Long-term trends in incidence, mortality and burden of liver cancer due to specific etiologies in Hubei Province.

Liver cancer, a chronic non-communicable disease, represents a serious public health problem. Long-term trends in the burden of liver cancer disease are heterogeneous across regions. Incidence and mortality of liver cancer, based on the Global Burden of Disease, were collected from the Chinese Centre for Disease Control and Prevention. Age-period-cohort model was utilized to reveal the secular trends and estimate the age, period and cohort effects on primary liver cancer due to specific etiologies. Both the age-standardized incidence and mortality rate of liver cancer in Hubei province were on the rise, although there were discrepancies between gender groups. From age-period-cohort analysis, both incidence and mortality of liver cancer due to Hepatitis B virus were the highest in all age groups. The incidence of all liver cancer groups increased with time period in males, while this upward trend was observed in females only in liver cancer due to alcohol use group. Cohort effects indicated the disease burden of liver cancer decreased with birth cohorts. Local drifts showed that the incidence of liver cancer due to specific etiologies was increasing in the age group of males between 40 and 75 years old. The impact of an aging population will continue in Hubei Province. the disease burden of liver cancer will continue to increase, and personalized prevention policies must be adopted to address these changes.

A Dataset on the Dynamic Monitoring of Health and Family Planning of China's Internal Migrants: A Multi-Wave Large-Scale, National Cross-Sectional Survey from 2009 to 2018.

This data article presents data from the China Migrants Dynamic Survey (CMDS), a multi-wave, large-scale national cross-sectional survey of China's internal migrants from 2009 to 2018. The CMDS is an annual questionnaire survey conducted by the former National Health and Family Planning Commission (NHFPC) of the People's Republic of China. The respondents included in this survey are internal migrants over 15 years old. The sample was drawn from the China Migrant Population Information System, using multi-stage stratified sampling method and the probability proportional-to-size (PPS) cluster sampling strategy. Between 2009 and 2018, there were 1,527,650 internal migrants from 23 provinces, 5 autonomous regions and 4 municipalities participated in the surveys. The survey tools were a series of self-designed questionnaires with high inheritance and consistency designed and implemented by the NHFPC. The questionnaires mainly contain basic information of the respondents and their family members, migration status, healthcare or health behaviors, public health service utilization, social insurance, social integration, and family planning. The dataset is currently the most widely used survey data on China's internal migrants, offering information on migration patterns, healthcare and health behaviors, use of public health services, access to social security, social integration, and family planning, which are valuable for health planning, health decision-making, and health equity research.

The Effect of Animation-Guided Mindfulness Meditation on the Promotion of Creativity, Flow and Affect.

Creativity is so important for social and technological development that people are eager to find an easy way to enhance it. Previous studies have shown that mindfulness has significant effects on positive affect (PA), working memory capacity, cognitive flexibility and many other aspects, which are the key to promoting creativity. However, there are few studies on the relationship between mindfulness and creativity. The mechanism between mindfulness and creativity is still uncertain. Meditation is an important method of mindfulness training, but for most people who do not have the basic training, it's difficult to master how to get into a state of mindfulness. Animation has been shown by many studies to help improve cognition and is often used as a guiding tool. Using animation as the guiding carrier of meditation is more convenient and easier to accept. Therefore, this study adopted the intervention method of animation-guided meditation, aiming to explore: (1) the effect of animation-guided meditation on enhancing creativity; (2) the role of flow and emotion in the influence of mindfulness on creativity. We advertised recruitment through the internal network of a creative industrial park, and the final 95 eligible participants were divided into two groups: animation (n = 48) and audio (n = 47) guided meditation. The animation group was given an animated meditation intervention, and the audio group was given an audio meditation intervention, both interventions were performed 3 times a week and last for 8 weeks. Results: (1) Animation-guided meditation significantly increased participants' mindfulness and creativity levels; Significantly reduced their cognitive load compared to audio-guided meditation. (2) Mindfulness has a significant direct effect on creativity, and significant indirect effects on creativity; Flow and PA act as the mediating variable. Conclusion: (1) Mindfulness, flow, and PA all helped to improve the subjects' work creativity. In addition to the direct positive impact of mindfulness on creativity, mindfulness can also have an indirect positive impact on creativity through flow and PA. (2) Compared with audio, animation can significantly reduce cognitive load and help improve users' cognitive ability, which is more suitable for the guidance materials of mindfulness meditation to enhance the effect of meditation.

Real-world persistence, adherence, health care resource utilization, and costs in people with type 2 diabetes switching from a first-generation basal insulin to a second-generation (insulin glargine 300 U/mL) vs an alternative first-generation basal insulin.

BACKGROUND: People with type 2 diabetes (T2D) who change their basal insulin (BI) may have variable persistence with therapy. Compared with first-generation (long-acting) BI analogs (insulin glargine 100U/mL [Gla-100]; insulin detemir [IDet]), second-generation (longer-acting) BI analogs (insulin glargine 300U/mL [Gla-300]; insulin degludec) have similar glycated hemoglobin (HbA1c) attainment and lowered hypoglycemia risk, which could impact treatment persistence. OBJECTIVE: To compare persistence, adherence, health care resource utilization (HRU), and costs for individuals switching from neutral protamine Hagedorn insulin or a first-generation BI analog with either the second-generation BI, Gla-300, or an alternative first-generation BI analog (Gla-100 or IDet). METHODS: We used Optum Clinformatics claims data from adults (aged ≥ 18 years) with T2D who had received BI (neutral protamine Hagedorn, Gla-100, IDet) in the 6-month baseline period, and switched to either Gla-300 or an alternative first-generation BI (Gla-100 or IDet; treatment switch = index date) between April 1, 2015, and August 31, 2019. Participants were followed for 12 months, until plan disenrollment, or until death, whichever occurred first. Cohorts were propensity score matched (PSM) on baseline characteristics. The primary outcome was the proportion who were persistent with therapy at 12 months. Secondary outcomes were adherence (proportion of days covered); change in HbA1c; and all-cause, diabetes-related, and hypoglycemia-related HRU and costs. RESULTS: PSM generated 3,077 participants/group (mean age: 68 years, 52% female). Cohorts were well balanced except for hospitalization, which was adjusted in models as a covariate. During the 12-month follow-up period, participants who received Gla-300 vs first-generation BI had greater persistence with (45.5% vs 42.1%; adjusted P = 0.0001), and adherence to (42.8% vs 38.2%; adjusted P = 0.0006), BI therapy and a statistically larger reduction in HbA1c at 12 months (-0.65% vs -0.45%; adjusted P = 0.0040). The proportion of participants achieving HbA1c less than 8% (47.2% vs 40.9%; P < 0.0001), but not less than 7% (21.2% vs 20.8%), was significantly higher for Gla-300 vs first-generation BI. All-cause (45.3 vs 65.9 per 100 patient-years [P100PY]) and diabetes-related (21.5 vs 29.1 P100PY), but not hypoglycemia-related, hospitalizations (1.0 vs 1.5 P100PY) were significantly (P < 0.0001) lower for Gla-300 vs first-generation BI. Similarly, all-cause (111.9 vs 148.8 P100PY), diabetes-related (54.8 vs 74.2 P100PY), and hypoglycemia-related (2.9 vs 5.7 P100PY) emergency department (ED) visits were significantly lower for Gla-300 (all P < 0.0001). Costs for all-cause hospitalizations and hypoglycemia-related ED visits were significantly lower for Gla-300 vs first-generation BI. Although pharmacy costs were significantly higher for Gla-300 vs first-generation BI, all-cause total health care costs were not significantly different: $41,255 vs $45,316 per person per year, respectively. CONCLUSIONS: In this claims-based analysis of people with T2D receiving BI, switching to Gla-300 was associated with significantly better persistence, adherence, and HbA1c reduction compared with switching to an alternative first-generation BI analog. All-cause HRU was significantly lower; despite significantly higher pharmacy costs, total health care costs were similar. DISCLOSURES: This study was funded by Sanofi US. Medical writing support was provided by Helen Jones, PhD, CMPP, of Evidence Scientific Solutions and funded by Sanofi US. Dr Wright is on the speakers' bureau and sits on the advisory boards for Abbot Diabetes, Bayer, Boehringer Ingelheim, Eli Lilly, and Sanofi; sits on the advisory board for Medtronic; and is a consultant for Abbot Diabetes, Bayer, Boehringer Ingelheim, and Eli Lilly. Dr Malone is on advisory boards for Novartis and Avalere and consults for Pear Therapeutics, Sarepta, and Strategic Therapeutics. Dr Trujillo sits on advisory boards for Novo Nordisk and Sanofi. Drs Gill, Zhou, and Preblick and Mr Li are employees and stockholders of Sanofi. Mr Huse is an employee of Evidera and a contractor for Sanofi. Dr Reid is a speaker and consultant for Novo Nordisk and Sanofi-Aventis and is a consultant for AstraZeneca and Intarcia.

Assessment of the feasibility of frozen sections for the detection of spread through air spaces (STAS) in pulmonary adenocarcinoma.

Spread through air spaces (STAS) is reportedly associated with worse prognosis in sublobar resections of lung adenocarcinoma. Recently, it was proposed that STAS detected on frozen sections can be an indication for lobectomy instead of sublobar resection. We undertook this study to evaluate the reliability of STAS assessment on frozen sections compared to permanent sections, as well as the associations among STAS, tumor grade, and recurrence-free survival (RFS) after sublobar resection. A total of 163 stage I lung adenocarcinoma resections with frozen sections were identified retrospectively. For each case, and for frozen and permanent sections separately, the presence or absence of STAS, as well as the tumor grade, were recorded. Compared to permanent sections, STAS detection on frozen sections had low sensitivity (55%), low positive predictive value (48%), and fair agreement (K = 0.34), whereas there was higher specificity (80%) and negative predictive value (85%). Accuracy was 74%. Tumor grade assessment on frozen sections showed higher sensitivity (77%), positive predictive value (90%), agreement (K = 0.72), specificity (94%), and accuracy (87%), and the same negative predictive value (85%). High-grade histology on frozen sections was associated with shorter RFS (p = 0.02), whereas STAS on frozen sections was not (p = 0.47). Our results suggest that the intraoperative detection of STAS has low sensitivity and positive predictive value. False-positive results may lead to overtreatment of patients with lung cancer. The determination of tumor grade on frozen sections offers better sensitivity and specificity, plus it is associated with RFS, whereas STAS on frozen sections is not. Further study is needed to explore the utility of assessing tumor grade on frozen sections.

Performance assessment of different machine learning approaches in predicting diabetic ketoacidosis in adults with type 1 diabetes using electronic health records data.

PURPOSE: To assess the performance of different machine learning (ML) approaches in identifying risk factors for diabetic ketoacidosis (DKA) and predicting DKA. METHODS: This study applied flexible ML (XGBoost, distributed random forest [DRF] and feedforward network) and conventional ML approaches (logistic regression and least absolute shrinkage and selection operator [LASSO]) to 3400 DKA cases and 11 780 controls nested in adults with type 1 diabetes identified from Optum® de-identified Electronic Health Record dataset (2007-2018). Area under the curve (AUC), accuracy, sensitivity and specificity were computed using fivefold cross validation, and their 95% confidence intervals (CI) were established using 1000 bootstrap samples. The importance of predictors was compared across these models. RESULTS: In the training set, XGBoost and feedforward network yielded higher AUC values (0.89 and 0.86, respectively) than logistic regression (0.83), LASSO (0.83) and DRF (0.81). However, the AUC values were similar (0.82) among these approaches in the test set (95% CI range, 0.80-0.84). While the accuracy values >0.8 and the specificity values >0.9 for all models, the sensitivity values were only 0.4. The differences in these metrics across these models were minimal in the test set. All approaches selected some known risk factors for DKA as the top 10 features. XGBoost and DRF included more laboratory measurements or vital signs compared with conventional ML approaches, while feedforward network included more social demographics. CONCLUSIONS: In our empirical study, all ML approaches demonstrated similar performance, and identified overlapping, but different, top 10 predictors. The difference in selected top predictors needs further research.

Target-responsive subcellular catabolism analysis for early-stage antibody-drug conjugates screening and assessment.

Events including antibody‒antigen affinity, internalization, trafficking and lysosomal proteolysis combinatorially determine the efficiency of antibody-drug conjugate (ADC) catabolism and hence the toxicity. Nevertheless, an approach that conveniently identifies proteins requisite for payload release and the ensuing toxicity for mechanistic studies and quality assessment is lacking. Considering the plethora of ADC candidates under development, we developed a target-responsive subcellular catabolism (TARSC) approach that examines ADC catabolism and probes changes in response to targeted interferences of proteins of interest. We firstly applied TARSC to study the commercial T-DM1 and the biosimilar. We recorded unequivocal catabolic behaviors regardless of the absence and presence of the targeted interferences. Their negligible differences in TARSC profiles agreed with their undifferentiated anti-tumoral efficacy according to further in vitro viability and in vivo tumor growth assays, highlighting TARSC analysis as a useful tool for biosimilarity assessment and functional dissection of proteins requisite for ADC catabolism. Additionally, we employed TARSC to investigate the catabolic behavior of a new trastuzumab-toxin conjugate. Collectively, TARSC can not only characterize ADC catabolism at (sub)cellular level but also comprehensively determine which protein targets affect payload release and therapeutic outcomes. Future use of TARSC is thus anticipated in early-stage screening, quality assessment and mechanistic investigations of ADCs.

MicroRNA-31-5p Exacerbates Lipopolysaccharide-Induced Acute Lung Injury via Inactivating Cab39/AMPKα Pathway.

Acute lung injury (ALI) and the subsequent acute respiratory distress syndrome remain devastating diseases with high mortality rates and poor prognoses among patients in intensive care units. The present study is aimed at investigating the role and underlying mechanisms of microRNA-31-5p (miR-31-5p) on lipopolysaccharide- (LPS-) induced ALI. Mice were pretreated with miR-31-5p agomir, antagomir, and their negative controls at indicated doses for 3 consecutive days, and then they received a single intratracheal injection of LPS (5 mg/kg) for 12 h to induce ALI. MH-S murine alveolar macrophage cell lines were cultured to further verify the role of miR-31-5p in vitro. For AMP-activated protein kinase α (AMPKα) and calcium-binding protein 39 (Cab39) inhibition, compound C or lentiviral vectors were used in vivo and in vitro. We observed an upregulation of miR-31-5p in lung tissue upon LPS injection. miR-31-5p antagomir alleviated, while miR-31-5p agomir exacerbated LPS-induced inflammation, oxidative damage, and pulmonary dysfunction in vivo and in vitro. Mechanistically, miR-31-5p antagomir activated AMPKα to exert the protective effects that were abrogated by AMPKα inhibition. Further studies revealed that Cab39 was required for AMPKα activation and pulmonary protection by miR-31-5p antagomir. We provide the evidence that endogenous miR-31-5p is a key pathogenic factor for inflammation and oxidative damage during LPS-induced ALI, which is related to Cab39-dependent inhibition of AMPKα.

Safety Assessment of Casting Workshop by Cloud Model and Cause and Effect-LOPA to Protect Employee Health.

Safety assessment of a casting workshop will provide a clearer understanding of the important safety level required for a foundry. The main purpose of this study was to construct a composite safety assessment method to protect employee health using the cloud model and cause and effect-Layer of Protection Analysis (LOPA). In this study, the weights of evaluation indicators were determined using the subjective analytic hierarchy process and objective entropy weight method respectively. Then, to obtain the preference coefficient of the integrated weight more precisely, a new algorithm was proposed based on the least square method. Next, the safety level of the casting workshop was presented based on the qualitative and quantitative analysis of the cloud model, which realized the uncertainty conversion between qualitative concepts and their corresponding quantitative values, as well as taking the fuzziness and randomness into account; the validity of cloud model evaluation was validated by grey relational analysis. In addition, cause and effect was used to proactively identify factors that may lead to accidents. LOPA was used to correlate corresponding safety measures to the identified risk factors. 6 causes and 19 sub-causes that may contribute to accidents were identified, and 18 potential remedies, or independent protection layers (IPLs), were described as ways to protect employee health in foundry operations. A mechanical manufacturing business in Hunan, China was considered as a case study to demonstrate the applicability and benefits of the proposed safety assessment approach.

Estimation of Annual Health Care Costs for Adults with Type 1 Diabetes in the United States.

BACKGROUND: Diabetes health care resource utilization (HCRU) studies tend to focus on patients with type 2 diabetes (T2D) or pool patients with T2D and type 1 diabetes (T1D). There is a paucity of recent data on the cost of treating patients with T1D in the United States. OBJECTIVES: To (a) estimate the per-patient per-year (PPPY) HCRU and costs, from a payer perspective, associated with treating U.S. adults with T1D and (b) compare these with the HCRU and costs for patients with T2D. METHODS: This retrospective cohort study used claims data from the Optum Clinformatics database between January 2015 and December 2017. Adults (aged ≥ 18 years) with a diagnosis of T1D were propensity score-matched to adults with T2D. Overall and nondiabetes-related HCRU and costs were assessed for T1D and T2D and compared between the 2 groups. RESULTS: Propensity scores were used to match 10,103 patient pairs from T1D and T2D cohorts (mean ages 54.4 and 56.9 years, respectively). In the T1D cohort, inpatient, emergency department (ED), outpatient, and prescription claims occurred in 14.0%, 17.3%, 85.5%, and 100% of patients, respectively, resulting in a mean total cost of U.S. $18,817 PPPY (diabetes-related = $11,002; nondiabetes-related = $7,816). The T1D cohort had significantly higher mean total costs than the T2D cohort ($18,817 vs. $14,148 PPPY; P < 0.001). When extrapolating these findings to a commercial health plan with 1 million covered lives, the estimated total direct medical costs of T1D would be $103.4 million. CONCLUSIONS: This study showed that the total annual cost of managing an adult with T1D is significantly higher than that of an adult with T2D. Nondiabetes costs accounted for 40% of the total per-patient cost, similar to patients with T2D, confirming that as patients with T1D live longer lives, they may also be at greater risk for cardiometabolic complications. DISCLOSURES: This study was funded by Sanofi U.S. and Lexicon Pharmaceuticals as part of a business partnership in a diabetes program at the time this study was conducted. Joish and Davies are employees and stockholders of Lexicon Pharmaceuticals. Zhou, Preblick, and Paranjape are employees and stockholders of Sanofi. Lin was a postdoctoral fellow at Sanofi through Rutgers University during this project. Deshpande provided consulting services through Communication Symmetry. Verma is an employee of Evidera, which was contracted by Sanofi for work on this study. Pettus is a consultant for Diasome, Insulet, Lexicon, Lilly, Mannkind, Novo Nordisk, Sanofi, and Senseonics.

Study protocol for a randomized controlled trial: Qiliqiangxin in heart failUre: assESsment of reduction in morTality (QUEST).

BACKGROUND: Qiliqiangxin (QLQX) capsule is a Traditional Chinese Medicine (TCM) that has been approved in China for the treatment of chronic heart failure (CHF). Our previous study showed with a background of standard HF treatment, QLQX capsules further reduced the levels of NT-proBNP and the incidence of composite cardiac events (CCEs) in CHF patients. This study aims to further assess the reduction in mortality when using QLQX compared with placebo for heart failure with reduced ejection fraction (HFrEF) patients. METHODS: This study is a randomized, double-blind, placebo-controlled, parallel-group, multi-center, event-driven clinical study of approximately 3080 patients for a targeted 620 events. Patients must have a diagnosis of heart failure for at least 3 months prior to screening. Patients will be randomized 1:1 to receive the placebo or QLQX in addition to their standard medications of CHF. The primary efficacy outcome event is a composite cardiovascular death and re-hospitalization due to the worsening of heart failure. DISCUSSION: The QUEST study is a randomized control study of TCM in chronic heart failure. It will determine the place of QLQX as an new treatment approach and provide additional and innovative information regarding TCM - and the specific used of QLQX in HFrEF. TRIAL REGISTRATION: The trial was registered at http://www.chictr.org.cn. ( Registration No.: ChiCTR1900021929); Date: 2019-03-16.

Assessment of Programmed Death-Ligand 1 (PD-L1) Immunohistochemical Expression on Cytology Specimens in Non-Small Cell Lung Carcinoma.

OBJECTIVES: To evaluate whether non-small cell lung carcinoma (NSCLC) cytology specimens are reliable for programmed death-ligand 1 (PD-L1) immunohistochemical (IHC) testing. METHODS: Fifty-two cell blocks (CBs) with corresponding surgical pathology PD-L1 IHC testing were stained with a Dako PD-L1 pharmDX antibody (clone-22C3). Tumor cellularity was recorded as <100 or ≥100 cells. PD-L1 IHC was scored by percentage of tumor cells staining (<1%, ≥1%-49%, ≥50%) and compared between matched cases. RESULTS: Substantial agreement (κ = 0.63; 95% CI, 0.53-0.73) was reached between matched CB and surgical cases in CBs with ≥100 tumor cells compared to CBs with <100 tumor cells (slight agreement, κ = 0.19; 95% CI, 0.04-0.35). Overall, there was 67% agreement among paired cases (35/52 cases, κ = 0.51; 95% CI, 0.42-0.60). CONCLUSIONS: CBs can be utilized for PD-L1 IHC testing, as illustrated by the 67% agreement between CB and surgical cases in our study. Disagreement is attributable to intratumoral heterogeneity and CB cellularity.

Comorbidity Type and Health Care Costs in Type 2 Diabetes: A Retrospective Claims Database Analysis.

INTRODUCTION: Previous studies suggest that the type and combination of comorbidities may impact diabetes care, but their cost implications are less clear. This study characterized how diabetes patients' health care utilization and costs may vary according to comorbidity type classified on the basis of the Piette and Kerr framework. METHODS: We conducted a retrospective observational study of privately insured US adults newly diagnosed with type 2 diabetes (n = 138,466) using the 2014-2016 Optum Clinformatics® Data Mart. Diabetes patients were classified into five mutually exclusive comorbidity groups: concordant only, discordant only, both concordant and discordant, any dominant, and none. We estimated average health care costs of each comorbidity group by using generalized linear models, adjusting for patient demographics, region, insurance type, and prior-year costs. RESULTS: Most type 2 diabetes patients had discordant conditions only (27%), dominant conditions (25%), or both concordant and discordant conditions (24%); 7% had concordant conditions only. In adjusted analyses, comorbidities were significantly associated with higher health care costs (p < 0.0001) and the magnitude of the association varied with comorbidity type. Diabetes patients with dominant comorbidities incurred substantially higher costs ($38,168) compared with individuals with both concordant and discordant conditions ($20,401), discordant conditions only ($9173), concordant conditions only ($9000), and no comorbidities ($3365). More than half of the total costs in our sample (53%) were attributable to 25% of diabetes patients who had dominant comorbidities. CONCLUSIONS: Diabetes patients with both concordant and discordant conditions and with clinically dominant conditions incurred substantially higher health costs than other diabetes patients. Our findings suggest that diabetes management programs must explicitly address concordant, discordant, and dominant conditions because patients may have distinctly different health care needs and utilization patterns depending on their comorbidity profiles. The Piette and Kerr framework may serve as a screening tool to identify high-need, high-cost diabetes patients and suggest targets for tailored interventions. FUNDING: Sanofi.

Real-world evidence concerning clinical and economic outcomes of switching to insulin glargine 300 units/mL vs other basal insulins in patients with type 2 diabetes using basal insulin.

This retrospective cohort study compared real-world clinical and healthcare-resource utilization (HCRU) data in patients with type 2 diabetes using basal insulin (BI) who switched to insulin glargine 300 units/mL (Gla-300) or another BI. Data from the Predictive Health Intelligence Environment database 12 months before (baseline) and 6 months after (follow-up) the switch date (index date, March 1, 2015 to May 31, 2016) included glycated haemoglobin A1c (HbA1c), hypoglycaemia, HCRU and associated costs. Baseline characteristics were balanced using propensity score matching. Change in HbA1c from baseline was similar in both matched cohorts (n = 1819 in each). Hypoglycaemia incidence and adjusted event rate were significantly lower with Gla-300. Patients switching to Gla-300 had a significantly lower incidence of HCRU related to hypoglycaemia. All-cause and diabetes-related hospitalization and emergency-department HCRU were also favourable for Gla-300. Lower HCRU translated to lower costs in patients using Gla-300. In this real-world study, switching to Gla-300 reduced the risk of hypoglycaemia in patients with type 2 diabetes when compared with those switching to another BI, resulting in less HCRU and potential savings of associated costs.

Relationship between treatment persistence and A1C trends among patients with type 2 diabetes newly initiating basal insulin.

This study examines the relationship between glycated haemoglobin (A1C) levels and treatment persistence with, or time to discontinuation of, basal insulin in patients with type 2 diabetes (T2D) newly initiating insulin. Claims data were extracted from the Optum Clinformatics database from January 2010 to June 2015. Adult patients with T2D initiating insulin glargine 100 U/mL (Gla-100) or insulin detemir (DET) with ≥1 A1C measurement during 12-month baseline and 18-month follow-up periods were included. Patients with a refill gap of >90 days were considered non-persistent; otherwise, patients were considered persistent with insulin. The main outcome was A1C, measured closest to the end of each quarter during the follow-up period. A total of 3993 of 109 934 patients met the inclusion criteria (43.0% persistent; 57.0% non-persistent). Persistent patients were older (54.7 vs 52.7 years; P < .001), were more likely to be male (59.4% vs 54.4%; P = .002), and had significantly lower mean unadjusted A1C values at 18 months (8.26% vs 8.60%; P < .001) and quarterly. Only 43.0% of adults initiating basal insulin persisted with treatment for 18 months, with earlier discontinuation associated with higher A1C.

Assessment of the use of immunosuppressants combined with cord blood for severe aplastic anemia.

BACKGROUND: The objective of this study was two-fold: 1) to investigate the changes of cytokines concentration in relation to severe aplastic anemia (SAA) when treated with immunosuppressants combined with cord blood (IS + CBI). and 2) to assess the curative effect of umbilical cord blood chimerism engraftment. METHODS: We selected 43 patients with SAA all treated with IS + CBI (newly diagnosed group). Among them, a total of 33 patients were treated effectively (effective group) while 10 cases were treated invalidly (invalid group). An additional 20 healthy individuals were selected as control (control group). The expression levels of IL-17, IL-22 and other cytokines in each group were detected by ELISA. The engraftment of cord blood stem cells was detected by using short tandem repeat-polymerase chain reaction (STR-PCR). RESULTS: 1. IL-17, IL-22 and other cytokines expressions in the newly diagnosed group were significantly higher than in the control group. 2. After six months, the levels in the effective group were significantly lower than pre-therapy levels (P < 0.05). The levels in the invalid group did not differ to those observed prior treatment. 3. After one and three months of treatment, a small amount of engraftment was found in the effective group. However, after six months, transplant rejection was observed in all patients. No effective engraftment was observed in the invalid group. CONCLUSION: 1) Th17 and Th22 producing cells in SAA patients significantly increased indicating a positive correlation between these biomarkers and the progression of SAA. 2) During the IS + CBI treatment the maintenance of a normal hematopoietic function depended on immunesup-pressants. Early umbilical cord blood chimerism engraftment may promote hematopoietic recovery.