Unraveling the molecular relevance of brain phenotypes: A comparative analysis of null models and test statistics.

Correlating transcriptional profiles with imaging-derived phenotypes has the potential to reveal possible molecular architectures associated with cognitive functions, brain development and disorders. Competitive null models built by resampling genes and self-contained null models built by spinning brain regions, along with varying test statistics, have been used to determine the significance of transcriptional associations. However, there has been no systematic evaluation of their performance in imaging transcriptomics analyses. Here, we evaluated the performance of eight different test statistics (mean, mean absolute value, mean squared value, max mean, median, Kolmogorov-Smirnov (KS), Weighted KS and the number of significant correlations) in both competitive null models and self-contained null models. Simulated brain maps (n = 1,000) and gene sets (n = 500) were used to calculate the probability of significance (Psig) for each statistical test. Our results suggested that competitive null models may result in false positive results driven by co-expression within gene sets. Furthermore, we demonstrated that the self-contained null models may fail to account for distribution characteristics (e.g., bimodality) of correlations between all available genes and brain phenotypes, leading to false positives. These two confounding factors interacted differently with test statistics, resulting in varying outcomes. Specifically, the sign-sensitive test statistics (i.e., mean, median, KS, Weighted KS) were influenced by co-expression bias in the competitive null models, while median and sign-insensitive test statistics were sensitive to the bimodality bias in the self-contained null models. Additionally, KS-based statistics produced conservative results in the self-contained null models, which increased the risk of false negatives. Comprehensive supplementary analyses with various configurations, including realistic scenarios, supported the results. These findings suggest utilizing sign-insensitive test statistics such as mean absolute value, max mean in the competitive null models and the mean as the test statistic for the self-contained null models. Additionally, adopting the confounder-matched (e.g., coexpression-matched) null models as an alternative to standard null models can be a viable strategy. Overall, the present study offers insights into the selection of statistical tests for imaging transcriptomics studies, highlighting areas for further investigation and refinement in the evaluation of novel and commonly used tests.

Pain control is comparable between opioid versus non-opioid management after otolaryngology procedures.

Objective: The current study aims to measure patient-reported satisfaction with pain control using opioid and non-opioid medications after undergoing the following otolaryngology procedures: parathyroidectomy, thyroid lobectomy, total thyroidectomy, and bilateral tonsillectomy. Materials and Methods: A prospective cohort study was performed at an academic medical center that included a telephone questionnaire and chart review. Opioid prescriptions, usage, and patient-reported pain outcomes were recorded. Bivariate analyses were used to compare opioid and non-opioid users. Results: Of the 107 total patients undergoing otolaryngology procedures included in the study, 49 (45.8%) used an opioid for pain management postoperatively and 58 (54.2%) did not. Among the 81 patients who underwent endocrine procedures (parathyroidectomy, total thyroidectomy/lobectomy), most patients reported being "very satisfied" or "satisfied" with pain control whether they used opioids (n = 27/30, 90%) or not (n = 50/51, 98%). Of the 26 patients who underwent bilateral tonsillectomy, 19 (73%) were prescribed opioids and among these, most (n = 17/19, 89%) reported they were "very satisfied" or "satisfied" with pain control. In the non-opioid usage group, all patients (n = 7/7, 100%) reported they were "satisfied" with pain control. There was no statistically significant difference in patient-reported satisfaction with pain control between opioid and non-opioid users for any of the procedures listed. Conclusion: The results of our study suggest that patients who did not use opioids have a similar level of satisfaction with pain control compared to those using opioids after thyroid, parathyroid and tonsillectomy surgeries. Considering the magnitude of the opioid crisis, providers should reassess the need for opioid prescriptions following certain ENT procedures. Level of Evidence: IV.

Effectiveness of Closed Incision Negative Pressure Wound Therapy for Infrainguinal Bypass in the Vascular Quality Initiative.

BACKGROUND: To analyze surgical site infections (SSIs) after infrainguinal bypass for standard dressings versus closed incision negative pressure wound therapy (ciNPWT) in the Society for Vascular Surgery's Vascular Quality Initiative (VQI). METHODS: We retrospectively analyzed SSI after infrainguinal bypass procedures in the VQI from December 2019 to December 2021 comparing ciNPWT and standard dressings. The primary outcome of any superficial or deep wound infection at 30 days was analyzed in a subset of procedures with 30-day follow-up data (cohort A, n = 1,575). Secondary outcomes including in-hospital SSI, return to the operating room (OR) for infection, and length of stay (LOS) were analyzed for all procedures (cohort B, n = 9,288). Outcomes were analyzed in propensity-matched cohorts. RESULTS: Patients who received ciNPWT (n = 1,389) were more likely to be female (34% vs. 32%, P = 0.04) with a higher rate of smoking history (90% vs. 86%, P = 0.003), diabetes (54% vs. 50%, P = 0.007), obesity (34% vs. 26%, P < 0.001), prior peripheral vascular intervention (57% vs. 51%, P < 0.001), and to prosthetic conduit (55% vs. 48%, P < 0.001) compared to patients with standard dressings (n = 7,899). After propensity matching of cohort A (n = 1,256), the 30-day SSI rate was 4% (12/341) in the ciNPWT and 6% (54/896) in the standard dressing group (P = 0.07, 95% CI 0.03-1.06). In the propensity-matched in-hospital cohort B (n = 5,435), SSI was 3% (35/1,371) in the ciNPWT group and 2% (95/4,064) in the standard dressing group (P = 0.66). There was no difference in the rate of return to the OR for infection, 1% (36/4,064) vs. 1% (19/1,371) (P = 0.13) or LOS, 9.0 vs. 9.0 days (P = 0.86) for the standard versus ciNPWT groups. CONCLUSIONS: In this analysis of the VQI registry, the use of ciNPWT after infrainguinal bypass did not result in a statistically significant decrease in 30-day SSI. We recommend that surgeons consider the use of ciNPWT as part of a bundled process of care for high risk rather than all patients, as it may reduce SSI after infrainguinal bypass.

Oncologic Safety of Close Margins in Patients With Low- to Intermediate-Grade Major Salivary Gland Carcinoma.

Importance: Postoperative radiation therapy for close surgical margins in low- to intermediate-grade salivary carcinomas lacks multi-institutional supportive evidence. Objective: To evaluate the oncologic outcomes for low- and intermediate-grade salivary carcinomas with close and positive margins. Design, Setting, and Participants: The American Head and Neck Society Salivary Gland Section conducted a retrospective cohort study from 2010 to 2019 at 41 centers. Margins were classified as R0 (negative), R1 (microscopically positive), or R2 (macroscopically positive). R0 margins were subclassified into clear (>1 mm) or close (≤1 mm). Data analysis was performed from June to October 2023. Main Outcomes and Measures: Main outcomes were risk factors for local recurrence. Results: A total of 865 patients (median [IQR] age at surgery, 56 [43-66] years; 553 female individuals [64%] and 312 male individuals [36%]) were included. Of these, 801 (93%) had parotid carcinoma and 64 (7%) had submandibular gland carcinoma, and 748 (86%) had low-grade tumors and 117 (14%) had intermediate-grade tumors, with the following surgical margins: R0 in 673 (78%), R1 in 168 (19%), and R2 in 24 (3%). Close margins were found in 395 of 499 patients with R0 margins (79%), for whom margin distances were measured. A total of 305 patients (35%) underwent postoperative radiation therapy. Of all 865 patients, 35 (4%) had local recurrence with a median (IQR) follow-up of 35.3 (13.9-59.1) months. In patients with close margins as the sole risk factor for recurrence, the local recurrence rates were similar between those who underwent postoperative radiation therapy (0 of 46) or observation (4 of 165 [2%]). Patients with clear margins (n = 104) had no recurrences. The local recurrence rate in patients with R1 or R2 margins was better in those irradiated (2 of 128 [2%]) compared to observed (13 of 64 [20%]) (hazard ratio [HR], 0.05; 95% CI, 0.01-0.24). Multivariable analysis for local recurrence found the following independent factors: age at diagnosis (HR for a 10-year increase in age, 1.33; 95% CI, 1.06-1.67), R1 vs R0 (HR, 5.21; 95% CI, 2.58-10.54), lymphovascular invasion (HR, 4.47; 95% CI, 1.43-13.99), and postoperative radiation therapy (HR, 0.10; 95% CI, 0.04-0.29). The 3-year local recurrence-free survivals for the study population were 96% vs 97% in the close margin group. Conclusions and Relevance: In this cohort study of patients with low- and intermediate-grade major salivary gland carcinoma, postoperative radiation therapy for positive margins was associated with decreased risk of local recurrence. In isolation from other risk factors for local recurrence, select patients with close surgical margins (≤1 mm) may safely be considered for observation.

Impact of the COVID-19 Pandemic on Infective Endocarditis Management and Outcomes: Analysis of a National Clinical Database.

COVID-19 has widely affected health care delivery, but its impact on the management of infective endocarditis (IE), including valve surgery, is uncertain. We compared the national trends in admissions, demographics, and outcomes of IE before and after COVID-19 onset, using a national sample of IE admissions between 2016 and 2022 from the Vizient Clinical Database. The pre-COVID-19 and post-COVID-19 time periods were separated by the start of the second quarter of 2020, the time during which the COVID-19 pandemic was declared. For all admissions and for admissions involving valve surgery, pre-COVID-19 versus post-COVID-19 baseline characteristics and outcomes were compared using 2-sample t tests or chi-square tests. Propensity score-matched cohorts were similarly compared. Before COVID-19, there were 82,867 overall and 11,337 valve-related surgical admissions, and after COVID-19, there were 45,672 overall and 6,322 valve-related surgical admissions. In the matched analysis for all admissions, the in-hospital mortality increased from 11.4% to 12.4% after COVID-19 onset (p <0.001); in-hospital stroke (4.9% vs 6.0%, p <0.001), myocardial infarction (1.3% vs 1.4%, p = 0.03), and aspiration pneumonia (1.8% vs 2.4%, p <0.001) also increased, whereas other complications remained stable. In the matched analysis of surgical admissions, there was decreased in-hospital mortality (7.7% vs 6.7%, p = 0.03) and intensive care unit stay (8.5 ± 12.5 vs 8.0 ± 12.6 days, p = 0.04); other outcomes remained stable. In conclusion, patients admitted with IE after COVID-19 were more medically complex with worsened outcomes and mortality, whereas patients who underwent valve surgery had stable outcomes and improved mortality despite the pandemic.

A Cluster Randomized Trial of Primary Care Practice Redesign to Integrate Behavioral Health for Those Who Need It Most: Patients With Multiple Chronic Conditions.

PURPOSE: Patient outcomes can improve when primary care and behavioral health providers use a collaborative system of care, but integrating these services is difficult. We tested the effectiveness of a practice intervention for improving patient outcomes by enhancing integrated behavioral health (IBH) activities. METHODS: We conducted a pragmatic, cluster randomized controlled trial. The intervention combined practice redesign, quality improvement coaching, provider and staff education, and collaborative learning. At baseline and 2 years, staff at 42 primary care practices completed the Practice Integration Profile (PIP) as a measure of IBH. Adult patients with multiple chronic medical and behavioral conditions completed the Patient-Reported Outcomes Measurement Information System (PROMIS-29) survey. Primary outcomes were the change in 8 PROMIS-29 domain scores. Secondary outcomes included change in level of integration. RESULTS: Intervention assignment had no effect on change in outcomes reported by 2,426 patients who completed both baseline and 2-year surveys. Practices assigned to the intervention improved PIP workflow scores but not PIP total scores. Baseline PIP total score was significantly associated with patient-reported function, independent of intervention. Active practices that completed intervention workbooks (n = 13) improved patient-reported outcomes and practice integration (P ≤ .05) compared with other active practices (n = 7). CONCLUSION: Intervention assignment had no effect on change in patient outcomes; however, we did observe improved patient outcomes among practices that entered the study with greater IBH. We also observed more improvement of integration and patient outcomes among active practices that completed the intervention compared to active practices that did not. Additional research is needed to understand how implementation efforts to enhance IBH can best reach patients.

Cardiac catheterization, coronary intervention, and wait times for transcatheter aortic valve replacement.

OBJECTIVES: Prolonged wait times for transcatheter aortic valve replacement (TAVR) are associated with increased morbidity and mortality. The incidence and predictors of short TAVR wait times (STWT: defined as ≤ 30 days from referral to TAVR procedure) have not been defined. This study examined the impact of clinical characteristics, demographics, and pre-TAVR cardiac catheterization on wait times for TAVR. METHODS: This was a retrospective observational analysis of 831 patients with severe aortic stenosis undergoing TAVR from 2019 to mid-2022 at the University of Vermont Medical Center. Demographics, timing of treatment [stratified by COVID-19 onset (1 March 2020)], TAVR center travel distance, baseline clinical factors, and process-related variables were analyzed to determine univariate STWT predictors (P < 0.10). Multivariable analysis was performed to determine independent STWT predictors. RESULTS: Approximately 50% of TAVR patients in this study achieved a STWT. The proportion of patients with STWT was higher (54.7% vs. 45.2%; P = 0.008) after the onset of COVID-19 pandemic. STWT was not related to travel distance (P = 0.61). Patients with left ventricular ejection fraction (LVEF) > 60% were less likely to achieve STWT compared to patients with LVEF < 40% (OR 0.45, P = 0.003). Patients who required catheterization or percutaneous coronary intervention (PCI) before TAVR were significantly less likely to achieve STWT (OR 0.65, P = 0.01). CONCLUSION: TAVR wait times were not affected by the COVID-19 pandemic or single rural TAVR center travel distance. Sicker patients were more likely to achieve STWT while catheterization/PCI before TAVR was associated with longer wait times.

Lipoprotein(a) and risk of cognitive impairment in Black and White Americans: the Reasons for Geographic and Racial Differences in Stroke cohort.

Background: Cognitive impairment has a substantial vascular etiology. Higher lipoprotein(a) [Lp(a)] is associated with cardiovascular disease risk, but its association with cognitive function is uncertain. We hypothesized that Lp(a) is a risk factor for cognitive impairment, a relationship that would be modified by race and sex. Objectives: To study the association of Lp(a) with cognitive impairment in a biracial cohort. Methods: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) study recruited 30,239 Black and White Americans aged >45 years from 2003 to 2007. After 3.4 years, among participants with normal baseline cognition, baseline Lp(a) was measured in 434 cases of incident cognitive impairment and 557 controls. Cognitive impairment was defined as scores below the sixth percentile based on age, sex, race, and education norms on 2 or 3 components of a 3-test battery administered every 2 years. Results: Median Lp(a) was higher in Black than in White individuals. Among Black participants, the adjusted odds ratio (OR) of cognitive impairment per SD higher increment Lp(a) was 1.39 (95% CI: 1.05, 1.84). The OR in White participants was 1.03 (95% CI: 0.87, 1.21; P for race difference = .03). The relationship of Lp(a) with cognitive trajectory differed by sex and race. Elevated Lp(a) was associated with worse baseline memory in Black men and a steeper trajectory of verbal fluency decline in Black men than in White men and women. Conclusion: Higher Lp(a) was associated with increased risk of cognitive impairment in Black but not White individuals. Future studies should evaluate the biological and social mechanisms through which race and Lp(a) interact to increase risk of cognitive impairment.

Nonalcoholic fatty liver disease and cognitive impairment: A prospective cohort study.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is prevalent and may affect cognitive function. We studied associations of NAFLD with risk of cognitive impairment. Secondarily we evaluated liver biomarkers (alanine aminotransferase (ALT), aspartate aminotransferase (AST), their ratio, and gamma-glutamyl transpeptidase). METHODS: In a prospective cohort study, the REasons for Geographic and Racial Differences in Stroke, among 30,239 black and white adults aged ≥45,495 cases of incident cognitive impairment were identified over 3.4 years follow up. Cognitive impairment was identified as new impairment in two of three cognitive tests administered every two years during follow up; word list learning and recall, and verbal fluency. 587 controls were selected from an age, race, sex-stratified sample of the cohort. The fatty liver index was used to define baseline NAFLD. Liver biomarkers were measured using baseline blood samples. RESULTS: NAFLD at baseline was associated with a 2.01-fold increased risk of incident cognitive impairment in a minimally adjusted model (95% CI 1.42, 2.85). The association was largest in those aged 45-65 (p interaction by age = 0.03), with the risk 2.95-fold increased (95% CI 1.05, 8.34) adjusting for cardiovascular, stroke and metabolic risk factors. Liver biomarkers were not associated with cognitive impairment, except AST/ALT >2, with an adjusted OR 1.86 (95% CI 0.81, 4.25) that did not differ by age. CONCLUSIONS: A laboratory-based estimate of NAFLD was associated with development of cognitive impairment, particularly in mid-life, with a tripling in risk. Given its high prevalence, NAFLD may be a major reversible determinant of cognitive health.

Integration of palliative care consultation into the management of patients with chronic limb-threatening ischemia.

OBJECTIVE: We assessed the feasibility of integrating palliative care consultation into the routine management of patients with chronic limb-threatening ischemia (CLTI). Additionally, we sought to describe patient-reported outcomes from the palliative care and vascular literature in patients with CLTI receiving a palliative care consultation at our institution. METHODS: This was a single-institution, prospective, observational study that aimed to assess feasibility of incorporating palliative care consultation into the management of patients admitted to our tertiary academic medical center with CLTI by looking at utilization of palliative care before and after implementation of a protocol-based palliative care referral system. A survey comprised of patient-reported outcomes from the palliative care literature was administered to patients before and after palliative consultation. Length of stay and mortality were compared between our study cohort and a historic cohort of patients admitted with CLTI. RESULTS: Over a 14-month enrollment period, 44% of patients (n = 39) with CLTI (rest pain, 36%; tissue loss, 64%) admitted to the vascular service received palliative care consultation, compared with 5% of patients (n = 4) who would have met criteria over the preceding 14 months before our protocol was instituted. The mean age was 69 years, 23% were female, 92% were white, and 49% were able to ambulate independently. Revascularization included bypass (46%), peripheral vascular intervention (23%), and femoral endarterectomy (21%). Additional procedures included minor amputation or wound debridement (26%) and major amputation (15%). No patients received medical management alone. After receiving palliative care consultation, patients reported experiencing less emotional distress than before consultation (P = .03). They also reported being less bothered by uncertainty regarding what to expect from the course of their illness (P = .002). Fewer patients reported being unsure of the purpose of their medical care after palliative care consultation (8%) vs before (18%), although this was not statistically significant (P = .10). Median length of stay was longer in the study group compared with the historic cohort (8 vs 7 days; P = .02). There was no difference in 30-day mortality (3% vs 8%; P = .42) between the study group and the historic cohort (n = 77). CONCLUSIONS: Integrating inpatient palliative care consultation into the routine management of patients with CLTI is feasible and may improve emotional domains of health-related quality of life. This study laid the foundation for future studies on longer term outcomes of patients with CLTI undergoing palliative care consultation as well as the benefit of outpatient palliative care consultation in patients with CLTI.

Opioid Use and Associated Patient Satisfaction With Pain Control After Endoscopic Surgery and Robotic-Assisted Radical Prostatectomy.

OBJECTIVE: To evaluate patient reported measures in patients undergoing endourologic procedures and robotic assisted radical prostatectomy (RARP) to demonstrate the efficacy of non-opioid postoperative pain management strategies. MATERIALS AND METHODS: A prospective cohort study performed at an academic medical center included a patient telephone questionnaire and chart review. Opioid prescriptions, opioid use, and patient reported outcomes were recorded. Bivariate analyses were used to compare patients who did and did not use opioids in the RARP cohort while overall trends were reported for the endourologic procedures. RESULTS: Of the 68 patients undergoing endoscopic intervention, 14 (21%) were prescribed an opioid and 6 (9%) reported any opioid use. 58 (85%) reported their pain was very well or well controlled while 9 reported their pain was poorly controlled. 59 (87%) were satisfied or very satisfied with their pain control. Fifty-three (93%) of the 57 patients undergoing RARP received an opioid prescription and only 23 reported any opioid use. All but 1 patient reported that their pain was well or very well controlled and almost all (54) of the patients were satisfied with their level of pain control. 36 (63%) reported their pain was less than expected while only 7 (12%) reported it was more than expected. CONCLUSION: Most patients undergoing endourologic procedures do not use postoperative opioids and report favorable outcomes regarding their pain control. Similarly, after RARP, most patients do not use opioids even when they are prescribed and are satisfied with their pain control.

Recalibrating single-study effect sizes using hierarchical Bayesian models.

Introduction: There are growing concerns about commonly inflated effect sizes in small neuroimaging studies, yet no study has addressed recalibrating effect size estimates for small samples. To tackle this issue, we propose a hierarchical Bayesian model to adjust the magnitude of single-study effect sizes while incorporating a tailored estimation of sampling variance. Methods: We estimated the effect sizes of case-control differences on brain structural features between individuals who were dependent on alcohol, nicotine, cocaine, methamphetamine, or cannabis and non-dependent participants for 21 individual studies (Total cases: 903; Total controls: 996). Then, the study-specific effect sizes were modeled using a hierarchical Bayesian approach in which the parameters of the study-specific effect size distributions were sampled from a higher-order overarching distribution. The posterior distribution of the overarching and study-specific parameters was approximated using the Gibbs sampling method. Results: The results showed shrinkage of the posterior distribution of the study-specific estimates toward the overarching estimates given the original effect sizes observed in individual studies. Differences between the original effect sizes (i.e., Cohen's d) and the point estimate of the posterior distribution ranged from 0 to 0.97. The magnitude of adjustment was negatively correlated with the sample size (r = -0.27, p < 0.001) and positively correlated with empirically estimated sampling variance (r = 0.40, p < 0.001), suggesting studies with smaller samples and larger sampling variance tended to have greater adjustments. Discussion: Our findings demonstrate the utility of the hierarchical Bayesian model in recalibrating single-study effect sizes using information from similar studies. This suggests that Bayesian utilization of existing knowledge can be an effective alternative approach to improve the effect size estimation in individual studies, particularly for those with smaller samples.

Intraclass Correlation and Variance in the Characteristics of Primary Care Patients Managing Chronic Medical and Behavioral Conditions.

Background To avoid statistical errors, researchers who recruit patients from selected medical practices and analyze them at the individual level need to account for the clustered nature of their sample. This is most often done using the intraclass correlation coefficients (ICCs), a measure of how strongly subjects recruited from the same cluster (in this case patients from a clinic) resemble each other. Aims The aim is to support the design of cluster-randomized studies by supplying estimates of variance and ICC of various measures using a population of patients from multiple primary care clinics. Materials and methods ICCs were extracted from a large cluster-randomized pragmatic clinical trial of adult primary care patients managing multiple chronic conditions, the Integrating Behavioral Health and Primary Care study (IBH-PC). IBH-PC collected demographics and patient-reported health outcomes on over 3,000 adults from 44 primary care practices in 13 states across the US. We present estimates of the standard deviation and ICC for gender, race, ethnicity, marital status, employment, income, education, social determinants of health, PROMIS-29 functional status, Duke Activity Status Index (DASI), nine-item Patient Health Questionnaire (PHQ-9) depression score, Generalized Anxiety Disorder (GAD-7) anxiety score, Asthma Symptom Utility Index, restricted activity days, medication adherence, health care visits in the past month, emergency room visits in the past year, hospital days in the past year, perception of quality and patient-centeredness of care, alcoholic drinks per month, and the GAIN substance use disorder screener. Results ICCs varied broadly with the highest values found for race and income and the lowest for short-term estimates of the GAIN. Conclusions These values can be used to inform the design, especially power estimates and sample size requirements, of future studies.

Evaluating the Rising Incidence of Thyroid Cancer and Thyroid Nodule Detection Modes: A Multinational, Multi-institutional Analysis.

Importance: There is epidemiologic evidence that the increasing incidence of thyroid cancer is associated with subclinical disease detection. Evidence for a true increase in thyroid cancer incidence has also been identified. However, a true increase in disease would likely be heralded by an increased incidence of thyroid-referable symptoms in patients presenting with disease. Objectives: To evaluate whether modes of detection (MODs) used to identify thyroid nodules for surgical removal have changed compared with historic data and to determine if MODs vary by geographic location. Design, Setting, and Participants: This was a retrospective analysis of pathology and medical records of 1328 patients who underwent thyroid-directed surgery in 16 centers in 4 countries: 4 centers in Canada, 1 in Denmark, 1 in South Africa, and 12 in the US. The participants were the first 100 patients (or the largest number available) at each center who had thyroid surgery in 2019. The MOD of the thyroid finding that required surgery was classified using an updated version of a previously validated tool as endocrine condition, symptomatic thyroid, surveillance, or without thyroid-referable symptoms (asymptomatic). If asymptomatic, the MOD was further classified as clinician screening examination, patient-requested screening, radiologic serendipity, or diagnostic cascade. Main Outcomes and Measures: The MOD of thyroid nodules that were surgically removed, by geographic variation; and the proportion and size of thyroid cancers discovered in patients without thyroid-referable symptoms compared with symptomatic detection. Data analyses were performed from April 2021 to February 2022. Results: Of the 1328 patients (mean [SD] age, 52 [15] years; 993 [75%] women; race/ethnicity data were not collected) who underwent thyroid surgery that met inclusion criteria, 34% (448) of the surgeries were for patients with thyroid-related symptoms, 41% (542) for thyroid findings discovered without thyroid-referable symptoms, 14% (184) for endocrine conditions, and 12% (154) for nodules with original MOD unknown (under surveillance). Cancer was detected in 613 (46%) patients; of these, 30% (183 patients) were symptomatic and 51% (310 patients) had no thyroid-referable symptoms. The mean (SD) size of the cancers identified in the symptomatic group was 3.2 (2.1) cm (median [range] cm, 2.6 [0.2-10.5]; 95% CI, 2.91-3.52) and in the asymptomatic group, 2.1 (1.4) cm (median [range] cm, 1.7 [0.05-8.8]; 95% CI, 1.92-2.23). The MOD patterns were significantly different among all participating countries. Conclusions and Relevance: This retrospective analysis found that most thyroid cancers were discovered in patients who had no thyroid-referable symptoms; on average, these cancers were smaller than symptomatic thyroid cancers. Still, some asymptomatic cancers were large, consistent with historic data. The substantial difference in MOD patterns among the 4 countries suggests extensive variations in practice.

Intranasal Fentanyl for On-the-Hill Analgesia by Ski Patrol.

INTRODUCTION: Intranasal fentanyl offers a means for safe and effective pain management in austere environments. Prehospital analgesia traditionally involves intravenous or intramuscular medication. However, for wilderness rescuers, these methods are often impractical. METHODS: We conducted a retrospective review of health records to evaluate the safety and efficacy of intranasal fentanyl administered by EMT-Basic certified ski patrollers. Our primary aim was to measure the reduction in initial pain scores to subsequent measurements at 5, 10, and 15 min using the pain numeric rating scale (0-10). Clinically significant reduction in severe pain has been established as ≥1.8 points. We used paired t-tests and multilevel modeling to measure statistical significance and potential interactions and reviewed patient charts for adverse events, including respiratory depression or the use of naloxone. RESULTS: We compiled the results from the winter seasons for 2007 through 2012 and 2016 through 2020. A total of 247 patients were included. The initial pain score was 8.6±1.5 (mean±SD). The decrease in pain scores from 0 to 5, 10, and 15 min, respectively, was -1.8, -2.4, and -2.9 (P<0.0001), which demonstrated a clinically and statistically significant decrease in pain scores. There were no adverse events. CONCLUSIONS: Traditional standard of care analgesics are invasive, elongate scene times, and increase the risk of environmental exposure and provider needlestick. Intranasal fentanyl offers a safe, noninvasive, and rapid analgesia that is well-suited for austere winter environments, such as those encountered at ski resorts. This study demonstrates the safety and efficacy of the administration of intranasal fentanyl by EMT-Basic certified providers.

Patient Factors Associated with High Opioid Consumption after Common Surgical Procedures Following State-Mandated Opioid Prescription Regulations.

BACKGROUND: State regulations have decreased prescribed opioids with more than 25% of patients abstaining from opioids. Despite this, 2 distinct populations of patients exist who consume "high" or "low" amounts of opioids. The aim of this study was to identify factors associated with postoperative opioid use after common surgical procedures and develop an opioid risk score. STUDY DESIGN: Patients undergoing 35 surgical procedures from 7 surgical specialties were identified at a 620-bed tertiary care academic center and surveyed 1 week after discharge regarding opioid use and adequacy of analgesia. Electronic medical record data were used to characterize postdischarge opioids, complications, demographics, medical history, and social factors. High opioid use was defined as >75th percentile morphine milligram equivalents for each procedure. An opioid risk score was calculated from factors associated with opioid use identified by backward multivariate logistic regression analysis. RESULTS: A total of 1,185 patients were enrolled between September 2017 and February 2019. Bivariate analyses revealed patient factors associated with opioid use including earlier substance use (p < 0.001), depression (p = 0.003), anxiety (p < 0.001), asthma (p = 0.006), obesity (p = 0.03), migraine (p = 0.004), opioid use in the 7 days before surgery (p < 0.001), and 31 Clinical Classifications Software Refined classifications (p < 0.05). Significant multivariates included: insurance (p = 0.005), employment status (p = 0.005), earlier opioid use (odds ratio [OR] 2.38 [95% CI 1.21 to 4.68], p = 0.01), coronary artery disease (OR 0.38 [95% CI 0.16 to 0.86], p = 0.02), acute pulmonary embolism (OR 9.81 [95% CI 3.01 to 32.04], p < 0.001), benign breast conditions (OR 3.42 [95% CI 1.76 to 6.64], p < 0.001), opioid-related disorders (OR 6.67 [95% CI 1.87 to 23.75], p = 0.003), mental and substance use disorders (OR 3.80 [95% CI 1.47 to 9.83], p = 0.006), headache (OR 1.82 [95% CI 1.24 to 2.67], p = 0.002), and previous cesarean section (OR 5.10 [95% CI 1.33 to 19.56], p = 0.02). An opioid risk score base was developed with an area under the curve of 0.696 for the prediction of high opioid use. CONCLUSIONS: Preoperative patient characteristics associated with high opioid use postoperatively were identified and an opioid risk score was derived. Identification of patients with a higher need for opioids presents an opportunity for improved preoperative interventions, the use of nonopioid analgesic therapies, and alternative therapies.

Association of Urine Findings with Metabolic Syndrome Traits in a Population of Patients with Nephrolithiasis.

Background: The odds of nephrolithiasis increase with more metabolic syndrome (MetS) traits. We evaluated associations of metabolic and dietary factors from urine studies and stone composition with MetS traits in a large cohort of stone-forming patients. Methods: Patients >18 years old who were evaluated for stones with 24-hour urine collections between July 2009 and December 2018 had their records reviewed retrospectively. Patient factors, laboratory values, and diagnoses were identified within 6 months of urine collection and stone composition within 1 year. Four groups with none, one, two, and three or four MetS traits (hypertension, obesity, dyslipidemia, and diabetes) were evaluated. Trends across groups were tested using linear contrasts in analysis of variance and analysis of covariance. Results: A total of 1473 patients met the inclusion criteria (835 with stone composition). MetS groups were 684 with no traits, 425 with one trait, 211 with two traits, and 153 with three or four traits. There were no differences among groups for urine volume, calcium, or ammonium excretion. There was a significant trend (P<0.001) for more MetS traits being associated with decreasing urine pH, increasing age, calculated dietary protein, urine uric acid (UA), oxalate, citrate, titratable acid phosphate, net acid excretion, and UA supersaturation. The ratio of ammonium to net acid excretion did not differ among the groups. After adjustment for protein intake, the fall in urine pH remained strong, while the upward trend in acid excretion was lost. Calcium oxalate stones were most common, but there was a trend for more UA (P<0.001) and fewer calcium phosphate (P=0.09) and calcium oxalate stones (P=0.01) with more MetS traits. Conclusions: Stone-forming patients with MetS have a defined pattern of metabolic and dietary risk factors that contribute to an increased risk of stone formation, including higher acid excretion, largely the result of greater protein intake, and lower urine pH.

Evaluating diversity in neurosurgery through the use of a multidimensional statistical model: a pilot study.

OBJECTIVE: There is a growing body of evidence demonstrating the benefits of diversity across many domains. However, neurosurgery consistently lags most of medicine in many aspects of diversity. Any inability to make progress in this arena is likely due to the multifactorial and complex nature of the issue, which makes it difficult to meaningfully measure and track diversity within the workforce. The goal of this pilot study was to assess the utilization of a multidimensional statistical model to quantify and assess diversity within neurosurgery. The authors sought to 1) assess the diversity of neurosurgery residents using Simpson's Diversity Index and Sullivan's Composite Diversity Index (CDI) and 2) determine if a medical school's intrinsic academic opportunities and resources, indicated by US News & World Report's (USNWR's) best research medical schools ranking, are related to the number of neurosurgery residents produced per medical school. METHODS: A cross-sectional study of all neurosurgery residents (projected graduation years 2020-2026) and 1st-year medical students (matriculating years 2016-2019) was undertaken. Biographical diversity data (gender and matriculation data) were collected from institutional websites between December 2019 and June 2020. The CDI expresses the diversity of a given population by representing the effective proportion of categories present across all diversity attributes and was calculated for neurosurgery residents and medical students. Statistical results are reported as the median and interquartile range. RESULTS: Neurosurgery residency program CDI (0.21, IQR 0.16-0.25) was significantly less (p < 0.001) than medical school CDI (0.42, 0.37-0.48). There was no significant difference in CDI between top-40 and non-top 40 Doximity ranked research output neurosurgery residency programs (p = 0.35) or between top-40 and non-top 40 USNWR ranked research medical schools (p = 0.11). Over a 7-year period, top-40 ranked research medical schools produced significantly more (p < 0.001) neurosurgery residents (11.9, IQR 7.1-18.9) than the non-top 40 ranked research medical schools (5.6, IQR 2.6-8.5). CONCLUSIONS: The authors demonstrated the feasibility of using a multidimensional statistical model as a measure to understand the complex issues of diversity. Their preliminary data suggested that neurosurgery's challenge in achieving the desired diversity relates to uneven attraction and/or recruitment across an increasingly diverse medical student body. In recent years, neurosurgery has made great progress in the arena of diversity and has shown a strong desire to do more. Utilization of these diversity measures will help the neurosurgery field to monitor progress along this valuable journey.