Urinary incontinence indicates mortality, disability, and infections in hospitalised stroke patients.

OBJECTIVES: To assess the impact of urinary incontinence (UI) on health outcomes over the entire spectrum of acute stroke severity (National Institutes of Health Stroke Scale [NIHSS] scores: 0-42), due to a paucity of data on patients with milder strokes. PATIENTS AND METHODS: Data were prospectively collected (2014-2016) from the Sentinel Stroke National Audit Programme (1593 men, 1591 women; mean [SD] age 76.8 [13.3] years) admitted to four UK hyperacute stroke units (HASUs). Relationships between variables were assessed by multivariable logistic regression. Data were adjusted for age, sex, comorbidities, pre-stroke disability and intra-cranial haemorrhage, and presented as odds ratios with 95% confidence intervals. RESULTS: Amongst patients with no symptoms or a minor stroke (NIHSS scores of 0-4), compared to patients without UI, patients with UI had significantly greater risks of poor outcomes including: in-hospital mortality; disability at discharge; in-hospital pneumonia; urinary tract infection within 7 days of admission; prolonged length of stay on the HASU; palliative care by discharge; activity of daily living (ADL) support, and new discharge to care home. In patients with more moderate stroke (NIHSS score of 5-15) the same outcomes were identified; being at greater risk for patients with UI, except for palliative care by discharge and ADL support. With the highest stroke severity group (NIHSS score of 16-48) all outcomes were identified except in-patient mortality, pneumonia, and ADL support. However, odds ratios diminished as NIHSS scores increased. CONCLUSIONS: Urinary incontinence is a useful indicator of poor short-term outcomes in older patients with an acute stroke, but irrespective of stroke severity. This provides valuable information to healthcare professionals to identify at-risk individuals.

Sex-specific independent risk factors of urinary incontinence in acute stroke patients: A multicentre registry-based cohort study.

BACKGROUND: The presence of urinary incontinence (UI) in acute stroke patients indicates poor outcomes in men and women. However, there is a paucity and inconsistency of data on UI risk factors in this group and hence we conducted a sex-specific analysis to identify risk factors. METHODS: Data were collected prospectively (2014-2016) from the Sentinel Stroke National Audit Program for patients admitted to four UK hyperacute stroke units. Relevant risk factors for UI were determined by stepwise multivariable logistic regression, presented as odds ratios (OR) and 95% confidence intervals (CI). RESULTS: The mean (±SD) age of UI onset in men (73.9 year ± 13.1; n = 1593) was significantly earlier than for women (79.8 year ± 12.9; n = 1591: p < 0.001). Older age between 70 and 79 year in men (OR = 1.61: CI = 1.24-2.10) and women (OR = 1.55: CI = 1.12-2.15), or ≥80 year in men (OR = 2.19: CI = 1.71-2.81), and women (OR = 2.07: CI = 1.57-2.74)-reference: <70 year-both predicted UI. In addition, intracranial hemorrhage (reference: acute ischemic stroke) in men (OR = 1.64: CI = 1.22-2.20) and women (OR = 1.75: CI = 1.30-2.34); and prestroke disability (mRS scores ≥ 4) in men (OR = 1.90: CI = 1.02-3.5) and women (OR = 1.62: CI = 1.05-2.49) (reference: mRS scores < 4); and stroke severity at admission: NIHSS scores = 5-15 in men (OR = 1.50: CI = 1.20-1.88) and women (OR = 1.72: CI = 1.37-2.16), and NIHSS scores = 16-42 in men (OR = 4.68: CI = 3.20-6.85) and women (OR = 3.89: CI = 2.82-5.37) (reference: NIHSS scores = 0-4) were also significant. Factors not selected were: a history of congestive heart failure, hypertension, atrial fibrillation, diabetes and previous stroke. CONCLUSIONS: We have identified similar risk factors for UI after stroke in men and women including age >70 year, intracranial hemorrhage, prestroke disability and stroke severity.

Impact of the COVID-19 pandemic on care-quality outcomes in older adults admitted to hospital with altered mental status.

OBJECTIVES: During the coronavirus disease (COVID-19) pandemic, patients with altered mental status (AMS: dementia, delirium and delirium superimposed on dementia) were profoundly affected by an abrupt transformation in healthcare systems. Here, we evaluated quality-care outcomes, including length of stay (LOS), in-hospital mortality, early readmission and mortality after hospital discharge, in older adults admitted for AMS during the pandemic and compared them to patients admitted prior to the pandemic. METHODS: Chi-squared and Fisher's exact tests were used to examine changes to admissions for AMS before and during the pandemic, and their outcomes. Logistic regression analyses, with reference to pre-pandemic data, were conducted to examine the impact of the pandemic on outcomes. DESIGN: Prospective data of 21,192 non-COVID admissions to an acute general medical department in a Surrey (UK) hospital were collected from patients admitted before (1st April 2019 to 29th February 2020) and during the pandemic (1st March 2020 to 31st March 2021). RESULTS: There were 10,173 (47.7% men) from the pre-pandemic and 11,019 (47.5% men) from the pandemic periods; overall mean age  =  68.3yr. During the pandemic AMS patients had significantly higher admission rates (1.1% vs 0.6%, P < 0.001). However, median LOS in hospital was shorter (9.0 days [IQR = 5.3-16.2] vs 15.5 days [IQR  =  6.2-25.7], P < 0.001) and thus were less likely to stay in hospital >3 weeks: adjusted OR  =  0.26 (95%CI  =  0.12-0.57). In-hospital mortality and readmission within 28 days of discharge did not change during the pandemic, but were less likely to die within 30 days of discharge: adjusted OR = 0.32 (95%CI = 0.11-0.96). CONCLUSIONS: This combination of higher admission rate, shorter LOS, and an unchanging early readmission suggests a higher admission-discharge turnover of different patients with AMS and provides important insights into the potential impact of the COVID-19 pandemic on healthcare delivery to individuals with AMS.

Benign prostatic hyperplasia/obstruction ameliorated using a soluble guanylate cyclase activator.

Benign prostatic hyperplasia (BPH) is a feature of ageing males. Up to half demonstrate bladder outlet obstruction (BOO) with associated lower urinary tract symptoms (LUTS) including bladder overactivity. Current therapies to reduce obstruction, such as α1-adrenoceptor antagonists and 5α-reductase inhibitors, are not effective in all patients. The phosphodiesterase-5 inhibitor (PDE5I) tadalafil is also approved to treat BPH and LUTS, suggesting a role for nitric oxide (NO• ), soluble guanylate cyclase (sGC), and cGMP signalling pathways. However, PDE5I refractoriness can develop for reasons including nitrergic nerve damage and decreased NO• production, or inflammation-related oxidation of the sGC haem group, normally maintained in a reduced state by the cofactor cytochrome-b5-reductase 3 (CYB5R3). sGC activators, such as cinaciguat (BAY 58-2667), have been developed to enhance sGC activity in the absence of NO• or when sGC is oxidised. Accordingly, their effects on the prostate and LUT function of aged mice were evaluated. Aged mice (≥24 months) demonstrated a functional BPH/BOO phenotype, compared with adult animals (2-12 months), with low, delayed voiding responses and elevated intravesical pressures as measured by telemetric cystometry. This was consistent with outflow tract histological and molecular data that showed urethral constriction, increased prostate weight, greater collagen deposition, and cellular hyperplasia. All changes in aged animals were attenuated by daily oral treatment with cinaciguat for 2 weeks, without effect on serum testosterone levels. Cinaciguat had only transient (1 h) cardiovascular effects with oral gavage, suggesting a positive safety profile. The benefit of cinaciguat was suggested by its reversal of an overactive cystometric profile in CYB5R3 smooth muscle knockout mice that mirrors a profile of oxidative dysfunction where PDE5I may not be effective. Thus, the aged male mouse is a suitable model for BPH-induced BOO and cinaciguat has a demonstrated ability to reduce prostate-induced obstruction and consequent effects on bladder function. © 2021 The Pathological Society of Great Britain and Ireland.

Nitric oxide signaling pathways in the normal and pathological bladder: Do they provide new pharmacological pathways?-ICI-RS 2023.

AIMS: The nitric oxide (NO•)/soluble guanylate cyclase/cyclic-GMP (cGMP) signaling pathway is ubiquitous and regulates several functions in physiological systems as diverse as the vascular, nervous, and renal systems. However, its roles in determining normal and abnormal lower urinary tract functions are unclear. The aim was to identify potential therapeutic targets associated with this pathway to manage lower urinary tract functional disorders. METHODS: This review summarizes a workshop held under the auspices of ICI-RS with a view to address these questions. RESULTS: Four areas were addressed: NO• signaling to regulate neurotransmitter release to detrusor smooth muscle; its potential dual roles in alleviating and exacerbating inflammatory pathways; its ability to act as an antifibrotic mediator; and the control by nitrergic nerves of lower urinary tract vascular dynamics and the contractile performance of muscular regions of the bladder wall. Central to much of the discussion was the role of the NO• receptor, soluble guanylate cyclase (sGC) in regulating the generation of the enzyme product, the second messenger cGMP. The redox state of sGC is crucial in determining its enzymic activity and the role of a class of novel agents, sGC activators, to optimize activity and to potentially alleviate the consequences of lower urinary tract disorders was highlighted. In addition, the consequences of a functional relationship between nitrergic and sympathetic nerves to regulate vascular dynamics was discussed. CONCLUSIONS: Several potential NO•-dependent drug targets in the lower urinary tract were identified that provide the basis for future research and translation to clinical trials.

How does the lower urinary tract contribute to bladder sensation? ICI-RS 2023.

AIM: Bladder sensation is critical for coordinating voluntary micturition to maintain healthy bladder function. Sensations are initiated by the activation of sensory afferents that innervate throughout the bladder wall. However, the physiological complexity that underlies the initiation of bladder sensory signaling in health and disease remains poorly understood. This review summarises the latest knowledge of the mechanisms underlying the generation of bladder sensation and identifies key areas for future research. METHODS: Experts in bladder sensory signaling reviewed the literature on how the lower urinary tract contributes to bladder sensation and identified key research areas for discussion at the 10th International Consultation on Incontinence-Research Society. RESULTS: The importance of bladder sensory signals in maintaining healthy bladder function is well established. However, better therapeutic management of bladder disorders with exaggerated bladder sensation, including overactive bladder syndrome (OAB) and interstitial cystitis/bladder pain syndrome (IC/BPS) is limited by a lack of knowledge in a number of key research areas including; the contribution of different nerves (pudendal, pelvic, hypogastric) to filling sensations in health and disease; the relative contribution of stretch sensitive (muscular) and stretch-insensitive (mucosal) afferents to bladder sensation in health and disease; the direct and indirect contributions of the muscularis mucosae to bladder contraction and sensation; and the impact of manipulating urothelial release factors on bladder sensation. CONCLUSION: Disturbances in bladder sensory signaling can have severe consequences for bladder sensation and function including the development of OAB and IC/BPS. Advancing therapeutic treatments for OAB and IC/BPS requires a deeper understanding of the mechanisms underlying the generation of bladder sensation, and key areas for future research have been identified.

Adverse stroke outcomes amongst UK ethnic minorities: a multi-centre registry-based cohort study of acute stroke.

OBJECTIVE: Socioeconomic and health inequalities persist in multicultural western countries. Here, we compared outcomes following an acute stroke amongst ethnic minorities with Caucasian patients. METHODS: Data were prospectively collected (2014-2016) from the Sentinel Stroke National Audit Programme for 3309 patients who were admitted with an acute stroke in four UK hyperacute stroke units. Associations between variables were examined by chi-squared tests and multivariable logistic regression, adjusted for age, sex, prestroke functional limitations and co-morbidities, presented as odds ratios (OR) with 95% CI. RESULTS: There were 3046 Caucasian patients, 95 from ethnic minorities (mostly South Asians, Blacks, mixed race and a few in other ethnic groups) and 168 not stated. Compared with Caucasian patients, those from ethnic minorities had a proportionately higher history of diabetes (33.7% vs 15.4%, P < 0.001), but did not differ in other chronic conditions, functional limitations or sex distribution. Their age of stroke onset was younger both in women (76.8 year vs 83.2 year, P < 0.001) and in men (69.5 year vs 75.9 year, P = 0.002). They had greater risk for having a stroke before the median age of 79.5 year: OR = 2.15 (1.36-3.40) or in the first age quartile (< 69 year): OR = 2.91 (1.86-4.54), requiring palliative care within the first 72 h: OR = 3.88 (1.92-7.83), nosocomial pneumonia or urinary tract infection within the first 7 days of admission: OR = 1.86 (1.06-3.28), and in-hospital mortality: OR = 2.50 (1.41-4.44). CONCLUSIONS: Compared with Caucasian patients, those from ethnic minorities had earlier onset of an acute stroke by about 5 years and a 2- to fourfold increase in many stroke-related adverse outcomes and death.

Evaluation of independent risk factors associated with surgical site infections from caesarean section.

BACKGROUND: The present study assessed factors associated with the risk of surgical site infections (SSI) after a caesarean section (C-section). METHODS: Data were collected in 1682 women undergoing elective (53.9%) and emergency (46.1%) C-sections between 1st August 2020, and 30th December 2021, at a National Health Service hospital (Surrey, UK). RESULTS: At the time of C-section, the mean age was 33.1 yr (SD ± 5.2). Compared to women with BMI < 30 kg/m2, those with a BMI ≥ 35 kg/m2 had a greater risk of SSI, OR 4.07 (95%CI 2.48-6.69). Women with a history of smoking had a greater risk of SSI than those who had never smoked, OR 1.69 (95%CI 1.05-2.27). Women with a BMI ≥ 30 kg/m2 and had a smoking history or emergency C-section had 3- to tenfold increases for these adverse outcomes. Ethnic minority, diabetes or previous C-section did not associate with any of the outcomes. CONCLUSIONS: High BMI, smoking, and emergency C-section are independent risk factors for SSI from C-section. Women planning conception should avoid excess body weight and smoking. Women with diabetes and from ethnic minority backgrounds did not have increased risks of SSI, indicating a consistent standard of care for all patients.

Determination of independent risk factors for early healthcare-associated infections acquired after acute stroke admission: A multi-centre registry-based cohort study.

OBJECTIVE: Healthcare-associated infections (HCAIs) in patients admitted with acute conditions pose a serious risk to patients and a major challenge to healthcare services. However, there is a lack of consistency in reporting aetiological risk factors, particularly in acute stroke patients. Here, we determined independent risk factors of two common HCAIs (urinary tract infection and pneumonia) acquired within 7-days of admission after an acute stroke. METHODS: Data were prospectively collected (2014-2016) from the Sentinel Stroke National Audit Programme for 3,309 patients (mean age=76.2yr, SD=13.5) admitted to four UK hyperacute stroke units. Associations between variables were assessed by forward stepwise multivariable logistic regression (odds ratios, 95 % confidence intervals). RESULTS: The rate of urinary tract infection and/or pneumonia occurring within 7-days of admission was 15.0 %. The risk of urinary tract infection and/or pneumonia was increased amongst women: OR = 1.35 (1.08-1.68); patients from ethnic minority backgrounds: OR = 1.77 (1.01-3.10); patients aged 70-79 years: OR = 2.08 (1.42-3.06), and ≥80 years: OR = 3.20 (2.26-4.55); history of hypertension: OR = 1.59 (1.27-1.98); history of atrial fibrillation: OR = 1.67 (1.32-2.12); pre-stroke disability: OR = 2.08 (1.44-3.00); intracranial haemorrhage: OR = 1.41 (1.07-1.86); severe stroke: OR = 3.21 (2.32-4.45); swallow screening within 4-72 h: OR = 1.42 (1.08-1.86); swallow screening beyond 72 h: OR = 1.70 (1.08-2.70). History of congestive heart failure, diabetes and previous stroke did not significantly associate with HCAIs. CONCLUSIONS: A profile of independent risk factors for two common HCAIs in acute stroke was identified. These findings provide valuable information for timely intervention to reduce HCAIs, and the ability to minimise subsequent adverse outcomes.

Selective reduction of neurotransmitter release by cAMP-dependent pathways in mouse detrusor.

Parasympathetic nerve-mediated contractions of detrusor smooth muscle are generated by ATP and acetylcholine (ACh) release from efferent nerve terminals. In humans, ACh is responsible for detrusor contractions in normal human bladders, whereas ATP has an additional role in overactive bladder pathologies. The ATP metabolite, adenosine, relaxes nerve-mediated contractions, with a potential action via presynaptic adenosine A1 receptor activation and subsequent suppression of neuronal ATP release. We investigated the effect of A1 receptor activation and downstream cAMP-dependent pathways on nerve-mediated ATP and ACh release, and detrusor contraction in mouse detrusor. Bladders from male C57BL/6 mice (12 wk) were used for in vitro experiments. Upon electrical field stimulation of intact preparations (detrusor and mucosal layers), ATP or ACh release was measured simultaneously with tension recordings. Activation of A1 receptors by adenosine or exogenous agonists reduced the lower frequency component of nerve-mediated contractions and neuronal ATP release. The A1 receptor antagonist abolished these effects. A1 receptor activation inhibits adenylyl cyclase (AC) activity and cAMP generation. The effect of A1 receptor activation was mimicked by a PKA antagonist but not by modulators of exchange proteins activated by cAMP, demonstrating that modulation of nerve-mediated ATP release is via PKA. Adenosine had no effect on ACh release or the higher frequency component of nerve-mediated contractions. Differential regulation of neurotransmitter release is possible at the detrusor nerve-muscle junction, as demonstrated by A1 receptor activation, and downstream inhibition of AC, cAMP generation, and PKA. The ability to specifically attenuate ATP release offers a potential to target purinergic motor pathways enhanced in overactive bladder pathologies.

Changes in Characteristics and Outcomes of Patients Undergoing Surgery for Hip Fractures Following the Initiation of Orthogeriatric Service: Temporal Trend Analysis.

The Blue Book published by the British Orthopaedic Association and British Geriatrics Society, together with the introduction of National Hip Fracture Database Audit and Best Practice Tariff, have been influential in improving hip fracture care. We examined ten-year (2009-2019) changes in hip fracture outcomes after establishing an orthogeriatric service based on these initiatives, in 1081 men and 2891 women (mean age = 83.5 ± 9.1 years). Temporal trends in the annual percentage change (APC) of outcomes were identified using the Joinpoint Regression Program v4.7.0.0. The proportions of patients operated beyond 36 h of admission fell sharply during the first two years: APC = - 53.7% (95% CI - 68.3, - 5.2, P = 0.003), followed by a small rise thereafter: APC = 5.8% (95% CI 0.5, 11.3, P = 0.036). Hip surgery increased progressively in patients > 90 years old: APC = 3.3 (95% CI 1.0, 5.8, P = 0.011) and those with American Society of Anaesthesiologists grade ≥ 3: APC = 12.4 (95% CI 8.8, 16.1, P < 0.001). There was a significant decline in pressure ulcers amongst patients < 90 years old: APC = - 17.9 (95% CI - 32.7, 0.0, P = 0.050) and also a significant decline in mortality amongst those > 90 years old: APC = - 7.1 (95% CI - 12.6, - 1.3, P = 0.024). Prolonged length of stay (> 23 days) declined from 2013: APC = - 24.6% (95% CI - 31.2, - 17.4, P < 0.001). New discharge to nursing care declined moderately over 2009-2016 (APC = - 10.6, 95% CI - 17.2, - 2.7, P = 0.017) and sharply thereafter (APC = - 47.5%, 95%CI - 71.7, - 2.7, P = 0.043). The rate of patients returning home was decreasing (APC = - 2.9, 95% CI - 5.1, - 0.7, P = 0.016), whilst new discharge to rehabilitation was increasing (APC = 8.4, 95% CI 4.0, 13.0; P = 0.002). In conclusion, the establishment of an orthogeriatric service was associated with a reduction of elapsed time to hip surgery, a progressive increase in surgery carried out on high-risk adults and a decline in adverse outcomes.

Frequency-dependent characteristics of nerve-mediated ATP and acetylcholine release from detrusor smooth muscle.

NEW FINDINGS: What is the central question of this study? Is the frequency dependence of co-transmitter release from postganglionic nerve fibres different for each transmitter? What is the main finding and its importance? Release of co-transmitters from the parasympathetic supply to detrusor smooth muscle can be independently regulated. This offers a targeted drug model to reduce selectively the release of transmitter associated with human pathologies (ATP) and may also be applicable to other smooth muscle-based disorders of visceral tissues. ABSTRACT: Nerve-mediated contractions of detrusor smooth muscle are mediated by acetylcholine (ACh) and ATP release in most animals. However, with the normal human bladder, only ACh is a functional transmitter, but in benign pathologies such as overactive bladder (OAB), ATP re-emerges as a secondary transmitter. The selective regulation of ATP release offers a therapeutic approach to manage OAB, in contrast to current primary strategies that target ACh actions. However, the release characteristics of nerve-mediated ACh and ATP are poorly defined and this study aimed to measure the frequency dependence of ACh and ATP release and determine if selective regulation of ATP or ACh was possible. Experiments were carried out in vitro with mouse detrusor with nerve-mediated ATP and ACh release measured simultaneously with tension recording. ATP was released in two frequency-dependent components, both at lower frequencies (mid-range 0.4 and 5.5 Hz stimulation) compared to a single compartment release of ACh at 14 Hz. Intervention with the phosphodiesterase type-5 inhibitor sildenafil attenuated ATP release, equally from both components, but had no effect on ACh release. These data demonstrate that nerve-mediated ACh and ATP release characteristics are distinct and may be separately manipulated. This offers a potential targeted drug model to manage benign lower urinary tract conditions such as OAB.

Adverse consequences of immediate thrombolysis-related complications: a multi-centre registry-based cohort study of acute stroke.

Complications following thrombolysis for stroke are well documented, and mostly concentrated on haemorrhage. However, the consequences of patients who experience any immediate thrombolysis-related complications (TRC) compared to patients without immediate TRC have not been examined. Prospectively collected data from the Sentinel Stroke National Audit Programme were analysed. Thrombolysis was performed in 451 patients (52.1% men; 75.3 years ± 13.2) admitted with acute ischaemic stroke (AIS) in four UK centres between 2014 and 2016. Adverse consequences following immediate TRC were assessed using logistic regression, adjusted for age, sex and co-morbidities. Twenty-nine patients (6.4%) acquired immediate TRC. Compared to patients without, individuals with immediate TRC had greater adjusted risks of: moderately-severe or severe stroke (National Institutes of Health for Stroke Scale score ≥ 16) at 24-h (5.7% vs 24.7%, OR 3.9, 95% CI 1.4-11.1); worst level of consciousness (LOC) in the first 7 days (score ≥ 1; 25.0 vs 60.7, OR 4.6, 95% CI 2.1-10.2); urinary tract infection or pneumonia within 7-days of admission (13.5% vs 39.3%, OR 3.2, 95% CI 1.3-7.7); length of stay (LOS) on hyperacute stroke unit (HASU) ≥ 2 weeks (34.7% vs 66.7%, OR 5.2, 95% CI 1.5-18.4); mortality (13.0% vs 41.4%, OR 3.7, 95% CI 1.6-8.4); moderately-severe or severe disability (modified Rankin Scale score ≥ 4) at discharge (26.8% vs 65.5%, OR 4.7, 95% CI 2.1-10.9); palliative care by discharge date (5.1% vs 24.1%, OR 5.1, 95% CI 1.7-15.7). The median LOS on the HASU was longer (7 days vs 30 days, Kruskal-Wallis test: χ2 = 8.9, p = 0.003) while stroke severity did not improve (NIHSS score at 24-h post-thrombolysis minus NIHSS score at arrival = - 4 vs 0, χ2 = 24.3, p < 0.001). In conclusion, the risk of nosocomial infections, worsening of stroke severity, longer HASU stay, disability and death is increased following immediate TRC. The management of patients following immediate TRC is more complex than previously thought and such complexity needs to be considered when planning an increased thrombolysis service.

Comparison of characteristics, management and outcomes in hospital-onset and community-onset stroke: a multi-centre registry-based cohort study of acute stroke.

OBJECTIVE: Hospital-onset stroke (HOS) is associated with poorer outcomes than community-onset stroke (COS). Previous studies have variably documented patient characteristics and outcome measures; here, we compare in detail characteristics, management and outcomes of HOS and COS. METHODS: A total of 1656 men (mean age ± SD = 73.1 years ± 13.2) and 1653 women (79.3 years ± 13.0), with data prospectively collected (2014-2016) from the Sentinel Stroke National Audit Programme, were admitted with acute stroke in four UK hyperacute stroke units (HASU). Associations between variables were examined by chi-squared tests and multivariable logistic regression (COS as reference). RESULTS: There were 272 HOS and 3037 COS patients with mean ages of 80.2 years ± 12.5 and 76.4 years ± SD13.5 and equal sex distribution. Compared to COS, HOS had higher proportions ≥ 80 years (64.0% vs 46.4%), congestive heart failure (16.9% vs 4.9%), atrial fibrillation (25.0% vs 19.7%) and pre-stroke disability (9.6% vs 5.1%), and similar history of stroke, hypertension, diabetes, stroke type and severity of stroke. After age, sex and co-morbidities adjustments, HOS had greater risk of pneumonia: OR (95%CI) = 1.9 (1.3-2.6); malnutrition: OR = 2.2 (1.7-2.9); immediate thrombolysis complications: OR = 5.3 (1.5-18.2); length of stay on HASU > 3 weeks: OR = 2.5 (1.8-3.4); post-stroke disability: OR = 1.8 (1.4-2.4); and in-hospital mortality: OR = 1.8 (1.2-2.4), as well as greater support at discharge including palliative care: OR = 1.9 (1.3-2.8); nursing care: OR = 2.0 (1.3-4.0), help for daily living activities: OR = 1.6 (1.1-2.2); and joint-care planning: OR = 1.5 (1.1-1.9). CONCLUSIONS: This detailed analysis of underlying differences in subject characteristics between patients with HOS or COS and adverse consequences provides further insights into understanding poorer outcomes associated with HOS.

Evaluation of the association of length of stay in hospital and outcomes.

BACKGROUND: There exist wide variations in healthcare quality within the National Health Service (NHS). A shorter hospital length of stay (LOS) has been implicated as premature discharge, that may in turn lead to adverse consequences. We tested the hypothesis that a short LOS might be associated with increased risk of readmissions within 28 days of hospital discharge and also post-discharge mortality. METHODS: We conducted a single-centred study of 32 270 (46.1% men) consecutive alive-discharge episodes (mean age = 64.0 years, standard deviation = 20.5, range = 18-107 years), collected between 01/04/2017 and 31/03/2019. Associations of LOS tertiles (middle tertile as a reference) with readmissions and mortality were assessed using observed/expected ratios, and logistic and Cox regressions to estimate odds (OR) and hazard ratios (HR) (adjusted for age, sex, patients' severity of underlying health status and index admissions), with 95% confidence intervals (CIs). RESULTS: The observed numbers of readmissions within 28 days of hospital discharge or post-discharge mortality were lower than expected (observed: expected ratio < 1) in patients in the bottom tertile (<1.2 days) and middle tertile (1.2-4.3 days) of LOS, whilst higher than expected (observed: expected ratio > 1) in patients in the top tertile (>4.3 days), amongst all ages. Patients in the top tertile of LOS had increased risks for one readmission: OR = 2.32 (95% CI = 1.86-2.88) or ≥2 readmissions: OR = 6.17 (95% CI = 5.11-7.45), death within 30 days: OR = 2.87 (95% CI = 2.34-3.51), and within six months of discharge: OR = 2.52 (95% CI = 2.23-2.85), and death over a two-year period: HR = 2.25 (95% CI = 2.05-2.47). The LOS explained 7.4% and 15.9% of the total variance (r2) in one readmission and ≥2 readmissions, and 9.1% and 10.0% of the total variance in mortality with 30 days and within six months of hospital discharge, respectively. Within the bottom, middle and top tertiles of the initial LOS, the median duration from hospital discharge to death progressively shortened from 136, 126 to 80 days, whilst LOS during readmission lengthened from 0.4, 0.9 to 2.8 days, respectively. CONCLUSION: Short LOS in hospital was associated with favourable post-discharge outcomes such as early readmission and mortality, and with a delay in time interval from discharge to death and shorter LOS in hospital during readmission. These findings indicate that timely discharge from our hospital meets the aims of the NHS-generated national improvement programme, Getting It Right First Time.

Predicting Stroke Complications in Hospital and Functional Status at Discharge by Clustering of Cardiovascular Diseases a Multi-Centre Registry-Based Study of Acute Stroke.

OBJECTIVE: Indicators for outcomes following acute stroke are lacking. We have developed novel evidence-based criteria for identifying outcomes of acute stroke using the presence of clusters of coexisting cardiovascular disease (CVD). MATERIALS AND METHODS: Analysis of prospectively collected data from the Sentinel Stroke National Audit Programme (SSNAP). A total of 1656 men (mean age ±SD=73.1yrs±13.2) and 1653 women (79.3yrs±13.0) were admitted with acute stroke (83.3% ischaemic, 15.7% intracranial haemorrhagic), 1.0% unspecified) in four major UK hyperacute stroke units (HASU) between 2014 and 2016. Four categories from cardiovascular disease Congestive heart failure, Atrial fibrillation, pre-existing Stroke and Hypertension (CASH).were constructed: CASH-0 (no coexisting CVD); CASH-1 (any one coexisting CVD); CASH-2 (any two coexisting CVD); CASH-3 (any three or all four coexisting CVD). These were tested against outcomes, adjusted for age and sex. RESULTS: Compared to CASH-0, individuals with CASH-3 had greatest risks of in-hospital mortality (11.1% vs 24.5%, OR=1.8, 95%CI=1.3-2.7) and disability (modified Rankin Scale score ≥4) at discharge (24.2% vs 46.2%, OR=1.9, 95%CI=1.4-2.7), urinary tract infection (3.8% vs 14.6%, OR= 3.3, 95%CI= 1.9-5.5), and pneumonia (7.1% vs 20.6%, OR= 2.6, 95%CI= 1.7-4.0); length of stay on HASU >14 days (29.8% vs 39.3%, OR=1.8, 95%CI=1.3-2.6); and joint-care planning (20.9% vs 29.8%, OR=1.4, 95%CI=1.0-2.0). CONCLUSIONS: We present a simple tool for estimating the risk of adverse outcomes of acute stroke including death, disability at discharge, nosocomial infections, prolonged length of stay, as well as any joint care planning. CASH-0 indicates a low level and CASH-3 indicates a high level of risk of such complications after stroke.

Changes in cortisol levels by continuous positive airway pressure in patients with obstructive sleep apnoea: Meta-analysis of 637 individuals.

BACKGROUND: Obesity, obstructive sleep apnoea (OSA) and hypertension frequently coexist and are associated with elevated cortisol levels. Identification and treatment of such patients is important when investigating for suspected Cushing's syndrome and hypertension. Studies of the impact of continuous positive airway pressure (CPAP) on cortisol and blood pressure are limited by the small sample size and show conflicting findings. We conducted a meta-analysis to document changes in the levels of cortisol and blood pressure in response to CPAP treatment of OSA. METHODS: Meta-analysis was conducted using RevMan (v5.3) and expressed in standardized mean difference (SMD) for catecholamines and mean difference for systolic (SBP) and diastolic blood pressure (DBP). The quality of the studies was evaluated using standard tools for assessing the risk of bias. RESULTS: A total of 22 studies met our search criteria; they consisted of 16 prospective cohort studies (PCS) that recruited 385 participants and six randomized control trials (RCT) totalling 252 participants. The range of mean age was 41-62 years and BMI 27.2-35.1 kg/m2 . CPAP treatment reduced plasma cortisol levels in PCS: SMD = -0.28 [95% confidence interval (95% CI) = -0.45 to -0.12], I2 = 0%, p = .79 and in RCT: SMD = -0.39 (95% CI = -0.75 to -0.03), I2 = 28.3%, p = .25. CPAP treatment reduced SBP by 5.4 mmHg (95% CI = 1.7-9.1) and DBP by 3.3 mmHg (95% CI = 1.0-5.7). Interstudy heterogeneity was low for all studies. Bias in most RCT arose from the lack of blinding of participants and personnel. CONCLUSION: CPAP treatment in individuals with OSA reduces cortisol levels and blood pressure.

Validity of the LACE index for identifying frequent early readmissions after hospital discharge in children.

The LACE index scoring tool has been designed to predict hospital readmissions in adults. We aimed to evaluate the ability of the LACE index to identify children at risk of frequent readmissions. We analysed data from alive-discharge episodes (1 April 2017 to 31 March 2019) for 6546 males and 5875 females from birth to 18 years. The LACE index predicted frequent all-cause readmissions within 28 days of hospital discharge with high accuracy: the area under the curve = 86.9% (95% confidence interval = 84.3-89.5%, p < 0.001). Two-graph receiver operating characteristic curve analysis revealed the LACE index cutoff to be 4.3, where sensitivity equals specificity, to predict frequent readmissions. Compared with those with a LACE index score = 0-4 (event rates, 0.3%), those with a score > 4 (event rates, 3.7%) were at increased risk of frequent readmissions: age- and sex-adjusted odds ratio = 12.4 (95% confidence interval = 8.0-19.2, p < 0.001) and death within 30 days of discharge: OR = 5.0 (95% CI = 1.5-16.7). The ORs for frequent readmissions were between 6 and 14 for children of different age categories (neonate, infant, young child and adolescent), except for patients in the child category (6-12 years) where odds ratio was 2.8.Conclusion: The LACE index can be used in healthcare services to identify children at risk of frequent readmissions. Focus should be directed at individuals with a LACE index score above 4 to help reduce risk of readmissions. What is Known: • The LACE index scoring tool has been widely used to predict hospital readmissions in adults. What is New: • Compared with children with a LACE index score of 0-4 (event rates, 0.3%), those with a score > 4 are at increased risk of frequent readmissions by 14-fold. • The cutoff of a LACE index of 4 may be a useful level to identify children at increased risk of frequent readmissions.

LACE index predicts age-specific unplanned readmissions and mortality after hospital discharge.

BACKGROUND: The LACE index scoring tool (Length of stay, Acuity of admission, Co-morbidities and Emergency department visits) has been designed to predict hospital readmissions. We evaluated the ability of the LACE index to predict age-specific frequent admissions and mortality. METHODS: Analysis of prospectively collected data of alive-discharge episodes between 01/04/2017 and 31/03/2019 in an NHS hospital. Data on 14,878 men and 17,392 women of mean age 64.0 years, SD = 20.5, range 18.0-106.7 years were analysed. The association of the LACE index with frequency of all-cause readmissions within 28 days of discharge and over a 2-year period, and with all-cause mortality within 30 days or within 6 months after discharge from hospital were evaluated. RESULTS: Within LACE index scores of 0-4, 5-9 or ≥ 10, the proportions of readmission ≥ 2 times within 28 days of discharge were 0.1, 1.3 and 9.2% (χ2 = 3070, p < 0.001) and over a 2-year period were 1.7, 4.8 and 19.1% (χ2 = 3364, p < 0.001). Compared with a LACE index score of 0-4, a score ≥ 10 increased the risk (adjusted for age, sex and frequency of admissions) of death within 6 months of discharge by 6.8-fold (5.1-9.0, p < 0.001) among all ages, and most strongly in youngest individuals (18.0-49.9 years): adjusted odds ratio = 16.1 (5.7-45.8, p < 0.001). For those aged 50-59.9, 60-69.9, 70-79.9 and ≥ 80 years, odds ratios reduced progressively to 9.6, 7.7, 5.1 and 2.3, respectively. Similar patterns were observed for the association of LACE index with mortality within 30 days of hospital discharge. CONCLUSIONS: The LACE index predicts short-term and long-term frequent admissions and short-term and medium-term mortality, most pronounced among younger individuals, after hospital discharge.

Prestroke Disability Predicts Adverse Poststroke Outcome: A Registry-Based Prospective Cohort Study of Acute Stroke.

Background and Purpose- Information on what effect disability before stroke can have on stroke outcome is lacking. We assessed prestroke disability in relation to poststroke hospital outcome. Methods- Analysis of prospectively collected data from the Sentinel Stroke National Audit Programme. A total of 1656 men (mean age ±SD =73.1±13.2 years) and 1653 women (79.3±13.0 years) were admitted to hyperacute stroke units with acute stroke in 4 major UK between 2014 and 2016. Prestroke disability, assessed by modified Rankin Scale (mRS), was tested against poststroke adverse outcomes, adjusted for age, sex, and coexisting morbidities. Results- Compared with patients with prestroke mRS score =0, individuals with prestroke mRS scores =3, 4, or 5 had greater adjusted risks of moderately severe or severe stroke on arrival (4.4% versus 16.7%; odds ratio [OR], 3.2 [95% CI, 2.3-4.6] P<0.001); urinary tract infection or pneumonia within 7 days of admission (9.6% versus 35.9%; OR, 3.7 [95% CI, 2.8-4.8] P<0.001); mortality (7.2% versus 37.1%; OR, 4.9 [95% CI, 3.7-6.5] P<0.001); requiring help with activities of daily living on discharge (12.3% versus 26.7%; OR, 3.1 [95% CI, 2.3-4.1] P<0.001); and transferred to new care home (2.4% versus 9.4%; OR, 2.1 [95% CI, 1.3-3.3] P=0.002). Patients with mRS scores =1 or 2 had intermediate risk of adverse outcomes. Overall, those with a mRS score =1 or 2 had length of stay on hyperacute stroke units extended by 5.3 days (95% CI, 2.8-7.7; P<0.001) and mRS score =3, 4 or 5 by 7.2 days (95% CI, 4.0-10.5; P<0.001). Conclusions- Individuals with evidence of prestroke disability, assessed by mRS, had significantly increased risk of poststroke adverse outcomes and longer length of stay on hyperacute stroke units and higher level of care on discharge.