Decision-making under uncertainty for species introductions into ecological networks.

Ecological communities are increasingly subject to natural and human-induced additions of species, as species shift their ranges under climate change, are introduced for conservation and are unintentionally moved by humans. As such, decisions about how to manage ecosystems subject to species introductions and considering multiple management objectives need to be made. However, the impacts of gaining new species on ecological communities are difficult to predict due to uncertainty in introduced species characteristics, the novel interactions that will be produced by that species, and the recipient ecosystem structure. Drawing on ecological and conservation decision theory, we synthesise literature into a conceptual framework for species introduction decision-making based on ecological networks in high-uncertainty contexts. We demonstrate the application of this framework to a theoretical decision surrounding assisted migration considering both biodiversity and ecosystem service objectives. We show that this framework can be used to evaluate trade-offs between outcomes, predict worst-case scenarios, suggest when one should collect additional data, and allow for improving knowledge of the system over time.

Variation in Low-Value Service Use Across Veterans Affairs Facilities.

BACKGROUND: It is unclear whether extensive variation in the use of low-value services exists even within a national integrated delivery system like the Veterans Health Administration (VA). OBJECTIVE: To quantify variation in the use of low-value services across VA facilities and examine associations between facility characteristics and low-value service use. DESIGN: In this retrospective cross-sectional study of VA administrative data, we constructed facility-level rates of low-value service use as the mean count of 29 low-value services per 100 Veterans per year. Adjusted rates were calculated via ordinary least squares regression including covariates for Veteran sociodemographic and clinical characteristics. We quantified the association between adjusted facility-level rates and facility geographic/operational characteristics. PARTICIPANTS: 5,242,301 patients across 139 VA facilities. MAIN MEASURES: Use of 29 low-value services within six domains: cancer screening, diagnostic/preventive testing, preoperative testing, imaging, cardiovascular testing and procedures, and surgery. KEY RESULTS: The mean rate of low-value service use was 20.0 services per 100 patients per year (S.D. 6.1). Rates ranged from 13.9 at the 10th percentile to 27.6 at the 90th percentile (90th/10th percentile ratio 2.0, 95% CI 1.8‒2.3). With adjustment for patient covariates, variation across facilities narrowed (S.D. 5.2, 90th/10th percentile ratio 1.8, 95% CI 1.6‒1.9). Only one facility characteristic was positively associated with low-value service use percent of patients seeing non-VA clinicians via VA Community Care, p < 0.05); none was associated with total low-value service use after adjustment for other facility characteristics. There was extensive variation in low-value service use within categories of facility operational characteristics. CONCLUSIONS: Despite extensive variation in the use of low-value services across VA facilities, we observed substantial use of these services across facility operational characteristics and at facilities with lower rates of low-value service use. Thus, system-wide interventions to address low-value services may be more effective than interventions targeted to specific facilities or facility types.

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.

Early Performance of Accountable Care Organizations in Medicare.

BACKGROUND: In the Medicare Shared Savings Program (MSSP), accountable care organizations (ACOs) have financial incentives to lower spending and improve quality. We used quasi-experimental methods to assess the early performance of MSSP ACOs. METHODS: Using Medicare claims from 2009 through 2013 and a difference-in-differences design, we compared changes in spending and in performance on quality measures from before the start of ACO contracts to after the start of the contracts between beneficiaries served by the 220 ACOs entering the MSSP in mid-2012 (2012 ACO cohort) or January 2013 (2013 ACO cohort) and those served by non-ACO providers (control group), with adjustment for geographic area and beneficiary characteristics. We analyzed the 2012 and 2013 ACO cohorts separately because entry time could reflect the capacity of an ACO to achieve savings. We compared ACO savings according to organizational structure, baseline spending, and concurrent ACO contracting with commercial insurers. RESULTS: Adjusted Medicare spending and spending trends were similar in the ACO cohorts and the control group during the precontract period. In 2013, the differential change (i.e., the between-group difference in the change from the precontract period) in total adjusted annual spending was -$144 per beneficiary in the 2012 ACO cohort as compared with the control group (P=0.02), consistent with a 1.4% savings, but only -$3 per beneficiary in the 2013 ACO cohort as compared with the control group (P=0.96). Estimated savings were consistently greater in independent primary care groups than in hospital-integrated groups among 2012 and 2013 MSSP entrants (P=0.005 for interaction). MSSP contracts were associated with improved performance on some quality measures and unchanged performance on others. CONCLUSIONS: The first full year of MSSP contracts was associated with early reductions in Medicare spending among 2012 entrants but not among 2013 entrants. Savings were greater in independent primary care groups than in hospital-integrated groups.

Performance differences in year 1 of pioneer accountable care organizations.

BACKGROUND: In 2012, a total of 32 organizations entered the Pioneer accountable care organization (ACO) program, in which providers can share savings with Medicare if spending falls below a financial benchmark. Performance differences associated with characteristics of Pioneer ACOs have not been well described. METHODS: In a difference-in-differences analysis of Medicare fee-for-service claims, we compared Medicare spending for beneficiaries attributed to Pioneer ACOs (ACO group) with other beneficiaries (control group) before (2009 through 2011) and after (2012) the start of Pioneer ACO contracts, with adjustment for geographic area and beneficiaries' sociodemographic and clinical characteristics. We estimated differential changes in spending for several subgroups of ACOs: those with and those without clear financial integration between hospitals and physician groups, those with higher and those with lower baseline spending, and the 13 ACOs that withdrew from the Pioneer program after 2012 and the 19 that did not. RESULTS: Adjusted Medicare spending and spending trends were similar in the ACO group and the control group during the precontract period. In 2012, the total adjusted per-beneficiary spending differentially changed in the ACO group as compared with the control group (-$29.2 per quarter, P=0.007), consistent with a 1.2% savings. Savings were significantly greater for ACOs with baseline spending above the local average, as compared with those with baseline spending below the local average (P=0.05 for interaction), and for those serving high-spending areas, as compared with those serving low-spending areas (P=0.04). Savings were similar in ACOs with financial integration between hospitals and physician groups and those without, as well as in ACOs that withdrew from the program and those that did not. CONCLUSIONS: Year 1 of the Pioneer ACO program was associated with modest reductions in Medicare spending. Savings were greater for ACOs with higher baseline spending than for those with lower baseline spending and were unrelated to withdrawal from the program. (Funded by the National Institute on Aging and others.).

Aminoglycoside impregnated cement spacer precipitating acute kidney injury requiring hemodialysis.

The current standard of care for prosthetic joint infection includes two-stage arthroplasty, with antibiotic-impregnated cement spacers (ACS) utilized between the stages. We report a 75-year-old woman with previously normal renal function, who developed acute kidney injury (AKI) secondary to biopsy-proven acute tubular necrosis and acute interstitial nephritis after ACS placement containing tobramycin and vancomycin. Peak tobramycin level measured 25.3 mcg/mL, the highest value reported in the literature after ACS placement. Intermittent hemodialysis was initiated with subsequent full recovery of renal function. This paper reviews the published literature regarding the accumulation, toxicity and removal dynamics of aminoglycoside (AG) antibiotics and vancomycin in renal patients. Obtaining serum AG level should be strongly considered in patients experiencing AKI after ACS. Renal replacement therapy may assist in reducing toxic AG levels.

National trends and in hospital outcomes for total hip arthroplasty in avascular necrosis in the United States.

PURPOSE: While a majority of total hip arthroplasty (THA) is performed for osteoarthritis (OA), a significant portion is performed in the setting of avascular necrosis (AVN). The purpose of this study is to evaluate recent trends, patient demographics, and in hospital outcomes for primary THA in the setting of AVN in the United States. METHODS: The National Hospital Discharge Survey database was searched for patients admitted to US hospitals after a primary THA for the years 2001-2010. Patients were then separated into two groups by ICD-9 diagnosis codes for OA and AVN. RESULTS: The rates of THA for AVN (r = 0.65) and THA for OA (r = 0.82) both demonstrated a positive correlation with time. The mean patient age of the AVN group was significantly lower (56.9 vs 65.9 years, p < 0.01). Men accounted for 51.9 % of the AVN group and 43.0 % of the OA group (p < 0.01). The AVN group had a significantly higher percentage of African Americans (11.2 % vs 5.4 %, p < 0.01) when compared to the OA group. The AVN group had a higher rate of myocardial infarction (0.3 % vs 0.07 %, p = 0.0163) and a higher average number of medical co-morbidities (5.16 vs 4.77, p < 0.01). CONCLUSIONS: Patients undergoing THA for AVN were more likely to be younger, male, African American, have more medical co-morbidities, and more likely to have a myocardial infarction than those with OA. While the number of primary THAs performed for AVN in the United States has increased over the past ten years, the rate of primary THA for OA increased at a much more rapid rate.

Comparison of prior authorization across insurers: cross sectional evidence from Medicare Advantage.

OBJECTIVE: To measure and compare the scope of US insurers' policies for prior authorization (PA), a process by which insurers assess the necessity of planned medical care, and to quantify differences in PA across insurers, physician specialties, and clinical service categories. DESIGN: Cross sectional analysis. SETTING: PA policies for five insurers serving most of the beneficiaries covered by privately administered Medicare Advantage in the US, 2021, as applied to utilization patterns observed in Medicare Part B. PARTICIPANTS: 30 540 086 beneficiaries in traditional Medicare Part B. MAIN OUTCOME MEASURES: Proportions of government administered traditional Medicare Part B spending and utilization that would have required PA according to Medicare Advantage insurer rules. RESULTS: The insurers required PA for 944 to 2971 of the 14 130 clinical services (median 1899; weighted mean 1429) constituting 17% to 33% of Part B spending (median 28%; weighted mean 23%) and 9% to 41% of Part B utilization (median 22%; weighted mean 18%). 40% of spending ($57bn; £45bn; €53bn) and 48% of service utilization would have required PA by at least one insurer; 12% of spending and 6% of utilization would have required PA by all insurers. 93% of Part B medication spending, or 74% of medication use, would have required PA by at least one Medicare Advantage insurer. For all Medicare Advantage insurers, hematology and oncology drugs represented the largest proportion of PA spending (range 27-34%; median 33%; weighted mean 30%). PA rates varied widely across specialties. CONCLUSION: PA policies varied substantially across private insurers in the US. Despite limited consensus, all insurers required PA extensively, particularly for physician administered medications. These findings indicate substantial differences in coverage policies between government administered and privately administered Medicare. The results may inform ongoing efforts to focus PA more effectively on low value services and reduce administrative burdens for clinicians and patients.

Trends in low-value cancer care during the COVID-19 pandemic.

OBJECTIVE: To assess the association between the onset of the COVID-19 pandemic and change in low-value cancer services. STUDY DESIGN: In this retrospective cohort study, we used administrative claims from the HealthCore Integrated Research Environment, a repository of medical and pharmacy data from US health plans representing more than 80 million members, between January 1, 2016, and March 31, 2021. METHODS: We used linear probability models to investigate the relation between the onset of the COVID-19 pandemic and 4 guideline-based metrics of low-value cancer care: (1) conventional fractionation radiotherapy instead of hypofractionated radiotherapy for early-stage breast cancer; (2) non-guideline-based antiemetic use for minimal-, low-, or moderate- to high-risk chemotherapies; (3) off-pathway systemic therapy; and (4) aggressive end-of-life care. We identified patients with new diagnoses of breast, colorectal, and/or lung cancer. We excluded members who did not have at least 6 months of continuous insurance coverage and members with prevalent cancers. RESULTS: Among 117,116 members (median [IQR] age, 60 [53-69] years; 72.4% women), 59,729 (51.0%) had breast cancer, 25,751 (22.0%) had colorectal cancer, and 31,862 (27.2%) had lung cancer. The payer mix was 18.7% Medicare Advantage or Medicare supplemental and 81.2% commercial non-Medicare. Rates of low-value cancer services exhibited minimal changes during the pandemic, as adjusted percentage-point differences were 3.93 (95% CI, 1.50-6.36) for conventional radiotherapy, 0.82 (95% CI, -0.62 to 2.25) for off-pathway systemic therapy, -3.62 (95% CI, -4.97 to -2.27) for non-guideline-based antiemetics, and 2.71 (95% CI, -0.59 to 6.02) for aggressive end-of-life care. CONCLUSIONS: Low-value cancer care remained prevalent throughout the pandemic. Policy makers should consider changes to payment and incentive design to turn the tide against low-value cancer care.

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.

Germline TFAM levels regulate mitochondrial DNA copy number and mutant heteroplasmy in C. elegans.

The mitochondrial genome (mtDNA) is packaged into discrete protein-DNA complexes called nucleoids. mtDNA packaging factor TFAM (mitochondrial transcription factor-A) promotes nucleoid compaction and is required for mtDNA replication. Here, we investigate how changing TFAM levels affects mtDNA in the Caenorhabditis elegans germ line. We show that increasing germline TFAM activity boosts mtDNA number and significantly increases the relative proportion of a selfish mtDNA mutant, uaDf5 . We conclude that TFAM levels must be tightly controlled to ensure appropriate mtDNA composition in the germ line.

ZIF-1-mediated degradation of endogenous and heterologous zinc finger proteins in the C. elegans germ line.

Rapid and conditional protein depletion is the gold standard genetic tool for deciphering the molecular basis of developmental processes. Previously, we showed that by conditionally expressing the E3 ligase substrate adaptor ZIF-1 in Caenorhabditis elegans somatic cells, proteins tagged with the first CCCH Zn finger (ZF1) domain from the germline regulator PIE-1 degrade rapidly, resulting in loss-of-function phenotypes. The described role of ZIF-1 is to clear PIE-1 and several other CCCH Zn finger proteins from early somatic cells, helping to enrich them in germline precursor cells. Here, we show that proteins tagged with the PIE-1 ZF1 domain are subsequently cleared from primordial germ cells in embryos and from undifferentiated germ cells in larvae and adults by ZIF-1. We harness germline ZIF-1 activity to degrade a ZF1-tagged heterologous protein from PGCs and show that its depletion produces phenotypes equivalent to those of a null mutation. Our findings reveal that ZIF-1 switches roles from degrading CCCH Zn finger proteins in somatic cells to clearing them from undifferentiated germ cells, and that ZIF-1 activity can be harnessed as a new genetic tool to study the early germ line.

ZIF-1-mediated degradation of zinc finger proteins in the Caenorhabditis elegans germ line.

Rapid and conditional protein depletion is the gold standard genetic tool for deciphering the molecular basis of developmental processes. Previously, we showed that by conditionally expressing the E3 ligase substrate adaptor ZIF-1 in Caenorhabditis elegans somatic cells, proteins tagged with the first CCCH Zn finger 1 (ZF1) domain from the germline regulator PIE-1 degrade rapidly, resulting in loss-of-function phenotypes. The described role of ZIF-1 is to clear PIE-1 and several other CCCH Zn finger proteins from early somatic cells, helping to enrich them in germline precursor cells. Here, we show that proteins tagged with the PIE-1 ZF1 domain are subsequently cleared from primordial germ cells (PGCs) in embryos and from undifferentiated germ cells in larvae and adults by ZIF-1. We harness germline ZIF-1 activity to degrade a ZF1-tagged fusion protein from PGCs and show that its depletion produces phenotypes equivalent to those of a null mutation. Our findings reveal that ZIF-1 transitions from degrading CCCH Zn finger proteins in somatic cells to clearing them from undifferentiated germ cells, and that ZIF-1 activity can be harnessed as a new genetic tool to study the early germline.