Long COVID incidence in adults and children between 2020 and 2023: a real-world data study from the RECOVER Initiative.

Estimates of post-acute sequelae of SARS-CoV-2 infection (PASC) incidence, also known as Long COVID, have varied across studies and changed over time. We estimated PASC incidence among adult and pediatric populations in three nationwide research networks of electronic health records (EHR) participating in the RECOVER Initiative using different classification algorithms (computable phenotypes). Overall, 7% of children and 8.5%-26.4% of adults developed PASC, depending on computable phenotype used. Excess incidence among SARS-CoV-2 patients was 4% in children and ranged from 4-7% among adults, representing a lower-bound incidence estimation based on two control groups - contemporary COVID-19 negative and historical patients (2019). Temporal patterns were consistent across networks, with peaks associated with introduction of new viral variants. Our findings indicate that preventing and mitigating Long COVID remains a public health priority. Examining temporal patterns and risk factors of PASC incidence informs our understanding of etiology and can improve prevention and management.

Compressing the Chronology of a Temporal Network with Graph Commutators.

Studies of dynamics on temporal networks often represent the network as a series of "snapshots," static networks active for short durations of time. We argue that successive snapshots can be aggregated if doing so has little effect on the overlying dynamics. We propose a method to compress network chronologies by progressively combining pairs of snapshots whose matrix commutators have the smallest dynamical effect. We apply this method to epidemic modeling on real contact tracing data and find that it allows for significant compression while remaining faithful to the epidemic dynamics.

Vaccine Effectiveness Against Long COVID in Children.

OBJECTIVES: Vaccination reduces the risk of acute coronavirus disease 2019 (COVID-19) in children, but it is less clear whether it protects against long COVID. We estimated vaccine effectiveness (VE) against long COVID in children aged 5 to 17 years. METHODS: This retrospective cohort study used data from 17 health systems in the RECOVER PCORnet electronic health record program for visits after vaccine availability. We examined both probable (symptom-based) and diagnosed long COVID after vaccination. RESULTS: The vaccination rate was 67% in the cohort of 1 037 936 children. The incidence of probable long COVID was 4.5% among patients with COVID-19, whereas diagnosed long COVID was 0.8%. Adjusted vaccine effectiveness within 12 months was 35.4% (95 CI 24.5-44.7) against probable long COVID and 41.7% (15.0-60.0) against diagnosed long COVID. VE was higher for adolescents (50.3% [36.6-61.0]) than children aged 5 to 11 (23.8% [4.9-39.0]). VE was higher at 6 months (61.4% [51.0-69.6]) but decreased to 10.6% (-26.8% to 37.0%) at 18-months. CONCLUSIONS: This large retrospective study shows moderate protective effect of severe acute respiratory coronavirus 2 vaccination against long COVID. The effect is stronger in adolescents, who have higher risk of long COVID, and wanes over time. Understanding VE mechanism against long COVID requires more study, including electronic health record sources and prospective data.

Temporal and probabilistic comparisons of epidemic interventions.

Forecasting disease spread is a critical tool to help public health officials design and plan public health interventions.However, the expected future state of an epidemic is not necessarily well defined as disease spread is inherently stochastic, contact patterns within a population are heterogeneous, and behaviors change. In this work, we use time-dependent probability generating functions (PGFs) to capture these characteristics by modeling a stochastic branching process of the spread of a disease over a network of contacts in which public health interventions are introduced over time. To achieve this, we define a general transmissibility equation to account for varying transmission rates (e.g. masking), recovery rates (e.g. treatment), contact patterns (e.g. social distancing) and percentage of the population immunized (e.g. vaccination). The resulting framework allows for a temporal and probabilistic analysis of an intervention's impact on disease spread, which match continuous-time stochastic simulations that are much more computationally expensive.To aid policy making, we then define several metrics over which temporal and probabilistic intervention forecasts can be compared: Looking at the expected number of cases and the worst-case scenario over time, as well as the probability of reaching a critical level of cases and of not seeing any improvement following an intervention.Given that epidemics do not always follow their average expected trajectories and that the underlying dynamics can change over time, our work paves the way for more detailed short-term forecasts of disease spread and more informed comparison of intervention strategies.

Temporal and Probabilistic Comparisons of Epidemic Interventions.

Forecasting disease spread is a critical tool to help public health officials design and plan public health interventions. However, the expected future state of an epidemic is not necessarily well defined as disease spread is inherently stochastic, contact patterns within a population are heterogeneous, and behaviors change. In this work, we use time-dependent probability generating functions (PGFs) to capture these characteristics by modeling a stochastic branching process of the spread of a disease over a network of contacts in which public health interventions are introduced over time. To achieve this, we define a general transmissibility equation to account for varying transmission rates (e.g. masking), recovery rates (e.g. treatment), contact patterns (e.g. social distancing) and percentage of the population immunized (e.g. vaccination). The resulting framework allows for a temporal and probabilistic analysis of an intervention's impact on disease spread, which match continuous-time stochastic simulations that are much more computationally expensive. To aid policy making, we then define several metrics over which temporal and probabilistic intervention forecasts can be compared: Looking at the expected number of cases and the worst-case scenario over time, as well as the probability of reaching a critical level of cases and of not seeing any improvement following an intervention. Given that epidemics do not always follow their average expected trajectories and that the underlying dynamics can change over time, our work paves the way for more detailed short-term forecasts of disease spread and more informed comparison of intervention strategies.

Vaccine Effectiveness Against Long COVID in Children: A Report from the RECOVER EHR Cohort.

Objective: Vaccination reduces the risk of acute COVID-19 in children, but it is less clear whether it protects against long COVID. We estimated vaccine effectiveness (VE) against long COVID in children aged 5-17 years. Methods: This retrospective cohort study used data from 17 health systems in the RECOVER PCORnet electronic health record (EHR) Program for visits between vaccine availability, and October 29, 2022. Conditional logistic regression was used to estimate VE against long COVID with matching on age group (5-11, 12-17) and time period and adjustment for sex, ethnicity, health system, comorbidity burden, and pre-exposure health care utilization. We examined both probable (symptom-based) and diagnosed long COVID in the year following vaccination. Results: The vaccination rate was 56% in the cohort of 1,037,936 children. The incidence of probable long COVID was 4.5% among patients with COVID-19, while diagnosed long COVID was 0.7%. Adjusted vaccine effectiveness within 12 months was 35.4% (95 CI 24.5 - 44.5) against probable long COVID and 41.7% (15.0 - 60.0) against diagnosed long COVID. VE was higher for adolescents 50.3% [36.3 - 61.0]) than children aged 5-11 (23.8% [4.9 - 39.0]). VE was higher at 6 months (61.4% [51.0 - 69.6]) but decreased to 10.6% (-26.8 - 37.0%) at 18-months. Discussion: This large retrospective study shows a moderate protective effect of SARS-CoV-2 vaccination against long COVID. The effect is stronger in adolescents, who have higher risk of long COVID, and wanes over time. Understanding VE mechanism against long COVID requires more study, including EHR sources and prospective data. Article Summary: Vaccination against COVID-19 has a protective effect against long COVID in children and adolescents. The effect wanes over time but remains significant at 12 months. What's Known on This Subject: Vaccines reduce the risk and severity of COVID-19 in children. There is evidence for reduced long COVID risk in adults who are vaccinated, but little information about similar effects for children and adolescents, who have distinct forms of long COVID. What This Study Adds: Using electronic health records from US health systems, we examined large cohorts of vaccinated and unvaccinated patients <18 years old and show that vaccination against COVID-19 is associated with reduced risk of long COVID for at least 12 months. Contributors' Statement: Drs. Hanieh Razzaghi and Charles Bailey conceptualized and designed the study, supervised analyses, drafted the initial manuscript, and critically reviewed and revised the manuscript.Drs. Christopher Forrest and Yong Chen designed the study and critically reviewed and revised the manuscript.Ms. Kathryn Hirabayashi, Ms. Andrea Allen, and Dr. Qiong Wu conducted analyses, and critically reviewed and revised the manuscript.Drs. Suchitra Rao, H Timothy Bunnell, Elizabeth A. Chrischilles, Lindsay G. Cowell, Mollie R. Cummins, David A. Hanauer, Benjamin D. Horne, Carol R. Horowitz, Ravi Jhaveri, Susan Kim, Aaron Mishkin, Jennifer A. Muszynski, Susanna Nagie, Nathan M. Pajor, Anuradha Paranjape, Hayden T. Schwenk, Marion R. Sills, Yacob G. Tedla, David A. Williams, and Ms. Miranda Higginbotham critically reviewed and revised the manuscript.All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work. Authorship statement: Authorship has been determined according to ICMJE recommendations.

CP110 and CEP135 localize near the proximal and distal centrioles of cattle and human spermatozoa.

Centrosomes play an important role in the microtubule organization of a cell. The sperm's specialized centrosome consists of the canonical barrel-shaped proximal centriole, the funnel-shaped distal centriole, and the pericentriolar material known as striated columns (or segmented columns). Here, we examined the localization of the centriole proteins CEP135 and CP110 in cattle and human spermatozoa. In canonical centrioles, CP110 is a centriole tip protein that controls cilia formation, while CEP135 is a structural protein essential for constructing the centriole. In contrast, we found antibodies recognizing CEP135 and CP110 label near the proximal and distal centrioles at the expected location of the striated columns and capitulum in cattle and humans in an antibody and species-specific way. These findings provide a pathway to understanding the unique functions of spermatozoan centrosome.

A machine learning-based phenotype for long COVID in children: An EHR-based study from the RECOVER program.

As clinical understanding of pediatric Post-Acute Sequelae of SARS CoV-2 (PASC) develops, and hence the clinical definition evolves, it is desirable to have a method to reliably identify patients who are likely to have post-acute sequelae of SARS CoV-2 (PASC) in health systems data. In this study, we developed and validated a machine learning algorithm to classify which patients have PASC (distinguishing between Multisystem Inflammatory Syndrome in Children (MIS-C) and non-MIS-C variants) from a cohort of patients with positive SARS- CoV-2 test results in pediatric health systems within the PEDSnet EHR network. Patient features included in the model were selected from conditions, procedures, performance of diagnostic testing, and medications using a tree-based scan statistic approach. We used an XGboost model, with hyperparameters selected through cross-validated grid search, and model performance was assessed using 5-fold cross-validation. Model predictions and feature importance were evaluated using Shapley Additive exPlanation (SHAP) values. The model provides a tool for identifying patients with PASC and an approach to characterizing PASC using diagnosis, medication, laboratory, and procedure features in health systems data. Using appropriate threshold settings, the model can be used to identify PASC patients in health systems data at higher precision for inclusion in studies or at higher recall in screening for clinical trials, especially in settings where PASC diagnosis codes are used less frequently or less reliably. Analysis of how specific features contribute to the classification process may assist in gaining a better understanding of features that are associated with PASC diagnoses.

Bioactive phytocompounds for oral cancer prevention and treatment: A comprehensive and critical evaluation.

The high incidence of oral cancer combined with excessive treatment cost underscores the need for novel oral cancer preventive and therapeutic options. The value of natural agents, including plant secondary metabolites (phytochemicals), in preventing carcinogenesis and representing expansive source of anticancer drugs have been established. While fragmentary research data are available on antioral cancer effects of phytochemicals, a comprehensive and critical evaluation of the potential of these agents for the prevention and intervention of human oral malignancies has not been conducted according to our knowledge. This study presents a complete and critical analysis of current preclinical and clinical results on the prevention and treatment of oral cancer using phytochemicals. Our in-depth analysis highlights anticancer effects of various phytochemicals, such as phenolics, terpenoids, alkaloids, and sulfur-containing compounds, against numerous oral cancer cells and/or in vivo oral cancer models by antiproliferative, proapoptotic, cell cycle-regulatory, antiinvasive, antiangiogenic, and antimetastatic effects. Bioactive phytochemicals exert their antineoplastic effects by modulating various signaling pathways, specifically involving the epidermal growth factor receptor, cytokine receptors, toll-like receptors, and tumor necrosis factor receptor and consequently alter the expression of downstream genes and proteins. Interestingly, phytochemicals demonstrate encouraging effects in clinical trials, such as reduction of oral lesion size, cell growth, pain score, and development of new lesions. While most phytochemicals displayed minimal toxicity, concerns with bioavailability may limit their clinical application. Future directions for research include more in-depth mechanistic in vivo studies, administration of phytochemicals using novel formulations, investigation of phytocompounds as adjuvants to conventional treatment, and randomized clinical trials.

COVID-19 Vaccine Safety First Year Findings in Adolescents.

BACKGROUND AND OBJECTIVES: The Food and Drug Administration expanded Emergency Use Authorization for use of Pfizer-BioNTech (BNT-162b2) coronavirus disease 2019 vaccine to include people ages 12 years and older on May 10, 2021. We describe adverse events observed during the first full year of the US coronavirus disease 2019 vaccination program for adolescents ages 12 to 17 years. METHODS: We conducted descriptive analyses using data from 2 complementary US vaccine safety monitoring systems: v-safe, a voluntary smartphone-based system that monitors reactions and health impacts, and the Vaccine Adverse Event Reporting System (VAERS), the national spontaneous reporting system. We reviewed reports and calculated adverse event reporting rates using vaccine administration data. RESULTS: Among 172 032 adolescents ages 12 to 17 years enrolled in v-safe, most reported reactions following BNT-162b2 were mild to moderate, most frequently reported on the day after vaccination, and more common after dose 2. VAERS received 20 240 adverse event reports; 91.5% were nonserious. Among adverse events of interest, we verified 40 cases of multisystem inflammation syndrome in children (1.2 cases per million vaccinations), 34 (85%) of which had evidence of prior severe acute respiratory syndrome coronavirus 2 infection; and 570 cases of myocarditis (17.7 cases per million vaccinations), most of whom (77%) reported symptom resolution at the time of report. CONCLUSIONS: During the first year BNT-162b2 was administered to adolescents ages 12 to 17 years, most reported adverse events were mild and appeared self-limited. Rates of myocarditis were lower than earlier reports. No new serious safety concerns were identified.

Contraception use among individuals with substance use disorder increases tenfold with patient-centered, mobile services: a quasi-experimental study.

BACKGROUND: Individuals with substance use disorders (SUD) have disproportionately high rates of unintended pregnancy. Reducing harm associated with this risk and its biopsychosocial consequences requires evidence-based, non-coercive interventions that ensure access to contraception for individuals who choose to prevent pregnancy. We examined feasibility and impact of SexHealth Mobile, a mobile unit-based intervention that aimed to increase access to patient-centered contraceptive care for individuals in SUD recovery programs. METHODS: We conducted a quasi-experimental study (enhanced usual care [EUC] followed by intervention) at three recovery centers with participants (n = 98) at risk for unintended pregnancy. EUC participants were offered printed information on community locations where they could access contraception care. SexHealth Mobile participants were offered same-day, onsite clinical consultation on a medical mobile unit and contraception if desired. The primary outcome was use of contraception (hormonal or intrauterine device) at one-month post-enrollment. Secondary outcomes were at two-weeks and three-months. Confidence in preventing unintended pregnancy, reasons for non-use of contraception at follow-up, and intervention feasibility were also assessed. RESULTS: Participants (median age = 31, range 19-40) enrolled in the intervention period were almost 10 times more likely to be using contraception at one-month (51.5%) versus the those enrolled in the EUC period (5.4%) (unadjusted relative risk [URR] = 9.3 [95%CI: 2.3-37.1]; adjusted relative risk [ARR] = 9.8 [95%CI: 2.4-39.2]). Intervention participants were also more likely to be using contraception at 2-weeks (38.7% vs. 2.6%; URR = 14.3 [95%CI: 2.0-104.1]) and three-months (40.9% vs. 13.9%; URR = 2.9 [95% CI: 1.1-7.4]). EUC participants reported more barriers (cost, time) and less confidence in preventing unintended pregnancies. Mixed-methods feasibility data indicated high acceptability and feasible integration into recovery settings. CONCLUSIONS: Mobile contraceptive care based on principles of reproductive justice and harm reduction reduces access barriers, is feasible to implement in SUD recovery settings, and increases contraception use. Expanding interventions like SexHealth Mobile may help reduce harm from unintended pregnancies among individuals in SUD recovery. Trial Registration NCT04227145.

Surveillance for Multisystem Inflammatory Syndrome in US Children Aged 5-11 Years Who Received Pfizer-BioNTech COVID-19 Vaccine, November 2021 through March 2022.

Multisystem inflammatory syndrome in children (MIS-C) is a complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; in the United States, reporting of MIS-C after coronavirus disease 2019 (COVID-19) vaccination is required for vaccine safety monitoring. Pfizer-BioNTech COVID-19 vaccine was authorized for children aged 5-11 years on 29 October 2021. Covering a period when approximately 7 million children received vaccine, surveillance for MIS-C ≤ 90 days postvaccination using passive systems identified 58 children with MIS-C and laboratory evidence of past/recent SARS-CoV-2 infection, and 4 without evidence. During a period with extensive SARS-CoV-2 circulation, MIS-C illness in children after COVID-19 vaccination who lacked evidence of SARS-CoV-2 infection was rare (<1 per million vaccinated children).

A machine learning-based phenotype for long COVID in children: an EHR-based study from the RECOVER program.

Background: As clinical understanding of pediatric Post-Acute Sequelae of SARS CoV-2 (PASC) develops, and hence the clinical definition evolves, it is desirable to have a method to reliably identify patients who are likely to have post-acute sequelae of SARS CoV-2 (PASC) in health systems data. Methods and Findings: In this study, we developed and validated a machine learning algorithm to classify which patients have PASC (distinguishing between Multisystem Inflammatory Syndrome in Children (MIS-C) and non-MIS-C variants) from a cohort of patients with positive SARS-CoV-2 test results in pediatric health systems within the PEDSnet EHR network. Patient features included in the model were selected from conditions, procedures, performance of diagnostic testing, and medications using a tree-based scan statistic approach. We used an XGboost model, with hyperparameters selected through cross-validated grid search, and model performance was assessed using 5-fold cross-validation. Model predictions and feature importance were evaluated using Shapley Additive exPlanation (SHAP) values. Conclusions: The model provides a tool for identifying patients with PASC and an approach to characterizing PASC using diagnosis, medication, laboratory, and procedure features in health systems data. Using appropriate threshold settings, the model can be used to identify PASC patients in health systems data at higher precision for inclusion in studies or at higher recall in screening for clinical trials, especially in settings where PASC diagnosis codes are used less frequently or less reliably. Analysis of how specific features contribute to the classification process may assist in gaining a better understanding of features that are associated with PASC diagnoses. Funding Source: This research was funded by the National Institutes of Health (NIH) Agreement OT2HL161847-01 as part of the Researching COVID to Enhance Recovery (RECOVER) program of research. Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the RECOVER Program, the NIH or other funders.

The Estradiol Synthesis Inhibitor Formestane Diminishes the Ability of Sevoflurane to Induce Neurodevelopmental Abnormalities in Male Rats.

BACKGROUND: In rodents, the period of increased vulnerability to the developmental effects of general anesthetics coincides with the period of age-specific organizing (masculinizing) effects of the major female sex hormone 17ß-estradiol (E2) in the male brain and excitatory GABA type A receptor (GABA A R) signaling. We studied whether E2 synthesis and excitatory GABA A R signaling are involved in the mediation of the developmental effects of sevoflurane in male rats. METHODS: Male Sprague-Dawley rats were pretreated with the inhibitors of E2 synthesis, formestane, or the Na+-K+-2Cl- (NKCC1) Cl- importer, bumetanide, prior to sevoflurane exposure for 6 h on postnatal (P) day 4, P5, or P6. We tested whether a subsequent exposure of these rats to sevoflurane on P∼10 would cause electroencephalography (EEG)-detectable seizures. We also evaluated their behavior during the elevated plus maze (EPM) test on P∼60, prepulse inhibition (PPI) of acoustic startle responses on P∼70, and corticosterone secretion to physical restraint on P∼80. RESULTS: The rats neonatally exposed to sevoflurane responded to repeated exposure to sevoflurane with increased EEG-detectable seizures (F ( 3,24 ) = 7.445, P = 0.001) and exhibited deficiencies during the EPM (F ( 3,55 ) = 4.397, P = 0.008) and PPI (F ( 3,110 ) = 5.222, P = 0.003) tests. They also responded to physical restraint with heightened secretion of corticosterone (F ( 3,16 ) = 11.906, P < 0.001). These parameters in the sevoflurane-exposed rats that were pretreated with formestane or bumetanide were not different from those in the control rats. CONCLUSION: These results, along with previously published data, suggest that sevoflurane-enhanced E2 synthesis and excitatory GABA A R signaling at the time of sevoflurane anesthesia are involved in the mediation of the neurodevelopmental effects of the anesthetic in male rats.

Perception of pain and influences on opioid use in implant-based breast reconstruction patients.

Although there has been a recent focus on decreasing opioid prescribing through alternative pain medication protocols, the patient's perception of pain related to breast reconstructive surgeries has not been well described. We sought to evaluate patient perception of pain control as it influences opioid use. We hypothesize that modifiable factors may influence patterns in pain perception and postoperative opioid use. Patients undergoing consultation for mastectomy with immediate, implant-based breast reconstruction were enrolled in a prospective, cohort survey study. A survey was administered at preoperative and postoperative appointments to collect data on pain expectations and pain control. Of 100 patients enrolled, 85% completed the postoperative survey. Over half of patients (52%) reported feeling anxious about pain control after surgery. Patients with preoperative opioid use were more likely to expect complete relief of pain postoperatively (P = .038). Patients with psychiatric comorbidity were more likely to report feeling anxious about postoperative pain (P = .012; 70% vs 42%; OR 3.0 CI 1.2-7.4). Patients who reported feeling anxious about pain control preoperatively were more likely to report trying opioids (P = .047; 67% vs 44%; OR 2.5 CI 1.0-6.1) and benzodiazepines (P = .020; 80% vs 56%; OR 3.0 CI 1.2-8.0) postoperatively. Anxiety related to pain control is common and results in an increased likelihood of trying opioid and benzodiazepine medications postoperatively. This presents an opportunity to educate patients preoperatively by addressing anxiety related to pain control to decrease controlled substance use.

Effects of Intraoperative Dexamethasone Administration in Adult Diabetic Burn Patients.

The steroid dexamethasone is used intraoperatively to prevent postoperative nausea. Studies of intraoperative steroid use in diabetic patients have shown conflicting effects on blood glucose and complications, and their use has not yet been studied in the burn population. A review of adult diabetic acute burn patients undergoing surgery at a verified burn center from 2012 to 2017 was conducted. Statistical analysis compared those who did and did not receive an intraoperative steroid. A total of 74 patients who underwent 121 operations were identified; steroid was administered in 14.0% of cases. There were no statistically significant differences in preoperative glucose, insulin requirements, TBSA, or hemoglobin A1C. Postoperatively, the steroid group had a 16.7 mg/dl (SD = 11.1) increase in blood glucose (P = .042) and 53.5 unit/24 hour (SD = 28.4) increase in insulin requirement (P = .019), compared with no change in controls. The complication rate in the steroid group was 52.9% compared with 20.1% in controls (P = .003); partial graft loss was the most common complication. Diabetic burn patients who receive intraoperative steroid have increased postoperative blood glucose levels, insulin requirements, and complication rates compared with patients who do not receive steroids. Discussion is warranted to avoid intraoperative steroid in this population.

Long-term Results from the Empowering a Multimodal Pathway Toward Healthy Youth Program, a Multimodal School-Based Approach, Show Marked Reductions in Suicidality, Depression, and Anxiety in 6,227 Students in Grades 6-12 (Aged 11-18).

Here, we report on findings from a 15-month follow-up of a school-based program called Empowering a Multimodal Pathway Toward Healthy Youth (EMPATHY). This was primarily intended to reduce suicidal thinking in pre-teens, adolescents, and youth students aged 11-18 in middle schools (Grades 6-8) and high SCHOOLS (Grades 9-12). It also aimed to reduce depression and anxiety. The EMPATHY multimodal program consisted of repeated data collection, identification of a high-risk group, a rapid intervention for this high-risk group including offering supervised online cognitive behavioral therapy (CBT) program, a universal CBT intervention for those in Grades 6-8, a variety of interactions with trained staff ("Resiliency Coaches"), and referral to external medical and psychiatric services where appropriate. There were four time-points at which assessments were made: baseline, 3, 7, and 15 months. Here, we report cross-sectional findings over 15 months in a total of 6,227 students who were assessed at least once during the study period. Additionally, we report longitudinal findings from the 1,884 students who completed all 4 assessments. Our results found highly statistically significant decreases in suicidality rates, with the percentage of the total school population who were actively suicidal decreasing from 4.4% at baseline (n = 143 of 3,244) to 2.8% at 15 months (n = 125 of 4,496) (p < 0.001). There were also highly statistically significant reductions in depression and anxiety scores at each time-point. Thus, Mean Depression scores at baseline for the entire student population were 3.73 ± 3.87 (n = 3,244) at baseline and decreased to 3.22 ± 3.52 (n = 4,496) (p < 0.001). Since most students were not depressed, whole population changes such as this may indicate impact in many areas. In the longitudinal analysis of students who completed all four assessments, there were also highly statistically significant improvements in depression and anxiety scores at all time-points. For example, depression scores decreased from a mean of 3.43 ± 3.67 (n = 1,884) at baseline to 2.95 ± 3.53 (n = 1,884) at 15-months (p < 0.001), while the number who were actively suicidal decreased from 69 to 37. These results suggest that school-based multimodal programs, utilizing a combination of interventions, can have meaningful benefits across entire school populations.

Depression Outcomes in Adults Attending Family Practice Were Not Improved by Screening, Stepped-Care, or Online CBT during a 12-Week Study when Compared to Controls in a Randomized Trial.

There is uncertainty regarding possible benefits of screening for depression in family practice, as well as the most effective treatment approach when depression is identified. Here, we examined whether screening patients for depression in primary care, and then treating them with different modalities, was better than treatment-as-usual (TAU) alone. Screening was carried out for depression using the 9-item Patient Health Questionnaire (PHQ-9), with a score of ≥10 indicating significant depressive symptoms. PHQ-9 scores were given to family physicians prior to patients being seen (except for the Control group). Patients (n = 1,489) were randomized to one of four groups. Group #1 were controls (n = 432) in which PHQ-9 was administered, but results were not shared. Group #2 was screening followed by TAU (n = 426). Group #3 was screening followed by both TAU and the opportunity to use an online cognitive behavioral therapy (CBT) treatment program (n = 440). Group #4 utilized an evidence-based Stepped-care pathway for depression (n = 191, note that this was not available at all clinics). Of the study sample 889 (60%) completed a second PHQ-9 rating at 12 weeks. There were no statistically significant differences in baseline PHQ-9 scores between these groups. Compared to baseline, mean PHQ-9 scores decreased significantly in the depressed patients over 12 weeks, but there were no statistically significant differences between any groups at 12 weeks. Thus, for those who were depressed at baseline Control group (Group #1) scores decreased from 15.3 ± 4.2 to 4.0 ± 2.6 (p < 0.001), Screening group (Group #2) scores decreased from 15.5 ± 3.9 to 4.6 ± 3.0 (p < 0.001), Online CBT group (Group #3) scores decreased from 15.4 ± 3.8 to 3.4 ± 2.7 (p < 0.01), and the Stepped-care pathway group (Group #4) scores decreased from 15.3 ± 3.6 to 5.4 ± 2.8 (p < 0.05). In conclusion, these findings from this controlled randomized study do not suggest that using depression screening tools in family practice improves outcomes. They also suggest that much of the depression seen in primary care spontaneously resolves and do not support suggestions that more complex treatment programs or pathways improve depression outcomes in primary care. Replication studies are required due to study limitations.

Victim Injury and Social Distance: A National Test of a General Principle of Conflict.

Our inquiry focuses on why some violent offenses but not others result in injury to the victim. Building on existing theory nested in the paradigm of pure sociology, we propose and test a general principle of conflict: Victim injury varies directly with social distance. This principle predicts that offenders are more likely to harm victims with whom they are less well acquainted and less similar culturally. We test three hypotheses derived from this principle with data from the National Crime Victimization Survey and find little support for the theory. Rather, findings suggest exactly the opposite of that predicted: As social distance between offender and victim increases, the odds of victim injury decreases. Recommendations of additional research are made.

Initial Findings from a Novel School-Based Program, EMPATHY, Which May Help Reduce Depression and Suicidality in Youth.

UNLABELLED: We describe initial pilot findings from a novel school-based approach to reduce youth depression and suicidality, the Empowering a Multimodal Pathway Towards Healthy Youth (EMPATHY) program. Here we present the findings from the pilot cohort of 3,244 youth aged 11-18 (Grades 6-12). They were screened for depression, suicidality, anxiety, use of drugs, alcohol, or tobacco (DAT), quality-of-life, and self-esteem. Additionally, all students in Grades 7 and 8 (mean ages 12.3 and 13.3 respectively) also received an 8-session cognitive-behavioural therapy (CBT) based program designed to increase resiliency to depression. Following screening there were rapid interventions for the 125 students (3.9%) who were identified as being actively suicidal, as well as for another 378 students (11.7%) who were felt to be at higher-risk of self-harm based on a combination of scores from all the scales. The intervention consisted of an interview with the student and their family followed by offering a guided internet-based CBT program. Results from the 2,790 students who completed scales at both baseline and 12-week follow-up showed significant decreases in depression and suicidality. Importantly, there was a marked decrease in the number of students who were actively suicidal (from n=125 at baseline to n=30 at 12-weeks). Of the 503 students offered the CBT program 163 (32%) took part, and this group had significantly lower depression scores compared to those who didn't take part. There were no improvements in self-esteem, quality-of-life, or the number of students using DAT. Only 60 students (2% of total screened) required external referral during the 24-weeks following study initiation. These results suggest that a multimodal school-based program may provide an effective and pragmatic approach to help reduce youth depression and suicidality. Further research is required to determine longer-term efficacy, reproducibility, and key program elements. TRIAL REGISTRATION: ClinicalTrials.gov NCT02169960.