Leadership development in health professions.

BACKGROUND AND PURPOSE: Despite changing clinical care dynamics, health professions education has been slow in addressing gaps in leadership development as teaching and assessment of clinical care-related knowledge, skills, and attitudes remain central across curricula. While accreditation standards across health professions programs acknowledge the importance of leadership development within curricula, it remains an underrepresented aspect of health professions training. EDUCATIONAL ACTIVITY AND SETTING: Given the varied approach to leadership training, we set out to develop a tailored approach to leadership development that integrated the Center for the Advancement of Pharmacy Education (CAPE) outcomes and was based on self-awareness, skill-building, and application. This pilot included three cohorts of doctor of pharmacy students and measured their knowledge, skills, and self-awareness as they progressed through this year-long program. It also measured leadership competency attainment using a pre- and post-assessment in one cohort. FINDINGS: Participant satisfaction was assessed using session and program evaluations, while self-perception of growth and leadership competency attainment was assessed using a survey that was administered before and after program participation. Participants found the program to be beneficial in meeting stated objectives and in creating a conducive learning environment. Results of the pre- and post-assessment indicated growth in all dimensions of self-perception of knowledge, skills, and self-awareness, as well as attainment of leadership competency personal leadership commitment and leadership knowledge. SUMMARY: Offering co-curricular leadership development programs based on CAPE outcomes and leadership competencies provided students with the opportunity to develop leadership skills and acquire knowledge needed to be effective healthcare leaders.

Longitudinal medication adherence group-based trajectories of aging adults in the US: A retrospective analysis using monthly proportion of days covered calculations.

BACKGROUND: It is thought that half of the patients with chronic conditions are not adherent to their medications, which contributes to significant health and economic burden. Many studies estimate medication non-adherence by implementing a threshold of ≥80% of Proportion of Days Covered (PDC), categorizing patients as either adherent or non-adherent. Healthcare quality metrics pertaining to medication use are based on this dichotomous approach of medication adherence, including the Medicare Part D Star Ratings. Among others, the Medicare Part D Star Ratings rewards part D plan sponsors with quality bonus payments based on this dichotomous categorization of beneficiaries' medication adherence. OBJECTIVES: Describe the longitudinal adherence trajectories of adults ≥65 years of age covered by Medicare for 3 classes of drugs in the Part D Star Ratings: diabetes medications, statins, and select antihypertensives. METHODS: This study used Medicare healthcare administrative claims data linked to participants from the Health Retirement Study between 2008 and 2016. Group-based trajectory models (GBTM) elicited the number and shape of adherence trajectories from a sample of N = 11,068 participants for the three pharmacotherapeutic classes considered in this study. Medication adherence was estimated using monthly PDC. RESULTS: GBTM were estimated for the sample population taking antihypertensives (n = 7,272), statins (n = 8,221), and diabetes medications (n = 3,214). The hypertension model found three trajectories: high to very high adherence (47.55%), slow decline (32.99%), and rapid decline (19.47%) trajectories. The statins model found 5 trajectories: high to very high adherence (35.49%), slow decline (17.12%), low then increasing adherence (23.58%), moderate decline (12.62%), and rapid decline (11.20%). The diabetes medications model displayed 6 trajectories: high to very high adherence (24.15%), slow decline (16.84%), high then increasing adherence (25.56%), low then increasing (13.58%), moderate decline (10.60%), and rapid decline (9.27%). CONCLUSIONS: This study showed the fluid nature of long-term medication adherence to the medications considered in the Medicare Part D Star Ratings and how it varies by pharmacotherapeutic class. These challenge previous assumptions about which patients were considered adherent to chronic medications. Policy and methodological implications about medication adherence are discussed.

Building an alliance to map global supply networks.

New firm-level data can inform policy-making.

Simulation-based training in obstetric anesthesia: an update.

In this update we explore the current applications of simulation in obstetric anesthesia, describe what is known regarding its impacts on care and consider the different settings in which simulation programs are required. We will introduce practical strategies, such as cognitive aids and communication tools, that can be applied in the obstetric setting and share ways in which a program might apply these tools. Finally, we provide a list of common obstetric emergencies essential for a program's curriculum and common teamwork pitfalls to address within a comprehensive obstetric anesthesia simulation program.

Global issues in obstetric anaesthesia: perspectives from South Africa, Japan, China, Latin America and North America.

South Africa is classified as a low- and middle-income country, with a complex mixture of resource-rich and resource-limited settings. In the major referral hospitals, the necessary skill level exists for the management of complex challenges. However, this contrasts with the frequently-inadequate skill levels of anaesthesia practitioners in resource-limited environments. In Japan, obstetricians administer anaesthesia for 40% of caesarean deliveries and 80% of labour analgesia. Centralisation of delivery facilities is now occurring and it is expected that obstetric anaesthesiologists will be available 24 h a day in centralised facilities in the future. In China, improvements in women's reproductive, maternal, neonatal, child, and adolescent health are critical government policies. Obstetric anaesthesia, especially labour analgesia, has received unprecedented attention. Chinese obstetric anaesthesiologists are passionate about clinical research, focusing on efficacy, safety, and topical issues. The Latin-American region has different landscapes, people, languages, and cultures, and is one of the world's regions with the most inequality. There are large gaps in research, knowledge, and health services, and the World Federation of Societies of Anaesthesiologists is committed to working with governmental and non-governmental organisations to improve patient care and access to safe anaesthesia. Anaesthesia workforce challenges, exacerbated by coronavirus disease 2019, beset North American healthcare. Pre-existing struggles by governments and decision-makers to improve health care access remain, partly due to unfamiliarity with the role of the anaesthesiologist. In addition to weaknesses in work environments and dated standards of work culture, the work-life balance demanded by new generations of anaesthesiologists must be acknowledged.

Current perspectives on maternity critical care.

Maternal critical care is a developing area of clinical practice. Looking after a critically ill woman requires a multidisciplinary team that must endeavour to maintain the relative normality of pregnancy. Whilst consideration of the fetus should be taken when making clinical decisions regarding maternal care, unfounded concerns for the fetus can contribute to therapeutic inertia such that potentially life-saving therapies are denied to pregnant women. The management of a critically ill obstetric patient must reflect, as closely as possible, the management of critical illness outside pregnancy. We will discuss some of the current evidence and concepts around this emerging area in obstetrics, including enhanced maternity care, maternal medicine networks and clinical care.

Pair correlation function based on Voronoi topology.

The pair correlation function (PCF) has proven an effective tool for analyzing many physical systems due to its simplicity and its applicability for simulated and experimental data. However, as an averaged quantity, the PCF can fail to capture subtle structural differences in particle arrangements, even when those differences can have a major impact on system properties. Here, we use Voronoi topology to introduce a discrete version of the PCF that highlights local interparticle topological configurations. The advantages of the Voronoi PCF are demonstrated in several examples including crystalline, hyperuniform, and active systems showing clustering and giant number fluctuations.

Mixed-species bacterial swarms show an interplay of mixing and segregation across scales.

Bacterial swarms are a highly-researched example of natural active matter. In particular, the interplay between biological interactions and the physics underlying the swarming dynamics is of both biological and physical interest. In this paper, we study mixed swarms of Bacillus subtilis and Pseudomonas aeruginosa. We find intricate interactions between the species, showing both cooperation and segregation across different spatial and temporal scales. On one hand, even though axenic colonies grow on disparate time scale, an order of magnitude apart, the two-species swarm together, forming a single, combined colony. However, the rapidly moving populations are locally segregated, with different characteristic speeds and lengths (or cluster sizes) that depend on the ratio between the species. Comparison with controlled mutant strains suggest that both the physical and known biological differences in species characteristics may not be enough to explain the segregation between the species in the mixed swarm. We hypothesize that the heterogeneous spatial distribution is due to some mechanism that enables bacteria to recognize their own kind, whose precise origin we could not identify.

Initial experience with a continuous mechanical aspiration system for thrombus removal before percutaneous coronary intervention.

OBJECTIVES: Here we investigate the safety and efficacy of a continuous mechanical aspiration system when used before percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS). BACKGROUND: Historically, trials of routine manual aspiration thrombectomy in ACS patients have reported mixed results. This may be due to the technical limitations of manual aspiration, which suffers from decreasing vacuum power as aspiration is performed. METHODS: This is a retrospective case series of all patients treated with continuous mechanical aspiration (Indigo CAT RX Aspiration System; Penumbra Inc.) before PCI between August 2017 and July 2020 at five centers in the United States. Data regarding angiographic assessments, procedure, and safety were examined. RESULTS: Seventy-two patients (mean age 60 ± 12.5 years, 34.7% female) with ST Elevation Myocardial Infarction (STEMI) (80.6%) or Non-ST Elevation Myocardial Infarction (NSTEMI) (19.4%) were included. Target vessels were the right coronary (43.1%), left anterior descending (33.3%), and left circumflex (23.6%). Preprocedure, 94.4% had a high thrombus burden (thrombolysis in myocardial infarction [TIMI] thrombus grade ≥ 3). Median aspiration time was 35 s and median access-to-reperfusion time was 10 min. After CAT RX alone, 86.1% had complete perfusion (TIMI flow grade 3). After the procedure, 94.4% had TIMI thrombus grade <3% and 97.2% had TIMI flow grade 3. There were no cases of ischemic stroke. Cardiovascular mortality at 30 days was 1.4%. CONCLUSIONS: In our initial experience, aspirating thrombus from ACS patients using the Indigo CAT RX Aspiration System before PCI was safe and effective for reducing thrombus burden and restoring flow.

In Vivo Clonal Analysis Reveals Random Monoallelic Expression in Lymphocytes That Traces Back to Hematopoietic Stem Cells.

Evaluating the epigenetic landscape in the stem cell compartment at the single-cell level is essential to assess the cells' heterogeneity and predict their fate. Here, using a genome-wide transcriptomics approach in vivo, we evaluated the allelic expression imbalance in the progeny of single hematopoietic cells (HSCs) as a read-out of epigenetic marking. After 4 months of extensive proliferation and differentiation, we found that X-chromosome inactivation (XCI) is tightly maintained in all single-HSC derived hematopoietic cells. In contrast, the vast majority of the autosomal genes did not show clonal patterns of random monoallelic expression (RME). However, a persistent allele-specific autosomal transcription in HSCs and their progeny was found in a rare number of cases, none of which has been previously reported. These data show that: 1) XCI and RME in the autosomal chromosomes are driven by different mechanisms; 2) the previously reported high frequency of genes under RME in clones expanded in vitro (up to 15%) is not found in clones undergoing multiple differentiation steps in vivo; 3) prior to differentiation, HSCs have stable patterns of autosomal RME. We propose that most RME patterns in autosomal chromosomes are erased and established de novo during cell lineage differentiation.

Saliva molecular testing bypassing RNA extraction is suitable for monitoring and diagnosing SARS-CoV-2 infection in children.

BACKGROUND: Adults are being vaccinated against SARS-CoV-2 worldwide, but the longitudinal protection of these vaccines is uncertain, given the ongoing appearance of SARS-CoV-2 variants. Children remain largely unvaccinated and are susceptible to infection, with studies reporting that they actively transmit the virus even when asymptomatic, thus affecting the community. METHODS: We investigated if saliva is an effective sample for detecting SARS-CoV-2 RNA and antibodies in children, and associated viral RNA levels to infectivity. For that, we used a saliva-based SARS-CoV-2 RT-qPCR test, preceded or not by RNA extraction, in 85 children aged 10 years and under, admitted to the hospital regardless of COVID-19 symptomatology. Amongst these, 29 (63.0%) presented at least one COVID-19 symptom, 46 (54.1%) were positive for SARS-CoV-2 infection, 28 (32.9%) were under the age of 1, and the mean (SD) age was 3.8 (3.4) years. Saliva samples were collected up to 48 h after a nasopharyngeal swab-RT-qPCR test. RESULTS: In children aged 10 years and under, the sensitivity, specificity, and accuracy of saliva-RT-qPCR tests compared to NP swab-RT-qPCR were, respectively, 84.8% (71.8%-92.4%), 100% (91.0%-100%), and 91.8% (84.0%-96.6%) with RNA extraction, and 81.8% (68.0%-90.5%), 100% (91.0%-100%), and 90.4% (82.1%-95.0%) without RNA extraction. Rescue of infectious particles from saliva was limited to CT values below 26. In addition, we found significant IgM positive responses to SARS-CoV-2 in children positive for SARS-CoV-2 by NP swab and negative by saliva compared to other groups, indicating late infection onset (>7-10 days). CONCLUSIONS: Saliva is a suitable sample type for diagnosing children aged 10 years and under, including infants aged <1 year, even bypassing RNA extraction methods. Importantly, the detected viral RNA levels were significantly above the infectivity threshold in several samples. Further investigation is required to correlate SARS-CoV-2 RNA levels to viral transmission.

Biophysical aspects underlying the swarm to biofilm transition.

Bacteria organize in a variety of collective states, from swarming-rapid surface exploration, to biofilms-highly dense immobile communities attributed to stress resistance. It has been suggested that biofilm and swarming are oppositely controlled, making this transition particularly interesting for understanding the ability of bacterial colonies to adapt to challenging environments. Here, the swarm to biofilm transition is studied in Bacillus subtilis by analyzing the bacterial dynamics both on the individual and collective scales. We show that both biological and physical processes facilitate the transition. A few individual cells that initiate the biofilm program cause nucleation of large, approximately scale-free, stationary aggregates of trapped swarm cells. Around aggregates, cells continue swarming almost unobstructed, while inside, trapped cells are added to the biofilm. While our experimental findings rule out previously suggested purely physical effects as a trigger for biofilm formation, they show how physical processes, such as clustering and jamming, accelerate biofilm formation.

Mutant IL7R collaborates with MYC to induce T-cell acute lymphoblastic leukemia.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive pediatric cancer. Amongst the wide array of driver mutations, 10% of T-ALL patients display gain-of-function mutations in the IL-7 receptor α chain (IL-7Rα, encoded by IL7R), which occur in different molecular subtypes of this disease. However, it is still unclear whether IL-7R mutational activation is sufficient to transform T-cell precursors. Also, which genes cooperate with IL7R to drive leukemogenesis remain poorly defined. Here, we demonstrate that mutant IL7R alone is capable of inducing T-ALL with long-latency in stable transgenic zebrafish and transformation is associated with MYC transcriptional activation. Additionally, we find that mutant IL7R collaborates with Myc to induce early onset T-ALL in transgenic zebrafish, supporting a model where these pathways collaborate to drive leukemogenesis. T-ALLs co-expressing mutant IL7R and Myc activate STAT5 and AKT pathways, harbor reduced numbers of apoptotic cells and remake tumors in transplanted zebrafish faster than T-ALLs expressing Myc alone. Moreover, limiting-dilution cell transplantation experiments reveal that activated IL-7R signaling increases the overall frequency of leukemia propagating cells. Our work highlights a synergy between mutant IL7R and Myc in inducing T-ALL and demonstrates that mutant IL7R enriches for leukemia propagating potential.

Dermo-cosmetic spray containing Rhealba oat plantlets and Uncaria tomentosa extract in patients with mild-to-moderate cutaneous pain.

BACKGROUND: Chronic cutaneous pain has a substantial negative impact on quality of life (QoL). Dermo-cosmetics can support therapies for treatment of chronic skin diseases, providing symptomatic relief from chronic cutaneous pain and improved QoL. OBJECTIVES: To assess the global tolerance and efficacy of a dermo-cosmetic spray containing Rhealba® Oat Plantlet and Uncaria tomentosa extracts in reducing cutaneous pain when used as a monotherapy or in association with drug or dermo-cosmetic treatments in patients with an underlying skin pathology. METHODS: Patients aged ≥1 month with a cutaneous pain level ≥3 and an underlying skin pathology were provided with the spray to use up to six times daily for 6-8 weeks. Immediate effect on cutaneous pain and patient satisfaction were assessed after the first application. Global efficacy and tolerance, reduction in symptoms, improvement in QoL, pain reduction and patient overall satisfaction were assessed after 6-8 weeks. RESULTS: Immediately after the first application, significant reductions in cutaneous pain were observed across all age groups (P < 0.0001), with 94% of patients reporting a reduction in pain. After 6-8 weeks, global tolerance was rated 'very good' or 'good' for 97% of patients, and the spray was efficacious in 95% of patients. Patient satisfaction with the efficacy of the spray was 95%. QoL scores improved in 86% and 94% of patients aged ≥12 and <12 years, respectively. Findings were similar across underlying pathology and therapy types (monotherapy or in association with another therapy). CONCLUSIONS: The spray was well-tolerated and efficacious in providing symptom relief in patients with mild-to-moderate cutaneous pain, irrespective of the underlying pathology or therapy type.

Using the Business Model Canvas to Guide Doctor of Pharmacy Students in Building Business Plans.

Objective. To review the use of the business model canvas, a one-page visual description of a business initiative, as a tool for teaching pharmacy students about entrepreneurship and business planning in pharmacy practice settings.Findings. Students often struggle to develop the mindset, skillset, and toolset to effectively apply business modeling and planning processes to pharmacy practice settings. Over years of experimentation and various iterations in a pharmacy practice management class, a new business model canvas was developed and refined. The canvas contains 13 sections which emphasize key terms, concepts, and ideas crucial for achieving entrepreneurial competencies. Using the zone of proximal development as a framework, the course structure offered a range of supportive activities that guided students to independent competence. The business model canvas formed a framework around which assigned course readings, exercises, and group assignments helped pharmacy students build confidence and competence in completing a capstone business plan assignment.Summary. This paper provides recommendations and examples of how to structure a course in the Doctor of Pharmacy curricula using an entrepreneurial tool, the business model canvas, to help students master business competencies. Recommendations and lessons-learned are provided.

How production networks amplify economic growth.

Technological improvement is the most important cause of long-term economic growth. In standard growth models, technology is treated in the aggregate, but an economy can also be viewed as a network in which producers buy goods, convert them to new goods, and sell the production to households or other producers. We develop predictions for how this network amplifies the effects of technological improvements as they propagate along chains of production, showing that longer production chains for an industry bias it toward faster price reduction and that longer production chains for a country bias it toward faster growth. These predictions are in good agreement with data from the World Input Output Database and improve with the passage of time. The results show that production chains play a major role in shaping the long-term evolution of prices, output growth, and structural change.

Interleukin-7 receptor α mutational activation can initiate precursor B-cell acute lymphoblastic leukemia.

Interleukin-7 receptor α (encoded by IL7R) is essential for lymphoid development. Whether acute lymphoblastic leukemia (ALL)-related IL7R gain-of-function mutations can trigger leukemogenesis remains unclear. Here, we demonstrate that lymphoid-restricted mutant IL7R, expressed at physiological levels in conditional knock-in mice, establishes a pre-leukemic stage in which B-cell precursors display self-renewal ability, initiating leukemia resembling PAX5 P80R or Ph-like human B-ALL. Full transformation associates with transcriptional upregulation of oncogenes such as Myc or Bcl2, downregulation of tumor suppressors such as Ikzf1 or Arid2, and major IL-7R signaling upregulation (involving JAK/STAT5 and PI3K/mTOR), required for leukemia cell viability. Accordingly, maximal signaling drives full penetrance and early leukemia onset in homozygous IL7R mutant animals. Notably, we identify 2 transcriptional subgroups in mouse and human Ph-like ALL, and show that dactolisib and sphingosine-kinase inhibitors are potential treatment avenues for IL-7R-related cases. Our model, a resource to explore the pathophysiology and therapeutic vulnerabilities of B-ALL, demonstrates that IL7R can initiate this malignancy.

Turbulence-induced clustering in compressible active fluids.

We study a novel phase of active polar fluids, which is characterized by the continuous creation and destruction of dense clusters due to self-sustained turbulence. This state arises due to the interplay between self-advection of the aligned swimmers and their defect topology. The typical cluster size is determined by the characteristic vortex size. Our results are obtained by investigating a continuum model of compressible polar active fluids, which incorporates typical experimental observations in bacterial suspensions, in particular a non-monotone dependence of speed on density.

X-Chromosome Inactivation and Autosomal Random Monoallelic Expression as "Faux Amis".

X-chromosome inactivation (XCI) and random monoallelic expression of autosomal genes (RMAE) are two paradigms of gene expression regulation where, at the single cell level, genes can be expressed from either the maternal or paternal alleles. X-chromosome inactivation takes place in female marsupial and placental mammals, while RMAE has been described in mammals and also other species. Although the outcome of both processes results in random monoallelic expression and mosaicism at the cellular level, there are many important differences. We provide here a brief sketch of the history behind the discovery of XCI and RMAE. Moreover, we review some of the distinctive features of these two phenomena, with respect to when in development they are established, their roles in dosage compensation and cellular phenotypic diversity, and the molecular mechanisms underlying their initiation and stability.