Study design factors that affected cost estimates included use of national samples vs. more selected populations, age groups examined, inclusion of all medical costs vs. obesity-related costs only, and body mass index cut-offs for defining overweight and obesity. Depending on the source of total national healthcare expenditures used, the direct medical cost of overweight and obesity combined is approximately 5.0% to 10% of US healthcare spending. Future studies should include nationally representative samples, evaluate adults of all ages, report all medical costs and use standard body mass index cut-offs.

Is treatment with ICS and LABA cost-effective for COPD? Multinational economic analysis of the TORCH study.

The TOwards a Revolution in COPD Health (TORCH) study was a 3-yr multicentre trial of 6,112 patients randomised to salmeterol (Salm), fluticasone propionate (FP), a Salm/FP combination (SFC) or placebo (P). Here the cost-effectiveness of treatments evaluated in the TORCH study is assessed. For four regions, 3-yr all-cause hospitalisation, medication and outpatient care costs were calculated. The sample was restricted to the 21 countries (n = 4,237) in which European quality of life five-dimension (EQ-5D) data were collected in order to estimate the number of quality-adjusted life years (QALYs). Regression models were fitted to survival, study medication cost, other medication cost and EQ-5D data in order to estimate total cost, number of QALYs and cost per QALY, adjusted for missing data and region. SFC had a trial-wide estimate of cost per QALY of 43,600 US dollars (USD) compared with P (95% confidence interval 21,400-123,500 USD). Estimates for Salm versus P (197,000 USD) and FP versus P (78,000 USD) were less favourable. The US estimates were greater than those from other regions; for SFC versus P, the cost per QALY was 77,100 (46,200-241,700) USD compared to 24,200 (15,200-56,100) USD in Western Europe. Compared with P, SFC has a lower incremental cost-effectiveness ratio than either FP or Salm used alone, and is, therefore, preferred to these monotherapies on the grounds of cost-effectiveness.

The incremental value of troponin-I testing in patients with intermediate risk unstable angina.

BACKGROUND: Classification of patients with unstable angina (UA) by Agency for Health Care Policy and Research (AHCPR) guidelines in the emergency department reliably stratifies risk of death or myocardial infarction (MI) for triage to outpatient evaluation (low-risk), hospitalization (high-risk), or additional testing (intermediate-risk). Cardiac troponin-I elevation may identify patients at higher risk, but the incremental value may vary with AHCPR clinical risk. HYPOTHESIS: The objective of this study was to determine whether cardiac troponin-I had any additional value beyond triage based upon history, physical examination, and electrocardiogram, in the evaluation of patients with UA. METHODS: In all, 212 consecutive patients with UA and normal serum creatine kinase (CK)-MB levels and elevated troponin-I were risk stratified by AHCPR guidelines to evaluate the incremental value of adding routine troponin-I measurements to our current model for risk stratification. RESULTS: Primary events (death/nonfatal MI) occurred in 35% of high-risk, 15% of intermediate-risk, and 0% of low-risk patients (p < 0.001 by chi-square for trend). High troponin-I (> or =2.0 ng/dl) occurred in 48% of high-risk, 21% of intermediate-risk, and 19% of low-risk patients. The remaining patients in each risk group had indeterminate troponin-I levels (> or =0.4 < 2 ng/dl). Of those with high troponin-I, a primary event occurred in 36, 42, and 0% in the respective high-, intermediate-, and low-risk groups (p < 0.001). High troponin-I levels corresponded with a statistically significant increased rate of primary events only in patients at AHCPR intermediate risk: 42.4 vs. 7.3%, p < 0.001. CONCLUSION: The AHCPR guidelines risk stratify patients with UA. High troponin-I adds significant (p < 0.001) prognostic value in the patients at AHCPR intermediate risk and should be evaluated further in larger trials of such patients.

Economic analysis of conventional-dose chemotherapy compared with high-dose chemotherapy plus autologous hematopoietic stem-cell transplantation for metastatic breast cancer.

We performed an economic analysis of data from 180 women in a clinical trial of conventional-dose chemotherapy vs high-dose chemotherapy plus stem-cell transplantation for metastatic breast cancer responding to first-line chemotherapy. Data on resource use, including hospitalizations, medical procedures, medications, and diagnostic tests, were abstracted from subjects' clinical trial records. Resources were valued using the Medicare Fee Schedule for inpatient costs at one academic medical center and average wholesale prices for medications. Monthly costs were calculated and stratified by treatment group and clinical phase. Mean follow-up was 690 days in the transplantation group and 758 days in the conventional-dose chemotherapy group. Subjects in the transplantation group were hospitalized for more days (28.6 vs 17.8, P=0.0041) and incurred higher costs (US dollars 84055 vs US dollars 28169) than subjects receiving conventional-dose chemotherapy, with a mean difference of US dollars 55886 (95% CI, US dollars 47298-US dollars 63666). Sensitivity analyses resulted in cost differences between the treatment groups from US dollars 36528 to US dollars 75531. High-dose chemotherapy plus stem-cell transplantation resulted in substantial additional morbidity and costs at no improvement in survival. Neither the survival results nor the economic findings support the use of this procedure outside of the clinical trial setting.

Self-reported quality of life across mood states in bipolar disorder.

In distinction to the classic conceptualization of mania and hypomania, a growing body of work indicates that these episodes are not typically characterized by euphoric mood and sense of increased well-being, but rather by significant dysphoric symptoms. However, few data exist concerning self-perceived quality of life in mania or hypomania. Such data are important both for better understanding of the illness, and are particularly important for developing appropriate cost-utility studies. Accordingly, we hypothesized that two measures of self-reported quality of life, the mental subscale of the Short Form-12 (SF-12) and the EuroQol, would show reduced quality of life in patients in manic/hypomanic or mixed episodes, compared to those who were euthymic. Eighty-six patients with bipolar disorder from four Department of Veterans Affairs (VA) medical centers were assessed in a cross-sectional design. Mood state was categorized by physician diagnosis and separately by patient self-report using the Internal State Scale (ISS). Self-reported quality of life was quantified using the SF-12 and EuroQol. Findings were identical regardless of how mood state was determined. The SF-12 mental subscale and EuroQol differed significantly across mood states. Patients with mania/hypomania were either less than (SF-12 mental subscale) or equal to (EuroQol) euthymic patients, while patients in a mixed episode resembled those in a depressive episode on both indices. In contrast, SF-12 physical subscale scores showed no intergroup differences. These quality-of-life data provide further support for the conceptualization that mania and hypomania are syndromes characterized by reduced, rather than increased, sense of well-being and quality of life. Moreover, depressive symptoms appear to be the primary determinant of quality of life in bipolar disorder, although other factors may be associated with both depression and reduced quality of life in bipolar disorder.

Blood lead in children and its determinants in Nagpur, India.

In a community-based cross-sectional study of 297 children aged 6 months to 6 years in an Indian city, the authors assessed the prevalence of elevated (> or = 10 microg/dL) blood lead (PbB) levels, their risk factors, and the lead contents in potential environmental sources. Mean PbB was 18.4 microg/dL +/- 16.5. The prevalence of elevated PbB was 67%. Anticipated risk factors for elevated PbB were living in houses painted with lead-based paint, odds ratio (OR) 6.42 (1.75, 23.6; p = 0.005), recent exposures to lead-based paint, OR 2.61 (1.07, 6.66; p = 0.03), and the use of the eye cosmetic ma," OR 2.63 (1.24, 5.56; p = 0.01). Unanticipated results were effect of upper caste as a risk factor, OR (adjusted) 1.85 (95% CI = 0.96, 3.57; p = 0.06), and the lack of effect of traffic, parental occupational exposure, or nutritional status. Analysis of various environmental sources such as paint, pencils, crayons, and clay revealed high lead levels. These results demonstrate the existence of a major environmental health problem in Indian children, with risk factors that differ from those in other countries.

Comparison of length of hospital stay for patients with known or suspected methicillin-resistant Staphylococcus species infections treated with linezolid or vancomycin: a randomized, multicenter trial.

STUDY OBJECTIVE: To compare hospital length of stay (LOS), weekly discharges, and days of antibiotic treatment with linezolid (intravenous with oral follow-up) and vancomycin (intravenous only). DESIGN: Multinational, randomized, phase III trial. SETTINGS: Hospitals in North America, Latin America, and Europe. PATIENTS: Four hundred sixty hospitalized patients with infections of known or suspected methicillin-resistant Staphylococcus species. INTERVENTION: Administration of linezolid or vancomycin. MEASUREMENTS AND MAIN RESULTS: For linezolid recipients, median LOS was 5 and 8 days shorter (p=0.05 and 0.003) in the complicated skin and soft tissue infection intent-to-treat (230 patients) and clinically evaluable (144) samples, and slightly but not significantly shorter in the overall intent-to-treat (460) and clinically evaluable (254) samples. In all samples, linezolid recipients had more discharges in the first week of treatment and fewer days of intravenous therapy than vancomycin recipients. CONCLUSION: Our results support linezolid's ability to reduce medical resource use.

A comparison of scoring weights for the EuroQol derived from patients and the general public.

OBJECTIVE: General health state classification systems, such as the EuroQol instrument, have been developed to improve the systematic measurement and comparability of health state preferences. In this paper we generate valuations for EuroQol health states using responses to this instrument's visual analogue scale made by patients enrolled in a randomized clinical trial evaluating tirilazad mesylate, a new drug used to treat subarachnoid haemorrhage. We then compare these valuations derived from patients with published valuations derived from responses made by a sample from the general public. METHODS: The data were derived from two sources: (1) responses to the EuroQol instrument from 649 patients 3 months after enrollment in the clinical trial, and (2) from a published study reporting a scoring rule for the EuroQol instrument that was based upon responses made by the general public. We used a linear regression model to develop an additive scoring rule. This rule enables direct valuation of all 243 EuroQol health states using patients' scores for their own health states elicited using a visual analogue scale. We then compared predicted scores generated using our scoring rule with predicted scores derived from a sample from the general public. RESULTS: The predicted scores derived using the additive scoring rules met convergent validity criteria and explained a substantial amount of the variation in visual analogue scale scores (R(2)=0.57). In the pairwise comparison of the predicted scores derived from the study sample with those derived from the general public, we found that the former set of scores were higher for 223 of the 243 states. Despite the low level of correspondence in the pairwise comparison, the overall correlation between the two sets of scores was 87%. CONCLUSIONS: The model presented in this paper demonstrated that scoring weights for the EuroQol instrument can be derived directly from patient responses from a clinical trial and that these weights can explain a substantial amount of variation in health valuations. Scoring weights based on patient responses are significantly higher than those derived from the general public. Further research is required to understand the source of these differences.

Quantifying stochastic uncertainty and presenting results of cost-effectiveness analyses.

In the last decade, major advances have been made in the statistical methods for quantifying uncertainty in stochastic cost-effectiveness studies. In this paper, we provide a guide to the literature in which we highlight the preferred methods for confidence interval estimation, new developments in the formulation of the cost-effectiveness problem, suggested ways for presenting results and the areas in which future research may develop. The overall approach taken is nontechnical, with an emphasis on graphical rather than algebraic presentation of methods.

Principles of effectiveness trials and their implementation in VA Cooperative Study #430: 'Reducing the efficacy-effectiveness gap in bipolar disorder'.

Despite the availability of efficacious treatments for bipolar disorder, their effectiveness in general clinical practice is greatly attenuated, resulting in what has been called an 'efficacy-effectiveness gap'. In designing VA Cooperative Studies Program (CSP) Study #430 to address this gap, nine principles for conducting an effectiveness (in contrast to an efficacy) study were identified. These principles are presented and discussed, with specific aspects of CSP #430 serving as illustrations of how they can be implemented in an actual study. CSP #430 hypothesizes that an integrated, clinic-based treatment delivery system that emphasizes (1) algorithm-driven somatotherapy, (2) standardized patient education, and (3) easy access to a single primary mental health care provider to maximize continuity-of-care, will address the efficacy-effectiveness gap and improve disease, functional, and economic outcome. It is an 11-site, randomized controlled clinical trial of this multi-modal, clinic-based intervention versus usual VA care running from 1997 to 2003. The trial has enrolled 191 subjects in each arm, using minimal exclusion criteria to maximize the external validity of the study. Subjects are followed for 3 years. The intervention is highly specified in a series of operations manuals for each of the three components. Several continuous quality improvement (CQI) interventions, process measures, and statistical techniques deal with drift of care in both the intervention and usual care arms to ensure the internal validity of the study. CSP #430 is designed to have impact well beyond the VA, since it evaluates a basic health care operational principle: that augmenting ambulatory access for major mental illness will improve outcome and reduce overall treatment costs. If results are positive, this study will provide a reason to reconsider the prevailing trend toward limitation of ambulatory services that is characteristic of many managed care systems today.

A claims data approach to defining an episode of care.

OBJECTIVE: To utilize health services research techniques in developing an episode of care using an administrative data set. This method is demonstrated for an episodic clinical condition, migraine. DATA SOURCES: Medicaid administrative data set of 3,372 patients with a diagnosis of migraine (ICD-9-CM 346.0, 346.1) in the state of Pennsylvania between May 1990 and March 1992. STUDY DESIGN: The duration of a migraine episode was measured by assessing the magnitude of resource utilization and the proportion of patients with charges in the period after the index migraine as compared to the period before the index migraine. A confidence interval (CI) was developed around each measure using bootstrap techniques. DATA COLLECTION METHODS: All charge data were extracted daily for a 113-day observation period surrounding each index migraine in order to observe the duration of impact of a migraine diagnosis on resource utilization. PRINCIPAL FINDINGS: The lower limits of both the 95% and 99% CIs for the difference in charges are greater than 0 for three weeks. The lower limits of both CIs for the difference in the proportion of patients with charges are above 0 for six weeks. CONCLUSIONS: Our analysis demonstrates that a health services research framework can be used to define an episode of care for a chronic disease category such as migraine. This method can be used to evaluate episodes of care for clinical studies of limited or episodic conditions and to complement clinical expertise in developing time horizons for clinical trials.

Predicting 10-year care requirements for older people with suspected Alzheimer's disease.

OBJECTIVE: To describe the types and costs of care received for 10 years after the identification of an older person with suspected Alzheimer's disease (AD) by using data from 3254 patients with suspected AD who participated in the National Long Term Care Survey (NLTCS). METHODS: By using a Markov model derived using grade of membership techniques, the following were determined: survival probabilities at 10 years; years of survival during the 10 years; years in institutions; years with two or more impairments in basic activities of daily living; hours of paid and informal care while the older person lived in the community; and costs of paid community, institutional, and medical care. RESULTS: Greater degrees of cognitive impairment present when AD was identified were associated with reduced predicted probability of surviving 10 years, increased predicted number of years spent in institutions, increased hours of care required while affected individuals remained in the community, and increased costs of paid community, institutional, and medical care. Substantial differences between men and women were seen: severity-adjusted 10-year costs were almost two times higher for women with AD than for men ($75,000 compared with $44,000); according to sensitivity analysis, average 10-year costs might be as high as $109,000 for women and $67,000 for men. CONCLUSIONS: AD imposes a substantial burden on older persons. Interventions that slow the progression of the disease may therefore affect community survival as well as healthcare costs.

Relationship between CD4 count, viral burden, and quality of life over time in HIV-1-infected patients.

BACKGROUND: Although surrogate markers such as CD4 counts and viral burden (HIV-1 RNA) are predictive of AIDS-related disease progression, little is known about the relationship between changes in surrogate markers and health-related quality of life (HRQOL) outcomes. This study investigated how changes in CD4/mm3 and viral burden (RNA copies/mL) are related to changes in HRQOL as indexed by the Medical Outcomes Study HIV Health Survey (MOS-HIV-30). METHODS: Subjects were HIV-1-infected patients with CD4 counts <300/mm3 enrolled in a double-blind, randomized clinical trial of delavirdine. As part of the clinical protocol, patients completed the MOS-HIV-30, from which the Physical Health (PHS) and Mental Health (MHS) summary scores were used for analyses. HRQOL and surrogate marker data assessed up to 2 years after randomization were analyzed for a total of 1,112 patients. RESULTS: Individual patients' initial status (intercepts) and rates of change (slopes) over time for log CD4, log RNA, PHS, and MHS were estimated with the use of empirical Bayes. Early response to treatment correlated with HRQOL better for RNA than for CD4. However, the relationship between weekly change and HRQOL was stronger for CD4 than for RNA. CONCLUSIONS: Surrogate markers are significantly associated with HRQOL outcomes. Improvements in HRQOL over time are associated with lower initial viral load and with increases in CD4 counts. Limitations concerning the restricted variability of the change scores are addressed.

The Internal State Scale: replication of its discriminating abilities in a multisite, public sector sample.

OBJECTIVE: The Internal State Scale (ISS) is a self-report instrument that has been validated for discriminating mood states in patients with bipolar disorder. This study a) extends investigation to a multisite public sector sample and b) tests a revised scoring algorithm that formally identifies patients in mixed states. METHODS: Eighty-six patients with bipolar disorder from four Veterans Affairs medical centers were assessed in a cross-sectional design. Physician-conducted semi-structured interviews used DSM-IV criteria to identify subjects as meeting criteria for euthymia, mania or hypomania, depression, or mixed state (mania or hypomania plus depression). A revised ISS scoring algorithm independently assigned mood state. Mean subscale scores were analyzed across groups. Receiver-operating characteristic (ROC) curve analysis was conducted to determine optimal algorithm structure. RESULTS: Analysis of mean scores for the ISS subscales replicated original results for Activation, Well-Being, and Perceived Conflict, but indicated differences from the original results for the Depression Index. The ROC curve analysis identified optimal cut-off scores for the revised algorithm. The overall kappa score indicated moderate agreement between ISS and physician ratings of mood state, including mixed states. LIMITATIONS: The study used a sample consisting primarily of male veterans. Mood state was assigned by experts using expert clinician diagnosis, not structured interviews. CONCLUSION: The performance of the ISS in this multisite, public sector sample was similar to the performance in the initial research clinic sample. This finding confirms the validity of the ISS as a discriminator of mood states in bipolar disorder. The development of a revised scoring algorithm makes feasible formal identification of mixed episodes with the ISS.

Towards a composite scoring solution for the Neurobehavioral Functioning Inventory.

Little research has been conducted towards the development and evaluation of a measure of quality of life specific to head/brain injury populations. Accordingly, we examined responses to the Neurobehavioral Functioning Inventory in the context of a clinical trial for head injury patients (n = 655) conducted in 14 countries. To reduce the 66 item scale into a smaller number of composite scales, principal components analysis was conducted. Scales were constructed assessing four categories of symptoms: cognitive deficits, depression, aggression and somatization. The internal reliabilities (alpha coefficient) of the four scales were generally acceptable (range = 0.79-0.92). Scores on all four scales correlated significantly with patient-rated overall quality of life and all but the aggression scale correlated significantly with overall clinical severity. The need for more formal evaluation of this and other disease-specific measures is discussed.