Comorbid diabetes and copd: impact of corticosteroid use on diabetes complications

OBJECTIVE: To identify if there is a dose-dependent risk of diabetes complications in patients treated with corticosteroids who have both diabetes and chronic obstructive pulmonary disorder (COPD). RESEARCH DESIGN AND METHODS: A retrospective study of administrative claims data from the Australian Government Department of Veterans' Affairs, from 1 July 2001 to 30 June 2008, of diabetes patients newly initiated on metformin or sulfonylurea. COPD was identified by dispensings of tiotropium or ipratropium in the 6 months preceding study entry. Total corticosteroid use (inhaled and systemic) in the 12 months after study entry was determined. The outcome was time to hospitalization for a diabetes-related complication. Competing risks and Cox proportional hazard regression analyses were conducted with adjustment for a number of covariates. RESULTS: A total of 18,226 subjects with diabetes were identified, of which 5.9% had COPD. Of those with COPD, 67.2% were dispensed corticosteroids in the 12 months from study entry. Stratification by dose of corticosteroids demonstrated a 94% increased likelihood of hospitalization for a diabetes complication for those who received a total defined daily dose (DDD) of corticosteroids≥0.83/day (subhazard ratio 1.94 [95% CI 1.14-3.28], P=0.014), by comparison with those who did not receive a corticosteroid. Lower doses of corticosteroid (<0.83 DDD/day) were not associated with an increased risk of diabetes-related hospitalization. CONCLUSIONS: In patients with diabetes and COPD, an increased risk of diabetes-related hospitalizations was only evident with use of high doses of corticosteroids. This highlights the need for constant revision of corticosteroid dose in those with diabetes and COPD, to ensure that the minimally effective dose is used, together with review of appropriate response to therapy.Gillian E. Caughey, Adrian K. Preiss, Agnes I. Vitry, Andrew L. Gilbert, Elizabeth E. Roughea

Comparative effectiveness and safety of low-strength and high-strength direct oral anticoagulants compared with warfarin: a sequential cohort study

OBJECTIVES:The aim of this study was to compare effectiveness and safety of low-strength and high-strength direct oral anticoagulants (DOACs) with warfarin in the Australian Veteran population. DESIGN:Sequential cohort study using inverse probability of treatment weighting (IPTW) and propensity score matching. Initiators of high-strength (apixaban 5 mg, dabigatran 150 mg, rivaroxaban 20 mg) and low-strength DOACS (apixaban 2.5 mg, dabigatran 110 mg, rivaroxaban 15 mg) were compared with warfarin initiators. SETTING:Australian Government Department of Veterans' Affairs claims database. PARTICIPANTS:4836 patients who initiated oral anticoagulants (45.8%, 26.0% and 28.2% on low-strength, high-strength DOACs and warfarin, respectively) between August 2013 and March 2015. Mean age was 85, 75 and 83 years for low-strength, high-strength DOACs and warfarin initiators, respectively. MAIN OUTCOME MEASURES:One-year risk of hospitalisation for ischaemic stroke, any bleeding event or haemorrhagic stroke. Secondary outcomes were 1-year risk of hospitalisation for myocardial infarction and death. RESULTS:Using the IPTW method, no difference in risk of ischaemic stroke or bleeding was found with low-strength DOACs compared with warfarin. As a class, no increased risk of myocardial infarction was found for low-strength DOACs, however, risk was elevated for apixaban (HR 2.25, 95% CI 1.23 to 4.13). For high-strength DOACs, no difference was found for ischaemic stroke compared with warfarin, however, there was a significant reduction in risk of bleeding events (HR 0.63, 95% CI 0.44 to 0.89) and death (HR 0.40, 95% CI 0.28 to 0.58). Propensity score matching showed no difference in risk of ischaemic stroke or bleeding. CONCLUSION:We found that in the practice setting both DOAC formulations were similar to warfarin with regard to effectiveness and had no increased risk of bleeding.Nicole L Pratt, Emmae Ramsay, Lisa M Kalisch Ellett, Katherine Duszynski, Sepehr Shakib, Mhairi Kerr, Gillian Caughey, Elizabeth Ellen Roughea

Reduction of cardiovascular risk in patients with metabolic syndrome in a community health center after a pharmaceutical care program of pharmacotherapy follow-up

The objective of this study was to determine the impact of a pharmaceutical care (PC) program in a sample of public outpatients with metabolic syndrome (MS) who were being treated in Brazil's health system; the patients were randomized into PC or standard care. The pharmacotherapy follow-up (PF) was performed in a total of 120 patients with type 2 diabetes for 6 months. Adherence to treatment (measured with the Morisky test), negative outcomes associated with medication (NOM) and anthropometric and biochemical parameters were measured before and after PF. The Framingham scoring method was used to estimate changes in 10-year coronary heart disease risk scores in all patients. Ninety-six of 120 patients had characteristics of MS and were randomized into two groups (G): the control group (CG: 36) and the intervention group (IG: 38). Among the MS patients, 100% were taking a glucose-lowering drug; many were also taking anti-hypertensive drugs (CG: 72%; IG: 73%), and some patients were also taking hypolipemic drugs (CG: 12.0%; IG: 14.7%). Only 20.7% of the IG patients were considered adherent to their prescribed drugs. In the CG, an increase of coronary heart disease (CHD) risk (22±2 to 26±3; pO objetivo deste estudo foi o de determinar o impacto de um Programa de atenção Farmacêutica (AF) em uma amostra de pacientes ambulatoriais de Sistema Público de Saúde do Brasil portadores de Síndrome Metabólica, randomizados em AF ou atenção à saúde usual. Realizou-se o seguimento farmacoterapêutico com 120 pacientes com diabetes tipo 2 durante seis meses. Avaliou-se o nível de aderência ao tratamento (teste Morisky), resultados clínicos negativos associados a medicamentos (RNM), parâmetros bioquímicos e antropométricos, antes e após o seguimento. O método de Framingham foi usado para calcular as variações no risco de doenças coronarianas em 10 anos em todos os pacientes. Dos 120 pacientes, 96 tiveram características de SM e foram então randomizados em dois grupos (G): Controle (GC: 36) e Intervenção (GI: 38). Entre os pacientes com SM, 100% faziam uso de medicamentos para diminuir a glicose, anti-hipertensivos (GC: 72%; GI: 73%) e hipoglicemiantes (GC: 12.0%; GI: 14.7%). Apenas 20,7% do GI foram considerados aderentes aos fármacos prescritos. No GC foi observado aumento do risco de Doença Arterial Coronariana (DAC) (22±2 para 26±3; p<0,05), enquanto no GI foi observado redução (22±2 para 14±2%; p<0,01). O Programa de AF para pacientes com SM monitorados na atenção primária do Sistema de Saúde Pública brasileiro melhora o funcionamento do serviço resultando na melhoria clínica dos pacientes com redução do risco de doença cardiovascular em um período de dez anos

Use of medicines that may exacerbate heart failure in older adults: therapeutic complexity of multimorbidity

BACKGROUND:Multimorbidity is common in older patients with heart failure (HF), complicating therapeutic management and increasing the risk of harm. OBJECTIVE:This study sought to examine the prevalence of medicines for the treatment of comorbid conditions potentially associated with harm in older people, before and after HF hospitalization. METHODS:A retrospective cohort study of older people hospitalized with a primary diagnosis of HF over a 12-month period was conducted using administrative health claims data from the Department of Veterans' Affairs (DVA) Australia. We examined the prevalence of medicines that may exacerbate or worsen HF as defined by the American Heart Association (AHA) and Australian HF clinical guidelines, in the 30 days prior and 120 days before and after discharge for HF. RESULTS:A total of 4069 older adults were hospitalized for HF during the study period; almost 60% (n = 2435) received at least one medicine associated with an increased risk of harm before hospitalization, with the majority (66.7%, n = 1623) dispensed in the 30 days prior. A small but significant reduction after hospitalization was observed, but 56% (n = 1638) received at least one of these medicines after hospitalization (p = 0.001). Over one-quarter received two or more medicines before hospitalization, and this only reduced to 22% post-hospitalization (p < 0.0001). CONCLUSIONS:Little change in the prescribing of potentially harmful medicines for HF was observed; 56% of older adults received at least one following hospitalization for HF, highlighting the therapeutic complexity of multimorbidity in HF. Use of the AHA list to facilitate identification of potentially harmful medicines, followed by prioritization of treatment goals and appropriate risk mitigation are needed to facilitate reduction in hospitalization for patients with HF with multimorbidity.Gillian E. Caughey, Sepehr Shakib, John D. Barratt, Elizabeth E. Roughea

Predicting infections after total joint arthroplasty using a prescription based comorbidity measure

This study evaluated the association and predictive ability of co-morbidities measured by RxRisk-V, Elixhauser and Charlson measures and post-total hip (THA) and total knee arthroplasties (TKA) infection. THAs and TKAs (2001–2012) were identified using the Australian Department of Veterans’ Affairs data. Infections within 90 days post-surgery were the study endpoint. Co-morbidities were identified using pharmacy (RxRisk-V) and hospitalization history (Elixhauser, Charlson). Of the 11,848 THAs, 3.1% (N = 364) had infections and out of 18,972 TKAs 3.4% (N = 648). Comorbidity burden and specific conditions were associated with infection likelihood. RxRisk-V performed better than other measures, but none had high predictive ability and differences were small. The best performing infection prediction models resulted when a combination of conditions identified by all measures was used.Maria C.S.Inacio, Nicole L.Pratt, Elizabeth E.Roughead, Stephen E.Graves ... et al

Sequence symmetry analysis as a signal detection tool for potential heart failure adverse events in an administrative claims database

The potential for routine sequence symmetry analysis (SSA) signal detection in health claims databases to detect new safety signals of medicines is unknown.Our objective was to assess the potential utility of SSA as a signal detection tool in health claims data for detecting medicines with potential heart failure (HF) adverse event signals.We applied the SSA method to all subsidized single-ingredient medicines in Australia. The source of data was the Australian Government Department of Veterans' Affairs (DVA) administrative claims database using data collected between 2002 and 2011. We used first ever HF hospitalization and frusemide initiation as indicators for HF. A signal was considered to be present if the lower limit of the 95 % confidence interval for the adjusted sequence ratio was greater than one. To identify potential new signals of HF, we excluded medicines where HF or edema was listed in the product information (PI) of that medicine or for any other medicine in the same class. We also excluded medicines that were used in HF treatment and medicines indicated for diseases that may contribute to the development of HF.We tested 691 medicines. HF signals were detected for 12 % (80/691) using the hospitalization event and 22 % (153/691) using frusemide initiation. Among medicines that did not have HF listed in the PI, SSA found 11 % (44/397) associated with HF hospitalization and 15 % (60/397) associated with frusemide initiation. Of the medicines tested in which no other medicine in the same class had HF or edema in the PI, and where the medicine was not indicated for a disease that is a risk factor for HF, potential new signals were generated for 2-3 % of these medicines tested (12 of 397 medicines using HF hospitalization and 9 of 397 medicines using frusemide initiation).SSA generated potential new signals of HF for some anti-glaucoma and anti-dyspepsia medicines. For some of the potential signals, the event is biologically plausible and some have pre-marketing and post-marketing case reports to support the finding. Confirmation of these signals using cohort studies is required.Izyan A. Wahab, Nicole L. Pratt, Lisa Kalisch Ellett, Elizabeth E. Roughea

Concomitant prescribing of opioids and benzodiazepines in Australia, 2012–2017

Abstract not availableGillian E Caughey, Svetla Gadzhanova, Sepehr Shakib, Elizabeth E Roughea

Using post-market utilisation analysis to support medicines pricing policy: an Australian case study of aflibercept and ranibizumab use

Objectives: To describe how post-market utilisation analysis in Australia informs cost-effectiveness assessment and pricing decisions, using aflibercept and ranibizumab as case studies. Methods: Pharmaceutical claims were used to identify initiators of aflibercept and ranibizumab in the year after aflibercept-listing (December 2012), and ranibizumab initiators in the year before aflibercept listing. The dispensing rates for each cohort were calculated, and their demographic and clinical characteristics compared using Kruskal–Wallis tests. Results: Aflibercept and ranibizumab each accounted for half the age-related macular degeneration market following aflibercept listing. Aflibercept initiators had similar dispensing rates to ranibizumab initiators in the pre- and post-aflibercept era (~ three scripts during the first 90 days, and eight to nine scripts during the following 12 months). All cohorts were similar in terms of their age, sex, residential aged-care status and geographic remoteness, and no differences were observed in their overall co-morbidity scores and history of thromboembolic events. Conclusions: Contrary to clinical trial protocols, post-market utilisation research for ranibizumab and aflibercept demonstrates equivalent use in practice in terms of dose frequency, and the demographic and clinical characteristics of initiators. This supports Australia’s decision to pay the same price for each rather than giving a premium to aflibercept. Many other countries are likely overpaying for aflibercept if their utilization patterns are similar to Australia’s, and could benefit from incorporating routine utilisation assessment.Anna Kemp-Casey, Nicole Pratt, Emmae Ramsay, Elizabeth E. Roughea

Medication use and potentially high-risk prescribing in older patients hospitalized for diabetes: a missed opportunity to improve care?

To examine the appropriateness of medicine use and potentially high-risk prescribing before and after hospitalization for diabetes.A retrospective cohort study of patients hospitalized for diabetes was conducted using administrative data from the Australian Government Department of Veterans' Affairs for the period between 1 January 2012 and 31 December 2012. The appropriateness of medicine use and potentially high-risk prescribing, including hyper-polypharmacy and associated treatment conflicts, were examined for the 120-day periods before and after hospitalization.A total of 876 patients were hospitalized for a diabetes-related complication. Of these, 25% were not dispensed an antidiabetic medicine 4 months before hospitalization and 25% had not had their HbA1c levels measured in the preceding 6 months. The use of antidiabetic medicines increased to 85% after hospitalization, with a 25.6% relative increase (95% CI 10.9-42.1) in the proportion of those dispensed insulin. The prevalence of high-risk prescribing before hospital admission was high; 70% had >10 medicines dispensed, a third had at least one treatment conflict and half were dispensed a potentially inappropriate medicine. The use of long-acting sulphonylureas and corticosteroids had relative decreases of 46.0% (95% CI 17.0-64.9) and 29.9% (95% CI 8.8-46.0), respectively; however, few changes in other high-risk prescribing patterns were observed after discharge.This study has identified poor medication-related care and, in particular, high-risk-prescribing in people subsequently hospitalized for diabetes. While diabetes medicine use improved after hospitalization, there was little change in potentially inappropriate medicine use, which suggests that an opportunity to improve medication use in this older vulnerable population has been missed. This article is protected by copyright. All rights reserved.G. E. Caughey, J. D. Barratt, S. Shakib, A. Kemp-Casey, E. E. Roughea

Increase in total joint arthroplasty projected from 2014 to 2046 in Australia: a conservative local model with international implications

Background: The incidence of joint arthroplasty is increasing worldwide. International estimates of future demand for joint arthroplasty have used models that propose either an exponential future increase, despite obvious system constraints, or static increases, which do not account for past trends. Country-specific projection estimates that address limitations of past projections are necessary. In Australia, a high-income country with the 7th highest incidence of TKA and 15th highest incidence of THA of the Organization for Economic Cooperation and Development (OECD) countries, the volume of TKAs and THAs increased 198% between 1994 and 2014. Questions/purpose: To determine the projected incidence and volume of primary TKAs and THAs from 2014 to 2046 in the Australian population older than 40 years. Methods: Australian State and Territory Health Department data were used to identify TKAs and THAs performed between 1994 and 1995 and 2013 and 2014. The Australian Bureau of Statistics was the source of the population estimates for the same periods and population-projected estimates until 2046. The incidence rate (IR), 95% CI, and prediction interval (PI) of TKAs and THAs per 100,000 Australian citizens older than 40 years were calculated. Future IRs were estimated using a logistic model, and volume was calculated from projected IR and population. The logistic growth model assumes the existence of an upper limit of the TKA and THA incidences and a growth rate directly related to this incidence. At the beginning, when the observed incidence is much lower than the asymptote, the increase is exponential, but it decreases as it approaches the upper limit. Results: A 66% increase in the IR of primary THAs between 2013 and 2046 is projected for Australia (2013: IR = 307 per 100,000, [95% CI, 262-329 per 100,000] compared with 2046: IR= 510 per 100,000, [95% PI, 98-567 per 100,000]), which translates to a 219% increase in the volume during this period. For TKAs the IR is expected to increase by 26% by 2046 (IR = 575 per 100,000; 95% PI, 402-717 per 100,000) compared with 2013 (IR = 437 per 100,000; 95% CI, 397-479 per 100,000) and the volume to increase by 142%. Conclusion: A large increase in the volume of arthroplasties is expected using a conservative projection model that accounts for past surgical trends and future population changes in Australia. These findings have international implications, as they show that using country- specific, conservative projection approaches, a substantial increase in the number of these procedures is expected. This increase in joint arthroplasty volume will require appropriate workforce planning, resource allocation, and budget planning so that demand can be met.Maria C. S. Inacio, Stephen E. Graves, Nicole L. Pratt, Elizabeth E. Roughead, Szilard Neme