The impact of post-operative enteral nutrition on duodenal injury outcomes: A post hoc analysis of an EAST multicenter trial.

BACKGROUND: Leak following surgical repair of traumatic duodenal injuries results in prolonged hospitalization and oftentimes nil per os(NPO) treatment. Parenteral nutrition(PN) has known morbidity; however, duodenal leak(DL) patients often have complex injuries and hospital courses resulting in barriers to enteral nutrition(EN). We hypothesized EN alone would be associated with 1)shorter duration until leak closure and 2)less infectious complications and shorter hospital length of stay(HLOS) compared to PN. METHODS: This was a post-hoc analysis of a retrospective, multicenter study from 35 Level-1 trauma centers, including patients >14 years-old who underwent surgery for duodenal injuries(1/2010-12/2020) and endured post-operative DL. The study compared nutrition strategies: EN vs PN vs EN + PN using Chi-Square and Kruskal-Wallis tests; if significance was found pairwise comparison or Dunn's test were performed. RESULTS: There were 113 patients with DL: 43 EN, 22 PN, and 48 EN + PN. Patients were young(median age 28 years-old) males(83.2%) with penetrating injuries(81.4%). There was no difference in injury severity or critical illness among the groups, however there were more pancreatic injuries among PN groups. EN patients had less days NPO compared to both PN groups(12 days[IQR23] vs 40[54] vs 33[32],p = <0.001). Time until leak closure was less in EN patients when comparing the three groups(7 days[IQR14.5] vs 15[20.5] vs 25.5[55.8],p = 0.008). EN patients had less intra-abdominal abscesses, bacteremia, and days with drains than the PN groups(all p < 0.05). HLOS was shorter among EN patients vs both PN groups(27 days[24] vs 44[62] vs 45[31],p = 0.001). When controlling for predictors of leak, regression analysis demonstrated EN was associated with shorter HLOS(ß -24.9, 95%CI -39.0 to -10.7,p < 0.001). CONCLUSION: EN was associated with a shorter duration until leak closure, less infectious complications, and shorter length of stay. Contrary to some conventional thought, PN was not associated with decreased time until leak closure. We therefore suggest EN should be the preferred choice of nutrition in patients with duodenal leaks whenever feasible. LEVEL OF EVIDENCE: IV.

Prospective derivation and validation of a NECROtizing Soft tissue InfectionS (NECROSIS) score: An EAST multicenter trial.

BACKGROUND: Although several risk indices have been developed to aid in the diagnosis of NSTIs, these instruments suffer from varying levels of reproducibility and failure to incorporate key clinical variables in model development. The objective of this study was to derive and validate a clinical risk index score - NECROSIS - for identifying NSTIs in emergency general surgery (EGS) patients being evaluated for severe skin and soft tissue infections. METHODS: We performed a prospective study across 16 sites in the US of adult EGS patients with suspected NSTIs over a 30-month period. Variables analyzed included demographics, admission vitals and labs, physical exam, radiographic, and operative findings. The main outcome measure was the presence of NSTI diagnosed clinically at the time of surgery. Multivariate analysis was performed to identify independent predictors for the presence of NSTI using the Hosmer-Lemeshow test and the Akaike information criteria. RESULTS: Of 362 patients, 297 (82%) were diagnosed with a NSTI. Overall mortality was 12.3%. Multivariate analysis identified 3 independent predictors for NSTI: systolic blood pressure ≤ 120 mmHg, violaceous skin, and WBC ≥15 (x103/uL). Multivariate modelling demonstrated Hosmer-Lemeshow goodness of fit (p = 0.9) with a c-statistic for the prediction curve of 0.75. Test characteristics of the NECROSIS score were similar between the derivation and validation cohorts. CONCLUSION: NECROSIS is a simple and potentially useful clinical index score for identifying at-risk EGS patients with NSTIs. Future validation studies are warranted. LEVEL OF EVIDENCE: Diagnostic Tests or Criteria, Level III.

Effects of Preoperative COVID-19 Status on Emergent or Urgent Colectomy Outcomes.

OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 has been described as eliciting a powerful immune response. The association of coronavirus disease 2019 (COVID-19) infection with diseases requiring emergent or urgent colectomies may exacerbate the risk of surgical complications. We investigated the effect of preoperative COVID-19 infection on the clinical outcomes of patients who underwent a nonelective colectomy in 2021. METHODS: We queried the American College of Surgeons National Surgical Quality Improvement Program Targeted Colectomy database for all of the patients who underwent a colectomy in 2021 and filtered for patients classified as "Urgent" or "Emergent." Two groups were created based on preoperative COVID-19 status: COVID+ (n = 242) and COVID- cohorts (n = 11,049). Several clinical variables were compared. RESULTS: Before filtering for urgent/emergent operations, a large percentage of COVID+ patients were found to have undergone an urgent or emergency colectomy (68.36% vs 25.05%). Preoperatively, these patients were more likely to be taking steroids (21.49% vs 12.41%) or have a bleeding issue requiring a transfusion (19.42% vs 11.00%). A larger percentage of infected patients returned to the operating room (14.05% vs 8.13%) and had a hospital stay >30 days (18.18% vs 5.35%). COVID-19 infection was associated with a higher rate of mortality (14.05% vs 8.08%) but did not independently predict it (odds ratio 1.25, P = 0.233), with all P ≤ 0.001. CONCLUSIONS: Urgent or emergent colectomy patients who were COVID-19+ preoperatively were more likely to present with comorbidities, which, along with the recent viral infection, contributed to markedly worse clinical outcomes, including an increased rate of mortality.

Accidental substance-related acute toxicity deaths among youth in Canada: a descriptive analysis of a national chart review study of coroner and medical examiner data. / Décès accidentels attribuables à une intoxication aiguë due à une substance chez les jeunes au Canada : analyse descriptive d'une étude nationale portant sur l'examen des dossiers des données de coroners et de médecins légistes.

INTRODUCTION: Substance-related acute toxicity deaths (ATDs) are a public health crisis in Canada. Youth are often at higher risk for substance use due to social, environmental and structural factors. The objectives of this study were to understand the characteristics of youth (aged 12-24 years) dying of accidental acute toxicity in Canada and examine the substances contributing to and circumstances surrounding youth ATDs. METHODS: Data from a national chart review study of coroner and medical examiner data on ATDs that occurred in Canada between 2016 and 2017 were used to conduct descriptive analyses with proportions, mortality rates and proportionate mortality rates. Where possible, youth in the chart review study were compared with youth in the general population and youth who died of all causes, using census data. RESULTS: Of the 732 youth who died of accidental acute toxicity in 2016-2017, most (94%) were aged 18 to 24 years. Youth aged 20 to 24 who were unemployed, unhoused or living in collective housing were overrepresented among accidental ATDs. Many of the youth aged 12 to 24 who died of accidental acute toxicity had a documented history of substance use. Fentanyl, cocaine and methamphetamine were the most common substances contributing to death, and 38% of the deaths were witnessed or potentially witnessed. CONCLUSION: The findings of this study point to the need for early prevention and harm reduction strategies and programs that address mental health, exposure to trauma, unemployment and housing instability to reduce the harms of substance use on Canadian youth.

Fiduciary assignment as a potential intervention for substance use disorder: a retrospective chart review.

Background: Assignment of fiduciaries to veterans with disability payments is an intervention thought to improve quality of life; however, in veterans who use substances, a proportion of these payments may be misspent on drugs and/or alcohol. While fiduciary assignment may reduce funds available to purchase substances, clinical efficacy of this intervention in the management of substance use disorders has not been rigorously demonstrated.Objectives: The purpose of this study is to evaluate changes in clinical status before and after fiduciary assignment.Methods: This was a retrospective chart review of 50 (44 male, 6 female) veterans who were assigned a fiduciary and determined to have a substance use disorder (SUD). SUD-related data including outpatient and inpatient treatment, toxicology testing, and measures of psychosocial functioning for the three years before and after fiduciary assignment were extracted and compared.Results: Veterans were found to have higher rates of any form of employment after fiduciary assignment (Wilcoxon, Signed Ranked S-statistic = 0.22, pr = 0.02). Two changes in measures of substance use were found after fiduciary assignment. There was a reduction in positive screens for heroin (tstatistic = -2.7, p = .01), but an increase in positive screens for fentanyl (t statistic = 2.53, p = .02). There were some potentially clinically but not statistically significant trends in increased adherence with mental health appointments, number of medical hospitalizations, and rates of employment post-fiduciary assignment.Conclusions: Understanding the clinical impact of fiduciary assignment for veteran's benefits is desirable but still pending at this time.

Effects of the COVID-19 Pandemic on Colectomy Outcomes for Inflammatory Bowel Disease.

OBJECTIVES: Inflammatory bowel disease (IBD) encompasses Crohn's disease (CD) and ulcerative colitis (UC). These two chronic inflammatory conditions can differ in severity, presentation, and anatomical localization, and can greatly affect quality of life if not managed properly. Given the many healthcare challenges during the coronavirus disease 2019 pandemic, we studied the effects of the pandemic and corresponding changes to medical resources on surgical outcomes for patients with IBD. METHODS: Deidentified data from patients who underwent a colectomy for CD or UC were collected from the National Surgical Quality Improvement Program database of the American College of Surgeons. We analyzed clinical factors and surgical outcomes between 2019 and 2020. RESULTS: Patients with IBD were more likely to have lost >10% of their body mass before the operation in 2020. Operations for patients with UC were significantly shorter in the first year of the pandemic. Patients with CD were less likely to have a urinary tract infection or sepsis postoperatively in 2020, whereas patients with UC were more likely to require a repeat operation. Interestingly, both patient populations were less likely to undergo an emergency operation in 2020 than in 2019. CONCLUSIONS: Colectomy outcomes for patients with CD in 2020 were similar or improved in comparison with those seen in 2019, whereas colectomies for UC saw a statistically but not clinically significant increase in the rate of repeat operations. Overall, these patients seem to have been well managed despite the coronavirus disease 2019 pandemic-induced strain on the healthcare system.

Trauma Surgeons Experience Compassion Fatigue - A Major Metropolitan Area Survey.

INTRODUCTION: Compassion Fatigue (CF), the physical, emotional, and psychological impact of helping others, is composed of three domains: Compassion Satisfaction (CS), Secondary Traumatic Stress (STS), and Burnout (BO). Trauma surgeons (TS) experience work-related stress resulting in high rates of CF which can manifest as physical and psychological disorders. We hypothesized that TS experience CF and there are potentially modifiable systemic factors to mitigate its symptoms. METHODS: All TS in a major metropolitan area were eligible. Personal and professional demographic information was obtained. Each participant completed six validated surveys: 1) Professional Quality of Life Scale (Pro-QOL), 2) Perceived Stress Scale (PSS), 3) Multidimensional Scale of Perceived Social Support (MSPSS), 4) Adverse Childhood Events (ACE) Questionnaire, 5) Brief Coping Inventory (BCI), and 6) Toronto Empathy Questionnaire (TEQ). CF subscale risk scores (low:<23, moderate:23-41, high:>41) were recorded. Linear regression analysis assessed the demographic and environmental factors association with BO, STS, and CS. Variables significant on univariate analysis were included in multivariate models to determine the independent influence on BO, STS, and CS. Significance was p ≤ 0.05. RESULTS: There were 57 TS (response rate:75.4% (n = 43); Caucasian: 65% (n = 28), male:67% (n = 29)). TS experienced CF (BO:26 (IQR: 21-32), STS:23 (IQR: 19-32), CS:39 (IQR: 34-45)). The PSS score was significantly associated with increased BO (Coef: 0.52, 95% CI: 0.28-0.77) and STS (Coef: 0.44. 95% CI: 0.15-0.73), and decreased CS (Coef: -0.51, 95% CI: -0.80- -0.23) (p < 0.01). Night shifts were associated with higher BO (Coef: 1.55, 95% CI: 0.07-3.03, p = 0.05), conversely day shifts were associated with higher STS (Coef: 1.94, 95% CI: 0.32-3.56, p = 0.03). Higher TEQ scores were associated with greater CS (Coef: 0.33, 95% CI: 0.12-0.55, p < 0.01). CONCLUSION: TS experience moderate BO and STS associated with modifiable system- and work-related stressors. Efforts to reduce CF should focus on addressing sources of workplace stress and promoting empathic care. LEVEL OF EVIDENCE: III, Prognostic and Epidemiological.

Apolipoprotein E and Its Association With Cognitive Change and Modification of Treatment Effects of Vitamin D3 and Omega-3s on Cognitive Change: Results From the In-Clinic Subset of a Randomized Clinical Trial.

BACKGROUND: Apolipoprotein E (APOE)-ε4 allele is associated with cognitive decline; however, its potential to modify effects of vitamin D3 and omega-3s supplementation on later-life cognition is unclear. Our objectives were to estimate among the in-clinic subset of a randomized trial: (1) associations between APOE-ε4 and global and domain-specific cognitive change, with exploration of potential sex and race differences; and (2) modification by APOE-ε4 of effects of vitamin D3 and omega-3s supplementation on cognitive change. METHODS: From an ancillary study of depression prevention within a completed 2 × 2 factorial trial testing vitamin D3 (2 000 IU per day), omega-3s (1 g per day), and/or placebos, we included 743 older adults with baseline in-person neuropsychiatric assessments and APOE genotyping data. The primary outcome was change in global cognition (averaging z-scores of 9 tests) over 2 years. Secondarily, episodic memory and executive function/attention z-scores were examined. General linear models of response profiles with multiplicative interaction terms were constructed; stratified results were reported. RESULTS: Mean age (standard deviation) was 67.1 (5.3) years; 50.6% were females; 24.9% were APOE-ε4 carriers. Compared to noncarriers, APOE-ε4 carriers had worse 2-year change in global cognition and episodic memory; differences were more apparent among females than males. There was no variation by race in APOE-ε4 associations with cognition. APOE-ε4 did not significantly modify effects of vitamin D3 or omega-3s, compared to placebo, on change in global cognition, episodic memory, or executive function/attention. CONCLUSIONS: APOE-ε4 was associated with worse cognition but did not modify overall effects of vitamin D3 or omega-3 supplementation on cognition over 2 years.

How the COVID-19 pandemic affected the severity and clinical presentation of diverticulitis.

BACKGROUND/AIMS: Single-institution studies showed that patients presented with more severe diverticulitis and underwent more emergency operations during the coronavirus disease 2019 (COVID-19) pandemic. Therefore, we studied this trend using nationwide data from the American College of Surgeons National Surgical Quality Improvement Program database. METHODS: Patients (n = 23,383) who underwent a colectomy for diverticulitis in 2018 (control year) and 2020 (pandemic year) were selected. We compared these groups for differences in disease severity, comorbidities, perioperative factors, and complications. RESULTS: During the pandemic, colonic operations for diverticulitis decreased by 13.14%, but the rates of emergency operations (17.31% vs. 20.04%, P< 0.001) and cases with a known abscess/perforation (50.11% vs. 54.55%, P< 0.001) increased. Likewise, the prevalence of comorbidities, such as congestive heart failure, acute renal failure, systemic inflammatory response syndrome, and septic shock, were higher during the pandemic (P< 0.05). During this same period, significantly more patients were classified under American Society of Anesthesiologists classes 3, 4, and 5, suggesting their preoperative health states were more severe and life-threatening. Correspondingly, the average operation time was longer (P< 0.001) and complications, such as organ space surgical site infection, wound disruption, pneumonia, acute renal failure, septic shock, and myocardial infarction, increased (P< 0.05) during the pandemic. CONCLUSIONS: During the pandemic, surgical volume decreased, but the clinical presentation of diverticulitis became more severe. Due to resource reallocation and possibly patient fear of seeking medical attention, diverticulitis was likely underdiagnosed, and cases that would have been elective became emergent. This underscores the importance of monitoring patients at risk for diverticulitis and intervening when criteria for surgery are met.

Racial Disparities in Clinical Outcomes of Emergency Colectomies for Diverticulitis.

OBJECTIVES: The literature suggests that there are ongoing racial disparities in healthcare outcomes between patients in White and non-White populations. As such, we examined the outcomes of patients who underwent an emergency colectomy for diverticulitis. METHODS: We identified 4841 White and 590 non-White patients, which include Black/African American and Asian patients, using the 2016-2019 American College of Surgeons National Surgical Quality Improvement Program databases. We compared Black/African American and Asian patients with White patients for differences in surgical outcomes. RESULTS: Non-White patients had more comorbidities than White patients (P < 0.05). These patients underwent longer operations, developed more postoperative complications, and were more likely to have lengths of stay >30 days. When controlling for all of the covariates in multivariate logistic regression models, White race was independently associated with a 22.14% lower odds of a hospital stay >30 days compared with non-White patients (P = 0.001). CONCLUSIONS: In this study, non-White patients developed more complications than did White patients and had longer hospitalizations. These disparities represent a more complex societal issue that cannot be managed perioperatively alone.

Sympathetic innervation of the supraclavicular brown adipose tissue: A detailed anatomical study.

BACKGROUND: The supraclavicular fossa is the dominant location for human brown adipose tissue (BAT). Activation of BAT promotes non-shivering thermogenesis by utilization of glucose and free fatty acids and has been the focus of pharmacological and non-pharmacological approaches for modulation in order to improve body weight and glucose homeostasis. Sympathetic neural control of supraclavicular BAT has received much attention, but its innervation has not been extensively investigated in humans. METHODS: Dissection of the cervical region in human cadavers was performed to find the distribution of sympathetic nerve branches to supraclavicular fat pad. Furthermore, proximal segments of the 4th cervical nerve were evaluated histologically to assess its sympathetic components. RESULTS: Nerve branches terminating in supraclavicular fat pad were identified in all dissections, including those from the 3rd and 4th cervical nerves and from the cervical sympathetic plexus. Histology of the proximal segments of the 4th cervical nerves confirmed tyrosine hydroxylase positive thin nerve fibers in all fascicles with either a scattered or clustered distribution pattern. The scattered pattern was more predominant than the clustered pattern (80% vs. 20%) across cadavers. These sympathetic nerve fibers occupied only 2.48% of the nerve cross sectional area on average. CONCLUSIONS: Human sympathetic nerves use multiple pathways to innervate the supraclavicular fat pad. The present finding serves as a framework for future clinical approaches to activate human BAT in the supraclavicular region.

Assessment of Risk Factors for Iatrogenic Genitourinary Injuries During a Proctectomy.

BACKGROUND: It is critical to avoid iatrogenic injuries affecting genitourinary organs in order to prevent postoperative urinary or sexual dysfunction, which lead to lengthier recovery and possibly reoperation. METHODS: Using the 2016-2019 American College of Surgeons National Quality Improvement Program (ACS NSQIP) Targeted Proctectomy Database, we collated 2577 patients with non-metastatic rectal cancer who underwent a laparoscopic or open proctectomy. Univariate analysis was used to identify differences in perioperative factors and genitourinary injuries (GUIs) between operative approaches, and multivariate logistic regression was used to identify independent risk factors for sustaining an intraoperative GUI. RESULTS: The rates of preoperative comorbidities were significantly higher among patients who received an open operation. The proportion of GUIs was also significantly higher in this patient population. Multivariate logistic regression demonstrated that patients who underwent a laparoscopic proctectomy were associated with a 51.4% lower risk of sustaining a GUI. Furthermore, >10% body weight loss in the past 6 months and ASA class 3 status were independently associated with a higher risk of GUI regardless of operation type. CONCLUSION: Patients who undergo a laparoscopic proctectomy are associated with a lower risk of GUI. On the other hand, patients with >10% body weight loss and ASA class 3: Severe Systemic Disease were associated with a higher risk of GUI.

Relation of serum BDNF to major depression and exploration of mechanistic roles of serum BDNF in a study of vitamin D3 and omega-3 supplements for late-life depression prevention.

This study: 1) examined cross-sectional and longitudinal relations of serum brain-derived neurotrophic factor (BDNF) to late-life depression (LLD); 2) tested effects of vitamin D3 and omega-3s on change in BDNF; 3) explored modifying or mediating roles of BDNF on effects of vitamin D3 and omega-3s for LLD. We selected 400 adults from a completed trial of vitamin D3 and omega-3 supplements for LLD prevention. BDNF was measured using an enzyme-linked immunosorbent assay. We administered semi-structured diagnostic interviews and Patient Health Questionnaire [PHQ]-9 to ascertain outcomes at baseline (depression caseness vs. non-caseness; PHQ-9) and at 2-year follow-up among baseline non-depressed individuals (incident vs. no incident MDD; change in PHQ-9). At baseline, while there were no significant differences in mean serum BDNF comparing depression cases and non-cases, being in the lowest vs. highest serum BDNF quartile was significantly associated with worse depressive symptoms. There were no significant longitudinal associations between serum BDNF and LLD. Neither supplement significantly affected change in BDNF; serum BDNF did not appear to modify or mediate treatment effects on LLD. In conclusion, we observed significant cross-sectional but not longitudinal associations between serum BDNF levels and LLD. Vitamin D3 or omega-3s did not alter serum BDNF over 2 years.

When public health crises collide: 5 years of pediatric firearm injury prevention opportunities.

Objectives: Prior publications on pediatric firearm-related injuries have emphasized significant social disparities. The pandemic has heightened a variety of these societal stresses. We sought to evaluate how we must now adapt our injury prevention strategies. Patients and methods: Firearm-related injuries in children 15 years old and under at five urban level 1 trauma centers between January 2016 and December 2020 were retrospectively reviewed. Age, gender, race/ethnicity, Injury Severity Score, situation, timing of injury around school/curfew, and mortality were evaluated. Medical examiner data identified additional deaths. Results: There were 615 injuries identified including 67 from the medical examiner. Overall, 80.2% were male with median age of 14 years (range 0-15; IQR 12-15). Black children comprised 77.2% of injured children while only representing 36% of local schools. Community violence (intentional interpersonal or bystander) injuries were 67.2% of the cohort; 7.8% were negligent discharges; and 2.6% suicide. Median age for intentional interpersonal injuries was 14 years (IQR 14-15) compared with 12 years (IQR 6-14, p<0.001) for negligent discharges. Far more injuries were seen in the summer after the stay-at-home order (p<0.001). Community violence and negligent discharges increased in 2020 (p=0.004 and p=0.04, respectively). Annual suicides also increased linearly (p=0.006). 5.5% of injuries were during school; 56.7% after school or during non-school days; and 34.3% were after legal curfew. Mortality rate was 21.3%. Conclusions: Pediatric firearm-related injuries have increased during the past 5 years. Prevention strategies have not been effective during this time interval. Prevention opportunities were identified specifically in the preteenage years to address interpersonal de-escalation training, safe handling/storage, and suicide mitigation. Efforts directed at those most vulnerable need to be reconsidered and examined for their utility and effectiveness. Level of evidence: Level III; epidemiological study type.

Effects of Vitamin D3 and Marine Omega-3 Fatty Acids Supplementation on Indicated and Selective Prevention of Depression in Older Adults: Results From the Clinical Center Sub-Cohort of the VITamin D and OmegA-3 TriaL (VITAL).

Objective: To test vitamin D3 and omega-3 fatty acids (omega-3s) for late-life depression prevention under the National Academy of Medicine framework for indicated (targeting subthreshold depression) and selective (targeting presence of high-risk factors) prevention.Methods: The VITamin D and OmegA-3 TriaL (VITAL) is a 2 × 2 factorial trial of vitamin D3 (2,000 IU/d) and/or omega-3s (1 g/d) for cardiovascular and cancer prevention (enrollment: November 2011-March 2014; end date: December 31, 2017). In this targeted prevention study, we included 720 VITAL clinical sub-cohort participants who completed neurobehavioral assessments at baseline and 2 years (91.9% retention). High-risk factors were subthreshold or clinical anxiety, impaired activities of daily living, physical/functional limitation, medical comorbidity, cognitive impairment, caregiving burden, problem drinking, and low psychosocial support. Coprimary outcomes were incident major depressive disorder (MDD), adjudicated using DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition), and change in mood (Patient Health Questionnaire-9 [PHQ-9]). We used exact tests to determine treatment effects on MDD incidence and repeated-measures models to determine treatment effects on PHQ-9.Results: A total of 11.1% had subthreshold depression, 60.8% had ≥ 1 high-risk factor, MDD incidence was 4.7% (5.1% among completers), and mean PHQ-9 score change was 0.02 points. Among those with subthreshold depression, the MDD risk ratio (95% confidence interval) was 0.36 (0.06 to 1.28) for vitamin D3 and 0.85 (0.25 to 2.92) for omega-3s, compared to placebo; results were also null among those with ≥ 1 high-risk factor (vitamin D3 vs placebo: 0.63 [0.25 to 1.53]; omega-3s vs placebo: 1.08 [0.46 to 2.71]). There were no significant differences in PHQ-9 score change comparing either supplement with placebo.Conclusions: Neither vitamin D3 nor omega-3s showed benefits for indicated and selective prevention of late-life depression; statistical power was limited.Trial Registration: ClinicalTrials.gov identifier: NCT01696435.

Pilot Study of Second-Generation DNA Methylation Epigenetic Markers in Relation to Cognitive and Neuropsychiatric Symptoms in Older Adults.

BACKGROUND: Associations between epigenetic aging with cognitive aging and neuropsychiatric measures are not well-understood. OBJECTIVE: 1) To assess cross-sectional correlations between second-generation DNA methylation (DNAm)-based clocks of healthspan and lifespan (i.e., GrimAge, PhenoAge, and DNAm-based estimator of telomere length [DNAmTL]) and cognitive and neuropsychiatric measures; 2) To examine longitudinal associations between change in DNAm markers and change in cognition over 2 years. METHODS: Participants were members of VITAL-DEP (VITamin D and OmegA-3 TriaL- Depression Endpoint Prevention) study. From previously ascertained cognitive groups (i.e., cognitively normal and mild cognitive impairment), we randomly selected 45 participants, aged≥60 years, who completed in-person neuropsychiatric assessments at baseline and 2 years. The primary outcome was global cognitive score (averaging z-scores of 9 tests). Neuropsychiatric Inventory severity scores were mapped from neuropsychiatric symptoms (NPS) from psychological scales and structured diagnostic interviews. DNAm was assayed using Illumina MethylationEPIC 850K BeadChip at baseline and 2 years. We calculated baseline partial Spearman correlations between DNAm markers and cognitive and NPS measures. We constructed multivariable linear regression models to examine longitudinal relations between DNAm markers and cognition. RESULTS: At baseline, we observed a suggestive negative correlation between GrimAge clock markers and global cognition but no signal between DNAm markers and NPS measures. Over 2 years: each 1-year increase in DNAmGrimAge was significantly associated with faster declines in global cognition; each 100-base pair increase in DNAmTL was significantly associated with better global cognition. CONCLUSION: We found preliminary evidence of cross-sectional and longitudinal associations between DNAm markers and global cognition.

Screening young adult cancer survivors for depression and anxiety with the Primary Care Evaluation of Mental Disorders (PRIME-MD): Comparisons with a structured clinical diagnostic interview.

OBJECTIVE: Survivorship guidelines recommend screening for depression and anxiety in young adult cancer survivors (YACS), but research validating measures in this population is limited. The current study aimed to examine use of the Primary Care Evaluation of Mental Disorders (PRIME-MD) to screen for depression and anxiety in YACS. METHODS: 249 YACS (aged 18-40, 50% male) completed PRIME-MD via Telephone Automated Computer Assisted Structured Interview and the Structured Clinical Interview for the DSM-IV (SCID) via in-person interview. SCID responses were scored to identify depressive and anxiety symptoms and diagnoses. PRIME-MD was scored to identify YACS reaching the symptom threshold (≥1 depressive or anxiety symptom) and diagnostic threshold for depressive or anxiety disorder. ROC analyses evaluated concordance of the PRIME-MD with the SCID. RESULTS: The PRIME-MD depressive symptom threshold had excellent discrimination compared to SCID depressive diagnosis (AUC = 0.83) with high sensitivity (86%) and specificity (81%). Similarly, the PRIME-MD depressive diagnosis threshold had excellent discrimination compared to SCID depressive diagnosis (AUC = 0.86) as well as high sensitivity (86%) and specificity (86%). No PRIME-MD threshold met sensitivity (≥0.85) and specificity (≥0.75) criteria for identifying SCID depressive symptoms, anxiety disorders, or anxiety symptoms. CONCLUSIONS: PRIME-MD has potential utility as a screening measure of depressive disorders in YACS. The PRIME-MD depressive symptom threshold may be particularly useful in survivorship clinics as it requires only two items be administered. However, PRIME-MD does not meet study criteria for a standalone screen for anxiety disorders, anxiety symptoms, or depressive symptoms in YACS.

Reducing Prenatal Alcohol Exposure and the Incidence of FASD: Is the Past Prologue?

PURPOSE: This narrative review summarizes and synthesizes the clinical trials and randomized clinical trials that evaluated selected and targeted approaches to reducing preconception and prenatal alcohol exposure (PAE) and alcohol-exposed pregnancy (AEP) since 2011. SEARCH METHODS: A professional hospital librarian completed the primary search using strategies specified within this review, resulting in 94 records returned in PubMed, Ovid MEDLINE, Clinical Key, the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. The author completed two supplementary literature searches. SEARCH RESULTS: From the total of 238 records returned from the three searches, 217 records were eliminated. Elimination reasons included other medical problem (119); duplicate entry (34); no content/results (23); secondary analysis (16); focus on effects of PAE (9); treatment of childhood fetal alcohol spectrum disorders (FASD) (6); maternal risk factors (3); and other (7). The remaining 21 studies were included with four overarching themes: (1) case management efforts (n = 4); (2) preconception efforts to reduce AEP (n = 5); (3) motivational interviewing and screening, brief intervention, and referral to treatment (n = 2); and (4) use of technology to deliver the intervention (n = 10). DISCUSSION AND CONCLUSIONS: Case management and home visits did not appear to have strong current empirical support. Study limitations included small sample sizes and no comparison groups, whereas larger efforts did not demonstrate definitive advantages to justify this intensive approach. The studies of preconception efforts, all based on the Project CHOICES approach, had similar outcomes, with the reduction in AEP risk largely due to improved contraception in women of childbearing age who were sexually active and drank alcohol but were not pregnant. It is unknown whether these women refrained from alcohol use when they became pregnant. Two studies of motivational interviewing to reduce prenatal alcohol use did not demonstrate the efficacy of the intervention. Both were small, with less than 200 pregnant women combined; moreover, the study samples had low baseline levels of alcohol use, allowing little opportunity for improvement. Finally, studies evaluating the impact of technological approaches to reducing AEP were reviewed. These exploratory investigations had small sample sizes and provided preliminary evaluations of techniques such as text messages, telephone contact, computer-based screening, and motivational interviewing. The potentially promising findings may inform future research and clinical efforts. Future directions may include research to address the limitations of the evidence to date and should reflect the complexities of FASD that include the biological and social context associated with prenatal alcohol use.

Outcomes among trauma patients with duodenal leak following primary versus complex repair of duodenal injuries: An Eastern Association for the Surgery of Trauma multicenter trial.

BACKGROUND: Duodenal leak is a feared complication of repair, and innovative complex repairs with adjunctive measures (CRAM) were developed to decrease both leak occurrence and severity when leaks occur. Data on the association of CRAM and duodenal leak are sparse, and its impact on duodenal leak outcomes is nonexistent. We hypothesized that primary repair alone (PRA) would be associated with decreased duodenal leak rates; however, CRAM would be associated with improved recovery and outcomes when leaks do occur. METHODS: A retrospective, multicenter analysis from 35 Level 1 trauma centers included patients older than 14 years with operative, traumatic duodenal injuries (January 2010 to December 2020). The study sample compared duodenal operative repair strategy: PRA versus CRAM (any repair plus pyloric exclusion, gastrojejunostomy, triple tube drainage, duodenectomy). RESULTS: The sample (N = 861) was primarily young (33 years) men (84%) with penetrating injuries (77%); 523 underwent PRA and 338 underwent CRAM. Complex repairs with adjunctive measures were more critically injured than PRA and had higher leak rates (CRAM 21% vs. PRA 8%, p < 0.001). Adverse outcomes were more common after CRAM with more interventional radiology drains, prolonged nothing by mouth and length of stay, greater mortality, and more readmissions than PRA (all p < 0.05). Importantly, CRAM had no positive impact on leak recovery; there was no difference in number of operations, drain duration, nothing by mouth duration, need for interventional radiology drainage, hospital length of stay, or mortality between PRA leak versus CRAM leak patients (all p > 0.05). Furthermore, CRAM leaks had longer antibiotic duration, more gastrointestinal complications, and longer duration until leak resolution (all p < 0.05). Primary repair alone was associated with 60% lower odds of leak, whereas injury grades II to IV, damage control, and body mass index had higher odds of leak (all p < 0.05). There were no leaks among patients with grades IV and V injuries repaired by PRA. CONCLUSION: Complex repairs with adjunctive measures did not prevent duodenal leaks and, moreover, did not reduce adverse sequelae when leaks did occur. Our results suggest that CRAM is not a protective operative duodenal repair strategy, and PRA should be pursued for all injury grades when feasible. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Evaluating posttraumatic stress in young adult cancer survivors: Implications of revised DSM-5 traumatic event criteria.

OBJECTIVE: The Diagnostic and Statistical Manual for Psychiatric Diagnoses (DSM-5) significantly narrowed conditions under which life-threatening illnesses meet qualifying traumatic event (QTE) criteria for posttraumatic stress disorder (PTSD). To investigate the impact of this change on identification of PTSD in young adult cancer survivors (YACS), we compared prevalence of QTE exposure using DSM-5 and earlier DSM-IV criteria. METHODS: The Structured Clinical Interview for the DSM-5 (SCID-5) was customized for study goals and administered to a convenience sample of 250 YACS ages 18-40 followed at a single cancer center. RESULTS: The SCID-5 was well-tolerated by participants and estimated duration was brief (33 min; range 12-75). Only 35 interviews (14%) presented complex scoring questions. 168 participants (67.2%) identified cancer as their "most stressful or traumatic experience." Applying DSM-IV criteria, 227 YACS (90.8%) reported any QTEs; prevalence was significantly reduced following more restrictive DSM-5 QTE criteria, with only 124 YACS (49.6%) reporting ≥1 QTE (z = -9.68, p < 0.001). CONCLUSIONS: The SCID-5 can be successfully adapted to assess QTEs in YACS following both DSM-IV and DSM-5 criteria. DSM-5 criteria significantly limit prevalence of QTE exposures compared with DSM-IV. As the majority of YACS identify cancer as their most stressful life event, it is critically important to investigate its impact on their psychological functioning. Until more is known about how PTSD symptoms may arise after cancer, clinicians and researchers should adapt PTSD assessments to systematically evaluate the role of cancer as a traumatic event that may lead to PTSD symptoms in YACS.