Prevention of mood disorder after stroke: a randomised controlled trial of problem solving therapy versus volunteer support.

BACKGROUND: Mood disorder after stroke is common but drug and psychosocial treatments have been assessed with disappointing results. Preventing mood disorder from developing in the first place could be a better approach and might reduce the need for pharmacotherapy in this predominantly older patient group. We used a brief problem-solving therapy and evaluated its effect in reducing mood disorder in the 12 months after stroke. METHODS: A 3-group, parallel, randomised controlled trial. Four hundred fifty patients with stroke were randomised within 1 month of hospital admission to problem-solving therapy from a psychiatric nurse, non-specific support given by volunteers or treatment-as-usual. Follow up took place at 6 and 12 months after stroke. Standardised measures of mood (Present State Examination, GHQ-28), cognitive state (mini-mental state examination) and function (Barthel ADL index, Frenchay Activities Index) were taken at baseline, 6 and 12 months after randomisation. Satisfaction with care was recorded at follow up. RESULTS: At 6 months, all psychological and activity measures favoured problem-solving therapy. At 12 months, patients in the problem-solving therapy group had significantly lower GHQ-28 scores and lower median Present State Examination symptom scores. There were no statistically significant differences in activity. The problem-solving therapy group were more satisfied with some aspects of care. CONCLUSIONS: The results are encouraging and suggest it is possible to prevent mood disorder in stroke patients using a psychological intervention. The differences between the groups at 12 months may indicate a sustained impact of psychological therapies, by comparison with non-specific support. TRIAL REGISTRATION: ISRCTN: ISRCTN33773710 Registered: 23/01/2004 (Retrospectively).

Isosorbide Mononitrate and Cilostazol Treatment in Patients With Symptomatic Cerebral Small Vessel Disease: The Lacunar Intervention Trial-2 (LACI-2) Randomized Clinical Trial.

Importance: Cerebral small vessel disease (cSVD) is a common cause of stroke (lacunar stroke), is the most common cause of vascular cognitive impairment, and impairs mobility and mood but has no specific treatment. Objective: To test the feasibility, drug tolerability, safety, and effects of 1-year isosorbide mononitrate (ISMN) and cilostazol treatment on vascular, functional, and cognitive outcomes in patients with lacunar stroke. Design, Setting, and Participants: The Lacunar Intervention Trial-2 (LACI-2) was an investigator-initiated, open-label, blinded end-point, randomized clinical trial with a 2 × 2 factorial design. The trial aimed to recruit 400 participants from 26 UK hospital stroke centers between February 5, 2018, and May 31, 2021, with 12-month follow-up. Included participants had clinical lacunar ischemic stroke, were independent, were aged older than 30 years, had compatible brain imaging findings, had capacity to consent, and had no contraindications to (or indications for) the study drugs. Data analysis was performed on August 12, 2022. Interventions: All patients received guideline stroke prevention treatment and were randomized to ISMN (40-60 mg/d), cilostazol (200 mg/d), ISMN-cilostazol (40-60 and 200 mg/d, respectively), or no study drug. Main Outcomes: The primary outcome was recruitment feasibility, including retention at 12 months. Secondary outcomes were safety (death), efficacy (composite of vascular events, dependence, cognition, and death), drug adherence, tolerability, recurrent stroke, dependence, cognitive impairment, quality of life (QOL), and hemorrhage. Results: Of the 400 participants planned for this trial, 363 (90.8%) were recruited. Their median age was 64 (IQR, 56.0-72.0) years; 251 (69.1%) were men. The median time between stroke and randomization was 79 (IQR, 27.0-244.0) days. A total of 358 patients (98.6%) were retained in the study at 12 months, with 257 of 272 (94.5%) taking 50% or more of the allocated drug. Compared with those participants not receiving that particular drug, neither ISMN (adjusted hazard ratio [aHR], 0.80 [95% CI, 0.59 to 1.09]; P = .16) nor cilostazol (aHR, 0.77 [95% CI, 0.57 to 1.05]; P = .10) alone reduced the composite outcome in 297 patients. Isosorbide mononitrate reduced recurrent stroke in 353 patients (adjusted odds ratio [aOR], 0.23 [95% CI, 0.07 to 0.74]; P = .01) and cognitive impairment in 308 patients (aOR, 0.55 [95% CI, 0.36 to 0.86]; P = .008). Cilostazol reduced dependence in 320 patients (aHR, 0.31 [95% CI, 0.14 to 0.72]; P = .006). Combination ISMN-cilostazol reduced the composite (aHR, 0.58 [95% CI, 0.36 to 0.92]; P = .02), dependence (aOR, 0.14 [95% CI, 0.03 to 0.59]; P = .008), and any cognitive impairment (aOR, 0.44 [95% CI, 0.23 to 0.85]; P = .02) and improved QOL (adjusted mean difference, 0.10 [95% CI, 0.03 to 0.17]; P = .005) in 153 patients. There were no safety concerns. Conclusions and Relevance: These results show that the LACI-2 trial was feasible and ISMN and cilostazol were well tolerated and safe. These agents may reduce recurrent stroke, dependence, and cognitive impairment after lacunar stroke, and they could prevent other adverse outcomes in cSVD. Therefore, both agents should be tested in large phase 3 trials. Trial Registration: ClinicalTrials.gov Identifier: NCT03451591.

Late onset AMACR deficiency with metabolic stroke-like episodes and seizures.

Alpha-methylacyl-CoA racemase (AMACR) deficiency is a rare peroxisomal disorder causing pristanic acid accumulation. Only 16 cases have been described so far. A female in her seventh decade presented with episodes of dysphasia, headache and sensory disturbance inconsistent with migraine, epilepsy or transient ischaemic attack. An MRI demonstrated unusual changes in the pons, red nuclei, thalami and white matter. Mitochondrial disease was suspected but detailed testing was negative. After eight years of symptoms, she developed a febrile encephalopathy with hemispheric dysfunction, focal convulsive seizures and coma. Her condition stabilised after one month. Lacosamide was continued for seizure prevention. The diagnosis remained elusive until whole genome sequencing revealed AMACR deficiency. Pristanic acid levels were highly elevated and dietary modification was recommended. Genetic peroxisomal disorders can present in older age; our patient is the oldest in the AMACR deficiency literature. Novel features in our case include central apnoea, dystonia and rapid eye movement behaviour disorder.

Oxfordshire Community Stroke Project Classification: A proposed automated algorithm.

INTRODUCTION: The Oxfordshire Community Stroke Project (OCSP) proposed a clinical classification for Stroke patients. This classification has proved helpful to predict the risk of neurological complications. However, the OCSP was initially based on findings on the neurological assesment, which can pose difficulties for classifying patients. We aimed to describe the development and the validation step of a computer-based algorithm based on the OCSP classification. MATERIALS AND METHODS: A flow-chart was created which was reviewed by five board-certified vascular neurologists from which a computer-based algorithm (COMPACT) was developed. Neurology residents from 12 centers were invited to participate in a randomized trial to assess the effect of using COMPACT. They answered a 20-item questionnaire for classifying the vignettes according to the OCSP classification. Each correct answer has been attributed to 1-point for calculating the final score. RESULTS: Six-two participants agreed to participate and answered the questionnaire. Thirty-two were randomly allocated to use our algorithm, and thirty were allocated to adopt a list of symptoms alone. The group who adopted our algorithm had a median score of correct answers of 16.5[14.5, 17]/20 versus 15[13, 16]/20 points, p = 0.014. The use of our algorithm was associated with the overall rate of correct scores (p = 0.03). DISCUSSION: Our algorithm seemed a useful tool for any postgraduate year Neurology resident. A computer-based algorithm may save time and improve the accuracy to classify these patients. CONCLUSION: An easy-to-use computer-based algorithm improved the accuracy of the OCSP classification, with the possible benefit of further improvement of the prediction of neurological complications and prognostication.

Elevated C-reactive protein and long-term mortality after ischaemic stroke: relationship with markers of endothelial cell and platelet activation.

BACKGROUND AND PURPOSE: Inflammatory biomarkers predict development of atherothrombotic events. In the present study we examined the relationships between C-reactive protein (CRP), complement C3, and long-term mortality after acute ischemic stroke. METHODS: CRP and C3 were analyzed by in-house enzyme-linked immunosorbent assay in 394 subjects with acute ischemic stroke who survived for >30 days, followed-up for a median of 7.4 years. RESULTS: CRP was higher in subjects who died (10.8 mg/L; 95% CI, 9.1-12.8) compared with survivors (3.8 mg/L; 95% CI, 3.1-4.7), whereas C3 was similar in both groups (P=0.26). CRP remained predictive for mortality after adjusting for conventional clinical and demographic risk factors (the adjusted hazard ratio for those with CRP in the highest compared with the lowest quartile was 2.0; 95% CI, 1.3-3.1). However, CRP was no longer independently predictive of mortality after additionally adjusting for beta-thromboglobulin or von Willebrand factor. CONCLUSIONS: Our data suggest that the relationship between CRP and poststroke mortality may in part reflect inflammation-induced endothelial cell dysfunction and platelet activation.

The design and validation of a parent-report questionnaire for assessing the characteristics and quality of early intervention over time.

This article concerns a parent-report repeat questionnaire to evaluate the quality of multiprofessional early intervention following early identification of deafness. It discusses the rationale for the design of the instrument, its theoretical underpinnings, its psychometric properties, and its usability. Results for the validity and reliability of the instrument are based on completion by 82 parents. The questionnaire is divided into four sections. "The description of the structure of professional services" demonstrated good face and content validity; the "content of intervention scale" yielded high internal consistency (Cronbach's alpha = 0.88) and reliability (6-month test-retest correlations, rho = 0.88, r = .68; 12-month test-retest correlations, rho = 0.60, r = .82); the "process of intervention" scale yielded high internal consistency (Cronbach's alpha = 0.93) and high reliability on test-retest administration (6-month test-retest correlations, r = 0.64; 12 month test-retest correlations, r = .82); and the short "overall impact" questions were answered well. The Trait Emotional Intelligence Questionnaire was used to control for influence of parental disposition on ratings of quality of intervention. Evaluating the goodness of fit between early intervention and parental priorities/values is discussed as a vital component in improving child and family outcomes.

Predictive variables for mortality after acute ischemic stroke.

BACKGROUND AND PURPOSE: Stroke is a major healthcare issue worldwide with an incidence comparable to coronary events, highlighting the importance of understanding risk factors for stroke and subsequent mortality. METHODS: In the present study, we determined long-term (all-cause) mortality in 545 patients with ischemic stroke compared with a cohort of 330 age-matched healthy control subjects followed up for a median of 7.4 years. We assessed the effect of selected demographic, clinical, biochemical, hematologic, and hemostatic factors on mortality in patients with ischemic stroke. Stroke subtype was classified according to the Oxfordshire Community Stroke Project criteria. Patients who died 30 days or less after the acute event (n=32) were excluded from analyses because this outcome is considered to be directly attributable to the acute event. RESULTS: Patients with ischemic stroke were at more than 3-fold increased risk of death compared with the age-matched control cohort. In multivariate analyses, age, stroke subtype, atrial fibrillation, and previous stroke/transient ischemic attack were predictive of mortality in patients with ischemic stroke. Albumin and creatinine and the hemostatic factors von Willebrand factor and beta-thromboglobulin were also predictive of mortality in patients with ischemic stroke after accounting for demographic and clinical variables. CONCLUSIONS: The results indicate that subjects with acute ischemic stroke are at increased risk of all-cause mortality. Advancing age, large-vessel stroke, atrial fibrillation, and previous stroke/transient ischemic attack predict mortality; and analysis of albumin, creatinine, von Willebrand factor, and beta-thromboglobulin will aid in the identification of patients at increased risk of death after stroke.

Glucose-potassium-insulin infusions in the management of post-stroke hyperglycaemia: the UK Glucose Insulin in Stroke Trial (GIST-UK).

BACKGROUND: Hyperglycaemia after acute stroke is a common finding that has been associated with an increased risk of death. We sought to determine whether treatment with glucose-potassium-insulin (GKI) infusions to maintain euglycaemia immediately after the acute event reduces death at 90 days. METHODS: Patients presenting within 24 h of stroke onset and with admission plasma glucose concentration between 6.0-17.0 mmol/L were randomly assigned to receive variable-dose-insulin GKI (intervention) or saline (control) as a continuous intravenous infusion for 24 h. The purpose of GKI infusion was to maintain capillary glucose at 4-7 mmol/L, with no glucose intervention in the control group. The primary outcome was death at 90 days, and the secondary endpoint was avoidance of death or severe disability at 90 days. Additional planned analyses were done to determine any differences in residual disability or neurological and functional recovery. The trial was powered to detect a mortality difference of 6% (sample size 2355), with 83% power, at the 5% two-sided significance level. This study is registered as an International Standard Randomised Controlled Trial (number ISRCTN 31118803) FINDINGS: The trial was stopped due to slow enrolment after 933 patients were recruited. For the intention-to-treat data, there was no significant reduction in mortality at 90 days (GKI vs control: odds ratio 1.14, 95% CI 0.86-1.51, p=0.37). There were no significant differences for secondary outcomes. In the GKI group, overall mean plasma glucose and mean systolic blood pressure were significantly lower than in the control group (mean difference in glucose 0.57 mmol/L, p<0.001; mean difference in blood pressure 9.0 mmHg, p<0.0001). INTERPRETATION: GKI infusions significantly reduced plasma glucose concentrations and blood pressure. Treatment within the trial protocol was not associated with significant clinical benefit, although the study was underpowered and alternative results cannot be excluded.

A patient with neuro-Behçet's disease is successfully treated with etanercept: further evidence for the value of TNFalpha blockade.

Behçet's disease is a chronic relapsing multisystem vasculitis with 49% of cases involving the CNS. Recently there have been two reports of neuro-Behçet's disease (NB) successfully treated with the tumour necrosis factor alpha (TNFalpha) monoclonal antibody infliximab. We describe a patient with longstanding NB who was poorly responsive to azathioprine, cyclosporin, thalidomide and methotrexate. She showed a remarkable response when treated with the recombinant human TNFalpha receptor protein, etanercept. To the best of our knowledge this is the first report of NB successfully treated with etanercept.

Maternal anxiety following newborn hearing screening: the moderating role of knowledge.

OBJECTIVES: To describe the impact upon maternal anxiety of newborn hearing screening and examine the Possible moderating role of knowledge. METHODS: Questionnaires assessing maternal state anxiety, worry and certainty about the baby's hearing, and knowledge about screening, were sent to four groups of mothers three weeks after screening: Group 1 consisted of mothers whose babies had clear responses on a first or second screening test (n=103); Group 2 consisted of mothers whose babies had clear responses on the third screening test (n=81); Group 3 consisted of mothers whose babies did not have clear responses in one ear at the third screening test and were referred for audiological assessment (n=105); and Group 4 consisted of mothers whose babies did not have clear responses in either ear at the third hearing test and were referred for audiological assessment (n=55). RESULTS: Although mean anxiety levels were in the normal range, there was a significant trend for anxiety to rise as testing increased (F(1,327)=4.280, P<0.05). Worry increased significantly (F(1,337)=70.432, P<0.001) and certainty decreased significantly (F(1,339)=27.474, P=0.001) as the number of tests increased. Although total knowledge did not significantly moderate anxiety (R(2)=0.016, P=0.096), there was a significant interaction between mothers' group and one knowledge item, understanding that receipt of no clear responses was unlikely to mean that the baby had a hearing loss: mothers in Group 4 who understood this had lower anxiety (F(3,323)=4.791, P<0.01) and lower worry (F(3,332)=3.565, P<0.01) compared with mothers who did not. CONCLUSIONS: Understanding the meaning of being recalled following screening may avoid some of the anxiety associated with this.

Neonatal hearing screening: modelling cost and effectiveness of hospital- and community-based screening.

BACKGROUND: Children with congenital hearing impairment benefit from early detection and management of their hearing loss. These and related considerations led to the recommendation of universal newborn hearing screening. In 2001 the first phase of a national Newborn Hearing Screening Programme (NHSP) was implemented in England. Objective of this study was to assess costs and effectiveness for hospital and community-based newborn hearing screening systems in England based on data from this first phase with regard to the effects of alterations to parameter values. DESIGN: Clinical effectiveness analysis using a Markov Model. OUTCOME MEASURE: quality weighted detected child months (QCM). RESULTS: Both hospital and community programmes yielded 794 QCM at the age of 6 months with total costs of 3,690,000 pound sterling per 100,000 screened children in hospital and 3,340,000 pound sterling in community. Simulated costs would be lower in hospital in 48% of the trials. Any statistically significant difference between hospital and community in prevalence, test sensitivity, test specificity and costs would result in significant differences in cost-effectiveness between hospital and community. CONCLUSION: This modelling exercise informs decision makers by a quantitative projection of available data and the explicit and transparent statements about assumptions and the degree of uncertainty. Further evaluation of the cost-effectiveness should focus on the potential differences in test parameters and prevalence in these two settings.

Screening for hearing loss in childhood: issues, evidence and current approaches in the UK.

Until recently, screening for childhood hearing loss in the UK was based on two universal (i.e. whole population) screens: the infant distraction test screen at age eight months and the school entry hearing screen at age four to five years. Evidence reviewed in the 1990s indicated that the infant distraction test screen was seriously underperforming, but that (based on technology that had become available in the 1980s and 1990s) universal newborn hearing screening could be efficacious. At the same time, evidence was emerging on the importance and value of very early identification and intervention for permanent congenital childhood hearing loss. This led to the decision to implement a national newborn hearing screening programme (NHSP) in England and to phase out the distraction test at eight months. The initial implementation of the programme will be completed in 2005, and we summarize the evidence on the effectiveness of the first phase of the programme here. A number of important issues concerning childhood hearing loss and its management remain unresolved: the burden of late-onset and temporary childhood hearing losses, the most effective approaches to intervention and management, the case for screening for mild and/or unilateral hearing loss, and the role of the School entry screen. Some of the current research efforts to address these are outlined.

Maternal anxiety and satisfaction following infant hearing screening: a comparison of the health visitor distraction test and newborn hearing screening.

BACKGROUND: Newborn hearing screening is currently replacing the health visitor distraction test (HVDT) conducted at eight months. Our previous research indicates that recall for further tests following newborn hearing screening can have a negative impact on the emotional well being of mothers, but it is not known if this is greater than that caused by recall following the distraction test. OBJECTIVE: To compare the impact on maternal anxiety and satisfaction of recall following newborn hearing screening and the HVDT. METHODS: Four groups participated: 27 mothers of babies receiving a satisfactory result and 21 mothers of babies recalled after the HVDT 26 mothers of babies receiving a satisfactory result and 16 mothers of babies recalled after newborn hearing screening. Questionnaires assessing maternal anxiety, worry and certainty about the babies' hearing, satisfaction with and attitudes towards the screening test were sent to mothers three weeks and six months following screening. RESULTS: Comparison of the effects of receipt of different results showed no significant differences in maternal anxiety, worry and certainty between the two tests. Those mothers whose babies had a newborn hearing screening test were significantly more satisfied, regardless of the result received. Those who received a satisfactory result on the newborn hearing screening programme also had more positive attitudes towards that screening test than those receiving a satisfactory result following the HVDT. CONCLUSION: These results suggest that newborn hearing screening does not have a more negative emotional impact than the HVDT.

Increased fibrinogen, von Willebrand factor and tissue plasminogen activator levels in insulin resistant South Asian patients with ischaemic stroke.

The aim of this study was to determine differences in atherothrombotic risk factors in South Asian subjects with a history of ischaemic stroke and South Asian subjects free from personal and family history of clinically detectable stroke. Eighty South Asian patients with ischaemic stroke (confirmed on cranial computerised scan) and 80 South Asian controls with similar age and gender distributions were recruited at random. The frequency of hypertension (P=<0.0001), myocardial infarction (P=0.003) and diabetes mellitus (<0.0001) were significantly higher in stroke patients. Stroke patients had lower high-density lipoprotein cholesterol (0.95 vs. 1.1 mmol/l, P=<0.0001), higher plasma glucose (8.1 vs. 6.6 mmol/l, P=0.01) and trendwise higher HBA(1C) (6.4 vs. 6.0%, P=0.09). There was no difference in insulin levels but insulin resistance was significantly higher in stroke patients (3.75 vs. 2.66, P=0.01). Stroke patients showed elevated levels of fibrinogen (3.78 vs. 3.41 mg/dl, P=0.02), von Willebrand factor (1.78 vs. 1.50 IU/ml, P=0.006) and tissue plasminogen activator (12.8 vs. 11.3 ng/ml, P=0.04), but the differences did not persist after adjustment for glucose, triglycerides, HDL, WHR, and BMI. Higher levels of fibrinogen, von Willebrand factor and t-PA in South Asian stroke patients disappeared after adjustment for features of insulin resistance syndrome but persisted after adjustment for presence of diabetes, confirming that these changes are essentially dependant on features of insulin resistance syndrome. A prospective study would be required to elucidate the role of thrombotic risk factors in South Asians with ischaemic stroke.

Coagulation factor VII activity, Arg/Gln353 polymorphism and features of insulin resistance in first-degree-relatives of South Asian patients with stroke.

The aim of the study was to determine associations of factor VII:C levels in 140 South Asian stroke subjects and 143 first-degree relatives versus age-sex matched 146 control subjects without a personal or a family history of stroke subjects living in UK. There were no significant differences in Factor VII:C levels or FVII Msp I gene polymorphism (Arg-Gln 353) R353Q genotype frequency between the groups. R353Q genotype determined Factor VII:C levels in all the three groups. Factor VII:C levels correlated with triglycerides (patients, r = 0.23; relatives r = 27; control subjects, r = 0.24) and plasminogen activator inhibitor activity (patients, r = 0.30; relatives r = 0.22; control subjects r = 0.20) in all the three groups, but with insulin only in patients (p = 0.19). Circulating levels of Factor VII:C are determined by R353Q genotype and cluster with other risk factors associated with insulin resistance in South Asian ischaemic stroke patients, first-degree relatives and control subjects but are not related to stroke or a family history of stroke.

Increasing knowledge about a screening test: preliminary evaluation of a structured, chart-based, screener presentation.

The provision and understanding of good quality information is one of the key characteristics of an informed choice. However, written materials alone often fail to achieve good understanding of screening tests. The present study describes the preliminary evaluation of a structured, chart-directed presentation, aimed at increasing knowledge of a screening test. Forty mothers of babies undergoing a newborn hearing test received either a standard, or a standard plus structured, presentation of the screening test. Standard presentation was a leaflet and short verbal explanation of the test. Structured presentation comprised an illustrated chart explaining the process and possible outcomes of screening, followed by screeners checking mothers understanding of key points and, if necessary, giving further explanation. After screening, maternal knowledge of the test was assessed using seven multiple choice items. Overall knowledge was high. For women with lower levels of education, the structured presentation resulted in significantly higher levels of knowledge than the standard presentation only.

To what extent do the characteristics of the object of evaluation influence the choice of epistemological framework? The case of universal newborn hearing screening.

In this article, the authors explore the role that characteristics and circumstances attendant on the object of an evaluation might play in the choice of epistemological framework underpinning research design. They consider examples from the consumer-focused evaluation of the introduction of universal newborn hearing screening in England. In particular, they look at how screen- and program-specific issues exerted influence at the levels of epistemology and method, arguing that these choices are not simply a product of values and questions that underpinned one kind of approach to knowledge production in comparison with another.

Use of magnetic resonance angiography to select candidates with recently symptomatic carotid stenosis for surgery: systematic review.

OBJECTIVE: To determine if sufficient evidence exists to support the use of magnetic resonance angiography as a means of selecting patients with recently symptomatic high grade carotid stenosis for surgery. DESIGN: Systematic review of published research on the diagnostic performance of magnetic resonance angiography, 1990-9. MAIN OUTCOME MEASURES: Performance characteristics of diagnostic test. RESULTS: 126 potentially relevant articles were identified, but many articles failed to examine the performance of magnetic resonance angiography as a diagnostic test at the surgical decision thresholds used in major clinical trials on endarterectomy. 26 articles were included in a meta-analysis that showed a maximal joint sensitivity and specificity of 99% (95% confidence interval 98% to 100%) for identifying 70-99% stenosis and 90% (81% to 99%) for identifying 50-99% stenosis. Only four articles evaluated contrast enhanced magnetic resonance angiography. CONCLUSIONS: Magnetic resonance angiography is accurate for selecting patients for carotid endarterectomy at the surgical decision thresholds established in the major endarterectomy trials, but the evidence is not very robust because of the heterogeneity of the studies included. Research is needed to determine the diagnostic performance of the most recent developments in magnetic resonance angiography, including contrast enhanced techniques, as well as to assess the impact of magnetic resonance angiography on surgical decision making and outcomes.