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Objectives: This study aimed, following both single‐ and multi‐event trauma, to ascertain prevalence and course of the dissociative subtype of post‐traumatic stress disorder (PTSD‐DS) in youth; how well early PTSD‐DS predicts later PTSD; and whether dissociation accounts for unique variance in post‐traumatic stress symptoms (PTSS) and functional impairment over and above the effect of other post‐trauma cognitive processing factors and PTSS respectively. Design and Methods: This study is a secondary analysis of data from the Acute Stress Programme for Children and Teenagers study (n = 234) and the Coping in Care After Trauma study (n = 110) in which children had experienced single‐ and multi‐event trauma respectively. Results: PTSD‐DS diagnosis was common in children with PTSD regardless of trauma experienced (>39.0%). PTSD‐DS showed a similar trajectory of natural recovery to PTSD, and it was similarly predictive of later PTSD following single‐event trauma. Finally, dissociation was a significant factor in PTSS and functional impairment. Conclusions: These results should be viewed in the context of several limitations including narrow sample of participants which reduces the generalizability of results, concerns around children's ability to conceptualize challenging concepts such as dissociation and the use of self‐report measures to form diagnostic groups. The PTSD‐DS diagnosis may offer clinical utility to the extant PTSD diagnosis in children and adolescents, as dissociation has been shown to be a contributory factor in the maintenance of both PTSS and functional impairment. Further research is required to inform further editions of the DSM and other diagnostic systems. [ABSTRACT FROM AUTHOR]

The article discusses the importance of extending model-informed drug development (MIDD) by incorporating epidemiological and health economic considerations. It presents examples of extended MIDD in various therapeutic areas and emphasizes the need to go beyond safety and efficacy evaluation during regulatory approval. The article highlights the role of extended MIDD in assessing the public health impact of drugs, evaluating cost-effectiveness, and informing clinical trial design. It also discusses the application of extended MIDD in infectious diseases, cardiovascular diseases, and rare diseases. The authors emphasize the benefits of early adoption of modular approaches in drug development and suggest that continued progress in extended MIDD will enable better decision-making and optimization of drug use. [Extracted from the article]

This open‐label, phase 1 study was conducted with healthy adult participants to evaluate the potential drug‐drug interaction between rilzabrutinib and quinidine (an inhibitor of P‐glycoprotein [P‐gp] and CYP2D6) or rifampin (an inducer of CYP3A and P‐gp). Plasma concentrations of rilzabrutinib were measured after a single oral dose of rilzabrutinib 400 mg administered on day 1 and again, following a wash‐out period, after co‐administration of rilzabrutinib and quinidine or rifampin. Specifically, quinidine was given at a dose of 300 mg every 8 hours for 5 days from day 7 to day 11 (N = 16) while rifampin was given as 600 mg once daily for 11 days from day 7 to day 17 (N = 16) with rilzabrutinib given in the morning of day 10 (during quinidine dosing) or day 16 (during rifampin dosing). Quinidine had no significant effect on rilzabrutinib pharmacokinetics. Rifampin decreased rilzabrutinib exposure (the geometric mean of Cmax and AUC0‐∞ decreased by 80.5% and 79.5%, respectively). Single oral doses of rilzabrutinib, with or without quinidine or rifampin, appeared to be well tolerated. These findings indicate that rilzabrutinib is a substrate for CYP3A but not a substrate for P‐gp. [ABSTRACT FROM AUTHOR]

Background: Complex PTSD (CPTSD) is a relatively new diagnosis. The objective of the present study was to investigate how trauma characteristics, comorbid psychopathology and cognitive and social factors experienced by children and adolescents with a posttraumatic stress disorder (PTSD) diagnosis following exposure to multiple traumatic events differs between those who meet the criteria for CPTSD and those who do not. Method: The present research used baseline data from the DECRYPT trial (BMJ Open, 2021, 11, e047600). Participants (n = 120) were aged 8–17 years and had exposure to multiple traumas and a PTSD diagnosis. The data collected comprised self‐report and parent/caregiver‐report questionnaires and interviews. Three primary analyses were conducted, comparing number of trauma types, prevalence of sexual trauma and prevalence of intrafamilial abuse between the CPTSD and PTSD‐only groups. A range of comorbid psychopathology and cognitive and social factors were compared between the groups in an exploratory secondary analysis. All analyses were preregistered. Results: The CPTSD group (n = 72, 60%) had a significantly higher frequency of sexual trauma than the PTSD‐only group (n = 48, 40%). The groups did not significantly differ on number of trauma types or prevalence of intrafamilial abuse. From the secondary analysis, the CPTSD group were found to have significantly higher scores on measures of negative post‐traumatic cognitions, depression and panic. These results were replicated in correlation analyses using a continuous measure of CPTSD symptoms. Conclusions: A large proportion of youth exposed to multiple traumatic events met criteria for CPTSD. Sexual trauma appears to be related to CPTSD symptoms. Youth with CPTSD appear to have greater severity of comorbid depression and panic symptoms, as well as more negative post‐traumatic cognitions. Further investigation could focus on the directionality and mechanisms for these associations. [ABSTRACT FROM AUTHOR]

Insomnia and poor sleep are associated with an increased risk of developing cardiovascular disease (CVD) and its precursors, including hypertension. In 2022, the American Heart Association (AHA) added inadequate sleep to its list of health behaviors that increase the risk for CVD. It remains unknown, however, whether the successful treatment of insomnia and inadequate sleep can reduce heightened CVD risk. SLEEPRIGHT is a single‐site, prospective clinical trial designed to evaluate whether the successful treatment of insomnia results in improved markers of CVD risk in patients with untreated hypertension and comorbid insomnia disorder. Participants (N = 150) will undergo baseline assessments, followed by a 6‐week run‐in period after which they will receive cognitive behavior therapy for insomnia (CBT‐I), comprised of 6 hourly sessions with an experienced CBT‐I therapist over a 6‐week period. In addition to measures of insomnia severity, as well as both subjective and objective measures of sleep, the primary outcome measures are nighttime blood pressure (BP) and BP dipping assessed by 24‐h ambulatory BP monitoring (ABPM). Secondary outcomes include several CVD risk biomarkers, including clinic BP, lipid profile, vascular endothelial function, arterial stiffness, and sympathetic nervous system (SNS) activity. Data analysis will evaluate the association between improvements in insomnia and sleep with primary and secondary CVD risk biomarker outcomes. The SLEEPRIGHT trial (ClinicalTrials.Gov NCT04009447) will utilize CBT‐I, the current gold standard treatment for insomnia disorder, to evaluate whether reducing insomnia severity and improving sleep are accompanied by improved biomarkers of CVD risk in patients with untreated hypertension. [ABSTRACT FROM AUTHOR]

Low self‐esteem can impair daily functioning and is a risk or maintenance factor for several mental health problems. Sexual minority young adults, for example, those identifying as lesbian, gay or bisexual, on average have lower self‐esteem than their heterosexual peers. Compassion‐based interventions for low self‐esteem might be especially beneficial for sexual minority young adults, whose higher levels of shame and self‐criticism are likely to be contributing to maintenance of their low self‐esteem. This study explored the acceptability, feasibility and preliminary efficacy of a new compassion‐based cognitive behavioural intervention for low self‐esteem tailored to sexual minority young adults. Participants were a community sample of 24 sexual minority young adults aged 16–24 experiencing clinically significant low self‐esteem. An uncontrolled pre‐/post‐design was used with qualitative feedback and quantitative outcomes. Self‐report standardised measures were completed at baseline, pre‐intervention, intervention mid‐point, post‐intervention and 2‐month follow up. Preliminary efficacy was examined through post‐intervention changes in self‐esteem, functioning, anxiety and depression. Potential mechanisms of change were examined through changes in self‐compassion, self‐criticism and unhelpful coping responses to minority stress. Results showed good acceptability and feasibility and preliminary evidence of intervention efficacy for improving self‐esteem, functioning, depression and anxiety. There was evidence for improvement in self‐compassion and reduction in self‐criticism, and these constructs could be investigated in future studies as treatment mediators. Randomised controlled studies are needed to further examine efficacy of the intervention. [ABSTRACT FROM AUTHOR]

Collaboration between the arts and health sectors is gaining momentum. Artists are contributing significantly to public health efforts such as vaccine confidence campaigns. Artists and the arts are well positioned to contribute to the social conditions needed to build trust in the health sector. Health professionals, organizations, and institutions should recognize not only the power that can be derived from the insights, artefacts, and expertise of artists and the arts to create the conditions that make trust possible. The health sector must also recognize that, while it can gain much from partnership with artists, artists risk much—namely, the public's trust—when they are in such partnerships. This essay unpacks these claims and considers the care and ethical considerations that must be brought to these partnerships to yield constructive pathways for ethical collaboration as well as for both establishing public trust and continuing to hold the health care profession accountable for becoming more trustworthy. [ABSTRACT FROM AUTHOR]

This single‐center, open‐label, non‐randomized, two‐part, phase I study was conducted (1) to evaluate the absolute oral bioavailability of rilzabrutinib 400 mg tablet following an i.v. microtracer dose of ~100 μg [14C]‐rilzabrutinib (~1 μCi) and single oral dose of 400 mg rilzabrutinib tablet (part 1), and (2) to characterize the absorption, metabolism, and excretion (AME) of 14C‐radiolabeled rilzabrutinib following single oral dose (300 mg) of [14C]‐rilzabrutinib (~1000 μCi; administered as a liquid) in healthy male participants (part 2). A total of 18 subjects were enrolled (n = 8 in part 1; n = 10 in part 2). The absolute bioavailability of 400 mg rilzabrutinib oral tablet was low (<5%). In part 1, rilzabrutinib was absorbed rapidly after single oral dose of rilzabrutinib 400 mg tablet with a median (range) time to maximum concentration (Tmax) value of 2.03 h (1.83–2.50 h). The geometric mean (coefficient of variation) terminal half‐life following the oral dose and i.v. microtracer dose of ~100 μg [14C]‐rilzabrutinib, were 3.20 (51.0%) and 1.78 (37.6%) h, respectively. In part 2, rilzabrutinib was also absorbed rapidly following single oral dose of 300 mg [14C]‐rilzabrutinib solution with a median (range) Tmax value of 1.00 h (1.00–2.00 h). The majority of total radioactivity was in the feces for both non‐bile collection subjects (92.9%) and bile collection subjects (87.6%), and ~5% of radioactivity was recovered in urine after oral administration. Urinary excretion of unchanged rilzabrutinib was low (3.02%). The results of this study advance the understanding of the absolute bioavailability and AME of rilzabrutinib and can help inform its further investigation. [ABSTRACT FROM AUTHOR]

We provide new evidence of the demand for better schools as manifested in bidding wars and changes to the built environment. Using repeat sales before and after a redistricting, we exploit shocks to school quality arising from the continuous, unexpected redistricting of school attendance boundaries in Atlanta. We find that houses redistricted to higher (lower) quality schools are more (less) likely to be involved in a market‐driven bidding war. Similarly, undeveloped, redistricted parcels that receive a positive (negative) school quality shock are more (less) likely to be developed. School quality shocks also have a causal effect on house prices and time‐on‐market. [ABSTRACT FROM AUTHOR]

The purpose of the American Dental Education Association (ADEA) Men of Color in the Health Professions Summit, held in August 2022 at ADEA's headquarters in Washington, DC, was to gather key thought leaders across a myriad of health professions and healthcare organizations and schools to cultivate intentional cross‐disciplinary efforts in championing the need to address the low number of men of color entering not only dental, but also medicine, pharmacy, and health‐related research careers. A pivotal follow‐up step from the inaugural ADEA President's Symposium on Men of Color in the Health Professions at the March 2022 ADEA Annual Session & Exhibition in Philadelphia, the summit brought together academic health professions leaders, government agencies, health professions associations, and other key stakeholders to develop an action plan to support men of color entering the health professions. Moving the needle forward and increasing opportunities for underrepresented men of color in the health professions requires all academic health professions to work together. Highlights of the Summit included a keynote presentation by David Satcher, MD, PhD, the 16th Surgeon General of the United States; workgroup consensus statement development; health career pathways program presentations; strategic forecasting regarding challenges and opportunities in developing a coalition of health professions organizations to support men of color in the health professions; and frameworks for exploring coalition building. [ABSTRACT FROM AUTHOR]

A 1.5‐year‐old, female, entire German shepherd dog was presented for evaluation of an abdominal mass. The dog had a 4‐month history of polydipsia, polyuria, diarrhoea, and weight loss despite polyphagia. Abdominal ultrasound confirmed a large abdominal mass suspected to be uterine in origin. An exploratory celiotomy revealed a 4.3 kg, 26 × 17 × 17 cm multinodular mass entirely encompassing the uterus, left ovary and left kidney. A combined ovariohysterectomy and left nephrectomy were undertaken. Histopathology confirmed stage ΙΙ renal nephroblastoma with favourable histology. Chemotherapy was declined and 86 days following surgery, significant abdominal metastases were identified on a computed tomography scan. The patient was euthanased 113 days after surgery due to progressive disease. This is the first report to display the rapid presumed metastasis of a canine nephroblastoma, without gross metastasis at initial surgical resection, through advanced imaging. This is also the first reported case of polyphagia despite weight loss as a presenting clinical sign. [ABSTRACT FROM AUTHOR]

Objectives: Several studies have suggested that anxiety disorders in childhood and adolescence often precede the onset of bipolar disorder. We therefore systematically reviewed the relationship between child and adolescent anxiety and later bipolar disorder. Methods: Online databases (Medline [for Ovid], EMBASE and PsychINFO) were searched for original, peer‐reviewed studies examining the relationship between child and adolescent anxiety and later bipolar disorder. Studies in both community samples and bipolar offspring samples were included. Results: A total of 16 studies were included in the review. The results were broadly consistent and revealed that child and adolescent anxiety disorders are associated with later bipolar disorder in community samples. In bipolar offspring, child and adolescent anxiety disorders are a marker of increased risk and predict the onset of bipolar disorder and other major mood disorders. Conclusions: There is evidence that anxiety disorders in childhood and adolescence increase the risk of later bipolar disorder. Anxiety disorders may be a useful target for early intervention in those at high‐risk of bipolar disorder. [ABSTRACT FROM AUTHOR]

Reactive inkjet printing (RIJ) is demonstrated as a new approach to the patterning of surfaces with metal–organic frameworks (MOFs). RIJ is an emerging manufacturing technique that jets solutions of reagents onto a substrate allowing them to react in situ to form the desired material. MOFs have the potential to perform a variety of useful sensing, catalytic, separation and storage applications within sophisticated devices, however, their insolubility makes them challenging to process into complex shapes and patterns. The RIJ approach offers advantages over conventional inkjet printing in that it allows stable solutions of different ligand and metal ions to be combined in a "mix‐and‐match" way. Here, the benefits of the RIJ approach are demonstrated to optimize the stoichiometry of the printed MOF, print a variety of different frameworks using common inks, and create gradients where the composition of the printed MOFs gradually varies between one isoreticular structure and another. Proof of principle is also demonstrated for the approach by demonstrating size selective encapsulation of a dye within a RIJ printed MOF. It is anticipated that this approach will be broadly applicable to the printing of MOFs and related materials enhancing their use across a variety of different applications. [ABSTRACT FROM AUTHOR]

Inclisiran is a novel N‐acetylgalactosamine (GalNAc) conjugated small‐interfering ribonucleic acid (siRNA) therapy designed to specifically target proprotein convertase subtilisin/kexin type 9 (PCSK9) mRNA in the liver for the treatment of hypercholesterolemia. Inclisiran's GalNAc attachment results in a rapid uptake into the liver, and thus a short plasma half‐life, but long duration of effects on PCSK9 inhibition and low‐density lipoprotein cholesterol (LDL‐C) lowering. The effects on PCSK9 inhibition and consequent LDL‐C reduction are sustained for more than 6 months following a single subcutaneous (s.c.) dose, despite inclisiran being detectable in the plasma only for up to 48 hours. A kinetic‐pharmacodynamic (K‐PD) model was developed to characterize inclisiran's dose‐related LDL‐C lowering effects and to evaluate the impact of intrinsic and extrinsic factors on LDL‐C lowering. To accommodate the long duration of action, the K‐PD model incorporated an effect compartment which represents the liver. Inclisiran concentration in the liver leads to decreased production of the PCSK9 protein and allow recycling of more LDL‐C receptors on the hepatocyte cell surface, which results in a reduction of circulating LDL‐C. The analysis of covariates identified PCSK9 and LDL‐C baseline levels as important factors for the effects of LDL‐C lowering. Observations and modeling and simulation results demonstrated that PCSK9 and LDL‐C reductions are achieved rapidly after dosing and sustained when patients are treated with a 300 mg s.c. dose once every 6 months. [ABSTRACT FROM AUTHOR]

Access lag to innovative therapies in Asian populations continues to present a challenge to global health. Recent progressive changes in the global regulatory landscape, including newer guidelines, are enabling simultaneous global drug development and near‐simultaneous global drug registration. The International Conference on Harmonization (ICH) E17 guideline outlines general principles for the design and analysis of multiregional clinical trials (MRCTs). We posit that translational research and quantitative clinical pharmacology tools are core enablers for Asia‐inclusive global drug development aligned with ICH E17 principles. Assessment of ethnic sensitivity should be initiated early in the development lifecycle to inform the need for, and extent of, Asian phase I ethno‐bridging data. Relevant ethno‐bridging data may be generated as standalone Asian phase I trials, as part of Western First‐In‐Human trials, or under accelerated development settings as a lead‐in phase in an MRCT. Quantitative understanding of human clearance mechanisms and pharmacogenetic factors is vital to forecasting ethnic sensitivity in drug exposure using physiologically‐based pharmacokinetic models. Stratification factors to control heterogeneity in MRCTs can be identified by reverse translational research incorporating pharmacometric disease models and model‐based meta‐analyses. Because epidemiological variations can extend to the molecular level, quantitative systems pharmacology models may be useful in forecasting how molecular variation in therapeutic targets or pathway proteins across populations might impact treatment outcomes. Through prospective evaluation of conservation in drug‐ and disease‐related intrinsic and extrinsic factors, a pooled East Asian region can be implemented in Asia‐inclusive MRCTs to maximize efficiency in substantiating evidence of benefit‐risk for the region at‐large with a Totality of Evidence approach. [ABSTRACT FROM AUTHOR]

Individuals with resistant hypertension (RH) have the greatest risk of cerebrovascular disease and cognitive impairment among individuals with hypertension. Elevated levels of pro‐inflammatory cytokines may represent a critical yet unexamined factor influencing the impact of healthy lifestyle changes on cognitive function. We explored the influence of inflammation on changes in cognition following lifestyle modification among individuals with RH participating in the TRIUMPH clinical trial. One hundred forty participants with RH completed a battery of neurocognitive tests along with the inflammatory marker C‐reactive protein (hsCRP) and were subsequently randomized to an intensive 4‐month lifestyle modification intervention or to education and physician advice control. Results indicated that the effects of lifestyle modification on Executive Function and Learning were moderated by pre‐intervention hsCRP levels (P =.049), with treatment efficacy increasing across levels of baseline inflammation levels (low: d = 0.12; mild: d = 0.43; moderate: d = 0.81). We conclude that inflammatory profiles may help identify individuals more likely to improve executive functioning resulting from lifestyle modification. [ABSTRACT FROM AUTHOR]

To assess the combined role of anti‐viral monoclonal antibodies (mAbs) and vaccines in reducing severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) transmission and mortality in the United States, an agent‐based model was developed that accounted for social contacts, movement/travel, disease progression, and viral shedding. The model was calibrated to coronavirus disease 2019 (COVID‐19) mortality between October 2020 and April 2021 (aggressive pandemic phase), and projected an extended outlook to estimate mortality during a less aggressive phase (April–August 2021). Simulated scenarios evaluated mAbs for averting infections and deaths in addition to vaccines and aggregated non‐pharmaceutical interventions. Scenarios included mAbs as a treatment of COVID‐19 and for passive immunity for postexposure prophylaxis (PEP) during a period when variants were susceptible to the mAbs. Rapid diagnostic testing paired with mAbs was evaluated as an early treatment‐as‐prevention strategy. Sensitivity analyses included increasing mAb supply and vaccine rollout. Allocation of mAbs for use only as PEP averted up to 14% more infections than vaccine alone, and targeting individuals ≥ 65 years averted up to 37% more deaths. Rapid testing for earlier diagnosis and mAb use amplified these benefits. Doubling the mAb supply further reduced infections and mortality. mAbs provided benefits even as proportion of the immunized population increased. Model projections estimated that ~ 42% of expected deaths between April and August 2021 could be averted. Assuming sensitivity to mAbs, their use as early treatment and PEP in addition to vaccines would substantially reduce SARS‐CoV‐2 transmission and mortality even as vaccination increases and mortality decreases. These results provide a template for informing public health policy for future pandemic preparedness. [ABSTRACT FROM AUTHOR]

Inclisiran is a small interfering RNA molecule that has been shown to provide an effective and sustained reduction in low‐density lipoprotein cholesterol levels. This study aimed to determine whether a supratherapeutic dose of inclisiran affects cardiac repolarization and conduction in healthy volunteers. A phase I, randomized, double‐blind, double‐dummy, placebo‐ and positive‐controlled, three‐way crossover study was performed in 48 healthy volunteers. Volunteers were assigned to three treatments in a randomized sequence: a supratherapeutic dose of inclisiran sodium (900 mg), placebo, or moxifloxacin 400 mg as a positive control, with a minimum 7‐day washout period between treatments. Continuous electrocardiogram monitoring was performed from >60 min before dosing until 48 h after dosing. Pharmacokinetics, pharmacodynamics, and safety were also assessed. Inclisiran, at a supratherapeutic dose, did not show a clinically significant effect on the QT interval (Fridericia correction formula [QTcF]; maximal placebo‐ and baseline‐corrected change: 2.5 ms [90% confidence interval: 0.6, 4.5]) near the maximal plasma concentrations at 4 h. In addition, inclisiran did not show any effects on other electrocardiogram intervals or ST‐ and T‐wave morphology. The positive control, moxifloxacin, demonstrated the expected changes in QTcF interval, validating the adequate sensitivity of the study. A supratherapeutic dose of inclisiran sodium (900 mg) had no effect on the QTcF interval or other electrocardiogram parameters, providing additional insight and reassurance regarding the safety profile of inclisiran. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this manuscript is to establish an antiracism framework for dental education. Since the accreditation process is an influential driver of institutional culture and policy in dental education, the focus of the framework is the Commission on Dental Accreditation (CODA) standards for predoctoral education.Methods: The authors of this manuscript reviewed each CODA predoctoral standard for opportunities to incorporate antiracism strategies. Eight standards were identified under themes of diversity (Standards 1-3, 1-4, 4-4), curriculum development (Standards 2-17, 2-26), and faculty recruitment and promotion (Standards 3-1, 3-4, 3-5). Guided primarily by National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care, a logic model approach was used to critically assess those standards for opportunities to establish antiracism strategies, with anticipated outcomes and impacts.Results: Strategies highlighted a need to improve recruitment, admissions, and accountability among dental schools to address the low numbers of historically underrepresented racial and ethnic (HURE) students and faculty. They emphasized the inclusion of racism in curricula geared toward training dental students to provide care to HURE populations. Finally, there are opportunities to improve accountability that dental schools are providing equitable opportunities for career advancement among HURE faculty, with consideration of conflicting demands for scholarship with HURE student mentoring, role modeling, teaching, and/or service.Conclusions: The framework identifies gaps in CODA standards where racism may be allowed to fester, provides specific antiracism strategies to strengthen antiracism through the accreditation process, and offers dental education programs, a process for evaluating and establishing their own antiracism strategies. [ABSTRACT FROM AUTHOR]

The purpose of the American Dental Education Association (ADEA) President's Symposium on men of color in the health professions, hosted at the 2022 ADEA Annual Session and Exhibition, was to draw attention to the need to address the low numbers of men of color not only entering dental education but also across medicine and health-related research careers and to identify strategies for change. Stakeholders in health professions education shared their professional insights and best practices. Highlights of the Symposium included discussions of funding for pathway programs, leveraging data-driven metrics through strategic partnerships, mentorship, and accountability among dental schools, medical schools, and health science research organizations. [ABSTRACT FROM AUTHOR]

The purpose of this article is to discuss the challenges surrounding the underrepresentation of Black/African American (BAA) men in dentistry and dental education and present a rationale for anti-racism strategies to address them. Data and insights from the literature are presented to discuss how racism may derail BAA's opportunities to achieve a dental education through stereotyping, social, and academic isolation. Additionally, the authors present commentary and testimonials on the importance of mentorship to guide BAA men into and through dental careers. Additionally, the article describes two examples of successful career pathway programs, and highlights the significance of historically Black colleges and universities to promoting diversity within the dental profession. Anti-racism recommendations for change include more direct attention to how dental school humanistic environments support BAA men, committing human and financial resources for program development, and using data-driven metrics to assess those programs longitudinally. The commitment of dental education to promote oral health equity demands more than appreciation of BAA men's contributions, but a commitment to creating and advancing opportunities that assure their success. [ABSTRACT FROM AUTHOR]

Stated preference methods remain the only means capable of estimating non‐use values yet can suffer from many types of well‐known biases. We construct an approach to identify the role of social desirability bias, relative to other potential survey biases, using a stated preference survey for improving the status of species at risk. The survey respondents were asked how they would vote, how they think their fellow survey participants would vote, as well as how they think people in their region would vote in an actual referendum. We find that willingness‐to‐pay estimates for public good (passive use) values differ across these vote question types. Our results demonstrate how stated preference practitioners can use multiple referent groups to help disentangle social desirability bias from other survey biases. [ABSTRACT FROM AUTHOR]

Moral bioenhancement (MBE) aims to fix our moral agency itself in order to prevent us from engaging in negligent or harmful behavior. Although such (self)‐paternalistic practice might very well produce good outcomes, it can be argued – inspired by Kant – that it is intrinsically disrespectful towards our future agency. Hence, we are faced with the following ethical dilemma: the failure to engage in MBE seems reckless and negligent, which can be considered a serious moral wrong; but engaging in MBE presupposes that we treat our faculties (our future agency) in a disrespectful self‐paternalistic manner. In this article, we want to resolve the described dilemma by suggesting a novel way of understanding Kantian objections to MBE. We argue that a careful engagement with Kantian moral psychology does provide a space for MBE but that it also describes a potential danger of MBE that has, at best, been only superficially described. That is, we offer a different Kantian understanding of MBE as a means to bring our empirical and noumenal selves together as a coherent whole to achieve what Kant describes as 'genuine accountability to others'. [ABSTRACT FROM AUTHOR]

This study aimed to define the clinically relevant supratherapeutic dose of rilzabrutinib, an oral Bruton tyrosine kinase (BTK) inhibitor, and evaluate potential effects of therapeutic and supratherapeutic exposures on cardiac repolarization in healthy subjects. This was a two‐part phase I study (anzctr.org.au ACTRN12618001036202). Part A was a randomized, open‐label, three‐period, single‐dose crossover study (n = 12) with rilzabrutinib 100 mg ± ritonavir 100 mg or rilzabrutinib 1200 mg. Part B was a randomized, double‐blind, placebo‐controlled, four‐way, single‐dose crossover study (n = 39) with matched placebo, rilzabrutinib 400 mg ± ritonavir 100 mg, or moxifloxacin (positive control). Primary objectives: part A – pharmacokinetics (PK) of rilzabrutinib ± ritonavir, safety, and optimal dose for Part B; Part B – effect of rilzabrutinib therapeutic and supratherapeutic concentration on electrocardiogram (ECG) parameters. ECGs and PK samples were serially recorded before and post‐dose. In part A, rilzabrutinib 100 mg + ritonavir led to 17‐fold area under the concentration–time curve (AUC0–∞) and 7‐fold maximum plasma concentration (Cmax) increases over rilzabrutinib alone. Rilzabrutinib 1200 mg was discontinued due to mild‐to‐moderate gastrointestinal intolerance. In Part B, rilzabrutinib 400 mg + ritonavir increased rilzabrutinib mean AUC0–∞ from 454 to 3800 ng h/mL and Cmax from 144 to 712 ng/mL. The concentration–QTc relationship was slightly negative, shallow (−0.01 ms/ng/mL [90% CI −0.016 to −0.001]), and an effect >10 ms on QTcF could be excluded within the observed range of plasma concentrations, up to 2500 ng/mL. Safety was similar to other studies of rilzabrutinib. In conclusion, rilzabrutinib, even at supratherapeutic doses, had no clinically relevant effects on ECG parameters, including the QTc interval. [ABSTRACT FROM AUTHOR]

This essay takes as its starting point the claim that addressing anti‐Black racism is essential to the work of bioethics in the United States. The essay examines whether and how racism has been addressed in the field's central reference work, the Encyclopedia of Bioethics, throughout its four editions—in 1978, 1995, 2004, and 2014. With consideration of each edition's stated purpose and editorial framing, we find that the subject of racism is obscured by the Encyclopedia's inattention to African American approaches to bioethics, to racism as a bioethics issue, and specifically, to racism as a matter of justice. This essay suggests questions for guiding reflection necessary for giving racism its due in the field of bioethics. [ABSTRACT FROM AUTHOR]

This paper synthesizes Canada's environmental valuation literature over the last six decades. Focusing on primary valuation benefit estimates, we link multiple research outputs from the same data collection effort to obtain an accurate measure of unique studies. We identify a total of 269 unique valuation studies conducted in Canada between 1964 and 2019. The number of valuation studies conducted per year has not increased since 1975 and the median data collection year is 1996. Stated preference (SP) methods are the most popular valuation approaches being used in more than 50% of studies and this share has increased to over 80% within the last decade. We discuss numerous gaps in our knowledge for certain environmental resources and regions, in particular Canada's three Northern territories. The paper provides information on the state of environmental valuation research in Canada and identifies future research needs. [ABSTRACT FROM AUTHOR]

Background: Racism negatively affects the life experiences and subsequent health of Black men, including oral disease prevalence and outcomes. Few examples in the literature discuss how racism may affect successful, unsuccessful, and non-attempts to address Black men's oral health.Aims: This commentary describes anti-racism approaches to address Black men's oral health through community-based participatory research, oral health promotion, and workforce recruitment.Materials and Methods: Stakeholders from two organizations and one dental school share their experiences and key insights on how to strengthen efforts while minimizing the influence of racism on Black men's participation.Results: Common insights identified were a need to engage a diverse range of Black men within varying social and economic contexts, race and gender concordance among program leaders and participants, and the value of partnership to reach Black men in places where they feel comfortable and supported.Discussion and Conclusion: These examples stress the imperative of addressing racism among Black men in the development and improvement of targeted oral health interventions. They also emphasize the value of commitment from institutional leadership, relationship building with Black men, and the empowerment of Black men to lead program development and implementation efforts. [ABSTRACT FROM AUTHOR]

Objectives: Stigma has been found to be associated with lower self‐esteem, which increases the risk of difficulties across life domains including vulnerability to mental health problems. There are no previous studies of interventions for people experiencing low self‐esteem in the context of different stigmatized characteristics. This study evaluated feasibility, acceptability, and preliminary outcomes of an intervention targeting low self‐esteem in stigmatized people aged 16–24 years. Design: An uncontrolled study with repeated measures. Method: People with a range of stigmatized characteristics, who had low self‐esteem and associated impaired daily functioning, were recruited from the general population. The individual six‐session cognitive behavioural intervention had modules chosen according to participants' formulations. The CBT included compassion‐focussed therapy methods and was informed by stigma research. Feasibility was assessed in relation to recruitment, retention, and protocol adherence. Acceptability was assessed through participant feedback. Questionnaires assessing self‐esteem, functioning impairments, depression, anxiety, self‐criticism, self‐compassion, and responses to prejudice and discrimination were administered at baseline, pre‐, mid‐, post‐intervention, and two‐month follow‐up. Results: Forty‐four people completed screening; 73% were eligible. Of these, 78% consented and 69% (N = 22) started the intervention. Eighteen (82%) participants completed, and four dropped out. Follow‐up measures were completed by all treatment completers. Treatment completers reported the intervention was useful, improved their self‐esteem and coping, and would recommend it. Ratings of usefulness and frequency of use of intervention components were high at post‐treatment and follow‐up. Conclusions: The intervention was feasible and highly acceptable to treatment completers. This suggests the intervention warrants investigation in a randomized‐controlled trial. Practitioner points: Young people with low self‐esteem whom have been negatively affected by stigma may wish to access support and be willing to engage in psychological interventions.Cognitive behavioural therapy may be helpful for young people with low self‐esteem who have experienced stigma, prejudice, or discrimination.Cognitive behavioural techniques such as self‐compassionate thought records and behavioural experiments were considered acceptable and helpful by young people whose self‐esteem has been affected by stigma.Addressing responses to stigma in therapy, such as rumination, avoidance, and perfectionism, appears to be feasible and acceptable. [ABSTRACT FROM AUTHOR]

As a field concerned with ethical issues in health and health care, particularly how structures, policies, and practices unfairly advantage some and disadvantage others, bioethics has a moral obligation to address the long‐standing challenges that racism has posed to the overall health and well‐being of Black, Indigenous, and Latinx people and other people of color. Arguably, the premature death and disease disproportionately affecting Black Americans and the well‐documented association of such death and illness with racism are issues that have not gained due attention in bioethics. This multiauthored report highlights the intergenerational work of mostly Black scholars and aims to create an agenda for bioethics that addresses anti‐Black racism and the ways in which this form of racism threatens the actualization of justice in health and health care, not only for Black people and other minoritized groups but also for all people. This special report contains five major sections representing different approaches to scholarship, including theoretical, empirical, and narrative forms. The first section features two target articles focused on anti‐Black racism and health care settings, with each article accompanied by two commentaries. The second section includes four essays thematically centered around anti‐Black racism and health equity research and practice. Section three features four essays that explore anti‐Black racism and bioethics. The next section consists of four essays framing a braver, bolder, and broader bioethics. We conclude with a powerful tribute to the late Marian Gray Secundy, a bioethics luminary, friend, colleague, role model, and mentor, and a tie that binds together many bioethics scholars who prioritize social justice in their scholarship and praxis. [ABSTRACT FROM AUTHOR]

Bruton's tyrosine kinase (BTK), expressed in B cells and cells of innate immunity, including microglia, is an essential signaling element downstream of the B‐cell receptor and Fc‐receptors. Tolebrutinib (PRN2246, SAR442168) is a potent BTK inhibitor that covalently binds the kinase, resulting in durable inhibition with the potential to target inflammation in the periphery and central nervous system (CNS). Tolebrutinib crosses the blood‐brain barrier and potently inhibits BTK in microglial cells isolated from the CNS. A first‐in‐human randomized, double‐blind, placebo‐controlled study of tolebrutinib was conducted. The trial design consisted of five single ascending dose arms with oral administration of a single dose of 5, 15, 30, 60, and 120 mg (n = 6 per arm, n = 2 placebo), five multiple ascending dose arms with oral administration of 7.5, 15, 30, 60, and 90 mg (n = 8 per arm, n = 2 placebo) over 10 days, and one arm (n = 4) in which cerebral spinal fluid (CSF) exposure was measured 2 h after a single 120 mg dose. Tolebrutinib was well‐tolerated in the study and all treatment‐related treatment emergent adverse events were mild. Tolebrutinib was rapidly absorbed following oral administration with a rapid half‐life of ~ 2 h. Peripheral BTK occupancy was assessed at various timepoints by an enzyme‐linked immunosorbent assay‐based readout using an irreversible probe. Assessments demonstrated extensive and prolonged peripheral BTK occupancy at steady‐state with once daily doses as low as 7.5 mg. Further, CSF exposure was demonstrated 2 h after administration at 120 mg. [ABSTRACT FROM AUTHOR]

Background: The introduction of developmentally adapted criteria for posttraumatic stress disorder (PTSD) has improved the identification of ≤6‐year‐old children with clinical needs. Across two studies, we assess predictors of the development of PTSD in young children (PTSD‐YC), including the adult‐led acute stress disorder (ASD) diagnosis, and provide proof of principle for cognitive‐focused therapy for this age range, with the aim of increasing treatment options for children diagnosed with PTSD‐YC. Method: Study 1 (N = 105) assessed ASD and PTSD‐YC diagnosis in 3‐ to 8‐year‐old children within one month and at around three months following attendance at an emergency room. Study 2 (N = 37) was a preregistered (www.isrctn.com/ISRCTN35018680) randomized controlled early‐phase trial comparing CBT‐3M, a cognitive‐focused intervention, to treatment‐as‐usual (TAU) delivered within the UK NHS to 3‐ to 8‐year‐olds diagnosed with PTSD‐YC. Results: In Study 1, the ASD diagnosis failed to identify any young children. In contrast, prevalence of acute PTSD‐YC (minus the duration requirement) was 8.6% in the first month post‐trauma and 10.1% at 3 months. Length of hospital stay, but no other demographic or trauma‐related characteristics, predicted development of later PTSD‐YC. Early (within one month) diagnosis of acute PTSD‐YC had a positive predictive value of 50% for later PTSD‐YC. In Study 2, most children lost their PTSD‐YC diagnosis following completion of CBT‐3M (84.6%) relative to TAU (6.7%) and CBT‐3M was acceptable to recipient families. Effect sizes were also in favor of CBT‐3M for secondary outcome measures. Conclusions: The ASD diagnosis is not fit for purpose in this age‐group. There was a strong and encouraging signal of putative efficacy for young children treated using a cognitive‐focused treatment for PTSD, and a larger trial of CBT‐3M is now warranted. [ABSTRACT FROM AUTHOR]

Background: Older adults with similar health conditions often experience widely divergent outcomes following health stressors. Variable recovery after a health stressor may be due in part to differences in biological mechanisms at the molecular, cellular, or system level, that are elicited in response to stressors. We describe the PRIME‐KNEE study as an example of ongoing research to validate provocative clinical tests and biomarkers that predict resilience to specific health stressors. Methods: PRIME‐KNEE is an ongoing, prospective cohort study that will enroll 250 adults ≥60 years undergoing total knee arthroplasty. Data are collected at baseline (pre‐surgery), during surgery, daily for 7 days after surgery, and at 1, 2, 4, and 6 months post‐surgery. Provocative tests include a cognition‐motor dual‐task walking test, cerebrovascular reactivity assessed by functional near‐infrared spectroscopy, peripheral blood mononuclear cell reactivity ex vivo to lipopolysaccharide toxin and influenza vaccine, and heart rate variability during surgery. Cognitive, psychological, and physical performance batteries are collected at baseline to estimate prestressor reserve. Demographics, medications, comorbidities, and stressor characteristics are abstracted from the electronic medical record and via participant interview. Blood‐based biomarkers are collected at baseline and postoperative day 1. Repeated measures after surgery include items from a delirium assessment tool and pain scales administered daily by telephone for 7 days and cognitive change index (participant and informant), lower extremity activities of daily living, pain scales, and step counts assessed by Garmin actigraphy at 1, 2, 4, and 6 months after surgery. Statistical models use these measures to characterize resilience phenotypes and evaluate prestressor clinical indicators associated with poststressor resilience. Conclusion: If PRIME‐KNEE validates feasible clinical tests and biomarkers that predict recovery trajectories in older surgical patients, these tools may inform surgical decision‐making, guide pre‐habilitation efforts, and elucidate mechanisms underlying resilience. This study design could motivate future geriatric research on resilience. [ABSTRACT FROM AUTHOR]

For LPV, the steady-state total minimum plasma concentration (Cmin) at the standard HIV-1 treatment dose of 400/100 mg LPV/r is approximately 5 g/ml, or 0.075 g/ml of unbound (free) drug. INITIATION AND DURATION OF ANTIVIRAL TREATMENT SHOULD BE GUIDED BY VIRAL KINETICS Antiviral treatment must be initiated in an infected patient as soon as possible. As new treatment modalities are being explored for SARS-CoV-2, efforts to repurpose existing marketed drugs remain an attractive option, as these agents are readily available and have a known safety profile. [Extracted from the article]

Structural health monitoring (SHM) represents the next generation of carbon fiber‐reinforced composite nondestructive testing. One challenge facing the application of magnetostrictive SHM is the lightweighting and ease of installation of actuators and sensors. Inkjet printing (IJP) technology is well suited to produce miniaturized electronic induction sensors that can be paired with magnetostrictive actuators to detect strain. These sensors have several advantages: their thicknesses can be minimized, the surface area can be maximized to increase sensitivity, and complex multifilar coil configurations can be fabricated. A parametric study of the efficacy of IJP induction coils with different parameters (number of coils, monofilar/bifilar, size) tested on a number of actuator‐functionalized composite coupons (FeSiB ribbon and impregnated epoxy sensors) is conducted. The samples are characterized by measuring their inductance response through induced strains. Increased sensitivity and accuracy of the 10‐turn monofilar IJP sensor are shown with respect to 1) 70‐turn hand‐wound coils, 2) a three‐axis AMR sensor, and 3) other IJP actuators with <10 turns. This is attributed to increased contact area to the composite surface and the requirement of minimum sensitivity (i.e., the number of turns and surface area) for strain detection. [ABSTRACT FROM AUTHOR]

Peripheral nerve injuries are debilitating, and current clinical management is limited to surgical intervention, which often leads to poor functional outcomes. Development of pharmacological interventions aimed at enhancing regeneration may improve this. One potential pharmacological target is the P2X purinergic receptor 7 (P2X7R) expressed in Schwann cells, which is known to play a role during the development of the peripheral nerves. Herein, we analysed differences in regeneration between genetically engineered P2X7 knockout mice and wild‐type controls, using in vivo and ex vivo models of peripheral nerve regeneration. We have found that the speed of axonal regeneration is unaltered in P2X7 knockout mice, nevertheless regenerated P2X7 knockout nerves are morphologically different to wild‐type nerves following transection and immediate repair. Indeed, the detailed morphometric analysis at 4 and 8 weeks after injury showed evidence of delayed remyelination in P2X7 knockout mice, compared to the wild‐type controls. Furthermore, the Wallerian degeneration phase was unaltered between the two experimental groups. We also analysed gene expression changes in the dorsal root ganglia neurones as a result of the peripheral nerve injury, and found changes in pathways related to pain, inflammation and cell death. We conclude that P2X7 receptors in Schwann cells may be a putative pharmacological target to control cell fate following injury, thus enhancing nerve re‐myelination. [ABSTRACT FROM AUTHOR]

Perhaps the most important lesson learned from the COVID‐19 pandemic is that of preparedness. Enhanced surveillance systems for early threat detection will be crucial to maximizing response time for implementation of public health measures and mobilization of resources in containing an emerging pandemic. Recent outbreaks have been dominated by viral pathogens, with RNA respiratory viruses being the most likely to have pandemic potential. These should therefore be a preparedness priority. Tools in the areas of virology, drug discovery, clinical pharmacology, translational medicine and pharmacometrics should be considered key components in the rapid identification and development of existing and novel interventions for a pandemic response. Prioritization of therapeutics should be based on in vitro activity, likelihood of achieving effective drug concentrations at the site of action, and safety profile at the doses that will be required for clinical efficacy. Deployment strategies must be tailored to the epidemiology of the disease, and the adequacy of the response should be re‐evaluated in view of evolving epidemiological factors. An interdisciplinary framework integrating drug pharmacology, viral kinetics, epidemiology and health economics could help optimize the deployment strategy by improving decision‐making around who to treat, when to treat, and with what type of intervention for optimal outcomes. Lastly, while an effective vaccine will ultimately end a pandemic, antiviral drug intervention guided by clinical pharmacology principles will continue to play a critical role in any pandemic response. [ABSTRACT FROM AUTHOR]

Aims: We propose the use of in silico mathematical models to provide insights that optimize therapeutic interventions designed to effectively treat respiratory infection during a pandemic. A modelling and simulation framework is provided using SARS‐CoV‐2 as an example, considering applications for both treatment and prophylaxis. Methods: A target cell‐limited model was used to quantify the viral infection dynamics of SARS‐CoV‐2 in a pooled population of 105 infected patients. Parameter estimates from the resulting model were used to simulate and compare the impact of various interventions against meaningful viral load endpoints. Results: Robust parameter estimates were obtained for the basic reproduction number, viral release rate and infected‐cell mortality from the infection model. These estimates were informed by the largest dataset currently available for SARS‐CoV‐2 viral time course. The utility of this model was demonstrated using simulations, which hypothetically introduced inhibitory or stimulatory drug mechanisms at various target sites within the viral life‐cycle. We show that early intervention is crucial to achieving therapeutic benefit when monotherapy is administered. In contrast, combination regimens of two or three drugs may provide improved outcomes if treatment is initiated late. The latter is relevant to SARS‐CoV‐2, where the period between infection and symptom onset is relatively long. Conclusions: The use of in silico models can provide viral load predictions that can rationalize therapeutic strategies against an emerging viral pathogen. [ABSTRACT FROM AUTHOR]

Stimuli responsive hydrogels that can change shape in response to applied external stimuli are appealing for soft robotics, biomedical devices, drug delivery, and actuators. However, existing 3D printed shape morphing materials are non‐biodegradable, which limits their use in biomedical applications. Here, 3D printed protein‐based hydrogels are developed and applied for programmable structural changes under the action of temperature, pH, or an enzyme. Key to the success of this strategy is the use of methacrylated bovine serum albumin (MA–BSA) as a biodegradable building block to Pickering emulsion gels in the presence of N‐isopropylacrylamide or 2‐dimethylaminoethyl methacrylate. These shear‐thinning gels are ideal for direct ink write (DIW) 3D printing of multi‐layered stimuli‐responsive hydrogels. While poly(N‐isopropylacrylamide) and poly(dimethylaminoethyl methacrylate) introduce temperature and pH‐responsive properties into the printed objects, a unique feature of this strategy is an enzyme‐triggered shape transformation based on the degradation of the bovine serum albumin network. To highlight this technique, protein‐based hydrogels that reversibly change shape based on environmental temperature and pH are fabricated, and irreversibly altered by enzymatic degradation, which demonstrates the complexity that can be introduced into 4D printed systems. [ABSTRACT FROM AUTHOR]

Purpose: Dentists can address childhood obesity by educating patients about mediating factors, such as nutrition and dietary habits, facilitating behavioral interventions, and participating in interprofessional collaborations. Dental schools are encouraged to prepare future dentists to address childhood obesity. The aim of this study was to assess dental students' attitudes, comfort, and perceived barriers discussing nutrition and obesity prevention with parents and caregivers of children aged 0–5, after a one‐time service‐learning experience in a pediatric primary care setting to promote oral health. Methods: Following conversations with parents and caregivers, students completed an 11‐item survey via Qualtrics. Results: Of 144 second‐year dental students that participated in the service‐learning experience over 2 years, 101 participated in the survey for a response rate of 70.1%. Most students agreed that dentists' roles include discussing nutrition (98.0%) and obesity prevention (83.2%). During the service‐learning experience, 78.2 percent of students discussed nutrition, and 5.0% discussed obesity prevention, with 3.0% and 22.8% of students reporting some level of discomfort with each topic, respectively. The most reported barriers for discussing both nutrition and obesity prevention were concern for "appearing judgmental" and "fear of offending clients." Mean comfort scores among students who reported barriers of "appearing judgmental" (p = < 0.0001) and "fear of offending clients" (p = 0.017) for nutrition discussions, and a "lack of parental acceptance of guidance" as a barrier for discussing obesity prevention (p = 0.016), suggest that those barriers were associated with less comfort. Conclusion: Dental students' perceived barriers to discussing nutrition and obesity prevention with parents and caregivers may negatively influence dental students' comfort. [ABSTRACT FROM AUTHOR]

Post‐operative delirium after lung transplantation is common. Its associations with health‐related quality of life (HRQL), depression, and mortality remains unknown. In 236 lung transplant recipients, HRQL and depressive symptoms were assessed as part of a structured survey battery before and after transplantation. Surveys included the Geriatric Depressive Scale (GDS) and Short Form 12 (SF12). Delirium was assessed throughout the post‐operative intensive care unit (ICU) stay with Confusion Assessment Method for ICU. Delirium and mortality data were extracted from electronic medical records. We examined associations between delirium and changes in depressive symptoms and HRQL using linear mixed effects models and association between delirium and mortality with Cox‐proportional hazard models. Post‐operative delirium occurred in 34 participants (14%). Delirium was associated with attenuated improvements in SF12‐PCS (difference ₋4.0; 95%CI: −7.4, −0.7) but not SF12‐MCS (difference 2.2; 95%CI: −0.7,5.7) or GDS (difference ₋0.4; 95%CI: −1.5,0.7). Thirty‐two participants died during the study period. Delirium was associated with increased adjusted hazard risk of mortality (HR 17.9, 95%CI: 4.4,72.5). Delirium after lung transplantation identifies a group at increased risk for poorer HRQL and death within the first post‐operative year. Further studies should investigate potential causal links between delirium, and poorer HRQL and mortality risk after lung transplantation. [ABSTRACT FROM AUTHOR]

Background: We investigate whether marijuana use in living kidney donor candidates is associated with psychosocial risk factors that place donors at higher risk for adverse outcomes and the unique associations between marijuana use and donor candidacy. Methods: Medical records of 757 living kidney donor candidates were reviewed. Patients were grouped into marijuana users/abstainers; demographic, psychiatric, and substance use variables were compared. Multivariate logistic regression assessed the independent association of marijuana use on committee approval for donation. Results: Marijuana use was associated with lack of health insurance, legal history, lower education level, active and history of substance use disorder, active psychiatric disorder, history of multiple psychiatric diagnoses, and history of suicidality. Marijuana users were also more likely to be young, male, unmarried, and less likely to be approved for donation by the multidisciplinary selection committee. This latter association persisted in multivariate models. Conclusions: This is the first study to show that marijuana use is associated with psychosocial factors that could impact behavioral adherence following kidney donation, while reducing chances of committee approval for kidney donation. Special attention to potential overlay between psychosocial risk factors and marijuana use should be considered when evaluating kidney donors, particularly in context of increasingly legal use. [ABSTRACT FROM AUTHOR]

Vascularized composite allograft, including hand transplantation (HT), has gained wider usage as a reconstructive treatment over the past 30 years. HT recipients face unique psychosocial challenges compared to their solid organ and/or bone marrow transplant counterparts. Accordingly, the psychosocial evaluation among HT candidates continues to evolve, leaving a lack of consensus as to the critical psychosocial domains and psychometric testing instruments to help evaluate individuals considering HT. The present manuscript describes the psychosocial evaluation process within the Duke HT program, which been contacted by 80 potential candidates since 2014. The Duke HT evaluation process incorporates a comprehensive psychosocial assessment within domains including personality, cognitive function, mood, behavioral adherence, social support, and substance use history, among others. Our experience underscores the potential utility of collecting thorough psychosocial evaluations, supplemented by psychometric test data, to comprehensively assess potential HT candidates. [ABSTRACT FROM AUTHOR]

We evaluated the feasibility, safety, and efficacy of a mHealth‐supported physical rehabilitation intervention to treat frailty in a pilot study of 18 lung transplant recipients. Frail recipients were defined by a short physical performance battery (SPPB score ≤7). The primary intervention modality was Aidcube, a customizable rehabilitation mHealth platform. Our primary aims included tolerability, feasibility, and acceptability of use of the platform, and secondary outcomes were changes in SPPB and in scores of physical activity, and disability measured using the Duke Activity Status Index (DASI) and Lung Transplant‐Value Life Activities (LT‐VLA). Notably, no adverse events were reported. Subjects reported the app was easy to use, usability improved over time, and the app enhanced motivation to engage in rehabilitation. Comments highlighted the complexities of immediate post‐transplant rehabilitation, including functional decline, pain, tremor, and fatigue. At the end of the intervention, SPPB scores improved a median of 5 points from a baseline of 4. Physical activity and patient‐reported disability also improved. The DASI improved from 4.5 to 19.8 and LT‐VLA score improved from 2 to 0.59 at closeout. Overall, utilization of a mHealth rehabilitation platform was safe and well received. Remote rehabilitation was associated with improvements in frailty, physical activity and disability. Future studies should evaluate mHealth treatment modalities in larger‐scale randomized trials of lung transplant recipients. [ABSTRACT FROM AUTHOR]

Model‐informed drug development (MIDD) has a long and rich history in infectious diseases. This review describes foundational principles of translational anti‐infective pharmacology, including choice of appropriate measures of exposure and pharmacodynamic (PD) measures, patient subpopulations, and drug‐drug interactions. Examples are presented for state‐of‐the‐art, empiric, mechanistic, interdisciplinary, and real‐world evidence MIDD applications in the development of antibacterials (review of minimum inhibitory concentration‐based models, mechanism‐based pharmacokinetic/PD (PK/PD) models, PK/PD models of resistance, and immune response), antifungals, antivirals, drugs for the treatment of global health infectious diseases, and medical countermeasures. The degree of adoption of MIDD practices across the infectious diseases field is also summarized. The future application of MIDD in infectious diseases will progress along two planes; "depth" and "breadth" of MIDD methods. "MIDD depth" refers to deeper incorporation of the specific pathogen biology and intrinsic and acquired‐resistance mechanisms; host factors, such as immunologic response and infection site, to enable deeper interrogation of pharmacological impact on pathogen clearance; clinical outcome and emergence of resistance from a pathogen; and patient and population perspective. In particular, improved early assessment of the emergence of resistance potential will become a greater focus in MIDD, as this is poorly mitigated by current development approaches. "MIDD breadth" refers to greater adoption of model‐centered approaches to anti‐infective development. Specifically, this means how various MIDD approaches and translational tools can be integrated or connected in a systematic way that supports decision making by key stakeholders (sponsors, regulators, and payers) across the entire development pathway. [ABSTRACT FROM AUTHOR]

Background: The 11th edition of the International Classification of Diseases (ICD‐11) made a number of significant changes to the diagnostic criteria for post‐traumatic stress disorder (PTSD). We sought to determine the prevalence and 3‐month predictive values of the new ICD‐11 PTSD criteria relative to ICD‐10 PTSD, in children and adolescents following a single traumatic event. ICD‐11 also introduced a diagnosis of Complex PTSD (CPTSD), proposed to typically result from prolonged, chronic exposure to traumatic experiences, although the CPTSD diagnostic criteria do not require a repeated experience of trauma. We therefore explored whether children and adolescents demonstrate ICD‐11 CPTSD features following exposure to a single‐incident trauma. Method: Data were analysed from a prospective cohort study of youth aged 8–17 years who had attended an emergency department following a single trauma. Assessments of PTSD, CPTSD, depressive and anxiety symptoms were performed at two to four weeks (n = 226) and nine weeks (n = 208) post‐trauma, allowing us to calculate and compare the prevalence and predictive value of ICD‐10 and ICD‐11 PTSD criteria, along with CPTSD. Predictive abilities of different diagnostic thresholds were undertaken using positive/negative predictive values, sensitivity/specificity statistics and logistic regressions. Results: At Week 9, 15 participants (7%) were identified as experiencing ICD‐11 PTSD, compared to 23 (11%) experiencing ICD‐10 PTSD. There was no significant difference in comorbidity rates between ICD‐10 and ICD‐11 PTSD diagnoses. Ninety per cent of participants with ICD‐11 PTSD also met criteria for at least one CPTSD feature. Five participants met full CPTSD criteria. Conclusions: Reduced prevalence of PTSD associated with the use of ICD‐11 criteria is likely to reduce identification of PTSD relative to using ICD‐10 criteria but not relative to DSM‐4 and DSM‐5 criteria. Diagnosis of CPTSD is likely to be infrequent following single‐incident trauma. [ABSTRACT FROM AUTHOR]

The 2009 blowout from the Montara wellhead resulted the total loss of the West Atlas drilling rig and caused massive ecological damage in the Timor Sea of Australia. The incident preceded the 2010 Macondo Deepwater Horizon blowout and shared many parallels. An analysis is performed to assess the Montara incident and finds it stemmed from a series of human errors including, but not limited to, miscalculations, procedural errors, hasty decision making, and failure to follow the American Petroleum Institute Recommended Practices 75 on drilling mud circulation. Twelve specific errors were identified and classified into eight categories. The results show that 10 of the 12 errors were latent errors preceded by the 2004 relaxation of the Australian Government's off‐shore drilling industry regulations. Following industry guidelines, best practice procedures, and safe work practices are crucial to avoiding a well disaster and these were not a key aspect of the Montara wellhead operations; ultimately, safety was not a top priority. [ABSTRACT FROM AUTHOR]