A novel closed-loop biotechnology for recovery of cobalt from a lithium-ion battery active cathode material.

In recent years, the demand for lithium-ion batteries (LIBs) has been increasing rapidly. Conventional recycling strategies (based on pyro- and hydrometallurgy) are damaging for the environment and more sustainable methods need to be developed. Bioleaching is a promising environmentally friendly approach that uses microorganisms to solubilize metals. However, a bioleaching-based technology has not yet been applied to recover valuable metals from waste LIBs on an industrial scale. A series of experiments was performed to improve metal recovery rates from an active cathode material (LiCoO2; LCO). (i) Direct bioleaching of ≤0.5 % LCO with two prokaryotic acidophilic consortia achieved >80 % Co and 90 % Li extraction. Significantly lower metal recovery rates were obtained at 30 °C than at 45 °C. (ii) In contrast, during direct bioleaching of 3 % LCO with consortia adapted to elevated LCO levels, the 30 °C consortium performed significantly better than the 45 °C consortium, solubilizing 73 and 93 % of the Co and Li, respectively, during one-step bioleaching, and 83 and 99 % of the Co and Li, respectively, during a two-step process. (iii) The adapted 30°C consortium was used for indirect leaching in a low-waste closed-loop system (with 10 % LCO). The process involved generation of sulfuric acid in an acid-generating bioreactor (AGB), 2-3 week leaching of LCO with the biogenic acid (pH 0.9), selective precipitation of Co as hydroxide, and recirculation of the metal-free liquor back into the AGB. In total, 58.2 % Co and 100 % Li were solubilized in seven phases, and >99.9 % of the dissolved Co was recovered after each phase as a high-purity Co hydroxide. Additionally, Co nanoparticles were generated from the obtained Co-rich leachates, using Desulfovibrio alaskensis, and Co electrowinning was optimized as an alternative recovery technique, yielding high recovery rates (91.1 and 73.6% on carbon felt and roughened steel, respectively) from bioleachates that contained significantly lower Co concentrations than industrial hydrometallurgical liquors. The closed-loop system was highly dominated by the mixotrophic archaeon Ferroplasma and sulfur-oxidizing bacteria Acidithiobacillus caldus and Acidithiobacillus thiooxidans. The developed system achieved high metal recovery rates and provided high-purity solid products suitable for a battery supply chain, while minimizing waste production and the inhibitory effects of elevated concentrations of dissolved metals on the leaching prokaryotes. The system is suitable for scale-up applications and has the potential to be adapted to different battery chemistries.

Adherence to AUA guidelines for the work-up, medical management, surgical evaluation and treatment of BPH: Work from a quality improvement collaborative.

INTRODUCTION: Previous studies noted varied adherence to clinical practice guidelines (CPGs), but studies are yet to quantify adherence to American Urological Association BPH guidelines. We studied guideline adherence in the context of a new quality improvement collaborative (QIC). METHODS: Data were collected as part of a statewide QIC. Medical records for patients undergoing select CPT codes from January 2020 to May 2022 were retrospectively reviewed for adherence to selected BPH guidelines. RESULTS: Most men were treated with transurethral resection of the prostate. Notably, 53.3% of men completed an IPSS and 52.3% had a urinalysis. 4.7% were counseled on behavioral modifications, 15.0% on medical therapy, and 100% on procedural options. For management, 79.4% were taking alpha-blockers and 59.8% were taking a 5-ARI. For evaluation, 57% had a PVR, 63.6% had prostate size measurement, 37.4% had uroflowmetry, and 12.3% were counseled about treatment failure. Postoperatively, 51.6% completed an IPSS, 57% had a PVR, 6.50% had uroflowmetry, 50.6% stopped their alpha-blocker, and 75.0% stopped their 5-ARI. CONCLUSIONS: There was adherence to preoperative testing recommendations, but patient counseling was lacking in the initial work-up and preoperative evaluation. We will convey the data to key stakeholders, expand data collection to other institutions, and devise an improvement implementation plan.

Performance of health care service area definitions for capturing variation in inpatient care and social determinants of health.

OBJECTIVE: To quantify the degree to which health care service area (HCSA) definitions captured hospitalizations and heterogeneity in social determinants of health (SDOH). DATA SOURCES AND STUDY SETTING: Geospatial data from the Centers for Medicare and Medicaid Services, the Census Bureau, and the Dartmouth Institute. Drive-time isochrones from MapBox. Area Deprivation Index (ADI) data. 2017 inpatient discharge data from Arizona, Florida, Iowa, Maryland, Nebraska, New Jersey, New York, and Wisconsin, State Emergency Department Databases and State Inpatient Databases, Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality; and Fee-For-Service Medicare data in 48 states. STUDY DESIGN: Cross-sectional, descriptive analysis. DATA COLLECTION/EXTRACTION METHODS: The capture rate was the percentage of inpatient discharges occurring in the same HCSA as the hospital. We compared capture rates for each HCSA definition for different populations and by hospital type. We measured SDOH heterogeneity using the coefficient of variation of the ADI among ZIP codes within each HCSA. PRINCIPAL FINDINGS: HCSA definitions captured a wide range of inpatient discharges, ranging from 20% to 50% for Public Use Microdata Areas (PUMAs) to 93%-97% for Metropolitan Statistical Areas (MSAs). Three-quarters of inpatient discharges were from facilities within the same county as the patient's residential ZIP code, while nearly two-thirds were within the same Hospital Service Area. From the hospital perspective, 74.7% of inpatient discharges originated from within a 30-min drive and 90.1% within a 60-min drive. Capture rates were the lowest for teaching hospitals. PUMAs and drive-time-based HCSAs encompassed more homogenous populations while MSAs, Commuting Zones, and Hospital Referral Regions captured the most variation. CONCLUSIONS: The proportion of hospital discharges captured by each HCSA varied, with MSAs capturing the highest proportion of discharges and PUMAs capturing the lowest. Additionally, researchers face a trade-off between capture rate and population homogeneity when deciding which HCSA to use.

Primary Care Physician Network Overlap Between Medicaid and the Patient Protection and Affordable Care Act Marketplace.

This cross-sectional study quantifies Medicaid and the Patient Protection and Affordable Care Act (ACA) Marketplace overlap among primary care physicians.

Primary Care Physicians In Medicare Advantage Were Less Costly, Provided Similar Quality Versus Regional Average.

The use of many services is lower in Medicare Advantage (MA) compared with traditional Medicare, generating cost savings for insurers, whereas the quality of ambulatory services is higher. This study examined the role of selective contracting with providers in achieving these outcomes, focusing on primary care physicians. Assessing primary care physician costliness based on the gap between observed and predicted costs for their traditional Medicare patients, we found that the average primary care physician in MA networks was $433 less costly per patient (2.9 percent of baseline) compared with the regional mean, with less costly primary care physicians included in more networks than more costly ones. Favorable selection of patients by MA primary care physicians contributed partially to this result. The quality measures of MA primary care physicians were similar to the regional mean. In contrast, primary care physicians excluded from all MA networks were $1,617 (13.8 percent) costlier than the regional mean, with lower quality. Primary care physicians in narrow networks were $212 (1.4 percent) less costly than those in wide networks, but their quality was slightly lower. These findings highlight the potential role of selective contracting in reducing costs in the MA program.

Unsolicited Patient Complaints Following the 21st Century Cures Act Information-Blocking Rule.

Importance: The 21st Century Cures Act includes an information-blocking rule (IBR) that requires health systems to provide patients with immediate access to their health information in the electronic medical record upon request. Patients accessing their health information before they receive an explanation from their health care team may experience confusion and may be more likely to share unsolicited patient complaints (UPCs) with their health care organization. Objective: To evaluate the quantity of UPCs about physicians before and after IBR implementation and to identify themes in UPCs that may identify patient confusion, fear, or anger related to the release of information. Design, Setting, and Participants: This retrospective cohort study was conducted with an interrupted time-series analysis of UPCs spanning January 1, 2020, to June 30, 2022. The data were obtained from a single academic medical center, Vanderbilt University Medical Center, at which the IBR was implemented on January 20, 2021. Data analysis was performed from January 11 to July 15, 2023. Exposure: Implementation of the IBR on January 20, 2021. Main Outcomes and Measures: The primary outcome was the monthly rate of UPCs before and after IBR implementation. A qualitative analysis was performed for UPCs received after IBR implementation. The Wilcoxon rank-sum test was used to compare monthly complaints between the pre- and post-IBR groups. The Pearson χ2 test was used to compare proportions of complaints by UPC category between time periods. Results: The medical center received 8495 UPCs during the study period: 3022 over 12 months before and 5473 over 18 months after institutional IBR implementation. There was no difference in the monthly proportions of UPCs per 1000 patient encounters before (median, 0.81 [IQR, 0.75-0.88]) and after (median, 0.83 [IQR, 0.77-0.89]) IBR implementation (difference in medians, -0.02 [95% CI, -0.12 to 0.07]; P =.86). Segmented regression analysis revealed no difference in monthly UPCs (ß [SE], 0.03 [0.09]; P =.72). Conclusions and Relevance: In this cohort study, implementation of the Cures Act IBR was not associated with an increase in monthly rates of UPCs. These findings suggest that review of UPCs identified as IBR-specific complaints may allow clinicians and organizations to prepare patients that their test and procedure results may be available before clinicians are able to review them and respond.

Population Genomic Screening for Three Common Hereditary Conditions : A Cost-Effectiveness Analysis.

BACKGROUND: The cost-effectiveness of screening the U.S. population for Centers for Disease Control and Prevention (CDC) Tier 1 genomic conditions is unknown. OBJECTIVE: To estimate the cost-effectiveness of simultaneous genomic screening for Lynch syndrome (LS), hereditary breast and ovarian cancer syndrome (HBOC), and familial hypercholesterolemia (FH). DESIGN: Decision analytic Markov model. DATA SOURCES: Published literature. TARGET POPULATION: Separate age-based cohorts (ages 20 to 60 years at time of screening) of racially and ethnically representative U.S. adults. TIME HORIZON: Lifetime. PERSPECTIVE: U.S. health care payer. INTERVENTION: Population genomic screening using clinical sequencing with a restricted panel of high-evidence genes, cascade testing of first-degree relatives, and recommended preventive interventions for identified probands. OUTCOME MEASURES: Incident breast, ovarian, and colorectal cancer cases; incident cardiovascular events; quality-adjusted survival; and costs. RESULTS OF BASE-CASE ANALYSIS: Screening 100 000 unselected 30-year-olds resulted in 101 (95% uncertainty interval [UI], 77 to 127) fewer overall cancer cases and 15 (95% UI, 4 to 28) fewer cardiovascular events and an increase of 495 quality-adjusted life-years (QALYs) (95% UI, 401 to 757) at an incremental cost of $33.9 million (95% UI, $27.0 million to $41.1 million). The incremental cost-effectiveness ratio was $68 600 per QALY gained (95% UI, $41 800 to $88 900). RESULTS OF SENSITIVITY ANALYSIS: Screening 30-, 40-, and 50-year-old cohorts was cost-effective in 99%, 88%, and 19% of probabilistic simulations, respectively, at a $100 000-per-QALY threshold. The test costs at which screening 30-, 40-, and 50-year-olds reached the $100 000-per-QALY threshold were $413, $290, and $166, respectively. Variant prevalence and adherence to preventive interventions were also highly influential parameters. LIMITATIONS: Population averages for model inputs, which were derived predominantly from European populations, vary across ancestries and health care environments. CONCLUSION: Population genomic screening with a restricted panel of high-evidence genes associated with 3 CDC Tier 1 conditions is likely to be cost-effective in U.S. adults younger than 40 years if the testing cost is relatively low and probands have access to preventive interventions. PRIMARY FUNDING SOURCE: National Human Genome Research Institute.

Robot-assisted laparoscopic removal of an extraperitoneal pelvic solitary fibrous tumor.

•Pelvic SFTs are rare, typically benign soft tissue neoplasms that pose a diagnostic challenge for gynecologists.•Retroperitoneal pelvic SFTs can mimic gynecologic malignancies and should be considered in diagnosis of a solitary pelvic mass.•Pathologic diagnosis is typically confirmed by immunohistochemistry staining positively for CD34 and STAT6.•Complete surgical excision is recommended for these tumors and can be completed with a minimally invasive approach.•Close long-term follow-up is necessary due to possible recurrence or metastasis, especially for high-risk pathologic features.

Physician patient sharing relationships within insurance plan networks.

OBJECTIVE: To quantify shared patient relationships between primary care physicians (PCPs) and cardiologists and oncologists and the degree to which those relationships were captured within insurance networks. DATA SOURCES: Secondary analysis of Vericred data on physician networks, CareSet data on physicians' shared Medicare patients, and insurance plan attributes from Health Insurance Compare. Data validation exercises used data from Physician Compare and IQVIA. STUDY DESIGN: Cross-sectional study of the PCP-to-specialist in-network shared patient percentage (primary outcome). We also categorized networks by insurance market segment (Medicare Advantage [MA], Medicaid managed care, small-group or individually purchased), insurance plan type, and network breadth. DATA EXTRACTION: We analyzed data on 219,982 PCPs, 29,400 cardiologists, and 22,745 oncologists who, in 2021, accepted MA (n = 941 networks), Medicaid managed care (n = 293), and individually-purchased (n = 332) and small-group (n = 501) plans. PRINCIPAL FINDINGS: Networks captured, on average, 64.6% of PCP-cardiology shared patient ties, and 61.8% of PCP-oncologist ties. Less than half of in-network ties (44.5% and 38.9%, respectively) were among physicians with a common organizational affiliation. After adjustment for network breadth, we found no evidence of differences in the shared patient percentage across insurance market segments or networks of different types (p-value >0.05 for all comparisons). An exception was among national versus local and regional networks, where we found that national plans captured fewer shared patient ties, particularly among the narrowest networks (58.4% for national networksvs. 64.7% for local and regional networks for PCP-cardiology). CONCLUSIONS: Given recent trends toward narrower networks, our findings underscore the importance of incorporating additional and nuanced measures of network composition to aid plan selection (for patients) and to guide regulatory oversight.

Access to In-Network Hospitals in Tennessee During the COVID-19 Pandemic.

This cross-sectional study assesses the daily percentage of floor and intensive care unit bed available at in-network hospitals for patients with COVID-19 in Tennessee.

Cost-effectiveness of population-wide genomic screening for Lynch syndrome in the United States.

PURPOSE: Genomic screening for Lynch syndrome (LS) could prevent colorectal cancer (CRC) by identifying high-risk patients and instituting intensive CRC screening. We estimated the cost-effectiveness of a population-wide LS genomic screening vs family history-based screening alone in an unselected US population. METHODS: We developed a decision-analytic Markov model including health states for precancer, stage-specific CRC, and death and assumed an inexpensive test cost of $200. We conducted sensitivity and threshold analyses to evaluate model uncertainty. RESULTS: Screening unselected 30-year-olds for LS variants resulted in 48 (95% credible range [CR] = 35-63) fewer overall CRC cases per 100,000 screened individuals, leading to 187 quality-adjusted life-years (QALYs; 95% CR = 123-260) gained at an incremental cost of $24.6 million (95% CR = $20.3 million-$29.1 million). The incremental cost-effectiveness ratio was $132,200, with an 8% and 71% probability of being cost-effective at $100,000 and $150,000 per QALY willingness-to-pay thresholds, respectively. CONCLUSION: Population LS screening may be cost-effective in younger patient populations under a $150,000 willingness-to-pay per QALY threshold and with a relatively inexpensive test cost. Further reductions in testing costs and/or the inclusion of LS testing within a broader multiplex screening panel are needed for screening to become highly cost-effective.

Difference-in-differences for categorical outcomes.

OBJECTIVE: To discuss and develop difference-in-difference estimators for categorical outcomes and apply them to estimate the effect of the Affordable Care Act's Medicaid expansion on insurance coverage. DATA SOURCES: Secondary analysis of Survey on Income and Program Participation (SIPP) data on health insurance coverage types before (January 2013) and after (December 2015) Medicaid expansion in 39 US states (19 expansion and 20 non-expansion). STUDY DESIGN: We develop difference-in-difference methods for repeated measures (panel data) of categorical outcomes. We discuss scale-dependence of DID assumptions for marginal and transition effect estimates and specify a new target estimand: the difference between outcome category transitions under treatment versus no treatment. We establish causal assumptions about transitions that are sufficient to identify this and a marginal target estimand. We contrast the marginal estimands identified by the transition approach versus an additive assumption only about marginal evolution. We apply both the marginal and transition approaches to estimate the effects of Medicaid expansion on health insurance coverage types (employer-sponsored; other private, non-group; public; and uninsured). DATA EXTRACTION: We analyzed 16,027 individual survey responses from people aged 18-62 years in the 2014 SIPP panel. PRINCIPAL FINDINGS: We show that the two identifying assumptions are equivalent (on the scale of the marginals) if either the baseline marginal distributions are identical or the marginals are constant in both groups. Applying our transitions approach to the SIPP data, we estimate a differential increase in transitions from uninsured to public coverage and differential decreases in transitions from uninsured to private, non-group coverage and in remaining uninsured. CONCLUSIONS: By comparing the assumption that marginals are evolving in parallel to an assumption about transitions across outcome values, we illustrate the scale-dependence of difference-in-differences. Our application shows that studying transitions can illuminate nuances obscured by changes in the marginals.

Biodistribution and Tolerability of AAV-PHP.B-CBh-SMN1 in Wistar Han Rats and Cynomolgus Macaques Reveal Different Toxicologic Profiles.

Recombinant adeno-associated viruses (AAVs) have emerged as promising vectors for human gene therapy, but some variants have induced severe toxicity in Rhesus monkeys and piglets following high-dose intravenous (IV) administration. To characterize biodistribution, transduction, and toxicity among common preclinical species, an AAV9 neurotropic variant expressing the survival motor neuron 1 (SMN1) transgene (AAV-PHP.B-CBh-SMN1) was administered by IV bolus injection to Wistar Han rats and cynomolgus monkeys at doses of 2 × 1013, 5 × 1013, or 1 × 1014 vg/kg. A dose-dependent degeneration/necrosis of neurons without clinical manifestations occurred in dorsal root ganglia (DRGs) and sympathetic thoracic ganglia in rats, while liver injury was not observed in rats. In monkeys, one male at 5 × 1013 vg/kg was found dead on day 4. Clinical pathology data on days 3 and/or 4 at all doses suggested liver dysfunction and coagulation disorders, which led to study termination. Histologic evaluation of the liver in monkeys showed hepatocyte degeneration and necrosis without inflammatory cell infiltrates or intravascular thrombi, suggesting that hepatocyte injury is a direct effect of the vector following hepatocyte transduction. In situ hybridization demonstrated a dose-dependent expression of SMN1 transgene mRNA in the cytoplasm and DNA in the nucleus of periportal to panlobular hepatocytes, while quantitative polymerase chain reaction confirmed the dose-dependent presence of SMN1 transgene mRNA and DNA in monkeys. Monkeys produced a much greater amount of transgene mRNA compared with rats. In DRGs, neuronal degeneration/necrosis and accompanying findings were observed in monkeys as early as 4 days after test article administration. The present results show sensory neuron toxicity following IV delivery of AAV vectors at high doses with an early onset in Macaca fascicularis and after 1 month in rats, and suggest adding the autonomic system in the watch list for preclinical and clinical studies. Our data also suggest that the rat may be useful for evaluating the potential DRG toxicity of AAV vectors, while acute hepatic toxicity associated with coagulation disorders appears to be highly species-dependent.

Comparison of Decision Modeling Approaches for Health Technology and Policy Evaluation.

We discuss tradeoffs and errors associated with approaches to modeling health economic decisions. Through an application in pharmacogenomic (PGx) testing to guide drug selection for individuals with a genetic variant, we assessed model accuracy, optimal decisions, and computation time for an identical decision scenario modeled 4 ways: using 1) coupled-time differential equations (DEQ), 2) a cohort-based discrete-time state transition model (MARKOV), 3) an individual discrete-time state transition microsimulation model (MICROSIM), and 4) discrete event simulation (DES). Relative to DEQ, the net monetary benefit for PGx testing (v. a reference strategy of no testing) based on MARKOV with rate-to-probability conversions using commonly used formulas resulted in different optimal decisions. MARKOV was nearly identical to DEQ when transition probabilities were embedded using a transition intensity matrix. Among stochastic models, DES model outputs converged to DEQ with substantially fewer simulated patients (1 million) v. MICROSIM (1 billion). Overall, properly embedded Markov models provided the most favorable mix of accuracy and runtime but introduced additional complexity for calculating cost and quality-adjusted life year outcomes due to the inclusion of "jumpover" states after proper embedding of transition probabilities. Among stochastic models, DES offered the most favorable mix of accuracy, reliability, and speed.

Changes in antimicrobial utilization during the coronavirus disease 2019 (COVID-19) pandemic after implementation of a multispecialty clinical guidance team.

OBJECTIVE: Evaluate changes in antimicrobial use during COVID-19 and after implementation of a multispecialty COVID-19 clinical guidance team compared to pre-COVID-19 antimicrobial use. DESIGN: Retrospective observational study. SETTING: Tertiary-care academic medical center. PARTICIPANTS: Internal medicine and medical intensive care unit (MICU) provider teams and hospitalized COVID-19 patients. METHODS: Difference-in-differences analyses of antibiotic days of therapy per 1,000 patient days present (DOT) for internal medicine and MICU teams treating COVID-19 patients versus teams that did not were performed for 3 periods: before COVID-19, initial COVID-19 period, and after implementation of a multispecialty COVID-19 clinical guidance team which included daily, patient-specific antimicrobial stewardship recommendations. Patient characteristics associated with antibiotic DOT were evaluated using multivariable Poisson regression. RESULTS: In the initial COVID-19 period, compared to the pre-COVID-19 period, internal medicine and MICU teams increased weekly antimicrobial use by 145.3 DOT (95% CI, 35.1-255.5) and 204.0 DOT (95% CI, -16.9 to 424.8), respectively, compared to non-COVID-19 teams. In the intervention period, internal medicine and MICU COVID-19 teams both had significant weekly decreases of 362.3 DOT (95% CI, -443.3 to -281.2) and 226.3 DOT (95% CI, -381.2 to -71.3). Of 131 patients hospitalized with COVID-19, 86 (65.6%) received antibiotics; no specific patient factors were significantly associated with an expected change in antibiotic days. CONCLUSIONS: Antimicrobial use initially increased for COVID-19 patient care teams compared to pre-COVID-19 levels but significantly decreased after implementation of a multispecialty clinical guidance team, which may be an effective strategy to reduce unnecessary antimicrobial use.

Breadth and Exclusivity of Hospital and Physician Networks in US Insurance Markets.

Importance: Little is known about the breadth of health care networks or the degree to which different insurers' networks overlap. Objective: To quantify network breadth and exclusivity (ie, overlap) among primary care physician (PCP), cardiology, and general acute care hospital networks for employer-based (large group and small group), individually purchased (marketplace), Medicare Advantage (MA), and Medicaid managed care (MMC) plans. Design, Setting, and Participants: This cross-sectional study included 1192 networks from Vericred. The analytic unit was the network-zip code-clinician type-market, which captured attributes of networks from the perspective of a hypothetical patient seeking access to in-network clinicians or hospitals within a 60-minute drive. Exposures: Enrollment in a private insurance plan. Main Outcomes and Measures: Percentage of in-network physicians and/or hospitals within a 60-minute drive from a hypothetical patient in a given zip code (breadth). Number of physicians and/or hospitals within each network that overlapped with other insurers' networks, expressed as a percentage of the total possible number of shared connections (exclusivity). Descriptive statistics (mean, quantiles) were produced overall and by network breadth category, as follows: extra-small (<10%), small (10%-25%), medium (25%-40%), large (40%-60%), and extra-large (>60%). Networks were analyzed by insurance type, state, and insurance, physician, and/or hospital market concentration level, as measured by the Hirschman-Herfindahl index. Results: Across all US zip code-network observations, 415 549 of 511 143 large-group PCP networks (81%) were large or extra-large compared with 138 485 of 202 702 MA (68%), 191 918 of 318 082 small-group (60%), 60 425 of 149 841 marketplace (40%), and 21 781 of 66 370 MMC (40%) networks. Large-group employer networks had broader coverage than all other network plans (mean [SD] PCP breadth: large-group employer-based plans, 57.3% [20.1]; small-group employer-based plans, 45.7% [21.4]; marketplace, 36,4% [21.2]; MMC, 32.3% [19.3]; MA, 47.4% [18.3]). MMC networks were the least exclusive (a mean [SD] overlap of 61.3% [10.5] for PCPs, 66.5% [9.8] for cardiology, and 60.2% [12.3] for hospitals). Networks were narrowest (mean [SD] breadth 42.4% [16.9]) and most exclusive (mean [SD] overlap 47.7% [23.0]) in California and broadest (79.9% [16.6]) and least exclusive (71.1% [14.6]) in Nebraska. Rising levels of insurer and market concentration were associated with broader and less exclusive networks. Markets with concentrated primary care and insurance markets had the broadest (median [interquartile range {IQR}], 75.0% [60.0%-83.1%]) and least exclusive (median [IQR], 63.7% [52.4%-73.7%]) primary care networks among large-group commercial plans, while markets with least concentration had the narrowest (median [IQR], 54.6% [46.8%-67.6%]) and most exclusive (median [IQR], 49.4% [41.9%-56.9%]) networks. Conclusions and Relevance: In this study, narrower health care networks had a relatively large degree of overlap with other networks in the same geographic area, while broader networks were associated with physician, hospital, and insurance market concentration. These results suggest that many patients could switch to a lower-cost, narrow network plan without losing in-network access to their PCP, although future research is needed to assess the implications for care quality and clinical integration across in-network health care professionals and facilities in narrow network plans.

Cost-effectiveness of Population-Wide Genomic Screening for Hereditary Breast and Ovarian Cancer in the United States.

Importance: Genomic screening for hereditary breast and ovarian cancer (HBOC) in unselected women offers an opportunity to prevent cancer morbidity and mortality, but the potential clinical impact and cost-effectiveness of such screening have not been well studied. Objective: To estimate the lifetime incremental incidence of HBOC and the quality-adjusted life-years (QALYs), costs, and cost-effectiveness of HBOC genomic screening in an unselected population vs family history-based testing. Design, Setting, and Participants: In this study conducted from October 27, 2017, to May 3, 2020, a decision analytic Markov model was developed that included health states for precancer, for risk-reducing mastectomy (RRM) and risk-reducing salpingo-oophorectomy (RRSO), for earlier- and later-stage HBOC, after cancer, and for death. A complimentary cascade testing module was also developed to estimate outcomes in first-degree relatives. Age-specific RRM and RRSO uptake probabilities were estimated from the Geisinger MyCode Community Health Initiative and published sources. Parameters including RRM and RRSO effectiveness, variant-specific cancer risk, costs, and utilities were derived from published sources. Sensitivity and scenario analyses were conducted to evaluate model assumptions and uncertainty. Main Outcomes and Measures: Lifetime cancer incidence, QALYs, life-years, and direct medical costs for genomic screening in an unselected population vs family history-based testing only were calculated. The incremental cost-effectiveness ratio (ICER) was calculated as the difference in cost between strategies divided by the difference in QALYs between strategies. Earlier-stage and later-stage cancer cases prevented and total cancer cases prevented were also calculated. Results: The model found that population screening of 30-year-old women was associated with 75 (95% credible range [CR], 60-90) fewer overall cancer cases and 288 QALYs (95% CR, 212-373 QALYs) gained per 100 000 women screened, at an incremental cost of $25 million (95% CR, $21 millon to $30 million) vs family history-based testing; the ICER was $87 700 (78% probability of being cost-effective at a threshold of $100 000 per QALY). In contrast, population screening of 45-year-old women was associated with 24 (95% CR, 18-29) fewer cancer cases and 97 QALYs (95% CR, 66-130 QALYs) gained per 100 000 women screened, at an incremental cost of $26 million (95% CR, $22 million to $30 million); the ICER was $268 200 (0% probability of being cost-effective at a threshold of $100 000 per QALY). A scenario analysis without cascade testing increased the ICER to $92 600 for 30-year-old women and $354 500 for 45-year-old women. A scenario analysis assuming a 5% absolute decrease in mammography screening in women without a variant was associated with the potential for net harm (-90 QALYs per 100 000 women screened; 95% CR, -180 to 10 QALYs). Conclusions and Relevance: The results of this study suggest that population HBOC screening may be cost-effective among younger women but not among older women. Cascade testing of first-degree relatives added a modest improvement in clinical and economic value. The potential for harm conferred by inappropriate reduction in mammography among noncarriers should be quantified.

Genome-wide SNPs resolve spatiotemporal patterns of connectivity within striped marlin (Kajikia audax), a broadly distributed and highly migratory pelagic species.

Genomic methodologies offer unprecedented opportunities for statistically robust studies of species broadly distributed in environments conducive to high gene flow, providing valuable information for wildlife conservation and management. Here, we sequence restriction site-associated DNA to characterize genome-wide single nucleotide polymorphisms (SNPs) in a broadly distributed and highly migratory large pelagic fish, striped marlin (Kajikia audax). Assessment of over 4,000 SNPs resolved spatiotemporal patterns of genetic connectivity throughout the species range in the Pacific and, for the first time, Indian oceans. Individual-based cluster analyses identified six genetically distinct populations corresponding with the western Indian, eastern Indian, western South Pacific, and eastern central Pacific oceans, as well as two populations in the North Pacific Ocean (F ST = 0.0137-0.0819). F ST outlier analyses identified a subset of SNPs (n = 59) putatively under the influence of natural selection and capable of resolving populations separated by comparatively high degrees of genetic differentiation. Temporal collections available for some regions demonstrated the stability of allele frequencies over three to five generations of striped marlin. Relative migration rates reflected lower levels of genetic connectivity between Indian Ocean populations (m R ≤ 0.37) compared with most populations in the Pacific Ocean (m R ≥ 0.57) and highlight the importance of the western South Pacific in facilitating gene flow between ocean basins. Collectively, our results provide novel insights into rangewide population structure for striped marlin and highlight substantial inconsistencies between genetically distinct populations and stocks currently recognized for fisheries management. More broadly, we demonstrate that species capable of long-distance dispersal in environments lacking obvious physical barriers to movement can display substantial population subdivision that persists over multiple generations and that may be facilitated by both neutral and adaptive processes. Importantly, surveys of genome-wide markers enable inference of population-level relationships using sample sizes practical for large pelagic fishes of conservation concern.