ABSTRACT
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include small workforce and high workload, culture and beliefs, risks, lack of safety measures and required resources, outdated policies, poor salaries, lack of funds for medication, distance, power, influence, and stigma.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.
Subject(s)
Mental Health Services , Nurse's Role , Humans , Sierra Leone , Mental Health , Focus GroupsABSTRACT
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.
Subject(s)
Quinazolines/pharmacology , Receptor, Muscarinic M1/metabolism , Allosteric Regulation/drug effects , Animals , Cognition/drug effects , Dose-Response Relationship, Drug , Electroencephalography/drug effects , Humans , Macaca mulatta , Male , Quinazolines/pharmacokinetics , Translational Research, BiomedicalABSTRACT
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.
Subject(s)
Behavior Therapy/organization & administration , Community Health Services/organization & administration , Evidence-Based Practice/organization & administration , Health Behavior , Pediatric Obesity/prevention & control , Adult , Child, Preschool , Female , Humans , Male , Parks, Recreational , Pediatric Obesity/psychology , Pilot Projects , Program Evaluation , Qualitative Research , Surveys and QuestionnairesABSTRACT
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.
Subject(s)
Capacity Building , Family Health , Health Promotion/methods , Health Services Research/methods , Organizations , Pediatric Obesity/therapy , Residence Characteristics , Child , Evidence-Based Medicine , Health Knowledge, Attitudes, Practice , Health Services Needs and Demand , Humans , Leadership , Parks, Recreational , Pilot Projects , Qualitative Research , Social Environment , Surveys and QuestionnairesABSTRACT
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.
Subject(s)
Fluorine Radioisotopes , Isoquinolines/chemistry , Neurofibrillary Tangles/metabolism , Positron-Emission Tomography/methods , Radiochemistry/methods , Radiopharmaceuticals/chemistry , Halogenation , Humans , Isoquinolines/chemical synthesis , Quality Control , Radiopharmaceuticals/chemical synthesisABSTRACT
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.
Subject(s)
Consumer Health Information , Diabetes Mellitus, Type 2/psychology , Health Literacy/statistics & numerical data , Information Seeking Behavior , Internet/statistics & numerical data , Adult , Comprehension , Humans , Learning , Reading , Search EngineABSTRACT
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.
Subject(s)
Stroke/epidemiology , Stroke/therapy , Aged , Atrial Fibrillation/complications , Atrial Fibrillation/epidemiology , Brain Ischemia/complications , Brain Ischemia/epidemiology , Disability Evaluation , Female , Hospitals/statistics & numerical data , Humans , Hypertension/complications , Hypertension/epidemiology , Income , Ireland/epidemiology , Ischemic Attack, Transient/epidemiology , Ischemic Attack, Transient/therapy , Male , Pilot Projects , Poisson Distribution , Population , Risk Factors , Survival Rate , Treatment OutcomeABSTRACT
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.
Subject(s)
Guideline Adherence , Medical Audit , Physical Therapy Modalities/standards , Practice Guidelines as Topic/standards , Stroke Rehabilitation , Activities of Daily Living , Aged , Aged, 80 and over , Australia , Female , Humans , Inpatients/statistics & numerical data , Male , Middle Aged , Outcome Assessment, Health Care , Pain Measurement , Recovery of Function , Rehabilitation Centers/standards , Stroke/diagnosis , Treatment OutcomeABSTRACT
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.
ABSTRACT
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.
Subject(s)
COVID-19 , Stroke , Adolescent , Adult , Community Support , Humans , Multicenter Studies as Topic , Patient Readmission , Randomized Controlled Trials as Topic , SARS-CoV-2 , Stroke/therapy , Treatment OutcomeABSTRACT
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.
Subject(s)
Brain Ischemia/drug therapy , Brain Ischemia/mortality , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Stroke/drug therapy , Stroke/mortality , Aged , Aged, 80 and over , Brain Ischemia/physiopathology , Cholesterol/metabolism , Cohort Studies , Comorbidity , Female , Humans , Ireland/epidemiology , Male , Middle Aged , Prospective Studies , Recovery of Function/drug effects , Recovery of Function/physiology , Stroke/physiopathology , Survival Rate/trends , TimeABSTRACT
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.
Subject(s)
Anticoagulants/administration & dosage , Atrial Fibrillation/drug therapy , Atrial Fibrillation/mortality , International Normalized Ratio , Stroke/drug therapy , Stroke/mortality , Warfarin/administration & dosage , Aged , Aged, 80 and over , Anticoagulants/adverse effects , Atrial Fibrillation/complications , Disease-Free Survival , Female , Follow-Up Studies , Humans , Ireland/epidemiology , Male , Prospective Studies , Stroke/etiology , Survival Rate , Time Factors , Warfarin/adverse effectsABSTRACT
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.
Subject(s)
Azepines/administration & dosage , Imidazoles/administration & dosage , Myocardial Ischemia/prevention & control , Adult , Aged , Azepines/adverse effects , Cross-Over Studies , Double-Blind Method , Female , Humans , Imidazoles/adverse effects , Male , Middle Aged , Migraine Disorders/complications , Migraine Disorders/drug therapy , Myocardial Ischemia/complications , Myocardial Ischemia/diagnosisABSTRACT
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.
ABSTRACT
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.
Subject(s)
Brain Ischemia/classification , Cardiovascular Diseases/complications , Stroke/classification , Aged , Aged, 80 and over , Algorithms , Analysis of Variance , Brain Ischemia/etiology , Cardiovascular Diseases/classification , Cohort Studies , Female , Humans , Ireland , Male , Middle Aged , Prospective Studies , Reproducibility of Results , Risk Factors , Sex Factors , Smoking , Stroke/etiologyABSTRACT
BACKGROUND AND PURPOSE: Transient ischemic attack (TIA) etiologic data and the ABCD(2) score may improve early stroke risk prediction, but studies are required in population-based cohorts. We investigated the external validity of the ABCD(2) score, carotid stenosis, and atrial fibrillation for prediction of early recurrent stroke after TIA. METHODS: Patients with TIA in the North Dublin city population (N=294 529) were ascertained by using overlapping hospital and community sources. The relations between individual ABCD(2) items, carotid stenosis, atrial fibrillation, and early stroke were examined. RESULTS: In confirmed TIA cases (n=443), carotid stenosis predicted 90-day stroke (hazard ratio=2.56; 95% CI, 1.27 to 5.15, P=0.003). Stroke risk rose with increasing grade of carotid stenosis, ranging from 5.4% (95% CI, 3.3% to 8.7%) with <50% stenosis to 17.2% (95% CI, 9.7% to 29.7%) with severe stenosis/occlusion (hazard ratio=3.3; 95% CI, 1.5 to 7.4, P=0.002). In confirmed TIA cases (n=443), the ABCD(2) score performed no better than chance for prediction of 90-day stroke (c-statistic=0.55; 95% CI, 0.45 to 0.64), largely related to the 24.2% (8/33) of patients who experienced a recurrence and had low ABCD(2) scores (0-3). However, in nonspecialist-suspected TIA cases (n=700), the predictive utility improved for stroke at 28 (c-statistic=0.61; 95% CI, 0.50 to 0.72) and 90 (c-statistic=0.61; 95% CI, 0.52 to 0.71) days. CONCLUSIONS: In a population-based TIA cohort, significant predictive information was provided by carotid stenosis. The ABCD(2) score had predictive utility in patients with TIA suspected by nonspecialists. Low scores occurred in several patients with stroke recurrences, suggesting that caution is needed before using the score in isolation.
Subject(s)
Atrial Fibrillation/diagnosis , Carotid Stenosis/diagnosis , Ischemic Attack, Transient/diagnosis , Severity of Illness Index , Stroke/diagnosis , Aged , Aged, 80 and over , Atrial Fibrillation/complications , Atrial Fibrillation/epidemiology , Carotid Stenosis/complications , Carotid Stenosis/epidemiology , Cohort Studies , Early Diagnosis , Female , Follow-Up Studies , Humans , Ireland/epidemiology , Ischemic Attack, Transient/complications , Ischemic Attack, Transient/epidemiology , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Risk Factors , Stroke/epidemiology , Stroke/etiologyABSTRACT
BACKGROUND: Prospective population-based studies are important to accurately determine the incidence and characteristics of stroke associated with atrial fibrillation (AF), while avoiding selection bias which may complicate hospital-based studies. METHODS: We investigated AF-associated stroke within the North Dublin Population Stroke Study, a prospective cohort study of stroke/transient ischaemic attack in 294,592 individuals, according to recommended criteria for rigorous stroke epidemiological studies. RESULTS: Of 568 stroke patients ascertained in the first year, 31.2% (177/568) were associated with AF (90.4%, i.e. 160/177 ischaemic infarcts). The crude incidence rate of all AF-associated stroke was 60/100,000 person-years (95% CI = 52-70). Prior stroke was almost twice as common in AF compared to non-AF groups (21.9 vs. 12.8%, p = 0.01). The frequency of AF progressively increased across ischaemic stroke patients stratified by increasing stroke severity (NIHSS 0-4, 29.7%; 5-9, 38.1%; 10-14, 43.8%; >or=15, 53.3%, p < 0.0001). The 90-day trajectory of recovery of AF-associated stroke was identical to that of non-AF stroke, but Rankin scores in AF stroke remained higher at 7, 28 and 90 days (p < 0.001 for all). DISCUSSION: AF-associated stroke occurred in one third of all patients and was associated with a distinct profile of recurrent, severe and disabling stroke. Targeted strategies to increase anticoagulation rates may provide a substantial benefit to prevent severe disabling stroke at a population level.
Subject(s)
Anticoagulants/therapeutic use , Atrial Fibrillation/complications , Brain Ischemia/etiology , Stroke/etiology , Adult , Aged , Aged, 80 and over , Atrial Fibrillation/diagnosis , Atrial Fibrillation/drug therapy , Atrial Fibrillation/epidemiology , Brain Ischemia/diagnosis , Brain Ischemia/epidemiology , Brain Ischemia/prevention & control , Disability Evaluation , Female , Humans , Incidence , Ireland/epidemiology , Male , Middle Aged , Odds Ratio , Population Surveillance , Prospective Studies , Recovery of Function , Recurrence , Risk Assessment , Risk Factors , Severity of Illness Index , Stroke/diagnosis , Stroke/epidemiology , Stroke/prevention & control , Time Factors , Treatment OutcomeABSTRACT
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.
ABSTRACT
BACKGROUND AND PURPOSE: Transient ischemic attack (TIA) diagnosis is frequently difficult in clinical practice. Noncerebrovascular symptoms are often misclassified as TIA by nonspecialist physicians. Clinical prediction rules such as ABCD(2) improve the identification of patients with TIA at high risk of early stroke. We hypothesized that the ABCD(2) score may partly improve risk stratification due to improved discrimination of true TIA and minor ischemic stroke (MIS) from noncerebrovascular events. METHODS: Consecutive patients with TIA were identified within a prospective population-based cohort study of stroke and TIA. The cohort was expanded by inclusion of patients with MIS and noncerebrovascular events referred to a daily TIA clinic serving the population. Diagnosis was assigned by a trained stroke physician independent of ABCD(2) score. RESULTS: Five hundred ninety-four patients were included (292 [49.2%] TIA, 45 [7.6%] MIS, and 257 [43.3%] noncerebrovascular). The mean ABCD(2) score showed a graded increase across diagnostic groups (MIS mean 4.8 [SD 1.4] versus TIA mean 3.9 [SD 1.5] versus noncerebrovascular mean 2.9 [SD 1.5]; P<0.00001). The ABCD(2) score discriminated well between noncerebrovascular and cerebrovascular events-TIA (c-statistic 0.68; 95% CI, 0.64 to 0.72), any vascular event (TIA+MIS; c-statistic 0.7; 95% CI, 0.66 to 0.74), and MIS (c-statistic 0.81; 95% CI, 0.75 to 0.87)-from noncerebrovascular events. Of ABCD(2) items, unilateral weakness (OR, 4.5; 95% CI, 3.1 to 6.6) and speech disturbance (OR, 2.5; 95% CI, 1.6, 4.1) were most likely overrepresented in TIA compared with noncerebrovascular groups. CONCLUSIONS: The ABCD(2) score had significant diagnostic usefulness for discrimination of true TIA and MIS from noncerebrovascular events, which may contribute to its predictive usefulness.
Subject(s)
Ischemic Attack, Transient/diagnosis , Research Design/standards , Stroke/diagnosis , Aged , Aged, 80 and over , Brain Ischemia/diagnosis , Brain Ischemia/epidemiology , Cohort Studies , Female , Humans , Ireland/epidemiology , Ischemic Attack, Transient/epidemiology , Male , Middle Aged , Prospective Studies , Stroke/epidemiologyABSTRACT
Insertion of the T3 DNA polymerase thioredoxin binding domain (TBD) into the distantly related thermostable Taq DNA polymerase at an analogous position in the thumb domain, converts the Taq DNA polymerase from a low processive to a highly processive enzyme. Processivity is dependent on the presence of thioredoxin. The enhancement in processivity is 20-50-fold when compared with the wild-type Taq DNA polymerase or to the recombinant polymerase in the absence of thioredoxin. The recombinant Taq DNA pol/TBD is thermostable, PCR competent and able to copy repetitive deoxynucleotide sequences six to seven times more faithfully than Taq DNA polymerase and makes 2-3-fold fewer AT-->GC transition mutations.