Management of Cochlear Implant Electrode Arrays Misplaced in the Internal Auditory Canal: A Systematic Review.

OBJECTIVE: Misplacement of electrode arrays in the internal auditory canal (IAC) presents a unique clinical challenge. Speech recognition is limited for cochlear implant (CI) users with misplaced arrays, and there are risks with revision surgery including facial and/or cochlear nerve injury. DATABASES REVIEWED: PubMed, Embase, and Scopus. METHODS: A literature search was performed from inception to September 2023. The search terms were designed to capture articles on misplaced arrays and the management options. Articles written in English that described cases of array misplacement into the IAC for children and adults were included. The level of evidence was assessed using Oxford Center for Evidence Based Medicine guidelines. Descriptive statistical analyses were performed. RESULTS: Twenty-eight cases of arrays misplaced in the IAC were identified. Thirteen (46%) were patients with incomplete partition type 3 (IP3), and 7 (25%) were patients with common cavity (CC) malformations. Most misplaced arrays were identified postoperatively (19 cases; 68%). Of these cases, 11 (58%) were managed with array removal. No facial nerve injuries were reported with revision surgery. Eight cases (42%) were left in place. Several underwent mapping procedures in an attempt improve the sound quality with the CI. CONCLUSION: Electrode array misplacement in the IAC is a rare complication that reportedly occurs predominately in cases with IP3 and CC malformations. Removal of misplaced arrays from the IAC reportedly has not been associated with facial nerve injuries. Cases identified with IAC misplacement postoperatively can potentially be managed with modified mapping techniques before proceeding with revision surgery.

COVID-19 Vaccination in Patients with Inborn Errors of Immunity Reduces Hospitalization and Critical Care Needs Related to COVID-19: a USIDNET Report.

BACKGROUND: The CDC and ACIP recommend COVID-19 vaccination for patients with inborn errors of immunity (IEI). Not much is known about vaccine safety in IEI, and whether vaccination attenuates infection severity in IEI. OBJECTIVE: To estimate COVID-19 vaccination safety and examine effect on outcomes in patients with IEI. METHODS: We built a secure registry database in conjunction with the US Immunodeficiency Network to examine vaccination frequency and indicators of safety and effectiveness in IEI patients. The registry opened on January 1, 2022, and closed on August 19, 2022. RESULTS: Physicians entered data on 1245 patients from 24 countries. The most common diagnoses were antibody deficiencies (63.7%). At least one COVID-19 vaccine was administered to 806 patients (64.7%), and 216 patients received vaccination prior to the development of COVID-19. The most common vaccines administered were mRNA-based (84.0%). Seventeen patients were reported to seek outpatient clinic or emergency room care for a vaccine-related complication, and one patient was hospitalized for symptomatic anemia. Eight hundred twenty-three patients (66.1%) experienced COVID-19 infection. Of these, 156 patients required hospitalization (19.0%), 47 required ICU care (5.7%), and 28 died (3.4%). Rates of hospitalization (9.3% versus 24.4%, p < 0.001), ICU admission (2.8% versus 7.6%, p = 0.013), and death (2.3% versus 4.3%, p = 0.202) in patients who had COVID-19 were lower in patients who received vaccination prior to infection. In adjusted logistic regression analysis, not having at least one COVID-19 vaccine significantly increased the odds of hospitalization and ICU admission. CONCLUSION: Vaccination for COVID-19 in the IEI population appears safe and attenuates COVID-19 severity.

A pragmatic randomized clinical trial of multilevel interventions to improve adherence to lung cancer screening (The Larch Study): Study protocol.

BACKGROUND: In real-world settings, low adherence to lung cancer screening (LCS) diminishes population-level benefits of reducing lung cancer mortality. We describe the Larch Study protocol, which tests the effectiveness of two patient-centered interventions (Patient Voices Video and Stepped Reminders) designed to address barriers and improve annual LCS adherence. METHODS: The Larch Study is a pragmatic randomized clinical trial conducted within Kaiser Permanente Washington. Eligible patients (target n = 1606) are aged 50-78 years with an index low-dose CT (LDCT) of the chest with negative or benign findings. With a 2 × 2 factorial-design, patients are individually randomized to 1 of 4 arms: video only, reminders only, both video and reminders, or usual care. The Patient Voices video addresses patient education needs by normalizing LCS, reminding patients when LCS is due, and encouraging social support. Stepped Reminders prompts primary care physicians to order patient's repeat screening LDCT and patients to schedule their scan. Intervention delivery is embedded within routine healthcare, facilitated by shared electronic health record components. Primary outcome is adherence to national LCS clinical guidelines, defined as repeat LDCT within 9-15 months. Patient-reported outcomes are measured via survey (knowledge of LCS, perception of stigma) approximately 8 weeks after index LDCT. Our mixed-methods formative evaluation includes process data, collected during the trial, and interviews with trial participants and stakeholders. DISCUSSION: Results will fill an important scientific gap on multilevel interventions to increase annual LCS adherence and provide opportunities for spread and scale to other healthcare settings. REGISTRATION: Trial is registered at clinicaltrials.gov (#NCT05747443).

Relationship of Blood Pressure, Health Behaviors, and New Diagnosis and Control of Hypertension in the BP-CHECK Study.

BACKGROUND: Undiagnosed hypertension and uncontrolled blood pressure (BP) are common and contribute to excess cardiovascular morbidity and mortality. We examined whether BP control, changes in BP, and patient behaviors and attitudes were associated with a new hypertension diagnosis. METHODS: We performed a post hoc analysis of 323 participants from BP-CHECK (Blood Pressure Checks for Diagnosing Hypertension), a randomized diagnostic study of BP measuring methods in adults without diagnosed hypertension with elevated BP recruited from 12 primary care clinics of an integrated health care system in Washington State during 2017 to 2019. All 323 participants returned a positive diagnostic test for hypertension based on 24-hour ambulatory BP monitoring and were followed for 6 months. We used linear regression to examine the relationships between a new hypertension diagnosis (primary independent variable) and differences in the change in study outcomes from baseline to 6-month. RESULTS: Mean age of study participants was 58.3 years (SD, 13.1), 147 (45%) were women, and 253 (80%) were of non-Hispanic White race. At 6 months, 154 of 323 (48%) participants had a new hypertension diagnosis of whom 88 achieved target BP control. Participants with a new hypertension diagnosis experienced significantly larger declines from baseline in BP (adjusted mean difference: systolic BP, -7.6 mm Hg [95% CI, -10.3 to -4.8]; diastolic BP, -3.8 mm Hg [95% CI, -5.6 to -2.0]) compared with undiagnosed peers. They were also significantly more likely to achieve BP control by 6 months compared with undiagnosed participants (adjusted relative risk, 1.5 [95% CI, 1.1 to 2.0]). At 6 months, 101 of 323 participants (31%) with a positive ambulatory BP monitoring diagnostic test remained with undiagnosed hypertension, uncontrolled BP, and no antihypertensive medications. CONCLUSIONS: Approximately one-third of participants with high BP on screening and ambulatory BP monitoring diagnostic testing remained with undiagnosed hypertension, uncontrolled BP, and no antihypertensive medications after 6 months. New strategies are needed to enhance integration of BP diagnostic testing into clinical practice. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03130257.

Factors that influence performance in pediatric cochlear implant recipients with cochlear nerve deficiency.

OBJECTIVES: Children with cochlear nerve deficiency (CND) have wide variability in outcomes with cochlear implant (CI) use. The current study aims to report a large cohort of pediatric CI recipients with CND and to evaluate for factors that may predict improved performance. METHODS: The current study is a retrospective review of pediatric CI recipients with CND at a tertiary academic hospital. Variables including cochlear nerve status (hypoplasia vs aplasia), age at implantation, cochleovestibular malformation, bony cochlear nerve aperture, internal auditory canal aperture, and cognitive delay were evaluated for predictors of postoperative performance. A stepwise multinomial regression analysis was performed. RESULTS: Forty-seven CI recipients (54 ears) were included in the analysis. A majority (59%) showed auditory capabilities with their CI. Twenty percent of recipients achieved some level of open-set speech perception with their CI. The regression analysis identified cochlear nerve status and cognitive delay as predictors of performance. CI recipients with cochlear nerve hypoplasia had significantly improved performance compared to those with aplasia (p = 0.003). Recipients with cognitive delay had more limited benefit than those without cognitive delay (p = 0.033). CONCLUSIONS: Children with CND can benefit from CI use, with outcomes spanning from non-use to development of spoken language. Predictive factors for improved performance include a lack of cognitive delay and cochlear hypoplasia rather than aplasia. These can be important considerations for parent counseling and decision making.

Preventing severe hypoglycemia in adults with type 2 diabetes (PHT2): Design, delivery and evaluation framework for a randomized controlled trial.

BACKGROUND: Severe hypoglycemia is a common and feared complication of medications used to lower blood glucose levels in individuals with diabetes. Psychoeducational interventions can prevent severe hypoglycemia in individuals with type 1 diabetes (T1D). We aim to determine the effectiveness of this approach among adults with type 2 diabetes (T2D) at elevated risk for severe hypoglycemia. METHODS: Preventing Hypoglycemia in Type 2 diabetes (PHT2) is a two-arm, parallel, randomized controlled trial. Participants are eligible if they are adults with T2D receiving care at an integrated group practice in Washington state and have experienced one or more episodes of severe hypoglycemia in the prior 12 months or have impaired awareness of hypoglycemia (Gold score ≥ 4). Participants are randomized to proactive nurse care management with or without my hypo compass, an evidence-based, psychoeducational intervention combining group and individual self-management training. For this study, my hypo compass was adapted to be suitable for adults with T2D and from an in-person to a virtual intervention over videoconference and telephone. The primary outcome is any self-reported severe hypoglycemia in the 12 months following the start of the intervention. Secondary outcomes include biochemical measures of hypoglycemia, self-reported hypoglycemia awareness, fear of hypoglycemia, and emergency department visits and hospitalizations for severe hypoglycemia. The study includes a process evaluation to assess implementation fidelity and clarify the causal pathway. CONCLUSION: The PHT2 trial will compare the effectiveness of two approaches for reducing severe hypoglycemia in adults with T2D. TRIAL REGISTRATION: clinicaltrials.gov, # NCT04863872.

Integrative data analysis to identify persistent post-concussion deficits and subsequent musculoskeletal injury risk: project structure and methods.

Concussions are a serious public health problem, with significant healthcare costs and risks. One of the most serious complications of concussions is an increased risk of subsequent musculoskeletal injuries (MSKI). However, there is currently no reliable way to identify which individuals are at highest risk for post-concussion MSKIs. This study proposes a novel data analysis strategy for developing a clinically feasible risk score for post-concussion MSKIs in student-athletes. The data set consists of one-time tests (eg, mental health questionnaires), relevant information on demographics, health history (including details regarding the concussion such as day of the year and time lost) and athletic participation (current sport and contact level) that were collected at a single time point as well as multiple time points (baseline and follow-up time points after the concussion) of the clinical assessments (ie, cognitive, postural stability, reaction time and vestibular and ocular motor testing). The follow-up time point measurements were treated as individual variables and as differences from the baseline. Our approach used a weight-of-evidence (WoE) transformation to handle missing data and variable heterogeneity and machine learning methods for variable selection and model fitting. We applied a training-testing sample splitting scheme and performed variable preprocessing with the WoE transformation. Then, machine learning methods were applied to predict the MSKI indicator prediction, thereby constructing a composite risk score for the training-testing sample. This methodology demonstrates the potential of using machine learning methods to improve the accuracy and interpretability of risk scores for MSKI.

Collegiate Athletes With Diabetes: Baseline Medical Comorbidities and Preseason Concussion Testing Performance.

CONTEXT: People with diabetes mellitus (DM) are at increased risk for adverse health events and complications throughout their lifetime. Whether DM significantly affects collegiate athletes' concussion baseline testing performance remains unclear. OBJECTIVES: To (1) describe the prevalence of DM and associated comorbidities and (2) compare concussion baseline testing performance between student-athletes with DM and student-athletes without DM (NoDM). DESIGN: Retrospective, cross-sectional study. SETTING: University. PATIENTS OR OTHER PARTICIPANTS: Using the Concussion, Assessment, Research and Education (CARE) Consortium research database, we matched athletes with self-reported DM (N = 229) by institution, sex, age, sport, position, testing year, and concussion history to athletes with NoDM (N = 229; total sample mean age = 19.6 ± 1.4 years, women = 42%). MAIN OUTCOME MEASURE(S): Descriptive statistics and χ2 tests of independence with subsequent odds ratios were calculated. Independent-samples t tests compared baseline symptoms, neurocognitive testing, and balance performance between athletes with DM and athletes with NoDM. Effect sizes were determined for significant group differences. RESULTS: At baseline, athletes with DM had higher rates of self-reported pre-existing balance disorders, sleep disorders, seizure disorders, motion sickness, learning disorders, vision and hearing problems, psychiatric disorders, depression, bipolar disorder, nonmigraine headaches, and meningitis than athletes with NoDM (P values < .05). We found balance differences between groups (P = .032, Cohen d = 0.17) such that, on average, athletes with DM had 1 additional error on the Balance Error Scoring System (DM = 13.4 ± 6.5; NoDM = 12.1 ± 5.9). No other comparisons yielded significant results. CONCLUSIONS: Although athletes with DM had high rates of self-reported balance disorders, sleep disorders, seizures, and meningitis, their baseline neurocognitive testing results were largely identical to those of athletes with NoDM. Our findings suggested that nonclinically meaningful differences were present in concussion baseline balance testing but no significant differences were noted in cognitive testing; however, the effect of DM on concussion recovery remains unknown.

Strategies to Increase Cervical Cancer Screening With Mailed Human Papillomavirus Self-Sampling Kits: A Randomized Clinical Trial.

Importance: Optimal strategies for increasing cervical cancer screening may differ by patient screening history and health care setting. Mailing human papillomavirus (HPV) self-sampling kits to individuals who are overdue for screening increases adherence; however, offering self-sampling kits to screening-adherent individuals has not been evaluated in the US. Objective: To evaluate the effectiveness of direct-mail and opt-in approaches for offering HPV self-sampling kits to individuals by cervical cancer screening history (screening-adherent and currently due, overdue, or unknown). Design, Setting, and Participants: Randomized clinical trial conducted in Kaiser Permanente Washington, a US integrated health care delivery system. Individuals aged 30 to 64 years with female sex, a primary care clinician, and no hysterectomy were identified through electronic health records (EHRs) and enrolled between November 20, 2020, and January 28, 2022, with follow-up through July 29, 2022. Interventions: Individuals stratified as due (eg, at the time of randomization, these individuals have been previously screened and are due for their next screening in ≤3 months) were randomized to receive usual care (patient reminders and clinician EHR alerts [n = 3671]), education (usual care plus educational materials about screening [n = 3960]), direct mail (usual care plus educational materials and a mailed self-sampling kit [n = 1482]), or to opt in (usual care plus educational materials and the option to request a kit [n = 3956]). Individuals who were overdue for screening were randomized to receive usual care (n = 5488), education (n = 1408), or direct mail (n = 1415). Individuals with unknown history for screening were randomized to receive usual care (n = 2983), education (n = 3486), or to opt in (n = 3506). Main Outcomes and Measures: The primary outcome was screening completion within 6 months. Primary analyses compared direct-mail or opt-in participants with individuals randomized to the education group. Results: The intention-to-treat analyses included 31 355 randomized individuals (mean [SD] age, 45.9 [10.4] years). Among those who were due for screening, compared with receiving education alone (1885 [47.6%]), screening completion was 14.1% (95% CI, 11.2%-16.9%) higher in the direct-mail group (914 [61.7%]) and 3.5% (95% CI, 1.2%-5.7%) higher in the opt-in group (2020 [51.1%]). Among individuals who were overdue, screening completion was 16.9% (95% CI, 13.8%-20.0%) higher in the direct-mail group (505 [35.7%]) compared with education alone (264 [18.8%]). Among those with unknown history, screening was 2.2% (95% CI, 0.5%-3.9%) higher in the opt-in group (634 [18.1%]) compared with education alone (555 [15.9%]). Conclusions and Relevance: Within a US health care system, direct-mail self-sampling increased cervical cancer screening by more than 14% in individuals who were due or overdue for cervical cancer screening. The opt-in approach minimally increased screening. To increase screening adherence, systems implementing HPV self-sampling should prioritize direct-mail outreach for individuals who are due or overdue for screening. For individuals with unknown screening history, testing alternative outreach approaches and additional efforts to document screening history are warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT04679675.

Identifying strategies to advance equitable implementation of co-occurring mental health and substance use disorder treatment in drug treatment courts: A study protocol.

Introduction: Behavioral health treatment disparities by race and ethnicity are well documented across the criminal legal system. Despite criminal legal settings such as drug treatment courts (DTCs) increasingly adopting evidence-based programs (EBPs) to improve care, there is a dearth of research identifying strategies to advance equitable implementation of EBPs and reduce racial/ethnic treatment disparities. This paper describes an innovative approach to identify community- and provider-generated strategies to support equitable implementation of an evidence-based co-occurring mental health and substance use disorder intervention, called Maintaining Independence and Sobriety through Systems Integration, Outreach and Networking-Criminal Justice (MISSION-CJ), in DTCs. Methods/design: Guided by the Health Equity Implementation Framework, qualitative interviews and surveys will assess factors facilitating and hindering equitable implementation of MISSION-CJ in DTCs among 30 Black/African American and/or Hispanic/Latino persons served and providers. Concept mapping with sixty Black/African American and/or Hispanic/Latino persons served and providers will gather community- and provider-generated strategies to address identified barriers. Finally, an advisory board will offer iterative feedback on the data to guide toolkit development and inform equitable implementation of MISSION-CJ within DTCs. Conclusions: The paper illustrates a protocol of a study based in community-engaged research and implementation science to understand multilevel drivers of racial/ethnic disparities in co-occurring disorder treatment and identify opportunities for intervention and improvements within criminal legal settings.

Online Education in Allergy and Immunology: An Update to Conferences Online in Allergy (COLA).

PURPOSE OF REVIEW: Online resources have become an essential component of medical education. We describe here our long standing but unique approach to providing online education in the specialty of allergy and immunology and its impact.  RECENT FINDINGS: In this article, we report the process and updates to our online conferencing curriculum known as Conferences Online in Allergy (COLA). The program was developed at Children's Mercy Kansas City almost two decades ago for the utilization of fellows in training, as well as practicing allergists. Since its inception viewership has continued to grow. COLA has served as a significant resource for both the new and practicing allergists. With rapidly continuing advancements in medical knowledge and technology, coupled with the aftereffects of a pandemic and remote learning, COLA will continue to play a significant role in allergy and immunology medical education.

Barriers and facilitators to the inclusion of deaf people in clinical trials.

BACKGROUND/AIMS: This article discusses the barriers that prevent deaf people from participating in clinical trials and offers recommendations to overcome these barriers and ensure equal access to study participation. METHODS: Between April and May 2022, we conducted six focus groups with 20 deaf adults who use American Sign Language, all of whom had previous experience as research study participants. Focus group prompts queried community awareness of clinical trial opportunities, barriers and facilitators to deaf people's participation in clinical trials, and recommended resources to improve clinical trial access. This qualitative focus group data is supplemented by survey data gathered from 40 principal investigators and clinical research coordinators between November 2021 and December 2021. The survey queried researchers' prior experiences with enrolling deaf participants in clinical trials and strategies they endorse for enrollment of deaf participants in future clinical trials. RESULTS: Focus group participants unanimously agreed that, compared to the general hearing population, deaf sign language users lack equivalent access to clinical trial participation. Reported barriers included lack of awareness of clinical trial opportunities, mistrust of hearing researchers, and refusal by clinical trial staff to provide accessible communication (e.g. denial of requests for sign language interpreters). Survey data from 40 principal investigators and clinical research coordinators corroborated these barriers. For example, only 2 out of 40 survey respondents had ever enrolled a deaf person in a clinical trial. Respondents indicated that the most helpful strategies for including deaf sign language users in future clinical trials would be assistance with making recruitment information accessible to deaf sign language users and assistance in identifying qualified interpreters to hire to help facilitate the informed consent process. CONCLUSION: The lack of communication accessibility is the most common factor preventing deaf sign language users from participating in clinical trials. This article provides recommendations for hearing researchers to improve deaf people's access to clinical trials moving forward, drawing from mixed-methods data.

Self-Reported Mental Health Measures of Incoming Collegiate Student-Athletes With a History of COVID-19.

BACKGROUND: People with a history of COVID-19 may experience persistent neuropsychological disruptions such as lower satisfaction with life, depression, and anxiety. Although student-athletes are at low risk for severe COVID-19 complications, the effect of COVID-19 on mental health has not been elucidated. OBJECTIVE: To compare patient-reported mental health outcomes for incoming collegiate athletes with (COVID+) or without (COVID-) a history of COVID-19. DESIGN: Case-control study. SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: A total of 178 student-athletes, consisting of 79 in the COVID+ group (44.3%; age = 18.90 ± 0.16 years) and 99 in the COVID- group (55.6%; age = 18.95 ± 0.16 years). MAIN OUTCOME MEASURE(S): Participants completed the Satisfaction With Life Scale (SWLS), the Hospital Anxiety and Depression Scale (HADS), and the State-Trait Anxiety Inventory (STAI). Unadjusted 1-way analyses of variance were conducted across all patient-reported outcomes. Analyses of covariance were calculated to determine the interaction of COVID-19 group, sex, and race and ethnicity on outcomes. Post hoc Bonferroni testing was performed to identify specific differences between groups. A χ2 analysis was computed to compare the number of athletes in each group who met the standard clinical cut points. RESULTS: We observed a between-groups difference for HADS depression (P = .047), whereby athletes in the COVID+ group had higher ratings (2.86 ± 0.26). We found group differences for the SWLS (P = .02), HADS anxiety (P = .003), and STAI state anxiety (P = .01) such that all scores were higher for the COVID+ group in the adjusted model. Post hoc testing revealed that female student-athletes in the COVID+ group had worse HADS anxiety (P = .01) and STAI trait anxiety (P = .002) scores than individuals in all other groups. We did not demonstrate differences between groups in the percentage of responses below established diagnostic thresholds. CONCLUSIONS: Incoming collegiate student-athletes who reported a previous COVID-19 diagnosis displayed higher depression scores, suggesting that clinicians may need to provide appropriate identification and referral for mental health conditions. However, we were encouraged that most participants, regardless of a history of COVID-19 diagnosis, had mental health scores that did not exceed established diagnostic threshold values.

Quantifying head impact biomechanical differences between commonly employed cleaning levels: a critical research interpretation consideration.

INTRODUCTION: Wearable accelerometry devices quantify on-field frequency and severity of head impacts to further improve sport safety. Commonly employed post-data collection cleaning techniques may affect these outcomes. OBJECTIVE: Our purpose was to compare game impact rates and magnitudes between three different cleaning levels (Level-1: impacts recorded within start and end times, Level-2: impacts during pauses/breaks removed, Level-3: video verified) for male youth tackle football. METHODS: Participants (n = 23, age = 10.9 ± 0.3 yrs, height = 150.0 ± 8.3 cm, mass = 41.6 ± 8.4 kg) wore Triax SIM-G sensors throughout Fall 2019. Impact rates, ratios (IRRs), and 95% confidence intervals (95%CI) were used to compare levels. Random-effects general linear models were used to compare peak linear acceleration (PLA;g) and angular velocity (PAV;rads/s). RESULTS: Level-1 resulted in higher impact rates (4.57; 95%CI = 4.14-5.05) compared to Level-2 (3.09; 95%CI = 2.80-3.42; IRR = 1.48; 95%CI = 1.34-1.63) and Level-3 datasets (2.56; 95%CI = 2.30-2.85; IRR = 1.78; 95%CI = 1.60-1.98). Level-2 had higher impact rates compared to Level-3 (1.21; 95%CI = 1.08-1.35). Level-1 resulted in higher PAV than Level-2 and Level-3 (p < 0.001) datasets. PLA did not differ across datasets (p = 0.296). CONCLUSIONS: Head impact data should be filtered of pauses/breaks, and does not substantially differ outcome estimates compared to time-intensive video verification.

Development of an icIEF assay for monitoring AAV capsid proteins and application to gene therapy products.

Adeno-associated virus (AAV) gene therapy vectors, which contain a DNA transgene packaged into a protein capsid, have shown tremendous therapeutic potential in recent years. Methods traditionally used in quality control labs, such as high-performance liquid chromatography (HPLC) and capillary electrophoresis (CE), do not provide a complete understanding of capsid viral protein (VP) charge heterogeneity. In the present study, we developed simple, one-step sample preparation and charge-based VP separation using imaged capillary isoelectric focusing (icIEF) for monitoring AAV products. The robustness of the method was confirmed through a design of experiments (DoE) exercise. An orthogonal reverse-phase (RP) HPLC method coupled with mass spectrometry was developed to separate and identify charge species. Additionally, capsid point mutants demonstrate the capability of the method to resolve deamidation at a single site on the viral proteins. Finally, case studies using two different AAV serotype vectors establish the icIEF method as stability indicating and demonstrate that increases in acidic species measured by icIEF correlate with increased deamidation, which, we show, results in decreased transduction efficiency. The addition of a rapid and robust icIEF method to the AAV capsid analytical toolkit enables development and consistent manufacturing of well-characterized gene therapy products.

Sleep, Immune Function, and Vaccinations in Military Personnel: Challenges and Future Directions.

The U.S. military invests substantial resources to vaccinate all personnel, including recruits, against operationally important infectious disease threats. However, research suggests that vaccine immune response and, therefore, vaccine effectiveness may be inadvertently reduced because of chronic and/or acute sleep deficiency experienced by recipients around the time of vaccination. Because sleep deficiency is expected and even necessary in deployed and training contexts, research investigations of the impacts of sleep and related physiological systems such as circadian rhythms on vaccine effectiveness in military settings are needed. Specifically, research should be aimed at understanding the effects of sleep deficiency, as well as vaccine administration schedules, on response to vaccination and clinical protection. Furthermore, knowledge gaps among military medical leadership on sleep, vaccines, and immune health should be assessed. This area of research may benefit the health and readiness of service members while also decreasing health care utilization and associated costs from illness.

Motor vehicle crash concussion mechanism displays a greater total number of symptoms and greater affective symptom severity but no neurocognitive differences compared with sport-related concussion mechanism.

Previous research among adolescents has shown differences in symptoms and neurocognitive performance between sport-related (SRC) and motor vehicle crash (MVC) concussion mechanisms. Limited research has focused on young adults. The purpose of our study was to compare symptoms, balance, and neurocognitive performance between SRC and MVC mechanisms in young adults. Forty-three (58.1% female, age = 25.5 ± 3.2 years, days since concussion = 12.8 ± 12.7) and 26 (76.9% female, age = 24.1 ± 5.6 years, days since concussion = 12.6 ± 8.3) individuals with an SRC and MVC mechanism, respectively, participated. Primary outcome measures included the total number, severity, cluster (disorientation, migraine, lethargy, and affective) of post-concussion symptoms endorsed, Balance Error Scoring System (BESS), and CNS Vital Signs scores. Clusters are subgroups of symptoms used for targeted rehabilitation. We used independent t-tests and Mann-Whitney U tests to compare symptoms, BESS, and neurocognitive performance. Cliff's Delta effect size was interpreted as negligible (<0.15), small (0.15-0.33), medium (0.34-0.47), and large (≥0.48). There were no group differences for any demographic factors or preexisting conditions (p-range = 0.112-0.991). Participants with an MVC mechanism reported a greater number of total post-concussion symptoms (p = 0.025, Cliff's Delta = 0.32) and a more severe affective symptom cluster (p = 0.010, Cliff's Delta = 0.37). There were no group differences for BESS or neurocognitive performance after correcting for multiple comparisons. The MVC mechanism resulted in a greater total symptom burden relative to the SRC mechanism. Medical practitioners and individuals experiencing a concussion should know that concussions are heterogeneous within and across various mechanisms.

Computerized and functional reaction time in varsity-level female collegiate athletes with and without a concussion history.

OBJECTIVES: To 1) determine the association between computerized and functional reaction time, and 2) compare functional reaction times between female athletes with and without a concussion history. DESIGN: Cross-sectional study. METHODS: Twenty female college athletes with concussion history (age = 19.1 ±â€¯1.5 years, height = 166.9 ±â€¯6.7 cm, mass = 62.8 ±â€¯6.9 kg, median total concussion = 1.0 [interquartile range = 1.0, 2.0]), and 28 female college athletes without concussion history (age = 19.1 ±â€¯1.0 years, height = 172.7 ±â€¯8.3 cm, mass = 65.4 ±â€¯8.4 kg). Functional reaction time was assessed during jump landing and dominant and non-dominant limb cutting. Computerized assessments included simple, complex, Stroop, and composite reaction times. Partial correlations investigated the associations between functional and computerized reaction time assessments while covarying for time between computerized and functional reaction time assessments. Analysis of covariance compared functional and computerized reaction time, covarying for time since concussion. RESULTS: There were no significant correlations between functional and computerized reaction time assessments (p-range = 0.318 to 0.999, partial correlation range = -0.149 to 0.072). Reaction time did not differ between groups during any functional (p-range = 0.057 to 0.920) or computerized (p-range = 0.605 to 0.860) reaction time assessments. CONCLUSIONS: Post-concussion reaction time is commonly assessed via computerized measures, but our data suggest computerized reaction time assessments are not characterizing reaction time during sport-like movements in varsity-level female athletes. Future research should investigate confounding factors of functional reaction time.

Economic Evaluation of Mailed Home-Based Human Papillomavirus Self-sampling Kits for Cervical Cancer Screening.

Importance: Human papillomavirus (HPV) self-sampling addresses barriers to cervical cancer screening, and mailed self-sampling kits have been reported to increase screening uptake. International research suggests mailed kits are cost-effective in certain settings. However, the cost-effectiveness of mailing HPV self-sampling kits for increasing screening uptake has not been evaluated in the US. Objective: To conduct an economic evaluation of a mailed HPV self-sampling intervention among underscreened women enrolled in an integrated US health care system. Design, Setting, and Participants: This economic evaluation involved a cost-effectiveness analysis of results from a randomized clinical trial of 19 851 women aged 30 to 64 years enrolled in a health plan from Kaiser Permanente Washington (KPWA), a US-based integrated health care system. Women were identified through electronic medical records, and eligible participants were enrolled in a health plan for at least 3 years and 5 months, had a primary care clinician, had not received a Papanicolaou test for at least 3 years and 5 months, and had not received a hysterectomy. Enrollment occurred from February 25, 2014, to August 29, 2016, with follow-up through February 25, 2018. The current economic evaluation was conducted between August 2, 2021, and July 30, 2022. Intervention delivery costs were calculated from both the KPWA and Medicare perspectives and were based on either wellness visit or Papanicolaou test-only visit costs. Intervention: Participants in the control group received usual care, which comprised patient reminders and ad hoc outreach for screening. Participants in the intervention group received usual care plus a mailed HPV self-sampling kit. Main Outcome and Measures: The primary economic outcome was the incremental cost-effectiveness ratio (ICER) for increased screening uptake, defined as the incremental difference in cost (intervention group minus control group) divided by the difference in the number of participants completing screening (intervention group minus control group) within 6 months of randomization. Results: Among 19 851 women (mean [SD] age, 50.1 [9.5] years; 76.7% White), 9960 were randomized to the intervention group, and 9891 were randomized to the control group. Baseline ICERs ranged from $85.84 (95% CI, $85.68-$85.99) using KPWA wellness visits as the cost basis to $146.29 (95% CI, $146.20-$146.38) using Medicare Papanicolaou test-only visits as the cost source. Subgroups of participants aged 50 to 64 years and participants most recently overdue for screening achieved cost-effectiveness at lower levels of willingness to pay for an additional completed screening than other subgroups. Conclusions and Relevance: In this economic evaluation, mailing HPV self-sampling kits to women overdue for cervical cancer screening was cost-effective for increased screening uptake relative to usual care. These results support mailing HPV kits as an efficient outreach strategy for increasing screening rates among eligible women in US health care systems.

A patient-centered nurse-supported primary care-based collaborative care program to treat opioid use disorder and depression: Design and protocol for the MI-CARE randomized controlled trial.

BACKGROUND: Opioid use disorder (OUD) contributes to rising morbidity and mortality. Life-saving OUD treatments can be provided in primary care but most patients with OUD don't receive treatment. Comorbid depression and other conditions complicate OUD management, especially in primary care. The MI-CARE trial is a pragmatic randomized encouragement (Zelen) trial testing whether offering collaborative care (CC) to patients with OUD and clinically-significant depressive symptoms increases OUD medication treatment with buprenorphine and improves depression outcomes compared to usual care. METHODS: Adult primary care patients with OUD and depressive symptoms (n ≥ 800) from two statewide health systems: Kaiser Permanente Washington and Indiana University Health are identified with computer algorithms from electronic Health record (EHR) data and automatically enrolled. A random sub-sample (50%) of eligible patients is offered the MI-CARE intervention: a 12-month nurse-driven CC intervention that includes motivational interviewing and behavioral activation. The remaining 50% of the study cohort comprise the usual care comparison group and is never contacted. The primary outcome is days of buprenorphine treatment provided during the intervention period. The powered secondary outcome is change in Patient Health Questionnaire (PHQ)-9 depression scores. Both outcomes are obtained from secondary electronic healthcare sources and compared in "intent-to-treat" analyses. CONCLUSION: MI-CARE addresses the need for rigorous encouragement trials to evaluate benefits of offering CC to generalizable samples of patients with OUD and mental health conditions identified from EHRs, as they would be in practice, and comparing outcomes to usual primary care. We describe the design and implementation of the trial, currently underway. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05122676. Clinical trial registration date: November 17, 2021.