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.

Early changes in the haemostatic and procoagulant systems after chemotherapy for breast cancer.

Venous thromboembolism (VTE) following breast cancer chemotherapy is common. Chemotherapy-induced alterations in markers of haemostasis occur during chemotherapy. It is unclear how rapidly this occurs, whether this is upregulated in patients developing VTE and whether changes predict for VTE. Markers of haemostasis, functional clotting assays and vascular endothelial growth factor were measured before chemotherapy and at 24 h, 4 days, 8 days and 3 months following commencement of chemotherapy in early and advanced breast cancer patients and in age- and sex-matched controls. Duplex ultrasound imaging was performed after 1 month or if symptomatic. Of 123 patients, 9.8% developed VTE within 3 months. Activated partial thromboplastin time (APTT), prothrombin time (PT), D-dimer, fibrinogen, platelet count, VEGF and fibrinogen were increased in cancer. Fibrinogen, D-dimer, VEGF and tissue factor were increased, at baseline, in patients subsequently developing VTE. D-dimer of less than 500 ng ml(-1) has a negative predictive value of 97%. Activated partial thromboplastin time, PT and thrombin-antithrombin showed significantly different trends, as early as within 24 h, in response to chemotherapy in patients subsequently developing VTE. Markers of coagulation and procoagulants are increased, before chemotherapy, in patients who subsequently develop VTE. A group of patients at minimal risk of VTE can be identified, allowing targeted thrombopropylaxis to the higher risk group.

Angiogenic characteristics of circulating and tumoural thrombospondin-1 in breast cancer.

In cancer models, thrombospondin-1 (TSP-1) has been shown to inhibit angiogenesis or promote metastasis by increasing adhesion of malignant cells to endothelium. To determine the role of TSP-1 in breast cancer and breast cancer angiogenesis, we have measured TSP-1 in plasma and tumour cytosols and compared levels to established clinicopathological prognostic parameters and intratumoural microvessel density. TSP-1 was measured, by radioimmunoassay, in plasma (pTSP-1) and tumour cytosols (cTSP-1) of women with early breast cancer (EBC) (n=71). pTSP-1 in EBC was compared to pTSP-1 levels in women with advanced breast cancer (ABC) (n=66), normal controls (n=77) and was correlated with prognostic features and microvessel density (MVD) (measured by CD31 immunostaining). cTSP-1 levels were compared to prognostic features and microvessel density. pTSP-1 in women with EBC (median 484, IQR 344-877 ng/ml) and ABC (median 588, IQR 430-952 ng/ml) were elevated when compared to normal controls (median 21, IQR 175-247) (p<0.001). Women with lymph node metastases (n=35) had higher levels of TSP-1 (median 799 ng/ml, IQR 455-943) than women who were node negative (median 343 ng/ml, IQR 267-514) (n=36) (p<0.05). Levels of pTSP-1 in EBC correlated with MVD (R=0.39, p<0.05). Levels of TSP-1 in tumour cytosols of women with EBC (median 1714, IQR 893-5283 ng/ml) correlated with microvessel density (R=0.46, p<0.01). Circulating levels of TSP-1 appear to be a marker of breast cancer aggressiveness and in breast cancer may have a pro-angiogenic rather than anti-angiogenic role.

Serum vascular endothelial growth factor in breast cancer.

Many studies have reported elevated serum concentrations of vascular endothelial growth factor (VEGF) in patients with cancer and claimed that the measurement of circulating VEGF is a surrogate marker of angiogenesis and/or metastasis. To determine the value of VEGF measurement in the diagnosis and prognosis of breast cancer, we measured levels in women with and without breast cancer. Platelet-depleted plasma VEGF levels were measured in premenopausal women at four-day intervals across the menstrual cycle, postmenopausal women and postmenopausal women who had undergone hysterectomy. Platelet-depleted plasma VEGF was also measured in pre- and postmenopausal women with early breast cancer (EBC) and levels compared with intratumoral levels, clinicopathological prognostic parameters and microvessel density. Levels of VEGF were determined using ELISA and immuno-histochemistry. Microvessel density was determined by immunohistochemical CD34 staining. Plasma VEGF in premenopausal women remained stable across the menstrual cycle except for a peak between days 8 and 12. VEGF levels in postmenopausal women were higher than in premenopausal women unless postmenopausal women had undergone hysterectomy. Amongst premenopausal women, levels of VEGF were high in 22 EBC patients when compared to normal premenopausal controls. No correlation was found between plasma and intratumoral VEGF, clinicopathological prognostic parameters or tumour microvessel density. The origin of circulating VEGF differs between pre- and postmenopausal women. Its measurement is unlikely to provide clinically useful diagnostic and prognostic information in women with early and advanced breast cancer.

Serum soluble vascular cell adhesion molecule-1: role as a surrogate marker of angiogenesis.

BACKGROUND: Angiogenesis, the development of new blood vessels from pre-existing vasculature, is a prerequisite for tumor growth and metastasis. Surrogate markers for angiogenesis would be useful for studying the effectiveness of antiangiogenesis drugs. We examined the potential of three serum glycoproteins-vascular cell adhesion molecule-1 (VCAM-1), endothelial selectin (E-selectin), and von Willebrand factor (VWF)-to serve as markers for angiogenesis. METHODS: Preoperative serum levels of VCAM-1, E-selectin, and VWF were measured by enzyme-linked immunosorbent assay in 93 women with early breast cancer and were compared with microvessel density in each tumor, histologic features, and recurrence after surgery. Serum samples were taken from 55 women with advanced breast cancer who were commencing hormonal therapy, both immediately before therapy and 3 months later. Changes in serum levels of VCAM-1, E-selectin, and VWF were compared with the response of the disease to hormonal therapy assessed 6 months after the start of hormone therapy or at disease progression. All P: values are two-sided. RESULTS: In women with early breast cancer, serum levels of VCAM-1 (but not of E-selectin or VWF) correlated closely with microvessel density in tumors (r =.65; P:<.001), and women who developed early recurrence had higher preoperative levels of serum VCAM-1 than those who remained disease free (P: =.01). Serum VCAM-1 levels rose in women with advanced breast cancer whose disease progressed (P:<.001) but remained unchanged or fell in women with advanced breast cancer whose disease remained stable or showed a partial response to hormonal therapy. CONCLUSION: Serum VCAM-1 appears to be a surrogate marker of angiogenesis in breast cancer. Its measurement may, therefore, help in the assessment of antiangiogenesis drugs currently in phase II trials.

Alteration in platelet function in patients with early breast cancer.

The aim of this study was to examine our hypothesis that platelets of patients with breast cancer were functionally altered compared to healthy controls. The results have shown that the platelets from women with early breast cancer released significantly more vascular endothelial growth factor (VEGF) when stimulated with thrombin, tissue factor, clotting, or over a period of time. Similarly, release of thrombospondin (TSP) with thrombin and tissue factor was higher, but failed to reach a significant level. Thus, the observed differences in platelet response support our hypothesis, but warrant further work to determine the reason underlying the observed difference and potential clinical relevance of our findings.

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.

Surrogate markers of tumoral angiogenesis.

BACKGROUND: Angiogenesis is a prerequisite for tumor growth and metastasis. Vascular cell adhesion molecule1 (VCAM-1) is expressed on endothelial cells as a result of vascular endothelial growth factor (VEGF) stimulation. PURPOSE: To determine if measurement in serum of VEGF or VCAM-1 provides an accurate measure of tumor angiogenesis. METHODS: VCAM-1 and VEGF were measured in the serum of women with early and advanced breast cancer by ELISA. Levels were compared to levels of VCAM-1 and VEGF in women with normal breasts and levels of the endothelial glycoprotein von Willebrand factor. Levels of VEGF and VCAM-1 in women with early breast cancer were correlated with established clinicopathological prognostic markers and intratumoral microvessel density (IMD). RESULTS: In early breast cancer serum VCAM-1 correlated closely with the microvessel density in tumors (r=0.61, p<0.001). Women with lymph node-positive and high-grade tumors had higher levels of serum VCAM-1 than women with lymph node-negative and low-grade tumors. Serum VEGF demonstrated no correlation with established prognostic features or IMD. Levels of VCAM-1 and VEGF were raised in women with advanced breast cancer. CONCLUSION: Serum VCAM-1 is a surrogate marker of angiogenesis in breast cancer and its measurement may help in the assessment of antiangiogenic drugs currently in phase II trials.

Increased soluble intercellular adhesion molecule-1, breast cancer and the acute phase response.

Abnormal levels of soluble intercellular adhesion molecule-1 (sICAM-1), C-reactive protein (CRP) and von Willebrand factor (vWf) are commonly found in breast and other cancers. However, the relationship between these molecules is unclear as raised sICAM-1 and vWf may simply reflect an acute phase response. We tested the hypothesis that raised sICAM-1 and vWf are related to the acute phase response by measuring both markers by enzyme-linked immunosorbent assay, and CRP by dry chemistry, in 40 women with breast cancer (cases) and 40 age-matched controls. All three markers were raised in the cases compared with the controls [sICAM-1 (mean +/- SD), 281 +/- 70 versus 230 +/- 40 ng/ml; vWf (mean +/- SD), 139 +/- 33 versus 106 +/- 16 IU/dl; CRP (median), 7 (interquartile range, 5-11) versus 5 (4-6) mg/dl; all P < 0.01]. However, sICAM-1 correlated strongly with CRP (r = 0.67, P < 0.001) in the cases but there was no significant relationship between vWf and CRP (r = -0.15, P = 0.351). There were no significant correlations in the controls. We conclude that raised sICAM-1 in breast cancer, like the acute phase response, reflects inflammation, and that raised vWf seems likely to be independent of the acute phase response.

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.

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.

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.

Prevention of venous thromboembolism in surgical patients with breast cancer.

BACKGROUND: No randomized trial has yet studied venous thromboembolism (VTE) prophylaxis in patients undergoing surgery for breast cancer. METHODS: Relevant articles were identified using Medline searches. Secondary articles were identified from the reference lists of key papers. RESULTS AND CONCLUSION: The absence of randomized trials comparing different methods of VTE prophylaxis with controls makes an evidence-based consensus among breast cancer surgeons difficult. Intermittent pneumatic compression (IPC) and graduated compression (GC) are effective in reducing VTE without the haemorrhagic complications associated with heparin; their effects are additive. The authors suggest the following strategy. All patients undergoing surgery for breast cancer should receive both IPC and GC, with heparin reserved for those at very high risk. A controlled trial should randomize women to receive heparin or not, and all women should have both IPC and GC. The primary endpoints should be the development of VTE and/or haemorrhagic complications.

The clinical utility of the Hopkins Verbal Learning Test as a screening test for mild dementia.

OBJECTIVE: The purpose of this study was to determine whether the Hopkins Verbal Learning Test (HVLT) could be used as a valid and reliable screening test for mild dementia in older people, and to compare its performance to that of the Mini-Mental State Examination (MMSE). METHOD: Using a cross-sectional design, we studied three groups of older subjects recruited from a district geriatric psychiatry service: (1) 26 patients with DSM-IV dementia and MMSE scores of 18 or better; (2) 15 patients with psychiatric diagnoses other than dementia; and (3) 15 normal controls. The relationship of each potential cutting point on the HVLT and the MMSE was examined against the independently ascertained DSM-IV diagnoses of dementia using a Receiver Operating Characteristic (ROC) analysis. RESULTS: The subjects consisted of 21 (37.5%) males and 35 (62.5%) females with a mean age of 74.7 (SD 6.1) years and a mean of 8.5 (SD 1.8) years of formal education. ROC analysis indicated that the optimal cutting point for detecting mild dementia in this group of subjects using the HVLT was 18/19 (sensitivity=0.96, specificity=0.80) and using the MMSE was 25/26 (sensitivity=0.88, specificity=0.93). CONCLUSIONS: The HVLT can be recommended as a valid and reliable screening test for mild dementia and as an adjunct in the clinical assessment of older people. The HVLT had better sensitivity than the MMSE in detecting patients with mild dementia, whereas the MMSE had better specificity.

Disruptive vocalization and depression in older nursing home residents.

Screaming and other types of disruptive vocalization are commonly observed among nursing home residents. Depressive symptoms are also frequently seen in this group, although the relationship between disruptive vocalization and depressive symptoms is unclear. Accordingly, we sought to examine this relationship in older nursing home residents. We undertook a controlled comparison of 41 vocally disruptive nursing home residents and 43 nonvocally-disruptive nursing home residents. All participants were selected to have Mini-Mental State Examination (MMSE) scores of at least 10. Participants had a mean age of 81.0 years (range 63-97 years) and had a mean MMSE score of 17.8 (range 10-29). Nurse ratings of disruptive vocalization according to a semioperationalized definition were validated against the noisy behavior subscale of the Cohen-Mansfield Agitation Inventory. Subjects were independently rated for depressive symptoms by a psychiatrist using the Dementia Mood Assessment Scale, the Cornell Scale for Depression in Dementia, and the Depressive Signs Scale. Vocally disruptive nursing home residents scored significantly higher than controls on each of these three depression-in-dementia scales. These differences remained significant when the effects of possible confounding variables of cognitive impairment, age, and sex were removed. We conclude that depressive symptoms are associated with disruptive vocalization and may have an etiological role in the generation of disruptive vocalization behaviors in elderly nursing home residents.

The psychological symptoms of conjugal bereavement in elderly men over the first 13 months.

OBJECTIVE: The purpose of this study was to investigate the psychological symptoms experienced by recently widowed older men. It was hypothesized that conjugal bereavement in this group would be characterized by a mixture of depression, anxiety and loneliness. DESIGN: Double cohort study. SETTING: Suburban community population of Brisbane, Australia. PARTICIPANTS: Consecutive widowers (65+ years; N = 57) identified from official death records. Married men (65+ years; N = 57) identified from the electoral roll. Widowers interviewed at 6 weeks, 6 months and 13 months post-bereavement. Married men interviewed at similar intervals. MEASURES: Bereavement Phenomenology Questionnaire (BPQ), a 22-item self-report measure employing a four-point response scale to rate the frequency of phenomena over the previous fortnight. Zung Self-rating Depression Scale (SDS). State component of the Spielberger State/Trait Anxiety Inventory (STAI). Revised UCLA Loneliness Scale (ULS). 28-item General Health Questionnaire (GHQ). RESULTS: Widowers reported more state anxiety and general psychological distress, but not more depression or loneliness, than matched married men over the first 13 months post-bereavement. Widowers also reported more sleep disturbance and thoughts of death and suicide than married men. Level of state anxiety was strongly correlated with intensity of grief, but not with age, income, education, occupational prestige, cognitive function, duration of wife's final illness or expectedness of wife's death. CONCLUSIONS: The main hypothesis was not supported, as anxiety symptoms were the predominant clinical feature of recent conjugal bereavement among older men. The nature of these anxiety symptoms requires further investigation in recently widowed older persons.