Wangbi granule as a combination therapy to achieve clinical deep remission in rheumatoid arthritis: protocol for a multicenter, triple-blind, randomised, placebo-controlled trial.

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that may lead to bone erosion and disability. Although there are many biological therapies in RA treatment nowadays, such as etanercept and tofacitinib, there are still a considerable number of patients who cannot achieve clinical deep remission, which makes patients feel pain and stiffness of joints. As a traditional Chinese medicine preparation, Wangbi granule showed a synergistic role with methotrexate in the treatment of RA patients with "kidney deficiency and dampness" or "stasis blocking channels". Therefore, it is a promising therapeutic strategy for the clinical deep remission of RA. In this study, Wangbi granule will be used as the test drug. The investigators conduct this study to evaluate the efficacy and safety of Wangbi granule in the treatment of patients who have not achieved deep remission despite the use of methotrexate and tofacitinib. METHODS AND ANALYSIS: Two parallel randomized, triple-blind, placebo-controlled trials will be conducted. In six study centers, 340 eligible RA patients will be recruited and randomly allocated to either the intervention group or the control group (in a 1:1 ratio). They will receive Wangbi granule or Wangbi placebo 12.0 g each time, three times a day for 12 weeks. The primary outcome is the disease activity score derivative for 28 joints (DAS28). Secondary outcomes are patient-reported outcomes, American College of Rheumatology 50% response criteria (ACR50), fatigue scale-14 (FS-14), visual analogue scale for pain (VAS), health assessment questionnaire disability index (HAQ-DI) and biomarkers such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). EXPECTED OUTCOMES: The success of this study will provide strong evidence to confirm the efficacy and safety of Wangbi granule in the treatment of RA. Trial registration The trial has been registered in the ClinicalTrials Registry (NCT05540938, Date: 09/15/2022, https://clinicaltrials.gov/ct2/show/NCT05540938 ).

HBx-related long non-coding RNA 01152 promotes cell proliferation and survival by IL-23 in hepatocellular carcinoma.

Accumulating evidence suggests that long-noncoding RNA (lncRNA) plays important roles in hepatitis B virus (HBV) infections. However, the mechanism underlying how lncRNA regulate hepatocellular carcinoma process remains largely unknown. In this study we found that the expression of LINC01152 was significantly increased in HBV positive HCC tissues and cells and was induced by HBx in vitro. The overexpression of LINC01152 could increases HCC cell proliferation and promotes tumor formation in nude mice. Mechanistically, HBx could increase the transcription of LINC01152. Elevated LINC01152 binds to the promoter region of IL-23, promoting its transcriptional activity and upregulating the levels of Stat3 and p-Stat3. Our findings suggest that LINC01152 plays an important role in HBV-related hepatocellular carcinoma development and may serve as a therapeutic marker for hepatocellular carcinoma.

Readmission Patterns After GI Cancer Hospitalizations: The Medical Versus Surgical Patient.

PURPOSE: Readmission within 30 days has been used as a metric for quality of care received at hospitals for certain diagnoses. In the era of accountability, value-based care, and increasing cancer costs, policymakers are looking into cancer readmissions as well. It is important to describe the readmission profile of patients with cancer in the most clinically relevant approach to inform policy and health care delivery that can positively impact patient outcomes. PATIENTS AND METHODS: We conducted a retrospective cohort study using linked Texas Cancer Registry and Medicare claims data. We included elderly Texas residents diagnosed with GI cancer and identified risk factors for unplanned readmission using generalized estimating equations, comparing medical with surgical cancer-related hospitalizations. RESULTS: We analyzed 69,693 hospitalizations from 31,736 patients. The unplanned readmission rate was higher after medical hospitalizations than after surgical hospitalizations (21.6% v 13.4%, respectively). Shared risk factors for readmission after medical and surgical hospitalizations included advanced disease stage, high comorbidity index, and emergency room visit and radiation therapy within 30 days before index hospitalization. Several other associated factors and reasons for readmission were noted to be unique to medical or surgical hospitalizations alone. CONCLUSION: Unplanned readmissions among elderly patients with GI cancer are more common after medical hospitalizations compared with surgical hospitalizations. There are shared risk factors and unique risk factors for these hospitalizations that can inform policy, health care delivery, and interventions to reduce readmissions. Other findings underscore the importance of care coordination and comorbidity management in this patient population.

Impact of Rheumatoid Arthritis on the Mortality of Elderly Patients Who Develop Cancer: A Population-Based Study.

OBJECTIVE: Comorbidity among cancer patients poses additional risks for mortality. The possible impact of rheumatoid arthritis (RA) on cancer patient survival is unclear. Our objective was to examine survival among elderly patients with RA who develop cancer. METHODS: Patients diagnosed with breast, prostate, colorectal, or lung cancer between 2001 and 2010 were identified from the Texas Cancer Registry and Medicare-linked databases. The cohort was categorized into 3 groups according to the number of claims patients had with a diagnosis of RA in the year prior to the cancer diagnosis: 2-RA (patients with ≥2 claims), 1-RA (1 claim), and no claims. Overall survival was estimated for these groups and for each cancer, using Cox proportional hazards models adjusting for covariates. RESULTS: The cohort included 139,097 patients with cancer (35,026 breast, 43,181 prostate, 31,103 colorectal, and 29,787 lung); 1.7% had 1 RA claim, and 1.1% had 2 or more. Adjusted hazard ratios for patients in the 2-RA group were 1.41 (95% confidence interval [95% CI] 1.21-1.65) for breast and 1.53 (95% CI 1.26-1.85) for prostate. No significant differences were observed for those with colorectal or lung cancer. CONCLUSION: Mortality was increased by 40% and 50%, respectively, in elderly patients with RA who developed breast or prostate cancer, after controlling for other comorbidities. This association was not seen in cancers with shorter survival time (colorectal or lung). Research is needed to determine whether the increased risk is related to comorbid burden or to differential utilization of cancer or rheumatoid therapies in patients with both diseases.

[Meta-analysis on causes of ulcerative colitis].

OBJECTIVE: To analyze the main influencing factor of ulcerative colitis (UC). METHODS: Literature retrieval was conducted by using English databases (PubMed, Cochrane and Embase) and Chinese databases (CNKI, Wanfang, SinoMed and VIP) to collect the studies on the influencing factors of UC published both at home and abroad from January 2000 to October 2014. According to the inclusion and exclusion criteria, data were extracted and methodological quality was assessed. Then, a Meta-analysis was performed with Stata 12.0 software. RESULTS: A total of 24 case-control studies were included, involving 5 653 patients and 20 218 controls. The results of Meta-analysis showed that the influencing factors of UC would include family history of inflammatory bowel disease, ex-smoker, gastrointestinal infections, regular consumption of milk, fat diet, appendectomy, smoking and high educational level, with the pooled OR values as 4.68 (95%CI:3.59-6.11) , 1.81 (95%CI: 1.58-2.09) , 5.10 (95%CI: 2.38-10.92) , 2.26 (95%CI: 1.65-3.09) , 2.21 (95%CI: 1.49-3.27) , 0.40 (95%CI:0.32-0.51) , 0.44 (95%CI:0.32-0.60) and 0.50 (95%CI:0.36-0.69) , respectively. CONCLUSION: Current evidence showed that the risk factors influencing the incidence of UC were family history of inflammatory bowel disease, ex-smoker, gastrointestinal infections, regular consumption of milk and fat diet, whereas appendectomy, smoking and high educational level were protective factors for UC.

Patterns and predictors of unplanned hospitalization in a population-based cohort of elderly patients with GI cancer.

PURPOSE: Hospitalizations among patients with cancer are common and costly and, if unplanned, may interrupt oncologic treatment. The rate of unplanned hospitalizations in the population of elderly patients with cancer is unknown. We sought to describe and quantify patterns and risk factors for early unplanned hospitalization among elderly patients with GI cancer. PATIENTS AND METHODS: We conducted a retrospective cohort study using linked Texas Cancer Registry and Medicare claims data from 2001 to 2009. Texas residents age 66 years or older initially diagnosed with GI cancer between 2001 and 2007 were included in the study. The unplanned hospitalization rate was estimated, and reasons for unplanned hospitalization were evaluated. Risk factors were identified using adjusted Cox proportional hazards modeling. RESULTS: Thirty thousand one hundred ninety-nine patients were included in our study, 59% of whom had one or more unplanned hospitalizations. Of 60,837 inpatient claims, 58% were unplanned. The rate of unplanned hospitalization was 93 events per 100 person-years. The most common reasons for unplanned hospitalization were fluid and electrolyte disorders, intestinal obstruction, and pneumonia. Multivariable analysis showed that black race; residing in census tracts with poverty levels greater than 13.3%; esophageal, gastric, and pancreatic cancer; advanced disease stage; high Charlson comorbidity index score; and dual eligibility for Medicare and Medicaid increased the risk for unplanned hospitalization (all P values < .05). CONCLUSION: Unplanned hospitalizations among elderly patients with GI cancer are common. Some of the top reasons for unplanned hospitalization are potentially preventable, suggesting that comorbidity management and close coordination among involved health care providers should be promoted.

Reliability and clinically important improvement thresholds for osteoarthritis pain and function scales: a multicenter study.

OBJECTIVE: To assess the reliability and clinically meaningful thresholds of intermittent and constant osteoarthritis pain (ICOAP) score, the Knee injury and Osteoarthritis Outcome Score Physical function Short-form (KOOS-PS), the Hip disability and Osteoarthritis Outcome Score Physical function Short-form (HOOS-PS), and the Quality of life subscales of HOOS/KOOS (HOOS-QOL/KOOS-QOL) in patients with knee or hip arthritis. METHODS: One hundred and ninety-five patients (141 knee, 54 hip) seen at 2 orthopedic outpatient clinics with a diagnosis of knee or hip OA completed patient-reported questionnaires (ICOAP pain scale, KOOS-PS, HOOS-PS, KOOS-QOL, HOOS-QOL) at baseline and 2-week followup. Reliability was assessed using intraclass correlation coefficients (ICC). We calculated minimum clinically important difference (MCID) and moderate improvement in the subgroup that reported change in the status of their affected joint. RESULTS: The reliability as assessed by ICC was as follows: ICOAP pain scale, 0.63 (0.48, 0.74) in patients with knee arthritis, and 0.86 (0.73, 0.93) for hip arthritis; KOOS-PS, 0.66 (0.52, 0.77); HOOS-PS, 0.82 (0.66, 0.91); KOOS-QOL, 0.79 (0.69, 0.86); and HOOS-QOL, 0.67 (0.42, 0.83). MCID and moderate improvement estimates in patients with knee arthritis were ICOAP pain scale, 18.5 and 26.7; KOOS-PS, 2.2 and 15.0; and KOOS-QOL, 8.0 and 15.6. A smaller sample in patients with hip arthritis precluded MCID and moderate improvement estimates. CONCLUSION: We found that ICOAP pain and KOOS-PS/HOOS-PS scales were reasonably reliable in patients with hip OA. Reliability of these scales was much lower in patients with knee arthritis. Thresholds for clinically meaningful change in pain or function on these scales were estimated for patients with knee arthritis.

Low rates of bone mineral density measurement in Medicare beneficiaries with prostate cancer initiating androgen deprivation therapy.

BACKGROUND: Men with prostate cancer who undergo androgen deprivation therapy (ADT) are at risk for bone loss and fractures. Our objective was to determine if Medicare beneficiaries with prostate cancer in the state of Texas underwent DXA scans when initiating ADT. METHODS: We identified men diagnosed with prostate cancer between 2005 and 2007 in the Texas Cancer Registry/Medicare linked database, and who received parenteral ADT or orchiectomy. We identified DXA claims within 1 year before or 6 months after starting ADT. We examined use of bone conservation agents in the subgroup of patients enrolled in Medicare Part D. Multivariate logistic regression models were used to examine determinants of DXA use. RESULTS: The analysis included 2,290 men (2,262 parenteral ADT, 28 orchiectomy); 197 (8.6 %) underwent DXA within 1 year before and 6 months after starting ADT. Men aged 75 years or older were more likely to undergo DXA than men aged 66-74 years (OR 1.5; 95 % CI 1.1-2.1). Those living in small urban areas were less likely to undergo DXA than those in big areas (OR 0.40; 95 % CI 0.19-0.82). Of the 1,060 men enrolled in Medicare part D, 59 (5.6 %) received bone conservation agents when starting ADT; 134 (12.6 %) either received bone conservation agents or underwent DXA. CONCLUSIONS: Fewer than one in ten Medicare beneficiaries with prostate cancer initiating ADT underwent a DXA exam. Variation in utilization was also related to residence area size. Further research is needed to identify whether the use of DXA in patients with prostate cancer receiving ADT will result in fracture prevention.

Association of potentially inappropriate medication use with patient and prescriber characteristics in Medicare Part D.

PURPOSE: The use of potentially inappropriate medications (PIMs) in older people is associated with increased risk of adverse drug events and hospitalization. This study aimed to determine the contribution of primary prescribers to variation in PIM use. METHODS: This was a retrospective cohort study using 2008 Medicare Part D event files and claims data for a 100% sample of Texas beneficiaries. PIM use was defined as receiving any of 48 medications on the Beers 2003 list of PIMs. Patient characteristics associated with PIM use were determined using a multivariable model. A multilevel model for the odds of PIM use was constructed to evaluate the amount of variation in PIM use at the level of primary care prescriber, controlling for patient characteristics. RESULTS: Of 677,580 patients receiving prescriptions through Part D in 2008, 31.9% received a PIM. Sex, ethnicity, low-income subsidy eligibility, and hospitalization in 2007 were associated with PIM use. The strongest associations with higher PIM use were increasing number of prescribers and increasing number of medications. The odds ratio for PIM use was 1.50 (95%CI 1.47-1.53) for ≥4 prescribers versus only 1 prescriber. In the multilevel model, the adjusted average percent of patients prescribed a PIM ranged from 17.5% for the lowest decile to 28.9% for the highest decile of prescribers. CONCLUSIONS: PIM use was prevalent in Part D beneficiaries and varied among individual primary care prescribers. The association of PIM use with increasing numbers of prescribers suggests the need to reduce fragmentation of care to reduce inappropriate prescribing.

Ethnic disparities in adherence to antihypertensive medications of medicare part D beneficiaries.

OBJECTIVES: To determine the level of adherence to medications and characteristics of Part D beneficiaries associated with higher levels of antihypertensive medication adherence. DESIGN: Retrospective cohort study. SETTING: Medicare claims and Part D event files. PARTICIPANTS: Medicare Part D enrollees with prevalent uncomplicated hypertension who filled at least one antihypertensive prescription in 2006 and two prescriptions in 2007. MEASUREMENTS: Medication adherence was defined as an average medication possession ratio of 80% or greater. Potential factors associated with adherence evaluated were age, sex, race or ethnicity, socioeconomic factors, comorbidity, medication use, copayments, being in the coverage gap, and number of unique prescribers. RESULTS: Overall adherence was 79.5% of 168,522 Medicare Part D enrollees with prevalent uncomplicated hypertension receiving antihypertensive medicines in 2007. In univariate analysis, adherence varied significantly according to most patient factors. In multivariable analysis, lower odds of adherence persisted for blacks (odds ratio (OR) = 0.53, 95% confidence interval (CI) = 0.51-0.55), Hispanics (OR = 0.58, 95% CI = 0.55-0.61), and other non-white races (OR = 0.80 95% CI = 0.75-0.85) than for whites. Greater comorbidity and concurrent medication use were also associated with poorer adherence. Adherence was significantly different across several geographic regions. CONCLUSION: A number of associations were identified between patient factors and adherence to antihypertensive drugs, with significant differences in adherence according to ethnicity. Improving adherence could have significant public health implications and could improve outcomes specific to hypertension, as well as improving cost and healthcare utilization.

Molecular genetic analysis of partial 9p trisomy in two Chinese families with mental retardation and facial anomaly.

Mental retardation is defined by significant limitations in intellectual function and adaptive behavior that occur before 18 years of age. Many chromosomal diseases come with mental retardation. We reported two Chinese families with partial trisomy 9p and other chromosome partial monosomy, clinical features of mental retardation and mild facial and pinkie anomalies. In the family 1, we showed that the proband carried a trisomy 9p21.3→pter and monosomy 21q22.3→qter by using fluorescence in situ hybridization analysis. Molecular genetic analysis defined the precise breakpoint on chromosome 9p between markers D9S1846 and D9S171, an interval of about 2.9 Mb on 9p21.3, and the breakpoint on chromosome 21q between markers D21S1897 and D21S1446, a region of about 1.5 Mb on 21q22.3. In the family 2, a patient with trisomy 9p21.3→pter and monosomy 5p15.33→pter, and a de novo maternal balanced translocation between chromosomes 5 and 9 was identified in his mother. Cytogenetic and molecular genetic analysis defined the precise breakpoints on chromosome 9p21.3 and chromosome 5p15.33. Further clinical investigation found that any individual had no refractoriness eczema disease except the proband in this family. These results further implicate that trisomy 9p is associated with mental retardation, and that there may be key gene duplication on chromosome 9p21.3→9pter responsible for mental retardation and mild facial anomaly. This result has been applied successfully in prenatal diagnosis of the second family.

Molecular Genetic Analysis of Partial 9p Trisomy in Two Chinese Families with Mental Retardation and Facial Anomaly / 华中科技大学学报（医学）（英德文版）

Mental retardation is defined by significant limitations in intellectual function and adaptive behavior that occur before 18 years of age.Many chromosomal diseases come with mental retardation.We reported two Chinese families with partial trisomy 9p and other chromosome partial monosomy,clinical features of mental retardation and mild facial and pinkie anomalies.In the family 1,we showed that the proband carried a trisomy 9p21.3→pter and monosomy 21q22.3→qter by using fluorescence in situ hybridization analysis.Molecular genetic analysis defined the precise breakpoint on chromosome 9p between markers D9S1846 and D9S171,an interval of about 2.9 Mb on 9p21.3,and the breakpoint on chromosome 21q between markers D21S1897 and D21S1446,a region of about 1.5 Mb on 21q22.3.In the family 2,a patient with trisomy 9p21.3→pter and monosomy 5p15.33→pter,and a de novo maternal balanced translocation between chromosomes 5 and 9 was identified in his mother.Cytogenetic and molecular genetic analysis defined the precise breakpoints on chromosome 9p21.3 and chromosome 5p15.33.Further clinical investigation found that any individual had no refractoriness eczema disease except the proband in this family.These results further implicate that trisomy 9p is associated with mental retardation,and that there may be key gene duplication on chromosome 9p21.3→9pter responsible for mental retardation and mild facial anomaly.This result has been applied successfully in prenatal diagnosis of the second family.

Predictors of anticoagulation in hospice patients with lung cancer.

BACKGROUND: Guidelines recommend lifelong anticoagulation in patients with cancer and a history of thromboembolism, but the use of anticoagulation in hospice has not been described. A retrospective study of medication data was conducted to determine patterns of anticoagulant use and predictors of type of anticoagulant prescribed for hospice patients with lung cancer. METHODS: Medication data were evaluated for 16,896 hospice patients with lung cancer in 2006 to determine patient and hospice characteristics that predicted anticoagulant prescription. Independent predictors of warfarin versus low molecular weight heparin (LMWH) prescription were identified using a logistic regression model. RESULTS: One of every 11 patients was prescribed an anticoagulant, most commonly warfarin. Compared with patients prescribed LMWH, patients prescribed warfarin were older (71.6 vs 65.8 years, P<.001), were more likely white (81.2% vs 74.3%, P = .03), had a longer stay in hospice (median 21 days vs 17 days, P = .001), and were more likely to have ≥3 comorbid illnesses (37.5% vs 25.0%, P<.001). The strongest independent predictor of type of anticoagulant prescribed was geographic region, with hospices in the Northeast more likely to prescribe LMWH. CONCLUSIONS: Anticoagulant use is prevalent in patients with lung cancer enrolled in hospice. This study highlights the need to understand the benefits and risks of anticoagulation at the end of life.

[Cytogenetic analysis of partial trisomy 9p resulting from a reciprocal balanced 9/21 translocation].

In this study, a four-generation Chinese family in Nanyang, Henan Province was identified with partial trisomy 9p syndrome. Of the 23 family members studied, six were characterized with mental retardation and mild facial and little finger anomalies. All affected family members demonstrated significant intrafamilial homogeneous phenotype except concomitance epilepsy in proband. On the basis of G-banding, the proband showed a translocation between chromosomes of 9p and 21q and partial 9p trisomy. The karyotype was 46, XY, der (21) t (9; 21) (9p22.2; 21q22.3) pat. Further karyotyping of other affected members and their patients in this family revealed translocation of chromosomes of 9p and 21q, with partial 9p trisomy in all affected members. The partial 9p trisomy was the direct result of abnormal segregation of a balanced translocation cell between chromosome 9 and 21 in one of the parents. The extra distal half of the short arm of chromosome, 9pter-->9p21, is responsible for the major clinical features such as mental retardation and mild facial anomaly. The cause of epilepsy in proband was discussed.

The role of the surgeon in whether patients with lymph node-positive colon cancer see a medical oncologist.

BACKGROUND: Chemotherapy improves survival for patients with stage III colon cancer, but some older patients with lymph node-positive colon cancer do not see a medical oncologist and, thus, do not receive adjuvant chemotherapy. METHODS: To evaluate the role of the surgeon in determining referrals to medical oncology among patients with stage III colon cancer, the authors conducted a retrospective cohort study of 6158 patients aged >or=66 years who were diagnosed with stage III colon cancer from 1992 through 1999 by using the Surveillance, Epidemiology, and End Results-Medicare linked database. Multilevel analysis was used to simultaneously model variations in patients' seeing a medical oncologist at the patient and surgeon levels. RESULTS: Twenty-one percent of the total variance in seeing a medical oncologist was attributable to the surgeon after adjusting for available patient, tumor, and surgeon characteristics. The individual surgeon characteristics that significantly predicted whether the patient saw a medical oncologist were year since graduation (20 years; hazard ratio [HR], 1.60; 95% confidence interval [95% CI], 1.19-2.16), practicing in a teaching hospital (yes vs. no: HR; 1.30; 95% CI, 1.07-1.58), and volume of patients with colon cancer (<30 patients vs >or=121 patients; HR, 0.66; 95% CI, 0.46-0.94). Surgeon sex, race, board certification, and type of practice were not independent predictors of medical oncology referral. CONCLUSIONS: Surgeons accounted for approximately 20% of the variation in patients seeing a medical oncologist. Interventions at the level of the surgeon may be appropriate to improve the care of patients with colon cancer.

Referral to medical oncology: a crucial step in the treatment of older patients with stage III colon cancer.

PURPOSE: Adjuvant chemotherapy for stage III colon cancer produces a substantial survival benefit, but many older patients do not receive chemotherapy. This study examines factors associated with medical oncology consultation and evaluates the impact of such consultation on chemotherapy use. PATIENTS AND METHODS: We used the Surveillance Epidemiology and End Results-Medicare linked database and identified 7,569 patients, aged 66-99, with stage III colon cancer diagnosed from 1992-1999. Modified Poisson regression was used to assess the relative risk for seeing a medical oncologist and for receiving chemotherapy as a function of individual characteristics. RESULTS: 78.08% of patients saw a medical oncologist within 6 months of diagnosis. Patients who were female, white, married, had low comorbidity scores, were diagnosed in more recent years, or had four or more positive lymph nodes were more likely to see a medical oncologist. Patients seeing a medical oncologist were 10 times more likely to receive chemotherapy (odds ratio, 9.98; 95% confidence interval, 8.21-12.14), after controlling for demographic and tumor characteristics. Chemotherapy use increased over time, but was substantially lower among older, black, and unmarried patients. CONCLUSIONS: Referral to medical oncology is one of the most important factors associated with receipt of chemotherapy among older patients with stage III colon cancer. Comorbidity decreases the likelihood of receiving chemotherapy, but its effect is the same for those who see a medical oncologist and all patients combined. Ensuring that high-risk patients are referred to medical oncology is a crucial step in quality care for patients with colon cancer.