Predicting Airborne Infection Risk: Association Between Personal Ambient Carbon Dioxide Level Monitoring and Incidence of Tuberculosis Infection in South African Health Workers.

BACKGROUND: High rates of tuberculosis (TB) transmission occur in hospitals in high-incidence countries, yet there is no validated way to evaluate the impact of hospital design and function on airborne infection risk. We hypothesized that personal ambient carbon dioxide (CO2) monitoring could serve as a surrogate measure of rebreathed air exposure associated with TB infection risk in health workers (HWs). METHODS: We analyzed baseline and repeat (12-month) interferon-γ release assay (IGRA) results in 138 HWs in Cape Town, South Africa. A random subset of HWs with a baseline negative QuantiFERON Plus (QFT-Plus) underwent personal ambient CO2 monitoring. RESULTS: Annual incidence of TB infection (IGRA conversion) was high (34%). Junior doctors were less likely to have a positive baseline IGRA than other HWs (OR, 0.26; P = .005) but had similar IGRA conversion risk. IGRA converters experienced higher median CO2 levels compared to IGRA nonconverters using quantitative QFT-Plus thresholds of ≥0.35 IU/mL (P < .02) or ≥1 IU/mL (P < .01). Median CO2 levels were predictive of IGRA conversion (odds ratio [OR], 2.04; P = .04, ≥1 IU/mL threshold). Ordinal logistic regression demonstrated that the odds of a higher repeat quantitative IGRA result increased by almost 2-fold (OR, 1.81; P = .01) per 100 ppm unit increase in median CO2 levels, suggesting a dose-dependent response. CONCLUSIONS: HWs face high occupational TB risk. Increasing median CO2 levels (indicative of poor ventilation and/or high occupancy) were associated with higher likelihood of HW TB infection. Personal ambient CO2 monitoring may help target interventions to decrease TB transmission in healthcare facilities and help HWs self-monitor occupational risk, with implications for other airborne infections including coronavirus disease 2019.

Stroke risk factors and outcomes among hospitalized women with atrial fibrillation.

Observational cohort analyses suggest that women with atrial fibrillation (AF) endure a greater burden of stroke. We conducted an analysis of an observational cohort study completed at our tertiary care medical center to assess sex-related differences in cardiovascular risk factors, prescription of antithrombotic therapy, and 90-day outcomes. We analyzed 5000 hospitalized patients with AF: 1888 women and 3112 men. Clinical characteristics of AF, risk of stroke and bleeding, prescription of antithrombotic therapy, and 90-day clinical outcomes, including stroke and all-cause mortality, were compared. We observed a 50% higher relative frequency of stroke in hospitalized women with AF compared with men. While the frequencies of prescription of antithrombotic therapy at discharge were similar, anticoagulation was omitted in 40% of women with AF. The 90-day frequencies of major adverse events and mortality were increased in hospitalized women with AF not prescribed antithrombotic therapy at discharge. Prescription of anticoagulation in women with AF at hospital discharge was associated with a 60% and 40% relative reduction in the odds of mortality and major adverse events at 90 days. In conclusion, women hospitalized with AF have a higher risk of stroke at 90 days compared with men. Anticoagulation at hospital discharge was omitted in 40% of women with AF, but when prescribed, was associated with a reduction in mortality and major adverse events at 90 days, respectively. We analyzed 5000 hospitalized patients with atrial fibrillation (AF) (1888 women and 3112 men) in an observational cohort study completed at our tertiary care medical center to assess sex-related differences in cardiovascular risk factors, prescription of antithrombotic therapy, and 90-day outcomes. We observed a 50% higher relative frequency of stroke in hospitalized women with AF compared with men. The 90-day frequencies of major adverse events and mortality were increased in hospitalized women with AF not prescribed antithrombotic therapy at discharge. Prescription of anticoagulation in women with AF at hospital discharge was associated with a 60% and 40% relative reduction in the odds of mortality and major adverse events at 90 days.

Patients with perceived high-bleeding risk and computerized decision support for stroke prevention in atrial fibrillation: an AF-ALERT substudy : Piazza: outcomes of high-bleeding risk AF patients.

A perceived increased risk of bleeding is one of the most frequent reasons for withholding anticoagulation for stroke prevention in atrial fibrillation (AF). We previously conducted a randomized controlled trial of alert-based computerized decision support to increase prescription of anticoagulation in hospitalized patients with AF. To determine the clinical characteristics and outcomes of those patients whose inpatient health care providers received a computer alert, we analyzed all 248 patients in the alert group. Patients for whom providers elected to omit anticoagulation and provided a rationale of a perceived high risk of bleeding were compared with those who were not designated as high-risk. Perceived high risk of bleeding was the most common reason (77%) for omitting anticoagulation. Median HAS-BLED scores were similar in these patients compared with those who were not deemed to have an increased bleeding risk (3 vs. 3, p = 0.44). Despite being categorized as too high-risk for bleeding to receive antithrombotic therapy at the time of the alert, nearly 12% of these patients were ultimately prescribed anticoagulation by 90 days. The frequency of major and clinically-relevant non-major bleeding was similar between the groups. The frequency of death, myocardial infarction, stroke, or systemic embolic event was similar in both groups (10.2% vs. 12.4%, p = 0.59). In conclusion, a perceived high risk of bleeding was the most common reason for omission of anticoagulation in patients with AF after a computerized alert. Perceived high risk of bleeding was not reflected in a higher HAS-BLED score.Clinical trial registration: ClinicalTrials.gov Identifier: NCT02339493 https://clinicaltrials.gov/ct2/show/NCT02339493 In a randomized controlled trial of computerized decision support to increase prescription of antithrombotic therapy in hospitalized patients with atrial fibrillation (AF), a perceived high risk of bleeding was the most common reason (77%) for omitting antithrombotic therapy after an on-screen alert. Median HAS-BLED scores were similar in these patients compared with those who were not deemed to have an increased bleeding risk (3 vs. 3, p = 0.44). Despite being categorized as too high-risk for bleeding to receive antithrombotic therapy for stroke prevention at the time of the alert, nearly 12% of these patients were ultimately prescribed anticoagulation over the ensuing 90 days.

Alert-based computerized decision support for high-risk hospitalized patients with atrial fibrillation not prescribed anticoagulation: a randomized, controlled trial (AF-ALERT).

AIMS: Despite widely available risk stratification tools, safe and effective anticoagulant options, and guideline recommendations, anticoagulation for stroke prevention in atrial fibrillation (AF) is underprescribed. We created and evaluated an alert-based computerized decision support (CDS) strategy to increase anticoagulation prescription in hospitalized AF patients at high risk for stroke. METHODS AND RESULTS: We enrolled 458 patients (CHA2DS2-VASc score ≥1) with AF who were not prescribed anticoagulant therapy and were hospitalized at Brigham and Women's Hospital. Patients were randomly allocated, according to Attending Physician of record, to intervention (alert-based CDS) vs. control (no notification). The primary efficacy outcome was the frequency of anticoagulant prescription. The CDS tool assigned 248 patients to the alert group and 210 to the control group. Patients in the alert group were more likely to be prescribed anticoagulation during the hospitalization (25.8% vs. 9.5%, P < 0.0001), at discharge (23.8% vs. 12.9%, P = 0.003), and at 90 days (27.7% vs. 17.1%, P = 0.007). The alert reduced the odds of a composite outcome of death, myocardial infarction (MI), cerebrovascular event, and systemic embolic event at 90 days [11.3% vs. 21.9%, P = 0.002; odds ratio (OR) 0.45; 95% confidence interval (CI) 0.27-0.76]. The alert reduced the odds of MI at 90 days by 87% (1.2% vs. 8.6%, P = 0.0002; OR 0.13; 95% CI 0.04-0.45) and cerebrovascular events or systemic embolism at 90 days by 88% (0% vs. 2.4%, P = 0.02; OR 0.12; 95% CI 0.0-0.91). CONCLUSION: An alert-based CDS strategy increased anticoagulation in high-risk hospitalized AF patients and reduced major adverse cardiovascular events, including MI and stroke. CLINICALTRIALS.GOV IDENTIFIER: NCT02339493.

Automated Time-Released Reminders Improve Patient Access to Colonoscopy.

Unscheduled colonoscopy orders lead to missed opportunities for early diagnosis and screening. The aim of this study was to evaluate the effect of an automated time-released reminder program on conversion of colonoscopy orders to scheduled cases. In this prospective study, we compared patients ordered for a colonoscopy who were enrolled in an automated reminder program (intervention) with a historical cohort of patients ordered for a colonoscopy who did not receive scheduling reminders (control). The intervention group received automated text message and email reminders using a software platform at 1, 7, and 14 days after a colonoscopy order was placed. The percentage of colonoscopies scheduled within 14 days of order placement improved from 66.0% in the control group to 73.4% in the intervention group (p = .001). The percentage of colonoscopies scheduled within 30 days improved from 73.6% to 90.0% (p < .0001). For colonoscopies ordered by a nongastroenterologist, the percentage of cases scheduled within 30 days of order placement improved from 65.8% in the control group to 90.0% in the intervention group (p < .0001). There was a 10% decrease in phone calls with endoscopy staff for the intervention group relative to the control group. Automated reminders for colonoscopy scheduling improve efficiency in colonoscopy scheduling.

Impact of Automated Time-released Reminders on Patient Preparedness for Colonoscopy.

GOALS: To evaluate the effect of an automated time-released colonoscopy reminder program on preparation quality and the rates of canceled procedures. BACKGROUND: Patients missing colonoscopy appointments or arriving with inadequate bowel preparations result in delays in care and increase in health care costs. STUDY: We initiated a quality improvement program which included switching to a split-dose preparation and delivering preparation instructions and appointment reminders via text messages and emails sent with an automated time-released HIPAA-compliant software platform. All patients scheduled for a colonoscopy from March through June 2017 were enrolled unless mobile phone, email, or preparation type data was missing (nonintervention cohort). Primary outcome metrics were the rate of adequate bowel preparation and the rate of canceled procedures. Outcomes of the intervention group were compared with outcomes from colonoscopies performed from March through June 2016 (baseline cohort). RESULTS: There were 1497 patients (40.7% male, mean age 56.4 y) enrolled in the automated reminder program. Compared with the baseline cohort, the rate of adequate bowel preparation increased from 88.5% to 96.2% (P<0.0001). The rate of canceled procedures decreased from 6.1% to 4.3% (P=0.02). On multivariable analysis, the automated reminder program improved adequate preparation quality 2.85-fold (95% confidence interval, 2.03-3.99; P<0.0001). Sensitivity analysis comparing the intervention to nonintervention cohorts showed that improvement in preparation quality was attributable to the automated reminder program. CONCLUSIONS: Implementation of automated time-released colonoscopy preparation reminders via text messages and emails improved patient preparedness for colonoscopy, with significantly improved bowel preparation quality and fewer canceled procedures.

Hospital Length of Stay With a Proactive Psychiatric Consultation Model in the Medical Intensive Care Unit: A Prospective Cohort Analysis.

BACKGROUND: Previous studies have demonstrated that proactive psychiatric consultation reduces hospital length of stay (LOS) in the general medical setting; however this model has not been studied in the intensive care unit (ICU). OBJECTIVE: To compare outcomes between a conventional consultation model and a proactive psychiatric consultation model. METHODS: Two medical ICUs (MICUs) were randomized to proactive psychiatric consultation vs conventional consultation psychiatric models. Proactive consultation included embedding a psychiatrist into daily MICU team rounds on all patients. In the conventional consultation MICU, psychiatric consultations were activated when deemed necessary. Primary outcomes were hospital LOS and MICU LOS. Secondary outcomes included delirium-coma-free hours and ventilator-free hours. RESULTS: A total of 429 patients were admitted to the proactive consultation MICU; 393 patients were admitted to the conventional consultation MICU. The consultation rate for the intervention group was 24.2% vs 6.1% in the control group (p < 0.001). Time to psychiatric consultation was shorter in the intervention group. Median hospital LOS was 6.92 days, interquartile range 3.70-14.31 in the intervention group vs 7.69 days, interquartile range 3.95-16.21 in the control group (p = 0.113). MICU LOS, delirium-coma-free hours, and ventilator-free hours were not significantly different between the 2 groups. Among the respiratory failure subgroup, hospital LOS was shorter in the intervention vs control group (median 9.46 days, interquartile range 4.95-17.56 vs 12.29 days, interquartile range 6.58-21.10, p = 0.011). CONCLUSIONS: Proactive psychiatric consultation in a MICU was associated with decreased time to consultation among all patients and shorter hospital LOS among patients with respiratory failure.

Fatal warfarin-associated intracranial hemorrhage in atrial fibrillation inpatients.

Ischemic stroke and major bleeding, mostly due to intracranial hemorrhage (ICH), cause about the same rates of death in pivotal randomized trials of direct oral anticoagulants (DOACs) versus warfarin for stroke prevention in atrial fibrillation (AF). We analyzed our AF inpatient database to determine whether any ICH-related deaths were potentially preventable. Among 5008 patients admitted to our institution between May 2008 and September 2014 with a diagnosis of AF, eight had fatal ICH between admission and 90 days follow-up. The mean age of these patients was 85 years; 62% were male. Localization of the ICH was intraparenchymal in 62% and subdural in 38%. CHA2DS2-VASc scores ranged from 4 to 7, and the HAS-BLED scores ranged from 3 to 7. Three of the eight fatal ICHs were directly due to falls. All 8 patients were taking warfarin. One was taking concomitant aspirin. At the time ICH was diagnosed, one patient had an INR of 5.4. Five patients had an INR within the target therapeutic range of 2.0-3.0, and two had an INR less than 2.0. After multivariate adjustment, a history of falls was the sole independent predictor of fatal ICH (OR 22.3; 95% CI 2.5-60.3). In conclusion, most patients had achieved the target INR at the time of ICH, and the primary precipitant of fatal ICH was often a fall. Using DOACs instead of warfarin and implementing structured fall-prevention programs in high-risk patients could further reduce mortality from ICH in AF.

Effect of Preoperative Diabetes Management on Glycemic Control and Clinical Outcomes After Elective Surgery.

OBJECTIVE: The aim of this study was to evaluate whether preoperative diabetes management can improve glycemic control and clinical outcomes after elective surgery. BACKGROUND: There is lack of data on the importance of diabetes treatment before elective surgery. Diabetes is often ignored before surgery and aggressively treated afterwards. METHODS: Patients with diabetes were identified and treated proactively before their scheduled surgeries. Data for all elective surgeries over 2 years before and 2 years after implementation of the program were collected. RESULTS: Out of 31,392 patients undergoing first surgery, 3909 had diabetes; 2072 before and 1835 after the program. Mean blood glucose on the day of surgery was 146.4 ±â€Š51.9 mg/dL before and 139.9 ±â€Š45.6 mg/dL after the program (P = 0.0028). Proportion of patients seen by the inpatient diabetes team increased. Mean blood glucose during hospital stay was 166.7 ±â€Š42.9 mg/dL before and 158.3 ±â€Š46.6 mg/dL after program (P < 0.0001). The proportion of patients with hypoglycemic episodes (<50 mg/dL) was 4.93% before and 2.48% after the program (P < 0.0001). Length of hospital stay (LOS) decreased among patients with diabetes (4.8 ±â€Š5.3 to 4.6 ±â€Š4.3 days; P = 0.01) and remained unchanged among patients without diabetes (4.0 ±â€Š4.5 and 4.1 ±â€Š4.8, respectively; P = 0.42). Changes in intravenous antibiotic use, patients discharged to home, renal insufficiency, myocardial infarction, stroke, and in-hospital mortality were similar among diabetic and nondiabetic groups. CONCLUSIONS: Preoperative and inpatient diabetes management improves glycemic control on the day of surgery and postoperatively and decreases the incidence of hypoglycemia. These changes may eventually improve clinical outcomes. Although statistically significant, the decrease in LOS was of equivocal clinical significance in this study.

Biological Variability of Estimated GFR and Albuminuria in CKD.

RATIONALE & OBJECTIVE: Determining whether a change in estimated glomerular filtration rate (eGFR) or albuminuria is clinically significant requires knowledge of short-term within-person variability of the measurements, which few studies have addressed in the setting of chronic kidney disease. STUDY DESIGN: Cross-sectional study with multiple collections over less than 4 weeks. SETTING & PARTICIPANTS: Clinically stable outpatients with chronic kidney disease (N=50; mean age, 56.8 years; median eGFR, 40mL/min/1.73m2; median urinary albumin-creatinine ratio (UACR), 173mg/g). EXPOSURE: Repeat measurements from serially collected samples across 3 study visits. OUTCOMES: Measurements of urine albumin concentration (UAC), UACR, and plasma creatinine, cystatin C, ß2-microglobulin (B2M), and beta trace protein (BTP). ANALYTICAL APPROACH: We calculated within-person coefficients of variation (CVw) values and corresponding reference change positive and negative (RCVpos and RCVneg) values using log-transformed measurements. RESULTS: Median CVw (RCVpos; RCVneg) values of filtration markers were 5.4% (+16%; -14%) for serum creatinine, 4.1% (+12%; -11%) for cystatin C, 7.4% (+23%; -18%) for BTP, and 5.6% (+17%; -14%) for B2M. Results for albuminuria were 33.2% (+145%; -59%) for first-morning UAC, 50.6% (+276%; -73%) for random spot UAC, 32.5% (+141%; -58%) for first-morning UACR, and 29.7% (124%; -55%) for random spot UACR. CVw values for filtration markers were comparable across the range of baseline eGFRs. CVw values for UAC and UACR were comparable across the range of baseline albuminuria values. LIMITATIONS: Small sample size limits the ability to detect differences in variability across markers. Participants were recruited and followed up in a clinical and not research setting, so some preanalytical factors could not be controlled. CONCLUSIONS: eGFR markers appear to have relatively low short-term within-person variability, whereas variability in albuminuria appears to be high, making it difficult to distinguish random variability from meaningful biologic changes.

Outcome in middle-aged individuals with anomalous origin of the coronary artery from the opposite sinus: a matched cohort study.

AIMS: Anomalous origin of a coronary artery from the opposite sinus (ACAOS) has been associated with adverse cardiac events in the young. It remains unknown whether this holds true for middle-aged patients with uncorrected ACAOS as well. We assessed the outcome in middle-aged patients with newly diagnosed ACAOS by coronary computed tomography angiography (CCTA) compared with a matched cohort. METHODS AND RESULTS: We retrospectively identified 68 consecutive patients with ACAOS documented by CCTA. ACAOS with a course of the anomalous vessel between the aorta and pulmonary artery were classified as interarterial course (IAC). Each patient with ACAOS was matched to two controls without ACAOS. Major adverse cardiac events (i.e. myocardial infarction, revascularization and cardiac death) were recorded for all patients and controls. Two (3%) patients were lost to follow-up. Thus, 66 patients with ACAOS were included in the final analysis and matched with 132 controls. Mean age of patients was 56 ± 11 years, 73% were male and the mean follow-up was 49 months. Forty (65%) patients were classified as having ACAOS with IAC. The annual event rate of ACAOS vs. controls was 4.9 and 4.8%, the hazard ratio (HR) 0.94 (0.39-2.28, P = 0.89). The annual event rate of ACAOS with IAC compared with their matched controls was 5.2 and 4.3%, and the HR 1.01 (95% CI 0.39-2.58, P = 0.99). CONCLUSIONS: In middle-aged individuals with newly diagnosed ACAOS mid-term outcome is not statistically different to a matched control cohort without coronary artery anomalies, regardless of whether ACAOS with or without IAC variants are present.

Tackling inpatient penicillin allergies: Assessing tools for antimicrobial stewardship.

BACKGROUND: Reported penicillin allergy rarely reflects penicillin intolerance. Failure to address inpatient penicillin allergies results in more broad-spectrum antibiotic use, treatment failures, and adverse drug events. OBJECTIVE: We aimed to determine the optimal approach to penicillin allergies among medical inpatients. METHODS: We evaluated internal medicine inpatients reporting penicillin allergy in 3 periods: (1) standard of care (SOC), (2) penicillin skin testing (ST), and (3) computerized guideline application with decision support (APP). The primary outcome was use of a penicillin or cephalosporin, comparing interventions to SOC using multivariable logistic regression. RESULTS: There were 625 patients: SOC, 148; ST, 278; and APP, 199. Of 278 ST patients, 179 (64%) were skin test eligible; 43 (24%) received testing and none were allergic. In the APP period, there were 292 unique Web site views; 112 users (38%) completed clinical decision support. Although ST period patients did not have increased odds of penicillin or cephalosporin use overall (adjusted odds ratio [aOR] 1.3; 95% CI, 0.8-2.0), we observed significant increased odds of penicillin or cephalosporin use overall in the APP period (aOR, 1.8; 95% CI, 1.1-2.9) and in a per-protocol analysis of the skin tested subset (aOR, 5.7; 95% CI, 2.6-12.5). CONCLUSIONS: Both APP and ST-when completed-increased the use of penicillin and cephalosporin antibiotics among inpatients reporting penicillin allergy. While the skin tested subset showed an almost 6-fold impact, the computerized guideline significantly increased penicillin or cephalosporin use overall nearly 2-fold and was readily implemented.

Human Sepsis Eicosanoid and Proresolving Lipid Mediator Temporal Profiles: Correlations With Survival and Clinical Outcomes.

OBJECTIVE: To identify and measure recently described chemical mediators, termed specialized pro-resolving mediators that actively regulate the resolution of acute-inflammation, and correlate measurements with clinical outcomes. DESIGN: Herein, deidentified plasma was collected from sepsis patients (n = 22 subjects) within 48 hours of admission to the ICU and on days 3 and 7 thereafter and subjected to lipid mediator profiling. SETTING: Brigham and Women's Hospital Medical Intensive Care Unit. SUBJECTS: Patients in the medical ICU with sepsis. MEASUREMENTS AND MAIN RESULTS: In all patients, we identified more than 30 bioactive mediators and pathway markers in peripheral blood using established criteria for arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid metabolomes. These included inflammation initiating mediators leukotriene B4 and prostaglandin E2 and pro-resolving mediators resolvin D1, resolvin D2, and protectin D1. In sepsis nonsurvivors, we found significantly higher inflammation-initiating mediators including prostaglandin F2α and leukotriene B4 and pro-resolving mediators, including resolvin E1, resolvin D5, and 17R-protectin D1 than was observed in surviving sepsis subjects. This signature was present at ICU admission and persisted for 7 days. Further analysis revealed increased respiratory failure in nonsurvivors. Higher inflammation-initiating mediators (including prostaglandin F2α) and select proresolving pathways were associated with the development of acute respiratory distress syndrome, whereas other traditional clinical indices were not predictive of acute respiratory distress syndrome development. CONCLUSIONS: These results provide peripheral blood lipid mediator profiles in sepsis that correlate with survival and acute respiratory distress syndrome development, thus suggesting plausible novel biomarkers and biologic targets for critical illness.

Automated segmentation of cerebral deep gray matter from MRI scans: effect of field strength on sensitivity and reliability.

BACKGROUND: The cerebral subcortical deep gray matter nuclei (DGM) are a common, early, and clinically-relevant site of atrophy in multiple sclerosis (MS). Robust and reliable DGM segmentation could prove useful to evaluate putative neuroprotective MS therapies. The objective of the study was to compare the sensitivity and reliability of DGM volumes obtained from 1.5T vs. 3T MRI. METHODS: Fourteen patients with MS [age (mean, range) 50.2 (32.0-60.8) years, disease duration 18.4 (8.2-35.5) years, Expanded Disability Status Scale score 3.1 (0-6), median 3.0] and 15 normal controls (NC) underwent brain 3D T1-weighted paired scan-rescans at 1.5T and 3T. DGM (caudate, thalamus, globus pallidus, and putamen) segmentation was obtained by the fully automated FSL-FIRST pipeline. Both raw and normalized volumes were derived. RESULTS: DGM volumes were generally higher at 3T vs. 1.5T in both groups. For raw volumes, 3T showed slightly better sensitivity (thalamus: p = 0.02; caudate: p = 0.10; putamen: p = 0.02; globus pallidus: p = 0.0004; total DGM: p = 0.01) than 1.5T (thalamus: p = 0.05; caudate: p = 0.09; putamen: p = 0.03; globus pallidus: p = 0.0006; total DGM: p = 0.02) for detecting DGM atrophy in MS vs. NC. For normalized volumes, 3T but not 1.5T detected atrophy in the globus pallidus in the MS group. Across all subjects, scan-rescan reliability was generally very high for both platforms, showing slightly higher reliability for some DGM volumes at 3T. Raw volumes showed higher reliability than normalized volumes. Raw DGM volume showed higher reliability than the individual structures. CONCLUSIONS: These results suggest somewhat higher sensitivity and reliability of DGM volumes obtained from 3T vs. 1.5T MRI. Further studies should assess the role of this 3T pipeline in tracking potential MS neurotherapeutic effects.

Decreased FOXJ1 expression and its ciliogenesis programme in aggressive ependymoma and choroid plexus tumours.

Well-differentiated human cancers share transcriptional programmes with the normal tissue counterparts from which they arise. These programmes broadly influence cell behaviour and function and are integral modulators of malignancy. Here, we show that the master regulator of motile ciliogenesis, FOXJ1, is highly expressed in cells along the ventricular surface of the human brain. Strong expression is present in cells of the ependyma and the choroid plexus as well as in a subset of cells residing in the subventricular zone. Expression of FOXJ1 and its transcriptional programme is maintained in many well-differentiated human tumours that arise along the ventricle, including low-grade ependymal tumours and choroid plexus papillomas. Anaplastic ependymomas as well as choroid plexus carcinomas show decreased FOXJ1 expression and its associated ciliogenesis programme genes. In ependymomas and choroid plexus tumours, reduced expression of FOXJ1 and its ciliogenesis programme are markers of poor outcome and are therefore useful biomarkers for assessing these tumours. Transitions in ciliogenesis define distinct differentiation states in ependymal and choroid plexus tumours with important implications for patient care. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Delayed Deterioration of EEG Background Rhythm Post-cardiac Arrest.

BACKGROUND: Electroencephalogram (EEG) background continuity is associated with a favorable prognosis in cardiac arrest patients post-therapeutic hypothermia. However, the continuous EEG in a subset of patients will undergo 'delayed EEG deterioration'; they will invariably have poor outcome. The aim of this study was to characterize this phenomenon. METHODS: We studied a prospectively collected cohort of consecutive cardiac arrest patients who underwent therapeutic hypothermia between July 2012 and May 2015. We identified patients with an initially favorable EEG rhythm post-cooling and characterized a subset of patients with delayed EEG deterioration. RESULTS: A total of 133 patients were included in the analysis. Of these, 69/133 (51.9%) had an initially favorable EEG. Of those patients with initially favorable EEG, 7/69 (10.1%) had a subsequent deterioration. Delayed EEG deterioration was associated with poor outcome. The median time to deterioration was 55 h. CONCLUSIONS: Delayed EEG deterioration is associated with poor clinical outcomes. We hypothesize that this is the result of delayed neuronal degeneration, the exact mechanism requiring further exploration. Identifying patients with delayed EEG deterioration post-therapeutic hypothermia is paramount as further interventions may yet salvage their outcomes, though further study is needed.

Intensive treatment and survival outcomes in NUT midline carcinoma of the head and neck.

BACKGROUND: NUT midline carcinoma is a rare and aggressive genetically characterized subtype of squamous cell carcinoma frequently arising from the head and neck. The characteristics and optimal management of head and neck NUT midline carcinoma (HNNMC) are unclear. METHODS: A retrospective review of all known cases of HNNMC in the International NUT Midline Carcinoma Registry as of December 31, 2014, was performed. Forty-eight consecutive patients were treated from 1993 to 2014, and clinicopathologic variables and outcomes for 40 patients were available for analyses; they composed the largest HNNMC cohort studied to date. Overall survival (OS) and progression-free survival (PFS) according to patient characteristics and treatment were analyzed. RESULTS: This study identified a 5-fold increase in the diagnosis of HNNMC from 2011 to 2014. The median age was 21.9 years (range, 0.1-81.7 years); the male and female proportions were 40% and 60%, respectively; and 86% had bromodomain containing 4-nuclear protein in testis (BRD4-NUT) fusion. The initial treatment was initial surgery with or without adjuvant chemoradiation or adjuvant radiation (56%), initial radiation with or without chemotherapy (15%), or initial chemotherapy with or without surgery or radiation (28%). The median PFS was 6.6 months (range, 4.7-8.4 months). The median OS was 9.7 months (range, 6.6-15.6 months). The 2-year PFS rate was 26% (95% confidence interval [CI], 13%-40%). The 2-year OS rate was 30% (95% CI, 16%-46%). Initial surgery with or without postoperative chemoradiation or radiation (P = .04) and complete resection with negative margins (P = .01) were significant predictors of improved OS even after adjustments for age, tumor size, and neck lymphadenopathy. Initial radiation or chemotherapy and the NUT translocation type were not associated with outcomes. CONCLUSIONS: HNNMC portends a poor prognosis. Aggressive initial surgical resection with or without postoperative chemoradiation or radiation is associated with significantly enhanced survival. Chemotherapy or radiation alone is often inadequate. Cancer 2016;122:3632-40. © 2016 American Cancer Society.

Validity and Reliability of a Novel Ocular Pain Assessment Survey (OPAS) in Quantifying and Monitoring Corneal and Ocular Surface Pain.

PURPOSE: To validate the Ocular Pain Assessment Survey (OPAS), specifically designed to measure ocular pain and quality of life for use by eye care practitioners and researchers. DESIGN: A single-center cohort study was conducted among patients with and without corneal and ocular surface pain at initial and follow-up visits over a 6-month period. The content of the OPAS was guided by literature review, a body of experts, and incorporating conceptual frameworks from existing pain questionnaires. The Wong-Baker FACES Pain Rating Scale served as the gold standard for measuring the intensity of ocular pain. PARTICIPANTS: A total of 102 patients aged 18 to 80 years completed the OPAS at the initial visit. A total of 21 patients were followed up after treatment. METHODS: Indices of validity and internal consistency (Spearman's rank-order, rs, or Pearson's correlation coefficients, rp), and coefficient of reliability (Cronbach's α) were determined in addition to equivalence testing, exploratory factor analysis (EFA), and diagnostic analysis. MAIN OUTCOME MEASURES: Eye pain intensity was the primary outcome measure, and interference with quality of life (QoL), aggravating factors, associated factors, associated non-eye pain intensity, and self-reported symptomatic relief were the secondary outcome measures. RESULTS: The OPAS had criterion validity at both initial (rs = 0.71; n = 102; P < 0.01) and follow-up visits (rs = 0.97; n = 21; P < 0.01). Equivalence tests yielded OPAS and gold standard equivalence for both the initial and follow-up visits. The EFA supported 6 subscales (eye pain intensity at 24 hours and 2 weeks, non-eye pain intensity, QoL, aggravating factors, and associated factors) confirming multidimensionality. Cronbach's α >0.83 for all subscales established strong internal consistency, which correlated with the gold standard, including 24-hour eye pain intensity and QoL interference scores (rp = 0.81, 0.64, respectively P < 0.001). At follow-up, reduction in pain scores was accompanied by improvement in all dimensions of the OPAS. Percentage change in QoL correlated to percentage change in the gold standard (rp = 0.53; P < 0.05). The OPAS was sensitive (94%), specific (81%), and accurate (91%), with a diagnostic odds ratio >50. CONCLUSIONS: The OPAS is a valid, reliable, and responsive tool with strong psychometric and diagnostic properties in the multidimensional quantification of corneal and ocular surface pain intensity, and QoL.

Treatment with or without plasma exchange for patients with acquired thrombotic microangiopathy not associated with severe ADAMTS13 deficiency: a propensity score-matched study.

BACKGROUND: Therapeutic plasma exchange (TPE) is a proven treatment for thrombotic thrombocytopenic purpura (TTP) characterized by severe ADAMTS13 deficiency, but the efficacy of TPE in suspected TTP with an ADAMTS13 activity level of more than 10% remains controversial. STUDY DESIGN AND METHODS: We conducted a propensity score (PS)-matched study of 186 adult patients included in the Harvard Thrombotic Microangiopathy (TMA) Research Collaborative registry who presented with TMA suggestive of TTP but an ADAMTS13 activity level of more than 10%. RESULTS: Before matching, patients treated with TPE (n = 71) differed from untreated patients (n = 115) by several clinical measures. PS matching was performed to address clinical disparities between the two groups and resulted in a well-balanced cohort of 59 TPE-treated patients paired with 59 untreated controls, all of whom had TMA. After matching, we observed no significant difference in the primary outcome of 90-day survival between the treated and untreated groups (hazard ratio, 0.88; 95% confidence interval [CI], 0.44-1.77; p = 0.72). In-hospital mortality (odds ratio [OR], 0.77; 95% CI, 0.34-1.75; p = 0.53) and the percentage of patients with platelet count recovery (OR, 1.58; 95% CI, 0.77-3.26; p = 0.21) also did not differ significantly between the two matched groups. CONCLUSION: Our data suggest that routine use of TPE in the diverse group of TMA patients without severe ADAMTS13 deficiency may not significantly improve outcomes.