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Biomedical subjects

I Perez

Publications and source records attributed to I Perez.

At least 19 recordsLinked to original sources

Should stroke subtype influence anticoagulation decisions to prevent recurrence in stroke patients with atrial fibrillation?

BACKGROUND AND PURPOSE: Long-term anticoagulation is routinely used for secondary stroke prevention in atrial fibrillation, often regardless of stroke subtype. Although the role of warfarin in cardioembolic stroke is established, it may not prevent recurrence in other stroke subtypes, even in the presence of atrial fibrillation. METHODS: This was a 2-year, prospective, intervention study conducted in a district general hospital. Participants included 386 acute stroke patients with atrial fibrillation. Subjects were characterized for stroke subtype on clinical, neuroimaging, carotid ultrasonographic, and echocardiographic criteria. Eligible patients were treated with adjusted-dose warfarin (international normalized ratio, 2.0 to 3.0). Aspirin (75 to 300 mg/d) was used in patients with contraindications or those who refused anticoagulation. The main outcome measures were rate of recurrent stroke by subtype and major and minor bleeding complications. RESULTS: The aspirin group (n=172) was comparable to the warfarin group (n=214) in terms of age, sex, risk factors, and initial stroke subtype. The rate of recurrent stroke was higher (9.5% versus 4.9%, P<0.02) but that of major bleeding was lower (0.6% versus 2.5%, P<0.05) with aspirin. The increased stroke rate with aspirin was due predominantly to cardioembolic recurrence in patients presenting initially with cardioembolic stroke (8.4% versus 1.9%, P<0.01). The recurrence rate in aspirin-treated patients who presented with lacunar stroke and atrial fibrillation was similar to that seen in patients receiving warfarin (8.8% versus 8.9%). CONCLUSIONS: In this cohort of stroke patients with atrial fibrillation, anticoagulation was superior to aspirin in preventing cardioembolic but not lacunar recurrence. Determination of stroke subtype may be important in anticoagulation decisions for secondary prevention, and further studies are required.

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Can differences in management processes explain different outcomes between stroke unit and stroke-team care?

BACKGROUND: Stroke units reduce mortality and dependence, but the reasons are unclear. We have compared differences in management and complications of patients with acute stroke who were admitted to a stroke unit or to a general ward as part of a previously reported randomised trial. METHODS: 304 patients had been randomly assigned to stroke units (n=152) or to general wards supported by a specialist stroke team (152). We used a structured format to gather prospective data on the frequency of prespecified interventions in each of the major aspects of stroke care. Observations were undertaken daily for the first week and every week for the next 3 months by independent observers. The effect of differences in management on outcome at 3 months was assessed with the modified Rankin score, dichotomised to good (0-3) and poor (4-6) outcome. FINDINGS: Patients in the stroke unit were monitored more frequently (odds ratio 2.1 [1.3-3.4]) and more patients received oxygen (2.0 [1.3-3.2]), antipyretics (6.4 [1.5-27.5]), measures to reduce aspiration (6.0 [2.3-15.5]), and early nutrition (14.4 [5.1-40.9]) than those in general wards. Complications were less frequent in patients in the stroke unit than those in general wards (0.6 [0.2-0.7]), with fewer patients having progression of stroke, chest infection, or dehydration. Measures to prevent aspiration, early feeding, stroke unit management, and frequency of complications independently affected outcome. INTERPRETATION: Differences in management and complications between the stroke unit and general wards differ substantially, even when specialist support is provided. Such differences could be responsible for the more favourable outcome seen in patients on stroke units than those on general wards.

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A complex containing CstF-64 and the SL2 snRNP connects mRNA 3' end formation and trans-splicing in C. elegans operons.

Polycistronic pre-mRNAs from Caenorhabditis elegans are processed by 3' end formation of the upstream mRNA and SL2-specific trans-splicing of the downstream mRNA. These processes usually occur within an approximately 100-nucleotide region and are mechanistically coupled. In this paper, we report a complex in C. elegans extracts containing the 3' end formation protein CstF-64 and the SL2 snRNP. This complex, immunoprecipitated with alphaCstF-64 antibody, contains SL2 RNA, but not SL1 RNA or other U snRNAs. Using mutational analysis we have been able to uncouple SL2 snRNP function and identity. SL2 RNA with a mutation in stem/loop III is functional in vivo as a trans-splice donor, but fails to splice to SL2-accepting trans-splice sites, suggesting that it has lost its identity as an SL2 snRNP. Importantly, stem/loop III mutations prevent association of SL2 RNA with CstF-64. In contrast, a mutation in stem II that inactivates the SL2 snRNP still permits complex formation with CstF-64. Therefore, SL2 RNA stem/loop III is required for both SL2 identity and formation of a complex containing CstF-64, but not for trans-splicing. These results provide a molecular framework for the coupling of 3' end formation and trans-splicing in the processing of polycistronic pre-mRNAs from C. elegans operons.

Animals↗

Intramolecular electronic interactions in conjugated ferrocene-pi-extended-tetrathiafulvalene donor-pi-donor molecular hybrids

The synthesis of new hybrid ferrocene and pi-extended tetrathiafulvalene (TTF) donor(1)-pi-donor(2) molecular assemblies 16a-c has been carried out by a Wittig-Horner reaction of the respective phosphonate esters 15a-c with 2-(2-ferrocenylvinyl)-9, 10-anthraquinone (18) prepared by olefination of ferrocenecarboxaldehyde (14) and the anthraquinone phosphonium salt 17. Electrochemical studies show that the D(1)-pi-D(2) (D = donor) molecular assemblies 16a-c essentially retain the redox characteristics of both ferrocene and the pi-extended TTF components and the effects of solvent, temperature, scan rate, and working electrode are significant. Most importantly, pronounced intramolecular electronic interactions between the two donor moieties were observed by cyclic voltammetry and Osteryoung square wave voltammetry in both the ground and charged states. Semiempirical calculations support the electrochemical observations.

Journal Article↗

Alternative strategies for stroke care: a prospective randomised controlled trial.

BACKGROUND: Organised specialist care for stroke improves outcome, but the merits of different methods of organisation are in doubt. This study compares the efficacy of stroke unit with stroke team or domiciliary care. METHODS: A single-blind, randomised, controlled trial was undertaken in 457 acute-stroke patients (average age 76 years, 48% women) randomly assigned to stroke unit, general wards with stroke team support, or domiciliary stroke care, within 72 h of stroke onset. Outcome was assessed at 3, 6, and 12 months. The primary outcome measure was death or institutionalisation at 12 months. Analyses were by intention to treat. FINDINGS: 152 patients were allocated to the stroke unit, 152 to stroke team, and 153 to domiciliary stroke care. 51 (34%) patients in the domiciliary group were admitted to hospital after randomisation. Mortality or institutionalisation at 1 year were lower in patients on a stroke unit than for those receiving care from a stroke team (21/152 [14%] vs 45/149 [30%]; p<0.001) or domiciliary care (21/152 [14%] vs 34/144 [24%]; p=0.03), mainly as a result of reduction in mortality. The proportion of patients alive without severe disability at 1 year was also significantly higher on the stroke unit compared with stroke team (129/152 [85%] vs 99/149 [66%]; p<0.001) or domiciliary care (129/152 [85%] vs 102/144 [71%]; p=0.002). These differences were present at 3 and 6 months after stroke. INTERPRETATION: Stroke units are more effective than a specialist stroke team or specialist domiciliary care in reducing mortality, institutionalisation, and dependence after stroke.

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Synthesis and properties of conjugated hybrid tetrathiafulvalene dimers

The synthesis of new hybrid tetrathiafulvalene (TTF) dimers (11a-c) has been carried out by a Wittig-Horner reaction of the respective phosphonate esters (10a-c) with 2-(tetrathiafulvalenylvinyl)-9, 10-anthraquinone (9) prepared by olefination of formyltetrathiafulvalene (7) and the phosphonium salt of anthraquinone 8. Electrochemical studies show that the dimers 11a-c mainly retain the electrochemical properties of both TTF and the pi-extended TTF components, and most importantly, intramolecular electronic interactions between the two moieties are observed by cyclic voltammetry and Osteryoung square wave voltammetry. Semiempirical PM3 calculations reveal an almost planar geometry for the TTF and the benzene ring connected through the vinyl spacer. These compounds can form stable charge-transfer complexes with 2, 3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) showing a stoichiometry of 1:3 (D:A). Attempts to electrocrystallize the dimeric donors with different counteranions are discussed.

Journal Article↗

Prospective cohort study to determine if trial efficacy of anticoagulation for stroke prevention in atrial fibrillation translates into clinical effectiveness.

OBJECTIVE: To determine whether trial efficacy of prophylaxis with warfarin for patients with atrial fibrillation at high risk of stroke translates into effectiveness in clinical practice. DESIGN: Two year prospective cohort study. SETTING: District general hospital. PARTICIPANTS: 167 patients with atrial fibrillation and at high stroke risk who were eligible for anticoagulation. INTERVENTIONS: Long term anticoagulation with warfarin at adjusted doses to maintain an international normalised ratio of 2.0-3.0. MAIN OUTCOME MEASURES: Comparison of patient characteristics, comorbidity, anticoagulation control, stroke rate, and haemorrhagic complications with pooled data from five randomised controlled trials. RESULTS: Patients in the study group were seven years older (95% confidence interval 4 to 10) and comprised 33% more women than patients in the pooled trials. The international normalised ratio was in the target range for 61% of the time (range 37%-85%), below for 26% of the time (range 8%-32%), and above for 13% of the time (range 6%-26%). The time that patients in the study group spent in the target range was significantly less than in the pooled analysis. The incidence of stroke in the study group (2.0% per year, 0.7% to 4. 4%) was comparable to that of patients receiving warfarin in pooled studies (1.4%, 0.8% to 2.3%). Per year the incidence of major (1.7% v 1.6%) and minor (5.4% v 9.2%) bleeding complications was also similar. CONCLUSION: Rates of stroke and major haemorrhage after anticoagulation in clinical practice were comparable to those obtained from pooled data from randomised controlled studies for patients with atrial fibrillation at high risk of stroke.

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Does prior use of aspirin affect outcome in ischemic stroke?

BACKGROUND: Large intervention studies suggest that aspirin may reduce mortality when given to patients who present with strokes or transient ischemic attacks. We sought to determine whether patients who were already using aspirin at the time of an ischemic stroke had a lower mortality than those who were not. METHODS: A prospective cohort study was undertaken in patients (mean age 76 +/- 15 years) with acute ischemic stroke. Detailed information on demography, stroke characteristics, and aspirin use prior to the stroke was collected from patients, medical records, and other sources. Patients were classified by cause and subtype of stroke using standard criteria. Mortality was measured 4 weeks after the initial episode. RESULTS: Of the 1,457 patients, 650 (45%) were using aspirin (median dose 75 mg; range 75 to 300 mg) prior to the stroke. Prior use of aspirin was associated with lower 4-week mortality (14% versus 20%, P <0.01 ). Beneficial effects of prior aspirin use on mortality were seen in patients with atherosclerotic strokes (15% versus 21%, P <0.05) and with cardioembolic strokes (21% versus 34%, P <0.05), but not among patients with strokes due to small vessel occlusion (10% versus 11%, P = 0.8). Prior aspirin use was also associated with lower mortality in patients in whom the cause of ischemic stroke could not be determined (15% versus 22%, P <0.01). The effect of prior aspirin use on mortality was independent of age, gender, other risk factors, and use of other medication. CONCLUSIONS: Prior use of low-dose aspirin may be associated with a small but significant reduction in stroke mortality.

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Secular trends in the management of hypertension and atrial fibrillation in patients presenting with stroke.

We studied changes in stroke prevention in 2000 ischaemic stroke patients using prospectively collected data from an incident stroke register over 3 years. Patients were divided into those with risk factors but no previous history of a vascular event (asymptomatic vascular disease) and those with risk factors and a previous history of stroke or TIAs, ischaemic heart disease, angina, myocardial infarction or peripheral vascular disease (symptomatic vascular disease). Time trends were analysed for the use of aspirin, management of hypertension and atrial fibrillation prior to the presenting episode. Median age of those with known risk factors included in the study was 75 years (range 44-99 years); 60% were women. Year-by-year analysis showed no differences in demography, stroke characteristics or vascular risk profile. The use of aspirin for symptomatic vascular disease increased with time (28% to 72%) (p<0.001), but did not increase for asymptomatic vascular disease, despite risk factors being present. The proportion of patients receiving antihypertensive treatment for symptomatic vascular disease was unchanged with time (66% to 64%) but there was a significant increase in the number of patients receiving antihypertensive treatment for asymptomatic vascular disease (28% to 44%) (p<0.05). The proportion of patients with atrial fibrillation receiving antithrombotic treatment did not increase for asymptomatic vascular disease (23% to 21%) (p=0.54) but did increase for symptomatic vascular disease (19.5% to 37%) (p<0.01) over 3 years. The use of warfarin in atrial fibrillation increased both in the case of asymptomatic (4.5% to 42%) (p<0.01) and symptomatic vascular disease (12.5% to 33.0%) (p<0.01).

Adult↗

Randomized controlled trial of integrated (managed) care pathway for stroke rehabilitation.

BACKGROUND AND PURPOSE: Integrated Care Pathway (ICP) is an organized, goal-defined, and time-managed plan that has the potential of facilitating timely interdisciplinary coordination, improving discharge planning, and reducing length of hospital stay. METHODS: An ICP for stroke rehabilitation based on evidence of best practice, professional standards, and existing infrastructure was developed. Its effectiveness was tested in 152 stroke patients undergoing rehabilitation who were randomized to receive ICP care coordinated by an experienced nurse (n=76) or conventional multidisciplinary care (n=76). RESULTS: The age, sex, premorbid functional ability, and stroke characteristics of the 2 groups were comparable. There were no differences in mortality rates (10 [13%] versus 6 [8%]), institutionalization (10 [13%] versus 16 [21%]), or length of hospital stay (50+/-19 versus 45+/-23 days) between patients receiving ICP or multidisciplinary care. Patients receiving conventional multidisciplinary care improved significantly faster between 4 and 12 weeks (median change in Barthel Activities of Daily Living Index 6 versus 2; P<0.01) and had higher Quality of Life scores at 12 weeks (65 versus 59; P=0.07) and 6 months (72 versus 63; P<0.005). There were no significant differences in the mean duration of physiotherapy (42.8+/-41.2 versus 39.4+/-36.4 hours) or occupational therapy (8.5+/-7.5 versus 8.0+/-7.5 hours) received between the 2 groups. CONCLUSIONS: ICP management offered no benefit over conventional multidisciplinary care on a stroke rehabilitation unit. Functional recovery was faster and Quality of Life outcomes better in patients receiving conventional multidisciplinary care.

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Secondary stroke prevention in atrial fibrillation: lessons from clinical practice.

BACKGROUND AND PURPOSE: Secondary prevention trials do not distinguish outcomes according to stroke cause. The purpose of the study was to determine whether trial efficacy of anticoagulation for secondary prevention could be replicated in clinical practice in strokes of different etiology. METHODS: A 2-year observation study was undertaken in 288 stroke patients with atrial fibrillation (mean age 76 years; 55% women) who were receiving anticoagulation therapy to maintain an international normalized ratio of 2.0 to 3.0. Comparisons were made of (1) patient characteristics, anticoagulation control, and annual stroke/hemorrhage rates with those of the European Atrial Fibrillation Trial and (2) cause of recurrent stroke by initial stroke subtype. RESULTS: Subjects were 5 years older (95% CI 3 to 7 years), and more patients had small-vessel stroke (26% versus 14%; 95% CI 3% to 17%) compared with corresponding trial data. The duration spent in the target anticoagulation range (55% versus 59%), recurrent stroke rate (5.1% versus 3.6% per year), and major (2.3% versus 2.2% per year) or minor (9.5% versus 11.8% per year) hemorrhage rates were comparable with those in patients receiving warfarin in the randomized study. Ten of 14 (71%) of embolic recurrences occurred in patients with a previous cardioembolic episode, and 8 of 11 (73%) lacunar recurrences occurred in patients with previous lacunar stroke as the qualifying event for anticoagulation (P:=0.025). Only 3 of 14 cardioembolic compared with 8 of 11 lacunar recurrences occurred during adequate anticoagulation. CONCLUSIONS: Anticoagulation for secondary stroke prevention in clinical practice achieves outcomes comparable with those of randomized trials. Nearly 26% of qualifying strokes and 40% of recurrences were nonembolic; stroke subtype should be considered when making treatment decisions.

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Use of antithrombotic measures for stroke prevention in atrial fibrillation.

OBJECTIVE: To evaluate appropriateness of antithrombotic use to prevent stroke in atrial fibrillation. DESIGN, PATIENTS: 344 patients with atrial fibrillation, stratified by age, were assessed clinically for contraindications to anticoagulation and stroke risk. The use of warfarin and aspirin was compared with recommendations for anticoagulation derived from pooled clinical trial data. RESULTS: Low risk of stroke was seen in 47 (14%) patients, moderate risk in 213 (62%), and high risk in 84 (24%) patients included in the sample (mean (SD) age 68.4 (17.2) years, 42% men). The proportion of patients requiring anticoagulation varied from 258/344 (75%) to 72/344 (21%) depending upon criteria used, of whom 86/258 (33%) and 36/72 (50%) were receiving warfarin, respectively. Warfarin or aspirin were not being used in 124/297 (42%) patients with moderate to high risk, whereas anticoagulation was being undertaken in 13/47 (27%) patients at low risk of stroke. Antithrombotic use (warfarin or aspirin) was significantly less common in patients over 75 years of age, regardless of absence of contraindications and eligibility according to various criteria (p < 0.001). CONCLUSIONS: A clear need for anticoagulation using clinical criteria existed in about 25% of patients in atrial fibrillation presenting to medical clinics who were at high risk of stroke. Of these, only 50% of eligible patients were being anticoagulated. Appropriate anticoagulation needs to be based on risk assessment rather than age. Consensus is therefore needed on appropriate antithrombotic use in clinical practice.

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Risk assessment and anticoagulation for primary stroke prevention in atrial fibrillation.

BACKGROUND AND PURPOSE: Risk assessment before anticoagulation is important for effective stroke prevention in atrial fibrillation (AF). METHODS: A study was undertaken in patients with AF to investigate the contribution of clinical and echocardiography (ECHO) criteria to treatment decisions on anticoagulation. Patients were stratified by age and stroke risk; contraindications to anticoagulation and warfarin use were assessed. The value of ECHO in treatment decisions, effect of age, and existing anticoagulation practice were evaluated. RESULTS: The mean+/-SD age of 234 patients was 67.1+/-11.8 years, and 122 (52%) were women. Clinical risk factors were present in 74 of 80 patients (92%) aged >75 years compared with 99 of 154 patients (64%) </=75 years (P<0.01). ECHO risk was identified in 94 of 154 patients (61%) </=75 years, 16 (17%) of whom had no clinical risk factors. ECHO risk was present in 71 patients (88%) >75 years of age, and was associated with clinical risk factors in all patients. Eligibility for anticoagulation was seen in 72 of 154 (47%) to 105 of 154 (68%) patients aged </=75 years, depending on the criteria used, and in 66 of 80 patients (83%) >75 years, regardless of criteria used (P<0.01). Warfarin was being used in 55 of 105 patients (51%) </=75 years and 8 of 66 patients (12%) >75 years (P<0.001). Anticoagulation was being undertaken in 7 of 49 patients (14%) </=75 years despite no clinical or ECHO risks. CONCLUSIONS: Accurate assessments of eligibility and appropriateness of anticoagulation in AF can be made on clinical criteria alone, especially in older people. The value of ECHO in treatment decisions is limited to patients </=75 years of age with no clinical risk factors.

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Pharmacological treatment of dysphagia in stroke.

The pharynx is important for a normal swallow and it has been suggested that pharmacological agents may play a role in the management of pharyngeal dysphagia, but none have been formally evaluated. A pilot double-blind, placebo-controlled study was undertaken in 17 hospitalized patients with persistent dysphagia 2 weeks after stroke. Patients were randomized to treatment with slow-release nifedipine 30 mg orally (n = 8) or placebo (n = 9) following specialist swallowing assessment and videofluoroscopy to exclude severe dysphagia. Videofluoroscopy was repeated after 4 weeks of treatment. Fourteen patients (active 6, placebo 8) completed the study. Two patients died (active 1, placebo 1) and 1 patient in the active group had to be withdrawn because of progressive heart failure. Initial assessment showed impairment in the pharyngeal phase with delayed triggering of swallow, poor laryngeal elevation, and prolonged pharyngeal transit times in all patients. Silent aspiration was seen in 4 patients (active 2, placebo 2). Improvement in swallowing was seen in 8 patients (active 5, placebo 3) at the end of 4 weeks. There were significant changes in the pharyngeal transit time (mean -1.34 second; 95% C.I. -2.56, -0.11) and swallow delay (mean -1.91 seconds; 95% C.I. -3.58, -0.24) in the active group suggesting improvement in the initiation of pharyngeal contractions and reduction in the time taken for the bolus to transverse the pharynx. A similar change was not seen in the placebo group. It is suggested that pharmacological agents such as nifedipine may have a role in the management of stroke-related dysphagia and merit further investigation.

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Stroke risk management: changes in mainstream practice.

BACKGROUND: Research shows that identification and control of risk factors reduces ischemic stroke. The impact of this evidence and health initiatives on mainstream practice remains unknown. METHODS: The purpose of this observational study was to investigate prior management of risk factors (hypertension, atrial fibrillation, previous stroke/transient ischemic attacks) in patients with acute cerebral infarction. Data were collected on the frequency of known risk factors before the incident stroke and their management compared with predefined criteria for appropriateness. The proportion of patients receiving treatment for risk factors before the acute episode was studied over 3 years. RESULTS: One thousand seventy-four patients (median age, 76 years; 60% women) were included in the study over 3 years. The proportion of patients with known hypertension (41% to 46%), diabetes (12% to 13%), previous stroke or transient ischemic attack (TIA) (21% to 31%), and atrial fibrillation (16% to 21%) remained stable. Overall, approximately 45% patients with atrial fibrillation, 60% patients with hypertension, and 70% with cerebrovascular disease were being actively managed. Time trends analysis showed a significant increase in the proportion of patients being treated for risk due to known cerebrovascular disease (59% to 85%), atrial fibrillation (18% to 59%), ischemic heart disease (35% to 72%), and carotid disease (13% to 85%) between the first and third year. The proportion of patients receiving treatment for hypertension remained unchanged. Patients with preexisting symptomatic vascular disease were more likely to receive appropriate risk management compared with asymptomatic patients (72% versus 46%, P<.001). CONCLUSIONS: Although a significant number of ischemic events remain potentially preventable, there appears to be a positive trend in improved control of stroke risk.

Acute Disease↗

The process of rehabilitation and discharge planning in stroke: a controlled comparison between stroke units.

BACKGROUND AND PURPOSE: Stroke units improve outcome for stroke patients. Comparative controlled studies between stroke units are required to determine which components of stroke unit rehabilitation influence outcome and which may be investigated further in randomized controlled trials. This study compares 2 stroke units with regard to the effect differences in practice have on functional recovery (Barthel Index score) and discharge planning (length of stay). METHODS: Stroke unit patients with moderate disability (Barthel score of 4 to 10 at week 1) admitted over 18 months were studied. Barthel measurements were obtained weekly from week 1 to discharge. Details of stroke unit function were recorded. The core features of stroke units were in place in both units. Rehabilitation was impairment focused (theoretically driven) on one unit and disability oriented (pragmatic) on the other. RESULTS: Numbers of patients were comparable (85 versus 99). Median Barthel score at week 1 (6 versus 6), time to maximal Barthel score (14 versus 14 weeks), discharge Barthel score (14 versus 14), and institutionalization (32% versus 28%) were similar in both units. Median lengths of stay differed (68 versus 49 days; P<0.001). CONCLUSIONS: Comparisons with regard to the rehabilitation process can be made between stroke units. Differences in rehabilitation process between 2 units showed no effect on the rate of functional recovery. Length of stay was significantly different between units, an effect that cannot be attributed to functional recovery and therefore reflects differences in discharge planning, including postdischarge support.

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