Reduced asthma morbidity during COVID-19 in minority children: is medication adherence a reason?

OBJECTIVES: Asthma control improved during the COVID-19 pandemic. This study examined objectively measured medication adherence, asthma morbidity and quality of life (QoL) outcomes in Black and Latinx children by month for January-June 2019 (pre-COVID) compared to January-June 2020 (including first peak of COVID). METHODS: Secondary analyses of 94 children with asthma (ages 10-17 years, 64% Latinx, 36% Black) and their caregivers assigned to the comparison group of a longitudinal RCT intervention trial. Outcomes included mean aggregate electronic adherence for controller medications, oral steroid bursts, acute healthcare utilization, caregiver asthma QoL, and the Asthma Control Test. Repeated measures analyses were conducted due to multiple observations. RESULTS: Adherence to controller medications declined 48% from 2019 to 2020 (LS Mean = 33.9% vs. 17.6%, p=.0004, f=.92) with levels reaching a low in May 2020. A reduction in steroid bursts was observed over the same timeframe, 1.29 vs. 0.61, p = 0.006, f=.63. Caregiver QoL increased from 2019 to 2020 on total score (5.18 vs. 5.85, p = 0.002, f=.72), activity limitations (5.04 vs. 5.95), and emotional functioning (5.26 vs. 5.80). Although not statistically significant, a clinically meaningful 62% reduction in acute healthcare visits (p = 0.15) was reported in 2020. Children reported better asthma control (OR = 1.47, 95% CI 1.24, 1.73, p < 0.0001) in 2020 versus 2019 driven by improvements from May to June 2020. CONCLUSIONS: Decreased asthma morbidity in minority children during COVID was coupled with decreased adherence to controller medications. This observed decrease in morbidity is not explained by improvements in adherence.

Levothyroxine Dosing in Older Adults: Recommendations Derived From The Baltimore Longitudinal Study of Aging.

OBJECTIVE: As thyroid hormone metabolism slows with advancing age, treatment dosing requirements change. Guidelines recommend titration from a low starting dose for older adults with hypothyroidism while providing weight-based estimates for younger populations. However, rapid replacement may be appropriate with acute onset of overt hypothyroidism. Therefore, a weight-based recommendation specific to older adults is needed. METHODS: We determined mean levothyroxine dose using actual and ideal body weight (IBW) ratios for the outcome of euthyroid on therapy relative to assay-specific and proposed age-specific ranges for independently living participants aged ≥65 years in the Baltimore Longitudinal Study of Aging. We examined risk factors to identify those at highest risk of overtreatment using regression analyses adjusted for potential covariables and clustering to account for multiple visits per individual. RESULTS: One hundred eighty-five participants aged ≥65 years were on levothyroxine at 645 eligible visits. At euthyroid visits, participants were on an average dose of 1.09 µg/kg (1.35 µg/kg IBW), with 84% of euthyroid individuals on a dose of <1.6 µg/kg. Average euthyroid dose did not differ by sex using either actual body weight (ABW) or IBW. For obese individuals, mean euthyroid dose was lower if calculated using ABW (0.9 µg/kg vs 1.14 µg/kg; P < .01) but similar if calculated using IBW (1.42 vs 1.32 µg/kg IBW; P = .41) compared with those with a body mass index of <30. CONCLUSION: Thyroid hormone dose per body weight estimates for replacement in older adults (1.09 µg/kg ABW or 1.35 µg/kg IBW) are one-third lower than current weight-based dose recommendations for younger populations.

A multilevel perspective on goals, barriers, and facilitators of school-based asthma management.

BACKGROUND: School based asthma care is being increasingly used to combat uncontrolled pediatric asthma. OBJECTIVE: The purpose of these secondary analyses was to explore multi-level perspectives regarding school-based asthma medical management for inner city, school-aged children with poor asthma control. METHODS: Sixty-six participants from two large U.S. urban school districts and key stakeholders participated in 1:1 interviews and focus groups. Participants were selected from across the asthma care community (children/caregivers, school personnel, nurses, pharmacists, healthcare providers, and administrators/insurers). Qualitative and descriptive techniques were used to analyze data. RESULTS: Goals: Children/caregivers prioritized living a normal active life with few asthma worries. Other stakeholders prioritized reducing student's asthma related emergency room visits and lost learning time. Facilitators: Continuity of care, strong relationships between care community members, and incentivizers were commonly suggested facilitators. School-based asthma management was viewed as a strong facilitator, particularly in the presence of a full-time school nurse. Barriers: Four themes were identified. (1) Greater systems and policy support for asthma management is needed in general, and at school in particular. (2) Overburdened families and systems often operate in crisis-mode, and asthma management is often not a priority until crisis is reached. (3) Discordance and distrust between members of the asthma care community can hinder shared asthma management. (4) Better communication is needed at all levels to improve care. CONCLUSION: Moving away from a crisis-based approach to asthma management for high-risk children will require increased systemic support for proactive asthma care and optimized communication within the asthma care community.Supplemental data for this article is available online at https://dx.doi.org/10.1080/02770903.2021.2018704.

Going mobile with primary care: smartphone-telemedicine for asthma management in young urban adults (TEAMS).

BACKGROUND: The majority of adults with persistent asthma have chronically uncontrolled disease and interventions to improve outcomes are needed. We evaluated the efficacy, feasibility, and acceptability of a multi-component smartphone-telemedicine program (TEAMS) to deliver asthma care remotely, support provider adherence to asthma management guidelines, and improve patient outcomes. METHODS: TEAMS utilized: (1) remote symptom monitoring, (2) nurse-led smartphone-telemedicine with self-management training for patients, and (3) Electronic medical record-based clinical decision support software. Adults aged 18-44 (N = 33) and primary care providers (N = 4) were recruited from a safety-net practice in Upstate New York. Asthma control, quality of life, and FEV1 were measured at 0, 3 and 6 months. Acceptability was assessed via survey and end-of-study interviews. Paired t-test and mixed effects modeling were used to evaluate the effect of the intervention on asthma outcomes. RESULTS: At baseline, 80% of participants had uncontrolled asthma. By 6-months, 80% classified as well-controlled. Improvements in control and quality of life were large (d = 1.955, d = 1.579). FEV%pred increased 4.2% (d = 1.687) with the greatest gain in males, smokers, and lower educational status. Provider adherence to national guidelines increased from 43.3% to 86.7% (CI = 22.11-64.55) and patient adherence to medication increased from 45.58% to 85.29% (CI = 14.79-64.62). Acceptability was 95.7%; In follow up interviews, 29/30 patients and all providers indicated TEAMS worked better than usual care, supported effective self-management, and reduced symptoms over time, which led to greater self-efficacy and motivation to manage asthma. DISCUSSION: Based on these findings, we conclude that smartphone telemedicine could substantially improve clinical asthma management, adherence to guidelines, and patient outcomes.

A mixed-methods analysis of younger adults' perceptions of asthma, self-management, and preventive care: "This isn't helping me none".

BACKGROUND: Young adults (ages 18-44) have increased emergency department use for asthma and poor adherence to medications. The objective of this mixed-methods study was to understand experiences with and approaches to managing asthma, of which little is known in this age group. METHODS: Surveys (Asthma Control Questionnaire, Asthma Quality of Life Questionnaire) and 1:1 semi-structured interviews were used to explore experiences with asthma, symptoms, self-management behaviours, and relationship to asthma control and quality of life. Qualitative data were analysed using content analysis techniques. Descriptive statistics and bivariate correlations were used to examine distributive characteristics and associations between variables. RESULTS: Forty urban adults participated (mean age 32.7 ± 6.2, 1σ). Coughing was reported nearly 46% more often than wheezing, with 42.5% (17/40) coughing until the point of vomiting most days. Most participants delayed using medication for symptoms due to misperceptions about inhalers. Higher symptom frequency and worse asthma control were associated with greater use of non-pharmacologic symptom management strategies (r = 0.645, P < .001; r = 0.360, P = .022, respectively). Five themes were identified regarding young adults experiences with asthma: (1) having asthma means being limited and missing out on life; (2) health care for asthma is burdensome, and other things are more important; (3) there is not enough personal benefit in medical interactions to make preventive care worthwhile; (4) there are insufficient support and education about asthma for adults; and (5) people normalize chronic symptoms over time and find ways of coping that fit with their lifestyle. CONCLUSIONS AND CLINICAL RELEVANCE: Young adults may tolerate symptoms without using quick-relief medication or seeking preventive care. Increasing engagement with preventive services will require decreasing perceived burdens and increasing the personal benefits of care. Evaluating for non-pharmacologic approaches to managing symptoms and asthma-related coughing may identify uncontrolled asthma. Enhanced training for clinicians in patient-centric asthma care may be needed.

Health-related internet use among adolescents with uncontrolled persistent asthma.

OBJECTIVES: To describe internet use for health information among adolescents with uncontrolled persistent asthma, and to examine whether health-related internet use is associated with responsibility for home asthma management. METHODS: We analyzed baseline data from the School-Based Asthma Care for Teens (SB-ACT) Trial, which included adolescents (12-16 years) in an urban school district who had uncontrolled persistent asthma per caregiver report. We asked adolescents whether they had ever used the Internet to look for health or medical information (Y/N). Teens then described family responsibility for 9 asthma management tasks (e.g. full caregiver responsibility, shared responsibility, or full teen responsibility). We examined responsibility sum scores in addition to responsibility for individual management tasks. We used bivariate and multivariate analyses to compare health-related internet use with participant characteristics, teen-reported asthma symptoms, and management responsibility. RESULTS: We examined data for 425 adolescents (mean age 13.4 years). Almost half (45%) reported seeking health information on the Internet. In adjusted analyses, health-related internet use was strongly associated with teen responsibility (sum score and tasks relating to carrying and using medications); internet use was also more likely among teens who were older, female, or reported uncontrolled disease. CONCLUSIONS: Adolescents with persistent asthma who share responsibility for home management or report uncontrolled disease are more likely to seek health information online. Future interventions to support teens who co-manage asthma should work to engage patients in both clinical and digital spaces, and ensure that all patients can access accurate, patient-centered asthma information when needed.

Additional Surgery for Occult Risk Factors After Lobectomy in Solitary Thyroid Nodules is Predicted by Cytopathology Classification and Tumor Size.

OBJECTIVE: Clinical practice for differentiated thyroid cancer is moving towards lobectomy rather than total thyroidectomy in patients at low risk of recurrence. However, recurrence risk assessment depends on post-operative findings, while the surgical decision is based on preoperative factors. We determined the preoperative predictors of occult higher-risk pathology and rates of completion thyroidectomy among surgical candidates with nonbenign thyroid nodules 10 to 40 mm and no evidence of extrathyroidal extension or metastasis on preoperative evaluation. METHODS: Thyroid surgery cases at a single institution from 2005-2015 were reviewed to identify those meeting American Thyroid Association (ATA) criteria for lobectomy. ATA-based risk stratification from postoperative surgical pathology was compared to preoperative cytopathology, ultrasound, and clinical findings. RESULTS: Of 1,995 thyroid surgeries performed for nonbenign thyroid nodules 10 to 40 mm, 349 met ATA criteria for lobectomy. Occult high-risk features such as tall cell variant, gross extrathyroidal invasion, or vascular invasion were found in 36 cases (10.7%), while intraoperative lymphadenopathy led to surgical upstaging in 13 (3.7%). Intermediate risk features such as moderate lymphadenopathy or minimal extrathyroidal extension were present in an additional 44 cases. Occult risk features were present twice as often in Bethesda class 6 cases (35%) as in lower categories (12 to 17%). In multivariable analysis, Bethesda class and nodule size, but not age, race, sex, or ultrasound features, were significant predictors of occult higher-risk pathology. CONCLUSION: Most solitary thyroid nodules less than 4 cm and with cytology findings including atypia of undetermined significance through suspicious for papillary thyroid cancer would be sufficiently treated by lobectomy. ABBREVIATIONS: ATA = American Thyroid Association; CND = central neck dissection; DTC = differentiated thyroid cancer; ETE = extrathyroidal extension; FNA = fine needle aspiration; FTC/HCC = follicular thyroid carcinoma/Hurthle cell carcinoma; NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features; OR = odds ratio; PTC = papillary thyroid cancer; US = ultrasound.

Mixed-methods content and sentiment analysis of adolescents' voice diaries describing daily experiences with asthma and self-management decision-making.

BACKGROUND: Accurate symptom assessment remains challenging in teen populations. Little is known of usual symptom/response patterns, and self-reported paper diaries have traditionally low compliance rates. Therefore, we used concurrent digital voice diaries to capture daily asthma experiences. OBJECTIVE: (a) To qualitatively explore usual symptom patterns and self-management responses and (b) to quantitatively explore relationships between symptom severity and sentiment scores (a marker of emotional response to events). METHODS: Fourteen minority and nonminority teenagers (age 13-17) with controlled (50%) and uncontrolled asthma used digital recorders to report about their asthma once daily over 14 days. Dairy entries were coded for symptom frequency, severity, type, and self-management responses, while sentiment analysis was used to evaluate the emotional valence of diary entries and to explore whether increased symptom levels correlated with greater negative sentiment. RESULTS: Symptom frequency and severity recorded in voice diaries were much higher than teens indicated at baseline and were discordant with clinical assessments of asthma control. Of 175 entries, teens had symptoms 69.1% of days (121/175) and severe symptoms on one-third of these. Atypical symptoms (coughing, throat clearing) were reported twice as often as traditional symptoms (wheezing, chest tightness) and often not recognized as asthma, but rather attributed to being "sick" (25.6% of symptom days). Teens frequently minimized symptoms, used rescue and controller medication inconsistently, and resorted to alternative strategies to manage symptoms. Sentiment was not significantly correlated with assessed control (ß = 0.14, P = 0.28), but for teens reporting severe symptoms, sentiment scores decreased by 0.31 relative to teens without symptoms (P = 0.006). CONCLUSIONS AND CLINICAL RELEVANCE: Teens may minimize symptoms and have greater symptom frequency and severity than is recognized by themselves or providers. Screening for specific symptoms including coughing, throat clearing, and respiratory illness may be needed to identify those experiencing burden from asthma.

Comparing Asthma Control Questionnaire (ACQ) and National Asthma Education and Prevention Program (NAEPP) asthma control criteria.

BACKGROUND: Adequate assessment of control is critical to asthma management. The Asthma Control Questionnaire (ACQ) and the National Asthma Education and Prevention Program (NAEPP) criteria are commonly used measures of asthma control. OBJECTIVE: To examine the associations between the ACQ and NAEPP criteria and compare the validity in association with lung function, asthma exacerbation, and quality of life. METHODS: The ACQ and the NAEPP criteria were administered to 373 adolescents with asthma aged 12 to 20 years. The 2 measures correlated with forced expiratory volume in 1 second (FEV1), asthma exacerbation (oral corticosteroid use, hospitalization, and emergency department [ED] use) in the past 12 months, and quality of life. RESULTS: Agreement between the ACQ and NAEPP criteria was moderate (κ = 0.40-0.61). Neither of the 2 measures was a reliable predictor of FEV1 less than 80% because of the high rate of false-positive results for the ACQ (68%) and low sensitivity for the NAEPP (49%). The NAEPP identified more cases of uncontrolled asthma (84.6%) than the ACQ (64.6%). The ACQ was a significant predictor of recent oral corticosteroid use, hospitalization, and ED visits (area under the curve = 0.66, 0.66, and 0.64, respectively; P < .001), as was NAEPP (area under the curve = 0.63, 0.66, and 0.61, respectively; P < .001). Both measures were significantly associated with quality of life, and the associations were particularly strong for the ACQ (r = -0.87 for symptom subscale, r = -0.76 for activity subscale, and r = -0.78 for emotional function subscale). CONCLUSION: Neither the ACQ nor the NAEPP appears to reliably predict lung function, whereas both measures reasonably associate with acute asthma exacerbation. The ACQ may be the superior measure in gauging the psychosocial effect of asthma control given its particularly strong associations with quality of life. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02293499.

An integrated operational definition and conceptual model of asthma self-management in teens.

OBJECTIVES: A previous definition of adolescent asthma self-management was derived from interviews with clinicians/researchers and published literature; however, it did not incorporate perspectives of teens or parents. Therefore, we conducted in-depth interviews with teens and parents and synthesized present findings with the prior analysis to develop a more encompassing definition and model. METHODS: Focal concepts were qualitatively extracted from 14-day self-management voice-diaries (n = 14) and 1-hour interviews (n = 42) with teens and parents (28 individuals) along with concepts found in the previous clinical/research oriented analysis. Conceptual structure and relationships were identified and key findings synthesized to develop a revised definition and model of adolescent asthma self-management. RESULTS: There were two primary self-management constructs: processes of self-management and tasks of self-management. Self-management was defined as the iterative process of assessing, deciding, and responding to specific situations in order to achieve personally important outcomes. Clinically relevant asthma self-management tasks included monitoring asthma, managing active issues through pharmacologic and non-pharmacologic strategies, preventing future issues, and communicating with others as needed. Self-management processes were reciprocally influenced by intrapersonal factors (both cognitive and physical), interpersonal factors (family, social and physical environments), and personally relevant asthma and non-asthma outcomes. CONCLUSION: This is the first definition of asthma self-management incorporating teen, parent, clinician, and researcher perspectives, which suggests that self-management processes and behaviors are influenced by individually variable personal and interpersonal factors, and are driven by personally important outcomes. Clinicians and researchers should investigate teens' symptom perceptions, medication beliefs, current approaches to symptom management, relevant outcomes, and personal priorities.

Beyond concept analysis: Uses of mind mapping software for visual representation, management, and analysis of diverse digital data.

Mind mapping is a visual-spatial method of representing information using nodes (information segments) to show ideas and connecting lines to define relationships between content. As a critical thinking tool, it is applicable to a range of research activities, including information management, project development, and data analysis. The purposes of this manuscript are to describe the use of mapping for qualitative data analysis, provide step-by-step instructions of how to construct mind maps, and present examples specific to qualitative data analysis. An example from a recent study of patient and provider perceptions of virtual visits demonstrates the use of Xmind in conjunction with Atlas.ti for qualitative content analysis of open-ended survey data. While coding in Atlas.ti, we used Xmind to develop dynamic memos, code networks, and themes. The memo map served to identify common coding patterns and informed subsequent coding stages. After coding in Atlas.ti, the entire code list was imported into a new map in Xmind and iteratively organized to identify conceptual groupings, similarities/differences, and key ideas. Themes were identified through pattern coding and refining code networks within the Xmind map. Map iterations formed part of the analytic trail and facilitated peer-to-peer discussions. The final map served as the model for publication. The use of mind mapping enhanced the rigor, credibility, and transparency of analyses and facilitated peer-to-peer communication. This technique can be used to manage diverse content (documents, audio/video file, image, web links, and personal notes) and thus has great potential to contribute to a variety of data management tasks.

Patient and Physician Perceptions of Virtual Visits for Parkinson's Disease: A Qualitative Study.

Background and Introduction: Delivering care through telemedicine directly into the patient's home is increasingly feasible, valuable, and beneficial. However, qualitative data on how patients' and physicians' perceive these virtual house calls are lacking. We conducted a qualitative analysis of perceptions of these visits for Parkinson's disease to (1) determine how patients and physicians perceive virtual visits and (2) identify components contributing to positive and negative perceptions. MATERIALS AND METHODS: Qualitative survey data were collected from patients and physicians during a 12-month randomized controlled trial of virtual house calls for Parkinson's disease. Data from 149 cases were analyzed using case-based qualitative content analysis and quantitative sentiment analysis techniques. RESULTS: Positive and negative perceptions of virtual visits were driven by three themes: (1) personal benefits of the virtual visit, (2) perceived quality of care, and (3) perceived quality of interpersonal engagement. In general, participants who identified greater personal benefit, high quality of care, and good interpersonal engagement perceived visits positively. Technical problems with the software were commonly mentioned. The sentiment analysis for patients was strongly favorable (+2.5) and moderately favorable for physicians (+0.8). Physician scores were lowest (-0.3) for the ability to perform a detailed motor examination remotely. DISCUSSION: Patients and providers generally view telemedicine favorably, but individual experiences are dependent on technical issues. CONCLUSIONS: Satisfaction with and effectiveness of remote care will likely increase as common technical problems are resolved.

Perceptions and experiences underlying self-management and reporting of symptoms in teens with asthma.

BACKGROUND: Teens often have inadequate asthma self-management and control. However, little is known of their perceptions of or rationales for self-management behaviors. OBJECTIVES: To explore how teens self-manage asthma, including experiences, perceptions, responses to and reporting of symptoms. METHODS: A case-based, qualitative-descriptive design was used. Data were collected from minority and non-minority teens with controlled and uncontrolled asthma and their respective parents (N = 28). There were four data-collection points, including: (1) a primary teen interview; (2) parent interview; (3) 2-week self-management voice-diary; and (4) follow-up teen interview, incorporating symptom-response card-sorting to map symptoms and associated self-management responses. Seventy data sources were included in the analysis. RESULTS: Teens thought of their asthma symptoms as normal or unusual relative to their personal baseline symptom pattern; Those with uncontrolled asthma normalized higher levels of asthma symptoms than their counterparts with controlled asthma. Second, teens' decisions to treat symptoms of asthma with rescue medication were based on perceived benefits, burdens and accessibility of treatment balanced against perceived normalcy of symptoms. Teens with uncontrolled asthma had substantially higher treatment thresholds and delayed responses to symptoms compared to controlled peers. Third, teens never reported perceived normal symptoms of asthma to parents or providers, who were thus only aware of unusual or visible/audible symptoms. CONCLUSIONS: Teen's perceptions of symptoms and understanding of what is normal is the basis for self-management decisions. Improving self-management will likely entail modifying perceptions of symptoms and benefits/burdens of treatment to achieve healthier self-management patterns.

Thyroid and Aging.

Older adults are more vulnerable to the negative effects of excess thyroid hormone and may even be protected by lower levels of thyroid hormone. The diagnosis and management of thyroid disease in older adults needs to account for aging-related changes in function and resilliance.

Endogenous and Exogenous Thyrotoxicosis and Risk of Incident Cognitive Disorders in Older Adults.

Importance: Thyroid hormone is among the most common prescriptions in the US and up to 20% may be overtreated. Endogenous hyperthyroidism may be a risk factor for dementia, but data are limited for iatrogenic thyrotoxicosis. Objective: To determine whether thyrotoxicosis, both endogenous and exogenous, is associated with increased risk of cognitive disorders. Design, Setting, and Participants: This cohort study performed a longitudinal time-varying analysis of electronic health records for patients receiving primary care in the Johns Hopkins Community Physicians Network between January 1, 2014, and May 6, 2023. Patients 65 years and older with at least 2 visits 30 days apart to their primary care physicians were eligible. None of the 65 931 included patients had a history of low thyrotropin (TSH) level or cognitive disorder diagnoses within 6 months of their first visit. Data analysis was performed from January 1 through August 5, 2023. Exposure: The exposure variable was a low TSH level, characterized based on the clinical context as due to endogenous thyrotoxicosis, exogenous thyrotoxicosis, or unknown cause, excluding those attributable to acute illness or other medical factors such as medications. Main Outcomes and Measures: The outcome measure was cognitive disorders, including mild cognitive impairment and all-cause dementia, to improve sensitivity and account for the underdiagnosis of dementia in primary care. Results: A total of 65 931 patients were included in the analysis (median [IQR] age at first visit, 68.0 [65.0-74.0] years; 37 208 [56%] were female; 46 106 [69.9%] were White). Patients exposed to thyrotoxicosis had cognitive disorder incidence of 11.0% (95% CI, 8.4%-14.2%) by age 75 years vs 6.4% (95% CI, 6.0%-6.8%) for those not exposed. After adjustment, all-cause thyrotoxicosis was significantly associated with risk of cognitive disorder diagnosis (adjusted hazard ratio, 1.39; 95% CI, 1.18-1.64; P < .001) across age groups. When stratified by cause and severity, exogenous thyrotoxicosis remained a significant risk factor (adjusted hazard ratio, 1.34; 95% CI, 1.10-1.63; P = .003) with point estimates suggestive of a dose response. Conclusions and Relevance: In this cohort study among patients 65 years and older, a low TSH level from either endogenous or exogenous thyrotoxicosis was associated with higher risk of incident cognitive disorder. Iatrogenic thyrotoxicosis is a common result of thyroid hormone therapy. With thyroid hormone among the most common prescriptions in the US, understanding the negative effects of overtreatment is critical to help guide prescribing practice.

Endocrine Dysfunction From Immune Checkpoint Inhibitors: Pearls and Pitfalls in Evaluation and Management.

Immune checkpoint inhibitors (ICPis) have proven extremely efficacious in cancer therapy but also lead to a plethora of immune-related adverse events (irAEs). The endocrine irAEs are not only quite common but also may pose a challenge to the clinician while managing a patient with cancer treated with ICPis. The clinical features of endocrine dysfunction are usually nonspecific and may overlap with concurrent illnesses, underlying the importance of accurate hormone testing and efforts toward case-finding. The management of endocrine irAEs is unique in the focus being on hormone replacement rather than curtailing the autoimmune process. Although the management of thyroid irAEs appears straightforward, adrenal insufficiency and insulin-dependent diabetes can be life-threatening if not promptly recognized and treated. This clinical review synthesizes the studies to provide pearls and pitfalls in the evaluation and management of endocrine irAEs with specific reference to guidelines from oncologic societies.

Higher thyroid hormone has a negative association with lower limb lean body mass in euthyroid older adults: Analysis from the Baltimore Longitudinal study of aging.

Background: Hyperthyroidism is associated with lower lean body mass, as a result of catabolic actions of thyroid hormone. Therefore, higher thyroid hormone levels could be a factor in the development of sarcopenia and age associated functional decline. The relationship between thyroid hormone and muscle mass in ambulatory, euthyroid older adults is not known. Method: We used mixed-effects models to estimate the cross-sectional relationships (accounting for inter-person variability) between thyroid axis hormone measures and lower limb composition or sarcopenia at visits in the Baltimore Longitudinal Study of Aging (BLSA) at which DEXA scans were available and both thyrotropin (TSH) and free thyroxine (FT4) were in the reference range. Analyses were adjusted for levothyroxine use, age, race, sex, BMI, smoking, alcohol intake, cholesterol, and systolic blood pressure. Results: 1442 euthyroid participants (median age 68, 50% female, and 69% white) contributed to 5306 visits from 2003 to 2019. FT4 was negatively associated with lower limb lean mass (beta: 88.49; 95% Confidence Interval (CI): 122.78, -54.20; p < 0.001) and positively associated with sarcopenia (OR: 1.11%, 95% CI: 1.01, 1.22) in the whole cohort. Additionally, higher FT4 was associated with lower leg lean mass (beta: 66.79; 95% CI: 102.24, -31.33; p < 0.001) and sarcopenia (OR:1.09%, 95% CI:1.01, 1.18) in older adults, but not in younger adults alone. Conclusion: In euthyroid older adults, higher FT4 is associated with lower leg lean mass and higher odds of sarcopenia. Understanding the relationship between thyroid hormone and sarcopenia is needed to improve clinical decision-making and avoid functional decline from excess thyroid hormone use in older adults.

Levothyroxine use and longitudinal changes in thigh muscles in at-risk participants for knee osteoarthritis: preliminary analysis from Osteoarthritis Initiative cohort.

BACKGROUND: We examined the association between levothyroxine use and longitudinal MRI biomarkers for thigh muscle mass and composition in at-risk participants for knee osteoarthritis (KOA) and their mediatory role in subsequent KOA incidence. METHODS: Using the Osteoarthritis Initiative (OAI) data, we included the thighs and corresponding knees of participants at risk but without established radiographic KOA (baseline Kellgren-Lawrence grade (KL) < 2). Levothyroxine users were defined as self-reported use at all annual follow-up visits until the 4th year and were matched with levothyroxine non-users for potential confounders (KOA risk factors, comorbidities, and relevant medications covariates) using 1:2/3 propensity score (PS) matching. Using a previously developed and validated deep learning method for thigh segmentation, we assessed the association between levothyroxine use and 4-year longitudinal changes in muscle mass, including cross-sectional area (CSA) and muscle composition biomarkers including intra-MAT (within-muscle fat), contractile percentage (non-fat muscle CSA/total muscle CSA), and specific force (force per CSA). We further assessed whether levothyroxine use is associated with an 8-year risk of standard KOA radiographic (KL ≥ 2) and symptomatic incidence (incidence of radiographic KOA and pain on most of the days in the past 12 months). Finally, using a mediation analysis, we assessed whether the association between levothyroxine use and KOA incidence is mediated via muscle changes. RESULTS: We included 1043 matched thighs/knees (266:777 levothyroxine users:non-users; average ± SD age: 61 ± 9 years, female/male: 4). Levothyroxine use was associated with decreased quadriceps CSAs (mean difference, 95%CI: - 16.06 mm2/year, - 26.70 to - 5.41) but not thigh muscles' composition (e.g., intra-MAT). Levothyroxine use was also associated with an increased 8-year risk of radiographic (hazard ratio (HR), 95%CI: 1.78, 1.15-2.75) and symptomatic KOA incidence (HR, 95%CI: 1.93, 1.19-3.13). Mediation analysis showed that a decrease in quadriceps mass (i.e., CSA) partially mediated the increased risk of KOA incidence associated with levothyroxine use. CONCLUSIONS: Our exploratory analyses suggest that levothyroxine use may be associated with loss of quadriceps muscle mass, which may also partially mediate the increased risk of subsequent KOA incidence. Study interpretation should consider underlying thyroid function as a potential confounder or effect modifier. Therefore, future studies are warranted to investigate the underlying thyroid function biomarkers for longitudinal changes in the thigh muscles.

A Phase 1b, Open-Label Study to Evaluate the Safety and Tolerability of the Putative Remyelinating Agent, Liothyronine, in Individuals with MS.

Thyroid hormones are essential during developmental myelination and may play a direct role in remyelination and repair in the adult central nervous system by promoting the differentiation of oligodendrocyte precursor cells into mature oligodendrocytes. Since tri-iodothyronine (T3) is believed to mediate the majority of important thyroid hormone actions, liothyronine (synthetic T3) has the potential to induce reparative mechanisms and limit neurodegeneration in multiple sclerosis (MS). We completed a phase 1b clinical trial to determine the safety and tolerability of ascending doses of liothyronine in individuals with relapsing and progressive MS. A total of 20 people with MS were enrolled in this single-center trial of oral liothyronine. Eighteen participants completed the 24-week study. Our study cohort included mostly women (11/20), majority relapsing MS (12/20), mean age of 46, and baseline median EDSS of 3.5. Liothyronine was tolerated well without treatment-related severe/serious adverse events or evidence of disease activation/clinical deterioration. The most common adverse events included gastrointestinal distress and abnormal thyroid function tests. No clinical thyrotoxicosis occurred. Importantly, we did not observe a negative impact on secondary clinical outcome measures. The CSF proteomic changes suggest a biological effect of T3 treatment within the CNS. We noted changes primarily in proteins associated with immune cell function and angiogenesis. Liothyronine appeared safe and was well tolerated in people with MS. A larger clinical trial will help assess whether liothyronine can promote oligodendrogenesis and enhance remyelination in vivo, limit axonal degeneration, or improve function.