Effect of intermittent pneumatic compression on disability, living circumstances, quality of life, and hospital costs after stroke: secondary analyses from CLOTS 3, a randomised trial

Background

The results of the CLOTS 3 trial showed that intermittent pneumatic compression (IPC) reduced the risk of deep vein thrombosis and improved survival in immobile patients with stroke. IPC is now being widely used in stroke units. Here we describe the disability, living circumstances, quality of life, and hospital costs of patients in CLOTS 3.

Methods

In CLOTS 3, a parallel group trial in 94 UK hospitals, immobile patients with stroke from days 0 to 3 of admission were assigned with a computer-generated allocation sequence in a 1:1 ratio to IPC or no IPC through a central randomisation system. We followed up patients at about 6 months with postal or telephone questionnaire to assess the secondary endpoints: disability (Oxford Handicap Scale [OHS]), living circumstances, health-related quality of life (EQ5D-3L), and hospital costs (based on use of IPC and length of hospital stay). Patients and carers who completed the postal questionnaires were not masked to treatment allocation, but telephone follow-up in non-responders was masked. All analyses were by intention to treat. This trial is registered, number ISRCTN93529999.

Findings

Between Dec 8, 2008, and Sept 6, 2012, we enrolled 2876 patients, with 1438 in each group. Despite the previously reported reduction in the risk of proximal deep vein thrombosis at 30 days (primary endpoint), there were no significant differences in disability (OHS 0—2 vs 3—6, adjusted odds ratio [OR] 0·98, 95% CI 0·80 to 1·19, p=0·83; adjusted ordinal analysis common OR 0·97, 95% CI 0·86 to 1·11), living circumstances (institutional care vs not; adjusted OR 1·11, 95% CI 0·89 to 1·37; p=0·358), or health-related quality of life (median utility value 0·26, IQR −0·07 to 0·66 with IPC, and 0·27, −0·06 to 0·64, with no IPC; p=0·952). The estimated cost of IPC was £64·10 per patient (SD 28·3). The direct costs of preventing a deep vein thrombosis and death were £1282 (95% CI 785 to 3077) and £2756 (1346 to not estimable), respectively, with IPC. Hospital costs increased by £451 with IPC compared with no IPC because of a longer stay in hospital (mean 44·5 days [SD 37·6] vs 42·8 days [37·2]; mean difference 1·8 days, 95% CI −1·0 to 4·5). By 6 months, despite an increase in survival (IPC 152·5 days [SD 60·6] vs no IPC 148·1 days [64·3]; mean difference 4·5 days, 95% CI −0·2 to 9·1), there was a non-significant increase in quality-adjusted survival associated with IPC (IPC 27·6 days [SD 40·6] vs no IPC 26·7 days [39·6]; mean difference 0·9 days, 95% CI −2·1 to 3·9).

Interpretation

IPC is inexpensive, prevents deep vein thrombosis, improves survival but not functional outcomes, and does not lead to a significant gain in quality-adjusted survival. When deciding whether to treat patients with IPC, clinicians need to take into account all these potential effects

Neurology 2014

Dementia Risk After Traumatic Brain Injury vs Nonbrain Trauma The Role of Age and Severity

Importance  Epidemiologic evidence regarding the importance of traumatic brain injury (TBI) as a risk factor for dementia is conflicting. Few previous studies have used patients with non-TBI trauma (NTT) as controls to investigate the influence of age and TBI severity.

Objective  To quantify the risk of dementia among adults with recent TBI compared with adults with NTT.

Design, Setting, and Participants  This retrospective cohort study was performed from January 1, 2005, through December 31, 2011 (follow-up, 5-7 years). All patients 55 years or older diagnosed as having TBI or NTT in 2005 and 2006 and who did not have baseline dementia or die during hospitalization (n = 164 661) were identified in a California statewide administrative health database of emergency department (ED) and inpatient visits.

Exposures  Mild vs moderate to severe TBI diagnosed by Centers for Disease Control and Prevention criteria using International Classification of Diseases, Ninth Revision (ICD-9)codes, and NTT, defined as fractures excluding fractures of the head and neck, diagnosed using ICD-9 codes.

Main Outcomes and Measures  Incident ED or inpatient diagnosis of dementia (using ICD-9codes) 1 year or more after initial TBI or NTT. The association between TBI and risk of dementia was estimated using Cox proportional hazards models before and after adjusting for common dementia predictors and potential confounders. We also stratified by TBI severity and age category (55-64, 65-74, 75-84, and ≥85 years).

Results  A total of 51 799 patients with trauma (31.5%) had TBI. Of these, 4361 (8.4%) developed dementia compared with 6610 patients with NTT (5.9%) (P < .001). We found that TBI was associated with increased dementia risk (hazard ratio [HR], 1.46; 95% CI, 1.41-1.52; P < .001). Adjustment for covariates had little effect except adjustment for age category (fully adjusted model HR, 1.26; 95% CI, 1.21-1.32; P < .001). In stratified adjusted analyses, moderate to severe TBI was associated with increased risk of dementia across all ages (age 55-64: HR, 1.72; 95% CI, 1.40-2.10; P < .001; vs age 65-74: HR, 1.46; 95% CI, 1.30-1.64; P < .001), whereas mild TBI may be a more important risk factor with increasing age (age 55-64: HR, 1.11; 95% CI, 0.80-1.53; P = .55; vs age 65-74: HR, 1.25; 95% CI, 1.04-1.51; P = .02; age interaction P < .001).

JAMA Neurology 2014 

Genetic Movement Disorders in Patients of Jewish Ancestry

Importance  Genetic diseases often cluster in different ethnic groups and may present with recognizable unique clinical manifestations.

Objective  To summarize current knowledge about movement disorders overrepresented among patients of Jewish ancestry.

Evidence Review  We searched PubMed and the OMIM and Israeli National Genetic Databases for articles published from 1969 through March 31, 2014, using the search terms Parkinson’s disease,movement disorders, ataxia, dystonia, chorea, and Creutzfeldt-Jakob with and Jewish. The final reference list was generated by giving priority to articles directly related to the topic, articles with the latest information, and comprehensive but relevant reviews.

Findings  About one-third of patients with sporadic Parkinson disease (PD) and more than 40% of patients with familial PD of Ashkenazi Jewish descent likely carry the G2019S mutation in the LRRK2gene, a mutation in the glucocerebrosidase (GBA) gene, or both. This finding contrasts with only a 10% frequency of these mutations in patients with PD who are of non-Jewish ancestry. A dystonia due to a TOR1A gene mutation is responsible for most early-onset autosomal dominant dystonia, and 90% of Ashkenazi Jews who develop early-onset disease have TOR1A-related dystonia. Familial Creutzfeldt-Jakob disease and cerebrotendinous xanthomatosis tend to cluster among Jews of North African descent, and Machado-Joseph disease is particularly frequent in Yemenite Jews.

Conclusions and Relevance  Genetic forms of PD are much more common in patients of Ashkenazi Jewish ancestry with sporadic and familial PD than in the non-Jewish population. The recognition of the particular movement disorder phenotype, coupled with information about the ethnic origin of the patients, may point to specific genetic testing and lead to early and correct diagnosis.

Neurology 2014

White Matter Integrity Determined With Diffusion Tensor Imaging in Older Adults Without Dementia Influence of Amyloid Load and Neurodegeneration

Importance  Pathophysiologic mechanisms leading to loss of white matter integrity and the temporal positioning of biomarkers of white matter integrity relative to the biomarkers of gray matter neurodegeneration and amyloid load in the course of Alzheimer disease (AD) are poorly understood.

Objective  To investigate the effects of AD-related gray matter neurodegeneration and high β-amyloid on white matter microstructure in older adults without dementia.

Design, Setting, and Participants  A population-based, longitudinal cohort study was conducted. Participants included in the Mayo Clinic Study of Aging (N = 701) who underwent magnetic resonance imaging, diffusion tensor imaging (DTI), and positron emission tomography studies with diagnoses of cognitively normal ([CN] n = 570) or mild cognitive impairment ([MCI] n = 131) were included. Both groups were divided into biomarker-negative, amyloid-positive-only, neurodegeneration-positive-only, and amyloid plus neurodegeneration-positive groups based on their amyloid load shown on carbon 11–labeled Pittsburgh Compound B positron emission tomography, AD hypometabolic pattern shown on fludeoxyglucose F 18 positron emission tomography, and/or hippocampal atrophy shown on magnetic resonance imaging.

Main Outcomes and Measures  Fractional anisotropy (FA) determined using DTI.

Results  No FA alterations were observed in biomarker-negative MCI and amyloid-positive-only CN and MCI groups compared with biomarker-negative CN participants on voxel-based analysis (P < .05; familywise error corrected). Conversely, the neurodegeneration-positive-only and amyloid plus neurodegeneration-positive CN and MCI groups consistently had decreased FA in the fornix, which correlated with cognitive performance (ρ = 0.38; P < .001). Patients with MCI had more extensive white matter involvement than did those with CN, and the greatest FA decreases were observed in the amyloid plus neurodegeneration-positive MCI group (P < .05; familywise error corrected).

Conclusions and Relevance  A high amyloid load does not influence diffusion tensor imaging–based measures of white matter integrity in the absence of coexistent gray matter neurodegeneration in older adults without dementia

JAMA Neurology 2014

Familial occurrence and heritable connective tissue disorders in cervical artery dissection

Objective: In a large series of patients with cervical artery dissection (CeAD), a major cause of ischemic stroke in young and middle-aged adults, we aimed to examine frequencies and correlates of family history of CeAD and of inherited connective tissue disorders.

Methods: We combined data from 2 large international multicenter cohorts of consecutive patients with CeAD in 23 neurologic departments participating in the CADISP-plus consortium, following a standardized protocol. Frequency of reported family history of CeAD and of inherited connective tissue disorders was assessed. Putative risk factors, baseline features, and 3-month outcome were compared between groups.

Results: Among 1,934 consecutive patients with CeAD, 20 patients (1.0%, 95% confidence interval: 0.6%–1.5%) from 17 families (0.9%, 0.5%–1.3%) had a family history of CeAD. Family history of CeAD was significantly more frequent in patients with carotid location of the dissection and elevated cholesterol levels. Two patients without a family history of CeAD had vascular Ehlers-Danlos syndrome with a mutation in COL3A1. This diagnosis was suspected in 2 additional patients, but COL3A1 sequencing was negative. Two patients were diagnosed with classic and hypermobile Ehlers-Danlos syndrome, one patient with Marfan syndrome, and one with osteogenesis imperfecta, based on clinical criteria only.

Conclusions: In this largest series of patients with CeAD to date, family history of symptomatic CeAD was rare and inherited connective tissue disorders seemed exceptional. This finding supports the notion that CeAD is a multifactorial disease in the vast majority of cases.

Neurology 2014

Motoric cognitive risk syndrome Multicenter incidence study

Objective: To report incidence and risk factors for motoric cognitive risk syndrome (MCR), a newly described predementia syndrome characterized by slow gait and cognitive complaints.

Methods: We examined incidence rates of MCR in 3,128 adults aged 60 years and older, MCR- and dementia-free at baseline, participating in 4 US-based cohort studies. Hazard ratios (HRs) with 95% confidence intervals (CIs) for the association of modifiable risk factors with risk of MCR were computed using Cox models.

Results: Over a median follow-up time of 3.2 years, 823 of the 3,128 participants met MCR criteria. The overall age- and sex-adjusted incidence of MCR was 65.2/1,000 person-years (95% CI: 53.3–77.1), and ranged from 50.8/1,000 person-years to 79.6/1,000 person-years in the individual cohorts. MCR incidence was higher with older age but there were no sex differences. In the pooled sample adjusted for age, sex, education, and cohort source, strokes (HR 1.42, 95% CI: 1.14–1.77), Parkinson disease (HR 2.52, 95% CI: 1.68–3.76), depressive symptoms (HR 1.65, 95% CI: 1.28–2.13), sedentariness (HR 1.76, 95% CI: 1.44–2.17), and obesity (HR 1.39, 95% CI: 1.17–1.65) predicted risk of incident MCR.

Conclusions: The incidence of MCR is high in older adults. Identification of modifiable risk factors for MCR will improve identification of high-risk individuals and help develop interventions to prevent cognitive decline in aging

Neurology 2014.

Neurologic complications in dengue virus infection

Objective: This study aimed to evaluate the incidence and clinical spectrum of neurologic complications, predictors of central and peripheral nervous system involvement, and their outcome in patients with dengue virus infection (DENV).

Methods: To determine the extent of neurologic complications, we used a hospital-based prospective cohort study design, which included laboratory-confirmed cases of dengue and follow-up for 3 months. We also analyzed clinical and laboratory data to assess predictors of neurologic involvement.

Results: The study included enrollment of 486 cases. Two were lost to follow-up and excluded. Forty-five patients developed neurologic complications. Of these, 28 patients had CNS and 17 had peripheral nervous system (PNS) involvement, representing an incidence rate for neurologic complications of 9.26%. Significant predictors of CNS involvement were higher mean body temperature (p = 0.012), elevated hematocrit (p = 0.009), low platelet count (p = 0.021), and liver dysfunction (p < 0.001). Predictors of PNS involvement were higher mean body temperature (p = 0.031), rash (p = 0.002), and elevated hematocrit (p < 0.001). The mortality rate was 4.5%. The remainder of the patients recovered.

Conclusion: An increasingly wide spectrum and higher incidence of neurologic complications of DENV are reported. Clinical and laboratory parameters such as higher mean body temperature, rash, increases in hematocrit, thrombocytopenia, and liver dysfunction are independent predictors of neurologic complications.

Neurology 2014