A Capstone Course for Senior Medical Students: from Innovative Elective to Required Core Curriculum.

We describe our institution's development and implementation of our Capstone course from a small elective course to the only required fourth-year course. The course's structure evolved from mostly didactic to one including various workshops and simulation sessions. Course content has become increasingly specialty-specific. Implementation requires high faculty and resident involvement. Evaluations indicate a positive impact of the course on participants' self-reported confidence and residency preparedness. Assessment remains pass/fail with more specialty-specific questions. As steadily increasing numbers of medical schools are developing transition to residency courses, we share our Capstone course's evolution and lessons learned over the past nine years. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-023-01880-2.

Wilms tumor treatment protocol compliance and the influence on outcomes for children in Tanzania.

BACKGROUND: Standardized Wilms tumor treatment protocols exist for low- and middle-income countries, but outcomes equivalent to high-income countries are not achieved outside of clinical trials. As Wilms tumor treatment protocols in Africa shift with increasing resource capacity, it is not known how treatment compliance to each stage of therapy affects outcomes and where the critical breakpoints are for protocol adherence in clinical practice. PROCEDURE: We describe both treatment outcomes and treatment protocol adherence in a retrospective single-center cohort study of pediatric Wilms tumor patients at a zonal cancer referral hospital in Tanzania from 2016 to 2019, treated per the International Society of Paediatric Oncology standard (2016-2017) or Tanzania adapted (2018-2019) therapy protocols. RESULTS: A total of 69 patients were evaluated. The two-year overall survival and event-free survival rates were 40% and 29%, respectively. Only 29% of patients completed recommended chemotherapy per protocol, and completion of preoperative and postoperative chemotherapy was predictive of two-year overall survival (odds ratio [OR] 14.4, p < .001). There were delays at almost every stage of treatment, especially time from preoperative chemotherapy to surgery (56 days), from surgery to pathology report (30 days), and from surgery to initiation of postoperative chemotherapy (38 days). CONCLUSIONS: Nonadherence with recommended Wilms tumor treatment guidelines due to key health system delays correlated to reduced overall survival rates, with chemotherapy nonadherence due to abandonment, lack of surgery, and deaths on therapy as the strongest contributors. Future interventions targeting health system delays and reducing deaths during therapy are critical to improving protocol compliance and increasing overall survival for pediatric Wilms tumor patients in low-resource settings.

Interventional pharmacoeconomics for immune checkpoint inhibitors through alternative dosing strategies.

Immune checkpoint inhibitors (ICIs) are approved for the treatment of a variety of cancer types. The doses of these drugs, though approved by the Food and Drug Administration (FDA), have never been optimised, likely leading to significantly higher doses than required for optimal efficacy. Dose optimisation would hypothetically decrease the risk, severity, and duration of immune-related adverse events, as well as provide an opportunity to reduce costs through interventional pharmacoeconomic strategies such as off-label dose reductions or less frequent dosing. We summarise existing evidence for ICI dose optimisation to advocate for the role of interventional pharmacoeconomics.

Patient Factors Associated With Biased Language in Nightly Resident Verbal Handoff.

This cross-sectional study uses audio recordings of resident handoff of inpatient general medicine and general pediatrics teams to measure the extent of stigmatizing language and describes associations between patient factors and biased language in handoffs.

Project Optimus: Is the US Food and Drug Administration Waiving Dose Optimization for Orphan Drugs?

This Viewpoint discusses the US Food and Drug Administration's Project Optimus, which focuses on new oncology drug dose optimization and examines concerns about the accelerated postmarketing approval of adjusted dosing of oncologic drugs.

Developing Targeted Therapies for T Cell Acute Lymphoblastic Leukemia/Lymphoma.

PURPOSE OF REVIEW: Largely, treatment advances in relapsed and/or refractory acute lymphoblastic leukemia (ALL) have been made in B cell disease leaving T cell ALL reliant upon high-intensity chemotherapy. Recent advances in the understanding of the biology of T-ALL and the improvement in immunotherapies have led to new therapeutic pathways to target and exploit. Here, we review the more promising pathways that are able to be targeted and other therapeutic possibilities for T-ALL. RECENT FINDINGS: Preclinical models and early-phase clinical trials have shown promising results in some case in the treatment of T-ALL. Targeting many different pathways could lead to the next advancement in the treatment of relapsed and/or refractory disease. Recent advances in cellular therapies have also shown promise in this space. When reviewing the literature as a whole, targeting important pathways and antigens likely will lead to the next advancement in T-ALL survival since intensifying chemotherapy.

Three-year outcomes for women newly initiated on lifelong antiretroviral therapy during pregnancy - Malawi option B.

INTRODUCTION: Antiretroviral therapy (ART) is very effective in preventing vertical transmission of HIV but some women on ART experience different virologic, immunologic, and safety profiles. While most pregnant women are closely monitored for short-term effects of ART during pregnancy, few women receive similar attention beyond pregnancy. We aimed to assess retention in care and clinical and laboratory-confirmed outcomes over 3 years after starting ART under Malawi's Option B + program. METHODS: We conducted a prospective cohort study of pregnant women newly diagnosed with HIV who started tenofovir disoproxil fumarate/emtricitabine/efavirenz (TDF/3TC/EFV) for the first time at Bwaila Hospital in Lilongwe, Malawi between May 2015 and June 2016. Participants were followed for 3 years. We summarized demographic characteristics, pregnancy outcomes, and clinical and laboratory adverse events findings using proportions. Log-binomial regression models were used to estimate the overall risk ratios (RR) and the corresponding 95% confidence interval (CI) for the association between index pregnancy (i.e. index pregnancy vs. subsequent pregnancy) and preterm birth, and index pregnancy and low birthweight. RESULTS: Of the 299 pregnant women who were enrolled in the study, 255 (85.3%) were retained in care. There were 340 total pregnancies with known outcomes during the 36-month study period, 280 index pregnancies, and 60 subsequent pregnancies. The risks of delivering preterm (9.5% for index pregnancy and13.5% for subsequent pregnancy: RR = 0.70; 95% CI: 0.32-1.54), or low birth weight infant (9.8% for index pregnancy and 4.2% for subsequent pregnancy: RR = 2.36; 95% CI: 0.58-9.66) were similar between index and subsequent pregnancies. Perinatally acquired HIV was diagnosed in 6 (2.3%) infants from index pregnancies and none from subsequent pregnancies. A total of 50 (16.7%) women had at least one new clinical adverse event and 109 (36.5%) women had at least one incident abnormal laboratory finding. Twenty-two (7.3%) women switched to second line ART: of these 64.7% (8/17) had suppressed viral load and 54.9% (6/17) had undetectable viral load at 36 months. CONCLUSION: Most of the women who started TDF/3TC/EFV were retained in care and few infants were diagnosed with perinatally acquired HIV. Despite switching, women who switched to second line therapy continued to have higher viral loads suggesting that additional factors beyond TDF/3TC/EFV failure may have contributed to the switch. Ongoing support during the postpartum period is necessary to ensure retention in care and prevention of vertical transmission.

Role-Specific Curricular Needs for Identification and Management of Immune-Related Adverse Events.

Immune checkpoint inhibitors (ICIs) activate the immune system against cancer and have become standard of care for many cancers. With increased ICI use, their toxicities known as immune-related adverse events (irAEs) are becoming more common, but it is unclear how prepared relevant clinicians feel to diagnose and treat irAEs. The objective of this study was to assess irAE knowledge, confidence, and experience among generalists and oncology clinicians to guide future curricular interventions related to irAEs. A 25-item survey with questions assessing knowledge, experience level, confidence, and resource utilization regarding irAE diagnosis and management was sent to University of Chicago-affiliated (UChicago) internal medicine residents and hospitalists (inpatient irAE management) along with UChicago oncology fellows, attendings, nurse practitioners (NPs), and physician assistants (PAs) (inpatient and outpatient) as well as Chicago community oncologists (outpatient) in June 2022. Overall response rate was 37% (171/467). Knowledge scores averaged below 70% for all clinicians. "No idea" responses were most common with knowledge questions on steroid-sparing agent use and ICI use for patients with preexisting autoimmune disease. IrAE experience correlated with higher knowledge for oncology attendings (p = 0.015) and hematology/oncology NPs/PAs (p = 0.031). IrAE experience correlated with higher confidence for residents (p = 0.026), oncology fellows (p = 0.047), and hematology/oncology NPs/PAs (p = 0.042). Most commonly utilized resources were colleagues and UpToDate, and most clinicians were very likely to use online resources in the future. Knowledge and confidence gaps exist, and they were somewhat mitigated by experience. Future irAE curricula can fill these needs through online role-specific resources: irAE identification for generalists versus irAE identification and management for oncologists.

Adolescent and Young Adult Perspectives on Quality and Value in Health Care.

OBJECTIVE: To describe adolescent and young adult (AYA) perspectives on defining quality and value in health care and to gain understanding of their knowledge of value-based payment. METHODS: A text message-based survey was sent to a convenience sample of AYAs aged 14 to 24 in 2019. Participants were asked 4 open-ended questions: 1) how they would define "good health care," 2) what factors to consider in rating doctors, 3) whose opinions should matter most when rating doctors, and 4) the best ways to collect AYA opinions on doctors, and one yes/no question on their awareness of value-based payment. Analyses included descriptive demographic statistics and an inductive thematic approach with multivariable models comparing adolescent (14-18) and young adult (19-24) responses. RESULTS: Response rate was 61.0% (782/1283). Most participants were White (63.3%), female (53.3%), and adolescents (55.6%). Common themes from the first 2 questions included accessibility (specifically affordability), coverage benefits, and care experience (including compassion, respect, and clinical competence). Young adults more commonly mentioned affordability than adolescents (54.4% vs 43.3%, P = .001) and more commonly felt their opinion should matter more than their parents when rating doctors (80.6% vs 62.0%, P < .001). Only 21.0% of AYAs were familiar with the potential value-based link between physician payment and care quality. CONCLUSIONS: When considering quality and value in health care, AYAs expressed their desired agency in rating the quality of their care and clinicians. AYAs' perspectives on health care quality, including the importance of care accessibility and affordability, should be considered when designing youth-centered care delivery and value-based payment models.

Utilization of Text Messages to Supplement Rounding Communication: a Randomized Feasibility Study.

BACKGROUND: Fragmented communication with patients and families during hospitalizations often leaves patients confused about the daily plan. OBJECTIVE: To pilot a supplemental text message-based platform for improving bidirectional communication about the clinical plan and patients' goals. DESIGN: Randomized controlled trial PARTICIPANTS: Thirty adult patients, thirty caregivers of pediatric patients, and the interns caring for them on inpatient general medicine and pediatric services. INTERVENTIONS: Patients and caregivers were texted or emailed daily to report their personal goal and assess their understanding of the team's clinical plan. Interns were texted daily to report the team's clinical plan and to assess their understanding of the patient's personal goal. MAIN MEASURES: Primary outcomes were feasibility, defined as survey response rates, and acceptability. Secondary outcomes were patient comprehension of the clinical plan, trainee comprehension of the patient's goal, patient-centered communication scores, and educational satisfaction scores. KEY RESULTS: Thirty adult patients, thirty caregivers of pediatric patients, fourteen general medicine interns, and six general pediatric interns enrolled. Intervention feasibility was met, with survey response rates of 80% for general medicine trainees, 67% for general pediatric trainees, 58% for adult patients, and 70% for caregivers. Patients and caregivers in the intervention arm had higher understanding of medication changes (76% vs 50%, p = 0.02) and new consultations (90% vs 61%, p = 0.002). Interns had higher understanding of patients' goals in the intervention arm (93% vs 40%, p < 0.001), particularly for adult patients (97% vs 17%, p < 0.001). Caregivers rated communication higher regarding information to help make decisions (p = 0.04). Interviews demonstrated high acceptability. CONCLUSIONS: Our text message-based communication intervention was feasible and acceptable to all involved participants, with preliminary signals of efficacy. The intervention may contribute to improved understanding of medication changes and new consultations, as well as help in making decisions. A large, randomized efficacy trial of this intervention is warranted. Graphical abstract.

Growth and Neurodevelopment Outcomes in HIV-, Tenofovir-, and Efavirenz-Exposed Breastfed Infants in the PMTCT Option B+ Program in Malawi.

BACKGROUND: Pregnant and breastfeeding women in Option B+ in Malawi received antiretroviral drugs (ARVs) containing efavirenz (EFV) and tenofovir disoproxil fumarate (TDF). However, effects on growth, renal, bone metabolism, and neurodevelopment of long-term exposure to low doses of these drugs through breast milk in HIV-exposed infants are unclear. METHODS: Prospective cohorts of TDF-and-EFV-exposed and TDF-and-EFV-unexposed breastfed infants of HIV-infected and HIV-uninfected mothers in Option B+ were recruited in 2:1 ratio, respectively, followed from birth to 18 months. Infants with low birth weight, premature birth, and congenital abnormalities were excluded. Anthropometrics were assessed at birth, 6 weeks, 3, 6, 12, and 18 months. Neurodevelopment assessments used the Bayley Scales of Infant and Toddler Development III from 6 weeks. Creatinine, alkaline phosphatase, and phosphorus were assessed at 3, 6, and 12 months. RESULTS: Of 260 HIV-and-ARV-exposed and 125 HIV-and-ARV-unexposed infants enrolled at birth, 87% and 57%, 78% and 59%, 77% and 54%, 73% and 51%, and 65% and 43% completed 6-weeks, 3, 6, 12, and 18 months visits, respectively. There were no significant differences in the mean Z-scores for length-for-age, weight-for-age, weight-for-length, mid-upper arm circumference-for-age, and head circumference-for-age between groups except at 6-weeks for length-for-age. No bone fractures occurred. Neurodevelopment outcomes were similar between groups. Of creatinine, alkaline phosphatase, and serum phosphate measurements, 1.7%, 2.6%, and 3.3% reached any toxicity levels grades 1-4, respectively, with no differences between groups. CONCLUSION: Long-term exposure to EFV and TDF through breastfeeding in infants of HIV-infected mothers does not seem to result in significant growth, neurodevelopment, renal, or bone adverse outcomes. Data support safety of breastfeeding through 18 months within the Option B+ program.

Newly Named Klebsiella aerogenes (formerly Enterobacter aerogenes) Is Associated with Poor Clinical Outcomes Relative to Other Enterobacter Species in Patients with Bloodstream Infection.

Enterobacter aerogenes was recently renamed Klebsiella aerogenes This study aimed to identify differences in clinical characteristics, outcomes, and bacterial genetics among patients with K. aerogenes versus Enterobacter species bloodstream infections (BSI). We prospectively enrolled patients with K. aerogenes or Enterobacter cloacae complex (Ecc) BSI from 2002 to 2015. We performed whole-genome sequencing (WGS) and pan-genome analysis on all bacteria. Overall, 150 patients with K. aerogenes (46/150 [31%]) or Ecc (104/150 [69%]) BSI were enrolled. The two groups had similar baseline characteristics. Neither total in-hospital mortality (13/46 [28%] versus 22/104 [21%]; P = 0.3) nor attributable in-hospital mortality (9/46 [20%] versus 13/104 [12%]; P = 0.3) differed between patients with K. aerogenes versus Ecc BSI, respectively. However, poor clinical outcome (death before discharge, recurrent BSI, and/or BSI complication) was higher for K. aerogenes than Ecc BSI (32/46 [70%] versus 42/104 [40%]; P = 0.001). In a multivariable regression model, K. aerogenes BSI, relative to Ecc BSI, was predictive of poor clinical outcome (odds ratio 3.3; 95% confidence interval 1.4 to 8.1; P = 0.008). Pan-genome analysis revealed 983 genes in 323 genomic islands unique to K. aerogenes isolates, including putative virulence genes involved in iron acquisition (n = 67), fimbriae/pili/flagella production (n = 117), and metal homeostasis (n = 34). Antibiotic resistance was largely found in Ecc lineage 1, which had a higher rate of multidrug resistant phenotype (23/54 [43%]) relative to all other bacterial isolates (23/96 [24%]; P = 0.03). K. aerogenes BSI was associated with poor clinical outcomes relative to Ecc BSI. Putative virulence factors in K. aerogenes may account for these differences.

Female adherence self-efficacy before and after couple HIV testing and counseling within Malawi's Option B+ program.

Adherence self-efficacy, belief in one's ability to adhere to daily medication, is strongly associated with antiretroviral therapy (ART) adherence and preventing mother-to-child HIV transmission. Couple-based interventions could enhance self-efficacy and adherence. We assessed the relationship between couple HIV testing and counseling (cHTC) and adherence self-efficacy using a 100-point culturally-adapted adherence self-efficacy scale (ASES). Secondarily, we explored the relationship between ASES and ART adherence. Ninety HIV-positive pregnant women at an antenatal clinic in Lilongwe, Malawi were enrolled in an observational cohort study. They were assessed with ASES immediately before and one month after receiving cHTC. Median ASES scores were 100 (IQR 95, 100) before and 100 (IQR 99, 100) after cHTC; there was a significant median difference (p = 0.02) for participants before and after cHTC. This change in ASES scores was associated with the odds of self-reported ART adherence in the full population (OR 1.1, p = 0.01), and there was a trend in the same direction for participants with imperfect baseline ASES scores (OR 1.1, p = 0.2). In our population, adherence self-efficacy and ART adherence were both quite high, and those who had room to improve in self-efficacy may have benefited from cHTC, which in turn could impact ART adherence and ultimately mother-to-child transmission.

The impact of HIV couple testing and counseling on social support among pregnant women and their partners in Lilongwe, Malawi: an observational study.

Couples HIV testing and counseling (couple counseling) promotes safer sexual behaviors, increases communication between couples, and decreases HIV transmission. However, the impact of couple counseling on social support, critical for persons living with HIV, has not been examined. Ninety couples with a recently tested HIV-positive pregnant woman (female-positive couples) and 47 couples with a recently tested HIV-negative pregnant woman (female-negative couples) were enrolled in an observational study at an antenatal clinic in Malawi. Each couple member was assessed immediately before and one month after couple counseling for partner, family, and peer social support using the Multidimensional Scale of Perceived Social Support. Before couple counseling, social support was lower among women than men in both female-positive couples (ß = -10.00, p < .01) and female-negative couples (ß = -8.43, p < .01). After couple counseling, social support increased for women in female-positive couples (ß = 4.01, p < .01) and female-negative couples (ß = 4.69, p < .01) but not for men in either type of couple. Couple counseling could be an effective strategy to increase social support for women, including those with recent HIV diagnoses.

Individual, Partner, and Couple Predictors of HIV Infection among Pregnant Women in Malawi: A Case-Control Study.

We aimed to understand drivers of HIV-infection in pregnant women in Malawi. The study was conducted in antenatal and labor and delivery wards. HIV-infected women and their partners (cases) were frequency matched in a 1:2 ratio based on age and screening location to HIV-uninfected women and their partners (controls) in a prevalent case-control study. Characteristics associated with female HIV infection were assessed using logistic regression modeling. At screening, HIV-infected women were more likely to have partners outside Lilongwe than HIV-uninfected women (24% vs. 0%, p < 0.0001). Case females were more likely to have HIV-infected study partners than control females (75% vs. 4%, p < 0.0001). The odds of female HIV-infection were higher if either couple member reported ≥ 2 lifetime marriages (OR 9.0, CI 2.6-30.9) or ≥ 3 lifetime partners (OR 18.0, CI 3.1-103.6) and lower if either reported past couple HIV testing and counseling (OR 0.1, CI 0.04-0.3). Targeting women with migrating partners, promoting couple HIV testing and counseling, and limiting partners could slow HIV transmission.

Tying knots: an activity theory analysis of student learning goals in clinical education.

CONTEXT: Learning goal programmes are often created to help students develop self-regulated learning skills; however, these programmes do not necessarily consider the social contexts surrounding learning goals or how they fit into daily educational practice. OBJECTIVES: We investigated a high-frequency learning goal programme in which students generated and shared weekly learning goals with their clinical teams in core Year 3 clerkships. Our study explores: (i) how learning goals were incorporated into the clinical work, and (ii) the factors that influenced the use of students' learning goals in work-based learning. METHODS: We conducted semi-structured interviews with 14 students and 14 supervisors (attending physicians and residents) sampled from all participating core clerkships. Interviews were coded for emerging themes. Using cultural historical activity theory and knotworking as theoretical lenses, we developed a model of the factors that influenced students' learning goal usage in a work-based learning context. RESULTS: Students and supervisors often faced the challenge of reconciling contradictions that arose when the desired outcomes of student skill development, grading and patient care were not aligned. Learning goals could function as tools for developing new ways of acting that overcame those contradictions by facilitating collaborative effort between students and their supervisors. However, for new collaborations to take place, both students and supervisors had to engage with the goals, and the necessary patients needed to be present. When any one part of the system did not converge around the learning goals, the impact of the learning goals programme was limited. CONCLUSIONS: Learning goals are potentially powerful tools to mediate interactions between students, supervisors and patients, and to reconcile contradictions in work-based learning environments. Learning goals provide a means to develop not only learners, but also learning systems.