Description of the condition
Stroke is now the third leading cause of disability (Murray 2012) and the second leading cause of mortality (Lozano 2012) worldwide. The global disease burden of stroke increased by 19% between 1990 and 2010 (Murray 2012) and current projections estimate the number of deaths worldwide will rise to 6.5 million in 2015 and to 7.8 million in 2030 (Strong 2007). Interventions that are applicable to a majority of stroke patients and that aim to reduce associated mortality and disability are essential.
During their initial illness, stroke patients are frequently admitted to hospital where they can receive care in a variety of ways and in a range of settings. Traditionally, the care of stroke patients was provided within departments of general (internal) medicine, neurology or medicine for the elderly where they would be managed alongside a range of other patient groups. A more-focused approach to the management of stroke patients in hospital has been developed.
Description of the intervention
Organised inpatient (stroke unit) care is a term used to describe the focusing of care for stroke patients in hospital under a multidisciplinary team who specialise in stroke management (SUTC 1997a). This concept is not new and its value has been debated for more than 20 years (Ebrahim 1990; Garraway 1985; Langhorne 1993; Langhorne 1998; Langhorne 2012). In essence, the debate has concerned whether the perceived effort and cost of focusing the care of hospitalised stroke patients within specially organised units would be matched by tangible benefits for the patients receiving that care. In particular, would more patients survive and make a good recovery as a result of organised inpatient (stroke unit) care?
Why it is important to do this review
A systematic review of all available trials (SUTC 1997a) previously described the range of characteristics of stroke unit care and addressed the question of whether improving the organisation of inpatient stroke care can bring about improvements in important patient outcomes. This review continues to be extended and updated within The Cochrane Library (SUTC 2001; SUTC 2007).
To assess the effect of stroke unit care compared with alternative forms of care for people following a stroke.
Originally, there were four broad objectives for this systematic review. To establish:
- the characteristic features of organised inpatient (stroke unit) care;
- if organised inpatient (stroke unit) care could provide better patient outcomes than alternative forms of care;
- if benefits were apparent across a range of patient groups;
- if different approaches to organised stroke unit care were effective (in particular, we hypothesised that organised care would be more effective than that of general medical wards, but that different forms of organised care would achieve similar outcomes).
Within the current version of this review, we wished to establish whether the previous conclusions were altered by the inclusion of new outcome data from recent trials and further subgroup analyses based on patient and intervention characteristics. We have structured the review to allow the inclusion of future trials that address important questions about the optimal ways to organise stroke patient care.
Criteria for considering studies for this review
Types of studies
We included all randomised controlled clinical trials that compared an organised system of inpatient (stroke unit) care with an alternative form of inpatient care. This was usually the contemporary conventional care but could include an alternative model of organised inpatient care (see Types of interventions). Previous versions of this review (SUTC 1997a; SUTC 2001; SUTC 2007) have included trials with quasi-random treatment allocation (such as bed availability or date of admission). However, in an effort to ensure this ongoing systematic review focuses on data from trials with strict randomisation procedures we excluded all quasi-randomised trials for this update.
Types of participants
Any person admitted to hospital who had suffered a stroke was eligible. We recorded the delay between stroke onset and hospital admission but did not use this as an exclusion criterion. We used a clinical definition of stroke: focal neurological deficit due to cerebrovascular disease, excluding subarachnoid haemorrhage and subdural haematoma.
Types of interventions
Organised inpatient (stroke unit) care can be considered a complex organisational intervention comprising multidisciplinary staffing providing a complex package of care to stroke patients in hospital. In the original version of this review (SUTC 1997a), the primary question was whether organised inpatient (stroke unit) care could improve outcomes compared with the contemporary conventional care (usually in general medical wards). We have now modified the analyses in a minor way to reflect the emerging hierarchy of service organisation and to allow the comparison of 'more-organised' versus 'less-organised' services. We have done this because some recent trials have addressed new questions and included comparisons of two services both of which met the basic definition of organised (stroke unit) care and so could not really be described as conventional care. However, the original service descriptions used in this review (SUTC 1997a) indicated that service organisation could be considered as a hierarchy which, in descending order, was as follows.
- Stroke ward: where a multidisciplinary team including specialist nursing staff based in a discrete ward cares exclusively for stroke patients. This category included the following subdivisions:
- acute stroke units that accept patients acutely but discharge early (usually within seven days); these appear to fall into three broad subcategories:
- 'intensive' model of care with continuous monitoring, high nurse staffing levels and the potential for life support;
- 'semi-intensive' with continuous monitoring, high nurse staffing but no life support facilities; and
- 'non-intensive' with none of the above;
- rehabilitation stroke units that accept patients after a delay, usually of seven days or more, and focus on rehabilitation; and
- comprehensive (ie combined acute and rehabilitation) stroke units that accept patients acutely but also provide rehabilitation for at least several weeks if necessary. Both the rehabilitation unit and comprehensive unit models offer prolonged periods of rehabilitation.
- Mixed rehabilitation ward: where a multidisciplinary team including specialist nursing staff in a ward provides a generic rehabilitation service but not exclusively caring for stroke patients.
- Mobile stroke team: where a peripatetic multidisciplinary team (excluding specialist nursing staff) provides care in a variety of settings.
- General medical ward: where care is provided in an acute medical or neurology ward without routine multidisciplinary input.
Types of outcome measures
The primary analysis examined death, dependency and the requirement for institutional care at the end of scheduled follow-up of the original trial (four trials subsequently extended follow-up). We categorised dependency into two groups where we took 'independent' to mean that an individual did not require physical assistance for transfers, mobility, dressing, feeding or toileting. We considered individuals who failed any of these criteria 'dependent'. The criteria for independence were approximately equivalent to a modified Rankin score of 0 to 2, or a Barthel Index of more than 18 out of 20 (Wade 1992). We took the requirement for long-term institutional care to mean care in a residential home, nursing home or hospital at the end of scheduled follow-up.
Secondary outcome measures included patient quality of life, patient and carer satisfaction, and duration of stay in hospital or institution or both.
Search methods for identification of studies
See the 'Specialized register' section in the Cochrane Stroke Group module. We searched for trials in all languages and arranged the translation of relevant papers published in languages other than English.
We searched the trials registers of the Cochrane Stroke Group (January 2013) and the Cochrane Effective Practice and Organisation of Care (EPOC) Group (January 2013). In addition, in collaboration with the Cochrane Stroke Group Trials Search Co-ordinator, we searched MEDLINE (2008 to September 2012) (Appendix 1), EMBASE (2008 to September 2012) (Appendix 2) and CINAHL (1982 to September 2012) (Appendix 3). To avoid duplication of effort we restricted the searches of MEDLINE and EMBASE from January 2008 as these databases have already been searched to that date for all stroke trials and relevant trials added to the Cochrane Stroke Group Trials Register.
We searched the following registers of ongoing trials using the keyword 'stroke' (January 2013):
- ClinicalTrials.gov (http://clinicaltrials.gov/);
- The Australian New Zealand Clinical Trials Registry (www.anzctr.org.au);
- CenterWatch Clinical Trials Listing Service (www.centerwatch.com);
- Chinese Clinical Trial Register (www.chictr.org);
- Community Research & Development Information Service (of the European Union) (cordis.europa.eu/en/home.html);
- WHO International Clinical Trials Registry (www.who.int/trialsearch);
- Hong Kong clinical trials register (www.hkclinicaltrials.com);
- Clinical Trials Registry - India (CTRI) (www.ctri.in);
- Nederlands Trialregister (www.trialregister.nl/trialreg/index.asp);
- South African National Clinical Trial Register (www.sanctr.gov.za);
- UK Clinical Research Network Portfolio database (portal.nihr.ac.uk/Pages/Portfolio.aspx);
- UK Clinical Trials Gateway (www.controlled-trials.com/ukctr);
- UK National Research Register (NRR) (trials and other research - archived September 2007) (portal.nihr.ac.uk/Pages/NRRArchive.aspx);
- University Hospital Medical Information Network (UMIN) Clinical Trials Registry (for Japan) (www.umin.ac.jp/ctr/);
- The Internet Stroke Center - Stroke Trials Registry (www.strokecenter.org/trials);
- Clinical Trials Results register (www.clinicaltrialresults.org).
Searching other resources
In an effort to identify further published, unpublished and ongoing trials, we:
- performed citation tracking using Web of Science Cited Reference Search for all included studies;
- searched the reference lists of included trials and all relevant articles;
- obtained further information from individual trialists;
- contacted other researchers in the field and publicised our preliminary findings at stroke conferences in the UK, Scandinavia, Germany, the Netherlands, Switzerland, Spain, Canada, South America, Australia, Belgium, USA and Hong Kong.
Data collection and analysis
Selection of studies
For this updated review, one author (PF) read the titles and abstracts of the records obtained from the electronic searches and excluded obviously irrelevant studies. We obtained the full copy of the remaining studies and two review authors (PF, PL) independently selected studies for inclusion based on the following eligibility criteria:
- randomised controlled trial;
- service intervention providing a form of organised inpatient (stroke unit) care;
- service aim is to improve functional recovery and survival after stroke;
- trial of stroke patients.
We established the characteristics of unpublished trials through discussion with the trial co-ordinator prior to analysis of the results.
Data extraction and management
If possible, the principal review author (PL) obtained descriptive information about the service characteristics of the organised inpatient (stroke unit) care and conventional care settings through a structured interview or correspondence conducted with the trial co-ordinators (n = 17). We obtained outstanding information from published sources. We then allocated trials to service subgroups. We confirmed outcome data from published sources and supplemented them with unpublished information provided by the co-ordinator of each individual trial. We asked trialists to provide information on the number of participants who were dead, dependent, requiring institutional care or missing at the end of scheduled follow up. For this updated review, for which data were available only from published sources, two review authors (PF, PL) independently extracted data using a standard data extraction form.
We sought subgroup information primarily for the combined outcome of death or requiring institutional care. We obtained unpublished aggregated data for a majority of trials but insufficient amounts of individual patient data were available to allow a comprehensive individual patient data analysis.
We obtained subgroup data regarding the following participant groups (see SUTC 1997a for details):
- age: up to 75 years or greater than 75 years;
- sex: male or female;
- stroke severity: dependency at the time of randomisation (usually within one week of the index stroke):
- mild stroke: equivalent to a Barthel Index of 10 to 20 out of 20 during the first week;
- moderate stroke: equivalent to a Barthel Index of 3 to 9 out of 20 during the first week;
- severe stroke: equivalent to a Barthel Index of 0 to 2 out of 20 during the first week;
- stroke type: ischaemic or haemorrhagic based on neuroimaging.
Assessment of risk of bias in included studies
We assessed risk of bias using The Cochrane Collaboration's risk of bias tool, as described in Chapter 8 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We identified the method of concealment of treatment allocation, the presence of an intention-to-treat analysis and the presence of blinding of outcome assessment as potentially important factors for sensitivity analyses, but we did not use them as exclusion criteria.
Measures of treatment effect
Where our primary outcomes of death, dependency or institutionalisation after the end of scheduled follow-up were reported, we analysed these using the odds ratio (OR) and 95% confidence interval (CI) of an adverse outcome.
As a secondary outcome, we aimed to record length of stay in hospital or an institution as the mean and standard deviation (SD). Where only medians were available, we assumed these were approximate to the mean. Where no other data were provided with the mean value, we inferred the SD as being at least as large as those in the comparable trials using the same measure. Because length of stay was reported in a variety of ways we used standardised mean difference (SMD) and 95% CI.
Unit of analysis issues
We anticipated that the majority of trials would have a simple parallel-group design in which each individual was randomised to one of two treatment groups. We planned to perform subgroup analyses should a trial have three (or more) treatment groups.
Dealing with missing data
Where data were missing for the outcomes of death, dependency or institutionalisation we assumed the participant to be alive, independent and living at home. We aimed to explore the implications of these assumptions in sensitivity analyses.
Assessment of heterogeneity
We planned to determine heterogeneity using the I² statistic. We defined significant heterogeneity as an I² of greater than 50%. Where significant heterogeneity occurred, we explored potential sources using pre-planned sensitivity analyses.
Assessment of reporting biases
We employed a comprehensive search strategy in an effort to avoid reporting biases. To identify unpublished studies we searched trial registers and contacted trialists and other experts in the field.
We checked all individual patient data for internal consistency and consistency with published reports. One review author entered data into the Review Manager software (RevMan 5.2) (RevMan 2012) and a second review author checked the entries. We analysed binary outcome data using OR and 95% CI. We analysed continuous outcome data using SMD and 95% CI. We used a fixed-effect model first but replaced this with a random-effects model if there was significant heterogeneity.
Subgroup analysis and investigation of heterogeneity
Subgroup analyses involved a reanalysis stratified by participant or service subgroup using tabular subgroup data provided by the trialists. We used a fixed-effect approach unless there was statistically significant heterogeneity, in which case results were confirmed using a random-effects statistical model.
We planned sensitivity analyses around the key aspects of trial quality that we identified during our assessment of risk of bias (that is method of randomisation (concealment of treatment allocation), blinding of outcome assessment and a fixed period of follow-up).
Description of studies
Results of the search
The search strategy for previous versions of this review identified 48 potentially eligible trials, of which we excluded 13 (Abissi 1995; Asplund 2000; Davis 2000; Di Lauro 2003; Durastanti 2005; Koton 2005; Langhorne 2001; Moloney 1999; Ricauda 2004; Ronning 1998a; Ronning 1998b; Silva 2004; Walter 2005), two were ongoing (Stone 1998; Wang 2004) and two were awaiting further assessment (HAMLET 2009; Pearson 1988). Therefore, the previous version of this review included 31 trials (6936 participants) in quantitative data syntheses.
For this updated review, the searches of MEDLINE, EMBASE and CINAHL identified 5478 records and from these and the searches of the Cochrane trials registers and other sources, we identified 18 new potentially eligible trials for consideration using the four selection criteria (Figure 1). In addition, we identified newly published data for one previously included trial (Athens 1995).
|Figure 1. Flow diagram illustrating the results of the updated searches|
The assessors agreed on the inclusion of four trials (Guangdong 2008; Guangdong 2009; Huaihua 2004; Hunan 2007) and the exclusion of four trials (Diagana 2008; Middleton 2006; Pappa 2009; Shiraishi 2004) (see Excluded studies), which were newly identified for this updated review. We require further information for seven trials (Anhui 2008; China (Hao) 2010; China (Pei) 2011; China (Wang) 2008; China (Wu) 2007; Haikou 2007; Shanghai 2006) in order to assess eligibility, and an additional three trials (Baden 2007; Beijing 2009; Shanghai 2009) do not yet have available outcome data.
After formal risk of bias assessment the assessors also agreed on the exclusion of seven of the 31 trials included in the previous version of this review. These seven trials employed informal randomisation procedures (quasi-randomised) based on bed availability (Cavallini 2003; Strand 1985; von Arbin 1980; Yagura 2005), a strict admission rota (Hamrin 1982; Patel 2000) or patient date of birth (Ronning 1998). Of the four trials that were awaiting further assessment or were ongoing at the time of the previous literature search, the assessors excluded three trials as no outcome data were available (Pearson 1988; Stone 1998; Wang 2004) and one trial as no data for the comparison of intensive monitoring versus standard ward-based care have been reported for non-surgical control participants (HAMLET 2009).
Therefore, this updated review incorporates an individual patient data meta-analysis for 28 randomised controlled trials with 5855 participants.
Service characteristics within organised (stroke unit) care and conventional care settings
Descriptive information was available for all trials: in seven trials we had access to published information only (Birmingham 1972; Guangdong 2008; Guangdong 2009; Huaihua 2004; Hunan 2007; Illinois 1966; New York 1962), in two trials we had detailed unpublished information (Beijing 2004; Joinville 2003) and in the remaining 19 trials a structured interview was carried out with the trial co-ordinator to determine the service characteristics.
Our original publication outlined the features of the stroke unit trials (SUTC 1997a). In summary, organised inpatient (stroke unit) care was characterised by: (1) co-ordinated multidisciplinary rehabilitation, (2) staff with a specialist interest in stroke or rehabilitation, (3) routine involvement of carers in the rehabilitation process and (4) regular programmes of education and training. Several factors indicating a more intensive or more comprehensive input of care were also associated with the stroke unit setting. Various service models of care exist ( Table 1) but the core characteristics (SUTC 1997a) that were invariably included in the stroke unit setting were: (1) multidisciplinary staffing - that is medical, nursing and therapy staff (usually including physiotherapy, occupational therapy, speech therapy, social work); and (2) co-ordinated multidisciplinary team care incorporating meetings at least once per week. Where both the services compared could satisfy the description of stroke unit care the more-organised system of care was taken as the index service.
Service comparisons within the 28 trials with outcome data are detailed in Table 2. The total number of comparisons is greater than the number of trials because in three trials participants could be randomised to one of two alternatives to stroke unit care; two of these trials used a stratified randomisation procedure (Nottingham 1996; Orpington 1993) and one did not (Dover 1984). In two small trials the conventional care (general medical) group also received some input from a specialist nurse (Illinois 1966; New York 1962). Although this was not strictly general medical ward care, we have included this information since relatively little novel nursing input appears to have been available. The exclusion of these trials would not alter the conclusions of the systematic review substantially. In one trial, some participants appear to have been treated outside the rehabilitation wards (that is by peripatetic team care) but the number is unclear (New York 1962). This trial is currently classified as a mixed rehabilitation ward.
Of the four trials newly identified for this update, three compared a model of stroke unit care using integrated traditional Chinese medicine (TCM) (e.g. acupuncture and herbal remedies) versus standard 'Western medicine' stroke unit care (Guangdong 2008; Hunan 2007) or a general medical ward (Guangdong 2009); one trial compared a comprehensive stroke ward within a neurology unit with a general medical ward (Huaihua 2004). The duration of rehabilitation provided in all four newly identified trials was unclear and in only two trials was the timing of randomisation reported (Guangdong 2009; Huaihua 2004).
Of the 24 previously included trials, 22 incorporated rehabilitation lasting several weeks if required; 16 of these units admitted participants acutely and eight after a delay of one or two weeks. Two trials evaluated an acute stroke (semi-intensive) unit with no continuing rehabilitation. One trial proved difficult to categorise as it contained elements of an acute (semi-intensive) unit but offered some rehabilitation (Athens 1995). It is classified here as a comprehensive stroke unit. No trials evaluated an 'intensive care' model of stroke unit.
Of the 28 excluded studies, 14 were not strictly randomised, four were evaluations of care pathways, four did not have available outcome data, three evaluated an intervention that did not fit our description of organised inpatient (stroke unit) care, two managed intervention and control participants within the same unit and one reported retrospective data from a previous study.
Risk of bias in included studies
|Figure 2. Risk of bias summary: review authors' judgements about each risk of bias item for each included study.|
|Figure 3. Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.|
Fifteen trials (Athens 1995; Dover 1984; Edinburgh 1980; Goteborg-Ostra 1988; Goteborg-Sahlgren 1994; Groningen 2003; Helsinki 1995; Kuopio 1985; Manchester 2003; Montreal 1985; Orpington 1993; Orpington 2000; Svendborg 1995; Tampere 1993; Trondheim 1991) used a clearly concealed randomisation procedure.
Eleven trials (Goteborg-Sahlgren 1994; Groningen 2003; Helsinki 1995; Hunan 2007; Joinville 2003; Kuopio 1985; Manchester 2003; Montreal 1985; Nottingham 1996; Orpington 2000; Perth 1997) used an unequivocally blinded final assessment for all participants.
Incomplete outcome data
Nine trials had minor omissions of death and place of residence data (18 stroke unit participants and 35 controls in total) (Birmingham 1972; Dover 1984; Edinburgh 1980; Manchester 2003; Montreal 1985; Nottingham 1996; Orpington 1993; Orpington 2000; Tampere 1993). For the purpose of our analysis these participants were assumed to be alive and living at home, which may have introduced a minor bias in favour of the control group.
Effects of interventions
The results of the systematic review are presented in six sections as follows.
Section 1: Organised inpatient (stroke unit) care versus alternative care. First, we have outlined the main outcomes for the comparison of organised inpatient (stroke unit) care with an alternative service. Therefore, this section examines the impact of increased levels of organisation of stroke care on patient outcomes. Where both services compared could satisfy the definition of stroke unit care, the more-organised system of care was taken as the index service.
Section 2: Organised inpatient (stroke unit) care versus general medical ward. We have then described the results for the most common comparison: organised stroke unit care versus a general medical ward. This section includes analyses of different subgroups of patient and service type.
Sections 3, 4, 5 and 6: Comparisons of different forms of organised inpatient (stroke unit) care. Finally, we have presented the results for direct comparisons of different forms of organised stroke unit care.
Section 1 : Organised stroke unit care versus alternative care
Comparison 1.1: Death by the end of scheduled follow-up
Outcome data were available for all 28 trials (5855 participants) in which a novel organised inpatient (stroke unit) intervention was compared with an alternative (less-organised) service ( Analysis 1.1). Case fatality recorded at the end of scheduled follow-up (median follow-up 12 months; range six weeks to 12 months) was lower in the organised (stroke unit) care group in 21 of 28 trials. The overall summary estimate was an OR of 0.76 (95% CI 0.66 to 0.88; P = 0.0001). There was a borderline significant subgroup interaction (P = 0.04) with more positive effects seen in subgroups based on trials of stroke wards. When we restricted the analysis to those trials in which scheduled follow-up was continued for a fixed period of six months or one year (that is excluding Beijing 2004; Goteborg-Ostra 1988; Groningen 2003; Guangdong 2008; Guangdong 2009; Illinois 1966; Montreal 1985; New York 1962; Orpington 1993; Orpington 1995), the overall OR was essentially unchanged (OR 0.80, 95% CI 0.69 to 0.93; P = 0.0001).
Comparison 1.2: Death or institutional care by the end of scheduled follow-up
Outcome data were available for 23 trials (4840 participants) ( Analysis 1.2). The median duration of follow-up was one year. The summary result indicated a significant reduction in the odds of a patient dying or requiring long-term institutional care (OR 0.76, 95% CI 0.67 to 0.86; P = 0.0001). There was a borderline significant subgroup interaction (P = 0.02) with more positive effects usually seen in subgroups based on trials of stroke wards. When we excluded trials that had a very short or variable period of follow-up (Beijing 2004; Goteborg-Ostra 1988; Groningen 2003; Illinois 1966; Montreal 1985; New York 1962; Orpington 1993; Orpington 1995), we found that the overall estimate of apparent benefit was unaffected (OR 0.75, 95% CI 0.65 to 0.86; P = 0.0001)
Comparison 1.3: Death or dependency by the end of scheduled follow-up
Outcome data were available for 23 trials (4807 participants) ( Analysis 1.3). The summary result indicated a significant reduction in the odds of the combined adverse outcomes of death or dependency (OR 0.80, 95% CI 0.67 to 0.97; P < 0.00001) with no significant heterogeneity. The conclusions were not altered by the exclusion of trials with a variable follow-up period. The main methodological difficulty when using dependency as an outcome was the degree of blinding at final assessment and the potential for bias if the assessor was aware of the treatment allocation. The results were unchanged (OR 0.74, 95% CI 0.61 to 0.90; P = 0.002) when restricted to those trials in which an unequivocally blinded final assessment for all participants was undertaken (Goteborg-Sahlgren 1994; Groningen 2003; Helsinki 1995; Joinville 2003; Kuopio 1985; Manchester 2003; Montreal 1985; Nottingham 1996; Orpington 2000).
Comparison 1.4 and 1.5: Length of stay (days) in a hospital or institution or both
Length of stay data were available for 18 individual trials (4115 participants) ( Analysis 1.4; Analysis 1.5). Mean (or median) length of stay ranged from 11 to 162 days in the stroke unit groups and from 12 to 129 days in the control groups. Twelve trials reported a shorter length of stay in the stroke unit group and six a more prolonged stay. The calculation of a summary result for length of stay was subject to major methodological limitations: length of stay was calculated in different ways (for example acute hospital stay, total stay in hospital or institution), two trials recorded median rather than mean length of stay and in two trials the SD had to be inferred from the P value or from the results of similar trials. Overall, using a random-effects model, there was no significant reduction in the length of stay in the stroke unit group (SMD -0.15, 95% CI -0.32 to 0.02; P = 0.09). The summary estimate was complicated by considerable heterogeneity that limits the extent to which more general conclusions can be inferred.
We reanalysed results according to whether length of stay was defined as stay in acute hospital only or the total length of stay in a hospital or institution in the first year after stroke ( Analysis 1.5). There was no significant difference between the two groups and no reduction in heterogeneity.
Comparisons 1.6, 1.7 and 1.8: Death, death or institutional care, and death or dependency at five-year follow-up
Three trials (1139 participants) carried out supplementary studies extending participant follow-up to five years post-stroke (Athens 1995; Nottingham 1996; Trondheim 1991) for the outcome of death, and two trials (535 participants) carried out supplementary studies extending participant follow-up to five years post-stroke (Nottingham 1996; Trondheim 1991) for the outcomes of death or institutionalisation and death or dependency. The OR for adverse outcomes continued to favour stroke unit care but with some heterogeneity: death 0.74 (95% CI 0.59 to 0.94; P = 0.01) ( Analysis 1.6), death or institutional care 0.59 (95% CI 0.33 to 1.05; P = 0.07) ( Analysis 1.7) and death or dependency 0.54 (95% CI 0.22 to 1.34; P = 0.18) ( Analysis 1.8).
Comparisons 1.9, 1.10 and 1.11: Death, death or institutional care, and death or dependency at 10-year follow-up
Three trials (1152 participants) extended follow-up to 10 years post stroke for the outcome of death (Athens 1995; Nottingham 1996; Trondheim 1991) and two trials (535 participants) extended follow-up to 10 years post stroke for the outcomes of death or institutionalisation and death or dependency (Nottingham 1996; Trondheim 1991). Again, the summary results continued to favour stroke unit care but with increased heterogeneity and a loss of statistical significance for the outcomes of death and death or dependency: OR for death 0.67 (95% CI 0.43 to 1.03; P = 0.07) ( Analysis 1.9), death or institutional care 0.57 (95% CI 0.37 to 0.88; P = 0.01) ( Analysis 1.10) and death or dependency 0.70 (95% CI 0.27 to 1.80; P = 0.45) ( Analysis 1.11).
Participant satisfaction and quality of life
Only three trials recorded outcome measures related to participant quality of life (Nottingham Health Profile; EuroQol Quality of Life Scale) (Manchester 2003; Nottingham 1996; Trondheim 1991). In Nottingham 1996 and Trondheim 1991, there was a pattern of improved results among stroke unit survivors with the results attaining statistical significance in the two trials. However, for the Manchester 2003 trial there was no statistically significant difference between the study groups. We could find no systematically gathered information on participant preferences.
Sensitivity analyses by trial characteristics
In view of the variety of trial methodologies described we carried out a sensitivity analysis based only on those trials with a low risk of bias: (1) secure randomisation procedures; (2) unequivocally blinded outcome assessment; (3) a fixed one-year period of follow-up. Seven trials met all of these criteria (Goteborg-Sahlgren 1994; Groningen 2003; Helsinki 1995; Kuopio 1985; Manchester 2003; Nottingham 1996; Orpington 2000). Stroke unit care was associated with a statistically non-significant reduction in the odds of death (OR 0.82, 95% CI 0.64 to 1.05; P = 0.12) and statistically significant reductions in the odds of death or institutional care (OR 0.77, 95% CI 0.63 to 0.96; P = 0.02) and death or dependency (OR 0.76, 95% CI 0.62 to 0.93; P = 0.009).
Subgroup analyses by patient characteristics
Predefined subgroup analyses were based on previous versions of this review (SUTC 1997a) and each subgroup analysis included data from at least nine trials (at least 1111 participants). These were based on participants' age, sex and initial stroke severity. For this updated version we have incorporated additional data based on pathological stroke type (ischaemic or haemorrhagic stroke). See Figure 4, Figure 5 and Figure 6.
|Figure 4. Analysis of patient characteristics on effectiveness of organised stroke unit care versus alternative service for the outcome of death by the end of scheduled follow-up.|
|Figure 5. Analysis of patient characteristics on effectiveness of organised stroke unit care versus alternative service for the outcome of death or institutionalisation by the end of scheduled follow-up.|
|Figure 6. Analysis of patient characteristics on effectiveness of organised stroke unit care versus alternative service for the outcome of death or dependency by the end of scheduled follow-up.|
Caution is needed when interpreting these subgroup analyses particularly as a relatively small number of outcome events were observed, which limits the statistical power. Furthermore, the results may change depending on the outcome chosen. These results indicate that in general the magnitude of benefit seemed greater for participants with more-severe stroke. However, stroke unit benefits are apparent across a range of participant subgroups (that is age, sex, initial stroke severity and stroke type). Analysis by stroke severity confirmed that there was no statistically significant reduction in case fatality in mild stroke patients (OR 1.03, 95% CI 0.67 to 1.58). However, mild stroke patients managed in stroke units had a reduced risk of dependency (OR 0.76, 95% CI 0.58 to 1.00).
Section 2: Organised stroke unit care versus general medical wards
Comparisons 2.1, 2.2 and 2.3: Death, death or institutional care, and death or dependency by the end of scheduled follow-up
A variety of predefined subgroup analyses were carried out based on service characteristics. Two different models of care (comprehensive stroke ward, mixed assessment or rehabilitation ward) tended to be more effective than general medical ward care. However, for the comparison of rehabilitation stroke wards or mobile team care (peripatetic service) versus general medical wards there were no statistically significant differences. Overall, stroke unit care showed reductions in the odds of death recorded at final (median one year) follow-up (OR 0.81, 95% CI 0.69 to 0.94; P = 0.005) ( Analysis 2.1), the odds of death or institutionalised care (OR 0.78, 95% CI 0.68 to 0.89; P = 0.0003) ( Analysis 2.2) and the odds of death or dependency (OR 0.79, 95% CI 0.68 to 0.90; P = 0.0007) ( Analysis 2.3). Interpretation of length of stay data was complicated by substantial heterogeneity. There was no evidence of a systematic increase in length of stay.
Sections 3, 4, 5 and 6: Comparisons of different forms of organised stroke unit care
In planning our analyses we specified in advance that an important question for service planning would be whether the benefits of stroke unit care depended upon the establishment of a ward dedicated only to stroke care (stroke ward) or could be achieved through a mobile stroke team or a generic disability service (mixed rehabilitation unit) that specialises in the management of disabling illness including stroke. We therefore analysed those trials that directly compared two different forms of organised stroke unit care that met the basic descriptive criteria of stroke unit care (see 'Description of Studies'): multidisciplinary staffing co-ordinated through regular team meetings.
Of the eight trials identified for which outcome data were available, one compared an acute (semi-intensive) stroke ward with a comprehensive stroke ward (Groningen 2003), one compared an acute (semi-intensive) stroke ward with a mixed rehabilitation ward (Tampere 1993), one compared a stroke ward that combined acute care and rehabilitation (comprehensive stroke ward) with a general medical ward where care was co-ordinated by a multidisciplinary team (mobile team care) (Orpington 2000), two compared a stroke ward with integrated TCM with a 'Western medicine' stroke ward (Guangdong 2008; Hunan 2007) and three incorporated designs in which patients could be randomised either to a stroke rehabilitation ward or to conventional care in either a general medical ward or mixed rehabilitation ward within a Department of Geriatric Medicine (Dover 1984; Nottingham 1996; Orpington 1993). Data were available for both these subgroups of participants.
Section 3: Acute stroke ward versus alternative service
Analysis 3.1, Analysis 3.2, Analysis 3.3 and Analysis 3.4: Death, death or institutional care, death or dependency by the end of scheduled follow-up and length of stay in hospital or institution
Overall, acute (monitoring) units did not have statistically significant different odds of death, death or requiring institutional care, or death or dependency when compared with acute (non-intensive) units. Interpretation of length of stay data was complicated by substantial heterogeneity. There was no evidence of a systematic increase in length of stay.
Section 4: Comprehensive stroke ward versus alternative service
Analysis 4.1, Analysis 4.2, Analysis 4.3 and Analysis 4.4: Death, death or institutional care, death or dependency by the end of scheduled follow-up and length of stay in hospital or institution
One trial compared a comprehensive stroke ward (providing acute care and rehabilitation) with admission to general wards where care was provided by a mobile stroke team (Orpington 2000). They found statistically significant (P < 0.001) reductions in death and the combined outcome of death or institutional care among the comprehensive stroke ward group. Fewer comprehensive stroke ward participants were dead or dependent at the end of follow-up, but this result did not achieve statistical significance. However, Orpington 2000 is the only trial in this analysis comparing comprehensive stroke wards with an alternative service so these results require confirmation. There was no significant difference in length of stay.
Section 5: Rehabilitation stroke ward versus alternative service
Analysis 5.1, Analysis 5.2, Analysis 5.3 and Analysis 5.4: Death, death or institutional care, death or dependency by the end of scheduled follow-up and length of stay in hospital or institution
There was a pattern of improved outcomes in the stroke rehabilitation ward with statistically significantly fewer deaths (P = 0.02) and a statistically non-significant trend for fewer participants with the composite end points of death or requiring institutional care and death or dependency. However, the numbers were small and no definite conclusions could be drawn. Interpretation of length of stay data was complicated by substantial heterogeneity. There was no evidence of a systematic increase in length of stay.
Section 6: Stroke ward plus TCM versus alternative service
Analysis 6.1: Death at the end of scheduled follow-up
There was no significant difference in the odds of death in a stroke ward with integrated TCM when compared with a standard 'Western medicine' stroke ward. The type of care provided in a stroke unit with integrated TCM has not been well described. The overall estimate is based on the results of a single trial and no definitive conclusions can be drawn.
Summary of main results
The updated information in Section 1 confirms our previous observations that people receiving organised inpatient (stroke unit) care were more likely to survive, regain independence and return home than those receiving a less-organised service. This apparent effect remains of moderate statistical significance for case fatality. The conclusions could be overturned by a number of unpublished randomised trials with neutral results. However, the observed reductions in the combined adverse outcomes (death or institutionalisation, death or dependency) are much more robust statistically. The three trials that have extended follow-up for five or 10 years have found a sustained benefit among stroke unit patients.
The requirement for long-term care is a useful surrogate for disability (Barer 1993) and is likely to show good inter-observer agreement. The absolute rates of institutionalisation, however, will be influenced by a variety of national and cultural factors. The combined adverse outcome of death or dependency is a more direct measure of patient outcome, but is subject to potential observer bias where final assessments were not carried out in a blinded manner. The sensitivity analysis based on those trials that used an unequivocally blinded assessment suggested that such bias has not seriously influenced the results.
The analysis of length of stay is complicated by the different methods of reporting results, the widely varying control group lengths of stay and the statistically significant heterogeneity between different trials. The most reasonable conclusion appears to be that there was no systematic increase in length of stay associated with organised (stroke unit) care and there may have been a modest reduction.
In any discussion of the comparison of results in different subgroups it is worth bearing in mind that the main issue is not whether a subgroup result is statistically different from zero but whether there is statistically significant heterogeneity between the estimates of effect in each of the relevant subgroups. Our analyses are limited by relatively low statistical power and so must be interpreted with great caution. The subgroup analyses indicate that the observed benefits of organised stroke unit care are not limited to any one subgroup of patients or models of stroke unit organisation that were examined. Apparent benefits were seen in people of both sexes, aged under and over 75 years, with ischaemic or haemorrhagic stroke and across a range of stroke severities.
The apparent relation between stroke severity and outcome must be interpreted with caution. People with more severe stroke symptoms are at greater risk of death or requiring institutional care and hence stand to gain more from treatment. Patients with a mild stroke appeared to benefit from stroke unit care when death or dependency was the chosen outcome (Figure 6), but this effect was less certain for the outcomes of death, or death or institutional care. Two approaches to stroke unit care, that is comprehensive units and mixed assessment/rehabilitation units, tended to be more effective than care in a general medical ward. There was a similar trend for rehabilitation stroke units. However, mobile stroke care appeared to have a more neutral effect. Apparent benefits were seen in units with acute admission policies as well as those with delayed admission policies and in units which could offer a period of rehabilitation lasting several weeks.
Comparison of different types of stroke unit care
Results Sections 3 to 6 of the review focused on those trials that directly compared two different forms of care, both of which met our basic definition of organised inpatient (stroke unit) care: multidisciplinary team care co-ordinated through regular meetings. The results of this analysis indicate statistically significantly improved results from a dedicated stroke ward over a mobile stroke team. There were also trends towards better outcomes within the dedicated stroke rehabilitation ward setting as opposed to the mixed rehabilitation ward, and within the acute (semi-intensive) ward as opposed to the comprehensive ward. However, in none of the three primary outcomes was there a convincing statistically significant result and more information is required. No firm conclusions could be drawn for the comparisons of a stroke ward integrated with TCM versus a 'Western medicine' stroke ward or an acute (semi-intensive) ward with a mixed rehabilitation unit.
Costs and benefits
Stroke units appear to improve outcomes, but at what cost? In cost terms, length of stay is likely to dominate any individual component of acute patient care and rehabilitation. Longer-term costs are likely to be dominated by the need for nursing care. Studies from several developed countries (Warlow 2008) have shown that fixed costs (particularly nursing staff salaries) account for over 90% of spending on people with acute stroke. Remedial therapy represents only a small proportion of the total cost of hospitalisation. In one analysis, stroke unit care was not clearly associated with an increase in total health and social care costs, but these conclusions were sensitive to some variations in cost estimates (Major 1998). More research is required to elucidate the cost implications of stroke units.
Overall completeness and applicability of evidence
Our original systematic review of organised inpatient (stroke unit) care (SUTC 1997a) addressed the question of whether improving the organisation of inpatient stroke care could bring about important improvements in patient outcomes in comparison with the contemporary conventional care. This analysis has now been extended and updated in Section 1 to reflect the comparison of 'more-organised' versus 'less-organised' care. We have done this because some recent trials have included service comparisons where a stroke unit service based in a stroke ward was compared with a less-organised alternative service (such as mixed rehabilitation ward or mobile stroke team) that was not strictly conventional care. This approach to analysis allows one to view all service comparisons before focusing on various subgroup comparisons.
This update includes four new trials (763 participants), but the overall conclusions remain unaltered in comparison with previous versions. The review now summarises data from a total of 28 trials (5855 participants) from 12 countries in Asia, Australasia, Europe, North America and South America. The majority of trials have been performed in high-income countries; the applicability of stroke unit care in low- or middle-income countries is less clear (Langhorne 2012).
As discussed, our subgroup analyses suggest the benefits of organised inpatient (stroke unit) care are seen across a wide range of stroke patients. This is supported by evidence from observational studies of stroke unit care (Seenan 2007), which have established that stroke units can operate effectively in routine settings beyond a specialised research environment. The current analysis does not explain how stroke units may improve patient outcomes. This could be due to greater staff expertise, better diagnostic procedures, better nursing care, early mobilisation, the prevention of complications or more effective rehabilitation procedures (Langhorne 1998).
Quality of the evidence
The quality of evidence in this updated review has been made more uniform by the exclusion of several quasi-randomised prospective controlled clinical trials that were previously included in the data synthesis (see Description of studies). The main reason for this change was to simplify the inclusion criteria for this and future updates. However, it is worth noting that the exclusion of these trials did not affect the overall estimate of treatment effect.
We judged some trials to be at high risk of bias due to poor allocation concealment and unblinded outcome assessment; in others, these important methodological aspects were not clearly reported making a judgement of risk of bias difficult. The improvement in survival observed with stroke unit care no longer remained statistically significant in sensitivity analyses restricted to the seven trials at low risk of bias. It is possible that methodological limitations within the trials led to an overestimation of the effect size for this outcome. It is reassuring that effect sizes for the composite adverse outcomes of death or institutionalisation or death or dependency remained largely unaltered.
We recognise that some of the included trials are relatively old, possibly with entirely different standards of care from those used currently. Similarly, although a majority of included trials were fairly recent, most would still have been undertaken in an era without routine access to intravenous thrombolysis for acute stroke. While essentially all stroke patients would be eligible for admission to a stroke unit, only a small proportion would be eligible for treatment with thrombolysis even in the most established acute centres. Moreover, all included trials were randomised, therefore any differences in the standard of care should not have had a confounding effect on the final conclusions.
Potential biases in the review process
Through a comprehensive search strategy and established connections with other researchers in the field we are confident that we have identified all potentially relevant studies. We did not search the Chinese databases. However, we were unable to classify or obtain useable outcome data for seven of the 11 Chinese studies we did identify for this update (Anhui 2008; China (Hao) 2010; China (Pei) 2011; China (Wang) 2008; China (Wu) 2007; Haikou 2007; Shanghai 2006). We recognise that the absence of data from these studies in our meta-analysis could potentially introduce bias.
Methodological limitations may also have influenced the analysis of descriptive information about service organisation (SUTC 1997a). We collated service descriptions retrospectively through discussion with the trialists who ran the organised (stroke unit) care. Our findings may therefore be biased towards the expectations of the trialists and by a tendency to discuss the results with the trialists who ran the organised stroke unit care more so than with those who ran the conventional care. At best, this represents a strictly factual account of service characteristics; at worst, it represents a consensus view of the trialists about which features of stroke unit care were effective.
Implications for practice
People with acute stroke are more likely to survive, return home and regain independence if they receive organised inpatient (stroke unit) care. This is typically provided by a co-ordinated multidisciplinary team operating within a discrete stroke ward that can offer a substantial period of rehabilitation if required. There are no firm grounds for restricting access according to a person's age, sex, stroke severity or pathological stroke type (that is ischaemic or haemorrhagic).
Since the original publication of this review, stroke services in many developed countries have undergone substantial reorganisation in line with national strategies and clinical practice guidelines to enable improvements in access to stroke unit care. More recently, stroke services in many countries have been further reorganised to reflect a two-tiered (or hub-and-spoke) model of care in which a central 'comprehensive stroke centre' (or 'hyper-acute stroke unit') is equipped with facilities for acute intravenous or intra-arterial treatments, intensive monitoring, advanced imaging and neurosurgery. These then serve a number of 'primary stroke centres' or stroke units within a hospital network or geographical location. Although this approach seems almost intuitive to many stroke clinicians, it has never been formally tested in randomised controlled trials. Until such trials are available, stroke services should ensure that every stroke patient receives the core service characteristics identified in the randomised trials.
Implications for research
Future trials should focus on examining the potentially important components of stroke unit care and direct comparisons of different models of organised stroke unit care, particularly with regard to the hyper-acute stroke unit model. In low-income healthcare settings, appropriately powered clinical trials could help define how barriers to the establishment of stroke units could be overcome (Langhorne 2012). Outcome measures should not only include the outcomes of death, dependency and institutionalisation, but also domains of patient satisfaction, quality of life and cost. Pre-planned collaboration between comparable trials could alleviate some of the problems of retrospective systematic reviews such as ensuring that similar variables and outcomes are recorded in any new trial.
Anyone carrying out a relevant randomised trial of a stroke service component is invited to contact Peter Langhorne regarding a future collaborative review.
This review is dedicated to the memory of Peter Berman, Mona Britton and Richard Stevens.
Data and analyses
- Top of page
- Authors' conclusions
- Data and analyses
- What's new
- Contributions of authors
- Declarations of interest
- Sources of support
- Index terms
Appendix 1. MEDLINE search strategy
MEDLINE (Ovid) search strategy
1. cerebrovascular disorders/ or exp basal ganglia cerebrovascular disease/ or exp brain ischemia/ or exp carotid artery diseases/ or exp intracranial arterial diseases/ or exp "intracranial embolism and thrombosis"/ or exp intracranial hemorrhages/ or stroke/ or exp brain infarction/ or exp vertebral artery dissection/
2. (stroke or cerebrovasc$ or brain vasc$ or cerebral vasc$ or cva$ or apoplex$).tw.
3. ((brain$ or cerebr$ or cerebell$ or vertebrobasilar or hemispher$ or intracran$ or intracerebral or infratentorial or supratentorial or MCA or anterior circulation or posterior circulation or basal ganglia) adj5 (isch?emi$ or infarct$ or thrombo$ or emboli$)).tw.
4. ((brain$ or cerebr$ or cerebell$ or intracerebral or intracran$ or parenchymal or intraventricular or infratentorial or supratentorial or basal gangli$) adj5 (haemorrhage$ or hemorrhage$ or haematoma$ or hematoma$ or bleed$)).tw.
5. 1 or 2 or 3 or 4
6. hospital units/ or patient care team/
7. (stroke adj3 (unit or units or ward or wards or hospital or hospitals or centre$ or team or teams)).tw.
8. ((organi?ed or structured) adj3 care).tw.
9. (rehabilitation adj3 (unit or units or ward or wards or hospital or hospitals or centre$ or team or teams)).tw.
10. (multidisciplinary adj3 (team or teams or staff$ or care or rehabilitation or unit or units or ward or wards)).tw.
11. ((dedicated or discrete or comprehensive) adj5 (ward or wards or unit or units or stroke care)).tw.
12. ((specialist or specialized or specialised) adj5 (nurs$ or staff$ or care or unit or units or ward or wards)).tw.
13. (organi?ed adj3 (unit or units or ward or wards)).tw.
14. focus$ care.tw.
15. (package$ adj care).tw.
16. (intensive adj3 stroke adj3 care).tw.
17. Intensive Care Units/ or critical care/ or intensive care/
19. 5 and 18
20. Randomized Controlled Trials as Topic/
21. random allocation/
22. Controlled Clinical Trials as Topic/
23. control groups/
24. clinical trials as topic/
25. double-blind method/
26. single-blind method/
27. Research Design/
28. Program Evaluation/
29. randomised controlled trial.pt.
30. controlled clinical trial.pt.
31. clinical trial.pt.
33. (controlled adj5 (trial$ or stud$)).tw.
34. (clinical$ adj5 trial$).tw.
35. ((control or treatment or experiment$ or intervention) adj5 (group$ or subject$ or patient$)).tw.
36. (quasi-random$ or quasi random$ or pseudo-random$ or pseudo random$).tw.
37. ((control or experiment$ or conservative) adj5 (treatment or therapy or procedure or manage$)).tw.
38. ((singl$ or doubl$ or tripl$ or trebl$) adj5 (blind$ or mask$)).tw.
39. (assign$ or allocat$).tw.
43. 19 and 42
44. exp animals/ not humans.sh.
45. 43 not 44
46. limit 45 to ed=20080101-20120904
Appendix 2. EMBASE search strategy
EMBASE (Ovid) search strategy
1. cerebrovascular disease/ or basal ganglion hemorrhage/ or exp brain hematoma/ or exp brain hemorrhage/ or exp brain infarction/ or exp brain ischemia/ or exp carotid artery disease/ or cerebral artery disease/ or cerebrovascular accident/ or exp intracranial aneurysm/ or exp occlusive cerebrovascular disease/ or stroke/
2. stroke patient/
3. (stroke or cerebrovasc$ or brain vasc$ or cerebral vasc$ or cva$ or apoplex$).tw.
4. ((brain$ or cerebr$ or cerebell$ or vertebrobasilar or hemispher$ or intracran$ or intracerebral or infratentorial or supratentorial or MCA or anterior circulation or posterior circulation or basal ganglia) adj5 (isch?emi$ or infarct$ or thrombo$ or emboli$)).tw.
5. ((brain$ or cerebr$ or cerebell$ or intracerebral or intracran$ or parenchymal or intraventricular or infratentorial or supratentorial or basal gangli$) adj5 (haemorrhage$ or hemorrhage$ or haematoma$ or hematoma$ or bleed$)).tw.
6. 1 or 2 or 3 or 4 or 5
7. "hospital subdivisions and components"/
8. ward/ or emergency ward/ or nursing unit/
9. intensive care unit/
10. exp intensive care/
11. (stroke adj3 (unit or units or ward or wards or hospital or hospitals or centre$ or team or teams)).tw.
12. ((organi?ed or structured) adj3 care).tw.
13. (rehabilitation adj3 (unit or units or ward or wards or hospital or hospitals or centre$ or team or teams)).tw.
14. (multidisciplinary adj3 (team or teams or staff$ or care or rehabilitation or unit or units or ward or wards)).tw.
15. ((dedicated or discrete or comprehensive) adj5 (ward or wards or unit or units or stroke care)).tw.
16. ((specialist or specialized or specialised) adj5 (nurs$ or staff$ or care or unit or units or ward or wards)).tw.
17. (organi?ed adj3 (unit or units or ward or wards)).tw.
18. focus$ care.tw.
19. (package$ adj care).tw.
20. (intensive adj3 stroke adj3 care).tw.
22. 6 and 21
23. stroke unit/
24. 22 or 23
25. Randomized Controlled Trial/
27. Controlled Study/
28. control group/
29. clinical trial/
30. Double Blind Procedure/
31. Single Blind Procedure/ or triple blind procedure/
32. Parallel Design/
34. (controlled adj5 (trial$ or stud$)).tw.
35. (clinical$ adj5 trial$).tw.
36. ((control or treatment or experiment$ or intervention) adj5 (group$ or subject$ or patient$)).tw.
37. (quasi-random$ or quasi random$ or pseudo-random$ or pseudo random$).tw.
38. ((control or experiment$ or conservative) adj5 (treatment or therapy or procedure or manage$)).tw.
39. ((singl$ or doubl$ or tripl$ or trebl$) adj5 (blind$ or mask$)).tw.
40. (assign$ or alternate or allocat$ or counterbalance$ or multiple baseline).tw.
44. 24 and 43
45. heart stroke volume/ or heat stroke/ or stroke volume.tw. or heat stroke.tw.
46. 44 not 45
47. limit 46 to em=200801-201249
48. limit 47 to human
Appendix 3. CINAHL search strategy
CINAHL search strategy (1982 to September 2012)
S44 .S28 and S43
S43 .S29 or S30 or S31 or S32 or S33 or S34 or S35 or S36 or S38 or S39 or S40 or S41 or S42
S42 .TI trial
S41 .TI controls OR AB controls
S40 .TI ( assign* or allocat* ) OR AB ( assign* or allocat* )
S39 .TI ( (singl* or doubl* or tripl* or trebl*) N5 (blind* or mask*) ) OR AB ( (singl* or doubl* or tripl* or trebl*) N5 (blind* or mask*) )
S38 .TI ( (control or experiment* or conservative) N5 (treatment or therapy or procedure or manage*) ) OR AB ( (control or experiment* or conservative) N5 (treatment or therapy or procedure or manage*) )
S37 .TI ( quasi-random* or quasi random* or pseudo-random* or pseudo random* ) OR AB ( quasi-random* or quasi random* or pseudo-random* or pseudo random* )
S36 .TI ( (control or treatment or experiment* or intervention) N5 (group* or subject* or patient*) ) OR AB ( (control or treatment or experiment* or intervention) N5 (group* or subject* or patient*) )
S35 .TI clinical* N5 trial* OR AB clinical* N5 trial*
S34 .TI ( controlled N5 (trial* or stud*) ) OR AB ( controlled N5 (trial* or stud*) )
S33 .TI random* OR AB random*
S32 .(MH "Program Evaluation")
S31 .(MH "Random Assignment")
S30 .(ZT "clinical trial") or (ZT "randomised controlled trial")
S29 .(MH "Clinical Trials") OR (MH "Double-Blind Studies") OR (MH "Intervention Trials") OR (MH "Randomized Controlled Trials") OR (MH "Single-Blind Studies") OR (MH "Therapeutic Trials") OR (MH "Triple-Blind Studies")
S28 .S1 or S27
S27 .S11 and S26
S26 .S12 or S13 or S14 or S15 or S16 or S17 or S18 or S19 or S20 or S21 or S22 or S23 or S24 or S25
S25 .TI intensive N3 stroke N3 care OR AB intensive N3 stroke N3 care
S24 .TI package* N3 care OR AB package* N3 care
S23 .TI focus* care OR AB focus* care
S22 .TI ( organi?ed N3 (unit or units or ward or wards) ) OR AB ( organi?ed N3 (unit or units or ward or wards) )
S21 .TI ( (specialist or specialized or specialised) N5 (nurs* or staff* or care or unit or units or ward or wards) ) OR AB ( (specialist or specialized or specialised) N5 (nurs* or staff* or care or unit or units or ward or wards) )
S20 .TI ( (dedicated or discrete or comprehensive) N5 (ward or wards or unit or units or stroke care) ) OR AB ( (dedicated or discrete or comprehensive) N5 (ward or wards or unit or units or stroke care) )
S19 .TI ( multidisciplinary N3 (team or teams or staff* or care or rehabilitation or unit or units or ward or wards) ) OR AB ( multidisciplinary N3 (team or teams or staff* or care or rehabilitation or unit or units or ward or wards) )
S18 .TI ( rehabilitation N3 (unit or units or ward or wards or hospital or hospitals or centre* or team or teams) ) OR AB ( rehabilitation N3 (unit or units or ward or wards or hospital or hospitals or centre* or team or teams) )
S17 .TI ( (organi?ed or structured) N3 care ) OR AB ( (organi?ed or structured) N3 care )
S16 .TI ( stroke N3 (unit or units or ward or wards or hospital or hospitals or centre* or team or teams) ) OR AB ( stroke N3 (unit or units or ward or wards or hospital or hospitals or centre* or team or teams) )
S15 .(MH "Critical Care Nursing")
S14 .(MH "Critical Care")
S13 .(MH "Multidisciplinary Care Team")
S12 .(MH "Hospital Units") OR (MH "Intensive Care Units")
S11 .S2 or S3 or S4 or S7 or S10
S10 .S8 and S9
S9 .TI ( haemorrhage* or hemorrhage* or haematoma* or hematoma* or bleed* ) or AB ( haemorrhage* or hemorrhage* or haematoma* or hematoma* or bleed* )
S8 .TI ( brain brain* or cerebr* or cerebell* or intracerebral or intracran* or parenchymal or intraventricular or infratentorial or supratentorial or basal gangli* ) or AB (brain* or cerebr* or cerebell* or intracerebral or intracran* or parenchymal or intraventricular or infratentorial or supratentorial or basal gangli* )
S7 .S5 and S6
S6 .TI ( ischemi* or ischaemi* or infarct* or thrombo* or emboli* ) or AB ( ischemi* or ischaemi* or infarct* or thrombo* or emboli* )
S5 .TI (brain* or cerebr* or cerebell* or vertebrobasilar or hemispher* or intracran* or intracerebral or infratentorial or supratentorial or MCA or anterior circulation or posterior circulation or basal ganglia) or AB (brain* or cerebr* or cerebell* or vertebrobasilar or hemispher* or intracran* or intracerebral or infratentorial or supratentorial or MCA or anterior circulation or posterior circulation or basal ganglia )
S4 .TI (stroke or cerebrovasc* or brain vasc* or cerebral vasc* or cva* or apoplex*) or AB (stroke or cerebrovasc* or brain vasc* or cerebral vasc* or cva* or apoplex* )
S3 .(MH "Stroke Patients")
S2 .(MH "Cerebrovascular Disorders") OR (MH "Basal Ganglia Cerebrovascular Disease+") OR (MH "Carotid Artery Diseases+") OR (MH "Cerebral Ischemia+") OR (MH "Cerebral Vasospasm") OR (MH "Intracranial Arterial Diseases+") OR (MH "Intracranial Embolism and Thrombosis") OR (MH "Intracranial Hemorrhage+") OR (MH "Stroke") OR (MH "Vertebral Artery Dissections")
S1 .(MH "Stroke Units")
The 95% CI includes 1.0 for patients with mild stroke. I would conclude that for this subgroup, there is no significant benefit insofar as preventing death or institutional care. I certify that I have no affiliations with or involvement in any organisation or entity with a direct financial interest in the subject matter of my criticisms.
Don Hess 2000-09-12 16:05
Criticism editor summary
Regarding the outcome 'death or institutional care' for patients with mild stroke, the 95% CIs around the odds ratio suggest that stroke unit care is not beneficial in this subgroup of patients. This is not made clear in the review's abstract, results and discussion.
Thank you for your comment. The proper test in a subgroup analysis is not whether a subgroup result is statistically different from zero but whether there is statistically significant heterogeneity between the estimates of effect in each of the relevant subgroups. In our subgroup analysis the mild stroke patient group does indeed have CIs which include no effect (odds ratio = 1.0). However, we do not believe we can at present conclude that this subgroup of patients have a different result from the totality of patients. First, the statistical power of this analysis is limited because the mild stroke subgroup had relatively few outcome events (death or institutional care). Second, the mild stroke subgroup result is not significantly different from that of the moderate and severe subgroups. These analyses are explored in more detail in Stroke Unit Trialists' Collaboration. How do stroke units improve patient outcomes? A collaborative systematic review of the randomised trials. Stroke 1997;28:2139-44.
Peter Langhorne 07/03/2001
Numerical error, 30 June 2014
Possible typo? The abstract states "... odds of death recorded at final (median one year) follow-up (odds ratio (OR) 0.87..." but text on page 15 (Comparisons 2.1, 2.2, 2.3 ...) and forest plot for 2.1 report OR = 0.81.
Dr Zekowski is correct. There appears to have been an error when updating the review. In the abstract the correct OR for death should be (OR 0.81, 95% CI 0.69 to 0.94; P = 0.005). This has now been corrected in the text.
Feedback: Steven Zekowski MD
Response: Peter Langhorne
Last assessed as up-to-date: 28 February 2013.
Protocol first published: Issue 1, 1995
Review first published: Issue 1, 1995
Contributions of authors
For this version of the review, Patricia Fearon performed the updated literature searches, reanalysed the data and redrafted the manuscript.
Peter Langhorne initiated and co-ordinated the review project, was principal grant holder and revised the updated report.
Peter Langhorne and Patricia Fearon formed the writing committee that was responsible for the re-drafting of the report.
The following collaborators provided original data, advice and comment, and assisted with the redrafting of the report: C Blomstrand (Goteborg, Sweden); NL Cabral (Joinville, Brazil); A Cavallini (Pavia, Italy); P Dey (Manchester, England); E Hamrin (Uppsala, Sweden); G Hankey (Perth, Australia); B Indredavik (Trondheim, Norway); L Kalra (Orpington, England); M Kaste (Helsinki, Finland); SO Laursen (Svendborg, Denmark); RH Ma (Beijing, China); N Patel (Cape Town, South Africa); H Rodgers (Newcastle, England); MO Ronning (Akershus, Norway); J Sivenius (Kuopio, Finland); G Sulter (Groningen, Netherlands); A Svensson (Goteborg, Sweden); K Vemmos (Athens, Greece); S Wood-Dauphinee (Montreal, Canada); H Yagura (Osaka, Japan).
Previous versions of the review also received data, advice and comment from: K Asplund (Umea, Sweden); P Berman (Nottingham, England); M Britton (Stockholm, Sweden); J Douglas (Administrator); T Erila (Tampere, Finland); M Garraway (Edinburgh, Scotland); M Ilmavirta (Tampere, Finland); R Stevens (Dover, England); SP Stone (London, England); Brian Williams (Glasgow, Scotland).
Important contributions were also made by the following who supplied useful information and comment: D Deleo (Perth, Australia); A Drummond (Nottingham, England); R Fogelholm (Jyvaskyla, Finland); N Lincoln (Nottingham, England); H Palomaki (Helsinki, Finland); J Slattery (London, England); T Strand (Umea, Sweden); CP Warlow (Edinburgh, Scotland); L Wilhelmsen (Goteborg, Sweden).
Declarations of interest
Most of the Stroke Unit Trialists Collaboration members carried out trials that are included in the review.
Sources of support
- University of Glasgow, UK.
- University of Edinburgh, UK.
- Chest, Heart and Stroke Scotland, UK.
Medical Subject Headings (MeSH)
MeSH check words
* Indicates the major publication for the study