Effectiveness of an HbA1c tracking tool on primary care management of diabetes mellitus: glycaemic control, clinical practice and usability

Objective To determine if a laboratory data report (the HbA1c Tracking Tool) could be used as an effective intervention to improve diabetes management. Design A longitudinal quasi-experimental cohort design was used to test the effectiveness of an HbA1c summary report sent to primary care physicians for all patients having HbA1c levels greater than 7%. Setting Moncton, New Brunswick, Canada. Sample selection Administrative data from all adult patients with diabetes who had had at least two HbA1c measurements within the year prior to the initiation of the HbA1c Tracking Tool, and who had had five years of HbA1c measurements (2002-2007) overall was included. Interventions In March 2006 all primary care physicians began receiving HbA1c summary reports (through the HbA1c Tracking Tool) as a means to improving the management of diabetes. Main outcome measures (a) patient glycaemic control as indicated by HbA1c levels, (b) physician adherence to practice guidelines as indicated by measuring the mean number of HbA1c tests ordered per patient per year, and (c) physician usage rates of the HbA1c Tracking Tool in clinical practice. Results The sample (n=955)was divided into three subgroups based on flagged HbA1c level (7_9%). The strongest effect of the intervention was found in the two groups with the poorest glycaemic control. The effect was stronger in the >9% group (from 10.1 to 9.3%), than in the 8_9% group (a drop of 8.5 to 8.3%). Longitudinal analyses over a five-year period indicated the same findings. Patients were also found to receive more tests across time (from 2.45 tests per year to 3.0 across five years). In terms of usage, 92.1% of the physicians surveyed used the tool in their practice. Conclusion Routinely collected hospital laboratory data can be used both as the basis for an information- based intervention and as a tool to monitor quality of diabetes care

Development of a Biodegradable Subcutaneous Implant for Prolonged Drug Delivery Using 3D Printing

Implantable drug delivery devices offer many advantages over other routes of drug delivery. Most significantly, the delivery of lower doses of drug, thus, potentially reducing side-effects and improving patient compliance. Three dimensional (3D) printing is a flexible technique, which has been subject to increasing interest in the past few years, especially in the area of medical devices. The present work focussed on the use of 3D printing as a tool to manufacture implantable drug delivery devices to deliver a range of model compounds (methylene blue, ibuprofen sodium and ibuprofen acid) in two in vitro models. Five implant designs were produced, and the release rate varied, depending on the implant design and the drug properties. Additionally, a rate controlling membrane was produced, which further prolonged the release from the produced implants, signalling the potential use of these devices for chronic conditions

Development of drug loaded cardiovascular prosthesis for thrombosis prevention using 3D printing

Cardiovascular disease (CVD) is a general term for conditions which are the leading cause of death in the world. Quick restoration of tissue perfusion is a key factor to combat these diseases and improve the quality and duration of patients' life. Revascularization techniques include angioplasty, placement of a stent, or surgical bypass grafting. For the latter technique, autologous vessels remain the best clinical option; however, many patients lack suitable autogenous due to previous operations and they are often unsuitable. Therefore, synthetic vascular grafts providing antithrombosis, neointimal hyperplasia inhibition and fast endothelialization are still needed. To address these limitations, 3D printed dipyridamole (DIP) loaded biodegradable vascular grafts were developed. Polycaprolactone (PCL) and DIP were successfully mixed without solvents and then vascular grafts were 3D printed. A mixture of high and low molecular weight PCL was used to better ensure the integration of DIP, which would offer the biological functions required above. Moreover, 3D printing technology provides the ability to fabricate structures of precise geometries from a 3D model, enabling to customize the vascular grafts' shape or size. The produced vascular grafts were fully characterized through multiple techniques and the last step was to evaluate their drug release, antiplatelet effect and cytocompatibility. The results suggested that DIP was properly mixed and integrated within the PCL matrix. Moreover, these materials can provide a sustained and linear drug release without any obvious burst release, or any faster initial release rates for 30 days. Compared to PCL alone, a clear reduced platelet deposition in all the DIP-loaded vascular grafts was evidenced. The hemolysis percentage of both materials PCL alone and PCL containing 20% DIP were lower than 4%. Moreover, PCL and 20% DIP loaded grafts were able to provide a supportive environment for cellular attachment, viability, and growth

Functions of Candida albicans cell wall glycosidases Dfg5p and Dcw1p in biofilm formation and HOG MAPK pathway

Background Candida albicans is a commensal fungus that inhabits the oral mucosal surface and causes oral and systemic candidiasis. Oral candidiasis most commonly occurs in patients with AIDS, denture wearers and newborn children. Systemic candidiasis occurs mainly in immunocompromised patients and patients admitted to hospitals for prolonged periods. C. albicans homologous genes, DFG5 and DCW1, encode for two closely related cell wall proteins with putative glycosyltransferase enzyme activity and C-terminal GPI-anchors. Past studies have shown that individual DFG5 and DCW1 mutations are viable but simultaneous deletion of DFG5 and DCW1 in C. albicans results in lethality. However, the exact functions of these cell wall based enzymes, which represent potential drug targets, are not understood. Methods C. albicans DFG5/DCW1 heterologous and conditional double mutant strains were assessed for growth and biofilm formation in comparison to wild type and parental strains. Cell wall and heat stress susceptibility of the mutant and control strains were assessed using agar spotting assays. Growth was assessed under normal and osmotic stress conditions along with light microscopy imaging. Biofilm dry weight and microscopic imaging analysis of biofilms was performed. Hypha formation in response to serum was analyzed using light microscopy imaging. Western blot analysis of mutant strains and control strains was performed to assess Hog1 basal levels and phosphorylation status. Results Analysis of the heterologous mutants indicated that Dfg5p is more important for growth while Dcw1p appeared to play a role in cell wall integrity response. The conditional double mutant was observed to be less resistant to cell wall stress. However, growth of the mutants was similar under control and osmotic stress conditions. The mutants were also able to grow similar to wild type under heat stress. Biofilm formation was reduced in the mutants where DFG5 was deleted or suppressed. Hyphal morphogenesis was reduced although germ tube formation was observed in the biofilms of the mutant strains. Basal Hog1 protein levels were reduced or absent in the DFG5 and DCW1 mutants. However, osmotic stress was able to induce Hog1 protein levels comparable to wild type. Hog1 phosphorylation appeared to be slightly reduced although not significantly. In addition to biofilm assays, serum dose response imaging analysis indicated that hyphae formation in DFG5 and DCW1 mutants was defective. Conclusions These data indicate that DFG5 and DCW1 are required for hyphal morphogenesis and biofilm formation in C. albicans. These functions may be regulated via basal Hog1 MAPK which is required for transcriptional regulation of chitin synthesis

Assessing the Effects of Weather Conditions on Physical Activity Participation Using Objective Measures

Habitual physical activity is an important determinant of health, yet many people are considered to be inactive. Identification of the obstacles to greater participation is necessary for the development of strategies to overcome those obstacles. The weather has been identified as a perceived barrier to participation in physical activity, but exactly which adverse weather conditions are most important, and the extent to which they contribute to decreases in physical activity have rarely been quantified in populations. In the past decade, a small number of studies have used publicly available databases to examine the quantitative effects of weather (e.g., temperature, precipitation, wind) on physical activity in children, adolescents and adults. This review examines our historical, qualitative versus emerging, quantitative understanding of how specific weather conditions affect a population’s activity

Monitoring activities of teenagers to comprehend their habits: study protocol for a mixed-methods cohort study

Abstract: Background: Efforts to increase physical activity in youth need to consider which activities are most likely to be sustained over time in order to promote lifelong participation in physical activity. The Monitoring Activities of Teenagers to Comprehend their Habits (MATCH) study is a prospective cohort study that uses quantitative and qualitative methods to develop new knowledge on the sustainability of specific physical activities. Methods/design: Eight hundred and forty-three grade 5 and 6 students recruited from 17 elementary schools in New Brunswick, Canada, are followed-up three times per year. At each survey cycle, participants complete self-report questionnaires in their classroom under the supervision of trained data collectors. A sub-sample of 24 physically active students is interviewed annually using a semi-structured interview protocol. Parents (or guardians) complete telephone administered questionnaires every two years, and a health and wellness school audit is completed for each school. Discussion: MATCH will provide a description of the patterns of participation in specific physical activities in youth, and enable identification of the determinants of maintenance, decline, and uptake of participation in each activity. These data will inform the development of interventions that take into account which activities are the most likely to be maintained and why activities are maintained or dropped

Thymidine Kinase 2 Deficiency-Induced Mitochondrial DNA Depletion Causes Abnormal Development of Adipose Tissues and Adipokine Levels in Mice

Mammal adipose tissues require mitochondrial activity for proper development and differentiation. The components of the mitochondrial respiratory chain/oxidative phosphorylation system (OXPHOS) are encoded by both mitochondrial and nuclear genomes. The maintenance of mitochondrial DNA (mtDNA) is a key element for a functional mitochondrial oxidative activity in mammalian cells. To ascertain the role of mtDNA levels in adipose tissue, we have analyzed the alterations in white (WAT) and brown (BAT) adipose tissues in thymidine kinase 2 (Tk2) H126N knockin mice, a model of TK2 deficiency-induced mtDNA depletion. We observed respectively severe and moderate mtDNA depletion in TK2-deficient BAT and WAT, showing both tissues moderate hypotrophy and reduced fat accumulation. Electron microscopy revealed altered mitochondrial morphology in brown but not in white adipocytes from TK2-deficient mice. Although significant reduction in mtDNA-encoded transcripts was observed both in WAT and BAT, protein levels from distinct OXPHOS complexes were significantly reduced only in TK2-deficient BAT. Accordingly, the activity of cytochrome c oxidase was significantly lowered only in BAT from TK2-deficient mice. The analysis of transcripts encoding up to fourteen components of specific adipose tissue functions revealed that, in both TK2-deficient WAT and BAT, there was a consistent reduction of thermogenesis related gene expression and a severe reduction in leptin mRNA. Reduced levels of resistin mRNA were found in BAT from TK2-deficient mice. Analysis of serum indicated a dramatic reduction in circulating levels of leptin and resistin. In summary, our present study establishes that mtDNA depletion leads to a moderate impairment in mitochondrial respiratory function, especially in BAT, causes substantial alterations in WAT and BAT development, and has a profound impact in the endocrine properties of adipose tissues

The Actin-Binding Protein Capulet Genetically Interacts with the Microtubule Motor Kinesin to Maintain Neuronal Dendrite Homeostasis

BACKGROUND: Neurons require precise cytoskeletal regulation within neurites, containing microtubule tracks for cargo transport in axons and dendrites or within synapses containing organized actin. Due to the unique architecture and specialized function of neurons, neurons are particularly susceptible to perturbation of the cytoskeleton. Numerous actin-binding proteins help maintain proper cytoskeletal regulation. METHODOLOGY/PRINCIPAL FINDINGS: From a Drosophila forward genetic screen, we identified a mutation in capulet--encoding a conserved actin-binding protein--that causes abnormal aggregates of actin within dendrites. Through interaction studies, we demonstrate that simultaneous genetic inactivation of capulet and kinesin heavy chain, a microtubule motor protein, produces elongate cofilin-actin rods within dendrites but not axons. These rods resemble actin-rich structures induced in both mammalian neurodegenerative and Drosophila Alzheimer's models, but have not previously been identified by loss of function mutations in vivo. We further demonstrate that mitochondria, which are transported by Kinesin, have impaired distribution along dendrites in a capulet mutant. While Capulet and Cofilin may biochemically cooperate in certain circumstances, in neuronal dendrites they genetically antagonize each other. CONCLUSIONS/SIGNIFICANCE: The present study is the first molecularly defined loss of function demonstration of actin-cofilin rods in vivo. This study suggests that simultaneous, seemingly minor perturbations in neuronal dendrites can synergize producing severe abnormalities affecting actin, microtubules and mitochondria/energy availability in dendrites. Additionally, as >90% of Alzheimer's and Parkinson's cases are sporadic this study suggests mechanisms by which multiple mutations together may contribute to neurodegeneration instead of reliance on single mutations to produce disease

Systematic meta-review of supported self-management for asthma: a healthcare perspective

BACKGROUND: Supported self-management has been recommended by asthma guidelines for three decades; improving current suboptimal implementation will require commitment from professionals, patients and healthcare organisations. The Practical Systematic Review of Self-Management Support (PRISMS) meta-review and Reducing Care Utilisation through Self-management Interventions (RECURSIVE) health economic review were commissioned to provide a systematic overview of supported self-management to inform implementation. We sought to investigate if supported asthma self-management reduces use of healthcare resources and improves asthma control; for which target groups it works; and which components and contextual factors contribute to effectiveness. Finally, we investigated the costs to healthcare services of providing supported self-management. METHODS: We undertook a meta-review (systematic overview) of systematic reviews updated with randomised controlled trials (RCTs) published since the review search dates, and health economic meta-analysis of RCTs. Twelve electronic databases were searched in 2012 (updated in 2015; pre-publication update January 2017) for systematic reviews reporting RCTs (and update RCTs) evaluating supported asthma self-management. We assessed the quality of included studies and undertook a meta-analysis and narrative synthesis. RESULTS: A total of 27 systematic reviews (n = 244 RCTs) and 13 update RCTs revealed that supported self-management can reduce hospitalisations, accident and emergency attendances and unscheduled consultations, and improve markers of control and quality of life for people with asthma across a range of cultural, demographic and healthcare settings. Core components are patient education, provision of an action plan and regular professional review. Self-management is most effective when delivered in the context of proactive long-term condition management. The total cost (n = 24 RCTs) of providing self-management support is offset by a reduction in hospitalisations and accident and emergency visits (standard mean difference 0.13, 95% confidence interval -0.09 to 0.34). CONCLUSIONS: Evidence from a total of 270 RCTs confirms that supported self-management for asthma can reduce unscheduled care and improve asthma control, can be delivered effectively for diverse demographic and cultural groups, is applicable in a broad range of clinical settings, and does not significantly increase total healthcare costs. Informed by this comprehensive synthesis of the literature, clinicians, patient-interest groups, policy-makers and providers of healthcare services should prioritise provision of supported self-management for people with asthma as a core component of routine care. SYSTEMATIC REVIEW REGISTRATION: RECURSIVE: PROSPERO CRD42012002694 ; PRISMS: PROSPERO does not register meta-reviews