Intra-arterial thrombolysis is the treatment of choice for basilar thrombosis: con.
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Basilar Artery↗
Biomedical subjects
Gary A Ford
Publications and source records attributed to Gary A Ford.
Consent for research in hyperacute stroke.
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Acute Disease↗
Research and development in stroke services.
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Biomedical Research↗
Lifestyle interventions to reduce raised blood pressure: a systematic review of randomized controlled trials.
PURPOSE: To quantify effectiveness of lifestyle interventions for hypertension. DATA SOURCES: Electronic bibliographic databases from 1998 onwards, existing guidelines, systematic reviews. STUDY SELECTION AND DATA ABSTRACTION: We included randomized, controlled trials with at least 8 weeks' follow-up, comparing lifestyle with control interventions, enrolling adults with blood pressure at least 140/85 mmHg. Primary outcome measures were systolic and diastolic blood pressure. Two independent reviewers selected trials and abstracted data; differences were resolved by discussion. RESULTS: We categorized trials by type of intervention and used random effects meta-analysis to combine mean differences between endpoint blood pressure in treatment and control groups in 105 trials randomizing 6805 participants. Robust statistically significant effects were found for improved diet, aerobic exercise, alcohol and sodium restriction, and fish oil supplements: mean reductions in systolic blood pressure of 5.0 mmHg [95% confidence interval (CI): 3.1-7.0], 4.6 mmHg (95% CI: 2.0-7.1), 3.8 mmHg (95% CI: 1.4-6.1), 3.6 mmHg (95% CI: 2.5-4.6) and 2.3 mmHg (95% CI: 0.2-4.3), respectively, with corresponding reductions in diastolic blood pressure. Relaxation significantly reduced blood pressure only when compared with non-intervention controls. We found no robust evidence of any important effect on blood pressure of potassium, magnesium or calcium supplements. CONCLUSIONS: Patients with elevated blood pressure should follow a weight-reducing diet, take regular exercise, and restrict alcohol and salt intake. Available evidence does not support relaxation therapies, calcium, magnesium or potassium supplements to reduce blood pressure.
Administrative Personnel↗
The Recognition of Stroke in the Emergency Room (ROSIER) scale: development and validation of a stroke recognition instrument.
BACKGROUND: In patients with acute stroke, rapid intervention is crucial to maximise early treatment benefits. Stroke patients commonly have their first contact with medical staff in the emergency room (ER). We designed and validated a stroke recognition tool-the Recognition of Stroke in the Emergency Room (ROSIER) scale-for use by ER physicians. METHODS: We prospectively collected data for 1 year (development phase) on the clinical characteristics of patients with suspected acute stroke who were admitted to hospital from the ER. We used logistic regression analysis and clinical reasoning to develop a stroke recognition instrument for application in this setting. Patients with suspected transient ischaemic attack (TIA) with no symptoms or signs when assessed in the ER were excluded from the analysis. The instrument was assessed using the baseline 1-year dataset and then prospectively validated in a new cohort of ER patients admitted over a 9-month period. FINDINGS: In the development phase, 343 suspected stroke patients were assessed (159 stroke, 167 non-stroke, 32 with TIA [17 with symptoms when seen in ER]). Common stroke mimics were seizures (23%), syncope (23%), and sepsis (10%). A seven-item (total score from -2 to +5) stroke recognition instrument was constructed on the basis of clinical history (loss of consciousness, convulsive fits) and neurological signs (face, arm, or leg weakness, speech disturbance, visual field defect). When internally validated at a cut-off score greater than zero, the instrument showed a diagnostic sensitivity of 92%, specificity of 86%, positive predictive value (PPV) of 88%, and negative predictive value (NPV) of 91%. Prospective validation in 173 consecutive suspected stroke referrals (88 stroke, 59 non-stroke, 26 with TIA [13 with symptoms]) showed sensitivity of 93% (95% CI 89-97), specificity 83% (77-89), PPV 90% (85-95), and NPV 88% (83-93). The ROSIER scale had greater sensitivity than existing stroke recognition instruments in this population. INTERPRETATION: The ROSIER scale was effective in the initial differentiation of acute stroke from stroke mimics in the ER. Introduction of the instrument improved the appropriateness of referrals to the stroke team.
Aged↗
Swallow respiratory patterns and aging: presbyphagia or dysphagia?
BACKGROUND: Assessment referrals are increasing for unexpected dysphagia, particularly for older people. It is unclear if this is due to more impaired swallows or healthy age-related changes. Swallow respiration coordination prevents aspiration, and may deteriorate with age. Nonpathological features of the swallow in healthy aging and the factors that influence an individual's ability to eat and drink safely need greater understanding. Some changes might predispose an older person to dysphagic complications in the event of an insult such as a stroke. We investigated the effects of healthy aging on resting and swallow respiratory patterns. METHODS: Fifty healthy volunteers (aged 20-78 years) were recruited to have swallow respiration patterns recorded on a computer. Bolus volume and consistency variations were studied: 5 and 20 ml of water and 5 ml of yogurt. RESULTS: Measurable swallows significantly decreased with age for water boluses. Swallow apnea increased with age (5 ml of water r = 0.433, p = .002; 5 ml of yogurt r = 0.367, p = .023). Independent of age were: breathing out (occurred after 98% of boluses); multiple swallowing (occurred with all bolus types); post-swallow respiration reset pattern (more irregular after yogurt, Wilcoxon signed rank Z = -2.236, p = .025); and resting respiration. CONCLUSIONS: Subtle changes occur in swallow respiration coordination with age. These changes may be compensatory protective mechanisms rather than the result of decreased muscle mobility or reaction times, and not indicative of impairment. Misattributing healthy age-related changes to impairment affects patient care and the use of healthcare resources.
Adult↗
The diabetogenic potential of thiazide-type diuretic and beta-blocker combinations in patients with hypertension.
BACKGROUND: Recently published trials addressing the pharmacological management of hypertension have reported an increase in new-onset diabetes mellitus when comparing certain older and newer treatment regimens. Thiazide-type diuretics (thiazides) and beta-blockers have been individually implicated, but these drugs are frequently combined, and the magnitude of risk associated with their combined use has not been quantified. METHODS AND RESULTS: Randomized control trials were retrieved that: (i) featured stepped treatment to manage hypertension; (ii) compared initial treatment using a thiazide or beta-blocker (older drug) with an angiotensin-converting enzyme inhibitor, angiotensin receptor blocker or calcium antagonist (newer drug); (iii) assessed cardiovascular outcomes; (iv) reported new-onset diabetes; and (v) provided at least 1-year follow-up. A meta-analysis of available trials indicated that patients exposed to treatment regimens combining thiazides and beta-blockers are at greater risk of developing diabetes than regimens avoiding this combination of drugs (risk ratio for alternative therapy 0.81, 95% confidence interval 0.77-0.86). Current data cannot inform reliably about the risks associated with individual older drugs because of similar overall exposures in patients starting on newer and older drugs. INTERPRETATION AND IMPLICATIONS: The results suggest that the routine combined use of a thiazide with a beta-blocker should be questioned in the early management of hypertension, particularly in patients who are at increased risk of developing new-onset diabetes. In such patients, the increased risk of developing diabetes may exceed the benefit of blood pressure lowering.
Adrenergic beta-Antagonists↗
Thrombolysis for stroke in the over 80s.
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Age Factors↗
Reliability and validity of cervical auscultation: a controlled comparison using videofluoroscopy.
Cervical auscultation is experiencing a renaissance as an adjunct to the clinical swallowing assessment. It is a controversial technique with a small evidence base. We have aimed to establish whether cervical auscultation interpretation is based on the actual sounds heard or, in practice, influenced by information gleaned from other aspects of the clinical assessment, medical notes, or previous knowledge. We sought to determine (a) rater reliability and its impact on the clinical value of cervical auscultation and (b) how judgments compare with the "gold standard": videofluoroscopy. Swallow sounds were computer recorded via a Littmann stethoscope. Sounds were sampled from 10 healthy control swallows with no aspiration/penetration and 10 patient swallows with aspiration/penetration, all recorded during simultaneous videofluoroscopy. The system generated sound quality similar to "live" bedside listening, a feature rarely seen in cervical auscultation studies. The 20 sound clips were classified as "normal" or "abnormal" by 19 volunteer speech-language pathologists with experience in cervical auscultation. After at least four weeks, 11 of these judges rated the sounds rerandomized on a new CD. Intrarater reliability kappa ranged from -0.12 to 0.71. Individual reliability did not correlate with years of experience, practice pattern, or frequency of use. Interrater reliability kappa = 0.17. Comparison with radiologically defined aspiration/penetration yielded 66% specificity, 62% sensitivity, and majority consensus gave 90% specificity, 80% sensitivity. There was a significant relationship between individual reliability and true positive rate (r(s) = 0.623, p = 0.040). The reliability of individual judges varied widely and thus, inevitably, agreement between judges was poor. Validity is dependent upon reliability: Improving the poor raters would improve the overall accuracy of this technique in predicting abnormality in swallowing. The group consensus correctly identified 17 of the 20 clips so we may speculate that the swallow sound contains audible cues that should in principle permit reliable classification.
Aged↗
Development and validation of NEWSQOL, the Newcastle Stroke-Specific Quality of Life Measure.
BACKGROUND: A review of stroke-specific quality of life (QOL) measures indicated little evidence of their validity/reliability. PURPOSE: To describe the development/validation of a new measure - the Newcastle Stroke-Specific Quality of Life Measure (NEWSQOL). METHODS: Phase I: qualitative interviews (28 stroke patients) determined QOL issues for inclusion in the measure. Initial items/response categories were pre-tested (30 patients). Administration of the NEWSQOL in the item reduction stage (100 patients) identified poorly performing items and factor analysis showed likely domains. Internal consistency was examined. Phase II: NEWSQOL and comparator measures were administered (106 patients) to examine validity/test-retest reliability. RESULTS: Phase I: 140 items were identified for initial inclusion. Qualitative pre-testing led to an extensive revision. Item reduction resulted in a final measure of 56 items in 11 domains (feelings, activities of daily living/self-care, cognition, mobility, emotion, sleep, interpersonal relationships, communication, pain/sensation, vision, fatigue; Cronbach's alpha = 0.71-0.90). Phase II: NEWSQOL domain scores, except cognition, were moderately/highly correlated (0.45-0.76) with relevant comparator measures. NEWSQOL domains feelings, communication and cognition low/moderately correlated with Barthel Index scores (-0.49 to -0.28), as predicted. Test-retest reliability was high (intraclass correlation coefficient range 0.78-0.92). CONCLUSIONS: NEWSQOL is an acceptable, patient-derived, interviewer-administered, stroke-specific QOL measure with evidence of reliability and validity, making it a promising instrument for assessing QOL after stroke. Involvement of relevant patients in determining the content and format considerably enhances confidence in its validity.
Adult↗
Acute Stroke Therapy by Inhibition of Neutrophils (ASTIN): an adaptive dose-response study of UK-279,276 in acute ischemic stroke.
BACKGROUND AND PURPOSE: UK-279,276 (neutrophil inhibitory factor) reduced infarct volume in a rat middle cerebral artery occlusion reperfusion model. ASTIN (Acute Stroke Therapy by Inhibition of Neutrophils) was an adaptive phase 2 dose-response-finding, proof-of-concept study to establish whether UK-279,276 improves recovery in acute ischemic stroke. The prime objective was to determine the dose that gave a clinically relevant effect in patients. METHODS: A Bayesian sequential design with real-time efficacy data capture and continuous reassessment of the dose response allowed double-blind, randomized, adaptive allocation to 1 of 15 doses (dose range, 10 to 120 mg) or placebo and early termination for efficacy or futility. The primary end point was change from baseline to day 90 on the Scandinavian Stroke Scale (DeltaSSS), adjusted for baseline SSS, aiming for a 3-point additional mean recovery above placebo. RESULTS: Nine hundred sixty-six acute stroke patients (887 ischemic, 204 cotreated with intravenous tissue plasminogen activator; mean baseline SSS score, 28; range, 10 to 40) were treated within 6 hours of symptom onset. Mean DeltaSSS was approximately +17 points of improvement on SSS for the overall evaluable population. There was no treatment effect for UK-279,276 (posterior probability of futility, 0.89). The trial was stopped early for futility. Post hoc analysis indicated a mean 1.6-point additional improvement on DeltaSSS in the tissue plasminogen activator-treated subset (credible interval=0.5, 2.6). UK-279,276 was generally well tolerated, with no increased incidence of infections. CONCLUSIONS: UK-279,276 did not improve recovery in acute ischemic stroke patients but was devoid of serious side effects. The adaptive design facilitated early termination for futility.
Acute Disease↗
Effects of hypertension on attention, memory, and executive function in older adults.
Hypertension is associated with impairments in cognitive function in older adults, but the nature and extent of these deficits are unclear. Brief cognitive measures lack sensitivity, whereas comprehensive assessments produce numerous variables that are difficult to interpret. The authors performed a principal-components analysis using a computerized cognitive assessment battery and neuropsychological measures of executive function in 506 hypertensive and normotensive older participants. Composite factor scores were used to reanalyze data from 223 untreated participants without vascular complications. The hypertensive group had deficits in Speed of Cognition, Episodic and Working Memory, and Executive Function but not Continuity of Attention. Using composite scores simplified data interpretation and suggested differential effects of hypertension on cognitive performance not clearly evident in individual test results.
Aged↗
Regulation of attention and response to therapy in dementia by butyrylcholinesterase.
OBJECTIVES: To determine the response of patients with different butyrylcholinesterase genotypes to therapy, and the influence of butyrylcholinesterase on cognition. Acetylcholine plays a key role in attention and memory and reduced cortical acetylcholine is associated with the severity of dementia. Inhibitors of the enzyme acetylcholinesterase are an effective dementia treatment, though the role of the related enzyme butyrylcholinesterase is less well understood. METHODS: We examined the response of a cohort of dementia patients enrolled in a trial of a cholinesterase inhibitor who had been genotyped at the butyrylcholinesterase locus. Additionally a prospectively assessed cohort of dementia patients was genotyped and rate of cognitive decline examined, along with baseline cognitive performance in a group of elderly non-demented individuals. We identified that the presence of reduced-activity butyrylcholinesterase variants correlates with preserved attentional performance and reduced rate of cognitive decline. During cholinesterase inhibitor therapy, patients with normal butyrylcholinesterase show improved attention, though patients carrying reduced-activity enzyme do not, possibly due to being at ceiling performance. Butyrylcholinesterase did not however affect attentional performance in non-demented individuals with mild cognitive impairment. CONCLUSIONS: These findings indicate that the butyrylcholinesterase enzyme is a major regulator of attention especially in cholinergic deficiency states through its ability to hydrolyse acetylcholine. Pharmacologic manipulation of this enzyme may be a viable strategy in dementia treatment and, with butyrylcholinesterase genotyping, may provide pharmacogenomic treatment of dementia.
Acetylcholine↗
Diagnostic accuracy of stroke referrals from primary care, emergency room physicians, and ambulance staff using the face arm speech test.
BACKGROUND AND PURPOSE: Timely referral of appropriate patients to acute stroke units is necessary for effective provision of skilled care. We compared the characteristics of referrals with suspected stroke to an academic acute stroke unit via 3 primary referral routes: ambulance paramedics using a rapid ambulance protocol and stroke recognition instrument, the Face Arm Speech Test; primary care doctors (PCDs); and emergency room (ER) referrals. METHODS: Patient characteristics, final diagnosis, and admission delay were recorded in all suspected acute stroke referrals in a 6-month period. RESULTS: Four hundred eighty-seven patients (356 strokes/transient ischemic attacks) were admitted by the 3 routes: 178 by ambulance, 216 by PCDs, and 93 through the ER. The proportion of nonstrokes admitted by each route was similar (23%, 29%, and 29%, respectively). Ambulance paramedics' stroke diagnosis was correct in 144 of 183 (79%) stroke patients who initially presented to them. Thirty-nine of 66 strokes/transient ischemic attacks referred via ER were taken there following initial ambulance assessment. Compared with PCDs, paramedics referred more total anterior circulation (39% versus 14%, P<0.0001) and fewer lacunar strokes (14% versus 31%, P<0.001) and admitted more patients (46% versus 12%, P<0.01) within 3 hours of symptom onset. The most common nonstroke conditions were seizures, infections and confusion, cardiovascular collapse, and cerebral tumors. Paramedics admitted more patients with seizures. CONCLUSIONS: Misdiagnosis of stroke is common in the ER and by PCDs. Paramedics using the Face Arm Speech Test achieved high levels of detection and diagnostic accuracy of stroke.
Adult↗
Swallow-induced alterations in breathing in normal older people.
Respiratory parameters in 29 normal older subjects (mean age-73 years, SD = 5.7) were studied at rest, during single water swallows, and in continuous drinking. Respiration was recorded by intranasal air pressure changes and the moment of swallowing by pharyngoesophageal manometry. Compared with respiration at rest, respiratory rate increased immediately after 5 mL swallows as duration of breath cycles decreased from a mean of 3.8 s at rest to 3.5 s after swallowing (p = 0.003), but regularity of respiration was maintained. Deglutition apnea showed a trend toward increasing duration from a median of 1.06 to 1.24 s (p = 0.096) as bolus volume increased from 5 to 20 mL. Oxygen saturation levels were also compared, with a median fall of 2% during swallowing, but with larger and unexplained falls in several subjects. Direction of airflow monitoring showed 91% of single 5 mL swallows were followed by expiration, with postswallow inspiratory breaths occurring in 41% of subjects. Continuous swallowing of 100 mL of water from a cup and straw was typically performed with a pattern of multiple swallows per breath, with expiration occurring after 78.5% (cup) and 63.5% (straw) of swallows. This definition of swallowing-induced respiratory changes in normal older people forms a valuable basis for future comparison with elderly dysphagic patients.
Aged↗
Resting respiration in dysphagic patients following acute stroke.
The aim of this study was to examine respiration characteristics at rest in healthy volunteers and patients with poststroke dysphagia, using a simple notebook computer-based system. Eighteen patients (age range=51-82 years) with dysphagia poststroke and 50 healthy volunteers (age range=20-78 years) were recruited. The patient group had a wide range of stroke severity as assessed using the Scandinavian Stroke Score (SSS 6-51) and Barthel Index (BI 2-20). Length of breathing cycle, rate, and a measure of the variability of the cycle length were examined. The patient group had a shorter mean cycle length (2.93 s compared with 3.91 s, p < 0.01) and hence faster respiration rate (0.35 Hz compared with 0.26 Hz, p < 0.01). The control group showed greater variability in the cycle length (10.78% compared with 6.56%, p = 0.01). There was no correlation between the SSS and BI and resting respiration variables. This suggests that it is not stroke severity alone that affects breathing. The differences observed in resting respiratory rate suggest that respiratory monitoring as a useful adjunct to the clinical bedside assessment warrants further investigation.
Aged↗
Swallow respiration patterns in dysphagic patients following acute stroke.
The aim of this study was to examine swallow respiratory characteristics using a notebook computer system. A relatively simple system assessing easily identifiable features is more likely to be incorporated into everyday clinical practice. Eighteen patients (age range = 51-82 years) with dysphagia poststroke and 50 healthy volunteers (age range = 20-78 years) were recruited. The patient group was less likely to always breathe out postswallow on water (9/15 cf 46/49), and some did not breathe out immediately postswallow at all (3/15 cf 0/49, p < 0.01). The pattern was similar with yogurt. Multiple swallowing was identified in the patient group and surprisingly with a large number of the volunteers for all bolus types but was more common in the patient group (p < 0.01). This trait is usually attributed to impaired swallows; that it is prevalent in the normal population has implications for using it as a dysphagia marker in clinical assessments. Yogurt has intrinsic features that increase multiple swallowing and caution should be used when identifying an impairment based on multiple swallowing with such a test substance. In the control group there was a high correlation of swallow apnea on 5 mL of water compared with 20 mL of water (r = 0.759, p < 0.01) and 5 mL of yogurt (r = 0.871, p < 0.01), indicating a possible individual swallow respiration pattern. This was also evident in the patient group. No significant difference in length of swallow apnea was found between the two groups. No evidence was found to link swallow respiration characteristics with aspiration as identified on simultaneous videofluoroscopy. The patient group had a wide range of impairments which suggests that stroke severity is not the sole determinant of swallow respiratory changes.
Aged↗
Flow-mediated nitric oxide activity in the forearm vasculature of premenopausal women.
AIMS: Nitric oxide (NO) is involved in acute flow-mediated vasodilatation in various vascular beds. We determined whether acutely increasing flow in the human forearm of premenopausal women increases vascular NO activity. METHODS: Forearm blood flow (FBF) was measured by venous occlusion plethysmography. Responses to brachial artery infusion of noradrenaline (a control vasoconstrictor, 20, 50, and 100 ng min(-1), each for 5 min) and NG-monomethyl l-arginine (L-NMMA), an NO synthase inhibitor (200, 400, and 800 microg min(-1), each for 5 min), were determined in eight premenopausal women before and following elevation of basal FBF with glyceryl trinitrate (GTN) on two separate occasions. RESULTS: Flow elevation with GTN increased responses to L-NMMA (summary measure 103 +/- 12 vs 65 +/- 12 arbitrary units, P<0.05), but not to noradrenaline (95 +/- 35 vs 74 +/- 12, P=0.50). CONCLUSIONS: Acute elevation of FBF in nonpregnant women is associated with enhanced responses to NO synthase inhibition, consistent with flow-mediated increased NO activity.
Adult↗