Assessing the Impact of Nutritional Support Teams on Clinical Outcomes: Compliance and Feasibility of Micronutrient Supplementation.

Background: Micronutrient (MN) supplementation has a positive impact on clinical outcomes. However, the evidence for the impact of MN supplementation remains controversial. Therefore, our study aims to assess the impact on nutritional outcomes according to exploring the implementation of MN support with multidisciplinary collaboration. Methods: This retrospective cohort study was conducted at a university hospital in Incheon, Korea. All patients referred to a nutrition support team (NST) between July and November 2022 were included. The NST reviews the MN protocol, which includes multivitamins and trace elements, based on international nutrient guidelines. All patients who were on nothing per oral and did not meet ≥70% of their nutritional requirements within 1 week were recommended MN supplements. Compliance with the MN protocol was evaluated, alterations in nutritional status based on the Nutrition Risk Screening 2002 (NRS 2002) scoring system and clinical outcomes were assessed after 7 day and at discharge. Multiple logistic regression analysis was used to identify factors associated with high nutritional risk in discharged patients. In addition, a sub-analysis was performed on changes in the nutritional of patients on the ward and in the ICU. Results: A total of 255 patients were eligible for analysis, with many patients requiring an MN supply of nothing per oral. The rate of implementation of MN supplementation was 50.2%. The findings indicate a significant decrease in the NRS 2002 score in the good compliance group with MN supplementation. No significant differences in protocol compliance were observed in terms of mortality, hospital stay, or length of stay in the intensive care unit. However, bad compliance with MN supplementation was correlated with risk factors for malnutrition at discharge. In subgroup analysis, nutritional status in the ICU and wards improved, with a significant difference between the two groups. Conclusions: The implementation of a MN supplementation protocol by a multidisciplinary NST is a feasible approach for improving the nutritional status of inpatients. Ensuring high compliance with this protocol is crucial, as poor compliance has been identified as a risk factor for malnutrition at discharge. Active intervention by the NST is essential to achieve optimal nutritional outcomes.

An update on the status of HSP90 inhibitors in cancer clinical trials.

The evolutionary conserved molecular chaperone heat shock protein 90 (HSP90) plays an indispensable role in tumorigenesis by stabilizing client oncoproteins. Although the functionality of HSP90 is tightly regulated, cancer cells exhibit a unique dependence on this chaperone, leading to its overexpression, which has been associated with poor prognosis in certain malignancies. While various strategies targeting heat shock proteins (HSPs) involved in carcinogenesis have been explored, only inhibition of HSP90 has consistently and effectively resulted in proteasomal degradation of its client proteins. To date, a total of 22 HSP90 inhibitors (HSP90i) have been tested in 186 cancer clinical trials, as reported by clinicaltrials.gov. Among these trials, 60 % have been completed, 10 % are currently active, and 30 % have been suspended, terminated, or withdrawn. HSP90 inhibitors (HSP90i) have been used as single agents or in combination with other drugs for the treatment of various cancer types in clinical trials. Notably, improved clinical outcomes have been observed when HSP90i are used in combination therapies, as they exhibit a synergistic antitumor effect. However, as single agents, HSP90i have shown limited clinical activity due to drug-related toxicity or therapy resistance. Recently, active trials conducted in Japan evaluating TAS-116 (pimitespib) have demonstrated promising results with low toxicity as monotherapy and in combination with the immune checkpoint inhibitor nivolumab. Exploratory biomarker analyses performed in various trials have demonstrated target engagement that suggests the potential for identifying patient populations that may respond favorably to the therapy. In this review, we discuss the advances made in the past 5 years regarding HSP90i and their implications in anticancer therapeutics. Our focus lies in evaluating drug efficacy, prognosis forecast, pharmacodynamic biomarkers, and clinical outcomes reported in published trials. Through this comprehensive review, we aim to shed light on the progress and potential of HSP90i as promising therapeutic agents in cancer treatment.

Effect of Multi-Dose Dispensing on Medication Regimen Complexity: A Real-World Study.

(1) Background: Older patients frequently require dosing aids, such as multi-dose medication dispensing (MMD) when they experience medication regimen complexity (MRC) with increased drug use. However, the evaluations of the efficacy of MMD alterations remain limited. (2) Methods: A total of 1120 patients were included in the study who were discharged from hospital during the study period of January to March 2019. The Medication Regimen Complexity Index (MRCI) score, a validated 65-item tool in Korea (MRCI-K), was used to quantify MRC. The original MRCI-K scores, representing the typical administration based on prescription information, were compared to recalculated MRCI-K scores measured following MMD during the hospital dispensing period. Differences in MRCI-K across the top four wards based on the numbers of discharge prescription medications were assessed, and the overall scores were categorized into quartiles to identify MMD's impact within each group. We confirmed the effect of MMD based on the patient's admission diagnosis depending on MRCI. (3) Results: The mean (standard deviation) of original MRCI scores was 26.2 (13.4), which decreased to 18.9 (8.8) after applying MMD. The decrease in MRCI scores after MMD was statistically significant in all four wards, with the Orthopedic Surgery ward showing the biggest decrease. The patients with MRCI scores in the highest quartile group demonstrated the greatest improvement as a result of the implementation of MMD. Respiratory diseases exhibited the highest baseline MRCI scores due to formulation complexity, and ear, nose, and throat patients demonstrated the most significant reduction in MRC after MMD, depending on the diagnostic criteria at administration. (4) Conclusions: We confirmed the reduction in MRC after applying MMD, as a significant decrease in MRCI-K scores. This study highlights the need to deliver effective pharmacist-led services to identify patients who would benefit from MMD.

Breast cancer screening among Medicare Advantage enrollees with dementia.

BACKGROUND: The decision to screen for breast cancer among older adults with dementia is complex and must often be individualized, as these individuals have an elevated risk of harm from over-screening. Medicare beneficiaries with dementia are increasingly enrolling in Medicare Advantage plans, which typically promote receipt of preventive cancer screening among their enrollees. This study examined the utilization of breast cancer screening among Medicare enrollees with dementia, in Medicare Advantage and in fee-for-service Medicare. METHODS: We conducted a pooled cross-sectional study of women with Alzheimer's disease and related dementias or cognitive impairment who were eligible for mammogram screening. We used Medicare Current Beneficiary Survey data to identify utilization of biennial mammogram screening between 2012 and 2019. Poisson regression models were used to estimate prevalence ratios of mammogram utilization and to calculate adjusted mammogram rates for Medicare Advantage and fee-for-service Medicare enrollees with dementia, and further stratified by rurality and by dual eligibility for Medicare and Medicaid. RESULTS: Mammogram utilization was 16% higher (Prevalence Ratio [PR] 1.16; 95% CI: 1.05, 1.29) among Medicare Advantage enrollees with dementia, compared to their counterparts in fee-for-service Medicare. Rural enrollees experienced no significant difference (PR 0.99; 95% CI: 0.72, 1.37) in mammogram use between Medicare Advantage and fee-for-service Medicare enrollees. Among urban enrollees, Medicare Advantage enrollment was associated with a 21% higher mammogram rate (PR 1.21; 95% CI: 1.09, 1.35). Dual-eligible Medicare Advantage enrollees had a 34% higher mammogram rate (PR 1.34; 95% CI: 1.10, 1.63) than dual-eligible fee-for-service Medicare enrollees. Among non-dual-eligible enrollees, adjusted mammogram rates were not significantly different (PR 1.11; 95% CI: 0.99, 1.24) between Medicare Advantage and fee-for-service Medicare enrollees. CONCLUSIONS: Medicare beneficiaries age 65-74 with Alzheimer's disease and related dementias or cognitive impairment had a higher mammogram use rate when they were enrolled in Medicare Advantage plans compared to fee-for-service Medicare, especially when they were dual-eligible or lived in urban areas. However, some Medicare Advantage enrollees with Alzheimer's disease and related dementias or cognitive impairment may have experienced over-screening for breast cancer.

Detecting DNA hydroxymethylation: exploring its role in genome regulation.

DNA methylation is one of the most extensively studied epigenetic regulatory mechanisms, known to play crucial roles in various organisms. It has been implicated in the regulation of gene expression and chromatin changes, ranging from global alterations during cell state transitions to locus-specific modifications. 5-hydroxymethylcytosine (5hmC) is produced by a major oxidation, from 5-methylcytosine (5mC), catalyzed by the ten-eleven translocation (TET) enzymes, and is gradually being recognized for its significant role in genome regulation. With the development of state-of-the-art experimental techniques, it has become possible to detect and distinguish 5mC and 5hmC at base resolution. Various techniques have evolved, encompassing chemical and enzymatic approaches, as well as thirdgeneration sequencing techniques. These advancements have paved the way for a thorough exploration of the role of 5hmC across a diverse array of cell types, from embryonic stem cells (ESCs) to various differentiated cells. This review aims to comprehensively report on recent techniques and discuss the emerging roles of 5hmC. [BMB Reports 2024; 57(3): 135-142].

Risk of sleep apnea associated with higher blood pressure among Chinese and Korean Americans.

OBJECTIVE: This study examines associations between sleep apnea risk and hypertension in a sample of immigrant Chinese and Korean Americans. DESIGN: The dataset included Chinese and Korean patients ages 50-75 recruited from primary care physicians' offices from April 2018 to June 2020 in the Baltimore-Washington DC Metropolitan Area (n = 394). Hypertension risk was determined using a combination of blood pressure measurements, self-reported diagnosis of hypertension by a medical professional, and/or self-reported use of antihypertensive medications. Linear regression models examined the associations between sleep apnea risk and blood pressure (systolic blood pressure [SBP] and diastolic blood pressure [DBP]). Poisson regression models examined associations sleep apnea risk and hypertension. Models controlled for body mass index (BMI), demographic, and socioeconomic risk factors. We further examined models for potential effect modification by age, gender, Asian subgroup, and obesity, as well as effect modification of daytime sleepiness on the association between snoring and hypertension risk. RESULTS: High risk of sleep apnea appeared to be associated positively with SBP (ß = 6.77, 95% CI: 0.00-13.53), but not with DBP. The association was positive for hypertension, but it was not statistically significant (PR = 1.11, 95% CI: 0.87-1.41). We did not find effect modification of the associations between sleep apnea and hypertension risk, but we did find that daytime sleepiness moderated the effect of snoring on SBP. Snoring was associated with higher SBP, primarily in the presence of daytime sleepiness, such that predicted SBP was 133.27 mmHg (95% CI: 126.52, 140.02) for someone with both snoring and daytime sleepiness, compared to 123.37 mmHg (95% CI: 120.40, 126.34) for someone neither snoring nor daytime sleepiness. CONCLUSION: Chinese and Korean immigrants living in the U.S. who are at high risk of sleep apnea have higher SBP on average, even after accounting for sociodemographic characteristics and BMI. CLINICAL TRAIL REGISTRATION: : NCT03481296, date of registration: 3/29/2018.

RFX4 is an intrinsic factor for neuronal differentiation through induction of proneural genes POU3F2 and NEUROD1.

Proneural genes play a crucial role in neuronal differentiation. However, our understanding of the regulatory mechanisms governing proneural genes during neuronal differentiation remains limited. RFX4, identified as a candidate regulator of proneural genes, has been reported to be associated with the development of neuropsychiatric disorders. To uncover the regulatory relationship, we utilized a combination of multi-omics data, including ATAC-seq, ChIP-seq, Hi-C, and RNA-seq, to identify RFX4 as an upstream regulator of proneural genes. We further validated the role of RFX4 using an in vitro model of neuronal differentiation with RFX4 knock-in and a CRISPR-Cas9 knock-out system. As a result, we found that RFX4 directly interacts with the promoters of POU3F2 and NEUROD1. Transcriptomic analysis revealed a set of genes associated with neuronal development, which are highly implicated in the development of neuropsychiatric disorders, including schizophrenia. Notably, ectopic expression of RFX4 can drive human embryonic stem cells toward a neuronal fate. Our results strongly indicate that RFX4 serves as a direct upstream regulator of proneural genes, a role that is essential for normal neuronal development. Impairments in RFX4 function could potentially be related to the development of various neuropsychiatric disorders. However, understanding the precise mechanisms by which the RFX4 gene influences the onset of neuropsychiatric disorders requires further investigation through human genetic studies.

Distress, multimorbidity, and complex multimorbidity among Chinese and Korean American older adults.

BACKGROUND: Studies suggest that distress is associated with various health conditions such as hypertension, asthma, diabetes, and coronary heart disease. However, only few studies focused on Asian Americans and little is known about the association with multiple comorbidity. METHODS: We conducted a cross-sectional analysis among 400 Chinese and Korean American participants (aged 50-75 years) of the STOP CRC randomized controlled trial. Perceived distress was assessed using the distress thermometer scale (range 0-10). Disease diagnosis was self-reported by the participants. Multimorbidity (MM) was defined as having ≥2 chronic conditions. Complex multimorbidity (CMM) was defined as having ≥3 of the following body system disorders: circulation disorder, endocrine-metabolic disorder, cancer, anxiety or depression, breathing problem, and other health problems. We performed logistic regression for CMM and Poisson regression with robust error variance for MM to estimate associations with distress, adjusting for potential confounders. RESULTS: The mean age was 58.4 years and mean distress score was 3.65. One-unit increase in distress score was associated with a 1.22-fold increase in the odds of having CMM (95% CI: 1.04-1.42). The magnitude of association slightly increased after additional adjustment for socioeconomic factors and health insurance status (OR: 1.29; 95% CI: 1.10-1.52). Higher distress score was positively associated with MM but the association was only marginally significant (PR: 1.04; 95% CI: 0.99-1.10), adjusting for socioeconomic factors and health insurance status. CONCLUSION: Our data suggest that higher perceived distress may be associated with simultaneous dysfunction of multiple distinct body systems among Chinese and Korean American older adults.

Risk of Sleep Apnea Is Associated with Abdominal Obesity Among Asian Americans: Comparing Waist-to-Hip Ratio and Body Mass Index.

OBJECTIVE: This study examines associations between the risk of sleep apnea and abdominal obesity (assessed by waist-to-hip ratio (WHR)) and general obesity (assessed by body mass index (BMI)) in a sample of Chinese and Korean American immigrants. METHODS: The dataset included Chinese and Korean participants aged 50-75 who were recruited from primary care physicians' clinics from April 2018 to June 2020 in the Baltimore-Washington D.C. Metropolitan area (n = 394). Abdominal obesity was determined if WHR ≥ 0.9 in men and WHR ≥ 0.85 in women. General obesity was determined if BMI ≥ 30. The risk of sleep apnea was determined by using the Berlin questionnaire. Poisson regression models examined associations between sleep apnea risk and obesity. Models controlled for socio-demographic risk factors. RESULTS: Twelve percent of the study participants were classified as a high risk for sleep apnea, and 75% had abdominal obesity whereas 6.4% had general obesity. High risk of sleep apnea was positively associated with abdominal obesity (PR = 1.31, 95% CI: 1.17-1.47) and general obesity (PR = 2.19, 95% CI: 0.90-5.32), marginally significant at p < 0.1). CONCLUSIONS: Chinese and Korean immigrants living in the USA who are at high risk of sleep apnea have higher abdominal obesity, even after accounting for sociodemographic characteristics. Abdominal obesity may be a better indicator than general obesity when examining the risk of sleep apnea among Asian Americans. INFORMATION ON CLINICAL TRIAL: Name: Screening To Prevent ColoRectal Cancer (STOP CRC) among At-Risk Asian American Primary Care Patients NCT Number: NCT03481296; Date of registration: March 29, 2018 URL: https://clinicaltrials.gov/ct2/show/NCT03481296?term=Sunmin+Lee&draw=2&rank=1.

Keratinized tissue augmentation using collagen-based soft tissue substitute with/without epidermal growth factor on buccally positioned implants: a pilot preclinical study.

OBJECTIVES: To investigate the effect of epithelial growth factor (EGF) with collagen matrix (CM) on the gain of KT for buccally positioned implants in dogs. MATERIALS AND METHODS: In five dogs, four implants were placed buccally with the whole part of KT excision on the buccal side (two implants per each hemi-mandible). After one month, KT augmentation was performed: 1) free gingival grafts (FGG), 2) collagen matrix (CM) only, 3) CM soaked with 1 µg/g of EGF, and 4) CM soaked with 10 µg/g of EGF (n = 5 in each group). The experimental animals were sacrificed three months post-KT augmentation. Clinical, histologic, and histomorphometric analyses were performed. RESULTS: The clinical KT zone was the highest in group FGG (5.16 ± 1.63 mm). Histologically, all groups presented buccal bony dehiscence. Regarding newly formed KT, no specific difference was found among the groups, but robust rete pegs formation in some specimens in group FGG. Histomorphometric KT height (4.66 ± 1.81 mm) and length (5.56 ± 2.25 mm) were the highest in group FGG, whereas similar increases were noted in the rest. The buccal soft tissue thickness at the coronal part of the implant did not exceed 2 mm in all groups. CONCLUSION: All groups presented increased KT zone, but FGG treatment was more favored. The addition of EGF to CM appeared not to enhance KT formation. CLINICAL RELEVANCE: FGG treatment was more favorable to re-establish the KT zone than other treatment modalities.

Do large thyroid nodules (≥4 cm) without suspicious cytology need surgery?

Background: Fine-needle aspiration biopsy (FNAB) is a good diagnostic tool for thyroid nodules; however, its high false-negative rate for giant nodules remains controversial. Many clinicians recommend surgical resection for nodules >4 cm owing to an increased risk of malignancy and an increased false-negative rate. This study aimed to examine the feasibility of this approach and investigate the incidence of malignancy in thyroid nodules >4 cm without suspicious cytology based on medical records in our center. Methods: This was a retrospective analysis of 453 patients that underwent preoperative FNAB for nodules measuring >4 cm between January 2017 and August 2022 at Severance Hospital, Seoul. Results: Among the 453 patients, 140 nodules were benign and 119 were indeterminate. Among 259 patients, the final pathology results were divided into benign (149) and cancerous (110) groups, and the prevalence of malignancy was 38.9% in the benign group and 55.5% in the indeterminate group. Among the malignancies, follicular carcinoma and follicular variants of papillary carcinoma were observed in 83% of the cytologically benign group and 62.8% of the indeterminate group. Conclusion: Preoperative FNAB had high false-negative rates and low diagnostic accuracy in patients with thyroid nodules >4 cm without suspicious cytologic features; therefore, diagnostic surgery may be considered a treatment option.

DMRT1 regulates human germline commitment.

Germline commitment following primordial germ cell (PGC) specification during early human development establishes an epigenetic programme and competence for gametogenesis. Here we follow the progression of nascent PGC-like cells derived from human embryonic stem cells in vitro. We show that switching from BMP signalling for PGC specification to Activin A and retinoic acid resulted in DMRT1 and CDH5 expression, the indicators of migratory PGCs in vivo. Moreover, the induction of DMRT1 and SOX17 in PGC-like cells promoted epigenetic resetting with striking global enrichment of 5-hydroxymethylcytosine and locus-specific loss of 5-methylcytosine at DMRT1 binding sites and the expression of DAZL representing DNA methylation-sensitive genes, a hallmark of the germline commitment programme. We provide insight into the unique role of DMRT1 in germline development for advances in human germ cell biology and in vitro gametogenesis.

A Single-Arm, Open-Label Phase II Study of ONC201 in Recurrent/Refractory Metastatic Breast Cancer and Advanced Endometrial Carcinoma.

BACKGROUND: ONC201 is a small molecule that can cause nonapoptotic cell death through loss of mitochondrial function. Results from the phase I/II trials of ONC201 in patients with refractory solid tumors demonstrated tumor responses and prolonged stable disease in some patients. METHODS: This single-arm, open-label, phase II clinical trial evaluated the efficacy of ONC201 at the recommended phase II dose (RP2D) in patients with recurrent or refractory metastatic breast or endometrial cancer. Fresh tissue biopsies and blood were collected at baseline and at cycle 2 day 2 for correlative studies. RESULTS: Twenty-two patients were enrolled; 10 patients with endometrial cancer, 7 patients with hormone receptor-positive breast cancer, and 5 patients with triple-negative breast cancer. The overall response rate was 0%, and the clinical benefit rate, defined by complete response (CR) + partial response (PR) + stable disease (SD), was 27% (n = 3/11). All patients experienced an adverse event (AE), which was primarily low grade. Grade 3 AEs occurred in 4 patients; no grade 4 AEs occurred. Tumor biopsies did not show that ONC201 consistently induced mitochondrial damage or alterations in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or the TRAIL death receptors. ONC201 treatment caused alterations in peripheral immune cell subsets. CONCLUSION: ONC201 monotherapy did not induce objective responses in recurrent or refractory metastatic breast or endometrial cancer at the RP2D dose of 625 mg weekly but had an acceptable safety profile (ClinicalTrials.gov Identifier: NCT03394027).

The iron chelator deferriferrichrysin induces paraptosis via extracellular signal-related kinase activation in cancer cells.

Cancer cells generally exhibit increased iron uptake, which contributes to their abnormal growth and metastatic ability. Iron chelators have thus recently attracted attention as potential anticancer agents. Here, we show that deferriferrichrysin (Dfcy), a natural product from Aspergillus oryzae acts as an iron chelator to induce paraptosis (a programmed cell death pathway characterized by ER dilation) in MCF-7 human breast cancer cells and H1299 human lung cancer cells. We first examined the anticancer efficacy of Dfcy in cancer cells and found that Dfcy induced ER dilation and reduced the number of viable cells. Extracellular signal-related kinase (ERK) was activated by Dfcy treatment, and the MEK inhibitor U0126, a small molecule commonly used to inhibit ERK activity, prevented the increase in ER dilation in Dfcy-treated cells. Concomitantly, the decrease in the number of viable cells upon treatment with Dfcy was attenuated by U0126. Taken together, these results demonstrate that the iron chelator Dfcy exhibits anticancer effects via induction of ERK-dependent paraptosis.

Rural-urban disparities in preventive breast and cervical cancer screening among women with early-onset dementia.

BACKGROUND: The early onset of Alzheimer's disease and related dementias (ADRD) before age 65 can introduce life and health care complications. Preserving an early-onset ADRD patient's daily functioning longer and delaying declines in health from non-ADRD conditions become important preventive goals. This study examined the differences in utilization of preventive cancer screenings between patients with and without early-onset ADRD, and compared utilization of the screenings in rural versus urban areas among women with early-onset ADRD in the United States. METHODS: We conducted a cross-sectional study of women aged 40 to 64 years eligible for mammogram and cervical cancer screenings using commercial insurance claims from 2012 to 2018. We measured the use of biennial mammogram among women 50 to 64 years old, and the use of triennial Pap smear test among women 40 to 64 years old. We used inverse probability weighted logistic regressions to estimate the odds of receiving preventive cancer screenings by the presence of early-onset ADRD or cognitive impairments (CI). We used multivariable logistic regressions to estimate the odds of receiving preventive cancer screenings by rural or urban residence among women with early-onset ADRD/CI. RESULTS: Among 6,349,308 women in the breast cancer screening sample (mean [SD] age, 56.52 [4.03] years), 36,131 had early-onset ADRD/CI (mean [SD] age, 57.99 [3.98] years). Among 6,583,088 women in the cervical cancer screening sample (mean [SD] age, 52.37 [6.81] years), 30,919 had early-onset ADRD/CI (mean [SD] age, 55.79 [6.22] years). Having early-onset ADRD/CI was associated with lower utilization of mammogram (OR: 0.92, 95% CI: 0.90-0.95). No significant difference was observed in Pap smear screening (OR: 0.99, 95% CI: 0.96-1.02) between patients with and without early-onset ADRD/CI. Among patients with early-onset ADRD/CI, those in rural areas were less likely than those in urban areas to have mammograms (OR: 0.91, 95% CI: 0.85-0.97) and Pap smears (OR: 0.65, 95% CI: 0.61-0.71). CONCLUSIONS: The observed pattern of rural-urban differences in cancer screening in our study emphasizes the need for efforts to promote evidence-based, individualized decision-making processes in the early-onset ADRD population.

Targeting Replication Stress and Chemotherapy Resistance with a Combination of Sacituzumab Govitecan and Berzosertib: A Phase I Clinical Trial.

PURPOSE: Despite promising preclinical studies, toxicities have precluded combinations of chemotherapy and DNA damage response (DDR) inhibitors. We hypothesized that tumor-targeted chemotherapy delivery might enable clinical translation of such combinations. PATIENTS AND METHODS: In a phase I trial, we combined sacituzumab govitecan, antibody-drug conjugate (ADC) that delivers topoisomerase-1 inhibitor SN-38 to tumors expressing Trop-2, with ataxia telangiectasia and Rad3-related (ATR) inhibitor berzosertib. Twelve patients were enrolled across three dose levels. RESULTS: Treatment was well tolerated, with improved safety over conventional chemotherapy-based combinations, allowing escalation to the highest dose. No dose-limiting toxicities or clinically relevant ≥grade 4 adverse events occurred. Tumor regressions were observed in 2 patients with neuroendocrine prostate cancer, and a patient with small cell lung cancer transformed from EGFR-mutant non-small cell lung cancer. CONCLUSIONS: ADC-based delivery of cytotoxic payloads represents a new paradigm to increase efficacy of DDR inhibitors. See related commentary by Berg and Choudhury, p. 3557.

Effect of Pharmacist-Led Intervention in Elderly Patients through a Comprehensive Medication Reconciliation: A Randomized Clinical Trial.

PURPOSE: Polypharmacy can cause drug-related problems, such as potentially inappropriate medication (PIM) use and medication regimen complexity in the elderly. This study aimed to investigate the feasibility and effectiveness of a collaborative medication review and comprehensive medication reconciliation intervention by a pharmacist and hospitalist for older patients. MATERIALS AND METHODS: This comprehensive medication reconciliation study was designed as a prospective, open-label, randomized clinical trial with patients aged 65 years or older from July to December 2020. Comprehensive medication reconciliation comprised medication reviews based on the PIM criteria. The discharge of medication was simplified to reduce regimen complexity. The primary outcome was the difference in adverse drug events (ADEs) throughout hospitalization and 30 days after discharge. Changes in regimen complexity were evaluated using the Korean version of the medication regimen complexity index (MRCI-K). RESULTS: Of the 32 patients, 34.4% (n=11/32) reported ADEs before discharge, and 19.2% (n=5/26) ADEs were reported at the 30-day phone call. No ADEs were reported in the intervention group, whereas five events were reported in the control group (p=0.039) on the 30-day phone call. The mean acceptance rate of medication reconciliation was 83%. The mean decreases of MRCI-K between at the admission and the discharge were 6.2 vs. 2.4, although it was not significant (p=0.159). CONCLUSION: As a result, we identified the effect of pharmacist-led interventions using comprehensive medication reconciliation, including the criteria of the PIMs and the MRCI-K, and the differences in ADEs between the intervention and control groups at the 30-day follow-up after discharge in elderly patients. TRIAL REGISTRATION: (Clinical trial number: KCT0005994).

A hypothetical intervention of the timing of dietary intake on weight and body composition after initial weight loss.

OBJECTIVE: This study estimated the effect of hypothetical interventions of higher and lower frequency of breakfast and post-dinner snack consumption (breakfast consumption 0-4 vs. 5-7 times/week and post-dinner snack consumption 0-2 vs. 3-7 times/week) on changes in body weight and composition over 18 months after a successful 6-month standard behavioral weight-loss program. METHODS: The study analyzed data from the Innovative Approaches to Diet, Exercise and Activity (IDEA) study. RESULTS: If all participants consumed a breakfast meal 5 to 7 times/week over 18 months, they would have regained 2.95 kg of body weight on average (95% CI: 2.01 to 3.96), which is 0.59 kg (95% CI: -0.86 to -0.32) lower than if all participants consumed breakfast 0 to 4 times/week. If all participants consumed a post-dinner snack 0 to 2 times/week, they would have regained 2.86 kg of body weight on average (95% CI: 0.99 to 5.25), which is 0.83 kg (95% CI: -1.06 to -0.59) lower than if all consumed a post-dinner snack 3 to 7 times/week. CONCLUSIONS: Regular breakfast consumption and minimizing post-dinner snacking may modestly mitigate weight and body fat regain over 18 months after initial weight loss.

Predicted Health Literacy Disparities Between Immigrant and US-Born Racial/Ethnic Minorities: a Nationwide Study.

BACKGROUND: Racial/ethnic minorities in the USA exhibit reduced health literacy (HL) proficiency, leading to increased health disparities. It is unclear how the effect of birth status (immigrant/US-born) affects HL proficiency among racial/ethnic minorities. OBJECTIVE: To identify the direct, indirect, and total effects of birth status on HL proficiency among a nationally representative population of racial/ethnic minority adults in the USA. DESIGN: A cross-sectional study of 2019 data from the Medial Expenditure Panel Survey. PARTICIPANTS: Participants aged 18 or older reporting as racial/ethnic minorities (Black, Asian, or Hispanic) with non-missing data. MAIN MEASURES: We predicted HL proficiency for each participant using a previously published model. Path analysis was used to estimate the direct, indirect, and total effects of birth status on HL proficiency, accounting for several other covariates. Prevalence ratios were estimated using adjusted Poisson regression to evaluate differences in the "Below Basic" HL category. KEY RESULTS: An estimated weighted 81,092,505 participants were included (57.5% US-born, 42.5% immigrant). More racial/ethnic minority immigrant participants fell into the lowest category of HL proficiency, "Below Basic" (14.3% vs 5.5%, p < 0.05). Results of the path analysis indicated a significant, negative direct effect of birth status on HL proficiency (standardized coefficient = - 0.24, SE = 0.01, 95%CI: - 0.26, - 0.23) in addition to an indirect effect mediated through insurance status, health-system resource use, and English proficiency. The total effect of birth status on HL proficiency was found to be - 0.29. The immigrant participant group had 81% higher prevalence of falling into the "Below Basic" HL category compared to US-born participants (prevalence ratio = 1.81, 95%CI: 1.52, 2.16). CONCLUSIONS: Immigrant status has a strong, negative, direct effect on HL proficiency among racial/ethnic minorities in the USA. This may be a result of barriers that prevent equitable access to resources that improve proper HL proficiency. US policymakers may consider several methods to reduce this disparity at the health-system-, provider-, and patient-levels.

Frequency of Consuming Breakfast Meals and After-Dinner Snacks Is not Associated with Postmenopausal Breast Cancer Risk: Women's Health Initiative Observational Study.

BACKGROUND: There has been little investigation into how the timing of meals and eating occasions associates with postmenopausal breast cancer risk. OBJECTIVE: We examined the association between the frequency of consuming breakfast meals and after-dinner snacks with the risk for postmenopausal breast cancer. METHODS: A prospective analysis of 74,825 postmenopausal women aged 49 to 81 y from the Women's Health Initiative Observational Study cohort. Breakfast and after-dinner snack intake were assessed at year 1 examination. Risk for invasive and in situ breast cancer diagnosed before 28 February 2020 was modeled with multivariable Cox proportional hazards regression models according to breakfast and after-dinner snack consumption frequencies. The models were adjusted for age, self-identified race/ethnicity, education, income, physical activity, smoking, alcohol intake, diet quality score (Healthy Eating Index 2015), energy intake, diabetic status, hormone therapy, and BMI. RESULTS: During the follow-up period, 5313 participants were diagnosed with invasive breast cancer and 1197 participants with in situ breast cancer. Compared with participants who did not eat breakfast, those with daily breakfast consumption was not associated with invasive breast cancer (HR: 1.04; 95% CI: 0.9, 1.19) nor in situ (HR: 1.25; 95% CI: 0.91, 1.74) breast cancer. There were monotonic higher point estimates of in situ breast cancer for each higher category of breakfast intake from 0 to 7 times per week (P-trend = 0.04, Wald test). Compared with consumption of daily after-dinner snacks, avoidance of after-dinner snacks was not associated with invasive breast cancer (HR: 0.97; 95% CI: 0.87, 1.08) nor in situ (HR: 1.12; 95% CI: 0.89, 1.42) breast cancer. CONCLUSIONS: There was no association between intake frequency of breakfast meals or after-dinner snack habits and with risk of breast cancer in postmenopausal women.