Psychopathology and eating behaviour in people with type 2 diabetes referred for bariatric surgery.

PURPOSE: Psychopathology and disordered eating behaviours are putative pre-operative risk factors for suboptimal outcomes post-bariatric surgery. Documented psychopathology prevalence rates vary in bariatric candidate samples. Further, less attention has been paid to vulnerable subgroups such as people with diabetes who might be at an elevated risk. For these reasons, this study aimed to investigate the rates of psychopathology and disordered eating in pre-surgical candidates with type 2 diabetes mellitus (T2DM). METHODS: Participants were 401 consecutive patients from a state-wide bariatric surgery service for people with T2DM. Psychopathology was measured using multi-modal assessment including diagnostic interview and battery of validated questionnaires. The mean age of the sample was 51 years with a mean BMI of 46 kg/m2. The majority of the sample was female (60.6%), born in Australia (87%) and 18.2% identified as Aboriginal and/or Torres Strait Islander. RESULTS: Rates of current psychopathology in this sample included: major depressive disorder (MDD; 16.75%), generalised anxiety disorder (GAD; 20.25%), insomnia (17.75%) and binge eating disorder (BED; 10.75%). There were no significant differences on measures between people who endorsed Aboriginal and/or Torres Strait Islander status compared to those who did not endorse. The mean total score on the BES was 21.82 ± 10.40 (range 0-39), with 8.2% of participants meeting criteria for severe binge eating. Presence of an eating disorder was not significantly associated with degree of glycemic compensation. Average emotional eating scores were significantly higher in this study, compared to reference samples. Significantly increased binge eating severity and emotional eating severity was revealed for people with T2DM and comorbid MDD, social anxiety and eating disorders. Binge eating severity was associated with GAD, food addiction, substance use disorders, and history of suicide attempt but not emotional eating severity. CONCLUSION: Amongst people with T2DM seeking bariatric surgery, MDD, GAD and emotional eating were common. Psychopathology in a sample of people with T2DM seeking bariatric surgery was significantly associated with severity of disordered eating. These findings suggest people with T2DM seeking bariatric surgery may be vulnerable to psychopathology and disordered eating with implications for early identification and intervention. LEVEL OF EVIDENCE: Evidence obtained from cohort or case-control analytic studies.

Prescribing of psychotropic drugs and indicators for use in residential aged care and residents with dementia.

ABSTRACTIntroduction:It is well established that there is a high prescribing rate of psychotropic agents in residential aged care (RAC). The appropriateness of these medications has become controversial, given the limited data on efficacy and growing evidence of associated adverse outcomes. OBJECTIVE: To assess psychotropic prescribing in RAC including identification of potentially inappropriate prescriptions (PIPs) and common psychological and behavioral symptoms indicated for prescribing. These were viewed in context of dementia and different RAC facilities. METHODS: Electronic care plans of 779 RAC residents across 12 facilities were examined to elucidate psychotropic prescribing rates, PIPs, and indications for use. RESULTS: One in two residents (48.1%) were prescribed a psychotropic drug. The primary reasons for prescribing were depression (61.5%), anxiety (26.7%), sleep problems (25.4%), agitation (13.7%), psychosis (11.0%), and other behaviors (7.2%). Residents with dementia (56.6%) were more likely to be prescribed a drug for agitation and psychosis, and had a significantly increased prescription rate for antidepressants (OR = 1.50, 95% CI = 1.08-2.08, p = 0.01) and antipsychotics (OR = 1.88, 95% CI = 1.23-2.88, p < 0.01). Conversely, residents with dementia were less likely to receive medication to combat sleeping difficulties, with significantly lower benzodiazepine prescribing (OR = 0.63, 95% CI = 0.44-0.91, p = 0.01). Over half of all psychotropic prescriptions (54.0%) were potentially inappropriate based on the Beers Criteria. There was high variability of prescribing rates between homes. CONCLUSION: There is a high prescribing rate of potentially inappropriate medications. Residents with dementia are more likely to receive medication for agitation and psychosis, and are less likely to receive medication to combat sleeping difficulties.

Importance of air bubbles in the core of coated pellets: Synchrotron X-ray microtomography allows for new insights.

High-resolution X-ray microtomography was used to get deeper insight into the underlying mass transport mechanisms controlling drug release from coated pellets. Sugar starter cores were layered with propranolol HCl and subsequently coated with Kollicoat SR, plasticized with 10% TEC. Importantly, synchrotron X-ray computed microtomography (SR-µCT) allowed direct, non-invasive monitoring of crack formation in the film coatings upon exposure to the release medium. Propranolol HCl, as well as very small sugar particles from the pellets' core, were expulsed through these cracks into the surrounding bulk fluid. Interestingly, SR-µCT also revealed the existence of numerous tiny, air-filled pores (varying in size and shape) in the pellet cores before exposure to the release medium. Upon water penetration into the system, the contents of the pellet cores became semi-solid/liquid. Consequently, the air-pockets became mobile and fused together. They steadily increased in size (and decreased in number). Importantly, "big" air bubbles were often located in close vicinity of a crack within the film coating. Thus, they play a potentially crucial role for the control of drug release from coated pellets.

Silver nanoparticles induce pro-inflammatory gene expression and inflammasome activation in human monocytes.

A complete cytotoxic profile of exposure to silver (AgNP) nanoparticles investigating their biological effects on the innate immune response of circulating white blood cells is required to form a complete understanding of the risk posed. This was explored by measuring AgNP-stimulated gene expression of the pro-inflammatory cytokines interleukin-1 (IL-1), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) in THP-1 monocytes. A further study, on human monocytes extracted from a cohort of blood samples, was carried out to compare with the AgNP immune response in THP-1 cells along with the detection of pro-IL-1ß which is a key mediator of the inflammasome complex. The aims of the study were to clearly demonstrate that AgNP can significantly up-regulate pro-inflammatory cytokine gene expression of IL-1, IL-6 and TNF-α in both THP-1 cells and primary blood monocytes thus indicating a rapid response to AgNP in circulation. Furthermore, a role for the inflammasome in AgNP response was indicated by pro-IL-1ß cleavage and release. These results highlight the potential inflammatory effects of AgNP exposure and the responses evoked should be considered with respect to the potential harm that exposure may cause. Copyright © 2016 John Wiley & Sons, Ltd.

Investigation of proposed mechanisms of chemotherapy-induced venous thromboembolism: endothelial cell activation and procoagulant release due to apoptosis.

UNLABELLED: Venous thromboembolism (VTE) during chemotherapy is common, with 7% mortality in metastatic breast cancer (MBC). In a prospective cohort study of patients with breast cancer, we investigated whether vascular endothelial cell activation (VECA), and whether apoptosis, is the cause of chemotherapy-induced VTE. METHODS: Serum markers of VECA, E-selectin (E-sel), vascular cell adhesion molecule 1 (VCAM-1) and d-dimer (fibrin degradation and hypercoagulability marker) were measured prechemotherapy and at 1, 4, and 8 days following chemotherapy. Clinical deep vein thrombosis (DVT) or pulmonary embolism and occult DVT detected by duplex ultrasound imaging were recorded as VTE-positive (VTE+). In patients with MBC, hypercoagulable response to chemotherapy was compared between patients with and without cancer progression. Development of VTE and cancer progression was assessed 3 months following starting chemotherapy. RESULTS: Of the 134 patients, 10 (7.5%) developed VTE (6 [17%] of 36 MBC receiving palliation, 0 of 11 receiving neoadjuvant to downsize tumor, and 4 [5%] of 87 early breast cancer receiving adjuvant chemotherapy, P = .06). Levels of E-sel and VCAM-1 decreased in response to chemotherapy (P < .001) in both VTE+ and patients not developing VTE (VTE-). However, decrease in VECA markers was similar in VTE+ and VTE- patients, implying this is not the cause of VTE. In patients with MBC following chemotherapy, d-dimer (geometric mean) increased by 36% in the 21 patients with MBC responding to chemotherapy but steadily decreased by 11% in the 15 who progressed (day 4, P < .01), implying patients with tumor response (apoptosis) had an early hypercoagulable response. CONCLUSIONS: During chemotherapy for breast cancer, VECA is induced; however, this is not the primary mechanism for VTE. Chemotherapy-induced apoptosis may enhance hypercoagulability and initiate VTE.

Quantifying the large-scale hemodynamics of intracranial aneurysms.

BACKGROUND AND PURPOSE: Hemodynamics play an important role in the mechanisms that govern the initiation, growth, and possible rupture of intracranial aneurysms. The purpose of this study was to objectively characterize these dynamics, classify them, and connect them to aneurysm rupture. MATERIALS AND METHODS: Image-based computational fluid dynamic simulations were used to re-create the hemodynamics of 210 patient-specific intracranial aneurysm geometries. The hemodynamics were then classified according to their spatial complexity and temporal stability by using quantities derived from vortex core lines and proper orthogonal decomposition. RESULTS: The quantitative classification was compared with a previous qualitative classification performed by visual inspection. Receiver operating characteristic curves provided area-under-the-curve estimates for spatial complexity (0.905) and temporal stability (0.85) to show that the 2 classifications were in agreement. Statistically significant differences were observed in the quantities describing the hemodynamics of ruptured and unruptured intracranial aneurysms. Specifically, ruptured aneurysms had more complex and more unstable flow patterns than unruptured aneurysms. Spatial complexity was more strongly associated with rupture than temporal stability. CONCLUSIONS: Complex-unstable blood flow dynamics characterized by longer core line length and higher entropy could induce biologic processes that predispose an aneurysm for rupture.

Delirium in Australian hospitals: a prospective study.

Objectives. Australian data regarding delirium in older hospitalized patients are limited. Hence, this study aimed to determine the prevalence and incidence of delirium among older patients admitted to Australian hospitals and assess associated outcomes. Method. A prospective observational study (n = 493) of patients aged ≥70 years admitted to four Australian hospitals was undertaken. Trained research nurses completed comprehensive geriatric assessments using standardized instruments including the Confusion Assessment Method to assess for delirium. Nurses also visited the wards daily to assess for incident delirium and other adverse outcomes. Diagnoses of dementia and delirium were established through case reviews by independent physicians. Results. Overall, 9.7% of patients had delirium at admission and a further 7.6% developed delirium during the hospital stay. Dementia was the most important predictor of delirium at (OR = 3.18, 95% CI: 1.65-6.14) and during the admission (OR = 4.82; 95% CI: 2.19-10.62). Delirium at and during the admission predicted increased in-hospital mortality (OR = 5.19, 95% CI: 1.27-21.24; OR = 31.07, 95% CI: 9.30-103.78). Conclusion. These Australian data confirm that delirium is a common and serious condition among older hospital patients. Hospital clinicians should maintain a high index of suspicion for delirium in older patients.

Validation of the interRAI Cognitive Performance Scale against independent clinical diagnosis and the Mini-Mental State Examination in older hospitalized patients.

OBJECTIVE: To compare the diagnostic accuracy of the interRAI Acute Care (AC) Cognitive Performance Scale (CPS2) and the Mini-Mental State Examination (MMSE), against independent clinical diagnosis for detecting dementia in older hospitalized patients. DESIGN, SETTING, AND PARTICIPANTS: The study was part of a prospective observational cohort study of patients aged ≥70 years admitted to four acute hospitals in Queensland, Australia, between 2008 and 2010. Recruitment was consecutive and patients expected to remain in hospital for ≥48 hours were eligible to participate. Data for 462 patients were available for this study. MEASUREMENTS: Trained research nurses completed comprehensive geriatric assessments and administered the interRAI AC and MMSE to patients. Two physicians independently reviewed patients' medical records and assessments to establish the diagnosis of dementia. Indicators of diagnostic accuracy included sensitivity, specificity, predictive values, likelihood ratios and areas under receiver (AUC) operating characteristic curves. RESULTS: 85 patients (18.4%) were considered to have dementia according to independent clinical diagnosis. The sensitivity of the CPS2 [0.68 (95%CI: 0.58-0.77)] was not statistically different to the MMSE [0.75 (0.64-0.83)] in predicting physician diagnosed dementia. The AUCs for the 2 instruments were also not statistically different: CPS2 AUC = 0.83 (95%CI: 0.78-0.89) and MMSE AUC = 0.87 (95%CI: 0.83-0.91), while the CPS2 demonstrated higher specificity [0.92 95%CI: 0.89-0.95)] than the MMSE [0.82 (0.77-0.85)]. Agreement between the CPS2 and clinical diagnosis was substantial (87.4%; κ=0.61). CONCLUSION: The CPS2 appears to be a reliable screening tool for assessing cognitive impairment in acutely unwell older hospitalized patients. These findings add to the growing body of evidence supporting the utility of the interRAI AC, within which the CPS2 is embedded. The interRAI AC offers the advantage of being able to accurately screen for both dementia and delirium without the need to use additional assessments, thus increasing assessment efficiency.

Immunological indicators of coeliac disease activity are not altered by long-term oats challenge.

Coeliac disease is a gluten-sensitive enteropathy that develops in genetically susceptible individuals. The disease exhibits many features of an autoimmune disorder. These include the production of highly specific anti-endomysial autoantibodies directed against the enzyme tissue transglutaminase. It is well accepted that wheat-, barley- and rye-based foods should be excluded in the gluten-free diet. Although several studies report that oats ingestion is safe in this diet, the potential toxicity of oats remains controversial. In the current study, 46 coeliac patients ingested oats for 1 year and were investigated for a potential immunogenic or toxic effect. Stringent clinical monitoring of these patients was performed and none experienced adverse effects, despite ingestion of a mean of 286 g of oats each week. Routine histological analysis of intestinal biopsies showed improvement or no change in 95% of the samples examined. Furthermore, tissue transglutaminase expression in biopsy samples, determined quantitatively using the IN Cell Analyzer, was unchanged. Employing immunohistochemistry, oats ingestion was not associated with changes in intraepithelial lymphocyte numbers or with enterocyte proliferation as assessed by Ki-67 staining. Finally, despite the potential for tissue transglutaminase to interact with oats, neither endomysial nor tissue transglutaminase antibodies were generated in any of the patients throughout the study. To conclude, this study reaffirms the lack of oats immunogenicity and toxicity to coeliac patients. It also suggests that the antigenic stimulus caused by wheat exposure differs fundamentally from that caused by oats.

Prospective observational study of dementia and delirium in the acute hospital setting.

BACKGROUND: Dementia and delirium appear to be common among older patients admitted to acute hospitals, although there are few Australian data regarding these important conditions. AIM: The aim of this study was to determine the prevalence and incidence of dementia and delirium among older patients admitted to acute hospitals in Queensland and to profile these patients. METHOD: Prospective observational cohort study (n = 493) of patients aged 70 years and older admitted to general medical, general surgical and orthopaedic wards of four acute hospitals in Queensland between 2008 and 2010. Trained research nurses completed comprehensive geriatric assessments and obtained detailed information about each patient's physical, cognitive and psychosocial functioning using the interRAI Acute Care and other standardised instruments. Nurses also visited patients daily to identify incident delirium. Two physicians independently reviewed patients' medical records and assessments to establish the diagnosis of dementia and/or delirium. RESULTS: Overall, 29.4% of patients (n = 145) were considered to have cognitive impairment, including 102 (20.7% of the total) who were considered to have dementia. This rate increased to 47.4% in the oldest patients (aged ≥ 90 years). The overall prevalence of delirium at admission was 9.7% (23.5% in patients with dementia), and the rate of incident delirium was 7.6% (14.7% in patients with dementia). CONCLUSION: The prevalence of dementia and delirium among older patients admitted to acute hospitals is high and is likely to increase with population aging. It is suggested that hospital design, staffing and processes should be attuned better to meet these patients' needs.

The challenge of contemporary nurse education programmes. Perceived stressors of nursing students: mental health and related lifestyle issues.

This study aimed to identify the lifestyle behaviours of nursing students. The research tool was a 146-item questionnaire based upon the College Lifestyle and Attitudinal National survey. Most students considered their mental health as either good or very good. Those in the final year were more likely to rate their mental health poorly. Many experienced programme-related stressors including examinations and assignments and studies in general. More than one-third also reported stressors related to relationships with clinical staff and clinical assessment of competence. There is a concern that the added demands of modern nursing programmes place the student under considerably more pressure, because of competing demands. While many students talk to their peers or family, many do not and prefer rather to go it alone, with some choosing to escape through alcohol or drugs. The support and encouragement of healthy coping mechanisms among nursing students is paramount to ensure a healthy nursing workforce for the future. Nursing students support the mental and physical health of others, and therefore in many ways ought to a role model. Nurturing and supporting their mental health is crucial to the future of profession.

Complementary medicine use by middle-aged and older women: personality, mood and anxiety factors.

This study analysed NEO Five Factor Inventory (NEO-FFI) personality trait data in middle-aged and older Australian women and their CAM usage. Participants were women from the Longitudinal study of Ageing in Women (LAW study) aged 47 to 87 years (N = 419). Only the NEO-FFI trait of Openness was significantly correlated with cumulative CAM product use. Regression models revealed that number of specialists' consultations, number of CAM products used and reported level of physical and leisure activities were predictive of CAM therapy use; while age was predictive of CAM product use.

Prolonged cardiac allograft survival using iodine 131 after human sodium iodide symporter gene transfer in a rat model.

BACKGROUND: Radioiodine is efficiently concentrated by tissues expressing the human sodium iodide symporter (hNIS). OBJECTIVE: To analyze the effects of iodine 131 on acute cardiac allograft rejection after ex vivo hNIS gene transfer in a rat model of cardiac allotransplantation. MATERIALS AND METHODS: Hearts from Brown Norway rats were perfused ex vivo either with UW (University of Wisconsin) solution (n = 9) or UW solution containing 1 x 10(9) pfu/mL of adenovirus 5 plus NIS (Ad-NIS) (n = 18). Donor hearts were transplanted heterotopically into the abdomen of Lewis rats, and recipients were treated on postoperative day 3 with either 15,000 microCi of (131)I or saline solution. The hearts were explanted when no longer beating, and were evaluated histologically for evidence of rejection and other changes. RESULTS: Grafts perfused with the Ad-NIS vector survived significantly longer in recipients injected with (131)I (mean [SD], 11.3 [1.9] days) compared with control animals not treated with (131)I (5.7 [0.65] days) (P < .001). Treatment with (131)I did not prolong graft survival in recipients of hearts that were not perfused with Ad-NIS (5.5 [1.0] vs 5.3 [0.8] days). In Ad-NIS (131)I-treated transplants, the level of myocardial damage on day 6 after surgery, when control hearts were rejected, was significantly lower (60.8 [28.0] vs 99.7 [0.8]; P < .05). CONCLUSION: Our findings indicate that (131)I, after NIS gene transfer, can effectively prolong cardiac allograft survival. To our knowledge, this is the first report of the use of NIS-targeted (131)I therapy in cardiac transplantation. Further studies are required to determine the mechanism of this effect and its potential for clinical application.

Postmenopausal hormone therapy and cognition: effects of timing and treatment type.

SETTING: Hormone therapy used for the management of postmenopausal symptoms in older women appears to result in variable effects on cognitive function, depending on study design, subjects, tests used, and types of therapy. OBJECTIVE: To determine the effects of estrogen-only and estrogen plus progestogen preparations on cognitive performance (cognitive status, general and working memory) when taken 'early' and 'late' from the onset of menopause. METHOD: The study consisted of 410 women who were participants in a longitudinal study, first recruited at age 40-80 years. They were tested for change over 5 years as an observational cohort by the Mini-Mental State Examination, National Adult Reading Test and the Wechsler Memory Scale Version 3. Cognitive decline, measured by age-adjusted scores, was defined as >or=10% negative change in each individual woman. RESULTS: Controlling for age and lifestyle factors, and using the criterion of decrease in score >or=10% over 5 years for 'cognitive decline', 'early start' of hormone therapy (<3 years from menopause) was strongly associated with reduction in risk by the Mini-Mental State Examination (estrogen-only preparation, p = 0.005) but with increase in risk for general memory (with estrogen plus progestogen preparation, p = 0.02). Overall, there were no major effects on subgroups with type/timing of hormone therapy in relation to testing for a negative change in cognitive function. CONCLUSION: 'Early start' of estrogen-only hormone therapy was associated with reduced risk of global cognitive decline, and 'early start' estrogen-only and estrogen/progestogen hormone therapies showed increased risks of general memory decline. Even though this study did not have the power to discriminate between minor and mixed effects, it suggests that cognitive effects of hormone therapies may be mixed, depending on cognitive domain and timing of use/type of preparation.

The Kava Anxiety Depression Spectrum Study (KADSS): a randomized, placebo-controlled crossover trial using an aqueous extract of Piper methysticum.

RATIONALE: Piper methysticum (Kava) has been withdrawn in European, British, and Canadian markets due to concerns over hepatotoxic reactions. The WHO recently recommended research into "aqueous" extracts of Kava. OBJECTIVE: The objective of this study was to conduct the first documented human clinical trial assessing the anxiolytic and antidepressant efficacy of an aqueous extract of Kava. DESIGN AND PARTICIPANTS: The Kava Anxiety Depression Spectrum Study was a 3-week placebo-controlled, double-blind crossover trial that recruited 60 adult participants with 1 month or more of elevated generalized anxiety. Five Kava tablets per day were prescribed containing 250 mg of kavalactones/day. RESULTS: The aqueous extract of Kava reduced participants' Hamilton Anxiety Scale score in the first controlled phase by -9.9 (CI = 7.1, 12.7) vs. -0.8 (CI = -2.7, 4.3) for placebo and in the second controlled phase by -10.3 (CI = 5.8, 14.7) vs. +3.3 (CI = -6.8, 0.2). The pooled effect of Kava vs. placebo across phases was highly significant (p < 0.0001), with a substantial effect size (d = 2.24, eta(2)(p)). Pooled analyses also revealed highly significant relative reductions in Beck Anxiety Inventory and Montgomery-Asberg Depression Rating Scale scores. The aqueous extract was found to be safe, with no serious adverse effects and no clinical hepatotoxicity. CONCLUSIONS: The aqueous Kava preparation produced significant anxiolytic and antidepressant activity and raised no safety concerns at the dose and duration studied. Kava appears equally effective in cases where anxiety is accompanied by depression. This should encourage further study and consideration of globally reintroducing aqueous rootstock extracts of Kava for the management of anxiety.

Kava Anxiety Depression Spectrum Study (KADSS): a mixed methods RCT using an aqueous extract of Piper methysticum.

OBJECTIVES: To report on the design, significance and potential impacts of the first documented human clinical trial assessing the anxiolytic and thymoleptic efficacy of an aqueous mono-extract of Piper methysticum (kava). The significance of the qualitative element of our clinical trial is also explored. The Kava Anxiety Depression Spectrum Study (KADSS) is a 3-week placebo-controlled, double-blind, cross-over trial involving 60 adult participants (18-65) with elevated stable anxiety and varying levels of depressive symptoms. AIMS: The aims of KADSS are: (1) to determine whether an aqueous standardised extract of kava is effective for the treatment of anxiety; (2) to assess the effects of kava on differing levels of depression; and (3) to explore participants' experience of taking kava via qualitative research. The study also provides preliminary assessment of the safety of an aqueous extract of kava in humans. CONCLUSION: If results reveal that the aqueous kava preparation exerts significant anxiolytic effects and appears safe, potentially beneficial impacts may occur. Data supporting a safe and effective kava extract may encourage a re-introduction of kava to Europe, UK and Canada. This may provide a major socioeconomic benefit to Pacific Island nations, and to sufferers of anxiety disorders.