Upper-Limb High-Intensity Interval Training or Passive Heat Therapy to Optimize Cardiorespiratory Fitness Prior to Total Hip or Knee Arthroplasty: A Randomized Controlled Trial.

OBJECTIVE: Preoperative exercise training, or prehabilitation, aims to optimize cardiorespiratory fitness before surgery to reduce the risk of adverse perioperative events and delayed recovery. However, traditional exercise such as walking and cycling can be difficult for people with degenerative joint diseases of the lower limbs, such as osteoarthritis. The purpose of this study was to compare the effect of three low-impact interventions on cardiorespiratory fitness, physical function, and subjective health before total hip or knee arthroplasty. METHODS: This was a randomized controlled trial involving 93 participants with severe knee or hip osteoarthritis awaiting joint replacement surgery. Participants underwent cardiopulmonary exercise testing (to measure peak oxygen consumption [ V ̇ $$ \dot{V} $$ O2 ]), then were randomized to heat therapy (Heat; 20-30 min immersed in 40°C water followed by ~15 min light-resistance exercise), high-intensity interval training (HIIT; 6-8 × 60 s intervals on a cross-trainer or arm ergometer at ~90%-100% peak V ̇ $$ \dot{V} $$ O2 ), or home-based exercise (Home; ~15 min light-resistance exercise); for up to 36 sessions (3 sessions per week for 12 weeks). RESULTS: Peak V ̇ $$ \dot{V} $$ O2 increased by 16% across HIIT and to a greater extent than Heat (+2.5 mL × min-1 × kg-1 [95% CI: 0.5-4.4], P = 0.009) and Home (+3.2 mL × min-1 × kg-1 [1.2-5.2], P = 0.001). The anaerobic threshold increased across HIIT (+1.5 mL × min-1 × kg-1 [0.7-2.3], P < 0.001) and Heat (+1.2 mL × min-1 × kg-1 [0.4-1.9], P = 0.004), but not Home (-0.5 mL × min-1 × kg-1 [-1.3 to 0.3], P = 0.248). Subjective severity of osteoarthritis was unchanged with any intervention (P ≥ 0.250). CONCLUSION: Heat therapy and HIIT improved indices of cardiorespiratory fitness preoperatively in patients who have difficulty performing lower-limb exercise.

Learning Harmony: Medical Student Reflections on the Intersection of the Arts & Humanities and Medicine, A Mixed Methods Study.

Background: The arts and humanities form a critical part of medical education. In this study, we explore medical students' reflections following an arts and humanities experience. An intensive day and a half long program focused on music and reflection was designed for first-year students at Harvard Medical School. Methods: Students completed an evaluation of the experience with both open-ended and Likert scale questions. Data were analyzed using a mixed methods approach. Descriptive statistics were used to analyze quantitative data and inductive content analysis for qualitative data. Results: 168 first-year medical and dental students participated in the activity. Survey response rate was 73% (n =122). Quantitatively, the overall quality of the experience was assessed at a mean value of 4.86 points (SD = 0.37 points) out of a maximum of 5, with 5 being excellent. The qualitative evaluation illustrated how the arts and humanities experience encouraged students to reflect on their leadership and doctoring skills, taking a holistic approach to their medical education, and integrating the lessons of the arts and humanities into their medical practice. Conclusion: The arts and humanities program encouraged student reflection on profound questions in medicine related to empathy, vulnerability, and authenticity. This experience broadened students' perspectives regarding the relationship between medicine and the arts and humanities.

Implementing a virtual mind-body prehabilitation program for patients undergoing thoracic surgery: A quality improvement project.

Background: Prehabilitation before thoracic surgery has been found to improve outcomes in patients with cancer; however, COVID-19 presented challenges to access on-site programs. We describe the development, implementation, and evaluation of a synchronous, virtual mind-body prehabilitation program developed in response to COVID-19. Methods: Eligible participants were patients seen at a thoracic oncology surgical department of an academic cancer center, aged 18 years or older with a diagnosis of thoracic cancer and referred at least 1 week before surgery. The program offered 2 45-minute preoperative mind-body fitness classes each week delivered via Zoom (Zoom Video Communications, Inc). We collected data for referrals, enrollment, participation, and evaluated patient-reported satisfaction and experience. We conducted brief semistructured interviews about participants' experience. Results: Among 278 patients referred, 260 were approached, and of those 197 (76%) patients agreed to participate. Among participants, 140 (71%) attended at least 1 class, with an average of 11 attendees per class. The majority of participants reported being extremely satisfied (97.8%), extremely likely to recommend the classes to others (91.2%), and indicated that classes were very much helpful in preparing for surgery (90.8%). Patients also reported that the classes helped reduce anxiety/stress (94.2%), fatigue (88.5%), pain (80.7%), and shortness of breath (86.5%). Qualitative data further suggest that the program made participants feel stronger, more connected to their peers, and better prepared for surgery. Conclusions: This virtual mind-body prehabilitation program was well received with high satisfaction and benefits and is highly feasible to implement. This approach may help overcome some of the challenges to in-person participation.

Acute and adaptive cardiovascular and metabolic effects of passive heat therapy or high-intensity interval training in patients with severe lower-limb osteoarthritis.

Exercise is painful and difficult to perform for patients with severe lower-limb osteoarthritis; consequently, reduced physical activity contributes to increased cardiometabolic disease risk. The aim of this study was to characterize the acute and adaptive cardiovascular and metabolic effects of two low or no impact therapies in patients with severe lower-limb osteoarthritis: passive heat therapy (Heat) and high-intensity interval training (HIIT) utilizing primarily the unaffected limbs, compared to a control intervention of home-based exercise (Home). Participants completed up to 12 weeks of either Heat (20-30 min immersed in 40°C water followed by ~15-min light resistance exercise), HIIT (6-8 × 60-s intervals on a cross-trainer or arm ergometer at ~90-100% peak V ̇ $$ \dot{V} $$ O2 ) or Home (~15-min light resistance exercise); all 3 sessions/week. Reductions in systolic (12 & 10 mm Hg), diastolic (7 & 4 mm Hg), and mean arterial (8 & 6 mm Hg) blood pressure (BP) were observed following one bout of Heat or HIIT exposure, lasting for the duration of the 20-min monitoring period. Across the interventions (i.e., 12 weeks), resting systolic BP and diastolic BP decreased with Heat (-9 & -4 mm Hg; p < 0.001) and HIIT (-7 & -3 mm Hg; p ≤ 0.011), but not Home (0 & 0 mm Hg; p ≥ 0.785). The systolic and diastolic BP responses to an acute exposure of Heat or HIIT in the first intervention session were moderately correlated with adaptive responses across the intervention (r ≥ 0.54, p ≤ 0.005). Neither intervention improved indices of glycemic control (p = 0.310). In summary, both Heat and HIIT induced potent immediate and adaptive hypotensive effects, and the acute response was moderately predictive of the long-term response.

Quality of life and home parenteral nutrition: a survey of UK healthcare professionals' knowledge, practice and opinions.

BACKGROUND: There is increasing interest in the assessment of health-related quality of life (QoL) in the care of patients treated with home parenteral nutrition (HPN). However, it is not known whether healthcare professionals (HCPs) have embedded QoL assessment into routine clinical practice in line with current guidelines to favour a more holistic approach to HPN care. The aim of this study was to assess knowledge, current practice and the opinions of HCPs regarding QoL in care of patients on HPN. METHODS: An online survey was distributed via email to HCPs working with HPN patients throughout England, Scotland, Wales and Northern Ireland. Participants were identified using a mailing list for the British Intestinal Failure Alliance, a specialist group within the British Association for Parenteral and Enteral Nutrition. RESULTS: The survey was completed by 67 professionals comprising 24 dietitians, 17 nurses, 14 gastroenterologists, 6 pharmacists, 5 surgeons and 1 psychologist. Of these, 54 (80%) participants agreed that the measurement of QoL is useful. In contrast, 38 (57%) of all participants, including 27 (50%) of those participants who agreed that the measurement of QoL was useful, never measured QoL. Knowledge of QoL literature was rated as poor or very poor by 27 (40%) participants. CONCLUSIONS: Despite the perceived usefulness and importance of QoL assessment, very few HCPs embed it into clinical practice. Knowledge of QoL literature and QoL tools is variable, and there is significant variability in QoL practice. This is clear in terms of the frequency of QoL assessments and heterogeneity in methodology. In contrast, there was almost unanimous agreement that the complications associated with HPN contribute to poorer QoL. There is a need for specific, evidence-based, clinical practice guidelines detailing how to define and measure QoL in this patient population.

Multimodal correlative imaging and modelling of phosphorus uptake from soil by hyphae of mycorrhizal fungi.

Phosphorus (P) is essential for plant growth. Arbuscular mycorrhizal fungi (AMF) aid its uptake by acquiring P from sources distant from roots in return for carbon. Little is known about how AMF colonise soil pore-space, and models of AMF-enhanced P-uptake are poorly validated. We used synchrotron X-ray computed tomography to visualize mycorrhizas in soil and synchrotron X-ray fluorescence/X-ray absorption near edge structure (XRF/XANES) elemental mapping for P, sulphur (S) and aluminium (Al) in combination with modelling. We found that AMF inoculation had a suppressive effect on colonisation by other soil fungi and identified differences in structure and growth rate between hyphae of AMF and nonmycorrhizal fungi. Our results showed that AMF co-locate with areas of high P and low Al, and preferentially associate with organic-type P species over Al-rich inorganic P. We discovered that AMF avoid Al-rich areas as a source of P. Sulphur-rich regions were found to be correlated with higher hyphal density and an increased organic-associated P-pool, whilst oxidized S-species were found close to AMF hyphae. Increased S oxidation close to AMF suggested the observed changes were microbiome-related. Our experimentally-validated model led to an estimate of P-uptake by AMF hyphae that is an order of magnitude lower than rates previously estimated - a result with significant implications for the modelling of plant-soil-AMF interactions.

Current Trends of Practices in Nonclinical Toxicology: An Industry Survey.

The growth in drug development over the past years reflects significant advancements in basic sciences and a greater understanding of molecular pathways of disease. Benchmarking industry practices has been important to enable a critical reflection on the path to evolve pharmaceutical testing, and the outcome of past industry surveys has had some impact on best practices in testing. A survey was provided to members of SPS, ACT, and STP. The survey consisted of 37 questions and was provided to 2550 participants with a response rate of 24%. Most respondents (∼75%) came from the US and Europe. The survey encompassed multiple topics encountered in nonclinical testing of pharmaceuticals. The most frequent target indications were oncology (69%), inflammation (55%), neurology/psychiatry/pain (46%), cardiovascular (44%), and metabolic diseases (39%). The most frequent drug-induced toxicology issues confronted were hepatic, hematopoietic, and gastrointestinal. Toxicological effects that impacted the no observed adverse effect level (NOAEL) were most frequently based on histopathology findings. The survey comprised topics encountered in the use of biomarkers in nonclinical safety assessment, most commonly those used to assess inflammation, cardiac/vascular, renal, and hepatic toxicity as well as common practices related to the assessment of endocrine effects, carcinogenicity, genotoxicity, juvenile and male-mediated developmental and female reproductive toxicity. The survey explored the impact of regulatory meetings on program design, application of the 3 Rs, and reasons for program delays. Overall, the survey results provide a broad perspective of current practices based on the experience of the scientific community engaged in nonclinical safety assessment.

Tracing the fate of wastewater viruses reveals catchment-scale virome diversity and connectivity.

The discharge of wastewater-derived viruses in aquatic environments impacts catchment-scale virome composition. To explore this, we used viromic analysis of RNA and DNA virus-like particles to holistically track virus communities entering and leaving wastewater treatment plants and the connecting river catchment system and estuary. We reconstructed >40 000 partial viral genomes into 10 149 species-level groups, dominated by dsDNA and (+)ssRNA bacteriophages (Caudoviricetes and Leviviricetes) and a small number of genomes that could pose a risk to human health. We found substantial viral diversity and geographically distinct virus communities associated with different wastewater treatment plants. River and estuarine water bodies harboured more diverse viral communities in downstream locations, influenced by tidal movement and proximity to wastewater treatment plants. Shellfish and beach sand were enriched in viral communities when compared with the surrounding water, acting as entrapment matrices for virus particles. Extensive phylogenetic analyses of environmental-derived and reference sequences showed the presence of human-associated sapovirus GII in all sample types, multiple rotavirus A strains in wastewater and a diverse set of picorna-like viruses associated with shellfish. We conclude that wastewater-derived viral genetic material is commonly deposited in the environment and can be traced throughout the freshwater-marine continuum of the river catchment, where it is influenced by local geography, weather events and tidal effects. Our data illustrate the utility of viromic analyses for wastewater- and environment-based ecology and epidemiology, and we present a conceptual model for the circulation of all types of viruses in a freshwater catchment.

The value of multimodal imaging with 123I-FP-CIT SPECT in differential diagnosis of dementia with Lewy bodies and Alzheimer's disease dementia.

Reduced nigrostriatal uptake on N-(3-fluoropropyl)-2ß-carbomethoxy-3ß-(4-[123I]iodophenyl) nortropane (123I-FP-CIT) SPECT reflects dopamine dysfunction, while other imaging markers could be complementary when used together. We assessed how well 123I-FP-CIT SPECT differentiates dementia with Lewy bodies (DLBs) from Alzheimer's disease dementia (ADem) and whether multimodal imaging provides additional value. 123I-FP-CIT SPECT, magnetic resonance imaging, [18F]2-fluoro-deoxy-D-glucose-positron emission tomography (PET), and 11C-Pittsburgh compound B (PiB)-PET were assessed in 35 participants with DLBs and 14 participants with ADem (autopsy confirmation in 9 DLBs and 4 ADem). Nigrostriatal dopamine transporter uptake was evaluated with 123I-FP-CIT SPECT using DaTQUANT software. Hippocampal volume was calculated with magnetic resonance imaging, cingulate island sign ratio with FDG-PET, and global cortical PiB retention with PiB-PET. The DaTQUANT z-scores of the putamen showed the highest c-statistic of 0.916 in differentiating DLBs from ADem among the analyzed imaging biomarkers. Adding another imaging modality to 123I-FP-CIT SPECT had c-statistics ranging from 0.968 to 0.975, and 123I-FP-CIT SPECT in combination with 2 other imaging modalities presented c-statistics ranging from 0.987 to 0.996. These findings suggest that multimodal imaging with 123I-FP-CIT SPECT aids in differentiating DLBs and ADem and in detecting comorbid Lewy-related and Alzheimer's disease pathology in patients with DLBs and ADem.

Spectral characterization and impact of stepwise ablation protocol including LAA electrical isolation on persistent AF.

OBJECTIVES: To study how left atrial appendage electrical isolation (LAAEI) impacts atrial dominant frequency (DF) in patients with long-standing persistent atrial fibrillation (LSPAF). BACKGROUND: LAAEI is associated with a high probability of freedom from atrial fibrillation (AF) and spectral analysis may identify high-frequency sources. How LAAEI impacts the AF dynamics and the subgroup of LSPAF patients in whom LAAEI would be most beneficial, is unclear. METHODS: Twenty patients with LSPAF were included in the study. Fast Fourier transforms (FFT) were performed on atrial electrograms recorded from 13 sites in the LA and RA. The highest peak frequency was defined as DF. RESULTS: There was no significant difference in DF between atrial sites except for at the superior vena cava which had the lowest DF at baseline. Stepwise ablation consisting of circumferential pulmonary vein isolation and a linear ablation set of mitral isthmus and roof significantly reduced the DF within the coronary sinus (CS) (5.93 ± 0.98 Hz vs. 5.09 ± 0.72 Hz, p < .05) and the LA posterior wall (LApos) (6.26 ± 0.92 Hz vs. 5.43 ± 0.98 Hz, p < .01). LAAEI preferentially further decreased the DF at the LApos (p < .01), but not at the CS. In cases where there was < 13.6% reduction in the DF of the LApos following the stepwise ablation, the addition of LAAEI was associated with an increased restoration of sinus rhythm (55%, p < .05). CONCLUSION: LAAEI in addition to stepwise ablation results in further reduction of the DF in the LApos, which is associated with acute termination of AF and favorable ablation outcome.

A subset of pediatric-type thalamic gliomas share a distinct DNA methylation profile, H3K27me3 loss and frequent alteration of EGFR.

BACKGROUND: Malignant astrocytic gliomas in children show a remarkable biological and clinical diversity. Small in-frame insertions or missense mutations in the epidermal growth factor receptor gene (EGFR) have recently been identified in a distinct subset of pediatric-type bithalamic gliomas with a unique DNA methylation pattern. METHODS: Here, we investigated an epigenetically homogeneous cohort of malignant gliomas (n = 58) distinct from other subtypes and enriched for pediatric cases and thalamic location, in comparison with this recently identified subtype of pediatric bithalamic gliomas. RESULTS: EGFR gene amplification was detected in 16/58 (27%) tumors, and missense mutations or small in-frame insertions in EGFR were found in 20/30 tumors with available sequencing data (67%; 5 of them co-occurring with EGFR amplification). Additionally, 8 of the 30 tumors (27%) harbored an H3.1 or H3.3 K27M mutation (6 of them with a concomitant EGFR alteration). All tumors tested showed loss of H3K27me3 staining, with evidence of overexpression of the EZH inhibitory protein (EZHIP) in the H3 wildtype cases. Although some tumors indeed showed a bithalamic growth pattern, a significant proportion of tumors occurred in the unilateral thalamus or in other (predominantly midline) locations. CONCLUSIONS: Our findings present a distinct molecular class of pediatric-type malignant gliomas largely overlapping with the recently reported bithalamic gliomas characterized by EGFR alteration, but additionally showing a broader spectrum of EGFR alterations and tumor localization. Global H3K27me3 loss in this group appears to be mediated by either H3 K27 mutation or EZHIP overexpression. EGFR inhibition may represent a potential therapeutic strategy in these highly aggressive gliomas.

Health system integration with physician specialties varies across markets and system types.

OBJECTIVE: To examine system integration with physician specialties across markets and the association between local system characteristics and their patterns of physician integration. DATA SOURCES: Data come from the AHRQ Compendium of US Health Systems and IQVIA OneKey database. STUDY DESIGN: We examined the change from 2016 to 2018 in the percentage of physicians in systems, focusing on primary care and the 10 most numerous nonhospital-based specialties across the 382 metropolitan statistical areas (MSAs) in the US. We also categorized systems by ownership, mission, and payment program participation and examined how those characteristics were related to their patterns of physician integration in 2018. DATA COLLECTION/EXTRACTION METHODS: We examined local healthcare markets (MSAs) and the hospitals and physicians that are part of integrated systems that operate in these markets. We characterized markets by hospital and insurer concentration and systems by type of ownership and by whether they have an academic medical center (AMC), a 340B hospital, or accountable care organization. PRINCIPAL FINDINGS: Between 2016 and 2018, system participation increased for primary care and the 10 other physician specialties we examined. In 2018, physicians in specialties associated with lucrative hospital services were the most commonly integrated with systems including hematology-oncology (57%), cardiology (55%), and general surgery (44%); however, rates varied substantially across markets. For most specialties, high market concentration by insurers and hospital-systems was associated with lower rates of physician integration. In addition, systems with AMCs and publicly owned systems more commonly affiliated with specialties unrelated to the physicians' potential contribution to hospital revenue, and investor-owned systems demonstrated more limited physician integration. CONCLUSIONS: Variation in physician integration across markets and system characteristics reflects physician and systems' motivations. These integration strategies are associated with the financial interests of systems and other strategic goals (eg, medical education, and serving low-income populations).

Phase I, Pharmacogenomic, Drug Interaction Study of Sorafenib and Bevacizumab in Combination with Paclitaxel in Patients with Advanced Refractory Solid Tumors.

VEGF blockade does not uniformly result in clinical benefit. We evaluated safety, dose-limiting toxicities (DLT), recommended phase II dose (RP2D), antitumor efficacy, and exploratory biomarkers including pharmacogenomics and pharmacokinetics with sorafenib, bevacizumab, and paclitaxel in patients with refractory cancers. The study had a "3 + 3" design, using paclitaxel 80 mg/m2 every week for 3 weeks, in every 4 week cycles, bevacizumab 5 mg/kg every 2 weeks, and sorafenib 200 or 400 mg twice a day, 5 or 7 days/week (5/7, 7/7). The MTD cohort was expanded. Twenty-seven patients enrolled in 3 cohorts: sorafenib 200 mg twice a day 5/7, 200 mg twice a day 7/7, and 400 mg twice a day 5/7. DLTs were grade 3 neutropenia >7 days (cohort 1, 1), grade 3 hypertension (cohort 2, 1), grade 3 hand-foot skin reaction (HFSR; cohort 3, 2). MTD was sorafenib 200 mg twice a day 7/7. Six DLTs occurred in cohort 2 expansion: grade 3 HFSR (2), grade 2 HFSR with sorafenib delay >7 days (2), grade 4 cerebrovascular accident (1), grade 3 neutropenia >7 days (1). RP2D was sorafenib 200 mg twice a day 5/7. Most patients (62%) dose reduced sorafenib to 200 mg daily 5/7 after a median 3 (range, 2-17) cycles. Response rates were 48% overall (27) and 64% for ovarian cancers (14). VEGF-A-1154AA and -7TT recessive homozygous genotypes conferred worse overall survival versus alternative genotypes (7 vs. 22 months). Intermittent, low-dose sorafenib (200 mg twice a day 5/7) combined with bevacizumab and paclitaxel was tolerable and had high antitumor efficacy in patients with refractory cancer (NCT00572078).

Novel Encapsulated Calcium Butyrate Supplement Enhances On-Farm Dairy Calf Growth Performance and Body Conformation in a Pasture-Based Dairy Production System.

The effect of supplementing neonatal heifer calves with varying levels of ECAB on pre-weaning growth performance was investigated. Post-weaning growth was also measured, to determine any carry-over effect of pre-weaning supplementation of ECAB. Forty-eight heifer calves (7 ± 0.4 days old, average liveweight of 39.3 ± 5.3 kg) were utilized in a complete randomised experimental design, comprising 16 calves per pen, randomly allocated to one of the following three treatments: (1) Basal commercial calf starter mix without ECAB (Control); (2) control plus 4 kg/ton of ECAB (Low); and (3) control plus 6 kg/ton of ECAB (High). Calves were group-fed ad libitum for 77 days (11 weeks, pre-weaning period) with free choice access to water and 5.5 L of milk per head per day through an automated feeder. Calves were weighed weekly during the pre-weaning period, after which all calves were then weaned onto the same ryegrass pasture as one group. At approximately 9 months of age, calves were weighed to estimate post-weaning body weight gain. During the pre-weaning period, average daily dry matter feed intake was similar for 4 kg/ton and 6 kg/ton calves (649 g versus 688 g, respectively) and both were greater than that of the control calves (382 g). Average daily gain (ADG) was significantly higher for 4 kg/ton calves compared to 6 kg/ton calves or control calves (0.83 ± 0.03 kg, 0.74 ± 0.03 kg and 0.71 ± 0.03 kg, respectively; p = 0.0001). Similarly, 4 kg/ton calves had significantly increased chest girth (95.9 ± 0.7 cm), withers height (88.9 ± 0.5 cm), body length (82.9 ± 0.6 cm), and body condition score (1.99 ± 0.12) compared to 6 kg/ton calves (93.4 ± 0.7 cm, 87.4 ± 0.7, 81.5 ± 0.6 cm, and 1.67 ± 0.10, respectively) or control calves (92.9 ± 0.7 cm, 88.2 ± 0.5 cm, 80.1 ± 0.6 cm, and 1.30 ± 0.08, respectively). There was significant treatment × week interaction for all pre-weaning growth parameters. Breed differences were detected but there was no treatment × breed interaction. Post-weaning, 4 kg/t calves and 6 kg/t calves had significantly higher ADG compared to control calves (0.80 ± 0.03 kg, 0.85 ± 0.03 kg versus 0.70 ± 0.03 kg, respectively; p = 0.0047). It is concluded that under the conditions of this study, supplementing heifer calves with ECAB during pre-weaning period resulted in improved growth performance and there appears to be a post-weaning carry-over effect.

Consolidation Of Providers Into Health Systems Increased Substantially, 2016-18.

Provider consolidation into vertically integrated health systems increased from 2016 to 2018. More than half of US physicians and 72 percent of hospitals were affiliated with one of 637 health systems in 2018. For-profit and church-operated systems had the largest increases in system size, driven in part by a large number of system mergers and acquisitions.

Can vertically integrated health systems provide greater value: The case of hospitals under the comprehensive care for joint replacement model?

OBJECTIVE: We aim to assess whether system providers perform better than nonsystem providers under an alternative payment model that incentivizes high-quality, cost-efficient care. We posit that the payment environment and the incentives it provides can affect the relative performance of vertically integrated health systems. To examine this potential influence, we compare system and nonsystem hospitals participating in Medicare's Comprehensive Care for Joint Replacement (CJR) model. DATA SOURCES: We used hospital cost and quality data from the Centers for Medicare & Medicaid Services linked to data from the Agency for Healthcare Research and Quality's Compendium of US Health Systems and hospital characteristics from secondary sources. The data include 706 hospitals in 67 metropolitan areas. STUDY DESIGN: We estimated regressions that compared system and nonsystem hospitals' 2017 cost and quality performance providing lower joint replacements among hospitals required to participate in CJR. PRINCIPAL FINDINGS: Among CJR hospitals, system hospitals that provided comprehensive services in their local market had 5.8 percent ($1612) lower episode costs (P = .01) than nonsystem hospitals. System hospitals that did not provide such services had 3.5 percent ($967) lower episode costs (P = .14). Quality differences between system hospitals and nonsystem hospitals were mostly small and statistically insignificant. CONCLUSIONS: When operating under alternative payment model incentives, vertical integration may enable hospitals to lower costs with similar quality scores.

COVID-19 guidance for triage of operations for thoracic malignancies: A consensus statement from Thoracic Surgery Outcomes Research Network.

The extraordinary demands of managing the COVID-19 pandemic has disrupted the world's ability to care for patients with thoracic malignancies. As a hospital's COVID-19 population increases and hospital resources are depleted, the ability to provide surgical care is progressively restricted, forcing surgeons to prioritize among their cancer populations. Representatives from multiple cancer, surgical, and research organizations have come together to provide a guide for triaging patients with thoracic malignancies as the impact of COVID-19 evolves as each hospital.

Opportunities for use of one species for longer-term toxicology testing during drug development: A cross-industry evaluation.

An international expert working group representing 37 organisations (pharmaceutical/biotechnology companies, contract research organisations, academic institutions and regulatory bodies) collaborated in a data sharing exercise to evaluate the utility of two species within regulatory general toxicology studies. Anonymised data on 172 drug candidates (92 small molecules, 46 monoclonal antibodies, 15 recombinant proteins, 13 synthetic peptides and 6 antibody-drug conjugates) were submitted by 18 organisations. The use of one or two species across molecule types, the frequency for reduction to a single species within the package of general toxicology studies, and a comparison of target organ toxicities identified in each species in both short and longer-term studies were determined. Reduction to a single species for longer-term toxicity studies, as used for the development of biologicals (ICHS6(R1) guideline) was only applied for 8/133 drug candidates, but might have been possible for more, regardless of drug modality, as similar target organ toxicity profiles were identified in the short-term studies. However, definition and harmonisation around the criteria for similarity of toxicity profiles is needed to enable wider consideration of these principles. Analysis of a more robust dataset would be required to provide clear, evidence-based recommendations for expansion of these principles to small molecules or other modalities where two species toxicity testing is currently recommended.

Validation of Dipole Density Mapping During Atrial Fibrillation and Sinus Rhythm in Human Left Atrium.

OBJECTIVES: This study sought to validate the accuracy of noncontact electrograms against contact electrograms in the left atrium during sinus rhythm (SR) and atrial fibrillation (AF). BACKGROUND: Noncontact mapping offers the opportunity to assess global cardiac activation in the chamber of interest. A novel noncontact mapping system, which records intracardiac voltage to derive cellular charge sources (dipole density), allows real-time mapping of AF to guide ablation. METHODS: Noncontact and contact unipolar electrogram pairs were recorded simultaneously from multiple locations. Morphology correlation and timing difference of reconstructed electrograms obtained from a noncontact catheter were compared with those from contact electrograms obtained from a contact catheter at the same endocardial locations. RESULTS: A total of 796 electrogram pairs in SR and 969 electrogram pairs in AF were compared from 20 patients with persistent AF. The median morphology correlation and timing difference (ms) in SR was 0.85 (interquartile range [IQR]: 0.71 to 0.94) and 6.4 ms (IQR: 2.6 to 17.1 ms); in AF was 0.79 (IQR: 0.69 to 0.88) and 14.4 ms (IQR: 6.7 to 26.2 ms), respectively. The correlation was stronger and the timing difference was less when the radial distance (r) from the noncontact catheter center to the endocardium was ≤ 40 versus > 40 mm; 0.87 (IQR: 0.72 to 0.94) versus 0.73 (IQR: 0.56 to 0.88) and 5.7 ms (IQR: 2.6 to 15.4 ms) versus 15.1 ms (IQR: 4.1 to 27.7 ms); p < 0.01 when in SR; 0.81 (IQR: 0.69 to 0.89) versus 0.67 (IQR: 0.45 to 0.82) and 12.3 ms (IQR: 5.9 to 21.8 ms) versus 28.3 ms (IQR: 16.2 to 36.0 ms); p < 0.01 when in AF. CONCLUSIONS: This novel noncontact dipole density mapping system provides comparable reconstructed atrial electrogram measurements in SR or AF in human left atrium when the anatomical site of interest is ≤40 mm from the mapping catheter.

Landscape of Health Systems in the United States.

Despite the prevalence of vertical integration, data and research focused on identifying and describing health systems are sparse. Until recently, we lacked an enumeration of health systems and an understanding of how systems vary by key structural attributes. To fill this gap, the Agency for Healthcare Research and Quality developed the Compendium of U.S. Health Systems, a data resource to support research on comparative health system performance. In this article, we describe the methods used to create the Compendium and present a picture of vertical integration in the United States. We identified 626 health systems in 2016, which accounted for 70% of nonfederal general acute care hospitals. These systems varied by key structural attributes, including size, ownership, and geographic presence. The Compendium can be used to study the characteristics of the U.S. health care system and address policy issues related to provider organizations.