The profile of patients with venous leg ulcers: A systematic review and global perspective.

BACKGROUND: A holistic profile that includes demographic, medical history and wound characteristics of individuals with venous leg ulceration is lacking. Lack of such a profile negatively impacts the ability to develop interventions to improve patient outcomes. OBJECTIVES: To describe the profile of the patient population with venous leg ulceration from published observational (non-interventional) studies and to identify gaps in the knowledge base for future research in this area. METHODS: A systematic review of observational studies that included more than 50 patients, from any world region, of any age and in any care setting. RESULTS: twenty studies, involving 3395 patients, from all world regions met our criteria. Demographic characteristics were well reported and showed a female to male ratio of 1.2:1, average age of 47-65 years, high levels of co-morbidities including hypertension (53-71%) and diabetes (16-20%), and only one study reporting ethnicity. When reported, approximately 4-30% had high levels of depression. The average wound size was 18.6-43.39 cm2; mean wound duration was 13.8-65.5 months, mean number of recurrences was four. No study reported on demographic factors plus medical history plus wound characteristics together. CONCLUSION: a comprehensive, holistic profile of the population with VLU is lacking. There is a critical need for more comprehensive profiling to enable the development of targeted interventions to improve outcomes.

Diabetic charcot neuroarthropathy: prevalence, demographics and outcome in a regional referral centre.

BACKGROUND: Diabetic Charcot neuroarthropathy (DCN) is a devastating complication for people with diabetes mellitus. The failure to diagnose DCN and institute treatment in the acute phase leads to permanent deformity and significant morbidity. There is a paucity of data on the prevalence and characteristics of patients who have developed this complication of diabetes. AIMS: To determine the prevalence, clinical characteristics and outcomes of patients with DCN from 2006 to 2012. METHODS: Case finding was performed by searching three independent lists for the period 2006-2012 including: SYNGO radiology database, HIPE database of hospital discharges, and, combined list from podiatry, endocrinology, vascular surgery and orthopaedic clinics. A consensus meeting with chart review was undertaken to confirm diagnosis of DCN. A proforma was completed from chart review to determine clinical characteristics, initial treatment and outcomes for patients with DCN. RESULTS: Forty cases of DCN were identified, resulting in an estimated period prevalence of 0.3 %. The majority of patients were male (68 %); most patients had T2DM (73 %). Mean ± SD for age was 58 ± 10 years and mean duration of diabetes was 15 ± 9 years. In the acute phase of DCN, offloading was performed in 50 %. Bisphosphonates were administered to 5 % and surgery undertaken in 5 % of cases. 38 % of patients developed subsequent foot ulceration and 20 % required amputation. CONCLUSIONS: This is the first prevalence estimate of DCN in Ireland. These data suggest diagnosis of DCN is missed in the acute phase. There exists a significant risk of diabetic foot ulceration and amputation with DCN.

Fertility and genomics: comparison of gene expression in contrasting reproductive tissues of female cattle.

To compare gene expression among bovine tissues, large bovine RNA-seq datasets were used, comprising 280 samples from 10 different bovine tissues (uterine endometrium, granulosa cells, theca cells, cervix, embryos, leucocytes, liver, hypothalamus, pituitary, muscle) and generating 260 Gbases of data. Twin approaches were used: an information-theoretic analysis of the existing annotated transcriptome to identify the most tissue-specific genes and a de-novo transcriptome annotation to evaluate general features of the transcription landscape. Expression was detected for 97% of the Ensembl transcriptome with at least one read in one sample and between 28% and 66% at a level of 10 tags per million (TPM) or greater in individual tissues. Over 95% of genes exhibited some level of tissue-specific gene expression. This was mostly due to different levels of expression in different tissues rather than exclusive expression in a single tissue. Less than 1% of annotated genes exhibited a highly restricted tissue-specific expression profile and approximately 2% exhibited classic housekeeping profiles. In conclusion, it is the combined effects of the variable expression of large numbers of genes (73%-93% of the genome) and the specific expression of a small number of genes (<1% of the transcriptome) that contribute to determining the outcome of the function of individual tissues.

Exploring disparities in acute myocardial infarction events between Aboriginal and non-Aboriginal Australians: roles of age, gender, geography and area-level disadvantage.

We investigated disparities in rates of acute myocardial infarction (AMI) between Aboriginal and non-Aboriginal people in the 199 Statistical Local Areas (SLAs) in New South Wales, Australia. Using routinely collected and linked hospital and mortality data from 2002 to 2007, we developed multilevel Poisson regression models to estimate the relative rates of first AMI events in the study period accounting for area of residence. Rates of AMI in Aboriginal people were more than two times that in non-Aboriginal people, with the disparity greatest in more disadvantaged and remote areas. AMI rates in Aboriginal people varied significantly by SLA, as did the Aboriginal to non-Aboriginal rate ratio. We identified almost 30 priority areas for universal and targeted preventive interventions that had both high rates of AMI for Aboriginal people and large disparities in rates.

Use of a fibrin-based system for enhancing angiogenesis and modulating inflammation in the treatment of hyperglycemic wounds.

The complex pathophysiology of chronic ulceration in diabetic patients is poorly understood; diabetes-related lower limb amputation is a major health issue, which has limited effective treatment regimes in the clinic. This study attempted to understand the complex pathology of hyperglycemic wound healing by showing profound changes in gene expression profiles in wounded human keratinocytes in hyperglycemic conditions compared to normal glucose conditions. In the hyper-secretory wound microenvironment of hyperglycemia, Rab18, a secretory control molecule, was found to be significantly downregulated. Using a biomaterial platform for dual therapy targeting the two distinct pathways, this study aimed to resolve the major dysregulated pathways in hyperglycemic wound healing. To complement Rab18, and promote angiogenesis eNOS was also targeted, and this novel Rab18-eNOS therapy via a dynamically controlled 'fibrin-in-fibrin' delivery system, demonstrated enhanced wound closure, by increasing functional angiogenesis and reducing inflammation, in an alloxan-induced hyperglycemic preclinical ear ulcer model of compromised wound healing.

PP033. High blood pressure in pregnancy: an indicator of future health outcomes.

INTRODUCTION: Hypertensive disorders of pregnancy (HDP) remain a leading cause of maternal and perinatal morbidity and mortality worldwide. In Australia approximately 10% of all pregnancies are affected by HDP. There is growing evidence that endothelial damage caused by HDP remains after pregnancy and has long term consequences on maternal health. OBJECTIVES: The aim of our research was to determine the association between HDP and risk of having high blood pressure in later life. METHODS: Self-reported data regarding a physician's diagnosis of HDP and of high blood pressure later in life were obtained from women recruited from the 45 and Up Study, Australia. Relative risks (converted from odds ratios) and 99% confidence intervals were estimated using logistic regression, adjusting for demographic and lifestyle characteristics. RESULTS: A total of 82,164 women were included in the study, of which 9,845 reported having HDP. Women who had HDP had a significantly increased risk of having high blood pressure later in life compared to women who did not have HDP (adjusted relative risk of 2.05, 99% CI 1.99-2.11, p<0.001). The results showed that women who had HDP develop high blood pressure 6.3 years (99% CI 5.85-6.66, p<0.001) earlier compared to women without HDP. CONCLUSION: Women who have HDP are at a greater risk of future onset of high blood pressure compared to women who have a healthy pregnancy. Women with HDP should be monitored closely in the years following pregnancy for early identification and intervention of high blood pressure.

Study on the prevalence of Toxoplasma gondii and Neospora caninum and molecular evidence of Encephalitozoon cuniculi and Encephalitozoon (Septata) intestinalis infections in red foxes (Vulpes vulpes) in rural Ireland.

Thoracic fluid (pleural fluid and clotted blood) from 206 foxes were examined for antibodies to Toxoplasma gondii and 220 thoracic fluid samples were tested for Neospora caninum antibodies using indirect immunofluorescent antibody tests (IFAT). A total of 115 (56%) and six (3%) foxes had antibodies to T. gondii and N. caninum, respectively. The brains from 148 foxes were examined for histological lesions and pathological changes suggestive of parasitic encephalitis were observed in 33 (22%). Two thirds of these foxes had antibodies to T. gondii and one fox had antibodies to both T. gondii and N. caninum. PCR assays carried out on DNA extracted from the 33 brains with histological lesions were negative for N. caninum but one of the brains was positive for T. gondii. Microsporidian DNA was also amplified from the brains of two of these foxes. Sequencing these amplicons revealed 100% homology with Encephalitozoon (Septata) intestinalis in one fox and Encephalitozoon cuniculi in the second fox. This is the first report of Encephalitozoon infections in wildlife in Ireland.

Comparison and validation of three measures of quality of life in patients with pulmonary hypertension.

BACKGROUND: Pulmonary hypertension, when advanced, markedly limits exercise capacity, activities of daily living and quality of life (QoL). No measure of QoL has yet been validated for the assessment of pulmonary hypertension. The aim of the study was to compare the validity of the Minnesota Living with Heart Failure (MLwHF) questionnaire, the Short Form-36 (SF-36) questionnaire and the Australian Quality of Life (AQoL) measure for assessing pulmonary hypertension treatment. METHODS: Eighty-three patients were enrolled in three studies of pulmonary hypertension treatment (treprostinil, bosentan and sildenafil). They were assessed at baseline and 3 months with the MLwHF questionnaire. Treprostinil and bosentan groups also had 6 and 12 months' data. Twenty-one patients in the sildenafil trial completed concurrently, the SF-36 and AQoL measures at baseline and 3 months. QoL scores were correlated with the 6-min walk test distance, New York Heart Association functional class and right heart catheter-derived haemodynamic parameters of the disease for all matching time points and for changes in scores and clinical measurements over time. RESULTS: The MLwHF and SF-36 scores correlated well with the 6-min walk test distance and New York Heart Association functional class, but did not correlate with haemodynamic measurements. MLwHF and SF-36 scores also correlated with the rate of change of the 6-min walk test distance and New York Heart Association functional class over time. CONCLUSION: The MLwHF questionnaire and SF-36 are useful tools for the assessment of QoL in pulmonary hypertension and may be useful in the ongoing evaluation of QoL in the treatment and study of pulmonary hypertension.

Implementation of anticoagulation guidelines in general practice: a practice report.

There is evidence that patients with atrial fibrillation (AF) are not being anticoagulated according to the published guidelines. Difficulty in identifying such patients may partly explain this. In this study, we examined the yield of different methods for detecting people with AF in a single general practice: hospital discharge letters, referrals to cardiology, staff recall of cases, records of relevant prescriptions from the local pharmacist and similar records from the GMS Payments Board. A review of all files of patients over 45 was undertaken as the definitive method of case identification. Recommended anticoagulation guidelines were applied using structured patient interviews. The practice population was 5,473. Sixty-eight patients with AF were identified giving a practice prevalence of 1.2%. The GMS Payment Board records for the prescribing of all specified medications was the most sensitive method (58.8%) with a positive predictive value of 21.6%. Of nine patients without cognitive impairment at consultation, four (44.4%) opted to change to the recommended treatment. Reluctance of patients to adopt current treatment guidelines points to the need for further work in this area.