Treatment choices for the glycaemic management of patients with type 2 diabetes and chronic kidney disease: Analysis of the SAIL patient linked dataset

Aims

Chronic kidney disease (CKD) is common in type 2 diabetes and limits the treatment choices for glycaemic control. Our aim was to examine real-world prescribing for managing hyperglycaemia in the presence of CKD.

004 65岁以上收缩功能正常的心衰者的临床特点

众所周知,充血性心衰(CHF)为老年人较为常见的临床综合征之一.迄今关于左室收缩功能正常的CHF老人的相关临床特点远未清楚,本文特此进行了大样本分析. 对象与方法 4842例老年人,男1922例,女2920例,年龄66～103岁.尔后人均随访1年.旨在分析老年CHF年发病率,以及左室收缩功能正常的CHF老人相关临床特点. 结果随访期内,罹发1次或以上CHF者共425例次(8.8%/年).与未患发CHF老人相比,CHF老人平均年龄更大(79±6岁:77±5岁,P＜0.001),女性居多,尤以高龄女性更多,如85岁以上的高龄女性CHF年发病率约较65～69岁女性高2倍(14%∶6.6%,P＜0.001),AMI史、房颤、高血压、糖尿病、慢性阻塞型肺病、吸烟者均多,血脂及血肌酐亦高.多变量分析表明,罹患CHF与下列因素有关:老年尤其是高龄[年龄每增加5岁的患病奇数率(OR)女性1.2,男性1.1],AMI史(OR7.3),房颤者(OR3.0),糖尿病(OR2.1),肾功能不全(血肌酐≥1.5mg/dl的OR2.0),慢性阻塞肺病(仅老年女性的OR为1.8),以及左房、左室内径增大(内径每递增1cm的OR为2.0),和左室重量增加、左室收缩末期室壁张力增高、早期跨心房血流增多.超声心动图检测结果显示,CHF老人中,左室收缩功能正常者达55%,而仅有左室舒张功能不全,且左室收缩功能正常或轻度减退者高达80%.其中女性左室收缩功能正常者尤较男性多见(67%∶42%,P＜0.001),表现为单纯左室舒张功能不良.而在左室收缩功能正常的CHF老人,常伴有左室内径较小、左室收缩末期室壁张力较低、左室重量较轻、左室收缩末期室壁厚度增加,而左室射血分数正常或仅轻度降低. 讨论以上结果提示,在老年人群中,CHF年发病率相对较高,且随年龄而增加,多数左室收缩功能正常,仅有左室舒张功能障碍,尤其是在高龄女性,亦即高龄女性左室舒张功能不全性CHF更为常见.对此,临床上更应拟出合理的防范措施,来正确诊治老年CHF综合征. (袁志敏摘)     

Comparative Effectiveness of Commercial Bowel Preparations in Ambulatory Patients Presenting for Screening or Surveillance Colonoscopy

Digestive Diseases and Sciences - Inadequate bowel preparation (IBP) is associated with reduced adenoma detection. However, limited research has examined the impact of different commercial bowel...     

Common variants modify the age of onset for basal cell carcinomas in Gorlin syndrome

Gorlin syndrome is an autosomal dominant disorder, characterized by multiple early-onset basal cell carcinomas (BCCs) and jaw keratocysts. Through association studies in cohorts of sporadic BCC, nine genetic variants have previously been identified to increase the risk of BCC. The nine SNPs were genotyped by Taqman allelic discrimination in 125 individuals with Gorlin syndrome. Kaplan–Meier survival curves and Cox proportional-Hazard regression analysis were applied to determine the association between genotypes and age of first BCC in individuals with Gorlin syndrome. The p.(Arg151Cys) variant in MC1R (rs1805007) was associated with an earlier median age of onset of BCC of 27 years (95% CI: 20–34) compared with 34 years (95% CI: 30–40) for wild-type individuals (hazard ratio (HR)=1.64, 95% CI: 1.04–2.58, P=0.034). The risk allele of the variant at the chromosome 5p15 locus encompassing TERT-CLPTM1L (rs401681) was also associated with an earlier median onset of BCC, 31 years (95% CI: 28–37) compared with 41 years (95% CI: 32–48, HR=1.44, 95% CI: 1.08–1.93, P=0.014). In individuals with a risk allele at either rs1805007 or rs401681 the median time to BCC was 31 years of age (95% CI: 28–34) compared with 44 years of age (95% CI: 38–53) in wild-type individuals (HR=2.48, 95% CI: 1.47–4.17, P=0.0002). Our findings may have implications for future personalized risk estimates and BCC screening strategies in individuals with Gorlin syndrome.     

4D In-Situ Microscopy of Aerosol Filtration in a Wall Flow Filter

The transient nature of the internal pore structure of particulate wall flow filters, caused by the continuous deposition of particulate matter, makes studying their flow and filtration characteristics challenging. In this article we present a new methodology and first experimental demonstration of time resolved in-situ synchrotron micro X-ray computed tomography (micro-CT) to study aerosol filtration. We directly imaged in 4D (3D plus time) pore scale deposits of TiO2 nanoparticles (nominal mean primary diameter of 25 nm) with a pixel resolution of 1.6 μm. We obtained 3D tomograms at a rate of ∼1 per minute. The combined spatial and temporal resolution allows us to observe pore blocking and filling phenomena as they occur in the filter’s pore space. We quantified the reduction in filter porosity over time, from an initial porosity of 0.60 to a final porosity of 0.56 after 20 min. Furthermore, the penetration depth of particulate deposits and filtration rate was quantified. This novel image-based method offers valuable and statistically relevant insights into how the pore structure and function evolves during particulate filtration. Our data set will allow validation of simulations of automotive wall flow filters. Evolutions of this experimental design have potential for the study of a wide range of dry aerosol filters and could be directly applied to catalysed automotive wall flow filters.     

Novel markers of cell kinetics to evaluate progression from cirrhosis to hepatocellular carcinoma.

BACKGROUND: We investigated cell cycle kinetics of nodular lesions in cirrhosis to differentiate hepatocellular carcinoma (HCC) from its precursor lesions. METHODS: Twelve small HCC, 10 regenerative (RN), six large regenerative (LRN), and five dysplastic nodules (DN), identified in explant cirrhotic livers of five consecutive patients transplanted at Royal Free Hospital in 2002. Immunoperoxidase for MCM2, geminin and Ki67 was performed and the percentage of positive cells counted. RESULTS: The proportion of cells expressing MCM2 was more than those expressing Ki67, which in turn was more than those expressing geminin (overall median=16%, 2% and 0.5%, respectively, P<0.001). There was a statistically significant trend of increasing Ki67 expression (P=0.006), from RN to HCC; this trend was not statistically significant for geminin (P=0.18) or MCM2 (P=0.51). The median percentage of cells expressing Ki67 was 1% in RN, 0.5% in LRN, 2.2% in DN and 5.4% in HCC. The combination of these markers identified four different cell kinetics patterns: 'resting' (G0 cells: MCM2 -ve, Ki67 -ve, geminin -ve); 'licensed' (MCM2 +ve, Ki67 -ve, geminin -ve); 'slowly growing' (G1 phase arrest, MCM2 +ve, Ki67 +ve, low (0.4%) geminin) and expanding (MCM2 +ve, Ki67 +ve, geminin +ve) nodules. CONCLUSIONS: The combination of MCM2, geminin and Ki67 could represent a valuable tool in the understanding of HCC progression in cirrhosis.     

Onset of neck pain after a motor vehicle accident: a case-control study

OBJECTIVE: To assess the relative contribution of constitutional (individual) factors, pre-accident health, psychological and workplace psychosocial factors, and accident related (mechanical) factors in the development of neck pain (whiplash) following a motor vehicle accident. METHODS: We conducted a case-control study of drivers (ages 17-70 yrs) who reported a motor vehicle accident to their insurance company. A self-report mailed questionnaire retrospectively collected information on the driver's pre- and post-accident health, details of the accident, and other exposure data. Case/control status (post-accident neck pain) was ascertained using a preshaded manikin. RESULTS: In total, 26% of drivers reported post-accident neck pain. Women, younger individuals, and those with a history of neck pain were more likely to report neck pain following their accident (OR 1.50, 95% CI 0.98, 2.28; OR 1.62, 95% CI 0.96, 2.74; OR 1.75, 95% CI 1.09, 2.81, respectively). In addition, a number of accident related and psychosocial factors were independently associated with reporting post-accident neck pain: collision from behind (OR 2.55, 95% CI 1.41, 4.62); vehicle stationary at impact (OR 1.93, 95% CI 1.12, 3.33); collision severity (upper vs lowest tertile: OR 16.1, 95% CI 8.64, 30.1); not being at fault (OR 2.61, 95% CI 1.49, 4.59); and monotonous work (OR 2.19, 95% CI 1.19, 4.04). Based on these 8 factors, the likelihood of having neck pain increased from 7% with < or = 2 risk factors to 62% with > or = 5. CONCLUSION: Development of neck pain after a motor vehicle accident is a complex phenomenon resulting from the combined effects of constitutional, mechanical, and psychosocial factors. Using 8 such variables it is possible to identify those at high risk of developing neck pain.     

Relation of thrombogenesis in systemic hypertension to angiogenesis and endothelial damage/dysfunction (a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial [ASCOT])

Increasing evidence points toward a prothrombotic state in hypertension and atherosclerosis, conditions associated with thrombosis-related complications, such as myocardial infarction and stroke. We hypothesized that this increased risk of thrombogenesis may be related to endothelial damage/dysfunction and abnormal angiogenesis, and thus, an increased risk of future cardiovascular disease. Thrombogenesis, endothelial damage/dysfunction, and angiogenesis can be assessed by measurement of tissue factor (TF), von Willebrand Factor (vWF), flow-mediated dilatation (FMD), and vascular endothelial growth factor (VEGF), respectively. To test this hypothesis, we measured TF, vWF, FMD, and VEGF in 76 patients with systemic hypertension (71 men; mean age 64; mean blood pressure 167/72 mm Hg), considered additional risk factors such as diabetes, and related them to the patient's 10-year cardiovascular and cerebrovascular risk score using the Framingham equation. Patients were compared with 48 healthy normotensive controls. In these patients, the effects of 6 months of intensified blood pressure and (where appropriate) lipid-lowering treatment were investigated. In our patients, TF, VEGF, and vWF levels were higher, but FMD was lower (all p <0.001) compared with the controls. All markers correlated with each other and with both cardiovascular and cerebrovascular risk scores (all p <0.001). After intensified blood pressure and hypercholesterolemia treatment, total cholesterol, blood pressure, TF, VEGF, and vWF levels all decreased, whereas FMD increased (all p <0.001). Thus, in subjects with hypertension and other risk factors, endothelial damage/dysfunction (and thus, atherogenesis), thrombogenesis, and angiogenesis are abnormal, correlate with overall cardiovascular risk, and importantly, can be related to each other in a "Birmingham Vascular Triangle." Furthermore, these processes are beneficially affected by intensive blood pressure and lipid treatment.     

Germinal center phenotype and bcl-2 expression combined with the International Prognostic Index improves patient risk stratification in diffuse large B-cell lymphoma

The International Prognostic Index (IPI) identifies poor- and good-risk patients with diffuse large B cell lymphoma (DLBCL); however, the majority of patients have an intermediate IPI, with an uncertain prognosis. To determine whether cellular factors can be combined with the IPI to more accurately predict outcome, we have analyzed 177 presentation nodal DLBCLs for the expression of bcl-2 and a germinal center (GC) phenotype (defined by expression of bcl-6 and CD10). P53 gene band shifts were detected using single-stranded conformational polymorphism polymerase chain reaction analysis of exons 5-9 and were correlated with protein expression. In a Cox regression analysis, IPI (R = 0.22, P <.0001) and bcl-2 (R = 0.14, P =.0001) were independent poor prognostic factors and a GC phenotype predicted a favorable outcome (R = -0.025, P =.02). Neither p53 expression nor band shifts had a significant effect on survival. Using the IPI alone, 8% of patients were identified as high risk. Expression of bcl-2 in the intermediate IPI group identified a further 28% of patients with an overall survival comparable to the high IPI group. In the intermediate IPI, bcl-2(-) group, the presence of a GC phenotype improved overall survival to levels approaching the IPI low group. Following this analysis only 15% of patients failed to be assigned to a favorable- or poor-risk group. Sequential addition of bcl-2 expression and GC phenotype into the IPI significantly improves risk stratification in DLBCL. For the 36% of high-risk patients with a 2-year overall survival of 19%, alternative treatment strategies should be considered in future trials.