Search

ObjectiveTo compare the ability of current complication reporting scales (Contracted Accordion Scale, Expanded Accordion Scale, Clavien-Dindo Scale) to reflect the severity of patient outcomes after cytoreductive surgery for ovarian cancer.MethodsWe included all patients undergoing primary debulking surgery for stage IIIC/IV ovarian cancer from 2006 to 2016 at two expert centers for ovarian cancer. Complications within 30 days of surgery were graded according to three scales. Outcomes included length of stay, mortality (90-day), and delayed initiation of chemotherapy (>42 days after surgery). Correlations were assessed using the Spearman rank correlation, and comparisons between groups were evaluated using the Wilcoxon rank-sum test and the χ2test.ResultsAmong the 892 patients, 185 (20.7%) patients had a grade 3 or higher complication per all scales. Patients with grade 3 or higher complications (compared with those with none, grade 1 or grade 2) had longer length of stay, higher 90-day mortality, and delayed initiation of chemotherapy. The expanded scales (Expanded Accordion Scale and Clavien Dindo Scale) provided a more refined characterization of outcome compared with the Contracted Accordion Scale. However, mortality was actually found to be as high as 25.0% for grade 5 complications using the Expanded Accordion Scale. Patients with organ failure or requiring an invasive procedure had significantly worse outcomes than those without either complication, highlighting the importance of separating these events.ConclusionsAll three scales demonstrated general correlation with important outcomes after ovarian cancer surgery. However, the expanded scales (Clavien Dindo Scale and Expanded Accordion Scale) used important events commonly encountered after cytoreductive surgery, provided a more refined view of the severity of complications, and should be used in reporting outcomes in ovarian cancer.

ObjectiveWe developed an algorithm that identifies patients at high risk of morbidity/mortality after cytoreductive surgery for advanced ovarian cancer. We have previously shown that the Mayo triage algorithm reduces operative mortality internally, followed by validation using an external low complexity national dataset. However, validation in a higher complexity surgical setting is required before widespread acceptance of this approach, and this was the goal of our study.MethodsWe included patients who underwent debulking surgery (including primary or interval debulking surgery) for stage IIIC/IV ovarian cancer between October 2011 and November 2019 (SCORPION trial patients until May 2016 and non-trial patients thereafter) at Fondazione Policlinico A Gemelli, Italy. Using the algorithm, we classified patients as either high-risk or triage-appropriate and compared 30-day grade 3+ complications and 90-day mortality using a χ2test or Fisher’s exact test.ResultsA total of 625 patients were included. The mean age was 58.7±11.4 years, 73.6% (n=460) were stage IIIC, and 63.0% (n=394) underwent primary debulking surgery. Surgical complexity was intermediate or high in 82.6% (n=516) of patients (95.7% (n=377) for primary surgery and 60.2% (n=139) for interval surgery), and 20.3% (n=127) were classified as high-risk. When compared with triage-appropriate patients, high-risk patients had (1) a threefold higher rate of 90-day mortality (6.3% vs 2.0%, p=0.02); (2) a higher likelihood of 90-day mortality following a grade 3+ complication (25.9% vs 10.0%, p=0.05); and (3) comparable rates of grade 3+ complications (21.3% vs 16.1%, p=0.17).ConclusionThe evidence-based triage algorithm identifies patients at high risk of morbidity/mortality after cytoreductive surgery. Triage high-risk patients are poor candidates for surgery when complex surgery is required. This algorithm has been validated in heterogeneous settings (internal, national, and international) and degree of surgical complexity. Risk-based decision making should be standard of care when planning surgery for patients with advanced ovarian cancer, whether primary or interval surgery.

The aim of this study was to understand the risk of developing attention-deficit/hyperactivity disorder (ADHD) or learning disability (LD) after childhood traumatic brain injury (TBI) in a population-based birth cohort. Cases of TBI for children from birth to 10 years were confirmed and stratified by severity of injury. For each TBI case, two age-matched and sex-matched referents without TBI were identified from the same birth cohort. Presence of ADHD and LD before age 19 were confirmed using medical and/or school records. Associations between TBI exposure and subsequent ADHD or LD were assessed in multivariable Cox regression models, adjusting for maternal age, education, and race. The incidence rate of TBI before age 10 was 1,156 per 100,000 person-years. Children who had a TBI before age 10 were more likely to have met the research criteria for ADHD (hazard ratio [HR], 1.68; 95% CI, 1.15-2.45) or LD (HR, 1.29; 95% CI, 1.00-1.68) by age 19. No statistically significant associations were shown between TBI and ADHD or LD when restricted to definite and probable TBI cases (consistent with moderate to severe and mild TBI, respectively) and their referents. Significant associations were shown when the analysis was confined to possible TBI cases (consistent with concussive TBI) and their referents (ADHD: HR, 2.05; 95% CI, 1.31-3.20; and LD: HR, 1.42; 95% CI, 1.05-1.91). Increased risk for developing ADHD and LD by adulthood was shown particularly for children with the least-severe injuries, indicating that factors other than trauma-related altered brain function likely contribute to this risk.

We aimed to determine whether the use of remote infant viewing (RIV) in a neonatal intensive care unit (NICU) differed based on maternal sociodemographic factors.The number of RIV camera views and view duration were obtained for NICU patients between 10/01/2019 and 3/31/2021 and standardized relative to patient days. Maternal sociodemographic and neonatal characteristics were obtained from institutional databases.Families in which mothers were unmarried (aOR 1.42, 95% CI 1.03-1.95), did not require an interpreter (aOR 2.86, 95% CI 1.54-5.32), were multiparous (aOR 1.56, 95% CI 1.16-2.10), delivered prior to 37 weeks' gestation (aOR 1.57, 95% CI 1.17-2.12), or resided ≥50 miles from the NICU (aOR 1.38, 95% CI 1.02-1.87) were significantly more likely to use RIV.Family use of RIV in the NICU varied by multiple sociodemographic factors. Further investigation to understand and to address potential equity gaps revealed or created by RIV are warranted.

To evaluate the association of primary infertility with subsequent bilateral oophorectomy and hysterectomy, using a population-based cohort of women with primary infertility and age-matched women in a referent group.The Rochester Epidemiology Project record-linkage system was used to assemble a population-based cohort of women with primary infertility diagnosed between 1980 and 1999 (index date). Women were age-matched (±1 year) 1:1 to women without a history of infertility or hysterectomy at the index date (referent group). Cox proportional hazards models were fit to compare long-term risks of bilateral oophorectomy and hysterectomy, respectively, between women with infertility and women in the referent group.Among both groups of 1,001 women, the mean age at the index date was 29.2±4.4 years. Median duration of follow-up was 23.7 years for both groups. Women with primary infertility were 1.7 times (adjusted hazard ratio [aHR] 1.69, 95% CI 1.22-2.33) more likely to undergo bilateral oophorectomy compared with women in the referent group. In a sensitivity analysis that excluded women with a diagnosis of infertility related to endometriosis and their matched referent group participants, this association persisted (aHR 1.50, 95% CI 1.06-2.14). Women with primary infertility did not have a significant increased risk of hysterectomy (aHR 0.98, 95% CI 0.79-1.23). However, risk of hysterectomy was increased in those with primary infertility related to endometriosis (aHR 1.94, 95% CI 1.12-3.34). We observed that women with primary infertility were more likely to undergo hysterectomy with bilateral oophorectomy. Women in the referent group were more likely to undergo hysterectomy with ovarian conservation. Few women in either group had isolated bilateral oophorectomy.Primary infertility, with and without a diagnosis of endometriosis, is associated with an increased risk of bilateral oophorectomy. In women with endometriosis-related infertility, there is an association with future hysterectomy. These findings represent important confounders in the evaluation of long-term health outcomes related to primary infertility.

BackgroundSarcopenia is prevalent among older patients with cancer and is associated with poor outcomes.ObjectiveTo explore the relationship between muscle mass, quality, and patient age with overall survival after surgery for advanced ovarian cancer.MethodsPatients with advanced stage (IIIC/IV) ovarian cancer who underwent primary cytoreductive surgery between January 2006 and July 2016 were included. Body composition measures were calculated from pre-operative CT imaging: skeletal muscle index (skeletal muscle index=skeletal muscle area normalized for height), skeletal muscle density, and skeletal muscle gauge (product of skeletal muscle index and skeletal muscle density). Each measure was transformed to a z-score and evaluated for association with risk of death using Cox proportional hazards models. Recursive partitioning was used to classify patients into homogeneous subgroups considering age and skeletal muscle gauge as predictors of overall survival.ResultsThe study included 429 patients (mean age 64.2 years). Increased age moderately correlated with decreased skeletal muscle gauge (r=−0.45). Decreasing skeletal muscle density and skeletal muscle gauge were significantly associated with increased risk of death; HR (95% CI) per 1-unit decrease in z-score of 1.24 (1.10 to 1.39) for skeletal muscle density and 1.27 (1.12 to 1.44) for skeletal muscle gauge. Associations were diluted after adjusting for age (1.13 (1.00 to 1.29) skeletal muscle density and 1.14 (0.99 to 1.30) skeletal muscle gauge). Recursive partitioning identified three subgroups: ConclusionsSkeletal muscle gauge, a novel sarcopenia measure incorporating quantity and quality, was associated with poorer survival in patients with advanced ovarian cancer, particularly among patients older than 60. Expanding our knowledge of how sarcopenia relates to solid tumor outcomes among high-risk patients can modify our treatment approach.

ObjectiveTo identify high-risk disease in clinicopathologic low-risk endometrial cancer (EC) with high microsatellite instability (MSI-H) or no specific molecular profile (NSMP) and therapeutic insensitivity in clinicopathologic high-risk MSI-H/NSMP EC.MethodsWe searched The Cancer Genome Atlas for DNA sequencing, RNA expression, and surveillance data regarding MSI-H/NSMP EC. We used a molecular classification system of E2F1 and CCNA2 expression and sequence variations in POLE, PPP2R1A, or FBXW7 (ECPPF) to prognostically stratify MSI-H/NSMP ECs. Clinical outcomes were annotated after integrating ECPPF and sequence variations in homologous recombination (HR) genes.ResultsData were available for 239 patients with EC, which included 58 MSI-H and 89 NSMP cases. ECPPF effectively stratified MSI-H/NSMP EC into distinct molecular groups with prognostic implications: molecular low risk (MLR), with low CCNA2 and E2F1 expression, and molecular high risk (MHR), with high CCNA2 and E2F1 expression and/or PPP2R1A and/or FBXW7 variants. The 3-year disease-free survival (DFS) rate was 43.8% in the MHR group with clinicopathologic low-risk indicators and 93.9% in the MLR group (PPConclusionECPPF may resolve prognostic challenges for MSI-H/NSMP EC by identifying occult high-risk disease in EC with clinicopathologic low-risk indicators and therapeutic insensitivity in EC with clinicopathologic high-risk indicators.

Down syndrome (DS) research is advancing rapidly, yet efforts have raised ethical questions. This mixed methods study describes views of people with DS (self-advocates) and their parents regarding medical interventions for DS. Responses from 35/171 (20.5%) self-advocates and 430/867 (49.6%) parents showed the majority of self-advocates were glad they have DS (27/35; 77.1%) and liked who they are (33/35; 94.3%), but did want to learn faster (23/35; 65.7%). Parents much more commonly agreed with a willingness to give medications to prevent Alzheimer's disease (427/429; 99.5%) or blood cancer (428/430; 99.5%) as compared with a medicine to cure DS (225/425; 52.9%). Qualitative comments intertwined DS with identity, yet indicated desire for improved quality of life and opportunities. Responses decoupled DS itself from the complications of DS, with treatment of complications being more acceptable.

In-transit metastases (ITM) are a form of locoregional relapse representing intralymphatic metastatic spread and occur in approximately 4-9% of patients with melanoma1 mm Breslow thickness. Our objective was to evaluate a combination of clinicopathologic risk factors and gene expression biomarkers predictive of ITM risk.We used PCR to quantify gene expression in diagnostic biopsy tissue across a prospectively designed archival cohort of 854 consecutive thin and intermediate thickness primary cutaneous melanomas. The outcome of interest was ITM90 days after a melanoma diagnosis. Cox proportional hazard models were fit to estimate each clinicopathologic and molecular characteristic's association with the risk of ITM.The 5-year cumulative incidence of ITM was 3.2%. Clinical factors univariately associated with an increased risk of ITM were older age, greater Breslow thickness, greater mitotic rate, lower extremity location, ulceration, and a positive SLN biopsy. Of 108 genes tested, five were significantly upregulated and five significantly downregulated when evaluated in Cox models adjusted for age, Breslow thickness, mitotic rate, and lower extremity location. Among the upregulated genes, the strongest association was observed for interleukin-8 (IL8).A subset of gene expression biomarkers was identified as independently associated with the risk of ITM after adjusting for key covariates. Once sufficiently validated, our results may lead the way to regional therapy trials for a small, selected group of high-risk patients.

During pregnancy, certain viral infections are known to significantly affect fetal development. Data regarding the impact of COVID-19 viral infection in pregnancy, specifically in asymptomatic or mild cases, remains limited. This presents a challenge in providing prenatal counseling and antepartum surveillance in pregnancies complicated by COVID-19 infection. Placenta studies have demonstrated that vascular malperfusion patterns attributed to COVID-19 appear to depend on the timing of infection. Given these placental changes, we aim to evaluate the impact of COVID-19 on fetal growth in pregnant patients with asymptomatic or mild disease, stratified by trimester of infection. We hypothesize that COVID-19 infection, especially early in pregnancy, increases the risk of fetal growth restriction (FGR).This is a single institution, retrospective cohort study of patients ages 16-55 years old with a singleton delivery between December 10, 2020, and April 19, 2021 who had not received a COVID-19 vaccination prior to delivery. COVID-19 infection during pregnancy was defined as a positive SARS-CoV-2 RT-PCR test. FGR was defined as an estimated fetal weight less than the 10th percentile for gestational age or abdominal circumference less than the 10th percentile for gestational age. Maternal and fetal characteristics, including FGR, were compared between women with versus without COVID-19 infection during pregnancy.Among 1971 women with a singleton delivery, 208 (10.6 %) had a prior asymptomatic or mild COVID-19 infection during pregnancy. With the exception in the median prenatal BMI being significantly higher in the COVID-19 group (median, 27.5 vs 26.3, p = 0.04), there were no significant differences in demographics, baseline maternal comorbidities or gestational age between those with versus without COVID-19 infection during pregnancy, or in the proportion of their offspring with FGR (3.4 % (7/208) vs 4.8 % (84/1763), p = 0.36). When the 208 women were stratified by the timing of their COVID-19 infection, the proportion with an offspring with FGR was 8.7 % (2/23), 1.2 % (1/84), and 4.0 % (4/101), for those first diagnosed with COVID-19 during the 1st, 2nd, and 3rd trimesters, respectively (p = 0.72 Cochran-Armitage test for trend).Asymptomatic or mild COVID-19 infection in pregnancy, regardless of timing of infection, does not appear to be associated with FGR. Routine serial fetal growth assessment may not be warranted solely for history of COVID-19 infection.

Adolescents and emerging adults with chronic health conditions such as type 1 diabetes mellitus (T1D) are more likely to engage in high-risk behaviors. Previous studies regarding substance use in adolescents and emerging adults with T1D are mostly derived from cross-sectional studies utilizing self-administered questionnaires and are limited by lack of population-based comparison groups. In addition, despite the rising popularity of vaping, little is known about the incidence of vaping in adolescents and emerging adults with T1D. We explored the incidence and prospective risk of substance use disorders and vaping in adolescents and emerging adults with T1D compared to age and gender matched non-diabetic referents residing in Olmsted County, Rochester, MN. Risk of incident substance use disorder washigher in those with T1D compared to matched referents with alcohol, marijuana, and smoked tobacco being most common substances. When stratified by gender, these differences remained significant in males, but not females. While further work is needed to delineate the causative relationships between T1D, mental health, and substance abuse; our findings confirm the critical need for substance use screening and mental health support for adolescents and emerging adults with T1D. This article is protected by copyright. All rights reserved.

Background Abnormal uterine bleeding requires the investigation of the endometrium. Histology is typically used but there remains room for the improvement and use of cytology. Methods Women presenting for clinically indicated office endometrial biopsy were prospectively enrolled. Tao endometrial brushing and office endometrial biopsy were performed, and surgical procedure if clinically indicated. Tao brush cytology specimens were blindly reviewed by up to three pathologists, consensus obtained, and scored as: benign, atypical (favor benign), suspicious, positive for malignancy, or non‐diagnostic. Cytology and histology were compared to surgical pathology to determine sensitivity, specificity, positive, and negative predictive values to detect AH (atypical hyperplasia) or EC (endometrial cancer). Results Clinical indications of 197 enrolled patients included postmenopausal bleeding (90, 45.7%), abnormal uterine bleeding (94, 47.7%), and abnormal endometrium on ultrasound without bleeding (13, 6.6%). Of the 197 patients, 185 (93.9%) had cytology score consensus and a total of 196 (99.5%) had consensus regarding cytology positivity. Surgical pathology diagnoses (N = 85) were 13 (15.3%) FIGO grade 1 or 2 EC, 3 (3.5%) AH, and 69 (81.2%) benign endometrium. Sensitivity and specificity to detect EC or AH were 93.7% and 100%, respectively, via endometrial biopsy; 87.5% and 63.8%, respectively, via endometrial cytology when scores of malignancy, suspicious, or atypical were considered positive. Conclusions In a high‐risk population, Tao brush endometrial cytology showed high sensitivity to detect AH and EC comparable to biopsy histology when considering scores of malignancy, suspicious, atypical, and non‐diagnostic. Revisiting the potential value of endometrial cytology in the contemporary era of endometrial diagnostic workup is warranted., Tao brush cytology is a sensitive tool for endometrial cancer evaluation in symptomatic women. There is a high concordance of Tao brush readings amongst blinded pathologists

To compare perioperative costs and morbidity between open and robotic sacrocolpopexy after Enhanced Recovery After Surgery (ERAS) implementation.This retrospective cohort study of patients undergoing open or robotic sacrocolpopexy (January 1, 2014, through November 30, 2017) used ERAS protocol with liposomal bupivacaine infiltration of laparotomy incisions. Primary outcomes were costs associated with index surgery and hospitalization, determined with Medicare cost-to-charge ratios and reimbursement rates and adjusted for variables expected to impact costs. Secondary outcomes included narcotic use, length of stay (LOS), and complications from index hospitalization to postoperative day 30.For the total 231 patients (open cohort, 90; robotic cohort, 141), adjusted mean cost of robotic surgery was $3,239 higher compared to open sacrocolpopexy (95% CI, $1,331-$5,147; P.001). Rates were not significantly different for intraoperative complications (robotic, 4.3% [6/141]; open, 5.6% [5/90]; P=.754); 30-day postoperative complications (robotic, 11.4% [16/141]; open, 16.7% [15/90]; P=.322); or readmissions (robotic, 5.7% [8/141]; open, 3.3% [3/90]; P=.535). The percentage of patients dismissed on postoperative day 1 was greater in the robotic group (89.4% [126/141] vs 48.9% [44/90], P.001).Decreased LOS associated with ERAS provided significant cost savings with open sacrocolpopexy vs robotic sacrocolpopexy without adverse impacts on perioperative complications or readmissions.

PI3K-AKT pathway mutations initiate a kinase cascade that characterizes endometrial cancer (EC). As kinases seldom cause oncogenic transformation without dysregulation of antagonistic phosphatases, pivotal interactions governing this pathway were explored and correlated with clinical outcomes.After exclusion of patients with POLE mutations from The Cancer Genome Atlas EC cohort with endometrioid or serous EC, the study population was 209 patients with DNA sequencing, quantitative gene-specific RNA expression, copy number variation (CNV), and surveillance data available. Extracted data were annotated and integrated.A PIK3CA, PTEN, or PIK3R1 mutant (-mu) was present in 83% of patients; 57% harbored more than 1 mutation without adversely impacting progression-free survival (PFS) (P = .10). PIK3CA CNV of at least 1.1 (CNV high [-H]) was detected in 26% and linked to TP53-mu and CIP2A expression (P.001) but was not associated with PFS (P = .24). PIK3CA expression was significantly different between those with CIP2A-H and CIP2A low (-L) expression (the endogenous inhibitor of protein phosphatase 2A [PP2A]), when stratified by PIK3CA mutational status or by PIK3CA CNV-H and CNV-L (all P.01). CIP2A-H or PPP2R1A-mu mitigates PP2A kinase dephosphorylation, and FBXW7-mu nullifies E3 ubiquitin ligase (E3UL) oncoprotein degradation. CIP2A-H and PPP2R1A-mu (PP2A impairment) and FBXW7-mu (E3UL impairment) were associated with compromised PFS (P.001) and were prognostically discriminatory for PIK3CA-mu and PIK3CA CNV-H tumors (P.001). Among documented recurrences, 84% were associated with impaired PP2A (75%) and/or E3UL (20%).PP2A and E3UL deficiencies are seminal biological drivers in EC independent of PIK3CA-mu, PTEN-mu, and PIK3R1-mu and PIK3CA CNV.

Hidradenitis suppurativa (HS) is associated with substantial morbidity. Few studies have addressed the natural history and mortality rates associated with HS. A higher risk of cardiovascular death in patients with HS has been reported. We investigated whether patients with HS have an increased overall risk of death compared with age- and gender-matched referents.We performed a retrospective cohort study of residents of Olmsted County, Minnesota, with incident HS between January 1, 1980, and December 31, 2008, and age- and gender-matched referents. The main outcomes and measures were the overall and cause-specific risks of death.We identified 226 incident cases of HS and 678 age- and gender-matched referents among Olmsted County residents during the study period. Compared to referents, patients with HS had a significantly higher risk of all-cause death (hazard ratio [HR, 2.48; 95% CI, 1.53-4.03, P 0.001) and cardiovascular- or cerebrovascular-related death (HR, 2.85; 95% CI, 1.10-7.40, P = 0.03). However, these risks were attenuated by adjusting for smoking history: all-cause HR, 1.65 (95% CI, 0.97-2.82, P = 0.07) and cardiovascular- or cerebrovascular-related HR, 2.03 (95% CI, 0.71-5.81, P = 0.18). The 71% of patients were former or current smokers at the time of HS diagnosis.Hidradenitis suppurativa patients have a substantially increased risk of death from any cause, including cardiovascular or cerebrovascular causes; the risk is especially dependent on smoking history.

Little is known about acne incidence in preadolescents and its potential association with body mass index (BMI). Our study aims to determine acne incidence in preadolescents and its association with BMI.A population-based retrospective cohort study identified 7- to ≤12 year-olds with an initial acne diagnosis during 2010-2018, and incidence was calculated. Two age- and sex-matched controls without acne were randomly selected per case, and BMI was recorded.A total of 643 acne patients were identified. Annual age- and sex-adjusted incidence rate was 58.0 per 10,000 person-years, higher in females vs. males (89.2 vs. 28.2 per 10,000 person-years, p .001), and increased with age (4.3, 24.4, and 144.3 per 10,000 person-years among 7-8, 9-10, and 11-12 year-olds, respectively, p .001). Systemic medication use was associated with increasing BMI (odds ratio = 1.43 per 5 kg/mAcne incidence is higher in preadolescent girls than boys and increases with age. Preadolescents with acne are more likely to be obese than those without acne. Those with higher BMIs are more likely to be given systemic treatment.

Increased intraabdominal pressure (IAP) can result in compression of the abdominal-pelvic venous system leading to signs and symptoms of end organ dysfunction. It has been hypothesized as a pathophysiologic process of preeclampsia. We aim to evaluate the role of IAP in normotensive vs preeclamptic, and singleton vs twin pregnancies. We hypothesized that IAP would be higher in preeclamptics and twins.Women undergoing scheduled cesarean delivery were enrolled in four groups: Singletons- Preeclamptic and Normotensive, Twins- Preeclamptic and Normotensive. Elevated IAP was seen in singleton pregnancies with preeclampsia, representing a pathologic process; and in all twin pregnancies, suggesting a physiologic process.

Objective The aim of the study was to determine the prevalence of second victim experience (SVE) among obstetrics and gynecology (OBGYN) clinical and nonclinical healthcare workers and compare healthcare workers who did and did not identify as a second victim (SV) in the last year. Methods The validated Second Victim Experience and Support Tool and additional questions designed to explore SVE topics specific to OBGYN healthcare workers were administered to a multidisciplinary group. Results Of 571 individuals sent a survey link, 205 completed the survey: 117 worked in obstetrics (OB), 73 in gynecology (GYN), and 15 in both areas. Overall, 44.8% of respondents identified as an SV sometime during their career, 18.8% within the last 12 months. Among nonclinical staff respondents, 26.7% identified as an SV during their career and 13.3% in the last 12 months. Respondents who identified as an SV in the last 12 months reported experiencing significantly more psychological and physical distress, a greater degree to which colleague and institutional support were perceived as inadequate, decreased professional self-efficacy, and increased turnover intentions. The most common events identified as likely triggers for SVE were fetal or neonatal loss (72.7%) and maternal death (68.2%) in OB and patient accusations or complaints (69.3%) in GYN. Conclusions Among survey respondents, there was a high prevalence of SVs in OBGYN staff, distributed equally between OB and GYN. Nonclinical healthcare workers also identified as SVs. The OBGYN departments should consider using the Second Victim Experience and Support Tool to screen for potential SV among their healthcare workers to provide additional support after events.

Objective Serous endometrial cancer (USC) is a challenging malignancy associated with metastasis, recurrence and poor outcome. To identify clinically relevant prognostic biomarkers, we focused on a panel of proteins selected after a comprehensive literature review, for tumour profiling of a homogeneous cohort of USC patients. Methods Protein levels and localization were assessed by immunohistochemistry analysis in 36 hysterectomy samples. Tissue sections were stained with the following antibodies: Aurora A, phospho (T288) Aurora A, BRCA1, CHK1, CIP2A, Cyclin B1, Cyclin E, E2F-1, phospho (S364) E2F-1, FBXW7, FOXM1, phospho (S9) GSK3Beta, PLK1, phospho (T210) PLK1, PPP2R1B, p73, RAD51. Each marker was evaluated as a continuously-scaled variable for association with disease progression and death, using Cox proportional hazards models. The sample consisted of 36 patients with USC, half with stage III or IV disease. Results Results showed that higher CHK1 (Checkpoint kinase 1) expression was associated with a decreased risk of progression and death, after adjusting for stage. Interestingly, analysis of a TCGA data set of 109 USC patients corroborates our results showing a favourable prognostic role of CHEK1 after adjusting for stage. Higher FBXW7 (F-box and WD repeat domain containing 7) expression and higher cytoplasmic expression of PPP2R1B (Protein Phosphatase 2 A, Scaffold Subunit Abeta) were each associated with a decreased risk of progression, after adjusting for stage. Conclusions In conclusion, results from the present study identify new clinically relevant biomarkers and potential drug targets for uterine serous endometrial cancer.

OBJECTIVE: Morbidity and mortality (M/M) after primary debulking surgery (PDS) is often cited as a rationale for neoadjuvant chemotherapy and interval debulking surgery (IDS). We tested if using an evidence-based algorithm to identify patients fit for surgery would reduce M/M after PDS to that seen after IDS. METHODS: We included women who underwent PDS or IDS for advanced epithelial ovarian cancer (EOC) (1/2012–7/2016) guided by the use of a prospective triage algorithm. Outcomes were compared after applying inverse-probability of treatment weighting (IPTW) to adjust for covariate imbalance. RESULTS: Of 334 included patients, 232 (69.5%) underwent PDS and 102 (30.5%) were triaged to IDS. Relative to IDS group, PDS patients were younger (63.9 vs 67.5years, P=0.01), were less likely to have low albumin (16.8% vs. 32.4%, P

To assess the effect of Enhanced Recovery After Surgery (ERAS) with and without liposomal bupivacaine (LB) on opioid use, hospital length of stay (LOS), costs, and morbidity of women undergoing sacrocolpopexy.Retrospective cohort of women who underwent abdominal sacrocolpopexy between April 1, 2009 and November 30, 2017. Costs for relevant healthcare services were determined by assigning 2017 charges multiplied by 2017 Medicare Cost Report's cost to charge ratios. Outcomes were compared among periods with multivariable regression models adjusted for age, American Society of Anesthesiologists score, and concurrent hysterectomy and posterior repair.Patients were subdivided into pre-ERAS (G1, n = 128), post-ERAS (G2, n = 83), and post-ERAS plus LB (G3, n = 91). The proportion of patients needing opioids during postoperative days 0-2 was significantly less for G3 (75.8%) compared with G1 (97.7%) and G2 (92.8%); P 0.001). The median morphine equivalent units (MEU) with interquartile ranges, mean LOS, and adjusted mean standardized costs were significantly lower in G3 compared with the other two groups (35 [20-75] vs. 67 [31-109], and 60 [30-122] MEUs; 1.8 vs. 2.3 vs. 2.9 days; and $2391, $2975, and $3844, for G3, G2, and G1, respectively; P 0.001).Implementation of an ERAS pathway led to significant decreases in opioid use, LOS, and costs. Supplementation with LB further improved these measures.

ObjectiveEndometrial cancer surgical staging includes lymph node assessment which can lead to lower extremity lymphedema. The aim of this study was to estimate prevalence after sentinel lymph node biopsy versus lymphadenectomy.MethodsConsecutive patients who underwent minimally invasive surgery at the Mayo Clinic, Rochester, Minnesota, USA, between January 2009 and June 2016 for newly diagnosed endometrial cancer were mailed our validated 13 item lower extremity lymphedema screening questionnaire. We also ascertained via questionnaire whether the patient was ever diagnosed with lower extremity lymphedema.ResultsAmong 378 patients included in the analysis, 127 (33.5%) had sentinel lymph node biopsy with or without side specific lymphadenectomy (sentinel lymph node cohort) and 251 (66.4%) underwent bilateral lymphadenectomy prior to sentinel lymph node biopsy implementation at our institution or as 'backup' after sentinel lymph node mapping (lymphadenectomy cohort). The prevalence of lower extremity lymphedema was 41.5% (157/378), with 69 patients (18.3%) self-reporting a lower extremity lymphedema diagnosis after their endometrial cancer surgery at a median of 54.3 months (interquartile range 31.2–70.1 months), and an additional 88 patients (23.3%) identified by the screening questionnaire. The prevalence of lower extremity lymphedema was significantly higher in the lymphadenectomy cohort compared with the sentinel lymph node group (49.4% (124/251) vs 26.0% (33/127); pConclusionsSentinel lymph node biopsy was associated with a decreased risk of post-treatment lymphedema compared with lymphadenectomy in patients who underwent surgical staging for endometrial carcinoma.

Aim (s) To investigate second victim experiences and supportive resources for nurses in obstetrics and gynaecology. Background Nurses are at risk of developing second victim experiences after exposure to work related events. Methods Nurses at a single institution were invited to participate in an anonymous survey that included the validated Second Victim Experience and Support Tool to assess symptoms related to second victim experiences and current and desired supportive resources. Results Of 310 nurses, 115 (37.1%) completed the survey; 74.8% had not heard of the term 'second victim'. Overall, 47.8% reported feeling like a second victim during their career and 19.1% over the previous 12 months. As a result of a second victim experience, 18.4% experienced psychological distress, 14.3% turnover intentions, 13.0% decreased professional self-efficacy, and 12.2% felt that institutional support was poor. Both clinical and non-clinical events were reported as possible triggers for second victim experiences. Peer support was the most desired form of support as reported by 95.5%. Conclusion(s) Nurses in obstetrics and gynaecology face clinical and non-clinical situations that lead to potential second victim experiences. Implications for nursing management The second victim experiences of nurses should be acknowledged, and resources should be implemented to navigate it. Educational opportunities and peer supportive interventions specific to second victim experiences should be encouraged.

Objective: To identify patterns (“classes”) of outcomes for adults with and without childhood ADHD. Method: Subjects were 232 childhood ADHD cases and 335 non-ADHD referents from a 1976 to 1982 birth cohort. We used latent class analyses to identify classes based on a broad array of adult psychosocial outcomes and determined the proportion of subjects with childhood ADHD within each class. Results: A three class solution provided optimal model fit; classes were termed “good,” “intermediate,” and “poor” functioning. Subjects with childhood ADHD comprised 62.8% of the “poor,” 53.5% of the “intermediate,” and 24.9% of the “good” functioning class. The “poor” functioning class was distinguished by increased likelihood of legal trouble and substance use disorders and included more individuals with childhood ADHD and psychiatric disorder than the “intermediate” class (45.5% vs. 30.6%). Conclusion: Children with ADHD are at risk for adverse adult outcomes in multiple domains and co-morbid childhood psychiatric disorders increase risk.

ObjectivePrevious studies have investigated the impact of preoperative hysteroscopy on the staging and survival of predominantly grade 1 endometrial cancers. We sought to evaluate the effect of hysteroscopy on the peritoneal spread of tumor cells and disease course in a large series of patients with high-risk endometrial cancer.MethodsPatients who underwent hysterectomy for grade 3 endometrial carcinoma on final surgical pathology at the Mayo Clinic in Rochester, MN between January 2009 to June 2016 were included, noting hysteroscopy within 6 months from surgery. Intra-peritoneal disease was defined as any positive cytology OR adnexal invasion OR stage IV. The presence of intra-peritoneal disease OR peritoneal recurrence within 2 years from surgery was defined as peritoneal dissemination. Cox proportional hazards models were fit to evaluate associations between hysteroscopy exposure and progression within 5 years following surgery.ResultsAmong 831 patients, 133 underwent hysteroscopy. There was no difference in age, body mass index, ASA ≥3, or serous histology between patients who did or did not undergo hysteroscopy. Advanced stage disease (III/IV) was less common among patients who underwent hysteroscopy (30.1% vs 43.8%, P=0.003). No difference was observed between those with vs without hysteroscopy in the rate of positive cytology (22.0% vs 29.7%, P=0.09), stage IV (16.5% vs 21.9%, P=0.16), intra-peritoneal disease (28.6% vs 36.1%, P=0.09), or peritoneal dissemination (30.8% vs 39.3%, P=0.06). On stratifying by stage, hysteroscopy did not increase the risk of progression (HR 1.06, 95% CI 0.59 to 1.92 for stage I/II; HR 0.96, 95% CI 0.62 to 1.48 for stage III/IV).ConclusionIn this retrospective study of grade 3 endometrial cancer, we did not observe any significant association between pre-operative hysteroscopy and the incidence of positive cytology, peritoneal disease, peritoneal dissemination, or cancer progression.

PURPOSE: We aimed to define intrauterine insemination (IUI) cycle characteristics associated with viable birth, identify thresholds below which IUI treatments are consistent with very poor prognosis and futile care, and develop a nomogram for individualized application. METHODS: This retrospective cohort study evaluated couples using fresh partner ejaculate for IUI from January 2005 to September 2017. Variables included female age, semen characteristics, and ovarian stimulation type. Using cycle-level data, we evaluated the association of these characteristics with the probability of viable birth by fitting generalized regression models for a binary outcome with a logit link function, using generalized estimating equation methodology to account for the correlation between cycles involving the same patient. RESULTS: The cohort consisted of 1117 women with 2912 IUI cycles; viable birth was achieved in 275 (9.4%) cycles. Futile care (viable birth rate 43, regardless of stimulation type or inseminate motility (IM). Very poor prognosis (viable birth rate

BackgroundIn the primary treatment of apparent uterine-confined endometrial carcinoma, pelvic ± para-aortic lymphadenectomy has been considered the standard of care. Although some retrospective data suggest that the sentinel lymph node algorithm without complete lymphadenectomy can be used without jeopardizing oncologic outcome, prospective data are lacking.Primary ObjectivesTo assess the 36 month incidence of pelvic/non-vaginal recurrence in women with pathologically confirmed stage I intermediate-risk endometrioid endometrial carcinoma who have bilateral negative pelvic sentinel lymph nodes.Study HypothesisWe hypothesize that patients with stage I, intermediate-risk endometrioid endometrial carcinoma who have bilateral negative pelvic sentinel lymph nodes will demonstrate a pelvic/non-vaginal recurrence rate comparable to historical estimate of stage I, intermediate-risk endometrioid endometrial carcinoma patients (estimated 2.5%).Trial DesignThis prospective multicenter single-arm observational study will follow women with stage I, intermediate risk endometrioid endometrial adenocarcinoma who have undergone successful hysterectomy, bilateral salpingo-oophorectomy, and bilateral sentinel lymph node biopsies, for recurrence. All patients will undergo lymphatic mapping using indocynanine green and will either receive no adjuvant treatment or vaginal brachytherapy only. Patients will be followed for 36 months.Major Inclusion/Exclusion CriteriaPatients will be enrolled in the study cohort if all the following criteria are met: (i) at time of surgery: hysterectomy with bilateral adnexectomy, and successful bilateral pelvic sentinel lymph node mapping; (ii) on final pathology: pathologic stage I, intermediate-risk endometrioid endometrial carcinoma (grade 1 or grade 2 with ≥50% myometrial invasion, or grade 3 with Primary EndpointIncidence of pelvic/non-vaginal recurrence at 36 months.Sample Size182 patients for study cohortEstimated Dates for Completing Accrual and Presenting ResultsAccrual will be completed in 2023 with results reported in 2026.Trial RegistrationNCT04291612

American Academy of Pediatrics (AAP) guidelines for children with Down syndrome (DS) include assessment for celiac disease (CD), although data to support this recommendation have been inconsistent. We determined the incidence of CD among children with DS in a population-based birth cohort of children born from 1976 to 2000 in Olmsted County, Minnesota. Individuals with karyotype-confirmed DS and CD (using diagnosis codes, positive serology, and duodenal biopsies) were identified. The incidence of CD in DS was compared with the published incidence of CD for Olmsted County residents (17.4 [95% confidence interval = 15.2-19.6] per 100 000 person-years). Among 45 individuals with DS from the birth cohort, 3 (6.7%) were identified with positive celiac serology and confirmatory biopsies at ages 9, 12, and 23 years, for an incidence of 325 per 100 000 person-years. Thus, individuals with DS have more than 18 times the incidence rate of CD compared with the general population, supporting the AAP guidelines.

ObjectiveThe role of the different types of adjuvant treatments in endometrial cancer with para-aortic node metastases is unclear. The aim of this study was to report oncologic outcomes after adjuvant therapy in patients with stage IIIC2 endometrial cancer.MethodsThis retrospective single-institution study assessed patients with stage IIIC2 endometrial cancer who underwent primary surgery from January 1984 to December 2014. All patients had hysterectomy (±salpingo-oophorectomy) plus lymphadenectomy (para-aortic nodes, ±pelvic nodes). We included all patients with stage III endometrial cancer and documented para-aortic lymph node metastases (International Federation of Obstetrics and Gynecologists stage IIIC2). We excluded patients who did not provide consent, who had synchronous cancer, or who underwent neoadjuvant chemotherapy. Follow-up was restricted to the first 5 years post-operatively. Cox proportional hazards models, with age as the time scale, was used to evaluate associations of risk factors with disease-free survival and overall survival.ResultsAmong 105 patients with documented adjuvant therapy, external beam radiotherapy was administered to 25 patients (24%), chemotherapy to 24 (23%), and a combination (chemotherapy and external beam radiotherapy) to 56 (53%) patients. Most patients receiving chemotherapy and external beam radiotherapy (80%) had chemotherapy first. The majority of relapses had a distant component (31/46, 67%) and only one patient had an isolated para-aortic recurrence. Non-endometrioid subtypes had poorer disease-free survival (HR 2.57; 95% CI 1.38 to 4.78) and poorer overall survival (HR 2.00; 95% CI 1.09 to 3.65) compared with endometrioid. Among patients with endometrioid histology (n=60), chemotherapy and external beam radiotherapy improved disease-free survival (HR 0.22; 95% CI 0.07 to 0.71) and overall survival (HR 0.28; 95% CI 0.09 to 0.89) compared with chemotherapy or external beam radiotherapy alone. Combination therapy did not improve prognosis for patients with non-endometrioid histology (n=45).ConclusionsIn our cohort of patients with stage IIIC2 endometrioid endometrial cancer, those receiving chemotherapy and external beam radiotherapy had improved survival compared with patients receiving chemotherapy or external beam radiotherapy alone. However, the prognosis of patients with non-endometrioid endometrial cancer remained poor, regardless of the adjuvant therapy administered. Distant recurrences were the most common sites of failure.

Objective We previously reported an algorithm that identifies women at high risk of postoperative morbidity & mortality (M/M) as a tool to triage between neoadjuvant chemotherapy and primary surgery for epithelial ovarian cancer (EOC). We sought to independently validate its performance using multicenter data. Methods Women who underwent surgery for stage IIIC/IV EOC between 1/1/2014 and 12/31/2017 were identified from the National Surgical Quality Improvement Program database and classified as “high risk” or “triage appropriate” using our algorithm. Outcomes were compared between triage appropriate and high-risk women using the chi-square test. Results 1777 women met inclusion criteria; the mean age was 62.6 years and 81.9% had stage IIIC disease. Nationally, the surgical complexity scores were low (69.8% low, 25.2% intermediate and 5.0% high). “High risk” women had 2-fold higher rate of severe 30-day complication or death (6.2% vs 3.5%; p = 0.01), a 3-fold higher rate of 30-day mortality (1.4% vs 0.5%; p = 0.08), and a higher risk of death following a severe complication (11.1% vs. 0%, p = 0.11). A sensitivity analysis excluding women with unknown albumin who didn't meet other high risk criteria showed similar results: severe 30-day complications or death (6.2% vs 3.5%; p = 0.02) and 30-day mortality (1.4% vs 0.3%; p = 0.04) for “high risk” vs “triage appropriate” women. Conclusions Primary cytoreductive surgery to minimal residual disease remains the goal for EOC. We verify that our algorithm can identify women at risk of M/M using national multicenter data, despite a low complexity surgical setting and using 30-day mortality (vs. 90-day). Objective surgical risk assessment for ovarian cancer should be standard of care and can be incorporated into practice using the Mayo triage algorithm.

Objectives Accurate estimates of autism spectrum disorder (ASD)–associated medical costs are essential for predicting future care needs, allocating resources, identifying best practices, and modeling cost-effectiveness. Most existing studies have either employed subjective cost data or ascertained ASD using self-reported or International Classification of Diseases–coded diagnoses. Such ascertainment is especially problematic for identifying milder ASD among older individuals never diagnosed with ASD. Methods This 1976 through 2000 population-based birth-cohort study was set in Olmsted County, Minnesota. ASD cases and age- and sex-matched unaffected controls were identified by applying uniform operational research criteria for ASD (using the guidelines of the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision) after rigorous review of provider-linked medical and public, private, or home school records available for all members from birth to a maximum age of 21 years. Medical cost estimates for the 901 case-control pairs used line-item provider-linked billing data (including all payers) from 2003 through 2014 (ages 3-38 years). Outpatient pharmaceutical costs were unavailable. Temporal changes in diagnostic criteria, clinical practice, public awareness, and access were addressed by separating analyses into 5-year age group and 4-year calendar period cells. Unadjusted and adjusted (age and age plus co-occurring conditions) cost estimates were provided for cases, controls, and case-control differences. Additional factors (co-occurring conditions, percentage hospitalized, intellectual disability) were investigated using unadjusted descriptive analyses. Results Cell sample sizes ranged from 93 to 402 for age groups 3 through 19 years and from 45 to 395 for age groups 20 through 38 years. Unadjusted, age-adjusted, and fully adjusted medical costs were significantly higher for cases versus controls in 100% of cells for age groups 3 through 19 years and in 50% (unadjusted), 38% (age adjusted), and 12% (fully adjusted) of cells for age groups 20 through 38 years. Conclusions These unique estimates can help inform the construction of cost-effectiveness models; decisions by payers, providers, and policy makers; and predictions of lifetime costs.

To estimate the incidence of invasive pneumococcal disease (IPD) in the pre-13-valent pneumococcal conjugate vaccine (pre-PCV13; 7-valent pneumococcal conjugate vaccine era, 2002-2010) and post-PCV13 (2011-2018) time periods.Using the Rochester Epidemiology Project, we conducted a population-based cohort study of all IPD cases in Olmsted County, Minnesota, from January 1, 2002, to December 31, 2018.Overall, 187 cases of IPD were identified. The incidence of IPD decreased significantly from 11.1 (95% CI, 9.1 to 13.2) to 5.6 (95% CI, 4.3 to 6.9) per 100,000 person-years when the pre- and post-PCV13 periods (2002-2010 vs 2011-2018) were compared (P.001). Of the 187 patients with IPD, 112 (59.9%) had previously received at least 1 dose of pneumococcal vaccine. Among the IPD cases in the post-PCV13 period, there was an increase in non-PCV13 serotypes, mainly 11A (from 1.0% [1 of 105] to 6.2% [4 of 64]) and 33F (from 2.9% [3 of 105] to 15.6% [10 of 64]), while PCV13/non-7-valent pneumococcal conjugate vaccine serotypes declined from 38.1% (40 of 105) to 15.6% (10 of 64). At 30 days after an IPD diagnosis, the survival rate was 88.8% (95% CI, 84.4% to 93.4%).A marked decline in IPD incidence occurred during the post-PCV13 era. Because of the observed increase in non-PCV13 serotypes, coupled with multiple factors that impact the epidemiology of IPD, ongoing surveillance of patients with IPD, particularly due to non-PCV13 serotypes, is warranted.

Background: There is growing concern about the rising incidence and prevalence of food allergy globally. We previously reported the incidence of food allergy in Olmsted County, Minnesota, between 2002 and 2011. We sought to update the incidence and temporal trends of food allergies in our region through 2018. Methods: By using the Rochester Epidemiology Project, all Olmsted County residents, with an incident diagnosis of food allergy between January 2, 2012, and December 31, 2018, were identified and their medical records were reviewed. These cases were combined with the previously collected incidence cases from January 2, 2002, and December 31, 2011, to understand longitudinal trends in food allergy incidence rates. Results: Over the 17-year study period, 1076 patients (58.0% male patients, 72.1% white) were diagnosed with an incident food allergy. The median (interquartile range) age at first diagnosis was 2.0 years (1.1-8.4 years). The overall annual incidence rate for all ages was 3.9 (95% confidence interval [CI], 3.6‐4.1) per 10,000 person-years and was significantly higher in male than in female patients (4.4 [95% CI, 4.0‐4.7] and 3.3 [95% CI, 3.0‐3.6], respectively; p < 0.001). The most common food allergen was egg in infancy (57.7%), peanuts in ages 1‐4 years (58.3%), tree nuts in ages 5‐18 years (57.4%), and seafood in adults (≥19 years) (45.3%). Conclusion: The incidence of food allergy in Olmsted County steadily increased from 2002 to 2008, then remained relatively stable between the years 2008 and 2013, and again presented a rising trend over the next 5 years until 2018. This warrants further investigations into the effects of changes in guidelines for early introductions of allergenic foods and other factors that affect causality.

To evaluate recurrence-free survival (RFS) and cause-specific survival (CSS) after observation or vaginal brachytherapy (VB) alone in all subgroups of early-stage high-intermediate (HIR) and high-risk endometrial cancer (EC).We identified patients with stage I HIR (GOG-249 criteria) and stage II endometrioid EC, and stage I and II non-endometrioid EC who underwent surgery at Mayo Clinic and Cleveland Clinic between 1999 and 2016. Three-year RFS and CSS after observation or VB only were estimated in 16 subgroups defined by risk factors.Among 4156 ECs, we identified 447 (10.8%) stage I endometrioid HIR, 52 (1.3%) stage II endometrioid, 350 (8.4%) stage I non-endometrioid, and 17 (0.4%) stage II non-endometrioid ECs; observation or VB alone was applied in 349 (78.1%), 24 (46.2%), 187 (53.4%), and 2 (11.8%) patients, respectively. After observation or VB, stage I HIR endometrioid EC subgroups with2 factors among grade 3, LVSI, or stage IB had a 3-year CSS95% (lower 95% confidence intervals limit: 89.8%), whereas subgroups with ≥2 factors had poorer outcomes. No EC-related deaths after 3 years were reported in 97 stage IA non-endometrioid ECs without myometrial invasion. Stage II ECs had poor outcomes regardless of histology.Observation or VB only may be sufficient in stage I endometrioid HIR ECs with2 factors among grade 3, LVSI, or IB and in stage IA non-endometrioid ECs without myometrial invasion. Stratification of early-stage HIR and high-risk ECs into risk subgroups potentially alleviates the overtreatment and undertreatment risk and should be considered in future research.

The objective of this study was to identify characteristics associated with an increased risk of anxiety and mood disorder prior to 25 years of age, in children who sustained a traumatic brain injury (TBI) prior to age 10. This population-based study identified 562 TBI cases from a 1976–1982 birth cohort in Olmsted County, Minnesota. TBI cases were manually confirmed and classified by injury severity. Separate Cox proportional hazards regression models were fit to estimate the association of TBI and secondary non-TBI related characteristics with the risk of a subsequent clinically determined anxiety or mood disorder. Multivariable-adjusted population attributable risk (PAR) estimates were calculated for TBI characteristics. Older age at initial TBI and extracranial injury at time of initial TBI were significantly associated with an increased risk of anxiety (adjusted HR [95% CI]: 1.33 [1.16, 1.52] per 1-year increase and 2.41 [1.26, 4.59]), respectively. Older age at initial TBI was significantly associated with an increased risk of a mood disorder (adjusted HR 1.17 [1.08–1.27]). In individuals sustaining a TBI prior to age 10, age at injury greater than 5 years old was the largest contributor to development of a mood or anxiety disorder.