Disparities in access to anti-vascular endothelial growth factor treatment for neovascular age-related macular degeneration.

BACKGROUND: Late neovascular age-related macular degeneration (nvAMD) is very common and causes irreversible severe visual loss unless treated swiftly with vascular endothelial growth factor (VEGF) inhibitors. Although publicly subsidized access to treatment may be inequitable, which is why we assessed treatment provision across Australia. DESIGN: Secondary analysis of Australian data. PARTICIPANTS: All Pharmaceutical Benefits Scheme (including Repatriation PBS) beneficiaries. METHODS: Treatment and incidence data were obtained from Medicare Australia, the Royal Australian and New Zealand College of Ophthalmologists, Optometry Australia, the Blue Mountains Eye Study and the Australian Bureau of Statistics. Data were mapped using geographical information software, and factors associated with treatment provision were assessed using multiple linear regression models. MAIN OUTCOME MEASURE: Unmet need (%) for anti-VEGF treatment for nvAMD. RESULTS: On average, we estimated 7316 incident cases of nvAMD not to be treated per year from 2010 to 2014 (50.1% of total). Number of ophthalmologists and optometrists (per 1000, ß = -0.024; 95% confidence interval [CI] -0.041, -0.007) and being located in remote regions (ß = 0.186; 95% CI 0.110, 0.262) were associated with percentage of untreated cases. A higher proportion of the population speaking a language other than English at home was associated in univariate analyses only (ß = 0.0015; 95% CI -0.0004, 0.0027; P = 0.007). CONCLUSION: A large proportion of incident nvAMD is not treated with anti-VEGF. Not receiving treatment is more likely in regional or remote areas and areas with fewer service providers. Not speaking English at home may further limit access. Service delivery models for more equitable service provision are needed.

Predictors of psychological distress in caregivers of older persons with wet age-related macular degeneration.

OBJECTIVES: Several studies have investigated the biopsychosocial impacts of age-related macular degeneration (AMD) in regards to the older patient, little is known about the impacts associated with caring for individuals with AMD. We aimed to determine the predictors of subjective caregiver distress and other negative outcomes associated with caring for someone with advanced AMD. METHODS: Cross-sectional, self-complete survey involving 500 caregivers of persons with advanced AMD. Respondents were identified from the Macular Disease Foundation of Australia client database. Logistic regression tested the independent effects of care recipient and caregiver characteristics on study outcomes, including: caregiver psychological well-being, participation in recreational/social activities and retirement plans. RESULTS: Around one third of caregivers self-reported a high level of care recipient dependence. Over one in two caregivers reported a negative state of mind. Comorbid chronic illnesses in the care recipient were associated with the caregiver reporting psychological distress, multivariable-adjusted odds ratio, OR, 1.45 (95% confidence intervals, CI, 1.14-1.86). If the care recipient was highly dependent on the caregiver, there was 99% greater likelihood of caregiver distress, OR 1.99 (95% CI 1.01-3.93). Comorbid chronic conditions in the care recipient was associated with 49% and 31% higher odds of the caregiver reporting disruption to other areas of their life and retirement plans related to the caregiving experience, respectively. CONCLUSIONS: A high prevalence of caregiver distress related to caring for persons with advanced AMD was observed. Level of dependence on the caregiver and presence of comorbid chronic illnesses were independent predictors of the caregiver experiencing psychological distress.

In vitro and in vivo characterisation of a novel c-FLIP-targeted antisense phosphorothioate oligonucleotide.

Previous studies have suggested that the caspase 8 inhibitor FLIP is a promising anti-cancer therapeutic target. In this study, we characterised a novel FLIP-targeted antisense phosphorothioate oligonucleotide (AS PTO). FLIP AS and control PTOs were assessed in vitro in transient transfection experiments and in vivo using xenograft models in Balb/c nude mice. FLIP expression was assessed by QPCR and Western. Apoptosis induction was determined by flow cytometry and Western. Of 5 sequences generated, one potently down-regulated FLIP. AS PTO-mediated down-regulation of FLIP resulted in caspase 8 activation and apoptosis induction in non-small cell lung (NSCLC) cells but not in normal lung cells. Similar results were observed in colorectal and prostate cancer cells. Furthermore, the FLIP AS PTO sensitized cancer cells but not normal lung cells to apoptosis induced by rTRAIL. Moreover, the FLIP AS PTO enhanced chemotherapy-induced apoptosis in NSCLC cells. Importantly, compared to a control non-targeted PTO, intra-peritoneal delivery of FLIP AS PTO inhibited the growth of NSCLC xenografts and enhanced the in vivo antitumour effects of cisplatin. We have identified a novel FLIP-targeted AS PTO that has in vitro and in vivo activity and which therefore has potential for further pre-clinical development.

Intravenous glutamine enhances COX-2 activity giving cardioprotection.

BACKGROUND: Preconditioning, a highly evolutionary conserved endogenous protective response, provides the most powerful form of anti-infarct protection known. We investigated whether acute intravenous glutamine, through an effect on cyclooxygenase (COX)-2 and heat shock protein (HSP) 72, might induce preconditioning. MATERIALS AND METHODS: Male New Zealand white rabbits (n = 28) received either 0.5 g/kg glutamine in 0.9% saline or saline only in divided doses for 3 d. The large marginal branch of the left coronary was occluded for 30 min; cardiac function was assessed during 3 h of reperfusion, and infarct size was measured. 6-Keto-PGF-1alpha, nitrate, and malonaldehyde serum levels were determined. Hearts were taken from a further group of pretreated rabbits (n = 10) to assess myocardial COX-2 and HSP72 levels. RESULTS: Glutamine pretreatment resulted in a 39% reduction in infarct size (30.7 +/- 2.0% versus 50.4 +/- 2.1% controls; P < 0.01). Myocardial COX-2 levels were significantly elevated with pretreatment (P < 0.05) and were mirrored by higher serum 6-keto-PGF-1alpha levels prior to ischemia (69 +/- 13 versus 18 +/- 21 pg/mL in controls, P = 0.027). There was no significant difference in myocardial HSP72 or serum nitrate levels following pretreatment, or malonaldehyde levels during reperfusion. CONCLUSIONS: Glutamine pretreatment confers anti-infarct protection through up-regulation of COX-2, a key mediator of delayed preconditioning protection. Previous confirmation of its clinical safety profile at these doses suggests an acceptable strategy for inducing preconditioning for perioperative protection.

Implementing a multi-modal support service model for the family caregivers of persons with age-related macular degeneration: a study protocol for a randomised controlled trial.

INTRODUCTION: Age-related macular degeneration (AMD) is a leading cause of blindness and low vision among older adults. Previous research shows a high prevalence of distress and disruption to the lifestyle of family caregivers of persons with late AMD. This supports existing evidence that caregivers are 'hidden patients' at risk of poor health outcomes. There is ample scope for improving the support available to caregivers, and further research should be undertaken into developing services that are tailored to the requirements of family caregivers of persons with AMD. This study aims to implement and evaluate an innovative, multi-modal support service programme that aims to empower family caregivers by improving their coping strategies, enhancing hopeful feelings such as self-efficacy and helping them make the most of available sources of social and financial support. METHODS AND ANALYSIS: A randomised controlled trial consisting of 360 caregiver-patient pairs (180 in each of the intervention and wait-list control groups). The intervention group will receive the following: (1) mail-delivered cognitive behavioural therapy designed to improve psychological adjustment and adaptive coping skills; (2) telephone-delivered group counselling sessions allowing caregivers to explore the impacts of caring and share their experiences; and (3) education on available community services/resources, financial benefits and respite services. The cognitive behavioural therapy embedded in this programme is the best evaluated and widely used psychosocial intervention. The primary outcome is a reduction in caregiver burden. Secondary outcomes include improvements in caregiver mental well-being, quality of life, fatigue and self-efficacy. Economic analysis will inform whether this intervention is cost-effective and if it is feasible to roll out this service on a larger scale. ETHICS AND DISSEMINATION: The study was approved by the University of Sydney human research ethics committee. Study findings will be disseminated via presentations at national/international conferences and peer-reviewed journal articles. TRIAL REGISTRATION NUMBER: The trial registration number is ACTRN12616001461482; pre-results.