Tumor-suppressor gene promoter hypermethylation in saliva of head and neck cancer patients

Head and neck squamous cell carcinoma (HNSCC) accounts for a bulk of the oral and laryngeal cancers, the majority (70%) of which are associated with smoking and excessive drinking, major known risk factors for the development of HNSCC. In contrast to reports that suggest an inverse relationship between smoking and global DNA CpG methylation, hypermethylation of promoters of a number of genes was detected in saliva collected from patients with HNSCC. Using a sensitive methylation-specific polymerase chain reaction (MSP) assay to determine specific methylation events in the promoters of RASSF1A, DAPK1, and p16 genes, we demonstrate that we can detect tumor presence with an overall accuracy of 81% in the DNA isolated from saliva of patients with HNSCC (n = 143) when compared with the DNA isolated from the saliva of healthy nonsmoker controls (n = 31). The specificity for this MSP panel was 87% and the sensitivity was 80%(with a Fisher exact test P < .0001). In addition, the test panel performed extremely well in the detection of the early stages of HNSCCs, with a sensitivity of 94% and a specificity of 87%, and a high. concordance value of 0.8, indicating an excellent overall agreement between the presence of HNSCC and a positive MSP panel result. In conclusion, we demonstrate that the promoter methylation of RASSF1A, DAPK1, and p16 MSP panel is useful in detecting hypermethylation events in a noninvasive manner in patients with HNSCC.

Demographics and survivial of a cohort of blood and breast cancer patients who developed heart failure following cancer treatment

Background/Aim: Cardiotoxicity resulting in heart failure is a devastating complication of cancer therapy. It is possible that a patient may survive cancer only to develop heart failure (HF), which is more deadly than cancer. The aim of this project was to profile the characteristics of patients at risk of cancer treatment induced heart failure. Methods: Linked Health Data Analysis of Queensland Cancer Registry (QCR) from 1996-2009, Death Registry and Hospital Administration records for HF and chemotherapy admissions were reviewed. Index heart failure admission must have occurred after the date of cancer registry entry. Results: A total of 15,987 patients were included in this analysis; 1,062 (6.6%) had chemotherapy+HF admission (51.4% Female) and 14,925 (93.4%) chemotherapy_no HF admission. Median age of chemotherapy+HF patients was 67 years (IQR 58 to 75) vs. 54 years (IQR 44 to 64) for chemotherapy_no HF admission. Chemotherapy+HF patients had increased risk of all cause mortality (HR 2.79 [95% CI 2.58-3.02] and 1.67 [95% CI, 1.54 to 1.81] after adjusting for age, sex, marital status, country of birth, cancer site and chemotherapy dose). Index HF admission occurred within one year of cancer diagnosis in 47% of HF patients with 80% of patinets having there index admission with 3 years. The number of chemotherapy cycles was not associated with significant reduction in survival time in chemotherapy+HF patients. Mean survival for heart failure patients was 5.3 years (95% CI, 4.99 - 5.62) vs.9.57 years (95% CI, 9.47-9.68) for chemotherapy_no HF admission patients. Conclusion: All-cause mortality was 67% higher in patients diagnosed with HF following chemotherapy in adjusted analysis for covariates. Methods to improve and better coordinate of the interdisciplinary care for cancer patients with HF involving cardiologists and oncologists are required, including evidence-based guidelines for the comprehensive assessment, monitoring and management of this cohort.

Medication Management of Adult Patients Admitted to Hospital with Epilepsy, Seizure or Convulsion

Background: An inpatient medication chart review at the Gold Coast Hospital identified shortcomings with the prescribing and monitoring of antiepileptic medications. Aim: To evaluate medication management of patients with epilepsy, seizure or convulsion; to map their transition through the health system; and to identify lifestyle behaviours that may lead to overt risks for seizure occurrence. Method: A retrospective observational audit of adult patients (16 years and over) admitted to hospital with a diagnosis of epilepsy, seizure or convulsion from 1 to 31 January 2012. Results: Majority of the 62 episodes of care investigated involved patients who were discharged directly from the ED (68%). Only 30% of all patients discharged from an inpatient unit received a discharge medication record from a pharmacist. Non-adherence with antiepileptic medications, alcohol and/ or recreational drug use and prescription medication misuse were identified as overt risks for seizure occurrence. Conclusion: Valuable insights were gained into the management of seizure patients. The role of the ED pharmacist was reviewed to focus on high-risk seizure patients. An increase in the provision of discharge medication records and patient education on the overt risks for seizure occurrence is needed.

Enhanced cortisol suppression following administration of low-dose dexamethasone in first-episode psychosis patients

OBJECTIVE Impaired regulation of the hypothalamic-pituitary-adrenal (HPA) axis and hyper-activity of this system have been described in patients with psychosis. Conversely, some psychiatric disorders such as post-traumatic stress disorder (PTSD) are characterised by HPA hypo-activity, which could be related to prior exposure to trauma. This study examined the cortisol response to the administration of low-dose dexamethasone in first-episode psychosis (FEP) patients and its relationship to childhood trauma. METHOD The low-dose (0.25 mg) Dexamethasone Suppression Test (DST) was performed in 21 neuroleptic-naive or minimally treated FEP patients and 20 healthy control participants. Childhood traumatic events were assessed in all participants using the Childhood Trauma Questionnaire (CTQ) and psychiatric symptoms were assessed in patients using standard rating scales. RESULTS FEP patients reported significantly higher rates of childhood trauma compared to controls (p = 0.001) and exhibited lower basal (a.m.) cortisol (p = 0.04) and an increased rate of cortisol hyper-suppression following dexamethasone administration compared to controls (33% (7/21) vs 5% (1/20), respectively; p = 0.04). There were no significant group differences in mean cortisol decline or percent cortisol suppression following the 0.25 mg DST. This study shows for the first time that a subset of patients experiencing their first episode of psychosis display enhanced cortisol suppression. CONCLUSIONS These findings suggest there may be distinct profiles of HPA axis dysfunction in psychosis which should be further explored.

Changes in disability, physical/mental health states and quality of life during an 8-Week multimodal physiotherapy programme in patients with chronic non-specific neck pain: A prospective cohort study

Aim The aim of this study was to analyse the effect of an 8-week multimodal physiotherapy programme (MPP), integrating physical land-based therapeutic exercise (TE), adapted swimming and health education, as a treatment for patients with chronic non-specific neck pain (CNSNP), on disability, general health/mental states and quality of life. Methods 175 CNSNP patients from a community-based centre were recruited to participate in this prospective study. Intervention: 60-minute session (30 minutes of land-based exercise dedicated to improving mobility, motor control, resistance and strengthening of the neck muscles, and 30 minutes of adapted swimming with aerobic exercise keeping a neutral neck position using a snorkel). Health education was provided using a decalogue on CNSNP and constant repetition of brief advice by the physiotherapist during the supervision of the exercises in each session. Study outcomes: primary: disability (Neck Disability Index); secondary: physical and mental health states and quality of life of patients (SF-12 and EuroQoL-5D respectively). Differences between baseline data and that at the 8-week follow-up were calculated for all outcome variables. Results Disability showed a significant improvement of 24.6% from a mean (SD) of 28.2 (13.08) at baseline to 16.88 (11.62) at the end of the 8-week intervention. All secondary outcome variables were observed to show significant, clinically relevant improvements with increase ranges between 13.0% and 16.3% from a mean of 0.70 (0.2) at baseline to 0.83 (0.2), for EuroQoL-5D, and from a mean of 40.6 (12.7) at baseline to 56.9 (9.5), for mental health state, at the end of the 8-week intervention. Conclusion After 8 weeks of a MPP that integrated land-based physical TE, health education and adapted swimming, clinically-relevant and statistically-significant improvements were observed for disability, physical and mental health states and quality of life in patients who suffer CNSNP. The clinical efficacy requires verification using a randomised controlled study design.

Accelerated strategies in the assessment of emergency patients with possible acute coronary syndromes

This thesis synthesises advancements made in the method of assessment of emergency patients with possible acute cardiac disease and has defined new assessment strategies that supports the safe early discharge of patients at low risk for acute coronary syndromes. These important findings have informed clinicians and health services about improvements that can be made at this current time in the process of care of ED patients, and the studies have had local, national and international influence.

Letter: Brain natriuretic peptide is a potentially useful screening tool for the detection of cardiovascular disease in patients with rheumatoid arthritis

Patients with rheumatoid arthritis (RA) have a significantly higher risk of coronary heart disease, despite being less likely to report symptoms of angina, and are more likely to experience unrecognised myocardial infarction and sudden cardiac death than non-RA controls.1 Furthermore, left ventricular diastolic dysfunction has been described in up to 40% of patients with RA.2...

Efficacy and safety of adalimumab in patients with non-radiographic axial spondyloarthritis: Results of a randomised placebo-controlled trial (ABILITY-1)

Purpose: To evaluate the efficacy and safety of adalimumab in patients with non-radiographic axial spondyloarthritis (nr-axSpA). Methods: Patients fulfilled Assessment of Spondyloarthritis international Society (ASAS) criteria for axial spondyloarthritis, had a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of ≥ 4, total back pain score of ≥ 4 (10 cm visual analogue scale) and inadequate response, intolerance or contraindication to non-steroidal anti-inflammatory drugs (NSAIDs); patients fulfilling modified New York criteria for ankylosing spondylitis were excluded. Patients were randomised to adalimumab (N=91) or placebo (N=94). The primary endpoint was the percentage of patients achieving ASAS40 at week 12. Efficacy assessments included BASDAI and Ankylosing Spondylitis Disease Activity Score (ASDAS). MRI was performed at baseline and week 12 and scored using the Spondyloarthritis Research Consortium of Canada (SPARCC) index. Results: Significantly more patients in the adalimumab group achieved ASAS40 at week 12 compared with patients in the placebo group (36% vs 15%, p<0.001). Significant clinical improvements based on other ASAS responses, ASDAS and BASDAI were also detected at week 12 with adalimumab treatment, as were improvements in quality of life measures. Inflammation in the spine and sacroiliac joints on MRI significantly decreased after 12 weeks of adalimumab treatment. Shorter disease duration, younger age, elevated baseline C-reactive protein or higher SPARCC MRI sacroiliac joint scores were associated with better week 12 responses to adalimumab. The safety profile was consistent with what is known for adalimumab in ankylosing spondylitis and other diseases. Conclusions: In patients with nr-axSpA, adalimumab treatment resulted in effective control of disease activity, decreased inflammation and improved quality of life compared with placebo. Results from ABILITY-1 suggest that adalimumab has a positive benefit-risk profile in active nr-axSpA patients with inadequate response to NSAIDs.

Enrichment of circulating interleukin-17-secreting interleukin-23 receptor-positive γ/δ T cells in patients with active ankylosing spondylitis

Objective Ankylosing spondylitis (AS) is a common inflammatory arthritis affecting primarily the axial skeleton. IL23R is genetically associated with AS. This study was undertaken to investigate and characterize the role of interleukin-23 (IL-23) signaling in AS pathogenesis. Methods The study population consisted of patients with active AS (n = 17), patients with psoriatic arthritis (n = 8), patients with rheumatoid arthritis, (n = 9), and healthy subjects (n = 20). IL-23 receptor (IL-23R) expression in T cells was determined in each subject group, and expression levels were compared. Results The proportion of IL-23R-expressing T cells in the periphery was 2-fold higher in AS patients than in healthy controls, specifically driven by a 3-fold increase in IL-23R-positive γ/δ T cells in AS patients. The proportions of CD4+ and CD8+ cells that were positive for IL-17 were unchanged. This increased IL-23R expression on γ/δ T cells was also associated with enhanced IL-17 secretion, with no observable IL-17 production from IL-23R-negative γ/δ T cells in AS patients. Furthermore, γ/δ T cells from AS patients were heavily skewed toward IL-17 production in response to stimulation with IL-23 and/or anti-CD3/CD28. Conclusion Recently, mouse models have shown IL-17-secreting γ/δ T cells to be pathogenic in infection and autoimmunity. Our data provide the first description of a potentially pathogenic role of these cells in a human autoimmune disease. Since IL-23 is a maturation and growth factor for IL-17-producing cells, increased IL-23R expression may regulate the function of this putative pathogenic γ/δ T cell population.

Spinal inflammation in the absence of sacroiliac joint inflammation on magnetic resonance imaging in patients with active nonradiographic axial spondyloarthritis

Objective: To evaluate the presence of spinal inflammation with and without sacroiliac (SI) joint inflammation on magnetic resonance imaging (MRI) in patients with active nonradiographic axial spondyloarthritis (SpA), and to compare the disease characteristics of these subgroups. Methods: ABILITY-1 is a multicenter, randomized, controlled trial of adalimumab versus placebo in patients with nonradiographic axial SpA classified using the Assessment of SpondyloArthritis international Society axial SpA criteria. Baseline MRIs were centrally scored independently by 2 readers using the Spondyloarthritis Research Consortium of Canada (SPARCC) method for the SI joints and the SPARCC 6-discovertebral unit method for the spine. Positive evidence of inflammation on MRI was defined as a SPARCC score of >2 for either the SI joints or the spine. Results: Among patients with baseline SPARCC scores, 40% had an SI joint score of >2 and 52% had a spine score of >2. Forty-nine percent of patients with baseline SI joint scores of <2, and 58% of those with baseline SI joint scores of >2, had a spine score of >2. Comparison of baseline disease characteristics by baseline SI joint and spine scores showed that a greater proportion of patients in the subgroup with a baseline SPARCC score of >2 for both SI joints and spine were male, and patients with spine and SI joint scores of <2 were younger and had shorter symptom duration. SPARCC spine scores correlated with baseline symptom duration, and SI joint scores correlated negatively with the baseline Bath Ankylosing Spondylitis Disease Activity Index, but neither correlated with the baseline Ankylosing Spondylitis Disease Activity Score, total back pain, the patient's global assessment of disease activity, the Bath Ankylosing Spondylitis Functional Index, morning stiffness, nocturnal pain, or C-reactive protein level. Conclusion: Assessment by experienced readers showed that spinal inflammation on MRI might be observed in half of patients with nonradiographic axial SpA without SI joint inflammation.

Adjustment of apnea-hypopnea index with severity of obstruction events enhances detection of sleep apnea patients with the highest risk of severe health consequences

Introduction Presently, the severity of obstructive sleep apnea (OSA) is estimated based on the apnea-hypopnea index (AHI). Unfortunately, AHI does not provide information on the severity of individual obstruction events. Previously, the severity of individual obstruction events has been suggested to be related to the outcome of the disease. In this study, we incorporate this information into AHI and test whether this novel approach would aid in discriminating patients with the highest risk. We hypothesize that the introduced adjusted AHI parameter provides a valuable supplement to AHI in the diagnosis of the severity of OSA. Methods This hypothesis was tested by means of retrospective follow-up (mean ± sd follow-up time 198.2 ± 24.7 months) of 1,068 men originally referred to night polygraphy due to suspected OSA. After exclusion of the 264 patients using CPAP, the remaining 804 patients were divided into normal (AHI < 5) and OSA (AHI ≥ 5) categories based on conventional AHI and adjusted AHI. For a more detailed analysis, the patients were divided into normal, mild, moderate, and severe OSA categories based on conventional AHI and adjusted AHI. Subsequently, the mortality and cardiovascular morbidity in these groups were determined. Results Use of the severity of individual obstruction events for adjustment of AHI led to a significant rearrangement of patients between severity categories. Due to this rearrangement, the number of deceased patients diagnosed to have OSA was increased when adjusted AHI was used as the diagnostic index. Importantly, risk ratios of all-cause mortality and cardiovascular morbidity were higher in moderate and severe OSA groups formed based on the adjusted AHI parameter than in those formed based on conventional AHI. Conclusions The adjusted AHI parameter was found to give valuable supplementary information to AHI and to potentially improve the recognition of OSA patients with the highest risk of mortality or cardiovascular morbidity.

Finite element analysis of vulnerable atherosclerotic plaques: A comparison of mechanical stresses within carotid plaques of acute and recently symptomatic patients with carotid artery disease

Objectives: There is considerable evidence that patients with carotid artery stenosis treated immediately after the ischaemic cerebrovascular event have a better clinical outcome than those who have delayed treatment. Biomechanical assessment of carotid plaques using high-resolution MRI can help examine the relationship between the timing of carotid plaque symptomology and maximum simulated plaque stress concentration. Methods: Fifty patients underwent high-resolution multisequence in vivo MRI of their carotid arteries. Patients with acute symptoms (n=25) underwent MRI within 72 h of the onset of ischaemic cerebrovascular symptoms, whereas recently symptomatic patients (n=25) underwent MRI from 2 to 6 weeks after the onset of symptoms. Stress analysis was performed based on the geometry derived from in vivo MRI of the symptomatic carotid artery at the point of maximum stenosis. The peak stresses within the plaques of the two groups were compared. Results: Patient demographics were comparable for both groups. All the patients in the recently symptomatic group had severe carotid stenosis in contrast to patients with acute symptoms who had predominantly mild to moderate carotid stenosis. The simulated maximum stresses in patients with acute symptoms was significantly higher than in recently symptomatic patients (median (IQR): 313310 4 dynes/cm 2 (295 to 382) vs 2523104 dynes/cm 2 (236 to 311), p=0.02). Conclusions: Patients have extremely unstable, high-risk plaques, with high stresses, immediately after an acute cerebrovascular event, even at lower degrees of carotid stenoses. Biomechanical stress analysis may help us refine our risk-stratification criteria for the management of patients with carotid artery disease in future.

Comparison of the inflammatory burden of truly asymptomatic carotid atheroma with atherosclerotic plaques in patients with asymptomatic carotid stenosis undergoing coronary artery bypass grafting: An ultrasmall superparamagnetic iron oxide enhanced magnetic resonance study

Introduction: Inflammation is a recognized risk factor for the vulnerable atherosclerotic plaque. The aim of this study was to explore whether there is a difference in the degree of Magnetic Resonance (MR) defined inflammation using Ultra Small Super-Paramagnetic Iron Oxide (USPIO) particles, within carotid atheroma in completely asymptomatic individuals and the asymptomatic carotid stenosis in a cohort of patients undergoing coronary artery bypass grafting (CABG). Methods: 10 patients awaiting CABG with asymptomatic carotid disease and 10 completely asymptomatic individuals with no documented coronary artery disease underwent multi-sequence MR imaging before and 36 hours post USPIO infusion. Images were manually segmented into quadrants and signal change in each quadrant, normalised to adjacent muscle signal, was calculated following USPIO administration. Results: The mean percentage of quadrants showing signal loss was 94% in the CABG group, compared to 24% in the completely asymptomatic individuals (p < 0.001). The carotid plaques from the CABG patients showed a significant mean signal intensity decrease of 16.4% after USPIO infusion (95% CI 10.6% to 22.2%; p < 0.001). The truly asymptomatic plaques showed a mean signal intensity increase (i.e. enhancement) after USPIO infusion of 8.4% (95% CI 2.6% to 14.2%; p = 0.007). The mean signal difference between the two groups was 24.9% (95% CI 16.7% to 33.0%; p < 0.001). Conclusions: These findings are consistent with the hypothesis that inflammatory atheroma is a systemic disease. The carotid territory is more likely to take up USPIO if another vascular territory is symptomatic.

The development of a guideline of care for patients with a Sengstaken-Blakemore Tube insitu in a general Intensive Care Unit using translational change theory

Aims & Objectives - identify and diagnose the current problems associated with patient care with regard to the nursing management of patients with Sengstaken-Blakemore tubes insitu; - Identify current nursing practice currently in place within the ICU and the hospital; identify the method by which the assessment and provision of nursing care is delivered in the ICU

Serum immunoreactive pancreatic lipase and cationic trypsinogen for the assessment of exocrine pancreatic function in older patients with cystic fibrosis

Indirect and qualitative tests of pancreatic function are commonly used to screen patients with cystic fibrosis for pancreatic insufficiency. In an attempt to develop a more quantitative assessment, we compared the usefulness of measuring serum pancreatic lipase using a newly developed enzyme-linked immunosorbent immunoassay with that of cationic trypsinogen using a radioimmunoassay in the assessment of exocrine pancreatic function in patients with cystic fibrosis. Previously, we have shown neither lipase nor trypsinogen to be of use in assessing pancreatic function prior to 5 years of age because the majority of patients with cystic fibrosis in early infancy have elevated serum levels regardless of pancreatic function. Therefore, we studied 77 patients with cystic fibrosis older than 5 years of age, 41 with steatorrhea and 36 without steatorrhea. In addition, 28 of 77 patients consented to undergo a quantitative pancreatic stimulation test. There was a significant difference between the steatorrheic and nonsteatorrheic patients with the steatorrheic group having lower lipase and trypsinogen values than the nonsteatorrheic group (P < .001). Sensitivities and specificities in detecting steatorrhea were 95% and 86%, respectively, for lipase and 93% and 92%, respectively, for trypsinogen. No correlations were found between the serum levels of lipase and trypsinogen and their respective duodenal concentrations because of abnormally high serum levels of both enzymes found in some nonsteatorrheic patients. We conclude from this study that both serum lipase and trypsinogen levels accurately detect steatorrhea in patients with cystic fibrosis who are older than 5 years but are imprecise indicators of specific pancreatic exocrine function above the level needed for normal fat absorption.