Gene expression and immune infiltration analysis comparing lesioned and preserved subchondral bone in osteoarthritis.

Background: Osteoarthritis (OA) is a degenerative disease requiring additional research. This study compared gene expression and immune infiltration between lesioned and preserved subchondral bone. The results were validated using multiple tissue datasets and experiments. Methods: Differentially expressed genes (DEGs) between the lesioned and preserved tibial plateaus of OA patients were identified in the GSE51588 dataset. Moreover, functional annotation and protein-protein interaction (PPI) network analyses were performed on the lesioned and preserved sides to explore potential therapeutic targets in OA subchondral bones. In addition, multiple tissues were used to screen coexpressed genes, and the expression levels of identified candidate DEGs in OA were measured by quantitative real-time polymerase chain reaction. Finally, an immune infiltration analysis was conducted. Results: A total of 1,010 DEGs were identified, 423 upregulated and 587 downregulated. The biological process (BP) terms enriched in the upregulated genes included "skeletal system development", "sister chromatid cohesion", and "ossification". Pathways were enriched in "Wnt signaling pathway" and "proteoglycans in cancer". The BP terms enriched in the downregulated genes included "inflammatory response", "xenobiotic metabolic process", and "positive regulation of inflammatory response". The enriched pathways included "neuroactive ligand-receptor interaction" and "AMP-activated protein kinase signaling". JUN, tumor necrosis factor α, and interleukin-1ß were the hub genes in the PPI network. Collagen XI A1 and leucine-rich repeat-containing 15 were screened from multiple datasets and experimentally validated. Immune infiltration analyses showed fewer infiltrating adipocytes and endothelial cells in the lesioned versus preserved samples. Conclusion: Our findings provide valuable information for future studies on the pathogenic mechanism of OA and potential therapeutic and diagnostic targets.

Assessment of the glymphatic function in children with attention-deficit/hyperactivity disorder.

OBJECTIVES: Whether the alternation of the glymphatic system exists in neurodevelopmental disease still remains unclear. In this study, we investigated structural and functional changes in the glymphatic system in the treatment-naïve attention-deficit/hyperactivity disorder (ADHD) children by quantitatively measuring the Virchow-Robin spaces (VRS) volume and diffusion tensor image-analysis along the perivascular space (DTI-ALPS). METHODS: Forty-seven pediatric ADHD patients and 52 age- and gender-matched typically developing (TD) children were recruited in this prospective study. The VRS volume was calculated using a semi-automated approach in axial T2-weighted images. Diffusivities along the x-, y-, and z-axes in the projection, association, and subcortical neural fiber areas were measured. The ALPS index, a ratio that accentuated water diffusion along the perivascular space, was calculated. The Mann-Whitney U test was used to compare the quantitative parameters; Pearson's correlation was used to analyze the correlation with clinical symptoms. RESULTS: The cerebral VRS volume (mean, 15.514 mL vs. 11.702 mL) and the VRS volume ratio in the ADHD group were larger than those in the TD group (all p < 0.001). The diffusivity along the x-axis in association fiber area and ALPS index were significantly smaller in the ADHD group vs. TD group (mean, 1.40 vs.1.59, p < 0.05 after false discovery rate adjustment). Besides, the ALPS index was related to inattention symptoms of ADHD (r = - 0.323, p < 0.05). CONCLUSIONS: Our study suggests that the glymphatic system alternation may participate in the pathogenesis of ADHD, which may be a new research direction for exploring the mechanisms of psycho-behavioral developmental disorders. Moreover, the VRS volume and ALPS index could be used as the metrics for diagnosing ADHD. CLINICAL RELEVANCE STATEMENT: Considering the potential relevance of the glymphatic system for exploring the mechanisms of attention deficit/hyperactivity, the Virchow-Robin spaces volume and the analysis along the perivascular space index could be used as additional metrics for diagnosing the disorder. KEY POINTS: • Increased Virchow-Robin space volume and decreased analysis along the perivascular space index were found in the treatment-naïve attention-deficit/hyperactivity disorder children. • The results of this study indicate that the glymphatic system alternation may have a valuable role in the pathogenesis of attention-deficit/hyperactivity disorder. • The analysis along the perivascular space index is correlated with inattention symptoms of attention-deficit/hyperactivity disorder children.

Trends in the prevalence and treatment of comorbid depression among US adults with and without cancer, 2005-2020.

BACKGROUND: Understanding trend characteristics of depression among cancer survivors is essential for healthcare policies and planning. This study estimates longitudinal trends in the prevalence and treatment of depression among adults in the United States with and without cancer. METHODS: This cross-sectional study focused on adults aged 20 years or older based on nationally representative data from the National Health and Nutrition Examination Surveys 2005-2020. Weighted logistic regression model was established to assess association between depression and cancer status after adjusting various covariates potentially related to depression. RESULTS: Among the 37,283 participants (weighted mean age, 47.5; women, 50.9 %), 3648 (9.8 %) were diagnosed with cancer and 3343 (9.0 %) were screened positive for depression. The age-standardized prevalence of depression showed a U-shaped trend in cancer survivors, decreasing from 11.8 % (95 % confidence interval, 8.4 %-15.2 %) in 2005-2008 to 8.3 % (5.6 %-11.0 %) in 2013-2016, then increasing to 11.7 % (6.3 %-17.2 %) in 2017-2020. These trends varied by population subgroup. Among depressive patients with cancer, antidepressant use increased from 38.6 % (28.7 %-48.5 %) in 2005-2008 to 62.9 % (40.6 %-85.2 %) in 2017-2020, whereas mental health consultation increased slightly. LIMITATIONS: Using a screening questionnaire instead of diagnostic criteria to identify depression; small sample size of patients with cancer; and cross-sectional analysis without prospective outcomes. CONCLUSIONS: From 2005 to 2020, the depression disease burden in patients with cancer eased in 2009-2015, but deteriorated recently. A healthy lifestyle and reasonable treatment for depression, based on an objective examination of depression characteristics, would improve long-term cancer outcomes and quality of life.

A Novel and Robust Prognostic Model for Hepatocellular Carcinoma Based on Enhancer RNAs-Regulated Genes.

Evidence has demonstrated that enhancer RNAs (eRNAs) play a vital role in the progression and prognosis of cancers, but few studies have focused on the prognostic ability of eRNA-regulated genes (eRGs) for hepatocellular carcinoma (HCC). Using gene expression profiles of HCC patients from the TCGA-LIHC and eRNA expression profiles from the enhancer RNA in cancers (eRic) data portal, we developed a novel and robust prognostic signature composed of 10 eRGs based on Lasso-penalized Cox regression analysis. According to the signature, HCC patients were stratified into high- and low-risk groups, which have been shown to have significant differences in tumor immune microenvironment, immune checkpoints, HLA-related genes, DNA damage repair-related genes, Gene-set variation analysis (GSVA), and the lower half-maximal inhibitory concentration (IC50) of Sorafenib. The prognostic nomogram combining the signature, age, and TNM stage had good predictive ability in the training set (TCGA-LIHC) with the concordance index (C-index) of 0.73 and the AUCs for 1-, 3-, and 5-year OS of 0.82, 0.77, 0.74, respectively. In external validation set (GSE14520), the nomogram also performed well with the C-index of 0.71 and the AUCs for 1-, 3-, and 5-year OS of 0.74, 0.77, 0.74, respectively. In addition, an important eRG (AKR1C3) was validated using two HCC cell lines (Huh7 and MHCC-LM3) in vitro, and the results demonstrated the overexpression of AKR1C3 is related to cell proliferation, migration, and invasion in HCC. Altogether, our eRGs signature and nomogram can predict prognosis accurately and conveniently, facilitate individualized treatment, and improve prognosis for HCC patients.

Development and Validation of a Novel Prognostic Model for Lower-Grade Glioma Based on Enhancer RNA-Regulated Prognostic Genes.

Enhancer RNAs (eRNAs) are present specifically in tumors, where they affect the expression of eRNA-regulated genes (ERGs). Owing to this characteristic, ERGs were hypothesized to improve prognosis of overall survival in heterogeneous low-grade and intermediate-grade gliomas. This study aimed to construct and validate an ERG prognostic tool to facilitate clinical management, and offer more effective diagnostic and therapeutic biomarkers for glioma. Survival-related eRNAs were identified, and their ERGs were selected based on eRNA and target gene information. The ERG prognostic model was constructed and validated using internal and external validation cohorts. Finally, biological differences related to the ERG signature were analysed to explore the potential mechanisms influencing survival outcomes. Thirteen ERGs were identified and used to build an ERG risk signature, which included five super-enhancer RNA (seRNA)-regulated genes and five LGG-specific eRNA-regulated genes. The prognostic nomogram established based on combining the ERG score, age, and sex was evaluated by calibration curves, clinical utility, Harrell's concordance index (0.86; 95% CI: 0.83-0.90), and time-dependent receiver operator characteristic curves. We also explored potential immune-related mechanisms that might cause variation in survival. The established prognostic model displayed high validity and robustness. Several immune-related genes regulated by seRNAs or specific eRNAs were identified, indicating that these transcripts or their genes were potential targets for improving immunotherapeutic/therapeutic outcomes. The functions of an important specific eRNA-regulated gene (USP28) were validated in robust vitro experiments. In addition, the ERG risk signature was significantly associated with the immune microenvironment and other immune-related features.

Quantitative susceptibility mapping reveals brain iron deficiency in children with attention-deficit/hyperactivity disorder: a whole-brain analysis.

OBJECTIVES: To quantitatively measure and compare the whole-brain iron deposition between attention-deficit/hyperactivity disorder (ADHD) patients and typically developing (TD) children using the quantitative susceptibility mapping (QSM) technique. METHODS: This study was approved by the institutional review board of our institution (No. [2019]328). Fifty-one patients between 6 and 14 years with clinical diagnosis of ADHD and 51 age- and gender-paired TD children were enrolled. For each participant, the 3D T1 and multi-echo GRE sequence were performed to acquire the whole-brain data with 3.0-T MRI. The QSM maps were calculated using STISuite toolbox. After normalizing the QSM images to MNI space, the voxel-based analysis was used to compare the iron content between the two groups. Pearson's correlation test was used to assess the associations between the iron content and the score of the tablet-PC-based cancellation test, which was done to evaluate the attention concentration level. RESULTS: Iron deficiency was observed in several brain regions in children with ADHD, including bilateral striatums, anterior cingulum, olfactory gyrus, and right lingual gyri. In further correlation analysis, the left anterior cingulum was found to show positive correlation with the symptom severity (r = 0.326, p < 0.05). CONCLUSIONS: Our study demonstrated that the iron deficiency in several brain regions might be related with ADHD, which might be valuable for further studies. And QSM might have the potential efficacy in the auxiliary diagnosis of ADHD. KEY POINTS: • Iron deficiency was observed in several brain regions in children with ADHD, which include bilateral striatums, the critical regions in the dopaminergic transmitter system. • The iron content in the left ACG may have association with the symptom severity of ADHD. • QSM might have the potential efficacy in the auxiliary diagnosis of ADHD.

A Novel Prognostic Tool for Glioma Based on Enhancer RNA-Regulated Immune Genes.

Background: Gliomas are the most malignant tumors of the nervous system. Even though their survival outcome is closely affected by immune-related genes (IRGs) in the tumor microenvironment (TME), the corresponding regulatory mechanism remains poorly characterized. Methods: Specific enhancer RNAs (eRNAs) can be found in tumors, where they control downstream genes. The present study aimed to identify eRNA-regulated IRGs, evaluate their influence on the TME, and use them to construct a novel prognostic model for gliomas. Results: Thirteen target genes (ADCYAP1R1, BMP2, BMPR1A, CD4, DDX17, ELN, FGF13, MAPT, PDIA2, PSMB8, PTPN6, SEMA6C, and SSTR5) were identified and integrated into a comprehensive risk signature, which distinguished two risk subclasses. Discrepancies between these subclasses were compared to explore potential mechanisms attributed to eRNA-regulated genes, including immune cell infiltration, clinicopathological features, survival outcomes, and chemotherapeutic drug sensitivity. Furthermore, the risk signature was used to construct a prognostic tool that was evaluated by calibration curve, clinical utility, Harrell's concordance index (0.87; 95% CI: 0.84-0.90), and time-dependent receiver operator characteristic curves (AUCs: 0.93 and 0.89 at 3 and 5 years, respectively). The strong reliability and robustness of the established prognostic tool were validated in another independent cohort. Finally, potential subtypes were explored in patients with grade III tumors. Conclusion: Overall, eRNAs were associated with immune-related dysfunctions in the TME. Targeting of IRGs regulated by eRNAs could improve immunotherapeutic/therapeutic outcomes.

Construction of a disease-specific lncRNA-miRNA-mRNA regulatory network reveals potential regulatory axes and prognostic biomarkers for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a heterogeneous malignancy with a high incidence and poor prognosis. Exploration of the underlying mechanisms and effective prognostic indicators is conducive to clinical management and optimization of treatment. The RNA-seq and clinical phenotype data of HCC were retrieved from The Cancer Genome Atlas (TCGA), and differential expression analysis was performed. Then, a differential lncRNA-miRNA-mRNA regulatory network was constructed, and the key genes were further identified and validated. By integrating this network with the online tool-based ceRNA network, an HCC-specific ceRNA network was obtained, and lncRNA-miRNA-mRNA regulatory axes were extracted. RNAs associated with prognosis were further obtained, and multivariate Cox regression models were established to identify the prognostic signature and nomogram. As a result, 198 DElncRNAs, 120 DEmiRNAs, and 2827 DEmRNAs were identified, and 30 key genes identified from the differential network were enriched in four cancer-related pathways. Four HCC-specific lncRNA-miRNA-mRNA regulatory axes were extracted, and SNHG11, CRNDE, MYLK-AS1, E2F3, and CHEK1 were found to be related with HCC prognosis. Multivariate Cox regression analysis identified a prognostic signature, comprised of CRNDE, MYLK-AS1, and CHEK1, for overall survival (OS) of HCC. A nomogram comprising the prognostic signature and pathological stage was established and showed some net clinical benefits. The AUC of the prognostic signature and nomogram for 1-year, 3-year, and 5-year survival was 0.777 (0.657-0.865), 0.722 (0.640-0.848), and 0.630 (0.528-0.823), and 0.751 (0.664-0.870), 0.773 (0.707-0.849), and 0.734 (0.638-0.845), respectively. These results provided clues for the study of potential biomarkers and therapeutic targets for HCC. In addition, the obtained 30 key genes and 4 regulatory axes might also help elucidate the underlying mechanism of HCC.

Factors analysis on the use of key quality indicators for narrowing the gap of quality of care of breast cancer.

BACKGROUND: There are differences in the quality of care among breast cancer patients. Narrowing the quality differences could be achieved by increasing the utilization rate of indicators. Here we explored key indicators that can improve the quality of care and factors that may affect the use of these indicators. METHODS: A total of 3669 breast cancer patients were included in our retrospective study. We calculated patient quality-of-care composite score based on patient average method. Patients were divided into high- and low-quality groups according to the mean score. We obtained the indicators with large difference in utilization between the two groups. Multilevel logistic regression model was used to analyze the factors influencing quality of care and use of indicators. RESULTS: The mean composite score was 0.802, and the number of patients in the high- and low-quality groups were 1898 and 1771, respectively. Four indicators showed a difference in utilization between the two groups of over 40%. Histological grade, pathological stage, tumor size and insurance type were the factors affecting the quality of care. In single indicator evaluation, besides the above factors, age, patient income and number of comorbidities may also affect the use of these four indicators. Number of comorbidities may have opposite effects on the use of different indicators, as does pathological stage. CONCLUSIONS: Identifying key indicators for enhancing the quality-of-care of breast cancer patients and factors that affect the indicator adherence may provide guides for enhancing the utilization rate of these indicators in clinical practice.

[Genetic analysis and clinical features of a pedigree affected with hereditary coagulation factor â ¦ deficiency caused by compound heterozygotic mutations].

OBJECTIVE: To detect potential mutations of the coagulation factor Ⅶ (F7) gene in a pedigree affected with hereditary FⅦ deficiency and explore its molecular pathogenesis. METHODS: The FⅦ antigen (FⅦ:Ag) was analyzed by an enzyme-linked immunosorbent assay (ELISA) method. Prothrombin time (PT), FⅦ activity (FⅦ:C) and other coagulant parameters were quantified with an one-stage clotting assay. The F7 gene was amplified by PCR and sequenced. Mutational sites were confirmed by reverse sequencing. Impact of amino acid substitution was assessed using SIFT and PolyPhen-2 software. Structure of the mutant protein was analyzed using Swiss-pdb Viewer software based on the three-dimensional structure in the Protein Data Bank. RESULTS: The propositus had prolonged PT (36.3 s), with FⅦ:C and FⅦ:Ag significantly reduced to 2% and 44%, respectively. Her father, mother, younger sister and daughter had slightly prolonged PT and reduced FⅦ:C (86%-120%). The FⅦ:Ag of her father and younger sister were also reduced. DNA sequencing revealed that the propositus has carried compound heterozygous mutations (Lys341Glu and IVS6-1G>A) of the F7 gene. Her father and younger sister were heterozygous for the IVS6-1G>A mutation, while her mother and daughter were heterozygous for the Lys341Glu mutation. Bioinformatics analysis indicated that Lys341Glu mutation may affect the stability and function of the FⅦ protein. CONCLUSION: The Lys341Glu and IVS6-1G>A mutations probably underlie the reduced activity of FⅦ in this pedigree.

[Identification of compound heterozygous mutations of F11 gene in a pedigree affected with heriditary coagulation factor XI deficiency].

OBJECTIVE: To identify potential mutations of F11 gene in a pedigree affected with hereditary coagulation factor XI (FXI) deficiency and explore its molecular pathogenesis. METHODS: Prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), coagulation factor VIII activity (FVIIIC), coagulation factor IX activity (FIXC), coagulation factor XI activity (FXIC), coagulation factor XII activity (FXIIC) and lupus anticoagulation (LA) of the proband and eight family members were determined. FXI antigen (FXIAg) was determined by enzyme-linked immunosorbent assay (ELISA). For the proband, potential mutations in the exons, flanking introns and 5'-, 3'-untranslated regions of the F11 gene were screened by direct DNA sequencing. The results were confirmed by reverse sequencing. Suspected mutations were detected in other family members. ClustalX-2.1-win and four online bioinformatic tools (PolyPhen-2, PROVEAN, SIFT, and Mutation Taster) were used to study the conservation and possible impact of the mutations. The structure of the mutational sites was processed with Swiss-PdbViewer. RESULTS: The propositus had prolonged APTT (69.6 s), whose FXIC and FXIAg were reduced to 6.0% and 10.7%, respectively. Her mother, elder sister, one younger sister, little brother, daughter and son showed slightly prolonged APTT and moderate FXIC and FXIAg levels. Gene sequencing revealed that the propositus carried a heterozygous nonsense mutation c.738G>A (p.Trp228stop) in exon 7 and a heterozygous mutation c.1556G>C (p.Trp501Ser) in exon 13. Her mother, elder sister and daughter were heterozygous for the p.Trp228stop mutation, while one younger sister and little brother and son were heterozygous for p.Trp501Ser. Her husband and the youngest sister were of the wild type. Phylogenetic analysis suggested that Trp501 was highly conserved among all homologous species. The p.Trp501Ser was predicted to be "probably damaging","deleterious", "affect protein function" and "disease causing" corresponding to PolyPhen-2, PROVEAN, SIFT and Mutation Taster. Model analysis demonstrated that the non-polar Trp501 has two benzene rings, forming a hydrogen bond with Gln512 in the wild type. Once substituted by Ser501, the side chain may form another hydrogen bond with the benzene of His396. This may affect the normal space conformation and stability of FXI protein. CONCLUSION: The compound heterozygous mutations of the F11 gene probably accounted for the low FXI concentration in this pedigree.

A chemical biology screen identifies a vulnerability of neuroendocrine cancer cells to SQLE inhibition.

Aberrant metabolism of cancer cells is well appreciated, but the identification of cancer subsets with specific metabolic vulnerabilities remains challenging. We conducted a chemical biology screen and identified a subset of neuroendocrine tumors displaying a striking pattern of sensitivity to inhibition of the cholesterol biosynthetic pathway enzyme squalene epoxidase (SQLE). Using a variety of orthogonal approaches, we demonstrate that sensitivity to SQLE inhibition results not from cholesterol biosynthesis pathway inhibition, but rather surprisingly from the specific and toxic accumulation of the SQLE substrate, squalene. These findings highlight SQLE as a potential therapeutic target in a subset of neuroendocrine tumors, particularly small cell lung cancers.

Long-term effects of neoadjuvant radiotherapy, adjuvant radiotherapy, and chemotherapy-only on survival of locally advanced non-small cell lung Cancer undergoing surgery: a propensity-matched analysis.

BACKGROUND: The optimal timing of radiotherapy (RT) with respect to surgery remains controversial for locally advanced non-small cell lung cancer (LA NSCLC) undergoing surgery and the long-term effect of neoadjuvant RT, adjuvant RT, and chemotherapy-only on survival is unknown. METHODS: A retrospective study with Greedy 5 → 1 Digit propensity score matching technique was performed for locally advanced NSCLC patients identified from the Surveillance, Epidemiology, and End Results (SEER) database during 2004 to 2012. Kaplan-Meier and the log-rank test were conducted to compare NSCLC-specific survival. Cox proportional hazards multivariable regression was performed to assess the impact of different treatment regimens on cancer-specific mortality after adjustment for demographic factors, histology type, tumor grade, tumor size, nodal stage, and extent of resection. RESULTS: One thousand, two hundred and seventy-eight locally advanced NSCLC patients undergoing surgery were identified after propensity matching. Cox regression analyses showed the risk of cancer-specific mortality is not significantly different among neoadjuvant RT, adjuvant RT, and chemotherapy-only. Subgroup analyses showed that for patients with T1/2 & N2/3, the surgery plus chemotherapy-only group showed markedly higher mortality risk (HR = 1.42, 95%CI:1.10-1.83) than the neoadjuvant RT group. Other risk factors include older age, higher tumor grade, larger tumor size, and greater lymph node involvement. CONCLUSIONS: The findings of this study suggest that the benefit of additional neoadjuvant or adjuvant RT to chemotherapy may be linked to a proper selection of LA NSCLC patients who undergo surgery. The timing of radiotherapy should be decided on the premise of fully considering patients' condition and the quality of life after treatment.

The effect of low insurance reimbursement on quality of care for non-small cell lung cancer in China: a comprehensive study covering diagnosis, treatment, and outcomes.

BACKGROUND: The insurance reimbursement rate of medical cost affects the quality and quantity of health services provided in China. The nature of this relationship, however, has not been reliably described in the field of non-small cell lung cancer (NSCLC). The objective of the current study was to examine the impact of low reimbursement rates of medical costs on diagnosis, treatment and outcomes among patients with NSCLC. METHODS: We examined care of 2643 NSCLC patients and we divided the study cohort into a high reimbursement rate group and a low reimbursement rate group. The impact of reimbursement rates of medical costs on quality of care of NSCLC patients were examined using logistic regression and generalized linear models. RESULTS: Compared with patients insured with high reimbursement rate, patients insured through lower reimbursement rate programs were less likely to benefit from early detection and treatment services. Delayed detection was more common in low reimbursement group and they were less likely to be recommended for adjuvant chemotherapy, or to receive adjuvant chemotherapy and postoperative radiation therapy and they had lower odds to receipt chemotherapy response assessment. However, low reimbursement rate group had lower rate of in-hospital mortality and metastases. CONCLUSIONS: Low reimbursement rate mainly negatively influenced the diagnosis and treatment of NSCLC. Reducing the gap in reimbursement rate between the three health insurance schemes should be a focus of equalizing access to care and improving the level of medical compliance and finally improving quality of care of NSCLC.

Short- and long-term effects of clinical pathway on the quality of surgical non-small cell lung cancer care in China: an interrupted time series study.

OBJECTIVE: To examine the short- and long-term effect of clinical pathway for non-small cell lung cancer surgery on the length of stay, the compliance of quality indicators and risk-adjusted post-operative complication rate. DESIGN: A retrospective quasi-experimental study from June 2011 to October 2015. SETTING: A tertiary cancer hospital in China. PARTICIPANTS: Patients diagnosed as non-small cell lung cancer who underwent curative resection. INTERVENTION(S): Clinical pathway was implemented at January 2013. Hence, the study period was divided into three periods: pre-pathway, from June 2011 to December 2012; short-term period, from January 2013 to December 2013; long-term period, from January 2014 to October 2015. MAIN OUTCOME MEASURE(S): Three length of hospital stay indicators, four process performance indicators and one outcome indicator. RESULTS: ITS showed there was a significant decline of 2 days (P = 0.0421) for total length of stay and 2.23 days (P = 0.0199) for post-operative length of stay right after the implementation of clinical pathway. Short-term level changes were found in the compliance rate of required number of lymph node sampling (-8.08%, P = 0.0392), and risk-adjusted complication rate (9.02%, P = 0.0001). There were no statistically significant changes in other quality of care indicators. CONCLUSIONS: The clinical pathway had a positive impact on the length of stay but showed a transient negative effect on complication rate and the quality of lymph node sampling.

Marital status and survival in epithelial ovarian cancer patients: a SEER-based study.

Marital status has been proved to be correlated to the survival of patients in various cancer types, except for that in the large female population of epithelial ovarian cancer (EOC). In this study, we retrospectively extracted 10905 eligible EOC patients from the Surveillance, Epidemiology, and End Results (SEER) database in the period from 2004 to 2012. We categorized marital status as married, divorced/separated, widowed, and never married. Chi-square test was used to investigate the association between marital status and other variables. The Kaplan-Meier test was adopted to compare survival curves of different groups. Multivariate Cox regression analyses were conducted to estimate the effect of marital status on overall survival (OS) and epithelial ovarian cancer-specific survival (EOCSS). To explore how marital status affected patients diagnosed at the same stage, we further performed subgroup analyses according to TNM stage. The results showed that marital status was an independent predictor for OS and EOCSS. Subgroup analyses indicated that the relationship between marital status and prognosis varied according to different conditions. Widowed patients had poorer prognosis than the other groups in most conditions, while the never married group showed similar risk of mortality as the married ones.

The quality of invasive breast cancer care for low reimbursement rate patients: A retrospective study.

Though evidence-based treatments have been recommended for breast cancer, underuse of the treatments was still observed. To certain extent, patients' access to care, which can be enhanced by increasing the coverage of health insurance, could account for the current underuse in recommended care. This study aimed to examine the association between different proportions of reimbursement and quality of recommended breast cancer care, as well as length of hospital stay. In this retrospective study, 3669 patients diagnosed with invasive breast cancer between 1 June, 2011 and 30 June, 2013 were recruited. Seven quality indicators from preoperative diagnosis procedures to adjuvant therapy and one composite indicator were selected as dependent variables. Logistic regression and generalized linear models were used to explore the association between quality of care and length of hospital stay with different reimbursement rates. Compared with UEBMI (urban employment basic medical insurance), which represented high level reimbursement rate, patients with lower rates of reimbursement were less likely to receive core biopsy, HER-2 (human epidermal growth factor receptor-2) testing, BCS (breast conserving surgery), SLNB (sentinel lymph nodes biopsy), adjuvant therapy and hormonal treatment. No significant difference in preoperative length of hospital stay was observed among the three insurance schemes, however URBMI (urban resident basic medical insurance) insured patients stayed longer for total length of hospital stay. Significant disparities in utilization of evidence-based breast cancer care among patients with different proportions of reimbursement were observed. Patients with lower rate of reimbursement were less likely to receive recommended care. Our findings could provide important support for further healthcare reform and quality improvement in breast cancer care.

Development of quality indicators for non-small cell lung cancer care: a first step toward assessing and improving quality of cancer care in China.

BACKGROUND: Large gap exists between clinical practice and recommended care and large room exists for the improvement of care quality for non-small cell lung cancer (NSCLC) in China. Results of some studies have shown that assessment of care quality can help to make improvement and the development of quality indicators is deemed as the initial and most essential part. Yet there is no such an indicators system specifically suitable for Chinese health care system. The goal of the study is to set up a group of Chinese quality indicators for NSCLC care and make it the first step towards the improvement of NSCLC care quality in China. METHODS: We constructed a new indicator framework based on the characteristics of NSCLC care and the nature of Chinese health care system. Under the new framework, potential indicators were collected and a 3-round modified Delphi process was conducted by a national multi-disciplinary Expert Panel to develop a set of indicators until they reached the final consensus. RESULTS: A new indicator framework (structure, process, communication, management of symptoms or treatment toxicity and outcome) was developed. Seventy four indicators were extracted from guidelines and relevant literatures as potential indicators; 43 indicators plus 1 suggested indicator were remained after the discussion of Round 1; questionnaires of Round 2 were rated by Expert Panel and 19 indicators met the inclusion criteria and entered Round 3; 2 of the eliminated indicators in Round 2 were retrieved by the Expert Panel at the in-person meeting (Round 3). Therefore, 21 indicators got the final consensus of the Expert Panel. CONCLUSIONS: Guided by the new indicator structure, a set of indicators suitable for Chinese healthcare system was developed and can be utilized to measure and improve the care quality of non-small cell lung cancer.

Life years lost associated with diabetes: An individually matched cohort study using the U.S. National Health Interview Survey data.

AIM: Previous estimates of life-years lost to diabetes are highly inconsistent. This study provided the updated estimates of life-years lost to diabetes in the United States. METHODS: Each of a nationally representative sample of 21,829 adults with diabetes in the U.S. National Health Interview Survey 1997-2009 was individually matched to one without diabetes by age, sex, race, survey year, BMI, smoking status, pre-existing cardiovascular disease and pre-existing cancer. All-cause mortality from original surveys to 31 December 2011 and median survival ages were estimated for those with diabetes and their matched controls. RESULTS: Overall median survival age for adults with diabetes was 10.5years shorter than that for matched controls without diabetes. Estimated life-years lost associated with diabetes decreased with increasing age at diagnosis from 20.0years for those diagnosed before age 20years to no difference for those diagnosed after 80years. Hazard ratios for mortality decreased from 3.03 (95% CI: 2.41, 3.80) for those with diabetes diagnosed before 20years to 1.04 (95% CI: 0.78, 1.39) for those diagnosed after 80years. The estimate of life-years lost associated with diabetes was much higher among those with pre-existing cardiovascular disease (20.3years) than among those without cardiovascular disease (8.5years). CONCLUSIONS: The effect of diabetes on survival depends on age at first diagnosis of diabetes and the presence of pre-existing diseases. The life-years lost are higher for those with diabetes diagnosed at younger ages. This study provided the updated estimates of life-years lost associated with diabetes in the United States.