Management of type 2 diabetes:new and future developments in treatment

The increasing prevalence, variable pathogenesis, progressive natural history, and complications of type 2 diabetes emphasise the urgent need for new treatment strategies. Longacting (eg, once weekly) agonists of the glucagon-like-peptide-1 receptor are advanced in development, and they improve prandial insulin secretion, reduce excess glucagon production, and promote satiety. Trials of inhibitors of dipeptidyl peptidase 4, which enhance the effect of endogenous incretin hormones, are also nearing completion. Novel approaches to glycaemic regulation include use of inhibitors of the sodium-glucose cotransporter 2, which increase renal glucose elimination, and inhibitors of 11ß-hydroxysteroid dehydrogenase 1, which reduce the glucocorticoid effects in liver and fat. Insulin-releasing glucokinase activators and pancreatic-G-protein-coupled fatty-acid-receptor agonists, glucagon-receptor antagonists, and metabolic inhibitors of hepatic glucose output are being assessed. Early proof of principle has been shown for compounds that enhance and partly mimic insulin action and replicate some effects of bariatric surgery.

Synthesis and characterisation of hydrogel polymers for medical applications

A fundamental if poorly understood problem that hydrogels display is the tendency of these contact lens materials to dehydrate, causing certain complications of the corneal epithelium. However, recent studies have indicated that the evaporation rate of water from different hydrogel lenses is the same and the severity of conditions such as corneal staining is controlled by the states of water in the material. A study was therefore undertaken which concluded that increased corneal desiccating staining occurred as the proportion of water existing in the bound state decreased. The possibility of using dehydrated hydrogels as packaging materials with desiccating properties has also been investigated. As hydrogels have a high affinity for water they have adequate ability to function as a moisture scavenger in an enclosed atmosphere. It was concluded that this ability is maximised by a high total water content and an increase in the proportion of this water existing in the bound state for the material when it is fully hydrated. N-vinyl pyrrolidone has a low reactivity in vinyl polymerisation reactions which results in polymers with local domains of the same chemical type which can lead to deposition. As contact lenses comprising of this monomer are susceptible to deposition, a monomer with a higher reactivity in vinyl polymerisations is acryloylmorpholine and its incorporation in favour of NVP is encouraged. Unfortunately a large proportion of high EWC hydrogels are mechanically weak and attempts to increase this property by increasing hydrophobicity or cross-linking results in a decrease in EWC. Monomers with the potential to carry a positive charge were incorporated into a high EWC, AMO-HEMA copolymer and the physical properties were investigated. Although EWC increased, mechanical properties decreased only slightly. Therefore simultaneous incorporation of a positively charged monomer and a negatively charged monomer was investigated. The resulting copolymers showed increased water content and increased initial modulus. A technique for measuring the coefficient of friction of contact lenses during lubrication has been developed.

Impairment of calcium ATPases by high glucose and potential pharmacological protection

The review deals with impairment of Ca2+-ATPases by high glucose or its derivatives in vitro, as well as in human diabetes and experimental animal models. Acute increases in glucose level strongly correlate with oxidative stress. Dysfunction of Ca2+-ATPases in diabetic and in some cases even in nondiabetic conditions may result in nitration of and in irreversible modification of cysteine-674. Nonenyzmatic protein glycation might lead to alteration of Ca2+-ATPase structure and function contributing to Ca2+ imbalance and thus may be involved in development of chronic complications of diabetes. The susceptibility to glycation is probably due to the relatively high percentage of lysine and arginine residues at the ATP binding and phosphorylation domains. Reversible glycation may develop into irreversible modifications (advanced glycation end products, AGEs). Sites of SERCA AGEs are depicted in this review. Finally, several mechanisms of prevention of Ca2+-pump glycation, and their advantages and disadvantages are discussed. © 2013 Informa UK, Ltd.

Health related quality of life and perception of stigmatisation in adolescents living with sickle cell disease in Nigeria:a cross sectional study

Background: Sickle cell disease impacts the physical, emotional and psychological aspects of life of the affected persons, often times exposing them to disease associated stigma from the society and alters the health related quality of life (HRQoL). This study compared the HRQoL of adolescents with sickle cell disease with their healthy peers, identified socio-demographic and clinical factors impacting HRQoL, and determined the extent and effects of SCD related stigma on quality of life. Procedure: We conducted a cross-sectional survey among 160 adolescents, 80 with SCD and 80 adolescents without SCD. Socio-demographic and clinical data were collected using a pre-tested questionnaire. HRQoL was investigated using the Short Form (SF-36v2) Health Survey. SCD perceived stigma was measured using an adaptation of a perceived stigma questionnaire. Results: Adolescents with SCD have significantly worse HRQoL than their peers in all of the most important dimensions of HRQoL (physical functioning, physical roles limitation, emotional roles limitation, social functioning, bodily pain, vitality and general health perception) except mental health. Recent hospital admission and SCD related complication further lowered HRQoL scores. Over seventy percent of adolescents with SCD have moderate to high level of perception of stigmatisation. Hospitalisation, SCD complication, SCD stigma were inversely, and significantly associated with HRQoL. Conclusions: Adolescents living with SCD in Nigeria have lower health related quality of life compared to their healthy peers. They also experience stigma that impacts their HRQoL. Complications of SCD and hospital admissions contribute significantly to this impairment. Pediatr Blood Cancer 2015;62:1245-1251.

Modeling Data for Complications in Diabetics Using Logistic Regression

2010 Mathematics Subject Classification: 62P10.

Interventional radiology and the care of the oncology patient.

Interventional Radiology (IR) is occupying an increasingly prominent role in the care of patients with cancer, with involvement from initial diagnosis, right through to minimally invasive treatment of the malignancy and its complications. Adequate diagnostic samples can be obtained under image guidance by percutaneous biopsy and needle aspiration in an accurate and minimally invasive manner. IR techniques may be used to place central venous access devices with well-established safety and efficacy. Therapeutic applications of IR in the oncology patient include local tumour treatments such as transarterial chemo-embolisation and radiofrequency ablation, as well as management of complications of malignancy such as pain, organ obstruction, and venous thrombosis.

An Automated Surveillance Strategy to Identify Infectious Complications After Cardiac Implantable Electronic Device Procedures.

Background.  The optimum approach for infectious complication surveillance for cardiac implantable electronic device (CIED) procedures is unclear. We created an automated surveillance tool for infectious complications after CIED procedures. Methods.  Adults having CIED procedures between January 1, 2005 and December 31, 2011 at Duke University Hospital were identified retrospectively using International Classification of Diseases, 9th revision (ICD-9) procedure codes. Potential infections were identified with combinations of ICD-9 diagnosis codes and microbiology data for 365 days postprocedure. All microbiology-identified and a subset of ICD-9 code-identified possible cases, as well as a subset of procedures without microbiology or ICD-9 codes, were reviewed. Test performance characteristics for specific queries were calculated. Results.  Overall, 6097 patients had 7137 procedures. Of these, 1686 procedures with potential infectious complications were identified: 174 by both ICD-9 code and microbiology, 14 only by microbiology, and 1498 only by ICD-9 criteria. We reviewed 558 potential cases, including all 188 microbiology-identified cases, 250 randomly selected ICD-9 cases, and 120 with neither. Overall, 65 unique infections were identified, including 5 of 250 reviewed cases identified only by ICD-9 codes. Queries that included microbiology data and ICD-9 code 996.61 had good overall test performance, with sensitivities of approximately 90% and specificities of approximately 80%. Queries with ICD-9 codes alone had poor specificity. Extrapolation of reviewed infectious rates to nonreviewed cases yields an estimated rate of infection of 1.3%. Conclusions.  Electronic queries with combinations of ICD-9 codes and microbiologic data can be created and have good test performance characteristics for identifying likely infectious complications of CIED procedures.

Challenges in the Management of Geriatric Obesity in High Risk Populations.

The global prevalence of obesity in the older adult population is growing, an increasing concern in both the developed and developing countries of the world. The study of geriatric obesity and its management is a relatively new area of research, especially pertaining to those with elevated health risks. This review characterizes the state of science for this "fat and frail" population and identifies the many gaps in knowledge where future study is urgently needed. In community dwelling older adults, opportunities to improve both body weight and nutritional status are hampered by inadequate programs to identify and treat obesity, but where support programs exist, there are proven benefits. Nutritional status of the hospitalized older adult should be optimized to overcome the stressors of chronic disease, acute illness, and/or surgery. The least restrictive diets tailored to individual preferences while meeting each patient's nutritional needs will facilitate the energy required for mobility, respiratory sufficiency, immunocompentence, and wound healing. Complications of care due to obesity in the nursing home setting, especially in those with advanced physical and mental disabilities, are becoming more ubiquitous; in almost all of these situations, weight stability is advocated, as some evidence links weight loss with increased mortality. High quality interdisciplinary studies in a variety of settings are needed to identify standards of care and effective treatments for the most vulnerable obese older adults.

Fear of Falling and Balance Confidence in Older Adults with Diabetes Mellitus

Several determinants of fear of falling (FoF) and low balance confidence overlap with the consequences/complications of diabetes mellitus (DM). FoF is strongly associated with low balance confidence, and balance confidence mediates the relationship between FoF and balance and physical function. The purpose of this thesis was two-fold: (1) to examine the prevalence, severity and determinants of FoF in older adults (aged≥65) with DM, and (2) to evaluate the validity of the short version of the Activities-specific Balance Confidence scale (ABC-6) and its association with balance and postural control in older adults with DM. Three separate studies were conducted of older adults with DM (DM-group) and without DM (noDM-group). Study I revealed that although FoF prevalence adjusted for age and sex was not different between-groups, the DM-group had 8.8% fewer participants in the low and 8.4% more in the high Falls-Efficacy Scale International categories when compared to the noDM-group. Higher FoF severity in the DM-group was associated with poor physical performance, being female, fall history and clinical depressive symptoms. Study II provided evidence of convergent, discriminant and concurrent validity of the ABC-6 for use in older adults with DM with and without diabetic peripheral neuropathy (DPN). Notably, the ABC-6 was more sensitive in detecting subtle differences in balance confidence between the DM-group and noDM-group when compared to the original ABC scale (ABC-16), and can be administered in less time. Study III explored balance confidence (ABC-6) and its association with balance and postural control in older adults with DM. Subtle differences in axial segmental control (i.e., lower trunk roll velocity and higher head-trunk correlations) while walking and lower balance confidence were apparent in the DM-group, even in the absence of DPN, when compared to the noDM-group. Balance confidence partially explained the variance in head-trunk stiffening between-groups, and consequently low balance confidence in older adults with DM may contribute to the dependence on postural control strategies that are normally only utilized in high-risk situations. Findings from this thesis will help to guide the development of protocols for screening and intervention recommendations of patient education and targeted rehabilitation programs for older adults with DM.

Obestatin as a key regulator of metabolism and cardiovascular function with emerging therapeutic potential for diabetes

Obestatin is a 23-amino acid C-terminally amidated gastrointestinal peptide derived from preproghrelin and which forms an alpha helix. Although obestatin has a short biological half-life and is rapidly degraded, it is proposed to exert wide-ranging pathophysiological actions. Whilst the precise nature of many of its effects is unclear, accumulating evidence supports positive actions on both metabolism and cardiovascular function. For example, obestatin has been reported to inhibit food and water intake, body weight gain, and gastrointestinal motility, and to also mediate promotion of cell survival and prevention of apoptosis. Obestatin-induced increases in β-cell mass, enhanced adipogenesis and improved lipid metabolism have been noted along with upregulation of genes associated with β-cell regeneration, insulin production and adipogenesis. Furthermore, human circulating obestatin levels generally demonstrate an inverse association with obesity and diabetes, whilst the peptide has been shown to confer protective metabolic effects in experimental diabetes, suggesting that it may hold therapeutic potential in this setting. Obestatin also appears to be involved in blood pressure regulation and to exert beneficial effects on endothelial function, with experimental studies indicating that it may also promote cardioprotective actions against, for example, ischaemia-reperfusion injury. This review will present a critical appraisal of the expanding obestatin research area and discuss the emerging therapeutic potential of this peptide for both metabolic and cardiovascular complications of diabetes. 

Exercise rehabilitation following intensive care unit discharge for recovery from critical illness: Executive summary of a Cochrane Collaboration systematic review

Skeletal muscle wasting and weakness are major complications of critical illness and underlie the profound physical and functional impairments experienced by survivors after discharge from the intensive care unit (ICU). Exercise-based rehabilitation has been shown to be beneficial when delivered during ICU admission. This review aimed to determine the effectiveness of exercise rehabilitation initiated after ICU discharge on primary outcomes of functional exercise capacity and health-related quality of life. We sought randomized controlled trials, quasi-randomized controlled trials, and controlled clinical trials comparing an exercise intervention commenced after ICU discharge vs. any other intervention or a control or ‘usual care’ programme in adult survivors of critical illness. Cochrane Central Register of Controlled Trials, Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica Database, and Cumulative Index to Nursing and Allied Health Literature databases were searched up to February 2015. Dual, independent screening of results, data extraction, and quality appraisal were performed. We included six trials involving 483 patients. Overall quality of evidence for both outcomes was very low. All studies evaluated functional exercise capacity, with three reporting positive effects in favour of the intervention. Only two studies evaluated health-related quality of life and neither reported differences between intervention and control groups. Meta-analyses of data were precluded due to variation in study design, types of interventions, and selection and reporting of outcome measurements. We were unable to determine an overall effect on functional exercise capacity or health-related quality of life of interventions initiated after ICU discharge for survivors of critical illness. Findings from ongoing studies are awaited. Future studies need to address methodological aspects of study design and conduct to enhance rigour, quality, and synthesis.

Project Pró-Natal: population-based study of perinatal and infant mortality in Natal, Northeast Brazil

RAMOS, Ana Maria de Oliveira et al. Project Pró-Natal: population-based study of perinatal and infant mortality in Natal, Northeast Brazil. Pediatric and Developmental Pathology, v.3, n.1, p.29-35, 2000

Molecular Typing, Virulence Traits and Antimicrobial Resistance of Diabetic Foot Staphylococci

Diabetes mellitus is a major chronic disease that continues to increase significantly. One of the most important and costly complications of diabetes are foot infections that may be colonized by pathogenic and antimicrobial resistant bacteria, harboring several virulence factors, that could impair its successful treatment. Staphylococcus aureus is one of the most prevalent isolate in diabetic foot infections, together with aerobes and anaerobes.

Project Pró-Natal: population-based study of perinatal and infant mortality in Natal, Northeast Brazil

RAMOS, Ana Maria de Oliveira et al. Project Pró-Natal: population-based study of perinatal and infant mortality in Natal, Northeast Brazil. Pediatric and Developmental Pathology, v.3, n.1, p.29-35, 2000

Obstruction and infiltration: a proposal of a quality indicator.

Background The quest for continuous improvement of the quality of provided care is the objective of nursing care. However, the insertion and permanence of a peripheral venous catheter has been associated to complications, thus making a systematic evaluation of the performance of professionals and the management of health services important. Objective: Analyse complications that caused removal of intravenous catheters. Methods A prospective study with 64 patients of a health service of Portugal, from July to September/2015. Included patients with age 18 years, with a peripheral venous catheter. Descriptive analysis using SPSS. Ethical requirements were met. Results Two hundred three (203) intravenous catheters, in 64 patients, most elderly (section 95.3 %), with mean age of 80 years were evaluated. The catheters remained inserted between one and 12 days (mean 2 days), 66 % of the devices were removed because of complications, such as: removal by the patient (17.7 %), obstruction (17.2 %), infiltration (14.8 %), phlebitis (9.4 %) and fluid exiting the insertion site (6.4 %). The prevalence of obstruction and infiltration per patient was respectively 36 % and 39 %. Conclusions Obstruction and infiltration were the complications of higher prevalence that led to the removal and reinsertion of a new peripheral venous catheter with the possibility of increased pain, infection and hospital costs. Faced with the risk of compromising patient safety and being able to contribute to the improvement of health care, we suggest the inclusion of obstruction and infiltration in the indicators of quality of care, in order to have systematic evaluation of results, (re)plan and implement preventive measures.