Improved adherence to hip fracture standards reduces mortality after hip fractures.

BACKGROUND: Hip fractures are increasing in incidence due to increasing life expectancy. Mortality continues to improve but it is important to explore which factors are responsible for driving improvements. METHODS: A cohort of hip fracture patients predating SARS-CoV-2 was examined to determine the predictors of adherence to the six Irish Hip Fracture Standards (IHFS) and the impact of adherence on short (30 day) and long term (1 year) mortality. Our primary aim was assess the impact of a single HFS and cumulative number of HFS on mortality after hip fracture. Our secondary aim was to determine the impact of the HFS which are intrinsically linked to specialist Geriatric care. RESULTS: Across 962 patients, over 5 years, the factors which were associated with adherence to HFS were female gender, increasing ASA grade and being nursed on an orthopaedic ward. Patients with increasing ASA were more likely to have met HFS 4-6 (Geriatrician review HFS4, bone health HFS5 & specialist falls assessment HFS6), less likely to have surgery within 48 h are more likely to develop a pressure ulcer. If the patient was not nursed on an orthopaedic ward all HFS were less likely to be met. At 30 days HFS 4-6 were associated with a statistically significant odds ratio (OR) of being alive, while at one year HFS 1 (admitted to an orthopaedic ward within 4 h), 5 and 6 were associated with a statistically significant OR of being alive. As increasing numbers of hip fracture standards were met patients were more likely to be alive at 30 days and one year. CONCLUSION: This study has identified that improved adherence to hip fracture standards are associated with improved mortality at 30 days and one year.

Increased thrombin generation potential in symptomatic versus asymptomatic moderate or severe carotid stenosis and relationship with cerebral microemboli.

INTRODUCTION: The importance of thrombin generation in the pathogenesis of TIA or stroke and its relationship with cerebral microembolic signals (MES) in asymptomatic and symptomatic carotid stenosis has not been comprehensively assessed. METHODS: Plasma thrombin generation parameters from patients with moderate or severe (≥ 50%) asymptomatic carotid stenosis were compared with those from patients with symptomatic carotid stenosis in the early (≤ 4 weeks) and late phases (≥ 3 months) after TIA or stroke in this prospective, pilot observational study. Thrombin generation profile was longitudinally assessed in symptomatic patients with data at each time point. Bilateral transcranial Doppler ultrasound monitoring of the middle cerebral arteries was performed whenever possible to classify patients as MES-positive or MES-negative. RESULTS: Data from 31 asymptomatic, 46 'early symptomatic' and 35 'late symptomatic' patients were analysed. Peak thrombin (344.2 nM vs 305.3 nM; p = 0.01) and endogenous thrombin potential (1772.4 vs 1589.7; p = 0.047) were higher in early symptomatic than asymptomatic patients. Peak thrombin production decreased in symptomatic patients followed up from the early to late phase after TIA or stroke (339.7 nM vs 308.6 nM; p = 0.02). Transcranial Doppler ultrasound data were available in 25 asymptomatic, 31 early symptomatic and 27 late symptomatic patients. Early symptomatic MES-positive patients had a shorter 'time-to-peak thrombin' than asymptomatic MES-positive patients (p=0.04), suggesting a more procoagulant state in this early symptomatic subgroup. DISCUSSION: Thrombin generation potential is greater in patients with recently symptomatic than asymptomatic carotid stenosis, and decreases over time following TIA or stroke associated with carotid stenosis. These data improve our understanding of the haemostatic/thrombotic biomarker profile in moderate-severe carotid stenosis.

Increased endothelial activation in recently symptomatic versus asymptomatic carotid artery stenosis and in cerebral microembolic-signal-negative patient subgroups.

BACKGROUND AND PURPOSE: von Willebrand factor propeptide (VWF:Ag II) is potentially a more sensitive marker of acute endothelial activation than von Willebrand factor antigen (VWF:Ag). These biomarkers have not been simultaneously assessed in asymptomatic versus symptomatic carotid stenosis patients. The relationship between endothelial activation and cerebral microembolic signals (MESs) detected on transcranial Doppler ultrasound is unknown. METHODS: In this multicentre observational analytical study, plasma VWF:Ag and VWF:Ag II levels in patients with ≥50% asymptomatic carotid stenosis were compared with those from patients with ≥50% symptomatic carotid stenosis in the 'early' (≤4 weeks) and 'late' (≥3 months) phases after transient ischaemic attack or ischaemic stroke. Endothelial activation was also longitudinally assessed in symptomatic patients during follow-up. Transcranial Doppler ultrasound monitoring classified patients as MES-positive or MES-negative. RESULTS: Data from 31 asymptomatic patients were compared with those from 46 early symptomatic and 35 late phase symptomatic carotid stenosis patients, 23 of whom had undergone carotid intervention. VWF:Ag II levels were higher in early (12.8 µg/ml; P < 0.001), late (10.6 µg/ml; P = 0.01) and late post-intervention (10.6 µg/ml; P = 0.038) symptomatic patients than asymptomatic patients (8.9 µg/ml). VWF:Ag levels decreased in symptomatic patients followed up from the early to late phase after symptom onset (P = 0.048). Early symptomatic MES-negative patients had higher VWF: Ag II levels (13.3 vs. 9.0 µg/ml; P < 0.001) than asymptomatic MES-negative patients. CONCLUSIONS: Endothelial activation is enhanced in symptomatic versus asymptomatic carotid stenosis patients, in early symptomatic versus asymptomatic MES-negative patients, and decreases over time in symptomatic patients. VWF:Ag II levels are a more sensitive marker of endothelial activation than VWF:Ag levels in carotid stenosis. The potential value of endothelial biomarkers and concurrent cerebral MES detection at predicting stroke risk in carotid stenosis warrants further study.

Circulating Angiogenic and Senescent T Lymphocytes in Ageing and Frailty.

BACKGROUND: There is a need to identify vascular and geroscience-relevant markers and mediators that can physiologically link ageing to vascular disease. There is evidence of specific T cell subsets, all influenced by age, that exert positive and negative effects on vascular health. CD31+, termed angiogenic T cells, have been linked to vascular repair whereas CD28null, termed senescent T cells, display pro-inflammatory and cytotoxic effector functions. OBJECTIVE: This study sought to determine the combined influence of increasing age and frailty status on these circulating CD31+ and CD28null T cell subsets. METHODS: This cross-sectional study recruited four different cohorts of men and women; young (20-30 years, n=22), older (65-75 years, n=17), robust non-frail (76+ years, n=17), and frail (76+ years, n=15) adults. Frailty was determined using the Fried Frailty method. T cell subsets were determined by whole blood flow cytometry based on the expression of CD3, CD4, CD8, CD31 and CD28. Cognitive impairment (CI) was measured via the Montreal Cognitive Assessment test. RESULTS: Whether expressed as circulating counts or as a % of total T cells, there was a progressive decrease (p<0.05) in CD31+ T cells with increasing age but paradoxically higher values (p<0.05) in the frail compared to the robust non-frail group. These changes were similar in the CD4+ and CD8+ fractions. CD28null T cells were considerably higher (p<0.05) in the frail compared to the robust non-frail group, including in the CD8+ (47% vs 29%, p<0.05) and CD4+ (4% vs 1%, p<0.05) fractions. CD28null T cell percentage was also higher (p<0.05) in those with moderate CI compared to mild CI and normal function. CONCLUSION: CD8+CD28null T cells are considerably elevated in frailty and with cognitive impairment and may serve as a useful target for intervention. Currently, the utility of CD31+ T cells as an ageing biomarker may be confined to healthy ageing cohorts.

High on-treatment platelet reactivity on commonly prescribed antiplatelet agents following transient ischaemic attack or ischaemic stroke: results from the Trinity Antiplatelet Responsiveness (TRAP) study.

BACKGROUND AND PURPOSE: The prevalence of ex vivo 'high on-treatment platelet reactivity' (HTPR) to antiplatelet regimens in patients with ischaemic cerebrovascular disease (CVD) is uncertain. METHODS: HTPR was assessed with PFA-100 collagen-epinephrine (C-EPI) and collagen-ADP (C-ADP) cartridges. Platelet activation (CD62P, CD63 and leucocyte-platelet complex formation) was assessed with whole-blood flow cytometry. Patients were assessed at baseline [≤ 4 weeks of transient ischaemic attack (TIA) or ischaemic stroke], and at 14 days and ≥ 90 days after changing treatment from (i) no medication to aspirin monotherapy (N = 26) or (ii) aspirin to clopidogrel monotherapy (N = 22). HTPR was defined in a novel, 'longitudinal fashion' as failure to prolong relevant closure times compared with the patient's 'baseline value' before he/she underwent an antiplatelet change by more than twice the coefficient of variation of the assay. RESULTS: (i) C-EPI closure times increased at 14 days and 90 days after commencing aspirin (P = 0.002); 24% at 14 days and 18% at 90 days demonstrated HTPR on aspirin. (ii) C-ADP closure times increased at 14 days (P = 0.001) but not 90 days (P = 0.09) after changing from aspirin to clopidogrel; 41% at 14 days, and 35% at 90 days demonstrated HTPR on clopidogrel. Platelet activation was unaffected by aspirin (P = 0.09). The percentage neutrophil-platelet complexes decreased at 14 days (P = 0.02), but this reduction was not maintained 90 days after changing to clopidogrel (P = 0.3). No patient had a recurrent vascular event during prospective follow-up. CONCLUSIONS: Longitudinal definitions of HTPR in patients with ischaemic CVD who are undergoing a change in antiplatelet therapy have the potential to provide more clinically meaningful information than traditional 'cross-sectional definitions' of HTPR which are usually based on the comparison of patients' values with those in healthy controls. Using our novel, longitudinal definition of HTPR, the PFA-100 could be used to monitor ex vivo responsiveness to aspirin, and larger, prospective studies are warranted to assess the clinical predictive value of this and other platelet function tests in patients with ischaemic CVD.

The very small angle neutron scattering instrument at the National Institute of Standards and Technology.

A description and the performance of the very small angle neutron scattering diffractometer at the National Institute of Standards and Technology are presented. The measurement range of the instrument extends over three decades of momentum transfer q from 2 × 10-4 to 0.7 Å-1. The entire scattering angle range from 8 × 10-5 to π/6 rad (30°) can be measured simultaneously using three separate detector carriages on rails holding nine 2D detector arrays. Versatile choices of collimation options and neutron wavelength selection allow the q resolution and beam intensity to be optimized for the needs of the experiment. High q resolution is achieved using multiple converging-beam collimation with circular pinholes combined with refractive lenses and prisms. Relaxed vertical resolution with much higher beam intensity can be achieved with narrow slit collimation and a broad wavelength range chosen by truncating the moderator source distribution below 4 Šwith a Be crystalline filter and above 8 Šwith a supermirror deflector. Polarized beam measurements with full polarization analysis are also provided by a high-performance supermirror polarizer and spin flipper, capable of producing flipping ratios of over 100, along with a high-efficiency 3He polarization analyzer.

Key Service Improvements After the Introduction of an Integrated Orthogeriatric Service.

INTRODUCTION: Models of orthogeriatric care have been shown to improve functional outcomes for patients after hip fractures and can improve compliance with best practice guidelines for hip fracture care. METHODS: We evaluated improvements to key performance indicators in hip fracture care after implementation of a formal orthogeriatric service. Compliance with Irish Hip Fracture standards of care was reviewed, and additional outcomes such as length of stay, access to rehabilitation, and discharge destination were evaluated. RESULTS: Improvements were observed in all of the hip fracture standards of care. Mean length of stay decreased from 19 to 15.5 days (mean difference 3.5 days; P < .05). A higher proportion of patients were admitted to rehabilitation (16.7% vs 7.9%, P < .05), and this happened in a timelier fashion (17.8 vs 24.8 days, P < .05). We found that less patients required convalescence post-hip fracture. DISCUSSION: A standardized approach to integrated post-hip fracture care with orthogeriatrics has improved standards of care for patients. CONCLUSION: Introduction of orthogeriatric services has resulted in meaningful improvements in clinical outcomes for older people with hip fractures.

Cost of disorders of the brain in Ireland.

The "Cost of Disorders of the Brain in Europe" (CBDE) study was conducted by the European Brain Council (EBC) to estimate prevalence and cost of the twelve leading disorders encountered in Neurology, Neurosurgery, and Psychiatry. The data for Ireland are presented here. Prevalence and costing information was obtained by structured review of published literature for each country. Where such information was lacking, figures were estimated from European data. Costs included direct medical, direct non-medical, and indirect costs. None of the costs presented here are directly from Irish data and the prevalence figures are mostly estimated from known European rates. In 2004, 1.1 million people in Ireland were affected by a disorder of the brain. Total cost of included disorders in Ireland was 3.0 billion Euro, representing 3% of gross national product, and costing each Irish citizen Euro 775 per year. Brain disorders are prevalent and pose significant economic burden in Ireland.

The effect of dietary supplementation of algae rich in docosahexaenoic acid on boar fertility.

The objective of this study was to assess the effects of dietary supplementation of a commercial algal product rich in docosahexaenoic acid (DHA) on boar fertility as assessed in vitro and in vivo. Boars were fed one of three experimental diets for 19 weeks: (i) Control (Ctl) diet (n = 31), (ii) Ctl diet plus 75g All-G-Rich per day (n = 31) or (iii) Ctl diet plus 150g All-G-Rich per day (n = 30). Parameters assessed were (i) raw semen quality; volume, sperm concentration, total motility and morphology (ii) liquid semen quality; progressive motility, viability, hypotonic resistance and acrosomal integrity (iii) frozen-thawed semen quality; motility, thermal stress, viability, membrane fluidity and mitochondrial activity (iv) sperm and seminal plasma (SP) fatty acid composition (FAC) (v) total antioxidant capacity (TAC) of SP and (vi) farrowing rates and litter sizes of sows (n = 1158) inseminated with liquid semen. Boars consuming 75g All-G-Rich had a larger semen volume (P < 0.05) and a higher total sperm number (P < 0.01) than the Ctl treatment, however, there was no effect of treatment on any other semen quality parameter (P > 0.05). There was no effect of dietary treatment on the FAC and TAC of SP or on farrowing rate and litter size (P > 0.05). There was an effect of dietary treatment on the FAC of sperm, represented by an 1.72 and 1.60 fold increase in the DHA content for 75 and 150g treatments, respectively, compared to the Ctl treatment. In conclusion, a significant increase in semen volume and total sperm number in boars supplemented 75g All-G-Rich daily, resulted in an increase in production of 3 to 4 more doses per ejaculate, thus, indicating that the feeding regime described within this study has the potential for increasing the output of boar studs.

Profile of von Willebrand factor antigen and von Willebrand factor propeptide in an overall TIA and ischaemic stroke population and amongst subtypes.

INTRODUCTION: Von Willebrand factor propeptide (VWF:Ag II) is proposed to be a more sensitive marker of acute endothelial activation than von Willebrand factor antigen (VWF:Ag). Simultaneous data on VWF:Ag and VWF:Ag II profiles are very limited following TIA and ischaemic stroke. METHODS: In this prospective, observational, case-control study, plasma VWF:Ag and VWF:Ag II levels were quantified in 164 patients≤4weeks of TIA or ischaemic stroke (baseline), and then ≥14days (14d) and ≥90days (90d) later, and compared with those from 27 healthy controls. TIA and stroke subtyping was performed according to the TOAST classification. The relationship between VWF:Ag and VWF:Ag II levels and platelet activation status was assessed. RESULTS: 'Unadjusted' VWF:Ag and VWF:Ag II levels were higher in patients at baseline, 14d and 90d than in controls (p≤0.03). VWF:Ag levels remained higher in patients than controls at baseline (p≤0.03), but not at 14d or 90d after controlling for differences in age or hypertension, and were higher in patients at baseline and 90d after controlling for smoking status (p≤0.04). 'Adjusted' VWF:Ag II levels were not higher in patients than controls after controlling for age, hypertension or smoking (p≥0.1). Patients with symptomatic carotid stenosis (N=46) had higher VWF:Ag and VWF:Ag II levels than controls at all time-points (p≤0.002). There was no significant correlation between platelet activation status and VWF:Ag or VWF:Ag II levels. CONCLUSIONS: VWF:Ag and VWF:Ag II levels are increased in an overall TIA and ischaemic stroke population, especially in patients with recently symptomatic carotid stenosis. VWF:Ag II was not superior to VWF:Ag at detecting acute endothelial activation in this cohort and might reflect timing of blood sampling in our study.

An automated heteroduplex assay for the Pi(A) polymorphism of glycoprotein IIb/IIIa, multiplexed with two prothrombotic genetic markers.

Screening for the PIA polymorphism has been made faster and simpler with the advent of heteroduplex technology. Simultaneous screening for three common prothrombotic polymorphisms pl(A), factor V Leiden, and MTHFR(C677T) has been achieved with multiplex heteroduplex analysis. We describe a quick and simple method for PlA heteroduplex probe production. The probe was multiplexed with heteroduplex probes for MTHFR(C677T) and factor V Leiden polymorphisms in a one tube assay, allowing rapid automated genotyping of all three. This automated multiplex assay was applied to a cohort of 165 patients and showed excellent correlation with gel-based assays, both PAGE and RFLP. This approach will facilitate the analysis of multiple polymorphisms in complex disease in large populations.

Regression of iris neovascularization following panretinal photocoagulation.

A 57-year-old woman with proliferative diabetic retinopathy in both eyes also had iris surface neovascularization with early angle neovascularization in her right eye, which regressed completely following treatment with panretinal photocoagulation. Histopathologic examination confirmed the complete absence of abnormal vessels on the iris surface or in the iridocorneal angle of the right eye; an avascular fibrous membrane persisted on a segment of the posterior iris pigment epithelium near the pupil. There was advanced rubeosis in the untreated left eye.

Visual symptoms associated with choroidal neovascularization. Photopsias and the Charles Bonnet syndrome.

One hundred consecutive patients with macular choroidal neovascularization were studied in a cross-sectional fashion. Evidence of bilateral choroidal neovascularization was present in 31 patients. Among the 100 subjects, 59% related a history of seeing flickering or flashing lights (photopsias) in the affected eye or eyes. The colors varied, but in 59% of instances the lights were white. Twelve subjects experienced formed hallucinations (Charles Bonnet syndrome); in nine (75%) of these patients, the sequelae of choroidal neovascularization were bilateral. Symptoms that are commonly attributed to vitreoretinal tractional phenomena as well as neurologic and/or psychiatric disease are also frequently encountered in patients with macular degeneration associated with choroidal neovascularization.

The evolution of argon laser photocoagulation scars in patients with the ocular histoplasmosis syndrome.

In 34 patients (35 eyes) with successfully treated histoplasmic choroidal neovascular membranes with a mean follow-up of 10.1 years, neither the neovascular membrane size nor the distance to the center of the foveal avascular zone (FAZ) affected final visual acuity. For a subgroup of 18 patients who had a two-year follow-up visit, the average chorioretinal scar expanded in area 50.1% per year for the first two years and 4.6% per year thereafter. This corresponded to a migration rate toward the FAZ of 152 micron/y for the first two years and 22 micron/y thereafter. After ten years, the average scar was 3.23 times larger than the initial treatment area and 480 micron closer to the FAZ than the initial treatment edge. Of the eight patients whose scars expanded to involve the center of the FAZ, six had final visual acuities either equal to or better than the initial visual acuities.

Natural course of poorly defined choroidal neovascularization associated with macular degeneration.

We obtained follow-up data on 84 eyes with age-related macular degeneration and poorly defined angiographic leakage presumed to represent choroidal neovascularization. A poorly defined neovascular membrane was presumed to be present when subsensory retinal fluid was present in association with choroidal leakage on fluorescein angiography and in which the extent of leakage was not well defined. Among the 84 eyes, the average initial visual acuity was 20/80. In 75 (89%) of 84 eyes, the leakage involved the foveal center at initial presentation. At follow-up (average, 28 months; range, six to 53 months), the average visual acuity was 20/250; the final acuity declined at least three but less than six lines in 18 eyes (21%) and six or more lines in 35 eyes (42%). There was a statistically significant difference in the percentage of eyes that developed moderate or severe visual loss among eyes that progressed to disciform scarring compared with eyes that continued to manifest poorly defined leakage without evidence of scarring. Given that most severe visual loss associated with macular degeneration can be attributed to consequences of neovascular membranes and that many membranes associated with age-related macular degeneration are poorly defined, our study results support the possibility that poorly defined neovascular membranes represent a major cause of severe visual loss among the elderly in the United States.

Interval between onset of mild nonproliferative and proliferative retinopathy in type I diabetes.

OBJECTIVE: To describe the interval between first appearance of mild nonproliferative diabetic retinopathy (NPDR) and first appearance of neovascularization (NV) in type I diabetes. SETTING: A longitudinal study of 269 patients followed up annually. PARTICIPANTS: Participants had insulin-dependent diabetes and were free of proliferative diabetic retinopathy in both eyes at the baseline visit. MAIN OUTCOME MEASURE: Stereoscopic color fundus photographs of each eye at each study visit, graded for features of retinopathy. RESULTS: Among the 305 eyes for which the duration of diabetes at the first appearance of mild NPDR could be determined, NV developed in 28 by the end of the study. Survival analysis showed that the later the onset of mild NPDR was, the shorter the time from onset of mild NPDR to onset of NV (relative hazard for each additional year to onset of mild NPDR, 1.22; 95% confidence interval, 1.10-1.35). Adjustment for systolic and diastolic blood pressure, proteinuria, and glycosylated hemoglobin (Hgb A10) levels did not change the relative hazard estimate for onset of mild NPDR. Higher levels of Hgb A10 were associated with a shorter time from onset of mild NPDR to onset of NV (relative hazard, 1.26; 95% confidence interval, 1.05-1.51 [after adjusting for time at onset of mild NPDR]), as were higher levels of diastolic blood pressure, although not significantly (relative hazard for 10-mm Hg increase in diastolic blood pressure, 1.52; 95% confidence interval, 0.82-2.83 [adjusting for onset of mild NPDR, Hgb A10 level, systolic blood pressure, and proteinuria]). Neither proteinuria nor systolic blood pressure had an effect on time from onset of mild NPDR to onset of NV, after adjustment for time at onset of mild NPDR, Hgb A10 level, and diastolic blood pressure. CONCLUSION: Later onset of mild NPDR is not necessarily associated with delayed development of NV in patients with type I diabetes. Caution must therefore be used in assessing the value of interventions that delay the onset of mild NPDR without evidence of delayed onset of NV.

The relationship of puberty to diabetic retinopathy.

The presence of background and preproliferative retinopathy in 70 patients with type I diabetes was correlated with their pubertal development. Pubertal status was assessed by pediatricians using the sexual maturity ratings of Tanner. In young diabetics with comparable disease duration (5 to 10 years), postpubertal children had a greater prevalence of retinopathy than those who were not sexually mature. After adjusting for duration of diabetes and sex, the relative odds of having retinopathy in the postpubescent group relative to the prepubescent or pubescent groups was 4.8 (95% confidence interval: 1.5 to 15.3). This study suggests that minimal retinopathy in children is not rare and that postpubescent children have a greater prevalence of diabetic retinopathy than do prepubescent children with similar diabetes duration.