Overcoming silos in health care systems through meso-level organisations - a case study of health reforms in New South Wales, Australia.

Fragmented care delivery is a barrier to improving health system performance worldwide. Investment in meso-level organisations is a potential strategy to improve health system integration, however, its effectiveness remains unclear. In this paper, we provide an overview of key international and Australian integrated care policies. We then describe Collaborative Commissioning - a novel health reform policy to integrate primary and hospital care sectors in New South Wales (NSW), Australia and provide a case study of a model focussed on older person's care. The policy is theorised to achieve greater integration through improved governance (local stakeholders identifying as part of one health system), service delivery (communities perceive new services as preferable to status quo) and incentives (efficiency gains are reinvested locally with progressively higher value care achieved). If effectively implemented at scale, Collaborative Commissioning has potential to improve health system performance in Australia and will be of relevance to similar reform initiatives in other countries.

Promoting equitable health workforce distribution through improved migration governance: A mixed methods study of African health professionals' perceptions in Australia.

BACKGROUND: This study examined skilled health worker (SHW) migration governance in African countries and Australia, with an emphasis on areas of influence for achieving an equitable global health workforce distribution. METHODS: We used a mixed-methods research design with African SHW migrants in Australia. An institutional and rights-based framing of governance guided thematic analysis of the interviews, which was mapped to survey findings from a Bayesian Exploratory Factor Analysis. RESULTS: The findings imply that Australian state actors enforce laws that attract SHW migrants and promote safe clinical practice, but do not adequately address their integration concerns or role in health system strengthening. Non-state actors in Australia make donations to African health institutions but rarely promote health workforce equity. African state actors respond to increased SHW migration trends by increasing health worker training and limiting migration, but they lack a comprehensive governance framework for involving citizens and engaging foreign governments. There is limited evidence of a shared community definition of SHW migration governance in many African countries. CONCLUSION: When stakeholders in both sending and receiving countries recognise the indivisibility of the rights at stake (for example, SHW rights as migrants and the right to health), support for an equity-focused SHW migration governance system may increase. Promoting these rights can result in policies that enhance health system strengthening in destination and source countries. Similarly, growing adoption of these rights in sending countries should help inspire a coordinated plan for strengthening health system and SHW migration governance.

Safety and Effectiveness of Rivaroxaban Versus Warfarin Across GFR Levels in Atrial Fibrillation: A Population-Based Study in Australia and Canada.

Rationale & Objective: The benefit-risk profile of rivaroxaban versus warfarin for atrial fibrillation (AF) in patients with chronic kidney disease is uncertain. We compared rivaroxaban with warfarin across the range of kidney function in adults with AF. Study Design: Multicenter retrospective cohort. Setting & Participants: Adults with AF and a measure of estimated glomerular filtration rate (eGFR); using administrative data from 5 jurisdictions across Australia and Canada (2011-2018). Kidney function was categorized as eGFR ≥60, 45-59, 30-44, and <30 mL/min/1.73 m2. Patients receiving dialysis and kidney transplant recipients were excluded. Exposures: New dispensation of either rivaroxaban or warfarin. Outcomes: Composite (1) effectiveness outcome (all-cause death, ischemic stroke, or transient ischemic attack) and (2) major bleeding events (intracranial, gastrointestinal, or other) at 1 year. Analytical Approach: Cox proportional hazards models accounting for propensity score matching were performed independently in each jurisdiction and then pooled using random-effects meta-analysis. Results: 55,568 patients (27,784 rivaroxaban-warfarin user matched pairs; mean age 74 years, 46% female, 33.5% with eGFR <60 mL/min/1.73 m2) experienced a total of 4,733 (8.5%) effectiveness and 1,144 (2.0%) bleeding events. Compared to warfarin, rivaroxaban was associated with greater or similar effectiveness across a broad range of kidney function (pooled HRs of 0.72 [95% CI, 0.66-0.78], 0.78 [95% CI, 0.58-1.06], 0.70 [95% CI, 0.57-0.87], and 0.78 [95% CI, 0.62-0.99]) for eGFR ≥60, 45-59, 30-44, and <30 mL/min/1.73 m2, respectively). Rivaroxaban was also associated with similar risk of major bleeding across all eGFR categories (pooled HRs of 0.75 [95% CI, 0.56-1.00], 1.01 [95% CI, 0.79-1.30], 0.87 [95% CI, 0.66-1.15], and 0.63 [95% CI, 0.37-1.09], respectively). Limitations: Unmeasured treatment selection bias and residual confounding. Conclusions: In adults with AF, rivaroxaban compared with warfarin was associated with lower or similar risk of all-cause death, ischemic stroke and transient ischemic attack and similar risk of bleeding across a broad range of kidney function. Plain-Language Summary: This real-world study involved a large cohort of 55,568 adults with atrial fibrillation from 5 jurisdictions across Australia and Canada. It showed that the favorable safety (bleeding) and effectiveness (stroke or death) profile of rivaroxaban compared with warfarin was consistent across different levels of kidney function. This study adds important safety data on the use of rivaroxaban in patients with reduced kidney function, including those with estimated glomerular filtration rate <30 mL/min/1.73 m2 in whom the risks and benefits of rivaroxaban use is most uncertain. Overall, the study supports the use of rivaroxaban as a safe and effective alternative to warfarin for atrial fibrillation across differing levels of kidney function.

Cross-sectional survey of a convenience sample of Australians who use alcohol home delivery services.

INTRODUCTION: Online alcohol purchasing and home delivery has increased in recent years, accelerated by the onset of the coronavirus disease 2019 pandemic. This article aims to investigate the purchasing and drinking behaviour of Australians who use online alcohol delivery services. METHOD: A cross-sectional self-report survey with a convenience sample of 1158 Australians ≥18 years (49.3% female) who used an online alcohol delivery service in the past 3 months, recruited through paid social media advertisements from September to November 2021. Quota sampling was used to obtain a sample with age and gender strata proportional to the Australian adult population. Descriptive statistics were generated and logistic regression used to explore variables that predict hazardous/harmful drinking (Alcohol Use Disorders Identification Test score ≥8). RESULTS: One-in-five (20.1%, 95% confidence interval [CI] 17.8-22.5) participants had used an alcohol delivery service to extend a home drinking session because they had run out of alcohol and wanted to continue drinking and, of these, one-third (33.9%, 95% CI 27.9-40.4) indicated that if the service was not available they would have stopped drinking. Using delivery services in this way was associated with six times higher odds of drinking at hazardous/harmful levels (odds ratio 6.26, 95% CI 3.78-10.36). Participants ≤25 years were significantly more likely to report never having their identification verified when receiving their alcohol delivery at the door compared with purchasing takeaway alcohol in-person at a bottle shop (p < 0.001, McNemar). DISCUSSION AND CONCLUSION: Given the risks associated with alcohol delivery, regulation of these services should be improved to meet the same standards as bricks-and-mortar bottle shops.

Kidney function and the comparative effectiveness and safety of direct oral anticoagulants vs. warfarin in adults with atrial fibrillation: a multicenter observational study.

AIMS: The aim of this study was to determine the comparative effectiveness and safety of direct oral anticoagulants (DOACs) and warfarin in adults with atrial fibrillation (AF) by level of kidney function. METHODS AND RESULTS: We pooled findings from five retrospective cohorts (2011-18) across Australia and Canada of adults with; a new dispensation for a DOAC or warfarin, an AF diagnosis, and a measure of baseline estimated glomerular filtration rate (eGFR). The outcomes of interest, within 1 year from the cohort entry date, were: (1) the composite of all-cause death, first hospitalization for ischaemic stroke, or transient ischaemic attack (effectiveness), and (2) first hospitalization for major bleeding defined as an intracranial, upper or lower gastrointestinal, or other bleeding (safety). Cox models were used to examine the association of a DOAC vs. warfarin with outcomes, after 1:1 matching via a propensity score. Kidney function was categorized as eGFR ≥60, 45-59, 30-44, and <30 mL/min/1.73 m2. A total of 74 542 patients were included in the matched analysis. DOAC initiation was associated with greater or similar effectiveness compared with warfarin initiation across all eGFR categories [pooled HRs (95% CIs) for eGFR categories: 0.74(0.69-0.79), 0.76(0.54-1.07), 0.68(0.61-0.75) and 0.86(0.76-0.98)], respectively. DOAC initiation was associated with lower or similar risk of major bleeding than warfarin initiation [pooled HRs (95% CIs): 0.75(0.65-0.86), 0.81(0.65-1.01), 0.82(0.66-1.02), and 0.71(0.52-0.99), respectively). Associations between DOAC initiation, compared with warfarin initiation, and study outcomes were not modified by eGFR category. CONCLUSION: DOAC use, compared with warfarin use, was associated with a lower or similar risk of all-cause death, ischaemic stroke, and transient ischaemic attack and also a lower or similar risk of major bleeding across all levels of kidney function.

Utilisation of government-subsidised chronic disease management plans and cardiovascular care in Australian general practices.

BACKGROUND: Government-subsidised general practice management plans (GPMPs) facilitate chronic disease management; however, impact on cardiovascular disease (CVD) is unknown. We aimed to determine utilisation and impact of GPMPs for people with or at elevated risk of CVD. METHODS: Secondary analysis of baseline data from the CONNECT randomised controlled trial linked to Medicare Benefits Schedule (MBS) and Pharmaceutical Benefits Scheme (PBS) claims. Multivariate regression examining the association of GPMP receipt and review with: (1) ≥ 1 MBS-subsidised allied health visit in the previous 24 months; (2) adherence to dual cardioprotective medication (≥ 80% of days covered with a dispensed PBS prescription); and (3) meeting recommended LDL-cholesterol and blood pressure (BP) targets concurrently. RESULTS: Overall, 905 trial participants from 24 primary health care services consented to data linkage. Participants with a GPMP (46.6%, 422/905) were older (69.4 vs 66.0 years), had lower education (32.3% vs 24.7% high school or lower), lower household income (27.5% vs 17.0% in lowest bracket), and more comorbidities, particularly diabetes (42.2% vs 17.6%) compared to those without a GPMP. After adjustment, a GPMP was strongly associated with allied health visits (odds ratio (OR) 14.80, 95% CI: 9.08-24.11) but not higher medication adherence rates (OR 0.82, 95% CI: 0.52-1.29) nor meeting combined LDL and BP targets (OR 1.31, 95% CI: 0.72-2.38). Minor differences in significant covariates were noted in models using GPMP review versus GPMP initiation. CONCLUSIONS: In people with or at elevated risk of CVD, GPMPs are under-utilised overall. They are targeting high-needs populations and facilitate allied health access, but are not associated with improved CVD risk management, which represents an opportunity for enhancing their value in supporting guideline-recommended care.

Integrating Pharmacy and Registry Data Strengthens Clinical Assessments of Patient Adherence.

Background: Accurate clinical assessment of patient adherence using reliable and valid measures is essential in establishing the presence of adherence issues and support practices for pharmacists. Objective: This investigation aims to conduct a novel assessment of patient adherence to asthma controller therapy by combining 1) patient-specific dosage data found in pharmacy dispensing data with 2) centrally collected administrative claims records, to determine the added value of using both sources of data. Methods: A total of 381 clinically uncontrolled asthma patients, from 95 community pharmacies across three Australian States were recruited and provided consent for the retrieval of their claims records and pharmacy dispensing data. Patients were stratified as multiple or single pharmacy users and adherence scores were calculated via the proportion of days covered (PDC) method using 1) patient claims records, 2) patient pharmacy dispensing data, and 3) combined claims records and pharmacy dispensing data. Cohort and subgroup adherence estimates were then compared. Results: Low levels of adherence were evident amongst the cohort irrespective of the data source used. PDC estimates based on claims records alone or combined claims records and pharmacy dispensing data were significantly higher than estimates based on pharmacy dispensing data for the total cohort (56%, 52%, 42% respectively, p < 0.001) and more noticeably for multiple pharmacy users (67%, 64%, 35% respectively, p < 0.001). PDC estimates based on combined claims records and pharmacy dispensing data were significantly lower than estimates based on claims records alone, indicating that perhaps standard daily dose is not a robust proxy for prescribed dosage to inhaled respiratory devices in adherence approximations. Poorer adherence was found amongst single pharmacy users than multiple pharmacy users when combined claims records and pharmacy dispensing data (46% compared to 64% respectively, p < 0.001) or claims records alone (51% compared to 67% respectively, p < 0.001) were compared. Conclusion: Access to routine collected data increases clinical acuity over patient adherence to asthma controller medications and is a valuable resource for health care professionals. A policy of secure accessibility of such data at the patient-pharmacist or patient-GP interface may allow real-time intervention and assist in decision making across numerous therapeutic areas.

Prior Cardiovascular Treatments-A Key Characteristic in Determining Medication Adherence After an Acute Myocardial Infarction.

Objective: To investigate long-term adherence to guideline-recommended cardioprotective medications following hospitalization for an acute myocardial infarction (AMI), and identify characteristics associated with adherence. Methods: An Australian population-based cohort study was used to identify participants who had their first AMI between 2006 and 2014 and were alive after 12 months. Linked routinely collected hospital, and prescription medication claims data was used to study adherence over time. Predictors and rates of adherence to both lipid-lowering medication and renin-angiotensin system blockade at 12 months post-AMI was assessed. Results: 14,200 people (mean age 69.9 years, 38.7% female) were included in our analysis. At 12 months post-AMI, 29.5% (95% CI: 28.8-30.3%) of people were adherent to both classes of medication. Individuals receiving treatment with both lipid-lowering medication and renin-angiotensin system blockade during the 6 months prior to their AMI were over 9 times more likely to be adherent to both medications at 12 months post-AMI (66.2% 95% CI: 64.8-67.5%) compared to those with no prior medication use (treatment naïve) (7.1%, 95% CI: 6.4-7.9%). Prior cardiovascular treatment was the strongest predictor of long-term adherence even after adjusting for age, sex, education and income. Conclusions: Despite efforts to improve long-term medication adherence in patients who have experienced an acute coronary event, considerable gaps remain. Of particular concern are people who are commencing guideline-recommended cardioprotective medication at the time of their AMI. The relationship between prior cardiovascular treatments and post AMI adherence offers insight into the support needs for the patient. Health care intervention strategies, strengthened by enabling policies, are needed to provide support to patients through the initial months following their AMI.

Dysnatremia and 6-Month Functional Outcomes in Critically Ill Patients With Aneurysmal Subarachnoid Hemorrhage: A Prospective Cohort Study.

OBJECTIVES: To investigate the association between plasma sodium concentrations and 6-month neurologic outcome in critically ill patients with aneurysmal subarachnoid hemorrhage. DESIGN: Prospective cohort study. SETTING: Eleven ICUs in Australia and New Zealand. PARTICIPANTS: Three-hundred fifty-six aneurysmal subarachnoid hemorrhage patients admitted to ICU between March 2016 and June 2018. The exposure variable was daily measured plasma sodium. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Six-month neurologic outcome as measured by the modified Rankin Scale. A poor outcome was defined as a modified Rankin Scale greater than or equal to 4. The mean age was 57 years (± 12.6 yr), 68% were female, and 32% (n = 113) had a poor outcome. In multivariable analysis, including age, illness severity, and process of care measures as covariates, higher mean sodium concentrations (odds ratio, 1.17; 95% CI, 1.05-1.29), and greater overall variability-as measured by the sd (odds ratio, 1.53; 95% CI, 1.17-1.99)-were associated with a greater likelihood of a poor outcome. Multivariable generalized additive modeling demonstrated, specifically, that a high initial sodium concentration, followed by a gradual decline from day 3 onwards, was also associated with a poor outcome. Finally, greater variability in sodium concentrations was associated with a longer ICU and hospital length of stay: mean ICU length of stay ratio (1.13; 95% CI, 1.07-1.20) and mean hospital length of stay ratio (1.08; 95% CI, 1.01-1.15). CONCLUSIONS: In critically ill aneurysmal subarachnoid hemorrhage patients, higher mean sodium concentrations and greater variability were associated with worse neurologic outcomes at 6 months, despite adjustment for known confounders. Interventional studies would be required to demonstrate a causal relationship.

Prevalence, incidence and risk factors of diabetes in Australian adults aged ≥45 years: A cohort study using linked routinely-collected data.

AIMS: To use linked routinely-collected health data to estimate diabetes prevalence and incidence in an Australian cohort of adults aged ≥45 years, and examine risk factors associated with incident disease. RESEARCH DESIGN AND METHODS: The EXamining ouTcomEs in chroNic Disease in the 45 and Up Study (EXTEND45) Study is a linked data study that combines baseline questionnaire responses from the population-based 45 and Up Study (2006-2009, n = 267,153) with multiple routinely-collected health databases up to December 2014. Among participants with ≥1 linked result for any laboratory test, diabetes status was determined from multiple data sources according to standard biochemical criteria, use of glucose-lowering medication or self-report, and the prevalence and incidence rate calculated. Independent risk factors of incident diabetes were examined using multivariable Cox regression. RESULTS: Among 152,169 45 and Up Study participants with ≥1 linked laboratory result in the EXTEND45 database (mean age 63.0 years; 54.9% female), diabetes prevalence was 10.8% (95% confidence interval [CI] 10.6%-10.9%). Incident disease in those without diabetes at baseline (n = 135,810; mean age 62.5 years; 56.1% female) was 10.0 per 1,000 person-years (95% CI 9.8-10.2). In all age groups, diabetes incidence was lower in women compared to men, an association that persisted in the fully adjusted analyses. Other independent risk factors of diabetes were older age, being born outside of Australia (with the highest rate of 19.2 per 1,000 person-years observed in people born in South and Central Asia), lower education status, lower annual household income, residence in a major city, family history of diabetes, personal history of cardiovascular disease or hypertension, higher body mass index, smoking and long sleeping hours. CONCLUSIONS: Our study represents an efficient approach to assessing diabetes frequency and its risk factors in the community. The infrastructure provided by the EXTEND45 Study will be useful for diabetes surveillance and examining other important clinical and epidemiological questions.

EXamining ouTcomEs in chroNic Disease in the 45 and Up Study (the EXTEND45 Study): Protocol for an Australian Linked Cohort Study.

BACKGROUND: Chronic kidney disease (CKD) and diabetes are the major causes of death and disability worldwide. They are associated with high health service utilization persisting over many years. Their slow progression and wide clinical variation make them eminently suitable for study in population-based cohorts. However, current understanding of their prevalence, incidence, and progression is largely based on studies conducted in clinical populations. OBJECTIVE: This study aims to establish a novel link between an existing population-based cohort (the 45 and Up Study) and routinely collected laboratory and administrative data to facilitate research across the full disease spectrum of CKD and diabetes. METHODS: In the EXTEND45 Study (EXamining OuTcomEs in chroNic Disease in the 45 and Up Study), baseline questionnaire responses of over 260,000 participants of the 45 and Up Study aged ≥45 years living in New South Wales (NSW), collected between January 2006 and December 2009, are linked to data from laboratory service providers as well as national- and state-based administrative datasets via probabilistic linkage. Routinely collected data were obtained for participants who could be linked between January 2005 and July 2013. Laboratory data will enable the identification of early cases of chronic disease and the assessment of clinically relevant biochemical targets during the disease course. Health administrative datasets will allow for the examination of health service use, pharmacological management, and clinical outcomes. RESULTS: The study received ethics approval from the NSW Population and Health Services Research Ethics Committee in February 2014. Data linkage for 267,153 of the 45 and Up Study participants was completed in June 2016, with congruent linkage achieved for 265,086 (99.23%) individuals. To date, the CKD and diabetes cohorts have been identified (published elsewhere), and a diverse portfolio of research projects relating to disease burden, risk factors, health outcomes, and health service utilization is in development. CONCLUSIONS: The EXTEND45 Study represents an unparalleled opportunity to perform extensive research into diseases of considerable public health and clinical importance. Strengths include the population-based nature of the cohort and the availability of longitudinal information on the complete disease pathway for affected individuals. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/15646.

No association between sleep apnoea and macular telangiectasia type 2 and its markers of severity and progression: a case-control study and retrospective cohort study.

IMPORTANCE: Idiopathic Macular Telangiectasia Type 2 (MacTel) is an uncommon, progressive retinal disease usually affecting both eyes. Currently there is no know treatment however with similar comorbidities to Obstructive Sleep Apnoea (OSA) there is plausibility of an association which may accelerate disease progression. BACKGROUND: To identify an association between MacTel and OSA and whether OSA may result in increased disease progression. DESIGN: Matched case-control study and retrospective cohort analysis. PARTICIPANTS: Fifty-seven patients with MacTel and 165 matched controls from the Busselton Health Study. METHODS: MacTel participants were matched based on age, gender and body mass index (BMI) (and where possible hypertension and diabetes) on a 3:1 ratio with controls from the Busselton Health Study. Participants undertook a sleep questionnaire using a previously validated questionnaire. In a subset sleep apnoea severity was objectively measured via overnight ambulatory polygraphy (30 cases and 83 matched controls; ApneaLink device; ResMed, Sydney, Australia). In a retrospective analysis of the suspected MacTel cases we assessed whether major markers of OSA severity and MacTel progression were associated. MAIN OUTCOME MEASURES: Apnoea Hypopnea Index along with key markers of MacTel progression. RESULTS: MacTel patients did not have a higher risk of sleep apnoea when compared to age, sex and BMI -matched controls (mean ± SD Apnoea hypopnea index [AHI] cases 9.6 ± 14.7 vs. controls 9.7 ± 10.8, P = 0.95). No markers of disease progression in the cases were associated with any marker of OSA severity. CONCLUSIONS AND RELEVANCE: Sleep apnoea does not increase the risk or accelerate the progression of MacTel.

Anti-vascular endothelial growth factor combined with intravitreal steroids for diabetic macular oedema.

BACKGROUND: The combination of steroid and anti-vascular endothelial growth factor (VEGF) intravitreal therapeutic agents could potentially have synergistic effects for treating diabetic macular oedema (DMO). On the one hand, if combined treatment is more effective than monotherapy, there would be significant implications for improving patient outcomes. Conversely, if there is no added benefit of combination therapy, then people could be potentially exposed to unnecessary local or systemic side effects. OBJECTIVES: To assess the effects of intravitreal agents that block vascular endothelial growth factor activity (anti-VEGF agents) plus intravitreal steroids versus monotherapy with macular laser, intravitreal steroids or intravitreal anti-VEGF agents for managing DMO. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2018, Issue 1); Ovid MEDLINE; Ovid Embase; LILACS; the ISRCTN registry; ClinicalTrials.gov and the ICTRP. The date of the search was 21 February 2018. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of intravitreal anti-VEGF combined with intravitreal steroids versus intravitreal anti-VEGF alone, intravitreal steroids alone or macular laser alone for managing DMO. We included people with DMO of all ages and both sexes. We also included trials where both eyes from one participant received different treatments. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane.Two authors independently reviewed all the titles and abstracts identified from the electronic and manual searches against the inclusion criteria. Our primary outcome was change in best corrected visual acuity (BCVA) between baseline and one year. Secondary outcomes included change in central macular thickness (CMT), economic data and quality of life. We considered adverse effects including intraocular inflammation, raised intraocular pressure (IOP) and development of cataract. MAIN RESULTS: There were eight RCTs (703 participants, 817 eyes) that met our inclusion criteria with only three studies reporting outcomes at one year. The studies took place in Iran (3), USA (2), Brazil (1), Czech Republic (1) and South Korea (1). Seven studies used the unlicensed anti-VEGF agent bevacizumab and one study used licensed ranibizumab. The study that used licensed ranibizumab had a unique design compared with the other studies in that included eyes had persisting DMO after anti-VEGF monotherapy and received three monthly doses of ranibizumab prior to allocation. The anti-VEGF agent was combined with intravitreal triamcinolone in six studies and with an intravitreal dexamethasone implant in two studies. The comparator group was anti-VEGF alone in all studies; two studies had an additional steroid monotherapy arm, another study had an additional macular laser photocoagulation arm. Whilst we judged these studies to be at low risk of bias for most domains, at least one domain was at unclear risk in all studies.When comparing anti-VEGF/steroid with anti-VEGF monotherapy as primary therapy for DMO, we found no meaningful clinical difference in change in BCVA (mean difference (MD) -2.29 visual acuity (VA) letters, 95% confidence interval (CI) -6.03 to 1.45; 3 RCTs; 188 eyes; low-certainty evidence) or change in CMT (MD 0.20 µm, 95% CI -37.14 to 37.53; 3 RCTs; 188 eyes; low-certainty evidence) at one year. There was very low-certainty evidence on intraocular inflammation from 8 studies, with one event in the anti-VEGF/steroid group (313 eyes) and two events in the anti-VEGF group (322 eyes). There was a greater risk of raised IOP (Peto odds ratio (OR) 8.13, 95% CI 4.67 to 14.16; 635 eyes; 8 RCTs; moderate-certainty evidence) and development of cataract (Peto OR 7.49, 95% CI 2.87 to 19.60; 635 eyes; 8 RCTs; moderate-certainty evidence) in eyes receiving anti-VEGF/steroid compared with anti-VEGF monotherapy. There was low-certainty evidence from one study of an increased risk of systemic adverse events in the anti-VEGF/steroid group compared with the anti-VEGF alone group (Peto OR 1.32, 95% CI 0.61 to 2.86; 103 eyes).One study compared anti-VEGF/steroid versus macular laser therapy. At one year investigators did not report a meaningful difference between the groups in change in BCVA (MD 4.00 VA letters 95% CI -2.70 to 10.70; 80 eyes; low-certainty evidence) or change in CMT (MD -16.00 µm, 95% CI -68.93 to 36.93; 80 eyes; low-certainty evidence). There was very low-certainty evidence suggesting an increased risk of cataract in the anti-VEGF/steroid group compared with the macular laser group (Peto OR 4.58, 95% 0.99 to 21.10, 100 eyes) and an increased risk of elevated IOP in the anti-VEGF/steroid group compared with the macular laser group (Peto OR 9.49, 95% CI 2.86 to 31.51; 100 eyes).One study provided very low-certainty evidence comparing anti-VEGF/steroid versus steroid monotherapy at one year. There was no evidence of a meaningful difference in BCVA between treatments at one year (MD 0 VA letters, 95% CI -6.1 to 6.1, low-certainty evidence). Likewise, there was no meaningful difference in the mean CMT at one year (MD - 9 µm, 95% CI -39.87µm to 21.87µm between the anti-VEGF/steroid group and the steroid group. There was very low-certainty evidence on raised IOP at one year comparing the anti-VEGF/steroid versus steroid groups (Peto OR 0.75, 95% CI 0.16 to 3.55).No included study reported impact of treatment on patients' quality of life or economic data. None of the studies reported any cases of endophthalmitis. AUTHORS' CONCLUSIONS: Combination of intravitreal anti-VEGF plus intravitreal steroids does not appear to offer additional visual benefit compared with monotherapy for DMO; at present the evidence for this is of low-certainty. There was an increased rate of cataract development and raised intraocular pressure in eyes treated with anti-VEGF plus steroid versus anti-VEGF alone. Patients were exposed to potential side effects of both these agents without reported additional benefit. The majority of the evidence comes from studies of bevacizumab and triamcinolone used as primary therapy for DMO. There is limited evidence from studies using licensed intravitreal anti-VEGF agents plus licensed intravitreal steroid implants with at least one year follow-up. It is not known whether treatment response is different in eyes that are phakic and pseudophakic at baseline.

TWO YEAR OUTCOMES OF "TREAT AND EXTEND" INTRAVITREAL THERAPY USING AFLIBERCEPT PREFERENTIALLY FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To report 24-month outcomes of a treat and extend (T&E) regimen using aflibercept in eyes with neovascular age-related macular degeneration. METHODS: This was a database observational study that included treatment-naive eyes with neovascular age-related macular degeneration tracked by the Fight Retinal Blindness! outcome registry completing 24 months of sole monotherapy with aflibercept treatment under a T&E regimen between November 1, 2012 and January 31, 2014. Locally weighted scatterplot smoothing curves were used to display visual acuity outcomes. Main outcome measures were change in visual acuity at 24 months and number of injections and visits during the study period. RESULTS: The study population, identified by reviewing the database, consisted of 136 eyes from 123 patients completing 24 months of follow-up on aflibercept. Mean (SD) age was 77.2 (7.0) years, 59% were female. Mean visual acuity increased from 61.4 (∼20/60; SD 17.4) letters at baseline to 67.4 (∼20/45; SD 17.7) letters at 24 months (+6.0 letters [95% confidence interval: 3.3-8.5]; P < 0.001). From baseline to 24 months, the proportion of eyes with visual acuity ≥70 letters (20/40) increased (40%-58%, P < 0.001) and the proportion of eyes with visual acuity ≤35 letters (20/200) remained the same (10%; P = 0.547). Ninety-eight per cent of eyes starting with visual acuity ≥70 letters (20/40) were able to maintain this up to 24 months. From the first to the second year of treatment, the mean number of injections (7.8 [2.1] vs. 5.7 [2.6]; P < 0.001) and visits (8.7 [1.7] vs. 6.5 [2.4]; P < 0.001) decreased for eyes completing 24 months of treatment. When data from 60 eligible eyes that did not complete 2 years follow-up, along with 14 eyes that switched to ranibizumab, were included using last observation carried forward, the mean change in visual acuity from baseline was +5.6 letters (95% confidence interval: 3.3-7.7). CONCLUSION: These data indicate that eyes treated with aflibercept, as a sole therapy, in routine clinical practice with a T&E regimen can achieve good visual outcomes while decreasing the burden of treatments and clinic visits.

Effects of switching from ranibizumab to aflibercept in eyes with exudative age-related macular degeneration.

AIMS: To examine 12-month outcomes of eyes switching from intravitreal ranibizumab to aflibercept for neovascular age-related macular degeneration (nAMD). METHODS: Database observational study of eyes with nAMD tracked by the Fight Retinal Blindness outcome registry that received ranibizumab for at least 12 months before switching to aflibercept and followed for at least 12 months after the switch. Visual acuity (VA) recorded at 12 months after the switch was analysed using locally weighted scatterplot smoothing curves. Lesion activity was graded according to a prospectively identified definition. Main outcomes were change in VA and treatment intervals 12 months after the treatment switch. Secondary outcomes included change in activity grading, effect of duration of treatment before switching and analysis of eyes that switched back. RESULTS: A total of 384 eyes switched from ranibizumab to aflibercept after a mean duration of 39.8 months on the original treatment. The mean VA did not change from the time of switching treatment (63.4, SD 15.9 logarithm of the minimum angle of resolution letters) to 12 months later (63.3, SD 16.7). While 10% of eyes gained 10 or more letters 12 months after the switch, 13% lost the same amount. The mean number of injections decreased by around one injection in the 12 months after switching (p<0.001), with a decrease in the proportion of choroidal neovascular membrane lesions that were graded as active. Eyes that had been treated for the longest time (49 or more months) before switching had worse vision at the point of switch but neither change in VA nor treatment interval was different between groups. The small proportion (6.9%) of eyes that switched back again to ranibizumab had already lost a mean of 5.2 letters from the first switch to the switch back and continued to lose vision at a similar rate for at least 6 months. CONCLUSIONS: The mean VA of eyes that switched treatments from ranibizumab to aflibercept was not different 12 months later. There was a modest increase in treatment intervals and a somewhat greater proportion of eyes that were graded as inactive after the switch.

Efficacy of dexamethasone versus bevacizumab on regression of hard exudates in diabetic maculopathy: data from the BEVORDEX randomised clinical trial.

OBJECTIVE: To report the effect of bevacizumab versus dexamethasone on hard exudates (HEX) in diabetic macular oedema (DME). DESIGN: Post hoc analysis of 24-month data from the Randomised clinical trial of BEVacizumab OR DEXamethasone for diabetic macular oedema (BEVORDEX) phase 2 multicentre randomised clinical trial. Eyes with centre-involving DME resistant to or unlikely to benefit from macular laser therapy were included. Eyes were randomly assigned to bevacizumab every 4 weeks or Ozurdex dexamethasone implant (DEX) every 16 weeks, both as required. The 68 eyes from 48 patients that completed 24-month follow-up were analysed. Two masked graders assessed extent and location of HEX on baseline, 12-month and 24-month foveal-centred colour fundus photographs using validated grading software. RESULTS: Macular HEX was present in 60% of study eyes. Of these, 21 eyes were treated with DEX and 20 eyes with bevacizumab. Both treatments led to reduction in area of macular HEX at 12 months and 24 months. There was greater regression of HEX from the foveal centre in DEX-treated eyes (median change +890 µm, IQR=1040 µm) than bevacizumab-treated eyes (median change +7.0 µm, IQR=590 µm) at 12 months (p=0.04) but the difference was no longer statistically significant (p=0.10) by 24 months (DEX +1400 µm, IQR=1590 µm; bevacizumab +20 µm, IQR=2680 µm). Reassuringly, no study eye developed HEX at the foveal centre, a visually devastating consequence of diabetic maculopathy. CONCLUSIONS: Bevacizumab and DEX were effective in reducing area of HEX in eyes with DME. DEX provided more rapid regression of HEX from the foveal centre although bevacizumab-treated eyes started to catch up by 24 months. Distance from the foveal centre as well as total area of macular HEX should be assessed when evaluating treatments for foveal-threatening HEX. TRIAL REGISTRATION NUMBER: NCT01298076; Post-results.