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.

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.

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.

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.

Implementation of a surgical handover tool in a busy tertiary referral centre: a complete audit cycle.

BACKGROUND: The implementation of the European work-time directive has created increased transitions of care during weekends as doctors adhere to a shift-work structure. This raises concerns over continuity of care and patient safety. To address this, doctors must develop a time efficient yet safe system of handover of patients to the team on-call. Intuitively weekend care provides the ideal setting to develop a handover tool. AIM: To develop and implement a process of surgical handover and to improve weekend discharge rate on a surgical service. METHODS: Data was collected at three time-points over a 6 months period (October 2013-March 2014) encompassing development, implementation, re-evaluation and modification of the handover process. The outcomes measured were: number of inpatients, number of weekend discharges, length of stay (LOS) of inpatients recorded for the four weekends within the month, and total emergency response team (ERT) calls each month. RESULTS: Mean number of included patients each month was 294 (σ = 14). Following the introduction of weekend handover there was a 40 % increase in weekend discharges which was consistent for subsequent time-points (p < 0.05). Following the second intervention there was a statistically significant reduction in mean LOS from 13 to 5.4 days (p < 0.05) and the total number of ERT calls for the month reduced from 12 to 4 (p < 0.05). CONCLUSIONS: The standardisation of weekend handover using a combination of an electronic tool supplemented with verbal handover is feasible. It resulted in a significant improvement in surrogate markers of patient care quality.

Increased platelet activation in early symptomatic vs. asymptomatic carotid stenosis and relationship with microembolic status: results from the Platelets and Carotid Stenosis Study.

BACKGROUND: Cerebral microembolic signals (MES) may predict increased stroke risk in carotid stenosis. However, the relationship between platelet counts or platelet activation status and MES in symptomatic vs. asymptomatic carotid stenosis has not been comprehensively assessed. SETTING: University teaching hospitals. METHODS: This prospective, pilot observational study assessed platelet counts and platelet activation status, and the relationship between platelet activation and MES in asymptomatic vs. early (≤ 4 weeks after TIA/stroke) and late phase (≥ 3 months) symptomatic moderate or severe (≥ 50%) carotid stenosis patients. Full blood count measurements were performed, and whole blood flow cytometry was used to quantify platelet surface activation marker expression (CD62P and CD63) and circulating leucocyte-platelet complexes. Bilateral simultaneous transcranial Doppler ultrasound monitoring of the middle cerebral arteries was performed for 1 h to classify patients as MES positive or MES negative. RESULTS: Data from 31 asymptomatic patients were compared with 46 symptomatic patients in the early phase, and 35 of these patients were followed up to the late phase after symptom onset. The median platelet count (211 vs. 200 × 10(9)  L(-1) ; P = 0.03) and the median percentage of lymphocyte-platelet complexes was higher in early symptomatic than asymptomatic patients (2.8 vs. 2.4%; P = 0.001). The percentage of lymphocyte-platelet complexes was higher in early symptomatic than in asymptomatic patients with ≥ 70% carotid stenosis (P = 0.0005) and symptomatic patients recruited within 7 days of symptom onset (P = 0.028). Complete TCD data were available in 25 asymptomatic, 31 early phase symptomatic and 27 late phase symptomatic patients. Twelve per cent of asymptomatic vs. 32% of early phase symptomatic (P = 0.02) and 19% of late phase symptomatic patients (P = 0.2) were MES positive. Early symptomatic MES-negative patients had a higher percentage of lymphocyte-platelet complexes than asymptomatic MES-negative patients (2.8 vs. 2.3%; P = 0.0085). DISCUSSION: Recently, symptomatic carotid stenosis patients have had higher platelet counts (potentially reflecting increased platelet production, mobilization or reduced clearance) and platelet activation status than asymptomatic patients. MES were more frequently detected in early symptomatic than asymptomatic patients, but the differences between late symptomatic and asymptomatic groups were not significant. Increased lymphocyte-platelet complex formation in recently symptomatic vs. asymptomatic MES-negative patients indicates enhanced platelet activation in this early symptomatic subgroup. Platelet biomarkers, in combination with TCD, have the potential to aid risk-stratification in asymptomatic and symptomatic carotid stenosis patients.

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 cost utility of a multi-disciplinary foot protection clinic (MDFPC) in an Irish hospital setting.

BACKGROUND: Foot ulceration which may result in lower limb amputation is one of the most feared complications among patients with diabetes and the prevention of both ulceration and amputation is a major challenge facing the health service. Many studies have proposed dedicated diabetic foot teams as the future of diabetic foot care. AIMS: We aimed to quantify the cost benefit and sustainability of a multi-disciplinary foot protection clinic (MDFPC) in an Irish university hospital setting. METHODS: A dedicated bi-weekly consultant-led MDFPC including Vascular Surgery, Endocrinology, Orthopaedic Surgery, Podiatry, Orthotics and Tissue Viability was established in June 2008. RESULTS: Between 2006 and 2010, a total of 221 lower limb procedures (major/minor amputations and debridement) were performed. The number of major amputations decreased from 12 during the control period (2 years before the clinic) to 7 in the study period (2 years after the clinic). After costing all activity associated with the clinic, there was an overall saving of €114,063 per year associated with the introduction of the MDFPC. CONCLUSION: This is the first study in an Irish context, and one of few international studies, to demonstrate that an aggressive-coordinated approach to diabetic foot care is both cost effective and clinically efficient in reducing the burden of foot-related complications in a diabetic population.

Popliteo-pedal bypass surgery for critical limb ischemia.

BACKGROUND: Critical limb ischaemia due to distal arterial disease represents a significant challenge. Randomised controlled evidence suggests that open surgery may be superior to endovascular intervention but there is limited data on the specific clinical cohort with exclusively infra-popliteal disease. AIM: We analysed indications for, and outcome from all, popliteo-pedal bypass procedures performed between July 1998 to November 2008. PATIENTS AND METHODS: Twenty-eight bypass procedures were performed in 24 patients. Autologous vein was used exclusively. The proximal anastomosis was to the below-knee popliteal artery in all the patients; the distal anastomosis was to plantar artery (n = 15) or dorsalis pedis artery (n = 13). Mean patient age was 63.Eight years of age (range 37-92 years). Indications for surgery were tissue loss (n = 21) and rest pain (n = 7). Ultrasound graft surveillance was performed every 6-months. RESULTS: Using life table analysis, primary graft patency was 63.3% at 1-, 3- and 5-years and secondary patency (after three interventions) was 74.6% at 1-, 3- and 5-years. Limb salvage rate was 81.8% after 1-, 3- and 5-years as all five limb amputations were performed in the first 3-months following the surgery. Overall survival was 75, 75 and 47.1% at 1-, 3- and 5-years, respectively. The major amputation free survival rate was 54.2, 54.2 and 21.3% at 1-, 3- and 5-years, respectively. Seventy-nine percent (n = 19) patients were diabetic. CONCLUSION: Our data supports popliteo-pedal bypass as an effective treatment for distal vascular disease. Comparison with endovascular treatment in a randomised trial needs to be performed.

Preventing infection in general surgery: improvements through education of surgeons by surgeons.

Surgical patients are at particular risk of healthcare-associated infection (HCAI) due to the presence of a surgical site leading to surgical site infection (SSI), and because of the need for intravascular access resulting in catheter-related bloodstream infection (CRBSI). A two-year initiative commenced with an initial audit of surgical practice; this was used to inform the development of a targeted educational initiative by surgeons specifically for surgical trainees. Parameters assessed during the initial audit and a further audit after the educational initiative were related to intra- and postoperative aspects of the prevention of SSIs, as well as care of peripheral venous catheters (PVCs) in surgical patients. The proportion of prophylactic antibiotics administered prior to incision across 360 operations increased from 30.0% to 59.1% (P<0.001). Surgical site dressings were observed in 234 patients, and a significant decrease was found in the percentage of dressings that were tampered with during the initial 48h after surgery (16.5% vs 6.2%, P=0.030). In total, 574 PVCs were assessed over the two-year period. Improvements were found in the proportion of unnecessary PVCs in situ (37.9% vs 24.4%, P<0.001), PVCs in situ for >72h (10.6% vs 3.1%, P<0.001) and PVCs covered with clean and intact dressings (87.3% vs 97.6%, P<0.001). Significant improvements in surgical practice were established for the prevention of SSI and CRBSI through a focused educational programme developed by and for surgeons. Potentially, other specific measures may also be warranted to achieve further improvements in infection prevention in surgical practice.

Differing perspectives of sputum and its expectoration: a qualitative study involving patients with cystic fibrosis and physiotherapists.

Sputum specimens are frequently requested from individuals with chronic suppurative conditions such as cystic fibrosis (CF). For a proportion of people, expectorating sputum can be difficult. Our goal was to explore the potential barriers and facilitators to expectorating sputum from the perspective of those with CF and physiotherapists involved in their care. Eighteen interviews were conducted with people who have CF and three focus groups with physiotherapists. Data were recorded, transcribed verbatim, and analysed using a framework approach. Variation emerged in perceptions between physiotherapists and people with CF in terms of sputum's impact on everyday life and the importance of its role in managing the condition. These differences were reflected in the following themes: (1) seepage of bodily boundaries, (2) discrediting nature of sputum, (3) embodied representation of chronic illness, and (4) non-production as a decisional balance. Differing views between participants could have arisen from the personal nature of sputum for people with CF, whilst physiotherapists may see sputum specimens as a necessary part of holistic management of this condition. Education could assist individuals in overcoming some of the barriers associated with expectorating, but physiotherapists may have to individualise the collection of sputum, recognising not everyone will be at ease with this procedure.

Impact of a new electronic handover system in surgery.

Accurate handover of clinical information is imperative to ensure continuity of patient care, patient safety and reduction in clinical errors. Verbal and paper-based handovers are common practice in many institutions but the potential for clinical errors and inefficiency is significant. We have recently introduced an electronic templated signout to improve clarity of transfer of patient details post-surgical take. The aim of this study was to prospectively audit the introduction of this new electronic handover in our hospital with particular emphasis regarding efficacy and efficiency. The primary surrogate chosen to assess efficacy and efficiency was length of stay for those patients admitted through the emergency department. To do this we compared two separate, two-week periods before and after the introduction of this new electronic signout format. Users were not informed of the study. Information recorded on the signout included details of the emergency admissions, consults received on call and any issues with regard to inpatients. ASA grade, time to first intervention and admission diagnosis were also recorded. Our results show that introduction of this electronic signout significantly reduced median length of stay from five to four days (P=0.047). No significant difference in ASA grades, time to first intervention or overall admission diagnosis was obtained between the two time periods. In conclusion, this is the first study to show that the introduction of electronic signout post-call was associated with a significant reduction in patient length of stay and provided better continuity of care than the previously used paper-based handover.

Sputum issues as defined by patients with cystic fibrosis: a qualitative investigation.

OBJECTIVES: Patients with cystic fibrosis (CF) are asked to provide a sputum sample at clinic to test for potentially harmful pathogens. However, some appear to struggle with this request. Research into the difficulties experienced by these patients is lacking. This study set out to explore this issue in depth, using a qualitative research approach. METHODS: Semi-structured interviews were conducted with 18 patients identified as having difficulties with sputum by the physiotherapists involved in their care. Framework analysis was applied to collected data. RESULTS: An overarching concept derived from the interview material was a concern about sputum coming to be a defining feature of identity. This was reflected in the following four themes: (1) being seen as dirty because sputum is socially vilified as thus; (2) sputum exposing an invisible condition; (3) sputum acting as a reminder of having CF; (4) being seen as sputum producers by practitioners. DISCUSSION: Patients' difficulties with expectorating sputum were multifaceted and included psychosocial and physical factors. Practitioners need to appreciate that for some people, a request for sputum can cause significant discomfort. Individualized interventions to assist these patients may prove helpful.

Dose escalation of low molecular weight heparin to manage recurrent venous thromboembolic events despite systemic anticoagulation in cancer patients.

SUMMARY BACKGROUND: Cancer patients with venous thromboembolism (VTE) are at high risk of recurrent VTE despite standard anticoagulation. To date, very little published literature is available to guide the treatment of cancer patients with recurrent VTE. OBJECTIVES: To evaluate the benefit and risk of low molecular weight heparin (LMWH) dose escalation in cancer patients with recurrent VTE. PATIENTS AND METHODS: This was a retrospective cohort study of consecutive cancer outpatients referred for management of a symptomatic, recurrent VTE while receiving an anticoagulant. Confirmed episodes of recurrent VTE were treated with either dose escalation of LMWH in patients already anticoagulated with LMWH, or initiation of therapeutic dose LMWH in patients who were taking a vitamin K antagonist (VKA). All patients were followed for a minimum of 3 months after the index recurrent VTE unless they died during this period. RESULTS: Seventy cancer patients with a recurrent VTE despite ongoing anticoagulation were included. At the time of the recurrence, 67% of patients were receiving LMWH, and 33% were receiving a VKA. A total of six patients [8.6%; 95% confidence interval (CI) 4.0-17.5%] had a second recurrent VTE during the 3-month follow-up period, at an event rate of 9.9 per 100 patient-years (95% CI 2.0-17.8%). Three patients (4.3%; 95% CI 1.5-11.9%), or 4.8 per 100 patient-years (95% CI 0.0-10.3%) of follow-up, had bleeding complications. The median time between the index recurrent VTE to death was 11.4 months (range, 0-83.9 months). CONCLUSIONS: Cancer patients with recurrent VTE have a short median survival. Escalating the dose of LMWH can be effective for treating cases that are resistant to standard, weight-adjusted doses of LMWH or a VKA.

Changing trends in surgical treatment of carotid disease in Ireland (1996-2003).

BACKGROUND: Carotid endarterectomy (CEA) is a well-established method of stroke prevention in patients with symptomatic, high-grade internal carotid artery stenosis. AIMS: To assess the change in carotid surgery practice in health board regions in Ireland over two different time periods in the past 11 years (1996-1998/2001-2003). METHODS: Numbers of discharges of patients with a procedure code CEA (38.12) between 1996-1998 and 2001-2003 were obtained from the Hospital In-Patient Enquiry (HIPE) database maintained by the Economic and Social Research Institute (ESRI). Population data was obtained from national censuses. RESULTS: There has been considerable change in the level of carotid surgery activity in specific health board regions between the two periods. CONCLUSIONS: Still no region comes close to achieving levels of CEA recommended by population studies. This is important in the context of the MRC asymptomatic carotid surgery trial (ACST), as the numbers suitable for CEA will probably increase further in the future.

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.