"It feels like you have to choose one or the other": a qualitative analysis of obstetrician focus groups on periviability counseling.

OBJECTIVES: The objective of this study was to gain knowledge and ascertain challenges about periviability counseling among obstetricians to inform curricular development. METHODS: Focus groups were utilized. A series of open-ended questions was posed to each group of obstetricians; responses were audio recorded and transcribed. Transcriptions were analyzed by two coders using thematic analysis. RESULTS: Four focus groups were convened. Prominent themes included: (1) Obstetrician knowledge about neonatal outcomes is limited, (2) Periviability counseling is both time intensive and time-challenged, (3) Patient processing of information relies on the content, delivery and patient readiness, and (4) Obstetrician bias is toward advocating for maternal safety, which may run counter to parental instinct to "do everything." The last theme was specifically focused on the role of cesarean delivery. CONCLUSIONS: Curricula focused on improving obstetrician periviability counseling should focus on neonatal outcomes, the role of cesarean delivery, and utilization of shared decision-making.

Selective inhibition of MCL1 overcomes venetoclax resistance in a murine model of myelodysplastic syndromes.

Treatment for myelodysplastic syndromes (MDS) remains insufficient due to clonal heterogeneity and lack of effective clinical therapies. Dysregulation of apoptosis is observed across MDS subtypes regardless of mutations and represents an attractive therapeutic opportunity. Venetoclax (VEN), a selective inhibitor of anti-apoptotic protein B-cell lymphoma- 2 (BCL2), has yielded impressive responses in older patients with acute myeloid leukemia (AML) and high risk MDS. BCL2 family anti-apoptotic proteins BCL-XL and induced myeloid cell leukemia 1 (MCL1) are implicated in leukemia survival, and upregulation of MCL1 is seen in VEN-resistant AML and MDS. We determined in vitro sensitivity of MDS patient samples to selective inhibitors of BCL2, BCL-XL and MCL1. While VEN response positively correlated with MDS with excess blasts, all MDS subtypes responded to MCL1 inhibition. Treatment with combined VEN + MCL1 inhibtion was synergistic in all MDS subtypes without significant injury to normal hematopoiesis and reduced MDS engraftment in MISTRG6 mice, supporting the pursuit of clinical trials with combined BCL2 + MCL1 inhibition in MDS.

Optimization of hippocampus sparing during whole brain radiation therapy with simultaneous integrated boost-tutorial and efficacy of complete directional hippocampal blocking.

PURPOSE: Hippocampus-avoidance whole brain radiotherapy with simultaneous integrated boost (HA-WBRT+SIB) is a complex treatment option for patients with multiple brain metastases, aiming to prevent neurocognitive decline and simultaneously increase tumor control. Achieving efficient hippocampal dose reduction in this context can be challenging. The aim of the current study is to present and analyze the efficacy of complete directional hippocampal blocking in reducing the hippocampal dose during HA-WBRT+SIB. METHODS: A total of 30 patients with multiple metastases having undergone HA-WBRT+SIB were identified. The prescribed dose was 30 Gy in 12 fractions to the whole brain, with 98% of the hippocampus receiving ≤ 9 Gy and 2% ≤ 17 Gy and with SIB to metastases/resection cavities of 36-51 Gy in 12 fractions. Alternative treatment plans were calculated using complete directional hippocampal blocking and compared to conventional plans regarding target coverage, homogeneity, conformity, dose to hippocampi and organs at risk. RESULTS: All alternative plans reached prescription doses. Hippocampal blocking enabled more successful sparing of the hippocampus, with a mean dose of 8.79 ± 0.99 Gy compared to 10.07 ± 0.96 Gy in 12 fractions with the conventional method (p < 0.0001). The mean dose to the whole brain (excluding metastases and hippocampal avoidance region) was 30.52 ± 0.80 Gy with conventional planning and 30.28 ± 0.11 Gy with hippocampal blocking (p = 0.11). Target coverage, conformity and homogeneity indices for whole brain and metastases, as well as doses to organs at risk were similar between planning methods (p > 0.003). CONCLUSION: Complete directional hippocampal blocking is an efficient method for achieving improved hippocampal sparing during HA-WBRT+SIB.

Developing an opioid curriculum for medical students: A consensus report from a national symposium.

In June 2018, the Warren Alpert Medical School of Brown University hosted a national, multidisciplinary, interprofessional symposium on opioid curricula in undergraduate medical education. This article presents the consensus of an interprofessional group who attended a session focused on elements of an opioid curriculum, including key areas of content, teaching modalities, and learner assessment. This report also includes further directions and next steps for undergraduate medical education collaboration on opioid curricula.

BET inhibitors reduce cell size and induce reversible cell cycle arrest in AML.

Inhibitors of the bromodomain and extraterminal domain family (BETi) offer a new approach to treat hematological malignancies, with leukemias containing mixed lineage leukemia rearrangements being especially sensitive due to a reliance on the regulation of transcription elongation. We explored the mechanism of action of BETi in cells expressing the t(8;21), and show that these compounds reduced the size of acute myeloid leukemia cells, triggered a rapid but reversible G0 /G1 arrest, and with time, cause cell death. Meta-analysis of PRO-seq data identified ribosomal genes, which are regulated by MYC, were downregulated within 3 hours of addition of the BETi. This reduction of MYC regulated metabolic genes coincided with the loss of mitochondrial respiration and large reductions in the glycolytic rate. In addition, gene expression analysis showed that transcription of BCL2 was rapidly affected by BETi but this did not cause dramatic increases in cell death. Cell cycle arrest, lowered metabolic activity, and reduced BCL2 levels suggested that a second compound was needed to push these cells over the apoptotic threshold. Indeed, low doses of the BCL2 inhibitor, venetoclax, in combination with the BETi was a potent combination in t(8;21) containing cells. Thus, BET inhibitors that affect MYC and BCL2 expression should be considered for combination therapy with venetoclax.

Myeloid translocation gene 16 is required for maintenance of haematopoietic stem cell quiescence.

The t(8;21) and t(16;21) that are associated with acute myeloid leukaemia disrupt two closely related genes termed Myeloid Translocation Genes 8 (MTG8) and 16 (MTG16), respectively. Many of the transcription factors that recruit Mtg16 regulate haematopoietic stem and progenitor cell functions and are required to maintain stem cell self-renewal potential. Accordingly, we found that Mtg16-null bone marrow (BM) failed in BM transplant assays. Moreover, when removed from the animal, Mtg16-deficient stem cells continued to show defects in stem cell self-renewal assays, suggesting a requirement for Mtg16 in this process. Gene expression analysis indicated that Mtg16 was required to suppress the expression of several key cell-cycle regulators including E2F2, and chromatin immunoprecipitation assays detected Mtg16 near an E2A binding site within the first intron of E2F2. BrdU incorporation assays indicated that in the absence of Mtg16 more long-term stem cells were in the S phase, even after competitive BM transplantation where normal stem and progenitor cells are present, suggesting that Mtg16 plays a role in the maintenance of stem cell quiescence.

Biotechnologically produced microbial alginate dressings show enhanced gel forming capacity compared to commercial alginate dressings of marine origin.

Marine alginate fibre dressings are well established in wound management. Alginate fibres can absorb plenty of wound exudate due to their gel forming abilities and ion exchange. Alginates from bacteria have never been studied for medical applications so far, although the microbial polymer raises expectations for improved gelling capacity due to its unique O-acetylation. To prove the gelling capacity of bacterial alginate, we extracted the co-polymer from fermentation of the soil bacterium Azotobacter vinelandii ATCC 9046, cultivated on crude glycerol as an alternative carbon source. Bacterial alginate was isolated in high purity and extruded by a wet spinning method. Fibre structure and properties were characterised by infrared spectroscopy, NMR, GPC, scanning electron microscopy and tensile testing. The fibres could be processed into biocompatible needle web dressings, which showed more than twice the gel formation in saline compared to commercial dressings made of marine alginates. Gelled dressings of bacterial alginate formed stable hydrogels of sufficient shape and strength for wound healing applications. This work suggests that the increased gel formation of bacterial alginate from A. vinelandii may be optimal for the preparation of novel wound dressings.

Maternity Leave Satisfaction Among Physicians Compared with Nonphysician Professionals.

Objective: The objective of this study was to compare maternity leave satisfaction between physicians and nonphysicians. Currently, paid maternal leave is not guaranteed in the United States, resulting in palpable dissatisfaction among parents. Previous studies have shown associations between length of paid leave and career satisfaction and maternal happiness. Materials and Methods: A Qualtrics® electronic survey was distributed to female professionals through email and social media from April 2019 to March 2020. Inclusion criterion was ≥1 child by birth or adoption, or active pregnancy. Continuous and categorical data were analyzed using two-sample t-test and chi-square, respectively. Results: Of 808 respondents, 77% were physicians. Mean age at birth/adoption of first child was higher in physicians versus nonphysicians (32.1 years vs. 29.7 years; p < 0.001). Physicians took shorter maternity leave than nonphysicians (10.9 weeks vs. 12.0 weeks, p = 0.017) with half of that time paid by employers (5.4 weeks vs. 5.9 weeks, p = 0.2). Dissatisfaction was high among physicians (85.1%) and nonphysicians (92.4%) that correlates with maternity leave compensation dissatisfaction (49% vs. 71.3%, p < 0.001). Thirty-four percent of physicians versus 41% of nonphysicians stated that their health was negatively impacted by maternity leave length. Physicians and nonphysicians reported similar incidences of depression, and breastfeeding, delivery, and other postpartum complications. When queried, 38.8% of physicians and 57% of nonphysicians said they would desire >16 weeks of paid maternity leave (p < 0.001). Conclusions: In conclusion, dissatisfaction among professional women on maternity leave duration and compensation is high in the United States. Given health implications for both mother and child, this should invite further discussion and changes.

Rapid prototyping of perfusion cell culture devices for three-dimensional imaging of mesenchymal stem cell deposition and proliferation.

Perfusion of porous scaffolds transports cells to the surface to yield cellular constructs for 3D models of disease and for tissue engineering applications. While ceramic scaffolds mimic the structure and composition of trabecular bone, their opacity and tortuous pores limit the penetration of light into the interior. Scaffolds that are both perfusable and amenable to fluorescence microscopy are therefore needed to visualize the spatiotemporal dynamics of cells in the bone microenvironment. In this study, a hybrid injection molding approach was designed to enable rapid prototyping of collector arrays with variable configurations that are amenable to longitudinal imaging of attached human mesenchymal stem cells (hMSCs) using fluorescence microscopy. Cylindrical collectors were arranged in an array that is permeable to perfusion in the xy-plane and to light in the z-direction for imaging from below. The effects of the collector radius, number, and spacing on the collection efficiency of perfused hMSCs was simulated using computational fluid dynamics (CFD) and measured experimentally using fluorescence microscopy. The effect of collector diameter on simulated and experimental cell collection efficiencies followed a trend similar to that predicted by interception theory corrected for intermolecular and hydrodynamic forces for the arrays with constant collector spacing. In contrast, arrays designed with constant collector number yielded collection efficiencies that poorly fit the trend with collector radius predicted by interception theory. CFD simulations of collection efficiency agreed with experimental measurements within a factor of two. These findings highlight the utility of CFD simulations and hybrid injection molding for rapid prototyping of collector arrays to optimize the longitudinal imaging of cells without the need for expensive and time-consuming tooling.

Curricular Reform in Serious Illness Communication and Palliative Care: Using Medical Students' Voices to Guide Change.

PURPOSE: To gather and leverage the voices of students to drive creation of required, integrated palliative care curricula within undergraduate medical education in Massachusetts, which is lacking in a majority of U.S. medical schools. METHOD: The study was conducted by the Massachusetts Medical Schools' Collaborative, a working group committed to ensuring all medical students in Massachusetts receive foundational training in serious illness communication (SIC) and palliative care. Eight focus groups (2 per participating medical school) were conducted during January-May 2021 and included a total of 50 students from Boston University Chobanian & Avedisian School of Medicine, Harvard Medical School, Tufts University School of Medicine, and the UMass Chan Medical School. Data collected from focus groups were discussed and coded. Themes were identified using the immersion/crystallization qualitative data analysis approach. RESULTS: Six key themes emerged. Students viewed SIC as essential to high-quality medical practice regardless of specialty, and believed training in SIC skills and palliative care should be required in medical school curricula. Students preferred to learn and practice these skills using frameworks, particularly in real-world situations. Students recognized the expertise of palliative care specialists and described them as a scarce, often misunderstood resource in health care. Students reported it was mostly "luck" if they were included in family meetings and observed good role models. Finally, students desired practice in debriefing after difficult and emotional situations. CONCLUSIONS: This study confirms long-standing themes on students' experiences with SIC and palliative care topics, including feeling inadequately prepared to care for seriously ill patients as future physicians. Our study collected students' perspectives as actionable data to develop recommendations for curricular change. Collaborative faculty also created recommendations based on the focus group data for immediate and ongoing SIC and palliative care curricular change in Massachusetts, which can apply to medical schools nationwide.

Perioperative experience of pelvic organ prolapse repair with the Prolift and Elevate vaginal mesh procedures.

INTRODUCTION AND HYPOTHESIS: We compared the operative and immediate postoperative experience of the trocar-based Prolift and non-trocar-based Elevate techniques used to repair vaginal prolapse. METHODS: A retrospective review of Prolift and Elevate repairs was performed. Baseline characteristics and operative and postoperative variables evaluated included compartment(s) repaired, adjacent organ injury, operative time (OT), change in hemoglobin (ΔH), pain score, narcotic use, length of stay (LOS), and short-term complications. Categorical variables were assessed as counts and percent frequency. Data were compared using chi-squared analysis and paired t test. RESULTS: Prolift (n = 143) and Elevate (n = 77) patients were similar in age (p = 0.19). Concurrent hysterectomy was done in 22 (15.4 %) and 24 (31.2 %), respectively, and concurrent midurethral sling placed in 100 (70 %) and 50 (65 %), respectively. LOS (median, 25th,75th) after anterior/apical compartment repairs was shorter with Elevate, whether with (1.0; 1.0,1.5 vs. 2.0 days;1.0, 2.0; p = 0.003) or without (2.0; 1.0, 2.0 vs. 2.0 days; 2.0, 3.0; p = 0.024) hysterectomy, but no differences in OT, ΔH, pain score, or narcotic use occurred. Posterior compartment mean pain scores were lower with Prolift (3.6 ± 2.2 vs. 1.7 ± 1.5, p = 0.035), and three-compartment-repair pain scores were lower with Elevate (0.6 ± 1.3 vs 2.5 ± 1.9; p = 0.013). Three bladder injuries occurred with Prolift but none with Elevate. CONCLUSIONS: Operative and postoperative experiences were similar between groups; however, Elevate anterior/apical repairs had shorter LOS, which might reflect more aggressive discharge planning. There were no bowel or major vascular injuries, and the Prolift trocar bladder injuries did not alter the surgical procedure.

Nanoparticle STING Agonist Reprograms the Bone Marrow to an Antitumor Phenotype and Protects Against Bone Destruction.

When breast cancer metastasizes to bone, treatment options are limited. Failure to treat bone metastases is thought to be due to therapy-resistant features of the bone marrow microenvironment. Using a murine model of bone metastatic mammary carcinoma, we demonstrate that systemic delivery of polymer nanoparticles loaded with cyclic dinucleotide (CDN) agonists of stimulator of interferon genes (STING) inhibited tumor growth and bone destruction after 7 days of treatment. Each dose of STING-activating nanoparticles trafficked to the bone marrow compartment and was retained within the tumor microenvironment for over 24 hours, enhancing antitumor immunity through proinflammatory cytokine production and early T-cell activation. While acquired resistance mechanisms, including increased levels of immunosuppressive cytokines and the infiltration of regulatory T cells, ultimately limited antitumor efficacy after 2 weeks of treatment, bone protective effects remained. Overall, these studies demonstrate that STING pathway activation, here enabled using a nanomedicine approach to enhance CDN delivery to bone metastatic sites, can reprogram the immune contexture of the bone marrow to an antitumor phenotype that inhibits bone colonization of metastatic breast cancer cells and protects from tumor-mediated bone destruction. Significance: Bone metastases are difficult to treat due to the inaccessibility of the bone marrow compartment and the immunosuppressive microenvironment that protects resident stem cells. Packaging a STING agonist into a nanoparticle that enables systemic administration and drug accumulation at tumor sites overcomes both barriers to stymie metastatic breast cancer growth.

Comparison of blogged and written reflections in two medicine clerkships.

CONTEXT: academic medical centres may adopt new learning technologies with little data on their effectiveness or on how they compare with traditional methodologies. We conducted a comparative study of student reflective writings produced using either an electronic (blog) format or a traditional written (essay) format to assess differences in content, depth of reflection and student preference. METHODS: students in internal medicine clerkships at two US medical schools during the 2008-2009 academic year were quasi-randomly assigned to one of two study arms according to which they were asked to either write a traditional reflective essay and subsequently join in faculty-moderated, small-group discussion (n = 45), or post two writings to a faculty-moderated group blog and provide at least one comment on a peer's posts (n = 50). Examples from a pilot block were used to refine coding methods and determine inter-rater reliability. Writings were coded for theme and level of reflection by two blinded authors; these coding processes reached inter-rater reliabilities of 91% and 80%, respectively. Anonymous pre- and post-clerkship surveys assessed student perceptions and preferences. RESULTS: student writing addressed seven main themes: (i) being humanistic; (ii) professional behaviour; (iii) understanding caregiving relationships; (iv) being a student; (v) clinical learning; (vi) dealing with death and dying, and (vii) the health care system, quality, safety and public health. The distribution of themes was similar across institutions and study arms. The level of reflection did not differ between study arms. Post-clerkship surveys showed that student preferences for blogging or essay writing were predicted by experience, with the majority favouring the method they had used. CONCLUSIONS: our study suggests there is no significant difference in themes addressed or levels of reflection achieved when students complete a similar assignment via online blogging or traditional essay writing. Given this, faculty staff should feel comfortable in utilising the blog format for reflective exercises. Faculty members could consider the option of using either format to address different learning styles of students.

The delta isoform of phosphatidylinositol-3-kinase predominates in chronic myelomonocytic leukemia and can be targeted effectively with umbralisib and ruxolitinib.

Chronic myelomonocytic leukemia (CMML) is a myelodysplastic syndrome/myeloproliferative neoplasm overlap syndrome characterized by monocytic proliferation in the presence of dysplastic bone marrow changes, inflammatory symptoms, and propensity for transformation to acute myeloid leukemia (AML), with a poor prognosis and limited treatment options. Unlike the α and ß isoforms, the phosphatidylinositol-3-kinase (PI3K)-δ signaling protein is predominantly expressed by hematopoietic cells and therefore has garnered interest as a potential target for the treatment of lymphomas and leukemias. We revealed a pattern of increased PIK3CD:PIK3CA ratio in monocytic M5 AML patients and cell lines, and this ratio correlated with responsiveness to pharmacological PI3K-δ inhibition in vitro. Because CMML is a disease defined by monocytic clonal proliferation, we tested the PI3K-δ inhibitor umbralisib as a single agent and in combination with the JAK1/2 inhibitor ruxolitinib, in CMML. Our ex vivo experiments with primary CMML patient samples revealed synergistic inhibition of viability and clonogenicity with this combination. Phospho-specific flow cytometry revealed that dual inhibition had the unique ability to decrease STAT5, ERK, AKT, and S6 phosphorylation simultaneously, which offers a mechanistic hypothesis for the enhanced efficacy of the combination treatment. These preclinical data indicate promising activity by co-inhibition of PI3K-δ and JAK1/2 and support the use of ruxolitinib + umbralisib combination therapy in CMML under active clinical investigation.

BET Inhibition Enhances the Antileukemic Activity of Low-dose Venetoclax in Acute Myeloid Leukemia.

PURPOSE: The BCL2 inhibitor, venetoclax, has transformed clinical care in acute myeloid leukemia (AML). However, subsets of patients do not respond or eventually acquire resistance. Venetoclax-based regimens can lead to considerable marrow suppression in some patients. Bromodomain and extraterminal inhibitors (BETi) are potential treatments for AML, as regulators of critical AML oncogenes. We tested the efficacy of novel BET inhibitor INCB054329, and its synergy with venetoclax to reduce AML without induction of hematopoietic toxicity. EXPERIMENTAL DESIGN: INCB054329 efficacy was assessed by changes in cell cycle and apoptosis in treated AML cell lines. In vivo efficacy was assessed by tumor reduction in MV-4-11 cell line-derived xenografts. Precision run-on and sequencing (PRO-seq) evaluated effects of INCB054329. Synergy between low-dose BETi and venetoclax was assessed in cell lines and patient samples in vitro and in vivo while efficacy and toxicity was assessed in patient-derived xenograft (PDX) models. RESULTS: INCB054329 induced dose-dependent apoptosis and quiescence in AML cell lines. PRO-seq analysis evaluated the effects of INCB054329 on transcription and confirmed reduced transcriptional elongation of key oncogenes, MYC and BCL2, and genes involved in the cell cycle and metabolism. Combinations of BETi and venetoclax led to reduced cell viability in cell lines and patient samples. Low-dose combinations of INCB054329 and venetoclax in cell line and PDX models reduced AML burden, regardless of the sensitivity to monotherapy without development of toxicity. CONCLUSIONS: Our findings suggest low dose combinations of venetoclax and BETi may be more efficacious for patients with AML than either monotherapy, potentially providing a longer, more tolerable dosing regimen.

Development of a multi-component intervention to promote participation of Black and Latinx individuals in biomedical research.

INTRODUCTION: Barriers to research participation by racial and ethnic minority group members are multi-factorial, stem from historical social injustices and occur at participant, research team, and research process levels. The informed consent procedure is a key component of the research process and represents an opportunity to address these barriers. This manuscript describes the development of the Strengthening Translational Research in Diverse Enrollment (STRIDE) intervention, which aims to improve research participation by individuals from underrepresented groups. METHODS: We used a community-engaged approach to develop an integrated, culturally, and literacy-sensitive, multi-component intervention that addresses barriers to research participation during the informed consent process. This approach involved having Community Investigators participate in intervention development activities and using community engagement studios and other methods to get feedback from community members on intervention components. RESULTS: The STRIDE intervention has three components: a simulation-based training program directed toward clinical study research assistants that emphasizes cultural competency and communication skills for assisting in the informed consent process, an electronic consent (eConsent) framework designed to improve health-related research material comprehension and relevance, and a "storytelling" intervention in which prior research participants from diverse backgrounds share their experiences delivered via video vignettes during the consent process. CONCLUSIONS: The community engaged development approach resulted in a multi-component intervention that addresses known barriers to research participation and can be integrated into the consent process of research studies. Results of an ongoing study will determine its effectiveness at increasing diversity among research participants.

Selective Inhibition of JAK1 Primes STAT5-Driven Human Leukemia Cells for ATRA-Induced Differentiation.

BACKGROUND: All-trans retinoic acid (ATRA), a derivate of vitamin A, has been successfully used as a therapy to induce differentiation in M3 acute promyelocytic leukemia (APML), and has led to marked improvement in outcomes. Previously, attempts to use ATRA in non-APML in the clinic, however, have been underwhelming, likely due to persistent signaling through other oncogenic drivers. Dysregulated JAK/STAT signaling is known to drive several hematologic malignancies, and targeting JAK1 and JAK2 with the JAK1/JAK2 inhibitor ruxolitinib has led to improvement in survival in primary myelofibrosis and alleviation of vasomotor symptoms and splenomegaly in polycythemia vera and myelofibrosis. OBJECTIVE: While dose-dependent anemia and thrombocytopenia limit the use of JAK2 inhibition, selectively targeting JAK1 has been explored as a means to suppress inflammation and STAT-associated pathologies related to neoplastogenesis. The objective of this study is to employ JAK1 inhibition (JAK1i) in the presence of ATRA as a potential therapy in non-M3 acute myeloid leukemia (AML). METHODS: Efficacy of JAK1i using INCB52793 was assessed by changes in cell cycle and apoptosis in treated AML cell lines. Transcriptomic and proteomic analysis evaluated effects of JAK1i. Synergy between JAK1i+ ATRA was assessed in cell lines in vitro while efficacy in vivo was assessed by tumor reduction in MV-4-11 cell line-derived xenografts. RESULTS: Here we describe novel synergistic activity between JAK1i inhibition and ATRA in non-M3 leukemia. Transcriptomic and proteomic analysis confirmed structural and functional changes related to maturation while in vivo combinatory studies revealed significant decreases in leukemic expansion. CONCLUSIONS: JAK1i+ ATRA lead to decreases in cell cycle followed by myeloid differentiation and cell death in human leukemias. These findings highlight potential uses of ATRA-based differentiation therapy of non-M3 human leukemia.

Accelerated Graduation and the Deployment of New Physicians During the COVID-19 Pandemic.

The COVID-19 pandemic has presented unprecedented challenges and opportunities for medical schools in the United States. In this Invited Commentary, the authors describe a unique collaboration between the University of Massachusetts Medical School (UMMS), the only public medical school in the state; the University of Massachusetts Memorial Medical Center (UMMMC); and the Commonwealth of Massachusetts. Through this partnership, UMMS was able to graduate fourth-year medical students 2 months early and deploy them to UMMMC to care for patients and alleviate workforce shortages during the COVID-19 surge, which peaked in Massachusetts in April 2020. The authors describe how they determined if students had fulfilled graduation requirements to graduate early, what commencement and the accompanying awards ceremony looked like this year as virtual events, the special emergency 90-day limited license these new graduates were given to practice at UMMMC during this time, and the impact these new physicians had in the hospital allowing residents and attendings to be redeployed to care for COVID-19 patients.

Simulation-based power and sample size calculation for designing interrupted time series analyses of count outcomes in evaluation of health policy interventions.

OBJECTIVE: The purpose of this study was to present the design, model, and data analysis of an interrupted time series (ITS) model applied to evaluate the impact of health policy, systems, or environmental interventions using count outcomes. Simulation methods were used to conduct power and sample size calculations for these studies. METHODS: We proposed the models and analyses of ITS designs for count outcomes using the Strengthening Translational Research in Diverse Enrollment (STRIDE) study as an example. The models we used were observation-driven models, which bundle a lagged term on the conditional mean of the outcome for a time series of count outcomes. RESULTS: A simulation-based approach with ready-to-use computer programs was developed to calculate the sample size and power of two types of ITS models, Poisson and negative binomial, for count outcomes. Simulations were conducted to estimate the power of segmented autoregressive (AR) error models when autocorrelation ranged from -0.9 to 0.9, with various effect sizes. The power to detect the same magnitude of parameters varied largely, depending on the testing level change, the trend change, or both. The relationships between power and sample size and the values of the parameters were different between the two models. CONCLUSION: This article provides a convenient tool to allow investigators to generate sample sizes that will ensure sufficient statistical power when the ITS study design of count outcomes is implemented.

Design, analysis, power, and sample size calculation for three-phase interrupted time series analysis in evaluation of health policy interventions.

OBJECTIVE: To discuss the study design and data analysis for three-phase interrupted time series (ITS) studies to evaluate the impact of health policy, systems, or environmental interventions. Simulation methods are used to conduct power and sample size calculation for these studies. METHODS: We consider the design and analysis of three-phase ITS studies using a study funded by National Institutes of Health as an exemplar. The design and analysis of both one-arm and two-arm three-phase ITS studies are introduced. RESULTS: A simulation-based approach, with ready-to-use computer programs, was developed to determine the power for two types of three-phase ITS studies. Simulations were conducted to estimate the power of segmented autoregressive (AR) error models when autocorrelation ranged from -0.9 to 0.9 with various effect sizes. The power increased as the sample size or the effect size increased. The power to detect the same effect sizes varied largely, depending on testing level change, trend changes, or both. CONCLUSION: This article provides a convenient tool for investigators to generate sample sizes to ensure sufficient statistical power when three-phase ITS study design is implemented.