Siobhan Crichton

Survival Outcomes and Prognostic Factors in Mycosis Fungoides/Sézary Syndrome: Validation of the Revised International Society for Cutaneous Lymphomas/European Organisation for Research and Treatment of Cancer Staging Proposal

PURPOSE We have analyzed the outcome of mycosis fungoides (MF) and Sézary syndrome (SS) patients using the recent International Society for Cutaneous Lymphomas (ISCL)/European Organisation for Research and Treatment of Cancer (EORTC) revised staging proposal. PATIENTS AND METHODS Overall survival (OS), disease-specific survival (DSS), and risk of disease progression (RDP) were calculated for a cohort of 1,502 patients using univariate and multivariate models. RESULTS The mean age at diagnosis was 54 years, and 71% of patients presented with early-stage disease. Disease progression occurred in 34%, and 26% of patients died due to MF/SS. A significant difference in survival and progression was noted for patients with early-stage disease having patches alone (T1a/T2a) compared with those having patches and plaques (T1b/T2b). Univariate analysis established that (1) advanced skin and overall clinical stage, increased age, male sex, increased lactate dehydrogenase (LDH), and large-cell transformation were associated with reduced survival and increased RDP; (2) hypopigmented MF, MF with lymphomatoid papulosis, and poikilodermatous MF were associated with improved survival and reduced RDP; and (3) folliculotropic MF was associated with an increased RDP. Multivariate analysis established that (1) advanced skin (T) stage, the presence in peripheral blood of the tumor clone without Sézary cells (B0b), increased LDH, and folliculotropic MF were independent predictors of poor survival and increased RDP; (2) large-cell transformation and tumor distribution were independent predictors of increased RDP only; and (3) N, M, and B stages; age; male sex; and poikilodermatous MF were only significant for survival. CONCLUSION This study has validated the recently proposed ISCL/EORTC staging system and identified new prognostic factors.

Self-Reported Long-Term Needs After Stroke

Background and Purpose— Development of interventions to manage patients with stroke after discharge from the hospital requires estimates of need. This study estimates the prevalence of self-reported need in community-dwelling stroke survivors across the United Kingdom. Methods— We conducted a survey of stroke survivors 1 to 5 years poststroke recruited through Medical Research Council General Practice Research Framework general practices and 2 population-based stroke registers. Levels and type of need were calculated with comparisons among sociodemographic groups, disability level, and cognitive status using the &khgr;2 test or Fisher exact test, as appropriate. Results— From 1251 participants, response rates were 60% (national sample) and 78% (population registers sample) with few differences in levels of reported need between the 2 samples. Over half (51%) reported no unmet needs; among the remainder, the median number of unmet needs was 3 (range, 1 to 13). Proportions reporting unmet clinical needs ranged from 15% to 59%; 54% reported an unmet need for stroke information; 52% reported reduction in or loss of work activities, significantly more from black ethnic groups (P=0.006); 18% reported a loss in income and 31% an increase in expenses with differences by age, ethnic group, and deprivation score. In multivariable analysis, ethnicity (P=0.032) and disability (P=0.014) were associated with total number of unmet needs. Conclusions— Multiple long-term clinical and social needs remain unmet long after incident stroke. Higher levels of unmet need were reported by people with disabilities, from ethnic minority groups, and from those living in the most deprived areas. Development and testing of novel methods to meet unmet needs are required.

Socioeconomic Status and Stroke An Updated Review

Background and Purpose— Rates of stroke incidence and mortality vary across populations with important differences between socioeconomic groups worldwide. Knowledge of existing disparities in stroke risk is important for effective stroke prevention and management strategies. This review updates the evidence for associations between socioeconomic status and stroke. Summary of Review— Studies were identified with electronic searches of MEDLINE and EMBASE databases (January 2006 to July 2011) and reference lists from identified studies were searched manually. Articles reporting the association between any measure of socioeconomic status and stroke were included. Conclusions— The impact of stroke as measured by disability-adjusted life-years lost and mortality rates is >3-fold higher in low-income compared with high- and middle-income countries. The number of stroke deaths is projected to increase by >30% in the next 20 years with the majority occurring in low-income countries. Higher incidence of stroke, stroke risk factors, and rates of stroke mortality are generally observed in low compared with high socioeconomic groups within and between populations worldwide. There is less available evidence of an association between socioeconomic status and stroke recurrence or temporal trends in inequalities. Those with a lower socioeconomic status have more severe deficits and are less likely to receive evidence-based stroke services, although the results are inconsistent. Poorer people within a population and poorer countries globally are most affected in terms of incidence and poor outcomes of stroke. Innovative prevention strategies targeting people in low socioeconomic groups are required along with effective measures to promote access to effective stroke interventions worldwide.

Estimates of Outcomes Up to Ten Years after Stroke: Analysis from the Prospective South London Stroke Register

Charles Wolfe and colleagues collected data from the South London Stroke Register on 3,373 first strokes registered between 1995 and 2006 and showed that between 20% and 30% of survivors have poor outcomes up to 10 years after stroke.

Frequency and predictors for the risk of stroke recurrence up to 10 years after stroke: the South London Stroke Register

Background: Data estimating the risk of, and predictors for, long-term stroke recurrence are lacking. Methods: Data were collected from the population-based South London Stroke Register. Patients were followed up for a maximum of 10 years. Kaplan–Meier estimates and Cox proportional hazards models were used to assess the cumulative risk of and predictors for first stroke recurrence. Variables analysed included sociodemographic factors, stroke subtype (defined as cerebral infarction, intracerebral haemorrhage and subarachnoid haemorrhage), stroke severity markers and prior-to-stroke risk factors. Results: Between 1995 and 2004, 2874 patients with first-ever stroke were included. The mean follow-up period was 2.9 years. During 8311 person-years of follow-up, 303 recurrent events occurred. The cumulative risk of stroke recurrence at 1 year, 5 years and 10 years was 7.1%, 16.2% and 24.5% respectively. No differences in stroke recurrence were noted between the stroke subtypes. Factors increasing the risk of recurrence at 1 year were previous myocardial infarction (HR 1.73; 95% CI 1.08 to 2.78) and atrial fibrillation (HR 1.61; 95% CI 1.04 to 4.27); at 5 years, hypertension (HR 1.47; 95% CI 1.08 to 1.99) and atrial fibrillation (HR 1.79; 95% CI 1.29 to 2.49); and at 10 years, older age (p = 0.04), and hypertension (HR 1.38, 95% CI 1.04 to 1.82), myocardial infarction (HR 1.50, 95% CI 1.06 to 2.11) and atrial fibrillation (HR 1.51, 95% CI 1.09 to 2.09). Conclusions: Very-long-term risk of stroke recurrence is substantial. Different predictors for stroke recurrence were identified throughout the follow-up period. Risk factors prior to initial stroke have a significant role in predicting stroke recurrence up to 10 years.

The Natural History of Depression up to 15 Years After Stroke The South London Stroke Register

Background and Purpose— Evidence on the natural history of depression after stroke is still insufficient to inform prognosis and treatment strategies. This study estimates the incidence, cumulative incidence, prevalence, time of onset, duration, and recurrence rate of depression up to 15 years after stroke. Methods— Data from patients registered in the South London Stroke Register between 1995 and 2009 were used (N=4022 at registration. Maximum number of participants for these analyses n=1233). Depression was assessed in all patients with the Hospital Anxiety and Depression Scale (scores >7=depression) 3 months after stroke, 1 year after stroke, and annually thereafter up to 15 years after stroke. Inverse probability weighting was used to calculate the estimates accounting for missing data. Results— The poststroke incidence of depression ranged from 7% to 21% in the 15 years after a stroke, with cumulative incidence of 55% and prevalence ranging from 29% to 39%. Most episodes of depression started within a year of stroke, with 33% of the cases starting in the 3 months after a stroke, and none from year 10 onward. Fifty percent of the patients with depression at 3 months had recovered 1 year after stroke. The proportion of recurrent episodes of depression after stroke increased gradually from 38% in year 2 to 100% in years 14 and 15. Conclusions— The natural history of depression after stroke is dynamic. Depression affects most of the stroke patients with episodes that have a short duration but a high risk of recurrence in the long term.

Incidence and Associations of Poststroke Epilepsy: The Prospective South London Stroke Register

Background and Purpose— To describe the epidemiology and associations of poststroke epilepsy (PSE) because there is limited evidence to inform clinicians and guide future research. Methods— Data were collected from the population-based South London Stroke Register of first strokes in a multiethnic inner-city population with a maximum follow-up of 12 years. Self-completed forms and interviews notified study organizers of epilepsy diagnosis. Kaplan–Meier methods and Cox models were used to assess associations with sociodemographic factors, clinical features, stroke subtype, and severity markers. Results— Three thousand three-hundred ten patients with no history of epilepsy presented with first stroke between 1995 and 2007, with a mean follow-up of 3.8 years. Two-hundred thirteen subjects (6.4%) had development of PSE. PSE incidence at 3 months and 1, 5, and 10 years were estimated at 1.5%, 3.5%, 9.0%, and 12.4%, respectively. Sex, ethnicity, and socioeconomic status were not associations, but markers of cortical location, including dysphasia, visual neglect, and field defect, along with stroke severity indices at presentation, including low Glasgow Coma Scale, incontinence, or poor function on Barthel Index, were associated with PSE on univariate analysis. Young age was independently associated with PSE, affecting 10.7% of patients aged <65 years and 1.6% >85 years (P⩽0.001) on 10-year estimates. Independent predictors of PSE also included visual neglect, dysphasia, and stroke subtype, particularly total anterior circulation infarcts. Dysarthria was associated with reduced incidence. Conclusions— PSE is common, with risk continuing to increase outside the acute phase. Young age, cortical location, larger lesions, and hemorrhagic lesions are independent predictors.

The long-term outcomes of depression up to 10 years after stroke; the South London Stroke Register

Background Post-stroke depression is a frequent chronic and recurrent problem that starts shortly after stroke and affects patients in the long term. The health outcomes of depression after stroke are unclear. Aims (1) To investigate the associations between depression at 3 months and mortality, stroke recurrence, disability, cognitive impairment, anxiety and quality of life (QoL), up to 5 years post-stroke. (2) To investigate these associations in patients recovering from depression by year 1. (3) To investigate associations between depression at 5 years and these outcomes up to 10 years. Methods Data from the South London Stroke Register (1997–2010) were used. Patients (n at registration=3240) were assessed at stroke onset, 3 months after stroke and annually thereafter. Baseline data included sociodemographics and stroke severity measures. Follow-up assessments included anxiety and depression (Hospital Anxiety and Depression scale), disability, QoL and stroke recurrence. Multivariable regression models adjusted for age, gender, ethnicity, stroke severity and disability were used to investigate the association between depression and outcomes at follow-up. Results Depression at 3 months was associated with: increased mortality (HR: 1.27 (1.04 to 1.55)), disability (RRs up to 4.71 (2.96 to 7.48)), anxiety (ORs up to 3.49 (1.71 to 7.12)) and lower QoL (coefficients up to −8.16 (−10.23−6.15)) up to year 5. Recovery from depression by 1 year did not alter these risks to 5 years. Depression in year 5 was associated with anxiety (ORs up to 4.06 (1.92 to 8.58)) and QoL (coefficients up to −11.36 (−14.86 to −7.85)) up to year 10. Conclusions Depression is independently associated with poor health outcomes.

A cutaneous lymphoma international prognostic index (CLIPi) for mycosis fungoides and Sezary syndrome

BACKGROUND There is no prognostic index for primary cutaneous T-cell lymphomas such as mycosis fungoides (MF) and Sezary syndrome (SS). METHOD Two prognostic indices were developed for early (IA-IIA) and late stage (IIB-IVB) disease based on multivariate data from 1502 patients. End-points included overall survival (OS) and progression free survival (PFS). External validation included 1221 patients. FINDINGS Significant adverse prognostic factors at diagnosis consisted of male gender, age >60, plaques, folliculotropic disease and stage N1/Nx for early stage, and male gender, age >60, stages B1/B2, N2/3 and visceral involvement for late stage disease. Using these variables we constructed two separate models each defined using 3 distinct groups for early and late stage patients: 0-1 (low risk), 2 (intermediate risk), and 3-5 factors (high risk). 10 year OS in the early stage model was 90.3% (low), 76.2% (intermediate) and 48.9% (high) and for the late stage model 53.2% (low), 19.8% (intermediate) and 15.0% (high). For the validation set significant differences in OS and PFS in early stage patients (both p<0.001) were also noted. In late stage patients, only OS differed between the groups (p=0.002). INTERPRETATION This proposed cutaneous lymphoma prognostic index provides a model for prediction of OS in early and late stage MF/SS enabling rational therapeutic choices and patient stratification in clinical trials.

The effects of socioeconomic status on stroke risk and outcomes

The latest evidence on socioeconomic status and stroke shows that stroke not only disproportionately affects low-income and middle-income countries, but also socioeconomically deprived populations within high-income countries. These disparities are reflected not only in risk of stroke but also in short-term and long-term outcomes after stroke. Increased average levels of conventional risk factors (eg, hypertension, hyperlipidaemia, excessive alcohol intake, smoking, obesity, and sedentary lifestyle) in populations with low socioeconomic status account for about half of these effects. In many countries, evidence shows that people with lower socioeconomic status are less likely to receive good-quality acute hospital and rehabilitation care than people with higher socioeconomic status. For clinical practice, better implementation of well established treatments, effective management of risk factors, and equity of access to high-quality acute stroke care and rehabilitation will probably reduce inequality substantially. Overcoming barriers and adapting evidence-based interventions to different countries and health-care settings remains a research priority.