Improvements in Air Quality and Health Outcomes Among California Medicaid Enrollees Due to Goods Movement Actions.

INTRODUCTION: In 2006, the California Air Resources Board (CARB) and local air quality management districts implemented an Emission Reduction Plan for Ports and Goods Movement program (referred to hereinafter as GM policy actions) (CARB 2006). The GM policy actions comprise approximately 200 actions with an estimated investment value of $6 to $10 billion. These actions targeted the major sources and polluters related to goods movements, such as highways; ports and railyard trucks; ship fuel and shore power; cargo equipment; and locomotives. These actions aimed to reduce total statewide domestic GM emissions to 2001 levels or lower by the year 2010; to reduce the statewide diesel particulate matter (DPM) health risk from GM by 85% by the year 2020; and to reduce the nitrogen oxides (NOx) emissions from international GM in the South Coast Air Basin by 30% from projected 2015 levels and 50% from projected 2020 levels. The years 2006 and 2007 marked an important milestone in starting to regulate GM polluters and adopting stricter standards for traffic-related air pollution.This project aimed to examine the impact of the GM policy actions on reductions in ambient air pollution and subsequent improvements in health outcomes of Medi-Cal fee-for-service (FFS) beneficiaries with chronic conditions in 10 counties in California. Specifically, we examined whether the GM policy actions reduced air pollution near GMC corridors more than in control areas. We subsequently assessed whether there were greater decreases in emergency room (ER) visits and hospitalizations for enrollees with chronic conditions who lived in the GM corridors (GMCs) than for those who lived in other areas. METHODS: The study used a quasi-experimental design. We defined areas within 500 m of truck-permitted freeways and ports as GMCs. We further defined non-goods movement corridors (NGMCs) as locations within 500 m of truck-prohibited freeways or 300 m of a connecting roadway, and areas out of GMCs and NGMCs as controls (CTRLs). We defined years 2004-2007 as the pre-policy period and years 2008-2010 as the post-policy period. We developed linear mixed-effects land use regression models and created annual air pollution surfaces for nitrogen dioxide (NO2), fine particulate matter (PM2.5), and ozone (O3) across California for years 2004-2010 at a spatial resolution of 30 m, then assigned them to enrollees' home addresses.We used a retrospective cohort of 23,000 California Medicaid (Medi-Cal) FFS adult beneficiaries living in 10 California counties with six years of data (September 1, 2004, to August 31, 2010). Cohort beneficiaries had at least one of four chronic conditions, including asthma, chronic obstructive pulmonary disease (COPD), diabetes, and heart disease.We used a difference-in-differences (DiD) model to assess whether air pollutant concentration and health care utilization (ER visits and hospitalizations) for cohort beneficiaries declined more for those living in intervention corridors (GMCs, NGMCs) than those living in CTRLs. All the models controlled for age, sex, language spoken, race/ethnicity, number of comorbidities in baseline years, county, time-varying health indicator variables, and several neighborhood variables.To facilitate interpretation, we calculated the DiD estimates in each of the three years after the policy intervention. The DiD was used to assess the causal impact of regulatory policy on reductions of air pollution, as well as for the improvements in health outcomes.We explored whether improvements in health outcomes were due to the air pollution reduction by using a multi- level mediation model, in which the effect of GM actions on health outcomes was mediated through the effect of actual air pollution reductions in the post-policy years. We used the Generalized Structural Equation Models for the estimation and combined the effects of NO2 and PM2.5 in the model. To further verify the causal inferences of the GM actions on reductions of exposures and improvements in health outcomes, we performed sensitivity analyses with propensity score weighting. RESULTS: We observed statistically significant reductions in pollutant NO2 and PM2.5 concentrations for enrollees in all 10 counties. The enrollees in GMCs experienced greater reductions in NO2 and PM2.5 from the pre- to the post-policy periods than those in CTRLs. Greater reductions were also observed among beneficiaries living in NGMCs versus those in CTRLs, but those reductions were smaller than among beneficiaries living in GMCs. For O3 concentrations, an opposite trend was observed.Furthermore, we observed significantly greater reductions in ER visits for patients with asthma and COPD living in GMCs than those in CTRLS in the post-policy years. For example, we saw in the DiD modeling results there were 170 fewer ER visits for 1,000 beneficiaries with asthma per year in GMCs if the regionwide trend in the CTRL group was considered not related to the GM policy. Similarly, among the beneficiaries with COPD, there were 180 fewer ER visits per 1,000 patients estimated in the GMCs for the third year after the implementation of the policy.We also observed greater reductions in ER visits among those with asthma, when comparing NGMCs with CTRLs, but reductions were smaller than comparisons between GMCs and CTRLs. The ER visits for those with COPD, diabetes, and the total sample in NGMCs also had downward trends in the post-policy year in comparison with those in CTRLs but the differences were not statistically significant; similar phenomena were also observed for the ER visits among those with diabetes and heart diseases and in the total sample when GMCs versus CTRLs and GMCs versus NGMCs were compared. Although hospitalizations also decreased more in GMCs than in NGMCs and more in NGMCs than in CTRLs in the post-policy period, results were not statistically significant.Using the mediation models, we observed 0.129 more reductions in the expected number of ER visits among individuals with asthma for a composite reduction in one unit NO2 and one unit PM2.5 (DiD = -0.129, P < 0.05) from the pre-policy years to the post-policy years. The reductions in NO2 and PM2.5 due to policy change estimated by the mediation model are essentially the same as shown in the respective DiD models. Mediation analyses suggested that the effects of GM policy interventions on health improvements were largely due to exposure reductions. Finally, sensitivity analyses with propensity scores produced similar DiD results. CONCLUSIONS: This project has produced empirical evidence that air pollution control actions reduced pollution exposures among disadvantaged and susceptible populations. More importantly, our findings suggest that the reductions in air pollution led to health outcome improvements among low-income people with chronic conditions. Our investigation also contributed to scientific methods for assessing the health effects of long-term, large-scale, and complex regulatory actions with routinely collected pollutants and medical claims data. Therefore, the results strongly support both short-term and long-term efforts to improve air quality for all members of society and future studies on the impact of air pollution control policies.

Young-onset type 2 diabetes and younger current age: increased susceptibility to retinopathy in contrast to other complications.

BACKGROUND: Type 2 diabetes diagnosed during youth and early adulthood is aggressive and associated with a high burden of vascular complications. The increase in complications is often attributed to long disease duration and poor metabolic control. Whether people with young-onset type 2 diabetes are inherently more susceptible to long-term complications than those diagnosed in later adulthood is unclear. METHODS: Prospective data from 3322 individuals, diagnosed between the age of 15 and 70 years and collected 10-25 years after diabetes diagnosis, were analysed. The cross-sectional associations between age at diagnosis and microvascular and macrovascular complications were analysed using logistic regression models, adjusted for duration of diabetes exposure and metabolic risk factors including blood pressure, cholesterol and updated mean HbA1c . RESULTS: The prevalence of retinopathy was highest in those with young-onset type 2 diabetes (diagnosed at age 15 to <40 years). After 10-15 years' diabetes duration, the adjusted odds ratio for retinopathy in this population was 2.8 (95% CI 1.9-4.1; reference group those diagnosed at 60 to <70 years of age). The odds of retinopathy remained higher in people with young-onset type 2 diabetes after longer durations of diabetes exposure; the odds decreased with increasing age at diagnosis. This pattern was not observed in models of other complications: after 10-15 years' diabetes exposure, the adjusted odds ratios for albuminuria, peripheral neuropathy and macrovascular disease in people with young-onset type 2 diabetes were 0.5 (95% CI 0.4-0.8), 0.7 (95% CI 0.5-1.1) and 0.2 (95% CI 0.1-0.3), respectively. CONCLUSION: After accounting for disease duration and other important confounders, people with type 2 diabetes diagnosed in youth and early adulthood (or with a younger current age) appeared to be inherently more susceptible to retinopathy. For other complications, adjusted risk appears highest in the oldest age of diagnosis group. These data have screening and treatment target implications.

[Aspirin inhibits cell stemness of esophageal cancer by downregulation of chemokine CCL2].

Objective: To investigate the effect of tumor-associated macrophages on the stemness of esophageal cancer cells and the potential mechanism of antiproliferative effects of aspirin (ASA). Methods: The effects of aspirin on the stemness characteristics of KYSE-450 cells and KYSE-450 cells co-cultured with M2 macrophages (KYSE-450+ M2) were performed using spheroid formation assay. After treatment with aspirin, the expression of different chemokines, the core pluripotency gene Nanog and the stem cell marker CD90 in different cell groups were determined by real-time quantitative PCR, flow cytometry and Western blot. Results: The number of spheres formed in the ASA and KYSE-450+ M2 cell groups were 7.00±1.23 and 34.33±2.33, respectively, showing statistically significant difference compared with that of control group (14.50±2.33, all P<0.05). The number of spheres in KYSE-450+ M2+ ASA cell group were 20.67±2.33, which was significantly lower than that of KYSE-450+ M2 group (P<0.05). The expression levels of Nanog gene in control and ASA groups were 1.00 and 0.50±0.10, respectively, and the difference was statistically significant (P<0.05). Moreover, the expression of Nanog gene in cells of KYSE-450+ M2 group and M2+ KYSE-450+ ASA group was 1.74±0.13 and 1.43±0.05, showing statistically significant difference (P<0.05). When chemokine CCL2 was knocked down, the levels of Nanog gene in M2+ shCCL2-KYSE450+ ASA group and M2+ shCCL2-KYSE450 group were decreased to 1.22±0.11 and 1.17±0.08, respectively, and there was no statistically significant difference between them (P=0.69). Flow cytometry analyses showed that the expression levels of CD90 in control and ASA cells were (2.93±0.52)% and (1.30±0.17)%, respectively, and the difference was statistically significant (P<0.05). Moreover, the expression levels of CD90 in M2+ shCCL2-KYSE450 cells and M2+ shCCL2-KYSE450+ ASA cells were (4.07±0.12)% and (4.73±0.38)%, respectively, showing no statistically significant difference (P=0.17). Conclusions: Tumor-associated macrophages enhances the stemness of esophageal cancer cells, whereas aspirin attenuates the stemness by suppressing the expression of CCL2. Aspirin plays an anti-tumor effect in esophageal cancer cells.

IL6 derived from cancer-associated fibroblasts promotes chemoresistance via CXCR7 in esophageal squamous cell carcinoma.

Various factors and cellular components in the tumor microenvironment are key drivers associated with drug resistance in many cancers. Here, we analyzed the factors and molecular mechanisms involved in chemoresistance in patients with esophageal squamous cell carcinoma (ESCC). We found that interleukin 6 (IL6) derived mainly from cancer-associated fibroblasts played the most important role in chemoresistance by upregulating C-X-C motif chemokine receptor 7 (CXCR7) expression through signal transducer and activator of transcription 3/nuclear factor-κB pathway. CXCR7 knockdown resulted in the inhibition of IL6-induced proliferation and chemoresistance. In addition, CXCR7 silencing significantly decreased gene expression associated with stemness, chemoresistance and epithelial-mesenchymal transition and suppressed the proliferation ability of ESCC cells in three-dimensional culture systems and angiogenesis assay. In clinical samples, ESCC patients with high expression of CXCR7 and IL6 presented a significantly worse overall survival and progression-free survival upon receiving cisplatin after operation. These results suggest that the IL6-CXCR7 axis may provide a promising target for the treatment of ESCC.

Aurora-A-mediated phosphorylation of LKB1 compromises LKB1/AMPK signaling axis to facilitate NSCLC growth and migration.

Deletion or loss-of-function mutation of LKB1, frequently occurring in non-small cell lung cancers (NSCLCs), is a predominant caution of NSCLC initiation and progression. However, the upstream signaling pathways governing LKB1 activation are largely unknown. Here, we report that LKB1 undergoes Aurora kinase A (AURKA)-mediated phosphorylation, which largely compromises the LKB1/AMPK signaling axis, in turn leading to the elevation of NSCLC cell proliferation, invasion and migration. Mechanically, AURKA-mediated phosphorylation of LKB1 impairs LKB1 interaction with and phosphorylation of its downstream target AMPKα, which has critical roles in governing cancer cell energy metabolic homeostasis and tumorigenesis. Clinically, AURKA displays high levels in NSCLC patients, and correlates with poor outcome of patients with lung adenocarcinoma. Pathologically, the amplification or activation of AURKA-induced impairment of the LKB1/AMPK signaling pathway contributes to NSCLC initiation and progression, highlighting AURKA as a potential therapeutic target for combatting hyperactive AURKA-driven NSCLCs.

The effect of wilderness and medical training on injury and altitude preparedness among backcountry hikers in Rocky Mountain National Park / 世界急诊医学杂志（英文）

BACKGROUND:The purpose of this study was to document the correlation between medical and wilderness training with levels of preparedness for acute mountain sickness (AMS), illness, and injury among backcountry hikers. METHODS:We conducted a cross-sectional, convenience survey in Rocky Mountain National Park in July and August 2015. The study group consisted of 380 hikers who completed a written survey that collected information about demographics, wilderness experience, altitude experience, hiking equipment, communications devices, and trip planning. RESULTS:Factors such as wilderness training (wilderness first aid [WFA], wilderness first responder [WFR], or wilderness emergency medical technician [WEMT]), wilderness experience, and altitude experience all affected hikers' emergency preparedness. Respondents with medical training were more prepared to avoid or respond to AMS (62.3％ vs. 34.3％ [P<0.001]). They were also more prepared to avoid or manage injury/illness than hikers without medical training (37.7％vs. 20.7％ [P=0.003]). Participants with wilderness training were more likely to be prepared to avoid or respond to AMS (52.3％ vs. 36.8％ [P=0.025]) but not significantly more likely to be prepared to manage illness/injury (31.8％ vs. 22.0％ [P<0.11]). Adjusting for experience, wilderness training, age, and gender, we found that medical training was associated with increased preparedness for AMS (OR 2.72; 95％ CI 1.51–4.91) and injury/illness (OR 2.71; 95％ CI 1.5–4.89). CONCLUSION:Medically trained hikers were more likely to be prepared to avoid or manage AMS, medical emergencies, and injuries than their non-medically trained counterparts. Wilderness training increased hikers' preparedness for AMS but did not significantly alter preparedness for illness/injury.

Portobiliary fistula following laparoscopic cholecystectomy.

The laparoscopic approach has replaced open surgery as the gold standard for cholecystectomy. This technique is, however, associated with a greater incidence of bile duct injuries (BDIs). We report a case of portobiliary fistula (PBF), a rare complication of BDI, occurring post laparoscopic cholecystectomy (LC). PBF has been reported after procedures such as endoscopic retrograde cholangiopancreatography and pathologies such as liver abscesses, but only once previously in the setting of LC. We discuss the management of this patient with apparent dual pathology, and summarise other aetiologies that may give rise to this condition.

Cab45S promotes cell proliferation through SERCA2b inhibition and Ca2+ signaling.

Cytosolic Ca(2+), closely related to endoplasmic reticulum (ER) Ca(2+), plays a critical role in regulating cell proliferation and tumorigenesis. However, the role of ER lumen proteins in regulating cytosolic Ca(2+) level remains poorly understood. Here, we find that the Cab45S, localizes in the ER lumen, inhibits sarco/ER Ca(2+)-ATPase 2b (SERCA2b) activity through its first EF-hand domain directly binding to the intra-lumenal loop 4 of SERCA2b, and reduces ER Ca(2+). STIM1 activation, induced by the Cab45S-dependent drop in ER Ca(2+), together with the upregulation of the plasma membrane Ca(2+) channel TRPC1 ultimately increases extracellular Ca(2+) influx. Furthermore, increased cytosolic Ca(2+) level elicits Ca(2+)-NFAT signaling and promotes cell proliferation. Consistently, in cervical carcinoma patients, Cab45S is upregulated. Thus, our data reveal that the ability of Cab45S to inhibit SERCA2b activity is crucial for its role as a modulator of cell proliferation and tumor growth.

Sequence variability in internal transcribed spacers of nuclear ribosomal DNA among isolates of the oxyurid nematodes Syphacia obvelata and Aspiculuris tetraptera from mice reared in laboratories in China.

This study examined sequence variability in internal transcribed spacers (ITS) of nuclear ribosomal DNA among Syphacia obvelata and Aspiculuris tetraptera isolates from laboratory mice from different geographical locations in China. ITS1, 5.8S and ITS2 rDNA were amplified separately from adult S. obvelata and A. tetraptera individuals by polymerase chain reaction (PCR), and the amplicons were subjected to sequencing from both directions. The lengths of the sequences of ITS1, 5.8S and ITS2 rDNA from both nematodes were 314 bp and 456 bp, 157 bp, and 273 bp and 419 bp, respectively. The intraspecific sequence variations in S. obvelata ITS1 were 0-0.3%. For A. tetraptera they were 0-0.7% in ITS1 and 0-1.0% in ITS2. However, the interspecific sequence differences among members of the infraorder Oxyuridomorpha were significantly higher, being 54.0-65.5% for ITS1 and 55.3-64.1% for ITS2. Phylogenetic analysis based on the combined partial sequences of ITS1 and ITS2 using three inference methods - Bayesian inference, maximum likelihood and maximum parsimony - revealed that all the S. obvelata and A. tetraptera samples formed independent monophyletic groups. Syphacia obvelata was closer to Syphacia muris than to A. tetraptera, consistent with morphological classification. These results demonstrate that ITS1 and ITS2 rDNA sequences are useful markers for population genetic studies of oxyurid nematodes.

Triple assessment is not necessary in most young women referred with breast symptoms.

INTRODUCTION: A palpable lesion in the breast is usually subjected to triple assessment (clinical examination [CE], imaging and core biopsy [CB] or fine needle aspiration [FNA]) to minimise the risk of missing breast cancer. However, breast cancer is rare in young women, and triple assessment (especially CB) is invasive and expensive. Our aim was to see whether CB/FNA could be avoided in young women with benign findings on CE and imaging. METHODS: This study analysed data from a prospectively entered database on female patients aged under 25 years who attended a rapid diagnosis breast clinic over a 68-month period. RESULTS: Among 10,301 patients seen, 955 females (9.3%) were aged <25 years. The most common presenting complaint was a lump, followed by pain and nipple discharge. CE was normal or revealed benign findings in all except 15 patients, in whom it was indeterminate. Ultrasonography was performed in 692 patients (72%) and was normal (n=289) or benign (n=382) in all except 21 patients, in whom it was indeterminate. In six patients, both were indeterminate. A total of 317 patients (35%) had triple assessment: FNA in 106, CB in 239 and both in 9 cases. No cancers were diagnosed. CONCLUSIONS: It would appear safe to omit FNA/CB in patients aged under 25 years when clinical and ultrasonography findings are normal or benign. This approach would have avoided needle biopsies in all but 30 patients (3%) in the study.

Efficiency of fish propulsion.

The system efficiency of a self-propelled flexible body is ill-defined, hence we introduce the concept of quasi-propulsive efficiency, defined as the ratio of the power needed to tow a body in rigid-straight condition over the power it requires for self-propulsion, both measured for the same speed. Through examples we show that the quasi-propulsive efficiency is a rational non-dimensional metric of the propulsive fitness of fish and fish-like mechanisms, consistent with the goal to minimize fuel consumption under size and velocity constraints. We perform two-dimensional viscous simulations and apply the concept of quasi-propulsive efficiency to illustrate and discuss the efficiency of two-dimensional undulating foils employing first carangiform and then anguilliform kinematics. We show that low efficiency may be due to adverse body-propulsor hydrodynamic interactions, which cannot be accounted for by an increase in friction drag, as done previously, since at the Reynolds number Re = 5 000 considered in the simulations, pressure is a major contributor to both thrust and drag.

Edge contacts of graphene formed by using a controlled plasma treatment.

Despite the fact that the outstanding properties of graphene are well known, the electrical performance of the material is limited by the contact resistance at the metal-graphene interface. In this study, we demonstrate the formation of "edge-contacted" graphene through the use of a controlled plasma processing technique that generates a bond between the graphene edge and the contact metal. This technique controls the edge structure of the bond and significantly reduces the contact resistance. This simple approach requires no additional post-processing and has been proven to be very effective. In addition, controlled pre-plasma processing was applied in order to produce CVD-graphene field effect transistors with an enhanced adhesion and improved carrier mobility. The contact resistance attained by using pre-plasma processing was 270 Ω µm, which is a decrease of 77%.

Zinc transporter 8 autoantibodies: what is their clinical relevance in gestational diabetes?

AIMS: To investigate the prevalence, clinical significance and antepartum to postpartum trajectory of zinc transporter 8 autoantibodies, a novel marker of islet autoimmunity, in women with gestational diabetes mellitus. METHODS: A total of 302 consecutive women attending a multi-ethnic Australian gestational diabetes clinic were prospectively studied. Zinc transporter 8 autoantibodies were measured at gestational diabetes diagnosis and 3 months postpartum using an enzyme-linked immunosorbent assay, and were correlated with maternal phenotype, antepartum and postpartum glucose tolerance, treatment and perinatal outcomes. RESULTS: Of the 302 women, 30 (9.9%) were positive for one islet autoantibody antepartum. No participant had multiple islet autoantibodies. Zinc transporter 8 autoantibodies were the most prevalent autoantibody [zinc transporter 8 autoantibodies: 13/271 women (4.8%); glutamic acid decarboxylase 7/302 women (2.3%); insulinoma-associated antigen-2: 6/302 women (2.0%); insulin: 4/302 women (1.3%)]. Zinc transporter 8 autoantibody positivity was associated with a higher fasting glucose level on the antepartum oral glucose tolerance test, but not with BMI, insulin use, perinatal outcomes or postpartum glucose intolerance. Five of the six women who tested positive for zinc transporter 8 autoantibodies antepartum were negative for zinc transporter 8 autoantibodies postpartum, which corresponded to a significant decline in titre antepartum to postpartum (26.5 to 3.8 U/ml; P=0.03). This was in contrast to the antepartum to postpartum trajectory of the other islet autoantibodies, which remained unchanged. CONCLUSIONS: Zinc transporter 8 autoantibodies were the most common islet autoantibody in gestational diabetes. Zinc transporter 8 autoantibody positivity was associated with slightly higher fasting glucose levels and, unlike other islet autoantibodies, titres declined postpartum. Zinc transporter 8 autoantibodies may be a marker for islet autoimmunity in a proportion of women with gestational diabetes, but the clinical relevance of zinc transporter 8 autoantibodies in pregnancy and gestational diabetes requires further investigation.

Porous tantalum rods for treating osteonecrosis of the femoral head.

This study evaluated the outcomes of using porous tantalum rods for the treatment of osteonecrosis of the femoral head (ONFH). We performed core decompression and inserted porous tantalum implants in 149 patients (168 consecutive hips) with ONFH. Hips had large (65), medium (64), or small (39) lesions; 63 lesions were lateral, 68 were central, and 35 were medial. Conversion to total hip arthroplasty (THA) was the end point of this survey. A total of 130 cases (138 hips) were followed. The mean follow-up time was 38.46 ± 5.76 months; 43 hips (31%) were converted to or needed THA. Of the 43 hips requiring THA, 33 had large lesions, including 1 medial, 3 central, and 29 lateral lesions; 9 had medium, lateral lesions, and 1 hip had a small, lateral lesion. Bone grafting was used in 59 hips, with 3 hips failing; 40 of 79 hips without bone grafts failed. The sum distances between the tops of the rods and the lateral lesion boundaries (SDTL, mm) were measured in anteroposterior and lateral radiographs. In the failure and spared groups, the average SDTLs were 7.65 ± 2.759 and 0.83 ± 2.286 mm, respectively. The survival of porous tantalum rods used for treating early-stage ONFH was affected by the size and location of the lesion, whether or not a bone graft was used, as well as the distance between top of the rod and the lateral boundary of the lesion.

Dipeptidyl peptidase-4 inhibitors as a third-line oral antihyperglycaemic agent in patients with type 2 diabetes mellitus: the impact of ethnicity.

Aims. The aim of this study is to examine the efficacy of adding a dipeptidyl peptidase-4 (DPP-4) inhibitor to patients with type 2 diabetes inadequately controlled by metformin and sulphonylurea combination treatment. The response of Asian and non-Asian patients to this regimen was also examined. Methods. The medical and computerized records of 80 patients were examined. These patients had baseline HbA1c levels ranging from 7.0 to 12.5% and had a DPP-4 inhibitor add-on therapy for a minimum period of 12 weeks. The primary endpoint was the change in HbA1c level before and after DPP-4 inhibitor treatment. Results. During oral triple therapy, there was a reduction of HbA1c from 8.3% (7.7-8.9) to 7.2% (6.8-7.6) and 26 patients (32.5%) achieved an HbA1c <7%. Poor baseline glycaemic control, lower BMI, and younger age were associated with a better response, but duration of diabetes and gender did not affect outcome. The HbA1c reduction was not different between Asians and non-Asians group [-1.00% (0.6-1.3) vs -0.90% (0.4-1.6)]. Conclusions. DPP-4 inhibitor as a third-line add-on therapy can achieve significant glycaemic improvement in patients with type 2 diabetes inadequately controlled on the combination of metformin and sulphonylurea. The improvement in HbA1c was similar between Asian and non-Asian patients.

Efficacy and safety of canagliflozin over 52 weeks in patients with type 2 diabetes mellitus and chronic kidney disease.

AIM: This study evaluated the efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 inhibitor, in patients with type 2 diabetes mellitus (T2DM) and within a subset of Stage 3 chronic kidney disease (CKD; estimated glomerular filtration rate [eGFR] ≥ 30 and <50 ml/min/1.73 m(2)). METHODS: In this 52-week, randomized, double-blind, placebo-controlled study, patients (N = 269; mean eGFR, 39.4 ml/min/1.73 m(2)) received canagliflozin 100 or 300 mg and placebo once daily. Efficacy endpoints included changes in glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), body weight and systolic blood pressure (BP); adverse events (AEs) were also recorded. RESULTS: At week 52, canagliflozin 100 and 300 mg reduced HbA1c compared with placebo (-0.19, -0.33 and 0.07%, respectively); placebo-subtracted differences (95% confidence interval) were -0.27% (-0.53, 0.001) and -0.41% (-0.68, -0.14). Canagliflozin also lowered FPG, body weight and BP versus placebo. Overall AE incidence was 85.6, 80.9, and 86.7% with canagliflozin 100 and 300 mg and placebo, respectively. Osmotic diuresis-related AEs were more common with both canagliflozin doses, and incidences of urinary tract infections and volume depletion-related AEs were higher with canagliflozin 300 mg versus placebo. Decreases in eGFR (-2.1, -4.0 and -1.6 ml/min/1.73 m(2)) were seen with canagliflozin 100 and 300 mg compared with placebo. Canagliflozin 100 and 300 mg provided median percent reductions in urine albumin to creatinine ratio versus placebo (-16.4, -28.0 and 19.7%). CONCLUSIONS: Canagliflozin improved glycaemic control and was generally well tolerated in patients with T2DM and within a subset of Stage 3 CKD over 52 weeks.

Age of diabetes diagnosis and diabetes duration associate with glycated haemoglobin.

An earlier age of diagnosis (r=-0.28, p<0.0001) and longer duration of type 2 diabetes (r=0.26, p<0.0001) were each found to correlate with higher HbA1c level, on analysis of a diabetes centre database in people under regular shared care. When combined, these biological variables strongly associate with the current HbA1c level.