Analytical characterization of full, intermediate, and empty AAV capsids.

Manufacturing of recombinant adeno-associated virus (AAV) vectors produces three types of capsids: full, intermediate, and empty. While there are different opinions about the impact of intermediate and empty capsids on safety and efficacy of AAV products, they are generally considered impurities because they are not the intended fully intact vector product. The presence of these impurities could impact product efficacy due to potential competition with fully packaged AAVs for cellular transduction, as well as have potential implications to patient safety due to increased capsid load during dosing. To determine the impact of intermediate capsids on potency, an AAV preparation was separated into fractions enriched for full, intermediate, or empty capsids. Using a matrix of in vitro (infectivity, gene expression, biological activity) and in vivo potency assays to determine potency as a function of capsid content, our results indicate that while intermediate capsids contribute to the vector genome titer of the product and are equally as infectious as full capsids, they do not contribute to the potency of the AAV product. This study confirms the criticality of reducing and controlling the level of intermediate capsids to ensure a more efficacious AAV product.

Systematic Literature Review of the Association of Fever and Elevated Temperature with Outcomes in Critically Ill Adult Patients.

Although most commonly associated with infection, elevated temperature and fever also occur in a variety of critically ill populations. Prior studies have suggested that fever and elevated temperature may be detrimental to critically ill patients and can lead to poor outcomes, but the evidence surrounding the association of fever with outcomes is rapidly evolving. To broadly assess potential associations of elevated temperature and fever with outcomes in critically ill adult patients, we performed a systematic literature review focusing on traumatic brain injury, stroke (ischemic and hemorrhagic), cardiac arrest, sepsis, and general intensive care unit (ICU) patients. Searches were conducted in Embase® and PubMed® from 2016 to 2021, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, including dual-screening of abstracts, full texts, and extracted data. In total, 60 studies assessing traumatic brain injury and stroke (24), cardiac arrest (8), sepsis (22), and general ICU (6) patients were included. Mortality, functional, or neurological status and length of stay were the most frequently reported outcomes. Elevated temperature and fever were associated with poor clinical outcomes in patients with traumatic brain injury, stroke, and cardiac arrest but not in patients with sepsis. Although a causal relationship between elevated temperature and poor outcomes cannot be definitively established, the association observed in this systematic literature review supports the concept that management of elevated temperature may factor in avoidance of detrimental outcomes in multiple critically ill populations. The analysis also highlights gaps in our understanding of fever and elevated temperature in critically ill adult patients.

Exploration of children's value patterns in relation to environmental education programmes.

During childhood we begin to develop values, including valuing the natural environment (biospheric values). Although biospheric values are believed to provide the foundation for pro-environmental behavior throughout the course of one's life, little research has investigated these values in children. The present study aimed to investigate the relationships between children's endorsement of biospheric values, their pro-environmental behaviors, and their perception of their friends' and peers' endorsement of biospheric values. Moreover, we investigated whether these values and behaviors, as well as the hypothesized relationships, were affected by educational programmes that were already implemented at schools. The results showed that children generally strongly endorse biospheric values, and that biospheric values were positively related to some personal and group pro-environmental behaviors. The study also found that, as in previous research with adults, the participants believed that their friends and peers endorsed biospheric values significantly less than they themselves did. Environmental educational programs were partially effective in reducing the participants' underestimation of their friends' biospheric values and increased the likelihood of some group pro-environmental behaviors. Our findings highlight the need for further research to investigate the effects of group pro-environmental behaviors and the perception of group values.

Introduction of a Novel Ethics Curriculum to the Third-Year Psychiatry Clerkship Experience.

OBJECTIVE: The purpose of this study was to determine if a brief ethics curriculum embedded in a third-year required clerkship differentially impacted students' self-rated confidence versus competence (determined by a written examination) regarding ethical principles related to psychiatry. METHODS: Using a naturalistic design, 270 medical students at the University of Washington were assigned to one of three groups during their third-year psychiatry clerkship: a control group with no additional ethics content, a group with access to a pre-recorded video ethics curriculum, or a group with live didactic sessions in addition to the video curriculum. All students took a pre- and post-test that assessed their confidence and competence in ethical theory and behavioral health ethics. RESULTS: Confidence and competence were not statistically different across the three groups prior to completing the curriculum (p > 0.1). Post-test scores on confidence in behavioral health ethics were not significantly different between the three groups (p > 0.05). Post-test scores on confidence in ethical theory were significantly higher in the video-only and video + discussion group as compared to the control group (3.74 ± 0.55 and 4.00 ± 0.44 vs. 3.19 ± 0.59 respectively; p < 0.0001). Both the video-only and video + discussion group showed greater improvement in competence in ethical theory and application than the control group (0.68 ± 0.30 and 0.76 ± 0.23 vs. 0.31 ± 0.33, respectively; p < 0.0001) and behavioral health ethics (0.79 ± 0.14 and 0.85 ± 0.14 vs. 0.59 ± 0.15, respectively; p < 0.002). CONCLUSIONS: With the addition of this ethics curriculum, students showed both increased confidence and competence in their ability to analyze ethical situations as well as increased competence regarding behavioral health ethics.

Building research capacity in primary care practices that serve predominantly racial and ethnic minority populations.

Primary care research represents only 1% of all federally funded projects. However, innovation in primary care is central to advancing health care delivery. Indeed, leaders in health care innovation recently called for primary care payment reform proposals to be tested in accountable care organizations (ACOs) consisting of independent practices (ie, practices not owned by hospitals). Yet these same practices may have less experience with the kind of systematic innovation that leads to generalizable insights, because what little funding is available for primary care research is mostly awarded to large academic medical centers. In this commentary, we report on lessons learned over 2 years (2020-2022) from conducting primary care research through a novel alliance of an ACO consisting of independent practices, a health plan, and several academic researchers, with the support of a private foundation. This collaboration is also notable because it was specifically assembled to address racial and ethnic inequities in the midst of the COVID-19 pandemic.

A novel dual-plasmid platform provides scalable transfection yielding improved productivity and packaging across multiple AAV serotypes and genomes.

Transient transfection of mammalian cells using plasmid DNA is a standard method to produce adeno-associated virus (AAV) vectors allowing for flexible and scalable manufacture. Typically, three plasmids are used to encode the necessary components to facilitate vector production; however, a dual-plasmid system, termed pDG, was introduced over 2 decades ago demonstrating two components could be combined resulting in comparable productivity to triple transfection. We have developed a novel dual-plasmid system, pOXB, with an alternative arrangement of sequences that results in significantly increased AAV vector productivity and percentage of full capsids packaged in comparison to the pDG dual design and triple transfection. Here, we demonstrate the reproducibility of these findings across seven recombinant AAV genomes and multiple capsid serotypes as well as the scalability of the pOXB dual-plasmid transfection at 50-L bioreactor scale. Purified drug substance showed a consistent product quality profile in line with triple-transfected vectors, except for a substantial improvement in intact genomes packaged using the pOXB dual- transfection system. Furthermore, pOXB dual- and triple-transfection-based vectors performed consistently in vivo. The pOXB dual plasmid represents an innovation in AAV manufacturing resulting in significant process gains while maintaining the flexibility of a transient transfection platform.

A Systematic Literature Review to Assess Fever Management and the Quality of Targeted Temperature Management in Critically Ill Patients.

Targeted temperature management (TTM) has been proposed to reduce mortality and improve neurological outcomes in postcardiac arrest and other critically ill patients. TTM implementation may vary considerably among hospitals, and "high-quality TTM" definitions are inconsistent. This systematic literature review in relevant critical care conditions evaluated the approaches to and definitions of TTM quality with respect to fever prevention and the maintenance of precise temperature control. Current evidence on the quality of fever management associated with TTM in cardiac arrest, traumatic brain injury, stroke, sepsis, and critical care more generally was examined. Searches were conducted in Embase and PubMed (2016 to 2021) following PRISMA guidelines. In total, 37 studies were identified and included, with 35 focusing on postarrest care. Frequently-reported TTM quality outcomes included the number of patients with rebound hyperthermia, deviation from target temperature, post-TTM body temperatures, and number of patients achieving target temperature. Surface and intravascular cooling were used in 13 studies, while one study used surface and extracorporeal cooling and one study used surface cooling and antipyretics. Surface and intravascular methods had comparable rates of achieving target temperature and maintaining temperature. A single study showed that patients with surface cooling had a lower incidence of rebound hyperthermia. This systematic literature review largely identified cardiac arrest literature demonstrating fever prevention with multiple TTM approaches. There was substantial heterogeneity in the definitions and delivery of quality TTM. Further research is required to define quality TTM across multiple elements, including achieving target temperature, maintaining target temperature, and preventing rebound hyperthermia.

Risk of Upper Extremity Musculoskeletal Injury Within the First Year After a Concussion.

Background: Emerging evidence suggests that athletes and military personnel are at increased risk for lower extremity musculoskeletal injury after a concussion; however, the association between concussion and subsequent upper extremity (UE) musculoskeletal injury is unknown. Purpose: To prospectively examine the association between concussion and UE musculoskeletal injury risk within the first year after returning to unrestricted activity. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 316 cases of concussion 42% (132/316 women) were observed among 5660 Concussion Assessment, Research and Education Consortium participants at the United States Military Academy from May 2015 to June 2018. Active injury surveillance within the cohort was conducted for 12 months after unrestricted return to activity to identify any incident cases of acute UE musculoskeletal injury. Injury surveillance during the follow-up period was also conducted for nonconcussed controls who were matched by sex and competitive sport level. Univariate and multivariable Cox proportional hazards regression models were used to estimate hazard ratios between concussed cases and nonconcussed controls for time to UE musculoskeletal injury. Results: During the surveillance period, 19.3% of concussed cases and 9.2% of nonconcussed controls sustained a UE injury. In the univariate model, concussed cases were 2.25 times (95% CI, 1.45-3.51) more likely to sustain a UE injury during the 12-month follow-up period when compared with the nonconcussed controls. In the multivariable model, adjusted for history of concussion, sport level, somatization, and history of UE injury, concussed cases were 1.84 times (95% CI, 1.10-3.07) more likely to sustain a UE injury during the surveillance period compared with nonconcussed controls. Sport level remained an independent risk factor for UE musculoskeletal injury; however, concussion history, somatization, and history of UE injury were not independent risk factors. Conclusion: Concussed cases were more than twice as likely to sustain an acute UE musculoskeletal injury within the first 12 months after unrestricted return to activity when compared with nonconcussed controls. The higher hazard of injury remained in the concussed group after adjusting for other potential risk factors.

Expanding Underrepresented in Medicine to Include Lesbian, Gay, Bisexual, Transgender, and Queer Individuals.

In 2003, the Association of American Medical Colleges (AAMC) stopped using the term "underrepresented minority" and instead adopted "underrepresented in medicine." This was not the first time the AAMC revised this definition. In this article, the authors call on the AAMC to revise and expand this definition to include another group that is underrepresented in medicine: lesbian, gay, bisexual, transgender, and queer (LGBTQ) individuals. It is difficult to know whether LGBTQ populations are underrepresented in medicine; however, the data that do exist suggest a significant lack of LGBTQ representation in medicine. It is unclear if this underrepresentation is due to a true numerical lack of LGBTQ physicians, to LGBTQ physicians not publicly self-identifying due to anti-LGBTQ sentiments and reactions, or to both. The authors urge the AAMC to take 3 actions: to anonymously and sensitively poll physicians nationwide to obtain a better estimate of the current number of LGBTQ physicians, to formulate improved standards for an LGBTQ health curriculum for all medical trainees to consistently produce LGBTQ-competent physicians, and to once again expand its definition of underrepresented in medicine to include LGBTQ populations. Such a change to this definition would likely lead to concerted efforts to increase the number of LGBTQ physicians, which could then lead to increased visibility, inclusivity, and mentorship programs where LGBTQ trainees could thrive. With these 3 actions, the authors believe that the AAMC has the opportunity to forge a path forward that is not only beneficial to LGBTQ trainees but also to LGBTQ patients who currently face a myriad of health disparities due to the lack of LGBTQ-identifying and LGBTQ-competent physicians.

Test-Retest Reliability of Concussion Baseline Assessments in United States Service Academy Cadets: A Report from the National Collegiate Athletic Association (NCAA)-Department of Defense (DoD) CARE Consortium.

OBJECTIVE: In response to advancing clinical practice guidelines regarding concussion management, service members, like athletes, complete a baseline assessment prior to participating in high-risk activities. While several studies have established test stability in athletes, no investigation to date has examined the stability of baseline assessment scores in military cadets. The objective of this study was to assess the test-retest reliability of a baseline concussion test battery in cadets at U.S. Service Academies. METHODS: All cadets participating in the Concussion Assessment, Research, and Education (CARE) Consortium investigation completed a standard baseline battery that included memory, balance, symptom, and neurocognitive assessments. Annual baseline testing was completed during the first 3 years of the study. A two-way mixed-model analysis of variance (intraclass correlation coefficent (ICC)3,1) and Kappa statistics were used to assess the stability of the metrics at 1-year and 2-year time intervals. RESULTS: ICC values for the 1-year test interval ranged from 0.28 to 0.67 and from 0.15 to 0.57 for the 2-year interval. Kappa values ranged from 0.16 to 0.21 for the 1-year interval and from 0.29 to 0.31 for the 2-year test interval. Across all measures, the observed effects were small, ranging from 0.01 to 0.44. CONCLUSIONS: This investigation noted less than optimal reliability for the most common concussion baseline assessments. While none of the assessments met or exceeded the accepted clinical threshold, the effect sizes were relatively small suggesting an overlap in performance from year-to-year. As such, baseline assessments beyond the initial evaluation in cadets are not essential but could aid concussion diagnosis.

Factors Associated With Delayed Concussion Reporting by United States Service Academy Cadets.

CONTEXT: Approximately half of individuals who sustain a concussion do not immediately report their injuries. Motivators for not reporting include thinking the suspected concussion was not a serious injury and wanting to continue participating in activity. Additionally, military personnel have concerns about how concussions may affect their careers. However, delayed reporting can prolong neurobehavioral recovery. Understanding the frequency of delayed reporting and contributing factors will aid in identifying individuals who may be more likely to delay reporting. OBJECTIVE: To describe the frequency of delayed concussion reporting by service academy cadets and determine if sex, injury setting, sport level, or medical history is capable of predicting delayed reporting. DESIGN: Cohort study. SETTING: Service academies. PATIENTS OR OTHER PARTICIPANTS: A total of 316 patients with concussions were observed from January 2014 to August 2016. MAIN OUTCOME MEASURE(S): All cadets completed an annual concussion baseline collection of demographic, medical history, and sports participation information. Delayed concussion reporting served as the outcome variable. Predictor variables were sex, injury setting, and sport level, as well as concussion, headache, and learning disorder history. Frequencies were calculated to describe the proportion of participants who delayed reporting. Univariable and multivariable logistic regression models were used to assess if the predictor variables were associated with delayed concussion reporting. Odds ratios (ORs) and 95% confidence intervals were calculated for all variables included in the final model. RESULTS: Of the patients with concussion, 51% were classified as delayed reporting. In univariable models, females (OR = 1.70) and National Collegiate Athletic Association cadet-athletes (OR = 1.98) were more likely to delay reporting than males and intramural cadet-athletes, respectively. The multivariable model yielded similar findings. CONCLUSIONS: Roughly half of the cadets who sustained a concussion failed to immediately report their injury. Specifically, our data suggested that female cadets, cadets injured outside of competition, and highly competitive cadet-athletes were almost twice as likely to delay reporting as others.

Concussion-Recovery Trajectories Among Tactical Athletes: Results From the CARE Consortium.

CONTEXT: Assessments of the duration of concussion recovery have primarily been limited to sport-related concussions and male contact sports. Furthermore, whereas durations of symptoms and return-to-activity (RTA) protocols encompass total recovery, the trajectory of each duration has not been examined separately. OBJECTIVE: To identify individual (eg, demographics, medical history), initial concussion injury (eg, symptoms), and external (eg, site) factors associated with symptom duration and RTA-protocol duration after concussion. DESIGN: Cohort study. SETTING: Three US military service academies. PATIENTS OR OTHER PARTICIPANTS: A total of 10 604 cadets at participating US military service academies enrolled in the study and completed a baseline evaluation and up to 5 postinjury evaluations. A total of 726 cadets (451 men, 275 women) sustained concussions during the study period. MAIN OUTCOME MEASURE(S): Number of days from injury (1) until the participant became asymptomatic and (2) to complete the RTA protocol. RESULTS: Varsity athlete cadets took less time than nonvarsity cadets to become asymptomatic (hazard ratio [HR] = 1.75, 95% confidence interval = 1.38, 2.23). Cadets who reported less symptom severity on the Sport Concussion Assessment Tool, third edition (SCAT3), within 48 hours of concussion had 1.45 to 3.77 times shorter symptom-recovery durations than those with more symptom severity. Similar to symptom duration, varsity status was associated with a shorter RTA-protocol duration (HR = 1.74, 95% confidence interval = 1.34, 2.25), and less symptom severity on the SCAT3 was associated with a shorter RTA-protocol duration (HR range = 1.31 to 1.47). The academy that the cadet attended was associated with the RTA-protocol duration (P < .05). CONCLUSIONS: The initial total number of symptoms reported and varsity athlete status were strongly associated with symptom and RTA-protocol durations. These findings suggested that external (varsity status and academy) and injury (symptom burden) factors influenced the time until RTA.

The Influence of Self-Reported Tobacco Use on Baseline Concussion Assessments.

INTRODUCTION: Baseline symptom, balance, and neurocognitive scores have become an integral piece of the concussion management process. Factors such as sleep, learning disorders, fitness level, and sex have been linked to differences in performance on baseline assessments; however, it is unclear how tobacco use may affect these scores. The objective of this study was to compare baseline concussion assessment scores between service academy cadets who use and do not use tobacco. METHODS: Cadets completed a standard battery of concussion baseline assessments per standard of care and were classified into two groups: tobacco users (n = 1,232) and nonusers (n = 5,922). Dependent variables included scores on the Balance Error Scoring System, Standardized Assessment of Concussion, Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT), Brief Symptom Inventory-18, and Brief Sensation Seeking Scale (BSSS). Separate Mann-Whitney U-tests were used to compare all baseline assessment scores between groups with an adjusted P-value < 0.004. RESULTS: Cadets that used tobacco performed significantly worse on the impulse control (P < 0.001) section of the ImPACT, reported greater ImPACT symptom severity scores (P < 0.001), and were more likely to take risks as measured by the BSSS (P < 0.001). No differences were detected for Balance Error Scoring System, Standardized Assessment of Concussion, Brief Symptom Inventory-18, and Sport Concussion Assessment Tool-3 symptom scores, verbal memory, visual memory, visual-motor speed, or reaction time on the ImPACT (P > 0.004). CONCLUSIONS: Tobacco users performed significantly worse than tobacco nonusers on the impulse control section of the ImPACT, reported greater symptom severity scores on the ImPACT, and were more likely to take risks as measured by the BSSS. Despite statistical significance, these results should be interpreted with caution, as the overall effect sizes were very small. Future research should examine the influence of tobacco use on recovery post-concussion.

A cohort study to identify and evaluate concussion risk factors across multiple injury settings: findings from the CARE Consortium.

BACKGROUND: Concussion, or mild traumatic brain injury, is a major public health concern affecting 42 million individuals globally each year. However, little is known regarding concussion risk factors across all concussion settings as most concussion research has focused on only sport-related or military-related concussive injuries. METHODS: The current study is part of the Concussion, Assessment, Research, and Education (CARE) Consortium, a multi-site investigation on the natural history of concussion. Cadets at three participating service academies completed annual baseline assessments, which included demographics, medical history, and concussion history, along with the Sport Concussion Assessment Tool (SCAT) symptom checklist and Brief Symptom Inventory (BSI-18). Clinical and research staff recorded the date and injury setting at time of concussion. Generalized mixed models estimated concussion risk with service academy as a random effect. Since concussion was a rare event, the odds ratios were assumed to approximate relative risk. RESULTS: Beginning in 2014, 10,604 (n = 2421, 22.83% female) cadets enrolled over 3 years. A total of 738 (6.96%) cadets experienced a concussion, 301 (2.84%) concussed cadets were female. Female sex and previous concussion were the most consistent estimators of concussion risk across all concussion settings. Compared to males, females had 2.02 (95% CI: 1.70-2.40) times the risk of a concussion regardless of injury setting, and greater relative risk when the concussion occurred during sport (Odds Ratio (OR): 1.38 95% CI: 1.07-1.78). Previous concussion was associated with 1.98 (95% CI: 1.65-2.37) times increased risk for any incident concussion, and the magnitude was relatively stable across all concussion settings (OR: 1.73 to 2.01). Freshman status was also associated with increased overall concussion risk, but was driven by increased risk for academy training-related concussions (OR: 8.17 95% CI: 5.87-11.37). Medical history of headaches in the past 3 months, diagnosed ADD/ADHD, and BSI-18 Somatization symptoms increased overall concussion risk. CONCLUSIONS: Various demographic and medical history factors are associated with increased concussion risk. While certain factors (e.g. sex and previous concussion) are consistently associated with increased concussion risk, regardless of concussion injury setting, other factors significantly influence concussion risk within specific injury settings. Further research is required to determine whether these risk factors may aid in concussion risk reduction or prevention.

Descriptive Analysis of a Baseline Concussion Battery Among U.S. Service Academy Members: Results from the Concussion Assessment, Research, and Education (CARE) Consortium.

Introduction: The prevalence and possible long-term consequences of concussion remain an increasing concern to the U.S. military, particularly as it pertains to maintaining a medically ready force. Baseline testing is being used both in the civilian and military domains to assess concussion injury and recovery. Accurate interpretation of these baseline assessments requires one to consider other influencing factors not related to concussion. To date, there is limited understanding, especially within the military, of what factors influence normative test performance. Given the significant physical and mental demands placed on service academy members (SAM), and their relatively high risk for concussion, it is important to describe demographics and normative profile of SAMs. Furthermore, the absence of available baseline normative data on female and non-varsity SAMs makes interpretation of post-injury assessments challenging. Understanding how individuals perform at baseline, given their unique individual characteristics (e.g., concussion history, sex, competition level), will inform post-concussion assessment and management. Thus, the primary aim of this manuscript is to characterize the SAM population and determine normative values on a concussion baseline testing battery. Materials and Methods: All data were collected as part of the Concussion Assessment, Research and Education (CARE) Consortium. The baseline test battery included a post-concussion symptom checklist (Sport Concussion Assessment Tool (SCAT), psychological health screening inventory (Brief Symptom Inventory (BSI-18) and neurocognitive evaluation (ImPACT), Balance Error Scoring System (BESS), and Standardized Assessment of Concussion (SAC). Linear regression models were used to examine differences across sexes, competition levels, and varsity contact levels while controlling for academy, freshman status, race, and previous concussion. Zero inflated negative binomial models estimated symptom scores due to the high frequency of zero scores. Results: Significant, but small, sex effects were observed on the ImPACT visual memory task. While, females performed worse than males (p < 0.0001, pη2 = 0.01), these differences were small and not larger than the effects of the covariates. A similar pattern was observed for competition level on the SAC. There was a small, but significant difference across competition level. SAMs participating in varsity athletics did significantly worse on the SAC compared to SAMs participating in club or intramural athletics (all p's < 0.001, η2 = 0.01). When examining symptom reporting, males were more than two times as likely to report zero symptoms on the SCAT or BSI-18. Intramural SAMs had the highest number of symptoms and severity compared to varsity SAMs (p < 0.0001, Cohen's d < 0.2). Contact level was not associated with SCAT or BSI-18 symptoms among varsity SAMs. Notably, the significant differences across competition level on SCAT and BSI-18 were sub-clinical and had small effect sizes. Conclusion: The current analyses provide the first baseline concussion battery normative data among SAMs. While statistically significant differences may be observed on baseline tests, the effect sizes for competition and contact levels are very small, indicating that differences are likely not clinically meaningful at baseline. Identifying baseline differences and significant covariates is important for future concussion-related analyses to inform concussion evaluations for all athlete levels.

A framework for synthesis of safety justification for digitally enabled healthcare services.

BACKGROUND: Digitally enabled healthcare services combine socio-technical resources to deliver the required outcomes to patients. Unintended operation of these services may result in adverse effects to the patient. Eliminating avoidable harm requires a systematic way of analysing the causal conditions, identifying opportunities for intervention. Operators of such services may be required to justify, and communicate, their safety. For example, the UK Standardisation Committee for Care Information (SCCI) standards 0129 and 0160 require a safety justification for health IT (superseded versions were known as the Information Standards Board (ISB) 0129 & 0160. Initial as well as current standards are maintained by the NHS Digital. METHOD: A framework was designed, and applied as proof of concept, to an IT-supported clinical emergencies (A&E) service. Evaluation was done qualitatively based on the authors' experience, identifying potential benefits of the approach. RESULTS: The applied framework encapsulates analysis, and structures the generated information, into a skeleton of an evidence-based case for safety. The framework improved management of the safety activities, assigning ownership to stakeholders (e.g. IT developer), also creating a clear and compelling safety justification. CONCLUSIONS: Application of the framework significantly contributed to systematising an exploratory approach for analysing the service, in addition to existing methods such as reporting. Its application made the causal chain to harm more diaphanous. Constructing a safety case contributed to: (a) identifying potential assurance gaps, (b) planning production of information and evidence, and (c) communication of the justification by graphical unambiguous means.

Intervening to prevent repeat offending among moderate- to high-risk domestic violence offenders: a second-responder program for men.

Clear directions about best strategies to reduce recidivism among domestic violence offenders have remained elusive. The current study offers an initial evaluation of an RNR (Risk, Needs, and Responsivity)-focused second-responder program for men accused of assaulting their intimate partners and who were judged as being at moderate to high risk for re-offending. A quasi-experimental design was used to compare police outcomes for 40 men attending a second-responder intervention program to 40 men with equivalent levels of risk for re-offense who did not attend intervention (comparison group). Results showed that there were significant, substantial, and lasting differences across groups in all outcome domains. In terms of recidivism, rates of subsequent domestic-violence-related changes were more than double for men in the comparison group as compared with the intervention group in both 1-year (65.9% vs. 29.3%) and 2-year (41.5% vs. 12.2%) follow-up. Changes in the rates of arrest were consistent with reductions in men's general involvement with police, with men in the intervention group receiving fewer charges for violent offenses, administrative offenses, and property offenses over the 2 years following intervention than men in the comparison group. Not surprisingly, these differences result in a much lower estimated amount of police time with intervention men than for comparison men. Results are discussed with reference to the possible impact of sharing information with men about their assessed risk for re-offending within a therapeutic justice context.

Exposing clinicians to exposure: a randomized controlled dissemination trial of exposure therapy for anxiety disorders.

OBJECTIVE: The present study evaluated three technology-based methods of training mental health providers in exposure therapy (ET) for anxiety disorders. Training methods were designed to address common barriers to the dissemination of ET, including limited access to training, negative clinician attitudes toward ET, and lack of support during and following training. METHOD: Clinicians naïve to ET (N=181, Mage=37.4, 71.3% female, 72.1% Caucasian) were randomly assigned to (a) an interactive, multimedia online training (OLT), (b) OLT plus a brief, computerized motivational enhancement intervention (OLT+ME), or (c) OLT+ME plus a Web-based learning community (OLT+ME+LC). Assessments were completed at baseline, posttraining, and 6 and 12weeks following training. Outcomes include satisfaction, knowledge, self-efficacy, attitudes, self-reported clinical use, and observer-rated clinical proficiency. RESULTS: All three training methods led to large and comparable improvements in self-efficacy and clinical use of ET, indicating that OLT alone was sufficient for improving these outcomes. The addition of the ME intervention did not significantly improve outcomes in comparison to OLT alone. Supplementing the OLT with both the ME intervention and the LC significantly improved attitudes and clinical proficiency in comparison to OLT alone. The OLT+ME+LC condition was superior to both other conditions in increasing knowledge of ET. CONCLUSIONS: Multicomponent trainings that address multiple potential barriers to dissemination appear to be most effective in improving clinician outcomes. Technology-based training methods offer a satisfactory, effective, and scalable way to train mental health providers in evidence-based treatments such as ET.