Medicine (Northwest Academic Centre) - Research Publications
Now showing items 1-12 of 111
The association between poor dental health and depression: findings from a large-scale, population-based study (the NHANES study)
Objective: To examine the relationship of poor dental health and depression, controlling for markers of inflammation (C-reactive protein; CRP) and adiposity (body mass index; BMI).Method: Data from two National Health and Nutrition Examination Surveys (2005-2008) were utilized (n=10214). Dental health was assessed using the Oral Health Questionnaire (OHQ). Depression was measured using the Patient Health Questionnaire-9 (PHQ-9), where cases were identified using a cut off score of 10 or above. Logistic regression was applied to measure magnitude of associations, controlling for a range of covariates including CRP and BMI.Results: After adjustment for covariates, a significant dose-response relationship between number of oral health conditions and likelihood of PHQ-9 defined depression was observed. Compared with individuals without an oral health condition, adjusted odds ratio (95% confidence interval) for depression in those with two, four and six conditions were 1.60 (1.08-2.38), 2.13 (1.46-3.11) and 3.94 (2.72-5.72), respectively. Level of CRP and being underweight or obese were associated with being depressed.Conclusions: A positive association exists between poor dental health and depression that is independent of CRP and BMI.
Variation in age and physical status prior to total knee and hip replacement surgery: a comparison of centers in Australia and Europe
OBJECTIVE. To investigate whether variation exists in the preoperative age, pain, stiffness, and physical function of people undergoing total knee replacement (TKR) and total hip replacement (THR) at several centers in Australia and Europe. METHODS. Individual Western Ontario and McMaster Universities Osteoarthritis Index data (range 0–100, where 0 = best and 100 = worst) collected within 6 weeks prior to primary TKR and THR were extracted from 16 centers (n = 2,835) according to specified eligibility criteria. Analysis of covariance was used to evaluate differences in pain, stiffness, and physical function between centers, with adjustment for age and sex. RESULTS. There was marked variation in the age of people undergoing surgery between the centers (TKR mean age 67–73 years; F[6,1004] = 4.21, P < 0.01, and THR mean age 63–72 years; F[14,1807] = 7.27, P < 0.01). Large differences in preoperative status were observed between centers, most notably for pain (TKR adjusted mean pain 52.5–61.1; F[6,1002] = 4.26, P < 0.01, and THR adjusted mean pain 49.2–65.7; F[14,1802] = 8.44, P < 0.01) and physical function (TKR adjusted mean function 52.7–61.4; F[6,1002] = 5.27, P < 0.01, and THR adjusted mean function 53.3–71.0; F[14,1802] = 6.71, P < 0.01). Large effect sizes (up to 0.98) reflect the magnitude of variation between centers and highlight the clinical relevance of these findings. CONCLUSION. The large variations in age and preoperative status indicate substantial differences in the timing of joint replacement across the centers studied, with potential for compromised surgical outcomes due to premature or delayed surgery. Possible contributing factors include patient preferences, the absence of concrete indications for surgery, and the capacity of the health care systems.
Immunogenicity and Immunomodulatory Properties of Hepatocyte-like Cells Derived from Human Amniotic Epithelial Cells
(BENTHAM SCIENCE PUBL LTD, 2013-01-01)
Hepatocyte transplantation is being trialled as an alternative to whole organ transplant for patients with acute liver failure and liver specific metabolic diseases. Due to the scarcity of human hepatocytes, hepatocyte-like cells (HLC) generated from stem cells may become a viable alternative to hepatocyte transplantation. Human amniotic epithelial cells (hAEC) from the placenta have stem cell-like properties and can be differentiated into HLC. Naïve hAEC have low immunogenicity and exert immunomodulatory effects that may facilitate allogeneic transplantation. However, whether the immunogenicity and immunomodulatory properties alter with differentiation into HLC are unknown. We further characterized HLC generated from hAEC, examined changes in human leucocyte antigens (HLA) and co-stimulatory molecules and effects exerted by the HLC on human peripheral blood mononuclear cells (PBMC). HLC derived from hAEC expressed proteins found in hepatocytes, had CYP3A4 drug metabolizing enzyme activity and secreted urea. IFN-γ treatment increased HLA Class IA, Class II and co-stimulatory molecule CD40 expression in the HLC. IFN-γ treated HLC stimulated proliferation of PBMC in one-way mixed lymphocyte reactions and were more immunogenic than undifferentiated hAEC. However, the HLC showed immunomodulatory properties and inhibited mitogen induced PBMC proliferation in vitro. PBMC proliferation may have been inhibited by IL-6, TGF-β1, PGE2 and HLA-G secreted by the HLC. The retention of immunomodulatory properties may enable HLC grafts to survive for longer periods despite the immunogenicity of the HLC.
Cost Analysis of Endoscopic Mucosal Resection vs Surgery for Large Laterally Spreading Colorectal Lesions
(ELSEVIER SCIENCE INC, 2016-02-01)
BACKGROUND & AIMS: Large laterally spreading lesions (LSL) in the colon and rectum can be safely and effectively removed by endoscopic mucosal resection (EMR). However, many patients still undergo surgery. Endoscopic treatment may be more cost effective. We compared the costs of endoscopic versus surgical management of large LSL. METHODS: We performed a prospective, observational, multicenter study of consecutive patients referred to 1 of 7 academic hospitals in Australia for the management of large LSL (≥ 20 mm) from January 2010 to December 2013. We collected data on numbers of patients undergoing EMR, actual endoscopic management costs (index colonoscopy, hospital stay, adverse events, and first surveillance colonoscopy), characteristics of patients and lesions, outcomes, and adverse events, and findings from follow-up examinations 14 days, 4-6 months, and 16-18 months after treatment. We compared data from patients who underwent EMR with those from a model in which all patients underwent surgery without any complications. Event-specific costs, based on Australian refined diagnosis-related group codes, were used to estimate average cost per patient. RESULTS: EMR was performed on 1489 lesions (mean size, 36 mm) in 1353 patients (mean age, 67 years; 52.1% male). Total costs involved in the endoscopic management of large LSL were US $6,316,593 and total inpatient hospitalization length of stay was 1180 days. The total cost predicted for the surgical management group was US $16,601,502, with a total inpatient hospitalization length of stay of 4986 days. Endoscopic management produced a potential total cost saving of US $10,284,909; the mean cost difference per patient was US $7602 (95% confidence interval, $8458-$9220; P < .001). Inpatient hospitalization length of stay was reduced by 2.81 nights per patient (95% confidence interval, 2.69-2.94; P < .001). CONCLUSIONS: In a large multicenter study, endoscopic management of large LSL by EMR was significantly more cost-effective than surgery. Endoscopic management by EMR at an appropriately experienced and resourced tertiary center should be considered the first line of therapy for most patients with this disorder. This approach is likely to deliver substantial overall health expenditure savings. ClinicalTrials.gov, Number: NCT01368289.
Heightened Expression of CD39 by Regulatory T Lymphocytes Is Associated with Therapeutic Remission in Inflammatory Bowel Disease
Background:To evaluate whether changes in expression of CD39 by regulatory T lymphocytes (Treg) impact treatment response in inflammatory bowel disease. To then define the biological role of expression of CD39 on Treg in an animal model of colitis.Methods:A prospective study of consecutive patients commencing anti-tumor necrosis factor therapy with infliximab (IFX) or adalimumab (ADA), who were then followed for 12 months. Treatment responses were defined both symptomatically and by endoscopy showing mucosal healing. Peripheral blood Tregs were quantified by flow cytometry. Functional importance of CD39 expression by Treg was determined in an adoptive T-cell transfer model of colitis.Results:Forty-seven patients (ulcerative colitis, n = 22; Crohn's disease, n = 25) were recruited; 16 patients were complete responders and 13 nonresponders to anti-tumor necrosis factor. CD39 expression by Treg was lower in active inflammatory bowel disease and increased significantly after treatment in responders (CD39(+)Treg/total Treg; 8% at baseline to 22.5% at late time point, P < 0.001). Responders were more likely to have therapeutic drug levels and in multivariate analysis therapeutic drug levels were associated with higher expression of CD39 by FoxP3(+) Treg and lower frequencies of interleukin 17A expressing cells. Tregs with genetic deletion of CD39 exhibit decrements in potential to suppress intestinal inflammation in a murine (CD45RB(hi)) T-cell transfer model of colitis in vivo, when compared with wild-type Treg.Conclusions:Increased expression of CD39 by peripheral blood Treg is observed in the setting of clinical and endoscopic remission in inflammatory bowel disease. Deficiency of CD39 expression by Treg can be linked to inability to suppress experimental colitis.