Patient outcomes up to 15 years after stroke: survival, disability, quality of life, cognition and mental health

BACKGROUND: The global epidemiological shift of disease burden towards long-term conditions means understanding long-term outcomes of cardiovascular disease is increasingly important. More people are surviving stroke to experience its long-term consequences, but outcomes in people living more >10 years after stroke have not been described in detail. METHODS: Data were collected for the population-based South London Stroke Register, with participants followed up annually until death. Outcomes were survival, disability, activity, cognitive impairment, quality of life, depression and anxiety. FINDINGS: Of 2625 people having first-ever stroke, 262 (21%) survived to 15 years. By 15 years, 61% (95% CI 55% to 67%) of the survivors were male, with a median age of stroke onset of 58 years (IQR 48-66). 87% of the 15-year survivors were living at home and 33.8% (26.2% to 42.4%) had mild disability, 14.3% (9.2% to 21.4%) moderate disability and 15.0% (9.9% to 22.3%) severe disability. The prevalence of disability increased with time but 1 in 10 of the 15-year survivors had lived with moderate-severe disability since their stroke. At 15 years, the prevalence of cognitive impairment was 30.0% (19.5% to 43.1%), depression 39.1% (30.9% to 47.9%) and anxiety 34.9% (27.0% to 43.8%), and survivors reported greater loss of physical than mental quality of life. CONCLUSIONS: One in five people live at least 15 years after a stroke and poor functional, cognitive and psychological outcomes affect a substantial proportion of these long-term survivors. As the global population of individuals with cardiovascular long-term conditions grows, research and health services will need to increasingly focus on preventing and managing the long-term consequences of stroke

Can clinical audits be enhanced by pathway simulation and machine learning? An example from the acute stroke pathway

OBJECTIVE: To evaluate the application of clinical pathway simulation in machine learning, using clinical audit data, in order to identify key drivers for improving use and speed of thrombolysis at individual hospitals

Cost-effectiveness of stent-retriever thrombectomy in combination with IV t-PA compared with IV t-PA alone for acute ischemic stroke in the UK.

Objective: To evaluate the cost-effectiveness of neurothrombectomy with a stent retriever (Solitaire**Solitaire Revascularization Device is a registered trademark of Medtronic (Irvine, CA). View all notes Revascularization Device) in treating acute ischemic stroke patients from the UK healthcare provider perspective. Methods: A Markov model was developed to simulate health outcomes and costs of two therapies over a lifetime time horizon: stent-retriever thrombectomy in combination with intravenous tissue-type plasminogen activator (IV t-PA), and IV t-PA alone. The model incorporated an acute phase (0–90 days) and a rest of life phase (90+ days). Health states were defined by the modified Rankin Scale score. During the rest of life phase, patients remained in the same health state until a recurrent stroke or death. Clinical effectiveness and safety data were taken from the SWIFT PRIME study. Resource use and health state utilities were informed by published data. Results: Combined stent-retriever thrombectomy and IV t-PA led to improved quality-of-life and increased life expectancy compared to IV t-PA alone. The higher treatment costs associated with the use of stent-retriever thrombectomy were offset by long-term cost savings due to improved patient health status, leading to overall cost savings of £33 190 per patient and a net benefit of £79 402. Deterministic and probabilistic sensitivity analyses demonstrated that the results were robust to a wide range of parameter inputs. Limitations: The acute and long-term costs resource use data were taken from a study based on a patient population that was older and may have had additional comorbidities than the SWIFT PRIME population, resulting in costs that may not be representative of the cohort within this model. In addition, the estimates may not reflect stroke care today as no current evidence is available; however, the cost estimates were deemed reasonable by clinical opinion. Conclusions: Combined stent-retriever neurothrombectomy and IV t-PA is a cost-effective treatment for acute ischemic stroke compared with IV t-PA alone

Lateral Gene Expression in Drosophila Early Embryos Is Supported by Grainyhead-Mediated Activation and Tiers of Dorsally-Localized Repression

The general consensus in the field is that limiting amounts of the transcription factor Dorsal establish dorsal boundaries of genes expressed along the dorsal-ventral (DV) axis of early Drosophila embryos, while repressors establish ventral boundaries. Yet recent studies have provided evidence that repressors act to specify the dorsal boundary of intermediate neuroblasts defective (ind), a gene expressed in a stripe along the DV axis in lateral regions of the embryo. Here we show that a short 12 base pair sequence (“the A-box”) present twice within the ind CRM is both necessary and sufficient to support transcriptional repression in dorsal regions of embryos. To identify binding factors, we conducted affinity chromatography using the A-box element and found a number of DNA-binding proteins and chromatin-associated factors using mass spectroscopy. Only Grainyhead (Grh), a CP2 transcription factor with a unique DNA-binding domain, was found to bind the A-box sequence. Our results suggest that Grh acts as an activator to support expression of ind, which was surprising as we identified this factor using an element that mediates dorsally-localized repression. Grh and Dorsal both contribute to ind transcriptional activation. However, another recent study found that the repressor Capicua (Cic) also binds to the A-box sequence. While Cic was not identified through our A-box affinity chromatography, utilization of the same site, the A-box, by both factors Grh (activator) and Cic (repressor) may also support a “switch-like” response that helps to sharpen the ind dorsal boundary. Furthermore, our results also demonstrate that TGF-β signaling acts to refine ind CRM expression in an A-box independent manner in dorsal-most regions, suggesting that tiers of repression act in dorsal regions of the embryo

The Value of Success: Acquiring Gains, Avoiding Losses, and Simply Being Successful

A large network of spatially contiguous, yet anatomically distinct regions in medial frontal cortex is involved in reward processing. Although it is clear these regions play a role in critical aspects of reward-related learning and decision-making, the individual contributions of each component remains unclear. We explored dissociations in reward processing throughout several key regions in the reward system and aimed to clarify the nature of previously observed outcome-related activity in a portion of anterior medial orbitofrontal cortex (mOFC). Specifically, we tested whether activity in anterior mOFC was related to processing successful actions, such that this region would respond similarly to rewards with and without tangible benefits, or whether this region instead encoded only quantifiable outcome values (e.g., money). Participants performed a task where they encountered monetary gains and losses (and non-gains and non-losses) during fMRI scanning. Critically, in addition to the outcomes with monetary consequences, the task included trials that provided outcomes without tangible benefits (participants were simply told that they were correct or incorrect). We found that anterior mOFC responded to all successful outcomes regardless of whether they carried tangible benefits (monetary gains and non-losses) or not (controls). These results support the hypothesis that anterior mOFC processes rewards in terms of a common currency and is capable of providing reward-based signals for everything we value, whether it be primary or secondary rewards or simply a successful experience without objectively quantifiable benefits

Are you IDDSI ready?

The International Dysphagia Diet Standardisation Initiative (IDDSI) global framework was launched in November 2015. It was subsequently adopted by the Royal College of Speech and Language Therapists and the British Dietetic Association following expert review and professional membership consultation. In the UK, NHS England established an External IDDSI Reference Group comprising of stakeholders including professional, catering, industry and manufacturing representatives. The IDDSI External reference Group have endorsed a UK Aware, Prepare, Adopt model of implementation and all manufacturers and all healthcare settings are anticipated to be fully IDDSI compliant by April 2019. This requires whole system change with a comprehensive training programme. Those providing and delivering food and drink to individuals with swallowing difficulties need to familiarise themselves with food and drink consistencies and their testing methods. Resources are available to assist local healthcare institutions with implementation of the framework at www.rcslt.org / www.bda.org / www.iddsi.org

Does time of surgery influence the rate of false-negative appendectomies?:A retrospective observational study of 274 patients

Background Multiple disciplines have described an “after-hours effect” relating to worsened mortality and morbidity outside regular working hours. This retrospective observational study aimed to evaluate whether diagnostic accuracy of a common surgical condition worsened after regular hours. Methods Electronic operative records for all non-infant patients (age > 4 years) operated on at a single centre for presumed acute appendicitis were retrospectively reviewed over a 56-month period (06/17/2012–02/01/2017). The primary outcome measure of unknown diagnosis was compared between those performed in regular hours (08:00–17:00) or off hours (17:01–07:59). Pre-clinical biochemistry and pre-morbid status were recorded to determine case heterogeneity between the two groups, along with secondary outcomes of length of stay and complication rate. Results Out of 289 procedures, 274 cases were deemed eligible for inclusion. Of the 133 performed in regular hours, 79% were appendicitis, compared to 74% of the 141 procedures performed off hours. The percentage of patients with an unknown diagnosis was 6% in regular hours compared to 15% off hours (RR 2.48; 95% CI 1.14–5.39). This was accompanied by increased numbers of registrars (residents in training) leading procedures off hours (37% compared to 24% in regular hours). Pre-morbid status, biochemistry, length of stay and post-operative complication rate showed no significant difference. Conclusions This retrospective study suggests that the rate of unknown diagnoses for acute appendicitis increases overnight, potentially reflecting increased numbers of unnecessary procedures being performed off hours due to poorer diagnostic accuracy. Reduced levels of staffing, availability of diagnostic modalities and changes to workforce training may explain this, but further prospective work is required. Potential solutions may include protocolizing the management of common acute surgical conditions and making more use of non-resident on call senior colleagues

Mortality following Stroke, the Weekend Effect and Related Factors: Record Linkage Study

Increased mortality following hospitalisation for stroke has been reported from many but not all studies that have investigated a 'weekend effect' for stroke. However, it is not known whether the weekend effect is affected by factors including hospital size, season and patient distance from hospital.To assess changes over time in mortality following hospitalisation for stroke and how any increased mortality for admissions on weekends is related to factors including the size of the hospital, seasonal factors and distance from hospital.A population study using person linked inpatient, mortality and primary care data for stroke from 2004 to 2012. The outcome measures were, firstly, mortality at seven days and secondly, mortality at 30 days and one year.Overall mortality for 37 888 people hospitalised following stroke was 11.6% at seven days, 21.4% at 30 days and 37.7% at one year. Mortality at seven and 30 days fell significantly by 1.7% and 3.1% per annum respectively from 2004 to 2012. When compared with week days, mortality at seven days was increased significantly by 19% for admissions on weekends, although the admission rate was 21% lower on weekends. Although not significant, there were indications of increased mortality at seven days for weekend admissions during winter months (31%), in community (81%) rather than large hospitals (8%) and for patients resident furthest from hospital (32% for distances of >20 kilometres). The weekend effect was significantly increased (by 39%) for strokes of 'unspecified' subtype.Mortality following stroke has fallen over time. Mortality was increased for admissions at weekends, when compared with normal week days, but may be influenced by a higher stroke severity threshold for admission on weekends. Other than for unspecified strokes, we found no significant variation in the weekend effect for hospital size, season and distance from hospital

Obesity promotes 7,12-dimethylbenz(a)anthracene-induced mammary tumor development in female zucker rats

INTRODUCTION: High body mass index has been associated with increased risk for various cancers, including breast cancer. Here we describe studies using 7,12-dimethylbenz(a)anthracene (DMBA) to investigate the role of obesity in DMBA-induced mammary tumor susceptibility in the female Zucker rat (fa/fa), which is the most widely used rat model of genetic obesity. METHOD: Fifty-day-old female obese (n = 25) and lean (n = 28) Zucker rats were orally gavaged with 65 mg/kg DMBA. Rats were weighed and palpated twice weekly for detection of mammary tumors. Rats were killed 139 days after DMBA treatment. RESULTS: The first mammary tumor was detected in the obese group at 49 days after DMBA treatment, as compared with 86 days in the lean group (P < 0.001). The median tumor-free time was significantly lower in the obese group (P < 0.001). Using the days after DMBA treatment at which 25% of the rats had developed mammary tumors as the marker of tumor latency, the obese group had a significantly shorter latency period (66 days) than did the lean group (118 days). At the end of the study, obese rats had developed a significantly (P < 0.001) greater mammary tumor incidence (68% versus 32%) compared with the lean group. The tumor histology of the mammary tumors revealed that obesity was associated with a significant (P < 0.05) increase in the number of rats with at least one invasive ductal and lobular carcinoma compared with lean rats. CONCLUSION: Our results indicate that obesity increases the susceptibility of female Zucker rats to DMBA-induced mammary tumors, further supporting the hypothesis that obesity and some of its mediators play a significant role in carcinogenesis