Deprescribing in older patients by early-career general practitioners: Prevalence and associations.

RATIONALE AND AIMS: Deprescribing is the health-professional-supervised process of withdrawal of an inappropriate medication to manage polypharmacy and improve patient outcomes. Given the harms of polypharmacy and associated inappropriate medicines, practitioners, especially general practitioners (GPs), are encouraged to take a proactive role in deprescribing in older patients. While trial evidence for benefits of deprescribing is accumulating, there is currently little epidemiologic evidence of clinicians' (including GPs') deprescribing behaviours. We aimed to establish the prevalence and explore associations of deprescribing of inappropriate medicines by early-career GPs. METHODS: A cross-sectional analysis of the ReCEnT study of GP registrars' in-consultation experience, 2016-18. Participants recorded 60 consecutive consultations, three times at 6-month intervals, including medicines ceased (our measure of deprescribing). The outcome was deprescribing of an inappropriate medicine (defined by a synthesis of three accepted classification systems) in patients 65 years or older. Logistic regression determined the associations of deprescribing inappropriate medicines. RESULTS: One thousand one hundred and thirteen registrars reported 19 581 consultations with patients 65 years and older. Inappropriate medicines were deprescribed in 2.6% (95% CIs 2.4%-2.9%) of consultations. Of deprescribed medicines, 43% had been prescribed for three months or longer. Most commonly deprescribed were opioids (19%), proton pump inhibitors (9.2%), anti-inflammatory drugs (9.0%), statins (7.8%), and antidepressants (6.6%). The most common reason for deprescribing was: "no longer indicated" (38%). Significant adjusted associations of deprescribing included patients identifying as Aboriginal or Torres Strait Islander (OR 2.86); continuity-of-care (ORs 0.71 and 0.20 for the patient being new to practice and to the registrar, respectively); inner-regional compared to major-city location (OR 1.33); the problem/diagnosis being chronic (OR 1.90); and longer consultations (OR 1.03 per minute increase in duration). CONCLUSION: These findings will have important implications for the education of GPs in deprescribing as a clinical skill.

Antibiotic prescribing patterns of general practice registrars for infective conjunctivitis: a cross-sectional analysis.

INTRODUCTION Over-prescription of antibiotics for common infective conditions is an important health issue. Infective conjunctivitis represents one of the most common eye-related complaints in general practice. Despite its self-limiting nature, there is evidence of frequent general practitioner (GP) antibiotic prescribing for this condition, which is inconsistent with evidence-based guidelines. AIM To investigate the prevalence and associations of GP registrars' (trainees') prescription of antibiotics for infective conjunctivitis. METHODS We performed a cross-sectional analysis of the Registrar Encounters in Clinical Training (ReCEnT) ongoing prospective cohort study, which documents GP registrars' clinical consultations (involving collection of information from 60 consecutive consultations, at three points during registrar training). The outcome of the analyses was antibiotic prescription for a new diagnosis of conjunctivitis. Patient, registrar, practice and consultation variables were included in uni- and multivariable logistic regression analyses to test associations of these prescriptions. RESULTS In total, 2333 registrars participated in 18 data collection rounds from 2010 to 2018. There were 1580 new cases of infective conjunctivitis (0.31% of all problems). Antibiotics (mainly topical) were prescribed in 1170 (74%) of these cases. Variables associated with antibiotic prescription included patients' Aboriginal or Torres Strait Islander status, registrar organisation of a follow up (both registrar and other GP follow up), and earlier registrar training term (more junior status). DISCUSSION GP registrars, like established GPs, prescribe antibiotics for conjunctivitis in excess of guideline recommendations, but prescribing rates are lower in later training. These prescribing patterns have educational, social and economic consequences. Further educational strategies may enhance attenuation of registrars' prescribing during training.

The Characteristics of Patients With Possible Transient Ischemic Attack and Minor Stroke in the Hunter and Manning Valley Regions, Australia (the INSIST Study).

Background: Transient ischemic attack (TIA) and minor stroke (TIAMS) are risk factors for stroke recurrence. Some TIAMS may be preventable by appropriate primary prevention. We aimed to recruit "possible-TIAMS" patients in the INternational comparison of Systems of care and patient outcomes In minor Stroke and TIA (INSIST) study. Methods: A prospective inception cohort study performed across 16 Hunter-Manning region, Australia, general practices in the catchment of one secondary-care acute neurovascular clinic. Possible-TIAMS patients were recruited from August 2012 to August 2016. We describe the baseline demographics, risk factors and pre-event medications of participating patients. Results: There were 613 participants (mean age; 69 ± 12 years, 335 women), and 604 (99%) were Caucasian. Hypertension was the most common risk factor (69%) followed by hyperlipidemia (52%), diabetes mellitus (17%), atrial fibrillation (AF) (17%), prior TIA (13%) or stroke (10%). Eighty-nine (36%) of the 249 participants taking antiplatelet therapy had no known history of cardiovascular morbidity. Of 102 participants with known AF, 91 (89%) had a CHA2DS2-VASc score ≥ 2 but only 47 (46%) were taking anticoagulation therapy. Among 304 participants taking an antiplatelet or anticoagulant agent, 30 (10%) had stopped taking these in the month prior to the index event. Conclusion: This study provides the first contemporary data on TIAMS or TIAMS-mimics in Australia. Community and health provider education is required to address the under-use of anticoagulation therapy in patients with known AF, possibly inappropriate use of antiplatelet therapy and possibly inappropriate discontinuation of antiplatelet or anticoagulation therapy.

Cognition in the First Year After a Minor Stroke, Transient Ischemic Attack, or Mimic Event and the Role of Vascular Risk Factors.

Background: Cognitive impairment following a minor stroke or transient ischemic attack (TIA) is common; however, due to diagnostic difficulties, the prevalence and underlying cause of impairment remain poorly defined. We compared cognition in patients after a minor stroke, TIA, or mimic event at three time points in the first year following the event. We examine whether cognitive impairment occurs following these events and whether this impairment differs based on the event type. Further, we measure whether these findings persist after controlling for age, education, and the presence of vascular risk factors and whether the presence of vascular risk factors, independent of event etiology, is associated with cognitive impairment. Lastly, we investigate whether increased stroke risk, as assessed by the ABCD2, is associated with reduced cognition. Methods: Medical information, a cognitive screening test, and a measure of executive functioning were collected from 613 patients (123 minor stroke, 175 TIA, and 315 mimics) using phone interviews at three time points in the first year following the event. Linear mixed models were used to determine the effect of event type, vascular risk factors, and predicted stroke risk on cognitive performance while controlling for confounders. Results: There was no relationship between event type and performance on either cognitive measure. When all confounders are controlled for, performance on the cognitive screening test was uniquely accounted for by the presence of heart failure, myocardial infarction, angina, and hypertension (all p < 0.047), whereas the measure of executive functioning was uniquely accounted for by the presence of hypertension and angina (all p < 0.032). Increased stroke risk also predicted performance on the cognitive screening test and the measure of executive functioning (all p < 0.002). Conclusions: Our findings indicate that cognitive impairment following a minor stroke or TIA may be attributed to the high prevalence of chronic vascular risk factors in these patients. This highlights the importance of long-term management of vascular risk factors beyond event recovery to reduce the risk of cognitive impairment. Increased stroke risk (i.e., ABCD2 score) was also associated with reduced cognition, suggesting that it may be helpful in signaling the need for further cognitive evaluation and intervention post-event.

The International comparison of Systems of care and patient outcomes In minor Stroke and Tia (InSIST) study: A community-based cohort study.

RATIONALE: Rapid response by health-care systems for transient ischemic attack and minor stroke (TIA/mS) is recommended to maximize the impact of secondary prevention strategies. The applicability of this evidence to Australian non-hospital-based TIA/mS management is uncertain. AIMS: Within an Australian community setting we seek to document processes of care, establish determinants of access to care, establish attack rates and determinants of recurrent vascular events and other clinical outcomes, establish the performance of ABC2-risk stratification, and compare the processes of care and outcomes to those in the UK and New Zealand for TIA/mS. SAMPLE SIZE ESTIMATES: Recruiting practices containing approximately 51 full-time-equivalent general practitioners to recruit 100 TIA/mS per year over a four-year study period will provide sufficient power for each of our outcomes. METHODS AND DESIGN: An inception cohort study of patients with possible TIA/mS recruited from 16 general practices in the Newcastle-Hunter Valley-Manning Valley region of Australia. Potential TIA/mS will be ascertained by multiple overlapping methods at general practices, after-hours collaborative, and hospital in-patient and outpatient services. Participants' index and subsequent clinical events will be adjudicated as TIA/mS or mimics by an expert panel. STUDY OUTCOMES: Process outcomes-whether the patient was referred for secondary care; time from event to first patient presentation to a health professional; time from event to specialist acute-access clinic appointment; time from event to brain and vascular imaging and relevant prescriptions. Clinical outcomes-recurrent stroke and major vascular events; and health-related quality of life. DISCUSSION: Community management of TIA/mS will be informed by this study.

Contemporary prognosis of transient ischemic attack patients: A systematic review and meta-analysis.

BACKGROUND: Transient ischemic attacks are common and place patients at risk of subsequent stroke. The 2007 EXPRESS and SOS-TIA studies demonstrated the efficacy of rapid treatment initiation. We hypothesized that with these findings having informed subsequent transient ischemic attacks management protocols, transient ischemic attacks prognosis in contemporary (2008 and later) patient cohorts would be more favorable than in historical cohorts. METHODS: A systematic review and meta-analysis of cohort studies and randomized control trial placebo-arms of transient ischemic attack (published 2008-2015). The primary outcome was stroke. Secondary outcomes were mortality, transient ischemic attack, and myocardial infarction. Studies were excluded if the outcome of transient ischemic attack patients was not reported separately. The systematic review included all studies of transient ischemic attack. The meta-analysis excluded studies of restricted transient ischemic attack patient types (e.g. only patients with atrial fibrillation). The pooled cumulative risks of stroke recurrence were estimated from study-specific estimates at 2, 7, 30, and 90 days post-transient ischemic attack, using a multivariate Bayesian model. RESULTS: We included 47 studies in the systematic review and 40 studies in the meta-analysis. In the systematic review (191,202 patients), stroke at 2 days was reported in 13/47 (27.7%) of studies, at 7 days in 20/47 (42.6%), at 30 days in 12/47 (25.5%), and at 90 days in 33/47 (70.2%). Studies included in the meta-analysis recruited 68,563 patients. The cumulative risk of stroke was 1.2% (95% credible interval (CI) 0.6-2.2), 3.4% (95% CI 2.0-5.5), 5.0% (95% CI 2.9-8.9), and 7.4% (95% CI 4.3-12.4) at 2, 7, 30, and 90 days post-transient ischemic attack, respectively. CONCLUSION: In contemporary settings, transient ischemic attack prognosis is more favorable than reported in historical cohorts where a meta-analysis suggests stroke risk of 3.1% at two days.

Quality of referrals and guideline compliance for time to consultation at an acute neurovascular clinic.

BACKGROUND: The Age, Blood pressure, Clinical features, Duration of symptoms, Diabetes (ABCD2) score can be used to predict early recurrent stroke risk following Transient ischemic attack (TIA). Given that recurrent stroke risk can be as high as 20% in the first week, international guidelines recommend "high-risk" TIAs (ABCD2 >3) be seen by specialist services such as dedicated acute neurovascular clinics within 24 hours. The goal of this study was to examine the associations of both quality of referrals to a specialist acute clinic and of "guideline congruence" of time-to-clinic consultation after TIA/minor stroke. We hypothesized high-quality referrals containing key clinical elements would be associated with greater guideline congruence. METHODS: A retrospective analysis of referrals to an acute neurovascular clinic within a tertiary care hospital of consecutive patients with TIA/minor stroke. Quality of general practitioner and emergency department referrals was defined on the basis of information content enabling ABCD2-based risk stratification by the clinic triage service. Time-to-clinic consultation was used to define "guideline congruence." RESULTS: Referrals of 148 consecutive eligible patients were reviewed. Sixty-six percent of cases were subsequently neurologist-diagnosed as TIA or minor stroke. Seventy-nine percent were referred by general practitioners. Fifty-three percent of referrals were of high quality, but quality was not associated with guideline congruence. Of the high-risk patients, only 3.6% were seen at the clinic within 24 hours of index event and 31.3% within 24 hours of referral. CONCLUSIONS: Current guidelines are pathophysiologically logical and evidence based, but are difficult to implement. Improving quality of primary-secondary communication by improved referral quality is unlikely to improve guideline compliance. Alternative strategies are needed to reduce recurrent stroke risk after TIA/minor stroke.

Absolute cardiovascular risk and GP decision making in TIA and minor stroke.

BACKGROUND: Transient ischaemic attacks (TIA) and minor strokes (TIAMS) have the same pathophysiological mechanism as stroke and carry a high risk of recurrent ischaemic events. Diagnosis of TIAMS can be challenging and often occurs in general practice. Absolute cardiovascular risk (ACVR) is recommended as the basis for vascular risk management. Consideration of cardiovascular risk in TIAMS diagnosis has been recommended but its utility is not established. OBJECTIVES: Firstly, to document the ACVR of patients with incident TIAMS and with TIAMS-mimics. Secondly, to evaluate the utility of ACVR calculation in informing the initial diagnosis of TIAMS. METHODS: The International comparison of Systems of care and patient outcomes in minor Stroke and TIA (InSiST) study is an inception cohort study of patients of 17 Australian general practices presenting as possible TIAMS. An expert panel determines whether participants have had TIAMS or TIAMS-mimics. ACVR was calculated at baseline for each participating patient. In this cross-sectional baseline analysis, ACVR of TIAMS and TIAMS-mimics were compared univariately and, also, when adjusted for age and sex. The diagnostic utility of ACVR was evaluated via receiver operating characteristic (ROC) curves. RESULTS: Of 179 participants, 87 were adjudicated as TIAMS. The presence of motor and speech symptoms and body mass index were associated with a diagnosis of TIAMS. ACVR was associated with TIAMS diagnosis on univariate analysis, but not when age- and sex-adjusted. ACVR did not significantly improve area under ROC curves beyond that of age and sex. CONCLUSION: In patients presenting with transient or minor neurological symptoms, calculation of ACVR did not improve diagnostic accuracy for TIAMS beyond that of age and sex.

The influence of anterior cerebral artery flow diversion measured by transcranial Doppler on acute infarct volume and clinical outcome in anterior circulation stroke.

INTRODUCTION: Anterior cerebral artery flow diversion, measured by transcranial Doppler ultrasound, is correlated with leptomeningeal collateral flow on digital subtraction angiography in the setting of middle cerebral artery occlusion. We aimed to assess the influence of flow diversion as a marker of leptomeningeal collateralization on infarct size and penumbral volume. METHODS: We assessed consecutive patients presenting within six-hours of ischaemic stroke. Anterior cerebral artery flow diversion, defined as ipsilateral mean velocity of at least 30% greater than the contralateral artery, was used as the Doppler index of leptomeningeal collateralization. Multivariable regression analysis was performed to assess the impact of anterior cerebral artery flow diversion, controlling for other important clinical variables. Leptomeningeal collateralization was also graded on computed tomography angiography. Infarct core and penumbral volumes were defined using computed tomography perfusion thresholds of cerebral blood volume and mean transit time. Infarct volume, reperfusion, and vessel status were measured at 24 h using magnetic resonance techniques. RESULTS: Fifty-three patients qualified for analysis. Anterior cerebral artery flow diversion was associated with good collateral flow on computed tomography angiography (P < 0·001) and was an independent predictor of admission infarct core volume (P < 0·001), and 24 h infarct volume (P < 0·001). The likelihood of a favourable outcome (modified Rankin Score 0-2) was higher (odds ratio = 27·5, P < 0·001) in those with flow diversion. CONCLUSIONS: Anterior cerebral artery flow diversion indicates effective leptomeningeal collateralization as measured by computed tomography angiography, and independently predicts acute infarct size and 90-day clinical outcome. Flow diversion appears to provide penumbral perfusion, offering some protection against infarct expansion. Acute bedside transcranial Doppler assessment of flow diversion aids prognostication and therapeutic decision making in anterior circulation stroke.

HOBOE (Head-of-Bed Optimization of Elevation) Study: association of higher angle with reduced cerebral blood flow velocity in acute ischemic stroke.

BACKGROUND: Cerebral autoregulation can be impaired after ischemic stroke, with potential adverse effects on cerebral blood flow during early rehabilitation. OBJECTIVE: The objective of this study was to assess changes in cerebral blood flow velocity with orthostatic variation at 24 hours after stroke. DESIGN: This investigation was an observational study comparing mean flow velocities (MFVs) at 30, 15, and 0 degrees of elevation of the head of the bed (HOB). METHODS: Eight participants underwent bilateral middle cerebral artery (MCA) transcranial Doppler monitoring during orthostatic variation at 24 hours after ischemic stroke. Computed tomography angiography separated participants into recanalized (artery completely reopened) and incompletely recanalized groups. Friedman tests were used to determine MFVs at the various HOB angles. Mann-Whitney U tests were used to compare the change in MFV (from 30° to 0°) between groups and between hemispheres within groups. RESULTS: For stroke-affected MCAs in the incompletely recanalized group, MFVs differed at the various HOB angles (30°: median MFV=51.5 cm/s, interquartile range [IQR]=33.0 to 103.8; 15°: median MFV=55.5 cm/s, IQR=34.0 to 117.5; 0°: median MFV=85.0 cm/s, IQR=58.8 to 127.0); there were no significant differences for other MCAs. For stroke-affected MCAs in the incompletely recanalized group, MFVs increased with a change in the HOB angle from 30 degrees to 0 degrees by a median of 26.0 cm/s (IQR=21.3 to 35.3); there were no significant changes in the recanalized group (-3.5 cm/s, IQR=-12.3 to 0.8). The changes in MFV with a change in the HOB angle from 30 degrees to 0 degrees differed between hemispheres in the incompletely recanalized group but not in the recanalized group. LIMITATIONS: Generalizability was limited by sample size. CONCLUSIONS: The incompletely recanalized group showed changes in MFVs at various HOB angles, suggesting that cerebral blood flow in this group may be sensitive to orthostatic variation, whereas the recanalized group maintained stable blood flow velocities.

The rural Prehospital Acute Stroke Triage (PAST) trial protocol: a controlled trial for rapid facilitated transport of rural acute stroke patients to a regional stroke centre.

RATIONALE: Access to intravenous thrombolysis for acute ischaemic stroke is limited worldwide, particularly in regional and rural areas including in Australia. We are testing the effectiveness of a new rural Prehospital Acute Stroke Triage protocol that includes prehospital assessment and rapid transport of patients from a rural catchment to the major stroke centre in Newcastle, NSW, Australia. The local district hospitals within the rural catchment do not have the capability or infrastructure to deliver acute stroke thrombolysis. The trial has relevance to stroke clinicians, health service managers and planners responsible for rural populations. AIMS: To implement a system of rapid prehospital assessment and facilitated transport that will significantly increase stroke thrombolysis rates to 10% of ischaemic stroke cases in the rural catchment. Validate an eight-point modified National Institutes of Health Stroke Scale for use by paramedics in the prehospital setting to assess patients' potential eligibility for stroke thrombolysis. DESIGN: The joint project between the John Hunter Hospital Acute Stroke Team and the Ambulance Service of NSW will use a prospective cohort with an historical control group. Tools and protocols have been developed and education undertaken for ambulance field and operations centre personnel. These include a cut-down eight-item National Institutes of Health Stroke Scale (Hunter NIHSS-8) score to be used in the field by paramedics and a transport decision matrix to expedite transport for a suspected stroke patient (road or road plus air transport). OUTCOMES: The primary outcome measure will be the rate of intravenous tissue plasminogen activator delivery for those who suffer an ischaemic stroke following protocol implementation, in comparison with historical rates over a corresponding period prior to implementation, for residents within the catchment. Sixty cases are required in the postimplementation time epoch to demonstrate a statistically significant absolute increase in thrombolysis rates for ischaemic strokes from <1% to 10%, (power of 80%, α error of 0.05). The major secondary outcome will be inter-rater reliability of the Hunter NIHSS-8.

Improving access to acute stroke therapies: a controlled trial of organised pre-hospital and emergency care.

OBJECTIVE: To assess the effectiveness of the PAST (Pre-hospital Acute Stroke Triage) protocol in reducing pre-hospital and emergency department (ED) delays to patients receiving organised acute stroke care, thereby increasing access to thrombolytic therapy. DESIGN: Prospective cohort study using historical controls. SETTING: Hunter Region of New South Wales, September 2005 to March 2006 (pre-intervention) and September 2006 to March 2007 (post-intervention). PARTICIPANTS: Consecutive patients presenting with acute stroke to a regional, tertiary referral hospital. INTERVENTION: PAST protocol, comprising a pre-hospital stroke assessment tool for ambulance officers, an ambulance protocol for hospital bypass for potentially thrombolysis-eligible patients, and pre-hospital notification of the acute stroke team. MAIN OUTCOME MEASURES: Proportion of patients who received intravenous tissue plasminogen activator (tPA), process of care time points (symptom onset to ED arrival, ED arrival to tPA treatment, and ED transit time), and clinical outcomes of patients treated with tPA. RESULTS: The proportion of ischaemic stroke patients treated with tPA increased from 4.7% (pre-intervention) to 21.4% (post-intervention) (P < 0.001). Time point outcomes also improved, with a reduction in median times from symptom onset to ED arrival from 150 to 90.5 min (P = 0.004) and from ED arrival to stroke unit admission from 361 to 232.5 minutes (P < 0.001). Of those treated with tPA, 43% had minimal or no disability at 3 months. CONCLUSIONS: Organised pre-hospital and ED acute stroke care increases patient access to tPA treatment, which is proven to reduce stroke-related disability.