Increasing Blood Pressure Variability Predicts Poor Functional Outcome Following Acute Stroke.

INTRODUCTION: Increasing blood pressure variability has been reported following acute stroke, but there is uncertainty about how best to measure it and about the impact on prognosis following acute ischaemic stroke and transient ischaemic attack. METHODS: Enhanced casual blood pressure and ambulatory blood pressure monitoring were completed at baseline (≤48 h post symptom onset). Blood pressure variability was defined by standard deviation and coefficient of variation of systolic, diastolic, mean arterial pressure, and pulse pressure. Modified Rankin scale score ≥3 described poor functional outcome assessed at 1- and 12-months post-stroke. Multivariable logistic regression models incorporating blood pressure variability measurement and other factors were performed, and odds ratio and 95% confidence intervals reported. RESULTS: 232 patients were recruited; 45 were dependent at 1-month, and 37 at 12-months. Dependent patients were more likely to be older, with a higher burden of pre-morbid conditions, and with increased blood pressure variability. Enhanced casual standard deviations of diastolic blood pressure [1.19 (1.02 to 1.39)] and mean arterial pressure [1.20 (1.00 to 1.43)] predicted dependency at 1-month. Predictors of 12-month dependency included: enhanced casual standard deviation of mean arterial pressure [1.21 (1.0-1.46)]; 24 h ambulatory monitor standard deviations of diastolic blood pressure [2.30 (1.08-4.90)] and mean arterial pressure [1.72 (1.09-2.72)], and the coefficient of variation of mean arterial pressure [1.76 (1.05-2.94)]; day-time ambulatory monitor coefficient of variation of systolic blood pressure [1.44 (1.02-2.03)] and mean arterial pressure [1.46 (1.02-2.08)]; and night-time ambulatory standard deviation of diastolic blood pressure [1.65 (1.03 -2.63)], and the coefficient of variation of mean arterial pressure and [1.38 (1.00- 1.90)] and pulse pressure [1.29 (1.00-1.65)]. CONCLUSION: Increasing blood pressure variability is independently and modestly associated with poor functional outcome at 1- and 12-months following acute stroke.

A Multicenter Study of Nutritional Adequacy in Neonatal and Pediatric Extracorporeal Life Support.

BACKGROUND: Malnutrition in critically ill patients is common in neonates and children, including those that receive extracorporeal life support (ECLS). We hypothesize that nutritional adequacy is highly variable, overall nutritional adequacy is poor, and enteral nutrition is underutilized in this population. MATERIALS AND METHODS: A retrospective study of neonates and children (age<18 y) receiving ECLS at 5 centers from 2012 to 2014 was performed. Demographic, clinical, and outcome data were analyzed. Continuous variables are presented as median [IQR]. Adequate nutrition was defined as meeting 66% of daily caloric goals during ECLS support. RESULTS: Two hundred and eighty three patients received ECLS; the median age was 12 d [3 d, 16.4 y] and 47% were male. ECLS categories were neonatal pulmonary 33.9%, neonatal cardiac 25.1%, pediatric pulmonary 17.7%, and pediatric cardiac 23.3%. The predominant mode was venoarterial (70%). Mortality was 41%. Pre-ECLS enteral and parenteral nutrition was present in 80% and 71.5% of patients, respectively. The median percentage days of adequate caloric and protein nutrition were 50% [0, 78] and 67% [22, 86], respectively. The median percentage days with adequate caloric and protein nutrition by the enteral route alone was 22% [0, 65] and 0 [0, 50], respectively. Gastrointestinal complications occurred in 19.7% of patients including hemorrhage (4.2%), enterocolitis (2.5%), intra-abdominal hypertension or compartment syndrome (0.7%), and perforation (0.4%). CONCLUSIONS: Although nutritional delivery during ECLS is adequate, the use of enteral nutrition is low despite relatively infrequent observed gastrointestinal complications.

Pediatric near-drowning events: do they warrant trauma team activation?

BACKGROUND: The purpose of this study was to determine the incidence of traumatic injuries, factors associated with mortality, and need for pediatric trauma surgery involvement for drowning and near-drowning events in children. MATERIALS AND METHODS: An institutional review board-approved, retrospective chart review was performed at three American College of Surgeons-verified Pediatric Trauma Centers (2011-2014). Patients with International Classification of Diseases, Ninth Revision, codes or E-codes for fatal-nonfatal drowning, fall into water, accidental drowning, or submersion were included. Bivariate analysis using chi-square or Fisher exact test for nominal variables and Mann-Whitney U test for continuous variables was performed. RESULTS: A total of 363 patients (median 3.17 y [18 d-17 y]) met the inclusion criteria. Drowning sites included pool (81.5%), bathtub (12.9%), and natural water (5.2%). A witnessed fall or dive was reported in 34.9%, 57.9% did not fall or dive, and 7% had an unwitnessed event. Most patients did not undergo cervical spine (83%) or brain imaging (75.5%). Seven patients (1.92%) had associated soft tissue injuries. Two patients (0.006%) received surgical intervention (bronchoscopy and extracorporeal membrane oxygenation) within 24 h of presentation. Only 2.2% were admitted to the pediatric trauma service. The percentage of patients discharged home from the emergency department was 10.2%. Overall mortality was 12.4%. Factors associated with mortality included transfer from outside hospital (P = 0.016), presence of hypothermia on arrival (P < 0.0001), Glasgow Coma Scale of 3 on arrival (P < 0.0001), drowning in a pool (P = 0.013), or undergoing brain cooling at admission (P = 0.011). CONCLUSIONS: This is the largest reported series of pediatric near-drowning events. Only rarely did patients require immediate surgical attention and the majority were admitted to nonsurgical services. These data suggest that routine pediatric trauma surgery service involvement in patients with near-drowning events may be unnecessary.

Balancing satisfaction and stress: carer burden among White and British Asian Indian carers of stroke survivors.

OBJECTIVES: This paper presents the findings of a qualitative study exploring White and British Indian informal stroke carers' experiences of caring, factors contributing to their stress, and strategies used to overcome stress. DESIGN: A qualitative approach involving in-depth interviews was used to explore informal carers' experiences of caring for stroke survivors and the stress of caring at one and three to six months from the onset of stroke. Interviewers bilingual in English and Gujarati or Punjabi conducted interviews with carers. Socio-demographic data of carers and stroke survivors were collected at one, and three to six months by dedicated stroke research nurses. RESULTS: A total of 37 interviews with carers caring for stroke survivors with a wide range of physical and mental impairments were completed. A majority of carers had assumed the task of caring within a few weeks of the stroke. Irrespective of ethnicity, carers' emotional and physical well-being was undermined by the uncertainty and unpredictability of caring for stroke survivors, and meeting their expectations and needs. The strain of managing social obligations to care was common to all carers irrespective of gender and ethnicity, but the higher levels of anxiety and depression reported by Indian British female carers appeared to stem from the carers' pre-existing physical ailments, their cultural and religious beliefs, and household arrangements. Carers' strain in extended households was exacerbated by the additional responsibility of caring for other dependent relatives. CONCLUSION: Since the role of carers is clearly indispensable in the successful rehabilitation of survivors, it is vital to ensure that their well-being is not undermined by a lack of information and training, and that their need for professional support is prioritised.

Prognostic Significance of Short-Term Blood Pressure Variability in Acute Stroke: Systematic Review.

BACKGROUND AND PURPOSE: Blood pressure variability (BPV) may be an important prognostic factor acutely after stroke. This review investigated the existing evidence for the effect of BPV on outcome after stroke, also considering BPV measurement techniques and definitions. METHODS: A literature search was performed according to a prespecified study protocol. Two reviewers independently assessed study eligibility and quality. Where appropriate, meta-analyses were performed to assess the effect of BPV on poor functional outcome. RESULTS: Eighteen studies from 1359 identified citations were included. Seven studies were included in a meta-analysis for the effect of BPV on functional outcome (death or disability). Systolic BPV was significantly associated with poor functional outcome: pooled odds ratio per 10-mm Hg increment, 1.2; confidence interval (1.1-1.3). A descriptive review of included studies also supports these findings, and in addition, it suggests that systolic BPV may be associated with increased risk of intracranial hemorrhage in those treated with thrombolytic therapy. CONCLUSIONS: This systematic review and meta-analysis suggest that greater systolic BPV, measured early from ischemic stroke or intracerebral hemorrhage onset, is associated with poor longer-term functional outcome. Future prospective studies should investigate how best to measure and define BPV in acute stroke, as well as to determine its prognostic significance.

Short-term blood pressure variability in acute stroke: post hoc analysis of the controlling hypertension and hypotension immediately post stroke and continue or stop post-stroke antihypertensives collaborative study trials.

BACKGROUND AND PURPOSE: Short-term blood pressure variability (BPV) may predict outcome in acute stroke. We undertook a post hoc analysis of data from 2 randomized controlled trials to determine the effect of short-term BPV on 2-week outcome. METHODS: Controlling Hypertension and Hypotension Immediately Post Stroke (CHHIPS) was a trial of BP-lowering, enrolling 179 acute stroke patients (onset<36 hours). Continue or Stop Post-Stroke Antihypertensives Collaborative Study (COSSACS) compared a strategy of continuation versus temporarily stopping prestroke antihypertensive therapy in 763 acute stroke patients (onset<48 hours). BPV at baseline (defined as SD, coefficient of variation, variation independent of the mean, and average real variability) was derived from standardized casual cuff BP measures (6 readings<30 minutes). Adjusted logistic regression models were used to assess the relation between BPV and death and disability (modified Rankin scale>3) at 2 weeks. RESULTS: Seven hundred six (92.5%) and 171 (95.5%) participants were included in the analysis for the COSSACS and CHHIPS data sets, respectively. Adjusted logistic regression analyses revealed no statistically significant associations between any of the included BPV parameters with 2-week death or disability in either study data set: COSSACS, odds ratio SD systolic BP 0.98 (0.78-1.23); CHHIPS, odds ratio SD systolic BP 0.97 (0.90-1.11). CONCLUSIONS: When derived from casual cuff BP measures, short-term BPV is not a useful predictor of early (2 weeks) outcome after acute stroke. Differing methodology may account for the discordance with previous studies indicating long-term (casual BPV) and short-term (beat-to-beat BPV) prognostic value. CLINICAL TRIAL REGISTRATION: COSSACS was registered on the International Standard Randomised Controlled Trial Register; URL: http://www.isrctn.com. Unique identifier: ISRCTN89712435. CHHIPS was registered on the National Research Register; URL: http://public.ukcrn.org.uk. Unique identifier: N0484128008.

Control of blood pressure in hypertensive neurological emergencies.

Neurological hypertensive emergencies cause significant morbidity and mortality. Most occur in the setting of ischaemic stroke, spontaneous intracerebral hemorrhage (ICH), or subarachnoid hemorrhage (SAH), but other causes relate to hypertensive encephalopathy and reversible cerebral vasoconstriction syndrome (RCVS). Prompt and controlled reduction of blood pressure (BP) is necessary, although there remains uncertainty as to the optimal rate of decline and ideal antihypertensive agent. There is probably no single treatment strategy that covers all neurological hypertensive emergencies. Prompt diagnosis of the underlying disorder, recognition of its severity, and appropriate targeted treatment are required. Lack of comparative-effectiveness data leaves clinicians with limited evidence-based guidance in management, although significant developments have occurred recently in the field. In this article, we review the management of specific neurological hypertensive emergencies, with particular emphasis on recent evidence.

Lisa Manning.

Interview with Lisa Manning, Director of the BioInspired Institute at Syracuse University.

European Stroke Organisation (ESO) guidelines on blood pressure management in acute ischaemic stroke and intracerebral haemorrhage.

The optimal blood pressure (BP) management in acute ischaemic stroke (AIS) and acute intracerebral haemorrhage (ICH) remains controversial. These European Stroke Organisation (ESO) guidelines provide evidence-based recommendations to assist physicians in their clinical decisions regarding BP management in acute stroke. The guidelines were developed according to the ESO standard operating procedure and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. The working group identified relevant clinical questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence, and made specific recommendations. Expert consensus statements were provided where insufficient evidence was available to provide recommendations based on the GRADE approach. Despite several large randomised-controlled clinical trials, quality of evidence is generally low due to inconsistent results of the effect of blood pressure lowering in AIS. We recommend early and modest blood pressure control (avoiding blood pressure levels >180/105 mm Hg) in AIS patients undergoing reperfusion therapies. There is more high-quality randomised evidence for BP lowering in acute ICH, where intensive blood pressure lowering is recommended rapidly after hospital presentation with the intent to improve recovery by reducing haematoma expansion. These guidelines provide further recommendations on blood pressure thresholds and for specific patient subgroups. There is ongoing uncertainty regarding the most appropriate blood pressure management in AIS and ICH. Future randomised-controlled clinical trials are needed to inform decision making on thresholds, timing and strategy of blood pressure lowering in different acute stroke patient subgroups.

European Stroke Organisation (ESO) guidelines on blood pressure management in acute ischaemic stroke and intracerebral haemorrhage.

The optimal blood pressure (BP) management in acute ischaemic stroke (AIS) and acute intracerebral haemorrhage (ICH) remains controversial. These European Stroke Organisation (ESO) guidelines provide evidence-based recommendations to assist physicians in their clinical decisions regarding BP management in acute stroke.The guidelines were developed according to the ESO standard operating procedure and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. The working group identified relevant clinical questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence, and made specific recommendations. Expert consensus statements were provided where insufficient evidence was available to provide recommendations based on the GRADE approach. Despite several large randomised-controlled clinical trials, quality of evidence is generally low due to inconsistent results of the effect of blood pressure lowering in AIS. We recommend early and modest blood pressure control (avoiding blood pressure levels >180/105 mm Hg) in AIS patients undergoing reperfusion therapies. There is more high-quality randomised evidence for BP lowering in acute ICH, where intensive blood pressure lowering is recommended rapidly after hospital presentation with the intent to improve recovery by reducing haematoma expansion. These guidelines provide further recommendations on blood pressure thresholds and for specific patient subgroups. There is ongoing uncertainty regarding the most appropriate blood pressure management in AIS and ICH. Future randomised-controlled clinical trials are needed to inform decision making on thresholds, timing and strategy of blood pressure lowering in different acute stroke patient subgroups.

Highly pathogenic avian influenza virus A (H7N3) in domestic poultry, Saskatchewan, Canada, 2007.

Epidemiologic, serologic, and molecular phylogenetic methods were used to investigate an outbreak of highly pathogenic avian influenza on a broiler breeding farm in Saskatchewan, Canada. Results, coupled with data from influenza A virus surveillance of migratory waterfowl in Canada, implicated wild birds as the most probable source of the low pathogenicity precursor virus.

National Society for Histotechnology and Digital Pathology Association Online Self-Paced Digital Pathology Certificate of Completion Program.

The field of digital pathology has rapidly expanded within the last few years with increasing adoption and growth in popularity. As digital pathology matures, it is apparent that we need well-trained individuals to manage our whole-slide imaging systems. This editorial introduces the joint National Society for Histotechnology and Digital Pathology Association online self-paced digital pathology certificate program which was launched in May 2018 that was established to meet this demand. An overview of how this program was developed, the content of the educational modules, and the way that this program is being offered is discussed.

Fit-For-Purpose PD-L1 Biomarker Testing For Patient Selection in Immuno-Oncology: Guidelines For Clinical Laboratories From the Canadian Association of Pathologists-Association Canadienne Des Pathologistes (CAP-ACP).

Since 2014, programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) checkpoint inhibitors have been approved by various regulatory agencies for the treatment of multiple cancers including melanoma, lung cancer, urothelial carcinoma, renal cell carcinoma, head and neck cancer, classical Hodgkin lymphoma, colorectal cancer, gastroesophageal cancer, hepatocellular cancer, and other solid tumors. Of these approved drug/disease combinations, a subset also has regulatory agency-approved, commercially available companion/complementary diagnostic assays that were clinically validated using data from their corresponding clinical trials. The objective of this document is to provide evidence-based guidance to assist clinical laboratories in establishing fit-for-purpose PD-L1 biomarker assays that can accurately identify patients with specific tumor types who may respond to specific approved immuno-oncology therapies targeting the PD-1/PD-L1 checkpoint. These recommendations are issued as 38 Guideline Statements that address (i) assay development for surgical pathology and cytopathology specimens, (ii) reporting elements, and (iii) quality assurance (including validation/verification, internal quality assurance, and external quality assurance). The intent of this work is to provide recommendations that are relevant to any tumor type, are universally applicable and can be implemented by any clinical immunohistochemistry laboratory performing predictive PD-L1 immunohistochemistry testing.

A collaborative Canadian-United Kingdom evaluation of an immunohistochemistry protocol to diagnose bovine spongiform encephalopathy.

Collaboration was established in 2001 to evaluate a commercially available immunohistochemistry assay kit for the detection of bovine spongiform encephalopathy (BSE) disease-associated prion protein in formic acid-treated formalin-fixed samples of bovine brain. The kit protocol was evaluated at the National Centre for Foreign Animal Diseases (Winnipeg, Canada) and the Veterinary Laboratories Agency (Weybridge, U.K.). The U.K. laboratory provided paraffin-embedded blocks of brainstem (medulla oblongata at the level of the obex) from 100 positive cases defined by clinical signs and histopathology, and 100 clinically suspect but BSE-negative samples defined by histopathology and immunohistochemistry with anti-PrP monoclonal antibody R145. The Canadian laboratory provided 400 blocks from surveillance cases defined as clinically suspect but negative by histopathology and immunohistochemistry with anti-PrP antibody 6H4. Consecutive sections from each block were cut and coded. Each set of 600 slides was immunolabeled and read in each laboratory. Evaluation parameters included estimates of diagnostic sensitivity and specificity and reproducibility of the results. The kit performed with 100% sensitivity, specificity, and reproducibility in spite of minor differences between the laboratories in brain sample areas, fixation and processing, and in the immunolabeling protocol. Although enzyme linked immunosorbent assays are widely used in high throughput surveillance programs, standardized protocols and reagents for manual immunohistochemistry provide a useful adjunct to surveillance efforts, particularly in laboratories testing small numbers of samples or using immunohistochemistry for confirmation and characterization of BSE cases.

Suggested guidelines for immunohistochemical techniques in veterinary diagnostic laboratories.

This document is the consensus of the American Association of Veterinary Laboratory Diagnosticians (AAVLD) Subcommittee on Standardization of Immunohistochemistry on a set of guidelines for immunohistochemistry (IHC) testing in veterinary laboratories. Immunohistochemistry is a powerful ancillary methodology frequently used in many veterinary laboratories for both diagnostic and research purposes. However, neither standardization nor validation of IHC tests has been completely achieved in veterinary medicine. This document addresses both issues. Topics covered include antibody selection, fixation, antigen retrieval, antibody incubation, antibody dilutions, tissue and reagent controls, buffers, and detection systems. The validation of an IHC test is addressed for both infectious diseases and neoplastic processes. In addition, storage and handling of IHC reagents, interpretation, quality control and assurance, and troubleshooting are also discussed. Proper standardization and validation of IHC will improve the quality of diagnostics in veterinary laboratories.

Continuing or Temporarily Stopping Prestroke Antihypertensive Medication in Acute Stroke: An Individual Patient Data Meta-Analysis.

Over 50% of patients are already taking blood pressure-lowering therapy on hospital admission for acute stroke. An individual patient data meta-analysis from randomized controlled trials was undertaken to determine the effect of continuation versus temporarily stopping preexisting antihypertensive medication in acute stroke. Key databases were searched for trials against the following inclusion criteria: randomized design; stroke onset ≤48 hours; investigating the effect of continuation versus stopping prestroke antihypertensive medication; and follow-up of ≥2 weeks. Two randomized controlled trials were identified and included in this meta-analysis of individual patient data from 2860 patients with ≤48 hours of acute stroke. Risk of bias in each study was low. In adjusted logistic regression and multiple regression analyses (using random effects), we found no significant association between continuation of prestroke antihypertensive therapy (versus stopping) and risk of death or dependency at final follow-up: odds ratio 0.96 (95% confidence interval, 0.80-1.14). No significant associations were found between continuation (versus stopping) of therapy and secondary outcomes at final follow-up. Analyses for death and dependency in prespecified subgroups revealed no significant associations with continuation versus temporarily stopping therapy, with the exception of patients randomized ≤12 hours, in whom a difference favoring stopping treatment met statistical significance. We found no significant benefit with continuation of antihypertensive treatment in the acute stroke period. Therefore, there is no urgency to administer preexisting antihypertensive therapy in the first few hours or days after stroke, unless indicated for other comorbid conditions.

Noninvasive hemoglobin measurement in pediatric trauma patients.

INTRODUCTION: Hemorrhage is a major cause of preventable death secondary to traumatic injury. Diagnosis often requires multiple blood draws, which are psychologically stressful in pediatric patients. The Pronto device is a pulse co-oximeter that measures the total hemoglobin level using multiple wavelengths of light. The purpose of this study was to evaluate the accuracy of the noninvasive hemoglobin measurements relative to current invasive and point of care testing methods in pediatric trauma patients. METHODS: We performed a prospective observational trial involving patients younger than 17 years presenting to a Level I pediatric trauma center. Following admission, blood was sampled from each patient for testing using an i-Stat device (point-of-care hemoglobin) and a complete blood count within our core laboratory (invasive hemoglobin). Noninvasive hemoglobin analysis was performed within 15 minutes of phlebotomy. Data were evaluated using Spearman correlation and Bland-Altman analysis. RESULTS: Over 2 years, 114 patients had attempted noninvasive hemoglobin measurements, with a success rate of 89%. Mean ± SD age was 9.2 ± 5.1 years. Ninety percent of admissions were for blunt injury, 3% penetrating, 5% near drowning, and 1% burns. Mean invasive hemoglobin was 12.6 ± 1.9 g/dL, mean point-of-care hemoglobin was 12.2 ± 2.0 g/dL, and mean noninvasive hemoglobin was 12.3 ± 1.6 g/dL. Noninvasive hemoglobin values were strongly correlated with both invasive and point of care measurements (R = 0.672 and R = 0.645, respectively; p < 0.001). Bland-Altman analysis comparing noninvasive to point-of-care and invasive hemoglobin levels resulted in an estimated bias of -0.39 and -0.49, respectively. CONCLUSION: Noninvasive hemoglobin values had excellent correlation with both invasive and point-of-care hemoglobin measurements, although the device was not successful for all patients. Given the rapid availability of results and the lack of requirement of venipuncture, noninvasive hemoglobin monitoring may be a valuable adjunct in the initial evaluation and monitoring of pediatric trauma patients. LEVEL OF EVIDENCE: Diagnostic test study, level II.

New Insights into Blood Pressure Control for Intracerebral Haemorrhage.

Although blood pressure (BP) levels may rise in the weeks preceding intracerebral haemorrhage (ICH), in contrast to findings in the ischaemic stroke population, the initial post-ICH BP is often much higher than the last pre-morbid level. Elevated BP is therefore common in acute ICH, often with markedly elevated levels, and is associated with poor outcomes, though the exact pathophysiological mechanisms remain unclear. The Antihypertensive Treatment of Acute Cerebral Haemorrhage (ATACH) trial and the INTEnsive blood pressure Reduction in Acute Cerebral haemorrhage Trial (INTERACT) demonstrated that early and intensive lowering of elevated BP in the acute ICH period is feasible and safe. Importantly, recent CT perfusion studies have shown that early, intense BP reduction does not reduce cerebral blood flow or promote cerebral ischaemia. The recent, large INTERACT2 trial confirmed the safety of early BP lowering in ICH and suggested that intensive target-driven BP reduction may improve outcomes, with a non-significant trend towards reduced death and major disability and a significant favourable shift of scores on the modified Rankin scale compared with guideline-based treatment. BP lowering in acute ICH may reduce haematoma growth, particularly when target levels are achieved early and are sustained, though the evidence is partly conflicting. Other aspects of BP may also be important following acute ICH, with maximum systolic BP and systolic BP variability being independent predictors of poor outcomes in a recent study. This chapter gives an overview of the current evidence regarding BP in ICH and covers the following topics: the incidence of elevated BP in acute ICH and the patterns of BP observed before and after the event; the effect of elevated BP on outcomes in ICH and the potential underlying pathophysiological mechanisms; the safety and feasibility of BP lowering; the effects of BP lowering on clinical and radiological outcomes; other important aspects of BP in ICH; and the choice of antihypertensive agent.