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.

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.

Time to initial clinician-reported inactivation of neovascular age-related macular degeneration treated primarily with ranibizumab.

PURPOSE: To characterize in more detail routine treatment patterns of intravitreal ranibizumab for neovascular age-related macular degeneration (nAMD), we analyzed the length of time and the number of injections required until lesions with choroidal neovascularization (CNV) were first graded inactive. DESIGN: Database observational study. PARTICIPANTS: Treatment-naïve eyes receiving predominantly ranibizumab for nAMD in routine clinical practice that were tracked in the Fight Retinal Blindness! observational registry. METHODS: Eyes treated with ranibizumab were followed until CNV was first reported to be "inactive" (i.e., absence of intraretinal fluid and hemorrhages). MAIN OUTCOME MEASURES: The length of time until lesion inactivation occurred and the number of injections required. RESULTS: A total of 1096 eyes (65.8% from women) were included in the study. The median number of weeks until a lesion was graded as inactive after beginning treatment was 15 weeks. One to 3 injections were sufficient to inactivate the lesion in 61.1% of eyes. A mean change in visual acuity of +5.5 logarithm of the minimum angle of resolution letters (95% confidence interval, 4.8-6.3) was found from treatment initiation to the time that eyes were reported as inactive. In eyes with a mean treatment frequency less than every 5.3 weeks, a median of only 3 injections (mean=3.7) were required before lesions with CNV were graded as inactive, but if the mean treatment interval extended beyond 5.3 weeks, the median number of injections required increased sharply to 6 injections (mean, 7 injections). Occult lesions became inactive more slowly than classic lesions. CONCLUSIONS: Most lesions with CNV became inactive with 3 injections of ranibizumab, but a small proportion remained active for more than 12 months. Injection frequency and lesion type were the main factors that predicted the time and number of injections required to render lesions inactive.

Two-year outcomes of "treat and extend" intravitreal therapy for neovascular age-related macular degeneration.

PURPOSE: To report 24-month outcomes of anti-vascular endothelial growth factor (VEGF) therapy for treatment-naïve eyes with neovascular age-related macular degeneration (nAMD) using a treat and extend treatment regimen in routine clinical practice. DESIGN: Database observational study. PARTICIPANTS: We included treatment-naïve eyes receiving predominantly ranibizumab for nAMD in routine clinical practice treated using a treat and extend regimen that were tracked in the Fight Retinal Blindness observational registry. METHODS: A cohort of eyes treated by practitioners using exclusively a treat and extend regimen was extracted from the Fight Retinal Blindness observational registry. MAIN OUTCOME MEASURES: Change in visual acuity (VA) over 2 years and number of injections and visits. RESULTS: Data from 1198 eyes from 1011 patients receiving anti-VEGF therapy using a treat and extend regimen for treatment-naïve nAMD between January 2007 and December 2012 and with 24-month follow-up were included in the analysis. Mean VA increased by +5.3 logarithm of the minimum angle of resolution letters from 56.5 letters (20/80+1) at initial visit to 61.8 (20/60+2) letters at 24 months. Mean VA gains improved and number of injections increased with successive years from +2.7 letters for eyes commencing in 2007 after a mean of 9.7 injections in 2 years, to +7.8 letters for eyes commencing in 2012 after a mean of 14.2 injections over 2 years. The proportion of eyes with VA >20/40 increased from 27% when starting treatment to 45% after 24 months; the proportion with vision of <20/200 remained unchanged (13% initial, 11% at 24 months). Of the included eyes, 90.5% avoided a vision loss of ≥15 letters. There was an overall mean of 13.0 injections over the 24 months, 7.5 injections in the first year and 5.5 in the second year, with a mean of 14.8 clinic visits. CONCLUSIONS: These data indicate that eyes managed in routine clinical practice with a treat and extend regimen can achieve good visual outcomes while decreasing the burden of treatments and clinic visits.

Long-Term Outcomes of Treatment of Neovascular Age-Related Macular Degeneration: Data from an Observational Study.

PURPOSE: To analyze the long-term outcomes of eyes with neovascular age-related macular degeneration (AMD) starting treatment with vascular endothelial growth factor (VEGF) inhibitors at least 5 years earlier. DESIGN: Database observational study. PARTICIPANTS: Treatment-naïve eyes with neovascular AMD tracked by the Fight Retinal Blindness outcome registry that received at least 1 anti-VEGF injection. METHODS: Locally weighted scatterplot smoothing curves were used to display visual acuity (VA) results. MAIN OUTCOME MEASURES: Change in mean VA and number of injections and visits from baseline up to 7 years after initiating treatment. RESULTS: The mean follow-up time of all 1212 identified eyes was 53.5 months, and 549 (45%) continued attending after 60 months. Mean VA improved from 55.1 to 61.4 letters after 6 months and remained above the mean presenting VA for approximately 6 years. After 7 years, mean VA was 2.6 letters lower than baseline for the 131 eyes still being followed; 40% had VA ≥70 (20/40) letters, and 18% had VA ≤35 letters (20/200). Of those with 20/40 VA before treatment, 40% had lost it after 7 years. Geographic atrophy affecting the fovea was thought to be the cause of a ≥10-letter loss after 6.5 years in 37% of a subset of such eyes that were retrospectively analyzed. A median of 6 injections and 9 visits were recorded over the first 12 months, and then 5 treatments and 7 to 9 visits per annum thereafter through 7 years. Treatment was discontinued for 663 eyes (53%) within the first 5 years. Despite initial gains in vision, the mean VA of these eyes had deteriorated to baseline or worse around the time treatment was discontinued. The rate of serious adverse events was low. CONCLUSIONS: Good long-term outcomes of VEGF inhibition for neovascular AMD were found in this study. These results may be better than other reports because more injections were given to our patients, possibly associated with a greater incentive for the physician to treat. Further studies to determine how to maximize the proportion of eyes that retain the initial VA gains of anti-VEGF are warranted.

Patient experiences in retinal trials: a cross-sectional study.

BACKGROUND: Patient-centered care recognizes the obligation to understand and meet patient's expectations. An individual's satisfaction has been found to affect health-related decisions and treatment-related behaviours, which in turn affect medical compliance, follow-up, the success of treatment and the appropriate use of services. We studied the expectations, experiences and satisfaction of patients who participated in clinical trials for retinal diseases at the Sydney Eye Hospital. METHODS: The study was undertaken at the research clinic of the major public quaternary eye hospital in New South Wales, Australia. A 37-question survey was conducted on patients enrolled in or who had finished a clinical trial for macular disease in the 12 months preceding this study in November 2012. Patient satisfaction was assessed using close-ended, multiple choice questions. First, the decision making process for entering into the clinical trial was evaluated. Then the level of patient understanding and experience during the study was assessed. Finally, there was a series of questions to gauge the participants' perception of trial outcomes and overall impression gained from the experience. RESULTS: Eighty patients completed the questionnaire. Overall patient satisfaction was high with the majority of patients stating they would recommend participation in a retinal clinical trial (94 %) and participate in a subsequent trial (78 %). Most patients rated themselves as the most important factor in making the decision to join a trial. Patients felt well informed and expectations were generally felt to be met, however 14 % did not believe that they could withdraw from the study voluntarily. The most common reasons for trial participation were to contribute to medical science and to have improved treatment outcomes. CONCLUSIONS: We found that patients generally found participation in retinal clinical trials to be a positive experience. Factors contributing to dissatisfaction mainly related to inconvenience experienced by transportation and waiting times. We also found that patients felt well informed about the study, but some did not have a complete understanding of their rights, which had been communicated to them when they entered the study. There were both altruistic and self-motivated reasons behind patients' decisions to join a retinal trial.

A randomized clinical trial of intravitreal bevacizumab versus intravitreal dexamethasone for diabetic macular edema: the BEVORDEX study.

OBJECTIVE: To report the 12-month results of the first head-to-head comparison of a dexamethasone implant (Ozurdex; Allergan, Inc., Irvine, CA) versus bevacizumab (Avastin; Genentech, South San Francisco, CA) for center-involving diabetic macular edema (DME). DESIGN: Phase 2, prospective, multicenter, randomized, single-masked clinical trial (clinicaltrials.gov identifier NCT01298076). PARTICIPANTS: We enrolled 88 eyes of 61 patients with center-involving DME. METHODS: Forty-two eyes were randomized to receive bevacizumab every 4 weeks and 46 eyes were randomized to receive a dexamethasone implant every 16 weeks, both pro re nata. Results were analyzed using linear regression with generalized estimation equation methods to account for between-eye correlation. MAIN OUTCOME MEASURES: The primary outcome was the proportion of eyes that improved vision by 10 logarithm of minimum angle of resolution letters. Secondary outcomes included mean change in best-corrected visual acuity (BCVA), change in central macular thickness (CMT), injection frequency, and adverse events. Patient-reported outcomes were measured using the Impact of Vision Impairment (IVI) questionnaire. RESULTS: Improvement in BCVA of 10 or more letters was found in 17 of 42 eyes (40%) treated with bevacizumab compared with 19 of 46 dexamethasone implant-treated eyes (41%; P = 0.83). None of the 42 bevacizumab eyes lost 10 letters or more, whereas 5 of 46 (11%) dexamethasone implant eyes did, mostly because of cataract. Mean CMT decreased by 122 µm for bevacizumab eyes and by 187 µm for dexamethasone implant eyes (P = 0.015). Bevacizumab-treated eyes received a mean of 8.6 injections compared with 2.7 injections for dexamethasone implant eyes. Significant improvement in IVI scores occurred for both treatment groups. CONCLUSIONS: Dexamethasone implant achieved similar rates of visual acuity improvement compared with bevacizumab for DME, with superior anatomic outcomes and fewer injections. Both treatments were associated with improvement in visual quality-of-life scores. However, more dexamethasone implant-treated eyes lost vision, mainly because of cataract.

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.

A prediction model for viability at the end of the first trimester after a single early pregnancy evaluation.

OBJECTIVE: The aim was to develop a new model to predict the outcome at the end of the 1st trimester after a single visit to the early pregnancy unit (EPU). METHODS: Prospective observational study in the EPU at Nepean Hospital, between November 2006 and February 2009. Data were collected from all women in the 1st trimester of their pregnancy who had a live intrauterine pregnancy (IUP) at the 1st transvaginal ultrasound scan (TVS). 29 historical, clinical and ultrasound end points were recorded. Women were followed until the final diagnosis was established at the end of the 1st trimester: viability or nonviability. A multinomial logistic regression model was developed. The performance of this model was evaluated using receiver operating characteristic (ROC) curves. RESULTS: Data from 416 pregnancies were included: 92.1% were live beyond the 1st trimester, and 7.9% had miscarried. The most useful prognostic variables for developing the logistic regression model were gestational age by dates, vaginal (PV) bleeding, PV clots, gestational age by TVS, consistency with menstrual dates, mean gestational sac (GS) size, mean yolk sac (YS) size and number of previous caesarean sections. Used retrospectively on 416 women based on 25 imputations, the model gave an AUC of 0.88. Based on cross-validation, the independent predictive power obtained an AUC of 0.78. CONCLUSIONS: We have developed a new model to predict the outcome of the 1st trimester in women with live IUP at the 1st scan.

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.

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.

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.

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.

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.

Global identification of the genes and pathways differentially expressed in hypothalamus in early and established neurogenic hypertension.

The hypothalamus has an important etiological role in the onset and maintenance of hypertension and stress responses in the Schlager high blood pressure (BP) (BPH/2J) mouse, a genetic model of neurogenic hypertension. Using Affymetrix GeneChip Mouse Gene 1.0 ST Arrays we identified 1,019 hypothalamic genes whose expression differed between 6 wk old BPH/2J and normal BP (BPN/3J) strains, and 466 for 26 wk old mice. Of these, 459 were in 21 mouse BP quantitative trait loci. We validated 46 genes by qPCR. Gene changes that would increase sympathetic outflow at both ages were: Dynll1 encoding dynein light chain LC8-type 1, which physically destabilizes neuronal nitric oxide synthase, decreasing neuronal nitric oxide, and Hcrt encoding hypocretin and Npsr1 encoding neuropeptide S receptor 1, each involved in sympathetic response to stress. At both ages we identified genes for inflammation, such as CC-chemokine ligand 19 (Ccl19), and oxidative stress. Via reactive oxygen species generation, these could contribute to oxidative damage. Other genes identified could be responding to such perturbations. Atp2b1, the major gene from genome-wide association studies of BP variation, was underexpressed in the early phase. Comparison of profiles of young and adult BPH/2J mice, after adjusting for maturation genes, pointed to the proopiomelanocortin-α gene (Pomc) and neuropeptide Y gene (Npy), among others, as potentially causative. The present study has identified a diversity of genes and possible mechanisms involved in hypertension etiology and maintenance in the hypothalamus of BPH/2J mice, highlighting both common and divergent processes in each phase of the condition.