Long-term exposure to air pollution and hospital admissions for ischemic stroke. A register-based case-control study using modelled NOx as exposure proxy

Background: Long-term exposure to air pollution is a hypothesized risk factor for ischemic stroke. In a large case-control study with a complete study base, we investigated whether hospital admissions for ischemic stroke were associated with residential concentrations of outdoor NOx, as a proxy for exposure to air pollution, in the region of Scania, Southern Sweden. Methods: We used a two-phase case-control study design, including as first-phase controls all individuals born between 1923 and 1965 and residing in Scania in 2002 (N=556 912). We defined first-phase cases as first-time ischemic stroke patients residing in Scania and registered in the Swedish stroke register between 2001 and 2005 (N=4 904) and second-phase cases as cases for whom we had information on smoking status, diabetes, and medication for hypertension (N=4 375). For the controls, information on these covariables was collected from a public health survey, resulting in 4 716 second-phase controls. With a geographical information system and an emission database, individual residential outdoor annual mean NOx concentration was modelled. The data were analyzed with logistic regression. Results: We found no evident association between NOx and ischemic stroke. For example, the odds ratio for ischemic stroke associated with the NOx category 20-30 mu g/m(3) compared to the reference category of <10 mu g/m(3) was 0.95 (95% CI 0.86-1.06). Conclusion: In this study area, with generally low levels of air pollution, using a complete study base, high-quality ascertainment of cases, and individually modelled exposure, we did not observe any clear association between NOx and ischemic stroke hospital admissions

Applying a brain-computer interface to support motor imagery practice in people with stroke for upper limb recovery: A feasibility study

<p>Abstract</p> <p>Background</p> <p>There is now sufficient evidence that using a rehabilitation protocol involving motor imagery (MI) practice in conjunction with physical practice (PP) of goal-directed rehabilitation tasks leads to enhanced functional recovery of paralyzed limbs among stroke sufferers. It is however difficult to confirm patient engagement during an MI in the absence of any on-line measure. Fortunately an EEG-based brain-computer interface (BCI) can provide an on-line measure of MI activity as a neurofeedback for the BCI user to help him/her focus better on the MI task. However initial performance of novice BCI users may be quite moderate and may cause frustration. This paper reports a pilot study in which a BCI system is used to provide a computer game-based neurofeedback to stroke participants during the MI part of a protocol.</p> <p>Methods</p> <p>The participants included five chronic hemiplegic stroke sufferers. Participants received up to twelve 30-minute MI practice sessions (in conjunction with PP sessions of the same duration) on 2 days a week for 6 weeks. The BCI neurofeedback performance was evaluated based on the MI task classification accuracy (CA) rate. A set of outcome measures including action research arm test (ARAT) and grip strength (GS), was made use of in assessing the upper limb functional recovery. In addition, since stroke sufferers often experience physical tiredness, which may influence the protocol effectiveness, their fatigue and mood levels were assessed regularly.</p> <p>Results</p> <p>Positive improvement in at least one of the outcome measures was observed in all the participants, while improvements approached a minimal clinically important difference (MCID) for the ARAT. The on-line CA of MI induced sensorimotor rhythm (SMR) modulation patterns in the form of lateralized event-related desynchronization (ERD) and event-related synchronization (ERS) effects, for novice participants was in a moderate range of 60-75% within the limited 12 training sessions. The ERD/ERS change from the first to the last session was statistically significant for only two participants.</p> <p>Conclusions</p> <p>Overall the crucial observation is that the moderate BCI classification performance did not impede the positive rehabilitation trends as quantified with the rehabilitation outcome measures adopted in this study. Therefore it can be concluded that the BCI supported MI is a feasible intervention as part of a post-stroke rehabilitation protocol combining both PP and MI practice of rehabilitation tasks. Although these findings are promising, the scope of the final conclusions is limited by the small sample size and the lack of a control group.</p

Genotype- phenotype correlation and molecular heterogeneity in pyruvate kinase deficiency

Pyruvate kinase (PK) deficiency is a rare recessive congenital hemolytic anemia caused by mutations in the PKLR gene. This study reports the molecular features of 257 patients enrolled in the PKD Natural History Study. Of the 127 different pathogenic variants detected, 84 were missense and 43 non- missense, including 20 stop- gain, 11 affecting splicing, five large deletions, four in- frame indels, and three promoter variants. Within the 177 unrelated patients, 35 were homozygous and 142 compound heterozygous (77 for two missense, 48 for one missense and one non- missense, and 17 for two non- missense variants); the two most frequent mutations were p.R510Q in 23% and p.R486W in 9% of mutated alleles. Fifty- five (21%) patients were found to have at least one previously unreported variant with 45 newly described mutations. Patients with two non- missense mutations had lower hemoglobin levels, higher numbers of lifetime transfusions, and higher rates of complications including iron overload, extramedullary hematopoiesis, and pulmonary hypertension. Rare severe complications, including lower extremity ulcerations and hepatic failure, were seen more frequently in patients with non- missense mutations or with missense mutations characterized by severe protein instability. The PKLR genotype did not correlate with the frequency of complications in utero or in the newborn period. With ICCs ranging from 0.4 to 0.61, about the same degree of clinical similarity exists within siblings as it does between siblings, in terms of hemoglobin, total bilirubin, splenectomy status, and cholecystectomy status. Pregnancy outcomes were similar across genotypes in PK deficient women. This report confirms the wide genetic heterogeneity of PK deficiency.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154955/1/ajh25753.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154955/2/ajh25753_am.pd

Process skill rather than motor skill seems to be a predictor of costs for rehabilitation after a stroke in working age; a longitudinal study with a 1 year follow up post discharge

<p>Abstract</p> <p>Background</p> <p>In recent years a number of costs of stroke studies have been conducted based on incidence or prevalence and estimating costs at a given time. As there still is a need for a deeper understanding of factors influencing these costs the aim of this study was to calculate the direct and indirect costs in a younger (<65) sample of stroke patients and to explore factors affecting the costs.</p> <p>Methods</p> <p>Fifty-eight patients included in a study of home rehabilitation and followed for 1 year after discharge from the rehabilitation unit, were interviewed about their use of health care services, assistance, medications and assistive devices. Costs (defined as the cost for society) were calculated. A linear regression of cost and variables of functioning, ability, community integration and health-related quality of life was done.</p> <p>Results</p> <p>Inpatient care contributed substantially to the direct cost with a mean length of stay of 92 days. Rehabilitation during the first year constituted of an average of 28 days in day clinics, 38 physiotherapy sessions and 20 occupational therapy sessions. The total direct mean cost was 80 020 € and the indirect cost 35 129 €. The direct costs were influenced by the process skill (the ability to plan and perform a given task and to adapt when needed) and presence of aphasia. Indirect costs for informal care giving increased for patients with a lower health-related quality of life as well as a low score on home integration.</p> <p>Conclusion</p> <p>Costs are high in this group of young (< 65 years) stroke patients compared to other studies, partly due to the length of the stay and partly to loss of productivity.</p

Multiple clinical forms of dehydrated hereditary stomatocytosis arise from mutations in PIEZO1

Autosomal dominant dehydrated hereditary stomatocytosis (DHSt) usually presents as a compensated hemolytic anemia with macrocytosis and abnormally shaped red blood cells (RBCs). DHSt is part of a pleiotropic syndrome that may also exhibit pseudohyperkalemia and perinatal edema. We identified PIEZO1 as the disease gene for pleiotropic DHSt in a large kindred by exome sequencing analysis within the previously mapped 16q23-q24 interval. In 26 affected individuals among 7 multigenerational DHSt families with the pleiotropic syndrome, 11 heterozygous PIEZO1 missense mutations cosegregated with disease. PIEZO1 is expressed in the plasma membranes of RBCs and its messenger RNA, and protein levels increase during in vitro erythroid differentiation of CD341 cells. PIEZO1 is also expressed in liver and bone marrow during human and mouse development. We suggest for the first time a correlation between a PIEZO1 mutation and perinatal edema. DHSt patient red cells with the R2456H mutation exhibit increased ion-channel activity. Functional studies of PIEZO1 mutant R2488Q expressed in Xenopus oocytes demonstrated changes in ion-channel activity consistent with the altered cation content of DHSt patient red cells. Our findings provide direct evidence that R2456H and R2488Q mutations in PIEZO1 alter mechanosensitive channel regulation, leading to increased cation transport in erythroid cells

Fatigue after Stroke: Baseline Predictors and Influence on Survival. Analysis of Data from UK Patients Recruited in the International Stroke Trial

Little is known about the associations of post-stroke fatigue or its influence on survival. The vitality component of the Short Form 36 (SF-36) is a valid and reliable measure of post-stroke fatigue. We sought to identify associates of post-stroke fatigue and determine whether fatigue predicted survival.We used SF-36 vitality scores obtained by postal questionnaires from 1080 UK patients randomised in the International Stroke Trial, at a mean of 64 weeks after stroke onset. We used logistic regression to explore factors at randomisation which predicted SF-36 vitality at follow-up, and the relationship between SF-36 vitality and both SF-36 mental health and SF-36 emotional role function at follow-up. We used Cox proportional hazards to explore the influence of SF-36 vitality at follow-up on subsequent survival, using four different statistical models for handling missing data.Female sex, increasing age, lower mental health and lower emotional role function scores were associated with greater degrees of fatigue after stroke (i.e. lower vitality scores) but these factors explained <30% of the variance (R(2)) in fatigue. In two models, fatigue at follow-up was associated with shorter subsequent survival.Increasing age, female sex, emotional role function and mental health were associated with increased fatigue at a mean of 64 weeks after stroke onset, but explained less than 30% of the variance. Fatigue was associated with reduced subsequent long-term survival in 2/4 models. Further work is needed to identify the biological substrate of fatigue and to clarify its influence on survival

Stroke in women — from evidence to inequalities

Stroke is the second largest cause of disability-adjusted life-years lost worldwide. The prevalence of stroke in women is predicted to rise rapidly, owing to the increasing average age of the global female population. Vascular risk factors differ between women and men in terms of prevalence, and evidence increasingly supports the clinical importance of sex differences in stroke. The influence of some risk factors for stroke — including diabetes mellitus and atrial fibrillation — are stronger in women, and hypertensive disorders of pregnancy also affect the risk of stroke decades after pregnancy. However, in an era of evidence-based medicine, women are notably under-represented in clinical trials — despite governmental actions highlighting the need to include both men and women in clinical trials — resulting in a reduced generalizability of study results to women. The aim of this Review is to highlight new insights into specificities of stroke in women, to plan future research priorities, and to influence public health policies to decrease the worldwide burden of stroke in women