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Internal Medicine Journal 44 (2014)
B R I E F C O M M U N I C AT I O N S
Antithrombotic use following transient ischaemic attack or ischaemic stroke among older Australians with atrial fibrillation J. K. Sluggett,1 G. E. Caughey,1 M. B. Ward2 and A. L. Gilbert1 1
Quality Use of Medicines and Pharmacy Research Centre, Sansom Institute and 2School of Pharmacy and Medical Sciences, University of South
Australia, Adelaide, South Australia, Australia
Key words brain infarction, transient ischaemic attack, atrial fibrillation, anticoagulants, Australia. Correspondence Janet K. Sluggett, Quality Use of Medicines and Pharmacy Research Centre, Sansom Institute for Health Research, University of South Australia, GPO Box 2471, Adelaide, SA 5001, Australia. Email: [email protected]
Abstract Hospital audits may underestimate anticoagulant use among acute ischaemic stroke patients with atrial fibrillation (AF), as treatment may commence after discharge. To account for this, antithrombotic use in the 4 months after hospitalisation for transient ischaemic attack or ischaemic stroke among AF patients was assessed using claims data. Results suggest that treatment may be commenced soon after discharge and should be considered when assessing prevalence of use.
Received 19 March 2014; accepted 25 May 2014. doi:10.1111/imj.12582
Australian and international stroke management guidelines recommend patients diagnosed with transient ischaemic attack (TIA) or ischaemic stroke with atrial fibrillation (AF) receive ongoing anticoagulant therapy, as it is more efficacious than antiplatelet therapy in this setting.1 Despite this, suboptimal use of oral anticoagulants among these patients has been reported in the international literature.2 A recent analysis of data from the 2009 and 2011 Australian national stroke audits showed only 33% of ischaemic stroke patients with a diagnosis of AF were prescribed an oral anticoagulant at discharge from acute care.3 A similar Australian study conducted 10 years earlier also found 33% of TIA and ischaemic stroke patients with AF received warfarin at discharge,4 suggesting little change in use over this period. However, hospital audits may not fully capture oral anticoagulant use as the optimal time to commence therapy after ischaemic stroke in this patient group is uncertain1 and treatment may be started after discharge. In order to account for this, we undertook a population-based study to determine the use of antithrombotic medicines within 4 months of discharge for TIA or ischaemic stroke among patients with AF. Funding: J. K. Sluggett was supported by an Australian Postgraduate Award and University of South Australia scholarship to conduct this research. Conflict of interest: None.
1134
Ethics approval was obtained from the University of South Australia and Australian Government Department of Veterans’ Affairs (DVA) human research ethics committees prior to commencement. A retrospective observational study was conducted using data from DVA’s administrative health claims database. This national database includes claims for all health services and pharmaceuticals subsidised by DVA, with a treatment population of 263 433 Australian war veterans and eligible dependants in December 2009.5 Patients discharged alive between 1 January 2009 and 31 December 2009 following an episode of care for TIA (identified by International Classification of Diseases 10th revision, Australian modification (ICD10AM) codes G45.0; G45.1; G45.2; G45.8; G45.9) or ischaemic stroke (ICD-10AM code I63) and a diagnosis of AF (ICD-10AM code I48) were included in this study. Subjects included were eligible for subsidy of all health services by DVA. Data rules based on consultation with clinicians6 were applied to hospital claims recorded between 1 January 2008 and 30 June 2010 to construct episodes of care for TIA and ischaemic stroke and determine final admission and discharge dates. Where subjects had more than one episode of care for TIA or ischaemic stroke during 2009, analysis was limited to the first episode of care for each subject during this period. © 2014 The Authors Internal Medicine Journal © 2014 Royal Australasian College of Physicians
Brief Communications
Table 1 Patient characteristics Characteristics Age at admission, median (IQR) (years) Male gender (%) Resided in aged care before admission No. unique prescriptions dispensed in the 6 months before admission, median (IQR) No. comorbidities, median (IQR) Ischaemic heart disease Heart failure Diabetes Dementia Hospitalisation history: Prior TIA or stroke Myocardial infarction DVT or PE Prosthetic heart valve Length of stay, median (IQR) (days) Discharge destination Home Residential care Unrelated hospital admission Died within 120 days of discharge
TIA (n = 140)
Ischaemic stroke (n = 268)
86.9 (84.6–88.9) 65 (46.4%) 10 (7.1%) 10 (6–14) 5 (3–6) 63 (45.0%) 49 (35.0%) 14 (11.4%) 20 (14.3%)
86.0 (83.2–88.6) 124 (46.3%) 14 (5.2%) 10 (6–15) 4 (3–6) 85 (31.7%) 79 (29.5%) 49 (18.3%) 21 (7.8%)
22 (15.7%) 13 (9.3%) 5 (3.6%) 20 (14.3%) 6 (3–12)
29 (10.8%) 29 (10.8%) 11 (4.1%) 27 (10.1%) 28.5 (13–44)
122 (87.2%) 16 (11.4%) 2 (1.4%) 14 (10%)
185 (69.0%) 69 (25.8%) 14 (5.2%) 38 (14.2%)
DVT, deep vein thrombosis; IQR, interquartile range; PE, pulmonary embolism; TIA, transient ischaemic attack.
Claims for antithrombotic medicines (identified by Anatomic and Therapeutic Chemical code B01A) dispensed during the episode of care or within 120 days of discharge were analysed. This period was examined based on results of a previous validation study7 and quantities of antithrombotics subsidised in Australia. The proportion of subjects dispensed an antithrombotic was obtained from Kaplan–Meier estimates (using failure probabilities and 95% confidence intervals (CI) at 120 days after discharge). This method enabled inclusion of subjects who died within 120 days of discharge. Analyses for ischaemic stroke patients were further stratified by length of hospital stay (≤14 vs >14 days). Comorbidities were determined using the prescriptionbased comorbidity index Rx-Risk-V8 applied to pharmaceutical claims in the 6 months before admission and by screening hospital claims recorded between 1 January 2001 and the date of discharge. Analyses were performed using SAS version 9.4 (SAS Institute Inc., Cary, NC, USA).
In total, 408 (140 TIA, 268 ischaemic stroke) patients were included (Table 1). Most (90%) patients were aged ≥80 years, with 6% of patients residing in aged care prior to admission. The majority of patients (94% TIA, 90% ischaemic stroke) were dispensed antithrombotic therapy, and over half the population received warfarin within 4 months of discharge (Table 2). The majority of ischaemic stroke and TIA patients dispensed these therapies received them within 4 and 6 weeks of discharge, respectively (Kaplan–Meier plots not shown). Of the 268 ischaemic stroke patients included in this study, 74 (28%) patients were hospitalised for ≤14 days. When prevalence of use was stratified by length of stay, 61.1% (95% CI 49.8–72.5) of ischaemic stroke patients hospitalised for ≤ 14 days received warfarin compared with 50.1% (95% CI 43.2–57.5) of patients hospitalised for more than 14 days. Prevalence of use of warfarin within 4 months of leaving hospital was considerably higher than use observed in a recent national study examining treatment
Table 2 Percentage of AF patients (95% confidence interval) dispensed antithrombotic therapy within 4 months of TIA or ischaemic stroke Medicine Any antithrombotic Any anticoagulant Warfarin Any antiplatelet Aspirin Clopidogrel
ATC code
TIA
Ischaemic stroke
B01A B01AA, B01AC, B01AE, B01AF B01AA03 B01AC B01AC06 B01AC04
94.3 (89.3–97.5) 63.9 (55.8–72.0) 58.2 (50.0–66.6) 49.7 (41.6–58.4) 26.9 (20.2–26.9) 23.3 (17.1–31.3)
90.3 (86.1–93.6) 58.8 (52.8–64.9) 53.1 (47.1–59.4) 51.0 (45.0–57.2) 32.1 (26.8–38.2) 19.9 (15.5–25.2)
AF, atrial fibrillation; ATC, Anatomic and Therapeutic Chemical; TIA, transient ischaemic attack. © 2014 The Authors Internal Medicine Journal © 2014 Royal Australasian College of Physicians
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Brief Communications
at discharge from acute care.3 However, there is uncertainty about the optimal time to commence anticoagulant therapy among patients with acute cardioembolic stroke and initiation may be delayed for up to several weeks.9,10 The median length of stay for patients included in the recent national study of acute stroke care was 7 days (interquartile range 2–14 days),3 meaning anticoagulant use may have been underestimated as treatment may have commenced during rehabilitation or after discharge. One of the strengths of our approach is the ability to assess medicines supplied beyond discharge, as not all patients with AF can be commenced on anticoagulant therapy in the acute setting. The ICD-10 coding for TIA and ischaemic stroke with coexisting AF is highly reliable,11 and excellent adherence to Australian standards for ICD-10AM coding was demonstrated in a previous study.12 A potential limitation of this approach is that assessing prescriptions dispensed does not guarantee that the medicine was administered, and without clinical information, we could not assess if patients were adequately anticoagulated. Despite this, our results are similar to those reported in the international literature, including a systematic review that found prevalence of oral anticoagulant use among AF patients with a previous TIA or ischaemic stroke that was 60% or less in 21 of the 29 studies included in the review.2 Study findings are also likely to be generalisable to other older Australians hospitalised for treatment, as age-specific comparisons show the general Australian population and veterans without service-related disability have similar use of medicines and health services.13
References 1 National Stroke Foundation. Clinical Guidelines for Stroke Management 2010. Melbourne (Vic.): NSF; 2010. 2 Ogilvie IM, Newton N, Welner SA, Cowell W, Lip GYH. Underuse of oral anticoagulants in atrial fibrillation: a systematic review. Am J Med 2010; 123: 638–45, e4. 3 Andrew N, Kilkenny M, Harris D, Price C, Cadilhac DA. Outcomes for people with atrial fibrillation in an Australian national audit of stroke care. Int J Stroke 2014; 9: 270–7. 4 Duffy BK, Phillips PA, Davis SM, Donnan GA, Vedadhaghi ME. Evidence-based care and outcomes of acute stroke managed in hospital specialty units. Med J Aust 2003; 178: 318–23.
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We could not exclude patients with previous adverse reactions, treatment contraindications or those refusing treatment from this study, nor could we assess all factors impacting on anticoagulation decisions in the oldest old (such as poor functional outcome, limited life expectancy, logistics of monitoring and ability to manage medicines).14 For these reasons, it is possible that true prevalence of use is underestimated, as contraindications to treatment are more common among older patients. Prescription claims for warfarin were assessed as it was the preferred oral anticoagulant in Australia during the study period; however, in late 2013, three newer oral anticoagulants were made available under Australia’s national pharmaceutical subsidy scheme for stroke prevention among patients with non-valvular AF and at least one stroke risk factor (such as previous TIA or ischaemic stroke). The impact of increased accessibility to newer agents on therapeutic decisions and treatment rates among older Australians should be assessed once further data are available. In conclusion, the majority of older Australians with AF received an antithrombotic within 4 months of TIA or ischaemic stroke. Results suggest anticoagulant therapy may be commenced soon after discharge and this should be accounted for when assessing prevalence of use among this patient group.
Acknowledgements We thank the Australian Government Department of Veterans’ Affairs (DVA) for providing data to conduct this study. This paper was reviewed by DVA prior to submission.
5 Australian Government Department of Veterans’ Affairs. Treatment Population Statistics, Quarterly Report, June 2010. Canberra (ACT): DVA. 2010 [cited 2014 Mar 17]. Available from URL: http:// www.dva.gov.au/aboutDVA/Statistics/ Documents/TpopDec2010.pdf 6 Sluggett JK, Caughey GE, Ward MB, Roughead EE, Gilbert AL. Transient ischaemic attack and ischaemic stroke: constructing episodes of care using hospital claims data. BMC Res Notes 2013; 6: 128. 7 King MA, Purdie DM, Roberts MS. Matching prescription claims with medication data for nursing home residents: implications for prescriber feedback, drug utilisation studies and selection of prescription claims database. J Clin Epidemiol 2001; 54: 202–9.
8 Vitry A, Wong SA, Roughead EE, Ramsay E, Barratt J. Validity of medication-based co-morbidity indices in the Australian elderly population. Aust N Z J Public Health 2009; 33: 126–30. 9 Coutts S, Kelloway L. Chapter 2: prevention of stroke. In: Lindsay MP, Gubitz G, Bayley M, Phillips S, eds. Canadian Best Practice Recommendations for Stroke Care. Ottawa (ON): Canadian Stroke Network; 2012; 1–69. 10 Intercollegiate Stroke Working Party. National Clinical Guideline for Stroke, 4th edn. London: Royal College of Physicians; 2012. 11 Kokotailo RA, Hill MD. Coding of stroke and stroke risk factors using International Classification of Diseases, Revisions 9 and 10. Stroke 2005; 36: 1776–81.
© 2014 The Authors Internal Medicine Journal © 2014 Royal Australasian College of Physicians
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Brief Communications
12 Henderson T, Shepheard J, Sundararajan V. Quality of diagnosis and procedure coding in ICD-10 administrative data. Med Care 2006; 44: 1011–19. 13 Australian Institute of Health and Welfare. Health Care Usage and Costs.
A Comparison of Veterans and war Widows and Widowers within the Rest of the Community. Canberra (ACT): AIHW; 2002. AIHW Cat. no. PHE 42. 14 Somerfield JS, Barber PA, Anderson NE, Kumar A, Spriggs D, Charleston A et al. Not all patients with atrial fibrillation-
associated ischemic stroke can be started on anticoagulant therapy. Stroke 2006; 37: 1217–20.
Maturity-onset diabetes of the young type 5 in a family with diabetes and mild kidney disease diagnosed by whole exome sequencing J. M. Wentworth,1,2,4 V. Lukic,1 M. Bahlo,1,4,5 M. Finlay,3 C. Nguyen,6,7 G. Morahan6,7 and L. C. Harrison1,4 1 Molecular Medicine Division, The Walter and Eliza Hall Institute of Medical Research, Departments of 2Diabetes and Endocrinology and 3Anatomical Pathology, Royal Melbourne Hospital, Departments of 4Medical Biology and 5Mathematics and Statistics, The University of Melbourne, Melbourne, Victoria, 6Centre for Diabetes Research, The Western Australian Institute for Medical Research, and 7Centre for Medical Research, University of
Western Australia, Perth, Western Australia, Australia
Key words MODY5, HNF1B, glomerulocystic kidney disease, maturity-onset diabetes of the young, whole exome sequencing. Correspondence John M. Wentworth, Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Vic. 3052, Australia. Email: [email protected]
Abstract Exome sequencing is being increasingly used to identify disease-associated gene mutations. We used whole exome sequencing to determine the genetic basis of a syndrome of diabetes and renal disease affecting a mother and her son. We identified a mutation in the hepatocyte nuclear factor 1-b (HNF1B) gene that encoded a methionine to valine amino acid change (M160V) in the HNF1B protein. This leads us to the previously unappreciated diagnosis of maturity-onset diabetes of the young type 5 and provided a basis for genetic counselling of other family members.
Received 7 April 2014; accepted 10 June 2014. doi:10.1111/imj.12584
In 1967, the mother, aged 16 years and not overweight, presented with thirst and polyuria following a bout of tonsillitis. Hyperglycaemia was confirmed and she commenced insulin therapy for presumed type 1 diabetes. At the same time, she was noted to have moderate renal impairment (creatinine 0.17 μM), normal urine micros-
Funding: This work was funded by programme (1037321) and infrastructure grants from the National Health and Medical Research Council of Australia (NHMRC), a Victorian State Government Operational Infrastructure Support Grant, the Diabetes Australia Research Trust, and the Royal Australian College of Physicians Research Foundation. Conflict of interest: None. © 2014 The Authors Internal Medicine Journal © 2014 Royal Australasian College of Physicians
copy and
Internal Medicine Journal 44 (2014)
B R I E F C O M M U N I C AT I O N S
Antithrombotic use following transient ischaemic attack or ischaemic stroke among older Australians with atrial fibrillation J. K. Sluggett,1 G. E. Caughey,1 M. B. Ward2 and A. L. Gilbert1 1
Quality Use of Medicines and Pharmacy Research Centre, Sansom Institute and 2School of Pharmacy and Medical Sciences, University of South
Australia, Adelaide, South Australia, Australia
Key words brain infarction, transient ischaemic attack, atrial fibrillation, anticoagulants, Australia. Correspondence Janet K. Sluggett, Quality Use of Medicines and Pharmacy Research Centre, Sansom Institute for Health Research, University of South Australia, GPO Box 2471, Adelaide, SA 5001, Australia. Email: [email protected]
Abstract Hospital audits may underestimate anticoagulant use among acute ischaemic stroke patients with atrial fibrillation (AF), as treatment may commence after discharge. To account for this, antithrombotic use in the 4 months after hospitalisation for transient ischaemic attack or ischaemic stroke among AF patients was assessed using claims data. Results suggest that treatment may be commenced soon after discharge and should be considered when assessing prevalence of use.
Received 19 March 2014; accepted 25 May 2014. doi:10.1111/imj.12582
Australian and international stroke management guidelines recommend patients diagnosed with transient ischaemic attack (TIA) or ischaemic stroke with atrial fibrillation (AF) receive ongoing anticoagulant therapy, as it is more efficacious than antiplatelet therapy in this setting.1 Despite this, suboptimal use of oral anticoagulants among these patients has been reported in the international literature.2 A recent analysis of data from the 2009 and 2011 Australian national stroke audits showed only 33% of ischaemic stroke patients with a diagnosis of AF were prescribed an oral anticoagulant at discharge from acute care.3 A similar Australian study conducted 10 years earlier also found 33% of TIA and ischaemic stroke patients with AF received warfarin at discharge,4 suggesting little change in use over this period. However, hospital audits may not fully capture oral anticoagulant use as the optimal time to commence therapy after ischaemic stroke in this patient group is uncertain1 and treatment may be started after discharge. In order to account for this, we undertook a population-based study to determine the use of antithrombotic medicines within 4 months of discharge for TIA or ischaemic stroke among patients with AF. Funding: J. K. Sluggett was supported by an Australian Postgraduate Award and University of South Australia scholarship to conduct this research. Conflict of interest: None.
1134
Ethics approval was obtained from the University of South Australia and Australian Government Department of Veterans’ Affairs (DVA) human research ethics committees prior to commencement. A retrospective observational study was conducted using data from DVA’s administrative health claims database. This national database includes claims for all health services and pharmaceuticals subsidised by DVA, with a treatment population of 263 433 Australian war veterans and eligible dependants in December 2009.5 Patients discharged alive between 1 January 2009 and 31 December 2009 following an episode of care for TIA (identified by International Classification of Diseases 10th revision, Australian modification (ICD10AM) codes G45.0; G45.1; G45.2; G45.8; G45.9) or ischaemic stroke (ICD-10AM code I63) and a diagnosis of AF (ICD-10AM code I48) were included in this study. Subjects included were eligible for subsidy of all health services by DVA. Data rules based on consultation with clinicians6 were applied to hospital claims recorded between 1 January 2008 and 30 June 2010 to construct episodes of care for TIA and ischaemic stroke and determine final admission and discharge dates. Where subjects had more than one episode of care for TIA or ischaemic stroke during 2009, analysis was limited to the first episode of care for each subject during this period. © 2014 The Authors Internal Medicine Journal © 2014 Royal Australasian College of Physicians
Brief Communications
Table 1 Patient characteristics Characteristics Age at admission, median (IQR) (years) Male gender (%) Resided in aged care before admission No. unique prescriptions dispensed in the 6 months before admission, median (IQR) No. comorbidities, median (IQR) Ischaemic heart disease Heart failure Diabetes Dementia Hospitalisation history: Prior TIA or stroke Myocardial infarction DVT or PE Prosthetic heart valve Length of stay, median (IQR) (days) Discharge destination Home Residential care Unrelated hospital admission Died within 120 days of discharge
TIA (n = 140)
Ischaemic stroke (n = 268)
86.9 (84.6–88.9) 65 (46.4%) 10 (7.1%) 10 (6–14) 5 (3–6) 63 (45.0%) 49 (35.0%) 14 (11.4%) 20 (14.3%)
86.0 (83.2–88.6) 124 (46.3%) 14 (5.2%) 10 (6–15) 4 (3–6) 85 (31.7%) 79 (29.5%) 49 (18.3%) 21 (7.8%)
22 (15.7%) 13 (9.3%) 5 (3.6%) 20 (14.3%) 6 (3–12)
29 (10.8%) 29 (10.8%) 11 (4.1%) 27 (10.1%) 28.5 (13–44)
122 (87.2%) 16 (11.4%) 2 (1.4%) 14 (10%)
185 (69.0%) 69 (25.8%) 14 (5.2%) 38 (14.2%)
DVT, deep vein thrombosis; IQR, interquartile range; PE, pulmonary embolism; TIA, transient ischaemic attack.
Claims for antithrombotic medicines (identified by Anatomic and Therapeutic Chemical code B01A) dispensed during the episode of care or within 120 days of discharge were analysed. This period was examined based on results of a previous validation study7 and quantities of antithrombotics subsidised in Australia. The proportion of subjects dispensed an antithrombotic was obtained from Kaplan–Meier estimates (using failure probabilities and 95% confidence intervals (CI) at 120 days after discharge). This method enabled inclusion of subjects who died within 120 days of discharge. Analyses for ischaemic stroke patients were further stratified by length of hospital stay (≤14 vs >14 days). Comorbidities were determined using the prescriptionbased comorbidity index Rx-Risk-V8 applied to pharmaceutical claims in the 6 months before admission and by screening hospital claims recorded between 1 January 2001 and the date of discharge. Analyses were performed using SAS version 9.4 (SAS Institute Inc., Cary, NC, USA).
In total, 408 (140 TIA, 268 ischaemic stroke) patients were included (Table 1). Most (90%) patients were aged ≥80 years, with 6% of patients residing in aged care prior to admission. The majority of patients (94% TIA, 90% ischaemic stroke) were dispensed antithrombotic therapy, and over half the population received warfarin within 4 months of discharge (Table 2). The majority of ischaemic stroke and TIA patients dispensed these therapies received them within 4 and 6 weeks of discharge, respectively (Kaplan–Meier plots not shown). Of the 268 ischaemic stroke patients included in this study, 74 (28%) patients were hospitalised for ≤14 days. When prevalence of use was stratified by length of stay, 61.1% (95% CI 49.8–72.5) of ischaemic stroke patients hospitalised for ≤ 14 days received warfarin compared with 50.1% (95% CI 43.2–57.5) of patients hospitalised for more than 14 days. Prevalence of use of warfarin within 4 months of leaving hospital was considerably higher than use observed in a recent national study examining treatment
Table 2 Percentage of AF patients (95% confidence interval) dispensed antithrombotic therapy within 4 months of TIA or ischaemic stroke Medicine Any antithrombotic Any anticoagulant Warfarin Any antiplatelet Aspirin Clopidogrel
ATC code
TIA
Ischaemic stroke
B01A B01AA, B01AC, B01AE, B01AF B01AA03 B01AC B01AC06 B01AC04
94.3 (89.3–97.5) 63.9 (55.8–72.0) 58.2 (50.0–66.6) 49.7 (41.6–58.4) 26.9 (20.2–26.9) 23.3 (17.1–31.3)
90.3 (86.1–93.6) 58.8 (52.8–64.9) 53.1 (47.1–59.4) 51.0 (45.0–57.2) 32.1 (26.8–38.2) 19.9 (15.5–25.2)
AF, atrial fibrillation; ATC, Anatomic and Therapeutic Chemical; TIA, transient ischaemic attack. © 2014 The Authors Internal Medicine Journal © 2014 Royal Australasian College of Physicians
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Brief Communications
at discharge from acute care.3 However, there is uncertainty about the optimal time to commence anticoagulant therapy among patients with acute cardioembolic stroke and initiation may be delayed for up to several weeks.9,10 The median length of stay for patients included in the recent national study of acute stroke care was 7 days (interquartile range 2–14 days),3 meaning anticoagulant use may have been underestimated as treatment may have commenced during rehabilitation or after discharge. One of the strengths of our approach is the ability to assess medicines supplied beyond discharge, as not all patients with AF can be commenced on anticoagulant therapy in the acute setting. The ICD-10 coding for TIA and ischaemic stroke with coexisting AF is highly reliable,11 and excellent adherence to Australian standards for ICD-10AM coding was demonstrated in a previous study.12 A potential limitation of this approach is that assessing prescriptions dispensed does not guarantee that the medicine was administered, and without clinical information, we could not assess if patients were adequately anticoagulated. Despite this, our results are similar to those reported in the international literature, including a systematic review that found prevalence of oral anticoagulant use among AF patients with a previous TIA or ischaemic stroke that was 60% or less in 21 of the 29 studies included in the review.2 Study findings are also likely to be generalisable to other older Australians hospitalised for treatment, as age-specific comparisons show the general Australian population and veterans without service-related disability have similar use of medicines and health services.13
References 1 National Stroke Foundation. Clinical Guidelines for Stroke Management 2010. Melbourne (Vic.): NSF; 2010. 2 Ogilvie IM, Newton N, Welner SA, Cowell W, Lip GYH. Underuse of oral anticoagulants in atrial fibrillation: a systematic review. Am J Med 2010; 123: 638–45, e4. 3 Andrew N, Kilkenny M, Harris D, Price C, Cadilhac DA. Outcomes for people with atrial fibrillation in an Australian national audit of stroke care. Int J Stroke 2014; 9: 270–7. 4 Duffy BK, Phillips PA, Davis SM, Donnan GA, Vedadhaghi ME. Evidence-based care and outcomes of acute stroke managed in hospital specialty units. Med J Aust 2003; 178: 318–23.
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We could not exclude patients with previous adverse reactions, treatment contraindications or those refusing treatment from this study, nor could we assess all factors impacting on anticoagulation decisions in the oldest old (such as poor functional outcome, limited life expectancy, logistics of monitoring and ability to manage medicines).14 For these reasons, it is possible that true prevalence of use is underestimated, as contraindications to treatment are more common among older patients. Prescription claims for warfarin were assessed as it was the preferred oral anticoagulant in Australia during the study period; however, in late 2013, three newer oral anticoagulants were made available under Australia’s national pharmaceutical subsidy scheme for stroke prevention among patients with non-valvular AF and at least one stroke risk factor (such as previous TIA or ischaemic stroke). The impact of increased accessibility to newer agents on therapeutic decisions and treatment rates among older Australians should be assessed once further data are available. In conclusion, the majority of older Australians with AF received an antithrombotic within 4 months of TIA or ischaemic stroke. Results suggest anticoagulant therapy may be commenced soon after discharge and this should be accounted for when assessing prevalence of use among this patient group.
Acknowledgements We thank the Australian Government Department of Veterans’ Affairs (DVA) for providing data to conduct this study. This paper was reviewed by DVA prior to submission.
5 Australian Government Department of Veterans’ Affairs. Treatment Population Statistics, Quarterly Report, June 2010. Canberra (ACT): DVA. 2010 [cited 2014 Mar 17]. Available from URL: http:// www.dva.gov.au/aboutDVA/Statistics/ Documents/TpopDec2010.pdf 6 Sluggett JK, Caughey GE, Ward MB, Roughead EE, Gilbert AL. Transient ischaemic attack and ischaemic stroke: constructing episodes of care using hospital claims data. BMC Res Notes 2013; 6: 128. 7 King MA, Purdie DM, Roberts MS. Matching prescription claims with medication data for nursing home residents: implications for prescriber feedback, drug utilisation studies and selection of prescription claims database. J Clin Epidemiol 2001; 54: 202–9.
8 Vitry A, Wong SA, Roughead EE, Ramsay E, Barratt J. Validity of medication-based co-morbidity indices in the Australian elderly population. Aust N Z J Public Health 2009; 33: 126–30. 9 Coutts S, Kelloway L. Chapter 2: prevention of stroke. In: Lindsay MP, Gubitz G, Bayley M, Phillips S, eds. Canadian Best Practice Recommendations for Stroke Care. Ottawa (ON): Canadian Stroke Network; 2012; 1–69. 10 Intercollegiate Stroke Working Party. National Clinical Guideline for Stroke, 4th edn. London: Royal College of Physicians; 2012. 11 Kokotailo RA, Hill MD. Coding of stroke and stroke risk factors using International Classification of Diseases, Revisions 9 and 10. Stroke 2005; 36: 1776–81.
© 2014 The Authors Internal Medicine Journal © 2014 Royal Australasian College of Physicians
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Brief Communications
12 Henderson T, Shepheard J, Sundararajan V. Quality of diagnosis and procedure coding in ICD-10 administrative data. Med Care 2006; 44: 1011–19. 13 Australian Institute of Health and Welfare. Health Care Usage and Costs.
A Comparison of Veterans and war Widows and Widowers within the Rest of the Community. Canberra (ACT): AIHW; 2002. AIHW Cat. no. PHE 42. 14 Somerfield JS, Barber PA, Anderson NE, Kumar A, Spriggs D, Charleston A et al. Not all patients with atrial fibrillation-
associated ischemic stroke can be started on anticoagulant therapy. Stroke 2006; 37: 1217–20.
Maturity-onset diabetes of the young type 5 in a family with diabetes and mild kidney disease diagnosed by whole exome sequencing J. M. Wentworth,1,2,4 V. Lukic,1 M. Bahlo,1,4,5 M. Finlay,3 C. Nguyen,6,7 G. Morahan6,7 and L. C. Harrison1,4 1 Molecular Medicine Division, The Walter and Eliza Hall Institute of Medical Research, Departments of 2Diabetes and Endocrinology and 3Anatomical Pathology, Royal Melbourne Hospital, Departments of 4Medical Biology and 5Mathematics and Statistics, The University of Melbourne, Melbourne, Victoria, 6Centre for Diabetes Research, The Western Australian Institute for Medical Research, and 7Centre for Medical Research, University of
Western Australia, Perth, Western Australia, Australia
Key words MODY5, HNF1B, glomerulocystic kidney disease, maturity-onset diabetes of the young, whole exome sequencing. Correspondence John M. Wentworth, Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Vic. 3052, Australia. Email: [email protected]
Abstract Exome sequencing is being increasingly used to identify disease-associated gene mutations. We used whole exome sequencing to determine the genetic basis of a syndrome of diabetes and renal disease affecting a mother and her son. We identified a mutation in the hepatocyte nuclear factor 1-b (HNF1B) gene that encoded a methionine to valine amino acid change (M160V) in the HNF1B protein. This leads us to the previously unappreciated diagnosis of maturity-onset diabetes of the young type 5 and provided a basis for genetic counselling of other family members.
Received 7 April 2014; accepted 10 June 2014. doi:10.1111/imj.12584
In 1967, the mother, aged 16 years and not overweight, presented with thirst and polyuria following a bout of tonsillitis. Hyperglycaemia was confirmed and she commenced insulin therapy for presumed type 1 diabetes. At the same time, she was noted to have moderate renal impairment (creatinine 0.17 μM), normal urine micros-
Funding: This work was funded by programme (1037321) and infrastructure grants from the National Health and Medical Research Council of Australia (NHMRC), a Victorian State Government Operational Infrastructure Support Grant, the Diabetes Australia Research Trust, and the Royal Australian College of Physicians Research Foundation. Conflict of interest: None. © 2014 The Authors Internal Medicine Journal © 2014 Royal Australasian College of Physicians
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