Climate change disrupts the seasonal coupling of plant and soil microbial nutrient cycling in an alpine ecosystem.

The seasonal coupling of plant and soil microbial nutrient demands is crucial for efficient ecosystem nutrient cycling and plant production, especially in strongly seasonal alpine ecosystems. Yet, how these seasonal nutrient cycling processes are modified by climate change and what the consequences are for nutrient loss and retention in alpine ecosystems remain unclear. Here, we explored how two pervasive climate change factors, reduced snow cover and shrub expansion, interactively modify the seasonal coupling of plant and soil microbial nitrogen (N) cycling in alpine grasslands, which are warming at double the rate of the global average. We found that the combination of reduced snow cover and shrub expansion disrupted the seasonal coupling of plant and soil N-cycling, with pronounced effects in spring (shortly after snow melt) and autumn (at the onset of plant senescence). In combination, both climate change factors decreased plant organic N-uptake by 70% and 82%, soil microbial biomass N by 19% and 38% and increased soil denitrifier abundances by 253% and 136% in spring and autumn, respectively. Shrub expansion also individually modified the seasonality of soil microbial community composition and stoichiometry towards more N-limited conditions and slower nutrient cycling in spring and autumn. In winter, snow removal markedly reduced the fungal:bacterial biomass ratio, soil N pools and shifted bacterial community composition. Taken together, our findings suggest that interactions between climate change factors can disrupt the temporal coupling of plant and soil microbial N-cycling processes in alpine grasslands. This could diminish the capacity of these globally widespread alpine ecosystems to retain N and support plant productivity under future climate change.

Cost to Medicare of acute kidney injury in percutaneous coronary intervention.

BACKGROUND: Acute kidney injury (AKI), including contrast-induced AKI (CI-AKI), is an important complication of percutaneous coronary intervention (PCI), resulting in short- and long-term adverse clinical outcomes. While prior research has reported an increased cost burden to hospitals from CI-AKI, the incremental cost to payers remains unknown. Understanding this incremental cost may inform decisions and even policy in the future. The objective of this study was to estimate the short- and long-term cost to Medicare of AKI overall, and specifically CI-AKI, in PCI. METHODS: Patients undergoing inpatient PCI between January 2017 and June 2020 were selected from Medicare 100% fee-for-service data. Baseline clinical characteristics, PCI lesion/procedural characteristics, and AKI/CI-AKI during the PCI admission, were identified from diagnosis and procedure codes. Poisson regression, generalized linear modelling, and longitudinal mixed effects modelling, in full and propensity-matched cohorts, were used to compare PCI admission length of stay (LOS) and cost (Medicare paid amount inflated to 2022 US$), as well as total costs during 1-year following PCI, between AKI and non-AKI patients. RESULTS: The study cohort included 509,039 patients, of whom 104,033 (20.4%) were diagnosed with AKI and 9,691 (1.9%) with CI-AKI. In the full cohort, AKI was associated with +4.12 (95% confidence interval = 4.10, 4.15) days index PCI admission LOS, +$11,313 ($11,093, $11,534) index admission costs, and +$14,800 ($14,359, $15,241) total 1-year costs. CI-AKI was associated with +3.03 (2.97, 3.08) days LOS, +$6,566 ($6,148, $6,984) index admission costs, and +$13,381 ($12,118, $14,644) cumulative 1-year costs (all results are adjusted for baseline characteristics). Results from the propensity-matched analyses were similar. CONCLUSIONS: AKI, and specifically CI-AKI, during PCI is associated with significantly longer PCI admission LOS, PCI admission costs, and long-terms costs.

Shrub expansion modulates belowground impacts of changing snow conditions in alpine grasslands.

Climate change is disproportionately impacting mountain ecosystems, leading to large reductions in winter snow cover, earlier spring snowmelt and widespread shrub expansion into alpine grasslands. Yet, the combined effects of shrub expansion and changing snow conditions on abiotic and biotic soil properties remains poorly understood. We used complementary field experiments to show that reduced snow cover and earlier snowmelt have effects on soil microbial communities and functioning that persist into summer. However, ericaceous shrub expansion modulates a number of these impacts and has stronger belowground effects than changing snow conditions. Ericaceous shrub expansion did not alter snow depth or snowmelt timing but did increase the abundance of ericoid mycorrhizal fungi and oligotrophic bacteria, which was linked to decreased soil respiration and nitrogen availability. Our findings suggest that changing winter snow conditions have cross-seasonal impacts on soil properties, but shifts in vegetation can modulate belowground effects of future alpine climate change.

Device-related infection associated with increased mortality risk in de novo transvenous implantable cardioverter-defibrillator medicare patients.

INTRODUCTION: Transvenous implantable cardioverter-defibrillators (TV-ICD) infection is a serious complication that frequently requires complete device removal for attempted cure, which can be associated with patient morbidity and mortality. The objective of this study is to assess mortality risk associated with TV-ICD infection in a large Medicare population with de novo TV-ICD implants. METHODS: A survival analysis was conducted using 100% fee-for-service Medicare facility-level claims data to identify patients who underwent de novo TV-ICD implantation between 7/2016 and 1/2018. TV-ICD infection within 2 years of implantation was identified using International Classification of Disease, 10th Edition and current procedural terminology codes. Baseline patient risk factors associated with mortality were identified using the Charlson Comorbidity Index categories. Infection was treated as a time-dependent variable in a multivariate Cox proportional hazards model to account for immortal time bias. RESULTS: Among 26,742 Medicare patients with de novo TV-ICD, 518 (1.9%) had a device-related infection. The overall number of decedents was 4721 (17.7%) over 2 years, with 4555 (17%) in the noninfection group and 166 (32%) in the infection group. After adjusting for baseline patient demographic characteristics and various comorbidities, the presence of TV-ICD infection was associated with an increase of 2.4 (95% CI: 2.08-2.85) times in the mortality hazard ratio. CONCLUSION: The rate of TV-ICD infection and associated mortality in a large, real-world Medicare population is noteworthy. The positive association between device-related infection and risk of mortality further highlights the need to reduce infections.

Costs and complications associated with transvenous lead reoperation in cardiac implantable electronic devices.

BACKGROUND: Cardiac implantable electronic device transvenous (TV) lead reoperations are projected to increase, and robust economic data are needed to assess the resulting financial impact and the cost-effectiveness of prevention and treatment strategies. This study estimates Medicare costs, and describes patterns of complications, in patients who underwent TV lead reoperation. METHODS AND RESULTS: Medicare data (2010-2014) were used to identify patients who underwent TV lead reoperation. Cumulative costs to Medicare, and rates of infection and mechanical complications were calculated from 180 days before, to 180 days after, lead reoperation. Multivariate analysis was used to estimate adjusted costs, and to examine the impact of complications on medical resource use and costs. There were 1691 patients, 63.2% of whom underwent inpatient lead reoperation. Overall, the mean age was 78.2 years, 39.6% were female, and 92.3% were white. The mean cumulative cost was $36 199 (95% confidence interval [CI], $31 864-$40 535) for TV lead repositioning, $27 701 (95% CI, $19 869-$35 534) for repair, and $54 442 (95% CI, $51 651-$57 233) for removal. Underlying infection was associated with increased odds of inpatient reoperation and of lead removal, as well as longer length of stay and higher costs. CONCLUSIONS: The economic consequences of TV lead reoperation are substantial. Strategies aimed at reducing reoperation, particularly lead removal, are likely to result in considerable cost offsets.

Zones of influence for soil organic matter dynamics: A conceptual framework for data and models.

Soil organic matter (SOM) is an indicator of sustainable land management as stated in the global indicator framework of the United Nations Sustainable Development Goals (SDG Indicator 15.3.1). Improved forecasting of future changes in SOM is needed to support the development of more sustainable land management under a changing climate. Current models fail to reproduce historical trends in SOM both within and during transition between ecosystems. More realistic spatio-temporal SOM dynamics require inclusion of the recent paradigm shift from SOM recalcitrance as an 'intrinsic property' to SOM persistence as an 'ecosystem interaction'. We present a soil profile, or pedon-explicit, ecosystem-scale framework for data and models of SOM distribution and dynamics which can better represent land use transitions. Ecosystem-scale drivers are integrated with pedon-scale processes in two zones of influence. In the upper vegetation zone, SOM is affected primarily by plant inputs (above- and belowground), climate, microbial activity and physical aggregation and is prone to destabilization. In the lower mineral matrix zone, SOM inputs from the vegetation zone are controlled primarily by mineral phase and chemical interactions, resulting in more favourable conditions for SOM persistence. Vegetation zone boundary conditions vary spatially at landscape scales (vegetation cover) and temporally at decadal scales (climate). Mineral matrix zone boundary conditions vary spatially at landscape scales (geology, topography) but change only slowly. The thicknesses of the two zones and their transport connectivity are dynamic and affected by plant cover, land use practices, climate and feedbacks from current SOM stock in each layer. Using this framework, we identify several areas where greater knowledge is needed to advance the emerging paradigm of SOM dynamics-improved representation of plant-derived carbon inputs, contributions of soil biota to SOM storage and effect of dynamic soil structure on SOM storage-and how this can be combined with robust and efficient soil monitoring.

Quality of diabetes care in cancer: a systematic review.

PURPOSE: Overlooking other conditions during cancer could undermine gains associated with early detection and improved cancer treatment. We conducted a systematic review on the quality of diabetes care in cancer. DATA SOURCES: Systematic searches of Medline and Embase, from 1996 to present, were conducted to identify studies on the quality of diabetes care in patients diagnosed with cancer. STUDY SELECTION: Studies were selected if they met the following criteria: longitudinal or cross-sectional observational study; population consisted of diabetes patients; exposure consisted of cancer of any type and outcomes consisted of diabetes quality of care indicators, including healthcare visits, monitoring and testing, control of biologic parameters, or use of diabetes and other related medications. DATA EXTRACTION: Structured data collection forms were developed to extract information on the study design and four types of quality indicators: physician visits, exams or diabetes education (collectively 'healthcare visits'); monitoring and testing; control of biologic parameters; and medication use and adherence. RESULTS OF DATA SYNTHESIS: There were 15 studies from five countries. There was no consistent evidence that cancer was associated with fewer healthcare visits, lower monitoring and testing of biologic parameters or poorer control of biologic parameters, including glucose. However, the weight of the evidence suggests cancer was associated with lower adherence to diabetes medications and other medications, such as anti-hypertensives and cholesterol-lowering agents. CONCLUSION: Evidence indicates cancer is associated with poorer adherence to diabetes and other medications. Further primary research could clarify cancer's impact on other diabetes quality indicators.

Impact of subsequent metastases on costs and medical resource use for prostate cancer patients initially diagnosed with localized disease.

BACKGROUND: The impact of subsequent metastases on costs and medical resource use (MRU) for prostate cancer (PC) patients initially diagnosed with localized disease was estimated. METHODS: Surveillance, Epidemiology, and End Results data, linked to Medicare (1999-2012), were used to identify 7482 patients diagnosed with subsequent metastases 12 months or more after the initial diagnosis of localized PC (cases), and they were matched to 25,709 localized PC patients without subsequent metastases (controls). Patients were followed for costs and MRU from 12 months before their index date (subsequent metastases or a matched date for controls) up to 12 months after it. Costs and MRU were stratified by the setting/type of care/service. Multivariate mixed effects regression analyses were used to construct and compare longitudinal trajectories of marginal predicted costs and predicted probabilities of MRU between cases and controls. RESULTS: Among the controls, predicted monthly costs remained relatively stable throughout the entire observation period (weighted mean per patient per month, $2746; range during 24 months, $2603-2858). In contrast, among the cases, costs increased from $2622 (95% confidence interval [CI], $2525-2719) 12 months before the diagnosis of subsequent metastases to $4767 (95% CI, $4623-4910) 1 month before the diagnosis of subsequent metastases, peaked during the month of metastases at $13,291 (95% CI, $13,148-13,435), and remained significantly higher than costs for the controls thereafter (eg, $4677 at + 12 months; 95% CI, $4549-4805). Costs and MRU increased across a wide range of settings/types, including inpatient, outpatient, home health, and hospice settings. CONCLUSIONS: In PC patients initially diagnosed with localized disease, a diagnosis of subsequent metastases is associated with substantially increased costs and MRU. Cancer 2017;123:3591-601. © 2017 American Cancer Society.

Legacy effects of drought on plant-soil feedbacks and plant-plant interactions.

Interactions between aboveground and belowground biota have the potential to modify ecosystem responses to climate change, yet little is known about how drought influences plant-soil feedbacks with respect to microbial mediation of plant community dynamics. We tested the hypothesis that drought modifies plant-soil feedback with consequences for plant competition. We measured net pairwise plant-soil feedbacks for two grassland plant species grown in monoculture and competition in soils that had or had not been subjected to a previous drought; these were then exposed to a subsequent drought. To investigate the mechanisms involved, we assessed treatment responses of soil microbial communities and nutrient availability. We found that previous drought had a legacy effect on bacterial and fungal community composition that decreased plant growth in conspecific soils and had knock-on effects for plant competitive interactions. Moreover, plant and microbial responses to subsequent drought were dependent on a legacy effect of the previous drought on plant-soil interactions. We show that drought has lasting effects on belowground communities with consequences for plant-soil feedbacks and plant-plant interactions. This suggests that drought, which is predicted to increase in frequency with climate change, may change soil functioning and plant community composition via the modification of plant-soil feedbacks.

Global change pressures on soils from land use and management.

Soils are subject to varying degrees of direct or indirect human disturbance, constituting a major global change driver. Factoring out natural from direct and indirect human influence is not always straightforward, but some human activities have clear impacts. These include land-use change, land management and land degradation (erosion, compaction, sealing and salinization). The intensity of land use also exerts a great impact on soils, and soils are also subject to indirect impacts arising from human activity, such as acid deposition (sulphur and nitrogen) and heavy metal pollution. In this critical review, we report the state-of-the-art understanding of these global change pressures on soils, identify knowledge gaps and research challenges and highlight actions and policies to minimize adverse environmental impacts arising from these global change drivers. Soils are central to considerations of what constitutes sustainable intensification. Therefore, ensuring that vulnerable and high environmental value soils are considered when protecting important habitats and ecosystems, will help to reduce the pressure on land from global change drivers. To ensure that soils are protected as part of wider environmental efforts, a global soil resilience programme should be considered, to monitor, recover or sustain soil fertility and function, and to enhance the ecosystem services provided by soils. Soils cannot, and should not, be considered in isolation of the ecosystems that they underpin and vice versa. The role of soils in supporting ecosystems and natural capital needs greater recognition. The lasting legacy of the International Year of Soils in 2015 should be to put soils at the centre of policy supporting environmental protection and sustainable development.

Vegetation exerts a greater control on litter decomposition than climate warming in peatlands.

Historically, slow decomposition rates have resulted in the accumulation of large amounts of carbon in northern peatlands. Both climate warming and vegetation change can alter rates of decomposition, and hence affect rates of atmospheric CO2 exchange, with consequences for climate change feedbacks. Although warming and vegetation change are happening concurrently, little is known about their relative and interactive effects on decomposition processes. To test the effects of warming and vegetation change on decomposition rates, we placed litter of three dominant species (Calluna vulgaris, Eriophorum vaginatum, Hypnum jutlandicum) into a peatland field experiment that combined warming.with plant functional group removals, and measured mass loss over two years. To identify potential mechanisms behind effects, we also measured nutrient cycling and soil biota. We found that plant functional group removals exerted a stronger control over short-term litter decomposition than did approximately 1 degrees C warming, and that the plant removal effect depended on litter species identity. Specifically, rates of litter decomposition were faster when shrubs were removed from the plant community, and these effects were strongest for graminoid and bryophyte litter. Plant functional group removals also had strong effects on soil biota and nutrient cycling associated with decomposition, whereby shrub removal had cascading effects on soil fungal community composition, increased enchytraeid abundance, and increased rates of N mineralization. Our findings demonstrate that, in addition to litter quality, changes in vegetation composition play a significant role in regulating short-term litter decomposition and belowground communities in peatland, and that these impacts can be greater than moderate warming effects. Our findings, albeit from a relatively short-term study, highlight the need to consider both vegetation change and its impacts below ground alongside climatic effects when predicting future decomposition rates and carbon storage in peatlands.

Impact of the Prevalence of Concordant and Discordant Conditions on the Quality of Diabetes Care in Family Practices in England.

PURPOSE: The purpose of this study was to examine the association between the prevalence of both diabetes-concordant and diabetes-discordant conditions and the quality of diabetes care at the family practice level in England. We hypothesized that the prevalence of concordant (or discordant) conditions would be associated with better (or worse) quality of diabetes care. METHODS: We conducted a cross-sectional study using practice-level data (7,884 practices). We estimated the practice-level prevalence of diabetes and 15 other chronic conditions, which were classified as diabetes concordant (ie, with the same pathophysiologic risk profile and therefore more likely to be part of the same management plan) or diabetes discordant (ie, not directly related in either their pathogenesis or management). We measured quality of diabetes care with diabetes-specific indicators (8 processes and 3 intermediate outcomes of care). We used linear regression models to quantify the effect of the prevalence of the conditions on aggregate achievement rate for quality of diabetes care. RESULTS: Consistent with the proposed model, the prevalence rates of 4 of 7 concordant conditions (obesity, chronic kidney disease, atrial fibrillation, heart failure) were positively associated with quality of diabetes care. Similarly, negative associations were observed as predicted for 2 of the 8 discordant conditions (epilepsy, mental health). Observations for other concordant and discordant conditions did not match predictions in the hypothesized model. CONCLUSIONS: The quality of diabetes care provided in English family practices is associated with the prevalence of other major chronic conditions at the practice level. The nature and direction of the observed associations cannot be fully explained by the concordant-discordant model.

Niche specialization of terrestrial archaeal ammonia oxidizers.

Soil pH is a major determinant of microbial ecosystem processes and potentially a major driver of evolution, adaptation, and diversity of ammonia oxidizers, which control soil nitrification. Archaea are major components of soil microbial communities and contribute significantly to ammonia oxidation in some soils. To determine whether pH drives evolutionary adaptation and community structure of soil archaeal ammonia oxidizers, sequences of amoA, a key functional gene of ammonia oxidation, were examined in soils at global, regional, and local scales. Globally distributed database sequences clustered into 18 well-supported phylogenetic lineages that dominated specific soil pH ranges classified as acidic (pH <5), acido-neutral (5 ≤ pH <7), or alkalinophilic (pH ≥ 7). To determine whether patterns were reproduced at regional and local scales, amoA gene fragments were amplified from DNA extracted from 47 soils in the United Kingdom (pH 3.5-8.7), including a pH-gradient formed by seven soils at a single site (pH 4.5-7.5). High-throughput sequencing and analysis of amoA gene fragments identified an additional, previously undiscovered phylogenetic lineage and revealed similar pH-associated distribution patterns at global, regional, and local scales, which were most evident for the five most abundant clusters. Archaeal amoA abundance and diversity increased with soil pH, which was the only physicochemical characteristic measured that significantly influenced community structure. These results suggest evolution based on specific adaptations to soil pH and niche specialization, resulting in a global distribution of archaeal lineages that have important consequences for soil ecosystem function and nitrogen cycling.

Clinical and economic outcomes of assigning percutaneous coronary intervention patients to contrast-sparing strategies based on the predicted risk of contrast-induced acute kidney injury.

OBJECTIVE: Contrast-sparing strategies have been developed for percutaneous coronary intervention (PCI) patients at increased risk of contrast-induced acute kidney injury (CI-AKI), and numerous CI-AKI risk prediction models have been created. However, the potential clinical and economic consequences of using predicted CI-AKI risk thresholds for assigning patients to contrast-sparing regimens have not been evaluated. We estimated the clinical and economic consequences of alternative CI-AKI risk thresholds for assigning Medicare PCI patients to contrast-sparing strategies. METHODS: Medicare data were used to identify inpatient PCI from January 2017 to June 2021. A prediction model was developed to assign each patient a predicted probability of CI-AKI. Multivariable modeling was used to assign each patient two marginal predicted values for each of several clinical and economic outcomes based on (1) their underlying clinical and procedural characteristics plus their true CI-AKI status in the data and (2) their characteristics plus their counterfactual CI-AKI status. Specifically, CI-AKI patients above the predicted risk threshold for contrast-sparing were reassigned their no CI-AKI (counterfactual) outcomes. Expected event rates, resource use, and costs were estimated before and after those CI-AKI patients were reassigned their counterfactual outcomes. This entailed bootstrapped sampling of the full cohort. RESULTS: Of the 542,813 patients in the study cohort, 5,802 (1.1%) had CI-AKI. The area under the receiver operating characteristic curve for the prediction model was 0.81. At a predicted risk threshold for CI-AKI of >2%, approximately 18.0% of PCI patients were assigned to contrast-sparing strategies, resulting in (/100,000 PCI patients) 121 fewer deaths, 58 fewer myocardial infarction readmissions, 4,303 fewer PCI hospital days, $11.3 million PCI cost savings, and $25.8 million total one-year cost savings, versus no contrast-sparing strategies. LIMITATIONS: Claims data may not fully capture disease burden and are subject to inherent limitations such as coding inaccuracies. Further, the dataset used reflects only individuals with fee-for-service Medicare, and the results may not be generalizable to Medicare Advantage or other patient populations. CONCLUSIONS: Assignment to contrast-sparing regimens at a predicted risk threshold close to the underlying incidence of CI-AKI is projected to result in significant clinical and economic benefits.

An observational study of outcomes after initial infused therapy in Medicare patients diagnosed with chronic lymphocytic leukemia.

The study goal was to characterize older chronic lymphocytic leukemia (CLL) patients and to evaluate outcomes in those patients who initiated infused therapy. Patients 66 years of age and older in the Surveillance, Epidemiology, and End Results (SEER) program with a CLL diagnosis were matched to their Medicare Part A and Part B claims for long-term follow-up. Treatment patterns, survival after initiation of infused therapy, and both hematologic and hospitalization outcomes were assessed. There were 6433 CLL patients identified, and 2040 received infused therapy. Treated patients were categorized as receiving rituximab monotherapy (16%), rituximab plus chemotherapy (14%), and chemotherapy alone (70%) based on the initial 60 days after infusion. Rituximab plus chemotherapy compared with chemotherapy alone was associated with a 25% lower risk of overall mortality (95% confidence interval, 9%-38%). Restricting to patients age 70 years and older did not change the risk reduction for rituximab plus chemotherapy. Hematologic interventions were more common with rituximab plus chemotherapy compared with chemotherapy alone, but there was no difference in all-cause hospitalizations. These analyses, based on observational data, suggest that the benefits of initial therapy with rituximab in a heterogeneous group of older CLL patients are comparable with those demonstrated in younger patients.

Prevalence and incidence of comorbidities in elderly women with ovarian cancer.

OBJECTIVE: Studies suggest comorbidity plays an important role in ovarian cancer. We characterized the epidemiology of comorbid conditions in elderly U.S. women with ovarian cancer. METHODS: Women with ovarian cancer age ≥66 years, and matched cancer-free women, were identified using the National Cancer Institute's Surveillance, Epidemiology, and End Results registry linked to Medicare claims. Prevalence before diagnosis/index date and 3- and 12-month incidence rates (per 1000 person-years) after diagnosis/index date were estimated for 34 chronic and acute conditions across a broad range of diagnostic categories. RESULTS: There were 5087 each of women with ovarian cancer and cancer-free women. The prevalence of most conditions was similar between cancer and cancer-free patients, but exceptions included hypertension (51.8% and 43.5%, respectively), osteoarthritis (13.4% and 17.3%, respectively), and cerebrovascular disease (8.0% and 9.8%, respectively). In contrast, 3- and 12-month incidence rates (per 1000 person years) of most conditions were significantly higher in cancer than in cancer-free patients: hypertension (177.3 and 47.4, respectively); thromboembolic event (145.3 and 5.5, respectively); congestive heart failure (113.3 and 28.6, respectively); infection (664.4 and 55.2, respectively); and anemia (408.3 and 33.1, respectively) at 12 months. CONCLUSIONS: Comorbidities were common among elderly women. After cancer diagnosis, women with ovarian cancer had a much higher incidence of comorbidities than cancer-free women. The high incidence of some of these comorbidities may be related to the cancer or its treatment, but others may have been prevalent but undiagnosed until the cancer diagnosis. The presence of comorbidities may affect treatment decisions.

Misclassification of incident conditions using claims data: impact of varying the period used to exclude pre-existing disease.

BACKGROUND: Estimating the incidence of medical conditions using claims data often requires constructing a prevalence period that predates an event of interest, for instance the diagnosis of cancer, to exclude those with pre-existing conditions from the incidence risk set. Those conditions missed during the prevalence period may be misclassified as incident conditions (false positives) after the event of interest.Using Medicare claims, we examined the impact of selecting shorter versus longer prevalence periods on the incidence and misclassification of 12 relatively common conditions in older persons. METHODS: The source of data for this study was the National Cancer Institute's Surveillance, Epidemiology, and End Results cancer registry linked to Medicare claims. Two cohorts of women were included: 33,731 diagnosed with breast cancer between 2000 and 2002, who had ≥ 36 months of Medicare eligibility prior to cancer, the event of interest; and 101,649 without cancer meeting the same Medicare eligibility criterion. Cancer patients were followed from 36 months before cancer diagnosis (prevalence period) up to 3 months after diagnosis (incidence period). Non-cancer patients were followed for up to 39 months after the beginning of Medicare eligibility. A sham date was inserted after 36 months to separate the prevalence and incidence periods. Using 36 months as the gold standard, the prevalence period was then shortened in 6-month increments to examine the impact on the number of conditions first detected during the incidence period. RESULTS: In the breast cancer cohort, shortening the prevalence period from 36 to 6 months increased the incidence rates (per 1,000 patients) of all conditions; for example: hypertension 196 to 243; diabetes 34 to 76; chronic obstructive pulmonary disease 29 to 46; osteoarthritis 27 to 36; congestive heart failure 20 to 36; osteoporosis 22 to 29; and cerebrovascular disease 13 to 21. Shortening the prevalence period has less impact on those without cancer. CONCLUSIONS: Selecting a short prevalence period to rule out pre-existing conditions can, through misclassification, substantially inflate estimates of incident conditions. In incidence studies based on Medicare claims, selecting a prevalence period of ≥24 months balances the need to exclude pre-existing conditions with retaining the largest possible cohort.

Comparative effectiveness and cost of adding rituximab to first-line chemotherapy for elderly patients diagnosed with diffuse large B-cell lymphoma.

BACKGROUND: Clinical trials indicate that rituximab improves the survival of patients with diffuse large B-cell lymphoma (DLBCL). Economic models using multiple data sources, including clinical trials for survival outcomes, have projected cost offsets/savings and favorable cost-effectiveness associated with rituximab. In this study, the authors evaluated survival and cost impacts of adding rituximab to first-line chemotherapy for DLBCL using a single database that reflects routine clinical practice among elderly patients in the United States. METHODS: By using Surveillance, Epidemiology, and End Results (SEER) data linked to Medicare, the authors identified 5484 elderly patients who were diagnosed with DLBCL between January 1999 and December 2005 who had claims through December 2007. Included patients began chemotherapy with or without rituximab within 180 days of diagnosis. Multivariate analyses were conducted to estimate the impact of rituximab on mortality and costs to Medicare. The cost per life-year gained of rituximab was calculated using cost and survival estimates from the multivariate analyses. RESULTS: The mean patient age was 76 years, 43% of patients had stage III or IV disease, and 64% received rituximab. In a Cox regression model, rituximab resulted in lower 4-year all-cause mortality (hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.61-0.74) and cancer mortality, and the incremental cumulative survival was 0.37 years. In least-squares regression, rituximab resulted in higher 4-year total costs ($23,097; 95% CI, $19,129-$27,298), immunochemotherapy costs ($12,069; 95% CI, $10,687-$13,634), other cancer costs ($7655; 95% CI, $5067-$10,489), and noncancer costs ($3461; 95% CI, $1319-$5650). The cost per life-year gained was $62,424. CONCLUSIONS: In routine clinical practice, rituximab was associated with survival benefits comparable to those observed in clinical trials. However, these benefits did not translate into the previously reported cost savings.

Epidemiology and outcomes of previously undiagnosed diabetes in older women with breast cancer: an observational cohort study based on SEER-Medicare.

BACKGROUND: In breast cancer, diabetes diagnosed prior to cancer (previously diagnosed) is associated with advanced cancer stage and increased mortality. However, in the general population, 40% of diabetes is undiagnosed until glucose testing, and evidence suggests one consequence of increased evaluation and management around breast cancer diagnosis is the increased detection of previously undiagnosed diabetes. Biological factors - for instance, higher insulin levels due to untreated disease - and others underlying the association between previously diagnosed diabetes and breast cancer could differ in those whose diabetes remains undiagnosed until cancer. Our objectives were to identify factors associated with previously undiagnosed diabetes in breast cancer, and to examine associations between previously undiagnosed diabetes and cancer stage, treatment patterns, and mortality. METHODS: Using Surveillance, Epidemiology, and End Results-Medicare, we identified women diagnosed with breast cancer and diabetes between 01/2001 and 12/2005. Diabetes was classified as previously diagnosed if it was identified within Medicare claims between 24 and 4 months before cancer diagnosis, and previously undiagnosed if it was identified from 3 months before to ≤ 3 months after cancer. Patients were followed until 12/2007 or death, whichever came first. Multivariate analyses were performed to examine risk factors for previously undiagnosed diabetes and associations between undiagnosed (compared to previously diagnosed) diabetes, cancer stage, treatment, and mortality. RESULTS: Of 2,418 patients, 634 (26%) had previously undiagnosed diabetes; the remainder had previously diagnosed diabetes. The mean age was 77.8 years, and 49.4% were diagnosed with in situ or stage I disease. Age > 80 years (40% of the cohort) and limited health system contact (primary care physician and/or preventive services) prior to cancer were associated with higher adjusted odds of previously undiagnosed diabetes. Previously undiagnosed diabetes was associated with higher adjusted odds of advanced stage (III/IV) cancer (Odds Ratio = 1.37: 95% Confidence Interval (CI) 1.05 - 1.80; P = 0.02), and a higher adjusted mortality rate due to causes other than cancer (Hazard Ratio = 1.29; 95% CI 1.02 - 1.63; P = 0.03). CONCLUSIONS: In breast cancer, previously undiagnosed diabetes is associated with advanced stage cancer and increased mortality. Identifying biological factors would require further investigation.

Inverse probability weighted least squares regression in the analysis of time-censored cost data: an evaluation of the approach using SEER-Medicare.

OBJECTIVES: To assess the accuracy and precision of inverse probability weighted (IPW) least squares regression analysis for censored cost data. METHODS: By using Surveillance, Epidemiology, and End Results-Medicare, we identified 1500 breast cancer patients who died and had complete cost information within the database. Patients were followed for up to 48 months (partitions) after diagnosis, and their actual total cost was calculated in each partition. We then simulated patterns of administrative and dropout censoring and also added censoring to patients receiving chemotherapy to simulate comparing a newer to older intervention. For each censoring simulation, we performed 1000 IPW regression analyses (bootstrap, sampling with replacement), calculated the average value of each coefficient in each partition, and summed the coefficients for each regression parameter to obtain the cumulative values from 1 to 48 months. RESULTS: The cumulative, 48-month, average cost was $67,796 (95% confidence interval [CI] $58,454-$78,291) with no censoring, $66,313 (95% CI $54,975-$80,074) with administrative censoring, and $66,765 (95% CI $54,510-$81,843) with administrative plus dropout censoring. In multivariate analysis, chemotherapy was associated with increased cost of $25,325 (95% CI $17,549-$32,827) compared with $28,937 (95% CI $20,510-$37,088) with administrative censoring and $29,593 ($20,564-$39,399) with administrative plus dropout censoring. Adding censoring to the chemotherapy group resulted in less accurate IPW estimates. This was ameliorated, however, by applying IPW within treatment groups. CONCLUSION: IPW is a consistent estimator of population mean costs if the weight is correctly specified. If the censoring distribution depends on some covariates, a model that accommodates this dependency must be correctly specified in IPW to obtain accurate estimates.