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Introduction The COVID-19 pandemic has brought the decision-making process regarding cardiopulmonary resuscitation into focus. This study aims to analyse Do-Not-Attempt CPR (DNACPR) documentation in older hospitalised patients before and during the COVID-19 pandemic. Methods This was a retrospective repeated cross-sectional study. Data including co-morbidities and resuscitation status was collected on 300 patients with COVID-19 hospitalised from March 1st to May 31 s t 2020. DNACPR documentation rates in patients aged ≥65 years with a diagnosis of COVID-19 were compared to those without COVID-19 admitted during the same period. Pre-COVID-19 pandemic DNACPR documentation rates were also examined. Factors associated with DNACPR order instatement during the first wave of the COVID-19 pandemic were identified. Results Of 300 COVID-19-positive patients, 28% had a DNACPR order documented during their admission. 50% of DNAR orders were recorded within 24 hours of a positive swab result for SARS-CoV-2. Of 131 patients aged 65 years or over within the cohort admitted with COVID-19, 60.3% had a DNACPR order compared to 25.4% of 130 patients ≥65 without COVID-19 (p Conclusion The COVID-19 pandemic has prompted more widespread and earlier decision-making regarding resuscitation status. Although case-fatality-rates were higher for older hospitalised patients with COVID-19, many older patients survived the illness. Advance care planning should be prioritised in all patients and should remain clinical practice despite the pandemic.

Introduction Potentially inappropriate medications (PIMsare associated with falls, hospitalisation, and cognitive decline. Few studies have investigated the association between PIMsrelated to cognitive impairment (PIMCog) and mortality in dementia or mild cognitive impairment (MCI). Methods This was a retrospective observational study. Patients diagnosed with MCI or dementia (DSM-IV criteria) presenting to a tertiary-referral memory clinic from 2013–2019 were eligible. The primary outcome was all-cause death. Secondary outcomes were vascular death and non-vascular death defined according to formal certification. The primary exposure variable of interest was PIMCog, defined as any medication in the Beers 2015 or STOPP criteria, classified as potentially inappropriate for patients with cognitive impairment. Anticholinergic burden was measured using the anticholinergic cognitive burden (ACB) scale. Polypharmacy was defined as ≥5 medications. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs). Results There were 418 patients included (n = 261 dementia, n = 157 MCI). The median age was 79 (interquartile range {IQR} 74–82) and median follow-up was 809 days (IQR 552–1,571). One or more PIMCog was prescribed in 141 patients (33.4%). PIMCog use was associated with all-cause mortality after adjustment for age, sex, dementia severity, Charlson Co-morbidity Index, chronic obstructive pulmonary disease, congestive cardiac failure, and peripheral vascular disease. (HR 1.96, 95% CI 1.24–3.09). PIMCog use was associated with vascular death (HR 3.28, 95% CI 1.51–7.11) but not with non-vascular death (HR 1.40 95% CI: 0.78–2.52). Neither an ACB ≥3 (HR 0.87, 95% CI: 0.46–1.64) or polypharmacy (HR 1.87, 95% CI: 0.67–5.24) were associated with death. Conclusion The burden of PIMCog use in patients with cognitive impairment is high. PIMCog use is independently associated with all-cause mortality and vascular death. This is a potential modifiable risk factor for death in patients with neurocognitive disorders. Further research is required to independently validate this finding.

Background Clear and effective communication is central to all aspects of healthcare. Discussions centred on advance care planning are vital to ensure the person with dementia receives the support and care they need in the future based on their will and preferences. The aim of this study was to ascertain from those provided with information on advance care planning if it met their needs and assisted their understanding on planning for the future. Methods This study centred on eliciting the views of older persons diagnosed with dementia and their carers on the provision of an information booklet titled ‘I have dementia ... How do I plan for the future’. Ethical approval was sought and provided to conduct this study. Participants presenting to an acute hospital day ward for older persons were identified and recruited through the medicine for older person’s team. 42 people consented to participate with 20 people returning questionnaires, a 48% response rate. Thematic analysis was applied to qualitative comments and descriptive statistical analysis was undertaken with quantitative data. Results The overwhelming majority (95%) of respondents found the provision of an information booklet on advance care planning helpful. Nearly two thirds (65%) spoke with someone about advance care planning thereafter. 60% of all respondents reporting that the booklet was either ‘easy’ or ‘very easy’ (40%) to understand. Participants strongly endorsed the provision of information on advance care planning and the benefits that it bestowed to them. Conclusion The study has confirmed the importance of communication and the provision of information on advance care planning for people with dementia and their carers in the day ward setting for older persons. Findings strongly endorse the information provided whilst also suggesting minor amendments to the booklet to improve future editions.

Background In Ireland, the Assisted Decision-Making (ADM) (Capacity) Act and emerging Codes of Practice provide a legal framework for Healthcare Professionals (HCPs) to enable ADM for patients with impaired capacity. ADM ensures that a person’s will and preference is at the centre of all decisions related to their care. This study conducted a realist evaluation and developed a Programme Theory (PT) to highlight how ADM for older people can be operationalised within an Acute Care (AC) context. Methods Key informants with interest in ADM informed this evaluation. Interviews were conducted in two Acute Care (AC) sites with multidisciplinary HCPs working within older person services (n=20). Interviews with informants that recently received care within an AC setting involved older people (n=3) people with dementia (n=4) and family carers (n=5). Ethnographic observations from AC multidisciplinary team meetings also informed the review. The framework that guided the qualitative analysis was from a PT informed by literature on ADM implementation in healthcare (O'Donnell, Ní Shé, Davies et al.2018). Results The refined PT is supported by credible evidence that is informed by authentic experiences of decision making support in the AC setting. Validation groups (n=4) with the key informants verified the PT. Three mechanisms were identified as a positive climate and receptive environment for the adoption of formal ADM. These are: AC settings that adopt inter-professional accountability and shared responsibility for patient care that is guided by a clear policy process. Acute care and practice that is informed by a shared commitment to person-centred care and shared decision making. HCPs that operate within an AC setting where organisational learning informs practice through inter-professional training, mentorship and peer support. Conclusion Involving stakeholders in PT development enhances the utility, feasibility and applicability of the results. This PT provides a framework for those planning ADM implementation within the AC settings.

Background Ireland’s Assisted Decision-Making (Capacity) Act 2015 breaks from traditional views of capacity to consider the uniqueness of each decision with relation to topic, time and place for those with impaired or fluctuating capacity. It has yet to be commenced, however codes of practice and educational strategies are in development to support health and social care professionals (HSCPs) to practice in accordance with the Act. This study set out to examine barriers and enablers to the adoption of assisted decision making (ADM) involving older people in acute hospitals from multiple perspectives. It describes a pre-implementation formative evaluation informed by the perspectives of relevant stakeholders in ADM practice. Methods In total, 12 key informant interviews and two validation groups were conducted with family carers and older people with and without a diagnosis of dementia in two acute hospitals. In addition, 20 interviews and two validation groups were conducted with HSCPs. Interviews focused on contextual characteristics as well as barriers and enablers of ADM. Results Barriers and enablers included supporting capacity through adopting a functional approach, the physical environment where decision-making takes place, meeting information and support needs, methods of communication, upholding will and preferences, relationships and trust. Time and timing were consistently identified as a critical factor. HSCPs also highlighted the need for specialised education and training on ADM practice. Conclusion The issues identified around ADM will inform the development of a serious discussion game on acute care scenarios, which will be deployed for awareness raising and educational purposes. Findings will also help focus attention on how those working within complex health systems and organisations can practically implement changes to practice in line with ADM legislation.

Background Falls are a common cause of morbidity and mortality in older adults, with most being caused by identifiable risk factors. This study aimed to assess demographics and clinical characteristics of patients who had recurrent falls attending the medicine for the older person (MFTOP) outpatient department at a tertiary centre. Methods Retrospective analysis of patients seen at MFTOP OPD between January 2018 and December 2018. Data were obtained from clinical notes. Age, gender, blood pressure, cognitive tests, blood tests, diagnoses and medications that could contribute to falls were recorded. Results 100 patients were reviewed. 60% were female (60). Mean and median ages were 83. Causes of falls included; gait/balance disorders or weakness 36.0%, environment-related/'accident' 19.0%, alcohol 5.0%, dizziness/vertigo 5.0%, visual disorder 4.0%, confusion 4.0%, others 3.0%, drop attack 1.0%, unknown 5.0%. 18.4% (18/98) had orthostatic hypotension (OH), of which 44.4% (8/18) had low standing systolic BP Conclusion There is a high prevalence of co-morbidities and polypharmacy in patients with recurrent falls. Identifying modifiable causes may reduce the risk of falls in the future. Tighter glycaemic control was observed and relaxed glucose control in high-risk older adults are recommended.

Introduction the COVID-19 pandemic has brought the decision-making process regarding cardiopulmonary resuscitation (CPR) into focus. The aim of this study is to compare rates of Do-Not-Attempt-CPR (DNACPR) documentation in older hospitalised patients before and during the COVID-19 pandemic. Methods this was a retrospective repeated cross-sectional study. Data including co-morbidities and resuscitation status was collected on 300 patients with COVID-19 hospitalised from 1 March to 31 May 2020. DNACPR documentation rates in patients aged ≥65 years with a diagnosis of COVID-19 were compared to those without COVID-19 admitted during the same period and were also compared to the documentation rates pre-COVID-19 pandemic (1 March–31 May 2019). Results of 300 COVID-19-positive patients, 28% had a DNACPR order documented during their admission. Of 131 older (≥65 years) patients with COVID-19, 60.3% had a DNACPR order compared to 25.4% of 130 older patients without COVID-19 (P Conclusion the COVID-19 pandemic has prompted more widespread and earlier decision-making regarding resuscitation status. Although case fatality rates were higher for older hospitalised patients with COVID-19, many older patients survived the illness. Advance care planning should be prioritised in all patients and should remain as part of good clinical practice despite the pandemic.

Background and purpose The prevalence of chronic kidney disease (estimated glomerular filtration rate (eGFR) 2 for ≥3 months, chronic kidney disease (CKD)) in ischemic stroke and transient ischemic attack (TIA) is unknown, as estimates have been based on single-point estimates of renal function. Studies investigating the effect of renal dysfunction (eGFR 2, renal dysfunction) on post-stroke outcomes are limited to hospitalized cohorts and have provided conflicting results. Methods We investigated rates, determinants and outcomes of renal dysfunction in ischemic stroke and TIA in the North Dublin Population Stroke Study. We also investigate the persistence of renal dysfunction in 90-day survivors to determine the prevalence of CKD. Ascertainment included hot and cold pursuit using multiple overlapping sources. Survival analysis was performed using Kaplan–Meier survival curves and Cox proportional hazards modeling. Results In 547 patients (ischemic stroke in 76.4%, TIA in 23.6%), the mean eGFR at presentation was 63.7 mL/min/1.73 m2 (SD 22.1). Renal dysfunction was observed in 44.6% (244/547). Among 90-day survivors, 31.2% (139/446) met criteria for CKD. After adjusting for age and stroke severity, eGFR 2 (hazard ratio 2.53, p = 0.01) independently predicted 28-day fatality but not at two years. Poor post-stroke functional outcome (Modified Rankin Scale 3–5) at two years was more common in those with renal dysfunction (52.5% vs. 20.6%, p Conclusion Renal dysfunction and CKD are common in ischemic stroke and TIA. Renal dysfunction is associated with considerable post-stroke morbidity and mortality. Further studies are needed to investigate if modifiable mechanisms underlie these associations.

Posterior cortical atrophy (PCA) and logopenic variant primary progressive aphasia (LvPPA) are considered early-onset dementias most commonly caused by Alzheimer pathology. PCA is characterized by a progressive decline in higher order visual processing functions, whereas LvPPA is a form of primary progressive aphasia. The clinical presentation of both syndromes is typically earlier in life relative to the more typical "amnestic" form of Alzheimer disease. Prominent language deficits have been well described in PCA. Here, we describe the case of a 56-year-old man presenting with overlapping anatomic, clinical, and cognitive features of PCA and LvPPA and review the existing literature relating to the clinical features shared by these conditions, exploring the etiology, and implications for clinical practice in cases with a PCA-LvPPA overlap syndrome. In PCA, atrophy occurs in temporoparietal-occipital regions, whereas in LvPPA atrophy occurs at the temporoparietal junctions, with left-sided predominance. A defective phonological loop (a short-term storage system which holds speech sounds in memory for 1 to 2 s) seems to underlie the logopenic syndrome in both conditions. Other parietal lobe deficits, in proximity to both language and visual processing areas, such as dyscalculia and ideomotor apraxia are also commonly found in both conditions. We suspect that cases with an overlap PCA-LvPPA syndrome are relatively underreported which may relate to the fact that these cases occur on a spectrum depending on the stage of disease progression and do not easily fit into strict diagnostic categories according to existing criteria of PCA and LvPPA, respectively.

Background Few studies have directly compared stroke recurrence rates after stroke and transient ischemic attack, and the risk factors underlying early recurrence are poorly understood. We aimed to investigate risk factors for recurrent stroke after first stroke and transient ischemic attack in a population-based study. Methods The North Dublin Population Stroke Study applied multiple overlapping hot and cold pursuit methods, to ascertain hospital- and community-treated stroke and transient ischemic attack patients over a 12-month period. Inclusion criteria were: (1) Stroke-physician confirmed transient ischemic attack/ischemic stroke; (2) first-stroke/transient ischemic attack event within the ascertainment period. Patients were prospectively followed at 72 h, 7, 28 and 90 days. Results A total of 584 patients met eligibility criteria (172 transient ischemic attack, 412 stroke). More transient ischemic attack than stroke patients presented to medical attention with recurrent stroke (8.24% vs. 0.24%, p = 0.0002). Recurrent stroke was more common after transient ischemic attack than index stroke at each time-interval (at 72 h, 4.07% vs. 1.23%, p = 0.03; at 90 days, 13.45% vs. 5.72%, p = 0.002). Stroke recurrence at 90 days was also associated with delay seeking medical attention after the index event (OR 3.2, p = 0.001), delayed anti-platelet (OR 2.8, p = 0.001) and statin (OR 2.4, p = 0.009) treatment, carotid stenosis/occlusion (OR 2.4, p = 0.008). On multivariable analysis, transient ischemic attack as index event (adjusted OR 2.3, p = 0.02), delayed statin treatment (OR 2.5, p = 0.02), and carotid stenosis/occlusion (OR 2.4, p = 0.02) were independent predictors of 90-day recurrent stroke. Conclusion A combination of pathophysiological and behavioral factors was associated with early stroke recurrence risk. Improved public awareness to reduce delays to self-referral for transient ischemic attack symptoms is needed.

Background Numerous studies have identified comorbidities that are associated with Clostridioides difficile infection (CDI), but current CDC and CMS models for risk adjusting hospital CDI rates do not include patient comorbid conditions. Incorporating patient-level data could improve CDI risk adjustment, but comorbidities would need to be easily electronically available for widescale implementation. Ideally, they would also be causally related to CDI — i.e., true risk factors, not confounders — to facilitate more unbiased inter-hospital comparisons. The current study aimed to determine which comorbid conditions are causally related to CDI based upon expert consensus. Methods We used Delphi methodology to administer an iterative, two-round survey with an intervening teleconference, to eight infectious disease experts. Experts evaluated 40 comorbid conditions included in Charlson and Elixhauser comorbidity indices (and thus validated for electronic capture through administrative data), as well as other comorbidities commonly associated with CDI. Experts rated comorbid conditions from 1 (not at all related) to 5 (strongly related), based upon perceived relatedness with CDI. To assign causal relatedness, the following criteria had to be met at the end of round two: 1) majority (> 50%) of experts rating the condition at 3 (somewhat related) or higher; 2) inter-quartile range (IQR) < = 1; and 3) standard deviation (SD) < = 1. Results 8/40 (20%) comorbid conditions were ranked as causally related to CDI, including patient age, three malignancy comorbidities, two transplant-related comorbidities, HIV/AIDS, and inflammatory bowel disease. A further 18/40 (45%) qualified as indeterminately related, and 14/40 (35%) were ranked as not causally related to CDI (Table). Three of the eight causally related factors were not components of Elixhauser or Charlson indices. Table Conclusion We identified comorbid conditions that may be appropriate candidates to consider for inclusion in patient-level risk adjustment models. Some causal factors did not originate from established comorbidity indices. Thus, future work to validate electronic capture of these conditions could further reduce barriers to risk-adjustment implementation. Disclosures All Authors: No reported disclosures

BACKGROUND: Stroke patients are at increased risk of falls and fractures. The aim of this study was to determine the rate, predictors and consequences of falls within 2 years after stroke in a prospective population-based study in North Dublin, Ireland. DESIGN: Prospective population-based cohort study. SUBJECTS: 567 adults aged >18 years from the North Dublin Population Stroke Study. METHODS: Participants were enrolled from an Irish urban population of 294,592 individuals, according to recommended criteria. Patients were followed for 2 years. Outcome measures included death, modified Rankin Scale (mRS), fall and fracture rate. RESULTS: At 2 years, 23.5% (124/522) had fallen at least once since their stroke, 14.2% (74/522) had 2 or more falls and 5.4% (28/522) had a fracture. Of 332 survivors at 2 years, 107 (32.2%) had fallen, of whom 60.7% (65/107) had 2 or more falls and 23.4% (25/107) had fractured. In a multivariable model controlling for age and gender, independent risk factors for falling within the first 2 years of stroke included use of alpha-blocker medications for treatment of hypertension (P = 0.02). When mobility measured at Day 90 was included in the model, patients who were mobility impaired (mRS 2-3) were at the highest risk of falling within 2 years of stroke [odds ratio (OR) 2.30, P = 0.003] and those functionally dependent (mRS 4-5) displayed intermediate risk (OR 2.02, P = 0.03) when compared with independently mobile patients. CONCLUSION: Greater attention to falls risk, fall prevention strategies and bone health in the stroke population are required. Language: en

Clostridium difficile is an important enteric pathogen in humans causing infections in the healthcare environment and the community. Carriage of C. difficile and C. difficile-related enterocolitis has been reported in piglets worldwide. The aim of this study was to investigate the rates of C. difficile isolation from pigs in Ireland. Faecal samples from piglet litters and sows were collected from six farms in 2015. The sows were non-diarrhoeal at the time of sampling. The diarrhoeal status of the piglets was unknown. C. difficile was isolated from 34/44 (77%) of piglet litter samples and from 33/156 (21%) of sow samples. The isolation rate in sows varied from 3 to 39% and in piglet litters from 72 to 86% depending on farm location. Toxin A and toxin B were present in 99% (66/67) of isolates; and binary toxin in 85% (57/67). Only PCR-ribotypes 078 (88%) and 193 (12%) were identified in piglets. Seven PCR-ribotypes were detected in sow C. difficile isolates: PCR-ribotypes 078 (67%), 050 (12%), 014/020 (6%), 015 (6%), 029 (3%), 035 (3%) and 193 (3%). This study shows that toxigenic C. difficile strains such as PCR-ribotype 078 can be commonly isolated from pigs at different geographical locations in Ireland. Since PCR-ribotype 078 is frequently found in humans in Ireland, this highlights the potential for interspecies transmission.

Few population-based studies have assessed lipid adherence to international guidelines for primary and secondary prevention in stroke/transient ischaemic attack (TIA) patients. This study aims to evaluate adherence to lipid-lowering therapy (LLT) guidelines amongst patients with ischaemic stroke/TIA. Using hot and cold pursuit methods from multiple hospital/community sources, all stroke and TIA cases in North Dublin City were prospectively ascertained over a 1-year period. Adherence to National Cholesterol Education Programme (NCEP) III guidelines, before and after index ischaemic stroke/TIA, was assessed. Amongst 616 patients (428 ischaemic stroke, 188 TIA), total cholesterol was measured following the qualifying event in 76.5% (471/616) and low-density lipoprotein (LDL) in 60.1% (370/616). At initial stroke/TIA presentation, 54.1% (200/370) met NCEP III LDL goals. Compliance was associated with prior stroke (odds ratio [OR] 2.19, p = 0.02), diabetes (OR 1.91, p = 0.04), hypertension (OR 1.57, p = 0.03), atrial fibrillation (OR 1.78, p = 0.01), pre-event LLT (OR 2.85, p

Background and Purpose— Few recent studies have investigated the rates and predictors of early and late stroke recurrence using prospective population–based methodology. We investigated recurrent stroke at 2 years in the North Dublin Population Stroke Study (NDPSS). Methods— Patients were ascertained from December 2005 to 2006 from overlapping community and hospital sources using hot and cold pursuit. Stroke recurrence, survival, and functional outcome were ascertained at 72 hours, 7 days, 28 days, 90 days, 1 year, and 2 years. Results— Of 567 patients, cumulative 2-year stroke recurrence rate was 10.8% and case fatality was 38.6%. Recurrence subtype was associated with initial stroke subtype ( P P =0.005) and prior stroke (adjusted hazard ratio, 2.92; P =0.01) were independent predictors of 2-year recurrence in 28-day survivors. Conclusions— Despite rigorous ascertainment, recurrent stroke rates were lower in current study than in earlier studies. Our data suggest that large sample sizes may be needed for future secondary prevention trials in patients treated with modern preventive medications.

Host anti-toxin immune responses play important roles in Clostridium difficile disease and outcome. The relationship between host immune and inflammatory responses during severe C. difficile infection (CDI) and the risk of mortality has yet to be defined. We aimed to investigate the host systemic IgG anti-toxin immune responses, the in vitro cytotoxicity of the infecting C. difficile ribotyped strain, and the host inflammatory markers and their relationship to CDI disease severity and risk of mortality. Inflammatory markers, co-morbidities and CDI outcomes were recorded in a prospective cohort of 150 CDI cases. Serum anti-cytotoxin A (TcdA) and anti-TcdB IgG titres were measured by ELISA and the infecting C. difficile isolate was ribotyped and the in vitro cytotoxin titre assessed. A low median anti-TcdA IgG titre was significantly associated with 30-day all-cause mortality (PPP20×109 l−1 [odds ratio (OR) 11.53; 95 % confidence interval (CI) 2.38–55.92], creatinine concentration >133 µmol l−1 (OR 6.54; 95 % CI 1.47–29.07), Horn’s index >3 (OR 4.09; 95 % CI 0.76–22.18) and low anti-TcdA IgG (OR 0.97; 95 % CI 0.95–0.99), but not ribotype, cytotoxin titre or anti-TcdB IgG. Thus, host pro-inflammatory and humoral responses correlate with the cytotoxin titre of the infecting strain and effective anti-toxin immune responses reduce the risk of mortality.

A 65-year-old woman was referred to our medicine for the older person day hospital with a 2-year history of frequent falls and progressive memory decline. On examination, she was cautious in her gait, slightly leaning to her left side and very unsteady on turning. MRI of her brain revealed prominence of third and lateral ventricles and increased surrounding signal intensity suggestive of normal pressure hydrocephalus (NPH) (figure 1). She consented to a video-recorded cerebrospinal fluid (CSF) …

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 ( 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 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.

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 P =0.03). Admission INR was inversely correlated with early and late modified Rankin Scale score (2-year Spearman ρ=−0.65; P 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.

Objective: In the North Dublin Population Stroke Study, we investigated the risk of recurrent stroke within the 14-day time window recommended for endarterectomy. Methods: In a population-based prospective cohort study, all ischemic stroke patients were identified over 1 year and categorized into those with (CS-positive) and without (CS-negative) ipsilateral carotid stenosis (CS) (≥50% lumen narrowing). Nonprocedural stroke recurrence was determined at 72 hours and 7 and 14 days. Results: Of 365 ischemic stroke patients with carotid imaging, 51 were excluded due to posterior circulation or nonlateralizing stroke, ipsilateral carotid occlusion, or intracranial stenosis, leaving 314 included for analysis (36 CS-positive and 278 CS-negative). Recurrent stroke occurred in 5.6% (2/36) CS-positive and 0.4% (1/278) CS-negative patients by 72 hours of symptom onset ( p = 0.003), 5.6% (2/36) CS-positive and 0.7% (2/278) CS-negative patients ( p = 0.01) by 7 days, and in 8.3% (3/36) CS-positive and 1.8% (5/278) CS-negative patients by 14 days ( p = 0.02). On multivariable Cox regression analysis, CS was the only independent predictor of recurrence at 72 hours (adjusted hazard ratio [HR] 36.1, 95% confidence interval [CI] 1.6–837.5, p = 0.03), and 7 days (HR 9.1, 1.1–79.2, p = 0.05), with a trend at 14 days (HR 4.6, 0.9–22.8, p = 0.06). Conclusions: Although only a minority of patients with symptomatic CS had a recurrent stroke within 14 days, early recurrent stroke risk was high, particularly within the first 72 hours. Earlier carotid revascularization or improved acute medical treatment may reduce recurrence in this high-risk group.

Clostridium difficile is the most common cause of nosocomial bacterial diarrhoea in the Western world. Diarrhoea and colitis are caused by the actions of toxins A and B released by pathogenic strains of C. difficile. Adaptive immune responses to these toxins influence the outcomes of C. difficile infection (CDI). Symptomless carriers of toxinogenic C. difficile and those with a single episode of CDI without recurrence show more robust antitoxin immune responses than those with symptomatic and recurrent disease. Immune-based approaches to CDI therapy and prevention have been developed using active vaccination or passive immunotherapy targeting C. difficile toxins. Innate immune responses to C. difficile and its toxins are also central to the pathophysiology of CDI. An acute intestinal inflammatory response with prominent neutrophil infiltration and associated tissue injury is characteristic of CDI. Furthermore, inhibiting this acute inflammatory response can protect against the intestinal injury that results from exposure to C. difficile toxins in animal models. Studies examining host risk factors for CDI have led to validated clinical prediction tools for risk of primary and of recurrent disease. Risk factors associated with severe CDI with poor clinical outcomes have also been identified and include marked elevation of the peripheral white blood cell count and elevated creatinine. However, further work is needed in this area to guide the clinical application of new approaches to disease prevention and treatment including new antimicrobials as well as passive and active immunization.

Background Antimicrobial use is recognized as a risk factor for Clostridium difficile infection (CDI) and outbreaks. We studied the relationship between PCR ribotype, antimicrobial susceptibility and the genetic basis of resistance in response to exposure to antimicrobial agents. Methods C. difficile isolates were cultured from 133 CDI patients for whom recent antimicrobial drug exposure had been recorded. Isolates were ribotyped by PCR and assessed for their susceptibility to the macrolide-lincosamide-streptogramin B (MLS(B)) group of compounds (erythromycin and clindamycin) and fluoroquinolone antimicrobials (ciprofloxacin, levofloxacin and moxifloxacin). Where relevant, the genetic basis of resistance was determined. Results Prevalent ribotypes (including 027, 001 and 106) exhibited significantly greater antimicrobial resistance compared with ribotypes 078 and 014, among others. Clindamycin-resistant ribotype 078 was detected for the first time. Ribotypes 027 and 001 were more likely to exhibit MLS(B) resistance, a feature that was associated with the erm(B) gene. Exposure to MLS(B) or fluoroquinolone antimicrobial compounds in the 8 weeks prior to the onset of infection was not associated with specific genetic markers of resistance. Single amino acid substitutions in the A and B subunits of DNA gyrase were noted and were ribotype specific and linked to resistance to moxifloxacin. Conclusions Resistance to MLS(B) and fluoroquinolone antimicrobial compounds is common among prevalent ribotypes of C. difficile. The genetic basis for antimicrobial resistance appears to be ribotype specific and conserved in the absence of recent antimicrobial selection pressure.

Background Patients have a right to be given the information that will enable them understand their diagnosis. However, as 40% of patients have recalled their discharge diagnosis in previous studies, and understanding was sub-optimal. Our aim was to establish (1) patients' understanding of diagnosis and (2) factors which may influence this. Methods All medical patients discharged from a large urban hospital over a 30-day period were contacted within 7 days. Primary outcome was patients' understanding of primary diagnosis. Patient perception of understanding and agreement that diagnosis had been explained were also assessed. Results Seventy-four percent (336) of 452 patients were successfully surveyed. Mean age was 62.9 years (SDP 18.1); 10.7% (36) had AMTS less than 8. Seventy-two percent (243) had good understanding of their diagnosis, and could identify and/or explain the pathology. Three quarters (258) patients felt they understood their diagnosis; 81.3%; (273) asserted their diagnosis was explained during their stay. On multivariate analysis, increasing age, poorer cognition (both p p 0.02) were independent predictors of poor understanding. Older age and AMTS less than 8 independently predicted self-reported understanding of diagnosis, and patient-perceived lack of explanation (both p Conclusions While most patients understood their diagnoses well, even small misunderstandings may affect health behaviours. High-risk patients, including older patients or those with cognitive impairment, should be identified and offered additional assistance at discharge.

Background Four-point-two percent of older Irish persons reside in extended-care facilities. Patients and staff in these settings frequently form close relationships, and the death of a patient can be a traumatic event. Despite this, resources and education in bereavement management have been lacking to date. Purpose We sought to investigate the effect of the death of such residents on patients and staff in a 320-bed, long-stay elderly care facility. Methods In-depth qualitative interviews were conducted within 24 hrs following the death of a resident. Seven patients and three staff took part. Patients with moderate or severe cognitive impairment were excluded. The interviews were audio-transcribed, and analysed for recurring themes. Results 9/10 interviewees were female. Patients’ age range was 70–90 years, staff 40–60 years. Participants described feelings of loss, inadequacy, and the desirability for patients and family to have privacy during the dying phase. We identified a four-stage model to describe the fellow patient grief reaction: (1) remembrance; (2) reflection; (3) religiosity and (4) relations. Conclusion Most participants in this study experienced a grief reaction following the death of a resident. This highlights the need for bereavement care programmes in elderly care units, to allow appropriate care and support to other long-stay residents and members of staff, in addition to grieving relatives.

This review summarizes the most recent epidemiological data and advances in research into the pathogenesis, diagnosis and treatment of Clostridium difficile infection (CDI).The epidemiology of CDI has changed with the emergence of hypervirulent strains. CDI rates have increased in the community, in children and in patients with inflammatory bowel disease. Although the North American pulsed-field gel electrophoresis type 1, restriction endonuclease analysis group BI, PCR ribotype 027 (NAP1/BI/027) strain remains prevalent in North America, surveillance suggests that it is decreasing in Europe. A similar strain, PCR ribotype 078, is emerging which is associated with community-associated CDI and has been isolated in animals and food products. The Society for Healthcare Epidemiology of America and the Infectious Diseases Society of America have published new guidelines on the epidemiology, diagnosis, treatment, infection control and environmental management of C. difficile. Several novel therapies for CDI are at different stages of development. There have been promising trial results with fidaxomicin, a novel antibiotic for the treatment of CDI and monoclonal antibodies against toxins A and B, which have been shown to significantly reduce CDI recurrence rates.Major advances have been made in our understanding of the spread and pathogenesis of C. difficile and new treatment options are becoming available.

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 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 (κ=0.61 for TOAST/ASCO grade 1 small artery category) to excellent (κ=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. Conclusion— 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.

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 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.

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 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. Conclusion— 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.

Clostridium difficile is a leading cause of nosocomial infection in the developed world, causing antibiotic-associated disease in susceptible populations. The identity of immunogenic proteins is important in understanding the pathogenesis of disease and in the design of vaccines. This study analysed the sera of six patients infected during a hospital outbreak of a C. difficile ribotype 017 strain. Using a proteomics-based approach, cell wall proteins were separated by two-dimensional PAGE, and immunoreactive proteins were revealed by reaction with patient sera. The identity of immunoreactive proteins was established by MS. Forty-two different proteins were identified in total. All patient sera reacted with at least one component of the surface-layer protein (SLP), four reacted with both components (high- and low-molecular-mass SLPs), and five reacted with one other cell wall protein, suggesting that these are immunodominant antigens. The role of these proteins as potential vaccine candidates and their roles in pathogenesis deserve further study.

Background.Clostridium difficileis a major cause of infectious diarrhea in hospitalized patients. Between August 2003 and January 2004, we experienced an increase in the incidence ofC. difficile–associated disease. We describe the investigation into and management of the outbreak in this article.Methods.A total of 73 consecutive patients with nosocomialC. difficile–associated diarrhea were identified.C. difficileisolates were characterized using toxin-specific enzyme immunoassays, a tissue-culture fibroblast cytotoxicity assay, polymerase chain reaction (PCR), and antimicrobial susceptibility tests. Rates of recurrence and ofC. difficilecolitis were recorded. Changes in antibiotic use and infection control policies were documented.Results.The incidence ofC. difficile–associated diarrhea peaked at 21 cases per 1,000 patient admissions. Of theC. difficileisolates recovered, 85 (95%) were identical toxin A–negative and toxin B-positive strains, corresponding to toxinotype VIII and PCR ribotype 017. All clonal isolates were resistant to multiple antibiotics, including ofloxacin, ciprofloxacin, levofloxacin, moxifloxacin, and gatifloxacin (minimum inhibitory concentrations [MICs] of greater than 32μg/mL) and erythromycin, clarithromycin, and clindamycin (MICs of greater than 256μg/mL). RecurrentC. difficile–associated disease occurred in 26 (36%) of the patients. At least 10 (14%) of the patients developedC. difficilecolitis. Additional infection control measures introduced included the use of ward memos, a hand-hygiene awareness campaign, increased environmental cleaning, attention to prescribing practices for antibiotics, increased awareness of diarrheal illness, and early isolation of affected patients. Total use of fluoroquinolones did not change throughout the study period. Despite persistence of this toxin-variant strain, the incidence ofC. difficile–associated disease in our institution decreased to fewer than 5 cases per 1,000 admissions.Conclusions.We report on the emergence of a fluoroquinolone- and clindamycin-resistant, toxin A–negative, and toxin B–positive strain ofC. difficileassociated with an outbreak ofC. difficile–associated disease in our institution during a 6-month period. We found that careful attention to improvement of infection control interventions was the most important means of controlling this nosocomial pathogen.

SummaryClostridium difficile is a major cause of infectious diarrhea in hospitalized patients. Many pathogenic strains of Clostridium difficile produce two toxins TcdA and TcdB, both of which are pro-inflammatory and enterotoxic in human intestine. Clinically relevant toxin A-negative, toxin B-positive (A−B+) strains of Clostridium difficile that cause diarrhea and colitis in humans have been isolated with increasing frequency worldwide. This perspective describes these important toxin variant strains and highlights the need to use Clostridium difficile diagnostic methods that can detect both TcdA and TcdB.

Background and Purpose— Demographic trends in atrial fibrillation (AF) incidence may yield a substantial rise in the societal burden of AF-related stroke (AF-stroke). Accurate population-wide outcome data are essential to inform health service planning to improve AF-stroke prevention, and provision of rehabilitation, nursing home, and community supports for AF-stroke survivors. Methods— We investigated rates and determinants of 5-year fatality, stroke recurrence, functional outcomes, and prescribing of secondary prevention medications in AF-stroke in the North Dublin Population Stroke Study. Ascertainment included hot and cold pursuit using multiple overlapping sources. Survival analysis was performed using lifetables and Kaplan–Meier survival curves, and Cox proportional hazard modeling was performed to identify predictors of death and recurrent stroke. Results— Five hundred sixty-eight patients with new stroke were identified, including 177 (31.2%) AF-stroke. At 5 years, 39.2% (confidence interval, 31.5–46.8) of ischemic AF-stroke patients were alive. Congestive heart failure, hypertension, age 2 DS 2 -VASc) score (hazard ratio [HR], 1.34; P 2 score (HR 1.42, P =0.004), National Institute of Health Stroke Scale (HR, 1.09; P P =0.003) were independently associated with 5-year fatality, whereas warfarin (HR, 0.40; P =0.001) and statin use after index stroke (HR, 0.52; P =0.005) were associated with improved survival. The 5-year recurrence rate after ischemic AF-stroke was 21.5% (confidence interval, 14.5–31.3). Trends toward greater risk of recurrence were observed for persistent AF (HR, 3.09; P =0.07) and CHA 2 DS 2 -VASc score (HR, 1.34; P =0.07). Nursing home care was needed for 25.9% of patients. Conclusions— AF-stroke is associated with considerable long-term morbidity, fatality, stroke recurrence, and nursing home requirement. Adequately resourced national AF strategies to improve AF detection and prevention are needed.

OBJECTIVES: To determine the mechanism of high-level resistance to fluoroquinolone antimicrobials in toxin-A-negative, toxin-B-positive (A- B+) Clostridium difficile isolates. METHODS: Following culture 16-23S PCR ribotyping was used to determine genomic relationships between A- B+ C. difficile isolates. Antimicrobial susceptibilities were determined using Etests in the presence and absence of the efflux pump inhibitors reserpine (20 microg/mL), L-phenylalanine-L-arginine-beta-naphthylamide (PAbetaN; 20 microg/mL) and verapamil (100 microg/mL). Genomic regions including the quinolone-resistance-determining-region (QRDR) of gyrA and gyrB were amplified and characterized. RESULTS: PCR ribotyping profiles identified one major cluster of A- B+ C. difficile, universally resistant to the fluoroquinolones tested (ofloxacin, ciprofloxacin, levofloxacin, moxifloxacin and gatifloxacin; MICs > 32 mg/L). All isolates with high-level resistance had a transversion mutation (A-->T) resulting in the amino acid substitution Asp-426-->Val in gyrB. Non-clonal isolates were susceptible to moxifloxacin and gatifloxacin (MICs 0.3 and 0.4 mg/L, respectively) with reduced susceptibility to levofloxacin (MIC 3 mg/L) consistent with the wild-type genotype. The MICs for resistant isolates were not significantly affected by the addition of any of the efflux pump inhibitors. No amino acid substitutions were identified in the QRDR of gyrA. CONCLUSIONS: High-level resistance to fluoroquinolones in A- B+ C. difficile is associated with a novel transversion mutation in gyrB. The emergence of universal resistance in different C. difficile strain types may be a factor promoting outbreaks in hospitals.

Background & aims: Recurrent C difficile-associated diarrhea (CDAD) is associated with a lack of protective immunity to C difficile toxins. A parenteral C difficile vaccine containing toxoid A and toxoid B was reported previously to be safe and immunogenic in healthy volunteers. Our aim was to examine whether the vaccine is also well tolerated and immunogenic in patients with recurrent CDAD. Methods: Subjects received 4, 50-μg intramuscular inoculations of the C difficile vaccine over an 8-week period. Serum antitoxin antibodies were measured by ELISA, and toxin neutralizing activity was evaluated using the tissue culture cytotoxin assay. Results: Three patients with multiple episodes of recurrent CDAD were vaccinated. Two of the 3 showed an increase in serum IgG antitoxin A antibodies (3-fold and 4-fold increases, respectively) and in serum IgG antitoxin B antibodies (52-fold and 20-fold, respectively). Both also developed cytotoxin neutralizing activity against toxin A and toxin B. Prior to vaccination, the subjects had required nearly continuous treatment with oral vancomycin for 7, 9, and 22 months, respectively, to treat recurrent episodes of CDAD. After vaccination, all 3 subjects discontinued treatment with oral vancomycin without any further recurrence. Conclusions: A C difficile toxoid vaccine induced immune responses to toxins A and B in patients with CDAD and was associated with resolution of recurrent diarrhea. The results of this study support the feasibility of active vaccination against C difficile and its toxins in high-risk individuals but must be validated in larger, randomized, controlled trials.

Background: Following ischemic cerebrovascular accident (CVA) or transient ischemic attack (TIA) aggressive risk factor modification is undertaken to reduce the risk of recurrent events. Holter monitoring is advocated to facilitate the detection and treatment of Atrial Fibrillation (AF). Frequent Premature Atrial Contractions (PACs) are associated with the development of AF, but to date it is unknown whether the burden of PACs on Holters is of any prognostic importance following CVA/TIA. Objective: PACs on Holter monitoring may be a marker for recurrent cerebrovascular events post CVA/TIA. Methods: Retrospective analysis was performed on Holters of patients with CVA/TIA enrolled in a prior population based stroke study. Frequent PACs were defined as a rate of PACs ≥ 100 per 24 hours. The primary endpoint was recurrent CVA or TIA. Results: 84 cases (61.0% male) were reviewed. Mean age was 69.7 ± 12.4 years. Mean time to follow-up was 2514.6 ± 91.2 days. The average number of PACs in the frequent group (Hi-PAC, 21 patients) was 1610.8 ± 4541.4 compared with 21.8 ± 27.6 in those with less than 100 PACs (Lo-PAC, 63 patients). There was no statistically significant difference in age, gender, hypertension or diabetes between the two groups. On follow-up there were 20 recurrent events and 33 patients died. In the Hi-PAC group there were 8 (38.1%) recurrent events, and 16 (76.2%) patients died versus 12 (18.8%) and 17 (26.6%) respectively in Lo-PAC group. On Cox regression analysis the Hazard ratio (HR) for recurrent events was 2.75 (95% confidence interval (CI) 1.08 to 7.01). Kaplan Meier curves revealed a statistically significant difference in recurrance rates between the two groups (p < 0.05). There was also a statistically significant difference in overall mortality on Kaplan Meier survival analysis (p < 0.001), and with a hazard ratio on Cox regression analysis of 3.47 (95% CI 1.74 [[Unable to Display Character: –]] 6.91). There was no significant difference in incidence of MI or AF. Conclusion: Frequent PACs on Holter monitor represent a significant risk factor for both recurrent events and mortality following CVA/TIA. Further prospective studies should be performed to assess whether these patients may benefit from more aggressive anticoagulation, similar to those with AF.