Thyroid cancer.

The past 5-10 years have brought in a new era in the care of patients with thyroid cancer, with the introduction of transformative diagnostic and management options. Several international ultrasound-based thyroid nodule risk stratification systems have been developed with the goal of reducing unnecessary biopsies. Less invasive alternatives to surgery for low-risk thyroid cancer, such as active surveillance and minimally invasive interventions, are being explored. New systemic therapies are now available for patients with advanced thyroid cancer. However, in the setting of these advances, disparities exist in the diagnosis and management of thyroid cancer. As new management options are becoming available for thyroid cancer, it is essential to support population-based studies and randomised clinical trials that will inform evidence-based clinical practice guidelines on the management of thyroid cancer, and to include diverse patient populations in research to better understand and subsequently address existing barriers to equitable thyroid cancer care.

Modification of Association of Cystatin C With Kidney and Cardiovascular Outcomes by Obesity.

RATIONALE & OBJECTIVE: Cystatin C-based estimated glomerular filtration rate (eGFRcys) has stronger associations with adverse clinical outcomes than creatinine-based eGFR (eGFRcr). Obesity may be associated with higher cystatin C levels, independent of kidney function, but it is unknown whether obesity modifies associations of eGFRcys with kidney and cardiovascular outcomes. STUDY DESIGN: Cohort study. SETTING & PARTICIPANTS: 27,249 US adults in the Reasons for Geographic and Racial Differences in Stroke Study. PREDICTORS: eGFRcys, eGFRcr, waist circumference, and body mass index (BMI). OUTCOME: All-cause mortality, kidney failure, incident atherosclerotic cardiovascular disease (ASCVD), and incident heart failure (HF). ANALYTICAL APPROACH: Multivariable Cox and Fine-Gray models with multiplicative interaction terms were constructed to investigate whether waist circumference quartiles or BMI categories modified associations of eGFRcys with risks of 4 clinical outcomes. RESULTS: Participants had a mean age of 65 years; 54% were women, 41% were Black, and 21% had an eGFRcys<60mL/min/1.73m2. The baseline prevalence of abdominal obesity (waist circumference≥88cm for women or≥102cm for men) was 48% and obesity was 38%. In multivariable adjusted analyses, each 15mL/min/1.73m2 lower eGFRcys was associated with higher HR and 95% CI of mortality in each waist circumference quartile (first quartile, 1.19 [1.15-1.24]; second quartile, 1.22 [1.18-1.26]; third quartile, 1.20 [1.16-1.24]; fourth quartile, 1.19 [1.15-1.23]) as well as within each BMI category (BMI<24.9: 1.21 [1.17-1.25]; BMI 25.0-29.9: 1.21 [1.18-1.25]; BMI 30.0-34.9: 1.20 [1.16-1.25]; BMI≥35: 1.17, [1.12-1.22]). Neither waist circumference nor BMI modified the association of eGFRcys with mortality, kidney failure, incident ASCVD, or incident HF (all Pinteraction>0.05). LIMITATIONS: Included only Black and White persons in the United States. CONCLUSION: Obesity did not modify the association of eGFRcys with all-cause mortality, kidney failure, incident ASCVD, or incident HF. Among individuals with obesity, cystatin C may be used to provide eGFR-based risk prognostication for adverse outcomes. PLAIN-LANGUAGE SUMMARY: Cystatin C is increasingly used in clinical practice to estimate kidney function, and cystatin C-based eGFR (eGFRcys) may be used to determine risk for adverse clinical outcomes. Adiposity may increase serum levels of cystatin C, independent of kidney function. This cohort study investigated whether associations of eGFRcys with adverse kidney and cardiovascular outcomes are modified by measures of obesity, waist circumference, and body mass index. We found that obesity does not modify associations of eGFRcys with 4 clinical outcomes and conclude that among individuals with obesity, cystatin C may be used to provide eGFR-based risk prognostication for adverse outcomes.

Hidden Disparities: How Language Influences Patients' Access to Cancer Care.

BACKGROUND: Patients with limited English proficiency, a vulnerable patient population, remain understudied in the literature addressing cancer disparities. Although it is well documented that language discordance between patients and physicians negatively impacts the quality of patient care, little is known about how patients' preferred spoken language impacts their access to cancer care. PATIENTS AND METHODS: Between November 2021 and June 2022, we conducted an audit study of 144 hospitals located across 12 demographically diverse states. Using a standardized script, trained investigators assigned to the roles of English-speaking, Spanish-speaking, and Mandarin-speaking patients called the hospital general information telephone line seeking to access care for 3 cancer types that disproportionately impact Hispanic and Asian populations (colon, lung, and thyroid cancer). Primary outcome was whether the simulated patient caller was provided with the next steps to access cancer care, defined as clinic number or clinic transfer. We used chi-square tests and logistic regression analysis to test for associations between the primary outcome and language type, region type, hospital teaching status, and cancer care requested. We used multivariable logistic regression analysis to determine factors associated with simulated patient callers being provided the next steps. RESULTS: Of the 1,296 calls, 52.9% (n=686) resulted in simulated patient callers being provided next steps to access cancer care. Simulated non-English-speaking (vs English-speaking) patient callers were less likely to be provided with the next steps (Mandarin, 27.5%; Spanish, 37.7%; English, 93.5%; P<.001). Multivariable logistic regression found significant associations of the primary outcome with language spoken (Mandarin: odds ratio [OR], 0.02 [95% CI, 0.01-0.04] and Spanish: OR, 0.04 [95% CI, 0.02-0.06] vs English) and hospital teaching status (nonteaching: OR, 0.43 [95% CI, 0.32-0.56] vs teaching). CONCLUSIONS: Linguistic disparities exist in access to cancer care for non-English-speaking patients, emphasizing the need for focused interventions to mitigate systems-level communication barriers.

Real-World Use of Systemic Therapies for the Treatment of Advanced Thyroid Cancers.

OBJECTIVE: In the last decade, new systemic treatment options have been made available for patients with advanced thyroid cancer. However, little is known about the real-world utilization of these systemic therapies. METHODS: We used Optum's de-identified Clinformatics® Data Mart Database to characterize trends in the use of 15 systemic therapies that are available for the treatment of advanced thyroid cancer between 2013 and 2021. Joinpoint regression was used to calculate annual percentage changes in the use of systemic therapy by patients' race/ethnicity. The sequence of therapies was determined by the date of prescription claims. RESULTS: Between 2013 and 2021, the annual number of patients treated for advanced thyroid cancer with systemic therapy increased from 45 patients in 2013 to 114 patients in 2021 (N of total cohort = 885). Most patients were female (54.7%) and non-Hispanic White (62.1%). Between 2013 and 2021, there was a significant decrease in the proportion of non-Hispanic White patients treated for advanced thyroid cancer with systemic therapy (annual percentage change -3.9%, 95% confidence intervals, -6.0% to -1.8%). Since its approval by the US Food and Drug Administration (FDA) in 2015, lenvatinib remains the most frequently prescribed first-line therapy for the treatment of radioiodine-refractory thyroid cancer (48.8% of patients between 2017 and 2021). Between 2017 and 2021, most patients (79.7%) were initiated on 1 of the 10 FDA-approved agents and 81.7% received only a first-line therapy. CONCLUSIONS: Between 2013 and 2021, the use of systemic treatment options for advanced thyroid cancer increased significantly, largely driven by the prescription of lenvatinib following its approval by the FDA in 2015, with an increasing trend for use in non-White patients.

Association of Intra-individual Differences in Estimated GFR by Creatinine Versus Cystatin C With Incident Heart Failure.

RATIONALE & OBJECTIVE: Lower estimated glomerular filtration rate (eGFR) is associated with heart failure (HF) risk. However, eGFR based on cystatin C (eGFRcys) and creatinine (eGFRcr) may differ substantially within an individual. The clinical implications of these differences for risk of HF among persons with chronic kidney disease (CKD) are unknown. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 4,512 adults with CKD and without prevalent HF who enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study. EXPOSURE: Difference in GFR estimates (eGFRdiff; ie, eGFRcys minus eGFRcr). OUTCOME: Incident HF hospitalization. ANALYTICAL APPROACH: Fine-Gray proportional subhazards regression was used to investigate the associations of baseline, time-updated, and slope of eGFRdiff with incident HF. RESULTS: Of 4,512 participants, one-third had eGFRcys and eGFRcr values that differed by over 15 mL/min/1.73 m2. In multivariable-adjusted models, each 15 mL/min/1.73 m2 lower baseline eGFRdiff was associated with higher risk of incident HF hospitalization (hazard ratio [HR], 1.20 [95% CI, 1.07-1.34]). In time-updated analyses, those with eGFRdiff less than -15 mL/min/1.73 m2 had higher risk of incident HF hospitalization (HR, 1.99 [95% CI, 1.39-2.86]), and those with eGFRdiff ≥15 mL/min/1.73 m2 had lower risk of incident HF hospitalization (HR, 0.67 [95% CI, 0.49-0.91]) compared with participants with similar eGFRcys and eGFRcr. Participants with faster declines in eGFRcys relative to eGFRcr had higher risk of incident HF (HR, 1.49 [95% CI, 1.19-1.85]) compared with those in whom eGFRcys and eGFRcr declined in parallel. LIMITATIONS: Entry into the CRIC Study was determined by eGFRcr, which constrained the range of baseline eGFRcr-but not eGFRcys-values. CONCLUSIONS: Among persons with CKD who have large differences between eGFRcys and eGFRcr, risk for incident HF is more strongly associated with eGFRcys. Diverging slopes between eGFRcys and eGFRcr over time are also independently associated with risk of incident HF.

Disparities in risk perception of thyroid cancer recurrence and death.

BACKGROUND: To the authors' knowledge, studies regarding risk perception among survivors of thyroid cancer are scarce. METHODS: The authors surveyed patients who were diagnosed with differentiated thyroid cancer from the Surveillance, Epidemiology, and End Results registries of Georgia and Los Angeles County (2632 patients; 63% response rate). The analytic cohort was defined by a ≤5% risk of disease recurrence and mortality (1597 patients). Patients estimated their recurrence and mortality risks separately (increments of 10% and endpoints of ≤5% and ≥95%). Both outcomes were dichotomized between reasonably accurate estimates (risk perception of ≤5% or 10%) versus overestimation (risk perception of ≥20%). Multivariable logistic regression was used to identify factors associated with risk overestimation, and the relationships between overestimation and both worry and quality of life were evaluated. RESULTS: In the current study sample, 24.7% of patients overestimated their recurrence risk and 12.5% overestimated their mortality risk. A lower educational level was associated with overestimating disease recurrence (≤high school diploma: odds ratio [OR], 1.64 [95% CI, 1.16-2.31]; and some college: OR, 1.36 [95% CI, 1.02-1.81]) and mortality (≤high school diploma: OR, 1.86 [95% CI, 1.18-2.93]) risk compared with those attaining at least a college degree. Hispanic ethnicity was found to be associated with overestimating recurrence risk (OR, 1.44, 95% CI 1.02-2.03) compared with their white counterparts. Worry about recurrence and death was found to be greater among patients who overestimated versus those who had a reasonably accurate estimate of their risk of disease recurrence and mortality, respectively (P < .001). Patients who overestimated mortality risk also reported a decreased physical quality of life (mean T score, 43.1; 95% CI, 41.6-44.7) compared with the general population. CONCLUSIONS: Less educated patients and Hispanic patients were more likely to report inaccurate risk perceptions, which were associated with worry and a decreased quality of life.

Intensive BP Control and eGFR Declines: Are These Events Due to Hemodynamic Effects and Are Changes Reversible?

PURPOSE OF REVIEW: Acute declines in estimated glomerular filtration rate (eGFR) are often observed during intensive blood pressure (BP) lowering. This review focuses on identifying the various mechanisms of eGFR decline associated with intensive BP lowering and evaluates the evidence linking BP control with kidney and cardiovascular (CV) outcomes. RECENT FINDINGS: In 2017, the American College of Cardiology and the American Heart Association (ACC/AHA) began recommending treatment of all individuals to a BP target of < 130/80 mmHg. Since then, multiple post hoc analyses of BP trials have associated intensive BP lowering with acute declines in kidney function and acute kidney injury; whether these represent reversible changes in the kidney is still debated. There is ample evidence that intensive BP lowering is associated with declines in eGFR. The clinical implications of these events remain unclear. Individualizing the risks and benefits of intensive BP therapy continues to be warranted.

COMP Gene Coexpresses With EMT Genes and Is Associated With Poor Survival in Colon Cancer Patients.

BACKGROUND: About 1.2 million new cases of colon cancer (CC) and 0.6 million deaths are reported every year, establishing CC as an important contributor to worldwide cancer morbidity and mortality. Although the overall incidence and mortality of CC have declined over the past 3 decades, the number of early-onset colon cancer ([EOCC], patients <50 y old) continues to rise alarmingly. These young patients are often diagnosed at a more advanced stage and tend to have poor survival. Our recently published data showed that the cartilage oligomeric matrix protein (COMP) is overexpressed in early-onset colon cancer patients. COMP is also reported in several cancers to coexpress with epithelial-mesenchymal transition (EMT) transcription factors. Given the role of EMT in cancer metastasis and cell invasion, we assessed the correlation between COMP gene expression and EMT gene expression in CC, and COMP's relationship to patient survival. METHODS: mRNA expression of COMP was compared to that of EMT markers using the UCSC Cancer Genomics Browser. Survival analysis was performed using the UCSC Xena Browser for cancer genomics. RESULTS: Expression analysis revealed coexpression of COMP with the EMT markers CDH2, FN1, VIM, TWIST1, TWIST2, SNAI1, SNAI2, ZEB1, ZEB2, POSTN, MMP2, MMP9, and COL1A1. Samples that were more mesenchymal had higher expression levels of COMP and EMT markers, thus suggesting a potential role of COMP in EMT. Patients with increased COMP expression presented with poorer overall survival compared to patients with no change or reduced COMP expression (P = 0.02). CONCLUSIONS: These findings reveal COMP as a potential biomarker for CC especially in more aggressive CC and CC in young patients, with a likely role in EMT during tumor metastasis and invasion, and a contributing factor to patient survival.

Interprofessional Collaborative Practice in the Medical Intensive Care Unit: a Survey of Caregivers' Perspectives.

BACKGROUND: Research on caregivers, defined as designated family members or support persons, in the medical intensive care unit (MICU) has primarily focused on their emotional needs and experiences, thus leaving a gap in knowledge related to their perceptions of team dynamics. OBJECTIVE: To examine caregivers' perceptions of team interactions and competencies for interprofessional collaborative practice (IPCP) and overall satisfaction with the MICU team. METHODS: The Support Person Jefferson Teamwork Observation Guide (JTOG)™ was administered to a convenience sample of caregivers in the MICU at a large urban academic medical center between May 2016 and December 2016. RESULTS: One hundred sixty-one JTOG surveys were completed. Caregivers agreed on the importance of healthcare professionals working together as a team to provide patient care (3.97 out of 4.0 on Likert response scale where 1 is "Not at all important" and 4 is 'Extremely important") and were satisfied with the MICU team (3.74 out of 4.0), positively evaluating the four core competencies for IPCP (3.55 for values/ethics, 3.58 for interprofessional communication, 3.61 for roles/responsibilities, and 3.64 for teams/teamwork) and the patient/family-centeredness sub-competency (3.58 out of 4.0). There was a strong positive correlation between caregivers' Global JTOG scores and overall satisfaction with the MICU team (r = 0.596, p < 0.01). Caregivers' comments about factors that affected their experience focused on aspects of interprofessional communication and patient/family-centeredness. CONCLUSION: Findings underscore the importance of interprofessional communication and providing patient/family-centered care. Assessing caregivers' perceptions of IPCP can provide a critical lens into team functioning and, thus, be used to identify teams' strengths as well as opportunities for improvement.

Aspirin and clopidogrel high on-treatment platelet reactivity and genetic predictors in peripheral arterial disease.

OBJECTIVES: Our aims were to examine the prevalence and genetic predictors of aspirin and clopidogrel high on-treatment platelet reactivity (HoTPR), and associated adverse cardiovascular outcomes in patients with peripheral arterial disease (PAD). BACKGROUND: The association of aspirin and clopidogrel HoTPR with outcomes in PAD remains unclear. METHODS: This is a prospective cohort study of patients with angiographically documented PAD involving carotid and lower extremity arteries. Aspirin and clopidogrel HoTPR (using the VerifyNow Assay) and associated genetic predictors were compared to clinical outcomes. The primary end-point was a composite of major adverse cardiovascular events: all-cause mortality, myocardial infarction, stroke, target vessel revascularization (TVR) and limb-loss in patients who underwent extremity intervention. RESULTS: The study was stopped prematurely due to slow patient enrolment. Of 195 patients enrolled, the primary analysis was performed in 154 patients taking both drugs. Aspirin HoTPR was present in 31 (20%) and clopidogrel HoTPR in 76 (49%) patients. There was a trend toward more primary composite outcome events with PRU ≥ 235 (52% freedom-from-event rate vs. 70% for PRU < 235; P = 0.09). TVR was higher in those with PRU ≥ 235 (20 vs. 6%, unadjusted P = 0.02). There was no association between aspirin HoTPR and combined outcomes. Single nucleotide polymorphisms in serum paraoxonase/arylesterase 1 (PON1) gene was associated with aspirin HoTPR (P = 0.005) while SNP in phospholipase A2, group III (PLA2G3) gene was associated with clopidogrel HoTPR (P = 0.002). CONCLUSION: Clopidogrel HoTPR was significantly associated with TVR, while aspirin HoTPR was not associated with adverse clinical outcomes in patients with PAD.

Clinical implications of SCN1A missense and truncation variants in a large Japanese cohort with Dravet syndrome.

OBJECTIVE: Two major classes of SCN1A variants are associated with Dravet syndrome (DS): those that result in haploinsufficiency (truncating) and those that result in an amino acid substitution (missense). The aim of this retrospective study was to describe the first large cohort of Japanese patients with SCN1A mutation-positive DS (n = 285), and investigate the relationship between variant (type and position) and clinical expression and response to treatment. METHODS: We sequenced all exons and intron-exon boundaries of SCN1A in our cohort, investigated differences in the distribution of truncating and missense variants, tested for associations between variant type and phenotype, and compared these patterns with those of cohorts with milder epilepsy and healthy individuals. RESULTS: Unlike truncation variants, missense variants are found at higher density in the S4 voltage sensor and pore loops and at lower density in the domain I-II and II-III linkers and the first three segments of domain II. Relative to healthy individuals, there is an increased frequency of truncating (but not missense) variants in the noncoding C-terminus. The rate of cognitive decline is more rapid for patients with truncation variants regardless of age at seizure onset, whereas age at onset is a predictor of the rate of cognitive decline for patients with missense variants. SIGNIFICANCE: We found significant differences in the distribution of truncating and missense variants across the SCN1A sequence among healthy individuals, patients with DS, and those with milder forms of SCN1A-variant positive epilepsy. Testing for associations with phenotype revealed that variant type can be predictive of rate of cognitive decline. Analysis of descriptive medication data suggests that in addition to conventional drug therapy in DS, bromide, clonazepam and topiramate may reduce seizure frequency.

Angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use is associated with reduced major adverse cardiovascular events among patients with critical limb ischemia.

Angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) are recommended for secondary prevention in peripheral artery disease, but their effectiveness in patients with critical limb ischemia (CLI) is uncertain. We reviewed 464 patients with CLI who underwent diagnostic angiography or endovascular intervention from 2006-2013 at a multidisciplinary vascular center. ACEI or ARB use was assessed at the time of angiography. Major adverse cardiovascular events (MACE), mortality, and major adverse limb events (MALE) were assessed during three-year follow-up. Propensity weighting was used to adjust for baseline differences between patients taking and not taking ACEIs or ARBs. ACEIs or ARBs were prescribed to 269 (58%) patients. Patients prescribed ACEIs or ARBs had more baseline comorbidities including diabetes and hypertension (p<0.05). Patients prescribed ACEIs or ARBs had lower three-year unadjusted rates of MACE (40% versus 47%) and mortality (33% versus 43%). After propensity weighting, ACEI or ARB use was associated with significantly lower rates of MACE (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.58-0.99, p=0.04) and overall mortality (HR 0.71, 95% CI 0.53-0.95, p=0.02). There was no significant association between ACEI or ARB use and MALE (HR 0.97, 95% CI 0.69-1.35, p=0.2) or major amputation (HR 0.74, 95% CI 0.47-1.18, p=0.1). ACEI/ARB use is associated with lower MACE and mortality in patients with CLI, but there was no effect on limb-related outcomes.

Social Determinants of Health and Disparities in Thyroid Care.

BACKGROUND: There have been documented racial and ethnic disparities in the care and clinical outcomes of patients with thyroid disease. CONTEXT: Key to improving disparities in thyroid care is understanding the context for racial and ethnic disparities, which includes acknowledging and addressing social determinants of health. Thyroid disease diagnosis, treatment, and survivorship care are impacted by patient- and system-level factors, including socioeconomic status and economic stability, language, education, health literacy, and health care systems and health policy. The relationship between these factors and downstream clinical outcomes is intricate and complex, underscoring the need for a multifaceted approach to mitigate these disparities. CONCLUSION: Understanding the factors that contribute to disparities in thyroid disease is critically important. There is a need for future targeted and multilevel interventions to address these disparities, while considering societal, health care, clinician, and patient perspectives.

Survival Prognostication in Patients with Differentiated Thyroid Cancer and Distant Metastases: A SEER Population-Based Study.

Background: For patients with thyroid cancer, distant metastasis is a significant predictor of poor outcome. Since distant metastasis occurs in less than 10% of patients with differentiated thyroid cancer, correlates of survival in this vulnerable patient population remain understudied. This study aimed to identify prognostic groups among patients with differentiated thyroid cancer and distant metastases and to determine the role of, and interactions between, patient and tumor characteristics in determining survival. Methods: We identified adult patients diagnosed with differentiated thyroid cancer with distant metastases from the U.S. SEER-17 cancer registry (2010-2019). Analyses were performed using Cox proportional hazards regression, survival trees, and random survival forest. Relative importance of patient and tumor factors important for disease-specific and overall survival was assessed based on the random survival forest analyses. Results: Cohort consisted of 2411 patients with differentiated thyroid cancer with distant metastases followed for a median of 62 months. Most common histopathologic subtype (86.0%) was papillary thyroid cancer, and the most common sites of distant metastasis were the lungs (33.7%) and bone (18.9%). Cox proportional hazards model illustrated significant associations between survival and the following: patient age (p < 0.001), tumor size (p < 0.01), and site of distant metastasis (p < 0.05). Survival tree analyses identified three distinct prognostic groups based on disease-specific survival (DSS) (5-year survival of the prognostic groups was 92%, 64%, and 41%; p < 0.001) and four distinct prognostic groups based on overall survival (OS) (5-year survival of the prognostic groups was 96%, 84%, 57%, and 31%; p < 0.001). The first split in the survival trees for DSS and OS was by age at diagnosis (≤57 years vs. ≥58 years) with subsequent splits based on presence/absence of lung metastases, tumor size (≤4 cm vs. >4 cm), and patient age. A total of 558 patients (23.1%) died from thyroid cancer, and 757 patients (31.4%) died from all causes during the study period. Conclusions: This study identifies distinct prognostic groups for patients with differentiated thyroid cancer with distant metastases and highlights the importance of patient age, lung metastases, and tumor size for determining both disease-specific and overall survival. These findings inform risk stratification and treatment decision-making in this understudied patient population.

Access to New Clinic Appointments for Patients With Cancer.

Importance: Racial and ethnic disparities have been observed in the outpatient visit rates for specialist care, including cancer care; however, little is known about patients' experience at the critical step of attempting to access new clinic appointments for cancer care. Objective: To determine simulated English-speaking, Spanish-speaking, and Mandarin-speaking patient callers' ability to access new clinic appointments for 3 cancer types (colon, lung, and thyroid cancer) that disproportionately impact Hispanic and Asian populations. Design, Setting, and Participants: This cross-sectional audit study was conducted between November 2021 and March 2023 using 479 clinic telephone numbers that were provided by the hospital general information personnel at 143 hospitals located across 12 US states. Using standardized scripts, trained research personnel assigned to the roles of English-speaking, Spanish-speaking, and Mandarin-speaking patients called the telephone number for a clinic that treats colon, lung, or thyroid cancer to inquire about a new clinic appointment. Data analysis was conducted from June to September 2023. Main Outcomes and Measures: The primary outcome was whether the simulated patient caller was able to access cancer care (binary variable, yes or no), which was defined to include being provided with a clinic appointment date or scheduling information. Multivariable logistic regression analysis was performed to determine factors independently associated with simulated patient callers being able to access cancer care. Results: Of 985 total calls (399 English calls; 302 Spanish calls; 284 Mandarin calls), simulated patient callers accessed cancer care in 409 calls (41.5%). Differences were observed based on language type, with simulated English-speaking patient callers significantly more likely to access cancer care compared with simulated Spanish-speaking and Mandarin-speaking patient callers (English, 245 calls [61.4%]; Spanish, 110 calls [36.4%]; Mandarin, 54 calls [19.0%]; P < .001). A substantial number of calls ended due to linguistic barriers (291 of 586 Spanish or Mandarin calls [49.7%]) and workflow barriers (239 of 985 calls [24.3%]). Compared with English-speaking simulated patient callers, the odds of accessing cancer care were lower for Spanish-speaking simulated patient callers (adjusted odds ratio [aOR], 0.34; 95% CI, 0.25-0.46) and Mandarin-speaking simulated patient callers (aOR, 0.13; 95% CI, 0.09-0.19). Compared with contacting clinics affiliated with teaching hospitals, callers had lower odds of accessing cancer care when contacting clinics that were affiliated with nonteaching hospitals (aOR, 0.53; 95% CI, 0.40-0.70). Conclusions and Relevance: In this cross-sectional audit study, simulated patient callers encountered substantial barriers when attempting to access clinic appointments for cancer care. These findings suggest that interventions focused on mitigating these barriers are necessary to increase access to cancer care for all patients.

Cystatin C- and Creatinine-based Estimated GFR Differences: Prevalence and Predictors in the UK Biobank.

Rationale & Objective: Large differences between estimated glomerular filtration rate (eGFR) based on cystatin C (eGFRcys) and creatinine (eGFRcr) occur commonly. A comprehensive evaluation of factors that contribute to these differences is needed to guide the interpretation of discrepant eGFR values. Study Design: Cohort study. Setting & Participants: 468,969 participants in the UK Biobank. Exposures: Candidate sociodemographic, lifestyle factors, comorbidities, medication usage, and physical and laboratory predictors. Outcomes: eGFRdiff, defined as eGFRcys minus eGFRcr, categorized into 3 levels: lower eGFRcys (eGFRdiff, less than -15 mL/min/1.73 m2), concordant eGFRcys and eGFRcr (eGFRdiff, -15 to < 15 mL/min/1.73 m2), and lower eGFRcr (eGFRdiff, ≥15 mL/min/1.73 m2). Analytical Approach: Multinomial logistic regression models were constructed to identify predictors of lower eGFRcys or lower eGFRcr. We developed 2 prediction models comprising 375,175 participants: (1) a clinical model using clinically available variables and (2) an enriched model additionally including lifestyle variables. The models were internally validated in an additional 93,794 participants. Results: Mean ± standard deviation of eGFRcys was 88 ± 16 mL/min/1.73 m2, and eGFRcr was 95 ± 13 mL/min/1.73 m2; 25% and 5% of participants were in the lower eGFRcys and lower eGFRcr groups, respectively. In the multivariable enriched model, strong predictors of lower eGFRcys were older age, male sex, South Asian ethnicity, current smoker (vs never smoker), history of thyroid dysfunction, chronic inflammatory disease, steroid use, higher waist circumference and body fat, and urinary albumin-creatinine ratio >300 mg/g. Odds ratio estimates for these predictors were largely inverse of those in the lower eGFRcr group. The model's area under the curve was 0.75 in the validation set, with good calibration (1.00). Limitations: Limited generalizability. Conclusions: This study highlights the multitude of demographic, lifestyle, and health characteristics that are associated with large eGFRdiff. The clinical model may identify individuals who are likely to have discrepant eGFR values and thus should be prioritized for cystatin C testing.

Estimated glomerular filtration rate (eGFR) based on cystatin C and creatinine may differ substantially within an individual. Although most clinicians are aware that creatinine is influenced by muscle mass, there are additional numerous lifestyle and health characteristics that may affect serum concentrations of either biomarker. Our analyses of 468,969 individuals in the UK Biobank identified independent predictors of large differences between eGFR based on cystatin C and eGFR based on creatinine, which may inform the interpretation of discrepant eGFR values within an individual. We developed models that may be implemented at a population level to help health systems identify individuals who are likely to have large differences between eGFR based on cystatin C and eGFR based on creatinine and thus should be prioritized for cystatin C testing.

Repeated monitoring of corneal nerves by confocal microscopy as an index of peripheral neuropathy in type-1 diabetic rodents and the effects of topical insulin.

We developed a reliable imaging and quantitative analysis method for in vivo corneal confocal microscopy (CCM) in rodents and used it to determine whether models of type 1 diabetes replicate the depletion of corneal nerves reported in diabetic patients. Quantification was reproducible between observers and stable across repeated time points in two rat strains. Longitudinal studies were performed in normal and streptozotocin (STZ)-diabetic rats, with innervation of plantar paw skin quantified using standard histological methods after 40 weeks of diabetes. Diabetic rats showed an initial increase, then a gradual reduction in occupancy of nerves in the sub-basal plexus so that values were significantly lower at week 40 (68 ± 6%) than age-matched controls (80 ± 2%). No significant loss of stromal or intra-epidermal nerves was detected. In a separate study, insulin was applied daily to the eye of control and STZ-diabetic mice and this treatment prevented depletion of nerves of the sub-basal plexus. Longitudinal studies are viable in rodents using CCM and depletion of distal corneal nerves precedes detectable loss of epidermal nerves in the foot, suggesting that diabetic neuropathy is not length dependent. Loss of insulin-derived neurotrophic support may contribute to the pathogenesis of corneal nerve depletion in type 1 diabetes.