Safety of off-label stroke treatment with tissue plasminogen activator.

BACKGROUND: Many patients with acute ischaemic stroke do not receive intravenous thrombolysis due to contraindications. We aimed to assess safety, short-term clinical development, short-term outcome and mortality in patients treated off-label with tissue plasminogen activator (tPA). METHODS: Stroke patients treated with tPA within 4.5 h after symptom onset during 2006-2011 were prospectively included. Patients with contraindications to tPA according to national guidelines were compared to patients without any of these contraindications. Separate analyses were performed on patients who had compatible contraindications and did not receive tPA. Primary outcome was rate of symptomatic intracerebral haemorrhage (SICH). Secondary outcomes were short-term clinical development, short-term outcome and 30-day mortality. RESULTS: Of the 265 patients who received tPA, 135 patients (50.9%) had formal contraindications and 130 patients (49.1%) had no such contraindications. Rates of SICH were similar for patients with or without contraindications (P = 0.305). Patients with contraindications to tPA had a similar rate of clinical improvement (P = 0.504), a trend of less favourable outcome (P = 0.052) and higher mortality (P = 0.005) than patients without contraindications. Logistic regression analysis showed no association between presence of contraindications to tPA and short-term outcome or mortality when adjusted for age, sex and admission National Institute of Health Stroke Scale score. Short-term outcome and mortality were similar in patients with contraindications who received tPA and patients with contraindications who did not receive tPA (n = 134). CONCLUSIONS: Intravenous thrombolysis with tPA may be safe and efficient in stroke patients with a number of formal contraindications to tPA. Prospective randomized trials are imperative to clarify the need for a re-evaluation of the current contraindications to tPA.

Middle cerebral artery stenosis: transcranial color-coded sonography based on continuity equation versus CT-angiography.

PURPOSE: Transcranial color-coded sonography (TCCS) and CT-angiography (CTA) are reliable tools for detection of intracranial stenosis. Current ultrasonographic criteria for middle cerebral artery (MCA) stenosis are usually limited to a dichotomized grading (< or ≥ 50 %). As for carotid arteries, continuity equation might provide a more accurate evaluation of degree of MCA stenosis. We aimed to apply continuity equation to calculate degree of MCA stenosis with TCCS and to compare these results with CTA. MATERIALS AND METHODS: All patients admitted to our Neurovascular Center with ischemic stroke or TIA underwent TCCS examination. Degree of MCA stenosis was calculated based on continuity equation as (1 - [PSVprestenotic/PSVintrastenotic] × 100) %. CTA was performed when TCCS detected MCA stenosis, and degree of stenosis was calculated by diameter (D) as: (1 - [Dprestenotic/Dintrastenotic] × 100) %. Correlation between TCCS and CTA results was tested. Continuity equation method was compared to cut-off velocity method for detection of ≥ 50 % MCA stenosis. To assess TCCS inter-observer agreement, evaluation of MCA stenosis was repeated by another neurosonographer in a subgroup of patients. RESULTS: The overall correlation coefficient between TCCS and CTA was 0.85 (p < 0.0001). Correlation coefficient for stenosis defined with CTA as ≥ 50 % was 0.94 (p < 0.0001). TCCS inter-observer agreement on degree of stenosis was 0.85 (p = 0.001). In detection of ≥ 50 % MCA stenosis, continuity equation method showed a sensitivity of 78 % (14/18) and a specificity of 86 % (19/22), while the cut-off velocity method showed a sensitivity of 67 % (12/18) and a specificity of 86 % (19/22). CONCLUSION: This study shows that ultrasonographic evaluation of MCA stenosis applying the continuity equation provides reproducible and accurate results, and is more sensitive in detection of ≥ 50 % MCA stenosis than cut-off velocity method.

Depression predicts unfavourable functional outcome and higher mortality in stroke patients: the Bergen Stroke Study.

OBJECTIVE: To assess the influence of depression prior to stroke (PD) on stroke severity on admittance, functional outcome (short- and long-term), mortality, and long-term depression (PSD). METHODS: Consecutive acute stroke patients were screened for PD. The National Institute of Health Stroke Scale score was obtained on admission. Short-term functional state was registered by the modified Rankin scale and on long-term functional outcome by the Barthel Index. PSD was defined as depression subscale of the hospital anxiety and depression scale (HADSD) >or=11. HADSD and Barthel Index were obtained by postal questionnaire. Survival analyses were performed. RESULTS: Among 771 patients 21.7% had PD. Among 376 patients returning the questionnaire, 8.8% were depressed. On logistic regression analyses severity of stroke on admission, short-term, and long-term functional outcome were independently associated with PD. Logistic regression showed PSD to be independently associated with PD and being unmarried. Cox regression analyses showed that both PD and PSD were associated with high long-term mortality. CONCLUSIONS: This study has identified several factors associated with PSD. PD predicts more severe stroke on admittance and less functional improvement both in the short- and the long-term. Both PD and PSD predict higher long-term mortality.

Inverse relationship of baseline body temperature and outcome between ischemic stroke patients treated and not treated with thrombolysis: the Bergen stroke study.

BACKGROUND: High body temperature may promote clot lysis whereas low body temperature is neuroprotective in patients with cerebral infarction. We hypothesized that high body temperature is associated with favorable outcome in patients treated with tissue plasminogen activator (tPA) and that low body temperature is associated with favorable outcome in patients not treated with tPA. METHODS: Patients (n = 111) who were treated with tPA and patients (n = 139) who were not treated with tPA, but presented within 6 h of stroke onset were included. Patients with no temperature measurements within 6 h of stroke onset were excluded. National Institute of Health Stroke Scale (NIHSS) score was obtained on admission. Modified Rankin score (mRS) was obtained after 1 week. Favorable outcome was defined as mRS 0-2 and unfavorable outcome as mRS 3-6. RESULTS: On logistic regression analysis, high body temperature was independently associated with favorable outcome among patients treated with tPA (OR = 3.7, P = 0.009) and low body temperature was independently associated with favorable prognosis among patients not treated with tPA (OR = 2.0, P = 0.042). CONCLUSIONS: Our study suggests that the effect of high body temperature on clot lysis is more important than the neuroprotective effect of low body temperature in the early phase after cerebral infarction treated with tPA.

Characteristics of generalised epileptiform activity.

OBJECTIVE: To study the age-related occurrence of specific features of generalised epileptiform activity (GEA), their correlation with EEG background activity (BA), and their internal correlation. METHODS: 17,723 consecutive routine EEGs from 12,511 patients were annotated and categorised into a database. The first EEG containing GEA from all 325 patients with such activity were selected and categorised for GEA features. The BA was studied in multivariable fractional polynomial regression models including intervening variables. The GEA features were studied in similar models for age-dependency and internal correlation. RESULTS: High GEA-amplitude and low GEA-frequency correlated with BA slowing. The occurrence of 'irregular spike/sharp slow wave' pattern increased with age (p=0.003). Hyperventilation sensitivity was not age-related. There was no correlation between hyperventilation sensitivity and photoparoxysmal response. The age-related probability for specific GEA-types was established. CONCLUSIONS: High GEA-amplitude and low GEA-frequency correlate with BA slowing, indicating cerebral cortical dysfunction. Hyperventilation sensitivity and photoparoxysmal response independently increase the yield of EEG. There is no age-dependency for hyperventilation sensitivity showing that an upper age threshold for hyperventilation provocation is inappropriate. SIGNIFICANCE: The results extend our understanding of GEA and help the electroencephalographer in weighing the various GEA components.

Genetic association between COPD and polymorphisms in TNF, ADRB2 and EPHX1.

There is evidence of a hereditary component in chronic obstructive pulmonary disease (COPD). A number of genetic association studies have been performed to find susceptibility genes of COPD. The current authors performed a case-control, genetic-association study and a meta-analysis of 16 studies, involving seven polymorphisms in three well-studied genes: microsomal epoxide hydroxylase (EPHX1); tumour necrosis factor; and beta2-adrenoreceptor. A total of 492 Caucasian smokers and former smokers were recruited from hospital databases and population cohort studies. In the present study, a protective effect of the EPHX1 Tyr113His polymorphism was found (homozygous odds ratio (OR) 0.5). In the meta-analysis, homozygotes for this single nucleotide polymorphism (SNP) also had a pooled OR of 0.5. The same effect has been found in several lung cancer studies. Effects for other candidate SNPs were weak or statistically insignificant, and probable genotyping error was common. In conclusion, the present data and meta-analysis support a role for microsomal epoxide hydroxylase in the aetiology of chronic obstructive pulmonary disease.

The incidence of adult asthma: a review.

In recent years, several new studies have estimated the incidence of adult asthma. These studies vary in design and quality. The current paper summarises the findings of major population studies in the adult incidence of asthma. The pooled estimate of the adult incidence of asthma was 4.6 per 1000 person-years in women and 3.6 per 1000 person-years in men. The estimate among only general population cohort studies was higher, respectively 5.9 and 4.4 per 1000 person-years in women and men. The adult incidence of asthma was slightly higher in women than men. In the few studies that allowed the incidence of asthma to be estimated among those aged >50 years, there was a trend towards a higher incidence with age. It is thought likely that this is at least partly explained by misclassification with COPD. However, the current findings from these studies may imply that the incidence of asthma in the elderly has previously been under-estimated. Finally, the review shows that estimates of adult asthma incidence have tended to be higher in later studies, implying a rise in asthma incidence in adults within the timeframe of observation.

Bias in retrospective studies of trends in asthma incidence.

There is evidence for an increase in adult asthma prevalence. Several retrospective studies have shown an increase in asthma incidence by year of birth, consistent with an increasing trend in asthma incidence. The validity of this retrospective approach is unknown. Retrospective and prospective asthma incidence by year of birth were compared in the same community, during the same time period, from two independent studies; a cohort study and a cross-sectional study in Western Norway. In the prospective study, subjects without asthma were followed from 1985-1996/1997. In the retrospective study in 1998, subjects reported the age at which the disease started. Analyses of incident asthma in the period 1985-1996 were compared between the studies. The retrospective analysis showed a large increase in asthma incidence by year of birth, with an odds ratio (OR) of 2.9 comparing those born in 1969 with those born in 1927. The prospective study showed the opposite, with an OR of 0.2 comparing those born in 1969 with those born in 1927. There was only a 20% difference in the cumulative incidence of asthma. To conclude, retrospective estimates of trends in asthma incidence are likely to be severely biased by differential recall.

Trends in symptoms of obstructive lung disease in Norway.

SETTING: Evidence is accumulating that there has been an increase in the adult population burden of obstructive lung disease. Has this increased the burden of symptoms? It is possible that diagnostic efficiency has improved, so that milder asthma cases are being diagnosed. OBJECTIVE: To investigate changes in symptom burden by asthma diagnosis, age and sex. DESIGN: We performed two postal cross-sectional studies among adults aged 15-70 years in Oslo, Norway, in 1972 and again in 1998/1999 (total = 39998). Changes in 11 self-reported respiratory symptoms were investigated. RESULTS: The prevalence of having at least one symptom increased from 50% to 60% (P < 0.001), and the distribution of symptoms showed an overall increase. Nine symptoms increased in prevalence. The increase was largest among the young and females, and was present in both those with and those without asthma. For any given number of reported symptoms, asthma prevalence was higher in 1998 than in 1972, suggesting increased case finding. CONCLUSION: There has been an increase in the population burden of respiratory symptoms matching the observed increase in young adult asthma, together with a probable increase in the clinical willingness to give an asthma diagnosis.

Epidemiological aspects and early detection of chronic obstructive airway diseases in the elderly.

The burdens of chronic obstructive airway diseases among the elderly in Europe, and worldwide, are increasing. Although asthma is common in all ages, the main airway disease affecting the elderly is chronic obstructive pulmonary disease (COPD). The aim of this paper is to review the prevalence and incidence of COPD on the basis of population studies. As the prevalence estimates of asthma are probably well known, only the incidence and remission of asthma will be discussed. The underdiagnosis of obstructive airway diseases is huge. A Dutch programme for early detection of obstructive airway disease among the elderly has, thus, been included in the presentation. A prerequisite for fighting COPD is to acquire data on illnesses and death. COPD has only recently been defined by cut-off points of spirometric outcomes, which is why measures of the prevalence of COPD have been distorted by use of a large number of different diagnostic terms and lung function criteria. The prevalence of clinically-relevant COPD has been estimated in several community studies to 4-6% in adult population samples, with a considerable increase by age, particularly among smokers. The incidence of COPD not only increases heavily with age and smoking, but also occupational exposure to dust, gas and damp. Precise estimates of the incidence of COPD or spirometric airflow limitation are not available. Demographic changes will result in a further substantial increase of chronic obstructive airway disorders, mainly chronic obstructive pulmonary disease, among the elderly. The increasing burden of chronic obstructive pulmonary disease has to come to the awareness of the public, governments, health authorities, and industry.

Long-term changes in adult asthma prevalence.

There has been an increase in asthma prevalence among children. Little evidence is available regarding long-term changes in asthma prevalence in adults. Two cross-sectional studies were performed among adults aged 15-70 yrs in Oslo, Norway, in 1972 and again in 1998-1999 (n=39,998). A postal self-completed questionnaire was used. Exactly the same questions and survey methods were used in both studies. In 1998-1999, additional telephone follow-up was included for postal nonresponders. The crude prevalence of ever having had a doctor's diagnosis of asthma increased from 3.4 to 9.3%. The prevalence of wheezing increased from 17.8 to 25.8% and attacks of breathlessness from 12.6 to 16.7%. After controlling for smoking, the risk of asthma among those aged <40 yrs had tripled. The increase in asthma was 50% greater in females than males. The prevalence of symptoms increased less than asthma diagnosis. Wheezing increased by 50% in those aged <40 yrs, with smaller increases at greater ages. The increase in symptoms was seen among both asthmatics and nonasthmatics. There has been a large increase in the prevalence of asthma diagnosis and asthma-like symptoms in adults. The increase is less pronounced among those aged >40 yrs.

In-line versus pistol-grip handles in a laparoscopic simulators. A randomized controlled crossover trial.

BACKGROUND: Needleholders with in-line handles (ILH) and those with pistol-grip handles (PGH) were compared in terms of operative end-product quality (OEPQ), procedure effectiveness (PE), and surgeon forearm workload (SFWL) during suturing in a laparoscopic simulator. METHODS: A 90% power crossover design at alpha 0.05 required 46 surgeons. Block randomization generated ILH-PGH or PGH-ILH sequence allocation. The task involved suturing a perforated ulcer on a foam stomach in a simulator. In this study, OEPQ was measured by tissue damage, accuracy error, water leak; PE by operating time and motion analysis including goal-directed actions (GDA) and non-goal-directed actions (NGDA); and SFWL by electromyogram (EMG) of six forearm and thumb muscles. RESULTS: The 46 surgeons performed the tasks as allocated. All the variables but two were significantly different between the first and second tasks, ignoring the handle type. There was no evidence of an unequal carryover effect when the comparison was stratified by ILH-PGH or PGH-ILH sequence. As compared with ILH, PGH tissue damage (0.1 vs 0.2 mm; p = 0.06) and NGDA (1 vs 1 p = 0.09) were different, whereas accuracy error, leak rates, operating time, GDA, and EMG were not. CONCLUSIONS: As compared with ILH needleholders, the use of PGH needleholders led to increased tissue damage and non-goal-directed actions during a suturing task in a simulator.

[Smoking cessation practice among Norwegian hospital physicians]. / Norske sykehuslegers praksis ved røykeavvenning.

BACKGROUND: Limited data is available as to what extent Norwegian hospital doctors ask their patients about their smoking habits, and to what extent doctors offer their patients help in smoking cessation. MATERIAL AND METHODS: A random sample of 1,025 hospital doctors was mailed a questionnaire. After 14 days a reminder letter was sent to non-responders; 76% of the doctors responded. RESULTS: Altogether 98% of the doctors stated that they asked their patients with smoking-related disease about their smoking habits. In cases of non-smoking related disease, 73% of the doctors stated that they asked about the smoking habits of their patients (83% of female and 69% of male doctors). If doctors knew that a patient wanted to quit smoking, 25% of them stated that they often recommended nicotine replacement therapy. Less than 7% of the doctors regularly offered smoking cessation courses, handed out self-assistant material, or gave the patients other smoking cessation advice. INTERPRETATION: The study indicates that doctors often ask their patients about their smoking habits, but there is clear potential for improvement as to the smoking cessation advice.

Comparison of respiratory symptoms questionnaires.

SETTING: Comparisons in performance of questionnaires are of interest in international comparisons of prevalences and risk factors, after translation and development of new questionnaires. Factors such as sex, age, educational level and smoking habits may influence the performance of questionnaires. OBJECTIVE: 1) To discuss questionnaire comparisons in general, using as an example a Norwegian respiratory symptoms questionnaire compared with a translation of the British Medical Research Council questionnaire on chronic bronchitis; and 2) to examine whether reliability differs in subgroups. DESIGN: A population sample of 935 residents of Hordaland County, Norway, completed two questionnaires in a short interval of time. Agreement and Cohen's kappa were calculated. RESULTS: Prevalences were significantly different between the two questionnaires for most symptoms. Agreement decreased from non-smokers through ex-smokers to smokers, whereas the kappa statistic increased. Agreement increased as the educational level increased, whereas the kappa statistic declined. No significant age and sex effects on agreement and kappa were observed. CONCLUSION: Small changes in the phrasing of a question can have considerable effect on prevalence estimates. Reliability statistics are prevalence dependent. Reliability may differ according to smoking habit and educational level. Questionnaires should be tested in the population that they are to be used in.