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Background: Severe strokes and stroke-associated pneumonia (SAP) have long been associated with poorer patient health outcomes, for example, in-hospital mortality. However, it is unclear what role SAP plays in the risk of in-hospital mortality associated with a severe stroke at admission., Methods: Using the Sentinel Stroke National Audit Program data on stroke admissions (2013-2018) in England and Wales, we modeled the "total" effect for severe stroke on risk of in-hospital mortality. Through four-way decomposition methodology, we broke down the "total" observed risk into four components. The direct "severity on outcome only" effect, the pure indirect effect of severity mediated via SAP only, the interaction between severity and SAP when mediation is not present, and when mediation via SAP is present., Results: Of 339,139 stroke patients included, 9.4% had SAP and 15.6% died in hospital. Of SAP patients, 45% died versus 12% of non-SAP patients. The risk ratio for in-hospital mortality associated with severe versus mild/moderate stroke (i.e. total effect) was 4.72 (95% confidence interval: 4.60-4.85). Of this, 43%-increased risk was due to additive SAP interaction, this increased to 50% for "very severe" stroke. The remaining excess relative risk was due to the direct severity on outcome effect only, that is, there was no evidence here for a mediation effect via SAP., Conclusion: SAP was associated with a higher mortality in severe stroke patients. Prioritizing SAP prevention in severe stroke patients may improve in-hospital survival. Our results suggest that in severe stroke patients avoiding SAP might result in an up to 43% reduction in mortality., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: M.G., M.A.L.C., A.V., and C.J.S. have no conflicts related to this work. This study is additional follow-up work based on M.A.L.C.’s PhD thesis investigating stroke-associated pneumonia using the SSNAP data. M.A.L.C.’s work at Glaxosmithkline Biologicals is in no way related or in conflict to the work presented here.

Introduction: It is not known whether modern stroke unit care reduces the impact of stroke complications, such as stroke-associated pneumonia (SAP), on clinical outcomes. We investigated the relationship between SAP and clinical outcomes, adjusting for the confounding effects of stroke care processes and their timing., Methods: The Sentinel Stroke National Audit Programme provided patient data for all confirmed strokes between April 2013 and December 2018. SAP was defined as new antibiotic initiation for suspected pneumonia within the first 7 days from stroke admission. We compared outcomes after SAP versus non-SAP in appropriate multilevel mixed models. Each model was adjusted for patient and clinical characteristics, as well as markers of stroke care and their timing within the first 72 h. The appropriate effect estimates and corresponding 95% confidence intervals (CIs) were reported., Results: Of 201,778 patients, SAP was present in 14.2%. After adjustment for timing of acute stroke care processes and clinical characteristics, adverse outcomes remained for SAP versus non-SAP patients. In these adjusted analyses, patients with SAP maintained an increased risk of longer length of in-hospital stay (IRR of 1.27; 95% CI: 1.25, 1.30), increased odds of worse functional outcome at discharge (OR of 2.9; 95% CI: 2.9, 3.0), and increased risk of in-hospital mortality (HR of 1.78; 95% CI: 1.74, 1.82)., Conclusion: We show for the first time that SAP remains associated with worse clinical outcomes, even after adjusting for processes of acute stroke care and their timing. These findings highlight the importance of continued research efforts aimed at preventing SAP., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Background: Pneumonia is common in stroke patients and is associated with worse clinical outcomes. Prevalence of stroke-associated pneumonia varies between studies, and reasons for this variation remain unclear. We aimed to describe the variation of observed stroke-associated pneumonia in England and Wales and explore the influence of patient baseline characteristics on this variation., Methods: Patient data were obtained from the Sentinel Stroke National Audit Programme for all confirmed strokes between 1 April 2013 and 31 December 2018. Stroke-associated pneumonia was defined by new antibiotic initiation for pneumonia within the first seven days of admission. The probability of stroke-associated pneumonia occurrence within stroke units was estimated and compared using a multilevel mixed model with and without adjustment for patient-level characteristics at admission., Results: Of the 413,133 patients included, median National Institutes of Health Stroke Scale was 4 (IQR: 2-10) and 42.3% were aged over 80 years. Stroke-associated pneumonia was identified in 8.5% of patients. The median within stroke unit stroke-associated pneumonia prevalence was 8.5% (IQR: 6.1-11.5%) with a maximum of 21.4%. The mean and variance of the predicted stroke-associated pneumonia probability across stroke units decreased from 0.08 (0.68) to 0.05 (0.63) when adjusting for patient admission characteristics. This difference in the variance suggests that clinical characteristics account for 5% of the observed variation in stroke-associated pneumonia between units., Conclusions: Patient-level clinical characteristics contributed minimally to the observed variation of stroke-associated pneumonia between stroke units. Additional explanations for the observed variation in stroke-associated pneumonia need to be explored which could reduce variation in antibiotic use for stroke patients.

Objectives: Accurate and timely diagnosis of pneumonia complicating stroke remains challenging and the diagnostic accuracy of chest X-ray (CXR) in the setting of stroke-associated pneumonia (SAP) is uncertain. The overall objective of this study was to evaluate the use of pulmonary computed tomography (CT) in diagnosis of suspected SAP., Materials and Methods: Patients with acute ischemic stroke (IS) or intracerebral hemorrhage (ICH) were recruited within 24h of clinically suspected SAP and underwent non-contrast pulmonary CT within 48h of antibiotic initiation. CXR and pulmonary CT were reported by two radiologists. Pulmonary CT was used as the reference standard for final diagnosis of SAP. Sensitivity, specificity, positive and negative predictive values (PPV and NPV), and diagnostic odds ratio (OR) for CXR were calculated., Results: 40 patients (36 IS, 4 ICH) with a median age of 78y (range 44y-90y) and a median National Institute of Health Stroke Scale score of 13 (range 3-31) were included. All patients had at least one CXR and 35/40 patients (88%) underwent pulmonary CT. Changes consistent with pneumonia were present in 15/40 CXRs (38%) and 12/35 pulmonary CTs (34%). 9/35 pulmonary CTs (26%) were reported normal. CXR had a sensitivity of 58.3%, specificity of 73.9%, PPV of 53.8 %, NPV of 77.2 %, diagnostic OR of 3.7 (95% CI 0.7 - 22) and an accuracy of 68.5% (95% CI 50.7% -83.1%)., Discussion: CXR has limited diagnostic accuracy in SAP. The majority of patients started on antibiotics had no evidence of pneumonia on pulmonary CT with potential implications for antibiotic stewardship., Conclusions: Pulmonary CT could be applied as a reference standard for evaluation of clinical and biomarker diagnostic SAP algorithms in multi-center studies., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background and Aims: Concerns have arisen regarding patient access and delivery of acute stroke care during the COVID-19 pandemic. We investigated key population level events on activity of the three hyperacute stroke units (HASUs) within Greater Manchester and East Cheshire (GM & EC), whilst adjusting for environmental factors., Methods: Weekly stroke admission & discharge counts in the three HASUs were collected locally from Emergency Department (ED) data and Sentinel Stroke National Audit Programme core dataset prior to, and during the emergence of the COVID-19 pandemic (Jan 2020 to May 2020). Whilst adjusting for local traffic-related air pollution and ambient measurement, an interrupted time-series analysis using a segmented generalised linear model investigated key population level events on the rate of stroke team ED assessments, admissions for stroke, referrals for transient ischaemic attack (TIA), and stroke discharges., Results: The median total number of ED stroke assessments, admissions, TIA referrals, and discharges across the three HASU sites prior to the first UK COVID-19 death were 150, 114, 69, and 76 per week. The stable weekly trend in ED assessments and stroke admissions decreased by approximately 16% (and 21% for TIAs) between first UK hospital COVID-19 death (5 th March) and the implementation of the Act-FAST campaign (6 th April) where a modest 4% and 5% increase per week was observed. TIA referrals increased post Government intervention (23 rd March), without fully returning to the numbers observed in January and February. Trends in discharges from stroke units appeared unaffected within the study period reported here., Conclusion: Despite adjustment for environmental factors stroke activity was temporarily modified by the COVID-19 pandemic. Underlying motivations within the population are still not clear. This raises concerns that patients may have avoided urgent health care risking poorer short and long-term health outcomes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Poststroke dysphagia is common, associated with a poor outcome and has no definitive treatments. Repetitive transcranial magnetic stimulation (rTMS) targeting the cerebellum is a noninvasive technique requiring minimal physical or cognitive input from the patient, and has been shown to induce positive swallow-related brain changes in physiological studies as measured by increased cortical excitability., Aim: To explore in patients with acute/sub-acute poststroke dysphagia: (1) the feasibility and immediate effect; and (2) the optimal dose for long-term benefit, of cerebellar rTMS in patients with dysphagia in acute/sub-acute stroke., Methods: Two double-blind sham-controlled randomized phase II trials. Participants will be recruited from stroke units in Nottingham and Greater Manchester. Dysphagia will be confirmed via baseline videofluoroscopy (VFS). Participants will be blinded to treatment and receive cerebellar rTMS or sham stimulation: (1) single treatment of (10Hz, 250 pulse) in 24 participants; (2) daily for 3 days, twice-daily for 5 days, or twice-daily sham treatment for 5 days, in 48 participants., Results: The severity of dysphagia will be assessed with VFS, using the penetration aspiration scale (PAS) at: (1) 1-hour, (2) 2-weeks, post-treatment. Additional comparative measures will be taken from: (1) pharyngeal motor evoked potential (MEP) amplitudes, (2) the functional oral intake score and dysphagia severity rating scale., Conclusions: If these studies demonstrate feasibility and identify optimal dosing, further trials to assess the safety and efficacy of cerebellar rTMS as a treatment for poststroke dysphagia will be warranted., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The prevalence of reported penicillin allergy (PenA) and the impact these records have on health outcomes in the UK general population are unknown. Without such data, justifying and planning enhanced allergy services is challenging., Objectives: To determine: (i) prevalence of PenA records; (ii) patient characteristics associated with PenA records; and (iii) impact of PenA records on antibiotic prescribing/health outcomes in primary care., Methods: We carried out cross-sectional/retrospective cohort studies using patient-level data from electronic health records. Cohort study: exact matching across confounders identified as affecting PenA records. Setting: English NHS general practices between 1 April 2013 and 31 March 2014. Participants: 2.3 million adult patients. Outcome measures: prevalence of PenA, antibiotic prescribing, mortality, MRSA infection/colonization and Clostridioides difficile infection., Results: PenA prevalence was 5.9% (IQR = 3.8%-8.2%). PenA records were more common in older people, females and those with a comorbidity, and were affected by GP practice. Antibiotic prescribing varied significantly: penicillins were prescribed less frequently in those with a PenA record [relative risk (RR)  = 0.15], and macrolides (RR = 4.03), tetracyclines (RR = 1.91) nitrofurantoin (RR = 1.09), trimethoprim (RR = 1.04), cephalosporins (RR = 2.05), quinolones (RR = 2.10), clindamycin (RR = 5.47) and total number of prescriptions were increased in patients with a PenA record. Risk of re-prescription of a new antibiotic class within 28 days (RR = 1.32), MRSA infection/colonization (RR = 1.90) and death during the year subsequent to 1 April 2013 (RR = 1.08) increased in those with PenA records., Conclusions: PenA records are common in the general population and associated with increased/altered antibiotic prescribing and worse health outcomes. We estimate that incorrect PenA records affect 2.7 million people in England. Establishing true PenA status (e.g. oral challenge testing) would allow more people to be prescribed first-line antibiotics, potentially improving health outcomes., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Orolingual angio-oedema is a recognised complication of tissue plasminogen activator (tPA) for ischaemic stroke. We investigated its incidence, clinical characteristics and relationship with other factors in patients receiving tPA at a UK centre., Methods: 530 consecutive patients (median age 70 years) receiving tPA treatment for confirmed ischaemic stroke were included. Cases were defined as those developing angio-oedema within 24 h of initiation of tPA. Angio-oedema was retrospectively classified as mild, moderate or severe using predefined criteria. The primary analysis was the association between prior ACE inhibitor (ACE-I) treatment and angio-oedema., Results: Orolingual angio-oedema was observed in 42 patients (7.9%; 95% CI 5.5% to 10.6%), ranging from 5 to 189 min after initiation of tPA (median 65 min). 12% of the angio-oedema cases were severe (1% of all patients treated with tPA), requiring urgent advanced airway management. 172 patients (33%) were taking ACE-I. In multifactorial analyses, only prior ACE-I treatment remained a significant independent predictor of angio-oedema (odds ratio (OR) 2.3; 95% CI 1.1 to 4.7)., Conclusions: Angio-oedema occurs more frequently than previously reported and is associated with preceding ACE-I treatment. Angio-oedema may be delayed and progress to life-threatening airway compromise, which has implications for the assessment and delivery of thrombolysis., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Epidemiological studies of systemic amyloidosis are scarce and the burden of disease in England has not previously been estimated. In 1999, the National Health Service commissioned the National Amyloidosis Centre (NAC) to provide a national clinical service for all patients with amyloidosis. Data for all individuals referred to the NAC is held on a comprehensive central database, and these were compared with English death certificate data for amyloidosis from 2000 to 2008, obtained from the Office of National Statistics. Amyloidosis was stated on death certificates of 2543 individuals, representing 0·58/1000 recorded deaths. During the same period, 1143 amyloidosis patients followed at the NAC died, 903 (79%) of whom had amyloidosis recorded on their death certificates. The estimated minimum incidence of systemic amyloidosis in the English population in 2008, based on new referrals to the NAC, was 0·4/100 000 population. The incidence peaked at age 60-79 years. Systemic AL amyloidosis was the most common type with an estimated minimum incidence of 0·3/100 000 population. Although there are various limitations to this study, the available data suggest the incidence of systemic amyloidosis in England exceeds 0·8/100 000 of the population., (© 2013 John Wiley & Sons Ltd.)

Background: While several studies have investigated the effects of short-term air pollution on cardiovascular disease, less is known about its effects on cerebrovascular disease, including stroke and transient ischaemic attack (TIA). The aim of the study was to assess the effects of short-term variation in air pollutants on the onset of TIA and minor stroke., Methods: We performed secondary analyses of data collected prospectively in the North West of England in a multi-centre study (NORTHSTAR) of patients with recent TIA or minor stroke. A case-crossover study was conducted to determine the association between occurrence of TIA and the concentration of ambient PM10 or gaseous pollutants., Results: A total of 709 cases were recruited from the Manchester (n = 335) and Liverpool (n = 374) areas. Data for the Manchester cohort showed an association between ambient nitric oxide (NO) and risk of occurrence of TIA and minor stroke with a lag of 3 days (odds ratio 1.06, 95% CI: 1.01 - 1.11), whereas negative association was found for the patients from Liverpool. Effects of similar magnitude, although not statistically significant, were generally observed with other pollutants. In a two pollutant model the effect of NO remained stronger and statistically significant when analysed in combination with CO or SO2, but was marginal in combination with NO2 or ozone and non-significant with PM10. There was evidence of effect modification by age, gender and season., Conclusions: Our data suggest an association between NO and occurrence of TIA and minor stroke in Greater Manchester.

Background and Hypothesis: Inflammation is implicated in the pathogenesis and outcome of ischaemic injury. Poststroke inflammation is associated with outcome but it remains unclear whether such inflammation precedes or results from ischaemic injury. We hypothesised that inflammatory markers are associated with an increased risk of recurrent vascular events soon after transient ischaemic attack and minor stroke., Methods: This was a multicentre, prospective, nested case-control study. Plasma concentrations of C-reactive protein, interleukin-6, interleukin-1-receptor antagonist and fibrinogen, leucocyte counts, erythrocyte sedimentation rate and inflammatory gene allele frequencies were analysed in 711 patients with recent transient ischaemic attack or minor stroke. Cases were defined by the incidence of one or more recurrent vascular events during the three-month follow-up. Association of inflammatory markers with case-status was determined using conditional logistic regression., Results: Plasma concentrations of C-reactive protein, interleukin-1-receptor antagonist and interleukin-6 were not associated with case-status. In secondary analyses, only erythrocyte sedimentation rate was significantly associated with case-status (odds ratio 1·39, 95% confidence interval 1·03-1·85; P=0·03), but this effect did not persist after adjustment for smoking and past history of transient ischaemic attack or stroke. Single nucleotide polymorphisms in four inflammatory genes (interleukin-6, fibrinogen, P-selectin and vascular cell adhesion molecule-1) were nominally associated with case-status., Conclusions: Circulating inflammatory markers were not associated with recurrent vascular events. Nominally significant associations between genetic markers and case-status will require replication. These data provide little evidence for an inflammatory state predisposing to stroke and other vascular events in a susceptible population., (© 2011 The Authors. International Journal of Stroke © 2011 World Stroke Organization.)

Background: The ABCD2 score predicts stroke risk within a few days of transient ischaemic attack (TIA). It is not clear whether the predictive value of the ABCD2 score can be generalised to UK TIA services, where delayed presentation of TIA and minor stroke are common. We investigated prognosis, and the use of the ABCD2 score, in patients attending TIA services in the North West of England with a diagnosis of TIA or minor stroke., Methods: 711 patients with TIA or minor stroke were prospectively recruited from five centres (median duration from index event to recruitment 15 days). The primary outcome was the composite of incident TIA, stroke, acute coronary syndrome or cardiovascular death at the 3 month follow-up. Prognostic factors were analysed using Cox proportional hazards regression., Results: The primary outcome occurred in 126 (18%) patients. Overall, there were 30 incident strokes. At least one incident TIA occurred in 100 patients (14%), but only four had a subsequent stroke. In multifactorial analyses, the ABCD2 score was unrelated to the risk of the primary outcome, but predicted the risk of incident stroke: score 4-5: hazard ratio (HR) 3.4 (95% CI 1.0 to 12); score 6-7: HR 4.8 (1.3 to 18). Of the components of the ABCD2 score, unilateral motor weakness predicted both the primary outcome (HR 1.8 (1.2 to 2.8)) and stroke risk (HR 4.2 (1.3 to 14))., Conclusions: In patients attending typical NHS TIA services, the risk of incident stroke was relatively low, probably reflecting delays to assessment. Current provision of TIA services, where delayed presentation to "rapid access" TIA clinics is common, does not appear to provide an appropriate setting for urgent evaluation, risk stratification or timely secondary prevention for those who may be at highest risk.

OBJECTIVE. To investigate the effects of weight status, food type and exposure to food and non-food advertisements on children's preference for branded and non-branded foods. DESIGN. A within-subjects, counterbalanced design with control (toy advertisement) and experimental (food advertisement) conditions. Subjects. A total of 37 school students (age: 11-13 years; weight status: 24 lean, 10 overweight, 3 obese). Measurements. Advertisement recall list, two food preference measures; the Leeds Food Preference Measure (LFPM), the Adapted Food Preference Measure (AFPM) and a food choice measure; the Leeds Forced-choice Test (LFCT). RESULTS. Normal weight children selected more branded and non-branded food items after exposure to food advertisements than in the control (toy advertisement) condition. Obese and overweight children showed a greater preference for branded foods than normal weight children per se, and also in this group only, there was a significant correlation between food advertisement recall and the total number of food items chosen in the experimental (food advertisement) condition. CONCLUSION. Exposure to food advertisements increased the preference for branded food items in the normal weight children. This suggests that television food advertisement exposure can produce the same 'obesigenic' food preference response found in overweight and obese children in their normal weight counterparts.

Background: A 15-fold increased risk of gastrointestinal bleeding has been reported with concurrent use of selective serotonin reuptake inhibitors and non-steroidal anti-inflammatory drugs. Recent guidance cautions against concurrent prescription, particularly in older people., Aim: To quantify the risk of gastrointestinal bleeding associated with current exposure to non-steroidal anti-inflammatory drugs, selective serotonin reuptake inhibitors, and both drugs concurrently., Methods: We conducted a case-control analysis of 11,261 cases with upper gastrointestinal bleeding and 53,156 controls matched by gender, age and general practice from computerized primary care data. We coupled this with self-controlled case series analysis., Results: Both drugs were associated with a twofold increased risk of gastrointestinal bleeding (odds ratio =2.38, 95% confidence interval 2.08-2.72 for selective serotonin reuptake inhibitors and odds ratio = 2.15, 95% confidence interval 2.02-2.28 for non-steroidal anti-inflammatory drugs). This increased risk was marginally higher for concurrent prescription (odds ratio = 2.93, 95% confidence interval 2.25-3.82). The self-controlled analysis showed a greater incidence rate ratio for gastrointestinal bleeding with non-steroidal anti-inflammatory drugs (2.71, 95% confidence interval 2.51-2.91) and lower incidence rate ratio with selective serotonin reuptake inhibitors (1.71, 95% confidence interval 1.48-1.98). The incidence rate ratio when both drugs were combined was 3.25, 95% confidence interval 1.95-5.42. Estimates were similar after restricting to people over 80 years of age. Increased risk of gastrointestinal bleeding was not specifically related to class of non-steroidal anti-inflammatory drugs and was similar when we looked at tricyclic anti-depressants., Conclusions: Our study suggests that the risk of gastrointestinal bleeding is not substantially increased when non-steroidal anti-inflammatory drugs and selective serotonin reuptake inhibitors are prescribed together, compared with their use alone.

Aim: Although the benefits of antiretroviral therapy (ART) have been dramatic, studies have started to report a variety of drug-related side effects and toxicities. We sought to characterize the risk factors for cardiovascular disease present in an HIV-positive population., Methods: A total of 394 HIV-positive ambulant patients attending the Royal Free Hospital, London, were asked to complete a questionnaire. Questions focused on smoking habits and general health., Results: In total, 38% of patients were aged >40 years, 37% had a family history of heart disease, 3% had diabetes, 14% suffered from raised blood pressure, 20% had a body mass index (BMI)>26 kg/m3, 7% had an alcohol consumption above the recommended UK limit, and 18% had total cholesterol levels >6.3 mmol/L [corrected]. The rate of smoking observed (45%) was much higher than that observed amongst the general population in the British Health Survey for England (34%). There were significant differences between those receiving and not receiving ART. Those on ART tended to be younger (P<0.0001) and less likely to smoke cigarettes (P=0.06) or have an alcohol consumption above the recommended limit (P=0.08), but were more likely to have diabetes (P=0.05). More patients receiving ART reported, and so perceived themselves to have, raised blood fats (P<0.0001). This was confirmed when considering blood lipid levels, where those on ART had significantly raised total cholesterol levels compared to those not currently receiving ART (P<0.0001)., Conclusion: We have demonstrated an excess of cardiovascular risk factors in this cohort. These issues must be addressed if we wish to maintain the benefit of treating HIV infection.