Sex on premises venue (SOPV) health promotion project in response to sustained increases in HIV notifications

Background: Due to increases in HIV notifications in Queensland, a health promotion outreach project was developed with sex on premises venues (SOPV) in Brisbane. Methods: A health promotion officer (HPO) promoted safer sex behaviours among SOPV patrons over 14 months, including providing information, counselling and skills to enhance safer sexual behaviours and providing referrals. Surveys were introduced to facilitate discussions regarding HIV/sexually transmissible infections, testing and safer sex practices. Results: The project demonstrated feasibility within this highly sexualised environment, and was enhanced by careful monitoring and revising the procedure to improve patron/staff responses to the project. The introduction of a survey instrument was a significant contributor to the project’s effectiveness, providing opportunities for patrons to discuss a variety of key sexual health issues. Conclusions: This initiative reflected effective partnering between the Health Department, a community HIV/lesbian, gay, bisexual and transgender organisation and private industry. Despite initial difficulties, the presence of a health worker within an SOPV was acceptable to patrons and allowed for brief interventions to be conducted. This project was deemed effective for a limited time period and within certain constraints.

p53-independent NOXA induction overcomes apoptotic resistance of malignant melanomas

Once melanoma metastasizes, no effective treatment modalities prolong survival in most patients. This notorious refractoriness to therapy challenges investigators to identify agents that overcome melanoma resistance to apoptosis. Whereas many survival pathways contribute to the death-defying phenotype in melanoma, a defect in apoptotic machinery previously highlighted inactivation of Apaf-1, an apoptosome component engaged after mitochondrial damage. During studies involving Notch signaling in melanoma, we observed a gamma-secretase tripeptide inhibitor (GSI; z-Leu-Leu-Nle-CHO), selected from a group of compounds originally used in Alzheimer's disease, induced apoptosis in nine of nine melanoma lines. GSI only induced G2-M growth arrest (but not killing) in five of five normal melanocyte cultures tested. Effective killing of melanoma cells by GSI involved new protein synthesis and a mitochondrial-based pathway mediated by up-regulation of BH3-only members (Bim and NOXA). p53 activation was not necessary for up-regulation of NOXA in melanoma cells. Blocking GSI-induced NOXA using an antisense (but not control) oligonucleotide significantly reduced the apoptotic response. GSI also killed melanoma cell lines with low Apaf-1 levels. We conclude that GSI is highly effective in killing melanoma cells while sparing normal melanocytes. Direct enhancement of BH3-only proteins executes an apoptotic program overcoming resistance of this lethal tumor. Identification of a p53-independent apoptotic pathway in melanoma cells, including cells with low Apaf-1, bypasses an impediment to current cytotoxic therapy and provides new targets for future therapeutic trials involving chemoresistant tumors.

Malnutrition and chemotherapy-induced nausea and vomiting : implications for practice

PURPOSE/OBJECTIVES: To determine the prevalence of malnutrition and chemotherapy-induced nausea and vomiting (CINV) limiting dietary intake in a chemotherapy unit. DESIGN Cross sectional descriptive audit. SETTING: Chemotherapy ambulatory care unit in an Australian teaching hospital. SAMPLE 121 patients receiving chemotherapy for malignancies, ≥18yrs and able to provide verbal consent. METHODS: An Accredited Practicing Dietitian collected all data. Chi-square tests were used to determine the relationship of malnutrition with variables and demographic data. MAIN RESEARCH VARIABLES: Nutritional status, weight change, BMI, prior dietetic input, CINV and CINV that limited dietary intake. FINDINGS Thirty one (26%) participants were malnourished, 12 (10%) had intake-limiting CINV, 22 (20%) reported significant weight loss and 20 (18%) required improved nutrition symptom management. High nutrition risk diagnoses, CINV, BMI and weight loss were significantly associated with malnutrition. Thirteen (35%) participants with malnutrition, significant weight loss, intake-limiting CINV and/or critically requiring improved symptom management reported no dietetic input; the majority of whom were overweight or obese. CONCLUSIONS: This audit determined over one quarter of patients receiving chemotherapy in this ambulatory setting were malnourished and the majority of patients reporting intake-limiting CINV were malnourished. IMPLICATIONS FOR NURSING Patients with malnutrition and/or intake-limiting CINV and in need of improved nutrition symptom management may be overlooked, especially patients who are overweight or obese - an increasing proportion of the Australian population. Evidence-based practice guidelines recommend implementing validated nutrition screening tools, such as the Malnutrition Screening Tool, in patients undergoing chemotherapy to identify those at risk of malnutrition requiring dietitian referral.

A randomized trial of a telephone-delivered exercise intervention for non-urban dwelling women newly diagnosed with breast cancer : exercise for health

Physical activity is important following breast cancer. Trials of non-face-to-face interventions are needed to assist in reaching women living outside major metropolitan areas. This study seeks to evaluate the feasibility and effectiveness of a telephone-delivered, mixed aerobic and resistance exercise intervention for non-urban Australian women with breast cancer. A randomized controlled trial comparing an 8-month intervention delivered by exercise physiologists (n = 73) to usual care (n = 70). Sixty-one percent recruitment rate and 96% retention at 12 months; 79% of women in the intervention group received at least 75% of calls; odds (OR, 95% CI) of meeting intervention targets favored the intervention group for resistance training (OR 3.2; 1.2, 8.9) and aerobic (OR 2.1; 0.8, 5.5) activity. Given the limited availability of physical activity programs for non-urban women with breast cancer, results provide strong support for feasibility and modest support for the efficacy of telephone-delivered interventions.

Age-related loss of brain volume and T2 relaxation time in youth with type 1 diabetes

OBJECTIVE: Childhood-onset type 1 diabetes is associated with neurocognitive deficits, but there is limited evidence to date regarding associated neuroanatomical brain changes and their relationship to illness variables such as age at disease onset. This report examines age-related changes in volume and T2 relaxation time (a fundamental parameter of magnetic resonance imaging that reflects tissue health) across the whole brain. RESEARCH DESIGN AND METHODS: Type 1 diabetes, N = 79 (mean age 20.32 ± 4.24 years), and healthy control participants, N = 50 (mean age 20.53 ± 3.60 years). There were no substantial group differences on socioeconomic status, sex ratio, or intelligence quotient. RESULTS: Regression analyses revealed a negative correlation between age and brain changes, with decreasing gray matter volume and T2 relaxation time with age in multiple brain regions in the type 1 diabetes group. In comparison, the age-related decline in the control group was small. Examination of the interaction of group and age confirmed a group difference (type 1 diabetes vs. control) in the relationship between age and brain volume/T2 relaxation time. CONCLUSIONS: We demonstrated an interaction between age and group in predicting brain volumes and T2 relaxation time such that there was a decline in these outcomes in type 1 diabetic participants that was much less evident in control subjects. Findings suggest the neurodevelopmental pathways of youth with type 1 diabetes have diverged from those of their healthy peers by late adolescence and early adulthood but the explanation for this phenomenon remains to be clarified.

Prevalence of malnutrition risk and its relationship with risk factors of hospital re-admission in older adults

Background: Risk of malnutrition in older people continues to be a global problem. Malnutrition is often unrecognized and under-treated across health care settings and may result in undesirable health consequences, impaired recovery from illness and a poorer quality of life. Aim: This study aimed to determine the prevalence of malnutrition risk in a sample of older people at high risk of hospital re-admission. The association between risk factors of hospital re-admission and risk of malnutrition were also explored. Methods: One hundred and twenty five hospitalised patients aged 65 years and older at risk of hospital readmission (24% male, 76% female, mean age 77 ± 6 years) were recruited from a tertiary metropolitan hospital in Australia. The valid and reliable Malnutrition Screen Tool (MST) was employed to screen for malnutrition risk. It consists of two questions related to recent weight loss and appetite. Results: Prevalence of older adults at risk of malnutrition was 27.4%. Risk of malnutrition was not associated with age, gender and living arrangement. However, among risk factors of hospital readmission, lack of social support (χ2 = 4.18, N = 125, p = 0.028), and fair –poor self-rating of health (χ2 = 4.13, N = 125, p = 0.042) were statistically significant associated with risk of malnutrition. Conclusion: Risk of malnutrition in older people continues to be a concern in health care, and increasing psycho social support may help shed light on reducing risk of malnutrition.

Validity of the malnutrition screening tool for older adults at high risk of hospital readmission

Malnutrition is a serious problem in older adults, particularly for those at risk of hospital readmission. The essential step in managing malnutrition is early identification using a valid nutrition screening tool. The purpose of this study was to validate the Malnutrition Screening Tool (MST) in older adults at high risk of hospital readmission. Two registered nurses administered the MST to identify malnutrition risk, and compared it to the comprehensive Subjective Global Assessment (SGA) to assess nutritional status for patients aged 65 years who had at least one risk factor for hospital readmission. The MST demonstrates substantial sensitivity, specificity and agreement with the SGA. These findings indicate that nursing staff can use the MST as a valid tool for routine screening and rescreening to identify patients at risk of malnutrition. Use of the MST may prevent hospital-acquired malnutrition for acute hospitalized older adults at high risk of readmission.

PARP inhibition induces BAX/BAK-independent synthetic lethality of BRCA1-deficient non-small cell lung cancer

Evasion of apoptosis contributes to both tumourigenesis and drug resistance in non-small cell lung carcinoma (NSCLC). The pro-apoptotic BCL-2 family proteins BAX and BAK are critical regulators of mitochondrial apoptosis. New strategies for targeting NSCLC in a mitochondria-independent manner should bypass this common mechanism of apoptosis block. BRCA1 mutation frequency in lung cancer is low; however, decreased BRCA1 mRNA and protein expression levels have been reported in a significant proportion of lung adenocarcinomas. BRCA1 mutation/deficiency confers a defect in homologous recombination DNA repair that has been exploited by synthetic lethality through inhibition of PARP (PARPi) in breast and ovarian cells; however, it is not known whether this same synthetic lethal mechanism exists in NSCLC cells. Additionally, it is unknown whether the mitochondrial apoptotic pathway is required for BRCA1/PARPi-mediated synthetic lethality. Here we demonstrate that silencing of BRCA1 expression by RNA interference sensitizes NSCLC cells to PARP inhibition. Importantly, this sensitivity was not attenuated in cells harbouring mitochondrial apoptosis block induced by co-depletion of BAX and BAK. Furthermore, we demonstrate that BRCA1 inhibition cannot override platinum resistance, which is often mediated by loss of mitochondrial apoptosis signalling, but can still sensitize to PARP inhibition. Finally we demonstrate the existence of a BRCA1-deficient subgroup (11–19%) of NSCLC patients by analysing BRCA1 protein levels using immunohistochemistry in two independent primary NSCLC cohorts. Taken together, the existence of BRCA1-immunodeficient NSCLC suggests that this molecular subgroup could be effectively targeted by PARP inhibitors in the clinic and that PARP inhibitors could be used for the treatment of BRCA1-immunodeficient, platinum-resistant tumours.