Comprehensive Assessment of Ischemic Stroke in Nonhuman Primates: Neuroimaging, Behavioral, and Serum Proteomic Analysis.

Ischemic strokes, prevalence and impactful, underscore the necessity of advanced research models closely resembling human physiology. Our study utilizes nonhuman primates (NHPs) to provide a detailed exploration of ischemic stroke, integrating neuroimaging data, behavioral outcomes, and serum proteomics to elucidate the complex interplay of factors involved in stroke pathophysiology. We observed a consistent pattern in infarct volume, peaking at 1-month postmiddle cerebral artery occlusion (MCAO) and then stabilized. This pattern was strongly correlated to notable changes in motor function and working memory performance. Using diffusion tensor imaging (DTI), we detected significant alterations in fractional anisotropy (FA) and mean diffusivity (MD) values, signaling microstructural changes in the brain. These alterations closely correlated with the neurological and cognitive deficits that we observed, highlighting the sensitivity of DTI metrics in stroke assessment. Behaviorally, the monkeys exhibited a reliance on their unaffected limb for compensatory movements, a common response to stroke impairment. This adaptation, along with consistent DTI findings, suggests a significant impact of stroke on motor function and spatial perception. Proteomic analysis through MS/MS functional enrichment identified two distinct groups of proteins with significant changes post-MCAO. Notably, MMP9, THBS1, MB, PFN1, and YWHAZ were identified as potential biomarkers and therapeutic targets for ischemic stroke. Our results underscore the complex nature of stroke and advocate for an integrated approach, combining neuroimaging, behavioral studies, and proteomics, for advancing our understanding and treatment of this condition.

Characteristics, sources and health risk assessment of atmospheric carbonyls during multiple ozone pollution episodes in urban Beijing: Insights into control strategies.

Carbonyls have attracted continuous attention due to their critical roles in atmospheric chemistry and their potential hazards to the ecological environment and human health. In this study, atmospheric carbonyls were measured during several ground-level-ozone (O3) pollution episodes at three urban sites (CRAES, IEP and BJUT) in Beijing in 2019 and 2020. Comparative analysis revealed that the carbonyl concentrations were 20.25 ± 6.91 ppb and 13.43 ± 5.13 ppb in 2019 and 2020 in Beijing, respectively, with a significant spatial trend from north to south, and carbonyl levels in urban Beijing were in an upper-intermediate range in China, and higher than those in other countries reported in the literature. A particularly noteworthy phenomenon is the consistency of carbonyl concentrations with variations in O3 concentrations. On O3 polluted days, the carbonyl concentrations were 1.3-1.5 times higher than those on non-O3 polluted days. Secondary formation contributed more to formaldehyde (FA) and acetaldehyde (AA) on O3 polluted days, while the anthropogenic emissions were more significant for acetone (AC) on non-O3 polluted days. Vehicle exhaust and solvent utilization were the main primary contributors to carbonyls. Due to reduced anthropogenic emissions caused by the COVID-19 lockdown and the "Program for Controlling Volatile Organic Compounds in 2020" in China, the contributions of primary emissions to carbonyls decreased in 2020 in Beijing. Human cancer risks to exposed populations from FA and AA increased with elevated O3 levels, and the risks still remained on non-O3 polluted days. The residents around the BJUT site might experience relatively higher human cancer risks than those around the other two sites. The findings in this study confirmed that atmospheric carbonyl pollution and its potential human health hazards cannot be ignored in urban Beijing; therefore, more strict control strategies for atmospheric carbonyls are urgently needed to better protect human health in Beijing in the future.

Does Financial Literacy Affect Household Financial Behavior? The Role of Limited Attention.

Financial literacy is essential for every individual concerned with public welfare and household portfolio choices. In this study, we investigate the impact of household financial literacy on individuals' financial behavior using the China Household Financial Survey Data (CHFS) of 2015 and 2017. The results show that financial knowledge has significant current, long-term, and dynamic effects on financial behavior. This finding suggests that financial literacy is an important factor in shaping and improving financial behavior. Second, financial literacy can improve residents' limited attention, and residents with high attention tend to have formal bank accounts, participate in the stock market, and engage in financial behaviors in situations such as risky financial markets. High attention also helps to improve residents' financial behavior. This relationship suggests that financial literacy positively impacts formal bank account holding, participation in financial markets, participation in commercial insurance, participation in pension plans, and credit card holdings through limited attention channels that facilitate access to specific financial information. In addition, heterogeneity analysis showed that the impact of financial literacy on financial behavior differs significantly between urban and rural households, between men and women, and between high and low education levels. The study provides valuable insights for policy implications to enhance financial literacy, such as carrying out financial training to improve residents' knowledge about financial aspects, which further helps to optimize household financial decision-making.

PAHs and nitro-PAHs in urban Beijing from 2017 to 2018: Characteristics, sources, transformation mechanism and risk assessment.

Polycyclic aromatic hydrocarbons (PAHs) and their nitrated derivatives (NPAHs) attract continuous attention due to their distinct carcinogenicity and mutagenicity. To investigate the characteristics, sources, formation mechanism and health risk assessment of PAHs and NPAHs, PM2.5 were collected at an urban site in Beijing from 2017 to 2018. The highest PAHs and NPAHs concentrations were 77.92 ± 54.62 ng/m3 and 963.71 ± 695.06 pg/m3 in the winter campaign, which were several times larger than those in other seasonal campaigns. Distinct diurnal variations of nocturnal levels higher than daytime levels were shown for PAHs and NPAHs. Source analysis indicated that besides vehicle exhaust, biomass burning and coal combustion were important sources of PAHs and NPAHs in the fall and winter campaigns. Secondary formation in atmosphere was another source of NPAHs especially in the spring and summer campaigns. NO2 and RH could positively influence the heterogeneous formation of NPAHs when RH was less than 60%. Quantum calculation results confirmed the formation pathway of 2N-FLA from the OH/NO3-initiated oxidation of FLA. The results of health risk assessment showed the potential health risks for the residents, especially in the winter campaign. These results indicated that PAHs and NPAHs still deserve attention following with the decrease concentrations of particulate matter.

Atmospheric carbonyls in a heavy ozone pollution episode at a metropolis in Southwest China: Characteristics, health risk assessment, sources analysis.

Ambient carbonyls were continuously observed in the field during a heavy ozone pollution episode in Chengdu, China from August 4 to August 19, 2019, and the pollution characteristics, atmospheric photochemical reactivity, human health risk, and sources of carbonyls were analyzed. Fifteen carbonyls were quantified with average total mixing ratios of 20.38 ppbv Formaldehyde (9.86 ppbv), acetone (4.41 ppbv), and acetaldehyde (3.57 ppbv) were the three most abundant carbonyls. During the heavy ozone pollution episode, the concentration of carbonyls was found to be higher on pollution days than on the clean days, and relatively higher in the daytime, especially at noon on the pollution days. This was influenced by the intensity of photochemical reactions and precipitation. The "weekend effect" with the concentration of carbonyls was higher on the weekends than on the weekdays was pointed out. Formaldehyde, acetaldehyde and hexaldehyde were the dominant oxidative species during the observation. The carcinogenic and non-carcinogenic risk values of formaldehyde and acetaldehyde were higher on pollution days than on clean days, and these values were higher compared with those of other cities in China and abroad. Long-term exposure to these compounds should therefore be avoided. Diagnostic ratios and correlation analysis together with backward trajectory analysis showed that primary emission and secondary formation accounted 66%-76% and 24%-34% of carbonyls in Chengdu, respectively, with primary emission being the main sources of carbonyls, and carbonyls from the surrounding cities and emission from natural sources also had a significant contribution to the carbonyls in Chengdu.

Situation and Countermeasures of the Management Team of the Elderly Care Institutions from the Perspective of the Combination of Medical and Health Care: A Cross-Sectional Study.

Objective: In order to provide evidence for improving the quality of managers in elderly care institutions, this paper explored the situation of managers of elderly care institutions in a city in Central China under the national guidelines for the combination of medical and elderly health care. Design: A cross-sectional study carried out in a city in Central China was designed. Setting. The online questionnaire was distributed to the managers of six elderly care institutions in a city in Central China. Participants. The questionnaire was sent to 61 recipients; from this, 60 responses were obtained. Results: There was a 98% response rate. The study found that most managers in elderly care institutions were middle-aged, with low education level and years of management. The job mobility was high, and 27% of the managers had no relevant certificates. Management years had a significant influence on the rate of certificate holding (P < 0.05). Some managers were less than 30 years old and had college degree or above, which indicated that people with young and high levels of education were more likely to become managers. However, there was no significant difference in educational level among managers of different ages (P > 0.05). 56.6% of the managers have received provincial or municipal training, and few managers have received the national level training. The education level is positively related to the access to training opportunities. More than half of the managers earn less than ¥3000 a month. The study showed that the education level was positively related to the career growth space (P < 0.05). Conclusions: Specialized training and high salary should be provided for managers to improve their elderly care skills and hence the quality of elderly care service. In addition, in order to improve the education level of managers, a long-term continuing education system should be established gradually. Through expanding the enrollment scale of the nursing school, carrying out training about elderly care skills, and issuing vocational skills certificates to those who pass the examination, the number of local nurses for the elderly will be increasing, and the quality of the elderly care service will be improving.

Assessment of clinical sepsis-associated biomarkers in a septic mouse model.

Objective Clinical sepsis-associated biomarkers were utilized in a cecal ligation and puncture (CLP) septic mouse model to provide a reference for investigating pathophysiological mechanisms and evaluating novel therapeutic interventions for sepsis. Methods Sepsis in mice was induced by CLP, and clinical biomarkers were evaluated (survival rate, blood physiological and biochemical indices, cytokines, hepatorenal function parameters, and blood coagulation). Results The mortality rate was >70%. The body temperature, blood pressure, and heart rate decreased within 48 h. Low lactic acid was found at 8 h. The CLP mice showed typical inflammatory symptoms with decreased white blood cells and procalcitonin and increased levels of soluble triggering receptor expressed on myeloid cells-1, interleukin (IL)-6, IL-10, tumor necrosis factor-α, macrophage inflammatory protein (MIP)-1α, MIP-1ß, and MIP-2. The platelet count and activated partial thromboplastin time significantly decreased, and the prothrombin time and prothrombin time-international normalized ratio markedly increased. Phenotypes of multiple organ dysfunction were found in the CLP model, including increased liver alanine aminotransferase and aspartate transaminase; significantly reduced total protein, globulin, and serum albumin; increased blood urea nitrogen and creatinine; and decreased blood glucose. Conclusion The clinical features of the CLP mouse model were similar to those of human patients with sepsis.

Treatment Changes in Patients With Moderate to Severe Psoriasis: A Retrospective Chart Review.

BACKGROUND: Psoriasis treatment involves topical medications, oral medications, phototherapy, and/or biologics. The treatments used depend on a myriad of factors that change over time. OBJECTIVE: To characterise the frequency of and reasons for treatment changes in patients with moderate to severe psoriasis. METHODS: A chart review examined treatment changes at 902 visits by 116 patients seen between January 1, 2010, and June 30, 2015, for moderate to severe psoriasis and the physicians' justifications for those changes. 'Treatment change' was defined as switching between, adding, or removing medication classes or switching within the oral or biologic class. RESULTS: There were 221 visits with treatment changes identified, and a change occurred every 4.1 visits. On average, there were 1.2 treatment changes per year. Patients treated for at least 1 year averaged 1 treatment change every 16 months. The most common type of change was from one biologic to another biologic (24.9%), followed by adding a nonbiologic to a biologic (18.6%). The most common reason for switching was poor control or flare of psoriasis. Affordability was a more common problem for biologics than for nonbiologic treatments. CONCLUSIONS: Biologic treatment options provide a major improvement over older systemic treatments, but patients still undergo frequent treatment changes to help control their disease.

Drivers of Healthcare Costs Among the Costliest Patients With Psoriasis Over Three Years in a United States Health Plan.

OBJECTIVE: To compare patients with psoriasis by cost level over 3 years.

METHODS: Psoriasis patients in a large US health plan in 2011-2013 were identified. Four groups were created by healthcare costs excluding biologics: patients having top 10% of costs in all 3 years (Top), top 10% in 2 of 3 years (High), bottom 90% in 2 of 3 years (Medium), and bottom 90% in all 3 years (Bottom). Comorbidities, utilization, and costs between groups were compared.

RESULTS: The study included 18,653 patients: 514 (3%), 805 (4%), 2,443 (13%), and 14,891 (80%) patients in the Top, High, Medium, and Bottom groups, respectively. Significantly more patients in the Top vs Bottom group had diabetes (31.1% vs 9.4%), cardiovascular disease (26.5% vs 4.3%), psoriatic arthritis (25.7% vs 10.7%), depression (27.8% vs 6.9%), and anxiety (22.0% vs 7.9%) in 2011 (all P less than 0.05). Patients in the Top group had more unique 2011 prescriptions (17.7 vs 6.6; P less than 0.001) than the Bottom group, but similar biologic use (22.4% vs 21.6%). Patients in the Top, High, Medium, and Bottom groups had mean 2011 total costs of $68,913, $40,575, $24,292, and $8,815, and contributed to 14%, 13%, 23%, and 51% of the overall costs, respectively. Mean total costs increased 14-18% over time for all groups. Although mean 2011 total costs for patients in the Top group were 7.8 times of those in the Bottom group, psoriasis-related costs were less disparate ($8,716 vs $4,541). Compared with patients in the Bottom group, those in the Top group were more likely to have any 2011 hospitalization (36.8% vs 2.6%; psoriasis-related: 11.1% vs 0.7%) or emergency visit (50.8% vs 20.8%; psoriasis-related: 3.9% vs 1.0%).

CONCLUSION: The costliest patients with psoriasis had significantly higher prevalence of comorbidities, prescription fills, inpatient and emergency utilization, but not biologic medication use or biologic costs.

J Drugs Dermatol. 2017;16(7):651-658.

Economic impact of biologic utilization patterns in patients with psoriatic arthritis.

The aim of the study is to examine the frequency and costs associated with above-label dosing of biologics in patients with psoriatic arthritis (PsA). MarketScan identified adults with ≥1 International Classification of Diseases, Clinical Modification diagnosis for PsA and ≥1 pharmacy claim for biologics of interest between January 1, 2011 and December 31, 2013. The first biologic claim was the index date with a 1-year follow-up period and three additional months to confirm continuous biologic use. Exclusion criteria included switching to a different biologic or diagnosis with another autoimmune disease. During the follow-up period, duration was stratified into three groups: <30, 30-179, and ≥180 days of above-label dosing (>10% of the labeled dose). One-tailed t test was conducted to examine the impact of above-label duration on healthcare costs. We identified 4245 PsA patients receiving etanercept (n = 2342), adalimumab (n = 1788), and golimumab (n = 115). Above-label dosing of <30 days (85% adalimumab, 90.4% etanercept, and 95.7% golimumab) and ≥180 days (9.6% adalimumab, 4.1% etanercept, and 2.6% golimumab) was observed. All-cause total healthcare costs for <30 days of above-label use (etanercept $30,625, adalimumab $31,620, and golimumab $37,224), 30-179 days (etanercept $35,602, adalimumab $38,915, and golimumab $64,349), and ≥180 days (etanercept $55,349, adalimumab $54,176, and golimumab $47,993) were reported. Longer above-label duration (30-179 versus <30 days, ≥180 versus 30-179 and ≥180 days) with etanercept or adalimumab was significantly associated with higher mean increased total all-cause healthcare, PsA-specific healthcare, and biologic costs (p < 0.05). Above-label use of anti-TNF biologics does occur and is associated with significantly increased healthcare costs.

Economic Impact of Above-Label Dosing with Etanercept, Adalimumab, or Ustekinumab in Patients with Psoriasis.

BACKGROUND: Patients with moderate-to-severe psoriasis may be treated with above-label doses of biologics in an attempt to optimize outcomes. Dose escalation will have an effect on the cost of treatment. OBJECTIVE: To examine costs related to above-label use of etanercept, adalimumab, and ustekinumab among patients with moderate-to-severe psoriasis. METHODS: A retrospective study was performed using a large U.S. claims database. Patients were included in the study if they were aged ≥ 18 years with a diagnosis of psoriasis (excluding psoriatic arthritis) and had at least 1 medication fill for etanercept, adalimumab, or ustekinumab between January 1, 2011, and June 30, 2012. In addition, patients were required to have continuous enrollment for 12 months before, and 18 months after, the first biologic use (index biologic) during the maintenance period (defined as the period following the induction period in which each agent was titrated to its recommended maintenance dose per label) and at least 1 prescription filled for the index biologic during the 18 months after the maintenance period. Extensive above-label use was defined as taking an above-label dose (at least 10% higher than indicated in the label) for ≥ 180 days over a 12-month period following the maintenance period. Percentages of patients with extensive above-label use, mean number of days of above-label use, and additional costs associated with extensive above-label use (abovelabel cost minus on-label cost) were examined. RESULTS: The study included 3,310 patients who started treatment with etanercept (n = 1,443), adalimumab (n = 1,447), or ustekinumab (n = 420). Extensive above-label use occurred in 20.0% of etanercept patients, 2.6% of adalimumab patients, and 14.8% of ustekinumab patients. The mean duration of extensive above-label use was roughly similar for the 3 biologics (mean days [±SD]: 282 [±55] for etanercept, 279 [±57] for adalimumab, and 305 [±43] for ustekinumab). Additional annual costs per patient because of extensive above-label use were $19,458 for etanercept, $18,972 for adalimumab, and $21,045 for ustekinumab. Total additional annual costs were $5,623,362 for etanercept, $701,964 for adalimumab, and $1,304,790 for ustekinumab. CONCLUSIONS: Psoriasis patients treated with etanercept, adalimumab, or ustekinumab had extensive above-label use over the 12-month follow-up period, which subsequently led to higher costs. DISCLOSURES: Novartis Pharmaceuticals Corporation sponsored this study and the resultant publication. BioScience Communications provided medical writing and editorial support, which was also funded by Novartis Pharmaceuticals Corporation. Feldman was engaged by Novartis Pharmaceuticals as a paid clinical expert and scientific advisor for this study. He has received research support and speaking and/or consulting fees from AbbVie, Advance Medical, Amgen, Anacor, Astellas, Baxter, Boehringer Ingelheim, Caremark, Celgene, Eli Lilly, Galderma, GSK/Stiefel, Informa, Janssen, LEO Pharma, Merck, Merz, Mylan, National Biological, National Psoriasis Foundation, Pfizer, Qurient, Suncare Research, UpToDate, and Valeant; is the founder and majority owner of www.DrScore.com ; and is founder and part owner of Causa Research. Zhao, Herrera, Tian, and Li are employees of Novartis Pharmaceuticals. Zhou is a paid consultant for Novartis Pharmaceuticals and is an employee of KMK Consulting. Study concept and design were contributed by Feldman, Zhao, Herrera, and Li. Zhou and Li were responsible for data collection. Data were interpreted by Feldman and Zhao, with assistance from Zhou, Herrera, Tian, and Li. The manuscript was written primarily by Feldman and Zhao, with assistance from Zhou and Li. The manuscript was revised by Feldman and Zhao, assisted by Zhou, Herrera, Tian, and Li. Portions of this work were presented at the 34th Anniversary Fall Clinical Dermatology Conference in Las Vegas, Nevada, October 1-4, 2015.

Rethinking costs of psoriasis: 10% of patients account for nearly 40% of healthcare expenditures among enrollees with psoriasis in a U.S. health plan.

OBJECTIVE: To examine characteristics, healthcare utilization and costs among patients with psoriasis who have high medical costs. METHODS: This is a retrospective study of patients with psoriasis with continuous enrollment from 1 January 2011 to 31 December 2013 in a large US health plan. Total paid 2012 healthcare costs excluding biologics (to identify costliest not due to biologic costs) were used to create cohorts representing the top 10% (T10) and bottom 90% (B90) of expenditures. Demographics, comorbidities, prescriptions, all-cause and psoriasis-related healthcare utilization and costs were compared between cohorts. Logistic regression identified demographic and clinical characteristics associated with the 2012 T10 cohort status. RESULTS: 18,653 patients (mean age 48 years; 49% female) were included. Patients in the T10 group accounted for 26% (2011), 39% (2012) and 26% (2013) of all-cause costs including biologics and 13% (2011), 18% (2012) and 11% (2013) of psoriasis-related costs. Mean 2012 total costs were $58,030 for T10 vs. $10,295 for B90 (all-cause) and $10,475 vs. $5301 (psoriasis-related). T10 patients in 2012 filled more prescriptions and were more likely to use corticosteroids (57% vs. 31%); however, biologic use and costs were similar (any use: 23% vs. 24%; prescriptions: 1.5 vs. 1.7, biologic costs: $4959 vs. $5095). Compared with B90 patients, T10 patients were more likely to have hospitalizations (all-cause: 45% vs. 3%; psoriasis-related: 14% vs. 1%) and ER visits (all-cause: 53% vs. 21%; psoriasis-related: 3% vs. 1%), and more likely to have renal disease (odds ratio (OR) = 2.05), depression (OR =1.96), cardiovascular disease (OR =1.88), psoriatic arthritis (OR =1.57) and diabetes (OR =1.50) (all p < .05). CONCLUSIONS: The T10 patient cohort in 2012 accounted for nearly 40% of overall healthcare expenditures. However, cost differences between the T10 and B90 patients were not attributable to psoriasis-related biologic treatment utilization and costs. The T10 patients had significantly more inpatient and emergency utilization, and comorbid medical conditions.

Difference-in-Differences Method in Comparative Effectiveness Research: Utility with Unbalanced Groups.

BACKGROUND: Comparative effectiveness research (CER) often includes observational studies utilizing administrative data. Multiple conditioning methods can be used for CER to adjust for group differences, including difference-in-differences (DiD) estimation. OBJECTIVE: This study presents DiD and demonstrates how to apply this conditioning method to estimate treatment outcomes in the CER setting by utilizing the MarketScan® Databases for multiple sclerosis (MS) patients receiving different therapies. METHODS: The sample included 6762 patients, with 363 in the Test Cohort [glatiramer acetate (GA) switched to fingolimod (FTY)] and 6399 in the Control Cohort (GA only, no switch) from a US administrative claims database. A trend analysis was conducted to rule out concerns regarding regression to the mean and to compare relapse rates among treatment cohorts. DiD analysis was used to enable comparisons among the Test and Control Cohorts. Logistic regression was used to estimate the probability of relapse after switching from GA to FTY, and to compare group differences in the pre- and post-index periods. RESULTS: Crude DiD analysis showed that in the pre-index period more patients in the Test Cohort experienced an MS relapse and had a higher mean number of relapses than in the Control Cohort. During the pre-index period, numeric and relative data for MS relapses in patients in the Test Cohort were significantly higher than in the Control Cohort, while no significant between-group differences emerged during the post-index period. Generalized linear modeling with DiD regression estimation showed that the mean number of MS relapses decreased significantly in the post-index period among patients in the Test Cohort compared with patients in the Control Cohort. CONCLUSION: In this study, an MS population was utilized to demonstrate how DiD can be applied to estimate treatment effects in a heterogeneous population, where the Test and Control Cohorts varied greatly. The results show that DiD offers a robust method for comparing diverse cohorts when other risk-adjustment methods may not be adequate.

Treatment patterns and costs for anti-TNFα biologic therapy in patients with psoriatic arthritis.

BACKGROUND: Real-world data regarding anti-tumor necrosis factor alpha (anti-TNFα) biologic therapy use in psoriatic arthritis (PsA) are limited; therefore, we described treatment patterns and costs of anti-TNFα therapy in PsA patients in the United States. METHODS: PsA patients (N = 990) aged ≥18 years who initiated anti-TNFα therapy were selected from MarketScan claims databases (10/1/2009 to 9/30/2010). Number of patients on first- (n = 881), second- (n = 72), or third- or greater (n = 37) line of anti-TNFα therapy, persistence, time-to-switch or modification, pharmacy and medical costs (measured per patient per month [PPPM]) for each line of therapy were observed during the 3-year follow-up. RESULTS: PsA patients receiving only one line of anti-TNFα therapy remained on first-line for ~17 months while those who switched to second- or third- or greater persisted on first-line for ~11 to 12 months, respectively. Time to first-line modification was longer for patients who switched to third- or greater line therapy (7 months) than those who did not switch or switched to second-line (range, ~2 to 4 months). Time-to-switch and time to first-line modification was progressively shorter with each line of therapy for patients who received third- or greater line. PPPM medical costs were higher for patients who did not switch ($322) than those who switched to second- ($167) or third- or greater ($217) line. PPPM pharmacy costs were greater for patients with third- or greater line therapy ($2539) than those who did not switch ($1985) or switched to second-line ($2045). CONCLUSION: While the majority of patients received only one line of anti-TNFα therapy, a subset of patients switched to multiple lines of therapy during the 3-year follow-up period. Persistence and therapy modifications differed between these patients and those receiving only one line. Overall medical costs were highest for patients who did not switch, and pharmacy costs increased as patients switched to each new line of therapy.

Cluster analysis and its application to healthcare claims data: a study of end-stage renal disease patients who initiated hemodialysis.

BACKGROUND: Cluster analysis (CA) is a frequently used applied statistical technique that helps to reveal hidden structures and "clusters" found in large data sets. However, this method has not been widely used in large healthcare claims databases where the distribution of expenditure data is commonly severely skewed. The purpose of this study was to identify cost change patterns of patients with end-stage renal disease (ESRD) who initiated hemodialysis (HD) by applying different clustering methods. METHODS: A retrospective, cross-sectional, observational study was conducted using the Truven Health MarketScan® Research Databases. Patients aged ≥18 years with ≥2 ESRD diagnoses who initiated HD between 2008 and 2010 were included. The K-means CA method and hierarchical CA with various linkage methods were applied to all-cause costs within baseline (12-months pre-HD) and follow-up periods (12-months post-HD) to identify clusters. Demographic, clinical, and cost information was extracted from both periods, and then examined by cluster. RESULTS: A total of 18,380 patients were identified. Meaningful all-cause cost clusters were generated using K-means CA and hierarchical CA with either flexible beta or Ward's methods. Based on cluster sample sizes and change of cost patterns, the K-means CA method and 4 clusters were selected: Cluster 1: Average to High (n = 113); Cluster 2: Very High to High (n = 89); Cluster 3: Average to Average (n = 16,624); or Cluster 4: Increasing Costs, High at Both Points (n = 1554). Median cost changes in the 12-month pre-HD and post-HD periods increased from $185,070 to $884,605 for Cluster 1 (Average to High), decreased from $910,930 to $157,997 for Cluster 2 (Very High to High), were relatively stable and remained low from $15,168 to $13,026 for Cluster 3 (Average to Average), and increased from $57,909 to $193,140 for Cluster 4 (Increasing Costs, High at Both Points). Relatively stable costs after starting HD were associated with more stable scores on comorbidity index scores from the pre-and post-HD periods, while increasing costs were associated with more sharply increasing comorbidity scores. CONCLUSIONS: The K-means CA method appeared to be the most appropriate in healthcare claims data with highly skewed cost information when taking into account both change of cost patterns and sample size in the smallest cluster.

Healthcare Resource Use and Direct Costs in Patients with Ankylosing Spondylitis and Psoriatic Arthritis in a Large US Cohort.

OBJECTIVE: Direct costs of ankylosing spondylitis (AS) and psoriatic arthritis (PsA) have not been well characterized in the United States. This study assessed healthcare resource use and direct cost of AS and PsA, and identified predictors of all-cause medical and pharmacy costs. METHODS: Adults aged ≥ 18 with a diagnosis of AS and PsA were identified in the MarketScan databases between October 1, 2011, and September 30, 2012. Patients were continuously enrolled with medical and pharmacy benefits for 12 months before and after the index date (first diagnosis). Baseline demographics and comorbidities were identified. Direct costs included hospitalizations, emergency room and office visits, and pharmacy costs. Multivariable regression was used to determine whether baseline covariates were associated with direct costs. RESULTS: Patients with AS were younger and mostly men compared with patients with PsA. Hypertension and hyperlipidemia were the most common comorbidities in both cohorts. A higher percentage of patients with PsA used biologics and nonbiologic disease-modifying drugs (61.1% and 52.4%, respectively) compared with patients with AS (52.5% and 21.8%, respectively). Office visits were the most commonly used resource by patients with AS and PsA (∼11 visits). Annual direct medical costs [all US dollars, mean (SD)] for patients with AS and PsA were $6514 ($32,982) and $5108 ($22,258), respectively. Prescription drug costs were higher for patients with PsA [$14,174 ($15,821)] compared with patients with AS [$11,214 ($14,249)]. Multivariable regression analysis showed higher all-cause direct costs were associated with biologic use, age, and increased comorbidities in patients with AS or PsA (all p < 0.05). CONCLUSION: Biologic use, age, and comorbidities were major determinants of all-cause direct costs in patients with AS and PsA.

Costs and health care resource utilization among chronic obstructive pulmonary disease patients with newly acquired pneumonia.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are at increased risk for lung infections and other pathologies (eg, pneumonia); however, few studies have evaluated the impact of pneumonia on health care resource utilization and costs in this population. The purpose of this study was to estimate health care resource utilization and costs among COPD patients with newly acquired pneumonia compared to those without pneumonia. METHODS: A retrospective claims analysis using Truven MarketScan(®) Commercial and Medicare databases was conducted. COPD patients with and without newly acquired pneumonia diagnosed between January 1, 2004 and September 30, 2011 were identified. Propensity score matching was used to create a 1:1 matched cohort. Patient demographics, comorbidities (measured by Charlson Comorbidity Index), and medication use were evaluated before and after matching. Health care resource utilization (ie, hospitalizations, emergency room [ER] and outpatient visits), and associated health care costs were assessed during the 12-month follow-up. Logistic regression was conducted to evaluate the risk of hospitalization and ER visits, and gamma regression models and two-part models compared health care costs between groups after matching. RESULTS: In the baseline cohort (N=467,578), patients with newly acquired pneumonia were older (mean age: 70 versus [vs] 63 years) and had higher Charlson Comorbidity Index scores (3.3 vs 2.6) than patients without pneumonia. After propensity score matching, the pneumonia cohort was nine times more likely to have a hospitalization (odds ratio; 95% confidence intervals [CI] =9.2; 8.9, 9.4) and four times more likely to have an ER visit (odds ratio; 95% CI =4.4; 4.3, 4.5) over the 12-month follow-up period compared to the control cohort. The estimated 12-month mean hospitalization costs ($14,353 [95% CI: $14,037-$14,690]), outpatient costs ($6,891 [95% CI: $6,706-$7,070]), and prescription drug costs ($1,104 [95% CI: $1,054-$1,142]) were higher in the pneumonia cohort than in the control cohort. CONCLUSION: This study demonstrated elevated health care resource use and costs in patients with COPD after acquiring pneumonia compared to those without pneumonia.

Binocular disparity only comes into play when everything else fails; a finding with broader implications than one might suppose.

This paper calls attention to research showing that binocular disparity, which is an effective cue to depth, plays a secondary role, at best, in the perception of 3D shape. This claim has implications both for how shape should be studied and how this unique perceptual property should be modeled. These issues are discussed from a historical perspective, which shows how the failure to appreciate the importance of the Gestalt grouping principle called 'Figure-Ground Organization' led to many unfruitful efforts. It also calls attention to how this situation can be remedied.