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Importance The optimal inhaled reliever therapy for asthma remains unclear. Objective To compare short-acting β agonists (SABA) alone with SABA combined with inhaled corticosteroids (ICS) and with the fast-onset, long-acting β agonist formoterol combined with ICS for asthma. Data Sources The MEDLINE, Embase, and CENTRAL databases were searched from January 1, 2020, to September 27, 2024, without language restrictions. Study Selection Pairs of reviewers independently selected randomized clinical trials evaluating (1) SABA alone, (2) ICS with formoterol, and (3) ICS with SABA (combined or separate inhalers). Data Extraction and Synthesis Two reviewers independently extracted data and assessed risk of bias. Random-effects meta-analyses synthesized outcomes. GRADE (Grading of Recommendations Assessment, Development, and Evaluation) was used to evaluate the certainty of evidence. Main Outcomes and Measures Asthma symptom control (5-item Asthma Control Questionnaire; range, 0-6, lower scores indicate better asthma control; minimum important difference [MID], 0.5 points), asthma-related quality of life (Asthma Quality of Life Questionnaire; range, 1-7, higher scores indicate better quality of life; MID, 0.5 points), risk of severe exacerbations, and risk of serious adverse events. Results A total of 27 randomized clinical trials (N = 50 496 adult and pediatric patients; mean age, 41.0 years; 20 288 male [40%]) were included. Compared with SABA alone, both ICS-containing relievers were associated with fewer severe exacerbations (ICS-formoterol risk ratio [RR], 0.65 [95% CI, 0.60-0.72]; risk difference [RD], −10.3% [95% CI, −11.8% to −8.3%]; ICS-SABA RR, 0.84 [95% CI, 0.73-0.95]; RD, −4.7% [95% CI, −8.0% to −1.5%]) with high certainty. Compared with SABA alone, both ICS-containing relievers were associated with improved asthma control (ICS-formoterol RR improvement [MID] in total score, 1.07 [95% CI, 1.04-1.10]; RD, 4.1% [95% CI, 2.3%-5.9%]; ICS-SABA RR, 1.09 [95% CI, 1.03-1.15]; RD, 5.4% [95% CI, 1.8%-8.5%]) with high certainty. In an indirect comparison with ICS-SABA, ICS-formoterol was associated with fewer severe exacerbations (RR, 0.78 [95% CI, 0.66-0.92]; RD, −5.5% [95% CI, −8.4% to −2.0%]) with moderate certainty. Compared with SABA alone, ICS-formoterol (RD, −0.6% [95% CI, −1.3% to 0%]) was not associated with increased risk of serious adverse events (high certainty) and ICS-SABA (RD, 0% [95% CI, −1.1% to 1.2%]) was not associated with increased risk of serious adverse events (moderate certainty). Conclusions and Relevance In this network meta-analysis of patients with asthma, ICS combined with formoterol and ICS combined with SABA were each associated with reduced asthma exacerbations and improved asthma control compared with SABA alone.

ImportanceAsymmetric oropharynx uptake on positron emission tomography (PET)/computed tomography (CT) is a common incidental finding and often prompts otolaryngology referral to rule out malignancy; however, the true risk of malignancy based on this finding is unknown.ObjectiveTo identify the incidence of oropharynx cancer in patients with incidental asymmetric oropharynx PET uptake.Design, Setting, and ParticipantsIn this retrospective cohort study, patients 18 years and older undergoing PET/CT scans at Mayo Clinic between January 2001 and December 2018 were included. Patients with a history or pretest suspicion of oropharynx cancer were excluded. Data were analyzed from March 2021 to December 2023.ExposureBlinded radiologic review of imaging studies, including measurement of maximum standardized uptake values (SUVmax) of the ipsilateral side of concern and contralateral side. Retrospective medical record review for associated clinical data.Main Outcomes and MeasuresThe primary study outcome was the incidence of oropharynx cancer diagnosis in patients with asymmetric oropharynx PET uptake. The primary outcome was formulated before data collection.ResultsOf the 1854 patients identified with asymmetric oropharynx PET uptake, 327 (17.6%) met inclusion criteria. Of these, 173 (52.9%) were male, and the median (range) age was 65.0 (24.8-90.7) years. The mean (SD) follow-up interval was 52.1 (43.4) months. A total of 18 of 327 patients (5.5%) were newly diagnosed with oropharynx cancer. The most common diagnosis was squamous cell carcinoma (n = 9), followed by lymphoma (n = 8), and sarcoma (n = 1). Patients with an incidental diagnosis of oropharynx cancer had higher mean (SD) ipsilateral SUVmax (8.7 [3.7] vs 5.3 [1.9]) and SUVmax ratio (3.0 [1.6] vs 1.6 [0.6]) compared with patients with normal examination findings. SUVmax ratio and difference were found to be good discriminators of oropharynx cancer, with areas under the receiver operating characteristic curve of 86.3% (95% CI, 76.4-94.6) and 85.8% (95% CI, 74.8-94.6), respectively. Patients with a new diagnosis of oropharynx cancer were more likely to have a corresponding CT abnormality than those with normal examination findings (6 of 18 [33%] vs 24 of 295 [8.1%]). Patients with concerning lesions on oropharynx palpation by an otolaryngology health care professional were significantly more likely to be diagnosed with oropharynx cancer compared with patients with normal examination findings (odds ratio, 28.4; 95% CI, 6.6-145.8).Conclusions and RelevanceIn this cohort study, while incidental asymmetric oropharynx PET uptake was common, a new diagnosis of oropharynx cancer was not and potentially results in a large volume of unnecessary referrals and work-up. Using SUVmax ratio, SUVmax difference, and CT correlation may increase the benefit of referral. Patients with a palpable oropharynx lesion and asymmetric oropharynx PET uptake should undergo confirmatory biopsy.

ObjectiveTo evaluate the impact of age on disease recurrence in idiopathic subglottic stenosis (iSGS) patients.MethodsThis was a retrospective chart review of iSGS patients treated with laser wedge excision. Patients did not have prior surgery. Survival rates free of recurrence were estimated using the Kaplan–Meier methods, and associations were evaluated using Cox Proportional Hazards models.ResultsEighty‐five female patients were included in the study. Most patients (68%) were postmenopausal, had first period at or before 13 years of age, had at least one full‐term pregnancy (82%), were not undergoing hormone replacement therapy (93%), were not using hormonal birth control (88%), and were either partially or completely compliant with triple therapy regime (80%). There was a statistically significant average reduction in risk of recurrence of 5% for every additional year of age (p < 0.0001). When compared to patients older than 65 years of age, patients less than 35 were nearly 10 times more likely to recur (p = 0.002), and patients 55–65 and 45–55 years of age were 8 and 5 times more likely to recur, respectively (p = 0.003 and 0.009). Additionally, females on birth control showed decreased risk of recurrence of 74% compared with their counterparts (p = 0.04).ConclusionThis is the first study to demonstrate an inverse relationship between age and disease recurrence in patients with iSGS following surgery. Using age as a surrogate for menopausal status, these results suggest that increased age and/or birth control provide a protective effect through decreased recurrence rates, possibly mediated by decreased estrogen levels.Level of Evidence4 Laryngoscope, 2024

Background and Aims: Metabolic dysfunction–associated steatotic liver disease management guidelines have been published worldwide; we aimed to summarize, categorize, and compare their lifestyle intervention recommendations. Approach and Results: We searched metabolic dysfunction–associated steatotic liver disease/NAFLD management guidelines published between January 1, 2013, and June 31, 2024, through databases including PubMed/MEDLINE, Cochrane, and CINAHL. In total, 35 qualifying guidelines were included in the final analysis. Guideline recommendations were categorized into 5 domains (ie, weight reduction goals, physical activity, nutrition, alcohol, and tobacco smoking) and were ranked based on how frequently they appeared. A recommendation was defined as widely adopted if recommended in ≥24 (≥66.6%) of the guidelines. These included increasing physical activity; reducing body weight by 7%–10% to improve steatohepatitis and/or fibrosis; restricting caloric intake; undertaking 150–300 or 75–150 minutes/week of moderate or vigorous-intensity physical activity, respectively; and decreasing consumption of commercially produced fructose. The least mentioned topics, in ≤9 of the guidelines, evaluated environmental determinants of health, mental health, referring patients for psychological or cognitive behavioral therapy, using digital health interventions, and assessing patients’ social determinants of health. Conclusions: Most guidelines recommend weight reduction through physical activity and improving nutrition, as these have proven positive effects on health outcomes when sustained. However, gaps regarding mental health and the social and environmental determinants of metabolic dysfunction–associated steatotic liver disease were found. To optimize behavioral modifications and treatment, we recommend carrying out studies that will provide further evidence on social support, environmental factors, and mental health, as well as further exploring digital health interventions.

ObjectiveTo evaluate the impact of methotrexate and rituximab therapy on highly recurrent idiopathic subglottic stenosis (iSGS) patients with a negative antineutrophil cytoplasmic antibody titer cANCA(−).MethodsThis was a retrospective cohort study of highly recurrent iSGS patients who recurred within 1 year or less and were treated with methotrexate (MTX), and rituximab (RTX), or a combination of both at different time points (MTX/RTX). Average surgical durations before and after drug treatment were summarized, and the differences were calculated.ResultsA total of 21 female patients with median age of 62 years were included. Fifteen patients were treated with MTX, three were treated with RTX, and five treated with both. Patients treated with immunosuppressants showed a trend toward longer intervals between operations (mean pre‐drug interval: 338; mean post‐drug interval: 697 days) (p‐value = 0.25). Three patients did not recur following drug initiation with median follow‐up of 1265 days. All three treatment groups demonstrated a trend toward increased post‐drug recurrence intervals (MTX: 444 days, RTX: 374 days, MTX/RTX: 55 days), that was not statistically significant. Patients with prior dilations demonstrated longer post‐drug recurrence intervals (mean pre‐drug interval: 341 days, mean post‐drug interval 978 days) (p‐value = 0.17). Four patients in the cohort with the highest recurring disease improved from mean 129 days between operations to 509 days with drug therapy. The most common drug side effect was nausea (16%).ConclusionMTX and RTX may be treatment options for some highly recurrent iSGS patients. Initial results are variable and demonstrate a need for further research on drug candidacy.Level of Evidence3 Laryngoscope, 2024

Importance Hispanic adults with type 2 diabetes (T2D) are more likely to develop complications and die from the disease than the US general population. Digital storytelling interventions are narrative-based videos elicited through a community-based participatory research approach to surface the authentic voices of participants overcoming obstacles to health-promoting behaviors that perpetuate health inequities; research on the effect of digital storytelling on T2D outcomes among Hispanic adults is lacking. Objective To assess the impact of a digital storytelling intervention on glycemic control and its acceptability among Hispanic patients with poorly controlled T2D. Design, Setting, and Participants This was a multicenter, randomized clinical trial conducted within 2 primary care networks in Minnesota and Arizona among Hispanic adults with poorly controlled T2D (hemoglobin A 1c level ≥8%). Enrollment and follow-up were conducted between February 14, 2019, and November 1, 2023. Intervention The intervention group viewed a 12-minute digital storytelling video. The video included 4 Spanish-language stories that reinforced 4 diabetes self-management behavioral goals (healthful diet for diabetes, physical activity, medication adherence, and glucose self-monitoring). The control group received printed, culturally tailored T2D education materials. Main Outcomes and Measures The primary outcome was the mean change from baseline to 3 months for hemoglobin A 1c levels, adjusting for baseline hemoglobin A 1c , age, gender, education, and income. Acceptability and narrative quality of the intervention were assessed through questionnaires. Results There were 451 study participants, with 227 (mean [SD] age, 54.3 [9.3] years; 158 [69.3%] women) randomized to the intervention group and 224 (mean [SD] age, 54.5 [9.1] years; 156 [69.3%] women) to the control group. Of these, 390 completed 3-month follow-up of the primary outcome (86% retention). There was a small improvement in the mean (SD) hemoglobin A 1c level in the intervention group compared with the control group in the adjusted model (9.1% [1.7] to 8.4% [1.6] vs 9.4% [1.8] to 8.8% [2.0]; P = .04] but not in the unadjusted model. Acceptability and narrative quality of the intervention were high. Conclusions and Relevance In this randomized clinical trial, a digital storytelling intervention developed with and for Hispanic adults with T2D was highly acceptable and feasibly implemented within primary care settings and resulted in a modest improvement of glycemic control. This was a highly scalable intervention that may be integrated into clinical practice as part of a longitudinal diabetes self-management program for Hispanic adults. Trial Registration ClinicalTrials.gov Identifier: NCT03766438

Abstract Background: Pancreatic cancer is a leading cause of cancer-related death globally. Risk factors for pancreatic cancer include common genetic variants and potentially heavy alcohol consumption. We assessed if genetic variants modify the association between heavy alcohol consumption and pancreatic cancer risk. Methods: We conducted a genome-wide interaction analysis of single-nucleotide polymorphisms (SNP) by heavy alcohol consumption (more than three drinks per day) for pancreatic cancer in European ancestry populations from genome-wide association studies. Our analysis included 3,707 cases and 4,167 controls from case–control studies and 1,098 cases and 1,162 controls from cohort studies. Fixed-effect meta-analyses were conducted. Results: A potential novel region of association on 10p11.22, lead SNP rs7898449 (interaction P value (Pinteraction) = 5.1 × 10−8 in the meta-analysis; Pinteraction = 2.1 × 10−9 in the case–control studies; Pinteraction = 0.91 in the cohort studies), was identified. An SNP correlated with this lead SNP is an expression quantitative trait locus for the neuropilin 1 gene. Of the 17 genomic regions with genome-wide significant evidence of association with pancreatic cancer in prior studies, we observed suggestive evidence that heavy alcohol consumption modified the association for one SNP near LINC00673, rs11655237 on 17q25.1 (Pinteraction = 0.004). Conclusions: We identified a novel genomic region that may be associated with pancreatic cancer risk in conjunction with heavy alcohol consumption located near an expression quantitative trait locus for neuropilin 1, a protein that plays an important role in the development and progression of pancreatic cancer. Impact: This work can provide insights into the etiology of pancreatic cancer, particularly in heavy drinkers.