Caplacizumab in paediatric immune thrombotic thrombocytopenic purpura (iTTP): the UK TTP Registry experience.

Paediatric thrombotic thrombocytopenic purpura (TTP) is an ultra-rare disease. Immune TTP (iTTP) is driven by anti-ADAMTS13 autoantibodies causing an imbalanced VWF:ADAMTS13 axis, and rarer still in children, but potentially life-threatening. Caplacizumab is licensed for iTTP treatment in adults and adolescents aged 12 years and older who weigh 40kg plus. There is a need to clarify whether caplacizumab can be used in younger children. We retrospectively describe caplacizumab use in 16 patients under 18 years of age from the UK TTP Registry, including 4 children aged less than 12 years. For patients weighing less than 40kg (n=3), caplacizumab was dosed at 5mg od. The youngest patient was 33 months old at diagnosis. Plasma exchange (PEX) was used in 15 patients, with a median of 5 exchanges required before platelet count normalisation (range 2-9). One patient was managed without plasma exchange. All patients achieved normalisation of platelet count (median 5.5 days, range 3-28) and ADAMTS13 activity (median 35 days, range 8 to 149), with a median hospital admission of 11 days (range 5 to 26). There were no refractory patients. One patient relapsed at 9 months post presentation. Bleeding requiring VWF supplementation and reduction of caplacizumab use occurred in one patient with severe epistaxis, with no significant intracranial or gastrointestinal bleeding. We demonstrate the efficacy and safety of caplacizumab in the paediatric population, synonymous with the adult trial data: primarily, reduction of PEX compared with the pre-caplacizumab era. This has implications for intensification and duration of admission, particularly relevant in paediatric care.

Hospital behavior over the private equity life cycle.

Private equity is an increasing presence in US healthcare, with unclear consequences. Leveraging unique data sources and difference-in-differences designs, we examine the largest private equity hospital takeover in history. The affected hospital chain sharply shifts its advertising strategy and pursues joint ventures with ambulatory surgery centers. Inpatient throughput is increased by allowing more patient transfers, and crucially, capturing more patients through the emergency department. The hospitals also manage shorter, less treatment-intensive stays for admitted patients. Outpatient surgical care volume declines, but remaining cases focus on higher complexity procedures. Importantly, behavior changes persist even after private equity divests.

Training labor and treatment behavior: Evidence from physician residency programs.

Public and private investments in physician human capital support a healthcare workforce to provide future medical services nationwide. Yet, little is known about how introducing training labor influences hospitals' provision of care. We leverage all-payer data and emergency medicine (EM) and obstetrics (OBGYN) residency program debuts to estimate local access and treatment intensity effects. We find that the introduction of EM programs coincides with less treatment intensity and suggestive increases in throughput. OBGYN programs adopt the pre-existing surgical tendencies of the hospital but may also relax some capacity constraints-allowing the marginal mother to avoid a riskier nearby hospital.

Fitting in? Physician practice style after forced relocation.

OBJECTIVE: This study aims to examine how variation in physicians' treatment decisions for newborn deliveries responds to changes in the hospital-level norms for obstetric clinical decision-making. DATA SOURCES: All hospital-based births in Florida from 2003 through 2017. STUDY DESIGN: Difference-in-differences approach is adopted that leverages obstetric unit closures as the source of identifying variation to exogenously shift obstetricians to a new, nearby hospital with different propensities to approach newborn deliveries less intensively. DATA EXTRACTION: Births attributed to physicians continuously observed 2 years before the closure event and 2 years after the closure event (treatment group physicians) or for identical time periods around a randomly assigned placebo closure date (control group physicians). PRINCIPAL FINDINGS: All of the physicians meeting our inclusion criteria shifted their births to a new hospital less than 20 miles from the hospital shuttering its obstetric unit. The new hospitals approached newborn births more conservatively, and treatment group physicians sharply became less aggressive in their newborn birth clinical management (e.g., use of C-section). The immediate 11-percentage point (33%) increase in delivering newborns without any procedure behavior change is statistically significant (p value <0.01) and persistent after the closure event; however, the physicians' payer and patient mix are unchanged. CONCLUSIONS: Obstetric physician behavior change appears highly malleable and sensitive to the practice patterns of other physicians delivering newborns at the same hospital. Incentives and policies that encourage more appropriate clinical care norms hospital-wide could sharply improve physician treatment decisions, with benefits for maternal and infant outcomes.

Ultrasound elastography to quantify average percent pressure-normalized strain reduction associated with different aortic endografts in 3D-printed hydrogel phantoms.

Objective: Strain has become a viable index for evaluating abdominal aortic aneurysm stability after endovascular aneurysm repair (EVAR). In addition, literature has shown that healthy aortic tissue requires a degree of strain to maintain homeostasis. This has led to the hypothesis that too much strain reduction conferred by a high degree of graft oversizing is detrimental to the aneurysm neck in the seal zone of abdominal aortic aneurysms after EVAR. We investigated this in a laboratory experiment by examining the effects that graft oversizing has on the pressure-normalized strain ( ε ρ + ¯ /pulse pressure [PP]) reduction using four different infrarenal EVAR endografts and our ultrasound elastography technique. Approximate graft oversizing percentages were 20% (30 mm phantom-graft combinations), 30% (28 mm phantom-graft combinations), and 50% (24 mm phantom-graft combinations). Methods: Axisymmetric, 10% by mass polyvinyl alcohol phantoms were connected to a flow simulator. Ultrasound elastography was performed before and after implantation with the four different endografts: (1) 36 mm polyester/stainless steel, (2) 36 mm polyester/electropolished nitinol, (3) 35 mm polytetrafluoroethylene (PTFE)/nitinol, and (4) 36 mm nitinol/polyester/platinum-iridium. Five ultrasound cine loops were taken of each phantom-graft combination. They were analyzed over two different cardiac cycles (end-diastole to end-diastole), yielding a total of 10 maximum mean principal strain ( ε ρ + ¯ ) values. ε ρ + ¯ was divided by pulse pressure to yield pressure-normalized strain ( ε ρ + ¯ /PP). An analysis of variance was performed for graft comparisons. We calculated the average percent ε ρ + ¯ /PP reduction by manufacturer and percent oversizing. These values were used for linear regression analysis. Results: Results from one-way analysis of variance showed a significant difference in ε ρ + ¯ /PP between the empty phantom condition and all oversizing conditions for all graft manufacturers (F(3, 56) = 106.7 [graft A], 132.7 [graft B], 106.5 [graft C], 105.7 [graft D], P < .0001 for grafts A-D). There was a significant difference when comparing the 50% condition with the 30% and 20% conditions across all manufacturers by post hoc analysis (P < .0001). No significant difference was found when comparing the 20% and 30% oversizing conditions for any of the manufacturers or when comparing ε ρ + ¯ /PP values across the manufacturers according to percent oversize. Linear regression demonstrated a significant positive correlation between the percent graft oversize and the all-graft average percent ε ρ + ¯ /PP reduction ( R 2  = 0.84, P < .0001). Conclusions: This brief report suggests that a 10% increase in graft oversizing leads to an approximate 5.9% reduction in ε ρ + ¯ /PP on average. Applied clinically, this increase may result in increased stiffness in axisymmetric vessels after EVAR. Further research is needed to determine if this is clinically significant.

Agropastoral and dietary practices of the northern Levant facing Late Holocene climate and environmental change: Isotopic analysis of plants, animals and humans from Bronze to Iron Age Tell Tweini.

One of the largest isotopic datasets of the ancient Eastern Mediterranean region is evaluated, based on plants (n = 410), animals (n = 210) and humans (n = 16) from Tell Tweini (Syria). Diachronic analysis of plant and faunal specimens from four main periods of occupation: Early Bronze Age (2600-2000 BC), Middle Bronze Age (2000-1600 BC), Late Bronze Age (1600-1200 BC) and Iron Age (1200-333 BC) were investigated. Mean Δ13C results from seven plant species reveal emmer and free threshing wheat, olives, bitter vetch, rye grass and barley were adequately or well-watered during all periods of occupation. The grape Δ13C results suggest excellent growing conditions and particular care for its cultivation. The δ15N results indicate that especially the emmer and free threshing wheats received some manure inputs throughout the occupation sequence, while these were likely further increased during the Iron Age, encompassing also the olive groves and grape vineyards. Generally, domestic animals (cattle, sheep, goats) had C3 terrestrial diets and were kept together in similar environments. However, some animals consumed significant amounts of marine or C4 plants, possibly from disturbed habitats due to land use pressure or salt tolerant grasses and shrubs from wetland environments, which were recorded in the direct vicinity of the site. Middle Bronze Age humans consumed a C3 terrestrial diet with no measurable input from C4, freshwater or marine protein sources. Interestingly, the human diet was relatively low in animal protein and appears comparable to what is considered today a typical Mediterranean diet consisting of bread (wheat/barley), olives, grapes, pulses, dairy products and small amounts of meat. The combined isotopic analysis of plants, animals and humans from Tell Tweini represents unbroken links in the food chain which create unparalleled opportunities to enhance our current understanding of environmental conditions, climate change and lifeways in past populations from the Eastern Mediterranean.

Market landscape and insurer-provider integration: the case of ambulatory surgery centers.

Insurer-provider integration is a new form of vertical integration, with increasing prominence in health care markets. While there are potential benefits from tighter alignment between providers and payers, risks of perverse impacts on health care markets loom large. Yet, little is known about this new wave of consolidation, which limits options for policy or regulatory responses. We focus on a dominant insurer's acquisitions of ambulatory surgery centers (ASCs) to document the growth and geographic spread of these ownership events. We found that a diverse swathe of the United States has experienced an insurer-led ASC takeover. The acquisitions are also more frequently in areas where the insurer holds a higher enrollee market share at baseline, although a linear prediction of the likelihood of ASC acquisition shows a more nuanced picture.

Pharmacokinetics, pharmacodynamics, efficacy, and safety of ravulizumab in pediatric paroxysmal nocturnal hemoglobinuria.

ABSTRACT: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disease of uncontrolled terminal complement activation leading to intravascular hemolysis, thrombotic events and increased morbidity and mortality. This phase 3, open-label, single-arm, multicenter study evaluated ravulizumab treatment in eculizumab-naive or -experienced pediatric patients (aged <18 years) with PNH over a 26-week primary evaluation period (PEP) and 4-year extension period (EP). Patients included in the study received weight-based intravenous ravulizumab dosing. Primary end points were pharmacokinetic and pharmacodynamic parameters to confirm complement component 5 (C5) inhibition by ravulizumab; secondary end points assessed the efficacy (including percentage change in lactate dehydrogenase levels over time) and safety of ravulizumab. Thirteen patients, 5 (38.5%) eculizumab-naive and 8 (61.5%) eculizumab-experienced, were enrolled. Ravulizumab Ctrough levels were above the pharmacokinetic threshold of 175 µg/mL in the PEP and EP except in 1 patient. At the end of the study, pre- and post-infusion mean ± standard deviation serum ravulizumab concentrations were 610.50 ± 201.53 µg/mL and 518.29 ± 109.67 µg/mL for eculizumab-naive and eculizumab-experienced patients, respectively. After the first ravulizumab infusion, serum-free C5 concentrations were <0.5 µg/mL in both cohorts until the end of the study (0.061 ± 0.021 µg/mL and 0.061 ± 0.018 µg/mL for eculizumab-naive and eculizumab-experienced patients, respectively). Compared with baseline, ravulizumab improved and maintained efficacy outcomes in both groups. Ravulizumab had an acceptable safety profile with no new safety signals identified, and provided immediate, complete, and sustained terminal complement inhibition, translating to clinical benefit for pediatric patients with PNH. This trial was registered at www.ClinicalTrials.gov as #NCT03406507.

Randomized controlled trial of remote ischemic preconditioning in children having cardiac surgery.

BACKGROUND: Children undergoing cardiac surgery are at risk for acute kidney injury (AKI) and cardiac dysfunction. Opportunity exists in protecting end organ function with remote ischemic preconditioning. We hypothesize this intervention lessens kidney and myocardial injury. METHODS: We conducted a randomized, double blind, placebo controlled trial of remote ischemic preconditioning in children undergoing cardiac surgery. Pre-specified end points are change in creatinine, estimated glomerular filtration rate, development of AKI, B-type natriuretic peptide and troponin I at 6, 12, 24, 48, 72 h post separation from bypass. RESULTS: There were 45 in the treatment and 39 patients in the control group, median age of 3.5 and 3.8 years, respectively. There were no differences between groups in creatinine, cystatin C, eGFR at each time point. There was a trend for a larger rate of decrease, especially for cystatin C (p = 0.042) in the treatment group but the magnitude was small. AKI was observed in 21 (54%) of control and 16 (36%) of treatment group (p = 0.094). Adjusting for baseline creatinine, the odds ratio for AKI in treatment versus control was 0.31 (p = 0.037); adjusting for clinical characteristics, the odds ratio was 0.34 (p = 0.056). There were no differences in natriuretic peptide or troponin levels between groups. All secondary end points of clinical outcomes were not different. CONCLUSIONS: There is suggestion of RIPC delivering some kidney protection in an at-risk pediatric population. Larger, higher risk population studies will be required to determine its efficacy. Trial registration and date: Clinicaltrials.gov NCT01260259; 2021.

Private equity and healthcare firm behavior: Evidence from ambulatory surgery centers.

Healthcare firms regularly seek outside capital; yet, we have an incomplete understanding of external investor influence on provider behavior. We investigate the effects of private equity investment, divestment, and an initial public offering (IPO) on ambulatory surgery centers (ASCs). Throughput is unchanged while charges grow by up to 50% for the same service mix. Affected ASCs witness declines in privately insured cases and rely more on Medicare business. Private equity increases physician ASC ownership stakes, and both simultaneously divest when the ASC is sold. Our findings appear more consistent with private equity influencing the financing of ASCs, rather than treatment approaches.

Multi-isotope analysis of bone collagen of Late Pleistocene ungulates reveals niche partitioning and behavioural plasticity of reindeer during MIS 3.

Here we present stable carbon, nitrogen and sulfur isotope ratios of collagen extracted from Rangifer, Equus and Bison bone (n = 128) from different stratigraphic levels at the chronologically well-constrained Middle and Upper Palaeolithic site of Les Cottés, France. Samples were taken from five phases of site use (US08, US06, US04 [upper and lower], and US02; ~ 45.8-35.3 ka cal BP) to explore the dietary and spatial palaeoecology of these ungulate species during MIS 3, and the contemporary climate. Temporal trends in δ15N values of all species broadly align with other climatic indicators at the site and the lowest values in US04 correspond to the Heinrich 4 cooling event, reflecting changes in the composition of soil/plant nitrogen at this time. Rangifer collagen is 13C-enriched compared to the other species throughout, consistent with lichen consumption. However, this isotopic niche partitioning between Rangifer and Equus/Bison is most extensive during US04, indicating plasticity in reindeer feeding behaviour, and potentially overall increased lichen biomass during this cooler/more arid phase. Rangifer δ34S values are consistently lower than Equus and Bison, which could be indicative of their more extensive spatial ranges incorporating greater inland areas. Equus and Bison demonstrate a significant decrease in δ34S values through time, which may be linked to contemporary climatic decline.

Intermediate pressure-normalized principal wall strain values are associated with increased abdominal aortic aneurysmal growth rates.

Introduction: Current abdominal aortic aneurysm (AAA) assessment relies on analysis of AAA diameter and growth rate. However, evidence demonstrates that AAA pathology varies among patients and morphometric analysis alone is insufficient to precisely predict individual rupture risk. Biomechanical parameters, such as pressure-normalized AAA principal wall strain (ερ+¯/PP, %/mmHg), can provide useful information for AAA assessment. Therefore, this study utilized a previously validated ultrasound elastography (USE) technique to correlate ερ+¯/PP with the current AAA assessment methods of maximal diameter and growth rate. Methods: Our USE algorithm utilizes a finite element mesh, overlaid a 2D cross-sectional view of the user-defined AAA wall, at the location of maximum diameter, to track two-dimensional, frame-to-frame displacements over a full cardiac cycle, using a custom image registration algorithm to produce ερ+¯/PP. This metric was compared between patients with healthy aortas and AAAs (≥3 cm) and compared between small and large AAAs (≥5 cm). AAAs were then separated into terciles based on ερ+¯/PP values to further assess differences in our metric across maximal diameter and prospective growth rate. Non-parametric tests of hypotheses were used to assess statistical significance as appropriate. Results: USE analysis was conducted on 129 patients, 16 healthy aortas and 113 AAAs, of which 86 were classified as small AAAs and 27 as large. Non-aneurysmal aortas showed higher ερ+¯/PP compared to AAAs (0.044 ± 0.015 vs. 0.034 ± 0.017%/mmHg, p = 0.01) indicating AAA walls to be stiffer. Small and large AAAs showed no difference in ερ+¯/PP. When divided into terciles based on ερ+¯/PP cutoffs of 0.0251 and 0.038%/mmHg, there was no difference in AAA diameter. There was a statistically significant difference in prospective growth rate between the intermediate tercile and the outer two terciles (1.46 ± 2.48 vs. 3.59 ± 3.83 vs. 1.78 ± 1.64 mm/yr, p = 0.014). Discussion: There was no correlation between AAA diameter and ερ+¯/PP, indicating biomechanical markers of AAA pathology are likely independent of diameter. AAAs in the intermediate tercile of ερ+¯/PP values were found to have nearly double the growth rates than the highest or lowest tercile, indicating an intermediate range of ερ+¯/PP values for which patients are at risk for increased AAA expansion, likely necessitating more frequent imaging follow-up.

Dance movement therapy for dementia.

BACKGROUND: Dementia is a syndrome of acquired cognitive impairment which is severe enough to interfere with independent living. Over the course of the illness, people with dementia also experience changes in emotions, behaviour and social relationships. According to Alzheimer's Disease International, dementia affects approximately 55 million people worldwide. The latest NICE guideline for dementia highlights the value of diverse treatment options for the different stages and symptoms of dementia, including non-pharmacological treatments. Relevant literature also argues for the value of interventions that acknowledge the complexity of the condition and address the person as a whole, including their physical, emotional, social and cognitive processes. A growing literature highlights the capacity of the arts and has embodied practices to address this complexity. Dance movement therapy (DMT) is an embodied psychological intervention that can address complexity and thus may be useful for people with dementia, but its effectiveness remains unclear. OBJECTIVES: To assess the effects of dance movement therapy on behavioural, social, cognitive and emotional symptoms of people with dementia in comparison to no treatment, standard care or any other treatment. Also, to compare different forms of dance movement therapy (e.g. Laban-based dance movement therapy, Chacian dance movement therapy or Authentic Movement) SEARCH METHODS: We searched the Cochrane Dementia and Cognitive Improvement Group's register, MEDLINE (Ovid SP), Embase (Ovid SP), PsycINFO (Ovid SP), CINAHL (EBSCOhost), Web of Science Core Collection (Clarivate), LILACS (BIREME), ClinicalTrials.gov and the World Health Organization's meta-register of the International Clinical Trials Registry Portal until 8 December 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that included people with dementia, of any age and in any setting. The DMT intervention had to be delivered by a dance movement therapy practitioner who (i) had received formal training (ii) was a dance movement therapist in training or (iii) was otherwise recognised as a dance movement therapist in the country in which the study was conducted. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, extracted data and evaluated methodological quality. We expressed effect estimates using the mean difference (MD) between intervention groups and presented associated confidence intervals (CIs). We used GRADE methods to rate our certainty in the results. MAIN RESULTS: We found only one study eligible for inclusion in this review. This was a 3-arm parallel-group RCT conducted in Hong Kong involving 204 adults with mild neurocognitive disorder or dementia. The study examined the effects of short-term (12 weeks) group DMT in comparison with exercise and a waiting-list control group immediately post-intervention and three and nine months later. We found that, at the end of the intervention, DMT may result in little to no difference in neuropsychiatric symptoms assessed with the 12-item Neuropsychiatric Inventory when compared with waiting list (MD 0.3, 95% CI -0.96 to 1.56; low-certainty evidence) or exercise (MD -0.30, 95% CI -1.83 to 1.23; low-certainty evidence). Nor was there any evidence of effects at later time points. Cognitive functioning was assessed with a variety of instruments and there were no statistically significant between-group differences (low-certainty evidence). When compared to exercise or waiting list, DMT may result in little to no difference in cognitive function immediately after the intervention or at follow-up. In comparison to waiting list, DMT may result in a slight reduction in depression assessed with the 4-item Geriatric Depression Scale at the end of therapy (MD -0.60, 95% CI -0.96 to -0.24; low-certainty evidence). This slight positive effect of DMT on depression scores was sustained at three and nine months after the completion of the intervention. DMT may also reduce depression slightly in comparison with exercise at the end of therapy (MD -0.40, 95% CI -0.76 to -0.04, low-certainty evidence), an effect also sustained at three and nine months. Our fourth primary outcome, quality of life, was not assessed in the included study. There were data for two of our secondary outcomes, social and occupational functioning and dropouts (which we used as a proxy for acceptability), but in both cases the evidence was of very low certainty and hence our confidence in the results was very low. For all outcomes, we considered the certainty of the evidence in relation to our review objectives to be low or very low in GRADE terms due to indirectness (because not all participants in the included study had a diagnosis of dementia) and imprecision. AUTHORS' CONCLUSIONS: This review included one RCT with a low risk of bias. Due to the low certainty of the evidence, the true effects of DMT as an intervention for dementia may be substantially different from those found. More RCTs are needed to determine with any confidence whether DMT has beneficial effects on dementia.

When big data initiatives meet: Data sharing between THANADOS and IsoArcH for early medieval cemeteries in Austria.

This paper reports carbon, nitrogen, and sulfur stable isotope data obtained from bone collagen of humans from the early medieval cemeteries of Hemmaberg/Gora svete Heme and Oberleiserberg located in Austria. The Hemmaberg/Gora svete Heme cemetery, dating from the 8th to the 11th century, comprises 29 graves, from which 15 individuals were analyzed. The Oberleiserberg cemetery, established in the first half of the 11th century, includes 71 graves as well as several incidental finds of human bones, from which 75 samples were analyzed. Both cemeteries show comparable δ13C data (mean for Oberleiserberg: -17.5 ± 1.2 ‰, 1σ; mean for Hemmaberg: -16.4 ± 1.6‰, 1σ). However, the δ15N values of individuals from Oberleiserberg (mean: +10.4 ± 1.5‰, 1σ) are slightly higher than those of individuals from Hemmaberg/Gora svete Heme (mean: +8.8 ± 1.1‰,1σ). The δ34S values were only obtained on the individuals from Oberleiserberg, and show a mean value of -0.9 ± 2.0 ‰ (1σ). Beyond the isotopic data presented in this article, we lay the foundations for cooperation between the IsoArcH database (https://isoarch.eu) [1] and the THANADOS (https://thanados.net) [2] project. While IsoArcH primarily stores isotope-related datasets for bioarchaeology, THANADOS stores data on archaeologically and anthropologically researched burials. Moving forward, IsoArcH and THANADOS plan to work closely together to integrate their databases. This collaboration presents a promising opportunity for both projects to pool their resources and knowledge, offering a wealth of information for researchers and the general public who are interested in anthropology and archaeology.

A Deep Learning Framework to Estimate Elastic Modulus from Ultrasound Measured Displacement Fields.

Ultrasound (US) elastography is a technique that enables non-invasive quantification of material properties, such as stiffness, from ultrasound images of deforming tissue. The displacement field is measured from the US images using image matching algorithms, and then a parameter, often the elastic modulus, is inferred or subsequently measured to identify potential tissue pathologies, such as cancerous tissues. Several traditional inverse problem approaches, loosely grouped as either direct or iterative, have been explored to estimate the elastic modulus. Nevertheless, the iterative techniques are typically slow and computationally intensive, while the direct techniques, although more computationally efficient, are very sensitive to measurement noise and require the full displacement field data (i.e., both vector components). In this work, we propose a deep learning approach to solve the inverse problem and recover the spatial distribution of the elastic modulus from one component of the US measured displacement field. The neural network used here is trained using only simulated data obtained via a forward finite element (FE) model with known variations in the modulus field, thus avoiding the reliance on large measurement data sets that may be challenging to acquire. A U-net based neural network is then used to predict the modulus distribution (i.e., solve the inverse problem) using the simulated forward data as input. We quantitatively evaluated our trained model with a simulated test dataset and observed a 0.0018 mean squared error (MSE) and a 1.14% mean absolute percent error (MAPE) between the reconstructed and ground truth elastic modulus. Moreover, we also qualitatively compared the output of our U-net model to experimentally measured displacement data acquired using a US elastography tissue-mimicking calibration phantom.

County-level Factors and Treatment Access Among Insured Women With Opioid Use Disorder.

BACKGROUND: An over 40% increase in overdose deaths within the past 2 years and low levels of engagement in treatment call for a better understanding of factors that influence access to medication for opioid use disorder (OUD). OBJECTIVE: To examine whether county-level characteristics influence a caller's ability to secure an appointment with an OUD treatment practitioner, either a buprenorphine-waivered prescriber or an opioid treatment program (OTP). RESEARCH DESIGN AND SUBJECTS: We leveraged data from a randomized field experiment comprised of simulated pregnant and nonpregnant women of reproductive age seeking treatment for OUD among 10 states in the US. We employed a mixed-effects logistic regression model with random intercepts for counties to examine the relationship between appointments received and salient county-level factors related to OUD. MEASURES: Our primary outcome was the caller's ability to secure an appointment with an OUD treatment practitioner. County-level predictor variables included socioeconomic disadvantage rankings, rurality, and OUD treatment/practitioner density. RESULTS: Our sample comprised 3956 reproductive-aged callers; 86% reached a buprenorphine-waivered prescriber and 14% an OTP. We found that 1 additional OTP per 100,000 population was associated with an increase (OR=1.36, 95% CI: 1.08 to 1.71) in the likelihood that a nonpregnant caller receives an OUD treatment appointment from any practitioner. CONCLUSIONS: When OTPs are highly concentrated within a county, women of reproductive age with OUD have an easier time securing an appointment with any practitioner. This finding may suggest greater practitioners' comfort in prescribing when there are robust OUD specialty safety nets in the county.

Prevalence of Buprenorphine Providers Requiring Cash Payment From Insured Women Seeking Opioid Use Disorder Treatment.

CONTEXT: Medications for opioid use disorder (OUD) are known to be effective, especially in reducing the risk of overdose death. Yet, many individuals suffering from OUD are not receiving treatment. One potential barrier can be the patient's ability to access providers through their insurance plans. DATA AND METHODS: We used an audit (simulated patient) study methodology to examine appointment-granting behavior by buprenorphine prescribers in 10 different US states. Trained callers posed as women with OUD and were randomly assigned Medicaid or private insurance status. Callers request an OUD treatment appointment and then asked whether they would be able to use their insurance to cover the cost of care, or alternatively, whether they would be required to pay fully out-of-pocket. FINDINGS: We found that Medicaid and privately insured women were often asked to pay cash for OUD treatment--40% of the time over the full study sample. Such buprenorphine provider requests happened more than 60% of the time in some states. Areas with more providers or with more generous provider payments were not obviously more willing to accept the patient's insurance benefits for OUD treatment. Rural providers were less likely to require payment in cash in order for the woman to receive care. CONCLUSIONS: State-to-state variation was the most striking pattern in our field experiment data. The wide variation suggests that women of reproductive age with OUD in certain states face even greater challenges to treatment access than perhaps previously thought; however, it also reveals that some states have found ways to curtail this problem. Our findings encourage greater attention to this public health challenge and possibly opportunities for shared learning across states.

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.

Back to the future: The advantage of studying key events in human evolution using a new high resolution radiocarbon method.

Radiocarbon dating is the most widely applied dating method in archaeology, especially in human evolution studies, where it is used to determine the chronology of key events, such as the replacement of Neanderthals by modern humans in Europe. However, the method does not always provide precise and accurate enough ages to understand the important processes of human evolution. Here we review the newest method developments in radiocarbon dating ('Radiocarbon 3.0'), which can lead us to much better chronologies and understanding of the major events in recent human evolution. As an example, we apply these new methods to discuss the dating of the important Palaeolithic site of Bacho Kiro (Bulgaria).

Retail Health Clinic Growth as a Potential Primary Care Disruptor.

Retail health clinics (RHCs) have been described as a disruptive model of care delivery. We describe RHC market presence in the United States from 2008 to 2016 with a focus on the characteristics of counties where new clinics open. We merge national data on RHC openings and closings from Merchant Medicine with the Area Health Resources File. We examined county-level counts and ownership of RHCs over time. From 2008 to 2016, we found increasing ownership of RHCs by retail pharmacies, and, contrary to earlier predictions, RHCs continue to be located in affluent counties and did not open in underserved or provider shortage areas. Most new clinics opened in counties where RHCs already had a presence, and these counties also had greater primary care physician, nurse practitioner, and physician assistant density per capita (100,000). As RHCs expand and offer more services, they may place new competitive pressures on nearby primary care providers and practices.