Accuracy of digital chest x-ray analysis with artificial intelligence software as a triage and screening tool in hospitalized patients being evaluated for tuberculosis in Lima, Peru.

Tuberculosis (TB) transmission in healthcare facilities is common in high-incidence countries. Yet, the optimal approach for identifying inpatients who may have TB is unclear. We evaluated the diagnostic accuracy of qXR (Qure.ai, India) computer-aided detection (CAD) software versions 3.0 and 4.0 (v3 and v4) as a triage and screening tool within the FAST (Find cases Actively, Separate safely, and Treat effectively) transmission control strategy. We prospectively enrolled two cohorts of patients admitted to a tertiary hospital in Lima, Peru: one group had cough or TB risk factors (triage) and the other did not report cough or TB risk factors (screening). We evaluated the sensitivity and specificity of qXR for the diagnosis of pulmonary TB using culture and Xpert as primary and secondary reference standards, including stratified analyses based on risk factors. In the triage cohort (n = 387), qXR v4 sensitivity was 0.91 (59/65, 95% CI 0.81-0.97) and specificity was 0.32 (103/322, 95% CI 0.27-0.37) using culture as reference standard. There was no difference in the area under the receiver-operating-characteristic curve (AUC) between qXR v3 and qXR v4 with either a culture or Xpert reference standard. In the screening cohort (n = 191), only one patient had a positive Xpert result, but specificity in this cohort was high (>90%). A high prevalence of radiographic lung abnormalities, most notably opacities (81%), consolidation (62%), or nodules (58%), was detected by qXR on digital CXR images from the triage cohort. qXR had high sensitivity but low specificity as a triage in hospitalized patients with cough or TB risk factors. Screening patients without cough or risk factors in this setting had a low diagnostic yield. These findings further support the need for population and setting-specific thresholds for CAD programs.

Accuracy of digital chest x-ray analysis with artificial intelligence software as a triage and screening tool in hospitalized patients being evaluated for tuberculosis in Lima, Peru.

Introduction: Tuberculosis (TB) transmission in healthcare facilities is common in high-incidence countries. Yet, the optimal approach for identifying inpatients who may have TB is unclear. We evaluated the diagnostic accuracy of qXR (Qure.ai, India) computer-aided detection (CAD) software versions 3.0 and 4.0 (v3 and v4) as a triage and screening tool within the FAST (Find cases Actively, Separate safely, and Treat effectively) transmission control strategy. Methods: We prospectively enrolled two cohorts of patients admitted to a tertiary hospital in Lima, Peru: one group had cough or TB risk factors (triage) and the other did not report cough or TB risk factors (screening). We evaluated the sensitivity and specificity of qXR for the diagnosis of pulmonary TB using culture and Xpert as primary and secondary reference standards, including stratified analyses based on risk factors. Results: In the triage cohort (n=387), qXR v4 sensitivity was 0.91 (59/65, 95% CI 0.81-0.97) and specificity was 0.32 (103/322, 95% CI 0.27-0.37) using culture as reference standard. There was no difference in the area under the receiver-operating-characteristic curve (AUC) between qXR v3 and qXR v4 with either a culture or Xpert reference standard. In the screening cohort (n=191), only one patient had a positive Xpert result, but specificity in this cohort was high (>90%). A high prevalence of radiographic lung abnormalities, most notably opacities (81%), consolidation (62%), or nodules (58%), was detected by qXR on digital CXR images from the triage cohort. Conclusions: qXR had high sensitivity but low specificity as a triage in hospitalized patients with cough or TB risk factors. Screening patients without cough or risk factors in this setting had a low diagnostic yield. These findings further support the need for population and setting-specific thresholds for CAD programs.

Electronic alerts for ambulatory patients with atrial fibrillation not prescribed anticoagulation: A randomized, controlled trial (AF-ALERT2).

BACKGROUND: Despite widely available risk stratification tools, safe and effective anticoagulants, and guideline recommendations, anticoagulation for stroke prevention in atrial fibrillation (AF) is under-prescribed in ambulatory patients. To assess the impact of alert-based computerized decision support (CDS) on anticoagulation prescription in ambulatory patients with AF and high-risk for stroke, we conducted this randomized controlled trial. METHODS: Patients with AF and CHA2DS2-VASc score ≥ 2 who were not prescribed anticoagulation and had a clinic visit at Brigham and Women's Hospital were enrolled. Patients were randomly allocated, according to Attending Physician of record, to intervention (alert-based CDS) versus control (no notification). The primary efficacy outcome was the frequency of anticoagulant prescription. RESULTS: The CDS tool assigned 395 and 403 patients to the alert and control groups, respectively. Alert patients were more likely to be prescribed anticoagulation within 48 h of the clinic visit (15.4 % vs. 7.7 %, p < 0.001) and at 90 days (17.2 % vs. 9.9 %, p < 0.01). Direct oral anticoagulants were the predominantly prescribed form of anticoagulation. No significant differences were observed in stroke, TIA, or systemic embolic events (0 % vs. 0.8 %, p = 0.09), symptomatic VTE (0.5 % vs. 1 %, p = 0.43), all-cause mortality (2 % vs. 0.7 %, p = 0.12), or major adverse cardiovascular events (2.8 % vs. 2.5 %, p = 0.79) at 90 days. CONCLUSIONS: An alert-based CDS strategy increased a primary efficacy outcome of anticoagulation in clinic patients with AF and high-risk for stroke who were not receiving anticoagulation at the time of the office visit. The study was likely underpowered to assess an impact on clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier- NCT02958943.

Exploring the effect of glatiramer acetate on cerebral gray matter atrophy in multiple sclerosis.

BACKGROUND AND PURPOSE: Cerebral gray matter (GM) atrophy is a proposed measure of neuroprotection in multiple sclerosis (MS). Glatiramer acetate (GA) limits clinical relapses, MRI lesions, and whole brain atrophy in relapsing-remitting MS (RRMS). The effect of GA on GM atrophy remains unclear. We assessed GM atrophy in patients with RRMS starting GA therapy in comparison to a cohort of patients with clinically benign RRMS (BMS). DESIGN/METHODS: We studied 14 patients at GA start [age (mean ± SD) 44.2 ± 7.0 years, disease duration (DD) 7.2 ± 6.4 years, Expanded Disability Status Scale score (EDSS) (median,IQR) 1.0,2.0] and 6 patients with BMS [age 43.0 ± 6.1 years, DD 18.1 ± 8.4 years, EDSS 0.5,1.0]. Brain MRI was obtained at baseline and one year later (both groups) and two years later in all patients in the GA group except one who was lost to follow-up. Semi-automated algorithms assessed cerebral T2 hyperintense lesion volume (T2LV), white matter fraction (WMF), GM fraction (GMF), and brain parenchymal fraction (BPF). The exact Wilcoxon-Mann-Whitney test compared the groups. The Wilcoxon signed rank test assessed longitudinal changes within groups. RESULTS: During the first year, MRI changes did not differ significantly between groups (p > 0.15). Within the BMS group, WMF and BPF decreased during the first year (p = 0.03). Within the GA group, there was no significant change in MRI measures during each annual period (p > 0.05). Over two years, the GA group had a significant increase in T2LV and decrease in WMF (p < 0.05), while GMF and BPF remained stable (p > 0.05). MRI changes in brain volumes (GMF or WMF) in the first year in the GA group were not significantly different from those in the BMS group (p > 0.5). CONCLUSIONS: In this pilot study with a small sample size, patients with RRMS started on GA did not show significant GM or whole brain atrophy over 2 years, resembling MS patients with a clinically benign disease course.

Safety, tolerability, and efficacy of pirfenidone in patients with rheumatoid arthritis-associated interstitial lung disease: a randomised, double-blind, placebo-controlled, phase 2 study.

BACKGROUND: Interstitial lung disease is a known complication of rheumatoid arthritis, with a lifetime risk of developing the disease in any individual of 7·7%. We aimed to assess the safety, tolerability, and efficacy of pirfenidone for the treatment of patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). METHODS: TRAIL1 was a randomised, double-blind, placebo-controlled, phase 2 trial done in 34 academic centres specialising in interstitial lung disease in four countries (the UK, the USA, Australia, and Canada). Adults aged 18-85 years were eligible for inclusion if they met the 2010 American College of Rheumatology and European Alliance of Associations for Rheumatology criteria for rheumatoid arthritis and had interstitial lung disease on a high-resolution CT scan imaging and, when available, lung biopsy. Exclusion criteria include smoking, clinical history of other known causes of interstitial lung disease, and coexistant clinically significant COPD or asthma. Patients were randomly assigned (1:1) to receive 2403 mg oral pirfenidone (pirfenidone group) or placebo (placebo group) daily. The primary endpoint was the incidence of the composite endpoint of a decline from baseline in percent predicted forced vital capacity (FVC%) of 10% or more or death during the 52-week treatment period assessed in the intention-to-treat population. Key secondary endpoints included change in absolute and FVC% over 52 weeks, the proportion of patients with a decline in FVC% of 10% or more, and the frequency of progression as defined by Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02808871. FINDINGS: From May 15, 2017, to March 31, 2020, 231 patients were assessed for inclusion, of whom 123 patients were randomly assigned (63 [51%] to the pirfenidone group and 60 [49%] to the placebo group). The trial was stopped early (March 31, 2020) due to slow recruitment and the COVID-19 pandemic. The difference in the proportion of patients who met the composite primary endpoint (decline in FVC% from baseline of 10% or more or death) between the two groups was not significant (seven [11%] of 63 patients in the pirfenidone group vs nine [15%] of 60 patients in the placebo group; OR 0·67 [95% CI 0·22 to 2·03]; p=0·48). Compared with the placebo group, patients in the pirfenidone group had a slower rate of decline in lung function, measured by estimated annual change in absolute FVC (-66 vs -146; p=0·0082) and FVC% (-1·02 vs -3·21; p=0·0028). The groups were similar with regards to the decline in FVC% by 10% or more (five [8%] participants in the pirfenidone group vs seven [12%] in the placebo group; OR 0·52 [95% CI 0·14-1·90]; p=0·32) and the frequency of progression as defined by OMERACT (16 [25%] in the pirfenidone group vs 19 [32%] in the placebo group; OR 0·68 [0·30-1·54]; p=0·35). There was no significant difference in the rate of treatment-emergent serious adverse events between the two groups, and there were no treatment-related deaths. INTERPRETATION: Due to early termination of the study and underpowering, the results should be interpreted with caution. Despite not meeting the composite primary endpoint, pirfenidone slowed the rate of decline of FVC over time in patients with RA-ILD. Safety in patients with RA-ILD was similar to that seen in other pirfenidone trials. FUNDING: Genentech.

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.

FAST tuberculosis transmission control strategy speeds the start of tuberculosis treatment at a general hospital in Lima, Peru.

OBJECTIVE: To evaluate the effect of the FAST (Find cases Actively, Separate safely, Treat effectively) strategy on time to tuberculosis diagnosis and treatment for patients at a general hospital in a tuberculosis-endemic setting. DESIGN: Prospective cohort study with historical controls. PARTICIPANTS: Patients diagnosed with pulmonary tuberculosis during hospitalization at Hospital Nacional Hipolito Unanue in Lima, Peru. METHODS: The FAST strategy was implemented from July 24, 2016, to December 31, 2019. We compared the proportion of patients with drug susceptibility testing and tuberculosis treatment during FAST to the 6-month period prior to FAST. Times to diagnosis and tuberculosis treatment were also compared using Kaplan-Meier plots and Cox regressions. RESULTS: We analyzed 75 patients diagnosed with pulmonary tuberculosis through FAST. The historical cohort comprised 76 patients. More FAST patients underwent drug susceptibility testing (98.7% vs 57.8%; OR, 53.8; P < .001), which led to the diagnosis of drug-resistant tuberculosis in 18 (24.3%) of 74 of the prospective cohort and 4 (9%) of 44 of the historical cohort (OR, 3.2; P = .03). Overall, 55 FAST patients (73.3%) started tuberculosis treatment during hospitalization compared to 39 (51.3%) controls (OR, 2.44; P = .012). FAST reduced the time from hospital admission to the start of TB treatment (HR, 2.11; 95% CI, 1.39-3.21; P < .001). CONCLUSIONS: Using the FAST strategy improved the diagnosis of drug-resistant tuberculosis and the likelihood and speed of starting treatment among patients with pulmonary tuberculosis at a general hospital in a tuberculosis-endemic setting. In these settings, the FAST strategy should be considered to reduce tuberculosis transmission while simultaneously improving the quality of care.

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.

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.

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.

Registry of Arterial and Venous Thromboembolic Complications in Patients With COVID-19.

BACKGROUND: Cardiovascular complications, including myocardial infarction, ischemic stroke, and pulmonary embolism, represent an important source of adverse outcomes in coronavirus disease-2019 (COVID-19). OBJECTIVES: To assess the frequency of arterial and venous thromboembolic disease, risk factors, prevention and management patterns, and outcomes in patients with COVID-19, the authors designed a multicenter, observational cohort study. METHODS: We analyzed a retrospective cohort of 1,114 patients with COVID-19 diagnosed through our Mass General Brigham integrated health network. The total cohort was analyzed by site of care: intensive care (n = 170); hospitalized nonintensive care (n = 229); and outpatient (n = 715). The primary study outcome was a composite of adjudicated major arterial or venous thromboembolism. RESULTS: Patients with COVID-19 were 22.3% Hispanic/Latinx and 44.2% non-White. Cardiovascular risk factors of hypertension (35.8%), hyperlipidemia (28.6%), and diabetes (18.0%) were common. Prophylactic anticoagulation was prescribed in 89.4% of patients with COVID-19 in the intensive care cohort and 84.7% of those in the hospitalized nonintensive care setting. Frequencies of major arterial or venous thromboembolism, major cardiovascular adverse events, and symptomatic venous thromboembolism were highest in the intensive care cohort (35.3%, 45.9%, and 27.0 %, respectively) followed by the hospitalized nonintensive care cohort (2.6%, 6.1%, and 2.2%, respectively) and the outpatient cohort (0% for all). CONCLUSIONS: Major arterial or venous thromboembolism, major adverse cardiovascular events, and symptomatic venous thromboembolism occurred with high frequency in patients with COVID-19, especially in the intensive care setting, despite a high utilization rate of thromboprophylaxis.

Regional microglial activation in the substantia nigra is linked with fatigue in MS.

OBJECTIVE: The goal of our study is to assess the role of microglial activation in MS-associated fatigue (MSAF) using [F-18]PBR06-PET. METHODS: Fatigue severity was measured using the Modified Fatigue Impact Scale (MFIS) in 12 subjects with MS (7 relapsing-remitting and 5 secondary progressive) and 10 healthy control participants who underwent [F-18]PBR06-PET. The MFIS provides a total fatigue score as well as physical, cognitive, and psychosocial fatigue subscale scores. Standardized Uptake Value (SUV) 60-90 minute frame PET maps were coregistered to 3T MRI. Voxel-by-voxel analysis using Statistical Parametric Mapping and atlas-based regional analyses were performed. SUV ratios (SUVRs) were global brain normalized. RESULTS: Peak voxel-based level of significance for correlation between total fatigue score and PET uptake was localized to the right substantia nigra (T-score 4.67, p = 0.001). Similarly, SUVRs derived from atlas-based segmentation of the substantia nigra showed significant correlation with MFIS (r = 0.76, p = 0.004). On multiple regression, the right substantia nigra was an independent predictor of total MFIS (p = 0.02) and cognitive MFIS subscale values (p = 0.007), after adjustment for age, disability, and depression. Several additional areas of significant correlations with fatigue scores were identified, including the right parahippocampal gyrus, right precuneus, and juxtacortical white matter (all p < 0.05). There was no correlation between fatigue scores and brain atrophy and lesion load in patients with MS. CONCLUSION: Substantia nigra microglial activation is linked to fatigue in MS. Microglial activation across key brain regions may represent a unifying mechanism for MSAF, and further evaluation of neuroimmunologic basis of MSAF is warranted.

Incorporating dextrose gel and feeding in the treatment of neonatal hypoglycaemia.

OBJECTIVES: To determine the impact of incorporating dextrose gel in the treatment of neonatal hypoglycaemia (NH) and the role of feeding type in NH outcomes. STUDY DESIGN: We conducted a retrospective analysis of 2688 infants >35 weeks' gestation who were screened for NH before and after implementation of a clinical guideline for NH evaluation and treatment. We analysed the proportion of infants who required intravenous dextrose for NH before and after guideline implementation, the change in blood glucose concentrations with gel by feeding type and the odds of successful NH treatment with gel and feeding by feeding type. RESULTS: Following implementation of the guideline, a lower proportion of infants required intravenous dextrose for NH treatment (8.6% (60 infants) before guideline vs. 5.6% (112 infants) after guideline (p=0.007)). The median rise in blood glucose concentration with gel administration in the entire cohort was 0.61 mmol/L (11 mg/dL) (IQR 0.28-1.06 mmol/L (5-19 mg/dL)). Blood glucose concentration of formula-fed infants rose more in response to feeding and gel than breastfed infants (p≤0.0001). Formula feeding was associated with a lower odds of recurrent hypoglycaemia, as defined by requiring a second gel, in a fully adjusted model. Specifically, in infants with a pregel blood glucose of 2.00-2.17 mmol/L (36-39 mg/dL), formula feeding with gel was associated with a lower odds of recurrent hypoglycaemia. CONCLUSIONS: Dextrose gel is an effective tool in the treatment of NH. An infant's pregel blood glucose concentration may be helpful in guiding decisions around type of feeding provided.

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.

Virtual monitoring of suicide risk in the general hospital and emergency department.

OBJECTIVE: To determine whether continuous virtual monitoring, an intervention that facilitates patient observation through video technology, can be used to monitor suicide risk in the general hospital and emergency department (ED). METHOD: This was a retrospective analysis of a protocol in which select patients on suicide precautions in the general hospital and ED received virtual monitoring between June 2017 and March 2018. The primary outcome was the number of adverse events among patients who received virtual monitoring for suicide risk. Secondary outcomes were the percentage of patients for whom virtual monitoring was discontinued for behavioral reasons and the preference for observation type among nurses. RESULTS: 39 patients on suicide precautions received virtual monitoring. There were 0 adverse events (95% confidence interval (CI) = 0.000-0.090). Virtual monitoring was discontinued for behavioral reasons in 4/38 cases for which the reason for terminating was recorded (0.105, 95%CI = 0.029-0.248). We were unable to draw conclusions regarding preference for observation type among nurses due to a low response rate to our survey. CONCLUSIONS: Suicide risk can feasibly be monitored virtually in the general hospital or ED when their providers carefully select patients for low impulsivity risk.

The Design and Rationale of the Trail1 Trial: A Randomized Double-Blind Phase 2 Clinical Trial of Pirfenidone in Rheumatoid Arthritis-Associated Interstitial Lung Disease.

INTRODUCTION: Rheumatoid arthritis (RA) is the most common of the connective tissue diseases (CTD), affecting up to 0.75% of the United States (U.S.) population with an increasing prevalence. Interstitial lung disease is prevalent and morbid condition in RA (RA-ILD), affecting up to 60% of patients with RA, leading to premature death in 10% and accruing an average of US$170,000 in healthcare costs per patient over a 5-year period. Although there have been significant advances in the management of this joint disease, there are no ongoing randomized clinical trials looking at pharmacologic treatments for RA-ILD, and there currently are no U.S. Food and Drug Administration-approved drugs for RA-ILD. METHODS/DESIGN: We describe the Treatment for Rheumatoid Arthritis and Interstitial Lung Disease 1 (TRAIL1) trial, a multicenter randomized, double-blind, placebo-controlled, phase 2 study of the safety, tolerability and efficacy of pirfenidone in patients with RA-ILD. The study will enroll approximately 270 subjects across a network of sites who have RA and ILD as defined by a fibrotic abnormality involving greater than 10% of the lung parenchyma. The primary endpoint of the study is the incidence of the composite endpoint of decline in percent predicted forced vital capacity of 10 or greater or death during the 52-week study period. A number of secondary and exploratory endpoints have been chosen to evaluate the safety and efficacy in different domains. DISCUSSION: The TRAIL1 trial is designed to evaluate the safety and efficacy of pirfenidone in RA-ILD, a disease with significant impact on patients' quality of life and outcome. In addition to investigating the safety and efficacy of pirfenidone, this trial looks at a number of exploratory endpoints in an effort to better understand the impact of therapy on areas such as changes in quantitative high-resolution computed tomography scores and a patient's quality of life. Biospecimens will be collected in order to investigate biomarkers that could potentially predict the subtype of disease, its behavior over time, and its response to therapy. Finally, by creating a network of institutions and clinician investigators with an interest in RA-ILD, this trial will pave the way for future studies of investigational agents in an effort to reduce or eliminate the burden of disease for those suffering from RA-ILD. TRIAL FUNDING: Genentech, a member of the Roche Group. TRIAL REGISTRATION: Clinicaltrials.gov, identifier NCT02808871.

Gray matter microglial activation in relapsing vs progressive MS: A [F-18]PBR06-PET study.

Objective: To determine the value of [F-18]PBR06-PET for assessment of microglial activation in the cerebral gray matter in patients with MS. Methods: Twelve patients with MS (7 relapsing-remitting and 5 secondary progressive [SP]) and 5 healthy controls (HCs) had standardized uptake value (SUV) PET maps coregistered to 3T MRI and segmented into cortical and subcortical gray matter regions. SUV ratios (SUVRs) were global brain normalized. Voxel-by-voxel analysis was performed using statistical parametric mapping (SPM). Normalized brain parenchymal volumes (BPVs) were determined from MRI using SIENAX. Results: Cortical SUVRs were higher in the hippocampus, amygdala, midcingulate, posterior cingulate, and rolandic operculum and lower in the medial-superior frontal gyrus and cuneus in the MS vs HC group (all p < 0.05). Subcortical gray matter SUVR was higher in SPMS vs RRMS (+10.8%, p = 0.002) and HC (+11.3%, p = 0.055) groups. In the MS group, subcortical gray matter SUVR correlated with the Expanded Disability Status Scale (EDSS) score (r = 0.75, p = 0.005) and timed 25-foot walk (T25FW) (r = 0.70, p = 0.01). Thalamic SUVRs increased with increasing EDSS scores (r = 0.83, p = 0.0008) and T25FW (r = 0.65, p = 0.02) and with decreasing BPV (r = -0.63, p = 0.03). Putaminal SUVRs increased with increasing EDSS scores (0.71, p = 0.009) and with decreasing BPV (r = -0.67, p = 0.01). On SPM analysis, peak correlations of thalamic voxels with BPV were seen in the pulvinar and with the EDSS score and T25FW in the dorsomedial thalamic nuclei. Conclusions: This study suggests that [F-18]PBR06-PET detects widespread abnormal microglial activation in the cerebral gray matter in MS. Increased translocator protein binding in subcortical gray matter regions is associated with brain atrophy and may link to progressive MS.

Demographic, Clinical, and Counseling Factors Associated with the Selection of Pregnancy Termination Method in the Second Trimester for Fetal and Pregnancy Anomalies.

OBJECTIVE: Despite women's preference for induction of labor (IOL) or dilation and evacuation (D&E) for pregnancy termination in the setting of second trimester fetal or pregnancy abnormality, many women are not given a choice between delivery methods. We investigated patient and clinical related factors associated with selecting IOL or D&E. METHODS: This retrospective cohort experienced pregnancy termination at 17-24 weeks of gestation for fetal anomaly, intrauterine fetal demise, or premature previable rupture. We compared the demographic, reproductive, social, and clinical experience variables between women who select IOL and D&E, adjusting for confounders through logistic regression. RESULTS: One hundred eleven women (21.6%) selected IOL and 403 (78.4%) selected D&E. Greater proportions of women of color (p < .01), lower education (p < .01), lower employment (p < .01), and lower status jobs (p < .01) selected IOL. Women selected D&E more often for chromosomal anomaly (p < .01). In adjusted analyses, women with intrauterine fetal demise (odds ratio [OR], 9.8; 95% confidence interval [CI], 2.8-34.7), premature previable rupture (OR, 110; 95% CI, 23.0-526.8), prior substance use disorder (OR, 35.5; 95% CI-2.7, 473.7), or counseling from obstetrics (OR, 3.3; 95% CI-1.3, 8.4), pediatrics (OR, 3.3; 95% CI-1.3, 8.6), or social services (OR, 12.6; 95% CI, 4.2-37.3) had higher odds of selecting IOL. CONCLUSIONS: Patient characteristics, medical factors, and type of counseling are associated with the selection between D&E and IOL for anomalous pregnancies. Institutional, regional, and state policies should permit women both delivery methods to preserve autonomous decision-making at the time of pregnancy termination.