Validation of a Crisis Standards of Care Model for Prioritization of Limited Resources During the Coronavirus Disease 2019 Crisis in an Urban, Safety-Net, Academic Medical Center.

OBJECTIVES: The coronavirus disease 2019 pandemic has overwhelmed healthcare resources even in wealthy nations, necessitating rationing of limited resources without previously established crisis standards of care protocols. In Massachusetts, triage guidelines were designed based on acute illness and chronic life-limiting conditions. In this study, we sought to retrospectively validate this protocol to cohorts of critically ill patients from our hospital. DESIGN: We applied our hospital-adopted guidelines, which defined severe and major chronic conditions as those associated with a greater than 50% likelihood of 1- and 5-year mortality, respectively, to a critically ill patient population. We investigated mortality for the same intervals. SETTING: An urban safety-net hospital ICU. PATIENTS: All adults hospitalized during April of 2015 and April 2019 identified through a clinical database search. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 365 admitted patients, 15.89% had one or more defined chronic life-limiting conditions. These patients had higher 1-year (46.55% vs 13.68%; p < 0.01) and 5-year (50.00% vs 17.22%; p < 0.01) mortality rates than those without underlying conditions. Irrespective of classification of disease severity, patients with metastatic cancer, congestive heart failure, end-stage renal disease, and neurodegenerative disease had greater than 50% 1-year mortality, whereas patients with chronic lung disease and cirrhosis had less than 50% 1-year mortality. Observed 1- and 5-year mortality for cirrhosis, heart failure, and metastatic cancer were more variable when subdivided into severe and major categories. CONCLUSIONS: Patients with major and severe chronic medical conditions overall had 46.55% and 50.00% mortality at 1 and 5 years, respectively. However, mortality varied between conditions. Our findings appear to support a crisis standards protocol which focuses on acute illness severity and only considers underlying conditions carrying a greater than 50% predicted likelihood of 1-year mortality. Modifications to the chronic lung disease, congestive heart failure, and cirrhosis criteria should be refined if they are to be included in future models.

Continuity of Specialty Pharmacy Practice: A Survey of PGY-2 Pharmacy Residency Graduates.

BACKGROUND: Literature regarding career trajectory for postgraduate year 2 (PGY-2) pharmacy residency specialty-trained pharmacists is limited. OBJECTIVE: The objective of our study is to describe PGY-2 pharmacy residency training on career practice and satisfaction. METHODS: A cross-sectional study surveyed graduates of PGY-2 pharmacy residency programs. Respondents were identified by current PGY-2 residency program directors requesting participation from their program alumni. The primary outcome was whether PGY-2 residency-trained pharmacists continued working within their specialty or not. Secondary outcomes included alternative specialty areas, current satisfaction with their specialty, and the necessity of completing a PGY-2. RESULTS: Among 647 respondents, 84% completed their program in the past 6 years. The top 3 represented pharmacy specialties were critical care (19%), ambulatory care (14%), and oncology (13%). Most respondents continue to practice in the same specialty as their PGY-2 residency program (n = 572, 87%) compared with pharmacists who currently practice in other clinical specialties or areas of pharmacy (n = 83, 13%). Critical care (n = 28, 33%) had the largest specialty response no longer practicing in their PGY-2 residency program specialty with 42% (n = 12) now practicing within the emergency medicine specialty. The average satisfaction for their current specialty was 4.7 ± 0.82 (Likert scale of 1 = extremely dissatisfied to 5 = extremely satisfied). CONCLUSIONS: The vast majority PGY-2 pharmacy residency-trained pharmacists experienced training-practice concordance and are satisfied with their trained specialty. Among those with specialty training practice discordance, critical care training was most prevalent.

Physician Factors Associated with Polypharmacy and Potentially Inappropriate Medication Use.

BACKGROUND: Despite accumulating evidence about the harm of polypharmacy in family medicine, few studies have investigated factors related to polypharmacy. The objective of this study was to explore factors related to physicians' prescribing behavior. METHODS: We conducted a survey of physicians at 5 family medicine residency practices and a linked health record review of their patients ≥65 years old. The determinants of physicians' mean number of prescriptions and potentially inappropriate medications (PIMs) were examined using a generalized linear model. RESULTS: A total of 61 physicians (38 residents, 23 fellows/faculty) completed the survey, and 2103 visits by 932 patients seen by these physicians were analyzed. The mean numbers of prescriptions and PIMs per visit per physician were 9.50 and 0.46, respectively. After controlling for patient race and age, low prescribers were more likely to consider the number of medications (P = .007) and benefit/risk information for deprescribing (P = .017) when making prescribing decisions. Use of the Beers List was marginally significant in lower PIM prescribing (P = .05). Physicians' sex, duration of experience, and perceived confidence were not associated with prescribing patterns. CONCLUSIONS: Conscious consideration concerning the number of medications and benefit/risk information, as well as using the Beers List, were associated with less polypharmacy and fewer PIMs.

Transmembrane activator and calcium modulator and cyclophilin ligand interactor enhances CD40-driven plasma cell differentiation.

BACKGROUND: Transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) is a receptor used by B cell-activating factor of the TNF family and a proliferation-inducing ligand (APRIL) to induce isotype switching independently of CD40 and is mutated in patients with common variable immunodeficiency. OBJECTIVE: We sought to determine whether TACI and CD40 cooperate in inducing class switch recombination and immunoglobulin production. METHODS: Naive mouse B cells were stimulated with suboptimal concentrations of anti-CD40 plus IL-4 in the presence or absence of APRIL or anti-TACI. IgG(1) and IgE production was measured by means of ELISA. mRNA for Cgamma(1) and Cepsilon germ-line transcripts, activation-induced cytidine deaminase, and mature gamma(1) and epsilon transcripts were measured by means of RT-PCR. Plasmablasts were enumerated by using syndecan-1/CD138 staining. Interferon regulatory factor 4, B lymphocyte-induced maturation protein 1, and IL6 mRNA expression was measured by using quantitative PCR. RESULTS: TACI ligation enhanced IgG(1) and IgE secretion by naive murine B cells stimulated by anti-CD40 plus IL-4, with little effect on B-cell proliferation or class switch recombination. In contrast, TACI ligation of anti-CD40 plus IL-4-stimulated B cells induced a significant increase in syndecans-1/CD138-positive cells. TACI ligation caused a modest but significant increase in the expression of interferon regulatory factor 4, with no detectable change in B lymphocyte-induced maturation protein 1 expression. CONCLUSION: TACI and CD40 signaling converge to promote B-cell differentiation into plasmablasts. CLINICAL IMPLICATIONS: Our data suggest that TACI dysfunction could contribute to the impaired antibody response to T-dependent antigens in common variable immunodeficiency.

Racial differences in beliefs about genetic screening among patients at inner-city neighborhood health centers.

BACKGROUND: Genetic testing has the potential to identify persons at high risk for disease. Given the history of racial disparities in screening, early detection and accessing treatment, understanding racial differences in beliefs about genetics is essential to preventing disparities in some conditions. METHODS: In 2004, a sample of older adult patients from four inner-city health centers was surveyed to assess beliefs about genetic determinants of disease, genetic testing and religion. Logistic regression determined which beliefs were associated with race. RESULTS: Of the 314 respondents, 50% were African Americans. Most respondents thought that sickle cell disease, cystic fibrosis and diabetes are primarily genetic. African Americans were more likely than Caucasians to believe that genetic testing will lead to racial discrimination (Odds ratio (OR): 3.02, 95% confidence interval (CI): 1.5-6.0) and to think that all pregnant women should have genetic tests (OR=3.8, 95% CI: 1.7-8.6). African Americans were more likely to believe that God's Word is the most important source for moral decisions (OR: 3.6, 95% CI :1.5-8.7). CONCLUSION: African Americans and Caucasians differ in beliefs about genetic testing and the basis for moral decision-making. Acknowledging and understanding these differences may lead to better medical care.

TACI is mutant in common variable immunodeficiency and IgA deficiency.

The tumor necrosis factor receptor family member TACI (transmembrane activator and calcium-modulator and cyclophilin ligand interactor) mediates isotype switching in B cells. We found that 4 of 19 unrelated individuals with common variable immunodeficiency (CVID) and 1 of 16 individuals with IgA deficiency (IgAD) had a missense mutation in one allele of TNFRSF13B (encoding TACI). One of the four individuals with CVID had a single nucleotide insertion in the other TNFRSF13B allele. None of these mutations were present in 50 healthy subjects. TNFRSF13B mutations cosegregated with the phenotype of CVID or IgAD in family members of four index individuals that we studied. B cells from individuals with TACI mutations expressed TACI but did not produce IgG and IgA in response to the TACI ligand APRIL, probably reflecting impaired isotype switching. These results suggest that TACI mutations can result in CVID and IgAD.

TACI and BAFF-R mediate isotype switching in B cells.

The tumor necrosis factor family members BAFF and APRIL induce Ig isotype switching in human B cells. We analyzed the ability of BAFF and APRIL to induce isotype switching in murine B cells to IgG1, IgA, and IgE. APRIL and BAFF each engage two receptors, transmembrane activator and calcium-modulator and cytophilin ligand interactor (TACI) and B cell maturation antigen (BCMA), on B cells. In addition, BAFF engages a third receptor on B cells, BAFF-R. To determine the role of these receptors in isotype switching, we examined B cells from mice deficient in TACI, BCMA, and BAFF-R. The results obtained indicate that both TACI and BAFF-R are able to transduce signals that result in isotype switching.

Physician and practice factors related to influenza vaccination among the elderly.

BACKGROUND: Influenza vaccination rates among adults, especially in minority populations, remain below national goals of 90%. This study investigated in diverse settings, facilitators of and barriers to patient influenza vaccination from the physician's perspective. METHODS: Two-stage, stratified, random-cluster sampling was employed to select 71 clinicians from inner-city, rural, suburban, and Veterans Affairs (VA) practices, and a random sample of 925 of their patients aged >/=65 years. Questionnaires and interviews based on the PRECEDE-PROCEED framework assessed clinician factors. Associations among clinician beliefs, practice characteristics, patient beliefs, and self-reported influenza vaccination status were determined. RESULTS: The clinician response rate was 85% (60/71). Several factors of the PRECEDE-PROCEED framework were associated with higher influenza vaccination rates. For instance, patients at practices with express vaccination clinics had higher vaccination rates than at clinics without such immunization programs (87% v 76%, p =0.01). Using multivariate models, influenza vaccination status was related to several patient factors, including plans to receive influenza vaccination next year (p <0.001); belief that those who are not vaccinated will contract influenza (p =0.049); and history of being screened for colon cancer (p =0.023). Influenza vaccination status was also related to several physician factors, including awareness of recommendation to vaccinate asthmatics (p =0.024); agreement with these recommendations (p =0.004); and practice type and setting ("strata"), of which the VA was highest. CONCLUSION: Through proactive office systems and education, physicians may influence patients' intentions to be vaccinated and thereby increase influenza vaccination rates.