The prevalence of injection-site reactions with disease-modifying therapies and their effect on adherence in patients with multiple sclerosis: an observational study

<p>Abstract</p> <p>Background</p> <p>Interferon beta (IFNβ) and glatiramer acetate (GA) are administered by subcutaneous (SC) or intramuscular (IM) injection. Patients with multiple sclerosis (MS) often report injection-site reactions (ISRs) as a reason for noncompliance or switching therapies. The aim of this study was to compare the proportion of patients on different formulations of IFNβ or GA who experienced ISRs and who switched or discontinued therapy because of ISRs.</p> <p>Methods</p> <p>The Swiss MS Skin Project was an observational multicenter study. Patients with MS or clinically isolated syndrome who were on the same therapy for at least 2 years were enrolled. A skin examination was conducted at the first study visit and 1 year later.</p> <p>Results</p> <p>The 412 patients enrolled were on 1 of 4 disease-modifying therapies for at least 2 years: IM IFNβ-1a (n = 82), SC IFNβ-1b (n = 123), SC IFNβ-1a (n = 184), or SC GA (n = 23). At first evaluation, ISRs were reported by fewer patients on IM IFNβ-1a (13.4%) than on SC IFNβ-1b (57.7%; <it>P </it>< 0.0001), SC IFNβ-1a (67.9%; <it>P </it>< 0.0001), or SC GA (30.4%; <it>P </it>= not significant [NS]). No patient on IM IFNβ-1a missed a dose in the previous 4 weeks because of ISRs, compared with 5.7% of patients on SC IFNβ-1b (<it>P </it>= 0.044), 7.1% of patients on SC IFNβ-1a (<it>P </it>= 0.011), and 4.3% of patients on SC GA (<it>P </it>= NS). Primary reasons for discontinuing or switching therapy were ISRs or lack of efficacy. Similar patterns were observed at 1 year.</p> <p>Conclusions</p> <p>Patients on IM IFNβ-1a had fewer ISRs and were less likely to switch therapies than patients on other therapies. This study may have implications in selecting initial therapy or, for patients considering switching or discontinuing therapy because of ISRs, selecting an alternative option.</p

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Miracles in medicine: A narrative inquiry exploring extraordinary events in pediatrics

Abstract Background and Aims Whether miracles are seen as a source of conflict between healthcare teams and families, a foolish or even harmful belief, or a hindrance to system‐wide improvements and scientific inquiry, miracles within medicine have long been questioned. We were interested in the perspectives of pediatricians on miracles and how that has informed their care of patients. We also sought to explore the intersection and relationship between the medical sciences, faith, and how we view miracles. Methods Using narrative inquiry as a research methodology, we had conversations and explored the experiences of physicians who work directly within pediatric clinical care. We used purposeful sampling by emailing several pediatricians whom we felt might have been interested in the project and may have had experiences with perceived medical miracles. All conversations were conducted over Zoom and recorded. Results We conducted one to three conversations with each participant. During our analysis, we identified two threads. First, participants described miracles mostly as favorable and fortuitous events that invoked a sense of wonder due to contextual factors such as geography, access to resources, time in history but also previous experiences and the expectations of the clinician. Second, there is a complex dynamic within and between the medical sciences and the faith commitments of clinicians and families, especially when facing life‐limiting or end‐of‐life illness. Conclusions The stories that our participants told not only informed their past experiences and how they remembered them but also their present and future experiences. Exploring the topic of medical miracles allowed us to better understand the social discourses that shape our perceptions of miracles, death, and the role of the physician. These stories offer us hope and possibility in a time when we as a medical community may have lost our sense of wonder and the ability to notice miracles

A Survey of Residents’ Perceptions of the Effect of Large-Scale Economic Developments on Perceived Safety, Violence, and Economic Benefits

Background. Emerging research highlights the promise of community- and policy-level strategies in preventing youth violence. Large-scale economic developments, such as sports and entertainment arenas and casinos, may improve the living conditions, economics, public health, and overall wellbeing of area residents and may influence rates of violence within communities. Objective. To assess the effect of community economic development efforts on neighborhood residents’ perceptions on violence, safety, and economic benefits. Methods. Telephone survey in 2011 using a listed sample of randomly selected numbers in six Pittsburgh neighborhoods. Descriptive analyses examined measures of perceived violence and safety and economic benefit. Responses were compared across neighborhoods using chi-square tests for multiple comparisons. Survey results were compared to census and police data. Results. Residents in neighborhoods with the large-scale economic developments reported more casino-specific and arena-specific economic benefits. However, 42% of participants in the neighborhood with the entertainment arena felt there was an increase in crime, and 29% of respondents from the neighborhood with the casino felt there was an increase. In contrast, crime decreased in both neighborhoods. Conclusions. Large-scale economic developments have a direct influence on the perception of violence, despite actual violence rates

Response to Flavored Cartridge/Pod-Based Product Ban among Adult JUUL Users: “You Get Nicotine However You Can Get It”

In order to curb increasing youth electronic cigarette (e-cig) use, the United States Food and Drug Administration (FDA) banned the sale of flavored cartridge/pod-based products in February 2020. This mixed-methods study aimed to evaluate the impact of the FDA ban on adult JUUL users. The samples of current adult JUUL users were surveyed via Amazon Mechanical Turk at three time-points n = 76 (Sample 1); n = 128 (Sample 2); n = 86 (Sample 3) before and after the FDA flavored/pod ban. The participants were asked to report the JUUL flavored pod used most often and answer questions on purchasing generic pods or refilling (Quantitative). JUUL users were then interviewed in order to explore their perceptions and behaviors related to the FDA ban of flavored cartridge/pod-based products (Qualitative; n = 16). Quantitative data analysis evaluated the differences in variables by time-point. Qualitative data were coded into themes while using the constant comparative method. We found a significant decrease in the use of mint pods (43.4%, 22.7%, 16.3%) (p &lt; 0.01), while there was a significant increase in the use of menthol pods (6.6%, 26.6%, 37.2%) (p &lt; 0.01). Themes that emerged from the qualitative data included switching from mint to menthol pods, refilling pods, and switching to other products that are available in the desired flavors, such as generic pods or disposable e-cigs. Future research is needed in order to evaluate the impact of these behaviors on public health

Nicotine absorption during electronic cigarette use among regular users.

BackgroundThe capability of electronic cigarette devices (e-cigs) to deliver nicotine is key to their potential to replace combustible cigarettes. We compared nicotine delivery and subjective effects associated with the use of two classes of e-cigarettes and cigarettes.Methods14 e-cigarette users were instructed to vape their own e-cigarette device every 20 seconds for 10 minutes while blood was drawn at 1, 2, 4, 6, 8, 10,12, and 15 minutes after initiating vaping. Users rated withdrawal symptoms and side effects before and after vaping. E-cigarette devices were classified as first-generation (same size as cigarette, no activation button) or advanced (larger than cigarette with an activation button). Separately, 10 cigarette smokers completed a similar protocol. Fisher's Exact Test and two-sided t-tests were used as appropriate to determine differences in outcomes between first-generation e-cigarette users, advanced e-cigarette users, and smokers.ResultsCompared to first-generation devices, advanced devices were associated with greater serum nicotine Cmax (ng/ml) (11.5 v. 2.8, p = 0.0231) and greater nicotine boost (ng/ml) (10.8 v. 1.8, p = 0.0177). Overall, e-cigarettes users experienced a significant reduction in withdrawal and craving, although there were no significant differences between users of first-generation and advanced devices. Comparing e-cigarettes overall to cigarettes, cigarettes were associated with greater Cmax (25.9 v. 9.0, p = 0.0043) and greater nicotine boost (21.0 v. 8.2, p = 0.0128).ConclusionsAdvanced e-cigarettes delivered significantly more nicotine than first-generation devices but less than combustible cigarettes. Overall, e-cigarette use was associated with a reduction in withdrawal and craving with no reported side effects. The wide variation in nicotine absorption from different e-cigarette devices should be considered in studies of e-cigarettes for smoking cessation

A Comparison of Vaping Behavior, Perceptions, and Dependence among Individuals Who Vape Nicotine, Cannabis, or Both

Background: Electronic delivery systems (e.g., vapes, e-cigarettes) are now popular modes of cannabis and nicotine administration that are often used by the same individuals; however, we still know little about dual nicotine and cannabis vaping. Materials &amp; Methods: An online convenience sample of adult nicotine and/or cannabis vape users residing in the United States completed a 60 min survey on sociodemographic characteristics, cannabis and/or nicotine vape use behaviors and dependence, reasons for vape use, and perceptions of benefits and harms. After data cleaning, we compared dual vs. nicotine-only and cannabis-only vape users with univariate statistics and step-wise hierarchical linear regression analyses. Additionally, we assessed the factor structure, internal consistency, and criterion and convergent validity of the Penn State Cannabis Vaping Dependence Index (PSCVDI). Results: The final sample included 357 dual, 40 cannabis, and 106 nicotine vape users. Compared to nicotine- and cannabis-only vapers, dual vapers started using their nicotine and cannabis vapes at a younger age (p &lt; 0.001), used them for more years (p &lt; 0.001), and were less likely to use their nicotine vape to replace combustible cigarettes (p = 0.047). Dual users vs. single-substance users did not have significantly higher nicotine or cannabis vape dependence scores after controlling for sociodemographic and use behaviors. The PSCVDI showed adequate validity for measuring cannabis vape dependence. Conclusions: This survey is the first to highlight important differences in vape use behaviors and reasons for use between dual vs. cannabis- and nicotine-only vape users

Effects of sweet flavorings and nicotine on the appeal and sensory properties of e-cigarettes among young adult vapers: Application of a novel methodology

INTRODUCTION: Product characteristics that impact e-cigarette appeal by altering the sensory experience of vaping need to be identified to formulate evidence-based regulatory policies. While products that contain sweet flavorings and produce a “throat hit” (i.e., desirable airway irritation putatively caused by nicotine) are anecdotally cited as desirable reasons for vaping among young adults, experimental evidence of their impact on user appeal is lacking. This experiment applied a novel laboratory protocol to assess whether: (1) sweet flavorings and nicotine affect e-cigarette appeal; (2) sweet flavorings increase perceived sweetness; (3) nicotine increases throat hit; and (4) perceived sweetness and throat hit are associated with appeal. METHODS: Young adult vapers (N=20; age 19–34) self-administered 20 standardized doses of aerosolized e-cigarette solutions varied according to a 3 flavor (sweet [e.g., cotton candy] vs. non-sweet [e.g., tobacco-flavored] vs. flavorless) × 2 nicotine (6 mg/mL nicotine vs. 0 mg/mL [placebo]) double-blind, cross-over design. Participants rated appeal (liking, willingness to use again and perceived monetary value), perceived sweetness and throat hit strength after each administration. RESULTS: Sweet-flavored (vs. non-sweet and flavorless) solutions produced greater appeal and perceived sweetness ratings. Nicotine produced greater throat hit ratings than placebo, but did not significantly increase appeal nor interact with flavor effects on appeal. Controlling for flavor and nicotine, perceived sweetness was positively associated with appeal ratings; throat hit was not positively associated with appeal. CONCLUSIONS: Further identification of compounds in e-cigarette solutions that enhance sensory perceptions of sweetness, appeal, and utilization of e-cigarettes are warranted to inform evidence-based regulatory policies