Charlson Co‐morbidity Index and albumin significantly associated with fracture risk in peritoneal dialysis patients

Published literature on fracture in dialysis patients seldom addressed the effect of co‐morbidity and malnutrition. In this study, we reported the incidence and risk factors for fracture in peritoneal dialysis patients. Peritoneal dialysis patients who had fractures between 2006 and 2011 were recruited. Demographic data, details of fracture, Charlson Co‐morbidity Index (CCI) and biochemical parameters were also collected. Non‐fracture controls, matched for age, gender and duration of dialysis, were also recruited at ratio 1:1 for fracture risk analysis. The incidence of fracture was 1 in 37 patient‐years. The commonest site of fracture was neck of femur (n = 16, 55.2%). Twenty‐four patients (82.8%) developed fracture after slip and fall injury. Eight out of 17 self‐ambulatory patients (47.1%) became non‐ambulatory after fracture. Infection was the commonest complication during hospitalization. Univariant analysis demonstrated high CCI (P = 0.001), hypoalbuminaemia (P < 0.001), loss of self autonomy (P = 0.006) and non‐ambulatory state (P = 0.011) significantly associated with increased fracture risk. However, only CCI (odds ratio (OR) 1.373, P = 0.028) and albumin (OR 0.893, P = 0.025) increased fracture risk significantly on multivariant analysis. Bone profile and parathyroid hormone were not significant risk factors. To conclude, fracture associated with adverse outcome in peritoneal dialysis patients. High CCI score and hypoalbuminaemia significantly increase risk of fracture.     

Calreticulin-independent regulation of the platelet integrin alphaIIbbeta3 by the KVGFFKR alphaIIb-cytoplasmic motif

The platelet integrin alphaIIbbeta3 alters conformation in response to platelet activation and ligand binding, although the molecular mechanisms involved are not known. We previously showed that a lipid modified peptide, corresponding to the membrane proximal 989KVGFFKR995 portion of the alphaIIb cytoplasmic tail, independently activates platelet alphaIIbbeta3. Calreticulin (CRT) is a potential integrin regulatory protein based on its interaction with the highly conserved alpha-integrin sequence KxGFFKR. We therefore examined the possible interaction of calreticulin and alphaIIbbeta3 in human platelets. We demonstrate that calreticulin in platelets is localised to the granulomere. In contrast, the known integrin-binding protein talin accumulates at the periphery of spreading platelets and colocalises with alphaIIbbeta3 during the process of adhesion. An interaction between calreticulin and alphaIIbbeta3 could not be demonstrated using co-immunoprecipitation techniques under various platelet activation states, even in the presence of covalent chemical crosslinkers. Thus, calreticulin does not functionally interact with the major integrin in human platelets. In order to identify proteins that interact with the integrin KVGFFKR motif we then used a peptide 'pull-down' assay from platelet lysates with biotinylated peptides and demonstrate that only the alphaIIb and beta3 subunits selectively and individually interact with this sequence. This interaction is divalent cation-dependent, has high-affinity, and occurs both with purified alphaIIbbeta3 complex and with electroeluted alpha and beta subunits. Thus, our data show that the conserved integrin KVGFFKR domain interacts primarily with the alpha and beta cytoplasmic tails and not with CRT in human platelets.     

Effects of nutritional status on exercise performance in advanced cystic fibrosis

Initial evaluation of 22 patients with cystic fibrosis (CF) on entry into a trial of home oxygen therapy was used to elucidate the possible effects of poor nutritional status on exercise performance in CF. The patients had advanced lung disease (mean FEV1, 36 percent predicted) and all had a stable resting PaO2 less than or equal to 65 mm Hg. Nutritional status was determined by calculating weight as a percentage of ideal for height (Wt/Ht) for each subject. Exercise testing consisted of a progressive exercise test on a cycle ergometer to measure maximum work capacity (Wmax), and a steady state test at 50 percent of baseline Wmax. During the steady state test, cardiac output (Q) and stroke volume (SV) were computed by the indirect Fick (CO2) method. Wmax, SV, Q and lung function results are expressed as percent predicted. Mean (+/- SD) Wmax was 58 +/- 15 percent predicted. Wmax correlated with both FEV1 and Wt/Ht, but FEV1 and Wt/Ht were not related. During steady state exercise, 12 of 22 patients had a SV less than 80 percent predicted. SV correlated with Wt/Ht, but not with lung function. Thirteen of the 22 patients had a Wt/Ht less than or equal to 90 percent and were considered malnourished. When compared with the well-nourished patients (Wt/Ht greater than 90%), these malnourished subjects had significantly lower mean values for Wmax%, SV% and Q% predicted, but not for lung function parameters. We conclude that: in patients with CF and advanced lung disease, nutritional status plays a significant role in determining exercise capacity; lower exercise tolerance of malnourished patients is an independent effect, as nutritional status and lung function were not related; and malnourished patients with CF have an altered cardiac performance on exercise testing which is due to a reduced SV rather than an impaired heart rate response.     

Assistive technology and people: a position paper from the first global research,innovation and education on assistive technology (GREAT) summit

Abstract

Assistive technology (AT) is a powerful enabler of participation. The World Health Organization’s Global Collaboration on Assistive Technology (GATE) programme is actively working towards access to assistive technology for all. Developed through collaborative work as a part of the Global Research, Innovation and Education on Assistive Technology (GREAT) Summit, this position paper provides a “state of the science” view of AT users, conceptualized as “People” within the set of GATE strategic “P”s. People are at the core of policy, products, personnel and provision. AT is an interface between the person and the life they would like to lead. People’s preferences, perspectives and goals are fundamental to defining and determining the success of AT. Maximizing the impact of AT in enabling participation requires an individualized and holistic understanding of the value and meaning of AT for the individual, taking a universal model perspective, focusing on the person, in context, and then considering the condition and/or the technology. This paper aims to situate and emphasize people at the centre of AT systems: we highlight personal meanings and perspectives on AT use and consider the role of advocacy, empowerment and co-design in developing and driving AT processes.     

Psychological Comfort of Paramedics with Field Death Pronouncement: A National Asian Study to Prepare Paramedics for Field Termination of Resuscitation

Objectives: Paramedics' decision to terminate field resuscitation without a physician present may depend on personal and external factors. This study investigates factors associated with paramedic psychological comfort with termination of resuscitation (TOR) to inform future training. Methods: We administered an anonymous survey to all practicing paramedics in a large urban Asian Emergency Medical Services system where formal TOR training had not yet been conducted and field TOR was not routinely applied. The survey assessed psychological comfort using the validated Psychological Comfort Total (PCT) scale (summed score of 28 items, with higher scores representing greater comfort). We examined scores associated with four personal (prior resolution of personal loss, knowledge of survival probability, religious affiliation and experience with death pronouncements) and two external (location of patient and perceived trust of family) factors. Data were entered into Excel and analyzed by t-tests and ANOVA. Results: Response rate was 73.6% (254/345). Respondents were 30.3 years (mean, SD 7.1) with 7.2 years (mean, SD 5.54) of practice experience. Over 60% had been involved in 6 or more field death pronouncements in the prior 12 months. Higher PCT scores were associated with prior resolution of personal loss and knowledge of survival probability. Lower PCT scores were associated with patient location in a public place and perceived family lack of trust. PCT scores were not associated with paramedic religious affiliation or number of prior death pronouncements. Conclusions: Paramedic psychological comfort with field death pronouncement is associated with personal and external factors. Since paramedic comfort is important for protocol adoption, TOR education should target not only knowledge, but also public arena management, communication skills for engaging with families, and help paramedics resolve prior personal loss.     

Cranial Tumor Surgical Outcomes at a High-Volume Academic Referral Center

Objective

To determine adverse event rates for adult cranial neuro-oncologic surgeries performed at a high-volume quaternary academic center and assess the impact of resident participation on perioperative complication rates.

Transseptal Left Heart Catheterization in Infants and Children

Transseptal left heart catheterization was performed in 80 infants and children with various forms of congenital heart disease. The majority had left heart obstructive lesions. Forty percent were under 5 years of age and less than 20 kg in weight. Uncomplicated cardiac perforation occurred in two patients. The technique is described in detail with emphasis on measures which increase the safety of the procedure for the patient. We conclude that this is a useful technique and in selected patients may be the preferred approach to the left heart.     

Adiposity Measurements by BMI,Skinfolds and Dual Energy X-Ray Absorptiometry in relation to Risk Markers for Cardiovascular Disease and Diabetes in Adult Males

Background. Choice of adiposity measure may be important in the evaluation of relationships between adiposity and risk markers for cardiovascular disease and diabetes. Aim. We explored the strengths of risk marker associations with BMI, a simple measure of adiposity, and with measures provided by skinfold thicknesses and dual energy X-ray absorptiometry (DXA). Subjects and Methods. We evaluated in three subgroups of white males (n = 156–349), participating in a health screening program, the strengths of relationship between measures of total and regional adiposity and risk markers relating to blood pressure, lipids and lipoproteins, insulin sensitivity, and subclinical inflammation. Results. Independent of age, smoking, alcohol intake, and exercise, the strongest correlations with adiposity measures were seen with serum triglyceride concentrations and indices of insulin sensitivity, with strengths of association showing little difference between BMI and skinfold and DXA measures of total and percent body fat (R = 0.20–0.46, P < 0.01). Significant but weaker associations with adiposity were seen for serum HDL cholesterol and only relatively inconsistent associations with adiposity for total and LDL cholesterol and indices of subclinical inflammation. Conclusions. BMI can account for variation in risk markers in white males as well as more sophisticated measures derived from skinfold thickness measurements or DXA scanning.     

Combination Therapy Reverses Hyperglycemia in NOD Mice With Established Type 1 Diabetes

An increasing number of therapies have proven effective at reversing hyperglycemia in the nonobese diabetic (NOD) mouse model of type 1 diabetes (T1D), yet situations of successful translation to human T1D are limited. This may be partly due to evaluating the effect of treating immediately at diagnosis in mice, which may not be reflective of the advanced disease state in humans at disease onset. In this study, we treated NOD mice with new-onset as well as established disease using various combinations of four drugs: antithymocyte globulin (ATG), granulocyte-colony stimulating factor (G-CSF), a dipeptidyl peptidase IV inhibitor (DPP-4i), and a proton pump inhibitor (PPI). Therapy with all four drugs induced remission in 83% of new-onset mice and, remarkably, in 50% of NOD mice with established disease. Also noteworthy, disease remission occurred irrespective of initial blood glucose values and mechanistically was characterized by enhanced immunoregulation involving alterations in CD4⁺ T cells, CD8⁺ T cells, and natural killer cells. This combination therapy also allowed for effective treatment at reduced drug doses (compared with effective monotherapy), thereby minimizing potential adverse effects while retaining efficacy. This combination of approved drugs demonstrates a novel ability to reverse T1D, thereby warranting translational consideration.