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Consumers, public officials, and even managers of health care and insurance are unhappy about care quality, access, and costs. This book shows that is because efforts to do something about these problems often rely on hope or conjecture, not rigorous evidence of effectiveness. In this book, experts in the field separate the speculative from the proven with regard to how care is rendered, how patients can be in control, how providers should be paid, and how disparities can be reduced – and they also identify the issues for which evidence is currently missing. It provides an antidote to frustration and a clear-eyed guide for forward progress, helping health care and insurance innovators make better decisions on deciding whether to go ahead now based on current evidence, to seek and wait for additional evidence, or to move on to different ideas. It will be useful to practitioners in hospital systems, medical groups, and insurance organizations and can also be used in executive and MBA teaching.
This chapter has three main objectives. This chapter first describes multilingualism as a natural force, deeply rooted in Asian and African societies prior to the emergence of nation-states and currently flourishing and evolving in India. Parts 2– 4 of this chapter provide evidence from pre-colonial India and its neighboring countries to underscore the differential evolution of Indian and Chinese political multilingualism in both qualitative and quantitative terms. The chapter closes by investigating the dynamics of linguistic, non-linguistic, and cultural forces in Southeast Asia and China, forces that shaped, sustained, and spread pre-and post-fifteenth-century Indian multilingualism in and outside India. Super-diversity is a key marker of Ancient as well as Modern India. This region represents a microcosm of different languages, races, religions, and cultures that have blended and brought about a special unity in diversity. The chapter shows that sustainable and stable Indian multilingualism defies the conventional belief that multilingualism cannot survive or flourish without a writing system and/or government intervention. Salient linguistic and ecological features are identified to highlight the exceptional nature of Indian multilingualism and its spread to Southeast Asia and China.
Colley Cibber was one of the most derided men in eighteenth-century London. Mocked for his work in the theatre and as Poet Laureate, he was nevertheless a prolific actor and playwright, and co-managed the Theatre Royal Drury Lane for 24 years. His response to his critics, An Apology for the Life of Mr Colley Cibber, is often described as the first theatrical autobiography, and even as the first secular autobiography in English. But what kind of text is it – intimate confession or cunning pose? History of the stage or political polemic? Rambling or purposeful? Or perhaps, even, the first celebrity memoir? Including comprehensive notes and a detailed scholarly introduction, this modernised text makes Cibber's enigmatic literary landmark accessible to a wide readership for the first time and allows both specialists and general readers to explore Cibber's extraordinary career against the rich, turbulent background of London theatre in the eighteenth century.
The Hierarchical Taxonomy of Psychopathology (HiTOP) has emerged out of the quantitative approach to psychiatric nosology. This approach identifies psychopathology constructs based on patterns of co-variation among signs and symptoms. The initial HiTOP model, which was published in 2017, is based on a large literature that spans decades of research. HiTOP is a living model that undergoes revision as new data become available. Here we discuss advantages and practical considerations of using this system in psychiatric practice and research. We especially highlight limitations of HiTOP and ongoing efforts to address them. We describe differences and similarities between HiTOP and existing diagnostic systems. Next, we review the types of evidence that informed development of HiTOP, including populations in which it has been studied and data on its validity. The paper also describes how HiTOP can facilitate research on genetic and environmental causes of psychopathology as well as the search for neurobiologic mechanisms and novel treatments. Furthermore, we consider implications for public health programs and prevention of mental disorders. We also review data on clinical utility and illustrate clinical application of HiTOP. Importantly, the model is based on measures and practices that are already used widely in clinical settings. HiTOP offers a way to organize and formalize these techniques. This model already can contribute to progress in psychiatry and complement traditional nosologies. Moreover, HiTOP seeks to facilitate research on linkages between phenotypes and biological processes, which may enable construction of a system that encompasses both biomarkers and precise clinical description.
This chapter offers lessons from engineering and other industries that promise developments in healthcare, and practical guidance for clinician-engineer partnerships. Section 1 provides guidance on how to establish a shared vocabulary and common understanding between engineers and clinicians of what terms such as AI and ML do and don’t mean. Section 2 identifies challenges clinician-engineering partnerships must overcome to deliver sustained value and ways to avoid common causes of failure. Section 3 provides specific advice on how to design projects to produce value at a series of stages rather than rely on the success of one, ambitious final model. Section 4 concludes by drawing on cautionary lessons from healthcare and other industries.
The Lower–Middle Ordovician (Ibexian, Whiterockian) sedimentary rocks exposed at Rancho Las Norias includes the informally named Las Norias formation, which consists of an intercalation of carbonate and clastic sediments with abundant marine fauna. These deposits occur as the most austral sedimentary rocks of Ordovician age for Laurentia, providing a critical link to understand the distribution of Ordovician marine faunas of North America. An investigation of the gastropod fauna from the upper portion of the Las Norias formation, Sonora, Mexico, is undertaken for the first time. The gastropod assemblage includes Maclurites acuminatus, ?Monitorella sp., Lecanospira sp., Malayaspira aff. M. rugosa, Lophospira perangulata, and Hormotoma? sp. This assemblage indicates a paleogeographic relationship with Laurentia, including the USA (Nevada), Canada (British Columbia, Newfoundland), Greenland, and the Argentine Precordillera.
Automated virtual reality therapies are being developed to increase access to psychological interventions. We assessed the experience with one such therapy of patients diagnosed with psychosis, including satisfaction, side effects, and positive experiences of access to the technology. We tested whether side effects affected therapy.
In a clinical trial 122 patients diagnosed with psychosis completed baseline measures of psychiatric symptoms, received gameChange VR therapy, and then completed a satisfaction questionnaire, the Oxford-VR Side Effects Checklist, and outcome measures.
79 (65.8%) patients were very satisfied with VR therapy, 37 (30.8%) were mostly satisfied, 3 (2.5%) were indifferent/mildly dissatisfied, and 1 (0.8%) person was quite dissatisfied. The most common side effects were: difficulties concentrating because of thinking about what might be happening in the room (n = 17, 14.2%); lasting headache (n = 10, 8.3%); and the headset causing feelings of panic (n = 9, 7.4%). Side effects formed three factors: difficulties concentrating when wearing a headset, feelings of panic using VR, and worries following VR. The occurrence of side effects was not associated with number of VR sessions, therapy outcomes, or psychiatric symptoms. Difficulties concentrating in VR were associated with slightly lower satisfaction. VR therapy provision and engagement made patients feel: proud (n = 99, 81.8%); valued (n = 97, 80.2%); and optimistic (n = 96, 79.3%).
Patients with psychosis were generally very positive towards the VR therapy, valued having the opportunity to try the technology, and experienced few adverse effects. Side effects did not significantly impact VR therapy. Patient experience of VR is likely to facilitate widespread adoption.
Clozapine is the only drug licensed for treatment-resistant schizophrenia (TRS) but the real-world clinical and cost-effectiveness of community initiation of clozapine is unclear.
The aim was to assess the feasibility and cost-effectiveness of community initiation of clozapine.
This was a naturalistic study of community patients recommended for clozapine treatment.
Of 158 patients recommended for clozapine treatment, 88 (56%) patients agreed to clozapine initiation and, of these, 58 (66%) were successfully established on clozapine. The success rate for community initiation was 65.4%; which was not significantly different from that for in-patient initiation (58.82%, χ2(1,88) = 0.47, P = 0.49). Following clozapine initiation, there was a significant reduction in median out-patient visits over 1 year (from 24.00 (interquartile range (IQR) = 14.00–41.00) to 13.00 visits (IQR = 5.00–24.00), P < 0.001), and 2 years (from 47.50 visits (IQR = 24.75–71.00) to 22.00 (IQR = 11.00–42.00), P < 0.001), and a 74.71% decrease in psychiatric hospital bed days (z = −2.50, P = 0.01). Service-use costs decreased (1 year: –£963/patient (P < 0.001); 2 years: –£1598.10/patient (P < 0.001). Subanalyses for community-only initiation also showed significant cost reductions (1 year: –£827.40/patient (P < 0.001); 2 year: –£1668.50/patient (P < 0.001) relative to costs prior to starting clozapine. Relative to before initiation, symptom severity was improved in patients taking clozapine at discharge (median Positive and Negative Syndrome Scale total score: initial visit: 80 (IQR = 71.00–104.00); discharge visit 50.5 (IQR = 44.75–75.00), P < 0.001) and at 2 year follow-up (Health of Nation Outcome Scales total score median initial visit: 13.00 (IQR = 9.00–15.00); 2 year follow-up: 8.00 (IQR = 3.00–13.00), P = 0.023).
These findings indicate that community initiation of clozapine is feasible and is associated with significant reductions in costs, service use and symptom severity.
The study in this research paper was undertaken with a hypothesis that accelerometer data can be used to improve monitoring of energy balance in dairy cows. Animals of high (select, S) and average (control, C) genetic-merit lines were allocated to two feeding systems, by-product (BP) and homegrown (HG). This culminated in four production systems referred to as BPS, BPC, HGS and HGC. Cows between their first and fourth lactations were included and a total of 8602 records were used. The target crude protein (CP) and metabolisable energy (ME) content in the BP diet was 185 g/kg DM and 12.3 MJ/kg DM while it was 180 g/kg DM, and 11.5 MJ/kg DM for the HG diet, respectively. Milk yield, body energy content (BEC) and animal activity were monitored while the animals were all housed for winter. Results showed that cows on homegrown feeds were significantly (P < 0.05) more active than cows on by-product feeds as indicated by higher motion index and number of steps per day. Feeding duration was not significantly different (P > 0.05) between cows under by-product feeding system irrespective of the energy balance of the cows. However, there were significant differences for cows under homegrown feeding system. Cows in negative energy balance had a longer feeding duration per day than cows in positive energy balance. Milk yield was negatively correlated (P < 0.05) to motion index and number of steps per day but not to lying time and feeding duration. The results showed differences in cow activity were related to diet content and body energy status. This is useful in precision farming where feeds are provided according to specific animal behaviour and feed requirements.
OBJECTIVES/GOALS: Our goal is to explore and collaboratively identify the team science competencies essential for Clinical Research Professionals at all experience levels and how these competencies relate to the Joint Task Force for Clinical Translational Research Professionals Competencies. METHODS/STUDY POPULATION: Team science competencies for clinical research professionals are poorly defined. The JTF Clinical Trial Competencies lack sufficient emphasis on team science, though it is briefly included in two JTF competency domains: Leadership & Professionalism, and Communication & Teamwork. The competencies primarily focus on tasks related to clinical research and basic knowledge of product development; however, a conceptual model for applying the competencies using a team science lens is needed. Currently, the JTF competency figure is often thought of as sequential, given the competencies are numbered, creating the misconception that the last competencies are less important. We support a new figure showing the permeability of team science across competencies and the connectedness and equality of the competencies. RESULTS/ANTICIPATED RESULTS: Our anticipated results are to show the integral nature of team science in clinical research professional communities of practice. Once complete, we will have identified measurable team science competency-based skills essential for clinical research professionals at various levels of expertise. Understanding the multi-dimensional team science competencies will inform targeted team science education and training for clinical research professionals. Our revised competency framework provides an improved team science conceptual model for clinical translational science. DISCUSSION/SIGNIFICANCE: Our work will define team science competencies as related to clinical research professionals at all experience levels. The interdependence of teams across clinical trial activities necessitates a consideration of an improved conceptual framework for clinical translational team science competencies.
OBJECTIVES/GOALS: Osteoarthritis (OA) is a cartilage destroying disease. We are investigating abaloparatide (ABL) activation of parathyroid hormone receptor type 1 (PTH1R), which is expressed by articular chondrocytes in OA. We propose ABL treatment is chondroprotective in murine PTOA via stimulation of matrix production and inhibition of chondrocyte maturation. METHODS/STUDY POPULATION: 16-week-old C57BL/6 male mice received destabilization of the medial meniscus (DMM) surgery to induce knee PTOA. Beginning 2 weeks post-DMM, 40 Î¼g/kg of ABL (or saline) was administered daily via subcutaneous injection and tissues were harvested after 6 weeks of daily injections and 8 weeks after DMM surgery. Harvested joint tissues were used for histological and molecular assessment of OA using three 5 Î¼m thick sagittal sections from each joint, 50 Î¼m apart, cut from the medial compartment of injured knees. Safranin O/Fast Green tissue staining and immunohistochemistry-based detection of type 10 collagen (Col10) and lubricin (Prg4) was performed using standard methods. Histomorphometric quantification of tibial cartilage area and larger hypertrophic-like cells was performed using the Osteomeasure system. RESULTS/ANTICIPATED RESULTS: Safranin O/Fast Green stained sections showed a decreased cartilage loss in DMM joints from ABL-treated versus saline-treated mice. Histomorphometric analysis of total tibial cartilage area revealed preservation of cartilage tissue on the tibial surface. Immunohistochemical analyses showed that upregulation of Col10 in DMM joints was mitigated in the cartilage of ABL-treated mice, and chondrocyte expression of Prg4 was increased in uncalcified cartilage areas in ABL-treated group. The Prg4 finding suggests a matrix anabolic effect that may counter OA cartilage loss. Quantification of chondrocytes in uncalcified and calcified tibial cartilage areas revealed a reduction in the number of larger hypertrophic-like cells in ABL treated mice, suggesting deceleration of hypertrophic differentiation. DISCUSSION/SIGNIFICANCE: Cartilage preservation/regeneration therapies would fill a critical unmet need. We demonstrate that an osteoporosis drug targeting PTH1R decelerates PTOA in mice. ABL treatment was associated with preservation of cartilage, decreased Col10, increased Prg4, and decreased number of large hypertrophic-like chondrocytes in the tibial cartilage.
When and why do legislatures impeach presidents? We analyse six cases of attempted impeachment in Paraguay, Brazil and Peru to argue that intra-coalitional politics is central to impeachment outcomes. Presidents in Latin America often govern with multiparty, ideologically heterogeneous coalitions sustained by tenuous pacts. Coalitions are tested when crises, scandals or mass protests emerge, but presidents can withstand these threats if they tend to allies’ interests and maintain coalitions intact. Conversely, in the absence of major threats, presidents can be impeached if they fail to serve partners’ interests, inducing allies to support impeachment as acts of opportunism or self-preservation.
Many patients with mental health disorders become increasingly isolated at home due to anxiety about going outside. A cognitive perspective on this difficulty is that threat cognitions lead to the safety-seeking behavioural response of agoraphobic avoidance.
We sought to develop a brief questionnaire, suitable for research and clinical practice, to assess a wide range of cognitions likely to lead to agoraphobic avoidance. We also included two additional subscales assessing two types of safety-seeking defensive responses: anxious avoidance and within-situation safety behaviours.
198 patients with psychosis and agoraphobic avoidance and 1947 non-clinical individuals completed the item pool and measures of agoraphobic avoidance, generalised anxiety, social anxiety, depression and paranoia. Factor analyses were used to derive the Oxford Cognitions and Defences Questionnaire (O-CDQ).
The O-CDQ consists of three subscales: threat cognitions (14 items), anxious avoidance (11 items), and within-situation safety behaviours (8 items). Separate confirmatory factor analyses demonstrated a good model fit for all subscales. The cognitions subscale was significantly associated with agoraphobic avoidance (r = .672, p < .001), social anxiety (r = .617, p < .001), generalized anxiety (r = .746, p < .001), depression (r = .619, p < .001) and paranoia (r = .655, p < .001). Additionally, both the O-CDQ avoidance (r = .867, p < .001) and within-situation safety behaviours (r = .757, p < .001) subscales were highly correlated with agoraphobic avoidance. The O-CDQ demonstrated excellent internal consistency (cognitions Cronbach’s alpha = .93, avoidance Cronbach’s alpha = .94, within-situation Cronbach’s alpha = .93) and test–re-test reliability (cognitions ICC = 0.88, avoidance ICC = 0.92, within-situation ICC = 0.89).
The O-CDQ, consisting of three separate scales, has excellent psychometric properties and may prove a helpful tool for understanding agoraphobic avoidance across mental health disorders.
Fewer than half of patients with major depressive disorder (MDD) respond to psychotherapy. Pre-emptively informing patients of their likelihood of responding could be useful as part of a patient-centered treatment decision-support plan.
This prospective observational study examined a national sample of 807 patients beginning psychotherapy for MDD at the Veterans Health Administration. Patients completed a self-report survey at baseline and 3-months follow-up (data collected 2018–2020). We developed a machine learning (ML) model to predict psychotherapy response at 3 months using baseline survey, administrative, and geospatial variables in a 70% training sample. Model performance was then evaluated in the 30% test sample.
32.0% of patients responded to treatment after 3 months. The best ML model had an AUC (SE) of 0.652 (0.038) in the test sample. Among the one-third of patients ranked by the model as most likely to respond, 50.0% in the test sample responded to psychotherapy. In comparison, among the remaining two-thirds of patients, <25% responded to psychotherapy. The model selected 43 predictors, of which nearly all were self-report variables.
Patients with MDD could pre-emptively be informed of their likelihood of responding to psychotherapy using a prediction tool based on self-report data. This tool could meaningfully help patients and providers in shared decision-making, although parallel information about the likelihood of responding to alternative treatments would be needed to inform decision-making across multiple treatments.
From 2014 to 2020, we compiled radiocarbon ages from the lower 48 states, creating a database of more than 100,000 archaeological, geological, and paleontological ages that will be freely available to researchers through the Canadian Archaeological Radiocarbon Database. Here, we discuss the process used to compile ages, general characteristics of the database, and lessons learned from this exercise in “big data” compilation.
To describe the epidemiology of patients with nonintestinal carbapenem-resistant Enterobacterales (CRE) colonization and to compare clinical outcomes of these patients to those with CRE infection.
A secondary analysis of Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae 2 (CRACKLE-2), a prospective observational cohort.
A total of 49 US short-term acute-care hospitals.
Patients hospitalized with CRE isolated from clinical cultures, April, 30, 2016, through August 31, 2017.
We described characteristics of patients in CRACKLE-2 with nonintestinal CRE colonization and assessed the impact of site of colonization on clinical outcomes. We then compared outcomes of patients defined as having nonintestinal CRE colonization to all those defined as having infection. The primary outcome was a desirability of outcome ranking (DOOR) at 30 days. Secondary outcomes were 30-day mortality and 90-day readmission.
Of 547 patients with nonintestinal CRE colonization, 275 (50%) were from the urinary tract, 201 (37%) were from the respiratory tract, and 71 (13%) were from a wound. Patients with urinary tract colonization were more likely to have a more desirable clinical outcome at 30 days than those with respiratory tract colonization, with a DOOR probability of better outcome of 61% (95% confidence interval [CI], 53%–71%). When compared to 255 patients with CRE infection, patients with CRE colonization had a similar overall clinical outcome, as well as 30-day mortality and 90-day readmission rates when analyzed in aggregate or by culture site. Sensitivity analyses demonstrated similar results using different definitions of infection.
Patients with nonintestinal CRE colonization had outcomes similar to those with CRE infection. Clinical outcomes may be influenced more by culture site than classification as “colonized” or “infected.”
Whole-genome sequencing (WGS) shotgun metagenomics (metagenomics) attempts to sequence the entire genetic content straight from the sample. Diagnostic advantages lie in the ability to detect unsuspected, uncultivatable, or very slow-growing organisms.
To evaluate the clinical and economic effects of using WGS and metagenomics for outbreak management in a large metropolitan hospital.
Intensive care unit and burn unit of large metropolitan hospital.
Simulated intensive care unit and burn unit patients.
We built a complex simulation model to estimate pathogen transmission, associated hospital costs, and quality-adjusted life years (QALYs) during a 32-month outbreak of carbapenem-resistant Acinetobacter baumannii (CRAB). Model parameters were determined using microbiology surveillance data, genome sequencing results, hospital admission databases, and local clinical knowledge. The model was calibrated to the actual pathogen spread within the intensive care unit and burn unit (scenario 1) and compared with early use of WGS (scenario 2) and early use of WGS and metagenomics (scenario 3) to determine their respective cost-effectiveness. Sensitivity analyses were performed to address model uncertainty.
On average compared with scenario 1, scenario 2 resulted in 14 fewer patients with CRAB, 59 additional QALYs, and $75,099 cost savings. Scenario 3, compared with scenario 1, resulted in 18 fewer patients with CRAB, 74 additional QALYs, and $93,822 in hospital cost savings. The likelihoods that scenario 2 and scenario 3 were cost-effective were 57% and 60%, respectively.
The use of WGS and metagenomics in infection control processes were predicted to produce favorable economic and clinical outcomes.
Ambulance patients who are unable to be quickly transferred to an emergency department (ED) bed represent a key contributing factor to ambulance offload delay (AOD). Emergency department crowding and associated AOD are exacerbated by multiple factors, including infectious disease outbreaks such as the coronavirus disease 2019 (COVID-19) pandemic. Initiatives to address AOD present an opportunity to streamline ambulance offload procedures while improving patient outcomes.
The goal of this study was to evaluate the initial outcomes and impact of a novel Emergency Medical Service (EMS)-based Hospital Liaison Program (HLP) on ambulance offload times (AOTs).
Ambulance offload times associated with EMS patients transported to a community hospital six months before and after HLP implementation were retrospectively analyzed using proportional significance tests, t-tests, and multiple regression analysis.
A proportional increase in incidents in the zero to <30 minutes time category after program implementation (+2.96%; P <.01) and a commensurate decrease in the proportion of incidents in the 30 to <60 minutes category (−2.65%; P <.01) were seen. The fully adjusted regression model showed AOT was 16.31% lower (P <.001) after HLP program implementation, holding all other variables constant.
The HLP is an innovative initiative that constitutes a novel pathway for EMS and hospital systems to synergistically enhance ambulance offload procedures. The greatest effect was demonstrated in patients exhibiting potentially life-threatening symptoms, with a reduction of approximately three minutes. While small, this outcome was a statistically significant decrease from the pre-intervention period. Ultimately, the HLP represents an additional strategy to complement existing approaches to mitigate AOD.