Aligning patient values and code status: Choice of Diction's Effect (CODE) study.

BACKGROUND: Decisions regarding resuscitation after cardiac arrest are critical from ethical, patient satisfaction, outcome, and healthcare cost standpoints. Physician-reported discussion barriers include topic discomfort, fear of time commitment, and difficulty articulating end-of-life concepts. The influence of language used in these discussions has not been tested. This study explored whether utilizing the alternate term "allow (a) natural death" changed code status decisions in hospitalized patients versus "do not resuscitate" (DNR). METHODS: All patients age 65 and over admitted to a general medicine hospital teaching service were screened (English-speaking, not ICU-level care, no active psychiatric illness, no substance misuse, no active DNR). Participants were randomized to resuscitation discussions with either DNR or "allow natural death" as the "no code" phrasing. Outcomes included patient resuscitation decision, satisfaction with and duration of the conversation, and decision correlation with illness severity and predicted resuscitation success. RESULTS: 102 participants were randomized to the "allow natural death" (N = 49) or DNR (N = 53) arms. The overall "no code" rate for our sample of hospitalized general medicine inpatients age >65 was 16.7%, with 13% in the DNR and 20.4% in the "allow natural death" arms (p = 0.35). Discussion length was similar in the DNR and "allow natural death" arms (3.9 + 3.2 vs. 4.9 + 3.9 minutes), and not significantly different (p = 0.53). Over 90% of participants were highly satisfied with their code status decision, without difference between arms (p = 0.49). CONCLUSIONS: Participants' code status discussions did not differ in "no code" rate between "allow natural death" and DNR arms but were short in length and had high patient satisfaction. Previously reported code status discussion barriers were not encountered. It is appropriate to screen code status in all hospitalized patients regardless of phrasing used.

Factors associated with attitudes toward research MRI in older Asian Americans.

INTRODUCTION: South Asian (SA) and East Asian (EA) older adults represent the fastest-growing racial/ethnic groups of Americans at risk for dementia. While recruiting older SA adults into a brain health study, we encountered unexpected hesitancy toward structural brain magnetic resonance imaging (MRI) analysis and stigmatizing attitudes related to internal locus of control (LoC) for future dementia risks. We hypothesized that support for MRI-related research was influenced by these attitudes as well as personal MRI experience, perceived MRI safety, and concerns for personal risk for future dementia/stroke. METHODS: We developed a brief cross-sectional survey to assess older adults' MRI experiences and perceptions, desire to learn of six incidental findings of increasing impact on health, and attitudes related to dementia (including LoC) and research participation. We recruited a convenience sample of 256 respondents (74% reporting as 50+) from the New Jersey/New York City area to complete the survey (offered in English, Chinese, Korean, and Spanish) and modeled the proportional odds (PO) for favorable attitudes toward research activities. RESULTS: Seventy-seven SA and 84 EA respondents were analyzed alongside 95 White, Black, or Hispanic adults. White (PO = 2.54, p = 0.013) and EA (PO = 2.14, p = 0.019) respondents were both more likely than SA respondents to endorse healthy volunteers' participation in research, and the difference between White and SA respondents was mediated by the latter's greater internal LoC for dementia risks. EA respondents had more worries for future dementia/stroke than SA respondents (p = 0.006) but still shared SA respondents' lower wish (measured by proportion of total) to learn of incidental MRI findings. DISCUSSION: SA-and EA compared to SA-older adults had low desire to learn of incidental MRI findings but had different attitudes toward future dementia/stroke risks. A culturally appropriate protocol to disclose incidental MRI findings may improve SA and EA participation in brain health research. Highlights: Older Asian Americans have limited interest in incidental findings on research MRISouth Asians are most likely to attribute dementia to people's own behaviorsSouth Asians' attitudes mediate lower support for healthy volunteers in researchSouth and East Asians differ in dementia worries and research-related attitudes.

Electronic Health Record Prompt to Improve Lung Cancer Screening in Primary Care.

INTRODUCTION: Lung cancer is the leading cause of cancer death in the U.S. Combusted tobacco use, the primary risk factor, accounts for 90% of all lung cancers. Early detection of lung cancer improves survival, yet lung cancer screening rates are much lower than those of other cancer screening tests. Electronic health record (EHR) systems are an underutilized tool that could improve screening rates. METHODS: This study was conducted in the Rutgers Robert Wood Johnson Medical Group, a university-affiliated network in New Brunswick, NJ. Two novel EHR workflow prompts were implemented on July 1, 2018. These prompts included fields to determine tobacco use and lung cancer screening eligibility and facilitated low-dose computed tomography ordering for eligible patients. The prompts were designed to improve tobacco use data entry, allowing for better lung cancer screening eligibility identification. Data were analyzed in 2022 retrospectively for the period July 1, 2017 to June 30, 2019. The analyses represented 48,704 total patient visits. RESULTS: The adjusted odds of patient record completeness to determine eligibility for low-dose computed tomography (AOR=1.19, 95% CI=1.15, 1.23), eligibility for low-dose computed tomography (AOR=1.59, 95% CI=1.38, 1.82), and whether low-dose computed tomography was ordered (AOR=1.04, 95% CI=1.01, 1.07) all significantly increased after the electronic medical record prompts were implemented. CONCLUSIONS: These findings show the utility and benefit of EHR prompts in primary care settings to increase identification for lung cancer screening eligibility as well as increased low-dose computed tomography ordering.

Lung Cancer Screening Knowledge and Perceived Barriers Among Physicians in the United States.

Introduction: Lung cancer remains the leading cause of cancer death in the United States and has historically been detected late in its course. Low-dose computed tomography scan (LDCT) reduces lung cancer mortality by 20% and is currently recommended by clinical practice guidelines. However, compared with other cancer screening modalities, LDCT utilization remains low. This study surveyed office-based primary care physicians across the United States to better understand LDCT utilization. Methods: A total of 1500 family and internal medicine physicians selected from the American Medical Association's physician master file were surveyed between April and July 2019 regarding LDCT practices, eligibility, clinical scenarios, and perceived barriers. Results: The American Association for Public Opinion Research response rate 3 was 59% (652 respondents); 599 completed supplemental questions regarding lung cancer screening. A total of 88% of respondents discussed LDCT in the previous year, and 78% had ordered at least one LDCT. Most (59%) knew the tobacco exposure criteria for LDCT and correctly identified appropriate clinical scenarios (49%-86% responded correctly). Less than half of respondents correctly identified the age eligibility criteria (44%-45% responded correctly). In general, male physicians, those who graduated after 1990, and family medicine physicians were more likely to report accurate knowledge regarding LDCT eligibility. The top perceived barriers to LDCT were cost to the patient (48% identified as a major barrier), insurance not covering screening (46% major), and patients being unaware of lung cancer screening (40% major). Conclusion: Knowledge and practices about lung cancer screening are improving, though remain suboptimal. The most common barriers remain cost or insurance-based and suggest the need for a systems-based response to increase awareness and reduce the underutilization of LDCT.

Detection of ESR1 mutations in circulating cell-free DNA from patients with metastatic breast cancer treated with palbociclib and letrozole.

ESR1 mutations are frequently acquired in hormone-resistant metastatic breast cancer (MBC). CDK4/6 inhibition along with endocrine therapy is a promising strategy in hormone receptor-positive MBC. However, the incidence and impact of ESR1 mutations on clinical outcome in patients treated with CDK4/6 inhibitors have not been defined. In this study, we evaluated the frequency of ESR1 mutations in cfDNA from 16 patients with MBC undergoing palbociclib and letrozole therapy. Four common ESR1 mutations (D538G, Y537C, Y537N, and Y537S) were analyzed in serial blood draws using ddPCR. Mutation rate was 31.3% (5/16) (n=3; de novo, n=2; acquired). D538G was the most frequent mutation (n=3), followed by Y537N and Y537S (n=2). One patient showed multiple ESR1 mutations. Mutations were enriched during therapy. Progression-free survival (PFS) and overall survival (OS) were similar in patients with and without mutation detected at any given time during treatment. However, PFS was significantly shorter in patients with ESR1 mutation at initial blood draw (3.3 versus 9.0 months, P-value=0.038). In conclusion, ESR1 mutation prevalence is consistent with recent studies in hormone-refractory breast cancer. Further, treatment with palbociclib and letrozole does not prevent selection of ESR1 mutations in later lines of therapy. Larger studies are warranted to validate these findings.

The metalloprotease of Listeria monocytogenes is regulated by pH.

Listeria monocytogenes is an intracytosolic bacterial pathogen. Among the factors contributing to escape from vacuoles are a phosphatidylcholine phospholipase C (PC-PLC) and a metalloprotease (Mpl). Both enzymes are translocated across the bacterial membrane as inactive proproteins, whose propeptides serve in part to maintain them in association with the bacterium. We have shown that PC-PLC maturation is regulated by Mpl and pH and that Mpl maturation occurs by autocatalysis. In this study, we tested the hypothesis that Mpl activity is pH regulated. To synchronize the effect of pH on bacteria, the cytosolic pH of infected cells was manipulated immediately after radiolabeling de novo-synthesized bacterial proteins. Immunoprecipitation of secreted Mpl from host cell lysates revealed the presence of the propeptide and catalytic domain in samples treated at pH 6.5 but not at pH 7.3. The zymogen was present in small amounts under all conditions. Since proteases often remain associated with their respective propeptide following autocatalysis, we aimed at determining whether pH regulates autocatalysis or secretion of the processed enzyme. For this purpose, we used an Mpl construct that contains a Flag tag at the N terminus of its catalytic domain and antibodies that can distinguish N-terminal and non-N-terminal Flag. By fluorescence microscopy, we observed the Mpl zymogen associated with the bacterium at physiological pH but not following acidification. Mature Mpl was not detected in association with the bacterium at either pH. Using purified proteins, we determined that processing of the PC-PLC propeptide by mature Mpl is also pH sensitive. These results indicate that pH regulates the activity of Mpl on itself and on PC-PLC.