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Ayerbe L.,Kings College London | Ayis S.,Kings College London | Rudd A.G.,Guys and St. Thomas National Health Service Foundation Trust | Heuschmann P.U.,Charite - Medical University of Berlin | And 2 more authors.
Stroke | Year: 2011

Background and Purpose- The longer-term natural history of depression after stroke is poorly understood. We estimate frequency, predictors, and associations of depression up to 5 years after stroke in a population-based study. Methods- Data from 3689 patients registered in the South London Stroke Register 1995 to 2006 were used. Baseline data included age, sex, ethnicity, socioeconomic status, and stroke severity. At 3 months and at 1, 3, and 5 years, survivors were assessed for depression (Hospital Anxiety and Depression; depression subscale score >7 indicates depression), cognition, disability, activity, accommodation, employment, and social networks. Associations with depression were investigated with logistic regression. Data are reported with OR and 95% CI. Results- Depression frequencies were 33% (30%-36%), 28% (25%-30%), 32% (30%-35%), and 31% (27%-34%) at 3 months and at 1, 3, and 5 years after stroke, respectively. Forty-eight percent of patients were not depressed at any time point; 49% to 55% of depressed patients at 1 assessment remained depressed at follow-up; and 15% to 20% of patients at each assessment were new cases. Predictors of depression included stroke severity, inability to work, and impaired cognition. Associations with depression at follow-up included impaired cognition, lack of family support, institutionalization, inability to work, functional dependence, and low activity level. Conclusions- Frequency of depression up to 5 years after stroke is 30%; however, it is a dynamic situation with recovery and new cases diagnosed over time. These findings support the need for regular assessment of depression and its associated factors and for the development of effective interventions to reduce depression after stroke. Copyright © 2011 American Heart Association. All rights reserved.

Ntoumenopoulos G.,Guys and St. Thomas National Health Service Foundation Trust | Shannon H.,University College London | Main E.,University College London
Respiratory Care | Year: 2011

Background: Intubation and mechanical ventilation can impair mucociliary clearance and cause secretion retention, airway occlusion, atelectasis, and pneumonia. Animal and laboratory work has demonstrated that mechanical ventilator settings can generate a flow bias (inspiratory or expiratory) that may result in mucus movement either away from the ventilator (deeper into the lungs) or toward the ventilator (toward the mouth), respectively. An absolute difference of 17 L/ min, and a relative difference of ≥ 10%, between the expiratory and inspiratory flow have been reported as thresholds for mucus movement. Methods: We measured baseline peak inspiratory and expiratory flows during quiet mechanical ventilation in a convenience sample of 20 intubated and ventilated adult patients. Results: Nineteen patients had an inspiratory flow bias of ≥ 10%. Eight patients had an absolute mean inspiratory flow bias of ≥ 17 L/min. Conclusions: Commonly used mechanical ventilator settings generate an inspiratory flow bias that may promote secretion retention. © 2011 Daedalus Enterprises.

Harrison C.,Guys and St. Thomas National Health Service Foundation Trust
Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program | Year: 2010

The seminal discovery of the JAK2V617F mutation, which is highly prevalent in Philadelphia-negative myeloproliferative disorders, now renamed neoplasms, triggered an almost unprecedented explosion of interest and data in the field. Descriptions of additional mutations in exon 12 of JAK2, at position 515 in MPL, and a number of other mutations at low frequency followed these discoveries. These advances in our understanding of molecular pathogenesis of these conditions coincided with the publication of results from two major clinical studies, ECLAP and PT-1, which contributed important clinical insights and facilitated significant correlative data collection. This article, focusing mainly upon essential thrombocythemia and polycythemia vera, reviews four major themes: the impact upon classification of these disorders considering a radical review of current terminology, and then three areas pertinent to clinical management: the indications for cytoreductive therapy in which the key targets are to reduce thrombohemorrhagic complications, relieve disease-related symptoms, and minimize the risk of transformation to secondary myeloid malignancy such as myelodysplasia, leukemia, and secondary myelofibrosis; and second reviewing current and, last, future therapeutic options, in particular interferon and JAK2 inhibitors.

Pollock R.D.,Kings College London | Woledge R.C.,Kings College London | Martin F.C.,Guys and St. Thomas National Health Service Foundation Trust | Newham D.J.,Kings College London
Journal of Applied Physiology | Year: 2012

Whole body vibration (WBV) has been suggested to elicit reflex muscle contractions but this has never been verified. We recorded from 32 single motor units (MU) in the vastus lateralis of 7 healthy subjects (34 ± 15.4 yr) during five 1-min bouts of WBV (30 Hz, 3 mm peak to peak), and the vibration waveform was also recorded. Recruitment thresholds were recorded from 38 MUs before and after WBV. The phase angle distribution of all MUs during WBV was nonuniform (P < 0.001) and displayed a prominent peak phase angle of firing. There was a strong linear relationship (r = -0.68, P < 0.001) between the change in recruitment threshold after WBV and average recruitment threshold; the lowest threshold MUs increased recruitment threshold (P = 0.008) while reductions were observed in the higher threshold units (P = 0.031). We investigated one possible cause of changed thresholds. Presynaptic inhibition in the soleus was measured in 8 healthy subjects (29 ± 4.6 yr). A total of 30 H-reflexes (stimulation intensity 30% Mmax) were recorded before and after WBV: 15 conditioned by prior stimulation (60 ms) of the antagonist and 15 unconditioned. There were no significant changes in the relationship between the conditioned and unconditioned responses. The consistent phase angle at which each MU fired during WBV indicates the presence of reflex muscle activity similar to the tonic vibration reflex. The varying response in high- and low-threshold MUs may be due to the different contributions of the mono- and polysynaptic pathways but not presynaptic inhibition. Copyright © 2012 the American Physiological Society.

Oteng-Ntim E.,Kings College London | Oteng-Ntim E.,London School of Hygiene and Tropical Medicine | Meeks D.,Kings College London | Seed P.T.,Kings College London | And 4 more authors.
Blood | Year: 2015

A systematic review and meta-analysis of observational studies were conducted to quantify the association between sickle cell disease in pregnancy and adverse maternal and perinatal outcomes. Data sources (Medline, Embase, Maternity and Infant care, Cochrane, Web of Science, Popline) were searched for publications to June 2014. Eligibility criteria included observational studies reporting maternal and perinatal health outcomes in pregnant women with sickle cell disease against a comparative group of pregnant women without sickle cell disease. Twenty-one studies (including 26 349 women with sickle cell disease; 26 151 746 women without sickle cell disease) were eligible for inclusion. Pregnancies in women with HbSS genotype, compared with women without sickle cell disease, were at increased risk of maternal mortality (relative risk [RR], 5.98; 95% confidence interval [CI], 1.94-18.44), preeclampsia (RR, 2.43; 95% CI, 1.75-3.39), stillbirth (RR, 3.94; 95% CI, 2.60-5.96), preterm delivery (RR, 2.21; 95% CI, 1.47-3.31), and small for gestational age infants (RR, 3.72; 95% CI, 2.32-5.98). Meta-regression demonstrated that genotype (HbSS vs HbSC), low gross national income, and high study quality were associated with increased RRs. Despite advances in the management of sickle cell disease, obstetrics, and neonatal medicine, pregnancies complicated by the disease remain associated with increased risk of adverse maternal and perinatal outcomes. © 2015 by The American Society of Hematology.

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