Kjell Asplund

Major depression in stroke patients. A 3-year longitudinal study.

Background and Purpose This prospective study was designed to examine the contributions of neurobiological, functional, and psychosocial factors to major depression after stroke. In addition, the prevalence and longitudinal course of major depression were studied. Methods Major depression, functional ability, and social network were assessed repeatedly for a period of 3 years in a population-based cohort of 80 patients with acute stroke (mean age, 73 years). Cerebral atrophy and brain lesion parameters were determined from computed tomographic scans performed acutely and after 3 years. Results The prevalence of major depression was 25% at the acute stage and approximately the same at 3 months (31%). It decreased to 16% at 12 months, was 19% at 2 years, and increased to 29% at 3 years. The most important predictors of immediate major depression were left anterior brain lesion, dysphasia, and living alone. Dependence in activities of daily living was the most important predictor at 3 months. From 12 months on, the patients having few social contacts outside the immediate family contributed most to depression, and at 3 years cerebral atrophy also contributed. At 1 year, 60% of the patients with early depression (0 to 3 months) had recovered; those not recovered at this follow-up had a high risk of development of chronic depression. Conclusions The study has provided evidence of a differentiation of factors likely to be implicated in the development of depression after stroke based on the period of time since the stroke event.

Stroke Incidence, Case Fatality, and Mortality in the WHO MONICA Project

BACKGROUND AND PURPOSE This report compares stroke incidence, case fatality, and mortality rates during the first years of the WHO MONICA Project in 16 European and 2 Asian populations. METHODS In the stroke component of the WHO MONICA Project, stroke registers were established with uniform and standardized rules for case ascertainment and validation of events. RESULTS A total of 13,597 stroke events were registered from 1985 through 1987 in a total background population of 2.9 million people aged 35 to 64 years. Age-standardized stroke incidence rates per 100,000 varied from 101 to 285 in men and from 47 to 198 in women. The combined stroke attack rates for first and recurrent events were approximately 20% higher than incidence rates in most populations and varied to the same extent. Stroke incidence rates were very high among the population of Finnish men tested. The incidence of stroke was, in general, higher among populations in eastern than in western Europe. It was also relatively high in the Chinese population studied, particularly among women. The case-fatality rates at 28 days varied from 15% to 49% among men and from 18% to 57% among women. In half of the populations studied, there were only minor differences between official stroke mortality rates and rates measured on the basis of fatal events registered and validated for the WHO MONICA stroke study. CONCLUSIONS The WHO MONICA Project provides a unique opportunity to perform cross-sectional and longitudinal comparisons of stroke epidemiology in many populations. The present data show how large differences in stroke incidence and case-fatality rates contribute to the more than threefold differences in stroke mortality rates among populations.

Leptin is associated with increased risk of myocardial infarction

Abstract. Söderberg S, Ahrén B, Jansson J‐H, Johnson O, Hallmans G, Asplund K, Olsson T (Umeå University, Umeå; and Lund University, Malmö, Sweden). Leptin is associated with increased risk of myocardial infarction. J Intern Med 1999; 246: 409–418.

A Multinational Comparison of Subarachnoid Hemorrhage Epidemiology in the WHO MONICA Stroke Study

BACKGROUND AND PURPOSE By official, mostly unvalidated statistics, mortality from subarachnoid hemorrhage (SAH) show large variations between countries. Using uniform criteria for case ascertainment and diagnosis, a multinational comparison of attack rates and case fatality rates of SAH has been performed within the framework of the WHO MONICA Project. METHODS In 25- to 64-year-old men and women, a total of 3368 SAH events were recorded during 35.9 million person-years of observation in 11 populations in Europe and China. Strict MONICA criteria were used for case ascertainment and diagnosis of stroke subtype. Case fatality was based on follow-up at 28 days after onset. RESULTS Age-adjusted average annual SAH attack rates varied 10-fold among the 11 populations studied, from 2.0 (95% CI 1.6 to 2.4) per 100 000 population per year in China-Beijing to 22.5 (95% CI 20.9 to 24.1) per 100 000 population per year in Finland. No consistent pattern was observed in the sex ratio of attack rates in the different populations. The overall 28-day case fatality rate was 42%, with 2-fold differences in age-adjusted rates between populations but little difference between men and women. Case fatality rates were consistently higher in Eastern than in Western Europe. CONCLUSIONS Using a uniform methodology, the WHO MONICA Project has shown very large variations in attack rates of SAH across 11 populations in Europe and China. The generally accepted view that women have a higher risk of SAH than men does not apply to all populations. Marked differences in outcome of SAH add to the wide gap in the burden of stroke between East and West Europe.

Glycine antagonist (gavestinel) in neuroprotection (GAIN International) in patients with acute stroke: a randomised controlled trial

BACKGROUND Early treatment may improve acute ischaemic stroke outcome. Gavestinel is a selective antagonist at the glycine site of the N-methyl-D-aspartate (NMDA) receptor, and is neuroprotective in animal models of ischaemic stroke. METHODS We did a randomised, double-blind, placebo-controlled trial to test whether gavestinel could improve functional outcome after acute stroke in human beings. Conscious patients with stroke involving limb weakness received either gavestinel at an intravenous loading dose of 800 mg followed by 200 mg every 12 h for five doses, or matching placebo, within 6 h of stroke onset. Stratification variables were age and stroke severity. A computed tomography brain scan within 18 h of stroke onset identified the primary efficacy population with ischaemic stroke. Outcome was assessed by an independent observer with the Barthel index at 3 months. Three outcome categories were applied: good (Barthel index 95-100), moderate (60-90), and poor (0-55 or dead). Analysis was by intention to treat. FINDINGS Of 1804 patients randomised, 16 received no treatment, and 333 had primary intracranial haemorrhage. 891 patients received gavestinel and 897 received placebo. Outcome in 721 patients who received gavestinel and were analysed for the primary endpoint at 3 months was good in 246 (34.1%), moderate in 136 (18.8%), and poor in 339 (47.0%), compared with 256 (34.9%), 133 (18.1%), and 345 (47.0%), respectively, of 734 patients who received placebo (p=0.8). Mortality at 3 months was 147 (20.4%) in the gavestinel group and 138 (18.8%) in the placebo group. Outcomes within preplanned subgroup and secondary analyses were also neutral. There were no significant differences in serious side-effects between the groups. INTERPRETATION Treatment with gavestinel within 6 h of acute ischaemic stroke did not improve outcome.

Poststroke Fatigue A 2-Year Follow-Up Study of Stroke Patients in Sweden

Background and Purpose— Fatigue is common among stroke patients. This study determined the prevalence of fatigue among long-term survivors after stroke and what impact fatigue had on various aspects of daily life and on survival. Methods— This study was based on Riks-Stroke, a hospital-based national register for quality assessment of acute stroke events in Sweden. During the first 6 months of 1997, 8194 patients were registered in Riks-Stroke, and 5189 were still alive 2 years after the stroke. They were followed up by a mail questionnaire, to which 4023 (79%) responded. Patients who reported that they always felt depressed were excluded. Results— To the question, “Do you feel tired?” 366 (10.0%) of the patients answered that they always felt tired, and an additional 1070 (29.2%) were often tired. Patients who always felt tired were on average older than the rest of the study population (74.5 versus 71.5 years, P <0.001); therefore, all subsequent analyses were age adjusted. Fatigue was an independent predictor for having to move into an institutional setting after stroke. Fatigue was also an independent predictor for being dependent in primary activities of daily living functions. Three years after stroke, patients with fatigue also had a higher case fatality rate. Conclusions— Fatigue is frequent and often severe, even late after stroke. It is associated with profound deterioration of several aspects of everyday life and with higher case fatality, but it usually receives little attention by healthcare professionals. Intervention studies are needed.

Sex Differences in Management and Outcome After Stroke A Swedish National Perspective

Background and Purpose— It is disputed whether there are sex differences in management and outcome after stroke; early studies have shown inconsistent results. The objective of this study was to verify and explain differences between men and women in management and outcome after stroke in a national perspective. Methods— In 2001, 20 761 stroke patients were registered in Riks-Stroke, the national quality register for stroke care in Sweden in which all 84 hospitals participate. Data from 9 hospitals that had reported <70% of the estimated stroke events were excluded from analyses, leaving 19 547 patients (9666 women, 9881 men) at 75 hospitals for the present analyses. Results— Women were older than men (77.8 versus 73.2 years). After age adjustment, female patients were more often disabled, living at home with community support, or in institutions before the stroke. They also had a different cardiovascular risk factor profile. Case fatality ratios during the first 3 months were similar in men and women. After 3 months, more women were physically and mentally impaired and dependent on other persons. Female patients with atrial fibrillation received oral anticoagulants less often than men. Even after multiple adjustments for differences between sexes, female sex was independently associated with institutional living 3 months after the stroke (odds ratio, 1.2; 95% confidence interval, 1.0 to 1.4). Conclusions— Women have a worse prestroke condition. Except for case fatality ratios, they also have a worse outcome after stroke after adjustment for other prognostic factors. There are also sex differences in the medical management of stroke that need to be rectified.

Psychosocial function and life satisfaction after stroke.

This prospective study was designed to describe different aspects of psychosocial function after stroke and the development of changes over time. A major aim has been to identify mental, functional, and social factors associated with low life satisfaction late after stroke. Methods Social network, functional ability, leisure-time activities, experience of ill health, major depression, and life satisfaction were assessed repeatedly over 3 years in a population-based sample of 50 long-term survivors of stroke (mean age 71.4 years). Results Compared with a general elderly population, patients 3 years poststroke had more psychiatric symptoms, lower functional ability, and reduced life satisfaction. Contacts with children were maintained over the 3-year follow-up period, whereas contacts with friends and neighbors declined early after stroke and remained lower than in the general elderly population (p<0.05). When time dependency was analyzed, activities of daily living and somatic/neurological symptoms were found to change little after 3 months, while psychiatric symptoms showed changes later. Between 3 and 12 months poststroke, the prevalence of major depression decreased, leisure-time activities and social contacts were partly resumed, and life satisfaction improved (p<0.01). Once good life satisfaction was restored it was maintained, and poor life satisfaction at 1 year remained poor for the entire 3 years. Conclusions It is concluded that major depression early after stroke, functional disability, and an impaired social network interact to reduce life satisfaction for the long-term survivors of stroke.

A non-intensive stroke unit reduces functional disability and the need for long-term hospitalization.

In a prospective controlled trial we compared the clinical outcome for unselected acute stroke patients in a non-intensive stroke unit (n = 110) and in general medical wards (n = 183). The patients were comparable in age, marital state and functional impairment on admission. Case fatality rates over the first year after the stroke were similar in the two groups. By three months after the stroke, 15% of the survivors initially admitted to the stroke unit and 39% of those admitted to general medical wards remained hospitalized (p less than 0.001). The corresponding figures by one year after the cerebrovascular accident were 12% and 28%, respectively (p less than 0.05). A greater proportion of surviving stroke unit patients was independent in walking (0.10 greater than p greater than 0.05), personal hygiene (p less than 0.05) and dressing (p less than 0.001). Essential features of the stroke unit are team work headed by a stroke nurse, staff, patient and family education and very early onset of rehabilitation. We conclude that this strategy improves functional outcome and reduces the need for long-term hospital care.

Glibenclamide-associated hypoglycaemia: A report on 57 cases

SummaryIn the largest series of patients with glibenclamide-associated hypoglycaemia reported so far, 51 cases reported to the Swedish Adverse Drug Reactions Advisory Committee and six additional cases are reviewed and related to sales and prescription data of glibenclamide. Median age of the patients with hypoglycaemia was 75 years and 21% were 85 years or above. For comparison, the median age of a random sample (1 in 288 of all patients prescribed glibenclamide) was 70 years and only 5% were 85 years or older. In eight out of 40 cases where duration of glibenclamide treatment was recorded, the hypoglycaemic event occurred during the first month of treatment. The median daily dose of glibenclamide prescribed was 10 mg both in the hypoglycaemic cases and in the prescription sample. Coma or disturbed consciousness was the most common clinical presentation in this series and the minimum blood glucose value was 1.3 mmol/l (median). Twenty-two patients responded immediately to treatment, 24 had protracted hypoglycaemia of 12–72 h duration and 10 died. Fatal outcome was observed even with small doses of glibenclamide (2.5–5 mg/day). Previous strokes and cardiac disorders were isolated as two independent determinants of a serious course of the hypoglycaemia. Other contributing factors included impaired renal function, low food intake, diarrhoea, alcohol intake and interaction with other drugs. Thus, it is not uncommon for glibenclamide, like the first-generation sulphonylureas, to cause serious, protracted and even fatal hypoglycaemic events.