A resiliency intervention adapted for older women with HIV: Results from a pilot randomized controlled trial in the northeastern US.

Aging with HIV often results in psychosocial and health-related challenges for women; however, no resiliency interventions exist for older women with HIV (WWH). WWH aged ≥50 were randomized to 10 group sessions of an adapted resiliency intervention or time-matched supportive psychotherapy. Assessments were conducted at three timepoints. Feasibility and acceptability metrics were defined a priori; differences in resilience, stress coping, anxiety, and depression across timepoints were assessed. Overall, 44 WWH enrolled; participants were 58 years old on average, and 56.4% identified as Black/African American. Among those who attended any sessions, all feasibility metrics were met, and the intervention was acceptable. The interaction of study arm and time was associated with significant decreases in depression and a trend toward significant decreases in anxiety. The intervention was not associated with changes in resilience or stress coping. Adjusting delivery modality may further reduce barriers to attendance, improving feasibility and clinical outcomes.

The effect of a prospective intervention program with automated monitoring of hand hygiene performance in long-term and acute-care units at a Veterans Affairs medical center.

OBJECTIVE: To measure the impact of an automated hand hygiene monitoring system (AHHMS) and an intervention program of complementary strategies on hand hygiene (HH) performance in both acute-care and long-term care (LTC) units. DESIGN: Prospective, nonrandomized, before-and-after intervention study. SETTING: Single Veterans Affairs Medical Center (VAMC), with 2 acute-care units and 6 LTC units. METHODS: An AHHMS that provides group HH performance rates was implemented on 8 units at a VAMC from March 2021 through April 2022. After a 4-week baseline period and 2.5-week washout period, the 52-week intervention period included multiple evidence-based components designed to improve HH compliance. Unit HH performance rates were expressed as the number of dispenses (events) divided by the number of patient room entries and exits (opportunities) × 100. Statistical analysis was performed with a Poisson general additive mixed model. RESULTS: During the 4-week baseline period, the median HH performance rate was 18.6 (95% CI, 16.5-21.0) for all 8 units. During the intervention period, the median HH rate increased to 21.6 (95% CI, 19.1-24.4; P < .0001), and during the last 4 weeks of the intervention period (exactly 1 year after baseline), the 8 units exhibited a median HH rate of 25.1 (95% CI, 22.2-28.4; P < .0001). The median HH rate increased from 17.5 to 20.0 (P < .0001) in LTC units and from 22.9 to 27.2 (P < .0001) in acute-care units. CONCLUSIONS: The intervention was associated with increased HH performance rates for all units. The performance of acute-care units was consistently higher than LTC units, which have more visitors and more mobile veterans.

Mineralocorticoid Receptor Antagonism by Eplerenone and Arterial Inflammation in HIV: The MIRABELLA HIV Study.

Importance: The risk for atherosclerotic disease is increased 1.5- to 2.0-fold among persons with HIV (PWH). Increased activation of the renin-angiotensin-aldosterone system may contribute to increased arterial inflammation in this population. Objective: To determine the effects of eplerenone on arterial inflammation among well-treated PWH without known cardiovascular disease (CVD). Design, Setting, and Participants: Well-treated PWH who participated in the double-blinded, placebo-controlled, Mineralocorticoid Receptor Antagonism for Cardiovascular Health in HIV (MIRACLE HIV) study between February 2017 and March 2022 assessing the effects of eplerenone on myocardial perfusion were invited to participate in the Mineralocorticoid Receptor Antagonism By Eplerenone to Lower Arterial Inflammation in HIV (MIRABELLA) substudy if there was no current statin use. Participants were enrolled in the MIRABELLA study and underwent additional 18F-fludeoxyglucose-positron emission tomography/computed tomography (18F-FDG PET/CT) imaging of the aorta and carotid arteries to assess arterial inflammation over 12 months of treatment with eplerenone vs placebo. Interventions: Eplerenone, 50 mg, twice a day vs identical placebo. Main Outcomes and Measures: The primary outcome was change in target to background ratio (TBR), a measure of arterial wall inflammation, in the index vessel after 12 months of treatment. The index vessel was defined as the vessel (aorta, left carotid artery, or right carotid artery) with the highest TBR at baseline in each participant. Results: A total of 26 participants (mean [SD] age, 54 [7] years; 18 male [69%]) were enrolled in the study. Treatment groups (eplerenone, 13 vs placebo, 13) were of similar age, sex, and body mass index. Eplerenone was associated with a reduction in TBR of the primary end point, the index vessel (eplerenone vs placebo: model treatment effect, -0.31; 95% CI, -0.50 to -0.11; P = .006; percentage change, -12.4% [IQR, -21.9% to -2.6%] vs 5.1% [IQR, -1.6% to 11.0%]; P = .003). We further observed a significant reduction of the TBR of the most diseased segment (MDS) of the index vessel (eplerenone vs placebo: -19.1% [IQR, -27.0% to -11.9%] vs 6.8% [IQR, -9.1% to 12.1%]; P = .007). A similar result was seen assessing the index vessel of the carotids (eplerenone vs placebo: -10.0% [IQR, -21.8% to 3.6%] vs 9.7% [IQR, -9.8% to 15.9%]; P = .046). Reduction in the TBR of MDS of the index vessel on 18F-FDG PET/CT correlated with improvement in the stress myocardial blood flow on cardiac magnetic resonance imaging (Spearman ρ = -0.67; P = .01). Conclusion and Relevance: In this small randomized clinical trial, eplerenone was associated with reduction in arterial inflammation among well-treated PWH without known CVD. In addition, reductions in arterial inflammation as measured by 18F-FDG PET/CT were related to improvements in stress myocardial perfusion. Further larger studies should explore whether eplerenone is a potential treatment strategy for inflammatory-mediated CVD in PWH. Trial Registration: ClinicalTrials.gov Identifier: NCT02740179.

Randomized Placebo-Controlled Trial to Evaluate Effects of Eplerenone on Myocardial Perfusion and Function Among Persons With Human Immunodeficiency Virus (HIV)-Results From the MIRACLE HIV Study.

BACKGROUND: Increased renin angiotensin aldosterone system (RAAS) activity may contribute to excess cardiovascular disease in people with HIV (PWH). We investigated how RAAS blockade may improve myocardial perfusion, injury, and function among well-treated PWH. METHODS: Forty PWH, on stable ART, without known heart disease were randomized to eplerenone 50 mg PO BID (n = 20) or identical placebo (n = 20) for 12 months. The primary endpoints were (1) myocardial perfusion assessed by coronary flow reserve (CFR) on cardiac PET or stress myocardial blood flow (sMBF) on cardiac MRI or (2) myocardial inflammation by extracellular mass index (ECMi) on cardiac MRI. RESULTS: Beneficial effects on myocardial perfusion were seen for sMBF by cardiac MRI (mean [SD]: 0.09 [0.56] vs -0.53 [0.68] mL/min/g; P = .03) but not CFR by cardiac PET (0.01 [0.64] vs -0.07 [0.48]; P = .72, eplerenone vs placebo). Eplerenone improved parameters of myocardial function on cardiac MRI including left ventricular end diastolic volume (-13 [28] vs 10 [26] mL; P = .03) and global circumferential strain (GCS; median [interquartile range 25th-75th]: -1.3% [-2.9%-1.0%] vs 2.3% [-0.4%-4.1%]; P = .03), eplerenone versus placebo respectively. On cardiac MRI, improvement in sMBF related to improvement in global circumferential strain (ρ = -0.65, P = .057) among those treated with eplerenone. Selecting for those with impaired myocardial perfusion (CFR <2.5 and/or sMBF <1.8), there was a treatment effect of eplerenone versus placebo to improve CFR (0.28 [0.27] vs -0.05 [0.36]; P = .04). Eplerenone prevented a small increase in troponin (0.00 [-0.13-0.00] vs 0.00 [0.00-0.74] ng/L; P = .03) without effects on ECMi (0.9 [-2.3-4.3] vs -0.7 [-2.2--0.1] g/m2; P = .38). CD4+ T-cell count (127 [-38-286] vs -6 [-168-53] cells/µL; P = .02) increased in the eplerenone- versus placebo-treated groups. CONCLUSIONS: RAAS blockade with eplerenone benefitted key indices and prevented worsening of myocardial perfusion, injury, and function among PWH with subclinical cardiac disease when compared with placebo. CLINICAL TRIALS REGISTRATION: NCT02740179 (https://clinicaltrials.gov/ct2/show/NCT02740179?term=NCT02740179&draw=2&rank=1).

Cognitive concerns are a risk factor for mortality in people with HIV and coronavirus disease 2019.

BACKGROUND: Data supporting dementia as a risk factor for coronavirus disease 2019 (COVID-19) mortality relied on ICD-10 codes, yet nearly 40% of individuals with probable dementia lack a formal diagnosis. Dementia coding is not well established for people with HIV (PWH), and its reliance may affect risk assessment. METHODS: This retrospective cohort analysis of PWH with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR positivity includes comparisons to people without HIV (PWoH), matched by age, sex, race, and zipcode. Primary exposures were dementia diagnosis, by International Classification of Diseases (ICD)-10 codes, and cognitive concerns, defined as possible cognitive impairment up to 12 months before COVID-19 diagnosis after clinical review of notes from the electronic health record. Logistic regression models assessed the effect of dementia and cognitive concerns on odds of death [odds ratio (OR); 95% CI (95% confidence interval)]; models adjusted for VACS Index 2.0. RESULTS: Sixty-four PWH were identified out of 14 129 patients with SARS-CoV-2 infection and matched to 463 PWoH. Compared with PWoH, PWH had a higher prevalence of dementia (15.6% vs. 6%, P  = 0.01) and cognitive concerns (21.9% vs. 15.8%, P  = 0.04). Death was more frequent in PWH ( P  < 0.01). Adjusted for VACS Index 2.0, dementia [2.4 (1.0-5.8), P  = 0.05] and cognitive concerns [2.4 (1.1-5.3), P  = 0.03] were associated with increased odds of death. In PWH, the association between cognitive concern and death trended towards statistical significance [3.92 (0.81-20.19), P  = 0.09]; there was no association with dementia. CONCLUSION: Cognitive status assessments are important for care in COVID-19, especially among PWH. Larger studies should validate findings and determine long-term COVID-19 consequences in PWH with preexisting cognitive deficits.

Mogamulizumab for Treatment of Human T-lymphotropic Virus Type 1-Associated Myelopathy/Tropical Spastic Paraparesis: A Single-Center US-based Series.

BACKGROUND: Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic neurological condition characterized by progressive myelopathic symptoms including spasticity, pain, weakness, and urinary symptoms, without proven treatments. Mogamulizumab (MOG) is a monoclonal antibody that binds CCR4 and leads to the clearance of HTLV-1-infected CCR4+ cells. A phase 1-2a study in Japan evaluated MOG for the treatment of HAM/TSP and reported decreases in HTLV-1 proviral load and neuroinflammatory markers, with clinical improvement in some participants. METHODS: We administered MOG 0.1 mg/kg every 8 weeks to individuals with HAM/TSP as a compassionate and palliative treatment. Patients who received MOG had (1) a positive peripheral HTLV-1 antibody, (2) progressive myelopathic symptoms, and (3) a diagnosis of HAM/TSP. RESULTS: Four female patients, ages 45-68, received MOG (range, 2-6 infusions) between 1 November 2019 and 30 November 2022. Two patients with <3 years of symptoms had milder disease, with Osame scores <4. The other 2, with >7 years of symptoms, had Osame scores >5. One patient, with 6 total treatments, received dose-reduced MOG after she developed a rash at the initial dose. The 2 patients with milder baseline disease reported symptomatic improvement and saw reductions in Osame and/or modified Ashworth scale scores during follow-up. The other 2 patients showed no improvement. All 4 developed rashes after receiving MOG-a treatment-limiting event in some cases. CONCLUSIONS: Clinical trials are needed including diverse patient populations to assess the potential role of MOG for HAM/TSP. Our findings may help inform the development of these trials.

Classification of neurologic outcomes from medical notes using natural language processing.

Neurologic disability level at hospital discharge is an important outcome in many clinical research studies. Outside of clinical trials, neurologic outcomes must typically be extracted by labor intensive manual review of clinical notes in the electronic health record (EHR). To overcome this challenge, we set out to develop a natural language processing (NLP) approach that automatically reads clinical notes to determine neurologic outcomes, to make it possible to conduct larger scale neurologic outcomes studies. We obtained 7314 notes from 3632 patients hospitalized at two large Boston hospitals between January 2012 and June 2020, including discharge summaries (3485), occupational therapy (1472) and physical therapy (2357) notes. Fourteen clinical experts reviewed notes to assign scores on the Glasgow Outcome Scale (GOS) with 4 classes, namely 'good recovery', 'moderate disability', 'severe disability', and 'death' and on the Modified Rankin Scale (mRS), with 7 classes, namely 'no symptoms', 'no significant disability', 'slight disability', 'moderate disability', 'moderately severe disability', 'severe disability', and 'death'. For 428 patients' notes, 2 experts scored the cases generating interrater reliability estimates for GOS and mRS. After preprocessing and extracting features from the notes, we trained a multiclass logistic regression model using LASSO regularization and 5-fold cross validation for hyperparameter tuning. The model performed well on the test set, achieving a micro average area under the receiver operating characteristic and F-score of 0.94 (95% CI 0.93-0.95) and 0.77 (0.75-0.80) for GOS, and 0.90 (0.89-0.91) and 0.59 (0.57-0.62) for mRS, respectively. Our work demonstrates that an NLP algorithm can accurately assign neurologic outcomes based on free text clinical notes. This algorithm increases the scale of research on neurological outcomes that is possible with EHR data.

Non-alcoholic fatty liver disease is not associated with impairment in health-related quality of life in virally suppressed persons with human immune deficiency virus.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in persons with HIV (PWH) (HIV-NAFLD). It is unknown if HIV-NAFLD is associated with impairment in health-related quality of life (HRQOL). We examined HRQOL in PWH with and without NAFLD, compared HRQOL in HIV- versus primary NAFLD, and determined factors associated with HRQOL in these groups. Prospectively enrolled 200 PWH and 474 participants with primary NAFLD completed the Rand SF-36 assessment which measures 8 domains of HRQOL. Individual domain scores were used to create composite physical and mental component summary scores. Univariate and multivariate analyses determined variables associated with HRQOL in PWH and in HIV- and primary NAFLD. In PWH, 48% had HIV-NAFLD, 10.2% had clinically significant fibrosis, 99.5% were on antiretroviral therapy, and 96.5% had HIV RNA <200 copies/ml. There was no difference in HRQOL in PWH with or without NAFLD. Diabetes, non-Hispanic ethnicity, and nadir CD4 counts were independently associated with impaired HRQOL in PWH. In HIV-NAFLD, HRQOL did not differ between participants with or without clinically significant fibrosis. Participants with HIV-NAFLD compared to those with primary NAFLD were less frequently cisgender females, White, more frequently Hispanic, had lower BMI and lower frequency of obesity and diabetes. HRQOL of individuals with HIV-NAFLD was not significantly different from those with primary NAFLD. In conclusion, in virally suppressed PWH, HRQOL is not different between participants with or without HIV-NAFLD. HRQOL is not different between HIV-NAFLD and primary NAFLD.

Burden of fatty liver and hepatic fibrosis in persons with HIV: A diverse cross-sectional US multicenter study.

BACKGROUND AIMS: The current prevalence of fatty liver disease (FLD) due to alcohol-associated (AFLD) and nonalcoholic (NAFLD) origins in US persons with HIV (PWH) is not well defined. We prospectively evaluated the burden of FLD and hepatic fibrosis in a diverse cohort of PWH. APPROACH RESULTS: Consenting participants in outpatient HIV clinics in 3 centers in the US underwent detailed phenotyping, including liver ultrasound and vibration-controlled transient elastography for controlled attenuation parameter and liver stiffness measurement. The prevalence of AFLD, NAFLD, and clinically significant and advanced fibrosis was determined. Univariate and multivariate logistic regression models were used to evaluate factors associated with the risk of NAFLD. Of 342 participants, 95.6% were on antiretroviral therapy, 93.9% had adequate viral suppression, 48.7% (95% CI 43%-54%) had steatosis by ultrasound, and 50.6% (95% CI 45%-56%) had steatosis by controlled attenuation parameter ≥263 dB/m. NAFLD accounted for 90% of FLD. In multivariable analysis, old age, higher body mass index, diabetes, and higher alanine aminotransferase, but not antiretroviral therapy or CD4 + cell count, were independently associated with increased NAFLD risk. In all PWH with fatty liver, the frequency of liver stiffness measurement 8-12 kPa was 13.9% (95% CI 9%-20%) and ≥12 kPa 6.4% (95% CI 3%-11%), with a similar frequency of these liver stiffness measurement cutoffs in NAFLD. CONCLUSIONS: Nearly half of the virally-suppressed PWH have FLD, 90% of which is due to NAFLD. A fifth of the PWH with FLD has clinically significant fibrosis, and 6% have advanced fibrosis. These data lend support to systematic screening for high-risk NAFLD in PWH.

Perspectives on Adherence From the ACTG 5360 MINMON Trial: A Minimum Monitoring Approach With 12 Weeks of Sofosbuvir/Velpatasvir in Chronic Hepatitis C Treatment.

BACKGROUND: With the advent of efficacious oral direct-acting antivirals (DAAs) for hepatitis C virus (HCV), identification of characteristics associated with adherence is critical to treatment success. We examined correlates of sub-optimal adherence to HCV therapy in a single-arm, multinational, clinical trial. METHODS: ACTG A5360 enrolled HCV treatment-naive persons without decompensated cirrhosis from 5 countries. All participants received a 12-weeks course of sofosbuvir/velpatasvir at entry. In-person visits occurred at initiation and week 24, sustained virologic response (SVR) assessment. Adherence at week 4 was collected remotely and was dichotomized optimal (100%, no missed doses) versus sub-optimal (<100%). Correlates of sub-optimal adherence were explored using logistic regression. RESULTS: In total, 400 participants enrolled; 399 initiated treatment; 395/397 (99%) reported completing at week 24. Median age was 47 years with 35% female. Among the 368 reporting optimal adherence at week 4 SVR was 96.5% (95% confidence interval [CI] [94.1%, 97.9%]) vs 77.8% (95% CI [59.2%, 89.4%]) P value < .001. In the multivariate model age <30 years and being a US participant were independently associated with early sub-optimal adherence. Participants <30 years were 7.1 times more likely to have early sub-optimal adherence compared to their older counterparts. CONCLUSIONS: Self-reported optimal adherence at week 4 was associated with SVR. Early self-reported adherence could be used to identify those at higher risk of treatment failure and may benefit from additional support. Younger individuals <30 years may also be prioritized for additional adherence support. Clinical Trials Registration. NCT03512210.

Adapting, testing, and refining a resilience intervention for older women with HIV: An open pilot study.

Half of persons with HIV in the United States (US), many of whom are women, are over age 50. Aging women with HIV (WWH) face unique biopsychosocial challenges, including stigma, the physiological effects of aging, and illness-associated stressors. Resilience interventions can build awareness of such stressors and aid in facilitating the relaxation response; however, no existing interventions specifically cater to the needs of older WWH. The content of the Relaxation Response Resiliency Program, which teaches positive psychology strategies, relaxation techniques, and cognitive behavioral skills, was adapted for older WWH. Thirteen WWH over 50 participated in an open pilot of the adapted intervention to iteratively refine the program and its procedures. Participants attended either 8 or 10 weekly group sessions; three groups were conducted in total. Pre- and post-intervention assessments and qualitative exit interviews were conducted. Among completers, an increase in resilience was observed. Though significance testing was not conducted, social support also increased, and depression, anxiety, and HIV stigma decreased from pre- to post-intervention. Over half of eligible women enrolled; completers reported high satisfaction with the program. However, retention was difficult; six participants withdrew or were lost to follow-up. Mean number of sessions attended was 3.5 in the 8-session group and 5 in the 10-session groups. In this small sample, the adapted intervention led to a clinically meaningful increase in resilience, though recruitment and retention were challenging. Further refinements to the intervention are needed to minimize attrition and increase acceptability before additional testing is initiated.

Preventing cardiovascular disease in midlife women with HIV: An examination of facilitators and barriers to heart health behaviors.

Midlife women with HIV (WWH) are disproportionately impacted by cardiovascular disease (CVD), yet little is known about perceptions of CVD risk and the factors that influence engagement in heart health behaviors in this population. Few (if any) studies have used a qualitative approach to examine these perceptions, which has important implications for minimizing the negative impact of HIV-related noncommunicable diseases, the risk for which increases after midlife. Eighteen midlife WWH (aged 40-59) in Boston, MA, completed semistructured interviews to explore perceptions of CVD, HIV, and barriers and facilitators to healthy lifestyle behaviors. Interviews were analyzed via thematic analysis. Participants viewed heart health as important but were unaware of HIV-associated CVD risk. Facilitators included family and generational influences, social support, and access to resources. Physical symptoms, menopause, mental health challenges, and limited financial resources were barriers. Midlife WWH may benefit from tailored CVD prevention interventions that target their unique motivations and barriers to healthy behaviors.

Mental Health, Social Connectedness, and Fear During the COVID-19 Pandemic: A Qualitative Perspective from Older Women with HIV.

Older women with HIV (WWH) confront significant biopsychosocial challenges that may be exacerbated by the COVID-19 pandemic. Between May 2020 and April 2021, following a resiliency intervention conducted as part of a randomized parent trial, 24 cisgender WWH (M = 58 years old) completed quantitative assessments and qualitative interviews exploring the impact of COVID-19 on mental health. Qualitative data were analyzed via rapid analysis. Most participants were Black (62.5%) and non-Hispanic or Latina (87.5%). Emergent themes included (1) increased anxiety and depression; (2) a loss of social connectedness; (3) fear of unknown interactions among COVID-19, HIV, and other comorbidities; and (4) the use of largely adaptive strategies to cope with these issues. Findings suggest that older WWH face significant COVID-19-related mental health challenges, compounding existing stressors. As the pandemic persists, it will be important to assess the impact of these stressors on wellbeing, identify effective coping strategies, and provide increased support to mitigate COVID-19-related mental health issues over time. Trial Registration: ClinicalTrials.gov identifier: NCT03071887.

The importance of methods for site performance evaluation in REPRIEVE, a longitudinal, global, multicenter trial.

BACKGROUND: REPRIEVE, the Randomized Trial to Prevent Vascular Events in HIV, is a multicenter, primary prevention trial evaluating whether a statin can prevent major cardiovascular events in people with HIV. REPRIEVE is conducted at >100 clinical research sites (CRSs) globally. Detailed, comprehensive, and novel methods for evaluating and communicating CRS performance are required to ensure trial integrity and data quality. In this analysis we describe a comprehensive multidimensional methodology for evaluating CRS performance. METHODS: The REPRIEVE Data Coordinating and Clinical Coordinating Centers developed a robust system for evaluation of and communication with CRSs, designed to identify potential issues and obstacles to performance, provide real-time technical support, and make recommendations for process improvements to facilitate efficient trial execution. We describe these systems and evaluate their impact on participant retention, data management, and specimen management from 2019 to 2022, corresponding to the period from end of recruitment to present. This evaluation was based on pre-defined metrics, regular reviews, and bidirectional communication. RESULTS: Participant retention, data management, and specimen management all remained steady over the three-year period, although metrics varied by country of enrollment. Targeted messaging relating to certain performance metrics was effective. CONCLUSION: Site performance is vital to ensure trial integrity and achievement of key trial goals. This analysis demonstrates that utilization of a comprehensive approach allows for a thorough evaluation of CRS performance, facilitates data and specimen management, and enhances participant retention. Our approach may serve as a guidepost for maximizing future large-scale clinical trials' operational success and scientific rigor. CLINICALTRIALS: gov Identifier: NCT02344290.

Identifying Modifiable Predictors of COVID-19 Vaccine Side Effects: A Machine Learning Approach.

Side effects of COVID-19 or other vaccinations may affect an individual's safety, ability to work or care for self or others, and/or willingness to be vaccinated. Identifying modifiable factors that influence these side effects may increase the number of people vaccinated. In this observational study, data were from individuals who received an mRNA COVID-19 vaccine between December 2020 and April 2021 and responded to at least one post-vaccination symptoms survey that was sent daily for three days after each vaccination. We excluded those with a COVID-19 diagnosis or positive SARS-CoV2 test within one week after their vaccination because of the overlap of symptoms. We used machine learning techniques to analyze the data after the first vaccination. Data from 50,484 individuals (73% female, 18 to 95 years old) were included in the primary analysis. Demographics, history of an epinephrine autoinjector prescription, allergy history category (e.g., food, vaccine, medication, insect sting, seasonal), prior COVID-19 diagnosis or positive test, and vaccine manufacturer were identified as factors associated with allergic and non-allergic side effects; vaccination time 6:00-10:59 was associated with more non-allergic side effects. Randomized controlled trials should be conducted to quantify the relative effect of modifiable factors, such as time of vaccination.

Development and Evaluation of a Natural Language Processing Annotation Tool to Facilitate Phenotyping of Cognitive Status in Electronic Health Records: Diagnostic Study.

BACKGROUND: Electronic health records (EHRs) with large sample sizes and rich information offer great potential for dementia research, but current methods of phenotyping cognitive status are not scalable. OBJECTIVE: The aim of this study was to evaluate whether natural language processing (NLP)-powered semiautomated annotation can improve the speed and interrater reliability of chart reviews for phenotyping cognitive status. METHODS: In this diagnostic study, we developed and evaluated a semiautomated NLP-powered annotation tool (NAT) to facilitate phenotyping of cognitive status. Clinical experts adjudicated the cognitive status of 627 patients at Mass General Brigham (MGB) health care, using NAT or traditional chart reviews. Patient charts contained EHR data from two data sets: (1) records from January 1, 2017, to December 31, 2018, for 100 Medicare beneficiaries from the MGB Accountable Care Organization and (2) records from 2 years prior to COVID-19 diagnosis to the date of COVID-19 diagnosis for 527 MGB patients. All EHR data from the relevant period were extracted; diagnosis codes, medications, and laboratory test values were processed and summarized; clinical notes were processed through an NLP pipeline; and a web tool was developed to present an integrated view of all data. Cognitive status was rated as cognitively normal, cognitively impaired, or undetermined. Assessment time and interrater agreement of NAT compared to manual chart reviews for cognitive status phenotyping was evaluated. RESULTS: NAT adjudication provided higher interrater agreement (Cohen κ=0.89 vs κ=0.80) and significant speed up (time difference mean 1.4, SD 1.3 minutes; P<.001; ratio median 2.2, min-max 0.4-20) over manual chart reviews. There was moderate agreement with manual chart reviews (Cohen κ=0.67). In the cases that exhibited disagreement with manual chart reviews, NAT adjudication was able to produce assessments that had broader clinical consensus due to its integrated view of highlighted relevant information and semiautomated NLP features. CONCLUSIONS: NAT adjudication improves the speed and interrater reliability for phenotyping cognitive status compared to manual chart reviews. This study underscores the potential of an NLP-based clinically adjudicated method to build large-scale dementia research cohorts from EHRs.

Identifying Patients With Delirium Based on Unstructured Clinical Notes: Observational Study.

BACKGROUND: Delirium in hospitalized patients is a syndrome of acute brain dysfunction. Diagnostic (International Classification of Diseases [ICD]) codes are often used in studies using electronic health records (EHRs), but they are inaccurate. OBJECTIVE: We sought to develop a more accurate method using natural language processing (NLP) to detect delirium episodes on the basis of unstructured clinical notes. METHODS: We collected 1.5 million notes from >10,000 patients from among 9 hospitals. Seven experts iteratively labeled 200,471 sentences. Using these, we trained three NLP classifiers: Support Vector Machine, Recurrent Neural Networks, and Transformer. Testing was performed using an external data set. We also evaluated associations with delirium billing (ICD) codes, medications, orders for restraints and sitters, direct assessments (Confusion Assessment Method [CAM] scores), and in-hospital mortality. F1 scores, confusion matrices, and areas under the receiver operating characteristic curve (AUCs) were used to compare NLP models. We used the φ coefficient to measure associations with other delirium indicators. RESULTS: The transformer NLP performed best on the following parameters: micro F1=0.978, macro F1=0.918, positive AUC=0.984, and negative AUC=0.992. NLP detections exhibited higher correlations (φ) than ICD codes with deliriogenic medications (0.194 vs 0.073 for ICD codes), restraints and sitter orders (0.358 vs 0.177), mortality (0.216 vs 0.000), and CAM scores (0.256 vs -0.028). CONCLUSIONS: Clinical notes are an attractive alternative to ICD codes for EHR delirium studies but require automated methods. Our NLP model detects delirium with high accuracy, similar to manual chart review. Our NLP approach can provide more accurate determination of delirium for large-scale EHR-based studies regarding delirium, quality improvement, and clinical trails.

A minimal monitoring approach for the treatment of hepatitis C virus infection (ACTG A5360 [MINMON]): a phase 4, open-label, single-arm trial.

BACKGROUND: Despite widespread availability of direct-acting antivirals including generic formulations, limited progress has been made in the global adoption of hepatitis C virus (HCV) treatment. Barriers to treatment scale-up include availability and access to diagnostic and monitoring tests, health-care infrastructure, and requirement for frequent visits during treatment. METHODS: ACTG A5360 was a phase 4, open-label, single-arm trial across 38 sites in Brazil, South Africa, Thailand, Uganda, and the USA. Key inclusion criteria were age of 18 years or older, evidence of active HCV infection (HCV RNA >1000 IU/mL) and HCV treatment-naive; patients with compensated cirrhosis and HIV/HCV co-infection were included but their enrolment was capped. All participants received a fixed dose combination of oral sofosbuvir (400 mg) and velpatasvir (100 mg) once daily for 12 weeks. The minimal monitoring (MINMON) approach consisted of four components: (1) there was no pre-treatment genotyping; (2) the entire treatment course (84 tablets) was dispensed at entry; (3) there were no scheduled visits or laboratory monitoring; and (4) there were two points of remote contact, at week 4 for adherence and week 22, to schedule outcome assessment at week 24 (-2 weeks to +4 weeks). Participants who missed the week 24 window could return for a visit to assess treatment response any time before week 72. Unplanned visits for any reason were permissible before the week 24 visit. The primary efficacy outcome was sustained virological response (SVR), defined as HCV RNA less than the lower limit of quantification measured at least 22 weeks post-treatment initiation; the primary safety outcome was serious adverse events. The primary efficacy analysis included all participants who initiated treatment, using a missing=failure approach. The primary safety analysis included all participants who initiated treatment and had at least one post-treatment assessment. This trial is registered at ClinicalTrials.gov, NCT03512210. FINDINGS: Between Oct 22, 2018, and July 19, 2019, 400 participants were enrolled across all 38 sites; 399 initiated treatment. At the SVR assessment visit, 355 (89%) of 397 participants reported taking 100% of the trial medication during the 12-week treatment period; two patients did not have any follow-up visits after the entry visit and were excluded from the safety analyses. Overall, 379 of the 399 who initiated treatment had an SVR (95·0%, 95% CI 92·4-96·7). 14 (4%) of 397 participants reported serious adverse events between treatment initiation and week 28; none were treatment related or led to treatment discontinuation or death. 15 (4%) of 399 participants had unplanned visits; none were related to treatment. INTERPRETATION: In this diverse global population of people with HCV, the MINMON approach with sofosbuvir-velpatasvir treatment was safe and achieved SVR comparable to standard monitoring observed in real-world data. Coupled with innovative case finding strategies, this strategy could be crucial to the global HCV elimination agenda. FUNDING: US National Institutes of Health and Gilead Sciences.