Status Burden Research Articles

Fedratinib Improves Myelofibrosis-related Symptoms and Health-related Quality of Life in Patients with Myelofibrosis Previously Treated with Ruxolitinib: Patient-reported Outcomes from the Phase II JAKARTA2 Trial.

Myelofibrosis symptoms compromise health-related quality of life (HRQoL). Ruxolitinib can reduce myelofibrosis symptom severity, but many patients discontinue ruxolitinib due to loss of response or unacceptable toxicity. Fedratinib is an oral, selective JAK2 inhibitor approved in the United States for treatment of patients with intermediate-2 or high-risk myelofibrosis. The single-arm, phase II JAKARTA2 trial assessed fedratinib 400 mg/d (starting dose) in patients with myelofibrosis previously treated with ruxolitinib. Patient-reported changes in myelofibrosis symptom severity using the modified Myelofibrosis Symptom Assessment Form (MFSAF), and overall HRQoL and functional status using the EORTC QLQ-C30, were evaluated at each cycle. Clinically meaningful changes from baseline HRQoL scores were based on effect sizes. Ninety patients were MFSAF-evaluable. Myelofibrosis symptoms were mild-to-moderate at baseline. Patients showed statistically significant and clinically meaningful improvements in total symptom scores from baseline on the MFSAF at all post baseline visits through the end of cycle 6 (EOC6). Baseline global health status/QoL and functional domain scores on the EORTC QLQ-C30 were meaningfully worse than in the general population. At EOC6, 44% of patients reported clinically meaningful improvements in global health status/QoL, and 30%–53% of patients experienced clinically meaningful improvement in QLQ-C30 functional domains across post baseline timepoints. Over 80% of ongoing patients perceived fedratinib as beneficial on the Patient’s Global Impression of Change questionnaire. Fedratinib effects were consistent among prognostically relevant patient subgroups. Patients with myelofibrosis previously treated with ruxolitinib experienced clinically meaningful improvements in myelofibrosis symptom burden, overall HRQoL, and functional status in the first 6 months of fedratinib treatment.

Cross-sectional and prospective association between personality traits and IADL/ADL limitations.

Prior research has shown that personality traits are associated with activities of daily living (ADLs) and instrumental ADLs (IADLs). To advance research on the psychological factors related to aging-related functional limitations, this study examined the relation between personality traits and both concurrent and incident functional limitations, tested whether these associations are similar across IADLs and ADLs, and tested potential mediators of these associations. Participants were drawn from eight longitudinal samples from the U.S., England, and Japan. Participants provided data on demographic variables, the five major personality traits, and on the Katz ADL-scale and Lawton IADL-scales. IADL/ADL limitations were assessed again 3-18 years later. A consistent pattern of associations was found between personality traits and functional limitations, with associations slightly stronger for IADLs than ADLs, and robust across samples that used different measures and from different cultural contexts. The meta-analysis indicated that higher neuroticism was related to a higher likelihood of concurrent and incident IADL/ADL limitations, and higher conscientiousness, extraversion, and openness were associated with lower risk. Higher agreeableness was associated with lower risk of concurrent IADL/ADL, but unrelated to incident limitations. Physical activity, disease burden, depressive symptoms, self-rated health, handgrip strength, falls, and smoking status mediated the relation between personality traits and incident IADL/ADL limitations. The present study indicates that personality traits are risk factors for both IADL and ADL limitations across multiple national cohorts, identifies potential mediators, and informs conceptual models on psychological risk factors for functional decline. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Urban structure, commuting burden, and employment status of labour forces in an Australian city

Understanding the productivity effects of worker commuting burdens is essential for appraisals of urban planning and investment strategies designed to improve urban productivity. However, the extant urban planning literature lacks systematic analysis of the influence of commuting costs on labour mobility, employment engagement, and productivity. This paper provides the first ever detailed analysis of mobility and commuting burdens for workers in a range of industries and occupational groups in Melbourne, Australia. Linking commuting burdens and measures of employment status in urban areas, this paper finds that the labour force in areas experiencing high commuting burdens exhibit lower levels of engagement with job markets. This research further reveals important variations in such relationships across diverse industry and occupation groups. The results provide urban policy makers with better information about urban transport and employment patterns, thus enabling them to investigate alternative approaches to investing in housing and transport infrastructure to reduce worker commuting burdens and improve economic performance.

Analytic validation and clinical utilization of the comprehensive genomic profiling test, GEM ExTra®.

We developed and analytically validated a comprehensive genomic profiling (CGP) assay, GEM ExTra, for patients with advanced solid tumors that uses Next Generation Sequencing (NGS) to characterize whole exomes employing a paired tumor-normal subtraction methodology. The assay detects single nucleotide variants (SNV), indels, focal copy number alterations (CNA), TERT promoter region, as well as tumor mutation burden (TMB) and microsatellite instability (MSI) status. Additionally, the assay incorporates whole transcriptome sequencing of the tumor sample that allows for the detection of gene fusions and select special transcripts, including AR-V7, EGFR vIII, EGFRvIV, and MET exon 14 skipping events. The assay has a mean target coverage of 180X for the normal (germline) and 400X for tumor DNA including enhanced probe design to facilitate the sequencing of difficult regions. Proprietary bioinformatics, paired with comprehensive clinical curation results in reporting that defines clinically actionable, FDA-approved, and clinical trial drug options for the management of the patient’s cancer. GEM ExTra demonstrated analytic specificity (PPV) of > 99.9% and analytic sensitivity of 98.8%. Application of GEM ExTra to 1,435 patient samples revealed clinically actionable alterations in 83.9% of reports, including 31 (2.5%) where therapeutic recommendations were based on RNA fusion findings only.

Patient race and racial composition of delivery unit associated with disparities in severe maternal morbidity: a multistate analysis 2007–2014

BackgroundHigh Black-serving delivery units and high hospital safety-net burden have been associated with poorer patient outcomes. We examine these hospital-level factors and their association with severe maternal morbidity (SMM), independently and as effect modifiers of patient-level factors. MethodsUsing the 2007–2014 State Inpatient Databases (Florida, New York, California, Maryland, Kentucky), we analyzed delivery hospitalizations. We constructed generalized linear mixed models with patient- and hospital-level variables (Black-serving delivery units: high: top 5th percentile; medium: 5th-25th percentile; low: bottom 75th percentile; hospital safety-net burden status defined by insurance status) and report adjusted odds ratios (aOR) and 99% confidence intervals (CI). We repeated our mixed models with stratification and interaction analysis. Results6 879 332 delivery hospitalizations were included in the analysis. Deliveries at high (aOR 1.83; 99% CI 1.34 to2.50) or medium (aOR 1.27; 99% CI 1.10 to 1.46) Black-serving delivery units were more likely to have SMM than deliveries at low Black-serving delivery units. Hospital safety-net burden was not significantly associated with SMM. In stratified models by hospital category, deliveries of Black women were associated with an increase in SMM compared with deliveries of White women in all hospital categories. In interaction models, Black women giving birth in high Black-serving delivery units had more than twice the odds of White women in low Black-serving delivery units of experiencing SMM (aOR 2.42; 99% CI 1.90 to 3.08). ConclusionThe patient racial/ethnic composition of the delivery unit is associated with adjusted-odds of SMM, both independently and interactively with individual patient race.

Association of Refractory Pain in the Acute Phase After Subarachnoid Hemorrhage With Continued Outpatient Opioid Use.

Little is known about the prevalence of continued opioid use following aneurysmal subarachnoid hemorrhage (aSAH) despite guidelines recommending their use during the acute phase of disease. We sought to determine prevalence of opioid use following aSAH and test the hypothesis that acute pain and higher inpatient opioid dose increased outpatient opioid use. We reviewed consecutively admitted patients with aSAH from November 2015 through September 2019. We retrospectively collected pain scores and daily doses of analgesics. Pain burden was calculated as area under the pain-time curve. Univariate and multivariable regression models determined risk factors for continued opioid use at discharge and outpatient follow-up. We identified 234 patients with aSAH with outpatient follow-up. Continued opioid use was common at discharge (55% of patients) and follow-up (47% of patients, median 63 [interquartile range 49-96] days from admission). Pain burden, craniotomy, and racial or ethnic minority status were associated with discharge opioid prescription in multivariable analysis. At outpatient follow-up, pain burden (odds ratio [OR] 1.88, 95% confidence interval [CI] 1.5-2.4), depression (OR 3.1, 95% CI 1.1-8.8), and racial or ethnic minority status (OR 2.1, 95% CI 1.1-4.0) were independently associated with continued opioid use; inpatient opioid dose was not. Continued opioid use following aSAH is prevalent and related to refractory pain during acute illness, but not inpatient opioid dose. More efficacious analgesic strategies are needed to reduce continued opioid use in patients following aSAH. This study provides Class II evidence that continued opioid use following aSAH is associated with refractory pain during acute illness but not hospital opioid exposure.

The influence of social support on COPD outcomes mediated by depression.

BackgroundThe purpose of this study was to explore the association between perceived social support and COPD outcomes and to determine whether the associations are mediated by depressive symptoms.MethodsSubjects with COPD who were enrolled as part of SPIROMICS were included in this analysis. Questionnaires relating to quality of life, symptom burden, and functional status were administered at annual clinic visits for over a 3 year period. In both cross-sectional and longitudinal analyses, we examined the association of social support as measured by the FACIT-F with COPD outcomes. Cross sectional analyses used multivariable linear or logistic regression, adjusting for covariates. For longitudinal analyses, generalized linear mixed models with random intercepts were used. Models were adjusted with and without depressive symptoms and mediation analyses performed.ResultsOf the 1831 subjects with COPD, 1779 completed the FACIT- F questionnaire. In adjusted cross-sectional analysis without depressive symptoms, higher perceived social support was associated with better quality of life, well-being, 6 minute walk distance, and less dyspnea. When also adjusting for depressive symptoms, all associations between social support and COPD outcomes were attenuated and no longer statistically significant. Mediation analysis suggested that depressive symptoms explained the majority (> = 85%) of the association between social support and measured COPD outcomes. Results of the longitudinal analysis were consistent with the cross-sectional analyses. There was no association between social support and odds of exacerbations.ConclusionHigher social support was associated with better COPD outcomes across several measures of morbidity including quality of life, respiratory symptoms, and functional status. In addition, these associations were largely attenuated when accounting for depressive symptoms suggesting that the beneficial association of social support with COPD outcomes may be largely mediated by the association between social support and depression.Trial registrationSPIROMICS was approved by Institutional Review Boards at each center and all participants provided written informed consent (clinicaltrials.gov: NCT01969344).

Abstract P01: Development of a TMB classifier on NSCLC H&E images

Abstract A number of immunotherapy treatments in cancer can be guided by a patient’s tumor mutation burden (TMB) status. However typical TMB determination is performed via next generation sequencing which is problematic due to its high cost, low availability worldwide and operational challenges. The ability to screen patients for TMB determination using alternative methodologies is of interest, particularly in the use of H&E slides which are readily available for most cancer patients. Bio-AI Health has developed a machine learning (ML) classifier model capable of identifying TMB status in patients using H&E slides only. Our automated model is unique in that it uses an enriched signal from samples consisting of tumor region only while generating unique visualizers that provide an insight into the performance and mode of action of the model itself. This visualizer allows the pathologist a unique view into the ML performance therefore eliminating the black box concept and providing a crucial QC step to ensure proper algorithm performance. This test can increase the sensitivity of detection providing significant clinical utility. The dataset for model development was obtained from TCGA cohort and TMB status was calculated using whole exome sequencing data. We further developed automated ML segmentation models to accurately segment the tissue into multiple compartments and filter our all necrotic and non-neoplastic tissue regions. Taking into account only tumor regions, the classifier ML model uses an ensemble approach which integrates the prediction of multiple convolutional network probabilities and achieves an accuracy of 0.76 with a sensitivity of .79 and F1 score of .82 towards the classification of the tissue as TMB high or Low. Citation Format: Alan Jerusalmi. Development of a TMB classifier on NSCLC H&E images [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2021 Feb 3-5. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(6_Suppl):Abstract nr P01.

한국 중년층의 사전연명의료의향 의도 구조모형

Objectives: The aim of this study was to construct and verify a structural equation model of advance directive intent among a Korean group in their middle-age. Methods: Data were collected between May 1 and 30, 2017, from 398 people. The endogenous and exogenous variables of the hypothetical model consisted of elderly parents’ care burden, health status, attitude towards withdrawal of life sustaining treatment, advance directive efficacy, and advance directive intent. The collected data were analyzed using the SPSS/WIN 24.0 and Mplus 7.4. Results: The hypothetical model demonstrated a good fit: χ2=223.79(df=109, p<.001), CMIN/df=2.05 CFI=.96, TLI=.96, RMSEA=.05, SRMR=.06. Elderly parents’ care burden and health status showed statistically significant direct effects with attitude toward withdrawal of life sustaining treatment(β=.17, p=.001; β=.21, p<.001) and advance directive efficacy(β=.11, p=.040; β=.19, p=.002), respectively. Attitude toward withdrawal of life sustaining treatment and advance directive efficacy showed statistically significant direct effects on advance directive intent(β=.15, p=.007; β=.48, p<.001). Elderly parents’ care burden and health status had a significant indirect effect on advance directive intent through attitude toward withdrawal of life sustaining treatment(β=.01, p=.041; β=.05, p=.036) and advance directive efficacy(β=.06, p=.049; β=.16, p=.006), respectively. The variables accounted for 26.1% of advance directive intent of the Korean group in their middle-age. Conclusion: It is necessary to develop an advance directive education program based on variables affecting advance directive intent for individuals in their middle-age.

Real world clinicopathologic observations of patients with metastatic solid tumors receiving immune checkpoint inhibitor therapy: Analysis from Kentucky Cancer Registry.

The state of Kentucky has the highest cancer incidence and mortality in the United States. High‐risk populations such as this are often underrepresented in clinical trials. The study aims to do a comprehensive analysis of molecular landscape of metastatic cancers among these patients with detailed evaluation of factors affecting response and outcomes to immune checkpoint inhibitor (ICI) therapy. We performed a retrospective analysis of metastatic solid tumor patients who received ICI and underwent molecular profiling at our institution.Sixty nine patients with metastatic solid tumors who received ICI were included in the study. Prevalence of smoking and secondhand tobacco exposure was 78.3% and 14.5%, respectively. TP53 (62.3%), CDKN1B/2A (40.5%), NOTCH and PIK3 (33.3%) were the most common alterations in tumors. 67.4% were PDL1 positive and 59.4% had intermediate‐high tumor mutational burden (TMB). Median TMB (12.6) was twofold to fourfold compared to clinical trials. The prevalence of mutations associated with smoking, homologous recombinant repair and PIK3/AKT/mTOR pathway mutations was higher compared to historic cohorts.PDL1 expression had no significant effect on radiologic response, but PFS improvement in patients with tumors expressing PDL1 trended toward statistical significance (median 18 vs. 40 weeks. HR = 1.43. 95%CI 0.93, 4.46). Median PFS was higher in the high‐TMB cohort compared to low‐intermediate TMB (median not reached vs. 26 weeks; HR = 0.37. 95%CI 0.13, 1.05). A statistically significant improvement in PFS was observed in the PIK3 mutated cohort (median 123 vs. 23 weeks. HR = 2.51. 95%CI 1.23, 5.14). This was independent of tumor mutational burden (TMB) status or PDL1 expression status. PIK3 mutants had a higher overall response rate than the wild type (69.6% vs. 43.5%, OR 0.34; p = 0.045). The results should prompt further evaluation of these potential biomarkers and more widespread real‐world data publications which might help determine biomarkers that could benefit specific populations.

A retrospective evaluation of clinicalopathologic characteristics and prognostic factors for synchronous bilateral breast cancer in a single center

Objective: To investigate the clinicopathologic features of synchronous bilateral breast cancer (SBBC) and prognostic factors. Methods: The clinicopathologic features of patients with SBBC treated in Peking University First Hospital from January 2008 to March 2019 were retrospectively analyzed. Results: Of all 4 111 patients diagnosed with breast cancer, 57(1.4%) cases were diagnosed with SBBC.Forty-three (75.4%) patients were treated with bilateral mastectomy. The median follow-up time was 58 months. The 5-year disease-free survival of SBBC was 80.7% and 5-year overall survival was 84.1%. The N stage and HER2 status of second primary breast cancer were associated with prognosis by univariated analysis (Z=5.866 and 4.231, both P<0.05). Conclusion: Majority of patients with SBBC were treated with bilateral mastectomy. While therapeutic strategy of SBBC should take both tumor burden and biomarker status of bilateral breast cancer into consideration.

Genotype-Phenotype Correlation in Fibrous Dysplasia/McCune-Albright Syndrome

Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) is a rare bone and endocrine disorder resulting in fractures, pain, and disability. There are no targeted or effective therapies to alter the disease course. Disease arises from somatic gain-of-function variants at the R201 codon in GNAS, replacing arginine by either cysteine or histidine. The relative pathogenicity of these variants is not fully understood. This work aimed 1) to determine whether the most common GNAS variants (R201C and R201H) are associated with a specific clinical phenotype, and 2) to determine the prevalence of the most common GNAS variants in a large patient cohort. This retrospective cross-sectional analysis measured the correlation between genotype and phenotype characterized by clinical, biochemical, and radiographic data. Sixty-one individuals were genotyped using DNA extracted from tissue or circulating cell-free DNA. Twenty-two patients (36.1%) had the R201C variant, and 39 (63.9%) had the R201H variant. FD skeletal disease burden, hypophosphatemia prevalence, fracture incidence, and ambulation status were similar between the 2 groups. There was no difference in the prevalence of endocrinopathies, ultrasonographic gonadal or thyroid abnormalities, or pancreatic involvement. There was a nonsignificant association of cancer with the R201H variant. There is no clear genotype-phenotype correlation in patients with the most common FD/MAS pathogenic variants. The predominance of the R201H variant observed in our cohort and reported in the literature indicates it is likely responsible for a larger burden of disease in the overall population of patients with FD/MAS, which may have important implications for the future development of targeted therapies.

Phase 1b Study of Sintilimab Plus Anlotinib as First-line Therapy in Patients With Advanced NSCLC

IntroductionAlthough the interaction between tumor immune microenvironment and angiogenesis has been well established, evidence supporting the chemo-free combination of immune checkpoint inhibitors plus antiangiogenic tyrosine kinase inhibitors in treatment-naive patients with advanced NSCLC is insufficient. This report provides the efficacy and safety of sintilimab combined with anlotinib as first-line therapy for advanced NSCLC from a phase 1b trial (NCT03628521). MethodsEligible patients who were treatment-naive and had unresectable stage IIIB/C or IV NSCLC without EGFR/ALK/ROS1 mutations received sintilimab (200 mg, day 1) and anlotinib (12 mg, day 1–14) every 3 weeks till disease progression or unacceptable toxicity. Baseline programmed death-ligand 1 expression and tumor mutation burden status was assessed in all patients. The primary end points were objective response rate and safety. ResultsA total of 22 patients received sintilimab and anlotinib. Median follow-up was 15.8 months (range: 8.3–19.3). Sixteen patients achieved confirmed partial response with an objective response rate of 72.7% (95% confidence interval [CI]: 49.8%–89.3%) and disease control rate of 100% (95% CI: 84.6%–100%). Median progression-free survival was 15 months (95% CI: 8.3 m, not reached), and the 12-month progression-free survival rate was 71.4% (95% CI: 47.2%–86.0%). The incidence rate of grade 3 or higher treatment-related adverse events was 54.5%, and grade 3 hypertension was predominant (two of 22, 9.1%). No grade 4 treatment-related adverse events were observed, and one case of grade 5 immune-related pneumonitis occurred. ConclusionsTo the best of our knowledge, this is the first study that assessed an anti–programmed cell death protein 1 antibody combined with a multitarget antiangiogenic tyrosine kinase inhibitor in the frontline setting for patients with NSCLC. In view of its encouraging efficacy, durability, and safety profile, sintilimab plus anlotinib represents a novel chemotherapy-free regimen in this patient population.

First-Line Nivolumab Plus Ipilimumab Versus Chemotherapy in Advanced NSCLC With 1% or Greater Tumor PD-L1 Expression: Patient-Reported Outcomes From CheckMate 227 Part 1

IntroductionIn CheckMate 227 (NCT02477826), patients with treatment-naive stage IV or recurrent NSCLC and 1% or greater tumor programmed death ligand 1 expression had significantly improved overall survival with nivolumab plus ipilimumab versus chemotherapy. We present the patient-reported outcomes (PROs). MethodsPatients (N = 1189) were randomized to nivolumab plus ipilimumab, nivolumab, or chemotherapy. PROs were exploratory. Changes in Lung Cancer Symptom Scale (LCSS) average symptom burden index, LCSS 3-item global index, EQ-5D visual analog scale (VAS), and EQ-5D utility index were analyzed descriptively. Mixed-effect model repeated measures and time-to-first deterioration and improvement analyses were conducted. ResultsPRO completion rates were generally greater than 80%. On-treatment improvements from baseline in LCSS measures of symptom burden and global health status with nivolumab plus ipilimumab generally met or exceeded the minimal important difference (smallest clinically meaningful change) from weeks 24 and 30, respectively; improvements with chemotherapy generally remained below the minimal important difference. Mean on-treatment EQ-5D VAS scores for both treatments approached the U.K. population norm at week 24, remaining so throughout the treatment period. Mixed-effect model repeated measures analyses revealed numerically greater improvements from baseline with nivolumab plus ipilimumab versus chemotherapy across LCSS average symptom burden index and 3-item global index, and EQ-5D VAS and utility index. Nivolumab plus ipilimumab had delayed time-to-first deterioration (hazard ratio [95% confidence interval] 0.74 [0.56 to 0.98]) and a trend for more rapid time-to-first improvement (1.24 [0.98 to 1.59]) versus chemotherapy. ConclusionsNivolumab plus ipilimumab revealed delayed deterioration and numerical improvement in symptoms and health-related quality of life versus chemotherapy in patients with advanced NSCLC and 1% or greater programmed death ligand 1 expression.

Genomic profiling of gastrointestinal cancers by comprehensive tumor-normal sequencing.

109 Background: Gastrointestinal cancers (GIC) account for 26% of global cancer incidence and 35% of cancer-related deaths. We investigated the molecular landscape and therapeutic targets across 18 types of GIC using whole exome (WES) and whole transcriptome sequencing (WTS). Methods: GEM ExTra assay was performed on 603 paired samples (ages 18-90 years, median = 61 years). Targeted sequence coverage was 180X for germline DNA and 400X for tumor DNA. Reportable somatic alterations included single base substitutions, indels, Copy Number Alterations, gene fusions, alternate transcripts, as well as tumor mutational burden (TMB) and microsatellite instability (MSI) status. Germline subtraction identified somatic-specific alterations. Results: Analysis of 603 GIC patient samples, including esophageal, gastric cancer (GC), biliary tract (BT), pancreatic cancer (PC), colorectal cancer (CRC), and other cancers, identified 434 actionable targets. The median number of alterations was 3 per GIC patient. The 5 most common actionable alterations were in APC, KRAS, CDKN2A, ARID1A and PIK3CA. Activation of Wnt signaling was found in 264/603 (44%), with the majority being in CRC cases. Alterations in cell cycle genes including CDKN2A, CDK4/6 and others were noted in 129/603 (21%) cases, with the majority in PC, suggesting benefit from CDK4/6 inhibitors. Activation of PI3K/PTEN/Akt/mTOR pathway was noted in 105/603 (17%), with the majority harbored in CRC, suggesting benefit from targeting this pathway. ERBB2 amplification and mutations were noted in 22/603 (4%) across different GIC tumor types. Alterations in homologous recombination genes predicting platinum and PARP inhibitor response was noted in 181/603 (30%) samples distributed across GIC subtypes. KRAS (G12C) mutation was found in 7% of all KRAS mutations across GIC subtypes, thus allowing patients to enroll in clinical trials with G12C-specific inhibitors. The majority of cases with MSI- and TMB-high status were identified in GC and CRC tumors and may be predictive of response to immunotherapy. WTS identified actionable fusions, including FGFR1/2/3 and novel NRG1 fusions in BT cancers. Conclusions: Our study revealed actionable targets used in patient selection for precision therapies, in addition to other mutational profiles of clinical significance. Overall, comprehensive genomic profiling enabled detection of established and novel actionable alterations, including fusions, which may have gone undetected using hotspot panels.

Current situation and trend of cardiovascular disease burden in China from a global perspective

&lt;p&gt;&lt;strong&gt;Objective&lt;/strong&gt;: Based on the global burden of disease (GBD) 2019 study, to analyze the epidemic trend and risk factors of cardiovascular disease (CVD) in China by comparing the world, the United States, Japan and India. Methods data were obtained from the global health data exchange (ghdx) database. The prevalence, morbidity, mortality, disability adjusted life year (DALY) and other disease burden status and main risk factors of CVD in China were analyzed by sex and age; the age standardized rate was used to compare the change trend of CVD disease burden in China, the United States, Japan and India from 1990 to 2019. &lt;strong&gt;Results&lt;/strong&gt;: In 2019, the number of CVD patients in China was 12 billion, with 123.41 million new cases and 458.43 million deaths; the prevalence, incidence rate, mortality and Daly rates increased from 423,543/100,000, 44,781/100,000, 20,475/100,000 and 509,103/100,000 in 1990 to 84,608/100,000, 86,765/100,000, 32,230/100,000 and 646,347/100,000 in 2019 respectively. The prevalence, incidence rate, mortality and Daly rate increased with age, and the burden of CVD in men was higher than that in women. In addition, the top 4 risk factors for CVD in China in 2019 are hypertension, diet, air pollution and tobacco, which lead to higher CVD disease burden than the global average. &lt;strong&gt;Conclusion&lt;/strong&gt;: due to hypertension, dietary factors, air pollution, tobacco and other reasons, coupled with the rapid aging of the population, the disease burden of CVD in China is still very serious, which needs to be paid attention to by relevant departments.&lt;/p&gt;

Treatment of Large Hepatocellular Carcinoma using Transarterial Chemoembolisation Combined with Sorafenib

Introduction: Hepatocellular Carcinoma (HCC) is the most common primary malignant tumour of liver, accounts for 90% of all primary hepatic tumours, with second most common cause for cancer-related deaths worldwide. Majority of HCC presents in Barcelona Clinic Liver Cancer (BCLC) intermediate stage (B), for which Transarterial Chemoembolisation (TACE) is the most commonly available treatment . Even though overall prognosis of these locally advanced tumours is poor, significant improvement can still be made in overall survival and recurrence free survival with locoregional therapy like TACE. Aim: To assess the efficiency, safety and limitations of TACE in large HCC with specific focus on importance of appropriate patient selection. Materials and Methods: The study was conducted on 30 histopathologically proven cases of HCC with BCLC intermediate stage. All cases underwent TACE followed by repeat TACE or treated with sorafenib depending on their response and clinical status. Treatment-related complications, treatment response, recurrence free survival was assessed. Results: Of the 30 cases, six cases had lesion size less than 5 cm, six cases with lesion size 5-10 cm and remaining 18 cases had lesion size more than 10 cm, with the largest lesion being 16 cm. Twenty-one cases had elevated Alfa Fetoprotein (AFP), chronic liver disease was seen in 10 cases, with five cases having at least two lesions. Total 50% of cases with lesion less than 5 cm showed complete response at 15 months, four of six cases with lesion size of 5-10 cm showed partial response at 15 months, other two cases were lost for follow-up. Cases with lesion size more than 10 cm showed mixed response, at 15 months follow-up, 10 cases showed stable response, six cases showed progressive disease and two patients died due to liver dysfunction. Conclusion: Transarterial Chemoembolisation combined with sorafenib prolonged the overall survival in selected large tumours with high disease burden status.

Assessment of the dose burden and health status of the uranium processing workers of the Republic of Kazakhstan

The main objective of current study is to assess the dose burden and health status of workers at the uranium processing hydrometallurgical plant in order to develop measures aimed at reducing their incidence. This article presents the results of radiation monitoring and data on the health status of workers at the hydrometallurgical plant of the Stepnogorsk Mining and Chemical Combine (SMCC). The data of the accumulated effective dose for the entire length of service, as well as data on the incidence rate for the period 2013-2019, obtained from the base of the Industrial Radiation and Epidemiological Register, have been analyzed. Based on the results of measurements of the uranium content in urine, the expected effective dose of internal irradiation of the enterprise personnel was calculated. The assessment of the health status of workers was carried out based on the materials of outpatient and hospital visits, as well as the results of mandatory periodic medical examinations over the past 5 years. Based on the results, an excess of the expected effective dose of internal irradiation was revealed based on the analysis of a urine sample by 3 times. The most typical for the studied contingent of the main group turned out to be diseases of the eye and its adnexa (23%).

Aging With HIV: Inflammation Is Associated With Pain, Poorer Physical Function, and Frailty

With advances in antiretroviral therapies, people living with HIV have life expectancies similar to their HIV-negative peers. Yet, they experience elevated multi-morbidity that can compromise quality of life as they age. Links between inflammation and accelerated aging may inform interventions, but these links are understudied in older adults with HIV. We investigated cross-sectional relationships between inflammation, well-being, and geriatric syndromes among 161 HIV-positive older adults. Participants provided fasting blood samples (for serum cytokines and CRP) and completed surveys (MOS-HIV; falls) and cognitive (MoCA) and frailty assessments (using Fried criteria). Adjusted linear and logistic regression models tested relationships between inflammatory markers and age-related health outcomes, controlling for age, gender, BMI, race, comorbidity burden, statin use, and smoking status. 93% had suppressed viral load. 11% had CRP levels suggesting possible acute illness (>10 mg/L) and were excluded from analyses. Participants with higher IFN-γ reported greater pain (p=0.003), greater cognitive complaints (p=.02), and worse physical function (p=0.04), than those with lower IFN-γ. Similarly, higher IL-6 levels were related to worse physical function (p=0.01) and slightly greater cognitive complaints (p=0.06), but were not significantly related to pain in adjusted models. Compared to those with lower IL-6, those with higher IL-6 levels were more likely to be frail (p=0.04). CRP was not significantly related to these outcomes. Six-month fall history and objective cognitive scores were not significantly related to the assessed inflammatory markers. Our results illustrate key, expected links between inflammatory processes, frailty, physical function, and pain among older adults with HIV.

Determinants of Adherence to ADA Type II Diabetes Mellitus Guidelines: Implications for Longevity

The aim of this study was to identify the differences in terms of demographics, socioeconomic status and overall levels of morbidity-related health burden between population strata characterized by high levels of adherence to American Diabetes Association screening guidelines and their low-adherence counterparts. Factor analysis was used to create a single continuous measure of adherence which was stratified and analyzed using the Cox proportional hazards model to identify adherence levels associated with protective effects for mortality. Based on the results, the entire population of Health and Retirement Study respondents newly diagnosed with diabetes mellitus, type II was then stratified into four levels of adherence – excellent, sufficient, insufficient, poor – based on the strength of the protective effect associated with that level of the adherence factor and compared. Mortality in the group associated with excellent adherence was 41 to 57 percentage points lower than among their counterparts. High levels of adherence were associated with White and Hispanic race, low morbidity burden, high education and economic status, and low levels of functioning limitations. Based on race-specific survival function estimates we found that the life expectancy at age 65 of an individual newly diagnosed with type II diabetes mellitus could be improved from 14.97 to 19.64 years for whites, 13.36 to 19.58 years for African Americans and 14.92 to 21.28 for Hispanics if average adherence levels are increased to the highest levels observed in our study. Finally, we found that adherence levels were improving over the 1991-2015 period suggesting successful diabetes awareness efforts.