Changes of health-related quality of life after initiating basal insulin treatment among people with type 2 diabetes.

To assess the association between insulin regimens and health-related quality of life (HRQoL) after the introduction of basal insulin (BI) among people with type 2 diabetes in real-world clinical settings. 16,339 registered people with diabetes who had inadequate glycaemic control by oral agents initiated BI (either single BI or Basal-bolus) and completed a 6-month follow-up from 209 hospitals were included in the analyses. At the end of the follow-up, the switches of insulin regimens, change of HRQoL (EQ-5D-3L) and their associations were assessed. Initial insulin regimens of single BI and of basal-bolus (BI included Glargine, Detemir, and Neutral Protamine Hagedorn) accounted for 75.6% and 24.4%, respectively. At 6 months, regimens used were BI alone (65.2%), basal-bolus (10.4%), and premixed (6.4%), whereas 17.9% stopped all insulin therapy. The visual analogue scale score increased by 5.46 (P < .001), and the index value increased slightly by 0.02 (P < .001). Univariate analysis showed that people with diabetes taking basal-bolus regimen had the greatest improvement on HRQoL in all dimensions, especially in the reduction of the percentage of Pain/Discomfort (by 10.03%) and Anxiety/Depression (by 11.21%). In multivariable analysis, single BI or premixed insulin at 6 months was associated with more improvement of visual analogue scale score compared with stopping all insulin. Improved HRQoL was observed after initiating BI in people with type 2 diabetes . If the same achievement on HbA1c control can be guaranteed, single BI is preferred to other regimens from the viewpoint of HRQoL. Basal-bolus has the most significant potential to increase HRQoL, however, the people with diabetes characteristics differ from those initiating BI alone. Further longitudinal cohort study with a longer study period might be necessary to evaluate the certain effect.

Neoadjuvant Chemotherapy Compared with Surgery for Oesophageal Carcinoma: A Retrospective Study and Missing Evidence.

Background: Negative evidence for the use of neoadjuvant chemotherapy (NAC) to treat oesophageal squamous cell carcinoma (ESCC) has been reported in Western countries in the past century. However, in China, most ESCC patients underwent paclitaxel and platinum-based NAC without evidence from local RCTs. Empiricism or a lack of evidence does not necessarily mean that the evidence is negative. However, there was no way to compensate for the missing evidence. The only way to obtain evidence is by conducting a retrospective study using propensity score matching (PSM) to compare the effects of NAC and primary surgery on overall survival (OS) and disease-free survival (DFS) among ESCC patients in China, which is the country with the highest prevalence of ESCC patients. Methods: From January 1, 2015, to December 31, 2018, a total of 5443 patients with oesophageal cancer/oesophagogastric junction carcinoma who underwent oesophagectomy were retrospectively identified at Henan Cancer Hospital. After PSM, 826 patients were selected for the retrospective study and divided into the NAC and primary surgery groups. The median follow-up period was 54.08 months. Toxicity and tumour responses to NAC, intraoperative and postoperative outcomes, recurrence, DFS and OS were analysed. Results: The postoperative complication rates were not significantly different between the two groups. The 5-year DFS rates were 57.48% (95% CI, 52.05% to 62.53%) for the NAC group and 49.93% (95% CI, 44.56% to 55.05%) for the primary surgery group (P=0.0129). The 5-year OS rates were 62.95% (95% CI, 57.63% to 67.79%) for the NAC group and 56.29% (95% CI, 50.99% to 61.25%) for the primary surgery group (P=0.0397). Conclusion: Compared with primary surgery, NAC with paclitaxel and platinum-based chemotherapy and two-field extensive mediastinal lymphadenectomy might be associated with long-term survival benefits among ESCC patients.

Revealing Density Thresholds of Carbon Nanotube Cross-Links for Load Transfer: A Graph Theory Strategy.

We report that the load transfer in carbon nanotube (CNT) networks is determined by the cross-link density via three critical thresholds, namely, percolation, connection, and saturation, which divide the transfer into four different modes. Reminiscent of the connectivity problem in the graph theory, an individual path for the successive load transfer through the network is formed at the first threshold, then all CNTs are connected together by cross-links at the second one, and finally, the connections are gradually converted into tetrahedrons toward a rigidized connectivity until the third saturation threshold. The power-law distribution of the number of cross-links per CNT shows a preferential linking mechanism, i.e., that the CNTs with high cross-links are more attractive to form new cross-links than the CNTs with low cross-links, while repetitive cross-links could hardly improve the strength of CNT networks.

Effectiveness and safety of basal insulin therapy in type 2 diabetes mellitus patients with or without metformin observed in a national cohort in China.

BACKGROUND: Though many randomized control trials had examined the effectiveness and safety of taking insulin therapy with or without metformin, there are limited real-world data, especially among Chinese type 2 diabetes patients initiating basal insulin (BI) with uncontrolled hyperglycemia by oral agents. This study was designed to assess the effectiveness and safety of BI therapy combined with or without metformin in a real-world national cohort study. METHODS: Patients with type 2 diabetes mellitus who initiated BI treatment due to uncontrolled hyperglycemia (HbA1c≥7 %) by oral antidiabetic drugs (OADs) were recruited in Chinese real-world settings between 2011 and 2013. A total of 12,358 patients initiated BI without bolus insulin and completed a 6-month follow-up were selected as the study population and divided into BI with metformin or BI without metformin group based on whether metformin was simultaneously prescribed or not at baseline. Propensity score adjustment was used to balance baseline covariates between two groups. A sub-analysis was also conducted among 8,086 patients who kept baseline treatment regimen during the follow-up. Outcomes were HbA1c, hypoglycemia, weight gain and insulin dose in two groups. RESULTS: 53.6 % (6,621 out of 12,358) patients initiated BI therapy concomitant with metformin. After propensity score adjustment, multivariate regression analysis controlled with number of OADs, total insulin dose, physical activity and diet consumption showed that BI with metformin group had a slightly higher control rate of HbA1c <7.0 % (39.9 % vs. 36.4 %, P = 0.0011) at 6-month follow-up, and lower dose increment from baseline to 6-month (0.0064 vs. 0.0068 U/day/kg, P = 0.0035). The sub-analysis with patients remained at same BI therapy further showed that BI with metformin group had higher HbA1c control rate (47.9 % vs. 41.9 %, P = 0.0001), less weight gain (-0.12 vs. 0.15 kg P = 0.0013), and lower dose increment during 6-month follow-up (0.0033 vs. 0.0037 U/day/kg, P = 0.0073) when compared with BI without metformin group. CONCLUSIONS: In alliance with current guidelines, the real-world findings also support the insulin initiation together with metformin. Continuous patients' education and clinicians training are needed to improve the use of metformin when initiating BI treatment.

Associations Between Education Level and In-hospital Treatment and Outcomes Among Acute Coronary Syndrome in China.

BACKGROUND: Previous studies have shown an inverse relationship between education and clinical outcomes in coronary heart disease. Whether a similar association exists in patients presenting with suspected acute coronary syndromes (ACS) in China is unknown. METHODS: Clinical Pathways for Acute Coronary Syndromes - Phase 2 (CPACS-2) was a study to evaluate a quality improvement for ACS management in China which implemented in 75 hospitals between October 2007 and August 2010. All patients was divided into 6 groups by education level. We evaluated clinical managements and outcomes according to level of education. RESULTS: A total of 14350 patients were enrolled in current analysis. Patients with less education were older, had greater female representation and had a higher Killip class at admission. Compared to patients with lower education levels, more educated patients had a longer length of hospitalization (p for trend <0.001), greater likelihood of receiving appropriate coronary angiography (p for trend <0.001) and appropriate reperfusion therapy for ST-segment elevated myocardial infarction (STEMI) (p for trend <0.001) even after adjustment for differences in patient characteristics and comorbidities at presentation. Patients with less education were at higher risk of death, cardiac death and major adverse cardiovascular events but none of these differences remained statistically significant after adjustment for baseline characteristics. CONCLUSION: In China, less educated patients with ACS were less likely to receive appropriate coronary angiography and reperfusion therapy. Less educated patients were at higher risk for adverse clinical events; however this was explained by differences in baseline characteristics.

Association of renal insufficiency with treatments and outcomes in patients with acute coronary syndrome in China.

BACKGROUND: We aimed to analyze the association of estimated glomerular filtration rate (eGFR) levels of hospitalized patients with treatment decisions and clinical outcomes in Chinese patients with acute coronary syndrome (ACS). METHODS: This was a secondary analysis study from CPACS-2 Program which was a trial of a quality improvement intervention in China and recruited 15,141 patients from 75 hospitals between October 2007 and August 2010. All patients were divided into three groups by the eGFR level on admission. The primary outcomes were several key performance indicators (KPIs) reflecting the management of ACS and the secondary outcomes were clinical outcomes. RESULTS: A total of 14,437 ACS patients were enrolled in this analysis. Among patients with reduced eGFR levels, fewer patients received appropriate medical therapy (p for trend <0.001) and fewer high-risk patients received coronary angiography (p for trend <0.001) compared to patients with a normal eGFR. Furthermore, 436 cases of death, 357 cases of cardiac death, 686 cases of major adverse cardiovascular events, and 198 cases of major bleeding episodes were reported. Patients with a worse eGFR level had significantly higher rates of death (p for trend <0.001), cardiac death (p for trend <0.001), major adverse cardiovascular events (p for trend <0.001) and major bleeding episodes (p for trend <0.001). CONCLUSION: Among Chinese ACS patients, those with renal insufficiency have a lower percentage of adherence to guideline-recommended treatments and worse clinical prognosis. Renal insufficiency is an important factor affecting guideline implementation in Chinese ACS patients. CLINICAL TRIAL REGISTRATION: http://www.anzctr.org.au/default.aspx. Unique identifier: ACTRN12609000491268.

The effect of a multidisciplinary co-management program for the older hip fracture patients in Beijing: a "pre- and post-" retrospective study.

Hip fracture becomes a major public health issue with the growing aging population. This study evaluated a multidisciplinary co-management program for older hip fracture patients and found it significantly improved the best practice indicators. It provided preliminary evidence to support the use of such intervention in hip fracture management. PURPOSE/INTRODUCTION: Hip fracture leads to high morbidity and mortality in older people. A previous study found a significant disparity in hip fracture management in Beijing Jishuitan Hospital (JSTH) compared to best practice care in the United Kingdom (UK). Following this audit, JSTH launched a multidisciplinary co-management care plan for older hip fracture patients. This study aims to evaluate the effect of this program on the six standards recommended in the UK hip fracture best practice guidelines. METHODS: In this retrospective study, electronic medical record data were collected before and after the intervention. Eligible patients were aged ≥ 65 years, had X-ray confirmed hip fracture, and were admitted to JSTH within 30 days of injury. Patient demographic information, time from emergency department presentation to admission, time from admission to surgery, pressure ulcers, osteoporosis assessment, and falls prevention were collected. Multivariable logistic and median regression models were used for binary and continuous outcomes respectively. Segment regression was also performed for time-related outcomes. RESULTS: A total of 3540 eligible patients were identified. After the intervention, half of the patients who received co-management received surgery within 48 h of ward admission compared to 6.4% previously, 0.3% (vs 1.4%) developed pressure ulcers, and 76% (vs 19%) received osteoporosis assessment. No significant differences were observed in fall assessment rates. However, there was a higher rate of ward admission within 4 h of arrival in emergency for patients admitted pre-intervention (61% vs 34%). CONCLUSIONS: The introduction of the co-management model significantly reduced the time from admission to surgery and improved other practice outcomes. A multicenter randomized controlled trial is needed to evaluate the impact of this model on patient health outcomes.

Dose titration model and correlative factors analysis in Chinese patients with type-2 diabetes on basal insulin - results from an Observational Registry of Basal Insulin Treatment study.

INTRODUCTION: This study evaluates an insulin dose titration model and factors that impact insulin dose adjustment in Chinese adults with type-2 diabetes, who receive basal insulin in real-world settings. MATERIAL AND METHODS: A total of 19,894 patients from the ORBIT study were included. These patients were divided into four groups, according to the type of insulin dose adjustment: no insulin titration (group A), self-titration (group B), physician-led insulin titration (group C), and combined physician and patient-led insulin titration (group D). Data were collected and compared at baseline and after six months of treatment. RESULTS: A total of 12,865 patients completed the visits and were included in the analysis. Among these patients, 3187 (24.8%), 1971 (15.3%), 5165 (40.1%), and 2542 (19.8%) patients were included in groups A, B, C, and D, respectively. The multivariate logistic regression analysis revealed that the duration of diabetes, body mass index, microvascular complications, inpatient days, HbA1C level, and self-monitoring of blood glucose (SMBG) were positively correlated with insulin titration in group B, C, and D, compared with group A. The number of inpatient days and outpatient visits were positively correlated with dose adjustment for physician-led titration, while this was negatively correlated for self-titration. Self-titration encouraged by physicians and home blood glucose monitoring were positively correlated with self-titration and the combined physician and patient-led titration. CONCLUSIONS: High HbA1C level, SMBG, long disease duration, microvascular complications, and the encouragement of physicians while initiating insulin use prompt patients to perform dose adjustments in real-world settings.

Clinical characteristics of type 2 diabetes patients with discordance between HbA1c and fasting plasma glucose in the real world: An analysis of the ORBIT study.

BACKGROUND: We aimed to determine the clinical characteristics of type 2 diabetes patients on basal insulin therapy with inadequate glucose control due to discordance between glycated haemoglobin (HbA1c ) and fasting plasma glucose (FPG) in the real world. METHODS: This was a retrospective analysis of data from the ORBIT study in China. Clinical characteristics of patients with discordance between HbA1c and FPG at baseline and at the end of 6 months of follow-up were analysed using multinomial logistic regression in 4 study groups divided by HbA1c and FPG. RESULTS: Overall, of 6721 patients initiated on basal insulin, 853 achieved HbA1c  < 7% but FPG ≥ 7 mmol/L (group 2), while 997 had FPG < 7 mmol/L but HbA1c  ≥ 7% (group 3) at the end of follow-up. Patients in group 3 had a longer duration of type 2 diabetes compared with those in group 2 (7.22 ± 5.30 vs 6.00 ± 4.80 y, P < .05). Patients on glargine (32.90%) or detemir (36.88%) treatment accounted for a higher proportion of patients with both HbA1c and FPG controlled than those on neutral protamine Hagedorn therapy (23.45%; P < .05). Per the multinomial logistic analysis, higher frequency of self-monitoring of blood glucose (SMBG) and use of glargine or detemir therapy were significantly inversely associated with risk of discordance between HbA1c and FPG, while dose of insulin was a risk factor for discordance at the end of follow-up (all P < .05). CONCLUSIONS: Patients treated with insulin analogues (glargine or detemir), instead of neutral protamine Hagedorn, and with more frequent SMBG are more likely to exhibit concordance between HbA1c and FPG.

Observational Registry of Basal Insulin Treatment in Patients with Type 2 Diabetes in China: Safety and Hypoglycemia Predictors.

BACKGROUND: The Observational Registry of Basal Insulin Treatment (ORBIT) study evaluated the safety of basal insulin (BI) in real-world settings in China. METHODS: We analyzed 9002 patients with type 2 diabetes (T2D) inadequately controlled with oral hypoglycemic agents from 8 geographic regions and 2 hospital tiers in China who initiated and maintained BI treatment. Body weight and hypoglycemic episodes were recorded at baseline and 3 and 6 months. Serious adverse events (SAEs) were recorded at 3 and 6 months. RESULTS: Age, gender, inpatient/outpatient status, body mass index, glycated hemoglobin (HbA1c) at baseline and at the end of study, T2D duration, microvascular complications, BI type, combination with insulin secretagogues, self-monitoring of blood glucose frequency, and insulin dosage, all predicted hypoglycemia. BI use generally did not induce significant weight gain (0.02 kg); weight gain with insulin detemir (-0.30 kg) was less than that with neutral protamine Hagedorn (NPH) insulin (0.20 kg) or insulin glargine (0.05 kg). Overall, general hypoglycemia incidence (5.6% vs. 7.7%) and annual event rate (1.6 vs. 1.8) were similar before and after BI initiation, whereas a slight decrease was noted in severe hypoglycemia incidence (0.6%-0.3%) and frequency (0.05-0.03 events/patient-year). The general hypoglycemia rate was lowest with insulin glargine, whereas there was no significant difference in severe hypoglycemia among the three BI groups. Overall, 3.5% of patients had at least one SAE during the study. Most SAEs were found to be unrelated to BI treatment. CONCLUSIONS: Real-world BI use, particularly insulin detemir and glargine, was associated with only slight weight gain and low hypoglycemia risk in patients with T2D in China.

Comparative effectiveness and safety of different basal insulins in a real-world setting.

AIMS: To compare glucose control and safety of different basal insulin therapies (BI, including Insulin NPH, glargine and detemir) in real-world clinical settings based on a large-scale registry study. METHODS: In this multi-center 6-month prospective observational study, patients with type 2 diabetes (HbA1c ≥ 7%) who were uncontrolled by oral anti-diabetic drugs (OADs) and were willing to initiate BI therapy were enrolled from 209 hospitals within 8 regions of China. Type and dose of BI were at the physician's discretion and the patients' willingness. Interviews were conducted at 0 months (visit 1), 3 months (visit 2) and 6 months (visit 3). Outcomes included change in HbA1c, hypoglycemia rate and body weight from baseline at 6 months. RESULTS: A total of 16 341 and 9002 subjects were involved in Intention-To-Treat (ITT) and per-protocol (PP) analysis, respectively. After PS regression adjustment, ITT analysis showed that reduction in HbA1c in glargine (2.2% ± 2.1%) and detemir groups (2.2% ± 2.1%) was higher than that in the NPH group (2.0% ± 2.2%) (P < .01). The detemir group had the lowest weight gain (-0.1 ± 2.9 kg) compared with the glargine (+0.1 ± 3.0 kg) and NPH (+0.3 ± 3.1 kg) groups (P < .05). The glargine group had the lowest rate of minor hypoglycaemia, while there was no difference in severe hypoglycaemia among the 3 groups. The results observed in PP analyses were consistent with those in ITT analysis. CONCLUSION: In a real-world clinical setting in China, treatment with long-acting insulin analogues was associated with better glycaemic control, as well as less hypoglycaemia and weight gain than treatment with NPH insulin in type 2 diabetes patients. However, the clinical relevance of these observations must be interpreted with caution.

Observational Registry of Basal Insulin Treatment (ORBIT) in patients with type 2 diabetes uncontrolled with oral antihyperglycaemic drugs: Real-life use of basal insulin in China.

AIMS: To examine treatment patterns following basal insulin (BI) introduction in type 2 diabetes mellitus (T2DM) patients under real-world conditions across China. MATERIALS AND METHODS: Overall, 18 995 patients inadequately controlled (HbA1c ≥ 53 mmol/mol [7%]) with oral antihyperglycaemic drugs (OADs) and willing to receive BI treatment were registered at 209 hospitals and followed at baseline (visit 1), 3 months (visit 2) and 6 months (visit 3). Type of BI was initiated at physicians' discretion. RESULTS: Retention with BI therapy at 6 months was 75.6%. Use of long-acting BI predominated, with insulin glargine accounting for 71%, detemir 13% and Neutral Protamine Hagedorn (NPH) insulin 16%. Over 70% of long-acting users maintained the same initial BI at visit 3, while 40% of NPH users switched treatment and 24.4% of participants initiated BI with prandial insulin. The initial mean (± SD) dose of BI and total insulin was 0.18 ± 0.07 and 0.25 ± 0.19 IU/kg, respectively, with a mean increase of daily dose by 0.03 and 0.02 IU/kg after 6 months, respectively. Only 56.6% of insulin users reported dose titration at visit 3. Mean HbA1c was 81 mmol/mol (9.6%) at baseline and 57 mmol/mol (7.4%) at 6 months. The frequency of hypoglycaemia was 1.61 and 2.07 episodes/patient-year at baseline and 6 months, respectively. CONCLUSIONS: In real-world clinical settings, add-on BI therapy in T2DM patients is associated with significant improvement in glycaemic control without overtly compromising safety related to hypoglycaemia and weight gain. Evolution of insulin treatment regimens varied among patients, but dose titration was suboptimal. More active BI dose titration might further improve glycaemic outcome in patients receiving BI therapy. VIDEO ABSTRACT: A free Video Abstract to accompany this article is available at https://vimeo.com/212655959.

Impact of Prior Use of Four Preventive Medications on Outcomes in Patients Hospitalized for Acute Coronary Syndrome--Results from CPACS-2 Study.

BACKGROUND: It is widely reported that long-term use of four preventive medications (antiplatelet agents, angiotensin converting enzyme inhibitor / angiotensin receptor blocker, statin and beta-blockers) reduce the risk of subsequent acute coronary syndromes (ACS). It is unclear whether these four medications benefit patients who develop ACS despite its use. METHODS AND RESULTS: Logistic regression and propensity-score was applied among 14790 ACS patients to assess the association between prior use of four preventive medications and in-hospital outcomes including severity of disease at presentation (type of ACS, systolic blood pressure <90 mmHg, and heart rate> = 100 beats/min), complicating arrhythmia and major adverse cardiovascular events (MACEs, including all deaths, non-fatal myocardial infarction or re-infarction, and non-fatal stroke). Prior use of each of the four medications was significantly associated with less severity of disease (ORs ranged from 0.40 to 0.82, all P<0.05), less arrhythmia (ORs ranged from 0.45 to 0.64, all P<0.05), and reduced risk of MACEs (ORs ranged from 0.59 to 0.73, all P<0.05) during hospitalization. Multiple variable-adjusted ORs of MACEs were 0.77, 0.67, 0.48 and 0.59 respectively in patients with 1, 2, 3 and 4 medications in comparison with patients with none, and other clinical outcomes showed the same trend (P for trend < 0.05). CONCLUSIONS: Among ACS patients in our study, those with prior use of four preventive medications presented with less disease severity, developed less arrhythmia and had a lower risk of in-hospital MACEs. The value of taking these medications may beyond just preventing occurrence of the disease.

A Cluster-Randomized, Controlled Trial of a Simplified Multifaceted Management Program for Individuals at High Cardiovascular Risk (SimCard Trial) in Rural Tibet, China, and Haryana, India.

BACKGROUND: In rural areas in China and India, the cardiovascular disease burden is high but economic and healthcare resources are limited. This study (the Simplified Cardiovascular Management Study [SimCard]) aims to develop and evaluate a simplified cardiovascular management program delivered by community health workers with the aid of a smartphone-based electronic decision support system. METHODS AND RESULTS: The SimCard study was a yearlong cluster-randomized, controlled trial conducted in 47 villages (27 in China and 20 in India). Recruited for the study were 2086 individuals with high cardiovascular risk (aged ≥40 years with self-reported history of coronary heart disease, stroke, diabetes mellitus, and/or measured systolic blood pressure ≥160 mm Hg). Participants in the intervention villages were managed by community health workers through an Android-powered app on a monthly basis focusing on 2 medication use and 2 lifestyle modifications. In comparison with the control group, the intervention group had a 25.5% (P<0.001) higher net increase in the primary outcome of the proportion of patient-reported antihypertensive medication use pre- and post-intervention. There were also significant differences in certain secondary outcomes: aspirin use (net difference: 17.1%; P<0.001) and systolic blood pressure (-2.7 mm Hg; P=0.04). However, no significant changes were observed in the lifestyle factors. The intervention was culturally tailored, and country-specific results revealed important differences between the regions. CONCLUSIONS: The results indicate that the simplified cardiovascular management program improved quality of primary care and clinical outcomes in resource-poor settings in China and India. Larger trials in more places are needed to ascertain the potential impacts on mortality and morbidity outcomes. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01503814.