Venous thromboembolism is a frequent complication of acute hospital care, and this extends to inpatient rehabilitation. The timely use of appropriate thromboprophylaxis in patients who are at risk is a strong, evidence-based patient safety priority that has reduced clinically important venous thromboembolism, associated mortality and costs of care. While there has been extensive research on optimal approaches to venous thromboembolism prophylaxis in acute care, there is a paucity of high-quality evidence specific to patients in the rehabilitation setting, and there are no clinical practice guidelines that make recommendations for (or against) thromboprophylaxis across the broad spectrum of rehabilitation patients. Herein, we provide an evidence-informed review of the topic with practice suggestions. We conducted a series of literature searches to assess the risks of venous thromboembolism and its prevention related to inpatient rehabilitation as well as in major rehabilitation subgroups. Mobilization alone does not eliminate the risk of venous thromboembolism after another thrombotic insult. Low molecular weight heparins and direct oral anticoagulants are the principal current modalities of thromboprophylaxis. Based on the literature, we make suggestions for venous thromboembolism prevention and include an approach for consideration by rehabilitation units that can be aligned with local practice.

Hospital-associated venous thromboembolism (VTE) is defined as any case of VTE occurring during hospital admission and for up to 90 days post discharge. It accounts for over 50% of all cases of VTE internationally; indeed, there are an estimated 10 million cases of hospital-associated VTE annually. Over the last decade, there has been increasing interest in improving VTE risk assessment and thromboprophylaxis. This review summarises all the recent and ongoing major research studies and future challenges in the different areas, including medical, surgical and obstetric patients, as well as special areas such as lower limb immobilisation. We include sections on both pharmacological and mechanical thromboprophylaxis.

Although compression therapy (CT) is considered a crucial conservative treatment in chronic venous disease, strong evidence is missing for many clinical indications. This literature review aims to point out what strong evidence we have for CT and all the clinical scenarios where strong evidence still needs to be included.

The research was conducted on MEDLINE with PubMed, Scopus and Web of Science. The time range was set between January 1980 and October 2022. Only articles in English were included.

The main problem with CT is the low scientific quality of many studies on compression. Consequently, we have robust data on the effectiveness of CT only for advanced venous insufficiency (C3-C6), deep vein thrombosis and lymphedema. We have data on the efficacy of compression for venous symptoms control and in sports recovery, but the low quality of studies cannot result in a strong recommendation. For compression in postvenous procedures, superficial venous thrombosis, thromboprophylaxis, post-thrombotic syndrome prevention and treatment, and sports performance, we have either no data or very debated data not allowing any recommendation.

We need high-level scientific studies to assess if CT can be effective or definitely ineffective in the clinical indications where we still have a paucity of or contrasting data.

Identification of individuals with ischemic stroke at particularly high risk of venous thromboembolism (VTE) is crucial for targeted thromboprophylaxis. To guide clinical decision-making and development of risk prediction models, increased knowledge on risk factors and biomarkers is needed. Therefore, we set out to identify risk factors and predictors for VTE in people with ischemic stroke by conducting a systematic review of the literature. Medline and Embase were searched from January 1990 and onwards. Studies investigating demographic, clinical, and/or laboratory factors for stroke-related VTE were considered. Two reviewers screened all retrieved records, independently and in duplicate. Risk of bias assessments were guided by a structured framework (PROSPERO-ID: CRD42020176361). Of 4674 identified records, 26 studies were included. Twenty-six demographic, clinical, and laboratory factors associated with increased risk of stroke-related VTE after multivariable adjustments were identified. The following factors were reported by ≥2 studies: prior VTE, cancer, prestroke disability, leg weakness, increasing lesion volume of the brain infarct, infection, low Barthel Index, increasing length of hospital stay, biochemical indices of dehydration, as well as elevated levels of D-dimer, C-reactive protein, and homocysteine. The majority of the studies were of poor quality with moderate or high risk of bias. In conclusion, this systematic review informs on several potential risk factors and predictors for VTE in people with ischemic stroke. To improve risk stratification and guide development of risk prediction models, further confirmation is needed because there were few high-quality studies on each factor.

To evaluate the usefulness of soleal vein (SOV) diameter as a predictor of new onset of deep vein thrombosis (DVT) in acute stroke patients.

A total of 121 acute stroke patients who were admitted within 48 h of onset underwent a calf vein ultrasonography (CVUS) examination within 7 days after hospitalization. They were evaluated for the presence of DVT and risk factors including maximum SOV diameter. Next, the patients in whom DVT was not detected at the first CVUS examination underwent a second CVUS examination on the 21st hospital day, and were evaluated for the presence of new DVT.

DVT was detected in 27 of 121 patients at the first CVUS examination. A significant association was noted between the presence of DVT and higher levels of soluble fibrin monomer, D-dimer, and C-reactive protein, and a higher rate of having cancer concomitantly. Furthermore, 50 of 94 patients without DVT at the first CVUS examination underwent a second CVUS examination. Of the 94 patients, 44 were excluded, because they were discharged by the 21st day. Note that DVT was newly developed in 12 of the 50 patients who underwent the second CVUS. A significant association was found between the presence of new DVT and the rate of history of stroke, hematocrit level, and maximum SOV diameter at the first examination.

In our acute stroke patients, SOV dilation, history of stroke, and elevated hematocrit level were found to be associated with risk of developing a new DVT.

Venous thromboembolism (VTE) is a common complication after intracranial hemorrhage (ICH); the incidence has been reported to vary between 18% to 50% for deep vein thrombosis and between 0.5% to 5% for pulmonary embolism (PE). According to current clinical practice guidelines, patients with acute VTE should receive anticoagulant treatment for at least 3 months in the absence of contraindications. Anticoagulant treatment reduces mortality, prevents early recurrences and improves long-term outcome in patients with acute VTE. However, recent ICH is an absolute contraindication for anticoagulant treatment due to the potential increased risk of hematoma expansion or recurrent ICH. Hematoma expansion occurs in approximately a third of patients within 24 h following the diagnosis of a spontaneous ICH. The risk for recurrent ICH depends on patients' features as well as on the feature of index ICH. Limited evidence is available on the risks of therapeutic anticoagulation started shortly after ICH. Expert consensus around the introduction of therapeutic anticoagulation suggests delaying therapeutic anticoagulation for at least 2 weeks after spontaneous ICH, until the risk re-bleeding becomes acceptable. Vena cava filters should be inserted to reduce the risk for (non) fatal PE until therapeutic anticoagulation can be started; antithrombotic prophylaxis should be started as soon as possible to avoid recurrent VTE after vena cava filter insertion. For patients presenting PE with hemodynamic compromise, percutaneous embolectomy should be considered. Most patients will be able to receive anticoagulant treatment within 4 weeks following spontaneous ICH; direct oral anticoagulants are probably the treatment of choice for those ICH patients tolerating anticoagulant treatment.

Venous thromboembolism (VTE), which encompasses deep vein thrombosis and pulmonary embolism, is common among trauma patients and critically ill surgical patients admitted to the ICU. Critical care surgical patients are at an extremely high risk for VTE and the related morbidity and mortality associated with it. The present review aims to provide an overview of the importance of identifying risk factors, prescribing effective prohylaxis, accurate diagnosis, and timely appropriate treatment for trauma and critically ill surgical patients with VTE in the ICU.

VTE is a healthcare burden among critically ill surgical patients that is mostly preventable through adherence to prophylactic protocols that aim to recognize VTE risk factors while simultaneously providing guidance to appropriate timing and administration prophylaxis regimens. Newer pharmacologic therapies for prophylaxis and treatment, diagnostic modalities, and indications for therapy of VTE have continued to evolve.

Critical care surgical and trauma patients represent a population that are at a heightened risk for VTE and associated complications. Appropriate screening, prevention strategies, accurate diagnosis, and timely administration of appropriate treatment must be utilized to reduce morbidity and mortality.

Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population.

AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2-15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921.

Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76-1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months.

Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke.

National Health and Medical Research Council of Australia.

Medical compression therapy is used for non-invasive treatment of venous and lymphatic diseases. Medical compression therapy-associated adverse events and contraindications have been reported, although some contraindications are theoretically based. This consensus statement provides recommendations on medical compression therapy risks and contraindications.

A systematic literature search of medical compression therapy publications reporting adverse events up until November 2017 was performed. A consensus panel comprising 15 international experts critically reviewed the publications and formulated the recommendations.

Sixty-two publications reporting medical compression therapy adverse events were identified. The consensus panel issued 21 recommendations on medical compression therapy contraindications and adverse event risk mitigation, in addition to reviewing medical compression therapy use in borderline indications. The most frequently reported non-severe medical compression therapy-associated adverse events included skin irritation, discomfort and pain. Very rare but severe adverse events, including soft tissue and nerve injury, were also identified.

This consensus statement summarises published medical compression therapy-associated adverse events and contraindications, and provides guidance on medical compression therapy. Severe medical compression therapy-associated adverse events are very rarely encountered if compression is used correctly and contraindications are considered.

To summarize and compare the effectiveness of pharmacological thromboprophylaxis to pneumatic compression devices (PCD) for the prevention of venous thromboembolism in patients with acute intracerebral hemorrhage.

MEDLINE, PUBMED, EMBASE, and CENTRAL were systematically searched to identify randomized and non-randomized studies that compared each intervention directly to each other or against a common control (hydration, anti-platelet agents, stockings) in adults with acute spontaneous intracerebral hemorrhage. Two investigators independently screened the studies, extracted data, and appraised risk of bias. Studies with a high risk of bias were excluded from our final analysis. The primary outcome was the occurrence of venous thromboembolism (proximal deep vein thrombosis or pulmonary embolism) in the first 30 days.

8,739 articles were screened; four articles, all randomized control trials, met eligibility criteria. Bayesian network meta-analysis was performed to calculate risk estimates using both fixed and random effects analyses. 607 patients were included in the network analysis. PCD were associated with a significant decrease in venous thromboembolism compared to control (OR: 0.43, 95% Credible Limits [CrI]: 0.23-0.80). We did not find evidence of statistically significant differences between pharmacological thromboprophylaxis and control (OR: 0.93, 95% CrI: 0.19-4.37) or between PCD and pharmacological thromboprophylaxis (OR: 0.47, 95% CrI: 0.09-2.54).

PCDs are superior to control interventions, but meaningful comparisons with pharmacotherapy are not possible due to a lack of data. This requires further exploration via large pragmatic clinical trials.

PROSPERO: CRD42018090960.

Our Cochrane review of selective serotonin inhibitors for stroke recovery indicated that fluoxetine may improve functional recovery, but the trials were small and most were at high risk of bias.

The Fluoxetine Or Control Under Supervision (FOCUS) trial tested the hypothesis that fluoxetine improves recovery after stroke.

The FOCUS trial was a pragmatic, multicentre, parallel-group, individually randomised, placebo-controlled trial.

This trial took place in 103 UK hospitals.

Patients were eligible if they were aged ≥ 18 years, had a clinical stroke diagnosis, with focal neurological deficits, between 2 and 15 days after onset.

Patients were randomly allocated 20 mg of fluoxetine once per day or the matching placebo for 6 months via a web-based system using a minimisation algorithm.

The primary outcome was the modified Rankin Scale at 6 months. Patients, carers, health-care staff and the trial team were masked to treatment allocation. Outcome was assessed at 6 and 12 months after randomisation. Patients were analysed by their treatment allocation as specified in a published statistical analysis plan.

Between 10 September 2012 and 31 March 2017, we recruited 3127 patients, 1564 of whom were allocated fluoxetine and 1563 of whom were allocated placebo. The modified Rankin Scale score at 6 months was available for 1553 out of 1564 (99.3%) of those allocated fluoxetine and 1553 out of 1563 (99.4%) of those allocated placebo. The distribution across modified Rankin Scale categories at 6 months was similar in the two groups (common odds ratio adjusted for minimisation variables 0.951, 95% confidence interval 0.839 to 1.079; p = 0.439). Compared with placebo, patients who were allocated fluoxetine were less likely to develop a new episode of depression by 6 months [210 (13.0%) vs. 269 (16.9%), difference -3.78%, 95% confidence interval -1.26% to -6.30%; p = 0.003], but had more bone fractures [45 (2.9%) vs. 23 (1.5%), difference 1.41%, 95% confidence interval 0.38% to 2.43%; p = 0.007]. There were no statistically significant differences in any other recorded events at 6 or 12 months. Health economic analyses showed no differences between groups in health-related quality of life, hospital bed usage or health-care costs.

Some non-adherence to trial medication, lack of face-to-face assessment of neurological status at follow-up and lack of formal psychiatric diagnosis during follow-up.

20 mg of fluoxetine daily for 6 months after acute stroke did not improve patients' functional outcome but decreased the occurrence of depression and increased the risk of fractures. These data inform decisions about using fluoxetine after stroke to improve functional outcome or to prevent or treat mood disorders. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) (Australasia/Vietnam) and Efficacy oF Fluoxetine - a randomisEd Controlled Trial in Stroke (EFFECTS) (Sweden) trials recruited an additional 2780 patients and will report their results in 2020. These three trials have an almost identical protocol, which was collaboratively developed. Our planned individual patient data meta-analysis will provide more precise estimates of the effects of fluoxetine after stroke and indicate whether or not effects vary depending on patients' characteristics and health-care setting.

Current Controlled Trials ISRCTN83290762.

This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 22. See the NIHR Journals Library website for further project information. The Stroke Association (reference TSA 2011101) funded the start-up phase.

Patients with an intracerebral haemorrhage are at increased risk of venous thromboembolism. Pharmacotherapy and pneumatic compression devices are capable of preventing venous thromboembolism, however both interventions have limitations. There are no head-to-head comparisons between these two interventions. To address this knowledge gap, we plan to perform a systematic review and network meta-analysis to examine the comparative effectiveness of pharmacological prophylaxis and mechanical compression devices in the context of intracerebral haemorrhage.

MEDLINE, PUBMED, EMBASE, CENTRAL, ClinicalTrials.gov and the Internet Stroke Trials Registry will be searched with assistance from an experienced information specialist. Eligible studies will include those that have enrolled adults presenting with spontaneous intracerebral haemorrhage and compared one or more of the respective interventions against each other and/or a control. Primary outcomes to be assessed are occurrence of new venous thromboembolism (deep vein thrombosis and/or pulmonary embolism) and haematoma expansion, defined as a significant enlargement of baseline haemorrhage or new haemorrhage occurrence. Both randomised and non-randomised comparative studies will be included. Data on participant characteristics, study design, intervention details and outcomes will be extracted. Study quality will be assessed using the Cochrane Risk of Bias Tool and the Robins-I tool. Bayesian network meta-analyses will be performed to compare interventions based on all available direct and indirect evidence. If the transitivity assumption for network meta-analysis cannot be met, we will perform a qualitative assessment.

Formal ethics is not required as primary data will not be collected. The findings of this study will be disseminated through conference presentations, and peer-reviewed publications. In an area of clinical practice where equipoise exists, the findings of this study may assist in determining which treatment intervention is most effective in venous thromboembolism prevention.

CRD42018090960.

the patients presenting with severe post-stroke in the acute period of this condition are characterized by the high risk of venous thromboembolic complications (VTEC), with the most dangerous of them being pulmonary embolism that makes an appreciable contribution to the mortality rate of such patients at the hospital stage of their treatment. Among the physical methods for the prevention of VTE, such as wearing graduated compression stockings (GCS), myoelectrostimulation (MES), pneumatic intermittent compression (PIC), only the latter technique has been shown to be efficient when applied for the treatment of surgical patients during the post-stroke period with the level of evidence 2B and the very uncertain parameters of the impact.

The objective of the present study was to evaluate the advantages of the PIC in comparison with that of GCS and MES, substantiate the choice of the former method for the management of the high-risk post-stroke patients, and determine the impact parameters of PIC during the peracute and acute periods of the disease.

We conducted a series of analyses of the results of several controlled randomized studies and relevant reviews of the literature with a view to determining the feasibility and effectiveness of application of one or another approach and clarifying the parameters of the exposure to GCS, MES, and PIC for the prevention of VTEC.

The results of these studies gave evidence that the effectiveness of the GCS and MES is insufficient in contrast to that of PIC that was found to decrease the relative risk of deep vein thrombosis (DVT) by 62% compared with placebo and by 47% in comparison with GCS. The low risk of DVT associated with the application of PIC was apparent from the low OR value of 0.45 and the absolute reduction in the risk of DVT by 3.6%. The analysis of the parameters being used made it possible to identify side effects and thereby allowed to formulate the optimal method for the application of PIC for the purpose of prevention of VTEC in the post-stroke patients during the peracute and acute periods of the disease.

Only PIC of all the currently available methods for the physical prevention of VTEC in the group of high risk post-stroke patients during the peracute and acute periods of this condition can be practiced in the reliable evidence-based manner. The most rational PIC modality consists of exerting the external pressure on the lower extremities within the first 12-24 hours after stroke with the use of the cuffs of the «lower leg» type (i.e. at a pressure of 40-50 mm Hg in the wave mode with memorization for the multi-sectional cuffs, daily in the continuous manner throughout the daytime till the patient is downgraded to the group at lower risk of VTEC or actually till the discharge from the hospital.

Objective Medical compression stockings are a standard, non-invasive treatment option for all venous and lymphatic diseases. The aim of this consensus document is to provide up-to-date recommendations and evidence grading on the indications for treatment, based on evidence accumulated during the past decade, under the auspices of the International Compression Club. Methods A systematic literature review was conducted and, using PRISMA guidelines, 51 relevant publications were selected for an evidence-based analysis of an initial 2407 unrefined results. Key search terms included: 'acute', CEAP', 'chronic', 'compression stockings', 'compression therapy', 'lymph', 'lymphatic disease', 'vein' and 'venous disease'. Evidence extracted from the publications was graded initially by the panel members individually and then refined at the consensus meeting. Results Based on the current evidence, 25 recommendations for chronic and acute venous disorders were made. Of these, 24 recommendations were graded as: Grade 1A (n = 4), 1B (n = 13), 1C (n = 2), 2B (n = 4) and 2C (n = 1). The panel members found moderately robust evidence for medical compression stockings in patients with venous symptoms and prevention and treatment of venous oedema. Robust evidence was found for prevention and treatment of venous leg ulcers. Recommendations for stocking-use after great saphenous vein interventions were limited to the first post-interventional week. No randomised clinical trials are available that document a prophylactic effect of medical compression stockings on the progression of chronic venous disease (CVD). In acute deep vein thrombosis, immediate compression is recommended to reduce pain and swelling. Despite conflicting results from a recent study to prevent post-thrombotic syndrome, medical compression stockings are still recommended. In thromboprophylaxis, the role of stockings in addition to anticoagulation is limited. For the maintenance phase of lymphoedema management, compression stockings are the most important intervention. Conclusion The beneficial value of applying compression stockings in the treatment of venous and lymphatic disease is supported by this document, with 19/25 recommendations rated as Grade 1 evidence. For recommendations rated with Grade 2 level of evidence, further studies are needed.

Venous thromboembolism (VTE) prophylaxis is not always part of the usual care of ambulatory surgery patients, and few guidelines are available.

To collect data on the application of VTE prophylaxis in ambulatory patients.

The OPERA study is a large national survey performed in 221 healthcare facilities.

Among patients, 2174 who underwent one of ten selected procedures over two pre-defined days of investigation.

Assessment and management of the postoperative VTE risk.

The postoperative VTE risk was assessed as nil (4.1% of the physicians), low (74%) or moderate (20%). This risk was assessed as lower (71%) in ambulatory surgery as compared to conventional surgery. In most centres (94%), a personal patient history of VTE was recorded preoperatively, and in 72% a prophylaxis protocol was systematically applied but only 40% of the responding centres had a written protocol for VTE prophylaxis. The postoperative period (discharge at home) was covered by a VTE protocol for 75% of the centres, with VTE prophylaxis starting postoperatively in 21% of the patients. In these patients, different treatments were applied: below-knee compression stockings (25%); thigh-length compression stockings (21%); intermittent pneumatic compression in the recovery room (1.2%); unfractionated heparin (2.0%); low molecular weight heparins (65%); vitamin K antagonists (0.5%); other treatments, including direct oral anticoagulants (0.5%).

These data underline the need for a better assessment of the VTE risk in ambulatory patients and new studies either with conventional or new agents to be able to build guidelines in this new setting.

Wund-D.A.CH. is the umbrella organization of the various wound care societies in German-speaking countries. The present consensus paper on practical aspects pertinent to compression therapy in patients with venous leg ulcers was developed by experts from Germany, Austria, and Switzerland. In Europe, venous leg ulcers rank among the most common causes of chronic wounds. Apart from conservative and interventional wound and vein treatment, compression therapy represents the basis of all other therapeutic strategies. To that end, there are currently a wide variety of materials and systems available. While especially short-stretch bandages or multicomponent systems should be used in the initial decongestion phase, ulcer stocking systems are recommended for the subsequent maintenance phase. Another - to date, far less common - alternative are adaptive Velcro bandage systems. Medical compression stockings have proven particularly beneficial in the prevention of ulcer recurrence. The large number of treatment options currently available enables therapists to develop therapeutic concepts geared towards their patients' individual needs and abilities, thus resulting in good acceptance and adherence. Compression therapy plays a crucial role in the treatment of patients with venous leg ulcers. In recent years, a number of different treatment options have become available, their use and application differing among German-speaking countries. The present expert consensus is therefore meant to outline concrete recommendations for routine implementation of compression therapy in patients with venous leg ulcers.

We present a systemic review of available literature on the complications of deep venous thrombosis that develops in patients presenting with acute stroke. There are several pharmacological and physical treatment options available and used. We aim to summarize the management plans currently used at different centers. In conclusion, low-dose anticoagulant therapy for ischemic stroke is recommended. In the case of intracerebral hemorrhage, pneumatic sequential compression devices should be placed initially, followed by the administration of ultra-fractioned heparin on the next day, and then oral anticoagulant therapy to replace the heparin after a week in high-risk patients. Similar prophylactic treatment recommendations are used for subarachnoid hemorrhage.

Spontaneous non-traumatic intracerebral hemorrhage (ICH) remains a significant cause of mortality and morbidity throughout the world. To improve the devastating course of ICH, various clinical trials for medical and surgical interventions have been conducted in the last 10 years. Recent large-scale clinical trials have reported that early intensive blood pressure reduction can be a safe and feasible strategy for ICH, and have suggested a safe target range for systolic blood pressure. While new medical therapies associated with warfarin and non-vitamin K antagonist oral anticoagulants have been developed to treat ICH, recent trials have not been able to demonstrate the overall beneficial effects of surgical intervention on mortality and functional outcomes. However, some patients with ICH may benefit from surgical management in specific clinical contexts and/or at specific times. Furthermore, clinical trials for minimally invasive surgical evacuation methods are ongoing and may provide positive evidence. Upon understanding the current guidelines for the management of ICH, clinicians can administer appropriate treatment and attempt to improve the clinical outcome of ICH. The purpose of this review is to help in the decision-making of the medical and surgical management of ICH.

The global burden of intracerebral haemorrhage (ICH) is enormous. Developing evidence-based management strategies for ICH has been hampered by its diverse aetiology, high case fatality and variable cooperative organisation of medical and surgical care. Progress is being made through the conduct of collaborative multicentre studies with the large sample sizes necessary to evaluate therapies with realistically modest treatment effects. This narrative review describes the major consequences of ICH and provides evidence-based recommendations to support decision-making in medical management.

Venous thromboembolism (VTE) remains a common problem in critically ill patients. Pharmacologic prophylaxis is currently the standard of care based on high-level evidence from randomized controlled trials. However, limited evidence exists regarding the effectiveness of intermittent pneumatic compression (IPC) devices. The Pneumatic compREssion for preventing VENous Thromboembolism (PREVENT trial) aims to determine whether the adjunct use of IPC with pharmacologic prophylaxis compared to pharmacologic prophylaxis alone in critically ill patients reduces the risk of VTE.

The PREVENT trial is a multicenter randomized controlled trial, which will recruit 2000 critically ill patients from over 20 hospitals in three countries. The primary outcome is the incidence of proximal lower extremity deep vein thrombosis (DVT) within 28 days after randomization. Radiologists interpreting the scans are blinded to intervention allocation, whereas the patients and caregivers are unblinded. The trial has 80 % power to detect a 3 % absolute risk reduction in proximal DVT from 7 to 4 %.

The first patient was enrolled in July 2014. As of May 2015, a total of 650 patients have been enrolled from 13 centers in Saudi Arabia, Canada and Australia. The first interim analysis is anticipated in July 2016. We expect to complete recruitment by 2018.

Clinicaltrials.gov: NCT02040103 (registered on 3 November 2013). Current controlled trials: ISRCTN44653506 (registered on 30 October 2013).

Catatonia is a syndrome of motor and psychological disturbances, which is accompanied by blood stasis that increases the risk of deep vein thrombosis (DVT). The aim of this study was to examine the incidence of DVT in catatonic patients in comparison to that in non-catatonic physically restrained patients. We conducted a chart review of involuntarily hospitalized patients from 2010 to 2013 at Sakuragaoka Memorial Hospital in Japan. Routine screening of DVT has been conducted for catatonic patients and restrained patients in this hospital. Catatonic patients were identified based on descriptions of charts and sorted to two subtypes (i.e. retarded and excited forms). A Doppler ultrasound scanning was performed to examine the presence of DVT. The incidence of DVT was compared among retarded and excited catatonic patients and non-catatonic restrained patients. There were 79 catatonic patients, of whom 42 were retarded. The incidence of DVT was 25.3% (20/79) in the catatonic patients. The retarded catatonic patients demonstrated a significantly higher incidence rate than the restrained non-catatonic patients (35.7% [15/42] vs. 10.6% [31/272], adjusted OR, 4.47). The incidence of DVT in catatonic patients, especially in the retarded form, was considerably high, which suggests the importance of prophylaxis of DVT.

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.

To assess the clinical effectiveness of thigh length versus knee length antiembolism stockings for the prevention of deep vein thrombosis (DVT) in surgical patients.

Systematic review and meta-analysis using direct methods and network meta-analysis.

Previous systematic reviews and electronic databases were searched to February 2014 for randomised controlled trials (RCTs) of thigh length or knee length antiembolism stockings in surgical patients. Study quality was assessed using the Cochrane Risk of Bias Tool. The primary outcome was incidence of DVT. Analysis of the DVT data was performed using ORs along with 95% CIs. The I(2) statistic was used to quantify statistical heterogeneity.

23 RCTs were included; there was substantial variation between the trials and many were poorly reported with an unclear risk of bias. Five RCTs directly comparing thigh length versus knee length stockings were pooled and the summary estimate of effect favouring thigh length stockings was not statistically significant (OR 1.48, 95% CI 0.80 to 2.73). 13 RCTs were included in the network meta-analysis; thigh length stockings with pharmacological prophylaxis were more effective than knee length stockings with pharmacological prophylaxis, but again results were not statistically significant (OR 1.76, 95% credible intervals 0.82 to 3.53).

Thigh length stockings may be more effective than knee length stockings, but results did not reach statistical significance and the evidence base is weak. Further research to confirm this finding is unlikely to be worthwhile. While thigh length stockings appear to have superior efficacy, practical issues such as patient acceptability may prevent their wide use in clinical practice.

CRD42014007202.

Large hemispheric infarction (LHI), also known as malignant middle cerebral infarction, is a devastating disease associated with significant disability and mortality. Clinicians and family members are often faced with a paucity of high quality clinical data as they attempt to determine the most appropriate course of treatment for patients with LHI, and current stroke guidelines do not provide a detailed approach regarding the day-to-day management of these complicated patients. To address this need, the Neurocritical Care Society organized an international multidisciplinary consensus conference on the critical care management of LHI. Experts from neurocritical care, neurosurgery, neurology, interventional neuroradiology, and neuroanesthesiology from Europe and North America were recruited based on their publications and expertise. The panel devised a series of clinical questions related to LHI, and assessed the quality of data related to these questions using the Grading of Recommendation Assessment, Development and Evaluation guideline system. They then developed recommendations (denoted as strong or weak) based on the quality of the evidence, as well as the balance of benefits and harms of the studied interventions, the values and preferences of patients, and resource considerations.

To investigate the correlations between three vascular endothelial growth factor 2 (VEGFR2) gene polymorphisms, +1192C>T, +1719T>A, and -604T>C, and deep venous thrombosis (DVT) in Chinese Han population.

We conducted a case-control study, between September 2009 and September 2012, in a Chinese Han population with onset of lower extremity DVT. A total of 135 patients were enrolled in the case group and 156 healthy individuals in the control group. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the genotype and allele frequencies of the VEGFR2 gene polymorphisms +1192C>T, +1719T>A, and -604T>C. Haplotype analyses were conducted with SHEsis program. Logistic regression was used to detect the risk factors of DVT. Outpatient review and telephone follow-up were conducted to analyze the long-term treatment of DVT patients.

The allele and genotype frequencies of -604T>C VEGFR2 polymorphism exhibited significant differences between the case and control groups (both p < 0.05). Haplotype analyses showed remarkable differences between the case and control groups in the distribution frequency of TAC and CTT haplotypes in the VEGFR2 gene (both p < 0.05). Logistic regression analysis showed independent correlation between the incidence of DVT and TAC haplotype in the VEGFR2 gene (p < 0.05). In addition, the TAC haplotype may be a risk factor for DVT treatment failure.

Our findings suggest that the VEGFR2 gene -604T>C polymorphism and TAC haplotype are associated with DVT, and the TAC haplotype might affect the efficacy of long-term treatment of DVT patients.

Intracerebral hemorrhage (ICH) is a stroke subtype with high mortality and significant disability among survivors. The management of ICH has been influenced by the results of several major trials completed in the last decade. It is now recognized that hematoma expansion is a major cause of morbidity and mortality. However, efforts to improve clinical outcome through mitigation of hematoma expansion have so far been unsuccessful. Acute blood pressure management has recently been shown to be safe in the setting of acute ICH but there was no reduction in mortality with early blood pressure (BP) lowering. Two large trials of surgical evacuation of supratentorial ICH have not shown improvement in outcome with surgery, thus minimally invasive surgical strategies are currently being studied. Lastly, a better understanding of the pathophysiology of ICH has led to the identification of several new mechanisms of injury that could be potential therapeutic targets.

The aim of this guideline is to present current and comprehensive recommendations for the diagnosis and treatment of spontaneous intracerebral hemorrhage.

A formal literature search of PubMed was performed through the end of August 2013. The writing committee met by teleconference to discuss narrative text and recommendations. Recommendations follow the American Heart Association/American Stroke Association methods of classifying the level of certainty of the treatment effect and the class of evidence. Prerelease review of the draft guideline was performed by 6 expert peer reviewers and by the members of the Stroke Council Scientific Oversight Committee and Stroke Council Leadership Committee.

Evidence-based guidelines are presented for the care of patients with acute intracerebral hemorrhage. Topics focused on diagnosis, management of coagulopathy and blood pressure, prevention and control of secondary brain injury and intracranial pressure, the role of surgery, outcome prediction, rehabilitation, secondary prevention, and future considerations. Results of new phase 3 trials were incorporated.

Intracerebral hemorrhage remains a serious condition for which early aggressive care is warranted. These guidelines provide a framework for goal-directed treatment of the patient with intracerebral hemorrhage.

We are entering a challenging but exciting period when many new interventions may appear for stroke based on the use of devices. Hopefully these will lead to improved outcomes at a cost that can be afforded in most parts of the world. Nevertheless, it is vital that lessons are learnt from failures in the development of pharmacological interventions (and from some early device studies), including inadequate preclinical testing, suboptimal trial design and analysis, and underpowered studies. The device industry is far more disparate than that seen for pharmaceuticals; companies are very variable in size and experience in stroke, and are developing interventions across a wide range of stroke treatment and prevention. It is vital that companies work together where sales and marketing are not involved, including in understanding basic stroke mechanisms, prospective systematic reviews, and education of physicians. Where possible, industry and academics should also work closely together to ensure trials are designed to be relevant to patient care and outcomes. Additionally, regulation of the device industry lags behind that for pharmaceuticals, and it is critical that new interventions are shown to be safe and effective rather than just feasible. Phase IV postmarketing surveillance studies will also be needed to ensure that devices are safe when used in the 'real-world' and to pick up uncommon adverse events.

Graduated compression stockings carry a potential risk of pressure, vascular and other complications. Current understanding of deep vein thrombosis (DVT) risk leaves it uncertain whether patients with hip fracture should wear stockings on both legs.

To determine the association between the side of the hip fracture and the subsequent occurrence of symptomatic lower limb DVT.

Single tertiary trauma centre, Wales.

All 3657 patients presenting with hip fracture between 2007 and 2013 were identified from our unit's National Hip Fracture Database. We excluded 404 patients (11.0%) resident outside our catchment area, leaving a total of 3253. Median age was 83 years (±12.4).

We cross-linked patient details with Medical Physics records, to identify 634 (19.5%) who had undergone one or more lower-limb Doppler-ultrasound scans at some point during the study period. The distribution rates of DVT were calculated from this resulting data set.

Many of the total 634 scans were unrelated to the hip fracture, including 225 (35.5%) performed prior to the fracture. We calculated a baseline rate of DVT of 3.7/1000 patients per year, for the 3-month period immediately before the hip fracture. Scans performed following hip fracture showed DVT risk to be highest in the 3-month period after fracture (35.7/1000 patients per year). This resulted from a six-fold increase in DVTs on the side of the fracture (29.5/1000 patients per year, p<0.01). We found only a very small non-significant increase in DVT on the contralateral leg (6.1/1000 patients per year)

The additional risk of DVT after hip fracture is essentially confined to the fractured limb-the leg to which it is most painful to apply stockings. There appears little justification for the cost and potential risk of using stockings on the contralateral leg.