Immobile Stroke Patients Research Articles

A mobile application-based post-stroke care strategy for survivors and their caregivers for prevention and management of post-stroke complications - "Stroke Home Care:" Development and feasibility.

In developing nations such as India, a disparity exists between the available resources for stroke rehabilitation and the substantial burden of stroke cases. Consequently, the provision of cost-effective and multidisciplinary post-stroke rehabilitation care to stroke survivors becomes of paramount importance. The utilization of mobile applications (apps) for stroke care has been on the rise, offering a personalized and pragmatic solution with the potential for wider reach in settings constrained by limited resources. To address the unmet needs in the prevention and management of post-stroke complications, we conceptualized a strategy known as a mobile application-based post-stroke care strategy for both survivors and their caregivers. The scope of the app's focus was determined based on the incidence of post-stroke complications within a prospective cohort of stroke patients, in conjunction with existing literature. An initial "web-based mobile app" prototype was crafted to align with the identified focus area. Before the development of the final app version, a feasibility study was conducted involving 30 participant dyads (comprising a patient and a caregiver). Content validity was evaluated by a panel of 20 stroke experts encompassing neurologists, nurses, physiotherapists, and psychologists. The "Stroke Home Care" (SHC) mobile app was conceived as a web-based educational tool aimed at preventing and managing post-stroke complications. It seeks to train caregivers of immobile stroke patients in the administration of preventive and therapeutic care procedures, thereby potentially enhancing survivors' quality of life and alleviating caregivers' burden. The feasibility and validity studies indicated "high satisfaction" levels among most caregivers and experts (>75%), with the remainder expressing "satisfaction" and no "dissatisfaction" regarding app utilities. Stroke experts unanimously deemed the app "appropriate", with consensus on contents, video quality, video length, and voice clarity. Caregivers reported "satisfactory" user experiences, encountering no issues during app installation or operation. Suggestions from both caregivers and experts were integrated into the final app version. The "SHC" app represents a feasible and well-received innovation tailored for the use by caregivers of stroke survivors. Consequently, the initial feasibility of the developed app serves as a precursor to a randomized controlled clinical trial aimed at substantiating its effectiveness within the post-stroke survivor and caregiver population. Notably, within resource-constrained contexts, this app has the potential to be a pivotal tool for post-stroke care.

191 Intermittent: an audit of venous thromboembolism prophylaxis on our stroke unit

Abstract Background The National Clinical Guideline for Stroke for the United Kingdom and Ireland recommends immobile stroke patients receive Intermittent Compression Stockings (IPCs) to prevent Venous Thromboembolism (VTE) from days 3 to 30 of admission. We set out to audit IPC usage on the stroke unit in our hospital. Methods Data was collected for all 31 stroke unit patients on a single day by two NCHDs. We documented age, gender, length of stay, and mobility status. We recorded completion of the VTE risk section of the medication chart, and if the patient was prescribed single antiplatelet (SAPT), dual antiplatelet (DAPT), direct oral anticoagulant (DOAC) or IPCs. We also noted if the patient’s stroke was ischaemic or haemorrhagic. Results 16 patients were male (52%). Mean age was 72 years old. Median length of stay was 29 days. 23 patients had ischaemic strokes (74%), 8 had haemorrhagic strokes (26%). 21 patients had their VTE risk section completed (68%). 9 ischaemic stroke patients were on DOAC, 9 on SAPT, 4 on DAPT, and 1 was on no therapy. 19 patients (61%) were immobile (assistance of one or higher dependency). Of these, 9 had been admitted for between 3 and 30 days. None had IPCs prescribed and only 1 (11%) had them in situ. 3 were on DOAC therapy (33%). One other patient (admitted 41 days prior) had IPCs in situ but not prescribed. Conclusion 89% of appropriate stroke patients did not have IPCs in situ, and 56% had no VTE prophylaxis at all. The VTE risk section of the medication chart was blank in 32% of cases. Based on these results we are conducting a root cause analysis as to why guidelines are not adhered to. This will guide a planned quality improvement initiative.

Changes in bone mineral density in unconscious immobile stroke patients from the acute to chronic phases of brain diseases

ObjectivesDecreased bone mineral density (BMD) is observed in immobile stroke patients. But it is not clarified yet how rapidly BMD reduction occurs or what the most influencing factor to BMD loss is. MethodsBMDs in the lumbar vertebrae and the proximal femur of the paralyzed side were measured in 100 immobile stroke patients at 1 week (0 month), 1 month, and 2 months after admission. The levels of serum calcium, phosphorous, 25-hydroxyvitamin D, and urine cross-linked N-telopeptide of type I collagen (NTx) were also measured. ResultsThe average age of patients was 75.0 ± 11.4 years (31–94 years). No BMD reduction was identified in the lumbar vertebrae in 2 months; however, BMD in the femur significantly decreased in 2 months in female patients (P < 0.05). Serum calcium and phosphorous levels remained within the normal range during hospitalization, and 25-hydroxyvitamin D value rose in 2 months. Urine NTx significantly increased in both males and females in 2 months (male: P < 0.05, female: P < 0.01). ConclusionsWhile there was no significant change in lumbar spine BMD in the 2 month period of immobilization after stroke, BMD in the proximal femur showed a significant reduction, particularly in women. The differential loss of BMD in the 2 regions of interest could possibly be due to the physical forces acting on different body parts during mobilization and nutritional factors. More studies are needed with larger study samples and prolonged follow-up to check the accuracy of these observations.

Developing a Siamese Network for UTIs Risk Prediction in Immobile Patients Undergoing Stroke.

Stroke patients tend to suffer from immobility, which increases the possibility of post-stroke complications. Urinary tract infections (UTIs) are one of the complications as an independent predictor of poor prognosis of stroke patients. However, the incidence of new UTIs onsets during hospitalization was rare in most datasets with a prevalence of 4%. This imbalanced data distribution sets obstacles to establishing an accurate prediction model. Our study aimed to develop an effective prediction model to identify UTIs risk in immobile stroke patients, and (2) to compare its prediction performance with traditional machine learning models. We tackled this problem by building a Siamese Network leveraging commonly used clinical features to identifying patients with UTIs risk. Model derivation and validation were based on a nationwide dataset including 3982 Chinese patients. Results showed that the Siamese Network performed better than traditional machine learning models in imbalanced datasets (Sensitivity: 0.810; AUC: 0.828).

Prediction of post-stroke urinary tract infection risk in immobile patients using machine learning: an observational cohort study

Urinary tract infection (UTI) is one of major nosocomial infections significantly affecting the outcomes of immobile stroke patients. Previous studies have identified several risk factors, but it is still challenging to accurately estimate personal UTI risk. To develop predictive models for UTI risk identification for immobile stroke patients. Research data were collected from our previous multicentre study. Derivation cohort included 3982 immobile stroke patients collected from November 1st, 2015 to June 30th, 2016; external validation cohort included 3837 patients collected from November 1st, 2016 to July 30th, 2017. Six machine learning models and an ensemble learning model were derived, based on 80% of derivation cohort, and effectiveness was evaluated with the remaining 20%. Shapley additive explanation values were used to determine feature importance and examine the clinical significance of prediction models. In all, 2.59% (103/3982) patients were diagnosed with UTI in derivation cohort, 1.38% (53/3837) in external cohort. The ensemble learning model performed the best in area under the receiver operating characteristic (ROC) curve in internal validation (82.2%); second best in external validation (80.8%). In addition, the ensemble learning model performed the best sensitivity in both internal and external validation sets (80.9% and 81.1%, respectively). Seven UTI risk factors (pneumonia, glucocorticoid use, female sex, mixed cerebrovascular disease, increased age, prolonged length of stay, and duration of catheterization) were also identified. This ensemble learning model demonstrated promising performance. Future work should continue to develop a more concise scoring tool based on machine learning models and prospectively examining the model in practical use, thus improving clinical outcomes.

Impact of pulmonary embolism on in-hospital mortality of patients with ischemic stroke

BackgroundPulmonary embolism (PE) is a frequent complication in immobile stroke patients and an important cause of death in stroke patients. We aimed to investigate predictors of PE and the impact of PE on survival of ischemic stroke patients. MethodsPatients were selected by screening the German nationwide inpatient sample (2005–2017) for ischemic stroke (ICD-code I63) and stratified for occurrence of PE (ICD-code I26). Impact of PE on mortality and predictors for PE in ischemic stroke patients were analysed. ResultsOverall, 2,914,546 patients were hospitalized due to ischemic stroke (50.5% females; 69.3% aged ≥70 years) in Germany 2005–2017. Among these, 0.4% had PE and 7.2% died during hospitalization. In-hospital mortality rate of ischemic stroke patients with PE was substantially higher compared to those patients without PE (28.4% vs. 7.1%, P < 0.001). PE was strongly associated with in-hospital death (OR 5.786, 95%CI 5.515–6.070, P < 0.001). Important predictors of PE were cancer (OR 3.165, 95%CI 2.969–3.374, P < 0.001), coagulation abnormalities (OR 2.672, 95CI 2.481–2.878, P < 0.001), heart failure (OR 1.553, 95%CI 1.472–1.639, P < 0.001) and obesity (OR 1.559, 95%CI 1.453–1.672, P < 0.001).Systemic thrombolysis was not beneficial regarding survival in unselected ischemic stroke patients. In contrast, systemic thrombolysis was beneficial in ischemic stroke patients without PE, who had to undergo cardio-pulmonary resuscitation (OR 0.866, 95%CI 0.782–0.960, P = 0.006). ConclusionsPatients with ischemic stroke revealed still a high in-hospital mortality of 7.2% in Germany. While only a minority of 0.4% of the ischemic stroke patients suffered from occurrence of PE, PE was accompanied by a substantial increase regarding in-hospital mortality. Systemic thrombolysis was beneficial regarding short-term survival in ischemic stroke patients without PE, who had to undergo cardio-pulmonary resuscitation.

Cost-effectiveness of an intervention to improve the quality of nursing care among immobile patients with stroke in China: A multicenter study

BackgroundWhile a nursing intervention program for immobile patients with stroke can improve clinic outcomes, less is known about the cost-effectiveness of these interventions. ObjectivesThe goal of this study was to evaluate the cost-effectiveness of the intervention program for immobile patients with stroke in China. DesignA cost-effectiveness analysis alongside a pre-test/post-test (before and after) study was undertaken from a health care perspective. SettingsParticipants were recruited from 25 hospitals among six provinces or municipal cities in eastern (Guangdong province, Zhejiang province, and Beijing municipal city), western (Sichuan province), and central (Henan province and Hubei province) China. ParticipantsA total of 7,653 immobile stroke patients were included in our sample. Patients in routine care settings were recruited from November 2015 to June 2016, and the recruitment of the intervention group patients was from November 2016 to July 2017. MethodsTo adjust for potential bias from confounding variables, the 1:1 propensity score matching yielded matched pairs of 2,966 patients in the routine care group and 2,966 patients in the intervention group, with no significant differences in sociodemographic or clinical characteristics between two groups. All patients were followed-up 3 months after enrolment in the study. Total healthcare costs were extracted from the hospital information system, with the health outcome effectiveness of the intervention program measured using the EuroQol five-dimensional questionnaire (EQ-5D) instrument and the cost-effectiveness of the intervention measured by the incremental cost-effectiveness ratio with a time horizon of 3 months. ResultsCompared to routine care, the intervention program decreased the total costs of stroke patients by CN¥4,600 (95% confidence interval [CI]: [-7050, -2151]), while increasing quality-adjusted life year 0.009 (95% CI: [0.005, 0.013]). The incremental cost-effectiveness ratios over 3 months was CN¥–517,011 per quality-adjusted life year (95% CI: [-1,111,442, -203,912]). Subgroup analysis reveals that both the health-related quality of life and cost effectiveness improved significantly for ischemic patients and tertiary hospitals patients while for hemorrhagic patients and non-tertiary hospital patients only the health-related quality of life improved significantly. ConclusionsFindings from this first cost-effectiveness analysis in immobile stroke patients provide evidence that an intervention program provided significant cost saving, but mainly in ischemic patients and tertiary hospital patients. Wider adoption of such programs may be a sensible approach to reducing the burden of stroke and for immobile patients more generally.

Cost-Effectiveness of an Evidence-Based Standardized Nursing Intervention Model for Immobile Stroke Patients in China

Background: While an evidence-based standardized nursing intervention model (SNIM) for immobile patients can improve clinic outcomes, less is known about the cost-effectiveness of the SNIM. We evaluate the cost-effectiveness of the SNIM for immobile stroke patients in China. Methods: This is a pre-test/post-test study, using propensity score (PS) matching on 5932 patients divided into two groups based on a routine and SNIM nursing care cohort. Total healthcare costs were extracted from the hospital information system, with the health outcome effectiveness of the SNIM measured using the EQ-5D instrument and the cost-effectiveness of the SNIM measured by the incremental cost-effectiveness ratio (ICER) with a time horizon of 3 months. Findings: Compared to routine care, SNIM decreased the total costs of stroke patients CN¥4,600 (95%CI: [-7050, -2151]), while increasing QALY 0.009 (95%CI: [0.005, 0.013]). The ICERs over 3 months was CN¥-- 517,011/QALY (95%CI: [-1111442, -203912]). Subgroup analysis reveals that both the quality of life and cost effectiveness improved significantly for ischemic patients and in tertiary hospitals while for hemorrhagic patients and in non-tertiary hospitals only the quality of life improved significantly. Interpretation: Findings from this first cost-effectiveness analysis in immobile stroke patients provide evidence that an evidence-based SNIM provides significant cost saving, but mainly in ischemic patients and tertiary hospitals. Wider adoption of such SNIM programs may be a sensible approach to reducing the burden of stroke and for immobile patients more generally. Funding Statement: The National Health and Family Planning Commission (Beijing, China) [grant numbers 201502017]. Declaration of Interests: The authors declare no competing interests relevant to this manuscript. Ethics Approval Statement: The study was ethically approved by the authorities of the 25 cooperating hospitals and participants signed a written informed consent before enrollment. For patients with aphasia to consent, consent was signed by a family member.

The effects of a standardized nursing intervention model on immobile patients with stroke: a multicenter study in China.

Immobility complications, including pressure injuries (PIs), deep vein thrombosis (DVT), pneumonia, and urinary tract infections (UTIs), affect the clinical outcomes of stroke patients. A standardized nursing intervention model (SNIM) was constructed and implemented to improve the quality of care and clinical outcomes among immobile patients with stroke. To assess the benefit of SNIM for immobility complication rates, including PIs, DVT, pneumonia, and UTIs, and mortalities in immobile patients with stroke. A before and after study design was used. Patients were divided into a pre- and post-SNIM training original cohort and matched for socioeconomic, demographic, and disease characteristics using propensity score. We fitted logistic regression models to examine the effect of SNIM, and whether the benefit differed between tertiary and non-tertiary hospitals. In the original cohort, the rate of pneumonia, UTIs, and mortality was lower after SNIM training. Furthermore, in the matched cohort, the difference in PI rates was significant. Logistic regression analysis revealed that the probability of PIs, pneumonia, UTIs, and mortality were significantly reduced after SNIM training in the original cohort and this estimated value changed little in the matched cohort. Our results show that the decreased rates of pneumonia, UTIs, and mortality were mainly among non-tertiary hospitals. A structured and systematic SNIM benefited immobile stroke patients' clinical outcomes, but mainly in non-tertiary hospitals in China. Standardized nursing training is needed in non-tertiary hospitals.

Abstract WP367: Effect of the Introduction of a New Pathway for Prevention of Venous Thromboembolisim (VTE) Including Neuromuscular Electrical Stimulation (NMES) on Symptomatic VTE on Immobile Stroke Patients

Background: Venous Thromboembolism (VTE) prophylaxis using Intermittent Pneumatic Compression (IPC) is not possible in all stroke patients. We introduced a new VTE pathway which includes Neuromuscular Electrical Stimulation of the peroneal nerve using the geko TM device (Firstkind Ltd UK) as an alternative prevention strategy for this patient group. In addition, compliance with VTE prophylaxis was reviewed 4-hourly as part of comfort rounds. Methods: This is a prospective audit of the new pathway. All stroke patients admitted to the Acute Stroke Unit at Royal Stoke University Hospital between 1 Nov 2016 and 3 Mar 2018 were included. In line with UK guidelines patients unable to mobilize independently were prescribed IPC in addition to standard measures, e.g. hydration, mobilization, and aspirin where indicated, unless patients were palliative, fully anticoagulated, or refused the intervention. Patients who could not use IPC (intolerance, falls risk, out of stock) were switched to the geko TM device. Results: In total 999 stroke patients were included. Of these 187 (18.7%) required no prophylaxis, 125 (12.5%) were fully anti-coagulated, and 687 (68.7%) required mechanical VTE prophylaxis (MP). Of these 463 (67.3%) received IPC and 122 (17.7%) the geko TM device as their only intervention. A further 81 (11.8%) patients became intolerant to IPC and were prescribed the geko TM as a secondary intervention and 21 (3.1%) refused treatment. The geko TM was used in 203 (29.5% of MP). At 90 days there were 15 (1.5%) VTE (symptomatic DVT or PE). Of these 13 occurred in the MP group: 11 (6 DVT, 5 PE) in the ‘IPC only cohort’, 1 in ‘IPC with secondary geko TM ’, 0 in the ‘geko TM only’ cohort, and 1 (PE) in ‘refused prophylaxis’. A further 2 VTE where recorded: 1 (DVT) in ‘prophylaxis not required’ and 1 (DVT) in ‘on anticoagulant’. The geko TM was used for a mean of 9 days/patient and was well tolerated without serious adverse events. Conclusion: The new strategy of increased surveillance, and use of the geko TM device where indicated, for patients who cannot use IPC was associated with a low overall incidence of symptomatic VTE (1.5%). The incidence in high risk immobile patients requiring MP was 1.9% (13/687), which is lower than the 6.6% in a comparable patient population in the CLOTS-3 study.

Implementation of intermittent pneumatic compression in stroke patients

IntroductionThere is a higher risk of embolic complications in immobile stroke patients. Venous thromboembolism is a serious condition in which small clots form in the deep veins of the legs, called deep vein thrombosis (DVT), and these clots are carried through the blood circulation to the lungs, leading to pulmonary embolism. Intermittent pneumatic compression (IPC) has been proven to prevent deep vein thrombosis in 29.9% of stroke patients. Objectives1. Discover the effects of intermittent pneumatic compression protocol implementation in patients with severe stroke in relation to comfort and safety, and determine how long implementation would take and the work load of this new protocol. 2. Compare functional evolution after 3 months in patients on whom an IPC system was applied with the previous sample at the beginning of the system application. MethodObservational, transversal and descriptive study which evaluated the viability and safety of the IPC system in acute stroke patients in the Stroke Unit of the Hospital Vall d’Hebron. IPC was applied for 24h on patients with ischaemic stroke treated with reperfusion and on patients with intracranial haemorrhage during 72h. Results172 patients were included in the sample. The mean age was 71±14 years. 48% were women. 79.2% were diagnosed with ischaemic stroke. In the application phase the nurses reported that prior to training they had taken 15±2.3min to use the system and that after training application only took 6±1.5min. Practically all patients (98.8%) who were given IPC suffered no discomfort and did not present with any complications derived from its use. During this period no cases of DVT were detected. ConclusionsImplementation of the IPC systems protocol has been proven to have a preventative and efficient effect in the reduction of embolic complications, which is safe for the patient and with no discomfort in its use. The nurses’ work load is not increased with appropriate training. Following the introduction of the protocol a functional optimisation in patients 3 months post stroke was observed.

Implementación del sistema de compresión neumática intermitente en pacientes con ictus

IntroductionThere is a higher risk of embolic complications in immobile stroke patients. Venous thromboembolism is a serious condition in which small clots form in the deep veins of the legs, called deep vein thrombosis (DVT), and these clots are carried through the blood circulation to the lungs, leading to pulmonary embolism. Intermittent pneumatic compression (IPC) has been proven to prevent deep vein thrombosis in 29.9% of stroke patients. Objectives1. Discover the effects of intermittent pneumatic compression protocol implementation in patients with severe stroke in relation to comfort and safety, and determine how long implementation would take and the work load of this new protocol. 2. Compare functional evolution after 3 months in patients on whom an IPC system was applied with the previous sample at the beginning of the system application. MethodObservational, transversal and descriptive study which evaluated the viability and safety of the IPC system in acute stroke patients in the Stroke Unit of the Hospital Vall d’Hebron. IPC was applied for 24hours on patients with ischaemic stroke treated with reperfusion and on patients with intracranial haemorrhage during 72hours. Results172 patients were included in the sample. The mean age was 71±14 years. 48% were women. 79.2% were diagnosed with ischaemic stroke. In the application phase the nurses reported that prior to training they had taken 15±2,3minutes to use the system and that after training application only took 6±1,5minutes. Practically all patients (98.8%) who were given IPC suffered no discomfort and did not present with any complications derived from its use. During this period no cases of DVT were detected. ConclusionsImplementation of the IPC systems protocol has been proven to have a preventative and efficient effect in the reduction of embolic complications, which is safe for the patient and with no discomfort in its use. The nurses’ work load is not increased with appropriate training. Following the introduction of the protocol a functional optimisation in patients 3 months post stroke was observed.

Limiting exercise inhibits neuronal recovery from neurological disorders.

Patients who are bedridden often suffer from muscular atrophy due to reduced daily activities and can become depressed. However, patients who undergo physical therapy sometimes demonstrate positive benefits including a reduction of stressful and depressed behavior. Regenerative medicine has seen improvements in two stem cell-based therapies for central nervous system disorders. One therapy is through the transfer of exogenous stem cells. The other therapy is a more natural method and focuses on the increasing endogenous neurogenesis and restoring the neurological impairments. This study overviews how immobilization-induced disuse atrophy affects neurogenesis in rats, specifically hypothesizing that immobilization diminishes circulating trophic factor levels, like vascular endothelial growth factors or brain-derived neurotrophic factor, which in turn limits neurogenesis. This hypothesis requires the classification of the stem cell microenvironment by probing growth factors in addition to other stress-related proteins that correlate with exercise-induced neurogenesis. There is research examining the effects of increased exercise on neurogenesis while limiting exercise, which better demonstrates the pathological states of immobile stroke patients, remains relatively unexplored. To examine the effects of immobilization on neurogenesis quantitative measurements of movements, 5-bromo-2deoxyuridine labeling of proliferative cells, biochemical assays of serum, cerebrospinal fluid and neurological levels of trophic factors, growth factors, and stress-related proteins will indicate levels of neurogenesis. In further research, studies are needed to show how in vivo stimulation, or lack thereof, affects stem cell microenvironments to advance treatment procedures for strengthening neurogenesis in bedridden patients. This paper is a review article. Referred literature in this paper has been listed in the references section. The datasets supporting the conclusions of this article are available online by searching various databases, including PubMed. Some original points in this article come from the laboratory practice in our research center and the authors’ experiences.

The Clots in Legs Or sTockings after Stroke (CLOTS) 3 trial: a randomised controlled trial to determine whether or not intermittent pneumatic compression reduces the risk of post-stroke deep vein thrombosis and to estimate its cost-effectiveness.

Venous thromboembolism (VTE) is a common cause of death and morbidity in stroke patients. There are few data concerning the effectiveness of intermittent pneumatic compression (IPC) in treating patients with stroke. To establish whether or not the application of IPC to the legs of immobile stroke patients reduced their risk of deep vein thrombosis (DVT). Clots in Legs Or sTockings after Stroke (CLOTS) 3 was a multicentre, parallel-group, randomised controlled trial which allocated patients via a central randomisation system to IPC or no IPC. A technician blinded to treatment allocation performed compression duplex ultrasound (CDU) of both legs at 7-10 days and 25-30 days after enrolment. We followed up patients for 6 months to determine survival and later symptomatic VTE. Patients were analysed according to their treatment allocation. We enrolled 2876 patients in 94 UK hospitals between 8 December 2008 and 6 September 2012. patients admitted to hospital within 3 days of acute stroke and who were immobile on the day of admission (day 0) to day 3. age < 16 years; subarachnoid haemorrhage; and contra-indications to IPC including dermatitis, leg ulcers, severe oedema, severe peripheral vascular disease and congestive cardiac failure. Participants were allocated to routine care or routine care plus IPC for 30 days, or until earlier discharge or walking independently. The primary outcome was DVT in popliteal or femoral veins, detected on a screening CDU, or any symptomatic DVT in the proximal veins, confirmed by imaging, within 30 days of randomisation. The secondary outcomes included death, any DVTs, symptomatic DVTs, pulmonary emboli, skin breaks on the legs, falls with injury or fractures and duration of IPC use occurring within 30 days of randomisation and survival, symptomatic VTE, disability (as measured by the Oxford Handicap Scale), quality of life (as measured by the European Quality of Life-5 Dimensions 3 Level questionnaire) and length of initial hospital stay measured 6 months after randomisation. We allocated 1438 patients to IPC and 1438 to no IPC. The primary outcome occurred in 122 (8.5%) of 1438 patients allocated to IPC and 174 (12.1%) of 1438 patients allocated to no IPC, giving an absolute reduction in risk of 3.6% [95% confidence interval (CI) 1.4% to 5.8%] and a relative risk reduction of 0.69 (95% CI 0.55 to 0.86). After excluding 323 patients who died prior to any primary outcome and 41 who had no screening CDU, the primary outcome occurred in 122 of 1267 IPC participants compared with 174 of 1245 no-IPC participants, giving an adjusted odds ratio of 0.65 (95% CI 0.51 to 0.84; p = 0.001). Secondary outcomes in IPC compared with no-IPC participants were death in the treatment period in 156 (10.8%) versus 189 (13.1%) (p = 0.058); skin breaks in 44 (3.1%) versus 20 (1.4%) (p = 0.002); and falls with injury in 33 (2.3%) versus 24 (1.7%) (p = 0.221). Among patients treated with IPC, there was a statistically significant improvement in survival to 6 months (hazard ratio 0.86, 95% CI 0.73 to 0.99; p = 0.042), but no improvement in disability. The direct cost of preventing a DVT was £1282 per event (95% CI £785 to £3077). IPC is an effective and inexpensive method of reducing the risk of DVT and improving survival in immobile stroke patients. Further research should test whether or not IPC improves survival in other groups of high-risk hospitalised medical patients. In addition, research into methods to improve adherence to IPC might increase the benefits of IPC in stroke patients. Current Controlled Trials ISRCTN93529999. The start-up phase of the trial (December 2008-March 2010) was funded by the Chief Scientist Office of the Scottish Government (reference number CZH/4/417). The main phase of the trial was funded by the National Institute for Health Research Health Technology Assessment programme (reference number 08/14/03). Covidien Ltd (Mansfield, MA, USA) lent its Kendall SCD™ Express sequential compression system controllers to the 105 centres involved in the trial and donated supplies of its sleeves. It also provided logistical help in keeping our centres supplied with sleeves and training materials relevant to the use of their devices. Recruitment and follow-up were supported by the National Institute for Health Research-funded UK Stroke Research Network and by the Scottish Stroke Research Network, which was supported by NHS Research Scotland.

Which stroke patients gain most from intermittent pneumatic compression: further analyses of the CLOTS 3 trial.

The CLOTS 3 trial showed that intermittent pneumatic compression (IPC) reduced the risk of DVT and improved survival after stroke. To provide additional information which may help clinicians target IPC on the most appropriate patients by exploring the variation in its effects on subgroups defined by predicted prognosis. A multicentre, parallel group, randomized trial enrolled immobile acute stroke patients and allocated them to IPC or no IPC. The primary outcome was proximal DVT at 30 days. Secondary outcomes at six-months included survival, disability, quality of life, and hospital costs. We stratified patients into quintiles according to their predicted prognosis at randomization, based on the Six Simple Variable model. Between December 2008 and September 2012, we enrolled 2876 patients in 94 UK hospitals. Patients with the best predicted outcome had the lowest absolute risk of proximal DVT (6·7%) and death by six-months (9·3%). Allocation to IPC had little effect on DVT, survival, disability, quality of life, hospital length of stay, or costs. In patients with the worst predicted outcomes, the overall risk of DVT and death was 16·0% and 51·3%, respectively. IPC reduced DVT (odds reduction 34%) and improved survival 17% and significantly increased length of stay and hospital costs. In the three intermediate quintiles, IPC reduced the odds of DVT (35-43%) and improved survival (11-13%). Disability and quality of life at six-months depended on baseline severity but was not influenced significantly by IPC. IPC appears to reduce the risk of DVT and probably improves survival in all immobile stroke patients, other than the fifth with the best prognosis. It therefore seems reasonable to recommend that IPC should be considered in all immobile stroke patients, but that the final decision should be based on a judgment about the individual's prognosis. In some, their prognosis for survival with an acceptable quality of life will be so poor that use of IPC might be considered futile, while at the other end of the spectrum, patients' risk of DVT, and of dying from VTE, may not be high enough to justify the modest cost and inconvenience of IPC use.

Effectiveness of intermittent pneumatic compression in reduction of risk of deep vein thrombosis in patients who have had a stroke (CLOTS 3): a multicentre randomised controlled trial

Venous thromboembolism is a common, potentially avoidable cause of death and morbidity in patients in hospital, including those with stroke. In surgical patients, intermittent pneumatic compression (IPC) reduces the risk of deep vein thrombosis (DVT), but no reliable evidence exists about its effectiveness in patients who have had a stroke. We assessed the effectiveness of IPC to reduce the risk of DVT in patients who have had a stroke. The CLOTS 3 trial is a multicentre parallel group randomised trial assessing IPC in immobile patients (ie, who cannot walk to the toilet without the help of another person) with acute stroke. We enrolled patients from day 0 to day 3 of admission and allocated them via a central randomisation system (ratio 1:1) to receive either IPC or no IPC. A technician who was masked to treatment allocation did a compression duplex ultrasound (CDU) of both legs at 7-10 days and, wherever practical, at 25-30 days after enrolment. Caregivers and patients were not masked to treatment assignment. Patients were followed up for 6 months to determine survival and later symptomatic venous thromboembolism. The primary outcome was a DVT in the proximal veins detected on a screening CDU or any symptomatic DVT in the proximal veins, confirmed on imaging, within 30 days of randomisation. Patients were analysed according to their treatment allocation. ISRCTN93529999. Between Dec 8, 2008, and Sept 6, 2012, 2876 patients were enrolled in 94 centres in the UK. The included patients were broadly representative of immobile stroke patients admitted to hospital and had a median age of 76 years (IQR 67-84). The primary outcome occurred in 122 (8·5%) of 1438 patients allocated IPC and 174 (12·1%) of 1438 patients allocated no IPC; an absolute reduction in risk of 3·6% (95% CI 1·4-5·8). Excluding the 323 patients who died before any primary outcome and 41 without any screening CDU, the adjusted OR for the comparison of 122 of 1267 patients vs 174 of 1245 patients was 0·65 (95% CI 0·51-0·84; p=0·001). Deaths in the treatment period occurred in 156 (11%) patients allocated IPC and 189 (13%) patients allocated no IPC died within the 30 days of treatment period (p=0·057); skin breaks on the legs were reported in 44 (3%) patients allocated IPC and in 20 (1%) patients allocated no IPC (p=0·002); falls with injury were reported in 33 (2%) patients in the IPC group and in 24 (2%) patients in the no-IPC group (p=0·221). IPC is an effective method of reducing the risk of DVT and possibly improving survival in a wide variety of patients who are immobile after stroke. National Institute of Health Research (NIHR) Health Technology Assessment (HTA) programme, UK; Chief Scientist Office of Scottish Government; Covidien (MA, USA).

The Effect of Graduated Compression Stockings on Long-term Outcomes After Stroke

Background and Purpose— Most randomized controlled trials of venous thromboembolism prophylaxis have focused on reduction of deep vein thrombosis, predominantly asymptomatic deep vein thrombosis, detected on imaging. We aimed to estimate the effects of graduated compression stockings on venous thromboembolism events, survival, and functional status at 6 months after stroke. Methods— The CLOTS Trials adopted an international multicentre, parallel group design, with central randomization and a 1:1 treatment allocation. In CLOTS Trial 1, 2518 immobile stroke patients were allocated thigh-length graduated compression stockings or not, and in CLOTS trial 2, 3014 to thigh-length or below-knee graduated compression stockings. We measured vital status, Oxford Handicap Scale, and quality of life (EQ5D-3 L) at 6 months. Results— We compared survival in patients enrolled in Trials 1 and 2 with a Cox proportional hazards model, including variables included in our minimization algorithm. In both trials, allocation to thigh-length graduated compression stockings was associated with a very slight, but nonsignificant, increased hazard of death in the first 6 months (Trial 1: hazard ratio, 1.087; 95% confidence interval, 0.913–1.295; and Trial 2: hazard ratio, 1.037; 95% confidence interval, 0.892–1.205). There were no statistically significant differences in venous thromboembolism events, Oxford Handicap Scale, or EQ5D-3 L between the treatment groups in CLOTS Trials 1 or 2. Conclusions— Although underpowered to detect clinically important effects on long-term outcomes, our results effectively exclude a &gt;10% relative reduction in the hazard of death within 6 months associated with the use of thigh-length stockings. No other long-term benefits were apparent.

Does intermittent pneumatic compression reduce the risk of post stroke deep vein thrombosis? The CLOTS 3 trial: statistical analysis plan

BackgroundVenous thromboembolism (VTE) is a common and important complication of stroke. The CLOTS 3 trial aims to determine whether, compared with best medical care, best medical care plus intermittent pneumatic compression (IPC) in immobile stroke patients reduces the risk of proximal deep vein thrombosis (DVT).Methods/DesignThe CLOTS 3 trial is a multicenter, parallel group trial with centralized randomization (minimization) to ensure allocation concealment. The protocol has been published (Trials 2012, 13:26) and is available in full at: http://www.clotstrial.com. Between December 2008 and September 2012, 105 centers in the UK recruited 2,876 immobile stroke patients within the first 3 days of their hospital admission. Patients were allocated to best medical care or best medical care plus IPC. Ultrasonographers performed a compression Doppler ultrasound scan to detect DVT in each treatment group at 7 to 10 days and 25 to 30 days. The primary outcome cluster includes symptomatic or asymptomatic DVT in the popliteal or femoral veins detected on either scan. Patients will be followed up by postal or telephone questionnaire at 6 months from randomization to detect later symptomatic DVT and pulmonary embolism (PE), and to measure functional outcome (Oxford Handicap Scale) and quality of life (EQ-5D-3L). The ultrasonographers performing the scans are blinded to treatment allocation, whereas the patients and caregivers are not. The trial has more than 90% power to detect a 4% absolute difference (12% versus 8%) in risk of the primary outcome and includes a health economic analysis.Follow-up will be completed in April 2013 and the results reported in May 2013. In this update, we describe the statistical analysis plan.Trial registrationISRCTN: ISRCTN93529999

Does intermittent pneumatic compression reduce the risk of post stroke deep vein thrombosis? The CLOTS 3 trial: study protocol for a randomized controlled trial

BackgroundApproximately 80,000 patients each year are admitted to UK hospitals with an acute stroke and are immobile. At least 10% will develop a proximal Deep Vein Thrombosis in the first month and 1.5% a pulmonary embolus. Although hydration, antiplatelet treatment and early mobilisation may reduce the risk of deep vein thrombosis, there are currently no preventive strategies which have been clearly shown to be both effective and safe. Anticoagulation increases the risks of bleeding and compression stockings are ineffective. Systematic reviews of small randomized trials of intermittent pneumatic compression have shown that this reduces the risk of deep vein thrombosis in patients undergoing surgery, but that there are few data concerning its use after stroke. The CLOTS trial 3 aims to determine whether, compared with best medical care, best medical care plus intermittent pneumatic compression in immobile stroke patients reduces the risk of proximal deep vein thrombosis.Methods/DesignCLOTS Trial 3 is a parallel group multicentre trial; with centralized randomisation (minimisation) to ensure allocation concealment. Over 80 centres in the UK will recruit 2800 immobile stroke patients within the first 3 days of their hospital admission. Patients will be allocated to best medical care or best medical care plus intermittent pneumatic compression. Ultrasonographers will perform a Compression Duplex Ultrasound Scan to detect deep vein thrombosis in each treatment group at about 7-10 days and 25-30 days. The primary outcome cluster includes symptomatic or asymptomatic deep vein thrombosis in the popliteal or femoral veins detected on either scan. Patients are then followed up by postal or telephone questionnaire at 6 months from randomisation to detect later symptomatic deep vein thrombosis and pulmonary emboli and to establish their functional outcome (Oxford handicap scale) and quality of life (EQ5D-3 L). The ultrasonographers performing the scans are blinded to treatment allocation, whereas the patients and caregivers are not. The trial has 90% power to detect a 4% absolute difference in risk of the primary outcome and includes a health economic analysis.DiscussionThe trial started recruitment in Dec 2008 and will complete recruitment during 2012. It will report results in 2013.Trial registration numberISRCTN: ISRCTN93529999

The timing, extent, progression and regression of deep vein thrombosis in immobile stroke patients: observational data from the CLOTS multicenter randomized trials.

Deep vein thrombosis (DVT) is an important complication of stroke, but the evidence to support commonly used prophylactic strategies is conflicting. To describe the incidence, extent, associated clinical features and evolution of DVT after stroke. The CLOTS trials 1 and 2 together randomized 5632 immobile stroke patients in 135 hospitals in nine countries. We screened patients for asymptomatic DVT with compression duplex ultrasound (CDU) at about 7-10 days and again at about 25-30 days after enrollment. Six hundred and forty-one (11.4%) of 5632 patients had DVT detected on the first CDU scan at a median of 8 days (interquartile range [IQR] 7-10 days) after enrollment, and an additional 176 (3.1%) had a DVT on the second CDU scan at a median of 28 days (IQR 26-30 days). Of the 817 with DVTs, 289 (35%) were symptomatic and 39 (5%) had pulmonary embolism (PE) confirmed by imaging. Six hundred and seventy-six (83%) were unilateral, 141 (17%) were bilateral, 322 (39%) were limited to calf veins, 172 (21%) were popliteal, and 323 (40%) were femoral. Among the 542 patients with DVT and a weak leg, the DVT affected the weaker leg in 396 (73%), the stronger leg in 59 (11%), and was bilateral in 87 (16%). Among the 318 patients with a DVT detected on the first CDU scan who had a second scan, the DVT regressed in 148 (47%), stayed the same in 140 (44%), and progressed in only 30 (9%). Although most DVTs develop within the first week, some develop later, and some early DVTs progress. Any prophylaxis needs to be started early but ideally continued for at least 4 weeks.