Amit Mistri

Effects of antihypertensive treatment after acute stroke in the Continue Or Stop post-Stroke Antihypertensives Collaborative Study (COSSACS): a prospective, randomised, open, blinded-endpoint trial

BACKGROUND Up to 50% of patients with acute stroke are taking antihypertensive drugs on hospital admission. However, whether such treatment should be continued during the immediate post-stroke period is unclear. We therefore aimed to assess the efficacy and safety of continuing or stopping pre-existing antihypertensive drugs in patients who had recently had a stroke. METHODS The Continue or Stop Post-Stroke Antihypertensives Collaborative Study (COSSACS) was a UK multicentre, prospective, randomised, open, blinded-endpoint trial. Patients were recruited at 49 UK National Institute for Health Research Stroke Research Network centres from January 1, 2003, to March 31, 2009. Patients aged over 18 years who were taking antihypertensive drugs were enrolled within 48 h of stroke and the last dose of antihypertensive drug. Patients were randomly assigned (1:1) by secure internet central randomisation to either continue or stop pre-existing antihypertensive drugs for 2 weeks. Patients and clinicians who randomly assigned patients were unmasked to group allocation. Clinicians who assessed 2-week outcomes and 6-month outcomes were masked to group allocation. The primary endpoint was death or dependency at 2 weeks, with dependency defined as a modified Rankin scale score greater than 3 points. Analysis was by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial Register, number ISRCTN89712435. FINDINGS 763 patients were assigned to continue (n=379) or stop (n=384) pre-existing antihypertensive drugs. 72 of 379 patients in the continue group and 82 of 384 patients in the stop group reached the primary endpoint (relative risk 0.86, 95% CI 0.65-1.14; p=0.3). The difference in systolic blood pressure at 2 weeks between the continue group and the stop group was 13 mm Hg (95% CI 10-17) and the difference in diastolic blood pressure was 8 mm Hg (6-10; difference between groups p<0.0001). No substantial differences were observed between groups in rates of serious adverse events, 6-month mortality, or major cardiovascular events. INTERPRETATION Continuation of antihypertensive drugs did not reduce 2-week death or dependency, cardiovascular event rate, or mortality at 6 months. Lower blood pressure levels in those who continued antihypertensive treatment after acute mild stroke were not associated with an increase in adverse events. These neutral results might be because COSSACS was underpowered owing to early termination of the trial, and support the continuation of ongoing research trials. FUNDING The Health Foundation and The Stroke Association.

Measurement of cerebral blood flow responses to the thigh cuff maneuver: a comparison of TCD with a novel MRI method

Cerebral autoregulation (CA) describes the mechanism responsible for maintaining cerebral blood flow (CBF) relatively constant, despite changes in mean arterial blood pressure (ABP). This paper introduces a novel method for assessing CA using magnetic resonance imaging (MRI). Images are rapidly and repeatedly acquired using a gradient-echo echo-planar imaging pulse sequence for a period of 4minutes, during which a transient decrease in ABP is induced by rapid release of bilateral thigh cuffs. The method was validated by comparing the observed MRI signal intensity change with the CBF velocity change in the middle cerebral arteries, as measured by transcranial Doppler (TCD) ultrasound, using a standardized thigh cuff maneuver in both cases. Cross-correlation analysis of the response profiles from the left and right hemispheres showed a greater consistency for MRI measures than for TCD, both for interhemisphere comparisons and for repeated measures. The new MRI method may provide opportunities for assessing regional autoregulatory changes following acute stroke, and in other conditions in which poor autoregulation is implicated.

Quality of secondary prevention measures in TIA patients: a retrospective cohort study

Objective Pharmacological and lifestyle interventions are recommended for the reduction of stroke risk in people who have had a transient ischaemic attack (TIA). This study aimed to investigate the quality of secondary stroke prevention in primary care following diagnosis of TIA in a specialist clinic. Methods Quality standards were identified from the Royal College of Physicians (RCP) national clinical guideline for stroke and the general practice Quality and Outcomes Framework (QOF) indicators. Patients who were diagnosed with TIA between February and October 2009 were identified from a TIA clinic database. Achievement of quality standards was assessed 12–24 months following clinic attendance. Results General practices were sent structured data collection forms for 233 patients, and the response rate was 80% (n=186). Complete data were available for 163 eligible patients (70%). Overall, 94% were prescribed antithrombotic medication. QOF standards were achieved by 82% for blood pressure (≤150/90 mm Hg) and 61% for total cholesterol (≤5.0 mmol/l). RCP standards were achieved by 35% for blood pressure (≤130/80 mm Hg) and 28% for total cholesterol (<4.0 mmol/l). RCP standards for the provision of dietary and exercise advice were achieved by 29% and 34% of patients, respectively. Conclusion Only a minority of TIA patients achieved RCP standards whereas QOF standards were generally well achieved. Substantial benefits in terms of stroke prevention stand to be gained if risk factors are managed in line with more stringent RCP standards.

Dynamic cerebral autoregulation assessed by respiratory manoeuvres in non-insulin-treated Type 2 diabetes mellitus

Diabet. Med. 29, 609–613 (2012)

Is dynamic cerebral autoregulation measurement using transcranial Doppler ultrasound reproducible in the presence of high concentration oxygen and carbon dioxide

Reliability of cerebral blood flow velocity (CBFV) and dynamic cerebral autoregulation estimates (expressed as autoregulation index: ARI) using spontaneous fluctuations in blood pressure (BP) has been demonstrated. However, reliability during co-administration of O2 and CO2 is unknown. Bilateral CBFV (using transcranial Doppler), BP and RR interval recordings were performed in healthy volunteers (seven males, four females, age: 54  ±  10 years) on two occasions over 9  ±  4 d. Four 5 min recordings were made whilst breathing air (A), then 5%CO2 (C), 80%O2 (O) and mixed O2  +  CO2 (M), in random order. CBFV was recorded; ARI was calculated using transfer function analysis. Precision was quantified as within-visit standard error of measurement (SEM) and the coefficient of variation (CV). CBFV and ARI estimates with A (SEM: 3.85 & 0.87; CV: 7.5% & 17.8%, respectively) were comparable to a previous reproducibility study. The SEM and CV with C and O were similar, though higher values were noted with M; Bland-Altman plots indicated no significant bias across all gases for CBFV and ARI (bias  <0.06 cm s(-1) and  <0.05, respectively). Thus, transcranial-Doppler-ultrasound-estimated CBFV and ARI during inhalation of O2 and CO2 have acceptable levels of reproducibility and can be used to study the effect of these gases on cerebral haemodynamics.

Dynamic cerebral autoregulation assessed by respiratory manoeuvres in non-insulin-treated Type 2 diabetes mellitus.

Diabet. Med. 29, 609–613 (2012)

The Nottingham Fatigue after Stroke (NotFAST) study: factors associated with severity of fatigue in stroke patients without depression:

Objective: To identify factors associated with post-stroke fatigue in a sample of stroke survivors without depression. Design: Cross-sectional cohort study. Setting: Recruitment was from four stroke units in the UK. Subjects: Participants were assessed within four to six weeks of first stroke; those with high levels of depressive symptoms (score ⩾7 Brief Assessment Schedule Depression Cards) were excluded. Main measures: Participants were assessed after stroke on the Fatigue Severity Scale of the Fatigue Assessment Inventory, the Rivermead Mobility Index, Nottingham Extended Activities of Daily Living scale, Beck Anxiety Index, Sleep Hygiene Index, 6m walk test, and measures of cognitive ability. Results: Of the 371 participants recruited, 103 were excluded and 268 were assessed. Of the latter, the mean age was 67.7 years (SD 13.5) and 168 (63%) were men. The National Institutes of Health Stroke Scale mean score was 4.96 (SD 4.12). Post-stroke fatigue was reported by 115 (43%) of participants, with 71 (62%) reporting this to be a new symptom since their stroke. Multivariate analysis using the Fatigue Severity Scale as the outcome variable found pre-stroke fatigue, having a spouse/partner, lower Rivermead Mobility Index score, and higher scores on both the Brief Assessment Schedule Depression Cards and Beck Anxiety Index were independently associated with post-stroke fatigue, accounting for approximately 47% of the variance in Fatigue Severity Scale scores. Conclusions: Pre-stroke fatigue, lower mood, and poorer mobility were associated with post-stroke fatigue.

Controlling hypertension immediately post stroke: a cost utility analysis of a pilot randomised controlled trial

BackgroundElevated blood pressure (BP) levels are common following acute stroke. However, there is considerable uncertainty if and when antihypertensive therapy should be initiated.MethodEconomic evaluation alongside a double-blind randomised placebo-controlled trial (National Research Register Trial Number N0484128008) of 112 hypertensive patients receiving an antihypertensive regimen (labetalol or lisinopril) within 36 hours post stroke versus 59 receiving placebo. Outcomes were incremental cost per incremental: QALY, survivor, and patient free from death or severe disability (modified Rankin scale score < 4) at three months and 14 days post stroke.ResultsActively treated patients on average had superior outcomes and lower costs than controls at three months. From the perspective of the acute hospital setting, there was a 96.5% probability that the incremental cost per QALY gained at three months is below £30,000, although the probability may be overstated due to data limitations.ConclusionAntihypertensive therapy when indicated immediately post stroke may be cost-effective compared with placebo from the acute hospital perspective. Further research is required to confirm both efficacy and cost-effectiveness and establish whether benefits are maintained over a longer time horizon.

The Nottingham Fatigue After Stroke (NotFAST) study: results from follow-up six months after stroke

Abstract Background Post-stroke fatigue is common and disabling. Objectives The aim of NotFAST was to examine factors associated with fatigue in stroke survivors without depression, six months after stroke. Methods Participants were recruited from four UK stroke units. Those with high levels of depressive symptoms (score ≥7 on Brief Assessment Schedule Depression Cards) or aphasia were excluded. Follow-up assessment was conducted at six months after stroke. They were assessed on the Fatigue Severity Scale, Rivermead Mobility Index, Nottingham Extended Activities of Daily Living scale, Barthel Index, Beck Anxiety Index, Brief Assessment Schedule Depression Cards, Impact of Event Scale-Revised, and Sleep Hygiene Index. Results Of the 371 participants recruited, 263 (71%) were contacted at six months after stroke and 213 (57%) returned questionnaires. Approximately half (n = 109, 51%) reported fatigue at six months. Of those reporting fatigue initially (n = 88), 61 (69%) continued to report fatigue. ‘De novo’ (new) fatigue was reported by 48 (38%) of those not fatigued initially. Lower Nottingham Extended Activities of Daily Living scores and higher Beck Anxiety Index scores were independently associated with fatigue at six months. Conclusions Half the stroke survivors reported fatigue at six months post-stroke. Reduced independence in activities of daily living and higher anxiety levels were associated with the level of fatigue. Persistent and delayed onset fatigue may affect independence and participation in rehabilitation, and these findings should be used to inform the development of appropriate interventions.

Balancing satisfaction and stress: carer burden among White and British Asian Indian carers of stroke survivors

ABSTRACT Objectives: This paper presents the findings of a qualitative study exploring White and British Indian informal stroke carers’ experiences of caring, factors contributing to their stress, and strategies used to overcome stress. Design: A qualitative approach involving in-depth interviews was used to explore informal carers’ experiences of caring for stroke survivors and the stress of caring at one and three to six months from the onset of stroke. Interviewers bilingual in English and Gujarati or Punjabi conducted interviews with carers. Socio-demographic data of carers and stroke survivors were collected at one, and three to six months by dedicated stroke research nurses. Results: A total of 37 interviews with carers caring for stroke survivors with a wide range of physical and mental impairments were completed. A majority of carers had assumed the task of caring within a few weeks of the stroke. Irrespective of ethnicity, carers’ emotional and physical well-being was undermined by the uncertainty and unpredictability of caring for stroke survivors, and meeting their expectations and needs. The strain of managing social obligations to care was common to all carers irrespective of gender and ethnicity, but the higher levels of anxiety and depression reported by Indian British female carers appeared to stem from the carers’ pre-existing physical ailments, their cultural and religious beliefs, and household arrangements. Carers’ strain in extended households was exacerbated by the additional responsibility of caring for other dependent relatives. Conclusion: Since the role of carers is clearly indispensable in the successful rehabilitation of survivors, it is vital to ensure that their well-being is not undermined by a lack of information and training, and that their need for professional support is prioritised.