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New drugs to target different pathways in pulmonary hypertension has resulted in increased combination therapy, but details of this use in infants are not well described. In this large multicenter database study, we describe the pharmacoepidemiology of combination pulmonary vasodilator therapy in critically ill infants.
Methods:
We identified inborn infants discharged home from a Pediatrix neonatal ICU from 1997 to 2020 exposed to inhaled nitric oxide, sildenafil, epoprostenol, or bosentan for greater than two consecutive days. We compared clinical variables and drug utilisation between infants receiving simultaneous combination and monotherapy. We reported each combination’s frequency, timing, and duration and graphically represented drug use over time.
Results:
Of the 7681 infants that met inclusion criteria, 664 (9%) received combination therapy. These infants had a lower median gestational age and birth weight, were more likely to have cardiac and pulmonary anomalies, receive cardiorespiratory support, and had higher in-hospital mortality than those receiving monotherapy. Inhaled nitric oxide and sildenafil were most frequently used, and utilisation of combination and monotherapy for all drugs increased over time. Inhaled nitric oxide and epoprostenol were used in infants with a higher gestational age, earlier postnatal age, and shorter duration than sildenafil and bosentan. Dual therapy with inhaled nitric oxide and sildenafil was the most common combination therapy.
Conclusion:
Our study revealed an increased use of combination pulmonary vasodilator therapy, favouring inhaled nitric oxide and sildenafil, yet with considerable practice variation. Further research is needed to determine the optimal combination, sequence, dosing, and disease-specific indications for combination therapy.
The New Jersey Kids Study (NJKS) is a transdisciplinary statewide initiative to understand influences on child health, development, and disease. We conducted a mixed-methods study of project planning teams to investigate team effectiveness and relationships between team dynamics and quality of deliverables.
Methods:
Ten theme-based working groups (WGs) (e.g., Neurodevelopment, Nutrition) informed protocol development and submitted final reports. WG members (n = 79, 75%) completed questionnaires including de-identified demographic and professional information and a modified TeamSTEPPS Team Assessment Questionnaire (TAQ). Reviewers independently evaluated final reports using a standardized tool. We analyzed questionnaire results and final report assessments using linear regression and performed constant comparative qualitative analysis to identify central themes.
Results:
WG-level factors associated with greater team effectiveness included proportion of full professors (β = 31.24, 95% CI 27.65–34.82), team size (β = 0.81, 95% CI 0.70–0.92), and percent dedicated research effort (β = 0.11, 95% CI 0.09–0.13); age distribution (β = −2.67, 95% CI –3.00 to –2.38) and diversity of school affiliations (β = –33.32, 95% CI –36.84 to –29.80) were inversely associated with team effectiveness. No factors were associated with final report assessments. Perceptions of overall initiative leadership were associated with expressed enthusiasm for future NJKS participation. Qualitative analyses of final reports yielded four themes related to team science practices: organization and process, collaboration, task delegation, and decision-making patterns.
Conclusions:
We identified several correlates of team effectiveness in a team science initiative's early planning phase. Extra effort may be needed to bridge differences in team members' backgrounds to enhance the effectiveness of diverse teams. This work also highlights leadership as an important component in future investigator engagement.
Estimates of the elasticity of the marginal utility of income are necessary for determining distributional weights to correct for diminishing marginal utility of income, which is particularly important in light of increasing concern about accounting for distributional impacts in regulatory review. The elasticity is also necessary for computing the social discount rate using the Ramsey formula. Despite many attempts to estimate the elasticity of the marginal utility of income, considerable uncertainty exists about the magnitude of this key parameter. In this paper, we use meta-analysis of estimates of the elasticity from the US and UK to shed light on the appropriate elasticity values to use for both distributional weighting and discounting. Relying on our findings, we tentatively conclude that it is reasonable to base the social discount rate and distributional weights on an elasticity of 1.6, with lower- and upper-bound sensitivity testing at 1.2 and 2.0. This estimate results in distributional weights which appear plausible, and which we believe can contribute to a consensus on how to conduct distributional weighting. Moreover, the resulting social discount rate is within the range typically recommended when the Ramsey formula is used.
There are increasing calls for concrete suggestions on how to account for distributional impacts in policy analysis. Within the context of benefit-cost analysis, per se, one possibility is to apply “distributional weights,” to inflate costs and benefits experienced by poor or disadvantaged groups. We distinguish between “utility-weights,” intended to correct for the bias in willingness to pay caused by diminishing marginal utility of income, and “equity-weights,” intended to account for the possibility that decision makers might have disproportional concern about the welfare of the poor or other disadvantaged groups. We argue that utility-weights are appropriate and necessary to maintain the legitimacy of BCA as a measure of aggregate welfare, but that equity-weights are inappropriate because they involve moral judgments that should remain in the domain of democratically accountable decision makers, and because they conflate information about both the welfare and equity impacts of policies, making it impossible for decision-makers to apply their own moral values to the assessment of tradeoffs between welfare and equity. We offer concrete suggestions regarding the application of utility-weights and the calculation of a set of metrics to provide intuitively comprehensible and useful information about, and allow decision makers to quantitatively assess the tradeoffs between, welfare and equity caused by specific policies.
Post-traumatic growth (PTG) refers to beneficial psychological change following trauma.
Aims
This study explores the sociodemographic, health and deployment-related factors associated with PTG in serving/ex-serving UK armed forces personnel deployed to military operations in Iraq or Afghanistan.
Method
Multinomial logistic regression analyses were applied to retrospective questionnaire data collected 2014–2016, stratified by gender. PTG scores were split into tertiles of no/very low PTG, low PTG and moderate/large PTG.
Results
A total of 1447/4610 male personnel (30.8%) and 198/570 female personnel (34.8%) reported moderate/large PTG. Male personnel were more likely to report moderate/large PTG compared with no/very low PTG if they reported a greater belief of being in serious danger (relative risk ratio (RRR) 2.47, 95% CI 1.68–3.64), were a reservist (RRR 2.37, 95% CI 1.80–3.11), reported good/excellent general health (fair/poor general health: RRR 0.33, 95% CI 0.24–0.46), a greater number of combat experiences, less alcohol use, better mental health, were of lower rank or were younger. Female personnel were more likely to report moderate/large PTG if they were single (in a relationship: RRR 0.40, 95% CI 0.22–0.74), had left military service (RRR 2.34, 95% CI 1.31–4.17), reported better mental health (common mental disorder: RRR 0.37, 95% CI 0.17–0.84), were a reservist, reported a greater number of combat experiences or were younger. Post-traumatic stress disorder had a curvilinear relationship with PTG.
Conclusions
A moderate/large degree of PTG among the UK armed forces is associated with mostly positive health experiences, except for post-traumatic stress disorder.
Healthcare workers (HCWs) have faced considerable pressures during the COVID-19 pandemic. For some, this has resulted in mental health distress and disorder. Although interventions have sought to support HCWs, few have been evaluated.
Aims
We aimed to determine the effectiveness of the ‘Foundations’ application (app) on general (non-psychotic) psychiatric morbidity.
Method
We conducted a multicentre randomised controlled trial of HCWs at 16 NHS trusts (trial registration number: EudraCT: 2021-001279-18). Participants were randomly assigned to the app or wait-list control group. Measures were assessed at baseline, after 4 and 8 weeks. The primary outcome was general psychiatric morbidity (using the General Health Questionnaire). Secondary outcomes included: well-being; presenteeism; anxiety; depression and insomnia. The primary analysis used mixed-effects multivariable regression, presented as adjusted mean differences (aMD).
Results
Between 22 March and 3 June 2021, 1002 participants were randomised (500:502), and 894 (89.2%) followed-up. The sample was predominately women (754/894, 84.3%), with a mean age of 44⋅3 years (interquartile range (IQR) 34–53). Participants randomised to the app had a reduction in psychiatric morbidity symptoms (aMD = −1.39, 95% CI −2.05 to −0.74), improvement in well-being (aMD = 0⋅54, 95% CI 0⋅20 to 0⋅89) and reduction in insomnia (adjusted odds ratio (aOR) = 0⋅36, 95% CI 0⋅21 to 0⋅60). No other significant findings were found, or adverse events reported.
Conclusions
The app had an effect in reducing psychiatric morbidity symptoms in a sample of HCWs. Given it is scalable with no adverse effects, the app may be used as part of an organisation's tiered staff support package. Further evidence is needed on long-term effectiveness and cost-effectiveness.
Health economic evaluations are comparative analyses of alternative courses of action in terms of their costs and consequences. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement, published in 2013, was created to ensure health economic evaluations are identifiable, interpretable, and useful for decision making. It was intended as guidance to help authors report accurately which health interventions were being compared and in what context, how the evaluation was undertaken, what the findings were, and other details that may aid readers and reviewers in interpretation and use of the study. The new CHEERS 2022 statement replaces previous CHEERS reporting guidance. It reflects the need for guidance that can be more easily applied to all types of health economic evaluation, new methods and developments in the field, as well as the increased role of stakeholder involvement including patients and the public. It is also broadly applicable to any form of intervention intended to improve the health of individuals or the population, whether simple or complex, and without regard to context (such as health care, public health, education, social care, etc.). This summary article presents the new CHEERS 2022 28-item checklist and recommendations for each item. The CHEERS 2022 statement is primarily intended for researchers reporting economic evaluations for peer-reviewed journals, as well as the peer reviewers and editors assessing them for publication. However, we anticipate familiarity with reporting requirements will be useful for analysts when planning studies. It may also be useful for health technology assessment bodies seeking guidance on reporting, as there is an increasing emphasis on transparency in decision making.
The COVID-19 pandemic prompted the development and implementation of hundreds of clinical trials across the USA. The Trial Innovation Network (TIN), funded by the National Center for Advancing Translational Sciences, was an established clinical research network that pivoted to respond to the pandemic.
Methods:
The TIN’s three Trial Innovation Centers, Recruitment Innovation Center, and 66 Clinical and Translational Science Award Hub institutions, collaborated to adapt to the pandemic’s rapidly changing landscape, playing central roles in the planning and execution of pivotal studies addressing COVID-19. Our objective was to summarize the results of these collaborations and lessons learned.
Results:
The TIN provided 29 COVID-related consults between March 2020 and December 2020, including 6 trial participation expressions of interest and 8 community engagement studios from the Recruitment Innovation Center. Key lessons learned from these experiences include the benefits of leveraging an established infrastructure, innovations surrounding remote research activities, data harmonization and central safety reviews, and early community engagement and involvement.
Conclusions:
Our experience highlighted the benefits and challenges of a multi-institutional approach to clinical research during a pandemic.
We describe punctual categoricity in several natural classes, including binary relational structures and mono-unary functional structures. We prove that every punctually categorical structure in a finite unary language is ${\text {PA}}(0')$-categorical, and we show that this upper bound is tight. We also construct an example of a punctually categorical structure whose degree of categoricity is $0''$. We also prove that, with a bit of work, the latter result can be pushed beyond $\Delta ^1_1$, thus showing that punctually categorical structures can possess arbitrarily complex automorphism orbits.
As a consequence, it follows that binary relational structures and unary structures are not universal with respect to primitive recursive interpretations; equivalently, in these classes every rich enough interpretation technique must necessarily involve unbounded existential quantification or infinite disjunction. In contrast, it is well-known that both classes are universal for Turing computability.
The role of the law librarian or legal information professional is thought by some to have been diminished significantly by technological advances which provide instant access to an enormous range of materials direct to individual users at their desks. The reality is that the wide range of instantly accessible materials makes the experience and knowledge of the information professional more important, not less; and imminently expected advances in machine learning and artificial intelligence are likely to confirm the vital importance of the legal information professional at the centre of legal services.
Edited by
Lara J. Farrell, Griffith University, Queensland,Thomas H. Ollendick, Virginia Polytechnic Institute and State University,Peter Muris, Universiteit Maastricht, Netherlands
This article contributes to the general program of extending techniques and ideas of effective algebra to computable metric space theory. It is well-known that relative computable categoricity (to be defined) of a computable algebraic structure is equivalent to having a c.e. Scott family with finitely many parameters (e.g., [1]). The first main result of the article extends this characterisation to computable Polish metric spaces. The second main result illustrates that just a slight change of the definitions will give us a new notion of categoricity unseen in the countable case (to be stated formally). The second result also shows that the characterisation of computably categorical closed subspaces of ${\Cal R}^n $ contained in [17] cannot be improved. The third main result extends the characterisation to not necessarily separable structures of cardinality κ using κ-computability.
In creating a culture of service, can law firms engage transactional lawyers in pro bono work too? In this chapter, Daniel Greenberg argues that firms can, if their pro bono programs move beyond litigation and incorporate transactional projects that build on the skills and knowledge of what their transactional lawyers do. At Greenberg's firm, their pro bono program successfully recruits volunteer transactional lawyers to represent nonprofits just like they represent their corporate clients advising on real estate issues, drafting contract language, or addressing intellectual property concerns. –Eds.
Any analysis of access to justice for Americans of average means must take note of the pro bono programs of major law firms. They are a huge potential source of advocacy for individual Americans of average means, and for the organizations that advocate for them. To maximize that potential, these firms will need to expand their services not by doing more of the same, but by rethinking the structure of their pro bono programs. This chapter argues that when a firm adopts a transactional pro bono model, thus transforming the scope of its services, not only will Americans of average means benefit, but the firm, its partners and associates will end up benefitting as well.
Historically, as is still the case in most law firms today, pro bono work has been tied to the firm's litigation practice. In the 1950s, the NAACP Legal Defense Fund, Inc. used courts to jump-start the civil rights movement. In 1963, President John F. Kennedy enlisted fifty of the country's largest law firms to work for equal justice through litigation with the creation of The Lawyers Committee for Civil Rights under Law. Framing large issues in law reform terms, and using class action litigation as its tool, private lawyers attacked segregation, discriminatory education and election laws, and other civil rights violations in federal courts that were largely sympathetic to their cause. Simultaneously, new legal services arose with a focus on the rights of poor people. These programs collaborated with big law firms in their quest for housing rights, access to government benefits, and consumer protections. Later, advocates in the women's, anti-war, and environmental movements emulated this model.
We study the computable structure theory of linear orders of size $\aleph _1 $ within the framework of admissible computability theory. In particular, we characterize which of these linear orders are computably categorical.
We study the computable structure theory of linear orders of size $\aleph _1 $ within the framework of admissible computability theory. In particular, we study degree spectra and the successor relation.
The coastal ocean comprises the semi-enclosed seas on the continental shelf, including estuaries and extending to the shelf break. This region is the focus of many serious concerns, including coastal inundation by tides, storm surges or sea level change; fisheries and aquaculture management; water quality; harmful algal blooms; planning of facilities (such as power stations); port development and maintenance; and oil spills. This book addresses modeling and simulation of the transport, evolution and fate of particles (physical and biological) in the coastal ocean. It is the first to summarize the state of the art in this field and direct it toward diverse applications, for example in measuring and monitoring sediment motion, oil spills and larval ecology. This is an invaluable textbook and reference work for advanced students and researchers in oceanography, geophysical fluid dynamics, marine and civil engineering, computational science and environmental science.