Profile of reticulated platelets in the early, subacute and late phases after transient ischemic attack or ischemic stroke.

Information regarding the profile of reticulated platelets (RP) in ischemic cerebrovascular disease (CVD) patients is limited. Data from two prospective, observational, case-control studies were combined to compare the %RP using whole blood flow cytometry in patients ≤ 4 weeks of TIA/stroke onset (baseline, N = 210), and 14 ±7 days (14d, N = 182) and ≥ 90 days (90d, N = 145) after starting or changing antiplatelet therapy with healthy controls (N = 34). There were no differences in median %RP between the overall CVD patient population at baseline or 14d vs. controls (P ≥ 0.2). However, the median %RP was significantly higher in CVD patients overall at 90d (P = .036), and in the subgroup of patients with "lacunar" TIA/ischemic stroke at baseline (P = .04) and at 90d (P = .01), but not at 14d (P = .06) vs. controls. There were no significant differences in the median %RP between other TIA/stroke subgroups and controls (P ≥ 0.05). Elevated circulating reticulated platelets, as a marker of increased platelet production/turnover, may occur following an ischemic event in a well-phenotyped TIA/ischemic stroke population overall, but may precede symptom onset at least in the subgroup with small vessel occlusion. These data improve our understanding of the profile of reticulated platelets in CVD patients.

Nosocomial SARS-CoV-2 transmission in postoperative infection and mortality: analysis of 14 798 procedures.

This study used a national administrative database to estimate perioperative SARS-CoV-2 infection risk, and associated mortality, relative to nosocomial transmission rates. The impact of nosocomial transmission was greatest after major emergency surgery, whereas laparoscopic surgery may be protective owing to reduced duration of hospital stay. Procedure-specific risk estimates are provided to facilitate surgical decision-making and informed consent. Estimated risks.

A systematic review of interventions to increase physical activity among South Asian adults.

OBJECTIVES: To identify interventions aimed at increasing physical activity (PA) levels among South Asian (SA) adults and identify the specific changes in the content and delivery mode of interventions designed to increase PA levels among SA people aged ≥18 years. DESIGN: A systematic review of quantitative studies. DATA SYNTHESIS: Extracted data were synthesized using a narrative approach. DATA SOURCES: ASSIA, CINHAL, EMBASE, Medline, SPORTDiscus and PsychINFO were searched. Included articles met the following criteria: (1) population: community-dwelling SA adults aged ≥18 years and (2) outcome: reporting determinants of PA, exercise, or a combination of the two, measured objectively or using self-report. The search was restricted to articles published in the English language up to 31 January 2017. RESULTS: Fifteen trials/programmes (16 articles) met the review criteria. The findings show that involving the target community in developing culturally appropriate interventions appears to be important in their acceptability, delivery and uptake. Using community-based participation in intervention planning, evaluation and research appears to produce culturally and linguistically tailored interventions that address core values, attitudes, beliefs and norms, and encourage participation in PA. Furthermore, the use of community health workers and underpinning the interventions with a psychological theory show promise in increasing PA uptake. CONCLUSIONS: This systematic review suggests that making cultural adaptations to PA interventions shows promise, but the evidence base presented is not strong. This does not mean that adopting such an approach is ineffective but that the evidence base is currently lacking.

Postpartum inhibition of ovarian steroid action increases aspects of maternal caregiving and reduces medial preoptic area progesterone receptor expression in female rats.

The rapid peripartum onset of maternal caregiving involves progesterone synergizing with estradiol, but prolonging progesterone exposure past this time can prevent the emergence of mothering. Interestingly, there is a 7-10day-long rise in progesterone during mid-lactation, but its effects on mothering are unknown. Given progesterone's potential to inhibit mothering onset, this mid-lactational rise may contribute to the normal attenuation of caregiving behaviors across lactation. To evaluate this, recently-parturient rats were ovariectomized and caregiving observed from postpartum days (PPD) 7-18. Ovariectomized dams were found to lick, hover over, and nurse in kyphosis more frequently than controls. Ovariectomy also decreased medial preoptic area (mPOA) progesterone receptor (PR) mRNA, which was negatively correlated with pup licking and kyphosis, but it did not affect mPOA levels of oxytocin receptor or vasopressin V1a receptor mRNAs. In a second study, gonadally intact dams were given the PR antagonist, RU 486, and were found to display more kyphosis and less supine nursing compared to controls. Finally, progesterone sensitivity across lactation was examined by measuring numbers of PR immunoreactive (PR-ir) cells in the mPOA, ventral bed nucleus of the stria terminalis (BSTv) and periaqueductal gray (PAG). PR-ir was higher in the mPOA at parturition compared to virgins, while PR-ir in the mPOA and BSTv dropped from parturition to PPD 7 and remained low through PPD 18. The number of PR-ir cells in the PAG was constant. Thus, in addition to their well-known prepartum effects, ovarian hormones limit the display of some maternal behaviors during mid-to-late lactation and contribute to their decline as weaning approaches.

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.

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.

Assessment of on-treatment platelet reactivity at high and low shear stress and platelet activation status after the addition of dipyridamole to aspirin in the early and late phases after TIA and ischaemic stroke.

BACKGROUND: Data are limited on the ability of dipyridamole to additionally inhibit platelet function/reactivity in ischaemic cerebrovascular disease (CVD) patients on aspirin. AIMS: To assess inhibition of platelet function/reactivity and platelet activation with dipyridamole in CVD. METHODS: This prospective, observational study assessed TIA/ischaemic stroke patients before (baseline; N = 60), at 14 ±7 days (14d, N = 39) and ≥ 90 days (90d, N = 31) after adding dipyridamole to aspirin. Platelet function/reactivity at high shear stress (PFA-100® C-ADP) and low shear stress (VerifyNow® P2Y12 and Multiplate® ADP assays), and platelet activation status (% expression of CD62P, CD63 and leucocyte-platelet complexes on whole blood flow cytometry) were quantified. 'Dipyridamole-high on-treatment platelet reactivity (HTPR)' was defined as failure to inhibit ADP-induced platelet aggregation +/- adhesion compared with the patient's baseline on aspirin monotherapy by more than twice the coefficient-of-variation of the assay after adding dipyridamole to aspirin. RESULTS: Dipyridamole-HTPR was identified in 71.4-75% of patients on PFA-100 C-ADP, 83.9-86.8% of patients on VerifyNow P2Y12, and 81.5-83.3% of patients on Multiplate ADP assays. There were no changes in CD62P/CD63 expression (P ≥ 0.18), or consistent changes in leucocyte-platelet complexes in CVD patients overall at 14d or 90d vs. baseline after commencing dipyridamole. Monocyte-platelet complexes increased in the patient subgroup with dipyridamole-HTPR at 14d and 90d on PFA-100, and at 14d on VerifyNow (P ≤ 0.04), but not in those without dipyridamole-HTPR. DISCUSSION: Additional antiplatelet effects of dipyridamole are detectable under high and low shear stress conditions with user-friendly platelet function/reactivity tests ex vivo. Increasing circulating monocyte-platelet complexes over time are associated with dipyridamole-HTPR.

Five-year follow-up of patients treated with intra-dermal botulinum toxin for axillary hyperhidrosis.

BACKGROUND: Axillary hyperhidrosis is a common complaint affecting 5% of the general population. It can significantly impact quality of life (QOL) and may be extremely debilitating. Administration of intra-dermal botulinum toxin type-A (Botox) has been proven to be effective in managing axillary hyperhidrosis; however, to date, no long-term data has assessed its efficacy. AIM: We aim to assess long-term (> 5 years) QOL outcomes in this patient cohort. METHODS: In this single-centre series, all patients attending for axillary botox, with five or more years of follow-up, were prospectively included. QOL was assessed in all patients using the validated assessment tool, the modified Dermatology Life Quality Index (DLQI). Standard statistical methods were utilised with data reported as mean (± standard deviation). Subgroup analysis utilising previously published departmental data allowed for further assessment of change in QOL over time. RESULTS: A total of 75 patients (83% female) met the inclusion criteria with 67% completing the DLQI assessment. Follow-up ranged from 5 to 10 years with a mean age of 37.6 years (± 8.82). The mean number of treatments over the study period was 12 (± 3.1). Mean overall post-treatment DLQI score was 1.6 (± 2.01). This represented a significant improvement in patient QOL (p = < 0.0001) associated with long-term botox application. This statistical significance was identified consistently across all components of the DLQI tool. CONCLUSION: These data suggest that the established early QOL benefits associated with intra-dermal botox administration for AH are sustained in the long term. This benefit was seen across all subsets of the DLQI tool.

Relationship between 'on-treatment platelet reactivity', shear stress, and micro-embolic signals in asymptomatic and symptomatic carotid stenosis.

BACKGROUND: Assessment of 'high on-treatment platelet reactivity (HTPR)' could enhance understanding of the pathophysiology of first or recurrent vascular events in carotid stenosis patients on antiplatelet therapy. METHODS: This prospective, multi-centre study assessed antiplatelet-HTPR status and its relationship with micro-emboli signals (MES) in asymptomatic vs. symptomatic ≥ 50-99% carotid stenosis. Platelet function/reactivity was assessed under 'moderately high shear stress' with the PFA-100® and 'low shear stress' with VerifyNow® and Multiplate® analysers. Bilateral 1-h transcranial Doppler ultrasound of the middle cerebral arteries classified patients as MES + ve or MES - ve. RESULTS: Data from 34 asymptomatic patients were compared with 43 symptomatic patients in the 'early phase' (≤ 4 weeks) and 37 patients in the 'late phase' (≥ 3 months) after TIA/ischaemic stroke. Median daily aspirin doses were higher in early symptomatic (225 mg; P < 0.001), but not late symptomatic (75 mg; P = 0.62) vs. asymptomatic patients (75 mg). There was a lower prevalence of aspirin-HTPR in early (28.6%; P = 0.028), but not late symptomatic (38.9%; P = 0.22) compared with asymptomatic patients (56.7%) on the PFA-100®, but not on the VerifyNow® or Multiplate® (P ≤ 0.53). Early symptomatic patients had a higher prevalence of aspirin-HTPR on the PFA-100® (28.6%) vs. VerifyNow® (9.5%; P = 0.049), but not Multiplate® assays (11.9%, P = 0.10). There was no difference in aspirin-HTPR prevalence between any symptomatic vs. asymptomatic MES + ve or MES - ve subgroup. DISCUSSION: Recently symptomatic moderate-severe carotid stenosis patients had a lower prevalence of aspirin-HTPR than their asymptomatic counterparts on the PFA-100®, likely related to higher aspirin doses. The prevalence of antiplatelet-HTPR was positively influenced by higher shear stress levels, but not MES status.

What and how but where does the why fit in? The disconnection between practice and research evidence from the perspective of UK nurses involved in a qualitative study.

An emphasis has been placed on evidence during nurse training and practice over recent decades. A qualitative study was undertaken to explore the meaning of and involvement in evidence-based practice for recently qualified general nurses. A purposive sample of 11 general nurses was recruited. Semi-structured interviews were conducted between March-June 2017. All were audio-recorded and transcribed verbatim. Thematic analysis was applied to transcripts. An overarching theme of disconnection between research and evidence and the participants' perceptions of contemporary nursing practice was underpinned by three themes: 1) We should be using it … but we're not; 2) Leaving research behind at graduation; 3) Research is other people's business. Participants had been exposed to evidence-based practice during their training, but once qualified they appeared to move into a culture where this was not seen as a priority. Nurses on wards were unaware of research taking place locally and had limited contact with research staff in their organisation. Approaches to overcoming the disconnection between research/evidence and practice could include how it is introduced during training, and changes in nursing culture and leadership. This could include placements for student nurses within research teams.

Systemic glyceryl trinitrate reduces anal sphincter tone: is there a therapeutic indication?

BACKGROUND: Nitric oxide (NO) has diverse roles as a biological messenger. [1] Topically applied nitrate donors cause relaxation of the internal anal sphincter (IAS) and facilitate healing of anal fissures [2,3]. Systemic nitrates are commonly used for the treatment of ischaemic heart disease, yet the effects of systemically administered nitrates on the smooth muscle of the IAS are unknown. AIM: Our aim was to test the hypothesis that systemically administered nitrates at a normal dose, cause inhibition of anal sphincter activity. METHODS: With fully informed consent, anal manometry was performed on nine volunteers. Maximum and mean anal resting pressure (representing the IAS), maximum squeeze pressure (representing the external anal sphincter), heart rate and blood pressure were measured, before and after administration of a normal 400 µg dose of sublingual glyceryl trinitrate spray. RESULTS: Data are expressed as mean (± standard error of the mean (SEM)). In four females and five males ranging from 19 to 50 years of age, administration of GTN resulted in a significant reduction in systolic blood pressure from 138 ± 5 to 127 ± 4 mmHg, P < 0.01. Mean resting pressure, over 5 min, was significantly reduced from 70 ± 10 to 62 ± 10 mmHg P < 0.05. The maximum resting pressure was also significantly reduced from 109 ± 12 to 86 ± 10 mmHg P = 0.04. Maximum squeeze pressure, heart rate and diastolic blood pressure were not significantly reduced. CONCLUSION: Systemic nitrates significantly inhibit internal anal sphincter function.

Control and disordered eating in type 1 diabetes.

Control is a major topic associated with the management of diabetes due to the importance placed on maintaining healthy blood glucose levels in this condition. Such an outcome can be influenced by individuals' sense of mastery over the disease, and more generally over their environment. In response to a diagnosis of diabetes, the self-management requirements accompanying it, and/or difficulties in other areas of life, patients may decide to undertake behaviours that are detrimental to their well-being. For instance, they may adopt fixated attitudes towards their intake and weight. This paper explores the relationship between disordered eating habits, control and diabetes in those who are insulin dependent.

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.

Construct validation of a novel hybrid surgical simulator.

BACKGROUND: Simulated minimal access surgery has improved recently as both a learning and assessment tool. The construct validation of a novel simulator, ProMis, is described for use by residents in training. METHODS: ProMis is a surgical simulator that can design tasks in both virtual and actual reality. A pilot group of surgical residents ranging from novice to expert completed three standardized tasks: orientation, dissection, and basic suturing. The tasks were tested for construct validity. Two experienced surgeons examined the recorded tasks in a blinded fashion using an objective structured assessment of technical skills format (OSATS: task-specific checklist and global rating score) as well as metrics delivered by the simulator. RESULTS: The findings showed excellent interrater reliability (Cronbach's alpha of 0.88 for the checklist and 0.93 for the global rating). The median scores in the experience groups were statistically different in both the global rating and the task-specific checklists (p < 0.05). The scores for the orientation task alone did not reach significance (p = 0.1), suggesting that modification is required before ProMis could be used in isolation as an assessment tool. CONCLUSIONS: The three simulated tasks in combination are construct valid for differentiating experience levels among surgeons in training. This hybrid simulator has potential added benefits of marrying the virtual with actual, and of combining simple box traits and advanced virtual reality simulation.

Demands for vascular access in a renal dialysis unit: implications for a regional vascular unit.

BACKGROUND: The development of regional dialysis units and the expanding indications for dialysis has led to increased demand for vascular access surgery. Consequently, the provision and maintenance of access, and the management of related complications has created a considerable burden on vascular surgical units in hospitals providing renal replacement therapy (RRT). AIMS: The objectives of our study were to review our experience with a variety of vascular access modalities for haemodialysis and to quantify the associated surgical workload. METHODS: We reviewed our experience in a consecutive group of dialysis patients who had access surgery for RRT in a regional hospital setting. RESULTS: Between January 1995 and January 2000, 69 patients entered the long-term dialysis programme in the Mid-Western region (population = 320,000). Of the 158 procedures performed, 138 (87%) were for access creation, and 20 (13%) related to access revision procedures. Twenty patients (29%) developed a total of 30 access related complications. Vascular access procedures accounted for 10% of the vascular surgical workload (1598 procedures) in the five-year period. CONCLUSION: Vascular access is an important part of the haemodialysis services and surgical expertise should be available at local level to cope with likely demand.