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Objective: Describe dementia cases identified through International Classification of Diseases (ICD) coding in the Long-term Impact of Military-relevant Brain Injury Consortium - Chronic Effects of Neurotrauma Consortium (LIMBIC-CENC) multicenter prospective longitudinal study (PLS) of mild traumatic brain injury (mTBI)., Design: Descriptive case series using cross-sectional data., Methods: Veterans Affairs (VA) health system data including ICD codes were obtained for 1563 PLS participants through the VA Informatics and Computing Infrastructure (VINCI). Demographic, injury, and clinical characteristics of Dementia positive and negative cases are described., Results: Five cases of dementia were identified, all under 65 years old. The dementia cases all had a history of blast-related mTBI and all had self-reported functional problems and four had PTSD symptomatology at the clinical disorder range. Cognitive testing revealed some deficits especially in the visual memory and verbal learning and memory domains, and that two of the cases might be false positives., Conclusions: ICD codes for early dementia in the VA system have specificity concerns, but could be indicative of cognitive performance and self-reported cognitive function. Further research is needed to better determine links to blast exposure, blast-related mTBI, and PTSD to early dementia in the military population.

Objective: Physical function is associated with important outcomes, yet there is often a lack of continuity in routine assessment. The purpose of this study was to determine data elements and instruments for longitudinal measurement of physical function in routine care among patients transitioning from acute care hospital setting to home with home health care., Methods: A 4-round modified Delphi process was conducted with 13 participants with expertise in physical therapy, health care administration, health services research, physiatry/medicine, and health informatics. Three anonymous rounds identified important and feasible data elements. A fourth in-person round finalized the recommended list of individual data elements. Next, 2 focus groups independently provided additional perspectives from other stakeholders., Results: Response rates were 100% for online rounds 1, 3, and 4 and 92% for round 2. In round 1, 9 domains were identified: physical function, participation, adverse events, behavioral/emotional health, social support, cognition, complexity of illness/disease burden, health care utilization, and demographics. Following the fourth round, 27 individual data elements were recommended. Of these, 20 (74%) are "administrative" and available from most hospital electronic medical records. Additional focus groups confirmed these selections and provided input on standardizing collection methods. A website has been developed to share these results and invite other health care systems to participate in future data sharing of these identified data elements., Conclusion: A modified Delphi consensus process was used to identify critical data elements to track changes in patient physical function in routine care as they transition from acute hospital to home with home health., Impact: Expert consensus on comprehensive and feasible measurement of physical function in routine care provides health care professionals and institutions with guidance in establishing discrete medical records data that can improve patient care, discharge decisions, and future research., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Cognitive impairments in psychosis negatively impact functional recovery and quality of life. Existing interventions for improving cognitive impairment in recent-onset psychosis show inconsistent treatment efficacy, small effects, suboptimal engagement and limited generalizability to daily life functioning. In this perspective we explore how digital technology has the potential to address these limitations in order to improve cognitive and functional outcomes in recent-onset psychosis. Computer programs can be used for standardized, automated delivery of cognitive remediation training. Virtual reality provides the opportunity for learning and practicing cognitive skills in real-world scenarios within a virtual environment. Smartphone apps could be used for notification reminders for everyday tasks to compensate for cognitive difficulties. Internet-based technologies can offer psychoeducation and training materials for enhancing cognitive skills. Early findings indicate some forms of digital interventions for cognitive enhancement can be effective, with well-established evidence for human-supported computer-based cognitive remediation in recent-onset psychosis. Emerging evidence regarding virtual reality is favorable for improving social cognition. Overall, blending digital interventions with human support improves engagement and effectiveness. Despite the potential of digital interventions for enhancing cognition in recent-onset psychosis, few studies have been conducted to date. Implementation challenges affecting application of digital technologies for cognitive impairment in recent-onset psychosis are sustained engagement, clinical integration, and lack of quality in the commercial marketplace. Future opportunities lie in including motivational frameworks and behavioral change interventions, increasing service engagement in young people and lived experience involvement in digital intervention development., Competing Interests: The authors have declared that there are no conflicts of interest in relation to the subject of this study., (© 2022 The Authors.)

Background: A variety of shared care models have been developed, which aim to stratify glaucoma patients according to risk of disease progression. However, there is limited published data on the rate of glaucoma progression in the hospital vs community setting. Here we aimed to compare rates of glaucomatous visual field progression in the Cambridge Community Optometrist Glaucoma Scheme (COGS) and Addenbrooke's Hospital Glaucoma Clinic (AGC)., Methods: A retrospective comparative cohort review was performed. Patients with five or more visual field tests were included. Zeiss Forum software was used to calculate the MD progression rate (dB/year). Loss of sight years (LSY) were also calculated for both COGS and AGC., Results: Overall, 8465 visual field tests from 854 patients were reviewed. In all, 362 eyes from the AGC group and 210 eyes from COGS were included. The MD deterioration rate was significantly lower in the COGS patients compared with the AGC group (-0.1 vs -0.3 dB/year; p < 0.0001). No patients in the COGS group were predicted to become blind within their lifetime by LSY analysis. Fifteen patients were at risk in the AGC group., Conclusion: This service evaluation shows that COGS is an effective scheme to stratify lower risk glaucoma patients, increasing the capacity within hospital eye services. COGS patients have a lower rate of visual field deterioration compared to AGC patients. Effective communication between community and tertiary schemes is essential to facilitate transfer of patients requiring further hospital management reliably and efficiently, with the potential for low-risk patients to be followed safely in the community., (© 2021. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Background: People's sexual experiences have a strong association with contraceptive satisfaction and continuation, but no measures exist to specifically assess contraceptive-related sexual acceptability., Aim: This study developed and examined the psychometric properties of reliability, separation, and item fit of a new Contraceptive Sexual Acceptability (CSA) instrument., Methods: Enrolled participants initiating a new contraceptive method from the HER Salt Lake longitudinal cohort study contributed baseline survey responses for scale development. The study included the Female Sexual Function Index, the New Sexual Satisfaction Scale, measures of physical and mood-related side effects, and self-reported perceptions of contraception's sexual impacts. Items from these measures' served as the basis for analyses. We analyzed responses using descriptive techniques and modeled using exploratory factor (EFA) and bifactor analyses (BFA). The Masters' Partial Credit Rasch method modeled reliability, separation, and item fit statistics. Here we evaluate (i) the reproducibility of relative measure location on the modeled linear latent variable, (ii) the number of statistically unique performance levels that can be distinguished by the measure, and (iii) the discrepancy between item responses and expectations of the model. Psychometric findings and theoretical models informed item reduction and final scale development., Outcomes: We developed a 10-item Contraceptive Sexual Acceptability scale that exceeded the thresholds and sufficiently covered domains for use in contraceptive research and clinical settings., Results: Starting with data on 39-items from 4,387 individuals, we identified 10-items that best measured the CSA latent construct. The Rasch model included a total of 5 calibrations. We reduced items based on bifactor analysis and surpassed unidimensionality thresholds (OH = 0.84, ECV = 0.74) set a priori. The final items included questions with scaled responses about pleasure and orgasm (orgasm quality, orgasm frequency, giving partner pleasure), physical (arousal and function) and psychological (emotional connection, surrender) components, general questions of satisfaction and frequency, and a measure of perceived impact of contraception on sexual experiences in the previous 4 weeks., Clinical Implications: The 10-item CSA instrument covers physical and psychological aspects of contraceptive sexual acceptability and can be used in clinical settings., Strengths & Limitations: The unidimensional CSA instrument offers a brief, yet comprehensive assessment of sexual acceptability. Given the limited diversity of the sample, implementation of this scale in contraceptive research and clinical interactions should be evaluated and validated in more diverse settings., Conclusion: Attuning to sexual acceptability could ultimately help contraceptive clients find methods that better meet their needs and preferences. Sanders JN, Kean J, Zhang C, et al. Measuring the Sexual Acceptability of Contraception: Psychometric Examination and Development of a Valid and Reliable Prospective Instrument. J Sex Med 2022;19:507-520., (Copyright © 2022 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Understanding risk for epilepsy among persons who sustain a mild (mTBI) traumatic brain injury (TBI) is crucial for effective intervention and prevention. However, mTBI is frequently undocumented or poorly documented in health records. Further, health records are non-continuous, such as when persons move through health systems (e.g., from Department of Defense to Veterans Affairs [VA] or between jobs in the civilian sector), making population-based assessments of this relationship challenging. Here, we introduce the MINUTE (Military INjuries-Understanding post-Traumatic Epilepsy) study, which integrates data from the Veterans Health Administration with self-report survey data for post-9/11 veterans ( n  = 2603) with histories of TBI, epilepsy and controls without a history of TBI or epilepsy. This article describes the MINUTE study design, implementation, hypotheses, and initial results across four groups of interest for neurotrauma: 1) control; 2) epilepsy; 3) TBI; and 4) post-traumatic epilepsy (PTE). Using combined survey and health record data, we test hypotheses examining lifetime history of TBI and the differential impacts of TBI, epilepsy, and PTE on quality of life. The MINUTE study revealed high rates of undocumented lifetime TBIs among veterans with epilepsy who had no evidence of TBI in VA medical records. Further, worse physical functioning and health-related quality of life were found for persons with epilepsy + TBI compared to those with either epilepsy or TBI alone. This effect was not fully explained by TBI severity. These insights provide valuable opportunities to optimize the resilience, delivery of health services, and community reintegration of veterans with TBI and complex comorbidity.

Objective: To determine the diagnostic operating characteristics of The Patient Reported Outcomes Measurement Information Systems (PROMIS) depression scales in screening for major depression., Methods: Interview data from patients enrolled in clinical trials involving patients with chronic pain (2 trials) or post-stroke (1 trial) were analyzed. This included baseline and follow-up interviews in 648 and 586 study patients, respectively. Patients completed PROMIS depression scales of varying lengths (4-item, 6-item, and two 8-item scale versions) as well as the Patient Health Questionnaire 9-item (PHQ-9) depression scale. A Structured Clinical Interview for DSM Disorders (SCID) was administered to establish diagnoses of major depression and any depression. Sensitivity and specificity at various score cutpoints as well as area under the curve (AUC) were calculated., Results: PROMIS scales of varying lengths had similar diagnostic operating characteristics. The optimal screening cutpoint for PROMIS raw scores on the 4-, 6-, and 8-item scales was 8, 12, and 16, respectively, which corresponds to a PROMIS T-score of 55. The average sensitivity and specificity of the two PROMIS 8-item scales for major depression across the 3 trials using a T-score cutpoint ≥55 was 0.81 and 0.84, respectively. This was almost identical to 0.81 and 0.82 for the PHQ-9 at its standard cutpoint score ≥ 10. The average AUC for major depression was identical (0.91) for the two PROMIS 8-item scales and PHQ-9, and also similar for any depression (0.87 to 0.89)., Conclusion: PROMIS scales ranging from 4 to 8 items have strong operating characteristics comparable to the PHQ-9 in screening for depression., Trial Registration: ClinicalTrials.gov ID: NCT01236521, NCT01583985, NCT01507688., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction and Aims: Historically, people who inject image and performance enhancing drugs (IPED) were not perceived as being at high risk of HIV or hepatitis C virus (HCV) infection. However, recent studies indicate HCV and HIV prevalences are elevated, with many HCV infections undiagnosed., Design and Methods: Men who inject IPEDs recruited from community settings and specialist services, including needle-syringe programs, across UK during 2016 self-completed a questionnaire. Multivariate analyses examined factors associated with HCV/HIV testing., Results: The participants' (n=562; 24% service recruited) median age was 31 years, 4% identified as gay or bisexual, 18% had ever been imprisoned and 6% had ever injected a psychoactive drug. Those community recruited more often reported sharing drugs vials (16% vs. 8%, P=0.021) and, among those with 2+ sexual partners, poor condom use (50% vs. 36%, P=0.063), than those service recruited. Overall, one-third had ever been tested for HCV (31%) and/or HIV (34%). Testing uptake was associated with other risk factors for HCV/HIV, being recruited through services and having received metabolic tests. Participants' motivations for using IPEDs were associated with recruitment setting and HIV/HCV testing uptake., Discussion and Conclusions: The majority were untested for HCV/HIV. HCV/HIV testing and risks were associated with recruitment through services. Previous needle and syringe program-based studies have potentially overestimated testing uptake and underestimated risk. Targeted interventions are needed, particularly for those not accessing services. The association between HCV/HIV testing uptake and receipt of metabolic tests suggests that developing a combined offer of these tests as part of health monitoring could improve uptake., (© 2020 Australasian Professional Society on Alcohol and other Drugs.)

Background: The PROMIS depression scales are reliable and valid measures that have extensive normative data in general population samples. However, less is known about how responsive they are to detect change in clinical settings and how their responsiveness compares to legacy measures. The purpose of this study was to assess and compare the responsiveness of the PROMIS and Patient Health Questionnaire (PHQ) depression scales in three separate samples., Methods: We used data from three clinical trials (two in patients with chronic pain and one in stroke survivors) totaling 651 participants. At both baseline and follow-up, participants completed four PROMIS depression fixed-length scales as well as legacy measures: Patient Health Questionnaire 9-item and 2-item scales (PHQ-9 and PHQ-2) and the SF-36 Mental Health scale. We measured global ratings of depression change, both prospectively and retrospectively, as anchors to classify patients as improved, unchanged, or worsened. Responsiveness was assessed with standardized response means, statistical tests comparing change groups, and area-under-curve analysis., Results: The PROMIS depression and legacy scales had generally comparable responsiveness. Moreover, the four PROMIS depression scales of varying lengths were similarly responsive. In general, measures performed better in detecting depression improvement than depression worsening. For all measures, responsiveness varied based on the study sample and on whether depression improved or worsened., Conclusions: Both PROMIS and PHQ depression scales are brief public domain measures that are responsive (i.e., sensitive to change) and thus appropriate as outcome measures in research as well as for monitoring treatment in clinical practice. Trial registration ClinicalTrials.gov ID: NCT01236521, NCT01583985, NCT01507688.

Objective : The purpose of this study was to characterize health services utilization among individuals hospitalized with a traumatic brain injury (TBI) 1-year post-injury. Methods : Using a retrospective cohort design, adult patients (n = 32, 042) hospitalized with a traumatic brain injury between 2005 and 2014 were selected from a statewide traumatic brain injury registry. Data on health services utilization for 1-year post-injury were extracted from electronic medical and administrative records. Descriptive statistics and logistic regression were used to characterize the cohort and a subgroup of superutilizers of health services. Results : One year after traumatic brain injury, 56% of participants used emergency department services, 80% received inpatient services, and 93% utilized outpatient health services. Superutilizers had ≥3 emergency department visits, ≥3 inpatient admissions, or ≥26 outpatient visits 1-year post-injury. Twenty-six percent of participants were superutilizers of emergency department services, 30% of inpatient services, and 26% of outpatient services. Superutilizers contributed to 81% of emergency department visits, 70% of inpatient visits, and 60% of outpatient visits. Factors associated with being a superutilizer included sex, race, residence, and insurance type. Conclusions : Several patient characteristics and demographic factors influenced patients' healthcare utilization post-TBI. Findings provide opportunities for developing targeted interventions to improve patients' health and traumatic brain injury-related healthcare delivery.

Purpose: The purpose of this study was to measure the growth of the Cerebral Palsy (CP) Research Network towards becoming a Learning Health Network in order to guide future development., Methods: Thirteen CP Research Network leaders completed the Network Maturity Grid (NMG) which consists of six domains with eight to 10 components each. The six domains are Systems of Leadership, Governance and Management, Quality Improvement, Engagement and Community, Data and Analytics, and Research. Radar mapping was utilized to display mean scores on a 5-point ordinal scale (1 = not started to 5 = idealized state) across domains and for individual components within domains. Consensus was reached for top priorities for the next 3-5 years., Results: Domain scores ranged from 2.4 in Quality Improvement to 3.2 in System of Leadership. The lowest scoring component was clinician clinical decision support and the highest was common purpose. The following priority areas of focus were agreed upon moving forward: development of leaders, financial sustainability, quality improvement education and training, patient reported data, data quality and validation, and primary data collection., Conclusion: Results from this project will be utilized for strategic planning to improve the network. Conducting regular self-assessments of the network with the NMG will be useful in achieving the network's ultimate goal to improve care and outcomes for individuals with CP.

Background: The Defense Health Agency has prioritized system-level pain management initiatives within the Military Health System (MHS), with low back pain as one of the key focus areas. A stepped care model focused on nonpharmacologic treatment to promote self-management is recommended. Implementation of stepped care is complicated by lack of information on the most effective nonpharmacologic strategies and how to sequence and tailor the various available options. The Sequential Multiple-Assignment Randomization Trial for Low Back Pain (SMART LBP) is a multisite pragmatic trial using a SMART design to assess the effectiveness of nonpharmacologic treatments for chronic low back pain., Design: This SMART trial has two treatment phases. Participants from three military treatment facilities are randomized to 6 weeks of phase I treatment, receiving either physical therapy (PT) or Army Medicine's holistic Move2Health (M2H) program in a package specific to low back pain. Nonresponders to treatment in phase I are again randomized to phase II treatment of combined M2H + PT or mindfulness-based treatment using the Mindfulness-Oriented Recovery Enhancement (MORE) program. The primary outcome is the Patient-Reported Outcomes Measurement Information System pain interference computer-adapted test score., Summary: This trial is part of an initiative funded by the National Institutes of Health, Veterans Affairs, and the Department of Defense to establish a national infrastructure for effective system-level management of chronic pain with a focus on nonpharmacologic treatments. The results of this study will provide important information on nonpharmacologic care for chronic LBP in the MHS embedded within a stepped care framework., (The Author(s) 2020. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. This work is written by US Government employees and is in the public domain in the US.)

In response to the need to better define the natural history of emerging consciousness after traumatic brain injury and to better describe the characteristics of the condition commonly labeled posttraumatic amnesia, a case definition and diagnostic criteria for the posttraumatic confusional state (PTCS) were developed. This project was completed by the Confusion Workgroup of the American Congress of Rehabilitation Medicine Brain Injury Interdisciplinary Special Interest group. The case definition was informed by an exhaustive literature review and expert opinion of workgroup members from multiple disciplines. The workgroup reviewed 2466 abstracts and extracted evidence from 44 articles. Consensus was reached through teleconferences, face-to-face meetings, and 3 rounds of modified Delphi voting. The case definition provides detailed description of PTCS (1) core neurobehavioral features, (2) associated neurobehavioral features, (3) functional implications, (4) exclusion criteria, (5) lower boundary, and (6) criteria for emergence. Core neurobehavioral features include disturbances of attention, orientation, and memory as well as excessive fluctuation. Associated neurobehavioral features include emotional and behavioral disturbances, sleep-wake cycle disturbance, delusions, perceptual disturbances, and confabulation. The lower boundary distinguishes PTCS from the minimally conscious state, while upper boundary is marked by significant improvement in the 4 core and 5 associated features. Key research goals are establishment of cutoffs on assessment instruments and determination of levels of behavioral function that distinguish persons in PTCS from those who have emerged to the period of continued recovery., (Copyright © 2020. Published by Elsevier Inc.)

The COVID-19 pandemic has slowed research progress, with particularly disruptive effects on investigations of addressing urgent public health challenges, such as chronic pain. The National Institutes of Health (NIH) Department of Defense (DoD) Department of Veterans Affairs (VA) Pain Management Collaboratory (PMC) supports 11 large-scale, multisite, embedded pragmatic clinical trials (PCTs) in military and veteran health systems. The PMC rapidly developed and enacted a plan to address key issues in response to the COVID-19 pandemic. The PMC tracked and collaborated in developing plans for addressing COVID-19 impacts across multiple domains and characterized the impact of COVID-19 on PCT operations, including delays in recruitment and revisions of study protocols. A harmonized participant questionnaire will facilitate later meta-analyses and cross-study comparisons of the impact of COVID-19 across all 11 PCTs. The pandemic has affected intervention delivery, outcomes, regulatory and ethics issues, participant recruitment, and study design. The PMC took concrete steps to ensure scientific rigor while encouraging flexibility in the PCTs, while paying close attention to minimizing the burden on research participants, investigators, and clinical care teams. Sudden changes in the delivery of pain management interventions will probably alter treatment effects measured via PMC PCTs. Through the use of harmonized instruments and surveys, we are capturing these changes and plan to monitor the impact on research practices, as well as on health outcomes. Analyses of patient-reported measures over time will inform potential relationships between chronic pain, mental health, and various socioeconomic stressors common among Americans during the COVID-19 pandemic., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society of Behavioral Medicine.)

Importance: Acne is a common dermatologic condition and significantly affects psychosocial health and quality of life. An international task force recommended routine use of quality-of-life measures for clinic visits associated with acne management, but this has yet to translate into clinical practice., Objective: To assess mean Skindex-16 scores over time among patients with moderate to severe acne receiving isotretinoin treatment., Design, Setting, and Participants: A longitudinal, retrospective case series study of Skindex-16 data collected at monthly visits from 57 consecutive patients with acne receiving isotretinoin; data were collected and evaluated between November 23, 2016, and January 22, 2019. Continuous variables were compared using quantile regression. Multivariable linear mixed models evaluated mean (95% CI) score trajectory over time., Main Outcomes and Measure: Skindex-16 scores, including normalized scores for the emotional, symptomatic, and functional aspects of having skin disease as well as an overall score., Results: Fifty-seven patients (31 [54.4 %] males, with median [interquartile range] age of 17.2 [15.9-18.1] years) in this case series study completed the Skindex-16 at baseline and at least once during follow-up. Baseline Skindex-16 scores were similar by sex but worse with increasing age. Emotional impact was more bothersome to patients with acne requiring isotretinoin treatment than either symptoms or functioning. Improvements of greater than 50% in overall and Emotional domain scores were seen by month 2 of receiving isotretinoin treatment (eg, overall scores decreased from 39.4 to 17.5 by month 2; a decrease of 22.0; P < .001). Qualitatively, Skindex-16 scores reached their nadir between months 3 and 5; at month 4, overall Skindex-16 scores showed a 4.4-fold improvement (from 39.4 at baseline to 8.9; P < .001) and Emotional domain scores showed a 4.8-fold improvement (from 57.7 at baseline to 11.9; P < .001)., Conclusions and Relevance: The findings of this case series suggest that patients receiving isotretinoin treatment achieve greater than a 50% improvement in quality of life by month 2 and can expect approximately 4-fold to 5-fold improvements from baseline with a full course of isotretinoin. This study shows the potential of routine administration of quality of life measures to assess patient care in dermatology.

Objective: Delirium remains underdetected as a result of its broad constellation of symptoms and the inadequate neuropsychiatric expertise of most medical-surgical clinicians. Brief, accurate tools are needed to enhance detection., Methods: The authors extended validation of the Delirium Diagnostic Tool-Provisional (DDT-Pro), originally validated in a study of inpatients with traumatic brain injury for diagnosis of delirium by nonexpert clinicians, for 200 general medical inpatients in Colombia. The three structured, quantitatively rated items in DDT-Pro represent the three core delirium domains., Results: High interrater reliability between physician and nurse (0.873) administrators, internal consistency (>0.81), and content validity were found. Compared with independent reference standard diagnosis with DSM-5 or the Delirium Rating Scale-Revised-98, the area under the receiver operating characteristic (ROC) curve (global diagnostic accuracy) range was 93.8%-96.3%. ROC analysis revealed the same cutoff score (≤6) as that for the original study, with somewhat lower sensitivities of 88.0%-90.0% and specificities of 85.3%-81.2% (independent expert physician or nurse ratings). Even when rated by a trained expert physician, the original version of the Confusion Assessment Method algorithm (CAM-A) performed moderately, with lower sensitivities (61.8%-70.0%) than the DDT-Pro (88.0%-100%) and somewhat higher specificities (84.8%-95.3% versus 67.4%-86.7%), with values depending on dementia status, reference standard, and rater type. Accuracies for the DDT-Pro and CAM-A were comparable (DDT-Pro: 83.0%-87.5% versus CAM-A: 87.5%-88.5%), although lower in the dementia subgroup, especially for CAM-A. However, these tools were significantly discordant, especially in negative cases, which suggests that they do not detect diagnosis of patients in the same way., Conclusions: The DDT-Pro had high validity and reliability in provisional delirium diagnosis by physicians and nonexpert clinicians, although further validation is warranted before widespread use can be recommended.

Purpose: Epilepsy impacts patient lives in multidimensional ways. Although previous work has investigated epilepsy impact on health status, little is known about the overall quantified impact of epilepsy in Veterans. Our goal was to describe the impact of epilepsy on Veterans' lives using the Personal Impact of Epilepsy Scale (PIES) and determine the patient and clinical characteristics most strongly correlated with epilepsy impact. We described cohort characteristics and developed regression models to determine which characteristics were most strongly associated with PIES subscale (seizure, medication, comorbidity) scores and quality of life (QOL)., Results: Approximately 36% of those who were invited responded to the survey. Of the 438 respondents included in the analyses, roughly 50% were aged 45-64 years (35% >65; 14% 18-44); 19% were women. Almost 90% had previously received care by an epilepsy specialist, 37% of which was in Veterans Health Administration (VHA) and 38% in both VHA and community. The PIES scores were moderately low (mean: 88.68, [standard deviation (SD) = 63.24]; 300 total). The PIES overall and subscale scores were significantly lower for older Veterans with epilepsy (VWE) (>65) compared with younger (18-44 years) and middle-aged (45-64 years) VWE [p < 0.001], indicating that older Veterans had a lower epilepsy impact overall, and for seizures, medication, and comorbidity. The younger and middle-aged VWE had a significantly higher proportion with psychiatric diagnosis compared with older VWE [p < 0.001]. There was a trend for significance for the overall PIES scores by gender, with women having total higher (worse) scores (mean = 93.10, SD = 69.68) than men (mean = 74.39, SD = 59.97), which was driven by a statistically higher score on the seizure subscale for women (mean = 27.66, SD = 27.97) compared with men (mean = 19.29, SD 25.35; p = 0.04). Regression models revealed that frequent seizures (>1/month, >2/month) and diagnoses of dementia significantly predicted higher (more negative) Seizure Severity PIES score [all p < 0.05]. Frequent seizures (>1/month), number of antiepileptic drugs (AEDs), and diagnosis of dementia predicted negative impact, and older age predicted positive impact for medication subscale. Frequent seizures (>1/month) and diagnoses of depression and dementia predicted negative mood and social impact [all p < 0.05]. Seizure frequency (>2/month) was the only variable that significantly predicted lack of excellent QOL [p < 0.05]. Effects for gender were not significant after controlling for other variables., Conclusions: Findings were similar to a prior study of generic health outcomes in younger and older VWE using the 36-Item Short Form Survey (SF-36). Seizure frequency was consistently associated with negative impact of epilepsy in all age groups. While dementia and other diagnosed health conditions also contributed to epilepsy impact, older VWE had significantly lower PIES scores even after controlling for physical conditions and dementia. Lower (better) scores for comorbidity and medication scales in older VWE may be due to fewer diagnosed psychiatric comorbidities and psychiatric medication that have similar cognitive impact as AEDs, and which may also interact with AEDs. Implementation of patient self-management programs to improve seizure control may reduce epilepsy impact for Veterans and reduce Veterans Affairs (VA) healthcare utilization. The PIES may also be useful to measure outcomes of self-management interventions., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To determine the relationship between comorbid health conditions and the trajectory of functional recovery 5 years following traumatic brain injury (TBI) rehabilitation., Setting: Two acute rehabilitation facilities., Participants: A total of 407 patients with primary diagnosis of TBI., Design: Prospective, observational., Main Measures: Functional Independence Measure Cognitive and Motor scores., Results: Female gender was negatively associated with the trajectory of motor recovery (P < .001). TBI severity was negatively associated with both motor and cognitive recovery and interacted with time after injury (both Ps < .0001). Hypertension was negatively associated with both motor (P < .0001) and cognitive (P = .0121) recovery, although this relationship diminished over time for motor function (P = .0447). Cardiac conditions were negatively associated with motor recovery (P = .0204), and rate of cognitive recovery was more rapid for patients with cardiac conditions (P = .0088). Depressed patients recovered cognitive function more quickly than those who were not depressed (P = .0196). Diabetes was negatively associated with motor function (P = .0088). Drug/alcohol use was positively associated with motor function (P = .0036)., Conclusions: Injury severity remains an important predictor of long-term recovery; however, certain comorbid medical conditions are negatively associated with functional abilities over the first 5 years after injury. Patients being discharged from TBI rehabilitation with comorbid cardiac, hypertensive, diabetic, and/or depressive conditions may benefit from early and ongoing clinical surveillance.

Objective: To apply practice-based evidence to clinical management of cerebral palsy (CP). The process of establishing purpose, structure, logistics, and elements of a multi-institutional registry and the baseline characteristics of initial enrollees are reported., Design: A consensus-building process among consumers, clinicians, and researchers used a participatory action process., Setting: Community, hospitals, and universities., Participants: More than 100 clinicians, researchers, and consumers and more than 1858 enrollees in the registry., Main Outcome Measures: Not applicable., Results: Consensus was that the purpose of registry was to (1) quantify practice variation, (2) facilitate quality improvement (QI), and (3) perform comparative effectiveness research (CER). Collecting data during routine clinical care using the electronic medical record was determined to be a sustainable plan for data acquisition and management. Clinicians from multiple disciplines defined salient characteristics of individuals and interventions for the registry elements. The registry was central to the clinical research network, and a leadership structure was created. A leading electronic health record platform adopted the registry elements. Twenty-four sites have initiated the data collection process and agreed to export data to the registry. Currently 12 are collecting data. Number of enrollees and characteristics were similar to other population registers., Conclusions: This is the first multi-institutional CP registry that contains the patient and treatment characteristics needed for QI and CER. The Cerebral Palsy Research Network registry elements are implemented in a versatile electronic platform and minimize burden to clinicians. The resultant registry is available for any institution to participate and is growing rapidly., (© 2020 The Authors.)

Arboviruses are pathogens of humans and animals. A better understanding of the interactions between these pathogens and the arthropod vectors, such as mosquitoes, that transmit them is necessary to develop novel control measures. A major antiviral pathway in the mosquito vector is the exogenous small interfering RNA (exo-siRNA) pathway, which is induced by arbovirus-derived double-stranded RNA in infected cells. Although recent work has shown the key role played by Argonaute-2 (Ago-2) and Dicer-2 (Dcr-2) in this pathway, the regulatory mechanisms that govern these pathways have not been studied in mosquitoes. Here, we show that the Domino ortholog p400 has antiviral activity against the alphavirus Semliki Forest virus ( Togaviridae ) both in Aedes aegypti -derived cells and in vivo Antiviral activity of p400 was also demonstrated against chikungunya virus ( Togaviridae ) and Bunyamwera virus ( Peribunyavirida e) but not Zika virus ( Flaviviridae ). p400 was found to be expressed across mosquito tissues and regulated ago-2 but not dcr-2 transcript levels in A. aegypti mosquitoes. These findings provide novel insights into the regulation of an important aedine exo-siRNA pathway effector protein, Ago-2, by the Domino ortholog p400. They add functional insights to previous observations of this protein's antiviral and RNA interference regulatory activities in Drosophila melanogaster IMPORTANCE Female Aedes aegypti mosquitoes are vectors of human-infecting arthropod-borne viruses (arboviruses). In recent decades, the incidence of arthropod-borne viral infections has grown dramatically. Vector competence is influenced by many factors, including the mosquito's antiviral defenses. The exogenous small interfering RNA (siRNA) pathway is a major antiviral response restricting arboviruses in mosquitoes. While the roles of the effectors of this pathway, Argonaute-2 and Dicer-2 are well characterized, nothing is known about its regulation in mosquitoes. In this study, we demonstrate that A. aegypti p400, whose ortholog Domino in Drosophila melanogaster is a chromatin-remodeling ATPase member of the Tip60 complex, regulates siRNA pathway activity and controls ago-2 expression levels. In addition, we found p400 to have antiviral activity against different arboviruses. Therefore, our study provides new insights into the regulation of the antiviral response in A. aegypti mosquitoes., (Copyright © 2020 McFarlane et al.)

Background: Patient Reported Outcomes Measurement Information Systems (PROMIS) scales are increasingly being used to measure symptoms in research and practice. The purpose of this study was to determine the minimally important difference (MID) and severity thresholds (cut-points) for the four fixed-length PROMIS depression scales., Methods: The study sample was adult participants in three randomized clinical trials (N=651). MID was estimated using multiple distribution- and anchor-based approaches including assessing correspondence between Patient Health Questionnaire (PHQ-9) and PROMIS depression scores., Results: The best MID estimate was a PROMIS depression T-score of 3.5 points with most methods producing an MID in the 3 to 4 point range across all three samples. MID estimates were similar for all four PROMIS scales. A PHQ-9 1-point change equated to a PROMIS 1.25-point T-score change. PROMIS T-scores of 55, 60, 65, and 70 appeared to be reasonable thresholds for mild, moderate, moderately severe, and severe depression, respectively., Limitations: The study sample was predominantly male veterans with either chronic pain (2 trials) or previous stroke (1 trial). The severity of depression was mild to moderate., Conclusion: A T-score of 3 to 4 points is a reasonable MID for PROMIS depression scales and can be used to assess treatment effects in both practice and research as well to calculate sample sizes for clinical trials. Severity cut-points can help interpret the meaning of scores and action thresholds for treatment decisions., Competing Interests: Declaration of Competing Interest None, (Copyright © 2020. Published by Elsevier B.V.)

Background: Lung-protective ventilation (LPV) improves outcomes for patients with acute respiratory distress syndrome (ARDS) through the administration of low tidal volumes (≤ 6.5 ml/kg predicted body weight [PBW]) with co-titration of positive end-expiratory pressure and fraction of inspired oxygen. Many patients with ARDS, however, are not managed with LPV. The purpose of this study was to understand the implementation barriers and facilitators to the use of LPV and a computerized LPV clinical decision support (CDS) tool in intensive care units (ICUs) in preparation for a pilot hybrid implementation-effectiveness clinical trial., Methods: We performed an explanatory sequential mixed methods study from June 2018 to March 2019 to evaluate the variation in LPV adherence across 17 ICUs in an integrated healthcare system with > 4000 mechanically ventilated patients annually. We analyzed 47 key informant interviews of ICU physicians, respiratory therapists (RTs), and nurses in 3 of the ICUs using a qualitative content analysis paradigm to investigate site variation as defined by adherence level (low, medium, high) and to identify barriers and facilitators to LPV and LPV CDS tool use., Results: Forty-two percent of patients had an initial set tidal volume of ≤ 6.5 ml/kg PBW during the measurement period (site range 21-80%). LPV CDS tool use was 28% (site range 6-91%). This study's main findings revealed multi-factorial facilitators and barriers to use that varied by ICU site adherence level. The primary facilitator was that LPV and the LPV CDS tool could be used on all mechanically ventilated patients. Barriers included a persistent gap between clinician attitudes regarding the use of LPV and actual use, the perceived loss of autonomy associated with using a computerized protocol, the nature of physician-RT interaction in ventilation management, and the lack of clear organization measures of success., Conclusions: Variation in adherence to LPV persists in ICUs within a healthcare delivery system that was an early adopter of LPV. Potentially promising strategies to increase adherence to LPV and the LPV CDS tool for ARDS patients include initiating low tidal ventilation on all mechanically ventilated patients, establishing and measuring adherence measures, and focused education addressing the physician-RT interaction. These strategies represent a blueprint for a future hybrid implementation-effectiveness trial., Competing Interests: Competing interestsAK, JK, DW, LA, JJ, LC, CW, JB, and CG—the authors have no competing financial or non-financial interests. IP—Dr. Peltan has research grants to the author’s institution with Asahi Kasei Pharma, Immunexpress, Inc. and Janssen Pharmaceuticals. RS—Dr. Srivastava is a physician founder of the I-PASS Patient Safety Institute. His employer, Intermountain Healthcare, owns his equity in the I-PASS Patient Safety Institute. Dr. Srivastava is supported in part by the Children’s Hospital Association for his work as executive council member of the Pediatric Research in Inpatient Settings (PRIS) network. Dr. Srivastava has received monetary awards, honorariums, and travel reimbursement from multiple academic and professional organizations for talks about pediatric hospitalist research networks and quality of care., (© The Author(s) 2020.)

Objective: The 5 SPADE (sleep, pain, anxiety, depression, and low energy/fatigue) symptoms are among the most prevalent and disabling symptoms in clinical practice. This study evaluates the minimally important difference (MID) of Patient-Reported Outcomes Measurement Information System (PROMIS) measures and their correspondence with other brief measures to assess SPADE symptoms., Study Design and Setting: Three hundred primary care patients completed a 4-item PROMIS scale, a numeric rating scale (NRS), and a non-PROMIS legacy scale for each of the 5 SPADE symptoms. Optimal NRS cutpoints were examined, and cross-walk units for converting legacy measure scores to PROMIS scores were determined. PROMIS scores corresponding to standard deviation (SD) and standard error of measurement (SEM) changes in legacy scores were used to estimate MID., Results: At an NRS ≥5, the mean PROMIS T-score exceeded 55 (the operational threshold for a clinically meaningful symptom) for each SPADE symptom. Correlations were high (0.70-0.86) between each PROMIS scale and its corresponding non-PROMIS legacy scale. Changes in non-PROMIS legacy scale scores of 0.35 SD and 1 SEM corresponded to mean PROMIS T-scores of 2.92 and 3.05 across the 5 SPADE symptoms, with changes in 0.2 and 0.5 SD corresponding to mean PROMIS T-scores of 1.67 and 4.16., Conclusion: A 2-step screening process for SPADE symptoms might use single-item NRS scores, proceeding to PROMIS scales for NRS scores ≥5. A PROMIS T-score change of three points represents a reasonable MID estimate, with two to four points approximating lower and upper bounds., (Copyright © 2019 Elsevier Inc. All rights reserved.)

PRéCIS:: In this study, we found a high prevalence of obstructive sleep apnea (OSA) among patients with primary open-angle glaucoma (POAG) but this was not different (nor was OSA more severe) to matched people without glaucoma., Rationale: It has been proposed that OSA might be a contributing factor in the development of POAG and by extension that there could be a role for screening people with POAG for OSA., Objectives: To assess whether the prevalence of OSA among patients with POAG is different from that in people without glaucoma and to examine for associations between apnea-hypopnea index (AHI) and markers of functional and structural changes in POAG., Methods: Unselected POAG patients and control subjects were consecutively recruited in a single center. A comprehensive ocular assessment and nocturnal multichannel cardiorespiratory monitoring were performed., Results: Data from 395 participants, 235 POAG patients, and 160 controls were analyzed. The prevalence of OSA was 58% [95% confidence interval (CI), 52-65] in POAG patients and 54% (95% CI, 47-62) in controls, with 22% (95% CI, 16-27) of POAG patients and 16% (95% CI, 11-22) of controls diagnosed with moderate or severe OSA. A total of 160 POAG participants were matched to the controls using propensity score matching. There was no significant difference in OSA prevalence between the matched groups (P=0.91 for AHI≥5 and P=0.66 for AHI≥15). The AHI was not associated with the severity of visual field defect or retinal nerve fiber layer thinning after adjustment for confounders., Conclusions: This study confirms a high prevalence of OSA among patients with POAG which is, however, not higher than in people without glaucoma matched for known OSA risk factors. Our results do not support screening for OSA in patients with POAG.

The Patient-Reported Outcomes Measurement Information System Pain Interference (PROMIS-PI) scales are reliable and publicly accessible; however, little is known about how responsive they are to detect change in clinical trials and how their responsiveness compares with legacy measures. The study purpose was to evaluate responsiveness for the PROMIS-PI scales and to compare their responsiveness with legacy pain measures. We used data from 3 clinical trials totaling 759 participants. The clinical trials included patients with chronic low back pain (n = 261), chronic back or osteoarthritis pain (n = 240), and a history of stroke (n = 258). At both baseline and follow-up, participants completed PROMIS-PI scales and legacy pain measures (Brief Pain Inventory Interference scale; Pain, Enjoyment, General Activity scale; 36-Item Short Form Survey (SF-36) Bodily Pain scale; and Roland-Morris Disability Questionnaire). We measured global ratings of pain change, both prospectively and retrospectively, as anchors to identify patients as improved, unchanged, or worsened. Responsiveness was assessed with standardized response means, statistical tests comparing change groups, and area under the curve analysis. The PROMIS-PI scales had largely comparable responsiveness with the Brief Pain Inventory Interference and Pain, Enjoyment, General Activity scales. The 4 PROMIS-PI short forms had comparable responsiveness. For all pain questionnaires, responsiveness varied based on the study population and whether pain improved or worsened. PERSPECTIVE: This article presents 1) how responsive the PROMIS-PI scales were to detect change over time in the context of 3 clinical trials and 2) how their responsiveness compared with legacy pain measures. The findings can help researchers and clinicians choose between different patient-reported pain outcome measures., (Copyright © 2019 the American Pain Society. Published by Elsevier Inc. All rights reserved.)

Anabolic androgenic steroids (AAS) are the drug of choice in many cultures of the UK. Whilst there is an abundance of evidence relating to the physiological and psychological effects of steroid abuse on the individual, surprisingly there is a paucity of information relating to the perspectives of steroid users regarding the social impact of steroid use on self and society. The lack of data from steroid users has implications for forensic and legal medicine. Specifically, evidence is limited in terms of the user's voice. This is a crucial omission; the unheard voices of steroid users have much to offer into future research. 24 IPED using participants (using substituted names to protect anonymity), engaged in semi structured interviews to discuss their own personal usage, culture issues, social media and more., (Copyright © 2019. Published by Elsevier Ltd.)

Background: Poor attentional control, defined as difficulty focusing attention on a task or shifting attention flexibly between tasks, is a transdiagnostic construct theorized to confer risk for, and maintain, depression and anxiety. Research to date in non-clinical samples has suggested a dissociable relationship between the two factors of self-reported attentional control and psychopathology, with depression being associated with difficulties shifting and anxiety being associated with focusing. However, to our knowledge no study has tested this differential set of relationships in a clinical sample., Methods: Adults (N = 493) presenting for psychiatric treatment completed measures of depressive and anxiety symptom severity and self-reported attentional control. Hierarchical linear regression and Zou's (2007) confidence interval method were used to examine the relationship between clinical symptoms and attentional control., Results: Both shifting and focusing were significantly correlated with anxiety and depressive symptoms in this sample. However, focusing was more strongly associated with clinical symptomatology than shifting, which showed a weak correlation., Limitations: All constructs were measured cross-sectionally by self-report questionnaires., Conclusions: In contrast to studies conducted in non-clinical samples, attentional focusing appears to be more relevant than attentional shifting in a clinical sample for both depression and anxiety symptoms. These findings lend support to efforts to develop neurocognitive interventions that improve focusing. Replication of these findings, particularly in longitudinal studies, is warranted., (Copyright © 2019. Published by Elsevier B.V.)

Whilst athletes are the epitome of health, venous thromboembolisms (VTE) including deep vein thrombosis and pulmonary embolism have been demonstrated to occur in well-trained athletes. VTE is frequently misdiagnosed and poorly treated within this population, often resulting in career or life-threatening ramifications. Furthermore, VTE risk rises with increasing age (> 40 years), potentially affecting masters athletes. A 44-year-old well-trained male cyclist volunteered to participate in a research project investigating the influence of exercise on haemostasis in well-trained athletes. The cyclist presented with elevated D-Dimer levels both pre- (2251 ng/mL) and post-exercise (2653 ng/mL). The cyclist reported constant mild-pain in the left mid-calf region, with a cold tingling sensation in their left foot. Diagnosis of DVT was confirmed via a DVT squeeze test and Doppler ultrasound, with the clot located in the left popliteal vein. During the research project, the cyclist was exposed to numerous thrombogenic risk factors including travel, dehydration, prolonged sitting and exercise. The DVT in the popliteal vein may have resulted from repetitive movements associated with cycling. Additionally, hypertrophy of the gastrocnemius muscle may have impinged the vein. When diagnosing DVT within a cycling population, PVES should not be overlooked as a contributing factor.

Background: Impulsivity in response to negative mood (negative urgency) and positive mood (positive urgency) is common in psychiatric disorders. The aims of this study were to test if urgency predicts treatment response during partial hospitalization in a transdiagnostic sample, and if urgency is malleable over the course of brief treatment., Method: Participants (N = 348, 55% female, M age = 32.9) were patients presenting to a CBT-based partial hospitalization program. Urgency and a range of symptoms were assessed with self-report measures during treatment., Results: Higher negative urgency scores predicted worse outcome for depression and anxiety symptoms. Negative urgency (p < .001, Cohen's d z  = 0.61) and positive urgency (p < .001, Cohen's d z  = 0.39) significantly decreased during treatment., Discussion: Findings suggest that participants report decreases in urgency during brief partial hospitalization treatment. Higher negative urgency predicted poorer treatment response for symptoms of depression and anxiety, demonstrating the need for novel treatments for urgency., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Although psychological treatments for social anxiety disorder (SAD) can be highly effective, many individuals do not respond to treatment. Identifying factors associated with improved outcomes can facilitate individualized treatment choices. We investigated whether patterns of neural connectivity predicted treatment responses and whether treatment type, cognitive behavioral therapy (CBT) or acceptance and commitment therapy (ACT), moderated this effect., Methods: Participants with SAD (n = 34) underwent fMRI prior to treatment and completed implicit and explicit emotion regulation tasks. Neural connectivity measures were estimates of amygdala-prefrontal cortex connectivity. Treatment responder status was defined using the 'clinically significant change index' (Loerinc et al., 2015)., Results: Right amygdala-right ventrolateral prefrontal cortex connectivity during implicit emotion regulation was a significant predictor of treatment response (OR = 9.01, 95% CI = 1.77, 46.0, p = .008). Stronger inverse connectivity was associated with greater likelihood of treatment response. There were no significant neural moderators of treatment response to CBT versus ACT., Limitations: The primary limitation of this work was the small sample size which restricted the power to detect significant moderation effects, and results should be interpreted as preliminary., Conclusions: Amygdala-vlPFC connectivity during affect labeling predicted treatment responder status following CBT or ACT for social anxiety disorder. This suggests that the functioning of neural circuitry supporting emotion regulation capacities may be a 'gateway' to receiving benefit from psychological treatments. Future work should aim to replicate this effect in a larger sample and consider methods for enhancing functional connectivity within this circuitry as a potential treatment adjunct., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aim: To establish a patient-centered research agenda for cerebral palsy (CP)., Method: We engaged a large cross-section of the extended community of people living with CP and those providing healthcare to people with CP ('the community') in an educational series and collaborative survey platform to establish an initial list of prioritized research ideas. After online workshops, a facilitated Delphi process was used to select the 20 highest priorities. Select participants attended an in-person workshop to provide comment and work toward consensus of research priorities., Results: A research agenda for CP was developed by the community, which included consumers, clinicians, and researchers interested in advancing the established research agenda. The results included the top 16 research concepts produced by the process to shape and steward the research agenda, and an engaged cross-section of the community., Interpretation: It has been shown that proactively engaging consumers with clinical researchers may provide more meaningful research for the community. This study suggests that future research should have more focus on interventions and outcomes across the lifespan with increased emphasis on the following outcome measures: function, quality of life, and participation., What This Paper Adds: A patient-centered research agenda for cerebral palsy was established. Comparative effectiveness of interventions, physical activity, and understanding ageing were leading themes. Longitudinal studies across the lifespan, clinical spectrum, and ages were highly ranked. Participants reported high value for participation outcomes. Participants reported great appreciation for the engagement between consumers and clinician researchers., (© 2018 Mac Keith Press.)

Purpose: Sleep, pain, anxiety, depression, and low energy/fatigue (SPADE pentad) symptoms are common, but often unrecognized and undertreated in primary care. In an effort to improve symptom outcomes, primary care clinics are integrating patient-reported outcome measures (PROs), such as the Patient-Reported Outcome Measurement Information System (PROMIS), into practice. Whether patients with SPADE symptoms perceive these measures as useful is unknown. The purpose of this qualitative study was to explore patients' perceptions of the utility of symptom-based PROs in primary care., Methods: As part of a mixed-methods study, 23 patients (age 24-77 years) with one or more SPADE symptoms participated in one-on-one interviews about the use, implementation and visual display of PROMIS. All interviews were audio-recorded, transcribed, and analyzed using thematic analysis., Results: Five themes emerged: (1) PROs may foster communication about symptoms; (2) data from PROs may prompt clinical actions; (3) the visual display of symptom scores could be useful for patients and providers, though modifications may enhance interpretation; (4) implementation may vary according to patients' perception of PRO features (e.g., length); and (5) PROs may be useful, but only to the extent that they are valued, prioritized, and used., Conclusions: According to patients, the use of PROs to measure symptoms in primary care clinics has the potential to be useful. However, patients are reluctant to complete PROs if they perceive that clinicians do not use the measures to improve care. Barriers to implementation in primary care (e.g., duration of visit) should be addressed to enhance the utility of PROs. Clinical trial registration ClinicalTrials.gov ID: NCT02383862.

Theoretical models and empirical research point to negatively biased attention as a maintaining factor in depression. Although preliminary studies suggest experimentally modifying attentional biases (i.e., attentional bias modification; ABM) reduces depression symptoms and depression risk, relatively few rigorous studies with clinical samples have been completed. This clinical trial examines the impact of ABM on a sample of adults (N = 123) with elevated depression severity who also exhibit at least modest levels of negatively biased attention prior to treatment. Participants will be randomly assigned to either active ABM, placebo ABM, or an assessment-only control condition. Individuals assigned to ABM will complete 5 trainings per week (2 in-clinic, 3 brief trainings at-home) during a four-week period. Throughout this four-week period, participants will complete weekly assessments of symptom severity and putative treatment mediators measured across different levels of analysis (e.g., eye tracking, behavioral measures, and functional Magnetic Resonance Imaging). This article details the rationale and design of the clinical trial, including methodological issues that required more extensive consideration. Our findings may not only point to an easily-accessible, efficacious treatment for depression but may also provide a meaningful test of whether a theoretically important construct, negatively biased attention, maintains depression., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The authors aimed to evaluate whether the clinical phenotype of delirium differs if dichotomized either by sex or age (cutoff age, 65 years old) in a pooled sample of 406 nondemented adult patients with delirium as defined by DSM-IV criteria. Delirium characteristics were measured with the Delirium Rating Scale-Revised-98 (DRS-R-98). DRS-R-98 items were subgrouped to represent subscores representing the three core domains of delirium (cognitive, higher-order thinking, and circadian), noncore accessory symptoms (psychotic and affective), and diagnostic characteristics (temporal onset, fluctuation, and physical disorder). The authors compared means of the DRS-R-98 subscores and medians of individual items. Exploratory factor analyses evaluated delirium characteristics for each subgroup for each of the four groups-male, female, nongeriatric, and geriatric-while taking into account active medical diagnoses. Males had higher scores on motor agitation and affective lability (behavioral), whereas females had a higher frequency of hypoactive delirium. Delirium had a two-factor structure that emerged in all four study groups, and all its core domains loaded (i.e., correlated together) onto some of these two factors and with circadian domain correlating with accessory symptoms. Although the influence of a variety of active diagnoses on delirium was small and complex, traumatic brain injury had a clear influence on cognitive domain and abrupt onset. Age had a mild influence over delirium characteristics for both males and females. In conclusion, the authors confirmed a two-factor structure for delirium phenomenology, regardless of age and sex, with few significant differences between etiological groups.

Background: Symptoms account for more than 400 million clinic visits annually in the USA. The SPADE symptoms (sleep, pain, anxiety, depression, and low energy/fatigue) are particularly prevalent and undertreated., Objective: To assess the effectiveness of providing PROMIS (Patient-Reported Outcome Measure Information System) symptom scores to clinicians on symptom outcomes., Design: Randomized clinical trial conducted from March 2015 through May 2016 in general internal medicine and family practice clinics in an academic healthcare system., Participants: Primary care patients who screened positive for at least one SPADE symptom., Interventions: After completing the PROMIS symptom measures electronically immediately prior to their visit, the 300 study participants were randomized to a feedback group in which their clinician received a visual display of symptom scores or a control group in which scores were not provided to clinicians., Main Measures: The primary outcome was the 3-month change in composite SPADE score. Secondary outcomes were individual symptom scores, symptom documentation in the clinic note, symptom-specific clinician actions, and patient satisfaction., Key Results: Most patients (84%) had multiple clinically significant (T-score ≥ 55) SPADE symptoms. Both groups demonstrated moderate symptom improvement with a non-significant trend favoring the feedback compared to control group (between-group difference in composite T-score improvement, 1.1; P = 0.17). Symptoms present at baseline resolved at 3-month follow-up only one third of the time, and patients frequently still desired treatment. Except for pain, clinically significant symptoms were documented less than half the time. Neither symptom documentation, symptom-specific clinician actions, nor patient satisfaction differed between treatment arms. Predictors of greater symptom improvement included female sex, black race, fewer medical conditions, and receiving care in a family medicine clinic., Conclusions: Simple feedback of symptom scores to primary care clinicians in the absence of additional systems support or incentives is not superior to usual care in improving symptom outcomes., Trial Registration: clinicaltrials.gov identifier: NCT02383862.

Background: Despite recognition that the Anabolic Androgenic Steroid (AAS) using population is diverse, empirical studies to develop theories to conceptualise this variance in use have been limited., Methods: In this study, using cluster analysis and multinomial logistic regression, we identify typologies of people who use AAS and examine variations in motivations for AAS use across types in a sample of 611 men who use AAS., Results: The cluster analysis identified four groups in the data with different risk profiles. These groups largely reflect the ideal types of people who use AAS proposed by Christiansen et al. (2016): Cluster 1 (You Only Live Once (YOLO) type, n = 68, 11.1%) were younger and motivated by fat loss; Cluster 2 (Well-being type, n = 236, 38.6%) were concerned with getting fit; Cluster 3 (Athlete type, n = 155, 25.4%) were motivated by muscle and strength gains; Cluster 4 (Expert type, n = 152, 24.9%) were focused on specific goals (i.e. not 'getting fit')., Conclusion: The results of this study demonstrate the need to make information about AAS accessible to the general population and to inform health service providers about variations in motivations and associated risk behaviours. Attention should also be given to ensuring existing harm minimisation services are equipped to disseminate information about safe intra-muscular injecting and ensuring needle disposal sites are accessible to the different types., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Traumatic brain injury (TBI), spinal cord injury (SCI) and stroke are conditions of interest to public health as they can result in long-term outcomes and disabilities. Specialized registries can facilitate public health surveillance, however only 4% of hospitals in the United States actively engage in electronic reporting to these registries. We leveraged electronic claims and clinical data from a health information exchange to create a statewide TBI/SCI/Stroke registry to facilitate the study of long-term outcomes and health services utilization. The registry contains 109,943 TBI patients, 9,027 SCI patients and 117,084 stroke patients with a mean of 3 years of follow-up data after injury. Additionally, the registry contains data on individual patient encounters, prescriptions and clinical variables. The high-dimensional data with large sample sizes may present a valuable informatics resource for injury research as well as public health surveillance.

Minimally important difference (MID) refers to the smallest meaningful difference that carries implications for patient care. Minimally important differences are necessary to help interpret patient-reported pain outcomes in research and clinical practice. The PROMIS pain interference scales were validated across diverse samples; however, more information about their MIDs could improve their interpretability. The purpose of this study was to estimate MIDs for 4 fixed-length PROMIS pain interference scales, including the 6-item Pain Short Form and the 4-, 6-, and 8-item pain interference scales used in the PROMIS profile instruments. Data were analyzed from 3 randomized controlled trials (N = 759). The 3 samples, respectively, consisted of patients with chronic low back pain (n = 261), chronic back pain or hip/knee osteoarthritis pain (n = 240), and a history of stroke (n = 258). For each sample, anchor- and distribution-based approaches were used to estimate MIDs. Standard error of measurement and effect sizes were used as distribution-based MID estimates. Anchor-based MID estimates were established by mapping PROMIS pain interference scores onto established anchor measures, including the Brief Pain Inventory, and retrospective and prospective global ratings of change. The distribution- and anchor-based MID estimates showed convergence. For the pain samples, MID estimates ranged from 2 to 3 T-score points. For the nonpain sample, MID estimates ranged from 3.5 to 4.5 T-score points. The MID estimates were comparable across the 4 fixed-length scales. These MIDs can be used to evaluate treatment effects in research and clinical care and to calculate estimates for powering clinical trials.

Item response theory has its origins in educational measurement and is now commonly applied in health-related measurement of latent traits, such as function and symptoms. This application is due in large part to gains in the precision of measurement attributable to item response theory and corresponding decreases in response burden, study costs, and study duration. The purpose of this paper is twofold: introduce basic concepts of item response theory and demonstrate this analytic approach in a worked example, a Rasch model (1PL) analysis of the Eating Assessment Tool (EAT-10), a commonly used measure for oropharyngeal dysphagia. The results of the analysis were largely concordant with previous studies of the EAT-10 and illustrate for brain impairment clinicians and researchers how IRT analysis can yield greater precision of measurement., Competing Interests: Conflict Of Interest None

Objectives: To develop, for versions completed by individuals with traumatic brain injury (TBI) and an observer, a more precise metric for the Neuropsychiatric Inventory (NPI) Irritability and Aggression subscales using all behavioral item ratings for use with individuals with TBI and to address the dimensionality of the represented behavioral domains., Design: Rasch and confirmatory factor analyses of retrospective baseline NPI data from 3 treatment studies., Setting: Postacute rehabilitation clinic., Participants: NPI records (N = 525) consisting of observer ratings (n = 287) and self-ratings (n = 238) by participants with complicated mild, moderate, or severe TBI at least 6 months postinjury., Interventions: Not applicable., Main Outcome Measures: Frequency and severity ratings from NPI Irritability/Lability and Agitation/Aggression subscales., Results: Confirmatory factor analyses of both observer and participant ratings showed good fit for either a 1-factor or a 2-factor solution. Consistent with this, the Rasch model also fit the data well with aggression items indicating the more severe end of the construct and irritability items populating the milder end., Conclusions: Irritability and aggression appear to represent different levels of severity of a single construct. The derived Rasch metric offers a measure of this construct based on responses to all specific items that is appropriate for parametric statistical analysis and may be useful in research and clinical assessments of individuals with TBI., (Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: We examined patient and caregiver experiences of health services for moderate to severe traumatic brain injury (TBI) in Indiana. The objective was to provide an understanding of their lived experiences and to inform policies and practices for health services delivery for TBI., Methods: We conducted qualitative, semi-structured interviews with 62 participants (34 patients and 28 caregivers). Data analysis was guided by constructive grounded theory., Results: Three interrelated themes emerged from the data and characterised participants' experiences accessing health services for TBI: 1) inadequate access to health services; 2) unavailability of specialised, age-appropriate, and long-term health services; and 3) transportation barriers to health services that limit access to care and amplify rural health disparities for patients., Conclusion: Our findings identified significant barriers to health services for patients with TBI at different points in the care continuum. Gaps in health services and barriers to care transcend geographical boundaries within the state. We suggest ways to improve access to TBI care including: 1) decentralisation of trauma centers; 2) development of neurobehavioural and age-appropriate long-term care facilities; 3) increased workforce with expertise in TBI treatment; and 4) improved access to transportation services for patients with a TBI.

Several studies have indicated a chronic cognitive enhancing effect of Bacopa monnieri across different ages and cognitive impairment associated with vitamin and mineral deficiencies in children. Therefore, we investigated the effects of 4-month supplementation with a combination of B. monnieri extract and multiple micronutrients on cognitive functions in Indian school children aged 7-12 years. This was a randomized, double-blind, parallel design, single-center study in which 300 children were randomized to receive a beverage either fortified with B. monnieri and multiple micronutrients ("fortified") or a non-fortified isocaloric equivalent ("control") twice-daily for 4 months. Cognitive function was assessed by the Cambridge Neuropsychological Automated Test Battery (CANTAB) administered at baseline, Day 60 and Day 121. The primary endpoint was change in short-term memory (working memory) from baseline in subjects receiving "fortified" vs. "control" beverages after 4 months. Secondary endpoints included sustained attention, episodic memory, and executive function. The "fortified" beverage did not significantly improve short-term memory or any of the secondary outcomes tested relative to the "control" beverage. However, the spatial working memory "strategy" score showed significant improvement on Day 60 (difference between groups in change from baseline: -0.55; p < 0.05), but not on Day 121 due to the active intervention. Study products were well-tolerated. Reasons for these unexpected findings are discussed.

This corrects the article DOI: 10.1038/nature22800.

Objectives: To determine the Minimal Clinically Important Difference (MCID) and Robust Clinically Important Difference (RCID) of the Mayo-Portland Adaptability Inventory-4 (MPAI-4) as measures of response to intervention., Methods: Retrospective analysis of existing data. Both distribution- and anchor-based methods were used to triangulate on the MCID and to identify a moderate, that is, more robust, level of change (RCID) for the MPAI-4. These were further evaluated with respect to clinical provider ratings., Participants: Data for individuals with acquired brain injury in rehabilitation programs throughout the United States in the OutcomeInfo Database (n = 3087) with 2 MPAI-4 ratings., Main Measures: MPAI-4, Supervision Rating Scale, Clinician Rating of Global Clinical Improvement., Results: Initial analyses suggested 5 T-score points (5T) as the MCID and 9T as the RCID. Eighty-one percent to 87% of clinical raters considered a 5T change and 99% considered a 9T change to indicate meaningful improvement., Conclusions: 5T represents the MCID for the MPAI-4 and 9T, the RCID. Both values are notably less than the Reliable Change Index (RCI). While the RCI indicates change with a high level of statistical confidence, it may be insensitive to change that is considered meaningful by providers and participants as indicated by the MCID.

A theoretical debate about whether parasitoids should be time or egg limited now recognizes both as feasible, and interest has turned to determining the circumstances under which each might arise in the field, and their implications for parasitoid behaviour and evolution. Egg loads of parasitoids sampled from the field are predicted to show a negative response to host availability, but empirical support for this relationship is scarce. We measured how a parasitoid's egg load responded to seasonal fluctuations in host population density and recorded the predicted correlation. In early summer, parasitoids were at high risk of time limitation due to low host availability, and in late summer, their offspring were at greater risk of egg limitation due to high host availability. Despite clear seasonal changes in selection pressures on egg load and lifespan, the parasitoid showed no evidence of seasonal variation in its reproductive strategy. We made minor modifications to a previously published model to explore the effects of seasonal variation in host availability on optimal investments in eggs and lifespan and obtained several new results. In particular, under circumstances analogous to some of those observed in our field study, temporal stochasticity in reproductive opportunities can cause investments in eggs to increase, rather than decrease as previously predicted. Our model results helped to explain the parasitoid's lack of a seasonally varying reproductive strategy. Understanding the evolution of parasitoid egg load would benefit from a shift of research emphasis from purely stochastic variation in parasitoid reproductive opportunities to greater consideration of host dynamics., (© 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.)

Glucagon-like peptide 1 (GLP-1) regulates glucose homeostasis through the control of insulin release from the pancreas. GLP-1 peptide agonists are efficacious drugs for the treatment of diabetes. To gain insight into the molecular mechanism of action of GLP-1 peptides, here we report the crystal structure of the full-length GLP-1 receptor bound to a truncated peptide agonist. The peptide agonist retains an α-helical conformation as it sits deep within the receptor-binding pocket. The arrangement of the transmembrane helices reveals hallmarks of an active conformation similar to that observed in class A receptors. Guided by this structural information, we design peptide agonists with potent in vivo activity in a mouse model of diabetes.

The small interfering RNA (siRNA) pathway is a major antiviral response in mosquitoes; however, another RNA interference pathway, the PIWI-interacting RNA (piRNA) pathway, has been suggested to be antiviral in mosquitoes. Piwi4 has been reported to be a key mediator of this response in mosquitoes, but it is not involved in the production of virus-specific piRNAs. Here, we show that Piwi4 associates with members of the antiviral exogenous siRNA pathway (Ago2 and Dcr2), as well as with proteins of the piRNA pathway (Ago3, Piwi5, and Piwi6) in an Aedes aegypti -derived cell line, Aag2. Analysis of small RNAs captured by Piwi4 revealed that it is predominantly associated with virus-specific siRNAs in Semliki Forest virus-infected cells and, to a lesser extent, with viral piRNAs. By using a Dcr2 knockout cell line, we showed directly that Ago2 lost its antiviral activity, as it was no longer bound to siRNAs, but Piwi4 retained its antiviral activity in the absence of the siRNA pathway. These results demonstrate a complex interaction between the siRNA and piRNA pathways in A. aegypti and identify Piwi4 as a noncanonical PIWI protein that interacts with members of the siRNA and piRNA pathways, and its antiviral activities may be independent of either pathway. IMPORTANCE Mosquitoes transmit several pathogenic viruses, for example, the chikungunya and Zika viruses. In mosquito cells, virus replication intermediates in the form of double-stranded RNA are cleaved by Dcr2 into 21-nucleotide-long siRNAs, which in turn are used by Ago2 to target the virus genome. A different class of virus-derived small RNAs, PIWI-interacting RNAs (piRNAs), have also been found in infected insect cells. These piRNAs are longer and are produced in a Dcr2-independent manner. The only known antiviral protein in the PIWI family is Piwi4, which is not involved in piRNA production. It is associated with key proteins of the siRNA and piRNA pathways, although its antiviral function is independent of their actions.

The Weill Cornell Medical College Pain Registry database contains patient characteristics, treatments, and outcomes for a prospective cohort of 1,159 chronic pain patients who were seen at the Weill Cornell Medical College Pain Medicine outpatient clinic from July 8, 2011 to December 10, 2014. Patients aged 45 to 64 years comprised 43% followed by age ≥ 65 years at 37%. Fifty-eight percent were female. Average pain intensity (Brief Pain Inventory) was reported as mild by 22.3% of patients, moderate by 34.7%, and severe by 43.0%. For each pain intensity category, patient's report of average percent pain relief and health state (EuroQOL 5 Dimensions) was inversely related to average pain intensity category, whereas measures of pain interference, number of worst pain locations, and physical and psychological distress were directly related to pain intensity category. Seventy-seven percent of patients received an opioid at 1 or more clinic encounters. Median daily opioid dose in morphine equivalents was 55 with a range from 2 to 1,145 morphine equivalents. Regression analysis revealed that being male was associated with greater likelihood of an opioid ordered and higher average dosage than being female. The registry can identify patient characteristics and treatments that provide new insights into chronic pain management., Perspective: This article describes results of analyses of patient-reported outcomes and patient-related electronic health record data collected under standard of care from a prospective cohort of chronic pain outpatients at a New York City pain management clinic. The registry provides an opportunity to learn how to improve individualized chronic pain management., (Copyright © 2017 American Pain Society. Published by Elsevier Inc. All rights reserved.)

Background: The Press Ganey® Medical Practice Survey ("Press Ganey® survey") is a patient-reported questionnaire commonly used to measure patient satisfaction with outpatient health care in the United States. Our objective was to evaluate the reliability and validity of the Press Ganey® survey in a single institution setting., Methods: We analyzed surveys from 34,503 unique respondents seen by 624 providers from 47 specialties and 94 clinics at the University of Utah in 2013. The University of Utah is a health care system that provides primary through tertiary care for over 200 medical specialties. Surveys were administered online. The Press Ganey® survey consisted of 24 items organized into 6 scales: Access (4 items), Moving Through the Visit (2), Nurse Assistant (2), Care Provider (10), Personal Issues (4) and Overall Assessment (2). Missingness, ceiling and floor rates were summarized. Cronbach's alpha was used to evaluate internal consistency reliability. Confirmatory factor analysis was used to assess convergent and discriminant validities., Results: Missingness was 0.01% for the total score and ranged from 0.8 to 11.4% across items. The ceiling rate was high at 29.3% for the total score, and ranged from 55.4 to 84.1% across items. Floor rates were 0.01% for the total score, and ranged from 0.1 to 2.1% across items. Internal consistency reliability ranged from 0.79 to 0.96, and item-scale correlations ranged from 0.49 to 0.9. Confirmatory factor analysis supported convergent and discriminant validities., Conclusion: The Press Ganey® survey demonstrated suitable psychometric properties for most metrics. However, the high ceiling rate can have a notable impact on quarterly percentile scores within our institution. Multi-institutional studies of the Press Ganey® survey are needed to inform administrative decision making and institution reimbursement decisions based on this survey.