The combined diabetes and renal control trial (C-DIRECT) - a feasibility randomised controlled trial to evaluate outcomes in multi-morbid patients with diabetes and on dialysis using a mixed methods approach

Background: This cluster randomised controlled trial set out to investigate the feasibility and acceptability of the “Combined Diabetes and Renal Control Trial” (C-DIRECT) intervention, a nurse-led intervention based on motivational interviewing and self-management in patients with coexisting end stage renal diseases and diabetes mellitus (DM ESRD). Its efficacy to improve glycaemic control, as well as psychosocial and self-care outcomes were also evaluated as secondary outcomes. Methods: An assessor-blinded, clustered randomised-controlled trial was conducted with 44 haemodialysis patients with DM ESRD and ≥ 8% glycated haemoglobin (HbA1c), in dialysis centres across Singapore. Patients were randomised according to dialysis shifts. 20 patients were assigned to intervention and 24 were in usual care. The C-DIRECT intervention consisted of three weekly chair-side sessions delivered by diabetes specialist nurses. Data on recruitment, randomisation, and retention, and secondary outcomes such as clinical endpoints, emotional distress, adherence, and self-management skills measures were obtained at baseline and at 12 weeks follow-up. A qualitative evaluation using interviews was conducted at the end of the trial. Results: Of the 44 recruited at baseline, 42 patients were evaluated at follow-up. One patient died, and one discontinued the study due to deteriorating health. Recruitment, retention, and acceptability rates of C-DIRECT were generally satisfactory HbA1c levels decreased in both groups, but C-DIRECT had more participants with HbA1c < 8% at follow up compared to usual care. Significant improvements in role limitations due to physical health were noted for C-DIRECT whereas levels remained stable in usual care. No statistically significant differences between groups were observed for other clinical markers and other patient-reported outcomes. There were no adverse effects. Conclusions: The trial demonstrated satisfactory feasibility. A brief intervention delivered on bedside as part of routine dialysis care showed some benefits in glycaemic control and on QOL domain compared with usual care, although no effect was observed in other secondary outcomes. Further research is needed to design and assess interventions to promote diabetes self-management in socially vulnerable patients

A systematic review and meta-analysis of the effects of clinical pathways on length of stay, hospital costs and patient outcomes

Background. To perform a systematic review about the effect of using clinical pathways on length of stay (LOS), hospital costs and patient outcomes. To provide a framework for local healthcare organisations considering the effectiveness of clinical pathways as a patient management strategy. Methods. As participants, we considered hospitalized children and adults of every age and indication whose treatment involved the management strategy "clinical pathways". We include only randomised controlled trials (RCT) and controlled clinical trials (CCT), not restricted by language or country of publication. Single measures of continuous and dichotomous study outcomes were extracted from each study. Separate analyses were done in order to compare effects of clinical pathways on length of stay (LOS), hospital costs and patient outcomes. A random effects meta-analysis was performed with untransformed and log transformed outcomes. Results. In total 17 trials met inclusion criteria, representing 4,070 patients. The quality of the included studies was moderate and studies reporting economic data can be described by a very limited scope of evaluation. In general, the majority of studies reporting economic data (LOS and hospital costs) showed a positive impact. Out of 16 reporting effects on LOS, 12 found significant shortening. Furthermore, in a subgroup-analysis, clinical pathways for invasive procedures showed a stronger LOS reduction (weighted mean difference (WMD) -2.5 days versus -0.8 days)). There was no evidence of differences in readmission to hospitals or in-hospital complications. The overall Odds Ratio (OR) for re-admission was 1.1 (95% CI: 0.57 to 2.08) and for in-hospital complications, the overall OR was 0.7 (95% CI: 0.49 to 1.0). Six studies examined costs, and four showed significantly lower costs for the pathway group. However, heterogeneity between studies reporting on LOS and cost effects was substantial. Conclusion. As a result of the relatively small number of studies meeting inclusion criteria, this evidence base is not conclusive enough to provide a replicable framework for all pathway strategies. Considering the clinical areas for implementation, clinical pathways seem to be effective especially for invasive care. When implementing clinical pathways, the decision makers need to consider the benefits and costs under different circumstances (e.g. market forces)

Attenuation of Salt-Induced Cardiac Remodeling and Diastolic Dysfunction by the GPER Agonist G-1 in Female mRen2.Lewis Rats

The G protein-coupled estrogen receptor (GPER) is expressed in various tissues including the heart. Since the mRen2.Lewis strain exhibits salt-dependent hypertension and early diastolic dysfunction, we assessed the effects of the GPER agonist (G-1, 40 nmol/kg/hr for 14 days) or vehicle (VEH, DMSO/EtOH) on cardiac function and structure.Intact female mRen2.Lewis rats were fed a normal salt (0.5% sodium; NS) diet or a high salt (4% sodium; HS) diet for 10 weeks beginning at 5 weeks of age.Prolonged intake of HS in mRen2.Lewis females resulted in significantly increased blood pressure, mildly reduced systolic function, and left ventricular (LV) diastolic compliance (as signified by a reduced E deceleration time and E deceleration slope), increased relative wall thickness, myocyte size, and mid-myocardial interstitial and perivascular fibrosis. G-1 administration attenuated wall thickness and myocyte hypertrophy, with nominal effects on blood pressure, LV systolic function, LV compliance and cardiac fibrosis in the HS group. G-1 treatment significantly increased LV lusitropy [early mitral annular descent (e')] independent of prevailing salt, and improved the e'/a' ratio in HS versus NS rats (P<0.05) as determined by tissue Doppler.Activation of GPER improved myocardial relaxation in the hypertensive female mRen2.Lewis rat and reduced cardiac myocyte hypertrophy and wall thickness in those rats fed a high salt diet. Moreover, these advantageous effects of the GPER agonist on ventricular lusitropy and remodeling do not appear to be associated with overt changes in blood pressure

Diastolic time – frequency relation in the stress echo lab: filling timing and flow at different heart rates

A cutaneous force-frequency relation recording system based on first heart sound amplitude vibrations has been recently validated. Second heart sound can be simultaneously recorded in order to quantify both systole and diastole duration

miR-124 and miR-137 inhibit proliferation of glioblastoma multiforme cells and induce differentiation of brain tumor stem cells

Glioblastoma multiforme (GBM) is an invariably fatal central nervous system tumor despite treatment with surgery, radiation, and chemotherapy. Further insights into the molecular and cellular mechanisms that drive GBM formation are required to improve patient outcome. MicroRNAs are emerging as important regulators of cellular differentiation and proliferation, and have been implicated in the etiology of a variety of cancers, yet the role of microRNAs in GBM remains poorly understood. In this study, we investigated the role of microRNAs in regulating the differentiation and proliferation of neural stem cells and glioblastoma-multiforme tumor cells.status: publishe

Ontogenetic changes in leaf traits of tropical rainforest trees differing in juvenile light requirement

Relationships between leaf traits and the gap dependence for regeneration, and ontogenetic changes therein, were investigated in juvenile and adult tropical rainforest tree species. The juveniles of the 17 species included in the study were grown in high light, similar to the exposed crowns of the adult trees. The traits were structural, biomechanical, chemical and photosynthetic. With increasing species gap dependence, leaf mass per area (LMA) decreased only slightly in juveniles and remained constant in adults, whereas punch strength together with tissue density decreased, and photosynthetic capacity and chlorophyll increased. Contrary to what has been mostly found in evergreen tropical rainforest, the trade-off between investment in longevity and in productivity was evident at an essentially constant LMA. Of the traits pertaining to the chloroplast level, photosynthetic capacity per unit chlorophyll increased with gap dependence, but the chlorophyll a/b ratio showed no relationship. Adults had a twofold higher LMA, but leaf strength was on average only about 50% larger. Leaf tissue density, and chlorophyll and leaf N per area were also higher, whereas chlorophyll and leaf N per unit dry mass were lower. Ranking of the species, relationships between traits and with the gap dependence of the species were similar for juveniles and adults. However, the magnitudes of most ontogenetic changes were not clearly related to a species’ gap dependence. The adaptive value of the leaf traits for juveniles and adults is discussed

Brain energy rescue:an emerging therapeutic concept for neurodegenerative disorders of ageing

The brain requires a continuous supply of energy in the form of ATP, most of which is produced from glucose by oxidative phosphorylation in mitochondria, complemented by aerobic glycolysis in the cytoplasm. When glucose levels are limited, ketone bodies generated in the liver and lactate derived from exercising skeletal muscle can also become important energy substrates for the brain. In neurodegenerative disorders of ageing, brain glucose metabolism deteriorates in a progressive, region-specific and disease-specific manner — a problem that is best characterized in Alzheimer disease, where it begins presymptomatically. This Review discusses the status and prospects of therapeutic strategies for countering neurodegenerative disorders of ageing by improving, preserving or rescuing brain energetics. The approaches described include restoring oxidative phosphorylation and glycolysis, increasing insulin sensitivity, correcting mitochondrial dysfunction, ketone-based interventions, acting via hormones that modulate cerebral energetics, RNA therapeutics and complementary multimodal lifestyle changes

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease