Invasive Fungal Sinusitis in an Immunocompetent Patient After Sinus Surgery for Chronic Rhinosinusitis with Nasal Polyps and a Mycetoma.

Acute invasive fungal sinusitis (AIFS) classically presents as an aggressive fungal infection that can spread beyond its origin in the sinuses in immunocompromised patients. Although there have been reports of AIFS in immunocompetent, non-diabetic patients, it is extremely rare and the true mechanism behind it is unknown. A thirty-eight year old immunocompetent, non-diabetic woman underwent bilateral ESS for chronic rhinosinusitis with nasal polyps at a tertiary care center and post-operatively developed AIFS. Patient underwent uncomplicated ESS, was packed with foam containing triamcinolone and discharged on steroid rinses and a prednisone taper. Surgical pathology demonstrated left-sided colonization with non-invasive fungal elements consistent with a mycetoma. She presented on post-operative Day 11 with headache and left-sided retro-orbital pain. A culture of her left nasal cavity grew Rhizopus spp and MRI demonstrated evidence of invasive fungal infection of left sphenoid mucosa as well as inflammatory changes in the left orbit centered at the orbital apex. She was started on amphotericin and underwent a left-sided debridement with biopsies which demonstrated angioinvasive fungal disease. Her vision in her left eye worsened to 20/800 and she was treated with transcutaneous retrobulbar injection of amphotericin B. After stable interval imaging she was discharged on a long-term course of antifungals. Extensive immunologic work-up was unremarkable. We describe a case of an immunocompetent patient who developed AIFS after sinus surgery for CRS and a mycetoma likely as a result of local immune suppression and post-surgical trauma. Laryngoscope, 2024.

The Environment and Headache: a Narrative Review.

PURPOSE OF REVIEW: In this narrative review, we summarize the peer-reviewed literature published between 2017 and 2022 that evaluated ambient environmental risk factors for primary headache disorders, which affect more than half of the population globally. Primary headache disorders include migraine, tension-type headache (TTH), and trigeminal and autonomic cephalalgias (TAC). RECENT FINDINGS: We identified 17 articles that met the inclusion criteria via PubMed or Google Scholar. Seven studies (41%) relied on data from US populations. The remaining studies were conducted in China, Taiwan, Germany, Ghana, Japan, the Netherlands, South Korea, and Turkey. Air pollution was the most frequently assessed environmental risk factor. Most studies were cross-sectional and focused on all-cause or migraine headaches; one study included TTH, and none included TAC. Short-term exposure to fine particulate matter (PM2.5) was not consistently associated with headache endpoints, but long-term exposure to PM2.5 was associated with migraine headache prevalence and severity across multiple studies. Elevated ambient temperature, changes in weather, oil and gas well exposure, and less natural greenspace, but not noise pollution, were also associated with headache. No studies considered water pollution, metal exposure, ultrafine particulate matter, or wildfire smoke exposure. There is a need for ongoing research focused on headache and the environment. Study designs with the greatest explanatory power may include longitudinal studies that capture the episodic nature of headache and case-crossover analysis, which control for time-invariant individual-level confounders by design. There is also a clear need for research that considers comorbid psychiatric illness and socioeconomic position as powerful modifiers of the effect of the environment on headache.

Associations between PM2.5 and O3 exposures and new onset type 2 diabetes in regional and national samples in the United States.

BACKGROUND: Exposure to particulate matter ≤2.5 µm in diameter (PM2.5) and ozone (O3) has been linked to numerous harmful health outcomes. While epidemiologic evidence has suggested a positive association with type 2 diabetes (T2D), there is heterogeneity in findings. We evaluated exposures to PM2.5 and O3 across three large samples in the US using a harmonized approach for exposure assignment and covariate adjustment. METHODS: Data were obtained from the Veterans Administration Diabetes Risk (VADR) cohort (electronic health records [EHRs]), the Reasons for Geographic and Racial Disparities in Stroke (REGARDS) cohort (primary data collection), and the Geisinger health system (EHRs), and reflect the years 2003-2016 (REGARDS) and 2008-2016 (VADR and Geisinger). New onset T2D was ascertained using EHR information on medication orders, laboratory results, and T2D diagnoses (VADR and Geisinger) or report of T2D medication or diagnosis and/or elevated blood glucose levels (REGARDS). Exposure was assigned using pollutant annual averages from the Downscaler model. Models stratified by community type (higher density urban, lower density urban, suburban/small town, or rural census tracts) evaluated likelihood of new onset T2D in each study sample in single- and two-pollutant models of PM2.5 and O3. RESULTS: In two pollutant models, associations of PM2.5, and new onset T2D were null in the REGARDS cohort except for in suburban/small town community types in models that also adjusted for NSEE, with an odds ratio (95% CI) of 1.51 (1.01, 2.25) per 5 µg/m3 of PM2.5. Results in the Geisinger sample were null. VADR sample results evidenced nonlinear associations for both pollutants; the shape of the association was dependent on community type. CONCLUSIONS: Associations between PM2.5, O3 and new onset T2D differed across three large study samples in the US. None of the results from any of the three study populations found strong and clear positive associations.

In host evolution of beta lactam resistance during active treatment for Pseudomonas aeruginosa bacteremia.

Multidrug-resistant (MDR) Pseudomonas aeruginosa has been declared a serious threat by the United States Centers for Disease Control and Prevention. Here, we used whole genome sequencing (WGS) to investigate recurrent P. aeruginosa bloodstream infections in a severely immunocompromised patient. The infections demonstrated unusual, progressive increases in resistance to beta lactam antibiotics in the setting of active treatment with appropriate, guideline-directed agents. WGS followed by comparative genomic analysis of isolates collected over 44 days demonstrated in host evolution of a single P. aeruginosa isolate characterized by stepwise acquisition of two de-novo genetic resistance mechanisms over the course of treatment. We found a novel deletion affecting the ampC repressor ampD and neighboring gene ampE, which associated with initial cefepime treatment failure. This was followed by acquisition of a porin nonsense mutation, OprD, associated with resistance to carbapenems. This study highlights the potential for in-host evolution of P. aeruginosa during bloodstream infections in severely immunocompromised patients despite appropriate antimicrobial therapy. In addition, it demonstrates the utility of WGS for understanding unusual resistance patterns in the clinical context.

Identification of opioid use disorder using electronic health records: Beyond diagnostic codes.

BACKGROUND: We used structured and unstructured electronic health record (EHR) data to develop and validate an approach to identify moderate/severe opioid use disorder (OUD) that includes individuals without prescription opioid use or chronic pain, an underrepresented population. METHODS: Using electronic diagnosis grouper text from EHRs of ~1 million patients (2012-2020), we created indicators of OUD-with "tiers" indicating OUD likelihood-combined with OUD medication (MOUD) orders. We developed six sub-algorithms with varying criteria (multiple vs single MOUD orders, multiple vs single tier 1 indicators, tier 2 indicators, tier 3 and 4 indicators). Positive predictive values (PPVs) were calculated based on chart review to determine OUD status and severity. We compared demographic and clinical characteristics of cases identified by the sub-algorithms. RESULTS: In total, 14,852 patients met criteria for one of the sub-algorithms. Five sub-algorithms had PPVs ≥0.90 for any severity OUD; four had PPVs ≥0.90 for moderate/severe OUD. Demographic and clinical characteristics differed substantially between groups. Of identified OUD cases, 31.3% had no past opioid analgesic orders, 79.7% lacked evidence of chronic prescription opioid use, and 43.5% lacked a chronic pain diagnosis. DISCUSSION: Incorporating unstructured data with MOUD orders yielded an approach that adequately identified moderate/severe OUD, identified unique demographic and clinical sub-groups, and included individuals without prescription opioid use or chronic pain, whose OUD may stem from illicit opioids. Findings show that incorporating unstructured data strengthens EHR algorithms for identifying OUD and suggests approaches limited to populations with prescription opioid use or chronic pain exclude many individuals with OUD.

Skills, Not Just Knowledge: Infectious Diseases Fellows' Recommendations Regarding Antimicrobial Stewardship Training.

BACKGROUND: Antimicrobial stewardship (AS) is an important topic in infectious diseases (ID) training, yet many ID fellowships lack formal training, and little is known about fellows' learning preferences. METHODS: We conducted 24 in-depth interviews with ID fellows across the United States during 2018 and 2019 to explore their experiences with and preferences for AS education during fellowship. Interviews were transcribed, deidentified, and analyzed to identify themes. RESULTS: Fellows had variable exposure to AS before and during fellowship, which impacted their knowledge about and attitude toward stewardship as a career; however, all fellows expressed the importance of learning general stewardship principles during fellowship. Some fellows' training included mandatory stewardship lectures and/or rotations, but most fellows felt their primary stewardship learning occurred through informal experiences in the clinical setting, such as holding the antimicrobial approval pager. Fellows expressed a preference for a standardized, structured curriculum that included in-person practical, interactive discussions with multidisciplinary faculty along with the opportunity to practice and apply their skills; however, they emphasized that time needed to be set aside for those educational activities. Although they wanted to learn the evidence and rationale for stewardship recommendations, they especially wanted training in and feedback on how to communicate stewardship recommendations to other health professionals, particularly in the setting of conflict. CONCLUSIONS: ID fellows believe that standardized AS curricula should be included in their fellowship training, and they prefer structured, practical, and interactive learning experiences.

Sinus inflammation and chronic rhinosinusitis are associated with a diagnosis of new onset asthma in the following year.

BACKGROUND: Chronic rhinosinusitis (CRS) and asthma commonly co-occur. No studies have leveraged large samples needed to formally address whether preexisting CRS is associated with new onset asthma over time. METHODS: We evaluated whether prevalent CRS [identified in two ways: validated text algorithm applied to sinus computerized tomography (CT) scan or two diagnoses] was associated with new onset adult asthma in the following year. We used electronic health record data from Geisinger from 2008 to 2019. For each year we removed persons with any evidence of asthma through the end of the year, then identified those with new diagnosis of asthma in the following year. Complementary log-log regression was used to adjust for confounding variables (e.g., sociodemographic, contact with the health system, comorbidities), and hazard ratios (HRs) and 95% confidence intervals (CI) were calculated. RESULTS: A total of 35,441 persons were diagnosed with new onset asthma and were compared to 890,956 persons who did not develop asthma. Persons with new onset asthma tended to be female (69.6%) and younger (mean [SD] age 45.9 [17.0] years). Both CRS definitions were associated (HR, 95% CI) with new onset asthma, with 2.21 (1.93, 2.54) and 1.48 (1.38, 1.59) for CRS based on sinus CT scan and two diagnoses, respectively. New onset asthma was uncommonly observed in persons with a history of sinus surgery. CONCLUSION: Prevalent CRS identified with two complementary approaches was associated with a diagnosis of new onset asthma in the following year. The findings may have clinical implications for the prevention of asthma.

Mediation of an association between neighborhood socioeconomic environment and type 2 diabetes through the leisure-time physical activity environment in an analysis of three independent samples.

INTRODUCTION: Inequitable access to leisure-time physical activity (LTPA) resources may explain geographic disparities in type 2 diabetes (T2D). We evaluated whether the neighborhood socioeconomic environment (NSEE) affects T2D through the LTPA environment. RESEARCH DESIGN AND METHODS: We conducted analyses in three study samples: the national Veterans Administration Diabetes Risk (VADR) cohort comprising electronic health records (EHR) of 4.1 million T2D-free veterans, the national prospective cohort REasons for Geographic and Racial Differences in Stroke (REGARDS) (11 208 T2D free), and a case-control study of Geisinger EHR in Pennsylvania (15 888 T2D cases). New-onset T2D was defined using diagnoses, laboratory and medication data. We harmonized neighborhood-level variables, including exposure, confounders, and effect modifiers. We measured NSEE with a summary index of six census tract indicators. The LTPA environment was measured by physical activity (PA) facility (gyms and other commercial facilities) density within street network buffers and population-weighted distance to parks. We estimated natural direct and indirect effects for each mediator stratified by community type. RESULTS: The magnitudes of the indirect effects were generally small, and the direction of the indirect effects differed by community type and study sample. The most consistent findings were for mediation via PA facility density in rural communities, where we observed positive indirect effects (differences in T2D incidence rates (95% CI) comparing the highest versus lowest quartiles of NSEE, multiplied by 100) of 1.53 (0.25, 3.05) in REGARDS and 0.0066 (0.0038, 0.0099) in VADR. No mediation was evident in Geisinger. CONCLUSIONS: PA facility density and distance to parks did not substantially mediate the relation between NSEE and T2D. Our heterogeneous results suggest that approaches to reduce T2D through changes to the LTPA environment require local tailoring.

Risk of new-onset and prevalent disease in chronic rhinosinusitis: A prospective cohort study.

BACKGROUND: Chronic rhinosinusitis (CRS) is accompanied by burdensome comorbid conditions. Understanding the relative timing of the onset of these conditions could inform disease prevention, detection, and management. OBJECTIVE: To evaluate the association between CRS and new-onset and prevalent asthma, noncystic fibrosis bronchiectasis (NCFBE), chronic obstructive pulmonary disease (COPD), gastroesophageal reflux disease (GERD), and obstructive sleep apnea (OSA). METHODS: We conducted a prospective cohort study among primary care patients using a detailed medical and symptom questionnaire in 2014 and again in 2020. We used questionnaire and electronic health record (EHR) data to determine CRS status: CRSSE (moderate to severe symptoms with EHR evidence), CRSE (limited symptoms with EHR evidence), CRSS (moderate to severe symptoms without EHR evidence), CRSneg (limited symptoms and no EHR evidence; reference). We evaluated the association between CRS status and new-onset and prevalent disease using logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: There were 7847 and 4445 respondents to the 2014 and 2020 questionnaires, respectively. CRSSE (vs CRSneg ) was associated with increased odds of new-onset asthma (OR, 1.74 [CI, 1.09-2.77), NCFBE (OR, 1.87 [CI, 1.12-3.13]), COPD (OR, 1.73 [CI, 1.14-2.68]), GERD (OR, 1.95 [CI, 1.61-2.35]), and OSA (OR, 1.91 [CI, 1.39-2.62]). Similarly, increased odds were observed for associations with the prevalence of these conditions. CONCLUSION: The findings from the study support further exploration of CRS as a target for the prevention and detection of asthma, NCFBE, COPD, GERD, and OSA.

Assessing Measurement Invariance of a Land Use Environment Construct Across Levels of Urbanicity.

Variation in the land use environment (LUE) impacts the continuum of walkability to car dependency, which has been shown to have effects on health outcomes. Existing objective measures of the LUE do not consider whether the measurement of the construct varies across different types of communities along the rural/urban spectrum. To help meet the goals of the Diabetes Location, Environmental Attributes, and Disparities (LEAD) Network, we developed a national, census tract-level LUE measure which evaluates the road network and land development. We tested for measurement invariance by LEAD community type (higher density urban, lower density urban, suburban/small town, and rural) using multiple group confirmatory factor analysis. We determined that metric invariance does not exist; thus, measurement of the LUE does vary across community type with average block length, average block size, and percent developed land driving most shared variability in rural tracts and with intersection density, street connectivity, household density, and commercial establishment density driving most shared variability in higher density urban tracts. As a result, epidemiologic studies need to consider community type when assessing the LUE to minimize place-based confounding.

Associations of four indexes of social determinants of health and two community typologies with new onset type 2 diabetes across a diverse geography in Pennsylvania.

Evaluation of geographic disparities in type 2 diabetes (T2D) onset requires multidimensional approaches at a relevant spatial scale to characterize community types and features that could influence this health outcome. Using Geisinger electronic health records (2008-2016), we conducted a nested case-control study of new onset T2D in a 37-county area of Pennsylvania. The study included 15,888 incident T2D cases and 79,435 controls without diabetes, frequency-matched 1:5 on age, sex, and year of diagnosis or encounter. We characterized patients' residential census tracts by four dimensions of social determinants of health (SDOH) and into a 7-category SDOH census tract typology previously generated for the entire United States by dimension reduction techniques. Finally, because the SDOH census tract typology classified 83% of the study region's census tracts into two heterogeneous categories, termed rural affordable-like and suburban affluent-like, to further delineate geographies relevant to T2D, we subdivided these two typology categories by administrative community types (U.S. Census Bureau minor civil divisions of township, borough, city). We used generalized estimating equations to examine associations of 1) four SDOH indexes, 2) SDOH census tract typology, and 3) modified typology, with odds of new onset T2D, controlling for individual-level confounding variables. Two SDOH dimensions, higher socioeconomic advantage and higher mobility (tracts with fewer seniors and disabled adults) were independently associated with lower odds of T2D. Compared to rural affordable-like as the reference group, residence in tracts categorized as extreme poverty (odds ratio [95% confidence interval] = 1.11 [1.02, 1.21]) or multilingual working (1.07 [1.03, 1.23]) were associated with higher odds of new onset T2D. Suburban affluent-like was associated with lower odds of T2D (0.92 [0.87, 0.97]). With the modified typology, the strongest association (1.37 [1.15, 1.63]) was observed in cities in the suburban affluent-like category (vs. rural affordable-like-township), followed by cities in the rural affordable-like category (1.20 [1.05, 1.36]). We conclude that in evaluating geographic disparities in T2D onset, it is beneficial to conduct simultaneous evaluation of SDOH in multiple dimensions. Associations with the modified typology showed the importance of incorporating governmentally, behaviorally, and experientially relevant community definitions when evaluating geographic health disparities.

Climate change and the prevention of cardiovascular disease.

Climate change is a worsening global crisis that will continue negatively impacting population health and well-being unless adaptation and mitigation interventions are rapidly implemented. Climate change-related cardiovascular disease is mediated by air pollution, increased ambient temperatures, vector-borne disease and mental health disorders. Climate change-related cardiovascular disease can be modulated by climate change adaptation; however, this process could result in significant health inequity because persons and populations of lower socioeconomic status have fewer adaptation options. Clear scientific evidence for climate change and its impact on human health have not yet resulted in the national and international impetus and policies necessary to slow climate change. As respected members of society who regularly communicate scientific evidence to patients, clinicians are well-positioned to advocate on the importance of addressing climate change. This narrative review summarizes the links between climate change and cardiovascular health, proposes actionable items clinicians and other healthcare providers can execute both in their personal life and as an advocate of climate policies, and encourages communication of the health impacts of climate change when counseling patients. Our aim is to inspire the reader to invest more time in communicating the most crucial public health issue of the 21st century to their patients.

Urban and rural differences in new onset type 2 diabetes: Comparisons across national and regional samples in the diabetes LEAD network.

Introduction: Geographic disparities in diabetes burden exist throughout the United States (US), with many risk factors for diabetes clustering at a community or neighborhood level. We hypothesized that the likelihood of new onset type 2 diabetes (T2D) would differ by community type in three large study samples covering the US. Research design and methods: We evaluated the likelihood of new onset T2D by a census tract-level measure of community type, a modification of RUCA designations (higher density urban, lower density urban, suburban/small town, and rural) in three longitudinal US study samples (REGARDS [REasons for Geographic and Racial Differences in Stroke] cohort, VADR [Veterans Affairs Diabetes Risk] cohort, Geisinger electronic health records) representing the CDC Diabetes LEAD (Location, Environmental Attributes, and Disparities) Network. Results: In the REGARDS sample, residing in higher density urban community types was associated with the lowest odds of new onset T2D (OR [95% CI]: 0.80 [0.66, 0.97]) compared to rural community types; in the Geisinger sample, residing in higher density urban community types was associated with the highest odds of new onset T2D (OR [95% CI]: 1.20 [1.06, 1.35]) compared to rural community types. In the VADR sample, suburban/small town community types had the lowest hazard ratios of new onset T2D (HR [95% CI]: 0.99 [0.98, 1.00]). However, in a regional stratified analysis of the VADR sample, the likelihood of new onset T2D was consistent with findings in the REGARDS and Geisinger samples, with highest likelihood of T2D in the rural South and in the higher density urban communities of the Northeast and West regions; likelihood of T2D did not differ by community type in the Midwest. Conclusions: The likelihood of new onset T2D by community type varied by region of the US. In the South, the likelihood of new onset T2D was higher among those residing in rural communities.

Urban-Rural Differences in Health Care Utilization and COVID-19 Outcomes in Patients With Type 2 Diabetes.

INTRODUCTION: Two studies in Pennsylvania aimed to determine whether community type and community socioeconomic deprivation (CSD) 1) modified associations between type 2 diabetes (hereinafter, diabetes) and COVID-19 hospitalization outcomes, and 2) influenced health care utilization among individuals with diabetes during the COVID-19 pandemic. METHODS: The hospitalization study evaluated a retrospective cohort of patients hospitalized with COVID-19 through 2020 for COVID-19 outcomes: death, intensive care unit (ICU) admission, mechanical ventilation, elevated D-dimer, and elevated troponin level. We used adjusted logistic regression models, adding interaction terms to evaluate effect modification by community type (township, borough, or city census tract) and CSD. The utilization study included patients with diabetes and a clinical encounter between 2017 and 2020. Autoregressive integrated moving average time-series models evaluated changes in weekly rates of emergency department and outpatient visits, hemoglobin A1c (HbA1c) laboratory tests, and antihyperglycemic medication orders from 2018 to 2020. RESULTS: In the hospitalization study, of 2,751 patients hospitalized for COVID-19, 1,020 had diabetes, which was associated with ICU admission and elevated troponin. Associations did not differ by community type or CSD. In the utilization study, among 93,401 patients with diabetes, utilization measures decreased in March 2020. Utilization increased in July, and then began to stabilize or decline through the end of 2020. Changes in HbA1c tests and medication order trends during the pandemic differed by community type and CSD. CONCLUSION: Diabetes was associated with selected outcomes among individuals hospitalized for COVID-19, but these did not differ by community features. Utilization trajectories among individuals with diabetes during the pandemic were influenced by community type and CSD and could be used to identify individuals at risk of gaps in diabetes care.

Geographic disparities in new onset of internalizing disorders in Pennsylvania adolescents using electronic health records.

We evaluated associations of community types and features with new-onset internalizing disorders among Pennsylvania adolescents to identify the location and scale of risk. Using a nested case-control study, we drew subjects from electronic health records 2008-2016, requiring cases (n = 7974) to have two medication orders or diagnoses indicating an internalizing disorder; controls (n = 31,895) were frequency-matched. Subjects were assigned to three community classifications: townships, boroughs, city census tracts; urbanized areas, urban clusters, rural areas; and a combination. Using logistic regression with generalized estimating equations, we found that compared to rural-townships, the highest odds were in urban cluster-city census tracts (odds ratio, 95% confidence interval: 1.78, 1.41-2.26); lowest in urbanized area-city census tracts (0.85, 0.74-0.97). Higher community socioeconomic deprivation was associated with increased odds in urban clusters (1.21, 1.00-1.48) and higher greenness with decreased odds in urban clusters (0.73, 0.62-0.86).