Comparative Effectiveness of Mepolizumab, Benralizumab, and Dupilumab among Patients with Difficult-to-Control Asthma: A Multicenter Retrospective Propensity-matched Analysis.

Rationale: The comparative effectiveness of biologic agents used as add-on therapy in the management of difficult-to-control asthma is unclear. Objective: To compare the effectiveness of dupilumab, mepolizumab, and benralizumab among patients with difficult-to-control asthma. Methods: Retrospective multicenter cohort study of adult patients with difficult-to-control asthma starting treatment with dupilumab, mepolizumab, or benralizumab as documented in a multicenter electronic health record and claims-based database between October 19, 2018, and September 30, 2022. Propensity-score matching was used to minimize bias from nonrandomized treatment assignment; a prespecified α-level was set at 0.017 to account for three primary comparisons. The exposure of interest was the new initiation of dupilumab, benralizumab, or mepolizumab treatment. The primary outcome was the rate of asthma exacerbations in the 1 year after initiation of biologic therapy modeled using a negative binomial approach. Results: Among 893,668 patients with asthma who were prescribed an inhaled corticosteroid and were ⩾12 years old (65% female; mean age, 49 yr), 3,943 started dupilumab, 1,902 started benralizumab, and 2,012 started mepolizumab, all without an alternative indication for biologic therapy. After matching, there were 1,805 patients in each group for comparisons between dupilumab and benralizumab, 1,865 for comparisons between dupilumab and mepolizumab, and 1,721 for comparisons between mepolizumab and benralizumab. For all pairwise comparisons, covariates were well balanced after matching (all standardized mean differences <0.1). Patients who initiated dupilumab had a significantly lower rate of asthma exacerbations (1.07 per year) compared with benralizumab (1.47 per year), with a rate ratio (RR) of 0.73 (95% confidence interval, 0.63-0.85), and also had a significantly lower rate of asthma exacerbations compared with mepolizumab (1.04 per year vs. 1.45 per year), with an RR of 0.72 (0.62-0.84). There was no statistically significant difference in the rate of asthma exacerbations between mepolizumab (1.40 per year) and benralizumab (1.41 per year), with an RR of 1.00 (0.85-1.17). Conclusions: In patients with difficult-to-control asthma who had newly initiated biologic therapy, dupilumab was associated with a decreased rate of asthma exacerbations in the 1 year after initiation compared with mepolizumab or benralizumab.

Primary care use and depression screening among young adults with sickle cell disease during their final year of pediatric hematology care.

Depression may contribute to transition risk among young adults with sickle cell disease (SCD). It is unclear if they receive depression screening because primary care providers (PCPs) routinely perform this screening, but PCP use declines with age. This retrospective study of young adults with SCD during their final year of pediatric hematology care identified 51 (91%) had PCPs. Among those with hospital system PCPs, 20% saw their PCP and 50% of those were screened for depression by the PCP. This suggests young adults with SCD may not receive depression screening or see PCPs, leading to potential missed opportunities for intervention.

Inhibition of BET Proteins Regulates Fcγ Receptor Function and Reduces Inflammation in Rheumatoid Arthritis.

Overactivation of immune responses is a hallmark of autoimmune disease pathogenesis. This includes the heightened production of inflammatory cytokines such as Tumor Necrosis Factor α (TNFα), and the secretion of autoantibodies such as isotypes of rheumatoid factor (RF) and anticitrullinated protein antibody (ACPA). Fcγ receptors (FcγR) expressed on the surface of myeloid cells bind Immunoglobulin G (IgG) immune complexes. Recognition of autoantigen-antibody complexes by FcγR induces an inflammatory phenotype that results in tissue damage and further escalation of the inflammatory response. Bromodomain and extra-terminal protein (BET) inhibition is associated with reduced immune responses, making the BET family a potential therapeutic target for autoimmune diseases such as rheumatoid arthritis (RA). In this paper, we examined the BET inhibitor PLX51107 and its effect on regulating FcγR expression and function in RA. PLX51107 significantly downregulated expression of FcγRIIa, FcγRIIb, FcγRIIIa, and the common γ-chain, FcϵR1-γ, in both healthy donor and RA patient monocytes. Consistent with this, PLX51107 treatment attenuated signaling events downstream of FcγR activation. This was accompanied by a significant decrease in phagocytosis and TNFα production. Finally, in a collagen-induced arthritis model, PLX51107-treatment reduced FcγR expression in vivo accompanied by a significant reduction in footpad swelling. These results suggest that BET inhibition is a novel therapeutic approach that requires further exploration as a treatment for patients with RA.

Practice Changes Among Patients Without COVID-19 Receiving Mechanical Ventilation During the Early COVID-19 Pandemic.

The COVID-19 pandemic led to rapid changes in care delivery for critically ill patients, due to factors including increased numbers of ICU patients, shifting staff roles, and changed care locations. As these changes may have impacted the care of patients without COVID-19, we assessed changes in common ICU practices for mechanically ventilated patients with non-COVID acute respiratory failure at the onset of and during the COVID-19 pandemic. DESIGN: Interrupted time series analysis, adjusted for seasonality and autocorrelation where present, evaluating trends in common ICU practices prior to the pandemic (March 2016 to February 2020), at the onset of the pandemic (April 2020) and intra-pandemic (April 2020 to December 2020). SETTING: Premier Healthcare Database, containing data from 25% of U.S. discharges from January 1, 2016, to December 31, 2020. PATIENTS: Patients without COVID-19 receiving mechanical ventilation for acute respiratory failure. INTERVENTIONS: We assessed monthly rates of chest radiograph (CXR), chest CT scans, lower extremity noninvasive vascular testing (LENI), bronchoscopy, arterial catheters, and central venous catheters. MEASUREMENTS AND MAIN RESULTS: We identified 742,096 mechanically ventilated patients without COVID-19 at 545 hospitals. At the onset of the pandemic, CXR (-0.5% [-0.9% to -0.2%; p = 0.001]), LENI (LENI: -2.1% [-3.3% to -0.9%; p = 0.001]), and bronchoscopy rates (-1.0% [-1.5% to -0.6%; p < 0.001]) decreased; use of chest CT increased (1.5% [0.5-2.5%; p = 0.006]). Use of arterial lines and central venous catheters did not change significantly. Intra-pandemic, LENI (0.5% [0.3-0.7%; p < 0.001]/mo) and bronchoscopy (0.1% [0.05-0.2%; p < 0.001]/mo) trends increased relative to pre-pandemic trends, while the remainder of practices did not change significantly. CONCLUSIONS: We observed several statistically significant changes to practice patterns among patients without COVID-19 early during the pandemic. However, most of the changes were small or temporary, suggesting that routine practices in the care of mechanically ventilated patients in the ICU was not drastically affected by the pandemic.

Hospital-level variation in practices and outcomes for patients with severe acute exacerbations of idiopathic pulmonary fibrosis: a retrospective multicentre cohort study.

BACKGROUND: In the absence of evidence-based strategies to improve patient outcomes, the management of patients with severe idiopathic pulmonary fibrosis (IPF) exacerbations may vary widely across centres. We assessed between-hospital variation in practices and mortality for patients with severe IPF exacerbations. METHODS: Using the Premier Healthcare Database from 1 October 2015 to 31 December 2020, we identified patients admitted to intensive care unit (ICU) or intermediate care unit with an IPF exacerbation. We assessed idiosyncratic, between-hospital variation in ICU practices (invasive mechanical ventilation (IMV), non-invasive mechanical ventilation (NIMV), corticosteroid use, and immunosuppressive and/or antioxidant use) and hospital mortality by determining median risk-adjusted hospital rates and intraclass correlation coefficients (ICCs) from hierarchical multivariable regression models. A priori, an ICC>15% was deemed 'high variation'. RESULTS: We identified 5256 critically ill patients with a severe IPF exacerbation at 385 US hospitals. Hospital median risk-adjusted rates of practices were: IMV (14% (IQR: 8.3%-26%)), NIMV (42% (31%-54%)), corticosteroid use (89% (84%-93%)), and immunosuppressive and/or antioxidant use (3.3% (1.9%-5.8%)). Model ICCs were: IMV (19% (95% CI: 18% to 21%)), NIMV (15% (13% to 16%)), corticosteroid use (9.8% (8.3% to 11%)), and immunosuppressive and/or antioxidant use (8.5% (7.1% to 9.9%)). The median risk-adjusted hospital mortality was 16% (IQR: 11%-24%) with an ICC of 7.5% (95% CI: 6.2% to 8.9%). INTERPRETATION: We observed high variation in the use of IMV and NIMV, and less variation in corticosteroid and immunosuppressant and/or antioxidant use among patients hospitalised with severe IPF exacerbations. Further research is needed to guide the decisions surrounding initiation of IMV and role of NIMV and to understand the effectiveness of corticosteroids among patients with severe IPF exacerbations.

Integrating Social Determinants of Health With Tobacco Treatment for Individuals With Opioid Use Disorder: Feasibility and Acceptability Study of Delivery Through Text Messaging.

BACKGROUND: Individuals with opioid use disorder (OUD) have a high prevalence of smoking and frequently experience unmet social determinants of health (SDOH), which may be barriers to smoking cessation. Hospitalization is an opportunity to encourage smoking cessation. Unfortunately, many clinicians do not provide tobacco treatment to support the maintenance of cessation achieved during hospitalization. Interventions are required to support these high-risk individuals after hospital discharge. OBJECTIVE: This study aimed to test the feasibility and acceptability of a 28-day SMS text messaging program tailored to individuals with OUD, which provides smoking cessation support and addresses unmet SDOH needs. METHODS: From July to December 2019, we enrolled 25 individuals who were hospitalized with tobacco dependence and OUD at our large safety net hospital. The SMS text messaging program was initiated during hospitalization and continued for 28 days. Participants were enrolled in either the ready to quit within 30 days or the not ready to quit within 30 days program based on their readiness to quit. Automated SMS text messages were sent twice daily for 4 weeks. The topics included health and cost benefits of quitting, both general and opioid specific (16 messages); managing mood and stress (8 messages); motivation, coping strategies, and encouragement (18 messages); addressing medication misconceptions (5 messages); links to resources to address substance use (2 messages providing links to the Massachusetts Substance Use Helpline and Boston Medical Center resources), tobacco dependence (1 message providing a link to the Massachusetts Quitline), and unmet SDOH needs (6 messages assessing SDOH needs with links to resources if unmet SDOH needs were identified). Questionnaires and interviews were conducted at baseline and at 2 and 4 weeks after enrollment. RESULTS: The participants were 56% (14/25) female, 36% (9/25) African American, 92% (23/25) unemployed, and 96% (24/25) Medicaid insured. Approximately 84% (21/25) activated the program, and none of the participants unsubscribed. Approximately 57% (12/21) completed either the 2- or 4-week questionnaires. Program satisfaction was high (overall mean 6.7, SD 0.8, range 1-7). Many perceived that the SMS text messaging program provided social support, companionship, and motivation to stop smoking. Messages about the health benefits of quitting were well received, whereas messages on how quitting cigarettes may prevent relapse from other substances had mixed views, highlighting the importance of tailoring interventions to patient preferences. CONCLUSIONS: SMS text messaging to promote smoking cessation and address SDOH needs may be an effective tool for improving quit rates and health outcomes in individuals with tobacco dependence and OUD. Our study adds to the growing body of evidence that SMS text messaging approaches are feasible and acceptable for providing tobacco treatment to all individuals who smoke, even among low-income populations who have OUD and are not ready to quit.

Text-messaging to promote smoking cessation among individuals with opioid use disorder: quantitative and qualitative evaluation.

INTRODUCTION: Individuals with opioid use disorder (OUD) who smoke cigarettes have high tobacco-related comorbidities, lack of access to tobacco treatment, lack of inclusion in smoking cessation trials, and remain understudied in the mobile health field. The purpose of this study was to understand patients' with OUD perceptions of 1) text message programs to promote smoking cessation, 2) content and features to include in such a program, and 3) how message content should be framed. METHODS: From December 2018 to February 2019, we recruited 20 hospitalized individuals with a concurrent diagnosis of OUD and tobacco dependence at Boston Medical Center (BMC), the largest safety-net hospital in New England. We surveyed participants' cell phone use, their interest in a text message program to promote smoking cessation, and their reactions to and ratings of a series of 26 prototype texts. We then conducted open-ended interviews to elicit content and suggestions on how text message interventions can improve motivation to increase smoking cessation among individuals with OUD. The interviews also included open-ended inquiries exploring message ratings and message content, inquiries about preferences for message duration, frequency, and personalization. RESULTS: Quantitative analysis of questionnaire data indicated that the majority of participants owned a cell phone (95%, 19/20). Most participants (60%, 12/20) reported that they would be interested or very interested in receiving text messages about smoking cessation. Text messages about the health benefits of quitting were rated the highest among various categories of text messages. Qualitative analysis showed that almost every participant felt that text messages would help motivate smoking cessation given the support it would provide. CONCLUSIONS: This study demonstrates that individuals with OUD who smoke cigarettes perceive that a text message program designed to promote smoking cessation would motivate and support smoking cessation efforts. Our findings demonstrate that such a program is feasible as participants own cell phones, frequently send and receive text messages, and have unlimited text message plans. Findings from this study provide valuable insight into content and features to include when developing text message programs to address barriers to smoking cessation in individuals who have OUD and smoke cigarettes.

Process and Clinical Outcomes of a Biosimilar Adoption Program with Infliximab-Dyyb.

BACKGROUND: In 2016, the FDA approved infliximab-dyyb (IFX-dyyb) as a biosimilar to infliximab (IFX). Deemed to have comparable efficacy and safety to IFX, IFX-dyyb is 20%-30% less expensive, allowing significant cost savings for institutions and some payers. In 2018, IFX was reported to be the drug with the highest spend since 2013, costing $3.8 billion; however, transition to IFX-dyyb would save $1.1 billion. Regardless, many institutions have not transitioned to IFX-dyyb or other IFX biosimilars (e.g., IFX-abda) because of concerns about clinical outcomes, uncertainty regarding financial impact, and barriers to operationalizing biosimilar adoption. At Boston Medical Center, a decision was made in March 2018 to adopt IFX-dyyb and transition patients who have been on IFX for ≥ 6 months for all indications to IFX-dyyb. OBJECTIVES: To (a) describe a biosimilar adoption process of IFX-dyyb in patients on IFX for ≥ 6 months; (b) characterize cost savings of transitioning patients to IFX-dyyb; and (c) evaluate real-world clinical outcomes of adult patients with inflammatory bowel disease (IBD) who transitioned to IFX-dyyb. METHODS: This is a retrospective cohort study of patients eligible for the IFX-dyyb switch from March 2018 to June 2019 at a large academic medical center. For process outcomes, we collected the proportion of patients who transitioned to IFX-dyyb and calculated the cost savings generated. To assess clinical outcomes of adult IBD patients who transitioned, we collected IFX and IFX-dyyb dosage, Harvey Bradshaw Index (HBI) or Simple Clinical Colitis Activity Index (SCCAI) scores, c-reactive protein (CRP) levels, and colonoscopy results. Descriptive statistics, Wilcoxon signed-rank test, and McNemar's test were used for statistical analyses. RESULTS: Of 151 eligible patients, 146 (97%) successfully transitioned to IFX-dyyb. Based on our conversion rate to IFX-dyyb, our health system is forecasted to save approximately $500,000 annually. From March to June 2018, 63 of 75 (84%) eligible IBD patients transitioned from IFX to IFX-dyyb. In this cohort, of the 40 patients with HBI or SCCAI scores before and after transition, 36 (90%) maintained remission. For 32 patients, the mean CRP (SD) before transition was 11.2 (22) and 4.1 (4.8) after transition (P = 0.09). Since the IFX-dyyb transition, 9 patients had a colonoscopy, of which 5 (56%) were in endoscopic remission. As of October 2018, 56 (89%) patients continued with IFX-dyyb after transition. Of the 46 patients who had 12-15 months posttransition data, 38 (83%) remained on IFX-dyyb. CONCLUSIONS: Implementation of a biosimilar adoption program can be successful and result in significant cost savings without compromising clinical outcomes. A model that uses actionable strategies and embraces collaboration among stakeholders is described here, with outcomes demonstrating successful IFX-dyyb uptake and no changes in clinical outcomes of transitioned adult patients with IBD. DISCLOSURES: No outside funding supported this study. Farraye reports advisory board fees from Janssen, Merck, and Pfizer. Shah reports speaker fees from Pfizer. The other authors have nothing to disclose.

Factors Associated With Long-term Outcomes of Umbilical Hernia Repair.

Importance: Umbilical hernia repair is one of the most commonly performed general surgical procedures. However, there is little consensus about the factors that lead to umbilical hernia recurrence. Objective: To better understand the factors associated with long-term umbilical hernia recurrence. Design, Setting, and Participants: A retrospective cohort of 332 military veteran patients who underwent umbilical hernia repair was studied between January 1, 1998, and December 31, 2008, at the VA Boston Healthcare System. Recurrence and mortality outcomes were tracked from that period until June 1, 2014. Data were collected on patient characteristics, operative, and postoperative factors and univariate and multivariable analyses were used to assess which factors were significantly associated with umbilical hernia recurrence and mortality. All patients with primary umbilical hernia repair, with or without a concurrent unrelated procedure, were included in the study. Patients excluded were those who underwent umbilical hernia repair as a part of another major planned procedure with abdominal incisions. Data were collected from June 1, 2014, to November 1, 2015. Statistical analysis was performed from November 2, 2015, to April 1, 2016. Main Outcomes and Measures: The primary study outcomes were umbilical hernia recurrence and death. Results: Of the 332 patients in this study, 321 (96.7%) were male, mean age was 58.4 years, and mean (SD) time of follow-up was 8.5 (4.1) years. The hernia recurrence rate was 6.0% (n = 20) at a mean 3.1 years after index repair (median, 1.0-year; range, 0.33-13 years). The primary suture repair recurrence rate was 9.8% (16 of 163 patients), and the mesh repair recurrence rate was 2.4% (4 of 169 patients). On univariate analysis, ascites (P = .02), liver disease (P = .02), diabetes (P = .04), and primary suture (nonmesh) repairs (P = .04) were significantly associated with increased recurrence rates. Patients who had a history of hernias (125 [39%]) were less likely to have umbilical hernia recurrences (χ21 = 4.65, P = .03). On multivariable regression analysis, obesity and ascites were associated with significantly increased odds ratios of recurrence of 3.3 (95% CI, 1.0-10.1) and 8.0 (95% CI, 1.8-34.4), respectively. Mesh repair was seen to decrease recurrence with odds of 0.28 (95% CI, 0.08-0.95). There was no significant difference in complication rates between mesh repair and primary suture repair. The survival rate was 73% (n = 242) at the end of the study. Factors associated with mortality were older age, smoking, liver disease, ascites, emergency or semiurgent repair, and need for intraoperative bowel resection. Conclusions and Relevance: Ascites, liver disease, diabetes, obesity, and primary suture repair without mesh are associated with increased umbilical hernia recurrence rates. Elective umbilical hernia repair with mesh should be considered in patients with multiple comorbidities given that the use of mesh offers protection from recurrence without major morbidity.

Emotion modulates eye movement patterns and subsequent memory for the gist and details of movie scenes.

A basic question in vision research regards where people look in complex scenes and how this influences their performance in various tasks. Previous studies with static images have demonstrated a close link between where people look and what they remember. Here, we examined the pattern of eye movements when participants watched neutral and emotional clips from Hollywood-style movies. Participants answered multiple-choice memory questions concerning visual and auditory scene details immediately upon viewing 1-min-long neutral or emotional movie clips. Fixations were more narrowly focused for emotional clips, and immediate memory for object details was worse compared to matched neutral scenes, implying preferential attention to emotional events. Although we found the expected correlation between where people looked and what they remembered for neutral clips, this relationship broke down for emotional clips. When participants were subsequently presented with key frames (static images) extracted from the movie clips such that presentation duration of the target objects (TOs) corresponding to the multiple-choice questions was matched and the earlier questions were repeated, more fixations were observed on the TOs, and memory performance also improved significantly, confirming that emotion modulates the relationship between gaze position and memory performance. Finally, in a long-term memory test, old/new recognition performance was significantly better for emotional scenes as compared to neutral scenes. Overall, these results are consistent with the hypothesis that emotional content draws eye fixations and strengthens memory for the scene gist while weakening encoding of peripheral scene details.