Citations

Background: Underrepresented minority (URM) patients enroll in cancer clinical trials at low rates. We studied the perspectives of health care professionals to better understand the challenges and potential facilitators of recruiting URM patients into clinical trials. Methods: A purposeful sampling approach was utilized to recruit health care professionals and clinical research staff who recruited and cared for URM patients in a therapeutic cancer clinical trial at any Mayo Clinic site, from July 2018 through October 2021.Data were gathered using a semistructured qualitative interviews. Participants were interviewed about the challenges of recruiting URM patients into cancer clinical trials and possible strategies for improving URM patient enrollment. Data were analyzed using a thematic analysis. Results: Of the key themes that emerged from participant interviews ( n = 28), perceived barriers to recruiting URM patients into clinical trials included lack of workforce diversity, underutilization of patient navigators, ineffective community outreach and patient recruitment, restricted access to diverse patient populations, and restrictive clinical trial eligibility criteria. Other barriers reported were lack of insurance and access to care and transportation, low socioeconomic status, and mistrust of health care and research. Strategies suggested for improving the recruitment of URM patients into clinical trials included: diversifying and adding research staff, increasing and improving community outreach and advocacy, partnering with clinics closer to patients, increasing monetary and logistical support for patient participation, creating opportunities that build and enhance trust, and systematically examining and modifying clinical trial eligibility criteria. Conclusions: Our findings reveal barriers that have limited URM patient inclusion in cancer clinical trials and highlight strategies to overcoming these barriers.

Introduction: Dynamic vertebral artery insufficiency is a rare vascular phenomenon characterized by insufficient flow of the posterior cerebral circulation induced by dynamic motion of the head. Prior case reports have been limited to vertebral artery occlusion by cervical osteophytes or other structural impingements. Case Report: In this case report, we discuss the unusual case of a 61-year-old female with a history of vertigo, diplopia, nystagmus, and left subclavian stenosis admitted to the hospital for syncope elicited by a left head turn and left shoulder raise. Transcranial Doppler (TCD) ultrasound and angiography showed evidence of dynamic vertebrobasilar insufficiency elicited by a left-head turn. Percutaneous stenting of the left subclavian artery led to the resumption of normal vessel flow as assessed by TCD and the resolution of the patient’s symptoms. Conclusions: This case highlights an unusual cause of dynamic vertebrobasilar insufficiency induced by head turn and/or left shoulder raise due to subclavian stenosis, diagnosed by TCD and angiography, and successfully treated with subclavian artery stenting.

Abstract Thyroglobulin (Tg) is a 330-kDa homodimeric protein that that is the prohormone of thyroid hormones triiodothyronine (T3) and thyroxine (T4). The most critical steps of thyroid hormone synthesis by Tg are iodination and fusion of specific tyrosine residues that are in close proximity to each other in the folded Tg protein. The degree of Tg iodination has been studied widely to determine if it is correlated with thyroid autoimmune disease with mixed results, but these efforts have been limited by the lack of an effective quantitative technique. Simultaneously, the treatment of thyroid cancer has undergone a shift toward partial thyroidectomies, thus undermining the value of Tg measurements. A possible alternative to established monitoring techniques is measurement of Tg iodination states as it has been shown that tumor-derived Tg has significantly lower iodine content. Such measurements require a thorough understanding of normal iodination status. In this study, state-of-the-art liquid chromatography–tandem mass spectrometry (LC-MS/MS) instrumentation is used to perform bottom-up proteomics experiments and identify iodinated residues within commercially available Tg. Using this technique, sequence coverages greater than 90% were achieved, which resulted in identification of previously identified and novel hormone synthesis and donor sites. Based on the results of these discovery experiments, 5 iodination sites were selected for targeted quantitative LC-MS/MS measurements, which suggested that hormone synthesis occurs predominantly at Y24 and Y2766. The results presented herein lay the foundation for routine measurements of iodinated residues, which has the potential to overcome the limitations of current monitoring techniques and benefit patient care.

Abstract Recent clinical trials on slowing dementia progression have led to renewed focus on finding safer, more effective treatments. One approach to identify plausible candidates is to assess whether existing medications for other conditions may affect dementia risk. We conducted a systematic review to identify studies adopting a data‐driven approach to investigate the association between a wide range of prescribed medications and dementia risk. We included 14 studies using administrative or medical records data for more than 130 million individuals and 1 million dementia cases. Despite inconsistencies in identifying specific drugs that may modify Alzheimer's or dementia risk, some themes emerged for drug classes with biological plausibility. Antimicrobials, vaccinations, and anti‐inflammatories were associated with reduced risk, while diabetes drugs, vitamins and supplements, and antipsychotics were associated with increased risk. We found conflicting evidence for antihypertensives and antidepressants. Drug repurposing for use in dementia is an urgent priority. Our findings offer a basis for prioritizing candidates and exploring underlying mechanisms. Highlights We present a systematic review of studies reporting association between drugs prescribed for other conditions and risk of dementia including 139 million people and 1 million cases of dementia. Our work supports some previously reported associations, for example, showing decreased risk of dementia with drugs to treat inflammatory disease and increased risk with antipsychotic treatment. Antimicrobial treatment was perhaps more surprisingly associated with decreased risk, supportive of recent increased interest in this potential therapeutic avenue. Our work should help prioritize drugs for entry into adaptive platform trials in Alzheimer's disease and will serve as a useful resource for those investigating drugs or classes of drugs and risk of dementia.

ABSTRACTBackground/AimEosinophilic granulomatosis with polyangiitis (EGPA) is a multisystemic disease associated with nasal polyposis. Multiple biologics are used for managing EGPA, including some approved for nasal polyps (NP). This study investigated real‐world biologic prescription patterns for EGPA and their impact on NP and endoscopic sinus surgery (ESS) use.MethodsEGPA patients with NP treated with a biologic at any Mayo Clinic site (January 2010 to January 2024) were identified by querying the unified electronic medical record. Patterns of biologic therapy, clinical course, impact on NP, and performance of ESS were studied.ResultsEighty patients were identified. Overall, 71 of 80 (88.75%) patients underwent ESS, with 62 of 80 (77.5%) undergoing 131 ESS procedures prior to biologic therapy. ESS for recalcitrant NP (47 episodes) was performed on 38 of 80 (47.5%) patients on biologics. Biologic monotherapy was used in 90% (72) of patients; mepolizumab (81.9%) was the most common, followed by rituximab (23.6%), benralizumab (18.1%), and dupilumab (12.5%). Switching of biologics was observed in 28 of 80 patients. Concurrent dual‐biologic therapy was used in eight (10%) patients. For patients on single‐agent biologic therapy, ESS was performed on 52.5% of patients on mepolizumab, 23.5% on rituximab, 42.8% on benralizumab, and 22.2% on dupilumab.ConclusionsMultidisciplinary multi‐modality treatment with biologics and ESS appeared to be the mainstay of controlling NP in EGPA. Mepolizumab was the most frequently used biologic. Dual biologic therapy was necessary in 10% of patients. Overall, 71 of 80 (88.75%) patients had ESS, with almost half the study population (47.5%) undergoing ESS after initiating biologic treatment.

Introduction Taxane medications, paclitaxel, and docetaxel, are chemotherapy agents that have a higher incidence of reported hypersensitivity and infusion reactions. To help classify these reactions, the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) is utilized. Prophylactic medications have been used to decrease the incidence and severity of these events. At our institution, medications that patients can receive prior to the initiation of a taxane infusion are a histamine 1 receptor antagonist (H1RA), histamine 2 receptor antagonist (H2RA), a steroid or a combination of these medications. The purpose of this retrospective review was to compare the rates and severity of infusion reactions based on the timing of prophylactic medication administration in the first and second doses of taxane infusions. Methods Patients who received paclitaxel or docetaxel from January 30 th , 2022, through January 30 th , 2023, were included in the analysis. To assist in the identification of a reaction, taxane administrations were flagged for review if a rescue medication was administered after the start of a paclitaxel or docetaxel infusion. The rates and severity of infusion reactions were analyzed based on the timing of prophylactic medication administration. A sub-group analysis comparing infusion reaction characteristics between taxanes given, was performed. Results Of the 1486 taxane infusions that were completed within the year, 249 infusion reactions were confirmed and graded utilizing the NCI CTCAE. When examining the first and second doses of a taxane (N = 536), we identified 222 infusions reactions. The odds of a patient having an infusion reaction, during the first and second doses, was found to be less likely for patients given a prophylactic medication 30 min prior to receiving a taxane compared to those who did not receive a pre-medication (p = 0.037). Conclusion This multisite retrospective study showed that administration of prophylactic medications 30 to 80 min prior to the first and second infusion of a taxane was the optimal timing to decrease the likelihood of patients having an infusion reaction. No difference in the severity of the reaction was seen. Most patients were able to complete the entire infusion, regardless of what rescue medications were used following the infusion reaction.

ABSTRACTBackgroundWhile teleconsultation has proven feasible for adult cancer patients, its utility in childhood cancer care in India is unknown. This study assesses caregiver satisfaction, feasibility, and the economic impact of teleconsultation for children with cancer.ProcedureThis mixed methods study was conducted in the pediatric cancer outpatient service at a tertiary care cancer center in India. Routine care teleconsultations were performed via telephone or email. Caregivers who received teleconsultations during the study period or 6 months prior were interviewed by phone. Data collected included demographic details, teleconsultation usage patterns, caregiver satisfaction, reasons for satisfaction or dissatisfaction, and cost savings. Logistic regression identified baseline characteristics associated with satisfaction. In‐depth interviews were conducted in a separate cohort till thematic saturation.ResultsCaregivers of 465 children were included for telephonic and eight for in‐depth interviews Among the respondents, 72.8% (n = 339) were satisfied with teleconsultation, and 85.4% (n = 397) of those planned to continue using it. Significant reasons for satisfaction were cost and time savings, while difficulty explaining issues caused dissatisfaction. Multivariable analysis showed parental education above high school [OR: 1.59, p = 0.035] increased satisfaction likelihood, while a residential distance of greater than 100 km from the hospital [OR: 0.62, p = 0.033] decreased it. Median cost savings per visit was $24.2 (range: $1–$846). Cost savings did not determine satisfaction magnitude. Frequently cited themes included cost and time savings and the need for literacy to benefit from teleconsultation.ConclusionsTeleconsultation is feasible and effective for routine childhood cancer care, even in resource‐constrained settings.

Background: A vast amount of literature is available on the burden of acute ischemic stroke (AIS). Yet, most information on AIS burden does not stratify by stroke severity, and the inclusion of mild strokes (National Institute of Health Stroke Scale < 5) might obscure the true impact of moderate-to-severe AIS. Therefore, it is important to understand the literature as it pertains to the epidemiological, clinical, humanistic, and economic burden of moderate-to-severe AIS from a global perspective. Methods: A systematic literature review (SLR) was conducted, including articles published between January 2015 and June 2023. The clinical burden search focused on patients with moderate or severe AIS. Due to the paucity of evidence, the humanistic and economic burdens were evaluated based on overall AIS studies. Abstract and full-text screening were conducted by 2 reviewers, with data extraction completed by 1 reviewer. In all, 136 studies were included in the SLR. Results: AIS caused a substantial burden for patients and the healthcare system. The clinical burden of AIS (specifically severe AIS) resulted in high mortality and worse functional outcomes across multiple demographics (female sex, older age, and patients with comorbidities). The economic burden of overall AIS was substantial, with inpatient costs as the primary driver (a mean or median stay of 7 days). The highest inpatient costs were reported in South Korea ($45,180) and the United States ($38,470). Conclusions: The review highlighted the huge burden of moderate-to-severe AIS, with patients experiencing worse outcomes with increased stroke severity. Further focus is needed on outcomes relating to moderate-to-severe AIS to fully understand the burden of stroke in this patient population.