Citations

AbstractObjectivesTo report lessons from integrating the methods and perspectives of clinical informatics (CI) and implementation science (IS) in the context of Improving the Management of symPtoms during and following Cancer Treatment (IMPACT) Consortium pragmatic trials.Materials and MethodsIMPACT informaticists, trialists, and implementation scientists met to identify challenges and solutions by examining robust case examples from 3 Research Centers that are deploying systematic symptom assessment and management interventions via electronic health records (EHRs). Investigators discussed data collection and CI challenges, implementation strategies, and lessons learned.ResultsCI implementation strategies and EHRs systems were utilized to collect and act upon symptoms and impairments in functioning via electronic patient-reported outcomes (ePRO) captured in ambulatory oncology settings. Limited EHR functionality and data collection capabilities constrained the ability to address IS questions. Collecting ePRO data required significant planning and organizational champions adept at navigating ambiguity.DiscussionBringing together CI and IS perspectives offers critical opportunities for monitoring and managing cancer symptoms via ePROs. Discussions between CI and IS researchers identified and addressed gaps between applied informatics implementation and theory-based IS trial and evaluation methods. The use of common terminology may foster shared mental models between CI and IS communities to enhance EHR design to more effectively facilitate ePRO implementation and clinical responses.ConclusionImplementation of ePROs in ambulatory oncology clinics benefits from common understanding of the concepts, lexicon, and incentives between CI implementers and IS researchers to facilitate and measure the results of implementation efforts.

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.

ABSTRACT Wound infections, exacerbated by the prevalence of antibiotic-resistant bacterial pathogens, necessitate innovative antimicrobial approaches. Polymicrobial infections, often involving Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA), present challenges due to biofilm formation and antibiotic resistance. Hypochlorous acid (HOCl), a potent antimicrobial agent, holds promise as an alternative therapy. An electrochemical bandage (e-bandage) that generates HOCl in situ via precise polarization controlled by a miniaturized potentiostat was evaluated for the treatment of murine wound biofilm infections containing both P. aeruginosa with “difficult-to-treat” resistance and MRSA. Previously, HOCl-producing e-bandage was shown to reduce murine wound biofilms containing P. aeruginosa alone. Here, in 5-mm excisional skin wounds containing 48-h biofilms comprising MRSA and P. aeruginosa combined, polarized e-bandage treatment reduced MRSA by 1.1 log 10 CFU/g ( P = 0.026) vs non-polarized e-bandage treatment (no HOCl production), and 1.4 log 10 CFU/g (0.0015) vs Tegaderm only controls; P. aeruginosa was similarly reduced by 1.6 log 10 CFU/g ( P = 0.0032) and 1.6 log 10 CFU/g ( P = 0.0015), respectively. For wounds infected with MRSA alone, polarized e-bandage treatment reduced bacterial load by 1.1 log 10 CFU/g ( P = 0.0048) and 1.3 log 10 CFU/g ( P = 0.0048) compared with non-polarized e-bandage and Tegaderm only, respectively. The e-bandage treatment did not negatively impact wound healing or cause tissue toxicity. The addition of systemic antibiotics did not enhance the antimicrobial efficacy of e-bandages. This study provides additional evidence for the HOCl-producing e-bandage as a novel antimicrobial strategy for managing wound infections, including in the context of antibiotic resistance and polymicrobial infections. IMPORTANCE New approaches are needed to combat the rise of antimicrobial-resistant infections. The HOCl-producing electrochemical bandage (e-bandage) leverages in situ generation of HOCl, a natural biocide, for broad-spectrum killing of wound pathogens. Unlike traditional therapies that may exhibit limited activity against biofilms and antimicrobial-resistant organisms, the e-bandage offers a potent, standalone solution that does not contribute to further resistance or require adjunctive antibiotic therapy. Here, we show the ability of the e-bandage to address polymicrobial infection by antimicrobial resistant clinical isolates of Staphylococcus aureus and Pseudomonas aeruginosa , two commonly isolated, co-infecting wound pathogens. Effectiveness of the HOCl-producing e-bandage in reducing pathogen load while minimizing tissue toxicity and avoiding the need for systemic antibiotics underscores its potential as a tool in managing complex wound infections.

Abstract Background: Circulating levels of THC and CBD may be altered when administered with medications that strongly or moderately inhibit or induce CYP450 enzymes responsible for metabolizing both substances. THC and CBD levels can also theoretically be altered in individuals who carry germline genetic variants or atypical phenotypes of CYP450 enzymes. In individuals where drug and gene interactions occur together, there could be a heightened impact on the circulating levels of THC and CBD. Materials and Methods: We conducted a retrospective chart review using a database of participants who previously completed pharmacogenomic testing and reported oral cannabis use in a medical encounter. Two pharmacogenomic-trained pharmacists reviewed medications and atypical variants in each participant to characterize the predicted effect of cannabis-drug, cannabis-gene, and cannabis-drug-gene interactions on circulating levels of THC and CBD. Results: Oral cannabis use was confirmed in 71 participants, with an average age of 68.5 years and primarily White women. Regarding THC metabolism, drug-only interactions were noted in 1 participant; both drug and gene interactions were noted in 4 participants; single- or combination-gene-only interactions were noted in 38 participants; and 28 participants had no interactions. Concerning CBD metabolism, drug-only interactions were noted in 4 participants; both drug and gene interactions were noted in 4 participants; single- or combination-gene-only interactions were noted in 36 participants; and 27 participants had no interactions. Conclusion: This study is the first, to our knowledge, to conceptualize the potential impact of drugs and atypical phenotypes on altering circulating levels of THC and CBD in a clinical sample. The absence of published clinical outcomes in this field renders it challenging to estimate clinical significance of these findings. Until such data become available, leveraging the theoretical insights into drug interactions and atypical cannabis metabolism described in our study may serve as a tool to guide clinical care.

Cystic fibrosis is caused by biallelic pathogenic variants in the CFTR gene, which contains a polymorphic (TG)mTn sequence (the “poly-T/TG tract”) in intron 9. While T9 and T7 alleles are benign, T5 alleles with longer TG repeats, e.g., (TG)12T5 and (TG)13T5, are clinically significant. Thus, professional medical societies currently recommend reporting the TG repeat size when T5 is detected. Sanger sequencing is a cost-effective method of genotyping the (TG)mTn tract; however, its polymorphic length substantially complicates data analysis. We developed CFTR-TIPS, a freely available web-based software tool that infers the (TG)mTn genotype from Sanger sequencing data. This tool detects the (TG)mTn tract in the chromatograms, quantifies goodness of fit with expected patterns, and visualizes the results in a graphical user interface. It is broadly compatible with any Sanger chromatogram that contains the (TG)mTn tract ± 15 bp. We evaluated CFTR-TIPS using 835 clinical samples previously analyzed in a CLIA-certified, CAP-accredited laboratory. When operated fully automatically, CFTR-TIPS achieved 99.8% concordance with our clinically validated manual workflow, while generally taking less than 10 s per sample. There were two discordant samples: one due to a co-occurring heterozygous duplication that confounded the tool and the other due to incomplete (TG)mTn tract detection in the reverse chromatogram. No clinically significant misclassifications were observed. CFTR-TIPS is a free, accurate, and rapid tool for CFTR (TG)mTn tract genotyping using cost-effective Sanger sequencing. This tool is suitable both for automated use and as an aid to manual review to enhance accuracy and reduce analysis time.

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

Background: Understanding nutrition’s role in multiple sclerosis (MS) can guide recommendations and intervention-based studies. Objective: Evaluate the association between nutrition and pediatric-onset MS outcomes. Methods: Prospective longitudinal multicenter study conducted as part of the US Network of Pediatric MS centers. Predictors were collected using a food screener estimating intake of various dietary food groups (e.g. dairy and fruits) and additional calculated indices (e.g. Healthy Eating Index (HEI)). Outcomes included time-from-enrollment to clinical relapse, new magnetic resonance imaging (MRI) T2 lesions, and Expanded Disability Status Scale (EDSS) increase. Results: 353 children with MS were enrolled (mean ± SD age 15.4 ± 2.9, follow-up 3.9 ± 2.6 years). Multivariable analysis demonstrated that increased dairy by 50% of recommended intake was associated with increased relapse risk by 41% (adjusted hazard ratio (HR) 1.41, 95% CI 1.07–1.86), and risk of T2 progression by 40% (1.40, 1.12–1.74). Increased intake of fruit or vegetable above recommended, and every five-point HEI increase decreased relapse risk by 25% (0.75, 0.60–0.95), 45% (0.55, 0.32–0.96), and 15% (0.84, 0.74–0.96), respectively. No associations were found with EDSS. Conclusion: This work supports the influence of dietary intake on MS course, particularly with dairy intake. Future prospective study is required to establish causation.

Abstract Background Mortality prediction data may aid in identifying seriously ill transferred patients at high risk of dying and facilitate early goals-of-care discussions (GOCD); however, this is rarely evaluated. We recently developed a model for predicting 30-day inpatient mortality, which may be useful for promoting early GOCD. Objectives Our objectives were to examine the effects of sharing model-generated mortality risk with hospitalists by assessing (1) if hospitalists agreed with the mortality risk prediction, (2) if they planned to conduct GOCD or consult palliative care within 72 hours of transfer, and (3) if the communication alert affected GOCD timing and other clinical outcomes. We also aimed to measure the association between both the model-generated and hospitalists' stratified risk assessments with patient mortality. Methods This was a nonrandomized quasi-experimental pilot study with a historical control group. On the second day of hospitalization, the model-generated risk was communicated to the hospitalists. Hospitalists were asked to answer questions via a HIPAA (Health Insurance Portability and Accountability Act)-compliant mobile communication system, and clinical outcomes were extracted via chart review. Results Eighty-four patients (42 in the control and 42 in the intervention group) were included in this study. Hospitalists agreed that all patients in the intervention group were at risk for inpatient mortality. Hospitalists were more likely to indicate a plan to conduct GOCD in the intervention group (n = 9) compared with the control group (n = 4, p < 0.001). In this subset of patients, GOCD was completed within 72 hours in 78% of intervention patients (n = 7) as compared with 50% in the control group (n = 2). The greater absolute value of the model-generated mortality risk was significantly associated with deaths (p = 0.01), similar to the hospitalists' prediction of the mortality risk (p = 0.02). Conclusion Communicating model-generated mortality risk to hospitalists is a promising approach to promote timely GOCD.

OBJECTIVE To compare postprandial glucose excursions following a bolus with inhaled technosphere insulin (TI) or subcutaneous rapid-acting analog (RAA) insulin. RESEARCH DESIGN AND METHODS A meal challenge was completed by 122 adults with type 1 diabetes who were using multiple daily injections (MDI), a nonautomated pump, or automated insulin delivery (AID) and who were randomized to bolus with their usual RAA insulin (n = 61) or TI (n = 61). RESULTS The primary outcome, the treatment group difference in area under the curve for glucose &gt;180 mg/dL over 2 h, was less with TI versus RAA (adjusted difference −12 mg/dL, 95% CI −22 to −2, P = 0.02). With TI, the glucose excursion was smaller (P = 0.01), peak glucose lower (P = 0.01), and time to peak glucose shorter (P = 0.006). Blood glucose &lt;70 mg/dL occurred in one participant in each group. CONCLUSIONS Postmeal glucose excursion was smaller with TI than with RAA insulin in a cohort that included both AID and MDI users.