CRISPRi screen of long non-coding RNAs identifies LINC03045 regulating glioblastoma invasion.

INTRODUCTION: Glioblastoma (GBM) invasion studies have focused on coding genes, while few studies evaluate long non-coding RNAs (lncRNAs), transcripts without protein-coding potential, for role in GBM invasion. We leveraged CRISPR-interference (CRISPRi) to evaluate invasive function of GBM-associated lncRNAs in an unbiased functional screen, characterizing and exploring the mechanism of identified candidates. METHODS: We implemented a CRISPRi lncRNA loss-of-function screen evaluating association of lncRNA knockdown (KD) with invasion capacity in Matrigel. Top screen candidates were validated using CRISPRi and oligonucleotide(ASO)-mediated knockdown in three tumor lines. Clinical relevance of candidates was assessed via The Cancer Genome Atlas(TCGA) and Genotype-Tissue Expression(GTEx) survival analysis. Mediators of lncRNA effect were identified via differential expression analysis following lncRNA KD and assessed for tumor invasion using knockdown and rescue experiments. RESULTS: Forty-eight lncRNAs were significantly associated with 33-83% decrease in invasion (p<0.01) upon knockdown. The top candidate, LINC03045, identified from effect size and p-value, demonstrated 82.7% decrease in tumor cell invasion upon knockdown, while LINC03045 expression was significantly associated with patient survival and tumor grade(p<0.0001). RNAseq analysis of LINC03045 knockdown revealed that WASF3, previously implicated in tumor invasion studies, was highly correlated with lncRNA expression, while WASF3 KD was associated with significant decrease in invasion. Finally, WASF3 overexpression demonstrated rescue of invasive function lost with LINC03045 KD. CONCLUSION: CRISPRi screening identified LINC03045, a previously unannotated lncRNA, as critical to GBM invasion. Gene expression is significantly associated with tumor grade and survival. RNA-seq and mechanistic studies suggest that this novel lncRNA may regulate invasion via WASF3.

Crowdfunding for Gender-Affirming Mastectomy: Balancing Fundraising With Loss of Privacy.

INTRODUCTION: Limitations in insurance coverage may cause patients to turn to crowdfunding to raise money for gender-affirming procedures. In this study, we analyze the impact of Medicaid insurance coverage on gender-affirming mastectomy campaigns posted on GoFundMe.com. METHODS: Between March 1 and 12, 2021, we accessed GoFundMe.com to analyze available campaigns requesting monetary contributions for gender-affirming mastectomy. Campaigns were identified using the search term "top surgery" followed by the state's name. Duplicate campaigns, campaigns whose primary goal was not gender-affirming mastectomy, and ongoing campaigns were excluded. Campaigns were then categorized according to their state's coverage of gender-affirming surgery: explicit exclusion (EE), explicit inclusion (EI), or no explicit statement of gender-affirming care. We collected data on the number of donors and shares, the fundraising goal, and the total amount raised for each campaign. Common themes within campaign narratives were identified and assessed by each reviewer. Finally, we collected data on the photographs posted by campaign creators. RESULTS: Our search yielded 790 campaigns, with an overall mean of 58 ± 99 donors and 212 ± 288 shares. The mean fundraising goal and amount raised among all campaigns were $6811 ± $5027 and $2579 ± $3072, respectively. Fundraising goals were most likely to be met in an EI state than an EE state (26.3% vs 8.1%; P < 0.001). The mean amount sought was highest in EE states and lowest in EI states, whereas the mean amount raised was lowest in EE states and highest in EI states. Of the campaigns, 97.1% mentioned personal or situational characteristics in the narrative section; 16.2% of all campaigns expressed negative feelings about posting on GoFundMe.com to raise money for their surgeries. CONCLUSION: Disparities in health care coverage of gender-affirming surgeries were seen between state categories, with a decreased need for crowdfunding in states explicitly including coverage of gender-affirming surgery. Many transgender patients used crowdfunding to pay for transition-related health care costs, relying on the kindness of strangers and their social network at the expense of their personal privacy. Expansion of legislative coverage of gender-affirming surgeries may alleviate some of this financial burden and reduce transgender patients' reliance on crowdfunding campaigns.

Establishing an open and robotic pancreatic surgery program in a level 1 trauma center community teaching hospital and comparing its outcomes to high-volume academic center outcomes: a retrospective review.

BACKGROUND: The debate of whether to centralize hepato-pancreato-biliary surgery has been ongoing. The principal objective was to compare outcomes of a community pancreatic surgical program with those of high-volume academic centers. METHODS: The current pancreatic surgical study occurred in an environment where (1) a certified abdominal transplant surgeon performed all surgeries; (2) complementary quality enhancement programs had been developed; (3) the hospital's trauma center had been verified; and (4) the hospital's surgical training had been accredited. Pancreatic surgical outcomes at high-volume academic centers were obtained through PubMed literature searches. Articles were selected if they described diverse surgical procedures. Two-tailed Fisher exact and mid-P tests were used to perform 2 × 2 contingency analyses. RESULTS: The study patients consisted of 64 consecutive pancreatic surgical patients. The study patients had a similar pancreaticoduodenectomy proportion (59.4%) when compared to literature patients (66.8%; P = 0.227). The study patients also had a similar distal pancreatectomy proportion (25.0%) when compared to literature patients (31.9%; P = 0.276). The study patients had a significantly higher American Society of Anesthesiologists physical status ≥ 3 proportion (100%) than literature patients (28.1%; P < 0.001). The 90-day study mortality proportion (0%) was similar to the literature proportion (2.3%; P = 0.397). The study postoperative pancreatic fistula proportion was lower (3.2%), when compared to the literature proportion (18.4%; P < 0.001; risk ratio = 5.8). The study patients had a lower reoperation proportion (3.1%) than the literature proportion (8.7%; mid-P = 0.051; risk ratio = 2.8). The study patients had a lower surgical site infection proportion (3.1%) than those in the literature (21.1%; P < 0.001; risk ratio = 6.8). The study patients had equivalent delayed gastric emptying (15.6%) when compared to literature patients (10.6%; P = 0.216). The study patients had decreased Clavien-Dindo grades III-IV complications (10.9%) compared to the literature patients (21.8%; mid-P = 0.018). Lastly, the study patients had a similar readmission proportion (20.3%) compared to literature patients (18.4%; P = 0.732). CONCLUSION: Despite pancreatic surgical patients having greater preoperative medical comorbidities, the current community study outcomes were comparable to or better than high-volume academic center results.

Activity in nature mediates a park prescription intervention's effects on physical activity, park use and quality of life: a mixed-methods process evaluation.

BACKGROUND: This process evaluation explored the implementation and mechanisms of impact of a Park Prescription Intervention trial (PPI), including the effects of hypothesised mediators (motivation, social support, recreational physical activity [PA], park use and park PA) on trial outcomes. METHODS: Participants from the community were randomly allocated to intervention (n = 80) or control (n = 80) group. The intervention included baseline counselling, a prescription of exercise in parks, materials, three-month follow-up counselling and 26 weekly group exercise sessions in parks. Process evaluation indicators were assessed at three- and six-months. Implementation indicators included participation rates in intervention components and survey questions plus focus group discussions (FGDs) to understand which components participants valued. FGDs further assessed barriers and facilitators to intervention participation. To explore mechanisms of impact, linear regression was used to compare objectively measured PA between quantiles of group exercise participation. Structural equation modelling (SEM) explored hypothesised mediation of the significant intervention effects. Framework analysis was conducted for FGDs. RESULTS: Participants were middle-aged (mean 51, SD ± 6.3 years), predominantly female (79%) and of Chinese ethnicity (81%). All intervention participants received baseline counselling, the park prescription and materials, whilst 94% received the follow-up counselling. Mean minutes of moderate-to-vigorous PA/week (95% CI) differed by group exercise participation (p = 0.018): 0% participation (n = 18) 128.3 (69.3, 187.2) minutes, > 0-35.9% participation (n = 18) 100.3 (36.9, 163.6) minutes, > 35.9-67.9% participation (n = 17) 50.5 (- 4.9, 105.9) minutes and > 67.9% participation (n = 18) 177.4 (122.0, 232.8) minutes. Park PA at three-months had significant mediating effects (95% CI) on recreational PA 26.50 (6.65, 49.37) minutes/week, park use 185.38 (45.40, 353.74) minutes/month, park PA/month 165.48 (33.14, 334.16) minutes and psychological quality of life score 1.25 (0.19, 2.69) at six-months. Prioritising time with family and preferences for unstructured activities were barriers to intervention participation. Human interaction via follow-up or group exercise were facilitators. CONCLUSION: This process evaluation showed park PA consistently mediated effects of the PPI, suggesting activity in parks was a mechanism of its effects. To optimise effectiveness, participants' preference for prioritising time with family through family involvement and tailoring the intervention to participants' preferences for structured or unstructured PA could be considered in future studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT02615392 , 26 November 2015.

Tenacious Endemic Typhoid Fever in Samoa.

BACKGROUND: Typhoid fever has been endemic on the island nation of Samoa (2016 population, 195 979) since the 1960s and has persisted through 2019, despite economic development and improvements in water supply and sanitation. METHODS: Salmonella enterica serovar Typhi isolates from the 2 hospitals with blood culture capability and matched patient demographic and clinical data from January 2008 through December 2019 were analyzed. Denominators to calculate incidence by island, region, and district came from 2011 and 2016 censuses and from 2017-2019 projections from Samoa's Bureau of Statistics. Data were analyzed to describe typhoid case burden and incidence from 2008 to 2019 by time, place, and person. RESULTS: In sum, 53-193 blood culture-confirmed typhoid cases occurred annually from 2008 to 2019, without apparent seasonality. Typhoid incidence was low among children age < 48 months (17.6-27.8/105), rose progressively in ages 5-9 years (54.0/105), 10-19 years (60.7-63.4/105), and 20-34 years (61.0-79.3/105), and then tapered off; 93.6% of cases occurred among Samoans < 50 years of age. Most typhoid cases and the highest incidence occurred in Northwest Upolu, but Apia Urban Area (served by treated water supplies) also exhibited moderate incidence. The proportion of cases from short-cycle versus long-cycle transmission is unknown. Samoan S. Typhi are pansusceptible to traditional first-line antibiotics. Nevertheless, enhanced surveillance in 2019 detected 4 (2.9%) deaths among 140 cases. CONCLUSIONS: Typhoid has been endemic in Samoa in the period 2008-2019. Interventions, including mass vaccination with a Vi-conjugate vaccine coadministered with measles vaccine are planned.

Effectiveness of prescribing physical activity in parks to improve health and wellbeing - the park prescription randomized controlled trial.

BACKGROUND: Programs promoting population health through physical activity (PA) and exposure to nature are popular, but few have been evaluated in randomized-controlled trials (RCTs). OBJECTIVE: To investigate the effectiveness of a park prescription intervention (PPI) for improving total moderate-to-vigorous PA (MVPA), other PA related behaviors, quality of life (QoL) and cardio-metabolic health among adults. METHODS: Healthy individuals aged 40 to 65 years were recruited through community health screenings and randomly assigned to 1) PPI: face-to-face Park Prescription + invitation to weekly exercise sessions in parks, or 2) control: standard PA materials. After the six-month intervention, participants completed accelerometer assessments, questionnaires on health behaviors and QoL, and health screenings. Independent sample t-tests were used to compare outcomes between groups, with secondary analysis adjusted for co-variates via multiple linear regression. A p-value <0.05 was considered statistically significant. RESULTS: Eighty participants were allocated to each group. Participants with mean age of 51.1 (Standard Deviation: 6.3) years were predominantly female (79%) and of Chinese ethnicity (81%). Participation in the group exercise started at 48% and declined to 24% by week 26. At six-months, 145 (91%) participants attended health screenings for outcome measure collection, and 126 (79%) provided valid accelerometer data. Time spent in MVPA favored the PPI group but this difference was not statistically significant (4.4 (- 43.8, 52.7) minutes/week; when removing 2 extreme outliers 26.8 (- 9.7, 63.4) minutes/week). Time spent in parks (147.5 (2.1, 292.9) minutes/month), PA in parks (192.5 (59.5, 325.5) minutes/month), and recreational PA (48.7 (1.4, 96.0) minutes/week) were significantly greater in the PPI group. PPI also significantly improved psychological QoL (4.0 (0.0, 8.0). DISCUSSION: PPI improved park use, PA in parks, recreational PA, and psychological QoL but not total MVPA. Future RCTs' are warranted to investigate PPI in different target populations and to provide further evidence for improvements in health outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT02615392, 26 November 2015.

Indication for en bloc pancreatectomy with colectomy: when is it safe?

INTRODUCTION: Aggressive en bloc resection of adjacent organs is often necessary to resect pancreatic or colonic lesions. However, it is debated whether simultaneous pancreatectomy with colectomy (P+C) is warranted as it potentially increases morbidity and mortality (MM). We hypothesized that MM would be increased in P+C, especially in cases of pancreatitis. METHODS: All patients who underwent pancreatectomy (P) and simultaneous pancreatectomy with colectomy (P+C) at a high-volume center from November 2006 to 2015 were prospectively collected using ACS-NSQIP at our institution. Patients with additional multivisceral or enucleation procedures were excluded. Data were augmented to 90-day outcomes using our institutional database. RESULTS: Forty-three patients with a mean age of 62 years (27:16 male: female) underwent P+C, accounting for 2.39% (43/1797) of pancreatectomies performed. Pancreatoduodenectomy (PD) was performed in 61% (n = 26), distal pancreatectomy (DP) in 37% (n = 16), and total pancreatectomy (TP) in 2% (n = 1) of patients. The 30- and 90-day MM were higher in P+C than P (30-day: 54 vs. 37%, p = 0.037 and 9 vs. 2%, p = 0.022; 90-day: 61 vs. 42%, p = 0.019 and 14 vs. 3%, p = 0.002). Logistical regression modeling revealed an association between 90-day mortality and colectomy (p = 0.013, OR = 3.556). When P+C MM were analyzed according to intraoperative factors, there was no significant difference according to type of pancreatectomy (PD vs. DP vs. TP), origin of primary lesion (pancreas vs. colon), surgical indication (malignant vs. non-malignant), or case status (planned colectomy vs. intraoperative decision). CONCLUSIONS: Addition of colectomy to pancreatectomy substantially increased MM. Subanalysis revealed that type of resection performed, etiology, and planning status did not account for increased risk when performing P+C. However, colectomy was found to be an independent risk factor for mortality. Therefore, patients should be informed of the risk of increased postoperative complications until a further study can identify potential patients or perioperative factors that can be used for risk stratification.

ß-catenin regulates Pax3 and Cdx2 for caudal neural tube closure and elongation.

Non-canonical Wnt/planar cell polarity (PCP) signaling plays a primary role in the convergent extension that drives neural tube closure and body axis elongation. PCP signaling gene mutations cause severe neural tube defects (NTDs). However, the role of canonical Wnt/ß-catenin signaling in neural tube closure and NTDs remains poorly understood. This study shows that conditional gene targeting of ß-catenin in the dorsal neural folds of mouse embryos represses the expression of the homeobox-containing genes Pax3 and Cdx2 at the dorsal posterior neuropore (PNP), and subsequently diminishes the expression of the Wnt/ß-catenin signaling target genes T, Tbx6 and Fgf8 at the tail bud, leading to spina bifida aperta, caudal axis bending and tail truncation. We demonstrate that Pax3 and Cdx2 are novel downstream targets of Wnt/ß-catenin signaling. Transgenic activation of Pax3 cDNA can rescue the closure defect in the ß-catenin mutants, suggesting that Pax3 is a key downstream effector of ß-catenin signaling in the PNP closure process. Cdx2 is known to be crucial in posterior axis elongation and in neural tube closure. We found that Cdx2 expression is also repressed in the dorsal PNPs of Pax3-null embryos. However, the ectopically activated Pax3 in the ß-catenin mutants cannot restore Cdx2 mRNA in the dorsal PNP, suggesting that the presence of both ß-catenin and Pax3 is required for regional Cdx2 expression. Thus, ß-catenin signaling is required for caudal neural tube closure and elongation, acting through the transcriptional regulation of key target genes in the PNP.

The Society of Thoracic Surgeons voluntary public reporting initiative: the first 4 years.

OBJECTIVES: To evaluate participant characteristics and outcomes during the first 4 years of the Society of Thoracic Surgeons (STS) public reporting program. BACKGROUND: This is the first detailed analysis of a national, voluntary, cardiac surgery public reporting program using STS clinical registry data and National Quality Forum-endorsed performance measures. METHODS: The distributions of risk-adjusted mortality rates, multidimensional composite performance scores, star ratings, and volumes for public reporting versus nonreporting sites were studied during 9 consecutive semiannual reporting periods (2010-2014). RESULTS: Among 8929 unique observations (∼1000 STS participant centers, 9 reporting periods), 916 sites (10.3%) were classified low performing, 6801 (76.2%) were average, and 1212 (13.6%) were high performing. STS public reporting participation varied from 22.2% to 46.3% over the 9 reporting periods. Risk-adjusted, patient-level mortality rates for isolated coronary artery bypass grafting were consistently lower in public reporting versus nonreporting sites (P value range: <0.001-0.0077). Reporting centers had higher composite performance scores and star ratings (23.2% high performing and 4.5% low performing vs 7.6% high performing and 13.8% low performing for nonreporting sites). STS public reporting sites had higher mean annualized coronary artery bypass grafting volumes than nonreporting sites (169 vs 145, P < 0.0001); high-performing programs had higher mean coronary artery bypass grafting volumes (n = 241) than average (n = 139) or low-performing (n = 153) sites. Risk factor prevalence (except reoperation) and expected mortality rates were generally stable during the study period. CONCLUSIONS: STS programs that voluntarily participate in public reporting have significantly higher volumes and performance. No evidence of risk aversion was found.

Frailty is a Predictor of Increased Readmissions and Increased Postoperative Complications After Elective Treatment of Unruptured Aneurysms.

INTRODUCTION: Frailty is a state of decreased physiologic reserve associated with adverse treatment outcomes across surgical specialties. We sought to determine whether frailty affected patient outcomes after elective treatment (open microsurgical clipping or endovascular therapy [EVT]) of unruptured cerebral aneurysms (UCAs). METHODS: The National Readmissions Database was queried from 2010 to 2014 to identify patients who had a known UCA and underwent elective clipping or EVT. Frailty was assessed using the Johns Hopkins Adjusted Clinical Groups frailty indicator tool. Multivariable exact logistic regression analyses were conducted to assess the associations between frailty and the primary outcome variables of 30- and 90-day readmissions, complications, length of stay (LOS), and patient disposition. RESULTS: Of 18,483 patients who underwent elective treatment for UCAs, 358 (1.9%) met the criteria for frailty. After adjusting for patient- and hospital-based factors, frailty (30-day: odds ratio [OR], 1.55; 95% confidence interval [CI], 1.11-2.17; P = 0.01; 90-day: OR, 1.47; 95% CI, 1.05-2.06; P = 0.02) and clipping versus EVT (30-day: OR, 2.12; 95% CI, 1.85-2.43; P < 0.000; 90-day: OR, 1.80; 95% CI, 1.59-2.03; P < 0.0001) were associated with increased readmission rates. Furthermore, frailty was associated with an increased rate of complications (surgical: OR, 2.91; 95% CI, 2.27-3.72; P < 0.0001; neurological: OR, 3.04; 95% CI, 2.43-3.81; P < 0.0001; major: OR, 2.75; 95% CI, 1.96-3.84; P < 0.0001), increased LOSs (incidence rate ratio, 3.08; 95% CI, 2.59-3.66; P < 0.0001), and an increased rate of nonroutine disposition (OR, 3.94; 95% CI, 2.91-5.34; P < 0.0001). CONCLUSIONS: Frailty was associated with an increased likelihood of 30- and 90-day readmissions after elective treatment of UCAs. Frailty was notably associated with several postoperative complications, longer LOSs, and nonroutine disposition in the treatment of UCAs.

Simulated outcomes for durotomy repair in minimally invasive spine surgery.

Minimally invasive spine surgery (MISS) is increasingly performed using endoscopic and microscopic visualization, and the captured video can be used for surgical education and development of predictive artificial intelligence (AI) models. Video datasets depicting adverse event management are also valuable, as predictive models not exposed to adverse events may exhibit poor performance when these occur. Given that no dedicated spine surgery video datasets for AI model development are publicly available, we introduce Simulated Outcomes for Durotomy Repair in Minimally Invasive Spine Surgery (SOSpine). A validated MISS cadaveric dural repair simulator was used to educate neurosurgery residents, and surgical microscope video recordings were paired with outcome data. Objects including durotomy, needle, grasper, needle driver, and nerve hook were then annotated. Altogether, SOSpine contains 15,698 frames with 53,238 annotations and associated durotomy repair outcomes. For validation, an AI model was fine-tuned on SOSpine video and detected surgical instruments with a mean average precision of 0.77. In summary, SOSpine depicts spine surgeons managing a common complication, providing opportunities to develop surgical AI models.

Optimizing the Postoperative Management of Children Undergoing Resection of High-Risk Abdominal Neuroblastoma.

BACKGROUND: Surgical resection is a mainstay of treatment in high-risk neuroblastoma (HR-NB), but there exists wide variability in perioperative management practices. The aim of this study was to evaluate two standardized adult perioperative enhanced recovery practices (ERPs) in pediatric patients undergoing open resection of abdominal HR-NB. METHODS: All patients with abdominal HR-NB surgically resected at a free-standing children's hospital between 12/2010 and 7/2020 were retrospectively reviewed. Perioperative ERPs of interest included avoidance of routine nasogastric tube (NGT) use and the use of neuraxial anesthesia. Primary outcomes included time to enteral intake, urinary catheter use, opioid utilization, and length of stay (LOS). RESULTS: Overall, 37 children, median age 33 months (IQR: 20-48 months), were identified. Avoidance of an NGT allowed for earlier feeding after surgery (P = .03). Neuraxial anesthesia use more frequently required an indwelling urinary catheter (P < .01) for a longer duration (P = .02), with no difference in total opioid utilization (P = .77) compared to patients without neuraxial anesthesia. Postoperative LOS was unaffected by avoidance of routine NGT use (P = .68) or use of neuraxial anesthesia (P = .89). CONCLUSION: Children undergoing open resection of abdominal HR-NB initiated diet sooner when an NGT was not left postoperatively, and the need for a urinary catheter was significantly higher in patients who received neuraxial anesthesia. However, these two ERP components did not decrease postoperative LOS. To optimize the postoperative management of NB patients, postoperative NGTs should be avoided, while the benefit of neuraxial anesthesia is less clear as it necessitates the placement of a urinary catheter without decreasing opioid utilization.

Assessing Patient's Values When Selecting Treatments for Alopecia Areata: A Cross-Sectional Survey Study.

Introduction: Alopecia areata (AA) is an autoimmune condition that results in nonscarring hair loss. There is currently only one Food and Drug Administration (FDA)-approved treatment for AA; as a result, a wide range of treatments are commonly administered. This study aimed to determine how patients with AA prioritize treatment characteristics when choosing a therapy. Methods: A cross-sectional national survey was distributed using the National Alopecia Areata Foundation's (NAAF) email list. This study was approved by the Mass General Brigham Institutional Review Board. Participants were asked to rank the importance of five treatment domains. Results: Of the 1,074 completed surveys (completion rate 77.4%), most respondents were female (85.4%) and white (77.8%) with an average age of 49.3 ± 15.4 years. Respondents had AA for an average of 17.7 ± 15.4 years, with 90.0% experiencing current active hair loss. 95.6% of respondents considered the treatment's ability to achieve hair regrowth as important, 93.9% listed the availability of information about the treatment (e.g., via doctor or online) as important, 89.1% ranked the treatment side effects as important, 75.7% the cost, and 68.0% the convenience of use. A sub-analysis was performed examining responses between respondents who identify as white versus nonwhite, which showed that while the order of importance was the same between groups, a significantly larger proportion of nonwhite respondents attributed higher importance to cost (white: 73.8%, nonwhite: 82.4%; p = 0.006) and convenience (white: 65.3%, nonwhite: 77.3%; p < 0.001) than their white counterparts. Discussion/Conclusion: These findings identify key domains that can serve as a starting point in shared decision-making between patients and physicians. This knowledge can streamline dermatologist delivery of key information and highlight areas of improvement for future therapeutics. Limitations include the nonrandomized NAAF population with most participants being white females. Future studies should confirm these findings in other patient populations.

Trauma activation patient preinjury toxicology-positive proportions and associated risk conditions: A retrospective study.

BACKGROUND: Unlike prior guidelines for a positive toxicology screen, the 2022 national trauma data bank dictionary requires the exclusion of postinjury drugs. We aimed to (1) investigate the proportion of drugs in the toxicology screen that were given postinjury; (2) determine preinjury toxicology-positive associations with smoking, psychiatric, and drug abuse histories in an activation patient (ACT-Pt) cohort; and (3) explore whether ACT-Pt varied toxicology testing rates would produce similar preinjury toxicology-positive results. METHODS: In this retrospective study, the historic parent database included consecutive trauma center admissions where toxicology testing was discretionary. A supplementary electronic medical record audit of ACT-Pts age 18-60 years assessed smoking, psychiatric, and drug abuse histories. Subsequently, ACT-Pt age 18-100 years testing was encouraged by attending surgeons and, later routine testing was implemented. RESULTS: Of 2,076 patients in the historic parent database, discretionary toxicology testing occurred in 23.9% (n = 496) and the positive proportion was 58.9% (n = 292). However, 23.6% (n = 69) of the positive screens had the drug given postinjury. The preinjury positive-toxicology proportion was 45.0% (223/496). Preinjury toxicology positivity was greater in ACT-Pts age 18-60 years (52.3%) than in other patients (activations >60 years of age or consultations) (33.7%; p < 0.0001; odds ratio [OR] = 2.2). Smoking, psychiatric, and drug abuse histories were more common in ACT-Pts age 18-60 years preinjury toxicology-positive patients (74.4%, 51.3%, and 98.7%) than in negative patients (36.6%, 25.2%, and 25.2%; p < 0.0001). In ACT-Pts age 18-100 years, when compared to historic discretionary testing (32.7%), testing was increased with encouraged testing (62.1%; p < 0.0001; OR = 3.4) and routine testing (73.1%; p < 0.0001; OR = 5.6). ACT-Pt preinjury toxicology positivity was similar for historic discretionary (47.9%), encouraged (57.6%), and routine (51.3%) (p = 0.3670) testing. The meta-analytic toxicology-positive proportion for the three testing strategies was 49.8%. CONCLUSIONS: Substantial toxicology-positive findings are due to postinjury drug administration. Toxicology positivity is associated with ACT-Pts age 18-60 years and smoking, psychiatric, and drug abuse histories. ACT-Pt age 18-100 years preinjury toxicology positivity is 50% and does not vary with different testing proportions and strategies.