Stereotactic radiosurgery for nonfunctioning pituitary tumor: A multicenter study of new pituitary hormone deficiency.

BACKGROUND: Stereotactic radiosurgery (SRS) is used to treat recurrent or residual nonfunctioning pituitary neuroendocrine tumors (NFPA). The objective of the study was to assess imaging and development of new pituitary hormone deficiency. METHODS: Patients treated with single-session SRS for a NFPA were included in this retrospective, multicenter study. Tumor control and new pituitary dysfunction were evaluated using Cox analysis and Kaplan-Meier curves. RESULTS: A total of 869 patients (male 476 [54.8%], median age at SRS 52.5 years [Interquartile range (IQR): 18.9]) were treated using a median margin dose of 14Gy (IQR: 4) for a median tumor volume of 3.4 cc (IQR: 4.3). With a median radiological follow-up of 3.7 years (IQR: 4.8), volumetric tumor reduction occurred in 451 patients (51.9%), stability in 364 (41.9%) and 54 patients (6.2%) showed tumor progression.The probability of tumor control was 95.5% (95% Confidence Interval [CI]: 93.8-97.3) and 88.8% (95%CI: 85.2-92.5) at 5 and 10 years, respectively. A margin dose >14 Gy was associated with tumor control (Hazard Ratio [HR]:0.33, 95% CI: 0.18-0.60, P < 0.001). The probability of new hypopituitarism was 9.9% (95% CI: 7.3-12.5) and 15.3% (95% CI: 11-19.4) at 5 and 10 years, respectively. A maximum point dose >10 Gy in the pituitary stalk was associated with new pituitary hormone deficiency (HR: 3.47, 95% CI: 1.95-6.19). The cumulative probability of new cortisol, thyroid, gonadotroph, and growth hormone deficiency was 8% (95% CI: 3.9-11.9), 8.3% (95% CI: 3.9-12.5), 3.5% (95% CI: 1.7-5.2), and 4.7% (95% CI: 1.9-7.4), respectively at 10 years. CONCLUSIONS: SRS provides long-term tumor control with a 15.3% risk of hypopituitarism at 10 years.

Silent Corticotroph Staining Pituitary Neuroendocrine Tumors: Prognostic Significance in Radiosurgery.

BACKGROUND AND OBJECTIVES: There is conflicting evidence on the significance of adrenocorticotrophic hormone (ACTH) staining in the prognosis of nonfunctioning pituitary neuroendocrine tumors (NFpitNETs). The objective of this study was to define the effect of ACTH immunostaining on clinical and radiographic outcomes of stereotactic radiosurgery (SRS) for NFpitNETs. METHODS: This retrospective, multicenter study included patients managed with SRS for NFpitNET residuals. The patients were divided into 2 cohorts: (1) silent corticotroph (SC) for NFpitNETs with positive ACTH immunostaining and (2) non-SC NFpitNETs. Rates of local tumor control and the incidence of post-treatment pituitary and neurological dysfunction were documented. Factors associated with radiological and clinical outcomes were also analyzed. RESULTS: The cohort included 535 patients from 14 centers with 84 (15.7%) patients harboring silent corticotroph NFpitNETs (SCs). At last follow-up, local tumor progression occurred in 11.9% of patients in the SC compared with 8.1% of patients in the non-SC cohort (P = .27). No statistically significant difference was noted in new-onset hypopituitarism rates (10.7% vs 15.4%, P = .25) or visual deficits (3.6% vs 1.1%, P = .088) between the 2 cohorts at last follow-up. When controlling for residual tumor volume, maximum dose, and patient age and sex, positive ACTH immunostaining did not have a significant correlation with local tumor progression (hazard ratio = 1.69, 95% CI = 0.8-3.61, P = .17). CONCLUSION: In contemporary radiosurgical practice with a single fraction dose of 8-25 Gy (median 15 Gy), ACTH immunostaining in NFpitNETs did not appear to confer a significantly reduced rate of local tumor control after SRS.

Postoperative Serum Cortisol and Cushing Disease Recurrence in Patients With Corticotroph Adenomas.

CONTEXT: In Cushing disease, the association between the rate of serum cortisol decline and recurrent disease after corticotroph adenoma removal has not been adequately characterized. OBJECTIVE: To analyze postoperative serum cortisol and recurrence rates in Cushing disease. METHODS: Patients with Cushing disease and pathology-confirmed corticotroph adenoma were retrospectively studied. Cortisol halving time was estimated using exponential decay modeling. Halving time, first postoperative cortisol, and nadir cortisol values were collected using immediate postoperative inpatient laboratory data. Recurrence and time-to-recurrence were estimated and compared among cortisol variables. RESULTS: A total of 320 patients met inclusion/exclusion criteria for final analysis, and 26 of those patients developed recurrent disease. Median follow-up time was 25 months (95% CI, 19-28 months), and 62 patients had ≥ 5 years follow-up time. Higher first postoperative cortisol and higher nadir were associated with increased risk of recurrence. Patients who had a first postoperative cortisol ≥ 50 µg/dL were 4.1 times more likely to recur than those with a first postoperative cortisol < 50 µg/dL (HR 4.1, 1.8-9.2; P = .0003). Halving time was not associated with recurrence (HR 1.7, 0.8-3.8, P = .18). Patients with a nadir cortisol ≥2 µg/dL were 6.6 times more likely to recur than those with a nadir cortisol of < 2 µg/dL (HR 6.6, 2.6-16.6, P < .0001). CONCLUSION: Postoperative nadir serum cortisol is the most important cortisol variable associated with recurrence and time-to-recurrence. Compared to first postoperative cortisol and cortisol halving time, a nadir < 2 µg/dL showed the strongest association with long-term remission and typically occurs within the first 24 to 48 hours after surgery.

Risk Factors for Bloodstream Infections Due to ESBL-Producing Escherichia coli, Klebsiella spp., and Proteus mirabilis.

(1) Background: Risk factors for extended-spectrum beta-lactamase (ESBL) infections could vary geographically. The purpose of this study was to identify local risk factors for ESBL production in patients with Gram-negative bacteremia. (2) Methods: This retrospective observational study included adult patients admitted from January 2019 to July 2021 and had positive blood cultures for E. coli, K. pneumoniae, K. oxytoca, and P. mirabilis. Patients with ESBL infection were matched to a non-ESBL-producing infection with the same organism. (3) Results: A total of 150 patients were included: 50 in the ESBL group and 100 in the non-ESBL group. Patients in the ESBL group had a longer length of stay (11 vs. 7 days, p < 0.001), but not increased mortality (14% vs. 15%, p = 0.87) Multivariate analysis identified the receipt of >1 antibiotic in the last 90 days as a risk factor for ESBL infection (OR = 3.448, 95% CI = 1.494-7.957; p = 0.004); (4) Conclusions: Recent antimicrobial use was identified as an independent risk factors for ESBL-producing Enterobacterales infections. Knowledge of this risk may improve empirical therapy and reduce inappropriate use.

Effects of Neuroanatomic Structural Distances on Pituitary Function After Stereotactic Radiosurgery: A Multicenter Study.

BACKGROUND: Delayed hypopituitarism is the most common complication after stereotactic radiosurgery (SRS) for pituitary adenomas. OBJECTIVE: To investigate the relationship between neuroanatomic structure distances from the radiation target and anterior pituitary function preservation after SRS through multicenter study. METHODS: We retrospectively reviewed the International Radiosurgery Research Foundation database from January 2002 to December 2021 for adult patients undergoing SRS for pituitary adenomas with >6 months of follow-up. Distances between centers or edges of hypothalamic-pituitary axis structures and SRS target volumes were measured using MRI. The primary outcome was anterior pituitary function preservation. Predictors were analyzed using multivariable logistic regression and area under the receiver operating curve (AUROC) curve analyses. RESULTS: Four hundred eighty-seven patients were categorized by preservation (n = 384) and no preservation (n = 103) of anterior pituitary function. The mean margin dose was 19.1(6.2) Gy. Larger distance from the center of the stalk to the tumor margin isodose was a positive predictor (adjusted odds ratio [aOR] = 1.162 [1.046-1.291], P = .005), while pre-SRS hypopituitarism (aOR = 0.646 [0.405-1.031], P = .067) and larger treatment volume (aOR = 0.965 [0.929-1.002], P = .061) were near negative predictors of the primary outcome. An interaction between the treatment volume and center stalk to margin isodose distance was found (aOR = 0.980 [0.961-0.999], P = .045). Center stalk to margin isodose distance had an AUROC of 0.620 (0.557-0.693), at 3.95-mm distance. For patients with treatment volumes of <2.34 mL, center stalk to margin isodose distance had an AUROC of 0.719 (0.614-0.823), at 2.95-mm distance. CONCLUSION: Achieving a distance between the center of the pituitary stalk and the tumor margin isodose ≥3.95 mm predicted anterior pituitary function preservation. For smaller treatment volumes <2.34 mL, the optimal distance was ≥2.95 mm. This may be modifiable during trans-sphenoidal resection to preserve pituitary function.

Responding to Repeated Disasters: Time to Recovery in Public Health Workers.

OBJECTIVE: In times of repeated disaster events, including natural disasters and pandemics, public health workers must recover rapidly to respond to subsequent events. Understanding predictors of time to recovery and developing predictive models of time to recovery can aid planning and management. METHODS: We examined 681 public health workers (21-72 y, M(standard deviation [SD]) = 48.25(10.15); 79% female) 1 mo before (T1) and 9 mo after (T2) the 2005 hurricane season. Demographics, trauma history, social support, time to recover from previous hurricane season, and predisaster work productivity were assessed at T1. T2 assessed previous disaster work, initial emotional response, and personal hurricane injury/damage. The primary outcome was time to recover from the most recent hurricane event. RESULTS: Multivariate analyses found that less support (T1; odds ratio [OR] = .74[95% confidence interval [CI] = .60-.92]), longer previous recovery time (T1; OR = 5.22[95%CI = 3.01-9.08]), lower predisaster work productivity (T1; OR = 1.98[95%CI = 1.08-3.61]), disaster-related personal injury/damage (T2; OR = 3.08[95%CI = 1.70-5.58]), and initial emotional response (T2; OR = 1.71[95%CI = 1.34-2.19]) were associated with longer recovery time (T2). CONCLUSIONS: Recovery time was adversely affected in disaster responders with a history of longer recovery time, personal injury/damage, lower work productivity following prior hurricanes, and initial emotional response, whereas responders with social support had shorter recovery time. Predictors of recovery time should be a focus for disaster preparedness planners.

Effect of distance from target on hypopituitarism after stereotactic radiosurgery for pituitary adenomas.

INTRODUCTION: Delayed hypopituitarism is the most common complication after stereotactic radiosurgery (SRS) for pituitary adenomas. The aim of this study was to investigate the relationship between the distance from the hypothalamic-pituitary axis to the treatment target and anterior pituitary function preservation after SRS. METHODS: Between 2007 and 2020, consecutive adult patients who underwent single-session SRS for non-functioning or hormone-secreting pituitary adenomas with ≥ 6 months of follow-up were included. Distance measurements between hypothalamic-pituitary axis structures and the SRS target volume were quantified on MRI. The primary outcome was anterior pituitary function preservation. Outcomes were compared using multivariable regression and area under the receiver operator characteristic curve (AUROC) analyses. RESULTS: The study cohort comprised 224 patients, who were categorized by preservation (n = 168) and no preservation (n = 56) of anterior pituitary function after SRS. The mean and median clinical follow-up durations were 53.7 (38.0) and 46.0 (17.0-75.0) months, respectively. Independent predictors of anterior pituitary function preservation were a greater distance between the center of the pituitary gland and center of the SRS target [OR 1.101 (1.000-1.213), p = 0.050], and a shorter clinical follow-up duration [OR 0.985 (0.977-0.993), p < 0.0001]. The adjusted AUROC for the distance from the center of the pituitary gland and center of the SRS target in predicting anterior pituitary function preservation was 0.595. The sensitivity, specificity, positive predictive value and negative predictive value in predicting anterior pituitary function preservation at the optimal cut-off distance of 15 mm were 30.0, 88.0, 89.9 and 26.2%, respectively. CONCLUSIONS: Greater distance between the normal pituitary gland and the SRS target is associated with anterior pituitary function preservation and increasing this distance should be a goal of adenoma resection. Larger prospective, multi-center studies are necessary to corroborate this finding and establish the effects of distance on hypopituitarism after SRS for pituitary adenomas.

Characterization of a paradoxical post-operative increase in serum cortisol in Cushing disease.

PURPOSE: In Cushing disease, early post-operative serum cortisol fluctuations have not been adequately characterized, and their association with initial remission and recurrence is unclear. METHODS: A retrospective cohort study of patients with Cushing disease was conducted at two institutions. A "riser" was defined a priori as a paradoxical increase in serum cortisol with an immediate incremental increase in serum cortisol over three consecutive cortisol draws separated by roughly 6-h (definition 1). Post hoc analyses used a definition of two consecutive increases (definition 2). Risers were compared to non-risers for initial remission and time-to-recurrence. RESULTS: A total of 505 patients with Cushing disease were screened, and 469 had adequate data for group assignment. Analysis of post-operative cortisol showed a subgroup of "risers" with a frequency of 3.6% for definition 1 and 42.6% for definition 2. In these patients, cortisol levels were significantly higher until approximately 36 h post-operatively, and cortisol had a significantly longer mean serum half-life. In the post hoc analysis, definition 2 risers had a lower remission rate compared to non-risers (162/196, 82.7%, versus 243/264, 92.0%) with an odds ratio of 0.41 (0.23-0.73; p = 0.003). For both definitions, recurrence was similar between groups. CONCLUSIONS: We found that almost half of Cushing disease patients experienced a temporary increase in serum cortisol level during the early post-operative period. Serum cortisol half-life was longer, and the remission rates were lower, however, recurrence rates were similar to non-risers.

Disaster Behavioral Health Research Involving Military Facilities and Populations after Mass Violence: Insights from the 2013 Washington Navy Yard Shooting.

Research on disaster behavioral health presents significant methodological challenges. Challenges are even more complex for research on mass violence events that involve military members, families, and communities, due to the cultural and logistical considerations of working with this population. The current article aims to inform and educate on this specialized area of research, by presenting a case study on the experience of designing and conducting disaster behavioral health research after a mass violence event in a military setting: the 2013 mass shooting at the Washington Navy Yard, in Washington, D.C. Using the case example, the authors explore methodological challenges and lessons learned from conducting research in this context, and provide guidance for future researchers.

Longitudinal Study of Hurricane Preparedness Behaviors: Influence of Collective Efficacy.

OBJECTIVE: Community characteristics, such as collective efficacy, a measure of community strength, can affect behavioral responses following disasters. We measured collective efficacy 1 month before multiple hurricanes in 2005, and assessed its association to preparedness 9 months following the hurricane season. METHODS: Participants were 631 Florida Department of Health workers who responded to multiple hurricanes in 2004 and 2005. They completed questionnaires that were distributed electronically approximately 1 month before (6.2005-T1) and 9 months after (6.2006-T2) several storms over the 2005 hurricane season. Collective efficacy, preparedness behaviors, and socio-demographics were assessed at T1, and preparedness behaviors and hurricane-related characteristics (injury, community-related damage) were assessed at T2. Participant ages ranged from 21-72 (M(SD) = 48.50 (10.15)), and the majority were female (78%). RESULTS: In linear regression models, univariate analyses indicated that being older (B = 0.01, SE = 0.003, P < 0.001), White (B = 0.22, SE = 0.08, P < 0.01), and married (B = 0.05, SE = 0.02, p < 0.001) was associated with preparedness following the 2005 hurricanes. Multivariate analyses, adjusting for socio-demographics, preparedness (T1), and hurricane-related characteristics (T2), found that higher collective efficacy (T1) was associated with preparedness after the hurricanes (B = 0.10, SE = 0.03, P < 0.01; and B = 0.47, SE = 0.04, P < 0.001 respectively). CONCLUSION: Programs enhancing collective efficacy may be a significant part of prevention practices and promote preparedness efforts before disasters.

Risk of suicide attempt in reserve versus active component soldiers during deployment to the wars in Iraq and Afghanistan.

INTRODUCTION: Little is known about the degree to which U.S. Army soldiers in the Reserve Components (Army National Guard and Army Reserve) and Active Component (Regular Army) differ with respect suicide attempt (SA) risk during high-stress times, such as deployment. METHOD: Using administrative person-month records of enlisted soldiers on active duty during 2004-2009, we identified 1170 soldiers with a medically documented SA during deployment and an equal-probability control sample of other deployed soldiers (n = 52,828 person-months). Logistic regression analyses examined the association of Army component (Guard/Reserve vs. Regular) with SA before and after adjusting for socio-demographic and service-related predictors. RESULTS: Guard/Reserve comprised 32.1% of enlisted soldiers and 19.7% of suicide attempters in-theater, with a SA rate of 81/100,000 person-years (vs. 157/100,000 person-years among Regular; rate ratio = 0.5 [95% CI = 0.5-0.6]). Risk peaked near mid-deployment for both groups but was consistently lower for Guard/Reserve throughout deployment. Guard/Reserve had lower odds of SA after adjusting for covariates (OR = 0.7 [95%CI = 0.6-0.8]). Predictors of SA were similar between components. CONCLUSIONS: Guard/Reserve and Regular soldiers had similar patterns and predictors of SA during deployment, but Guard/Reserve had lower risk even after controlling for important risk factors. Additional research is needed to understand the lower SA risk among Guard/Reserve in-theater.

Dose to neuroanatomical structures surrounding pituitary adenomas and the effect of stereotactic radiosurgery on neuroendocrine function: an international multicenter study.

OBJECTIVE: Stereotactic radiosurgery (SRS) provides a safe and effective therapeutic modality for patients with pituitary adenomas. The mechanism of delayed endocrine deficits based on targeted radiation to the hypothalamic-pituitary axis remains unclear. Radiation to normal neuroendocrine structures likely plays a role in delayed hypopituitarism after SRS. In this multicenter study by the International Radiosurgery Research Foundation (IRRF), the authors aimed to evaluate radiation tolerance of structures surrounding pituitary adenomas and identify predictors of delayed hypopituitarism after SRS for these tumors. METHODS: This is a retrospective review of patients with pituitary adenomas who underwent single-fraction SRS from 1997 to 2019 at 16 institutions within the IRRF. Dosimetric point measurements of 14 predefined neuroanatomical structures along the hypothalamus, pituitary stalk, and normal pituitary gland were made. Statistical analyses were performed to determine the impact of doses to critical structures on clinical, radiographic, and endocrine outcomes. RESULTS: The study cohort comprised 521 pituitary adenomas treated with SRS. Tumor control was achieved in 93.9% of patients over a median follow-up period of 60.1 months, and 22.5% of patients developed new loss of pituitary function with a median treatment volume of 3.2 cm3. Median maximal radiosurgical doses to the hypothalamus, pituitary stalk, and normal pituitary gland were 1.4, 7.2, and 11.3 Gy, respectively. Nonfunctioning adenoma status, younger age, higher margin dose, and higher doses to the pituitary stalk and normal pituitary gland were independent predictors of new or worsening hypopituitarism. Neither the dose to the hypothalamus nor the ratio between doses to the pituitary stalk and gland were significant predictors. The threshold of the median dose to the pituitary stalk for new endocrinopathy was 10.7 Gy in a single fraction (OR 1.77, 95% CI 1.17-2.68, p = 0.006). CONCLUSIONS: SRS for the treatment of pituitary adenomas affords a high tumor control rate with an acceptable risk of new or worsening endocrinopathy. This evaluation of point dosimetry to adjacent neuroanatomical structures revealed that doses to the pituitary stalk, with a threshold of 10.7 Gy, and doses to the normal gland significantly increased the risk of post-SRS hypopituitarism. In patients with preserved pre-SRS neuroendocrine function, limiting the dose to the pituitary stalk and gland while still delivering an optimal dose to the tumor appears prudent.

Routine postoperative fluid restriction to prevent syndrome of inappropriate antidiuretic hormone secretion after transsphenoidal resection of pituitary adenoma.

OBJECTIVE: Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a common problem during the postoperative course after pituitary surgery. Although treatment of this condition is well characterized, prevention strategies are less studied and reported. The authors sought to characterize outcomes and predictive factors of SIADH after implementation of routine postoperative fluid restriction for patients undergoing endoscopic transsphenoidal surgery for pituitary adenoma. METHODS: In March 2018, routine postoperative fluid restriction to 1000 ml/day for 7 days was instituted for all patients who underwent surgery for pituitary adenoma. These patients were compared with patients who underwent surgery for pituitary adenoma between March 2016 and March 2018, prior to implementation of routine fluid restriction. Patients with preoperative history of diabetes insipidus (DI) or concern for postsurgical DI were excluded. Patients were followed by neuroendocrinologists and neurosurgeons, and sodium levels were checked between 7 and 10 days postoperatively. SIADH was defined by a serum sodium level less than 136 mmol/L, with or without symptoms within 10 days after surgery. Thirty-day readmission was recorded and reviewed to determine underlying reasons. RESULTS: In total, 82 patients in the fluid-unrestricted cohort and 135 patients in the fluid-restricted cohort were analyzed. The patients in the fluid-restricted cohort had a significantly lower rate of postoperative SIADH than patients in the fluid-unrestricted cohort (5% vs 15%, adjusted OR [95% CI] 0.1 [0.0-0.6], p = 0.01). Higher BMI was associated with lower rate of postoperative SIADH (adjusted OR [95%] 0.9 [0.9-1.0], p = 0.03), whereas female sex was associated with higher rate of SIADH (adjusted OR [95% CI] 3.1 [1.1-9.8], p = 0.03). There was no difference in the 30-day readmission rates between patients in the fluid-unrestricted and fluid-restricted cohorts (4% vs 7%, adjusted OR [95% CI] 0.5 [0-5.1], p = 0.56). Thirty-day readmission was more likely for patients with history of hypertension (adjusted OR [95% CI] 5.7 [1.3-26.3], p = 0.02) and less likely for White patients (adjusted OR [95% CI] 0.3 [0.1-0.9], p = 0.04). CONCLUSIONS: Routine fluid restriction reduced the rate of SIADH in patients who underwent surgery for pituitary adenoma but was not associated with reduction in 30-day readmission rate.

Predictors of Suicide Attempt Within 30 Days After First Medically Documented Suicidal Ideation in U.S. Army Soldiers.

OBJECTIVE: The authors sought to identify predictors of imminent suicide attempt (within 30 days) among U.S. Army soldiers following their first documented suicidal ideation. METHODS: Using administrative data from the Army Study to Assess Risk and Resilience in Servicemembers, the authors identified 11,178 active-duty Regular Army enlisted soldiers (2006-2009) with medically documented suicidal ideation and no prior medically documented suicide attempts. The authors examined risk factors for suicide attempt within 30 days of first suicidal ideation using logistic regression analyses, including sociodemographic and service-related characteristics, psychiatric diagnoses, physical health care visits, injuries, and history of family violence or crime perpetration or victimization. RESULTS: Among soldiers with first documented suicidal ideation, 830 (7.4%) attempted suicide, 46.3% of whom (N=387) attempted suicide within 30 days (rate, 35.4 per 1,000 soldiers). Following a series of multivariate analyses, the final model identified females (odds ratio=1.3, 95% CI=1.0, 1.8), combat medics (odds ratio=1.6, 95% CI=1.1, 2.2), individuals with an anxiety disorder diagnosis prior to suicidal ideation (odds ratio=1.3, 95% CI=1.0, 1.6), and those who received a sleep disorder diagnosis on the same day as the recorded suicidal ideation (odds ratio=2.3, 95% CI=1.1, 4.6) as being more likely to attempt suicide within 30 days. Black soldiers (odds ratio=0.6, 95% CI=0.4, 0.9) and those who received an anxiety disorder diagnosis on the same day as suicidal ideation (odds ratio=0.7, 95% CI=0.5, 0.9) were less likely. CONCLUSIONS: Suicide attempt risk is highest in the first 30 days following ideation diagnosis and is more likely among women, combat medics, and soldiers with an anxiety disorder diagnosis before suicidal ideation and a same-day sleep disorder diagnosis. Black soldiers and those with a same-day anxiety disorder diagnosis were at decreased risk. These factors may help identify soldiers at imminent risk of suicide attempt.

Predicting clinically significant response to primary care treatment for depression from electronic health records of veterans.

OBJECTIVE: To reduce delays in referral to specialty mental health care, we evaluated clinical prediction models estimating the likelihood of response to primary care treatment of depression in the VA healthcare system. METHODS: We included patients with a primary care depression diagnosis between October 1, 2015 and December 31, 2017, an initial PHQ-9 score ≥ 10 within 30 days, a follow-up PHQ-9 score within 2-8 months, and no specialty mental health care within three months prior to depression diagnosis. We evaluated eight ordinary least squares regression models, each with a different procedure for selecting predictors of percentage change in PHQ-9 score from baseline to follow-up. Predictors included patient characteristics from electronic health records and neighborhood characteristics from US census data. We repeated each modeling procedure 1,000 times, using different training and validation sets of patients. We used R2, RMSE, and MAE to evaluate model performance. RESULTS: The final cohort included 3,464 patients. The two best performing models included multiple iterations of backwards stepwise variable selection with R2 of 0.07, RMSE of 41.45, MAE of 33.30; and R2 of 0.07, RMSE of 41.39, MAE of 33.28. LIMITATIONS: Wide follow-up interval, possibility of misclassification error due to use of EHR data. CONCLUSIONS: Model performance did not suggest its use as a guide in clinical decision-making. Future research should explore whether obtaining additional risk factor data from patients (e.g., duration of symptoms) or modeling PHQ-9 scores over a narrower time interval improves performance of clinical risk prediction tools for depression.

Exposure to Workplace Trauma and Posttraumatic Stress Disorder Among Intern Physicians.

Importance: Physicians are exposed to traumatic events during their work, but the impact and outcomes of these exposures are understudied. Objective: To determine the prevalence and associations of work-related trauma exposure and posttraumatic stress disorder (PTSD) among a cohort of resident physicians in their internship year of training. Design, Setting, and Participants: This cohort study involved physicians entering internship at US residency programs nationwide in 2018. Participants completed a baseline survey 1 to 2 months before commencing internship, as well as follow-up surveys at 4 time points during internship. Statistical analysis was performed from April 2020 to January 2021. Exposures: Twelve months of internship. Main Outcomes and Measures: Prevalence of work-related trauma and prevalence of PTSD among those who experienced work-related trauma. Trauma exposure and PTSD symptoms were assessed using the Primary Care PTSD Screen for Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (PC-PTSD-5). Risk factors assessed included depression, anxiety, early family environment, stressful life experiences, medical specialty, hours worked, and concern about medical errors. Results: Among 1134 interns who completed the PC-PTSD-5 at month 12 of internship, 665 (58.6%) were female and 695 (61.6%) were non-Hispanic White; the mean (SD) age was 27.52 (2.50) years. There were 640 interns (56.4%) who reported work-related trauma exposure; among these interns with trauma exposure, 123 (19.0%) screened positive for PTSD. Overall, 123 of 1134 training physicians (10.8%) screened positive for PTSD by the end of internship year, as compared with a 12-month PTSD prevalence rate of 3.6% in the general population. Multivariable logistic regression analyses, adjusting for demographic characteristics, indicated that risk factors associated with trauma exposure included non-Hispanic White race/ethnicity (odds ratio [OR], 1.51 [95% CI, 1.14-2.01]; P = .004), more hours worked (OR, 1.01 [95% CI, 1.00-1.03]; P = .03), early family environment (OR, 1.03 [95% CI, 1.01-1.05]; P < .001), and stressful life experiences at baseline (OR, 1.46 [95% CI, 1.06-2.01]; P = .02). Risk factors associated with PTSD were being unmarried (OR, 2.00 [95% CI, 1.07-3.73]; P = .03) and non-Hispanic White (OR, 1.77 [95% CI, 1.01-3.11]; P = .05), concern about medical errors (OR, 1.21 [95% CI, 1.00-1.46]; P = .05), stressful life experiences during internship (OR, 1.43 [95% CI, 1.14-1.81]; P = .002), depression at month 12 of internship (OR, 2.52 [95% CI = 1.36-4.65], P = .003), and anxiety at month 12 of internship (OR, 2.14, [95% CI, 1.13-4.04]; P = .02). Conclusions and Relevance: This study found that work-related PTSD was 3 times more prevalent among intern physicians than the general population. These findings suggest that effective interventions to reduce trauma exposure and mitigate the effects of trauma are needed.

Stereotactic radiosurgery before bilateral adrenalectomy is associated with lowered risk of Nelson's syndrome in refractory Cushing's disease patients.

BACKGROUND: Nelson's syndrome is a rare but challenging sequelae of Cushing's disease (CD) after bilateral adrenalectomy (BLA). We sought to determine if stereotactic radiosurgery (SRS) of residual pituitary adenoma performed before BLA can decrease the risk of Nelson's syndrome. METHODS: Consecutive patients with CD who underwent BLA after non-curative resection of ACTH secreting pituitary adenoma and had at least one follow-up visit after BLA were studied. Nelson's syndrome was diagnosed based on the combination of rising ACTH levels, increasing volume of the pituitary adenoma and/or hyperpigmentation. RESULTS: Fifty patients underwent BLA for refractory CD, and 43 patients (7 men and 36 women) had at least one follow-up visit after BAL. Median endocrine, imaging, and clinical follow-up were 66 months, 69 months, and 80 months, respectively. Nine patients (22%) were diagnosed with the Nelson's syndrome at median time after BLA at 24 months (range: 0.6-119.4 months). SRS before BLA was associated with reduced risk of the Nelson's syndrome (HR = 0.126; 95%CI [0.022-0.714], p=0.019), while elevated ACTH level within 6 months after BLA was associated with increased risk for the Nelson's syndrome (HR = 9.053; 95%CI [2.076-39.472], p=0.003). CONCLUSIONS: SRS before BLA can reduce the risk for the Nelson's syndrome in refractory CD patients requiring BLA and should be considered before proceeding to BLA. Elevated ACTH concentration within 6 months after BLA is associated with greater risk of the Nelsons' syndrome. When no prior SRS is administered, those with a high ACTH level shortly after BLA may benefit from early SRS.

Sex Differences in US Army Suicide Attempts During the Wars in Iraq and Afghanistan.

OBJECTIVE: To examine sex differences in risk for administratively documented suicide attempt (SA) among US Army soldiers during the Iraq/Afghanistan wars. METHOD: Using administrative person-month records of Regular Army enlisted soldiers from 2004 to 2009, we identified 9650 person-months with a first documented SA and an equal-probability control sample (n=153,528 person-months). Person-months were weighted to the population and pooled over time. After examining the association of sex with SA in a logistic regression analysis, predictors were examined separately among women and men. RESULTS: Women (an estimated 13.7% of the population) accounted for 25.2% of SAs and were more likely than men to attempt suicide after adjusting for sociodemographic, service-related, and mental health diagnosis (MHDx) variables (odds ratio=1.6; 95% confidence interval, 1.5-1.7). Women with increased odds of SA in a given person-month were younger, non-Hispanic White, less educated, in their first term of enlistment, never or previously deployed (vs. currently deployed), and previously received a MHDx. The same variables predicted SA among men. Interactions indicated significant but generally small differences between women and men on 6 of the 8 predictors, the most pronounced being time in service, deployment status, and MHDx. Discrete-time survival models examining risk by time in service demonstrated that patterns for women and men were similar, and that women's initially higher risk diminished as time in service increased. CONCLUSIONS: Predictors of documented SAs are similar for US Army women and men. Differences associated with time in service, deployment status, and MHDx require additional research. Future research should consider stressors that disproportionately affect women.

Multidisciplinary management of acromegaly: A consensus.

The 13th Acromegaly Consensus Conference was held in November 2019 in Fort Lauderdale, Florida, and comprised acromegaly experts including endocrinologists and neurosurgeons who considered optimal approaches for multidisciplinary acromegaly management. Focused discussions reviewed techniques, results, and side effects of surgery, radiotherapy, and medical therapy, and how advances in technology and novel techniques have changed the way these modalities are used alone or in combination. Effects of treatment on patient outcomes were considered, along with strategies for optimizing and personalizing therapeutic approaches. Expert consensus recommendations emphasize how best to implement available treatment options as part of a multidisciplinary approach at Pituitary Tumor Centers of Excellence.