The Barriers and Facilitators to Decentralised Nurse-Led Mental Health Service Delivery in Sierra Leone.

In 2009, 98.0% of people with mental illness in Sierra Leone were not receiving treatment, partly due to the absence of public psychiatric facilities outside the capital. In response to this situation, the Ministry of Health and Sanitation rolled out nurse-led mental health units (MHUs) to every district. This study evaluates the barriers and facilitators to mental health service delivery in decentralised MHUs in Sierra Leone using key informant interviews and focus group discussions with 13 purposefully sampled clinical staff and senior management personnel. The interviews were audio-recorded, translated from Krio if necessary, transcribed, and analysed using manifest content analysis. The findings suggest that factors affecting nurse-led mental health service delivery include small workforce and high workload, culture and beliefs, risks, lack of safety measures and required resources, outdated policies, poor salaries, lack of funds for medication, distance, power, influence, and stigma. Factors that could facilitate nurse-led mental health services include: increasing motivation, increasing the workforce, knowledge sharing, mentorship, availability of medication, passion and modern psychiatry. The findings contribute towards understanding the challenges and opportunities faced by the recently established nurse-led decentralised mental health services across Sierra Leone, in order to address the large mental health treatment gap. We hope the findings will inform further policy and planning to improve the quality of decentralised mental healthcare.

A mixed-methods feasibility study of a new digital health support package for people after stroke: the Recovery-focused Community support to Avoid readmissions and improve Participation after Stroke (ReCAPS) intervention.

BACKGROUND: Evidence for digital health programmes to support people living with stroke is growing. We assessed the feasibility of a protocol and procedures for the Recovery-focused Community support to Avoid readmissions and improve Participation after Stroke (ReCAPS) trial. METHODS: We conducted a mixed-method feasibility study. Participants with acute stroke were recruited from three hospitals (Melbourne, Australia). Eligibility: Adults with stroke discharged from hospital to home within 10 days, modified Rankin Score 0-4 and prior use of Short Message System (SMS)/email. While in hospital, recruited participants contributed to structured person-centred goal setting and completed baseline surveys including self-management skills and health-related quality of life. Participants were randomised 7-14 days after discharge via REDCap® (1:1 allocation). Following randomisation, the intervention group received a 12-week programme of personalised electronic support messages (average 66 messages sent by SMS or email) aligned with their goals. The control group received six electronic administrative messages. Feasibility outcomes included the following: number of patients screened and recruited, study retainment, completion of outcome measures and acceptability of the ReCAPS intervention and trial procedures (e.g. participant satisfaction survey, clinician interviews). Protocol fidelity outcomes included number of goals developed (and quality), electronic messages delivered, stop messages received and engagement with messages. We undertook inductive thematic analysis of interview/open-text survey data and descriptive analysis of closed survey questions. RESULTS: Between November 2018 and October 2019, 312 patients were screened; 37/105 (35%) eligible patients provided consent (mean age 61 years; 32% female); 33 were randomised (17 to intervention). Overall, 29 (88%) participants completed the12-week outcome assessments with 12 (41%) completed assessments in the allocated timeframe and 16 also completing the satisfaction survey (intervention=10). Overall, trial participants felt that the study was worthwhile and most would recommend it to others. Six clinicians participated in one of three focus group interviews; while they reported that the trial and the process of goal setting were acceptable, they raised concerns regarding the additional time required to personalise goals. CONCLUSION: The study protocol and procedures were feasible with acceptable retention of participants. Consent and goal personalisation procedures should be centralised for the phase III trial to reduce the burden on hospital clinicians. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12618001468213 (date 31/08/2018); Universal Trial Number: U1111-1206-7237.

Protocol of a randomized controlled trial investigating the effectiveness of Recovery-focused Community support to Avoid readmissions and improve Participation after Stroke (ReCAPS).

RATIONALE: To address unmet needs, electronic messages to support person-centered goal attainment and secondary prevention may avoid hospital presentations/readmissions after stroke, but evidence is limited. HYPOTHESIS: Compared to control participants, there will be a 10% lower proportion of intervention participants who represent to hospital (emergency/admission) within 90 days of randomization. METHODS AND DESIGN: Multicenter, double-blind, randomized controlled trial with intention-to-treat analysis. The intervention group receives 12 weeks of personalized, goal-centered, and administrative electronic messages, while the control group only receive administrative messages. The trial includes a process evaluation, assessment of treatment fidelity, and an economic evaluation. Participants: Confirmed stroke (modified Rankin Score: 0-4), aged ≥18 years with internet/mobile phone access, discharged directly home from hospital. Randomization: 1:1 computer-generated, stratified by age and baseline disability. Outcomes assessments: Collected at 90 days and 12 months following randomization. OUTCOMES: Primary outcomes include hospital emergency presentations/admissions within 90 days of randomization. Secondary outcomes include goal attainment, self-efficacy, mood, unmet needs, disability, quality-of-life, recurrent stroke/cardiovascular events/deaths at 90 days and 12 months, and death and cost-effectiveness at 12 months. Sample size: To test our primary hypothesis, we estimated a sample size of 890 participants (445 per group) with 80% power and two-tailed significance threshold of α = 0.05. Given uncertainty for the effect size of this novel intervention, the sample size will be adaptively re-estimated when outcomes for n = 668 are obtained, with maximum sample capped at 1100. DISCUSSION: We will provide new evidence on the potential effectiveness, implementation, and cost-effectiveness of a tailored eHealth intervention for survivors of stroke.

The burden of mental disorder in Sierra Leone: a retrospective observational evaluation of programmatic data from the roll out of decentralised nurse-led mental health units.

BACKGROUND: In sub-Saharan Africa the treatment gap for mental disorders is high. In 2009, 98.0% of people with mental illness in Sierra Leone were not receiving treatment, partly due to the absence of public psychiatric facilities outside the capital. In response, the Ministry of Health and Sanitation rolled out nurse-led mental health units (MHU) to every district. This study aims to retrospectively evaluate the uptake of these services by examining the pathways to care, diagnosis, management, and treatment gap, to provide insight into the functioning of these units and the potential burden of mental health disorders in Sierra Leone. METHODS: We evaluated the roll out of MHU using summary data from all units between 1 st January 2015 and 1 st January 2017, to establish the burden of diagnoses among service users, pathways to care, treatments provided, and treatment gaps. Negative binomial regressions examine bivariate relationships between diagnoses, treatments, and medication inaccessibility with demographics (age and sex), location (Freetown vs the rest and Ebola endemic regions vs the rest) and year. RESULTS: We collected data from 15 MHU covering 13 districts in 24 months. There were 2401 referrals. The largest age category was 25-34 (23.4%). The prominent diagnoses were epilepsy (43.5%, associated with children) and psychosis (17.5%, associated with males). Reported depression (8.6%) and suicide attempts (33 patients) were low. Ebola endemic regions reported higher rates of grief, trauma, and medically unexplained symptoms. In 24.7% of cases where medication was required, it was not accessible. CONCLUSIONS: Nurse-led MHU can have a modest effect on the treatment gap in resource constrained environments such as Sierra Leone, particularly in epilepsy and psychosis.

Mental health in Sierra Leone.

Sierra Leone is a West African country with a population of just over 7 million. Many Sierra Leoneans lived through the psychologically distressing events of the civil war (1991-2002), the 2014 Ebola outbreak and frequent floods. Traditionally, mental health services have been delivered at the oldest mental health hospital in sub-Saharan Africa, with no services available anywhere else in the country. Mental illness remains highly stigmatised. Recent advances include revision of the Mental Health Policy and Strategic Plan and the strengthening of mental health governance and district services. Many challenges lie ahead, with the crucial next steps including securing a national budget line for mental health, reviewing mental health legislation, systematising training of mental health specialists and prioritising the procurement of psychotropic medications. National and international commitment must be made to reduce the treatment gap and provide quality care for people with mental illness in Sierra Leone.

Scale-out of a community-based behavioral intervention for childhood obesity: pilot implementation evaluation.

BACKGROUND: Expanding the use of evidence-based behavioral interventions in community settings has met with limited success in various health outcomes as fidelity and dose of clinical interventions are often diluted when translated to communities. We conducted a pilot implementation study to examine adoption of the rigorously evaluated Healthier Families Program by Parks and Recreation centers in 3 cities across the country (MI, GA, NV) with diverse socio-cultural environments. METHODS: Using the RE-AIM framework, we evaluated the program both quantitatively (pre/post surveys of health behavior change; attendance & fidelity) and qualitatively (interviews with Parks and Recreation staff and participants following the program). RESULTS: The 3 partner sites recruited a total of 26 parent-child pairs. REACH: Among the 24 participants who completed pre/post surveys, 62.5% were 25-34 years old, and average child age was 3.6 (SD 0.7) years. The distribution of self-reported race/ethnicity was 54% non-Hispanic White, 38% non-Hispanic Black, and 8% Latino. EFFECTIVENESS: Qualitative interviews with participants demonstrated increased use of the built environment for physical activity and continued use of key strategies for health behavior change. ADOPTION: Three of five (60%) collaborating sites proceeded with implementation of the program. IMPLEMENTATION: The average attendance for the 12-week program was 7.6 (SD 3.9) sessions, with 71% attending > 50% of sessions. Average fidelity for the 12 weekly sessions was 25.2 (SD 1.2; possible range 9-27). MAINTENANCE: All 3 partner sites continued offering the program after grant funding was complete. CONCLUSIONS: This pilot is among the first attempts to scale-out an evidence-based childhood obesity intervention in community Parks and Recreation centers. While this pilot was not intended to confirm the efficacy of the original trial on Body Mass Index (BMI) reduction, the effective and sustained behavior change among a geographically and ethnically diverse population with high attendance and fidelity demonstrates an effective approach on which to base future large-scale implementation efforts to reduce childhood obesity in community settings.

Preclinical to Human Translational Pharmacology of the Novel M1 Positive Allosteric Modulator MK-7622.

The current standard of care for treating Alzheimer's disease is acetylcholinesterase inhibitors, which nonselectively increase cholinergic signaling by indirectly enhancing activity of nicotinic and muscarinic receptors. These drugs improve cognitive function in patients, but also produce unwanted side effects that limit their efficacy. In an effort to selectively improve cognition and avoid the cholinergic side effects associated with the standard of care, various efforts have been aimed at developing selective M1 muscarinic receptor activators. In this work, we describe the preclinical and clinical pharmacodynamic effects of the M1 muscarinic receptor-positive allosteric modulator, MK-7622. MK-7622 attenuated the cognitive-impairing effects of the muscarinic receptor antagonist scopolamine and altered quantitative electroencephalography (qEEG) in both rhesus macaque and human. For both scopolamine reversal and qEEG, the effective exposures were similar between species. However, across species the minimum effective exposures to attenuate the scopolamine impairment were lower than for qEEG. Additionally, there were differences in the spectral power changes produced by MK-7622 in rhesus versus human. In sum, these results are the first to demonstrate translation of preclinical cognition and target modulation to clinical effects in humans for a selective M1 muscarinic receptor-positive allosteric modulator.

Community readiness assessment for obesity research: pilot implementation of the Healthier Families programme.

BACKGROUND: This article reports on the development of a systematic approach to assess for community readiness prior to implementation of a behavioural intervention for childhood obesity. Using the Consolidated Framework for Implementation Research (CFIR), we developed research tools to evaluate local community centres' organisational readiness and their capacity to implement the intervention. METHODS: Four community Parks and Recreation centres from different states expressed interest in piloting an approach for dissemination and implementation of an evidence-based obesity prevention program for families with young children (Healthier Families). We conducted a mixed methods pre-implementation evaluation using the CFIR to evaluate the alignment of organisational priorities with the Healthier Families programme. Written surveys assessed organisational readiness for change amongst organisational leaders, recreation programmers, and staff (N = 25). Key informant interviews were conducted among staff to assess organisational readiness and with community members to assess community readiness (N = 64). Surveys were analysed with univariate statistics. Interviews were transcribed, coded and analysed using inductive and deductive methods of analysis. RESULTS: Mixed-methods analysis led to the identification of three key domains on which to assess the organisational readiness to adopt a childhood obesity intervention, namely the physical infrastructure, the knowledge infrastructure, and the social infrastructure. The most critical measure of compatibility was the social infrastructure, since obstacles in the knowledge and physical infrastructures could be overcome by the strength of social resources, including the staff's ingenuity and commitment to a healthier community. This approach guided an assessment of organisational readiness prior to community organisations adopting and preparing to disseminate an obesity prevention community-based program in a wide-range of social and environmental contexts. CONCLUSIONS: Using a comprehensive pre-implementation assessment of the knowledge, physical and social infrastructures in a community is an essential step in effective dissemination for community-based behavioural interventions. Our research found that, when evaluating readiness and alignment, a responsive social infrastructure could provide the capacity to overcome potential barriers to implementation in either the knowledge or physical infrastructures.

cGMP production of the radiopharmaceutical [18 F]MK-6240 for PET imaging of human neurofibrillary tangles.

Fluorine-18-labelled 6-(fluoro)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine ([18 F]MK-6240) is a novel potent and selective positron emission tomography (PET) radiopharmaceutical for detecting human neurofibrillary tangles, which are made up of aggregated tau protein. Herein, we report the fully automated 2-step radiosynthesis of [18 F]MK-6240 using a commercially available radiosynthesis module, GE Healthcare TRACERlab FXFN . Nucleophilic fluorination of the 5-diBoc-6-nitro precursor with potassium cryptand [18 F]fluoride (K[18 F]/K222 ) was performed by conventional heating, followed by acid deprotection and semipreparative high-performance liquid chromatography under isocratic conditions. The isolated product was diluted with formulation solution and sterile filtered under Current Good Manufacturing Practices, and quality control procedures were established to validate this radiopharmaceutical for human use. At the end of synthesis, 6.3 to 9.3 GBq (170-250 mCi) of [18 F]MK-6240 was formulated and ready for injection, in an uncorrected radiochemical yield of 7.5% ± 1.9% (relative to starting [18 F]fluoride) with a specific activity of 222 ± 67 GBq/µmol (6.0 ± 1.8 Ci/µmol) at the end of synthesis (90 minutes; n = 3). [18 F]MK-6240 was successfully validated for human PET studies meeting all Food and Drug Administration and United States Pharmacopeia requirements for a PET radiopharmaceutical. The present method can be easily adopted for use with other radiofluorination modules for widespread clinical research use.

The Effect of Limited Health Literacy on How Internet Users Learn About Diabetes.

The Internet continues to be an important supplemental health information resource for an increasing number of U.S. adults, especially for those with a new or existing chronic condition. Here we examine how people use the Internet to learn about Type 2 diabetes and how health literacy (HL) influences this information-seeking behavior. We analyzed the searches of approximately 2 million people who queried for diabetes-related information on Microsoft's Bing search engine. The HL of searchers was imputed through a community-based HL score. Topics searched were categorized and subsequent websites were assessed for readability. Overall, diabetes information-seeking strategies via the Internet are similar among adults with limited and adequate HL skills. However, people with limited HL take a longer time to read pages that are quickly read by people with adequate HL and vice versa. Information seeking among the former is terminated prematurely, as is evident from a Hidden Markov Model of the search process. Our findings indicate that the reading level required to understand the majority of diabetes-related information is high. Especially on government websites, more than 80% of information requires a reading level corresponding to 7th grade or higher. Our results indicate that individuals with lower HL may disproportionately struggle with Internet searches and fail to get an equivalent benefit from this information resource compared to users with greater HL. Future interventions should target the quality and ease of navigation of health care websites and find ways to leverage other relevant professionals to encourage and promote successful information access on the Web.

Outcomes for people with atrial fibrillation in an Australian national audit of stroke care.

BACKGROUND: Atrial fibrillation is associated with poorer outcomes poststroke. It is unclear how the quality of stroke care in hospitals influences outcomes in these patients. AIMS: The study aims to compare outcomes in stroke patients with and without atrial fibrillation and identify hospital processes of care associated with poor outcomes. METHODS: Data were collected using retrospective, consecutive medical record audits from participating hospitals in the 2009 and 2011 National Stroke Foundation acute services audit program. Patient characteristics, stroke severity, and hospital management data were compared for those with and without atrial fibrillation. Multiple regression analyses for outcomes of in-hospital death, dependency at discharge (modified Rankin Score 3-5), and discharge destination were undertaken, adjusted for patient clustering by hospital. RESULTS: Atrial fibrillation status was known for 5473 (80%) cases; 2049 had atrial fibrillation. Atrial fibrillation was independently associated with in-hospital mortality (aOR 1.46, 95% CI 1.06, 2.02). Management on a stroke unit (aOR 0.57, 95% CI 0.40, 0.80) and having a swallow assessment within 24 h (aOR 0.71, 95% CI 0.51, 0.98) were associated with increased survival among all stroke types, as was receiving aspirin within 48 h poststroke (aOR 0.65, 95% CI 0.44, 0.97), for patients with an ischemic stroke. Stroke patients with atrial fibrillation were less likely to receive important processes of care associated with reduced mortality. CONCLUSIONS: Hospital processes of care can influence outcomes in stroke patients with atrial fibrillation. The greater in-hospital mortality experienced by stroke patients with atrial fibrillation may be attenuated by admission to a stroke unit, and for ischemic stroke, early administration of aspirin.

Hospital management and outcomes of stroke in Indigenous Australians: evidence from the 2009 Acute Care National Stroke Audit.

BACKGROUND: Indigenous Australians have greater stroke mortality rates than non-Indigenous people (97% Indigenous Australians are aged <65 years). Quality of care in hospital is an important factor for avoiding death and disability. No national review of acute stroke care for Indigenous Australians is available. AIMS: We aimed to compare adherence with clinical processes and outcomes among Indigenous and non-Indigenous patients with acute stroke admitted to hospital. METHODS: Hospitals participating in the National Stroke Audit of acute services in 2009 that provided data for at least one Indigenous patient were included (n = 33, 37%). Differences in death/dependency (modified Rankin Score 3-6) at discharge were determined using two-level multivariate analysis adjusting for hospital site and patient variables. A matched subgroup analysis in those aged 18 to 64 years was also undertaken. RESULTS: Among 1162 eligible patients (60% male; 18-64 years n = 305), 7% were Indigenous (18-64 years: 18%). Indigenous patients had a greater prevalence of stroke risk factors, e.g. diabetes, more had intracerebral hemorrhages (25% vs. 16% non-Indigenous, P = 0.05), and were less likely be treated in a stroke unit and receive timely allied health assessments than non-Indigenous patients. Indigenous patients aged 18-64 years had a threefold odds of dying or being dependent at discharge (Adjusted odds ratio = 3.09, 95% confidence interval = 1.07-8.95). CONCLUSIONS: Australian Indigenous patients with stroke received a reduced quality of care in hospitals and experienced worse outcomes than non-Indigenous patients. Indigenous patients require the provision of evidence-based care to increase their opportunities for optimal health outcomes following stroke. Further research to explain the differences is needed.

Incidence, event rates, and early outcome of stroke in Dublin, Ireland: the North Dublin population stroke study.

BACKGROUND AND PURPOSE: The World Health Organization has emphasized the importance of international population-based data for unbiased surveillance of stroke incidence and outcome. To date, few such studies have been conducted using recommended gold-standard ascertainment methods. We conducted a large, population-based stroke study in Dublin, Ireland. METHODS: Using gold-standard ascertainment methods, individuals with stroke and transient ischemic attack occurring over a 12-month period (December 1, 2005-November 30, 2006) in North Dublin were identified. Disability was assessed using the modified Rankin score and stroke severity (<72 hours) by the National Institutes of Health Stroke Scale. Stroke-related deaths were confirmed by review of medical files, death certificates, pathology, and coroner's records. Crude and standardized (to European and World Health Organization standard populations) rates of incidence, risk factors, severity, and early outcome (mortality, case-fatality, disability) were calculated, assuming a Poisson distribution for the number of events. RESULTS: Seven hundred one patients with new stroke or transient ischemic attack were ascertained (485 first-ever stroke patients, 83 recurrent stroke patients, 133 first-ever transient ischemic attack patients). Crude frequency rates (all rates per 1000 person-years) were: 1.65 (95% CI, 1.5-1.79; first-ever stroke), 0.28 (95% CI, 0.22-0.35; recurrent stroke), and 0.45 (95% CI, 0.37-0.53; first-ever transient ischemic attack). Age-adjusted stroke rates were higher than those in 9 other recent population-based samples from high-income countries. High rates of subtype-specific risk factors were observed (atrial fibrillation, 31.3% and smoking, 29.1% in ischemic stroke; warfarin use, 21.2% in primary intracerebral hemorrhage; smoking, 53.9% in subarachnoid hemorrhage; P<0.01 for all compared with other subtypes). Compared with recent studies, 28-day case-fatality rates for primary intracerebral hemorrhage (41%; 95% CI, 29.2%-54.1%) and subarachnoid hemorrhage (46%; 95% CI, 28.8%-64.5%) were greater in Dublin. CONCLUSIONS: Using gold-standard methods for case ascertainment, we found high incidence rates of stroke in Dublin compared with those in similar high-income countries; this is likely explained in part by high rates of subtype-specific risk factors.

Adherence to clinical guidelines improves patient outcomes in Australian audit of stroke rehabilitation practice.

OBJECTIVE: To study the correlation between adherence to recommended management and good recovery outcomes in an Australian cohort of inpatients receiving rehabilitation. DESIGN: Processes of care were audited and included those recommended in the Australian Clinical Guidelines for Stroke Rehabilitation and Recovery. SETTING: National audit data from 68 rehabilitation units were used, with each hospital contributing up to 40 consecutive cases. PARTICIPANTS: Not applicable. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Discharged home or an increase of greater than or equal to 22 in FIM scores between admission and discharge. Multivariable logistic regression models controlling for patient clustering were used to assess the associations between adherence to recommended management and recovery outcomes (dependent variables). RESULTS: Hospitals contributed 2119 patients (median age 75y, 53% men). We found that rehabilitation units providing evidence-based management (eg, treatment for sensorimotor impairment 38%, hypertonicity 56%, mobility 94%, and home assessments 71%) were more likely to provide better recovery outcomes for people with stroke. A discharge FIM score of 100 was clinically relevant and was strongly correlated with whether or not a patient was discharged home. We found very good correlation between admission and discharge FIM scores in stroke rehabilitation. CONCLUSIONS: This is one of the first study comparing adherence to recommended management in Australian rehabilitation units and stroke recovery outcomes based on national audit data. Novel findings include the significance of an FIM score between 80 and 100 and the clinical significance of various management processes.

Improved late survival and disability after stroke with therapeutic anticoagulation for atrial fibrillation: a population study.

BACKGROUND AND PURPOSE: Although therapeutic anticoagulation improves early (within 1 month) outcomes after ischemic stroke in hospital-admitted patients with atrial fibrillation, no information exists on late outcomes in unselected population-based studies, including patients with all stroke (ischemic and hemorrhagic). METHODS: We identified patients with atrial fibrillation and stroke in a prospective, population-based study in North Dublin. Clinical characteristics, stroke subtype, stroke severity (National Institutes of Health Stroke Scale), prestroke antithrombotic medication, and International Normalized Ratio (INR) at onset were documented. Modified Rankin Scale (mRS) score was measured before stroke and at 7, 28, and 90 days; 1 year; and 2 years after stroke. RESULTS: One hundred seventy-five patients had atrial fibrillation-associated stroke and medication data at stroke onset (159 ischemic, 16 hemorrhagic); 17% of those with ischemic stroke were anticoagulated before stroke (27 of 159.) On multivariable analysis, therapeutic INR was associated with improved late survival after ischemic stroke (adjusted 2-year odds ratio for death=0.08; 95% CI, 0.01 to 0.78; P=0.03). This survival benefit persisted when patients with hemorrhagic stroke were included (2-year survival; 70.5% therapeutic INR, 14.3% nontherapeutic INR; log-rank P<0.001; odds ratio for death=0.27; 95% CI, 0.09 to 0.88; P=0.03). Admission INR was inversely correlated with early and late modified Rankin Scale score (2-year Spearman ρ=-0.65; P<0.0003). An INR of 2 to 3 at ischemic stroke onset was associated with greater early (72 hours to 28 days) modified Rankin Scale score improvement (P=0.04) and good functional outcome (modified Rankin Scale score=0 to 2) at 1 year (adjusted odds ratio=4.8; 95% CI, 1.45 to 23.8; P=0.04). CONCLUSIONS: In addition to improving short-term outcome in selected hospital-treated patient groups, therapeutic anticoagulation may provide important benefits for long-term stroke outcomes in unselected populations.

Effect of telcagepant on spontaneous ischemia in cardiovascular patients in a randomized study.

OBJECTIVE: The primary purpose of the study was to explore the safety and tolerability of telcagepant in patients with stable coronary artery disease. BACKGROUND: Triptans are effective acute anti-migraine drugs whose vasoconstrictive effects limit their use in patients at risk for adverse cardiovascular events. Telcagepant, a calcitonin gene-related peptide receptor antagonist, is being developed for the acute treatment of migraine. Antagonism of calcitonin gene-related peptide, which does not appear to cause vasoconstriction, may allow for treatment of migraine in patients with coronary artery disease. METHODS: In this randomized, double-blind, placebo-controlled, crossover study, patients with documented stable coronary artery disease were assigned to 1 of 2 treatment sequences: telcagepant then placebo, or placebo then telcagepant. In each treatment period, patients received 2 doses of telcagepant 300-mg or placebo 2 hours apart. They remained in the research center for 24 hours after receiving the first dose of each period, during which time continuous 12-lead ambulatory electrocardiographic (Holter) monitoring was performed. RESULTS: Twenty-eight patients were enrolled; all patients completed the study and were included in all analyses. Telcagepant was generally well tolerated. No laboratory or serious adverse experiences were reported, and no patient discontinued due to an adverse experience. There were no consistent treatment-related changes in laboratory, vital signs or electrocardiogram safety parameters. Three patients (2 after receiving placebo and 1 after receiving telcagepant) experienced ST segment depression during the study; none of these patients reported chest pain. CONCLUSIONS: Two doses of 300-mg telcagepant, administered 2 hours apart, did not appear to exacerbate spontaneous ischemia and were generally well tolerated in a small cohort of patients with stable coronary artery disease. Results of this study support further evaluation of telcagepant in patients with stable coronary artery disease.

Assessments in Australian stroke rehabilitation units: a systematic review of the post-stroke validity of the most frequently used.

PURPOSE: In Australia, stroke is the leading cause of adult disability. For most stroke survivors, the recovery process is challenging, and in the first few weeks their recovery is supported with stroke rehabilitation services. Stroke clinicians are expected to apply an evidence-based approach to stroke rehabilitation and, in turn, use standardised and validated assessments to monitor stroke recovery. In 2008, the National Stroke Foundation conducted the first national audit of Australia's post acute stroke rehabilitation services and findings identified a vast array of assessments being used by clinicians. This study undertook a sub-analysis of the audit's assessment tools data with the aim of making clinically relevant recommendations concerning the validity of the most frequently selected assessments. METHOD: Data reduction ranked the most frequently selected assessments across a series of sub-categories. A serial systematic review of relevant literature using Medline and the Cumulative Index to Nursing and Allied Health Literature identified post-stroke validity ranking. RESULTS: The study found that standardised and non-standardised assessments are currently in use in stroke rehabilitation. It recommends further research in the sub-categories of strength, visual acuity, dysphagia, continence and nutrition and found strengths in the sub-categories of balance and mobility, upper limb function and mood. CONCLUSIONS: This is the first study to map national usage of post-stroke assessments and review that usage against the evidence. It generates new knowledge concerning what assessments we currently use post stroke, what we should be using and makes some practical post stroke clinical recommendations.

Association between acute statin therapy, survival, and improved functional outcome after ischemic stroke: the North Dublin Population Stroke Study.

BACKGROUND AND PURPOSE: Statins improve infarct volume and neurological outcome in animal stroke models. We investigated the relationship between statin therapy and ischemic stroke outcome in the North Dublin Population Stroke Study. METHODS: A population-based prospective cohort study was performed using rigorous ascertainment methods. Prestroke and acute (≤72 hours) poststroke medications were recorded. Modified Rankin score and fatality were assessed at 7, 28, and 90 days and 1 year. RESULTS: Of 448 ischemic stroke patients, statins were prescribed before stroke onset in 30.1% (134/445) and were begun acutely (≤72 hours) in an additional 42.5% (189/445). On logistic regression analysis, adjusting for age, prestroke disability (modified Rankin scale), NIHSS score, hypertension, and aspirin, new poststroke statin therapy was independently associated with improved early and late survival (compared with statin untreated patients: OR for death, 0.12; CI, 0.03-0.54 at 7 days; OR, 0.19; CI, 0.07-0.48 at 90 days; OR, 0.26; CI, 0.12-0.55 at 1 year; P≤0.006 for all). Similar findings were observed for statin therapy before stroke onset (adjusted OR for death compared with statin-untreated-patients, 0.04; CI, 0.00-0.33; P=0.003 at 7 days; OR, 0.23; CI, 0.09-0.58; P=0.002 at 90 days; OR, 0.48; CI, 0.23-1.01; P=0.05 at 1 year). CONCLUSIONS: Statin therapy at stroke onset and newly begun statins were associated with improved early and late outcomes, supporting data from experimental studies. Randomized trials of statin therapy for treatment of acute stroke are needed.

Stroke subtype classification to mechanism-specific and undetermined categories by TOAST, A-S-C-O, and causative classification system: direct comparison in the North Dublin population stroke study.

BACKGROUND AND PURPOSE: Reliable etiologic classification of ischemic stroke may enhance clinical trial design and identification of subtype-specific environmental and genetic risk factors. Although new classification systems (Causative Classification System [CCS] and ASCO [A for atherosclerosis, S for small vessel disease, C for cardiac source, O for other cause]) have been developed to improve subtype assignment, few comparative data exist from large studies. We hypothesized that both CCS and ASCO would reduce the proportion of patients classified as cause undetermined compared with the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) scheme in a large population-based stroke study. METHODS: A single rater classified all first-ever ischemic strokes in the North Dublin Population Stroke Study, a population-based study of 294 529 North Dublin residents. Published algorithms for TOAST, CCS, and ASCO were applied. RESULTS: In 381 first-ever ischemic stroke patients, CCS assigned fewer patients as cause undetermined (26.2% versus 39.4%; P<0.000001), with increased assignment of cardio-aortic embolism (relative increase 6.9%; P=0.004), large artery atherosclerosis (relative increase 44.1%; P=0.00006), small artery occlusion (relative increase 27.3%; P=0.00006), and other causes (relative increase 91.7%; P=0.001) compared with TOAST. When ASCO grade 1 evidence was applied, fewer patients were classified as small artery disease (relative decrease 29.1%; P=0.007) and more as large artery/atherothrombotic (relative increase 17.6%; P=0.03). ASCO grade 1 did not reduce the proportion of cause undetermined cases compared with TOAST (42.3% versus 39.4%; P=0.2). Agreement between systems ranged from good (kappa=0.61 for TOAST/ASCO grade 1 small artery category) to excellent (kappa=0.95 for TOAST/CCS and ASCO grade 1/CCS cardio/aorto-embolism category). Application of ASCO grades 1 to 3 indicated evidence of large artery/atherosclerosis (73.3%), cardio-embolism (31.3%), small artery (64.7%), and other cause (12%) in TOAST-undetermined cases. CONCLUSIONS: Both CCS and ASCO schemes showed good-to-excellent agreement with TOAST, but each had specific characteristics compared with TOAST for subtype assignment and data retention. The feasibility of a single combined classification system should be considered.