Estimating intracluster correlation for ordinal data.

In this paper, we consider the estimation of intracluster correlation for ordinal data. We focus on pure-tone audiometry hearing threshold data, where thresholds are measured in 5 decibel increments. We estimate the intracluster correlation for tests from iPhone-based hearing assessment applications as a measure of test/retest reliability. We present a method to estimate the intracluster correlation using mixed effects cumulative logistic and probit models, which assume the outcome data are ordinal. This contrasts with using a mixed effects linear model which assumes that the outcome data are continuous. In simulation studies, we show that using a mixed effects linear model to estimate the intracluster correlation for ordinal data results in a negative finite sample bias, while using mixed effects cumulative logistic or probit models reduces this bias. The estimated intracluster correlation for the iPhone-based hearing assessment application is higher when using the mixed effects cumulative logistic and probit models compared to using a mixed effects linear model. When data are ordinal, using mixed effects cumulative logistic or probit models reduces the bias of intracluster correlation estimates relative to using a mixed effects linear model.

Cortical determinants of loudness perception and auditory hypersensitivity.

Parvalbumin-expressing inhibitory neurons (PVNs) stabilize cortical network activity, generate gamma rhythms, and regulate experience-dependent plasticity. Here, we observed that activation or inactivation of PVNs functioned like a volume knob in the mouse auditory cortex (ACtx), turning neural and behavioral classification of sound level up or down over a 20dB range. PVN loudness adjustments were "sticky", such that a single bout of 40Hz PVN stimulation sustainably suppressed ACtx sound responsiveness, potentiated feedforward inhibition, and behaviorally desensitized mice to loudness. Sensory sensitivity is a cardinal feature of autism, aging, and peripheral neuropathy, prompting us to ask whether PVN stimulation can persistently desensitize mice with ACtx hyperactivity, PVN hypofunction, and loudness hypersensitivity triggered by cochlear sensorineural damage. We found that a single 16-minute bout of 40Hz PVN stimulation session restored normal loudness perception for one week, showing that perceptual deficits triggered by irreversible peripheral injuries can be reversed through targeted cortical circuit interventions.

The molecular mechanism of on-demand sterol biosynthesis at organelle contact sites.

Contact-sites are specialized zones of proximity between two organelles, essential for organelle communication and coordination. The formation of contacts between the Endoplasmic Reticulum (ER), and other organelles, relies on a unique membrane environment enriched in sterols. However, how these sterol-rich domains are formed and maintained had not been understood. We found that the yeast membrane protein Yet3, the homolog of human BAP31, is localized to multiple ER contact sites. We show that Yet3 interacts with all the enzymes of the post-squalene ergosterol biosynthesis pathway and recruits them to create sterol-rich domains. Increasing sterol levels at ER contacts causes its depletion from the plasma membrane leading to a compensatory reaction and altered cell metabolism. Our data shows that Yet3 provides on-demand sterols at contacts thus shaping organellar structure and function. A molecular understanding of this protein's functions gives new insights into the role of BAP31 in development and pathology.

Multimodal exercise training to reduce frailty in people with multiple sclerosis: study protocol for a pilot randomized controlled trial.

BACKGROUND: Frailty, a syndrome characterized by decreased reserve and resistance to stressors across multiple physiologic systems, is highly prevalent in people living with multiple sclerosis (pwMS), independent of age or disability level. Frailty in MS is strongly associated with adverse clinical outcomes, such as falls, and may aggravate MS-related symptoms. Consequently, there is a pressing necessity to explore and evaluate strategies to reduce frailty levels in pwMS. The purpose of this pilot randomized controlled trial (RCT) will be to examine the feasibility and preliminary efficacy of a multimodal exercise training program to reduce frailty in pwMS. METHODS: A total of 24 participants will be randomly assigned to 6 weeks of multimodal exercise or to a waitlist control group with a 1:1 allocation. PwMS aged 40-65 years and living with frailty will be eligible. The multimodal exercise program will consist of cognitive-motor rehabilitation (i.e., virtual reality treadmill training) combined with progressive, evidence-based resistance training. At baseline and post-intervention, participants will complete the Evaluative Frailty Index for Physical Activity (EFIP), measures of fall risk, and quality of life. Frailty-related biomarkers will also be assessed. In addition, the feasibility of the multimodal exercise program will be systematically and multidimensionally evaluated. DISCUSSION: To date, no RCT has yet been conducted to evaluate whether targeted exercise interventions can minimize frailty in MS. The current study will provide novel data on the feasibility and preliminary efficacy of multimodal exercise training as a strategy for counteracting frailty in pwMS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT06042244 (registered in September 2023).

Investigating the Impact of Polypharmacy and Anticholinergic Medication Burden on Objective Cognitive Performance in Adults With Multiple Sclerosis.

BACKGROUND: Polypharmacy, or the use of 5 or more daily medications, is common in adults with multiple sclerosis (MS), and is often due to various physical, cognitive, and emotional symptoms. However, research regarding the association between polypharmacy and cognitive outcomes in MS is sparse. Furthermore, individuals with MS often use medications with anticholinergic properties, which are commonly associated with cognitive impairment and other central nervous system adverse effects. Currently, the utility of scales measuring anticholinergic burden in MS is unknown. This study aims to investigate the relationship between polypharmacy, anticholinergic burden, and objective cognitive performance in MS. METHODS: We recruited 90 individuals with MS during routine visits at an MS specialty clinic in Kansas City. Participants completed a brief, virtual cognitive assessment and answered questions about their health. Participants provided their medication lists from which we determined polypharmacy and scores on several anticholinergic burden scales. Statistical analyses included Spearman correlations and linear regression models. RESULTS: Approximately 44% of the individuals surveyed met the criteria for polypharmacy. The number of daily medications was negatively correlated with cognitive performance (rs = -0.45, P < .001). Further, the Drug Burden Index accounted for additional variance in cognitive performance beyond that explained by age, education, MS disease duration, and comorbidities [ΔR2 = .12, F(5, 84) = 7.84, P < .001.]. CONCLUSIONS: Clinicians should consider the possible negative consequences of polypharmacy when addressing cognitive concerns in MS. Anticholinergic burden scales may be valuable in this regard. Future investigations could explore behavioral and pharmacological interventions aimed at reducing polypharmacy in MS.

Rim aperture of yeast autophagic membranes balances cargo inclusion with vesicle maturation.

Autophagy eliminates cytoplasmic material by engulfment in membranous vesicles targeted for lysosome degradation. Nonselective autophagy coordinates sequestration of bulk cargo with the growth of the isolation membrane (IM) in a yet-unknown manner. Here, we show that in the budding yeast Saccharomyces cerevisiae, IMs expand while maintaining a rim sufficiently wide for sequestration of large cargo but tight enough to mature in due time. An obligate complex of Atg24/Snx4 with Atg20 or Snx41 assembles locally at the rim in a spatially extended manner that specifically depends on autophagic PI(3)P. This assembly stabilizes the open rim to promote autophagic sequestration of large cargo in correlation with vesicle expansion. Moreover, constriction of the rim by the PI(3)P-dependent Atg2-Atg18 complex and clearance of PI(3)P by Ymr1 antagonize rim opening to promote autophagic maturation and consumption of small cargo. Tight regulation of membrane rim aperture by PI(3)P thus couples the mechanism and physiology of nonselective autophagy.

Sex differences in the pleiotropy of hearing difficulty with imaging-derived phenotypes: a brain-wide investigation.

Hearing difficulty (HD) is one of the major health burdens in older adults. While aging-related changes in the peripheral auditory system play an important role, genetic variation associated with brain structure and function could also be involved in HD predisposition. We analyzed a large-scale HD genome-wide association study (GWAS; Ntotal = 501,825, 56% females) and GWAS data related to 3,935 brain imaging-derived phenotypes (IDPs) assessed in up to 33,224 individuals (52% females) using multiple magnetic resonance imaging modalities. To investigate HD pleiotropy with brain structure and function, we conducted genetic correlation, latent causal variable, Mendelian randomization, and multivariable generalized linear regression analyses. Additionally, we performed local genetic correlation and multi-trait colocalization analyses to identify genomic regions and loci implicated in the pleiotropic mechanisms shared between HD and brain IDPs. We observed a widespread genetic correlation of HD with 120 IDPs in females, 89 IDPs in males, and 171 IDPs in the sex-combined analysis. The latent causal variable analysis showed that some of these genetic correlations could be due to cause-effect relationships. For seven correlations, the causal effects were also confirmed by the Mendelian randomization approach: vessel volume→HD in the sex-combined analysis; hippocampus volume→HD, cerebellum grey matter volume→HD, primary visual cortex volume→HD, and HD→fluctuation amplitudes of node 46 in resting-state functional MRI dimensionality 100 in females; global mean thickness→HD and HD→mean orientation dispersion index in superior corona radiata in males. The local genetic correlation analysis identified 13 pleiotropic regions between HD and these seven IDPs. We also observed a colocalization signal for the rs13026575 variant between HD, primary visual cortex volume, and SPTBN1 transcriptomic regulation in females. Brain structure and function may have a role in the sex differences in HD predisposition via possible cause-effect relationships and shared regulatory mechanisms.

Text vs Patient Portal Messaging to Improve Influenza Vaccination Coverage: A Health System-Wide Randomized Clinical Trial.

Importance: Increasing influenza vaccination rates is a public health priority. One method recommended by the US Centers for Disease Control and Prevention and others is for health systems to send reminders nudging patients to be vaccinated. Objective: To evaluate and compare the effect of electronic health record (EHR)-based patient portal reminders vs text message reminders on influenza vaccination rates across a health system. Design, Setting, and Participants: This 3-arm randomized clinical trial was conducted from September 7, 2022, to April 30, 2023, among primary care patients within the University of California, Los Angeles (UCLA) health system. Interventions: Arm 1 received standard of care. The health system sent monthly reminder messages to patients due for an influenza vaccine by portal (arm 2) or text (arm 3). Arm 2 had a 2 × 2 nested design, with fixed vs responsive monthly reminders and preappointment vs no preappointment reminders. Arm 3 had 1 × 2 design, with preappointment vs no preappointment reminders. Preappointment reminders for eligible patients were sent 24 and 48 hours before scheduled primary care visits. Fixed reminders (in October, November, and December) involved identical messages via portal or text. Responsive portal reminders involved a September message asking patients about their plans for vaccination, with a follow-up reminder if the response was affirmative but the patient was not yet vaccinated. Main Outcomes and Measures: The primary outcome was influenza vaccination by April 30, 2023, obtained from the UCLA EHR, including vaccination from pharmacies and other sources. Results: A total of 262 085 patients (mean [SD] age, 45.1 [20.7] years; 237 404 [90.6%] adults; 24 681 [9.4%] children; 149 349 [57.0%] women) in 79 primary care practices were included (87 257 in arm 1, 87 478 in arm 2, and 87 350 in arm 3). At the entire primary care population level, none of the interventions improved influenza vaccination rates. All groups had rates of approximately 47%. There was no statistical or clinically significant improvement following portal vs text, preappointment reminders vs no preappointment reminders (portal and text reminders combined), or responsive vs fixed monthly portal reminders. Conclusions and Relevance: At the population level, neither portal nor text reminders for influenza vaccination were effective. Given that vaccine hesitancy may be a major reason for the lack of impact of portal or text reminders, more intensive interventions by health systems are needed to raise influenza vaccination coverage levels. Trial Registration: ClinicalTrials.gov Identifier: NCT05525494.

Association of Contact Sexual Violence Victimization and Health in the U.S.

INTRODUCTION: Sexual violence victimization is related to negative impacts, including chronic health conditions. Less is known about possible confounders of this relationship. This study examines the association between lifetime experience of contact sexual violence (CSV) and health conditions by sex, controlling for demographics and other victimization. METHODS: Data are from the 2016/2017 National Intimate Partner and Sexual Violence Survey, a nationally representative study of English- or Spanish-speaking adults. Ten health conditions (e.g., HIV/AIDS) and four activity limitations (e.g., difficulty dressing) were examined related to CSV victimization. Logistic regression models examined the association between CSV victimization and health controlling for demographics and other victimization experiences. Analyses were conducted in 2022 to 2023. RESULTS: For women and men, many health conditions and activity limitations were significantly associated with CSV after controlling for demographics. Accounting for other victimization, female CSV victims had higher odds of experiencing difficulty sleeping (Adjusted Odds Ratio [AOR]=1.3); difficulty concentrating, remembering, or making decisions (AOR=1.7); and difficulty doing errands alone (AOR=1.4) than nonvictims. Male victims had higher odds than nonvictims of having HIV/AIDS (AOR=5.2); frequent headaches (AOR=1.5); chronic pain (AOR=1.5); difficulty sleeping (AOR=1.4); serious difficulty hearing (AOR=1.3); and difficulty concentrating, remembering, or making decisions (AOR=1.5). CONCLUSIONS: CSV had a negative impact on health, although other types of victimization appear to also have an impact, especially for women. Demographic characteristics also aid the understanding of the relationship between CSV and health. Efforts to prevent CSV and other forms of violence can be coupled with healthcare- and population-level approaches to improve long-term health.

Genome-wide association study identifies human genetic variants associated with fatal outcome from Lassa fever.

Infection with Lassa virus (LASV) can cause Lassa fever, a haemorrhagic illness with an estimated fatality rate of 29.7%, but causes no or mild symptoms in many individuals. Here, to investigate whether human genetic variation underlies the heterogeneity of LASV infection, we carried out genome-wide association studies (GWAS) as well as seroprevalence surveys, human leukocyte antigen typing and high-throughput variant functional characterization assays. We analysed Lassa fever susceptibility and fatal outcomes in 533 cases of Lassa fever and 1,986 population controls recruited over a 7 year period in Nigeria and Sierra Leone. We detected genome-wide significant variant associations with Lassa fever fatal outcomes near GRM7 and LIF in the Nigerian cohort. We also show that a haplotype bearing signatures of positive selection and overlapping LARGE1, a required LASV entry factor, is associated with decreased risk of Lassa fever in the Nigerian cohort but not in the Sierra Leone cohort. Overall, we identified variants and genes that may impact the risk of severe Lassa fever, demonstrating how GWAS can provide insight into viral pathogenesis.

CT esophagogram in the emergency setting: typical findings and suggested workflow.

PURPOSE: Esophageal perforation (EP) can be a diagnostic challenge. Computed tomography (CT) and CT esophagography (CTE) are often used to rule out EP in the emergency setting with promising diagnostic performance, but the standard of care remains fluoroscopic esophagography (FE). We assess the diagnostic performance of CT and CTE when interpreted by expert and generalist radiologists and created an imaging workflow guide. METHODS: Retrospective study of patients presenting with suspected EP. Two expert radiologists independently reviewed blinded CT/CTE studies, recorded CT findings, and assigned an esophageal injury grade. We also collected initial (general radiologist) CT findings and interpretation and FE diagnoses. We assessed inter-reader reliability and diagnostic performance. RESULTS: EP was diagnosed in 46/139 (33%) encounters. The most common CT/CTE findings in EP were esophageal wall thickening (46/46, 100%), pneumomediastinum (42/46, 91%), and mediastinal stranding (39/46, 85%). CT and CTE sensitivity for detecting EP was 89% and 89% for expert radiologists, respectively, and 79% and 82% for general radiologists, compared with 46% for FE. Inter-reader agreement for detecting EP by CT and CTE was kappa 0.35 and 0.42 (both p < .001) between expert and generalist radiologists. We present radiographic images for key CT/CTE findings and a suggested workflow for the evaluation of possible EP. CONCLUSION: CT and CTE are more sensitive than FE for EP in the emergency setting. Due to the rarity of EP and current wide variability in imaging interpretation, an imaging workflow and injury grading system based on esophageal and mediastinal CT findings are offered to help guide management.

Rape and Sexual Coercion Related Pregnancy in the United States.

INTRODUCTION: Sexual violence is a major public health problem in the U.S. that is associated with numerous health impacts, including pregnancy. U.S. population-based estimates (2010-2012) found that three million women experienced a rape-related pregnancy during their lifetimes. The current study presents more recent estimates of rape and sexual coercion-related pregnancy and examines prevalence by demographic characteristics. METHODS: Data years 2016/2017 were pooled from the National Intimate Partner and Sexual Violence Survey, a random-digit-dial telephone survey of U.S. non-institutionalized adults 18 years and older. The analysis, conducted in 2023, examined lifetime experience of rape-related pregnancy, sexual coercion-related pregnancy, or both among U.S. women. Authors calculated prevalence estimates with 95% CIs and conducted pairwise chi-square tests (p-value<0.05) to describe experiences by current age, race/ethnicity, and region of residence among U.S. women overall and among victims. RESULTS: One in 20 women in the U.S., or over 5.9 million women, experienced a pregnancy from either rape, sexual coercion, or both during their lifetimes. Non-Hispanic Multiracial women experienced a higher prevalence of all three outcomes compared with non-Hispanic White, non-Hispanic Black, and Hispanic women. Among victims who experienced pregnancy from rape, 28% experienced a sexually transmitted disease, 66% were injured, and over 80% were fearful or concerned for their safety. CONCLUSIONS: Pregnancy as a consequence of rape or sexual coercion is experienced by an estimated six million U.S. women. Prevention efforts may include healthcare screenings to identify violence exposure and use of evidence-based prevention approaches to reduce sexual violence.

Sex work-related homicides: Insights from the National Violent Death Reporting System, 2012-2020.

Homicide is a prevalent cause of death among sex workers, given their increased risk of violence due to proximity to criminal activities such as drug trade and human trafficking. This study analyzes homicide data from the National Violent Death Reporting System (NVDRS) covering 49 US states, the District of Columbia, and Puerto Rico from 2012 to 2020. Case inclusion criteria included: (1) manner of death of homicide, and (2) sex work-related circumstance. Descriptive analyses examined victim and injury characteristics, suspect information, and circumstances. The study identified 321 sex work-related homicides (54% female, 41% male, 6% transgender). Among female victims, 94% were sex workers, and 54% of their suspects were clients. Money conflicts (23%) and other crimes (30%), most often in progress, commonly precipitated homicides of female victims. Substance use problems were reported in 49% of female victims, with 25% of their suspected perpetrators reportedly using substances in the preceding hours. For male victims, 54% were clients and 9% were sex workers. Suspects in male homicides were primarily sex workers (34%) or individuals engaged in sex work-adjacent criminal activities (36%). Money conflicts (49%), other crimes (47%) most often in progress, and sex trafficking involvement (25%) commonly precipitated homicides with male victims. Transgender sex worker victims were mostly transfeminine (94%) and non-Hispanic black (89%). Money conflicts (78%) most commonly precipitated homicides among transgender sex worker victims. These findings can inform prevention strategies addressing underlying risk factors for persons involved in sex work.

Prevalence estimates and factors associated with violence among older adults: National Intimate Partner and Sexual Violence (NISVS) Survey, 2016/2017.

Abuse of older adults is a public health problem. The National Intimate Partner and Sexual Violence Survey (NISVS) is a nationally-representative, telephone survey for non-institutionalized adults in the United States. To determine the prevalence and factors of intimate partner psychological aggression and physical violence and sexual violence by any perpetrator against older adults, we analyzed NISVS 2016/2017 data (n = 10,171, aged ≥ 60 years). Past 12-month prevalence of psychological aggression, physical violence, and sexual violence was 2.1%, 0.8%, and 1.7%, respectively. Odds of psychological aggression were significantly higher among those with hearing or vision impairment, and lower among those aged ≥70 years. Odds of physical violence were significantly higher for males and for those with hearing or vision impairment. Odds of sexual violence were significantly higher for unpartnered individuals and those with cognitive impairment; and lower for those aged ≥ 70 years. Epidemiologic studies of violence against older adults can inform population-specific prevention strategies.

Finerenone in Black Patients With Type 2 Diabetes and CKD: A Post hoc Analysis of the Pooled FIDELIO-DKD and FIGARO-DKD Trials.

Rationale & Objective: In FIDELITY, finerenone improved cardiorenal outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). This analysis explored the efficacy and safety of finerenone in Black patients. Study Design: Subanalysis of randomized controlled trials. Setting & Participants: Patients with T2D and CKD. Intervention: Finerenone or placebo. Outcomes: Composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure; composite of kidney failure, sustained ≥57% estimated glomerular filtration rate (eGFR) decline from baseline maintained for ≥4 weeks, or renal death. Results: Of the 13,026 patients, 522 (4.0%) self-identified as Black. Finerenone demonstrated similar effects on the cardiovascular composite outcome in Black (HR, 0.79 [95% CI, 0.51-1.24]) and non-Black patients (HR, 0.87 [95% CI, 0.79-0.96; P = 0.5 for interaction]). Kidney composite outcomes were consistent in Black (HR, 0.71 [95% CI, 0.43-1.16]) and non-Black patients (HR, 0.76 [95% CI, 0.66-0.88; P = 0.9 for interaction]). Finerenone reduced urine albumin-to-creatinine ratio by 40% at month 4 (least-squares mean treatment ratio, 0.60 [95% CI, 0.52-0.69; P < 0.001]) in Black patients and 32% at month 4 (least-squares mean treatment ratio, 0.68 [95% CI, 0.66-0.70; P < 0.001]) in non-Black patients, versus placebo. Chronic eGFR decline (month 4 to end-of-study) was slowed in Black and non-Black patients treated with finerenone versus placebo (between-group difference, 1.4 mL/min/1.73 m2 per year [95% CI, 0.33-2.44; P = 0.01] and 1.1 mL/min/1.73 m2 per year [95% CI, 0.89-1.28; P < 0.001], respectively). Safety outcomes were similar between subgroups. Limitations: Small number of Black patients; analysis was not originally powered to determine an interaction effect based on Black race. Conclusions: The efficacy and safety of finerenone appears consistent in Black and non-Black patients with CKD and T2D. Funding: Bayer AG. Trial Registration: ClinicalTrials.gov NCT02540993, NCT02545049. Plain-Language Summary: Diabetes is a major cause of chronic kidney disease (CKD), affecting more Black adults than White adults. Most adults with CKD ultimately die from heart and vascular complications (eg, heart attack and stroke) rather than kidney failure. This analysis of 2 recent trials shows that the drug finerenone was beneficial for patients with diabetes and CKD. Along with reducing kidney function decline and protein in the urine, it also decreased heart and vascular issues and lowered blood pressure in both Black and non-Black adults with diabetes and CKD. These findings have promising implications for slowing the progression of CKD and protecting against cardiovascular problems in diverse populations.

"What's up with price controls?" Stakeholders' views on the regulation of pharmaceutical pricing in Malaysia.

Escalating costs have made the accessibility of drugs one of the biggest challenges faced by the Malaysian government. The government agreed to regulate drug prices by means of external reference pricing, but its proposed policy had a setback owing to much opposition from the pharmaceutical industry. The policy did gain support from the public and from non-governmental organisations because it ensured easy access to affordable medicines. Comments from public consultations with key stakeholders were used to explore stakeholders' perceptions of the external reference pricing policy. A total of 140 comments were analysed for this study. Stakeholders' views were classified as being from the Socioeconomic, industrial, and government sectors. To summarise, the government must carefully manage and consider stakeholders' views to ensure a sound policy. Using Mendelow's stakeholder mapping, this study mapped out stakeholders' views in a systematic approach. The classification of different stakeholders' views and recommendations led to suggestions for reviewing current practices in pharmaceutical pricing regulations in the Malaysian healthcare system. The analyses can be extended to other countries that face similar concerns.

Recommendations for a Military Health System Auditory Blast Injury Prevention Standard.

INTRODUCTION: Although existing auditory injury prevention standards benefit warfighters, the Department of Defense could do more to understand and address auditory injuries (e.g., hearing loss, tinnitus, and central processing deficits) among service members. The Blast Injury Prevention Standards Recommendation (BIPSR) Process is designed to address the needs of all the Military Services for biomedically valid Military Health System (MHS) Blast Injury Prevention Standards. MATERIALS AND METHODS: Through the BIPSR Process, stakeholders provided their intended uses and requested functionalities for an MHS Blast Injury Prevention Standard. The BIPSR Process established a broad-based, non-advocacy panel of auditory injury Subject Matter Expert (SME) Panel with members drawn from industry, academia, and government. The SME Panel selected evaluation factors, weighted priorities, and then evaluated the resulting candidate MHS Auditory Blast Injury Prevention Standards against the evaluation criteria. The SME Panel members provided rationales for their decisions, documented discussions, and used iterative rounds of feedback to promote consensus building among members. The BIPSR Process used multi-attribute utility theory to combine members' evaluations and compare the candidate standards. RESULTS: The SME Panel identified and collated information about existing auditory injury datasets to identify gaps and promote data sharing and comprehensive evaluations of standards for preventing auditory blast injury. The panel evaluated the candidate standards and developed recommendations for an MHS Blast Injury Prevention Standard. CONCLUSIONS: The BIPSR Process illuminated important characteristics, capabilities, and limitations of candidate standards and existing datasets (e.g., limited human exposure data to evaluate the validity of injury prediction) for auditory blast injury prevention. The evaluation resulted in the recommendation to use the 8-hour Equivalent Level (LAeq8hr) as the interim MHS Auditory Blast Injury Prevention Standard while the community performs additional research to fill critical knowledge gaps.

Clinician Prompts for Human Papillomavirus Vaccination: A Cluster Randomized Trial.

OBJECTIVE: We assessed the impact of an online intervention using clinician prompts for human papillomavirus (HPV) vaccination with a cluster randomized controlled trial. METHODS: The randomized trial occurred July 2021-January 2022 in 48 primary care pediatric practices (24 intervention, 24 control) across the US. We trained clinicians via two online learning modules, plus weekly ''quick tips'' delivered via text or email. The training taught practices to implement a staff prompt to the clinician (e.g., printed reminders placed on the keyboard) plus electronic health record (EHR) prompts (if not already done) at well and acute/chronic visits for initial and subsequent HPV vaccination. We assessed missed opportunities for HPV vaccination using logistic regression models accounting for clustering by practice on an intent to treat basis. Surveys assessed facilitators and barriers to using prompts. RESULTS: During the 6-month intervention, missed opportunities for HPV vaccination increased (worsened) in both intervention and control groups. However, at well child care visits, missed opportunities for the initial HPV vaccine increased by 4.5 (95% CI: -9.0%, -0.1%) percentage points less in intervention versus control practices. Change in missed opportunities for subsequent doses at well child care and non-well child care visits did not differ between trial groups. An end-of trial survey found understaffing as a common challenge. CONCLUSIONS: Clinician prompts reduced missed opportunities for HPV vaccination at well child care visits. Understaffing related to the COVID-19 pandemic may have led to worsening missed opportunities for both groups and likely impeded practices in fully implementing changes.