IntroductionThe prevalence of chronic physical and mental disorders is increasing among children and adolescents in the United States. In this study, we investigated the association between mental health disorders and chronic physical conditions among children, and we assessed whether having mental disorders is associated with increased health care costs for children with chronic physical conditions, using Medical Expenditure Panel Survey data from 2008 through 2013.MethodsChildren aged 5 to 17 with at least 1 chronic physical condition were included in the study. Chronic physical conditions and mental disorders were identified using International Classification of Diseases, 9th Revision, Clinical Modification codes. We used logistic regression to assess the relationship between mental disorders and chronic physical conditions, and we used generalized linear models with gamma distribution and log link to estimate direct medical costs.ResultsOf 42,130 children, 4,640 had at least 1 chronic physical condition. After controlling for sociodemographic and health care access characteristics, we found that children with at least 1 chronic physical condition were 62% more likely to have a mental health disorder than were children without chronic physical conditions (odds ratio = 1.62; 95% confidence interval [CI], 1.37–1.92). Having a mental disorder was a significant predictor of total health care cost (β = 0.64; 95% CI, 0.43–0.85; P < .001). The adjusted annual incremental cost due to mental disorders among children with chronic physical conditions was $2,631 (P < .001).ConclusionHaving chronic physical conditions in childhood is a significant predictor of mental health disorders and total health care expenditures.

ObjectiveTo examine age, gender, and temporal differences in baseline characteristics and clinical outcomes of adult patients hospitalised with COVID-19.DesignA cohort study using deidentified electronic medical records from a Global Research Network.Setting/Participants67 456 adult patients hospitalised with COVID-19 from the USA; 7306 from Europe, Latin America and Asia-Pacific between February 2020 and January 2021.ResultsIn the US cohort, compared with patients 18–34 years old, patients ≥65 had a greater risk of intensive care unit (ICU) admission (adjusted HR (aHR) 1.73, 95% CI 1.58 to 1.90), acute respiratory distress syndrome(ARDS)/respiratory failure (aHR 1.86, 95% CI 1.76 to 1.96), invasive mechanical ventilation (IMV, aHR 1.93, 95% CI, 1.73 to 2.15), and all-cause mortality (aHR 5.6, 95% CI 4.36 to 7.18). Men appeared to be at a greater risk for ICU admission (aHR 1.34, 95% CI 1.29 to 1.39), ARDS/respiratory failure (aHR 1.24, 95% CI1.21 to 1.27), IMV (aHR 1.38, 95% CI 1.32 to 1.45), and all-cause mortality (aHR 1.16, 95% CI 1.08 to 1.24) compared with women. Moreover, we observed a greater risk of adverse outcomes during the early pandemic (ie, February–April 2020) compared with later periods. In the ex-US cohort, the age and gender trends were similar; for the temporal trend, the highest proportion of patients with all-cause mortality were also in February–April 2020; however, the highest percentages of patients with IMV and ARDS/respiratory failure were in August–October 2020 followed by February–April 2020.ConclusionsThis study provided valuable information on the temporal trends of characteristics and outcomes of hospitalised adult COVID-19 patients in both USA and ex-USA. It also described the population at a potentially greater risk for worse clinical outcomes by identifying the age and gender differences. Together, the information could inform the prevention and treatment strategies of COVID-19. Furthermore, it can be used to raise public awareness of COVID-19’s impact on vulnerable populations.

Objectives: Pharmacist interventions may prevent adverse events after hospital discharge and reduce the risk of readmission as well as healthcare costs. This study evaluates the impact of pharmacist-provided post-discharge services on healthcare utilization and cost for members of a US managed Medicaid health plan. MethOds: Synergy Pharmacy Solutions (SPS) provides ambulatory care pharmacy-based transitional care services for high risk hospital discharges covered by Kern Health Systems (KHS) managed Medicaid plan. Over 1,100 qualifying discharged patients from Bakersfield Memorial Hospital were referred to SPS. A control group of matched KHS discharges from neighboring hospitals were then identified by matching each to a hospitalization episode in the experimental group based on the number of prior hospitalizations and length of stay [±1 day]. Experimental patients could have more than one matched control hospitalization. Thirty-day and 180-day readmission rates were analyzed using logistic regression and Cox proportional hazards models. Thirty-day and 180-day inpatient, outpatient, prescription drug, emergency room, and total costs were analyzed by OLS and GLM regressions. Demographics, clinical characteristics, and comorbidity profiles were used as independent variables in all models. Results: We found a 28.0% reduction in 30-day readmissions [OR= 0.720 (95% CI 0.526 to 0.985)] and a 31.9% reduction in 180-day readmissions [OR= 0.681 (95% CI 0.507 to 0.914]. Cox model on time to readmission estimated the overall hazard ratio of readmission at 0.

Background: NSCLC is a deadly disease. Targeted therapy is very effective; however, only ∼ 20% of patients are candidates for this approach. In a search for new therapeutic targets in NSCLC, we have identified Polo like kinase (Plk). Plk1 regulates centrosomes at the G2/M transition and orchestrates cell cycle progression. Clinical trials have shown that a subgroup of refractory NSCLC patients responded to Plki as single agents. Our aim is to validate and identify biomarkers that predict sensitivity to Plki. Methods: To identify therapeutic targets, we evaluated 2 databases with 123 NSCLC cell lines tested with 130 drugs incorporating genomic and gene expression data seeking agents that were markedly effective in a subgroup of cell lines. To identify association between sensitivity to Plki and gene expression, we acquired the datasets from the databases and tested the correlation between IC50 and gene expression. Spearman rank was used to test the association between mutation in key genes and IC50. MTT assay was used to test drug sensitivity in NSCLC cell lines in our laboratory. Cell cycle was evaluated by flow cytometry using BrdU incorporation. Immunofluorescence with anti-phospho-H2yAX antibody was used to identify mitotic catastrophe. Results: In the databases, 12/19 NSCLC lines had IC50 &lt; Cmax of 1.6 µM for the PLKi BI2536 and 6/19 had IC50 &lt; 30 nM. The correlation analysis found mRNA overexpression of 20 genes to be significantly associated with sensitivity to both Plki. Based upon the likelihood of their expression influencing Plk1 function, 4 genes were selected for further study: CEP250, which encodes a core centrosomal protein, and TGFA, RHBDF1 and FOSL2, which are involved with epithelial cell proliferation. KRAS mutation was also correlated with sensitivity to Plki. Our preliminary cell line screening found that 10/37 NSCLC cell lines are exquisitely sensitive to BI2536 with IC70 &lt; 40 nM. The Plki's BI2536 and BI6727 cause complete Plk substrate (TCTP) inhibition with 25 and 100 nM respectively at 12 h as measured by Western blotting. However, in a resistant cell line, TCTP reactivation was observed following 24 h Plk inhibition, while in a sensitive cell line, there was sustained TCTP inhibition up to 120 h. Cell cycle analysis of sensitive cell lines showed a significant arrest in G2/M. Drug treatment caused mitotic catastrophe in sensitive lines. Conclusion: Our statistical analysis utilizing data from 2 databases demonstrated an association between CEP250, TGFA, RHBDF1 and FOSL2 overexpression and KRAS mutation and sensitivity to Plki. These results are being validated in a larger cell line screen that may identify additional biomarkers. Substrate reactivation was observed in one resistant cell line following 24h of Plk inhibition, demonstrating one potential mechanism for resistance. Screening of additional cell lines and mechanistic studies are ongoing to extend these findings. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A182. Citation Format: Renata Ferrarotto, Manasi Suryavanshi, Suk Young Yoo, Jing Wang, Lauren Byers, Bonnie S. Glisson, John Heymach, Faye M. Johnson. Identifying biomarkers of sensitivity to polo-like kinase inhibitors (Plki) in non small cell lung cancer (NSCLC). [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A182.

Regular screening is considered the most effective method to reduce the mortality and morbidity associated with breast cancer. Nevertheless, contradictory evidence about screening mammograms has led to periodic changes and considerable variations among different screening guidelines. This study is the first to examine the immediate impact of the 2009 US Preventive Services Task Force (USPSTF) guideline modification on physician recommendation of mammograms. The study included visits by women aged 40 years and older without prior breast cancer from the National Ambulatory and Medical Care Survey 2008-2010. Bivariate and multiple logistic regressions were used to determine the factors associated with mammography recommendation. Approximately 29,395 visits were included and mammography was recommended during 1350 visits; 50-64-year-old women had 72% higher odds, and 65-74-year-old women had twice the odds of getting a mammogram recommendation compared with 40-49-year-old women in 2009. However, there was no difference in recommendation by age groups in 2008 and 2010. Obstetricians and gynecologists did not modify their recommendation behavior in 2009, unlike all other specialists who reduced their recommendation for 40-49-year-old women in 2009. Other characteristics associated with mammogram recommendations were certain patient comorbidities, physician specialty and primary care physician status, health maintenance organization status of the clinic, and certain visit characteristics. This study demonstrated a temporary effect of the USPSTF screening guideline change on mammogram recommendation. However, in light of conflicting recommendations by different guidelines, the physicians erred toward the more rigorous guidelines and did not permanently reduce their mammogram recommendation for women aged 40-49 years.

The study was designed to investigate the influence of type 2 diabetes mellitus (T2DM) on articular syndrome and parameters of cytokines in patients with osteoarthritis (OA). Methods: The study involved 49 patients (10 males), aged 56.37±1.17 with OA and T2DM in Regional Hospital of Kharkov. All patients were divided into 2 groups: group 1 (n¼21)-with OA, group 2 (n¼28)-with combined course of OA and T2DM (BMI<30 kg/m2). Baseline characteristics of patients included history of OA (1st group-8.52±0.53 years; 2nd group-7.39±0.52 years), T2DM (9.85±0.97 years). The survey plan included anthropometric data, global knee pain [visual analog scale (VAS)], the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), indices of carbohydrate exchange (insulin, glucose, HbA1C, HOMA-IR). The level of HbA1C was <7.5% in all patients. The level of C-reactive protein (CRP) was determined by using of a latex test. The level of TNF-a and IL-1b was determined by ELISA. The X-ray examination of knees was performed for all patients. Results: A statistically significant relations between the degree of diagnosis complexity and radiological changes by Kellgren were found (M-L X^2¼15.58 p¼0.0036<0.05). The indices of WOMAC Pain score and WOMAC stiffness were similar in both groups, but the indices of WOMAC physical function subscore were significantly higher in the 2nd group (M-W U¼88, Z¼À4.167, p¼0.00003). The levels of TNF-a, IL-1b and CRP were higher in group with OA and T2DM, however the difference was not significant. We found significant correlation between TNF-a and IL-1b in both groups (1st-r¼0.66; р<0.05; 2nd-r¼0.70; р<0.05). The significant correlation between TNF-б and CRP was determined in group of patients with OA (r¼0.46; р<0.05) as well as in the group with combined course of OA and T2DM (r¼0.82; р<0.05). Also the correlation between IL-1b and CRP was determined in 1st group(r¼0.48; р<0.05) and in the 2nd group as well (r¼0.52; р<0.05). The level of indices of WOMAC Pain score correlated with TNF-a (r¼0.63; р<0.05), IL-1b (r¼0.45; р<0.05) and CRP (r¼0.66; р<0.05) among the patients of the 1st group. We determined significant correlation between WOMAC Pain score and TNF-a (r¼0.44; р<0.05), IL-1b (r¼0.47; р<0.05); between WOMAC stiffness and TNF-a (r¼0.39; р<0.05), also between WOMAC physical function score and CRP (r¼0.29; р<0.05) in the 2nd group with comorbid pathology. Conclusions: The study demonstrates that T2DM was associated with more pronounced radiographic changes and more severe changes of physical function in patients with comorbid OA. Significant correlation between TNF-a, IL-1b and CRP in patients with combined course of OA and T2DM suggests that T2DM can be an important factor that contributes to derangements of immune and metabolic processes and progression of OA.

Introduction: Racial and ethnic disparities in rheumatoid arthritis (RA) have been identified in the United States, with higher levels of disease activity and worse functional status reported in Hispanic patients compared with their white counterparts. Although RA is one of the most prevalent health conditions in Puerto Rico, few studies have previously examined the characteristics or treatment patterns of patients receiving biological and targeted synthetic disease-modifying anti-rheumatic drugs (b/ tsDMARDs) in this population. Methods: This was a retrospective cohort study using data extracted from the Advanced Business Management Organization database, which represents around 70% of pharmacy claims in Puerto Rico. Patients with RA were included if they had C 1 prescription for any approved b/tsDMARD during the index period (January 2016 to July 2018), and C 2 years of follow-up. The objective was to describe and compare the demographic and clinical characteristics of patients with RA being treated with b/tsDMARD therapy in Puerto Rico, and to evaluate the treatment patterns among these patients.Results: Most patients (74%) received tumor necrosis factor inhibitors (TNFis) as index therapy, followed by abatacept (17%), Janus kinase inhibitors (JAKis; 5%), and other non-TNFis (4%). Similar trends were observed in subsequent lines of therapy, although abatacept was more frequently used in these later lines versus index therapy. At 2 years, 62% of patients had discontinued their index therapy and 17% had switched to an alternative b/tsDMARD; only 21% persisted with index therapy. The percentage of patients who were persistent with their index therapy at the end of year 2 was 28% for JAKis, 36% for abatacept, 41% for TNFis, and 45% for other non-TNFis. Conclusions: These findings demonstrate that despite the availability of several b/tsDMARDs, patients with RA in Puerto Rico still experience substantial treatment disruption, with almost two-thirds of patients discontinuing their index therapy within 2 years.

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