Time-to-positivity in bloodstream infection for Candida species as a prognostic marker for mortality.

Time-to-positivity (TTP) may assist in predicting the outcome of candidaemia. We analysed a candidaemia dataset collected prospectively in Australia over 1 year (2014-2015). TTP was defined as the period from blood culture sampling to the blood culture flagging positive. Of 415 candidaemia episodes, overall, 30-day mortality was 29% (120/415); mortality with Candida albicans was 35% (59/169), C. glabrata complex, 37% (43/115), C. tropicalis, 43% (10/23), Pichia kudriavzevii 25% (3/12), and C. parapsilosis complex 7% (5/71). Each day of increased TTP multiplied the odds ratio (OR) of survival at 30 days by a factor of 1.32 [95% confidence interval (CI) 1.06-1.69]. Shorter TTP was associated with increased mortality, with 1-day TTP associated with 30-day mortality 37% (41/112) (95%CI: 28%-46%) and 5-day TTP 11% (2/18) (95%CI: 2%-36%).

Time-to-positivity is a measure that is available to clinicians when patients are identified as having candida in their bloodstream. Our data support the association of a shorter time to positivity with higher mortality.

Obstructive sleep apnea during REM sleep: effects on morning and evening blood pressure.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is linked to the emergence and progression of cardiovascular complications including hypertension, stroke, arrhythmias, coronary artery disease, and heart failure. Epidemiological studies have reported that hypertension is associated with respiratory events during REM sleep. We examined the relationship between respiratory events during REM and morning and evening hypertensive blood pressure (BP) levels in a clinical sleep population. METHODS: This study included data from in-laboratory diagnostic polysomnographic studies (n = 797) from adults attending for investigation of OSA. Hypertensive BP levels were defined using BP measurements taken in the evening before and morning after polysomnography, and the use of antihypertensive medication. Regression modeling was undertaken to examine the probability of evening and morning hypertensive BP levels according to REM apnea-hypopnea index (AHI), NREM AHI, gender, age, body mass index (BMI), alcohol use, total sleep time (TST), sleep time SpO2 <90%, and smoking status. RESULTS: The probability of morning hypertensive BP levels was significantly independently associated with age (p < .001), BMI (p < .001), and REM AHI (p < .001). No significant effect was found for the male gender, NREM AHI, alcohol use, TST, sleep time SpO2 <90%, or smoking (p > .05 for all). The probability of evening hypertensive BP levels was only significantly associated with age (p < .001), male gender (p = .012), BMI (p < .001), and TST (p = .032). CONCLUSIONS: Respiratory events during REM sleep are significantly associated with morning hypertensive BP levels. Future research is needed to determine whether treatment of these events can prevent or reverse morning hypertensive BP levels.

Negative predictive value of the FebriDx host response point-of-care test in patients presenting to a single Australian emergency department with suspected COVID-19: an observational diagnostic accuracy study.

OBJECTIVES: To determine the negative predictive value (NPV) of the FebriDx point-of-care host response device in patients presenting with symptoms suggestive of COVID-19 infection in a mostly immunised Australian emergency department (ED) population during the late 2021 phase of the COVID-19 pandemic. DESIGN: Observational diagnostic accuracy study comparing FebriDx point-of-care test to SARS-CoV-2 PCR. SETTING: An ED in Melbourne, Australia, with 63 000 annual presentations in 2021. PARTICIPANTS: Patients aged 16 and over who met the Victorian Department of Health case definition for suspected COVID-19 infection PCR testing. Patients meeting any of the following criteria were excluded: <16 years of age; acute respiratory symptom(s) with onset>14 days prior to testing; current immunosuppressive or interferon therapy; live immunisation within the last 30 days; fever lasting>7 days; antibiotic or antiviral use in the preceding 14 days; experience of major trauma, major surgical intervention or severe burns within the last 30 days. PRIMARY AND SECONDARY OUTCOME MEASURES: COVID-19 PCR results (detected, not detected) and FebriDx results (bacterial positive, viral negative, viral positive). RESULTS: 94 participants were enrolled (female: 46; male: 48), 34% of participants (tested positive for COVID-19 according to PCR results, with a background incidence among all adult ED attenders of 2.5%. The sensitivity of FebriDx for detection of COVID-19 was 56% (95% CI 40% to 100%) and specificity was 92% (95% CI 84% to 100%). For the population tested, this resulted in an NPV of 80% (95% CI 71% to 100%) and a positive predictive value of 78% (95% CI 60% to 100%). CONCLUSIONS: In the context of a population with low COVID-19 infection rates, an evolved variant of COVID-19 and a very high community COVID-19 vaccination rate, FebriDx demonstrated reduced sensitivity and NPV relative to results from earlier international tests. These contextual factors should be considered during any attempt to generalise the current results. TRIAL REGISTRATION NUMBER: ACTRN12620001029987 (Australian Clinical Trials).

Integrated Geriatric Assessment and Treatment Effectiveness (INTEGERATE) in older people with cancer starting systemic anticancer treatment in Australia: a multicentre, open-label, randomised controlled trial.

BACKGROUND: The effectiveness of comprehensive geriatric assessment (CGA) in improving health outcomes in cancer settings is unclear. We evaluated whether CGA can improve health-related quality of life (HRQOL) in older people with cancer who are starting systemic anticancer treatment. METHODS: INTEGERATE is a multicentre, open-label, pragmatic, parallel-group, randomised controlled trial that was done at three hospitals in Australia. Participants aged 70 years and older with solid cancer or diffuse large B-cell lymphoma planned for chemotherapy, targeted therapy, or immunotherapy, were randomly assigned (1:1; using a central computer-generated minimisation algorithm with a random element, balancing treatment intent, cancer type, age, sex, and performance status) to receive CGA integrated into oncology care (integrated oncogeriatric care) or usual care only. Group assignment was not concealed from the participants and clinicians. The primary outcome was HRQOL over 24 weeks, assessed at baseline, week 12, week 18, and week 24, using the Elderly Functional Index (ELFI; score range 0-100). Analyses were by intention to treat. The trial is registered with ANZCTR.org.au, ACTRN12614000399695, and is completed. FINDINGS: Between Aug 18, 2014, and Sept 5, 2018, 154 participants were randomly assigned to integrated oncogeriatric care (n=76) or usual care (n=78). 13 participants died by week 12 and 130 (92%) of the remaining 141 participants completed two or more ELFI assessments. Participants assigned to integrated oncogeriatric care reported better adjusted ELFI change scores over 24 weeks compared with those in the usual care group (overall main effect of group: t=2·1, df=213, p=0·039; effect size=0·38), with maximal between-group differences at week 18 (mean difference in change 9·8 [95% CI 2·4-17·2]; p=0·010, corrected p=0·030, effect size=0·48). The integrated oncogeriatric care group also had significantly fewer unplanned hospital admissions at 24 weeks (multivariable-adjusted incidence rate ratio 0·60 [95% CI 0·42-0·87]; p=0·0066). No statistically significant between-group difference was observed in overall survival. INTERPRETATION: CGA led to better quality of life and health-care delivery in older people receiving systemic anticancer treatment. Routine CGA-based interventions should be considered in at-risk older people starting systemic anticancer treatment. FUNDING: National Health and Medical Research Council (Australia), Monash University, and Eastern Health.

Large Vessel Occlusion Sites Affect Agreement Between Outputs of Three Computed Tomography Perfusion Software Packages.

OBJECTIVES: Computed tomography perfusion (CTP) data are important for hyperacute stroke decision making. Available comparisons between outputs of different CTP software packages show variable outcomes. Evaluation for factors associated with agreement between the volume estimates is limited. We assessed for differences in core and penumbra volume estimates of three CTP software packages - AutoMIStar, RAPID, and Vitrea - and analyzed factors associated with agreement between the volume estimates. MATERIALS AND METHODS: Differences between software estimates of penumbra and core volumes were calculated for each patient with suspected acute ischemic stroke who underwent CTP. Exploratory hierarchical clustering and principal component analysis were performed to identify factors of decreased volume estimate agreement. Two-sample t-tests were performed, stratified by large vessel occlusion (LVO) location. RESULTS: 579 CTP studies were performed; 267 were normal, 139 artifacts, with 172 included in the final analysis. 79/172 had LVO of internal carotid artery (ICA, n = 20), M1 (n = 38) and proximal M2 (n = 21). LVO was the only factor associated with decreased software package agreement, and proximal LVO location was associated with general trend of increasing mean differences and standard deviations between software packages (range of mean differences [SD]: non-LVO, -17-6 [4-33] ml; M2, -40-13 [5-39] ml; M1, -43-26 [16-58] ml; ICA, -76-39 [22-97] ml). CONCLUSIONS: Core and penumbra volume estimates can be affected by LVO location significantly between CTP software packages.

The quest to reduce stroke treatment delays at a Melbourne metropolitan primary stroke centre over the past two decades.

BACKGROUND: Reducing door-to-needle time (DNT) for intravenous thrombolysis in acute ischaemic stroke can lead to improved patient outcomes. Long-term reports on DNT trends in Australia are lacking in the setting of extension of the thrombolysis time window, addition of mechanical thrombectomy and increasing presentations. AIMS: To examine 17-year trends of DNT and identify factors associated with improved DNT at a high-volume, metropolitan primary stroke centre. METHOD: Retrospective study between 2003 and 2019 of all thrombolysis cases using departmental stroke database. Since most strategies were implemented from 2012 onwards, intervention period has been defined as period 2012-2019. Factors associated with DNT reduction were examined by regression modelling. RESULTS: Fifteen strategies were identified including alterations to 'Code Stroke' processes. One thousand, two hundred and fifty patients were thrombolysed, with 737 (58.8%) treated during the intervention period. The proportion of DNT ≤60-min rose from average of 22.5% during 2003-2012 to 63% during 2015-2018 and 71% in 2019. However, median DNT has only marginally improved from 58 to 51 min between 2015 and 2019. Faster DNT was independently associated with two modifiable workflow factors, 'Direct-to-CT' protocol (P < 0.001) and acute stroke nurse presence (P < 0.005). Over time, treated patients were older and less independent (P < 0.001), and the number of annual stroke admissions and 'Code Stroke' activations have risen by fourfold and 10-fold to 748 and 1298 by 2019 respectively. CONCLUSIONS: Targeted quality improvement initiatives are key to reducing thrombolysis treatment delays in the Australian metropolitan setting. Relative stagnation in DNT improvement is concerning and needs further investigation.

Point of care ankle pulse waveform: A biomarker for abdominal aortic aneurysm?

OBJECTIVE: To explore the potential relationship between the presence of abdominal aortic aneurysm and point of care ankle brachial index acquired posterior tibial artery Doppler waveform to inform on a potential novel biomarker of abdominal aortic aneurysm presence. METHODS: Abdominal aortic aneurysm presence and posterior tibial artery waveform acquired at time of routine point of care ankle brachial index were determined in 182 patients from an abdominal aortic aneurysm evaluation vascular outpatient clinic. Multivariate technical random forest analysis and logistical regression analysis assessed the outcome of abdominal aortic aneurysm presence and included the independent variables of monophasic initial posterior tibial artery waveform and known abdominal aortic aneurysm risk factors. RESULTS: Technical random forest analysis produced a model with an accuracy of 0.59. Initial waveform phase was the most important variable included in the model. Logistical regression analysis revealed a statistically significant negative association between initial monophasic posterior tibial artery waveform and abdominal aortic aneurysm presence in patients with ankle brachial index > 0.9. Leave one out cross validation analysis produced a bias-corrected prediction error value of 0.22. CONCLUSION: No robust association between abdominal aortic aneurysm and point of care ankle brachial index acquired posterior tibial artery waveform was found, suggesting that monophasic posterior tibial artery waveform alone may not be a biomarker of abdominal aortic aneurysm presence.

No Difference in Functional, Radiographic, and Survivorship Outcomes Between Direct Anterior or Posterior Approach THA: 5-Year Results of a Randomized Trial.

BACKGROUND: Both the direct anterior approach (DAA) and posterior approach (PA) to THA have known advantages and disadvantages. The comparison between DAA and PA THA has been widely explored during the early postoperative period. However, few randomized trials have compared these approaches at a minimum follow-up of 5 years; doing so would be important to establish any differences in mid-term outcomes or complications. QUESTIONS/PURPOSES: We performed a randomized trial comparing DAA and PA in THA in terms of (1) patient-reported outcome scores, (2) quality of life and functional outcomes assessed by the EQ-5D and 10-meter walk test results, (3) radiographic analysis, and (4) survivorship and surgical complications at a minimum of 5 years follow-up. METHODS: Two hip specialist surgeons performed both DAA and PA THA using the same THA components at two hospital sites. One hundred twelve patients on the elective THA surgical waitlist were invited to participate in the study. Thirty-four patients did not meet the study's inclusion criteria and were excluded, and three patients declined to participate in the study. The remaining 75 patients who were eligible were randomized into DAA and PA groups. Thirty-seven patients were initially randomized to receive DAA THA, but two did not and were excluded, resulting in 48% (35 of 73) of patients who received DAA THA; 52% (38 of 73) of patients were randomized into and received PA THA. Over a minimum 5 years of follow-up, 3% (1 of 35) of DAA patients were lost to follow-up, and none of the patients undergoing PA THA were lost. A per-protocol analysis was adopted, resulting in further patients being excluded from analysis. Of the 73 study patients, 99% (72; DAA: 35, PA: 37) were analyzed at 1 year, 95% (69; DAA: 34, PA: 35) were analyzed at 2 years, and 72% (52; DAA: 23, PA: 29) were analyzed at 5 years. The primary outcome was the Oxford Hip Score (OHS) and WOMAC score. Secondary outcomes included the EQ-5D and EQ-5D VAS scores, 10-meter walk test results, radiographic evidence of loosening (femoral: lucency > 2 mm at the implant-bone interface, subsidence > 2 mm; acetabular: migration or change in inclination), 5-year survivorship analysis from all-cause revisions, and surgical complications. The study was powered to detect a 10-point difference in the WOMAC score, which is equivalent to the minimum clinically important difference (MCID). RESULTS: There were no differences in primary outcomes (OHS and WOMAC scores) or secondary outcomes (EQ-5D scores, EQ-5D VAS scores, and 10-meter walk test result) between the DAA and PA groups at the 5-year follow-up interval. The median (range) OHS at 5 years was 46 (16 to 48) for DAA and 47 (18 to 48) for PA groups (p = 0.93), and the median WOMAC score was 6 (0 to 81) for DAA and 7 (0 to 59) for PA groups (p = 0.96). The median EQ-5D score was 1 (0.1 to 1) for DAA and 1 (0.5 to 1) for PA groups (p = 0.45), and the median EQ-5D VAS score was 85 (60 to 100) for DAA and 95 (70 to 100) for PA groups (p = 0.29). There were no cases of component loosening on radiographs. There was no difference in component survival between the two approaches at 5 years (DAA: 97% [95% CI 85% to 100%] versus PA: 97% [95% CI 87% to 100%]). Eight of 23 patients in the DAA group reported decreased sensation in the lateral femoral cutaneous nerve distribution. CONCLUSION: DAA and PA are both effective approaches in performing primary THA. Each approach has its associated risks and complications. The choice of THA should be based on individual patient factors, surgeon experience, and shared decision-making. Early registry data indicate DAA and PA THA are comparable, but longer-term data with larger numbers of patients will be required before one can safely conclude equal survivorship between both approaches. LEVEL OF EVIDENCE: Level I, therapeutic study.

Intraoperative fluoroscopy alone versus routine post-operative X-rays in identifying return to theatre after fracture fixation.

BACKGROUND: Post-operative imaging aims to assess fracture reduction and fixation with better resolution than intraoperative fluoroscopy (IF). However, this routine practice may increase costs and delay the discharge of patients. The aim of this study is to assess the role of post-operative imaging in identifying patients that require a return to theatre following the use of IF. METHODS: A retrospective cohort study was conducted in a single health network comprising of two hospitals over 1 year. All fracture fixations that required IF were included. Patients who had post-operative imaging were identified and complications requiring a return to theatre were obtained. Non-trauma patients and those who did not have IF were excluded. RESULTS: A total of 1319 patients had IF. Of these patients, 1131 patients had post-operative radiographs within 7 days of their operation. In total, 12 patients (1.1%) returned to theatre as a result of a finding identified in their post-operative imaging. The calculated number of X-rays required to be taken to identify a complication was 94. The main reasons identified for these cases to require a return to theatre despite having had IF included: (i) insufficient quality/views of IF, (ii) loss of position/new injury occurring in post-operative period and (iii) poor reduction/fixation demonstrated intraoperatively that was missed/accepted. CONCLUSION: The use of post-operative radiographs can identify significant complications despite the use of IF in trauma patients. However, further consideration needs to be made regarding the benefits and costs of this practice in evaluating its clinical effectiveness.

Endothelial glycocalyx damage in kidney disease correlates with uraemic toxins and endothelial dysfunction.

BACKGROUND: Damage to the endothelial glycocalyx is an early indicator of vascular damage and a potential marker of endothelial dysfunction. This study aimed to assess the relationship between markers of glycocalyx damage, endothelial dysfunction, and uraemic toxins in patients with chronic kidney disease. METHODS: Healthy controls, CKD patients, dialysis patients, and kidney transplant recipients had biochemical markers of glycocalyx damage (syndecan-1 and hyaluronan), endothelial dysfunction (von Willebrand factor; vWF and vascular cell adhesion molecule; VCAM-1), and uraemic toxins (indoxyl sulphate and p-cresyl sulphate) measured. In addition, Sidestream Darkfield imaging was performed using the novel GlycoCheck™ device to measure glycocalyx width by the perfused boundary region (PBR) in the sublingual microcirculation. RESULTS: Serum markers of glycocalyx damage were highest in the dialysis group (n = 33), followed by CKD patients (n = 32) and kidney transplant recipients (n = 30) compared to controls (n = 30): hyaluronan: 137 (16-1414), 79 (11-257), 57 (14-218) and 23 (8-116) ng/mL, respectively, p < 0.0001; syndecan-1: 81 (40-529), 46 (21-134), 39 (23-72), and 30 (12-138) ng/mL, respectively, p < 0.0001. Markers of endothelial dysfunction followed a similar pattern. No difference in the width of the PBR was detected between these groups (2.01 ± 0.35, 2.07 ± 0.27, 2.06 ± 0.28, and 2.05 ± 0.3 µm, respectively, p = 0.89). Glycocalyx damage correlated with markers of endothelial dysfunction (log-hyaluronan and log-VCAM-1: r = 0.64, p < 0.001) and levels of uraemic toxins (log-hyaluronan and log-indoxyl sulphate: r = 0.48, p < 0.001). CONCLUSIONS: Levels of biochemical markers of glycocalyx and endothelial cell damage are highest in patients receiving dialysis. Glycocalyx and endothelial damage markers correlated with each other, and with uraemic toxins. Although we could not demonstrate a change in PBR, the biochemical markers suggest that glycocalyx damage is most marked in patients with higher levels of uraemic toxins.

The Elderly Functional Index (ELFI), a patient-reported outcome measure of functional status in patients with cancer: a multicentre, prospective validation study.

BACKGROUND: Functional assessment of patients with cancer can be challenging and is often undertaken by the clinician with minimal direct input from the patient. We developed and aimed to validate the Elderly Functional Index (ELFI), a composite measure of self-reported functioning in older patients with cancer. METHODS: In this multicentre, prospective validation study, we validated ELFI in adult patients attending five oncology practices in Australia. ELFI is a 12-item composite measure of self-reported functioning derived from functional scales of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ): physical, role, and social functioning, and mobility. For evaluation of validity and internal consistency, participants self-completed ELFI, cognitive functioning and emotional functioning scales of the EORTC QLQ Core-30, Eastern Cooperative Oncology Group Performance Status (ECOG-PS), instrumental activities of daily living (IADL), and Clinical Frailty Scale (CFS) at baseline. For evaluation of test-retest reliability, participants opted in to repeat ELFI, cognitive functioning scale, emotional functioning scale, and ECOG-PS 1 week later, as well as completing the Global Rating of Change. Internal consistency reliability was assessed using Cronbach's α and test-retest reliability was assessed using intraclass correlation (ICC). We assessed ELFI for convergent and discriminant validity (Spearman's r), known-groups validity (ANOVA), and structural validity (exploratory factor analysis). FINDINGS: Between May 6 and Dec 15, 2017, 877 participants with cancer returned a total of 869 baseline questionnaires and 482 retest questionnaires. 621 (71%) participants (192 [31%] aged ≥70 years) were included in evaluations of validity and internal consistency and 278 (32%) participants (106 [38%] aged ≥70 years) in evaluations of test-retest reliability. ELFI demonstrated excellent internal consistency reliability (Cronbach's α=0·93 for all participants; p<0·0001) and test-retest reliability (overall ICC 0·90, 95% CI 0·87-0·92; p<0·0001). Hypotheses regarding convergent and discriminant validity were confirmed, with all item-scale correlations exceeding 0·40 except for one on the physical functioning scale. ELFI was better than its component scales and other function measures at differentiating between groups with different function and frailty scores (known-groups validity). Exploratory factor analysis provided empirical support to the structural validity of ELFI. Strong correlation was observed between ELFI and its component scales (r ranging from 0·67 to 0·79), ECOG-PS (-0·79), IADL (0·69), and CFS (-0·73). INTERPRETATION: ELFI is a validated and simple person-reported multidimensional measure of functional status, which captures broad dimensions of functioning. ELFI has enhanced statistical efficiency relative to its components, reducing the sample size required to detect a given effect. ELFI could be used as a clinical trial endpoint to assess functional domains of health-related quality of life. FUNDING: National Health and Medical Research Council, Monash University, Eastern Health.

Risk factors for candidaemia: A prospective multi-centre case-control study.

OBJECTIVES: Candidaemia carries a mortality of up to 40% and may be related to increasing complexity of medical care. Here, we determined risk factors for the development of candidaemia. METHODS: We conducted a prospective, multi-centre, case-control study over 12 months. Cases were aged ≥18 years with at least one blood culture positive for Candida spp. Each case was matched with two controls, by age within 10 years, admission within 6 months, admitting unit, and admission duration at least as long as the time between admission and onset of candidaemia. RESULTS: A total of 118 incident cases and 236 matched controls were compared. By multivariate analysis, risk factors for candidaemia included neutropenia, solid organ transplant, significant liver, respiratory or cardiovascular disease, recent gastrointestinal, biliary or urological surgery, central venous access device, intravenous drug use, urinary catheter and carbapenem receipt. CONCLUSIONS: Risk factors for candidaemia derive from the infection source, carbapenem use, host immune function and organ-based co-morbidities. Preventive strategies should target iatrogenic disruption of mucocutaneous barriers and intravenous drug use.

Masked Hypertension: A Systematic Review.

BACKGROUND: Masked phenomenon, Masked Hypertension (MHT) and Masked Uncontrolled Hypertension (MUCH) is a well-defined clinical entity. However, many aspects of MHT/MUCH remain unclear. METHODS: We systematically reviewed the published literature on MHT/MUCH from 1 January 2000 to 31 June 2018 with a particular focus on epidemiology, clinical significance, evaluation and management. Meta-analyses were performed with respect to prevalence, clinical significance and diagnostic agreement between home blood pressure (HBP) and ambulatory BP (ABP) measurements. RESULTS: The overall weighted-mean prevalence of masked phenomenon was 11% [9,14]; MHT 10% [9,11]; and MUCH 13% [8,17]. The weighted-mean prevalence when expressed as a proportion of patients with normal office BP was 32% [25,40]; MHT 28% [15,41]; and MUCH 43% [29,57]. The prevalence of masked phenomenon determined by ABP (11% [8,14]) and HBP (13% [9,16]), was similar. However, ABP appeared to have a greater sensitivity, i.e. proportion of patients diagnosed as having MHT/MUCH was greater with ABP than with HBP (22% v 16%, p<0.05), when both methodologies were applied to the same cohort of patients. The prevalence of MHT was influenced by ethnicities and comorbidities, and in case of MUCH by anti-hypertensive treatment. MHT/MUCH was associated with increased risk of fatal and non-fatal cardiac/cerebrovascular events (relative risk [RR] 2.09 [1.80, 2.44]), and the risk was comparable to sustained hypertension (SHT) (RR 2.26 [1.84, 2.78]). The increased risk occurred regardless of the method of out of office BP assessment; the relative risks for ABP and HBP were 2.38 [1.90, 2.98] and 1.90 [1.57, 2.29] respectively. The diagnostic agreement between ABP and HBP was only modest, kappa = 0.46 [0.40, 0.52], even though the percentage agreement was 83%. The evidence for the management of MHT was scant. CONCLUSIONS: MHT/MUCH is a common BP phenotype with a risk profile similar to that of SHT. Therefore, high risk patients should undergo out of office BP assessment, probably both by HBP and ABP, to confirm diagnosis and be considered for treatment.

Positive youth development and gender differences in high performance sport.

We examined positive youth development within a high performance sport environment. Youth football players (N = 455; Males = 315; Females = 140) completed a range of questionnaires including: the Youth Experiences Survey for Sport; Self-Confidence subscale of the Competitive State Anxiety Inventory-2 Revised; Sport Competence Inventory; Prosocial and Antisocial Behaviour in Sport Scale; and the modified Coach-Athlete Relationship questionnaire. The players reported a relatively high level of self-confidence, competence and positive youth experiences. They felt a strong coach-athlete relationship and displayed higher levels of prosocial than antisocial behaviour. Males scored significantly higher than females on self-confidence, perceived self-competence, antisocial behaviour to teammates and opponents, relationship with their coach, and cognitive skills. Findings suggest a relationship between high performance sport environments and positive youth development.

Door-in-Door-Out Time of 60 Minutes for Stroke With Emergent Large Vessel Occlusion at a Primary Stroke Center.

Background and Purpose- Rapid reperfusion with mechanical thrombectomy in ischemic strokes with emergent large vessel occlusions leads to significant reduction in morbidity and mortality. The door-in-door-out (DIDO) time is an important metric for stroke centers without an on-site mechanical thrombectomy service. We report the outcome of a continuous quality improvement program to improve the DIDO time since 2015. Methods- Retrospective analysis of consecutive patients transferred out from a metropolitan primary stroke center for consideration of mechanical thrombectomy between January 1, 2015, and October 31, 2018. Clinical records were interrogated for eligible patients with DIDO times and reasons for treatment delays extracted. Results- One hundred thirty-three patients were transferred over the 46-month period. Median DIDO time reduced by 14% per year, from 111 minutes interquartile range (IQR, 98- 142) in 2015 to 67 minutes (IQR, 55-94) in 2018. A median DIDO time of 59 minutes (IQR, 51-80) was achieved in 2018 during working hours (0800-1700 hours). Overall, 65 patients had no documented delays (49%) with a median DIDO time of 75 minutes (IQR, 54-93) and 103 minutes (IQR, 75-143) in those with at least one delay factor documented. Conclusions- A median DIDO time of <60 minutes can be achieved in a primary stroke center.

Etiology is the key determinant of neuroinflammation in epilepsy: Elevation of cerebrospinal fluid cytokines and chemokines in febrile infection-related epilepsy syndrome and febrile status epilepticus.

OBJECTIVE: To investigate intrathecal inflammation using cerebrospinal fluid (CSF) cytokines and chemokines in a subgroup of pediatric epilepsy patients with frequent daily seizures. METHODS: We measured 32 cytokines/chemokines using multiplex immunoassay in CSF collected from pediatric patients with febrile infection-related epilepsy syndrome (FIRES)/FIRES-related disorders (FRD; n = 6), febrile status epilepticus (FSE; n = 8), afebrile status epilepticus (ASE; n = 8), and chronic epilepsy with frequent daily seizures (n = 21) and compared the results with noninflammatory neurological disorders (NIND; n = 20) and encephalitis (n = 43). We also performed longitudinal CSF cytokine/chemokine studies in three cases with FIRES/FRD. RESULTS: The median age of onset of seizures was 2.4 years (range = 0.08-12.5). Median CSF timing from the onset of seizures was longer in chronic epilepsy (540 days), whereas FIRES, FSE, and ASE had CSF tested within 1-2 days of onset of seizures (P < .001). The elevation of cytokines/chemokines was higher in FIRES followed by FSE, when compared to chronic epilepsy and NIND controls. Th1-associated cytokines/chemokines (TNF-α, CXCL9, CXCL10, CXCL11), IL-6, CCL2, CCL19, and CXCL1 (P < .05) were elevated in FIRES, in contrast to the elevation of a broader network of cytokines/chemokines in encephalitis. The cytokines/chemokines (CXCL9, CXCL10, CXCL11, and CCL19) were elevated in FSE when compared to ASE despite the similar median seizure duration and timing of CSF testing in relation to seizures. Chronic epilepsy generally lacked significant elevation of cytokines/chemokines despite frequent daily seizures. The median concentrations of the cytokines/chemokines rapidly declined on serial testing during the course of illness in all three FIRES/FRD cases. SIGNIFICANCE: We identify significant differences in CSF cytokine/chemokine profile between FIRES/FRD and encephalitis. The prominent elevation of CSF cytokines and chemokines in FIRES/FRD and to a lesser extent FSE highlights that the cytokine/chemokine elevation is significantly associated with the etiology of the underlying process rather than purely reactive. However, it is unclear whether the immune activation contributes to the disease process.

Elevation of cerebrospinal fluid cytokine/chemokines involved in innate, T cell, and granulocyte inflammation in pediatric focal cerebral arteriopathy.

AIM: To determine the role of inflammation in pediatric transient focal cerebral arteriopathy using cerebrospinal fluid cytokine/chemokines as biomarkers. METHODS: We measured 32 cytokine/chemokines in acute cerebrospinal fluid collected from children with stroke due to focal cerebral arteriopathy (n = 5) using multiplex immunoassay and compared with two patients with arterial ischemic stroke due to other causes (non-focal cerebral arteriopathy group, vertebral dissection, n = 1; cryptogenic, n = 1), pediatric encephalitis (n = 43), and non-inflammatory neurological disease controls (n = 20). RESULTS: Median age in the focal cerebral arteriopathy group was 9.3 years (range, 2.8-13 years). In the focal cerebral arteriopathy group (n = 5), four patients had middle cerebral ± distal carotid arteriopathy; one patient had posterior circulation arteriopathy. The median time from symptom onset to cerebrospinal fluid sampling was four days (range, 0.6-7 days). Only IL-6, IL-8, CXCL1, and CXCL10 levels were significantly higher in the acute cerebrospinal fluid of focal cerebral arteriopathy patients compared to non-inflammatory neurological disease controls and non-focal cerebral arteriopathy stroke. In contrast to focal cerebral arteriopathy, a broad array of Th1, Th2, Treg, Th17, B-cell related, and other broad spectrum cytokine/chemokines were elevated in encephalitis. CONCLUSION: The elevated cerebrospinal fluid cytokine/chemokines support innate, T cell, and granulocyte inflammatory mechanisms in children with focal cerebral arteriopathy. This warrants larger cohort studies to discriminate primary inflammatory signals of the arteriopathy from secondary inflammation due to the stroke itself.

Contribution of peripheral airway function to changes in FEV1/FVC and RV/TLC with aging.

Multiple breath nitrogen washout (MBNW) indices provide insight into ventilation heterogeneity globally [lung clearance index (LCI)] and within acinar (Sacin) and conducting (Scond) airways. Normal aging leads to an accelerated deterioration of Sacin in older adults, but little is known about the contribution of peripheral airway function to changes in pulmonary function indices reflecting expiratory airflow [forced expiratory volume in one second (FEV1)/forced vital capacity (FVC)] and gas trapping [residual volume (RV)/total lung capacity (TLC)] with aging. We aimed to examine associations between MBNW and FEV1/FVC as well as RV/TLC in healthy adults, and to determine if these relationships differ in older (≥50 yr) versus younger subjects (<50 yr). Seventy-nine healthy adult volunteers aged 23-89 yr with no cardiac or respiratory disease and a smoking history of <5 pack-years underwent spirometry, plethysmography, and MBNW. After adjustment for sex, height, and body mass index, the following relationships were present across the entire cohort: Sacin was inversely related to FEV1/FVC (R2 = 0.22, P < 0.001); Sacin and Scond were positively related to RV/TLC (R2 = 0.53, P < 0.001); on separate analyses, the relationship between Sacin and FEV1/FVC was strongest in the older group (R2 = 0.20, P = 0.003) but markedly weaker in the younger group (R2 = 0.09, P = 0.04); and Sacin and Scond were related to RV/TLC in older (R2 = 0.20, P = 0.003) but not younger subgroups. No relationships were observed between LCI and FEV1/FVC or RV/TLC. Changes in FEV1/FVC and RV/TLC are at least in part due to changes in peripheral airway function with aging. Further studies of the relationships between MBNW and standard pulmonary function indices may prove useful for their combined application and interpretation in obstructive airways disease. NEW & NOTEWORTHY This study explores associations between multiple breath nitrogen washout (MBNW) and standard pulmonary function indices reflecting expiratory airflow [forced expiratory volume in one second (FEV1)/forced vital capacity (FVC)] and gas trapping [residual volume (RV)/total lung capacity (TLC)] in healthy adults across a wide range of ages. We have demonstrated statistically significant relationships between MBNW and FEV1/FVC as well as RV/TLC. These findings provide novel evidence of the contribution of peripheral airway function to changes in standard pulmonary function indices with aging.

Six-month clinical course and factors associated with non-improvement in migraine and non-migraine headaches.

Background Evidence on the medium-term clinical course of recurrent headaches is scarce. This study explored the six-month course and factors associated with non-improvement in migraine compared with tension-type headache and cervicogenic headache. Methods In this longitudinal cohort study, the six-month course of headaches was prospectively examined in participants (n = 37 with migraine; n = 42 with tension-type or cervicogenic headache). Participants underwent physical examination for cervical musculoskeletal impairments at baseline. Participants also completed questionnaires on pain, disability and other self-report measures at baseline and follow-up, and kept an electronic diary for 6 months. Course of headaches was examined using mixed within-between analyses of variance and Markov chain modeling. Multiple factors were evaluated as possible factors associated with non-improvement using regression analysis. Results Headache frequency, intensity, and activity interference in migraine and non-migraine headaches were generally stable over 6 months but showed month-to-month variations. Day-to-day variations were more volatile in the migraine than the non-migraine group, with the highest probability of transitioning from any headache state to no headache (probability = 0.82-0.85). The odds of non-improvement in disability was nearly six times higher with cervical joint dysfunction (odds ratio [95% CI] = 5.58 [1.14-27.42]). Conclusions Headache frequency, intensity, and activity interference change over 6 months, with day-to-day variation being more volatile in migraine than non-migraine headaches. Cervical joint dysfunction appears to be associated with non-improvement for disability in 6 months. These results may contribute to strategies for educating patients to help align their expectations with the nature of their headaches.

Mean population salt consumption in India: a systematic review.

BACKGROUND: Member states of the WHO, including India, have adopted a target 30% reduction in mean population salt consumption by 2025 to prevent noncommunicable diseases. Our aim was to support this initiative by summarizing existing data that describe mean salt consumption in India. METHOD: Electronic databases - MEDLINE via Ovid, EMBASE, CINAHL and the Cochrane Database of Systematic Reviews - were searched up to November 2015 for studies that reported mean or median dietary salt intake in Indian adults aged 19 years and older. Random effects meta-analysis was used to obtain summary estimates of salt intake. RESULTS: Of 1201 abstracts identified, 90 were reviewed in full text and 21 were included: 18 cross-sectional surveys (n = 225 024), two randomized trials (n = 255) and one case-control study (n = 270). Data were collected between 1986 and 2014, and reported mean salt consumption levels were between 5.22 and 42.30 g/day. With an extreme outlier excluded, overall mean weighted salt intake was 10.98 g/day (95% confidence interval 8.57-13.40). There was significant heterogeneity between the estimates for contributing studies (I = 99.97%) (P homogeneity ≤0.001), which was likely attributable to the different measurement methods used and the different populations studied. There was no evidence of a change in intake over time (P trend = 0.08). CONCLUSION: The available data leave some uncertainty about exact mean salt consumption in India but there is little doubt that population salt consumption far exceeds the WHO-recommended maximum of 5 g per person per day.