Linda Brewer

Stroke rehabilitation: recent advances and future therapies

Despite advances in the acute management of stroke, a large proportion of stroke patients are left with significant impairments. Over the coming decades the prevalence of stroke-related disability is expected to increase worldwide and this will impact greatly on families, healthcare systems and economies. Effective neuro-rehabilitation is a key factor in reducing disability after stroke. In this review, we discuss the effects of stroke, principles of stroke rehabilitative care and predictors of recovery. We also discuss novel therapies in stroke rehabilitation, including non-invasive brain stimulation, robotics and pharmacological augmentation. Many trials are currently underway, which, in time, may impact on future rehabilitative practice.

Current and future treatment options in osteoporosis

PurposeThe incidence of osteoporosis-related fractures will increase substantially over the coming decades as the population ages globally. This has important economic and public health implications, contributing substantially to morbidity and excess mortality in this population.MethodsWhen prescribing for older patients the effectiveness profile of drugs needs to be balanced against their tolerability in individual patients. ResultsCurrently we have good anti-fracture data to support the use of many available anti-resorptive and anabolic drugs including bisphosphonates, strontium ranelate and recombinant human parathyroid hormone. We also have evidence to demonstrate the importance of calcium and vitamin D repletion in these patients. However, in recent years our understanding of normal bone physiology and the mechanisms underlying the development of osteoporosis has significantly advanced and this has led to the development of new therapies. Novel agents, particularly denosumab, but also inhibitors of cathepsin K and anabolic agents that act on Wnt signalling, will increase the therapeutic options for clinicians in the coming years.ConclusionThis review discusses the evidence supporting the use of currently available treatment options for osteoporosis and potential future advances in drug therapy. Particular consideration should be given when prescribing for certain older patients who have issues with compliance or tolerance and also in those with co-morbidities or levels of frailty that may restrict the choice of therapy. Understanding the evidence for the benefit and possible harm of osteoporosis treatments is critical to appropriate management of this patient population.

Cognitive impairment six months after ischaemic stroke: a profile from the ASPIRE-S study

BackgroundCognitive impairment commonly occurs in the acute phase post-stroke, but may persist with over half of all stroke survivors experiencing some form of long-term cognitive deficit. Recent evidence suggests that optimising secondary prevention adherence is a critical factor in preventing recurrent stroke and the incidence of stroke-related cognitive impairment and dementia. The aim of this study was to profile cognitive impairment of stroke survivors at six months, and to identify factors associated with cognitive impairment post-stroke, focusing on indicators of adequate secondary prevention and psychological function.MethodsParticipants were assessed at six months following an ischaemic stroke as part of the Action on Secondary Prevention Interventions and Rehabilitation in Stroke study (ASPIRE-S), which examined the secondary preventive and rehabilitative profile of patients in the community post-stroke. Cognitive impairment was measured using the Montreal Cognitive Assessment (MoCA).ResultsTwo-hundred and fifty-six stroke patients were assessed at six months. Over half of the sample (56.6%) were found to have cognitive impairment, with significant associations between cognitive impairment and female sex (odds ratio (OR)u2009=u20091.6, 95% CI 1.01-2.57) and history of cerebrovascular disease (ORu2009=u20092.22, 95% CI 1.38-3.59). Treatment with antihypertensive medications (ORu2009=u2009.65, 95% CI .44-.96) and prescription of anticoagulant therapy (ORu2009=u2009.41, 95% CI .26-.68) were associated with reduced likelihood of cognitive impairment, however increasing number of total prescribed medications was moderately associated with poorer cognitive impairment (ORu2009=u20091.12, 95% CI 1.04-1.19).ConclusionsFindings reveal levels of cognitive impairment at 6xa0months post-stroke that are concerning. Encouragingly, aspects of secondary prevention were identified that may be protective in reducing the incidence of cognitive impairment post-stroke. Neuropsychological rehabilitation post-stroke is also required as part of stroke rehabilitation models to meet the burden of post-stroke cognitive impairment.

A population-based study of dosing and persistence with anti-dementia medications

PurposeCholinesterase inhibitors and memantine are the mainstay of pharmacological intervention for the cognitive symptoms of Alzheimer’s disease (AD). This study assessed the adequacy of dosing and persistence with AD medications and the predictors of these variables in the ‘real world’ (outside the clinical trial setting).MethodsThe Health Service Executive–Primary Care Reimbursement Services prescription claims database in the Republic of Ireland contains prescription information for 1.6 million people. Patients aged >70xa0years who received at least two prescriptions for donepezil, rivastigmine, galantamine and memantine between January 2006 and December 2010 were included in the study. Rates of dose-maximisation were recorded by examining the initiation dose of each AD drug commenced during the study period and any subsequent dose titrations. Non-persistence was defined by a gap in prescribing of more than 63 consecutive days. Predictors of dose-maximisation and non-persistence were also analysed.ResultsBetween January 2006 and December 2010, 20,729 patients aged >70xa0years received a prescription for an AD medication. Despite most patients on donepezil and memantine receiving a prescription for the maximum drug dose, this dose was maintained for 2 consecutive months in only two-thirds of patients. Patients were significantly more likely to have their doses of donepezil and memantine maximised if prescribed in more recent years (2010 vs. 2007). Rates of non-persistence were 30.1xa0% at 6 months and 43.8xa0% at 12xa0months. Older age [75+ vs. <75xa0years; hazards ratio (HR)u20091.16, 95xa0% confidence interval (CI) 1.06–1.27] and drug type (rivastigmine vs. donepezil; HRu20091.15, 95xa0% CI 1.03–1.27) increased the risk of non-persistence. Non-persistence was lower for those commencing therapy in more recent years (2010 vs. 2007; HRu20090.81, 95xa0% CI 0.73–0.89, pu2009<u20090.001) and for those on multiple anti-dementia medications (HRu20090.59, 95xa0% CI 0.54–0.65, pu2009<u20090.001). Persistence was significantly higher when memantine was co-prescribed with donepezil (pu2009<u20090.0001).ConclusionFuture studies should explore the reasons underlying non-persistence and failure to maintain dose-maximisation in patients on AD medications. There may be scope to improve the dosing and persistence with these medications in the community.

Implications of stroke for caregiver outcomes: findings from the ASPIRE-S study

Background Informal caregivers are vital to the long-term care and rehabilitation of stroke survivors worldwide. However, caregiving has been associated with negative psychological outcomes such as anxiety and depression, which leads to concerns about caregiver as well as stroke survivor well-being. Furthermore, caregivers may not receive the support and service provision they require from the hospitals and community. Aims This study examines caregiver psychological well-being and satisfaction with service provision in the context of stroke. Methods Caregiver data were collected as part of the ASPIRE-S study, a prospective study of secondary prevention and rehabilitation which assessed stroke patients and their carers at six-months post stroke. Carer assessment included measurement of demographics, satisfaction with care (UK Healthcare Commission National Patient Survey of Stroke Care), psychological distress (Hospital Anxiety and Depression Scale), and vulnerability (Vulnerable Elders Scale). Logistic regression analyses and chi-squared tests were performed using STATA version 12. Results Analyses from 162 carers showed substantial levels of dissatisfaction (37·9%) with community and hospital services, as well as notable levels of anxiety (31·3%) and depressive symptoms (18·8%) among caregivers. Caregiver anxiety was predicted by stroke survivor anxiety (OR = 3·47, 95% CI 1·35–8·93), depression (OR = 5·17, 95% CI 1·83–14·58), and stroke survivor cognitive impairment (OR 2·35, 95% CI 1·00–5·31). Caregiver depression was predicted by stroke survivor anxiety (OR = 4·41, 95% CI 1·53–12·72) and stroke survivor depression (OR = 6·91, 95% CI 2·26–21·17). Conclusion Findings indicate that caregiver and stroke survivor well-being are interdependent. Thus, early interventions, including increased training and support programs that include caregivers, are likely to reduce the risk of negative emotional outcomes.

Secondary prevention after ischaemic stroke: the ASPIRE-S study

BackgroundSurvivors of ischaemic stroke (IS) are at high-risk for future vascular events. Comprehensive information on the adequacy of secondary prevention after IS is lacking despite the knowledge that appropriate secondary prevention improves long-term patient outcomes. ASPIRE-S (Action on Secondary Prevention Interventions and Rehabilitation in Stroke) aimed to prospectively assess secondary prevention in patients 6xa0months following IS.MethodsConsenting patients admitted with IS to three Dublin hospitals were recruited over 1xa0year, from October 2011. At 6xa0months post IS a comprehensive assessment was completed, modelled on the EUROASPIRE protocol for evaluation of the adequacy of secondary prevention in post-discharge cardiac patients. This assessment included measurements of blood pressure, body mass index and fasting lipid and glucose profiles. Secondary preventive medications and smoking status were also documented.ResultsThree hundred two patients (58xa0% male) participated, of whom 256 (85xa0%) were followed-up at 6xa0months. Mean age was 69xa0years (range 22–95). At follow-up, 68xa0% of patients had a BMI >25xa0kg/m2 and 16.4xa0% were still smoking. Almost two-thirds (63.4xa0%) had a blood pressure >140/90 and 23xa0% had low-density-lipoprotein >2.5xa0mmol/L. 28xa0% of diabetic patients had HbA1c ≥7xa0%. Ninety seven percent of patients were on anti-platelet and/or anticoagulant therapy. Of those with atrial fibrillation, 82xa0% were anti-coagulated (mean INR of 2.4). Ninety-five percent were on lipid-lowering therapy and three-quarters were on anti-hypertensive therapy.ConclusionThis prospective multi-centre survey of IS patients demonstrated a high prevalence of remaining modifiable risk factors at 6xa0months post stroke, despite the widespread prescription of secondary preventive medications. There is scope to improve preventive measures after IS (in particular blood pressure) by incorporating evidence-based guidelines into quality assurance cycles in stroke care.

POOR RETURN OF FUNCTIONAL MOBILITY AFTER HIP FRACTURE IN OLDER PATIENTS—IT'S TIME TO IMPROVE ON HIP FRACTURE PREVENTION

and Medical Research Council of Australia. Author Contributions: JB was responsible for the study concept. All authors were responsible for the study design, interpretation of data, drafting and critical revision of the manuscript. JL and AD: statistical analysis and preparation of the data. All authors approved the final version of the article. DM is the guarantor. Sponsor’s Role: The funding sources had no role in the design or conduct of the study; collection, management, analysis, or interpretation of the data; or preparation, review, or approval of the manuscript.

A review of early supported discharge after stroke

Stroke is a leading cause of disability worldwide and patients with stroke frequently require prolonged periods of in-patient rehabilitation prior to discharge. This poses a large economic strain on health services, and the cost-effectiveness of this system has been questioned. However, in implementing changes in the delivery of post-acute stroke care it is important that patient outcome is not compromised. Early supported discharge (ESD) was introduced approximately 15 years ago and allows suitable patients to be discharged home early with increased support from a well co-ordinated, multi-disciplinary rehabilitation team in the patients own home. This paper focuses upon the evidence available from multiple international studies of ESD over the last decade, including both clinical benefit and cost-effectiveness. Findings from these trials are largely positive resulting from a reduction in bed days, therefore overall cost, and an improvement in function and independence reported in many studies. Suitable patient selection, careful discharge planning and continuity of care by the ESD linked to a stroke unit are essential components of the success of this service.

Patient behaviour at the time of stroke onset: a cross-sectional survey of patient response to stroke symptoms

Background and purpose Revascularisation treatment with thrombolysis must be initiated within 4.5u2005h following ischaemic stroke symptom onset. Despite its proven benefits, thrombolysis therapy is underused, with patient delay in presenting to hospital with symptoms identified as the leading barrier. This study aimed to examine help-seeking behaviour at stroke onset, in order to understand delays in accessing acute medical care for stroke symptoms. Methods 149 consecutive patients hospitalised with ischaemic stroke were interviewed at 72u2005h poststroke with the Stroke Awareness Questionnaire and the Response to Symptoms Questionnaire. Results Sixty per cent of stroke cases presented to the ED within 3.5u2005h of stroke onset. Knowledge of stroke symptoms and risk factors was poor, with 40% unable to correctly define a stroke. Bystander recognition of symptoms (p=0.03) and bystander initiation of Emergency Medical Services was associated with ED presentation within 3.5u2005h (p=0.03). Conclusions This study provides insights into patient response when a stroke occurs, with the presence and action of others highlighted as critical in fast response to stroke symptoms. Knowledge of stroke warning signs and risk factors was low among stroke survivors. Findings highlight the complexity of changing help-seeking behaviour during stroke onset, and provide directions for public education efforts to reduce prehospital delay.

Clinically Relevant Drug-Drug and Drug-Food Interactions

Drug interactions arise when the effects of a drug are altered by the co-administration of another drug or food substance. Many factors determine the clinical response seen, including specific drug characteristics, patient age, gender and co-morbidities. The absorption, distribution, metabolism and excretion of a drug all impact upon drug availability at its sites of action and alterations in these processes can result in adverse outcomes. Similarly, the effect of a drug may be altered if co-prescribed with another drug or food substance that acts on the same receptor or physiological system. In recent years, there is a greater understanding of the mechanisms underlying pharmacokinetic and pharmacodynamic drug interactions, including phase I metabolic reactions (involving the family of cytochrome P450 isoenzymes) and the important role played by drug transporter proteins including P-glycoprotein (expressed in many tissues) and organic anion transporters. There is also a growing awareness of the impact that pharmacogenomics has on drug interaction potential, resulting in interindividual variations in drug transport, metabolism and elimination. The number of potential drug interactions is extensive, but the lower incidence seen in clinical practice implies that many of these potential interactions are not clinically relevant. However, with an ageing population, an increasing number of new drugs, more polypharmacy and the growing use of herbal remedies and over-the-counter preparations, the potential for drug interactions is rising and increasing efforts are needed to avoid them. A good knowledge of the mechanisms underlying drug interactions and the promotion of rational and safe prescribing amongst prescribers are essential in predicting (and therefore preventing) drug interactions in clinical practice. A comprehensive evaluation of drug interaction potential is now an integral part of risk assessment during early drug development, and regulatory bodies including the US FDA and the European Medicines Agency have published guidance documents that outline the importance of in vitro and (where appropriate) in vivo studies to predict interactions during drug development. This article discusses the main mechanisms involved in clinically relevant drug-drug and drug-food interactions and outlines some of the studies used to predict them during drug development. Safe prescribing is discussed along with the central role played by regulatory bodies in supporting drug development and postmarketing pharmacovigilance.