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ESMO Open Jun 2024Paclitaxel resistance limits durability of response in patients with initial clinical benefit. Overexpression of spleen tyrosine kinase (SYK) has been proposed as a...
BACKGROUND
Paclitaxel resistance limits durability of response in patients with initial clinical benefit. Overexpression of spleen tyrosine kinase (SYK) has been proposed as a possible resistance mechanism. This phase I trial evaluated the safety and preliminary activity of the SYK inhibitor TAK-659 combined with paclitaxel in patients with advanced taxane-refractory solid tumors.
PATIENTS AND METHODS
Patients with advanced solid tumors and prior progression on taxane-based therapy received intravenous infusion of paclitaxel on days 1, 8, and 15 plus oral TAK-659 daily in 28-day cycles. The dose-escalation phase included six cohorts treated at different dose levels; the dose-expansion phase included patients with ovarian cancer treated at the highest dose level. Toxicity was graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Efficacy was evaluated using Response Evaluation Criteria in Solid Tumors version 1.1.
RESULTS
Our study included 49 patients. Maximum tolerated dose was not reached, but higher rates of adverse events were observed at higher dose levels. There were no treatment-related deaths. The most common treatment-related adverse events of any grade were increased aspartate aminotransferase (n = 31; 63%), increased alanine aminotransferase (n = 26; 53%), decreased neutrophil count (n = 26; 53%), and decreased white blood cell count (n = 26; 53%). Most adverse events were either grade 1 or 2. In the 44 patients with evaluable disease, 12 (27%) had stable disease as the best overall response, including three patients with prolonged stable disease, and 4 patients (9%) achieved a partial response.
CONCLUSIONS
The combination of paclitaxel and TAK-659 showed preliminary activity possibly overcoming resistance to taxane-based therapy as well as a tolerable safety profile in patients with advanced solid tumors.
Topics: Humans; Paclitaxel; Female; Middle Aged; Aged; Neoplasms; Male; Adult; Antineoplastic Combined Chemotherapy Protocols; Drug Resistance, Neoplasm; Taxoids; Maximum Tolerated Dose; Syk Kinase
PubMed: 38914452
DOI: 10.1016/j.esmoop.2024.103486 -
The Journal of Dermatological Treatment Dec 2024This noninterventional, cross-sectional survey estimated the prevalence and consequences of residual disease in apremilast-treated US adults with moderate to severe...
This noninterventional, cross-sectional survey estimated the prevalence and consequences of residual disease in apremilast-treated US adults with moderate to severe psoriasis. Residual disease was defined as experiencing moderate, severe, or very severe psoriasis over the past week or having ≥3% body surface area affected, despite treatment. Factors associated with residual disease and its effects on flare-ups, humanistic burden, and health care resource utilization (HCRU) were evaluated. Of the 344 apremilast users (mean age, 44.9 years; female, 65.4%), 174 (50.6%) had residual disease. It was more prevalent in Black versus White participants (OR, 4.5; 95% CI, 1.6-12.2), those receiving apremilast for ≥1 versus <1 year (OR, 16.5; 95% CI, 7.9-34.4), those reporting ≥2 versus 0 to 1 flare-ups during the past 3 months (OR, 10.0; 95% CI, 5.0-20.1), and those with ≥4 versus 1 to 3 body regions affected at time of survey (OR, 8.6; 95% CI, 3.8-19.8). Participants with versus without residual disease self-reported more psoriasis flare-ups over the past 3 months (mean, 4.7 vs 0.9; < .001) and more anxiety (89.7% vs 50.0%; < .001) and depression (69.0% vs 23.6%; < .001) over the past 30 days. Generally, participants with versus without residual disease also had significantly more comorbidities and greater HCRU.
Topics: Humans; Psoriasis; Thalidomide; Female; Male; Cross-Sectional Studies; Adult; Middle Aged; United States; Prevalence; Severity of Illness Index; Anti-Inflammatory Agents, Non-Steroidal; Surveys and Questionnaires; Symptom Flare Up
PubMed: 38914422
DOI: 10.1080/09546634.2024.2366532 -
The Journal of Dermatological Treatment Dec 2024Providers who treat patients with psoriasis are unevenly distributed across the United States, with more in urban than rural areas. This retrospective claims analysis...
PURPOSE
Providers who treat patients with psoriasis are unevenly distributed across the United States, with more in urban than rural areas. This retrospective claims analysis characterized disparities in access to care for US patients with psoriasis using data from the STATinMED database.
MATERIALS AND METHODS
Patients (≥18 years) had ≥1 claim with a psoriasis diagnosis and ≥1 claim for advanced psoriasis therapy (apremilast or biologics) between January 2015 and December 2019. Access to psoriasis care was determined using the proportion of patients with 0, 1-2, 3-4, or ≥5 providers in their local area.
RESULTS
Overall, 179,688 patients were included in the analysis, 80.0% in urban areas. The access ratio was highest for internal medicine physicians (97.1 per 1000 patients) and lowest for dermatologists (4.4 per 1000 patients) and family practice physicians (3.9 per 1000 patients). In urban areas, 41% of patients had access to ≥5 dermatologists versus 7% in rural areas. Whereas 2% of patients in urban areas sought care outside of their local area, 75% in rural areas did so. Use of advanced therapies was low in all states (<17%).
CONCLUSION
Access to psoriasis-treating providers varied widely. Regardless of access, utilization of advanced treatments was low, suggesting the need for effective, easy-to-administer therapy.
Topics: Humans; Psoriasis; United States; Health Services Accessibility; Retrospective Studies; Female; Male; Middle Aged; Healthcare Disparities; Adult; Rural Population; Aged; Urban Population; Young Adult
PubMed: 38914420
DOI: 10.1080/09546634.2024.2365820 -
International Journal of Medical... Jun 2024This study aims to assess the intercultural competence of general hospital workers in South Korea by examining their understanding of cultural diversity in healthcare...
OBJECTIVES
This study aims to assess the intercultural competence of general hospital workers in South Korea by examining their understanding of cultural diversity in healthcare and to identify factors influencing their intercultural competence.
METHODS
A cross-institutional survey was conducted with 439 participants from four South Korean general hospitals, employing inferential statistics such as one-way Analysis of Variance, Mann-Whitney U, and Kruskal-Wallis test followed by post-hoc, and multiple linear regression analyses.
RESULTS
While 85% (n = 362) of participants acknowledged the significance of multiculturalism in Korean society, only 11% (n = 49) felt competent in treating multicultural patients. Additionally, 72% (n = 315) experienced significant linguistic difficulties in medical communication. Multiple regression analysis identified advanced English competency, multicultural training experiences, and peer support with organizational awareness of multicultural importance as significant positive contributors to intercultural competence.
CONCLUSIONS
Despite recognizing the importance of multiculturalism, general hospital workers face significant language barriers and low self-efficacy in providing care to multicultural patients. To address these challenges, hospitals should designate resident translators for culturally appropriate communication. Furthermore, a tri-tiered training approach is proposed to enhance the five domains of intercultural competence among general hospital workers in Korea, including overarching multicultural training, occupation-specific courses, and long-term managerial programs aimed at managing cultural diversity effectively in healthcare settings.
Topics: Humans; Republic of Korea; Cultural Competency; Cultural Diversity; Female; Male; Adult; Surveys and Questionnaires; Communication Barriers; Middle Aged; Personnel, Hospital; Cross-Sectional Studies; Attitude of Health Personnel; Hospitals, General; Communication
PubMed: 38914074
DOI: 10.5116/ijme.6667.2270 -
JMIR Public Health and Surveillance Jun 2024The COVID-19 pandemic has profoundly affected out-of-hospital cardiac arrest (OHCA) and disrupted the chain of survival. Even after the end of the pandemic, the risk of... (Observational Study)
Observational Study
BACKGROUND
The COVID-19 pandemic has profoundly affected out-of-hospital cardiac arrest (OHCA) and disrupted the chain of survival. Even after the end of the pandemic, the risk of new variants and surges persists. Analyzing the characteristics of OHCA during the pandemic is important to prepare for the next pandemic and to avoid repeated negative outcomes. However, previous studies have yielded somewhat varied results, depending on the health care system or the specific characteristics of social structures.
OBJECTIVE
We aimed to investigate and compare the incidence, outcomes, and characteristics of OHCA during the prepandemic and pandemic periods using data from a nationwide multicenter OHCA registry.
METHODS
We conducted a multicenter, retrospective, observational study using data from the Korean Cardiac Arrest Resuscitation Consortium (KoCARC) registry. This study included adult patients with OHCA in South Korea across 3 distinct 1-year periods: the prepandemic period (from January to December 2019), early phase pandemic period (from July 2020 to June 2021), and late phase pandemic period (from July 2021 to June 2022). We extracted and contrasted the characteristics of patients with OHCA, prehospital time factors, and outcomes for the patients across these 3 periods. The primary outcomes were survival to hospital admission and survival to hospital discharge. The secondary outcome was good neurological outcome.
RESULTS
From the 3 designated periods, a total of 9031 adult patients with OHCA were eligible for analysis (prepandemic: n=2728; early pandemic: n=2954; and late pandemic: n=3349). Witnessed arrest (P<.001) and arrest at home or residence (P=.001) were significantly more frequent during the pandemic period than during the prepandemic period, and automated external defibrillator use by bystanders was lower in the early phase of the pandemic than during other periods. As the pandemic advanced, the rates of the first monitored shockable rhythm (P=.10) and prehospital endotracheal intubation (P<.001) decreased significantly. Time from cardiac arrest cognition to emergency department arrival increased sequentially (prepandemic: 33 min; early pandemic: 35 min; and late pandemic: 36 min; P<.001). Both survival and neurological outcomes worsened as the pandemic progressed, with survival to discharge showing the largest statistical difference (prepandemic: 385/2728, 14.1%; early pandemic: 355/2954, 12%; and late pandemic: 392/3349, 11.7%; P=.01). Additionally, none of the outcomes differed significantly between the early and late phase pandemic periods (all P>.05).
CONCLUSIONS
During the pandemic, especially amid community COVID-19 surges, the incidence of OHCA increased while survival rates and good neurological outcome at discharge decreased. Prehospital OHCA factors, which are directly related to OHCA prognosis, were adversely affected by the pandemic. Ongoing discussions are needed to maintain the chain of survival in the event of a new pandemic.
TRIAL REGISTRATION
ClinicalTrials.gov NCT03222999; https://classic.clinicaltrials.gov/ct2/show/NCT03222999.
Topics: Humans; Out-of-Hospital Cardiac Arrest; Republic of Korea; COVID-19; Registries; Female; Male; Aged; Middle Aged; Incidence; Retrospective Studies; Aged, 80 and over; Pandemics; Cardiopulmonary Resuscitation
PubMed: 38913998
DOI: 10.2196/52402 -
JMIR AI Jun 2024Breastfeeding benefits both the mother and infant and is a topic of attention in public health. After childbirth, untreated medical conditions or lack of support lead...
BACKGROUND
Breastfeeding benefits both the mother and infant and is a topic of attention in public health. After childbirth, untreated medical conditions or lack of support lead many mothers to discontinue breastfeeding. For instance, nipple damage and mastitis affect 80% and 20% of US mothers, respectively. Lactation consultants (LCs) help mothers with breastfeeding, providing in-person, remote, and hybrid lactation support. LCs guide, encourage, and find ways for mothers to have a better experience breastfeeding. Current telehealth services help mothers seek LCs for breastfeeding support, where images help them identify and address many issues. Due to the disproportional ratio of LCs and mothers in need, these professionals are often overloaded and burned out.
OBJECTIVE
This study aims to investigate the effectiveness of 5 distinct convolutional neural networks in detecting healthy lactating breasts and 6 breastfeeding-related issues by only using red, green, and blue images. Our goal was to assess the applicability of this algorithm as an auxiliary resource for LCs to identify painful breast conditions quickly, better manage their patients through triage, respond promptly to patient needs, and enhance the overall experience and care for breastfeeding mothers.
METHODS
We evaluated the potential for 5 classification models to detect breastfeeding-related conditions using 1078 breast and nipple images gathered from web-based and physical educational resources. We used the convolutional neural networks Resnet50, Visual Geometry Group model with 16 layers (VGG16), InceptionV3, EfficientNetV2, and DenseNet169 to classify the images across 7 classes: healthy, abscess, mastitis, nipple blebs, dermatosis, engorgement, and nipple damage by improper feeding or misuse of breast pumps. We also evaluated the models' ability to distinguish between healthy and unhealthy images. We present an analysis of the classification challenges, identifying image traits that may confound the detection model.
RESULTS
The best model achieves an average area under the receiver operating characteristic curve of 0.93 for all conditions after data augmentation for multiclass classification. For binary classification, we achieved, with the best model, an average area under the curve of 0.96 for all conditions after data augmentation. Several factors contributed to the misclassification of images, including similar visual features in the conditions that precede other conditions (such as the mastitis spectrum disorder), partially covered breasts or nipples, and images depicting multiple conditions in the same breast.
CONCLUSIONS
This vision-based automated detection technique offers an opportunity to enhance postpartum care for mothers and can potentially help alleviate the workload of LCs by expediting decision-making processes.
PubMed: 38913995
DOI: 10.2196/54798 -
JMIR Human Factors Jun 2024Physicians and patient-facing caregivers have increasingly used mobile health (mHealth) technologies in the past several years, accelerating during the COVID-19...
BACKGROUND
Physicians and patient-facing caregivers have increasingly used mobile health (mHealth) technologies in the past several years, accelerating during the COVID-19 pandemic. However, barriers and feedback surrounding adoption remain relatively understudied and varied across health systems, particularly in rural areas.
OBJECTIVE
This study aims to identify provider adoption, attitudes, and barriers toward mHealth in a large, multisite, rural US health care system. We investigated (1) mHealth apps that providers use for their own benefit and (2) mHealth apps that a provider uses in conjunction with a patient.
METHODS
We surveyed all patient-seeing providers within the Marshfield Clinic Health System with a brief, 16-item, web-based survey assessing attitudes toward mHealth, adoption of these technologies, and perceived barriers faced by providers, their peers, and the institution. Survey results were summarized via descriptive statistics, with log-binomial regression and accompanying pairwise analyses, using Kruskal-Wallis and Jonckheere-Terpstra tests for significance, respectively. Respondents were grouped by reported clinical role and specialty.
RESULTS
We received a 38% (n/N=916/2410) response rate, with 60.7% (n=556) of those sufficiently complete for analyses. Roughly 54.1% (n=301) of respondents reported mHealth use, primarily around decision-making and supplemental information, with use differing based on provider role and years of experience. Self-reported barriers to using mHealth included a lack of knowledge and time to study mHealth technologies. Providers also reported concerns about patients' internet access and the complexity of mHealth apps to adequately use mHealth technologies. Providers believed the health system's barriers were largely privacy, confidentiality, and legal review concerns.
CONCLUSIONS
These findings echo similar studies in other health systems, surrounding providers' lack of time and concerns over privacy and confidentiality of patient data. Providers emphasized concerns over the complexity of these technologies for their patients and concerns over patients' internet access to fully use mHealth in their delivery of care.
Topics: Humans; Telemedicine; Surveys and Questionnaires; COVID-19; Rural Health Services; Male; Attitude of Health Personnel; Female; Adult; Middle Aged; Mobile Applications; Internet
PubMed: 38913992
DOI: 10.2196/55443 -
Journal of Medical Internet Research Jun 2024Comprehensive management of multimorbidity can significantly benefit from advanced health risk assessment tools that facilitate value-based interventions, allowing for...
BACKGROUND
Comprehensive management of multimorbidity can significantly benefit from advanced health risk assessment tools that facilitate value-based interventions, allowing for the assessment and prediction of disease progression. Our study proposes a novel methodology, the Multimorbidity-Adjusted Disability Score (MADS), which integrates disease trajectory methodologies with advanced techniques for assessing interdependencies among concurrent diseases. This approach is designed to better assess the clinical burden of clusters of interrelated diseases and enhance our ability to anticipate disease progression, thereby potentially informing targeted preventive care interventions.
OBJECTIVE
This study aims to evaluate the effectiveness of the MADS in stratifying patients into clinically relevant risk groups based on their multimorbidity profiles, which accurately reflect their clinical complexity and the probabilities of developing new associated disease conditions.
METHODS
In a retrospective multicentric cohort study, we developed the MADS by analyzing disease trajectories and applying Bayesian statistics to determine disease-disease probabilities combined with well-established disability weights. We used major depressive disorder (MDD) as a primary case study for this evaluation. We stratified patients into different risk levels corresponding to different percentiles of MADS distribution. We statistically assessed the association of MADS risk strata with mortality, health care resource use, and disease progression across 1 million individuals from Spain, the United Kingdom, and Finland.
RESULTS
The results revealed significantly different distributions of the assessed outcomes across the MADS risk tiers, including mortality rates; primary care visits; specialized care outpatient consultations; visits in mental health specialized centers; emergency room visits; hospitalizations; pharmacological and nonpharmacological expenditures; and dispensation of antipsychotics, anxiolytics, sedatives, and antidepressants (P<.001 in all cases). Moreover, the results of the pairwise comparisons between adjacent risk tiers illustrate a substantial and gradual pattern of increased mortality rate, heightened health care use, increased health care expenditures, and a raised pharmacological burden as individuals progress from lower MADS risk tiers to higher-risk tiers. The analysis also revealed an augmented risk of multimorbidity progression within the high-risk groups, aligned with a higher incidence of new onsets of MDD-related diseases.
CONCLUSIONS
The MADS seems to be a promising approach for predicting health risks associated with multimorbidity. It might complement current risk assessment state-of-the-art tools by providing valuable insights for tailored epidemiological impact analyses of clusters of interrelated diseases and by accurately assessing multimorbidity progression risks. This study paves the way for innovative digital developments to support advanced health risk assessment strategies. Further validation is required to generalize its use beyond the initial case study of MDD.
Topics: Humans; Retrospective Studies; Multimorbidity; Female; Male; Middle Aged; Risk Assessment; Adult; Aged; Spain; Depressive Disorder, Major; Bayes Theorem; Disease Progression; United Kingdom; Depression; Finland
PubMed: 38913991
DOI: 10.2196/53162 -
The Oncologist Jun 2024To describe reasons for deviations from planned chemotherapy treatments in women with nonmetastatic breast cancer that contribute to less-than-planned receipt of...
BACKGROUND
To describe reasons for deviations from planned chemotherapy treatments in women with nonmetastatic breast cancer that contribute to less-than-planned receipt of chemotherapy.
METHODS
Electronic medical records for patients receiving chemotherapy were reviewed for adverse events and treatment modifications. Log-binomial regression models were used to estimate relative risks (RRs) with 95% CIs to examine associations between chemotherapy modifications, patient characteristics, and treatment modalities.
RESULTS
Delays in chemotherapy initiation (7%) were for surgical complications (58%), personal reasons (16%), and other (26%; port malfunction, infections, and obtaining extra imaging). Delays during chemotherapy (38%) were for infections (20%), neutropenia (13%), and personal reasons (13%). Dose reductions (38%) were for neuropathy (36%), unknown causes (9%), anemia (9%), and neutropenia (8%). Early treatment discontinuations (23%) were for neuropathy (29%). Patients receiving paclitaxel/nab-paclitaxel (RR 2.05; 95% CI, 1.47-2.87) and an anthracycline (RR 1.89; 95% CI, 1.39-2.57) reported more dose delays during chemotherapy. Black race (RR 1.46; 95% CI, 1.07-2.00), stage 3 (RR 1.79; 95% CI, 1.09-2.93), and paclitaxel/nab-paclitaxel receipt (RR 1.39; 95% CI, 1.02-1.90) increased the likelihood of dose reduction. Both Black race (RR 2.06; 95% CI, 1.35-3.15) and receipt of paclitaxel/nab-paclitaxel (RR 1.93; 95% CI, 1.19-3.13) increased the likelihood of early discontinuation. Patients receiving anthracyclines had higher rates of hospitalizations during chemotherapy (RR: 1.79; 95% CI, 1.11-2.89).
CONCLUSION
Toxicities are the most common reason for treatment modifications and need close monitoring in high-risk groups for timely intervention. Dose reductions and early treatment discontinuations occurred more for Black patients and need further study.
PubMed: 38913986
DOI: 10.1093/oncolo/oyae150 -
JMIR MHealth and UHealth Jun 2024Conversational chatbots are an emerging digital intervention for smoking cessation. No studies have reported on the entire development process of a cessation chatbot.
BACKGROUND
Conversational chatbots are an emerging digital intervention for smoking cessation. No studies have reported on the entire development process of a cessation chatbot.
OBJECTIVE
To describe the user-centered design development process for a novel and comprehensive quit smoking conversational chatbot called "QuitBot."
METHODS
The four years of formative research for developing QuitBot followed an eleven-step process: (1) specifying a conceptual model, (2) conducting content analysis of existing interventions (63 hours of intervention transcripts), (3) assessing user needs, (4) developing the chat's persona ("personality"), (5) prototyping content and persona, (6) developing full functionality, (7) programming the QuitBot, (8) conducting a diary study, (9) conducting a pilot randomized trial, (10) reviewing results of the trial, and (11) adding a free-form question and answer (QnA) function, based on user feedback from pilot trial results. The process of adding a QnA function itself involved a three-step process: (a) generating QnA pairs, (b) fine tuning Large Language Models (LLMs) on QnA pairs, and (c) evaluating the LLM model outputs.
RESULTS
A quit smoking program spanning 42 days of 2 to 3-minute conversations covering topics ranging from motivations to quit, setting a quit date, choosing FDA-approved cessation medications, coping with triggers, and recovering from lapses/relapses. In a pilot randomized trial with 96% three-month outcome data retention, QuitBot demonstrated high user engagement and promising cessation rates compared to the National Cancer Institute's SmokefreeTXT (SFT) text messaging program-particularly among those who viewed all 42 days of program content: 30-day complete-case, point prevalence abstinence (PPA) rates at three-month follow-up were 63% (39/62) for QuitBot vs. 38% (45/117) for SFT (OR = 2.58; 95% CI: 1.34, 4.99; P =.005). However, Facebook Messenger (FM) intermittently blocked participants' access to QuitBot so we transitioned from FM to a standalone smartphone app as the communication channel. Participants' frustration with QuitBot's inability to answer their open-ended questions lead to us develop a core conversational feature enabling users to ask open-ended questions about quitting cigarette smoking and for the QuitBot to respond with accurate and professional answers. To support this functionality, we developed a library of 11,000 QnA pairs on topics associated with quitting cigarette smoking. Model testing results showed that Microsoft's Azure-based QnA maker effectively handled questions that matched our library of 11,000 QnA pairs. A fine-tuned, contextualized GPT3.5 responds to questions that are not within our library of QnA pairs.
CONCLUSIONS
The development process yielded the first LLM-based quit smoking program delivered as a conversational chatbot. Iterative testing led to significant enhancements, including improvements to the delivery channel. A pivotal addition was the inclusion of a core LLM-supported conversational feature allowing users to ask open-ended questions.
CLINICALTRIAL
ClinicalTrials.gov Identifier, NCT03585231.
PubMed: 38913882
DOI: 10.2196/57318