Publications by authors named "Venkat N Vangaveti"

27 Publications

  • Page 1 of 1

Influence of Ethnicity on Outcomes of Diabetes Inpatient Hypoglycemia: an Australian Perspective.

J Endocr Soc 2020 Feb 31;4(2):bvaa009. Epub 2020 Jan 31.

The Townsville Hospital, Douglas, Queensland, Australia.

Aims: To evaluate outcomes of diabetic inpatient hypoglycemia among Aboriginal and Torres Strait Islander (ATSI) compared with Australian Caucasian patients.

Methods: A retrospective audit of diabetic patients aged > 18 years admitted at a regional hospital general ward between April 1, 2015, and March 31, 2016, was analyzed. The database contains clinical information at the time of admission and initial discharge and readmission within 4 weeks thereafter.

Results: A total of 1618 (of 6027) patients were admitted with diabetes representing 23.7% of the total ward admissions, of which 484 (29.9%) had inpatient hypoglycemia. Of the 91 patients with available data analyzed, ATSI origin with inpatient hypoglycemia was associated with longer length of stay (LOS) (hazard ratio [HR], 2.1, 95% confidence interval [CI], 1.2-3.5), whereas severe hypoglycemia (≤ 2.2 mmol/L) in both ATSI and non-ATSI was significantly associated with longer LOS (HR, 2.3; 95% CI, 1.2-4.2). No significant differences in LOS were found for gender, age, and Carlson comorbidity index (CCI). The adjusted model for likelihood of readmission, gender, indigenous status, and CCI were not significant risk factors for readmission to the hospital. Readmitted patients were older (50-59 years vs < 50 years,  = 0.001; 60-69 years vs < 50 years,  = 0.032; 70+ years vs < 50 years,  = 0.031).

Conclusion: We reported high rate of inpatient hypoglycemia in our study population. Indigenous Australian diabetic patients with inpatient hypoglycemia had significantly longer LOS compared with non-Indigenous Caucasian counterparts. Further prospective studies on a larger population are needed to confirm our findings.
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http://dx.doi.org/10.1210/jendso/bvaa009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7039405PMC
February 2020

A 14-year retrospective analysis of indications and outcomes of autologous haemopoietic stem cell transplantation in regional Queensland: a single-centre experience.

Intern Med J 2020 02;50(2):214-221

Icon Group, Brisbane, Queensland, Australia.

Background: The Townsville Hospital is a tertiary hospital in North Queensland with one of the largest regional transplant centres in Australia, performing primarily autologous haemopoietic stem cell transplants (HSCT) for various haematological malignancies.

Aims: This single-centre, retrospective, observational study aims to describe the activity and outcomes of autologous HSCT at The Townsville Hospital between 2003 and 2017 to verify safety standards.

Methods: Patient-level data were collected, including demographics, frequency and indication for transplant, conditioning, current clinical status and cause of death. Key outcomes included overall survival, non-relapse mortality, incidence of therapy-related neoplasm and causes of death. Progression-free survival in the multiple myeloma (MM) subgroup was also assessed.

Results: There were 319 autologous HSCT in 286 patients, with a median age of 58 years (range 14-71 years); 62% of patients were male. Indications for transplantation were: MM 53.7%, non-Hodgkin lymphoma 29.4%, Hodgkin lymphoma 5.0% and other 11.9%. Causes of death were: disease progression/relapse (65.2%), second malignancy (17.0%), infection (9.8%) and other (8.0%). Non-relapse mortality was 1.2% (95% confidence interval 0.4-3.0) and 3.2% (1.7-5.7) at 100 days and 1 year, respectively, post-HSCT. Overall survival at 2 years was 81.0% (73.8-86.4) for MM and 69.6% (58.8-78.1) for non-Hodgkin lymphoma. The median progression-free survival in the MM cohort was 3.3 years.

Conclusion: The Townsville Hospital transplant centre provides an important transplant service in regional Queensland, with outcomes comparable to national data. We reported a relatively high rate of second malignancy as a cause of death.
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http://dx.doi.org/10.1111/imj.14395DOI Listing
February 2020

Using sacral nerve modulation to improve continence and quality of life in patients suffering from low anterior resection syndrome.

ANZ J Surg 2018 11 22;88(11):E787-E791. Epub 2018 Oct 22.

School of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia.

Background: Sphincter preserving surgery for the treatment of rectal cancer is very often feasible, avoiding a permanent colostomy. It is well recognized that a large proportion of patients will experience altered bowel habit following low anterior resection (LAR). Faecal incontinence is a common symptom associated with LAR syndrome. The aim of this study is to evaluate the long-term improvement in continence and quality of life (QoL) in LAR patients treated with sacral nerve modulation.

Methods: Patients with ongoing faecal incontinence for >1 year after reversal of diverting ileostomy post ultra-LAR were selected for the study. Eligible patients underwent sacral nerve modulator implantation as a two-stage procedure. Bowel diaries and the Cleveland Clinic Faecal Incontinence Score were used to measure faecal incontinence and QoL.

Results: Twelve patients underwent permanent implantation of a sacral nerve stimulator. Median follow-up was 34 months (interquartile range (IQR) 20.25-62.5 months). The median improvement in faecal incontinence was 90% (IQR 76.25-98.75%) and the median improvement in patient QoL was 80% (IQR 71.25-93.75%). Patients who had previously been treated with biofeedback showed a median improvement in incontinence of 75% compared to 90% which was found in patients who had not had prior biofeedback treatment. The mean percentage improvement in patients with an internal anal sphincter defect was 80% compared to 90% seen in patients with an intact sphincter.

Conclusions: The results of this study suggest that sacral nerve modulation should be more widely considered as an effective treatment strategy for patients with faecal incontinence following LAR.
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http://dx.doi.org/10.1111/ans.14871DOI Listing
November 2018

Prevalence of low anterior resection syndrome at a regional Australian centre.

ANZ J Surg 2018 12 17;88(12):E813-E817. Epub 2018 Aug 17.

Division of General Surgery, The Townsville Hospital, Townsville, Queensland, Australia.

Background: With decreasing indication for abdominoperineal resection and an increase in sphincter preserving surgery, there is a growing population of patients who suffer from low anterior resection syndrome (LARS). The aim of this study is to use the LARS score to determine the prevalence of LARS at a regional centre in Australia and determine the effect of short- and long-course neoadjuvant therapy, anastomotic technique and interval from surgery will also be assessed.

Methods: Patients who had undergone an anterior resection (high, low or ultralow) at a regional centre over an 11-year period were identified. Eligible patients were contacted to complete a LARS score questionnaire. Results were analysed to determine the rate of major LARS and possible causative roles of certain patient and treatment-related variables.

Results: A total of 64 of 76 patients (84%) returned completed questionnaires. The prevalence of major LARS was 37.5%. Short-course neoadjuvant therapy appeared to be more likely to be associated with major LARS compared to long course (odds ratio (OR) = 2.4, 95% confidence interval (CI) 0.37-15.3, P = 0.35); however, this did not reach statistical significance. Rates of major LARS appear to decrease slowly over time and J-pouch colonic anastomosis appears to be slightly protective against major LARS (OR = 0.7, 95% CI 0.12-3.9, P = 0.70); however, neither results were statistically significant.

Conclusion: The rate of major LARS at this regional centre is 37.5%. Larger prospective multicentre studies are required to determine impact of variables such as type of neoadjuvant therapy, anastomotic techniques and progression of LARS over time.
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http://dx.doi.org/10.1111/ans.14749DOI Listing
December 2018

Serum procollagen type 1 N propeptide: A novel diagnostic test for diabetic foot osteomyelitis - A case-control study.

J Res Med Sci 2018 30;23:39. Epub 2018 May 30.

Translational Research in Endocrinology and Diabetes (TREAD), College of Medicine and Dentistry, James Cook University, Douglas QLD 4814, Australia.

Background: The objective of the study was to determine whether serum levels of procollagen type 1 propeptide (P1NP), a bone formation turnover marker, differs between diabetic foot ulcer with osteomyelitis (DFO) and diabetic foot ulcers without osteomyelitis serving as controls. It was also aimed to assess the usefulness of P1NP in diagnosing DFO compared to other common inflammatory markers.

Materials And Methods: A case-control study was designed comparing the aforementioned groups. Patients were classified as osteomyelitis and controls based on the International Working Group diagnostic criteria. Serum P1NP and three other inflammatory markers, namely, C-reactive protein (CRP), white blood cells (WBC), and platelets were analyzed on patients with DFO and controls.

Results: The mean serum P1NP levels were significantly higher in the DFO group (: 16), 10.5 ± 5.2 (ng/ml), than the control group (: 11) 3.1 ± 2.8 (ng/ml), = 0.001. P1NP showed the highest sensitivity/specificity 86.7%/80% compared to 70.6%/80%, 56.2%/45.4%, and 50%/37% for CRP, WBC and platelets, respectively. Receiver operator characteristic curves showed the best value of area under the curve of 0.9 for P1NP compared to 0.85, 0.54, and 0.46 for CRP, WBC, and platelets.

Conclusion: We found marked elevation of serum P1NP in diabetic foot ulcer with bone infection with potential value in using it to diagnose DFO.
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http://dx.doi.org/10.4103/jrms.JRMS_810_16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5996568PMC
May 2018

A meta-analysis of the prevalence of Low Anterior Resection Syndrome and systematic review of risk factors.

Int J Surg 2018 Aug 22;56:234-241. Epub 2018 Jun 22.

James Cook University, School of Medicine and Dentistry, 4814, Queensland, Australia. Electronic address:

Aim: To summarize the reported prevalence and causative factors of Low Anterior Resection Syndrome (LARS) from studies using the LARS score.

Methods: A systematic literature search was conducted using Pubmed, Ovid Medline and the Cochrane database. Searches were performed using a combination of MeSH (medical subject headings) terms and key terms. Studies that were included used the LARS score as their primary collection tool. Studies were excluded if initial surgery was not for malignancy, or if the majority of LARS scores were from patients less than 1 year post initial surgery or closure of diverting stoma. Eligible studies were assessed with a validated quality assessment tool prior to performing a meta-analysis with quality effects model. Meta-analysis was conducted with prevalence estimates that had been transformed using the double arcsine method.

Results: Following the initial search and implementation of inclusion and exclusion criteria 11 studies were deemed suitable for meta-analysis. Meta-analysis found the estimated prevalence of major LARS was 41% (95% CI 34 -48). Where possible outlier studies were excluded, the prevalence was 42% (95%CI 35-48). Radiotherapy and tumour height were the most consistently assessed variables, both showing a consistent negative effect on bowel function. Defunctioning ileostomy was found to have a statically significant negative impact on bowel function in 4 of 11 studies. The majority of reported data has been produced by groups in Denmark and the United Kingdom with limited numbers provided by other locations. Available data is heterogenous with some variables having limited numbers, making meta-analysis of certain variables impossible.

Conclusions: There is significant prevalence of Low Anterior Resection Syndrome following oncological rectal resection. A low anastomotic height or history of radiotherapy are major risk factors.
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http://dx.doi.org/10.1016/j.ijsu.2018.06.031DOI Listing
August 2018

Response to: Comment on "Prevalence and Risk Factors for Diabetic Lower Limb Amputation: A Clinic-Based Case Control Study".

J Diabetes Res 2018 20;2018:1908140. Epub 2018 Feb 20.

Department of Diabetes and Endocrinology, The Townsville Hospital and College of Medicine and Dentistry, James Cook University, 100 Angus Smith Drive, Douglas, QLD 4814, Australia.

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http://dx.doi.org/10.1155/2018/1908140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5838490PMC
May 2019

Delays in lung cancer management pathways between rural and urban patients in North Queensland: a mixed methods study.

Intern Med J 2018 Oct;48(10):1228-1233

College of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia.

Background: Despite advances in medical therapies, disparity in outcome between rural and urban patients remain in Australia and many Western countries.

Aims: To examine time delays in lung cancer referral pathways in North Queensland (NQ), Australia, and explore patients' perspective of factors causing these delays.

Methods: Prospective study of patients attending three cancer centres in Townsville, Cairns and Mackay in NQ from 2009 to 2012. Times along referral pathway were divided as follows: Onset of symptoms to treatment (T1), symptoms to general practitioner (GP) (T2), GP to specialist (T3) and Specialist to treatment (T4). Quantitative and qualitative methods were used for analysis.

Results: In total, 252 patients were participated. T1 was influenced by remoteness (125 days in Townsville vs 170 days for remote, P = 0.01), T2 by level of education (91 days for primary education vs 61 days for secondary vs 23 days for tertiary/Technical and Further Education (TAFE), P = 0.006), and age group (14 days for 31-50 years, 61 days for 51-70 years, 45 days for >71 years, P = 0.026), T3 by remoteness (15 days for Townville and 29.5 days for remote, P = 0.02) and T4 by stage of disease (21 days for Stage I, 11 days for Stage II, 34 days for Stage III 18 days for Stage IV, P = 0.041). Competing priorities of family and work and cost and inconvenience of travel were perceived as rural barriers.

Conclusion: Remoteness, age and level of education were related to delays in various time lines in lung cancer referral pathways in NQ. Provision of specialist services closer to home may decrease delays by alleviating burden of cost and inconvenience of travel.
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http://dx.doi.org/10.1111/imj.13934DOI Listing
October 2018

Ophthalmological injuries associated with fractures of the orbitozygomaticomaxillary complex.

Br J Oral Maxillofac Surg 2018 04 2;56(3):221-226. Epub 2018 Mar 2.

Maxillofacial Department, The Townsville Hospital, Townsville, Queensland, Australia.

Our aim was to evaluate ophthalmological injuries associated with fractures of the orbitozygomaticomaxillary complex that required operative treatment, and we collected data retrospectively over a period of five years (2012-2016 inclusive). Of the 190 patients, 162 were male with a median age of 31 (IQR 25 -39) years. Assault was the most common mechanism of injury (125/190, 66%). Minor ophthalmic injuries (those unlikely to cause permanent visual disturbance) and major ophthalmic injuries (those with the potential to cause permanent visual disturbance) were recorded. The common minor ophthalmic injuries were: diplopia, enophthalmos, proptosis, subconjunctival haemorrhage, and restriction of the extraocular muscles. Commotio retinae, traumatic mydriasis, retro-orbital haemorrhage, and hyphaema were the common major ophthalmic injuries. All 13 different major ophthalmic injuries were recorded in the group who had had orbital fractures reconstructed, which suggested that more intraocular damage can be caused by this type of fracture than by others. Visual acuity was reduced in 26/190 patients with only four having persistent postoperative changes at six weeks. The odds ratio for those patients who had a major ophthalmological injury and were unable to drive was 0.07 (95% CI 0.02 to 0.21, p=0.001), which was highly significant. Ophthalmological assessment is strongly recommended for patients with fractures of the orbitozygomaticomaxillary complex.
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http://dx.doi.org/10.1016/j.bjoms.2018.02.009DOI Listing
April 2018

Diabetic ketoacidosis incidence in children at first presentation of type 1 diabetes at an Australian regional hospital: The effect of health professional education.

Pediatr Diabetes 2018 08 24;19(5):993-999. Epub 2018 Mar 24.

Paediatric Unit, The Townsville Hospital, Townsville, Queensland, Australia.

Background: Diabetic ketoacidosis (DKA) is an acute life threatening, resource intensive preventable complication of type 1 diabetes which has major biopsychosocial effects on patients and families. Incidence of pediatric DKA has been studied nationally and internationally in metropolitan centers. This study analyzed the DKA incidence at first presentation of type 1 diabetes at Townsville Hospital, before and after an educational intervention. This is the first study of its kind in a regional center in Queensland, Australia.

Method: The inclusion criteria consisted of children (0-18 years) diagnosed with type 1 diabetes from January, 2006 to December, 2016. Medical and laboratory patient data was retrospectively collected. Quantitative analysis was conducted using SPSS. Education sessions were delivered to health professionals by a pediatric endocrinologist during 2015 and 2016. DKA and its severity were defined by the International Society of Pediatric Diabetes 2014 Guidelines.

Results: In total, 106 patients met inclusion criteria. Average incidence of DKA at first presentation of type 1 diabetes was 48.10%. Pre- and post-intervention incidences were 54.90% and 25%, respectively (P = 0.01). DKA severity pre- and post-intervention were severe (48.88%, 33.33%), moderate (26.67%, 16.67%), and mild (24.44%, 50%), respectively (P = 0.53).

Conclusions: DKA incidence at first presentation of type 1 diabetes prior to intervention, is higher than that reported by other studies in Australia: Brisbane (31.8%) and Sydney (37.7%). DKA incidence at first presentation of type 1 diabetes decreased significantly during the period of health professional education.
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http://dx.doi.org/10.1111/pedi.12666DOI Listing
August 2018

Intravenous versus oral paracetamol for acute pain in adults in the emergency department setting: a prospective, double-blind, double-dummy, randomised controlled trial.

Emerg Med J 2018 Mar 15;35(3):179-184. Epub 2017 Dec 15.

College of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia.

Objective: To determine if intravenous paracetamol was superior to oral paracetamol as an adjunct to opioids in the management of moderate to severe pain in the ED setting.

Methods: A prospective, randomised, double-blind, double-dummy, controlled trial was conducted at a single academic tertiary care ED. Adult patients with moderate to severe pain were randomly assigned to receive either the intravenous paracetamol or oral paracetamol. The primary outcome was Visual Analogue Scale (VAS) pain reduction at 30 min. A clinically significant change in pain was defined as 13 mm.

Results: 87 participants were included in the final analysis, with a median age of 43.5 years and 59.8% were female. Overall mean baseline VAS pain score was 67.9 mm (±16.0). Both formulations achieved a clinically significant mean pain score reduction at 30 min, with no significant difference between the groups with 16.0 mm (SD 19.1 mm) in the intravenous group and 14.6 mm (SD 26.4) in the oral group; difference -1.4 mm (95% CI -11.6 to 8.8, P=0.79). Secondary outcomes, including postintervention intravenous opioid administration, patient satisfaction, side effects and length of stay, did not differ between groups.

Conclusions: Overall, there was a small but clinically significant decrease in pain in each group. No superiority was demonstrated in this trial with intravenous paracetamol compared with oral paracetamol in terms of efficacy of analgesia and no difference in length of stay, patient satisfaction, need for rescue analgesia or side effects.
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http://dx.doi.org/10.1136/emermed-2017-206787DOI Listing
March 2018

Transcutaneous oximetry measurements of the leg: comparing different measuring equipment and establishing values in healthy young adults.

Diving Hyperb Med 2017 Jun;47(2):82-87

College of Medicine and Dentistry, James Cook University, Queensland, Australia.

Introduction: Transcutaneous oximetry measurement (TCOM) is a non-invasive method of determining oxygen tension at the skin level using heated electrodes.

Aim: To compare TCOM values generated by different machines and to establish lower limb TCOM values in a cohort of healthy individuals younger than 40 years of age.

Method: Sixteen healthy, non-smoking volunteers aged 18 to 39 years were recruited. TCOM was obtained at six locations on the lower leg and foot using three different Radiometer machines. Measurements were taken with subjects lying supine, breathing air.

Results: Except for one sensor site, there were no statistical differences in measurements obtained by the different TCOM machines. There was no statistical difference in measurements comparing left and right legs. Room air TCOM values for the different lower leg sites were (mean (SD) in mmHg): lateral leg 61.5 (9.2); lateral ankle 61.1 (9.7); medial ankle 59.1 (10.8); foot, first and second toe 63.4 (10.6); foot, fifth toe 59.9 (13.2) and plantar foot 74.1 (8.8). The overall mean TCOM value for the lower limb was 61 (10.8; 95% confidence intervals 60.05-62.0) mmHg.

Conclusion: Lower-leg TCOM measurements using different Radiometer TCOM machines were comparable. Hypoxia has been defined as lower-leg TCOM values of less than 40 mmHg in non-diabetic patients and this is supported by our measurements. The majority (96.9%) of the lower leg TCOM values in healthy young adults are above the hypoxic threshold.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6147223PMC
http://dx.doi.org/10.28920/dhm47.2.82-87DOI Listing
June 2017

Emerging Therapeutic Potential of Nanoparticles in Pancreatic Cancer: A Systematic Review of Clinical Trials.

Biomedicines 2016 Aug 19;4(3). Epub 2016 Aug 19.

Townsville Cancer Centre, The Townsville Hospital, Townsville QLD 4814, Australia.

Pancreatic cancer is an aggressive disease with a five year survival rate of less than 5%, which is associated with late presentation. In recent years, research into nanomedicine and the use of nanoparticles as therapeutic agents for cancers has increased. This article describes the latest developments in the use of nanoparticles, and evaluates the risks and benefits of nanoparticles as an emerging therapy for pancreatic cancer. The Preferred Reporting Items of Systematic Reviews and Meta-Analyses checklist was used. Studies were extracted by searching the Embase, MEDLINE, SCOPUS, Web of Science, and Cochrane Library databases from inception to 18 March 2016 with no language restrictions. Clinical trials involving the use of nanoparticles as a therapeutic or prognostic option in patients with pancreatic cancer were considered. Selected studies were evaluated using the Jadad score for randomised control trials and the Therapy CA Worksheet for intervention studies. Of the 210 articles found, 10 clinical trials including one randomised control trial and nine phase I/II clinical trials met the inclusion criteria and were analysed. These studies demonstrated that nanoparticles can be used in conjunction with chemotherapeutic agents increasing their efficacy whilst reducing their toxicity. Increased efficacy of treatment with nanoparticles may improve the clinical outcomes and quality of life in patients with pancreatic cancer, although the long-term side effects are yet to be defined. The study registration number is CRD42015020009.
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http://dx.doi.org/10.3390/biomedicines4030020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5344258PMC
August 2016

Prevalence and Risk Factors of Lower Limb Amputation in Patients with End-Stage Renal Failure on Dialysis: A Systematic Review.

Int J Nephrol 2016 27;2016:4870749. Epub 2016 Jul 27.

School of Medicine and Dentistry, James Cook University, Townsville, QLD 4811, Australia.

Background. Renal dialysis has recently been recognised as a risk factor for lower limb amputation (LLA). However, exact rates and associated risk factors for the LLA are incompletely understood. Aim. Prevalence and risk factors of LLA in end-stage renal failure (ESRF) subjects on renal dialysis were investigated from the existing literature. Methods. Published data on the subject were derived from MEDLINE, PubMed, and Google Scholar search of English language literature from January 1, 1980, to July 31, 2015, using designated key words. Results. Seventy studies were identified out of which 6 full-text published studies were included in this systematic review of which 5 included patients on haemodialysis alone and one included patients on both haemodialysis and peritoneal dialysis. The reported findings on prevalence of amputation in the renal failure on dialysis cohort ranged from 1.7% to 13.4%. Five out of the six studies identified diabetes as the leading risk factor for amputation in subjects with ESRF on renal dialysis. Other risk factors identified were high haemoglobin A1c, elevated c-reactive protein, and low serum albumin. Conclusions. This review demonstrates high rate of LLA in ESRF patients receiving dialysis therapy. It has also identified diabetes and markers of inflammation as risk factors of amputation in ESRF subjects on dialysis.
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http://dx.doi.org/10.1155/2016/4870749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4978825PMC
August 2016

Prevalence and Risk Factors for Diabetic Lower Limb Amputation: A Clinic-Based Case Control Study.

J Diabetes Res 2016 29;2016:5941957. Epub 2016 Jun 29.

Department of Diabetes and Endocrinology, The Townsville Hospital and College of Medicine and Dentistry, James Cook University, 100 Angus Smith Drive, Douglas, QLD 4814, Australia.

Objective. The aim of the study was to evaluate the prevalence of and risk factors for lower limb amputation in a specialist foot clinic-based setting. Methods. A retrospective quantitative study was conducted, using clinical and biochemical profiles of diabetic foot patients attending the High Risk Foot Clinic at The Townsville Hospital, Australia, between January 1, 2011, and December 31, 2013. Results. The total study sample included 129 subjects, comprising 81 males and 48 females with M : F ratio of 1.7 : 1. Twenty-three subjects were Indigenous Australians, representing 17.8% of the study population. The average age of the cohort was 63.4 years ± 14.1 years [CI 90.98-65.89]. Lower limb amputation was identified as a common and significant outcome (n = 44), occurring in 34.1%, more commonly amongst the Indigenous Australians (56.5% versus 29.2%; p = 0.94, OR 0.94). Risk factors most closely associated with amputation included diabetic retinopathy (p = 0.00, OR 4.4), coronary artery bypass graft (CABG) surgery (p = 0.01, OR 4.1), Charcot's arthropathy (p = 0.01, OR 2.9), and Indigenous ethnicity (p = 0.01, OR 3.4). Although average serum creatinine, corrected calcium, and glycosylated haemoglobin A1c (Hba1c) levels were higher amongst amputees they were statistically insignificant. Conclusions. Lower limb amputation is a common outcome and linked to ethnicity and neurovascular diabetic complications amongst subjects with diabetic foot ulcer. Further research is needed to identify why risk of lower limb amputation seems to differ according to ethnicity.
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http://dx.doi.org/10.1155/2016/5941957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4942664PMC
June 2017

Genetic and molecular basis of diabetic foot ulcers: Clinical review.

J Tissue Viability 2016 Nov 25;25(4):229-236. Epub 2016 Jun 25.

Translational Research on Endocrinology and Diabetes [TREAD], College of Medicine and Dentistry, James Cook University, QLD, Australia. Electronic address:

Diabetic Foot Ulcers (DFUs) are major complications associated with diabetes and often correlate with peripheral neuropathy, trauma and peripheral vascular disease. It is necessary to understand the molecular and genetic basis of diabetic foot ulcers in order to tailor patient centred care towards particular patient groups. This review aimed to evaluate whether current literature was indicative of an underlying molecular and genetic basis for DFUs and to discuss clinical applications. From a molecular perspective, wound healing is a process that transpires following breach of the skin barrier and is usually mediated by growth factors and cytokines released by specialised cells activated by the immune response, including fibroblasts, endothelial cells, phagocytes, platelets and keratinocytes. Growth factors and cytokines are fundamental in the organisation of the molecular processes involved in making cutaneous wound healing possible. There is a significant role for single nucleotide polymorphism (SNPs) in the fluctuation of these growth factors and cytokines in DFUs. Furthermore, recent evidence suggests a key role for epigenetic mechanisms such as DNA methylation from long standing hyperglycemia and non-coding RNAs in the complex interplay between genes and the environment. Genetic factors and ethnicity can also play a significant role in the development of diabetic neuropathy leading to DFUs. Clinically, interventions which have improved outcomes for people with DFUs or those at risk of DFUs include some systemic therapeutic drug interventions which improve microvascular blood flow, surgical interventions, human growth factors, and hyperbaric oxygen therapy, negative pressure wound therapy, skin replacement or shockwave therapy and the use of topical treatments. Future treatment modalities including stem cell and gene therapies are promising in the therapeutic approach to prevent the progression of chronic diabetic complications.
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http://dx.doi.org/10.1016/j.jtv.2016.06.005DOI Listing
November 2016

Non-traumatic lower limb amputation in patients with end-stage renal failure on dialysis: an Australian perspective.

Ren Fail 2016 Aug 8;38(7):1036-43. Epub 2016 Jun 8.

a School of Medicine and Dentistry, James Cook University , Townsville , Australia.

Background: End-stage renal failure (ESRF) and dialysis have been identified as a risk factor for lower limb amputations (LLAs). High rate of ESRF amongst the Australian population has been reported, however till date no study has been published identifying magnitude and risk factors of LLA in subjects on renal dialysis.

Objective: The study aims to document trends in the prevalence and identify risk factors of non-traumatic LLA in Australian patients on dialysis.

Methods: A retrospective review of all patients (218) who attended the regional dialysis center between 1st January 2009 and 31st December 2013 was conducted. Demographic, clinical and biochemical data were analyzed.

Results: We identified a high prevalence of 13.3% of LLAs amongst Australian patients with ESRF on dialysis at our center. The associated risk factors were the presence of diabetes (OR 1.67 [1.49-1.88] p < 0.001), history of foot ulceration (OR 81 [18.20-360.48] p < 0.001), peripheral arterial disease (OR 31.29 [9.02-108.56] p < 0.001), peripheral neuropathy (OR 31.29 [9.02-108.56] p < 0.001), foot deformity (OR 23.62 [5.82-95.93] p < 0.001), retinopathy (OR 6.08 [2.64-14.02] p < 0.001), dyslipidemia (OR 4.6 [1.05-20.05] p= 0.049) and indigenous background (OR 3.39 [1.38-8.33] p= 0.01). 75% of the amputees had aboriginal heritage. We also identified higher HbA1c and CRP levels as well as low serum albumin, hemoglobin and vitamin D levels to have a strong association with LLAs (p < 0.05).

Conclusion: There is high prevalence of LLAs amongst Australian indigenous patients with diabetes on dialysis in North Queensland. Other strongly associated risk factors include history of foot ulceration, foot deformity and peripheral neuropathy as well as high HbA1c levels and low serum albumin levels.
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http://dx.doi.org/10.1080/0886022X.2016.1193872DOI Listing
August 2016

Role of telehealth in diabetic foot ulcer management - A systematic review.

Aust J Rural Health 2016 Aug 21;24(4):224-9. Epub 2016 Apr 21.

Translational Research in Endocrinology and Diabetes [TREAD], James Cook University, Townsville, Queensland, Australia.

Objectives: To review the use of telehealth in subjects with diabetic foot ulcer; evaluating its clinical outcomes, diagnostic accuracy, cost-effectiveness and behavioural perceptions.

Design: Systematic review.

Setting: Selected studies were conducted in Australia, USA, the Netherlands, Denmark, Poland and UK.

Participants: A total of 948 identified studies were evaluated against the inclusion criteria. Eleven eligible studies were included for review. Patients with diabetic foot ulcer had to have telehealth guided management.

Main Outcome Measures: Telehealth systems were evaluated against at least one of the following: clinical implications on ulcer healing and disease prognosis; diagnostic accuracy; cost-effectiveness; behavioural perceptions among health professionals or patients.

Result: Eleven eligible studies were included for review. Studies that evaluated telehealth against clinical outcomes were underpowered by study design, sample sizes and short duration follow-up. Telehealth systems demonstrated good intra- and inter-observer reproducibility, high diagnostic accuracy and agreement with live assessments. Authors rationalised the cost-effectiveness of their respective telehealth systems, but could not support this with long-term cost analysis. Both patient and health professionals responded positively towards telehealth in surveys and face-to-face interviews.

Conclusion: Telehealth yields high diagnostic accuracy, reproducibility and positive behavioural perceptions. However, it is not clear if telehealth use in diabetic foot management has favourable clinical and economic outcomes. More long-term prospective controlled trials on larger populations are needed to further characterise our findings.
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http://dx.doi.org/10.1111/ajr.12284DOI Listing
August 2016

Geographical access to radiation therapy in North Queensland: a retrospective analysis of patient travel to radiation therapy before and after the opening of an additional radiotherapy facility.

Rural Remote Health 2016 Jan-Mar;16(1):3640. Epub 2016 Mar 10.

College of Medicine and Dentistry, School of Medicine, James Cook University, Townsville, Queensland, Australia.

Introduction: Access to radiation therapy (RT) underlies optimal care for prostate and breast cancer patients. This study investigates the impact of opening a new RT clinic on distance and road travel time to RT, and overall utilisation for prostate and breast cancer patients over a 3-year period in North Queensland (NQ), Australia.

Methods: The study used retrospective audit of two radiotherapy databases and a geographic information system to illustrate patient origins and distance to the RT clinic used over 3 years. Prostate and female breast cancer patients were selected from the radiation oncology databases of The Townsville Hospital (TTH) and Radiation Oncology Queensland (ROQ) Cairns between 1 July 2010 and 30 June 2013. Distance from a patient's home origin to the RT facility was mapped using a geographic information system (ArcGIS software), and travel time (minutes) and road distance (km) determined by Google Maps road directions.

Results: Overall number of prostate and breast cancer patients treated by RT in Cairns and Townsville clinics increased by 16% in 2011-2012 and by 29% in 2012-2013 from year 1 values. In 2010, 44% of the patients travelled 200-400 km to RT, which reduced to 21% in 2013. By 2013, with a second treatment facility, more than 70% of patients lived within 200 km of an RT facility (p<0.0001). Total median road travel time reduced annually from 201 minutes in 2010-2011 to 66 minutes in 2011-2012 and 56 minutes in 2012-2013 (p<0.0001), corresponding to a decrease in the median distance travelled to an RT facility.

Conclusions: An additional RT facility in NQ has led to an increase in patients treated with RT for prostate and breast cancer and, on average, less travel distance and time to treatment, suggesting improvement in access to RT in NQ.
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October 2016

Individual male perception of female genitalia.

Int Urogynecol J 2016 Feb 9;27(2):307-13. Epub 2015 Sep 9.

James Cook University Townsville, Douglas, QLD, Australia.

Introduction And Hypothesis: Australian Medicare data show that the rates of cosmetic labiaplasty have tripled over the last decade; however, there is little understanding about the social factors that contribute to the popularity of female genital cosmetic surgeries (FGCS). The aim of this study was to investigate male perception of female genitalia and to assess men's awareness of FGCS and whether these surgeries are viewed as a positive and acceptable option.

Methods: A cross-sectional study of male adults in the Townsville region was conducted via an online questionnaire.

Results: A total of 500 online surveys were sent out and 248 respondents were included in the study; 49.2 % of participants do not have a preferred appearance of labia minora and 70.4 % of men are aware of FGCS, but 53.8 % do not believe that FGCS is a good option for women. Only 14 % of men supported genital cosmetic surgery, while 29.6 % are undecided about the practice. The most common preferred pubic hair appearance is completely hairless (45 %).

Conclusions: This study indicates that the majority of men do not have a preferred appearance for female genitalia, nor do they support FGCS or consider discussing genital surgery with their partner. The major limitation of the study is that the participants' age distribution was skewed heavily towards the younger demographic, with 18- to 24-year-old men comprising 81.5 % of respondents.
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http://dx.doi.org/10.1007/s00192-015-2836-0DOI Listing
February 2016

Dipeptidyl peptidase-4 inhibitors and their potential role in the management of atherosclerosis--A review.

Diabetes Metab Syndr 2015 Oct-Dec;9(4):223-9. Epub 2015 Jun 2.

Translational Research on Endocrinology and Diabetes [TREAD], School of Medicine and Dentistry, James Cook University Townsville, Australia. Electronic address:

Background: Dipeptidyl peptidase-4 (DPP-4) inhibitors are a relatively new class of anti-diabetic drugs that have therapeutic potential in the management of atherosclerosis. Of the numerous DPP-4 inhibitors in clinical practice no studies have been conducted to compare their anti-atherosclerotic effects despite growing evidence of their usefulness in the high risk population.

Objective: The aim of the study was to review the anti-athero-thrombotic effects of DPP-4 inhibitors in atherosclerotic diseases.

Method: A literature search was conducted on MEDLINE and the COCHRANE Library using the terms "DPP-4 Inhibitors", "atherosclerosis", "GLP", "inflammation", "cytokines", "stroke", "ischaemic heart disease", "hypertension" and "peripheral vascular disease". A mathematical model devised by us was used to derive and compare the anti-inflammatory effects of the DPP-4 inhibitors using protective score [PS]. Data was analysed for alogliptin, linagliptin, saxagliptin, sitagliptin, and vildagliptin.

Results: Sixty two published studies collected in the search were assessed for relevance to this study. Sitagliptin had the highest PS [n=5] while linagliptin and saxagliptin yielded the lowest PS [n=1]. This comparison and scoring system was limited to the data collected; which did not investigate for all athero-thrombotic factors selected in this study.

Conclusion: The findings suggest potential usefulness of DPP-4 in atherosclerotic diseases. It also reflected a possible superiority of sitagliptin over the other DPP-4 inhibitors in the management of atherosclerosis. Further investigations are required to establish specific inflammatory cytokines influenced by the DPP-4 inhibitors and to elucidate their clinical application in athero-thrombotic disease.
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http://dx.doi.org/10.1016/j.dsx.2015.04.005DOI Listing
September 2016

Wound healing effects of dipeptidyl peptidase-4 inhibitors: An emerging concept in management of diabetic foot ulcer-A review.

Diabetes Metab Syndr 2016 Apr-Jun;10(2):113-9. Epub 2015 Apr 25.

Translational Research in Endocrinology and Diabetes [TREAD], College of Medicine and Dentistry, James Cook University, The Townsville Hospital, 100 Angus Smith Drive, Douglas 4814, QLD, Australia. Electronic address:

Objective: Dipeptidyl peptidase-4 (DPP-4) inhibitors have a well-known effect on glycaemic control in patients with diabetes but little is known on their wound healing role in this group of population. This paper reviews the effects of DPP-4 inhibitors on wound healing of diabetic foot ulcers.

Methods: Published data on effects and mechanism of DDP-4 inhibitors on wound healing were derived from Medline, PubMed and Google Scholar search of English language literature from 1994 to 2014 using the key words such as "DPP-4 inhibitors", "endothelial healing" "diabetes" and "chronic ulcers".

Results: DPP-4 inhibitors show a potential benefit in processes of wound healing in diabetic chronic foot ulcers. The enzyme inhibitors promote recruitment of endothelial progenitor cells and allow the final scaffolding of wounds. Furthermore DPP-4 inhibitors augment angiogenesis and have widespread effects on optimising the immune response to persistent hypoxia in chronic diabetes wounds.

Conclusion: DPP-4 inhibitors show promise in the local wound healing of diabetic foot ulcers in addition to its already established glycaemic control. In the light of high rate of amputations due to non-healing ulcers with profound psychological and economical liability, more investigations on the usefulness of DPP-4 inhibitors in the high risk diabetes population are needed.
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http://dx.doi.org/10.1016/j.dsx.2015.04.006DOI Listing
February 2017

Hydroxyoctadecadienoic acids: Oxidised derivatives of linoleic acid and their role in inflammation associated with metabolic syndrome and cancer.

Eur J Pharmacol 2016 Aug 15;785:70-76. Epub 2015 May 15.

College of Medicine and Dentistry, James Cook University, Queensland 4811, Australia; Townsville Hospital, Department of Diabetes & Endocrinology, 100 Angus Smith Drive, Townsville, Queensland 4814, Australia.

Linoleic acid (LA) is a major constituent of low-density lipoproteins. An essential fatty acid, LA is a polyunsaturated fatty acid, which is oxidised by endogenous enzymes and reactive oxygen species in the circulation. Increased levels of low-density lipoproteins coupled with oxidative stress and lack of antioxidants drive the oxidative processes. This results in synthesis of a range of oxidised derivatives, which play a vital role in regulation of inflammatory processes. The derivatives of LA include, hydroxyoctadecadienoic acids, oxo-​octadecadienoic acids, epoxy octadecadecenoic acid and epoxy-keto-octadecenoic acids. In this review, we examine the role of LA derivatives and their actions on regulation of inflammation relevant to metabolic processes associated with atherogenesis and cancer. The processes affected by LA derivatives include, alteration of airway smooth muscles and vascular wall, affecting sensitivity to pain, and regulating endogenous steroid hormones associated with metabolic syndrome. LA derivatives alter cell adhesion molecules, this initial step, is pivotal in regulating inflammatory processes involving transcription factor peroxisome proliferator-activated receptor pathways, thus, leading to alteration of metabolic processes. The derivatives are known to elicit pleiotropic effects that are either beneficial or detrimental in nature hence making it difficult to determine the exact role of these derivatives in the progress of an assumed target disorder. The key may lie in understanding the role of these derivatives at various stages of development of a disorder. Novel pharmacological approaches in altering the synthesis or introduction of synthesised LA derivatives could possibly help drive processes that could regulate inflammation in a beneficial manner. Chemical Compounds: Linoleic acid (PubChem CID: 5280450), 9- hydroxyoctadecadienoic acid (PubChem CID: 5312830), 13- hydroxyoctadecadienoic acid (PubChem CID: 6443013), 9-oxo-​octadecadienoic acid (PubChem CID: 3083831), 13-oxo-​octadecadienoic acid (PubChem CID: 4163990), 9,10-epoxy-12-octadecenoate (PubChem CID: 5283018), 12,13-epoxy-9-keto-10- trans -octadecenoic acid (PubChem CID: 53394018), Pioglitazone (PubChem CID: 4829).
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http://dx.doi.org/10.1016/j.ejphar.2015.03.096DOI Listing
August 2016

Short-chain fatty acids increase expression and secretion of stromal cell-derived factor-1 in mouse and human pre-adipocytes.

Hormones (Athens) 2014 Oct-Dec;13(4):532-42. Epub 2014 Nov 5.

Objective: Stromal cell-derived factor-1 (SDF-1) is expressed in pre-adipocytes but its role is unknown. We investigated butyrate (a histone deacetylase inhibitor--HDACi) and other short-chain fatty acids (SCFA) in the regulation of SDF-1. We further investigated whether effects of SCFA were signalled through G protein-coupled receptors FFA2 and FFA3.

Design And Results: SDF-1 mRNA expression and protein secretion were studied in 3T3-L1 cells and human pre-adipocytes. SDF-1 was abundant, with mRNA and protein levels increased by butyrate. This was replicated with acetate and propionate, but not with trichostatin or valproate. Trichostatin inhibited SDF-1 secretion. Pertussis toxin blocked stimulation by butyrate. The order of potency of SCFA in stimulating SDF-1 (C3 > C4 > C2) is consistent with action through FFA3. Silencing the FFA3 gene abolished butyrate-stimulated SDF-1 expression and secretion. FFA3 was expressed in both pre-adipocytes and adipocytes, while FFA2 was expressed in adipocytes only. SDF-1 expression was low in murine macrophage J774.2 cells, while the SDF-1 receptor CXCR4 was absent from 3T3-L1 cells but abundant in J774.2 macrophages. In human pre-adipocytes, FFA3 was also expressed and SCFA increased SDF-1 secretion.

Conclusions: SDF-1 and CXCR4 may mediate the interaction between adipose stromal cells and macrophages. Effects of SCFA are mediated through FFA3, but not histone deacetylase inhibition.
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http://dx.doi.org/10.14310/horm.2002.1519DOI Listing
October 2015

Hydroxyoctadecadienoic acids regulate apoptosis in human THP-1 cells in a PPARγ-dependent manner.

Lipids 2014 Dec 21;49(12):1181-92. Epub 2014 Oct 21.

School of Medicine and Dentistry, James Cook University, Townsville, QLD, Australia.

Macrophage apoptosis, a key process in atherogenesis, is regulated by oxidation products, including hydroxyoctadecadienoic acids (HODEs). These stable oxidation products of linoleic acid (LA) are abundant in atherosclerotic plaque and activate PPARγ and GPR132. We investigated the mechanisms through which HODEs regulate apoptosis. The effect of HODEs on THP-1 monocytes and adherent THP-1 cells were compared with other C18 fatty acids, LA and α-linolenic acid (ALA). The number of cells was reduced within 24 hours following treatment with 9-HODE (p < 0.01, 30 μM) and 13 HODE (p < 0.01, 30 μM), and the equivalent cell viability was also decreased (p < 0.001). Both 9-HODE and 13-HODE (but not LA or ALA) markedly increased caspase-3/7 activity (p < 0.001) in both monocytes and adherent THP-1 cells, with 9-HODE the more potent. In addition, 9-HODE and 13-HODE both increased Annexin-V labelling of cells (p < 0.001). There was no effect of LA, ALA, or the PPARγ agonist rosiglitazone (1 μM), but the effect of HODEs was replicated with apoptosis-inducer camptothecin (10 μM). Only 9-HODE increased DNA fragmentation. The pro-apoptotic effect of HODEs was blocked by the caspase inhibitor DEVD-CHO. The PPARγ antagonist T0070907 further increased apoptosis, suggestive of the PPARγ-regulated apoptotic effects induced by 9-HODE. The use of siRNA for GPR132 showed no evidence that the effect of HODEs was mediated through this receptor. 9-HODE and 13-HODE are potent--and specific--regulators of apoptosis in THP-1 cells. Their action is PPARγ-dependent and independent of GPR132. Further studies to identify the signalling pathways through which HODEs increase apoptosis in macrophages may reveal novel therapeutic targets for atherosclerosis.
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http://dx.doi.org/10.1007/s11745-014-3954-zDOI Listing
December 2014

Disease burden evaluation of fall-related events in the elderly due to hypoglycemia and other diabetic complications: a clinical review.

Clin Epidemiol 2014 14;6:287-94. Epub 2014 Aug 14.

Department of Medicine, Deakin University, VIC, Australia.

A hypoglycemia-induced fall is common in older persons with diabetes. The etiology of falls in this population is usually multifactorial, and includes microvascular and macrovascular complications and age-related comorbidities, with hypoglycemia being one of the major precipitating causes. In this review, we systematically searched the literature that was available up to March 31, 2014 from MEDLINE/PubMed, Embase, and Google Scholar using the following terms: hypoglycemia; insulin; diabetic complications; and falls in elderly. Hypoglycemia, defined as blood glucose <4.0 mmol/L (70 mg/dL) requiring external assistance, occurs in one-third of elderly diabetics on glucose-lowering therapies. It represents a major barrier to the treatment of diabetes, particularly in the elderly population. Patients who experience hypoglycemia are at a high risk for adverse outcomes, including falls leading to bone fracture, seizures, cognitive dysfunction, and prolonged hospital stays. An increase in mortality has been observed in patients who experience any one of these events. Paradoxically, rational insulin therapy, dosed according to a patient's clinical status and the results of home blood glucose monitoring, so as to achieve and maintain recommended glycemic goals, can be an effective method for the prevention of hypoglycemia and falls in the elderly. Contingencies, such as clinician-directed hypoglycemia treatment protocols that guide the immediate treatment of hypoglycemia, help to limit both the duration and severity of the event. Older diabetic patients with or without underlying renal insufficiency or other severe illnesses represent groups that are at high risk for hypoglycemia-induced falls and, therefore, require lower insulin dosages. In this review, the risk factors of falls associated with hypoglycemia in elderly diabetics were highlighted and management plans were suggested. A target hemoglobin A1c level between 7% and 8% seems to be more appropriate for this population. In addition, the first-choice drugs should have good safety profiles and have the lowest probability of causing hypoglycemia - such as metformin (in the absence of significant renal impairment) and incretin enhancers - while other therapies that may cause more frequent hypoglycemia should be avoided.
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http://dx.doi.org/10.2147/CLEP.S66821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4140240PMC
August 2014

Prevalence of hyponatremia in acute medical admissions in tropical Asia Pacific Australia.

Asian Pac J Trop Med 2014 Jan;7(1):40-3

Department of Medicine, Deakin University, Victoria, Australia.

Objective: To determine prevalence of hyponatremia in acute medical admissions in Northern Australasia.

Methods: We studied 469 consecutive acute medical admissions to a hospital in Australia's Far North Queensland during the colder months of June and July 2012. Prevalence of hyponatremia and its relationship with gender, age, diagnosis and prognosis in acute medical admissions were investigated.

Results: On admission, hyponatremia (plasma sodium <136 mmol/L) was present in 39.4% of patients, with mild (130-135 mmol/L), moderate (126-129 mmol/L) and severe (<126 mmol/L) hyponatremia being present in 25.2%, 10.7% and 3.6% respectively. Overall, adding together admission hyponatremia with that developing during admission, 45.2% of patients were affected with 11.5% moderate hyponatremia cases and 4.1% severe ones. Hypokalemia and hyperkalemia were present in 17.0% and 18.1%, respectively. Overall, 275/469 patients (58.6%) presented with an electrolyte abnormality. There were significant correlations of hyponatremia with age but not with gender and in-hospital mortality. Prevalence of hyponatremia was high across all diagnostic categories.

Conclusions: The prevalence of hyponatremia appears to be high in the tropical North Australian population, being the highest prevalence reported amongst acute hospital admissions. The previously reported correlations with age and mortality do appear to hold good for this population with a high prevalence of electrolyte disorders. Further prospective analysis on a larger population in the area is needed to confirm our findings.
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http://dx.doi.org/10.1016/S1995-7645(13)60189-3DOI Listing
January 2014