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To evaluate the time to and factors associated with treatment intensification in patients with type 2 diabetes who failed metformin monotherapy. In a retrospective analysis using a large US electronic medical record database, eligible patients included those with type 2 diabetes and an HbA of ≥7.0% or at least two fasting blood glucose levels of ≥126 mg/dl while on metformin monotherapy for at least 6 months within the period of 1 January 1997 to 31 December 2008. Time to treatment intensification was calculated as the time between index date (date on which HbA≥ 7% after metformin monotherapy for at least 6 months) and first prescription for additional antihyperglycaemic agent during follow-up period. All patients were required to have data for at least 12 months prior to and following the index date. A Cox proportional hazards model was employed to determine patient baseline characteristics associated with time to treatment intensification. Of the 12 566 patients identified, mean age at index date was 63 years and 51% were female. Mean index HbA was 8.0% overall, with 66, 19 and 15% of patients having an index HbA of 7 to <8%, 8 to <9% and ≥9%, respectively. Median time to treatment intensification was 14.0 months overall and 19.0, 8.7 and 4.5 months for patients with index HbA of 7 to <8%, 8 to <9% and ≥9%, respectively. Factors associated with treatment intensification included higher index HbA, younger age, higher Charlson co-morbidity index, metformin daily dose ≥ 1500 mg and later index date (all p < 0.05). In US clinical practice, median time to receive additional antihyperglycaemic medication is more than 1 year for patients with type 2 diabetes who failed metformin monotherapy. [ABSTRACT FROM AUTHOR]

The relationship between the weight-adjusted waist circumference index (WWI) and the senescence-inhibitory protein Klotho remains unknown. Therefore, this study aimed to investigate the relationship between WWI and soluble Klotho (s-Klotho). This study analyzed 9,928 participants based on the 2007-2016 National Health and Nutrition Examination Survey (NHANES). Three multiple linear regression models and a restricted cubic spline (RCS) were constructed to assess the association between WWI and s-Klotho levels. Further stratified analyses and interaction tests were performed to evaluate the stability of this association. Piecewise multivariate regression modeling was applied to detect threshold effects. The fully adjusted model showed a negative correlation between continuous WWI and s-Klotho levels (β = -23.65, 95% CI: -36.55, -10.76, P < 0.001). When WWI was grouped into quartiles, participants in the highest quartile had significantly lower circulating s-Klotho levels than those in the lowest quartile (β = -40.65, 95% CI: -64.20, -17.10, P = 0.001). The RCS curves showed a linear negative correlation between WWI and s-Klotho. Further stratified analyses showed that the correlation between WWI and s-Klotho remained stable in most conditions, except for gender. A nonlinear relationship and saturation effect were observed between WWI and s-Klotho in females, with an inflection point of 11.38 cm/√kg (P for overall < 0.001; P for non-linearity = 0.013). However, no significant correlation was observed in males. There is a significant negative correlation between WWI and s-Klotho levels. Proper management of central obesity in middle-aged and older women may be beneficial in delaying senescence., Competing Interests: Declarations. Ethics approval and consent to participate: The study program obtained informed consent from all participants and was conducted with the approval of the National Center for Health Statistics (NCHS) Ethics Review Committee. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: The COVID-19 pandemic accelerated the adoption of digital health technology, but it could also impact age-based disparities as existing studies have pointed out. Compared with the pre-pandemic period, whether the rapid digitalization of the health care system during the pandemic widened the age-based disparities over a long period remains unclear., Objective: This study aimed to analyze the long-term effects of the COVID-19 pandemic on the multifaceted landscape of digital health technology used across diverse age groups among US citizens., Methods: We conducted the retrospective observational study using the 2017-2022 Health Information National Trends Survey to identify the influence of the COVID-19 pandemic on a wide range of digital health technology use outcomes across various age groups. The sample included 15,505 respondents, which were categorized into 3 age groups: adults (18-44 years), middle-aged adults (45-64 years), and older adults (more than 65 years). We also designated the time point of March 11, 2020, to divide the pre- and post-pandemic periods. Based on these categorizations, multivariate linear probability models were used to assess pre-post changes in digital health technology use, controlling for demographic, socioeconomic, and health-related variables among different age groups., Results: Essentially, older adults were found to be significantly less likely to use digital health technology compared with adults, with a 26.28% lower likelihood of using the internet for health information (P<.001) and a 32.63% lower likelihood of using health apps (P<.001). The usage of digital health technology for all age groups had significantly increased after the onset of the pandemic, and the age-based disparities became smaller in terms of using the internet to look for health information. However, the disparities have widened for older adults in using the internet to look up test results (11.21%, P<.001) and make appointments (10.03%, P=.006) and using wearable devices to track health (8.31%, P=.01)., Conclusions: Our study reveals a significant increase in the use of digital health technology among all age groups during the pandemic. However, while the disparities in accessing online information have narrowed, age-based disparities, particularly for older adults, have widened in most areas such as looking up test results and making appointments with doctors. Therefore, older adults are more likely left behind by the rapidly digitalized US health care system during the pandemic. Policy makers and health care providers should focus on addressing these disparities to ensure equitable access to digital health resources for US baby boomers., (©Yuanbo Qiu, Huang Huang, Junjie Gai, Gianluca De Leo. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 04.12.2024.)

Purpose: Although low-carbohydrate and low-fat diets improve weight loss, cardiovascular disease, and diabetes, the relationship between these dietary patterns, highlighting macronutrient sources, and chronic obstructive pulmonary disease (COPD) remains unclear. This study aimed to assess the association between low-carbohydrate diets (LCDs) and low-fat diets (LFDs) and the odds of COPD and mortality among people with COPD in the National Health and Nutrition Examination Survey., Patients and Methods: Clinical data were extracted from the 2007-2008, 2009-2010, and 2011-2012 National Health and Nutrition Examination Survey (NHANES) cycles that met the inclusion criteria. Multivariable logistic regression was used to evaluate the associations between LCD and LFD scores and COPD, and multivariable Cox proportional hazards regression and restricted cubic spline (RCS) regression were used to assess the relationship between all-cause mortality and LCD and LFD scores., Results: Comparing extreme tertiles, multivariable-adjusted odds ratio (OR) were 1 (reference), 1.09 (95% CI, 0.77-1.55), 1.84 (95% CI, 1.09-3.09) ( P = 0.045 for trend) for unhealthy LFD scores. After multivariate adjustment, a per 5-point increase in unhealthy LCD score was associated with a 21% higher risk of total mortality (hazard ratio, 1.21; 95% CI, 1.03-1.43); while a per 5-point increase in healthy LFD scores was associated with a 21% lower risk of total mortality (HR, 0.79; 95% CI, 0.67-0.94)., Conclusion: Higher unhealthy LFD score was associated with an increased odds of COPD. Unhealthy LCD scores were significantly associated with higher total mortality, whereas healthy LFD scores were associated with lower total mortality in patients with COPD., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Hu et al.)

Objective: Few comparisons have been implemented between different prenatal care utilization indices and their effects on adverse outcomes. This study investigated the appropriateness of Chinese antenatal care (ANC) regulations and compared Chinese and American adequacy of prenatal care utilization (APNCU) scores., Methods: From 2010 to 2022, the medical records of 60,114 pregnant women were collected from the electronic medical record system (EMRS) in Zhoushan, China. ANC utilization was measured using the APNCU score and five times antenatal care (ANC5). Birth weight outcomes, including small for gestational age (SGA) and large for gestational age (LGA), low birth weight (LBW), macrosomia, birth weight, and preterm birth (PTB), were utilized as outcomes. Multinomial, linear, and logistic regression were used to analyze the association of ANC5 and APNCU with outcomes, respectively. Crossover analysis was implemented to compare the interaction between ANC5 and APNCU on the outcomes., Results: Women who received inadequate prenatal care had increased odds for PTB (ANC5: odds ratio (OR) = 1.12, 95% confidence interval (95%CI) = 1.03-1.21; APNCU: OR = 1.18, 95%CI: 1.07-1.29), delivering SGA infants (ANC5: OR = 1.13, 95%CI = 1.07-1.21; APNCU: OR = 1.11, 95%CI = 1.03-1.20). Crossover analysis revealed that inadequate prenatal care in APNCU only was significantly associated with an increased risk of PTB (OR = 1.48, 95%CI: 1.26-1.73)., Conclusion: Women with inadequate prenatal care in ANC5 or APNCU were more likely to suffer from adverse birth outcomes, including PTB, birth weight loss, SGA, and LBW. It indicated that adequate prenatal care is necessary for pregnant women. However, there were interactions between ANC5 and APNCU on PTB, with inadequate prenatal care use by APNCU showing the highest risk of PTB. This indicates that APNCU would be a better tool for evaluating prenatal care use., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhou, Yang, Chi, Cheng, Alifu, Qiu, Huang, Zhang, Ainiwan, Zhuang, Liu, Chen and Yu.)

Background: In 2014, the US Food and Drug Administration approved the first glucagon-like peptide-1 (GLP-1) receptor agonist product, liraglutide injection, for obesity treatment. Many GLP-1 obesity treatment clinical trials report significant weight loss and medication adherence at more than 85%. Little is known about the real-world GLP-1 obesity treatment adherence, persistence, and switch rates., Objective: To measure GLP-1 therapy persistence, adherence, and switch rates in a real-world cohort of members without diabetes using these drugs for obesity treatment., Methods: Integrated pharmacy and medical claims data from 16.5 million average monthly commercially insured membership were used to identify obese members without diabetes newly initiating GLP-1 therapy between January 1, 2021, and December 31, 2021. Members were required to be continuously enrolled 1-year before and after the GLP-1 therapy start date and aged 19 years of age or older. Persistence was measured as no greater than or equal to 60-day gap with allowance for GLP-1 switching. Adherence was measured as the proportion of days covered (PDC) and members with a PDC greater than or equal to 80% were considered adherent. GLP-1 product switching was also assessed descriptively., Results: 4,066 commercially insured obese members without diabetes that newly initiated GLP-1 therapy met all study criteria. The mean age was 46 years, and 81% were female. Overall, GLP-1 persistence was 46.3% at 180 days and 32.3% at 1 year. The highest and lowest persistence rates at 1 year were observed for semaglutide (Ozempic) at 47.1% and liraglutide (Saxenda) 19.2%, respectively. Average PDC during the 1-year assessment was 51.0% with 27.2% adherent to therapy and 11.1% switched GLP-1 drugs., Conclusions: This GLP-1 weight loss treatment real-world analysis, among obese individuals without diabetes, found poor 1-year persistence and adherence and low rates of switching between products. These findings will aid in assessing products cost-effectiveness, understanding obesity care management program needs, forecasting future GLP-1 use and cost trends, and negotiating GLP-1 pharmaceutical manufacturer value-based purchasing agreements.

Objective: We queried the Pediatric Health Information System (PHIS) to evaluate the presentation, management, and outcomes of renal trauma in children from birth to 18 years from 2007-2018., Methods: Patients were categorized as infants (0-1 year), toddlers (2-4 years), children (5-9 years), preteen (10-14 years), and teens (15-18 years), and patient demographics, grade of injury, and mechanism of injury including sports-related trauma (SRT) were collected. Each group was then evaluated for the level of management and patient outcome., Results: We identified 3720 patients with renal trauma. Our cohort was predominantly White (68.5%), male (68.6%), and required public insurance (38.5%). Most injuries were low grade (86.7%) and managed non-operatively (94.7%). The overall mortality was 51 (1.4%). Younger patients (infants, toddlers, children) were more likely to present with complex injuries and they were more likely to have been involved in a motor vehicle accident. They had higher blood transfusion rates, longer inpatient courses, higher levels of admission acuity, and higher mortality. Patients in the older age groups presented most after SRT. Across all age groups, the most common source of SRT was limited contact sports; however, when considering only teens, full contact sports were the primary offending activity. This review of the PHIS database provides insight to the rates and patterns of pediatric renal trauma in the United States., Conclusion: Our data suggest an age-related differences in the presentation, management, and outcomes of pediatric renal trauma patients., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Real-world data on the use, healthcare resource utilization (HCRU), and associated costs of antifibrotic therapies in patients with idiopathic pulmonary fibrosis (IPF) are limited., Objectives: To assess the prevalence of antifibrotic treatment, characteristics of patients receiving treatment, discontinuation rates, and HCRU and costs associated with treatment., Design: This retrospective study analyzed de-identified longitudinal and cross-sectional data, respectively, from two US claims databases: Optum's de-identified Clinformatics ® Data Mart Database (CDM; commercial claims, Medicare Advantage) and the Veterans Health Administration (VHA) database. The study periods were October 1, 2013-March 31, 2019 and October 1, 2014-September 30, 2019, respectively. Eligible individuals were adults with ⩾1 diagnosis claim for IPF., Methods: Antifibrotic prevalence, patient demographics, treatment discontinuation rates, and HCRU and costs were determined separately for each cohort and described using summary statistics. Bivariate comparisons were analyzed using Chi-square and Student's t -tests for categorical and continuous variables, respectively., Results: Overall, 4223 and 4459 eligible patients were identified in the CDM and VHA databases, respectively. Prevalence of antifibrotic uptake was 9.2% and 29.1% and the rate of index treatment discontinuation was 47% and 66% during follow-up in the CDM and VHA cohorts, respectively. Antifibrotic-treated patients were significantly younger ( p  < 0.0001) with lower mean Charlson Comorbidity Index scores at baseline versus untreated patients in both cohorts. In the CDM cohort, the number of outpatient and pharmacy visits was significantly higher in treated versus untreated patients during follow-up (both p  < 0.0001). A similar trend was observed for the VHA cohort. Total follow-up costs in both cohorts were significantly higher in treated versus untreated patients due to higher pharmacy costs (CDM; p  < 0.0001) or higher outpatient and pharmacy costs (VHA; p  < 0.0001)., Conclusion: The low prevalence of antifibrotic usage in both cohorts, together with the high rate of antifibrotic discontinuation, and increased HCRU and costs in treated versus untreated patients, support the need for novel treatment options for IPF., Trial Registration: Not applicable.

Purpose: Physician-scientists have long been considered an endangered species, and their extended training pathway is vulnerable to disruptions. This study investigated the effects of COVID-19-related challenges on the personal lives, career activities, stress levels, and research productivity of physician-scientist trainees and faculty., Method: The authors surveyed medical students (MS), graduate students (GS), residents/fellows (R/F), and faculty (F) using a tool distributed to 120 U.S. institutions with MD-PhD programs in April-June 2020. Chi-square and Fisher's exact tests were used to compare differences between groups. Machine learning was employed to select variables for multivariate logistic regression analyses aimed at identifying factors associated with stress and impaired productivity., Results: The analyses included 1,929 respondents (MS: n = 679, 35%; GS: n = 676, 35%; R/F: n = 274, 14%; F: n = 300, 16%). All cohorts reported high levels of social isolation, stress from effects of the pandemic, and negative impacts on productivity. R/F and F respondents were more likely than MS and GS respondents to report financial difficulties due to COVID-19. R/F and F respondents with a dual degree expressed more impaired productivity compared with those without a dual degree. Multivariate regression analyses identified impacted research/scholarly activities, financial difficulties, and social isolation as predictors of stress and impaired productivity for both MS and GS cohorts. For both R/F and F cohorts, impacted personal life and research productivity were associated with stress, while dual-degree status, impacted research/scholarly activities, and impacted personal life were predictors of impaired productivity. More female than male respondents reported increased demands at home., Conclusions: This national survey of physician-scientist trainees and faculty found a high incidence of stress and impaired productivity related to the COVID-19 pandemic. Understanding the challenges faced and their consequences may improve efforts to support the physician-scientist workforce in the postpandemic period., (Copyright © 2022 by the Association of American Medical Colleges.)

In a drug formulation (DFM), the major components by mass are not Active Pharmaceutical Ingredient (API) but rather Drug Inactive Ingredients (DIGs). DIGs can reach much higher concentrations than that achieved by API, which raises great concerns about their clinical toxicities. Therefore, the biological activities of DIG on physiologically relevant target are widely demanded by both clinical investigation and pharmaceutical industry. However, such activity data are not available in any existing pharmaceutical knowledge base, and their potentials in predicting the DIG-target interaction have not been evaluated yet. In this study, the comprehensive assessment and analysis on the biological activities of DIGs were therefore conducted. First, the largest number of DIGs and DFMs were systematically curated and confirmed based on all drugs approved by US Food and Drug Administration. Second, comprehensive activities for both DIGs and DFMs were provided for the first time to pharmaceutical community. Third, the biological targets of each DIG and formulation were fully referenced to available databases that described their pharmaceutical/biological characteristics. Finally, a variety of popular artificial intelligence techniques were used to assess the predictive potential of DIGs' activity data, which was the first evaluation on the possibility to predict DIG's activity. As the activities of DIGs are critical for current pharmaceutical studies, this work is expected to have significant implications for the future practice of drug discovery and precision medicine., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: COVID-19-related acute illness is associated with an increased risk of venous thromboembolism (VTE)., Objective: These evidence-based guidelines from the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in making decisions about the use of anticoagulation in patients with COVID-19., Methods: ASH formed a multidisciplinary guideline panel that included patient representatives and applied strategies to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline development process and performed systematic evidence reviews (through November 2021). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess evidence and make recommendations, which were subject to public comment. This is an update to guidelines published in February 2021 as part of the living phase of these guidelines., Results: The panel made one additional recommendation. The panel issued a conditional recommendation in favor of therapeutic-intensity over prophylactic-intensity anticoagulation in patients with COVID-19-related acute illness who do not have suspected or confirmed VTE. The panel emphasized the need for an individualized assessment of risk of thrombosis and bleeding. The panel also noted that heparin (unfractionated or low molecular weight) may be preferred because of a preponderance of evidence with this class of anticoagulants., Conclusion: This conditional recommendation was based on very low certainty in the evidence, underscoring the need for additional, high-quality, randomized controlled trials comparing different intensities of anticoagulation in patients with COVID-19-related acute illness., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Blue light cystoscopy (BLC) during transurethral resection of bladder tumor (TURBT) is guideline-recommended as it improves cancer detection and decreases recurrence of the disease. However, the extent to which BLC is used has not been established. We studied BLC use in the Premier Healthcare Database, a large, national sample that captured 158 870 index TURBT procedures between January 2011 and March 2020. Billing data were queried for the administration of hexaminolevulinate at TURBT as a proxy for BLC, and logistic regression models were constructed to identify variables associated with BLC use. BLC was used in 1.2% of index TURBT procedures over the study period. Its use increased following the American Urological Association non-muscle-invasive bladder cancer guideline publication in October 2016 but plateaued in late 2018. After adjusting for patient characteristics, higher odds for BLC use were found for academic hospitals and hospitals with higher TURBT volumes and higher radical cystectomy volumes. Within hospitals with BLC capability, predictors of a surgeon never using BLC included low surgeon TURBT volumes, low surgeon radical cystectomy volumes, and lack of mitomycin C use. Our findings highlight a concerning underutilization and stagnation in the adoption of evidence and guideline-supported intervention. PATIENT SUMMARY: Use of blue light visualization of the bladder improves the detection of cancer during removal of bladder tumors via the urethra. We reviewed records in a large US database for use of this technique and found that it is being underutilized. Since this technique improves detection of cancer in the bladder so that it can be removed to reduce recurrence, blue light visualization should be more widely used., (Copyright © 2021. Published by Elsevier B.V.)

Objectives: To access the trends and focuses of publications on public health emergency preparedness in the timeframe 1997-2019., Methods: Publications related to public health emergency preparedness (PHEP) were retrieved from the Web of Science Core Collection database. Bibliometric analyses including output statistics, co-authorship analysis, citation analysis, co-citation analysis, and co-occurrence analysis were performed and mapped using VOSviewer., Results: A total of 1058 publications on PHEP were included in this study. There was an increasing trend of publication output and citations since 2002. A total of 4605 authors from 1587 institutes and 92 countries contributed to the publications, and the United States lead the field. Disaster Medicine and Public Health Preparedness was the most active and co-cited journal among 243 journals. The knowledge foundation mainly focused on the professionals' capacity, education, and conceptions of PHEP. Epidemics, natural disasters, terrorism, education, and communication were the principle topics; while "vulnerable populations," "disaster medicine," and "hurricane" were the recent hotspots in this field., Conclusions: Significant progresses had been achieved worldwide in the past 2 decades, however, improvement of research activity and international collaboration is still a need for most countries.

Importance: Studies have shown that delayed initiation of surgery and adjuvant chemotherapy is associated with lower rates of breast cancer survival. However, it remains unclear whether delayed initiation of adjuvant hormone therapy (AHT) is associated with survival., Objective: To assess the association of time to adjuvant hormone therapy (TTH) with breast cancer survival and evaluate the factors associated with AHT., Design, Setting, and Participants: This cohort study examined data from the National Cancer Database from 2004 through 2014 to assess the association of TTH (stratified as ≤150 and >150 days) with cancer survival. All patients included were diagnosed with stage I to stage III hormone receptor-positive, human epidermal growth factor receptor-2 (ERBB2; formerly HER2)-negative invasive breast cancer and underwent AHT without chemotherapy. Data were analyzed from April 2019 to May 2020., Exposures: AHT was administered at different time points following surgical procedures for breast cancer treatment., Main Outcomes and Measures: An inverse probability of treatment weighting (IPTW) model was constructed to evaluate overall survival by adjusting for treatment facility, patient demographics, tumor characteristics, and treatment; multivariable logistic regression was conducted to assess factors associated with delayed treatment., Results: A total of 144 103 patients (median [IQR] follow-up, 36.6 months [25.5-49.2 months]; mean [SD] age, 63.7 [11.6] years) were identified, which included 142 916 (99.2%) women, 11 574 (8.0%) Black patients, and 126 013 (87.4%) White patients. Of these, 134 873 patients (93.6%) had a TTH of 150 days or less and 9230 patients (6.4%) had a TTH longer than 150 days. The IPTW-based Cox model demonstrated that patients with delayed AHT (ie, a TTH past 150 days) were associated with decreased survival (hazard ratio [HR], 1.31; 95% CI, 1.26-1.35; P < .001) compared with those receiving the timely treatment (TTH ≤150 days). Several sensitivity analyses (including IPTW with stabilized weight [HR, 1.31; 95% CI, 1.19-1.45; P < .001], propensity score matching [HR, 1.41; 1.13-1.76; P = .002], and propensity score regression adjustment [HR, 1.29; 95% CI, 1.16-1.43; P < .001]) and exploratory subgroup analyses yielded similar trends. Factors associated with delayed AHT included Black racial identity (OR, 1.66; 95% CI, 1.55-1.77), nonprivate insurance (eg, no insurance: OR, 1.46; 95% CI, 1.26-1.70), living in large metropolitan or metropolitan areas (reference vs urban, less urban, or rural: OR, 0.82; 95% CI, 0.76-0.87), treatment in a community hospital (reference vs academic or research: OR, 0.91; 95% CI, 0.84-0.98), Charlson-Deyo Comorbidity Index score 2 or higher (OR, 1.17; 95% CI, 1.04-1.32), poor grade differentiation (OR, 1.42; 95% CI, 1.32-1.53), II and III pathological stage (stage III: OR, 3.13; 95% CI, 2.76-3.54), estrogen receptor-positive (ER+)/progesterone receptor-negative (PR-) or ER-/PR+ (OR, 1.22; 95% CI, 1.13-1.31), receiving breast conservation surgery (reference vs mastectomy: OR, 0.87; 95% CI, 0.79-0.94), and radiotherapy (reference vs no radiotherapy: OR, 0.56; 95% CI, 0.52-0.61)., Conclusions and Relevance: The delay of the initiation of AHT past 150 days was associated with diminished survival in hormone receptor-positive, ERBB2-negative patients with breast cancer who did not receive chemotherapy. Efforts should be made to address factors associated with delayed treatment to improve survival.

Background: COVID-19-related acute illness is associated with an increased risk of venous thromboembolism (VTE)., Objective: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in decisions about the use of anticoagulation for thromboprophylaxis in patients with COVID-19 who do not have confirmed or suspected VTE., Methods: ASH formed a multidisciplinary guideline panel, including 3 patient representatives, and applied strategies to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline development process, including performing systematic evidence reviews (up to March 2021). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the grading of recommendations assessment, development, and evaluation (GRADE) approach to assess evidence and make recommendations, which were subject to public comment., Results: The panel agreed on 1 additional recommendation. The panel issued a conditional recommendation against the use of outpatient anticoagulant prophylaxis in patients with COVID-19 who are discharged from the hospital and who do not have suspected or confirmed VTE or another indication for anticoagulation., Conclusions: This recommendation was based on very low certainty in the evidence, underscoring the need for high-quality randomized controlled trials assessing the role of postdischarge thromboprophylaxis. Other key research priorities include better evidence on assessing risk of thrombosis and bleeding outcomes in patients with COVID-19 after hospital discharge., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: COVID-19-related critical illness is associated with an increased risk of venous thromboembolism (VTE)., Objective: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in making decisions about the use of anticoagulation for thromboprophylaxis in patients with COVID-19-related critical illness who do not have confirmed or suspected VTE., Methods: ASH formed a multidisciplinary guideline panel that included 3 patient representatives and applied strategies to minimize potential bias from conflicts of interest. The McMaster University Grading of Recommendations Assessment, Development and Evaluation (GRADE) Centre supported the guideline development process by performing systematic evidence reviews (up to 5 March 2021). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the GRADE approach to assess evidence and make recommendations, which were subject to public comment. This is an update on guidelines published in February 2021., Results: The panel agreed on 1 additional recommendation. The panel issued a conditional recommendation in favor of prophylactic-intensity over intermediate-intensity anticoagulation in patients with COVID-19-related critical illness who do not have confirmed or suspected VTE., Conclusions: This recommendation was based on low certainty in the evidence, which underscores the need for additional high-quality, randomized, controlled trials comparing different intensities of anticoagulation in critically ill patients. Other key research priorities include better evidence regarding predictors of thrombosis and bleeding risk in critically ill patients with COVID-19 and the impact of nonanticoagulant therapies (eg, antiviral agents, corticosteroids) on thrombotic risk., (© 2021 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: Definitions of postoperative hypoparathyroidism (hypoPT) have never reached consent until the American Thyroid Association (ATA) statement was released, with new characteristics and challenges., Methods: Patients with papillary thyroid carcinoma who underwent primary total thyroidectomy between January 2013 and June 2018 were retrospectively enrolled. Symptoms of hypocalcemia and their frequency were stringently followed. Patients were divided into groups according to the ATA statement. Incidence of postoperative hypoPT and serum parathyroid hormone levels accompanied by calcium levels, from 1-day to at least 24-month follow-up., Results: A total of 1749 patients were included: 458 (26.2%) had transient and 63 (3.6%) had permanent hypoPT. Transient hypoPT was found in 363 (20.7%) patients with biochemical hypoPT, 72 (4.1%) with clinical hypoPT, and 23 (1.3%) with relative hypoPT; permanent hypoPT was detected in 8 (0.5%) patients with biochemical hypoPT, 55 (3.1%) with clinical hypoPT, and none with relative hypoPT. Female sex, age ≥ 55 years, unintentional parathyroid gland resection, and autotransplantation of ≥ 2 parathyroid glands were independent risk factors for transient biochemical hypoPT. Age ≥ 55 years, bilateral central neck dissection, and isthmus tumor location were independent risk factors for transient clinical hypoPT. A postoperative 1-day percentage of parathyroid hormone (PTH) reduction of > 51.1% was an independent risk factor for relative hypoPT (odds ratio, 4.892; 95% confidence interval, 1.653-14.480; P = 0.004). No independent risk factor for permanent hypoPT was found., Conclusion: ATA diagnostic criteria for postoperative hypoPT are of great value in differentiating patients by hypocalcemia symptoms and choosing corresponding clinical assistance; however, they may underestimate the actual incidence., (© 2021. The Author(s).)

Background: Pharmacy benefit can be purchased as part of an integrated medical and pharmacy health package-a carve-in model-or purchased separately and administered by an external pharmacy benefit manager-a carve-out model. Limited peer-reviewed information is available assessing differences in use and medical costs among carve-in versus carve-out populations., Objective: To compare total medical costs per member per year (PMPY) and utilization between commercially self-insured members receiving carve-in to those receiving carve-out pharmacy benefits overall and by 7 chronic condition subgroups., Methods: This study used deidentified data of members continuously enrolled in Cambia Health Solutions self-insured Blue plans without benefit changes from 2017 through 2018. Cambia covers 1.6 million members in Oregon, Washington, Idaho, and Utah. The medical cost PMPY comparison was performed using multivariable general linear regression with gamma distribution adjusting for age, gender, state, insured group size, case or disease management enrollment, 7 chronic diseases, risk score (illness severity proxy), and plan paid to total paid ratio (benefit richness proxy). Medical event objectives were assessed using multivariable logistic regression comparing odds of hospitalization and emergency department (ED) visit adjusting for the same covariates. Sensitivity analyses repeated the medical cost PMPY comparison excluding high-cost members, greater than $250,000 annually. Chronic condition subgroup analyses were performed using the same methods separately for members having asthma, coronary artery disease, chronic obstructive pulmonary disease, heart failure, diabetes mellitus, depression, and rheumatoid arthritis., Results: There were 205,835 carve-in and 125,555 carve-out members meeting study criteria. Average age (SD) was 34.2 years (18.6) and risk score (SD) 1.1 (2.3) for carve-in versus 35.2 years (19.3) and 1.1 (2.4), respectively, for carve-out. Members with carve-in benefits had lower medical costs after adjustment (4%, P < 0.001), translating into an average $148 lower medical cost PMPY ($3,749 carve-out vs. $3,601 carve-in annualized). After adjustment, the carve-in group had an estimated 15% ( P < 0.001) lower hospitalization odds and 7% ( P < 0.001) lower ED visit odds. Of 7 chronic conditions, significantly lower costs (12%-17% lower), odds of hospitalization (22%-36% lower), and odds of ED visit (16%-20% lower) were found among members with carve-in benefits for 5 conditions (all P < 0.05)., Conclusions: These findings suggest that integrated, carve-in pharmacy and medical benefits are associated with lower medical costs, fewer hospitalizations, and fewer ED visits. This study focused on associations, and defining causation was not in scope. Possible reasons for these findings include plan access to both medical and pharmacy data and data-informed care management and coordination. Future research should include investigation of integrated data use and its effect across the spectrum of integrated health plan offerings, provider partnerships, and analytic strategies, as well as inclusion of analyzing pharmacy costs to encompass total cost of care., Disclosures: This study received no external funding. The study was jointly conducted by employees of Cambia Health Solutions and Prime Therapeutics, a pharmacy benefit manager servicing Cambia Health Solutions. Smith, Lam, Lockwood, and Pegus are employees of Cambia Health Solutions. Qiu and Gleason are employees of Prime Therapeutics.

Purpose: The present study aims to validate possible stage migration of lymph node metastasis related to the insufficient examined lymph node (ELN) count in pN3a gastric cancer (GC) patients., Methods: 1976 pN3 patients who underwent the R0 surgery in three high-capacity institutions in China were enrolled to explore the stage migration of nodal involvement, and 3146 pN3 cases from the Surveillance, Epidemiology, and End Results (SEER) Program Registry were used as an external validation cohort., Results: After the propensity score matching of the Chinese cohort, the ELN count, as an independent predictor for GC outcome, was confirmed to be associated with the stage migration of lymph node metastasis in pN3a patients based on the univariate and multivariate survival analyses. Logistic regress was adopted to elucidate that the ELN count was an independent factor related to the long-term survival status of GC patients after curative surgery. Likelihood ratio test showed that the ELN count had the smallest Bayesian information criterion value among the clinicopathologic variables, corresponding to an efficient model to predict outcomes. Subsequently, stage migration of lymph node metastasis was predominantly detected in pN3a patient sub-group with insufficient (less than 16) ELN count, who presented with similar prognosis as the pN3b patients (P = 0.463) as per the stratum analysis with Kaplan-Meier. These methods were further validated using data from the SEER cohort, and the similar promising results were obtained., Conclusion: pN3a patients with insufficient ELN count should be considered as pN3b cases to achieve accurate prognostic evaluation after curative gastrectomy.

Objective: Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) and is strongly associated with type 2 diabetes mellitus (T2DM). Patients with both T2DM and NASH have increased risk for adverse clinical outcomes, leading to higher risk for mortality and morbidity. We built a Markov model with 1-year cycles and 20-year horizon to estimate the economic burden of NASH with T2DM in the U.S., Research Design and Methods: Cohort size was determined by population size, prevalence of T2DM, and prevalence and incidence of NASH in 2017. The model includes 10 health states-NAFL, NASH fibrosis stages F0 through F3, compensated and decompensated cirrhosis, hepatocellular carcinoma, 1 year post-liver transplant, and post-liver transplant-as well as liver-related, cardiovascular, and background mortality. Transition probabilities were calculated from meta-analyses and literature. Annual costs for NASH and T2DM were taken from literature and billing codes., Results: We estimated that there were 18.2 million people in the U.S. living with T2DM and NAFLD, of which 6.4 million had NASH. Twenty-year costs for NAFLD in these patients were $55.8 billion. Over the next 20 years, NASH with T2DM will account for 65,000 transplants, 1.37 million cardiovascular-related deaths, and 812,000 liver-related deaths., Conclusions: This model predicts significant clinical and economic burden due to NASH with T2DM over the next 20 years. In fact, this burden may be greater since we assumed conservative inputs for our model and did not increase costs or the incidence of T2DM over time. It is highly likely that interventions reducing morbidity and mortality in NASH patients with T2DM could potentially reduce this projected clinical and economic burden., (© 2019 by the American Diabetes Association.)

Objectives: Hurricane Katrina was an intense tropical cyclone that made landfall in the United States (US) in August 2005, causing catastrophic damage in several states. This study examined the impact of Hurricane Katrina on mental health status among US adults. Methods: Multilevel regressions based on the difference-in-differences study design were performed on individual-level data (N = 70,267) retrieved from the Behavioral Risk Factor Surveillance System 2004-2006 surveys. Results: Hurricane Katrina was found to be associated with an increase of 0.68 poor mental health days among residents of Katrina-affected states. The negative impact of Hurricane Katrina on mental health status tended to be larger among Louisiana residents, women, young and middle-aged adults, lower income respondents, and those with poor/fair self-rated physical health than among Mississippi residents, men, older adults, higher income respondents, and those with good/excellent self-rated physical health. Conclusion: Hurricane Katrina adversely impacted mental health of residents in Katrina-affected states, and the impact differed across population subgroups. Future studies should investigate other potential risk and protective factors for the mental health consequences of disasters. They should examine long-term impacts on mental health following disasters to better inform population-based mental health interventions for disaster survivors.

Background: The prevalence of adolescent idiopathic scoliosis (AIS) in diverse regions of the world has been studied. Access to care varies widely, and differences in disease severity and operative treatment outcomes are not well understood. This study aimed to determine variation in disease presentation and operative complications for AIS patients from an international cohort., Methods: This is a retrospective study carried out at seven surgical centers in the United States (Manhattan and Miami), Ghana, Pakistan, Spain, Egypt, and China. A total of 541 consecutive patients with AIS were evaluated. Preoperative major curve magnitude, operative parameters, and complications were compared among sites using analysis of variance with post hoc tests and Pearson correlation coefficients. Univariate and multivariate forward stepwise binary logistic regressions determined the variables most predictive of complications., Results: Countries with lowest-access to care (Ghana, Egypt, and Pakistan) displayed larger curves, more levels fused, longer operative time (OT), and greater estimated blood loss (EBL) than the other countries (p ≤ .001). Increasing curve magnitude was correlated with greater levels fused, longer OT, and greater EBL in all groups (p = .01). In the univariate regression analysis, Cobb magnitude, levels fused, EBL, and OT were associated with complication occurrence. Only OT remained significantly associated with complication occurrence after adjusting for Cobb magnitude, levels fused, and site (odds ratio [OR] = 1.005, 95% confidence interval 1.001-1.007, p = .003). Complications were greatest in Pakistan and Ghana (21.7% and 13.5%, respectively) and lowest in Miami (6.5%)., Conclusions: Larger curve magnitudes in the least-access countries correlated with more levels fused, longer OT, and greater EBL, indicating that increased curve magnitude at surgery could explain the difference in operative morbidity between low- and high-access countries. With OT as the prevailing predictive factor of complications, we suggest that increased curve magnitude leads to longer OTs and more complications. A lack of access to orthopedic care may be the largest contributor to the postponement of treatment., Level of Evidence: Level II., (Copyright © 2019 Scoliosis Research Society. Published by Elsevier Inc. All rights reserved.)

We aimed to quantitatively estimate the amount of pressure that was placed on basic public health care services (BPHS) due to the universal two-child policy issued in 2015 by comparing the workload change in maternal and child health management and the immunization of children. BPHS performance surveillance data from 2014 to 2018 in Zhejiang Province, China were analyzed to calculate the workload of the above three services using the equivalent method of BPHS cost estimation of community health services. From 2014 to 2018, the numbers of births from the Statistical Yearbook in Zhejiang Province were 578,000, 581,000, 624,000, 670,000, and 628,000, respectively, and those from the surveillance data were 416,941, 41,490, 434,163, 546,816, and 45,964, respectively. The number of births reached a peak in 2017, with the yearbook and surveillance data showing increases of 15.92% and 31.15%, respectively, over 2014. The workload of maternal and child health management and children's immunization also peaked in 2017, increasing by 30.37%, 12.70%, and 4.33% over 2014, respectively. In 2018, the workload of maternal and child health management and children's immunization dropped to 107.34%, 107.73%, and 98.81% over 2014, respectively. The indicators of maternal and child health management and children's immunization services remained stable, and the related services did not decline, even in 2017. The maternal health management workload was more affected by the universal two-child policy than child health management and children's immunization.

The 30-day surgical mortality metric is endorsed by the National Quality Forum for value-based purchasing purposes. However, its integrity has been questioned, as there is documented evidence of hospital manipulation of this measure, by way of inappropriate palliative care designation and changes in patient selection. To determine if there is evidence of potential manipulation, we retrospectively analyzed 1,725,291 surgical admissions from 158 United States hospitals participating in the National Inpatient Sample from 2010 to 2011. As a way of evaluating unnecessary life-prolonging measures, we determined that a significant increase in mortality rate after post-operative day 30 (day 31-35) would indicate manipulation. We compared the post-operative mortality rates for each hospital between Post-Operative Day 26-30 and Post-Operative Day 31-35 using Wilcoxon signed-rank tests. After application of the Bonferroni correction, the results showed that none of the hospitals had a statistically significant increase in mortality after post-operative day 30. This analysis fails to impugn the integrity of this measure, as we did not identify any evidence of potential manipulation of the 30-day surgical mortality metric.

Postmenopausal osteoporosis (PMOP) has already become a major public health problem. However, there was no bibliometric analysis estimating the evolutionary process of PMOP research., Purpose: This study aimed to assess its scientific activity., Methods: Publications on PMOP were retrieved from Science Citation Index-Expanded (SCI-E) of the Web of Science (WoS) from 2008 to 2018. VOSviewer software was used for data mining and visualization. The quantity of papers, number of citations, citation frequency per year, and H-index were assessed and compared among different countries, institutes, and researchers., Results: A total of 11,142 papers were included and were cited 184,416 times. The USA contributed the most papers (3162), the most citations (83,270 times), and the highest H-index (115). Canada ranked first for the number of papers per million populations and per trillion GDP. Seven of the top ten funding agencies were industries. The key words were stratified into four clusters: cluster 1 ("basic research"), cluster 2 ("diagnosis"), cluster 3 ("treatment"), and cluster 4 ("others"). Average appearing years (AAY) of key words in cluster 1 were the largest compared to those in clusters 2 and 3. For hotspots, "miRNA" showed a relatively latest AAY of 2017.63, followed by "abaloparatide" and "adipokine"., Conclusion: We concluded that the USA and Europe were the most productive regions on PMOP, with a high prevalence of articles supported by pharmaceutical companies. Key word focus gradually shifted from "diagnosis" to "treatment" and then to precision medicine orientated "basic research". It is recommended to pay attention to potential research hotspots, such as "miRNA," "abaloparatide," and "adipokine".

Background: The pharmacological activation of thermogenesis in brown adipose tissue has long been considered promising strategies to treat obesity. However, identification of safe and effective agents remains a challenge. In this study, we addressed this challenge by developing a cellular system with a fluorescence readout, and applied in a high-throughput manner to screen for FDA-approved drugs that may activate endogenous UCP1 expression in adipocytes., Methods: We have generated a Ucp1-2A-GFP reporter mouse, in which GFP intensity serves as a surrogate of the endogenous expression level of UCP1 protein; and immortalized brown adipocytes were derived from this mouse model and applied in drug screening. Candidate drugs were further tested in mouse models either fed with normal chow or high fat diet to induce obesity., Findings: By using the cellular screening platform, we identified a group of FDA-approved drugs that can upregulate UCP1 expression in brown adipocyte, including previously known UCP1 activators and new candidate drugs. Further studies focusing on a previously unreported drug-sutent, revealed that sutent treatment could increase the energy expenditure and inhibit lipid synthesis in mouse adipose and liver tissues, resulting in improved metabolism and resistance to obesity., Interpretation: This study offered an easy-to-use cellular screening system for UCP1 activators, and provided a candidate list of FDA-approved drugs that can potentially treat obesity. Further study of these candidates may shed new light on the drug discovery towards obesity. FUND: National Key Research and Development Program and the Strategic Priority Research Program of the Chinese Academy of Sciences, etc. (250 words)., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Adolescent idiopathic scoliosis (AIS) is the most common type of spinal deformity and has a significant genetic background. Genome-wide association studies (GWASs) identified several susceptibility loci associated with AIS. Among them is a locus on chromosome 6q24.1 that we identified by a GWAS in a Japanese cohort. The locus is represented by rs6570507 located within GPR126. To ensure the association of rs6570507 with AIS, we conducted a meta-analysis using eight cohorts from East Asia, Northern Europe and USA. The analysis included a total of 6,873 cases and 38,916 controls and yielded significant association (combined P = 2.95 × 10 -20 ; odds ratio = 1.22), providing convincing evidence of the worldwide association between rs6570507 and AIS susceptibility. In silico analyses strongly suggested that GPR126 is a susceptibility gene at this locus.

Background: Nontransfusion-dependent thalassemia (NTDT) refers to a diverse group of thalassemia mutations and clinical phenotypes that do not require chronic transfusions. It is increasingly prevalent in the United States., Procedure: This study reviews the epidemiology and clinical characteristics of 138 patients with NTDT treated at four US thalassemia centers from 1997 to 2014. Data on laboratory results, transfusions, and clinical complications were collected from patient charts., Results: Overall, 84 patients with α-thalassemia (62 deletional hemoglobin H; 22 nondeletional hemoglobin H), 39 with β-thalassemia (26 with homozygous or double heterozygous β mutations; 13 with single β mutations with or without α triplication), and 15 with E/β-thalassemia (12 E/β 0 ; three E/β + ) were identified. At study entry, the median age for patients with α-thalassemia was 2.3 years; 9.2 years for patients with β-thalassemia and 2.2 years for patients with E/β-thalassemia. Most patients with α-thalassemia were Asian. Patients with β-thalassemia were predominantly Caucasian (46%) or of African descent (36%). Twenty percent of patients were born outside the United States and 5% were transfused before immigration. Complications varied by genotype and age. Individuals with nondeletional hemoglobin H were severely affected and, despite their young age, had many complications. Iron overload increased with age and was more common in patients who received transfusions., Conclusions: NTDT in the United States is a multi-ethnic disease with different genotypic mutations and phenotypic manifestations. A higher than expected proportion of patients was Black/African American. NTDT-related complications are common and increase with age, supporting a need for early diagnosis., (© 2018 Wiley Periodicals, Inc.)

Seroreactivity to H3N2 swine influenza viruses (SIVs)was evaluated in serum samples collected from 843 people aged 0 to 100 years in 2010 in Luxembourg.Sera were analysed by haemagglutination inhibition(HI) and virus neutralisation (VN) assays targeting a European H3N2 SIV, a North American H3N2 variant of swine origin (H3N2v) and human seasonal H3N2 viruses isolated in 1975, 1995 and 2005. HI antibodies(titre ≥ 10) against European H3N2 SIV were almost exclusively detected in those born before 1990, of whom 70% were seropositive. HI antibodies against H3N2v were predominantly found in those born before 2000, with 86% seropositive. Titres against the North American H3N2v were higher than against the European H3N2 SIV. VN patterns were similar, but with higher rates and titres. We also demonstrated lower seroreactivity to European H3N2 SIV than to North American H3N2v virus. Finally, we found a strong correlation between HI titres against the European H3N2SIV and H3N2v and their respective human ancestors,A/Victoria/3/75 and A/Nanchang/933/95. This finding and the minimal contacts between humans and pigs in Luxembourg suggest that anti-SIV antibodies inhuman serum samples reflect serological cross-reactivity with historical human H3N2 viruses. Our findings help assess the pandemic risk of H3N2 SIV.

Aim: To evaluate the risk of urinary tract infections (UTI) in subjects with newly diagnosed type 2 diabetes mellitus (T2DM)., Methods: Subjects aged ≥18years and diagnosed with T2DM between 1/1/10 and 12/31/10 were identified using the MarketScan® databases, which are representative of the commercially insured US population and those with both Medicare and supplemental coverage. The index date was the first T2DM diagnosis date in 2010 (date randomly selected for those without T2DM). Subjects without T2DM were matched (1:1) by index date, age, gender, urban/rural location, and region. All subjects had continuous enrollment for 12 months before (baseline) and after (follow-up) the index date. UTI diagnosis was defined using ICD-9-CM codes. Measurements of glycemic control and body weight were not available. An adjusted logistic regression model assessed the likelihood of UTI., Results: A total of 89,790 matched pairs were selected. During follow-up, a UTI diagnosis was more common in subjects with T2DM than without T2DM (9.4% vs. 5.7%; p<0.0001). Recurrence of UTI was also more likely with T2DM (1.6% vs. 0.6%; p<0.0001). In a logistic regression, subjects with T2DM had a greater likelihood of UTI during follow up (adjusted odds ratio [OR]=1.54 [95% CI: 1.47-1.60]). This relationship remained after stratifying by gender., Conclusion: Subjects with T2DM were more likely to experience a UTI and recurrent UTIs than subjects without T2DM during follow-up., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: Type 2 diabetes is a reported risk factor for more frequent and severe urinary tract infections (UTI). We sought to quantify the annual healthcare cost burden of UTI in type 2 diabetic patients., Methods: Adult patients diagnosed with type 2 diabetes were identified in MarketScan administrative claims data. UTI occurrence and costs were assessed during a 1-year period. We examined UTI-related visit and antibiotic costs among patients diagnosed with UTI, comparing those with versus without a history of UTI in the previous year (prevalent vs. incident UTI cases). We estimated the total incremental cost of UTI by comparing all-cause healthcare costs in patients with versus without UTI, using propensity score-matched samples., Results: Within the year, 8.2% (6,014/73,151) of subjects had ≥1 UTI, of whom 33.8% had a history of UTI. UTI-related costs among prevalent versus incident cases were, respectively, $603 versus $447 (p=0.033) for outpatient services, $1,607 versus $1,819 (p=NS) for hospitalizations, and $61 versus $35 (p<0.0001) for antibiotics. UTI was associated with a total all-cause incremental cost of $7,045 (95% CI: 4,130, 13,051) per patient with UTI per year., Conclusions: UTI is common and may impose a substantial direct medical cost burden among patients with type 2 diabetes., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

Body mass index (BMI), the prevalent indicator of obesity, is not easily grasped by patients nor physicians. Waist circumference (WC) is correlated to obesity, is better understood and has a stronger relationship to the metabolic syndrome. We compiled WC, complete blood count (CBC) parameters as well as other pertinent data of 6766 25-55-year-old US volunteers sampled in the US National Health and Nutrition Examination Survey, in the years 2005-2010. To determine reference intervals of typical US patients visiting their clinician, we used minimal exclusion criteria. We compiled hemoglobin, red blood cell count, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration, mean cell hemoglobin (MCH), red cell distribution width (RDW), platelet count, mean platelet volume, and counts of white blood cells (WBC), neutrophils, lymphocytes, monocytes, eosinophils, and basophils. In addition, we also compiled serum C reactive protein and serum iron. The three major US races were studied and reference interval diagrams were constructed for each CBC parameter plotted against WC. WBC count, RDW, lymphocyte, neutrophil, and red blood cell count increase with WC. Conversely, serum iron and MCH and MCV decrease. These relationships may be related to insulin resistance and chronic activation of the immune system and the resulting low-grade inflammatory state. WC is a strong predictor for many CBC parameters, suggesting that WC should be taken into account when evaluating blood count results. Clinicians who take care of obese patients should be aware of altered hematology and investigate and treat accordingly., (© 2014 Wiley Periodicals, Inc.)

Background: Reliable data regarding absolute and relative risks of death and graft failure after coronary artery bypass graft surgery (CABG) and percutaneous coronary intervention (PCI) in renal transplant patients are unavailable., Methods and Results: Renal transplant patients undergoing inpatient CABG (n=1400) or PCI (n=4097) were identified from United States Renal Data System data. Cumulative incidence of nonfatal graft failure and death was reported for observed events. A Cox model with the Fine-Gray method was used to account for competing risks in assessing relative hazards. Age and race were similarly distributed; patients who underwent CABG were more likely to have acute arrhythmia and congestive heart failure but less likely to have acute myocardial infarction on index admission. In-hospital death was more frequent after CABG (5.6% versus 3.0%, P<0.001). Cumulative incidence of death, graft failure, and the combined outcome at 3 years were 23.1%, 15.4%, and 38.5% after CABG and 22.9%, 13.3%, and 36.1% after PCI, respectively. In adjusted analyses, CABG was not associated with increased risk of graft failure versus PCI during the first 6 months (hazard ratio 1.06, 95% CI 0.79 to 1.43) or from 6 to 36 months (0.98, 0.78 to 1.22). Risk of death increased after CABG during the first 3 months (1.37, 1.08 to 1.73), but decreased from 6 months on (0.76, 0.63 to 0.93)., Conclusions: CABG does not appear to be associated with a difference in risk of graft failure compared with PCI in renal transplant patients. Compared with PCI, adjusted risk of early death is higher after CABG; however, mortality from 6 months on is lower.

Unlabelled:  , Background: In 2006, pharmacies began offering select generic prescription drugs at discount prices (e.g., $4 for a 30-day supply) through nonmembership and membership programs. As part of the contract in membership generic drug discount programs, the member agrees to forgo submission of the claim to the insurance company. Claims not submitted for insurance adjudication may result in incomplete pharmacy benefit manager (PBM) and health plan data, which could negatively influence adherence reporting and clinical programs. To address potentially missing claims data, the Centers for Medicare Medicaid Services (CMS) encourages Medicare Part D sponsors to incentivize network pharmacies to submit claims directly to the plan for drugs dispensed outside of a member's Part D benefit, unless a member refuses. The extent of PBM and health plan claims capture loss due to generic drug discount programs is unknown., Objective: To identify changes in levothyroxine utilizers' prescription claims capture rate following the advent of generic drug discount membership and nonmembership programs., Methods: This retrospective concurrent cohort study used claims data from 3.5 million commercially insured members enrolled in health plans located in the central and southern United States with Prime Therapeutics pharmacy benefit coverage. Members were required to be 18 years or older and younger than 60 years as of January 1, 2006, and continuously enrolled from January 1, 2006, through December 31, 2010. Members utilizing generic levothyroxine for at least 120 days during January 1, 2006, through June 30, 2006 (baseline period) from the same pharmacy group with supply on July 1, 2006, were placed into 1 of 3 pharmacy groups: (1) nonmembership (Walmart, Sam's Club, Target, Kroger, City Market, and King Soopers pharmacies), (2) membership (Walgreens, CVS, Albertsons, and Savon pharmacies), or (3) the reference group of all other pharmacies. The index date was defined as July 1, 2006. The levothyroxine claim providing supply on July 1, 2006, was the index claim. Members with a Kmart pharmacy index claim were excluded, since the Kmart membership drug discount program began prior to July 1, 2006. Levothyroxine claims capture nonpersistency, defined as the occurrence of a claim supply end date prior to a 180-day gap, was the primary outcome variable and was assessed from July 1, 2006, through June 30, 2010 (follow-up period). The odds of levothyroxine claims capture nonpersistency by pharmacy group were assessed using a logistic regression analysis adjusted for the following covariates: age, gender, median income in the ZIP code of residence (binomial for ≤ $50,000 vs. greater than $50,000), switch to a brand levothyroxine product during the follow-up period, index levothyroxine claim supply of 90 days or more, and index levothyroxine claim member cost share per 30-day supply in tertiles (≤ $5.00, $5.01-$7.99, ≥ $8.00)., Results: Of 2,632,855 eligible members aged 18 years or older, 13,427 met all study eligibility criteria. The baseline pharmacy groups were membership with 3,595 (26.8%), nonmembership with 1,919 (14.3%), and all other pharmacies with 7,913 (58.9%) members. The rates of levothyroxine claims capture persistency throughout the 4-year follow-up period were 85.4% for nonmembership (P = 0.593 vs. all other pharmacies), 77.7% for the membership group (P  less than  0.001 vs. all other pharmacies), and 85.9% for all other pharmacies. The Kaplan-Meier comparison of claims capture persistency found nearly identical claims capture loss for the nonmembership compared with all other pharmacies group, and when compared in a multivariate logistic regression model, there was no difference in the odds of levothyroxine claims capture over 4 years follow-up (OR = 1.01, 95% CI = 0.88-1.16, P = 0.900). The membership generic drug discount programs (Walgreens, CVS, Alberstons, and Savon pharmacies) had a statistically significant 61% higher odds (OR = 1.61, 95% CI = 1.45-1.79, P  less than  0.001) of levothyroxine claims capture nonpersistency. The onset of the difference between the membership group and the all other pharmacies group was temporally associated with the launch of the membership programs. In comparison to index levothyroxine member cost of ≤ $5.00 per 30-day supply, higher cost shares were associated with higher levothyroxine claims capture nonpersistency ($5.01 to $7.99 OR 1.34, 95% CI 1.19-1.52 and ≥ $8.00 OR 1.60, 95% CI 1.40-1.82)., Conclusions: Among levothyroxine utilizers in 2006 (prior to the advent of drug discount programs), those with claims from a pharmacy that subsequently implemented a nonmembership generic drug discount program did not appear to have a different rate of levothyroxine claims capture than members from the reference group when followed through June 2010. Utilizers with claims from a pharmacy that subsequently implemented a membership program had a significantly lower levothyroxine claims capture rate. Increasing index levothyroxine member cost was associated with higher levothyroxine claims capture loss. Because the analysis could not directly measure claims capture loss associated with members who switched to a new pharmacy group without presenting their insurance information (e.g., membership discount programs), further research is needed to confirm these findings.

Economic impacts of seasonal influenza vary across US counties, but little estimation has been conducted at the county level. This research computed annual economic costs of seasonal influenza for 3143 US counties based on Census 2010, identified inherent spatial patterns, and investigated cost-benefits of vaccination strategies. The computing model modified existing methods for national level estimation, and further emphasized spatial variations between counties, in terms of population size, age structure, influenza activity, and income level. Upon such a model, four vaccination strategies that prioritize different types of counties were simulated and their net returns were examined. The results indicate that the annual economic costs of influenza varied from $13.9 thousand to $957.5 million across US counties, with a median of $2.47 million. Prioritizing vaccines to counties with high influenza attack rates produces the lowest influenza cases and highest net returns. This research fills the current knowledge gap by downscaling the estimation to a county level, and adds spatial variability into studies of influenza economics and interventions. Compared to the national estimates, the presented statistics and maps will offer detailed guidance for local health agencies to fight against influenza.

Background: Data are scant regarding access to health care in patients with chronic kidney disease (CKD). We performed descriptive analyses using data from the National Kidney Foundation's Kidney Early Evaluation Program (KEEP), a nationwide health screening program for adults at high risk of CKD., Methods: From 2000-2010, a total of 122,502 adults without end-stage renal disease completed KEEP screenings; 27,927 (22.8%) met criteria for CKD (10,082, stages 1-2; 16,684, stage 3; and 1,161, stages 4-5). CKD awareness, self-rated health status, frequency of physician visits, difficulty obtaining medical care, types of caregivers, insurance status, and medication coverage and estimated costs were assessed., Results: Participants with CKD were more likely to report fair/poor health status than those without CKD. Health care utilization increased at later CKD stages; ~95% of participants at stages 3-5 had visited a physician during the preceding year compared with 83.7% of participants without CKD. More Hispanic and African American than white participants at all CKD stages reported not having a physician. Approximately 40% of participants younger than 65 years reported fair/poor health status at stages 4-5 compared with ~30% who were 65 years and older. Younger participants at all stages were more likely to report extreme or somewhat/moderate difficulty obtaining medical care. Comorbid conditions (diabetes, hypertension, and prior cardiovascular events) were associated with increased utilization of care. Utilization of nephrology care was poor at all CKD stages; <6% of participants at stage 3 and <30% at stages 4-5 reported ever seeing a nephrologist., Conclusions: Lack of health insurance and perceived difficulty obtaining medical care with lower health care utilization, both of which are consistent with inadequate access to health care, are more likely for KEEP participants who are younger than 65 years, nonwhite, and without previously diagnosed comorbid conditions. Nephrology care is infrequent in elderly participants with advanced CKD who are nonwhite, have comorbid disease, and have high-risk states for cardiovascular disease., (Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Posttransplant lymphoproliferative disorder (PTLD) is a major complication of kidney transplant., Study Design: Retrospective cohort study comparing PTLD incidence rates using US Medicare claims and Organ Procurement and Transplantation Network (OPTN) data, examining risk factors for PTLD in OPTN data, and studying recipient and graft survival after PTLD diagnosis., Setting & Participants: All adult first-transplant patients who underwent deceased or living donor kidney-only transplants in 2000-2006 (n = 89,485) followed up through 3 years posttransplant., Predictors: Recipient and donor characteristics, HLA mismatches, viral serologic test results, and initial immunosuppression., Outcomes: OPTN-reported or Medicare claims-based PTLD diagnosis, recipient and graft survival after OPTN-reported PTLD diagnosis., Measurements: Adjusted HRs for PTLD diagnosis estimated using a Cox proportional hazards model; probability of survival free of all-cause graft failure estimated using the Kaplan-Meier method., Results: The incidence rate of PTLD during the first posttransplant year was 2-fold higher in Medicare claims (0.46/100 patient-years; 95% CI, 0.39-0.53) than in OPTN data (0.22/100 patient-years; 95% CI, 0.17-0.27). Factors associated with increased rates of PTLD included older age, white race (vs African American), induction with T-cell-depleting antibodies, Epstein-Barr virus seronegativity at the time of transplant, and cytomegalovirus seronegativity at the time of transplant. The adjusted risk of death with graft function was 17.5 (95% CI, 14.3-21.4) times higher after a report of PTLD, and the risk of death-censored graft failure was 5.5 (95% CI, 3.9-7.7) times higher., Limitations: Shortcomings inherent in large databases, including inconsistencies in patient follow-up, reporting, and coding practices by transplant centers; insufficient registry data to analyze acute rejection episodes and antirejection treatment; no available data for potential effects of different types of PTLD treatment on patient outcomes., Conclusions: Despite the limitations of data collected by registries, PTLD clearly is an important complication; both mortality and death-censored graft failure increase after PTLD., (Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: To examine and quantify, at the US national level, the marginal differences in health-related quality of life (HRQoL) of diabetic patients with and without macrovascular comorbid conditions (MaVCC)., Methods: Using the pooled Medical Expenditure Panel Survey (MEPS) 2001 and 2003 data, a nationally representative community-dwelling adult sample (age ≥ 18) was included in the study. HRQoL measures included the preference-based EQ-5D index, Euroqol visual analogue scale (EQ-VAS), SF-12 physical component summary (PCS), and SF-12 mental component summary (MCS). Given the censored distribution of the data, a two-part model was used to identify the relationship between MaVCC and the EQ-5D index after controlling for age, sex, race, ethnicity, education, income, employment status, health insurance, smoking status, diabetes severity, and comorbidities. Censored least absolute deviation and ordinary least square models were employed to analyze EQ-VAS and SF-12 PCS/MCS, respectively., Results: Compared to diabetic patients without MaVCC (N = 2431), those with MaVCC (N = 747) had significantly lower EQ-5D index (-0.062), EQ-VAS (-9.2), SF-12 PCS (-5.0), and MCS (-2.1) after controlling for differences in sociodemographics, smoking status, diabetes severity, and comorbidities (all P < 0.001)., Conclusions: MaVCC is consistently associated with lower HRQoL for patients with diabetes in the United States. Results of this study are valuable for future comparative-effectiveness and cost-effectiveness analyses in diabetes.

Background and Objectives: Fluid overload in hemodialysis patients sometimes requires emergent dialysis, but the magnitude of this care has not been characterized. This study aimed to estimate the magnitude of fluid overload treatment episodes for the Medicare hemodialysis population in hospital settings, including emergency departments., Design, Setting, Participants, & Measurements: Point-prevalent hemodialysis patients were identified from the Centers for Medicare and Medicaid Renal Management Information System and Standard Analytical Files. Fluid overload treatment episodes were defined by claims for care in inpatient, hospital observation, or emergency department settings with primary discharge diagnoses of fluid overload, heart failure, or pulmonary edema, and dialysis performed on the day of or after admission. Exclusion criteria included stays >5 days. Cost was defined as total Medicare allowable costs for identified episodes. Associations between patient characteristics and episode occurrence and cost were analyzed., Results: For 25,291 patients (14.3%), 41,699 care episodes occurred over a mean follow-up time of 2 years: 86% inpatient, 9% emergency department, and 5% hospital observation. Heart failure was the primary diagnosis in 83% of episodes, fluid overload in 11%, and pulmonary edema in 6%. Characteristics associated with more frequent events included age <45 years, female sex, African-American race, causes of ESRD other than diabetes, dialysis duration of 1 to 3 years, fewer dialysis sessions per week at baseline, hospitalizations during baseline, and most comorbid conditions. Average cost was $6,372 per episode; total costs were approximately $266 million., Conclusions: Among U.S. hemodialysis patients, fluid overload treatment is common and expensive. Further study is necessary to identify prevention opportunities.

Purpose: Compare annual direct and indirect costs between privately insured U.S. patients with epileptic partial onset seizures (POS) and matched controls., Methods: One thousand eight hundred fifty-nine patients (including a subset of 758 employees) with >or=1 (POS) diagnosis (ICD-9-CM: 345.4.x-345.7.x), 1999-2004, ages 16-64 years, were identified from a privately insured claims database. Control group was an age- and gender-matched cohort of randomly chosen beneficiaries without epilepsy (ICD-9-CM: 345.x). All were required to have continuous health coverage during 2004 (baseline) and 2005 (study period). Chi-square tests were used to compare baseline comorbidities. Univariate and multivariate analyses were used for comparisons of annual direct (medical and pharmaceutical) and indirect costs during the study period., Results: Patients with POS were on average 42 years of age, and 57% were women. Patients with POS had significantly higher rates of mental health disorders, migraine, and other neurologic disorders, and higher Charlson comorbidity index (CCI) compared with controls. On average, direct annual costs were significantly higher for POS patients ($11,276) compared with controls ($4,087), p < 0.001; difference of $7,190. Epilepsy-related costs (i.e., costs for antiepileptic drugs, claims with epilepsy or convulsions diagnoses) accounted for $3,290 (29% of direct costs). Employees with POS had substantial and significantly higher indirect (disability- and medically related absenteeism) costs compared with controls ($3,431 vs. $1,511, p < 0.001). Multivariate analyses supported the matched-control univariate findings., Conclusion: Patients with POS had significantly higher costs compared with matched controls. Epilepsy-related costs underestimate the excess costs of patients with partial onset seizures.

Background: The direct cost burden of epilepsy in the US from a third-party payer perspective has not been evaluated. Furthermore, no study has quantified the indirect (work-loss) cost burden of epilepsy from an employer perspective in the US., Objective: To assess the annual direct costs for privately insured US patients diagnosed with epilepsy, and indirect costs for a subset of employees from an employer perspective., Methods: A retrospective analysis of a claims database for the privately insured, including employee disability claims from 1999 through 2005 and comprising 17 US companies, was conducted. A total of 4323 patients aged 16-64 years (including 1886 employees) with at least one epilepsy diagnosis (International Classification of Diseases, 9th edition, Clinical Modification [ICD-9-CM] code 345.x) over the period 1999-2004 were included. The control group was a demographically matched cohort of randomly chosen beneficiaries without an epilepsy diagnosis. All had continuous health coverage during 2004 (baseline) and 2005 (study period). Main outcome measures included annual direct (medical and pharmaceutical) costs and, for employees, indirect (disability and medically related absenteeism) and total costs for the study period. Wilcoxon rank-sum tests were used for univariate comparisons of annual direct costs, indirect costs (costs for the subset of employees with these data), and total (direct and indirect) costs during the study period. Two-part multivariate models that adjusted for patient characteristics were also used to compare costs between the study and control groups., Results: Patients with epilepsy were an average age of 43 years and 57% were female. They had more co-morbidities than controls. On average, direct annual costs were significantly higher per patient with epilepsy than per control ($US10 258 vs $US3862, respectively; p < 0.0001) [year 2005 values], with an annual per-patient difference of $US6396. Epilepsy-related costs ($US2057) accounted for 20% of direct costs for patients with epilepsy. Annual indirect costs were significantly higher for employees with epilepsy than for employed controls ($US3192 vs $US1242, respectively; p < 0.0001), with a difference of $US1950. Total direct plus indirect costs for employees with epilepsy were also higher than those for employed controls ($US13 595 vs $US5338, respectively; p < 0.0001), with a difference of $US8257., Conclusions: Epilepsy was associated with significant economic burden. The excess direct costs in patients with epilepsy are underestimated when only epilepsy-related costs are considered.

Background: A large body of clinical studies have demonstrated the efficacy of atypical antipsychotic use in the treatment of bipolar disorder. Facing increasing budget pressure, third-party payers, such as state Medicaid programmes in the US, are demanding better understanding of the medical costs beyond atypical antipsychotic drug costs alone in treating bipolar disorder., Objective: To examine healthcare costs associated with the atypical antipsychotic treatments for bipolar disorder from a US third-party payer perspective., Methods: This was a retrospective cohort study using an intent-to-treat approach. Using the North Carolina Medicaid claims database (August 2000 to January 2005), 3328 patients with bipolar disorder were identified who were continuously eligible for 3 months pre-initiation and 12 months post-initiation of treatment with an atypical antipsychotic (AP2) or mood stabilizer (MS). Patients were classified into three groups based on the treatment types during the first 30 days after treatment initiation: AP2 monotherapy, AP2 + MS combination therapy, and MS monotherapy. Bipolar-related and total health-related costs were examined for the 12-month period. Propensity score matching was employed to balance baseline characteristics among the three comparison groups. Generalized linear models were further employed to estimate the average treatment effect on the cost outcomes., Results: Compared with MS monotherapy, AP2 monotherapy and AP2 + MS combination therapy incurred higher medication costs during the 12-month treatment period. Patients receiving AP2 monotherapy had significantly lower bipolar-related medical costs (-$US698; p = 0.002) [year 2004 values] than patients receiving MS monotherapy. However, the inclusion of the medication cost produced no statistically significant difference in bipolar-related total cost (p = 0.14). Similar results were observed for all health-related costs. Patients receiving AP2 + MS therapy incurred significantly higher bipolar-related total costs (+$US1659; p < 0.0001) and all health-related total costs (+$US2115; p < 0.0001) than patients receiving MS monotherapy, which was attributable largely to the higher medication cost., Conclusions: From a third-party payer perspective, atypical antipsychotic monotherapy generated higher drug costs but lower medical care costs, resulting in equivalent total healthcare costs over a 1-year period.

Objective: To examine and quantify from the societal perspective the impact of macrovascular comorbid conditions (MVCCs) on health care and productivity costs in diabetic patients in the U.S., Research Design and Methods: With use of the pooled Medical Expenditure Panel Survey (MEPS) 2004 and 2006 data, a nationally representative adult sample (aged >or=18 years) was included in the study. Health care cost was measured by the annual health care expenditure. Productivity cost was calculated from the lost productivity from missed work days and additional bed days due to illness/injury based on the 2006 average national hourly wage. Both 2004 and 2006 cost data were adjusted to 2006 dollars. Given the heavily right-skewed distribution of the cost data, the generalized linear model with log-link function and gamma variance was used to identify the relationship between MVCCs and costs after controlling for age, sex, race, ethnicity, education, income, employment status, smoking status, health insurance, diabetes severity, and comorbidities. Negative binomial models were applied to analyze the outcomes of missed work days and bed days. All statistics were adjusted using the proper sampling weight from MEPS., Results: Compared with diabetic patients without MVCCs (n = 3,320), those with MVCCs (n = 913) had statistically significant higher annual health care costs (5,120 USD, P < 0.001), more missed work days (13.03 days, P < 0.001), and more bed days (7.60 days, P = 0.025) per patient after controlling for differences in sociodemographics, smoking, diabetes severity, and comorbidities. The marginal lost productivity cost was 2,388 USD annually per patient., Conclusions: From the U.S. societal perspective, MVCCs in diabetic patients are associated with increased health care and lost productivity costs.

Background: Use of atypical antipsychotics in treatment of patients with bipolar disorder is increasingly common, yet few studies have systematically investigated or compared medical costs associated with use of specific atypical antipsychotics., Objective: To evaluate the direct healthcare costs associated with olanzapine, risperidone, or quetiapine monotherapy among Medicaid patients diagnosed with bipolar disorder (ICD-9: 296.4x-296.8x)., Methods: North Carolina Medicaid patients with bipolar disorder were followed for 12 months after initiation of atypical antipsychotic monotherapy (index date). They had no bipolar-related medical visit, hospitalization, or use of atypical antipsychotics 90-days prior to the treatment initiation. Costs of index drug, all bipolar-related medical care, and all health-related costs were examined. A two-stage sample selection model was employed to account for potential confounders and sample selection bias. Medication adherence measures using cumulative medication acquisition and cumulative medication gap were calculated as separate outcomes., Results: Inclusion criteria were met by 838 continuously eligible patients (393 olanzapine, 262 risperidone, 183 quetiapine). Drug-taking adherence was similar across the drug cohorts. After adjusting for potential confounders, patients taking olanzapine incurred $863 (p < 0.001) and $449 higher (p < 0.01) index drug costs than patients taking risperidone and quetiapine, respectively. Bipolar-related medical costs for patients taking olanzapine were higher ($616; p = 0.06) than for patients taking risperidone at 10% significance level, while such costs for patients taking olanzapine and quetiapine were similar. Total health-related costs did not differ across patient cohorts, including or excluding the index drug costs., Limitations: The final study sample is a highly selected one based on the study design. This sample may not represent the entire bipolar population. The criteria used to guard against omitting bipolar disorder patients misdiagnosed with major depression need further validation., Conclusions: No evidence was identified that there is any difference for total health-related costs in using olanzapine, risperidone, or quetiapine monotherapy to treat bipolar disorder, from a Medicaid payer's perspective. The clinical difference between these atypical antipsychotic drugs for the treatment of bipolar disorder could be of more interest than the economic difference.