Use and Cost of Low-Value Services Among Veterans Dually Enrolled in VA and Medicare.

BACKGROUND: Over half of veterans enrolled in the Veterans Health Administration (VA) are also enrolled in Medicare, potentially increasing their opportunity to receive low-value health services within and outside VA. OBJECTIVES: To characterize the use and cost of low-value services delivered to dually enrolled veterans from VA and Medicare. DESIGN: Retrospective cross-sectional. PARTICIPANTS: Veterans enrolled in VA and fee-for-service Medicare (FY 2017-2018). MAIN MEASURES: We used VA and Medicare administrative data to identify 29 low-value services across 6 established domains: cancer screening, diagnostic/preventive testing, preoperative testing, imaging, cardiovascular testing, and surgery. We determined the count of low-value services per 100 veterans delivered in VA and Medicare in FY 2018 overall, by domain, and by individual service. We applied standardized estimates to determine each service's cost. KEY RESULTS: Among 1.6 million dually enrolled veterans, the mean age was 73, 97% were men, and 77% were non-Hispanic White. Overall, 63.2 low-value services per 100 veterans were delivered, affecting 32% of veterans; 22.9 services per 100 veterans were delivered in VA and 40.3 services per 100 veterans were delivered in Medicare. The total cost was $226.3 million (M), of which $62.6 M was spent in VA and $163.7 M in Medicare. The most common low-value service was prostate-specific antigen testing at 17.3 per 100 veterans (VA 55.9%, Medicare 44.1%). The costliest low-value service was percutaneous coronary intervention (VA $10.1 M, Medicare $32.8 M). CONCLUSIONS: Nearly 1 in 3 dually enrolled veterans received a low-value service in FY18, with twice as many low-value services delivered in Medicare vs VA. Interventions to reduce low-value services for veterans should consider their substantial use of such services in Medicare.

Veterans Affairs Medical Center Racial and Ethnic Composition and Initiation of Anticoagulation for Atrial Fibrillation.

Importance: Racial and ethnic disparities exist in anticoagulation therapy for atrial fibrillation (AF). Whether medical center racial and ethnic composition is associated with these disparities is unclear. Objective: To determine whether medical center racial and ethnic composition is associated with overall anticoagulation and disparities in anticoagulation for AF. Design, Setting, and Participants: Retrospective cohort study of Black, White, and Hispanic patients with incident AF from 2018 to 2021 at 140 Veterans Health Administration medical centers (VAMCs). Data were analyzed from March to November 2023. Exposure: VAMC racial and ethnic composition, defined as the proportion of patients from minoritized racial and ethnic groups treated at a VAMC, categorized into quartiles. VAMCs in quartile 1 (Q1) had the lowest percentage of patients from minoritized groups (ie, the reference group). Main Outcomes and Measures: The odds of initiating any anticoagulant, direct-acting oral anticoagulant (DOAC), or warfarin therapy within 90 days of an index AF diagnosis, adjusting for sociodemographics, medical comorbidities, and facility factors. Results: The cohort comprised 89 791 patients with a mean (SD) age of 73.0 (10.1) years; 87 647 (97.6%) were male, 9063 (10.1%) were Black, 3355 (3.7%) were Hispanic, and 77 373 (86.2%) were White. Overall, 64 770 individuals (72.1%) initiated any anticoagulant, 60 362 (67.2%) initiated DOAC therapy, and 4408 (4.9%) initiated warfarin. Compared with White patients, Black and Hispanic patients had lower rates of any anticoagulant and DOAC therapy initiation but higher rates of warfarin initiation across all quartiles of VAMC racial and ethnic composition. Any anticoagulant therapy initiation was lower in Q4 than Q1 (69.8% vs 74.9%; adjusted odds ratio [aOR], 0.80; 95% CI, 0.69-0.92; P < .001). DOAC and warfarin initiation were also lower in Q4 than in Q1 (DOAC, 69.4% vs 65.3%; aOR, 0.85; 95% CI, 0.74-0.97; P < .001; warfarin, 5.4% vs 4.5%; aOR, 0.82; 95% CI, 0.67-1.00; P < .001). In adjusted models, patients in Q4 were significantly less likely to initiate any anticoagulant therapy than those in Q1 (aOR, 0.88; 95% CI, 0.78-0.99). Patients in Q3 (aOR, 0.75; 95% CI, 0.60-0.93) and Q4 (aOR, 0.69; 95% CI, 0.55-0.87) were significantly less likely to initiate warfarin therapy than those in Q1. There was no significant difference in the adjusted odds of initiating DOAC therapy across racial and ethnic composition quartiles. Although significant Black-White and Hispanic-White differences in initiation of any anticoagulant, DOAC, and warfarin therapy were observed, interactions between patient race and ethnicity and VAMC racial composition were not significant. Conclusions and Relevance: In a national cohort of VA patients with AF, initiation of any anticoagulant and warfarin, but not DOAC therapy, was lower in VAMCs serving more minoritized patients.

Care cascades following low-value cervical cancer screening in dually enrolled Veterans.

BACKGROUND: Veterans dually enrolled in the Veterans Health Administration (VA) and Medicare commonly experience downstream services as part of a care cascade after an initial low-value service. Our objective was to characterize the frequency and cost of low-value cervical cancer screening and subsequent care cascades among Veterans dually enrolled in VA and Medicare. METHODS: This retrospective cohort study used VA and Medicare administrative data from fiscal years 2015 to 2019. The study cohort was comprised of female Veterans aged >65 years and at low risk of cervical cancer who were dually enrolled in VA and Medicare. Within this cohort, we compared differences in the rates and costs of cascade services related to low-value cervical cancer screening for Veterans who received and did not receive screening in FY2018, adjusting for baseline patient- and facility-level covariates using inverse probability of treatment weighting. RESULTS: Among 20,972 cohort-eligible Veterans, 494 (2.4%) underwent low-value cervical cancer screening with 301 (60.9%) initial screens occurring in VA and 193 (39%) occurring in Medicare. Veterans who were screened experienced an additional 26.7 (95% CI, 16.4-37.0) cascade services per 100 Veterans compared to those who were not screened, contributing to $2919.4 (95% CI, -265 to 6104.7) per 100 Veterans in excess costs. Care cascades consisted predominantly of subsequent cervical cancer screening procedures and related outpatient visits with low rates of invasive procedures and occurred in both VA and Medicare. CONCLUSIONS: Veterans dually enrolled in VA and Medicare commonly receive related downstream tests and visits as part of care cascades following low-value cervical cancer screening. Our findings demonstrate that to fully capture the extent to which individuals are subject to low-value care, it is important to examine downstream care stemming from initial low-value services across all systems from which individuals receive care.

Racial and Ethnic Differences in Health Care Experiences for Veterans Receiving VA Community Care from 2016 to 2021.

BACKGROUND: Prior research documented racial and ethnic disparities in health care experiences within the Veterans Health Administration (VA). Little is known about such differences in VA-funded community care programs, through which a growing number of Veterans receive health care. Community care is available to Veterans when care is not available through the VA, nearby, or in a timely manner. OBJECTIVE: To examine differences in Veterans' experiences with VA-funded community care by race and ethnicity and assess changes in these experiences from 2016 to 2021. DESIGN: Observational analyses of Veterans' ratings of community care experiences by self-reported race and ethnicity. We used linear and logistic regressions to estimate racial and ethnic differences in community care experiences, sequentially adjusting for demographic, health, insurance, and socioeconomic factors. PARTICIPANTS: Respondents to the 2016-2021 VA Survey of Healthcare Experiences of Patients-Community Care Survey. MEASURES: Care ratings in nine domains. KEY RESULTS: The sample of 231,869 respondents included 24,306 Black Veterans (mean [SD] age 56.5 [12.9] years, 77.5% male) and 16,490 Hispanic Veterans (mean [SD] age 54.6 [15.9] years, 85.3% male). In adjusted analyses pooled across study years, Black and Hispanic Veterans reported significantly lower ratings than their White and non-Hispanic counterparts in five of nine domains (overall rating of community providers, scheduling a recent appointment, provider communication, non-appointment access, and billing), with adjusted differences ranging from - 0.04 to - 0.13 standard deviations (SDs) of domain scores. Black and Hispanic Veterans reported higher ratings with eligibility determination and scheduling initial appointments than their White and non-Hispanic counterparts, and Black Veterans reported higher ratings of care coordination, with adjusted differences of 0.05 to 0.21 SDs. Care ratings improved from 2016 to 2021, but differences between racial and ethnic groups persisted. CONCLUSIONS: This study identified small but persistent racial and ethnic differences in Veterans' experiences with VA-funded community care, with Black and Hispanic Veterans reporting lower ratings in five domains and, respectively, higher ratings in three and two domains. Interventions to improve Black and Hispanic Veterans' patient experience could advance equity in VA community care.

Acute Liver Injury Caused by Cyclophosphamide in a Patient With Factor VIII Deficiency: A Rare Presentation.

Because of the variety of drugs, herbal, and dietary supplements used in clinical practice. Drug-induced liver injury (DILI) has become an important and common cause of acute liver injury and failure. Many drugs associated with DILI have been identified, but there remains some uncertainty about others. Cyclophosphamide is a commonly used antineoplastic medication, and its association with DILI has been reported in animals and has been established in humans with the use of high-dose IV. Oral cyclophosphamide has not been clearly shown to cause acute liver injury, thus highlighting many of the unique aspects of this manuscript. Here, we report a case of cyclophosphamide-induced DILI with the aim to alert clinicians regarding this potential association.

Introduction to the special issue on fish bioacoustics: Hearing and sound communicationa).

Fish bioacoustics, or the study of fish hearing, sound production, and acoustic communication, was discussed as early as Aristotle. However, questions about how fishes hear were not really addressed until the early 20th century. Work on fish bioacoustics grew after World War II and considerably in the 21st century since investigators, regulators, and others realized that anthropogenic (human-generated sounds), which had primarily been of interest to workers on marine mammals, was likely to have a major impact on fishes (as well as on aquatic invertebrates). Moreover, passive acoustic monitoring of fishes, recording fish sounds in the field, has blossomed as a noninvasive technique for sampling abundance, distribution, and reproduction of various sonic fishes. The field is vital since fishes and aquatic invertebrates make up a major portion of the protein eaten by a signification portion of humans. To help better understand fish bioacoustics and engage it with issues of anthropogenic sound, this special issue of The Journal of the Acoustical Society of America (JASA) brings together papers that explore the breadth of the topic, from a historical perspective to the latest findings on the impact of anthropogenic sounds on fishes.

Facility-Level Variation in Racial Disparities in Anticoagulation for Atrial Fibrillation: The REACH-AF Study.

BACKGROUND: Oral anticoagulation reduces stroke risk for patients with atrial fibrillation (AF). Prior research demonstrates lower anticoagulant prescribing in Black than in White individuals but few studies have examined racial differences in facility-level anticoagulant prescribing for AF. OBJECTIVE: To assess variation in anticoagulant initiation by race within Veterans Health Administration (VA) facilities. DESIGN: Retrospective cohort study. PARTICIPANTS: Black and White patients enrolled in the VA with incident AF from 2020 through 2021. MAIN MEASURES: The primary outcome was rate of any anticoagulant initiation (i.e., warfarin or direct oral anticoagulant [DOAC]) or any DOAC therapy within 90 days of an AF diagnosis, overall and for Black and White patients at each facility. We also estimated the adjusted Black-White risk difference. KEY RESULTS: In 82 VA facilities serving 26,832 Black and White patients, overall unadjusted rates of any anticoagulant therapy ranged from 56.8 to 87.1% across facilities; the corresponding ranges for Black and White patients were 47.6 to 91.3% and 58.2 to 87.1%, respectively. Overall unadjusted rates of DOAC therapy ranged from 55.1 to 85.5% by facility; ranges for Black and White patients were 42.8 to 86.9% and 56.4 to 85.5%, respectively. The adjusted risk difference between Black and White patients ranged from - 29.9 (95% CI, - 54.9 to - 4.8) to 14.2 (95% CI, - 9.1 to 25.0) across facilities for any anticoagulant therapy and from - 28.8 (95% CI, - 58.3 to 0.8) to 15.0 (95% CI, - 8.0 to 38.1) for DOAC therapy. For any anticoagulant therapy there were 3 facilities where prescribing was statistically higher in White than Black patients; for DOAC therapy there were 5 such facilities. CONCLUSIONS: In a national cohort of patients with AF, we observed large facility-level variation and adjusted risk differences in any anticoagulant and DOAC initiation, overall and by race. These findings represent a target for local quality improvement in AF care.

Assessing an electronic self-report method for improving quality of ethnicity and race data in the Veterans Health Administration.

Objective: Evaluate self-reported electronic screening (eScreening) in a VA Transition Care Management Program (TCM) to improve the accuracy and completeness of administrative ethnicity and race data. Materials and Methods: We compared missing, declined, and complete (neither missing nor declined) rates between (1) TCM-eScreening (ethnicity and race entered into electronic tablet directly by patient using eScreening), (2) TCM-EHR (Veteran-completed paper form plus interview, data entered by staff), and (3) Standard-EHR (multiple processes, data entered by staff). The TCM-eScreening (n = 7113) and TCM-EHR groups (n = 7113) included post-9/11 Veterans. Standard-EHR Veterans included all non-TCM Gulf War and post-9/11 Veterans at VA San Diego (n = 92 921). Results: Ethnicity: TCM-eScreening had lower rates of missingness than TCM-EHR and Standard-EHR (3.0% vs 5.3% and 8.6%, respectively, P < .05), but higher rates of "decline to answer" (7% vs 0.5% and 1.2%, P < .05). TCM-EHR had higher data completeness than TCM-eScreening and Standard-EHR (94.2% vs 90% and 90.2%, respectively, P < .05). Race: No differences between TCM-eScreening and TCM-EHR for missingness (3.5% vs 3.4%, P > .05) or data completeness (89.9% vs 91%, P > .05). Both had better data completeness than Standard-EHR (P < .05), which despite the lowest rate of "decline to answer" (3%) had the highest missingness (10.3%) and lowest overall completeness (86.6%). There was strong agreement between TCM-eScreening and TCM-EHR for ethnicity (Kappa = .92) and for Asian, Black, and White Veteran race (Kappas = .87 to .97), but lower agreement for American Indian/Alaska Native (Kappa = .59) and Native Hawaiian/Other Pacific Islander (Kappa = .50) Veterans. Conculsions: eScreening is a promising method for improving ethnicity and race data accuracy and completeness in VA.

Utilization and Outcomes of Clinically Indicated Invasive Cardiac Care in Veterans with Acute Coronary Syndrome and Chronic Kidney Disease.

SIGNIFICANCE STATEMENT: Of studies reporting an association of CKD with lower use of invasive cardiac care to treat acute coronary syndrome (ACS), just one accounted for the appropriateness of such care. However, its findings in patients hospitalized nearly 30 years ago may not apply to current practice. In a more recent cohort of 64,695 veterans hospitalized with ACS, CKD was associated with a 32% lower likelihood of receiving invasive care determined to be clinically indicated. Among patients with CKD, not receiving such care was associated with a 1.39-fold higher risk of 6-month mortality. Efforts to elucidate the reasons for this disparity in invasive care in patients with ACS and CKD and implement tailored interventions to enhance its use in this population may offer the potential to improve clinical outcomes. BACKGROUND: Previous studies have shown that patients with CKD are less likely than those without CKD to receive invasive care to treat acute coronary syndrome (ACS). However, few studies have accounted for whether such care was clinically indicated or assessed whether nonuse of such care was associated with adverse health outcomes. METHODS: We conducted a retrospective cohort study of US veterans who were hospitalized at Veterans Affairs Medical Centers from January 2013 through December 2017 and received a discharge diagnosis of ACS. We used multivariable logistic regression to investigate the association of CKD with use of invasive care (coronary angiography, with or without revascularization; coronary artery bypass graft surgery; or both) deemed clinically indicated based on Global Registry of Acute Coronary Events 2.0 risk scores that denoted a 6-month predicted all-cause mortality ≥5%. Using propensity scoring and inverse probability weighting, we examined the association of nonuse of clinically indicated invasive care with 6-month all-cause mortality. RESULTS: Among 34,430 patients with a clinical indication for invasive care, the 18,780 patients with CKD were less likely than the 15,650 without CKD to receive such care (adjusted odds ratio, 0.68; 95% confidence interval, 0.65 to 0.72). Among patients with CKD, nonuse of invasive care was associated with higher risk of 6-month all-cause mortality (absolute risk, 21.5% versus 15.5%; absolute risk difference 6.0%; adjusted risk ratio, 1.39; 95% confidence interval, 1.29 to 1.49). Findings were consistent across multiple sensitivity analyses. CONCLUSIONS: In contemporary practice, veterans with CKD who experience ACS are less likely than those without CKD to receive clinically indicated invasive cardiac care. Nonuse of such care is associated with increased mortality.

Impact of adherence to procalcitonin antibiotic prescribing guideline recommendations for low procalcitonin levels on antibiotic use.

BACKGROUND: The Procalcitonin Antibiotic Consensus Trial (ProACT) found provision of a procalcitonin antibiotic prescribing guideline to hospital-based clinicians did not reduce antibiotic use. Possible reasons include clinician reluctance to follow the guideline, with an observed 64.8% adherence rate. In this study we sought to determine the threshold adherence rate for reduction in antibiotic use, and to explore opportunities to increase adherence. METHODS: This study is a retrospective analysis of ProACT data. ProACT randomized 1656 patients presenting to 14 U.S. hospitals with suspected lower respiratory tract infection to usual care or provision of procalcitonin assay results and an antibiotic prescribing guideline to the treating clinicians. We simulated varying adherence to guideline recommendations for low procalcitonin levels and determined which threshold adherence rate could have resulted in rejection of the null hypothesis of no difference between groups at alpha = 0.05. We also performed sensitivity analyses within specific clinical settings and grouped patients initially prescribed antibiotics despite low procalcitonin into low, medium, and high risk of illness severity or bacterial infection. RESULTS: Our primary outcome was number of antibiotic-days by day 30 using an intention-to-treat approach and a null hypothesis of no difference in antibiotic use. We determined that an 84% adherence rate in the hospital setting (emergency department and inpatient) for low procalcitonin could have allowed rejection of the null hypothesis (3.7 vs 4.3 antibiotic-days, p = 0.048). The threshold adherence rate was 76% for continued guideline adherence after discharge. Even 100% adherence in the emergency department alone failed to reduce antibiotic-days. Of the 218 patients prescribed antibiotics in the emergency department despite low procalcitonin, 153 (70.2%) were categorized as low or medium risk. CONCLUSIONS: High adherence in the hospital setting to a procalcitonin antibiotic prescribing guideline is necessary to reduce antibiotic use in suspected lower respiratory tract infection. Continued guideline adherence after discharge and withholding of antibiotics in low and medium risk patients with low procalcitonin may offer impactful potential opportunities for antibiotic reduction. Trial registration Procalcitonin Antibiotic Consensus Trial (ProACT), ClinicalTrials.gov Identifier: NCT02130986. First posted May 6, 2014.

Prevalence and Cost of Care Cascades Following Low-Value Preoperative Electrocardiogram and Chest Radiograph Within the Veterans Health Administration.

BACKGROUND: Low-value care cascades, defined as the receipt of downstream health services potentially related to a low-value service, can result in harm to patients and wasteful healthcare spending, yet have not been characterized within the Veterans Health Administration (VHA). OBJECTIVE: To examine if the receipt of low-value preoperative testing is associated with greater utilization and costs of potentially related downstream health services in Veterans undergoing low or intermediate-risk surgery. DESIGN: Retrospective cohort study using VHA administrative data from fiscal years 2017-2018 comparing Veterans who underwent low-value preoperative electrocardiogram (EKG) or chest radiograph (CXR) with those who did not. PARTICIPANTS: National cohort of Veterans at low risk of cardiopulmonary disease undergoing low- or intermediate-risk surgery. MAIN MEASURES: Difference in rate of receipt and attributed cost of potential cascade services in Veterans who underwent low-value preoperative testing compared to those who did not KEY RESULTS: Among 635,824 Veterans undergoing low-risk procedures, 7.8% underwent preoperative EKG. Veterans who underwent a preoperative EKG experienced an additional 52.4 (95% CI 47.7-57.2) cascade services per 100 Veterans, resulting in $138.28 (95% CI 126.19-150.37) per Veteran in excess costs. Among 739,005 Veterans undergoing low- or intermediate-risk surgery, 3.9% underwent preoperative CXR. These Veterans experienced an additional 61.9 (95% CI 57.8-66.1) cascade services per 100 Veterans, resulting in $152.08 (95% CI $146.66-157.51) per Veteran in excess costs. For both cohorts, care cascades consisted largely of repeat tests, follow-up imaging, and follow-up visits, with low rates invasive services. CONCLUSIONS: Among a national cohort of Veterans undergoing low- or intermediate-risk surgeries, low-value care cascades following two routine low-value preoperative tests are common, resulting in greater unnecessary care and costs beyond the initial low-value service. These findings may guide de-implementation policies within VHA and other integrated healthcare systems that target those services whose downstream effects are most prevalent and costly.

Association of Neighborhood Disadvantage and Anticoagulation for Patients with Atrial Fibrillation in the Veterans Health Administration: the REACH-AF Study.

BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia, the management of which includes anticoagulation for stroke prevention. Although disparities in anticoagulant prescribing have been well documented for individual socioeconomic factors, less is known about the association of neighborhood-level disadvantage and anticoagulation for AF. OBJECTIVE: To assess the association between neighborhood disadvantage and anticoagulant initiation for patients with incident AF. DESIGN: Retrospective cohort study. PARTICIPANTS: A cohort of patients enrolled in the Veterans Health Administration (VA) with incident AF from January 2014 through December 2020 from the Race, Ethnicity, and Anticoagulant CHoice in Atrial Fibrillation (REACH-AF) Study. MAIN MEASURES: The primary exposure was neighborhood disadvantage quantified using area deprivation index (ADI), classified by quintiles (Q). The outcomes were initiation of any anticoagulant therapy (warfarin or direct oral anticoagulant, DOAC) within 90 days of AF diagnosis and DOAC use among initiators. We used mixed effects logistic regression to assess the association between ADI and anticoagulant therapy, incorporating a fixed effect for treatment site and baseline patient, provider, and facility covariates. KEY RESULTS: Among 161,089 patients, 105,489 (65.5%) initiated any anticoagulant therapy, and 78,903 (74.8%) used DOACs. Any anticoagulant therapy increased 3.2 percentage points (63.0% to 66.2%; p<.001) from Q1 to Q5, whereas DOAC use decreased 8.2 percentage points (79.4% to 71.2%; p<.0001) across quintiles. The adjusted odd ratios of any anticoagulant therapy were non-significantly different for Q2-Q5 than Q1. The adjusted odds of DOAC use decreased progressively from 0.89 (95% CI, 0.84-0.94) in Q2 to 0.77 (95% CI, 0.73-0.83) in Q5 compared to Q1 (p<.0001). CONCLUSIONS: Among Veterans with incident AF, we observed similar initiation of any anticoagulant, though neighborhood deprivation was associated with decreased DOAC use among anticoagulant initiators. Future interventions to improve pharmacoequity in anticoagulant prescribing for AF should consider the role of neighborhood-level determinants of health inequities.

A Structural Overview of TRPML1 and the TRPML Family.

This chapter explores the existing structural and functional studies on the endo-lysosomal channel TRPML1 and its analogs TRPML2, TRPML3. These channels represent the mucolipin subfamily of the TRP channel superfamily comprising important roles in sensory physiology, ion homeostasis, and signal transduction. Since 2016, numerous structures have been determined for all three members using either cryo-EM or X-ray crystallography. These studies along with recent functional analysis have considerably strengthened our knowledge on TRPML channels and its related endo-lysosomal function. This chapter, together with relevant reports in other chapters from this handbook, provides an informative and detailed tool to study the endo-lysosomal cation channels.

Assessment of Care Cascades Following Low-Value Prostate-Specific Antigen Testing Among Veterans Dually Enrolled in the US Veterans Health Administration and Medicare Systems.

Importance: Older US veterans commonly receive health care outside of the US Veterans Health Administration (VHA) through Medicare, which may increase receipt of low-value care and subsequent care cascades. Objective: To characterize the frequency, cost, and source of low-value prostate-specific antigen (PSA) testing and subsequent care cascades among veterans dually enrolled in the VHA and Medicare and to determine whether receiving a PSA test through the VHA vs Medicare is associated with more downstream services. Design, Setting, and Participants: This retrospective cohort study used VHA and Medicare administrative data from fiscal years (FYs) 2017 to 2018. The study cohort consisted of male US veterans dually enrolled in the VHA and Medicare who were aged 75 years or older without a history of prostate cancer, elevated PSA, prostatectomy, radiation therapy, androgen deprivation therapy, or a urology visit. Data were analyzed from December 15, 2020, to October 20, 2022. Exposures: Receipt of low-value PSA testing. Main Outcomes and Measures: Differences in the use and cost of cascade services occurring 6 months after receipt of a low-value PSA test were assessed for veterans who underwent low-value PSA testing in the VHA and Medicare compared with those who did not, adjusted for patient- and facility-level covariates. Results: This study included 300 393 male US veterans at risk of undergoing low-value PSA testing. They had a mean (SD) age of 82.6 (5.6) years, and the majority (264 411 [88.0%]) were non-Hispanic White. Of these veterans, 36 459 (12.1%) received a low-value PSA test through the VHA, which was associated with 31.2 (95% CI, 29.2 to 33.2) additional cascade services per 100 veterans and an additional $24.5 (95% CI, $20.8 to $28.1) per veteran compared with the control group. In the same cohort, 17 981 veterans (5.9%) received a PSA test through Medicare, which was associated with 39.3 (95% CI, 37.2 to 41.3) additional cascade services per 100 veterans and an additional $35.9 (95% CI, $31.7 to $40.1) per veteran compared with the control group. When compared directly, veterans who received a PSA test through Medicare experienced 9.9 (95% CI, 9.7 to 10.1) additional cascade services per 100 veterans compared with those who underwent testing within the VHA. Conclusions and Relevance: The findings of this cohort study suggest that US veterans dually enrolled in the VHA and Medicare commonly experienced low-value PSA testing and subsequent care cascades through both systems in FYs 2017 and 2018. Care cascades occurred more frequently through Medicare compared with the VHA. These findings suggest that low-value PSA testing has substantial downstream implications for patients and may be especially challenging to measure when care occurs in multiple health care systems.

Vocal repertoire and sound characteristics in the variegated cardinalfish, Fowleria variegata (Pisces: Apogonidae).

The variegated cardinalfish Fowleria variegata produces grunt and hoot calls during agonistic and courtship interactions. Both sounds are tonal and occur as single and multiunit calls. Grunts are of short duration with variable frequency spectra. Hoots are longer, have a higher fundamental frequency, and a more developed harmonic structure. Agonistic grunt calls and short hoot calls (1-2 hoots) are produced during chases and when striking an individual or a mirror. Grunts are produced primarily in male-female and mirror-image encounters, and short hoot calls are produced primarily in male-male interactions. During the reproductive period, long hoot calls (three and four hoots) are the main sound type in a mix-sexed tank and at Dongsha Atoll. These are likely produced by males because isolated females are silent, and isolated males emit long hoot calls. Courtship interactions are mostly silent, and males are silent after capturing eggs for oral brooding. Tank sounds peak at dusk to early evening with a smaller peak at noon, although there are dusk and dawn peaks at Dongsha Atoll. Tank sounds exhibit a semilunar rhythm with peaks at the new and full moon. Other cardinalfish species from the atoll produce grunts but not hoot calls.

Structure and mechanism of human cystine exporter cystinosin.

Lysosomal amino acid efflux by proton-driven transporters is essential for lysosomal homeostasis, amino acid recycling, mTOR signaling, and maintaining lysosomal pH. To unravel the mechanisms of these transporters, we focus on cystinosin, a prototypical lysosomal amino acid transporter that exports cystine to the cytosol, where its reduction to cysteine supplies this limiting amino acid for diverse fundamental processes and controlling nutrient adaptation. Cystinosin mutations cause cystinosis, a devastating lysosomal storage disease. Here, we present structures of human cystinosin in lumen-open, cytosol-open, and cystine-bound states, which uncover the cystine recognition mechanism and capture the key conformational states of the transport cycle. Our structures, along with functional studies and double electron-electron resonance spectroscopic investigations, reveal the molecular basis for the transporter's conformational transitions and protonation switch, show conformation-dependent Ragulator-Rag complex engagement, and demonstrate an unexpected activation mechanism. These findings provide molecular insights into lysosomal amino acid efflux and a potential therapeutic strategy.

Structural basis for gating mechanism of the human sodium-potassium pump.

P2-type ATPase sodium-potassium pumps (Na+/K+-ATPases) are ion-transporting enzymes that use ATP to transport Na+ and K+ on opposite sides of the lipid bilayer against their electrochemical gradients to maintain ion concentration gradients across the membranes in all animal cells. Despite the available molecular architecture of the Na+/K+-ATPases, a complete molecular mechanism by which the Na+ and K+ ions access into and are released from the pump remains unknown. Here we report five cryo-electron microscopy (cryo-EM) structures of the human alpha3 Na+/K+-ATPase in its cytoplasmic side-open (E1), ATP-bound cytoplasmic side-open (E1•ATP), ADP-AlF4- trapped Na+-occluded (E1•P-ADP), BeF3- trapped exoplasmic side-open (E2P) and MgF42- trapped K+-occluded (E2•Pi) states. Our work reveals the atomically resolved structural detail of the cytoplasmic gating mechanism of the Na+/K+-ATPase.