Evaluation of a Primary Care-Integrated Mobile Health Intervention to Monitor between-Visit Asthma Symptoms.

OBJECTIVES: This study aimed to evaluate implementation of a digital remote symptom monitoring intervention that delivered weekly symptom questionnaires and included the option to receive nurse callbacks via a mobile app for asthma patients in primary care. METHODS: Research questions were structured by the NASSS (Nonadoption, Abandonment, Scale-up Spread, and Sustainability) framework. Quantitative and qualitative methods assessed scalability of the electronic health record (EHR)-integrated app intervention implemented in a 12-month randomized controlled trial. Data sources included patient asthma control questionnaires; app usage logs; EHRs; and interviews and discussions with patients, primary care providers (PCPs), and nurses. RESULTS: We included app usage data from 190 patients and interview data from 21 patients and several clinician participants. Among 190 patients, average questionnaire completion rate was 72.3% and retention was 78.9% (i.e., 150 patients continued to use the app at the end of the trial period). App use was lower among Hispanic and younger patients and those with fewer years of education. Of 1,185 nurse callback requests offered to patients. Thirty-three (2.8%) were requested. Of 84 PCP participants, 14 (16.7%) accessed the patient-reported data in the EHR. Analyses showed that the intervention was appropriate for all levels of asthma control; had no major technical barriers; was desirable and useful for patient treatment; involved achievable tasks for patients; required modest role changes for clinicians; and was a minimal burden on the organization. CONCLUSION: A clinically integrated symptom monitoring intervention has strong potential for sustained adoption. Inequitable adoption remains a concern. PCP use of patient-reported data during visits could improve intervention adoption but may not be required for patient benefits.

Serum N-Glycan Changes in Rats Chronically Exposed to Glyphosate-Based Herbicides.

Glyphosate, the active ingredient in many herbicides, has been widely used in agriculture since the 1970s. Despite initial beliefs in its safety for humans and animals due to the absence of the shikimate pathway, recent studies have raised concerns about its potential health effects. This study aimed to identify glycomic changes indicative of glyphosate-induced toxicity. Specifically, the study focused on profiling N-glycosylation, a protein post-translational modification increasingly recognized for its involvement in various disorders, including neurological conditions. A comprehensive analysis of rat serum N-glycomics following chronic exposure to glyphosate-based herbicides (GBH) was conducted using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The results revealed significant changes in the N-glycan profile, particularly in sialylated and sialofucosylated N-glycans. The analysis of N-glycans across gender subgroups provided insights into gender-specific responses to GBH exposure, with the male rats exhibiting a higher susceptibility to these N-glycan changes compared to females. The validation of significantly altered N-glycans using parallel reaction monitoring (PRM) confirmed their expression patterns. This study provides novel insights into the impact of chronic GBH exposure on serum N-glycan composition, with implications for assessing glyphosate toxicity and its potential neurological implications.

Effect of Topical Vancomycin on Surgical Site Infections in Ankle Fractures: A Randomized, Double-Blind, Controlled Trial.

Background Applying topical vancomycin has shown a decrease in the likelihood of surgical site infections (SSIs) in surgeries linked to a heightened risk of severe and resistant infections. Nevertheless, the effectiveness of this prophylactic approach has not been assessed in open ankle surgeries with internal fixation. Objective This study aimed to assess whether topical vancomycin diminishes the risk of SSI in patients with ankle fractures undergoing open reduction with internal fixation. Methods A randomized, controlled, double-blind clinical trial was carried out. Patients were divided into two groups in a 1:1 ratio. The control group received the standard prophylactic treatment with IV cephalothin 1 g, while the intervention group was administered topical vancomycin (1 g) in addition to the standard prophylactic treatment. The main outcomes were the SSI rates at 14 days, 28 days, and three months post-surgery, based on relevant clinical signs and laboratory tests. Results One hundred thirty-two patients were randomized (51.2% female), with 66 subjects included in each intervention arm. A total of 97.7% of them completed the study. Both groups were homogeneous in baseline characteristics. There were two SSIs in both the vancomycin group (3.3%) and the control group (3.5%), with no statistical differences (p = 0.945). The microorganisms isolated as causal agents were Staphylococcus aureus and Acinetobacter baumannii. By the three-month follow-up, no infections were noted in both intervention groups. Conclusion These results indicate that the topical administration of vancomycin may not represent an advantage in preventing SSI in ankle fractures requiring open reduction with internal fixation at the three-month postoperative stage.

Lessons learned from a multi-site collaborative working toward a digital health use screening tool.

Digital health has the potential to expand health care and improve outcomes for patients-particularly for those with challenges to accessing in-person care. The acceleration of digital health (and particularly telemedicine) prompted by the Coronavirus-19 (COVID-19) pandemic facilitated continuity of care in some settings but left many health systems ill-prepared to address digital uptake among patients from underserved backgrounds, who already experience health disparities. As use of digital health grows and the digital divide threatens to widen, healthcare systems must develop approaches to evaluate patients' needs for digital health inclusion, and consequentially equip patients with the resources needed to access the benefits of digital health. However, this is particularly challenging given the absence of any standardized, validated multilingual screening instrument to assess patients' readiness for digital healthcare that is feasible to administer in already under-resourced health systems. This perspective is structured as follows: (1) the need for digital health exclusion risk screening, (2) our convening as a group of stakeholders, (3) our review of the known digital health screening tools and our assessment, (4) formative work with patients regarding their perceptions on language and concepts in the digital health screening tools, and (5) conclusion with recommendations for digital health advocates generated by this collaborative of digital health researchers and operations leaders. There is a need to develop a brief, effective tool to screen for digital health use that can be widely implemented in diverse populations. We include lessons learned from our experiences in developing and testing risk of digital health exclusion screening questions in our respective health systems (e.g., patient perception of questions and response options). Because we recognize that health systems across the country may be facing similar challenges and questions, this perspective aims to inform ongoing efforts in developing health system digital exclusion screening tools and advocate for their role in advancing digital health equity.

Exploring the Telephone Call Experience of Patients with Non-English Language Preference in Primary Care vs. Specialty.

BACKGROUND: Latine people, comprising 18.5% of the US population, constitute the largest ethnic minority group, with nearly one-third self-identifying as having non-English language preference (NELP). Despite the importance of the telephone in health care access, there is limited understanding of how NELP patients navigate telephone calls with primary and specialty care clinics. OBJECTIVE: This qualitative study aims to capture how Spanish speakers with NELP characterize their telephone call experiences with primary and specialty care clinics. DESIGN: Semi-structured interviews were conducted with 24 Spanish-speaking participants from primary care clinics with a sizeable proportion of patients who prefer to communicate in a language other than English at an urban academic medical center in Boston, MA. PARTICIPANTS: Participants were selected from primary care clinics that were well-equipped to serve Spanish-speaking patients. A total of 24 Spanish-speaking patients with NELP, mainly women (83%), with a mean age of 55.8 years, participated. They represented diverse countries of origin, with an average length of time in the USA of 21.7 years. APPROACH: Interview questions prompted participants to describe their telephone call experiences with front desk staff, with attention to interpreter availability, ancillary assistance, health outcomes stemming from a lack of language services, and emotional consequences of language discordance on calls. KEY RESULTS: Patients perceived primary care clinics as providing familiarity and language concordance during telephone interactions, contrasting with specialty care clinics, seen as sources of monolingual English communication. Participants utilized various strategies, such as requesting interpreters, using concise English phrases, or seeking assistance from acquaintances, relatives, or primary care clinic staff, to mitigate language barriers. CONCLUSIONS: The findings underscore significant challenges faced by Spanish-speaking patients with NELP in ambulatory specialty care telephone calls. The study emphasizes the importance of creating inclusive multilingual telephone environments, standardizing interpreter access, and reflecting the diversity of the communities served.

Sex Differences in Primary Care-Based Chronic Kidney Disease Management.

This retrospective study uses electronic health record data to investigate the sex differences in guideline-based management outcomes between male and female patients with chronic kidney disease.

A system-wide approach to digital equity: the Digital Access Coordinator program in primary care.

INTRODUCTION: The transition to digital tools prompted by the pandemic made evident digital disparities. To address digital literacy gaps, we implemented a system-wide digital navigation program. METHODS: The Digital Access Coordinator (DAC) program consists of 12 multilingual navigators who support patients in enrolling and using the patient portal and digital tools. We implemented the program in our primary care network which consists of 1.25 million patients across 1211 clinicians. RESULTS: From May 2021 to November 2022, the DACs completed outreach to 16 045 patients. Of the 13 413 patients they reached, they successfully enrolled 8193 (61%) patients in the patient portal. Of those patients they enrolled, most patients were of Other race, Hispanic ethnicity, and were English-speaking (44%) and Spanish-speaking patients (44%). Using our embedded model, we increased enrollment across 7 clinics (mean increase: 21.3%, standard deviation: 9.2%). Additionally, we identified key approaches for implementing a digital navigation program. CONCLUSION: Organizations can support patient portal enrollment, a key part of digital health equity, by creating and prioritizing digital navigation programs.

Telehealth Experience Among Patients With Limited English Proficiency.

This cross-sectional study assesses the implication of patients' English language skills for telehealth use and visit experience.

Leveraging large language models to foster equity in healthcare.

OBJECTIVES: Large language models (LLMs) are poised to change care delivery, but their impact on health equity is unclear. While marginalized populations have been historically excluded from early technology developments, LLMs present an opportunity to change our approach to developing, evaluating, and implementing new technologies. In this perspective, we describe the role of LLMs in supporting health equity. MATERIALS AND METHODS: We apply the National Institute on Minority Health and Health Disparities (NIMHD) research framework to explore the use of LLMs for health equity. RESULTS: We present opportunities for how LLMs can improve health equity across individual, family and organizational, community, and population health. We describe emerging concerns including biased data, limited technology diffusion, and privacy. Finally, we highlight recommendations focused on prompt engineering, retrieval augmentation, digital inclusion, transparency, and bias mitigation. CONCLUSION: The potential of LLMs to support health equity depends on making health equity a focus from the start.

Racial and Ethnic Differences in Telemedicine Use.

Importance: Individuals of racial and ethnic minority groups may be less likely to use telemedicine in part due to lack of access to technology (ie, digital divide). To date, some studies have found less telemedicine use by individuals of racial and ethnic minority groups compared with White individuals, and others have found the opposite. What explains these different findings is unclear. Objective: To quantify racial and ethnic differences in the receipt of telemedicine and total visits with and without accounting for demographic and clinical characteristics and geography. Design, Setting, and Participants: This cross-sectional study included individuals who were continuously enrolled in traditional Medicare from March 2020 to February 2022 or until death. Exposure: Race and ethnicity, which was categorized as Black non-Hispanic, Hispanic, White non-Hispanic, other (defined as American Indian/Pacific Islander, Alaska Native, and Asian), and unknown/missing. Main Outcomes and Measures: Total telemedicine visits (audio-video or audio); total visits (telemedicine or in-person) per individual during the study period. Multivariable models were used that sequentially adjusted for demographic and clinical characteristics and geographic area to examine their association with differences in telemedicine and total visit utilization by documented race and ethnicity. Results: In this national sample of 14 305 819 individuals, 7.4% reported that they were Black, 5.6% Hispanic, and 4.2% other race. In unadjusted results, compared with White individuals, Black individuals, Hispanic individuals, and individuals of other racial groups had 16.7 (95% CI, 16.1-17.3), 32.9 (95% CI, 32.3-33.6), and 20.9 (95% CI, 20.2-21.7) more telemedicine visits per 100 beneficiaries, respectively. After adjustment for clinical and demographic characteristics and geography, compared with White individuals, Black individuals, Hispanic individuals, and individuals of other racial groups had 7.9 (95% CI, -8.5 to -7.3), 13.2 (95% CI, -13.9 to -12.6), and 9.2 (95% CI, -10.0 to -8.5) fewer telemedicine visits per 100 beneficiaries, respectively. In unadjusted and fully adjusted models, and in 2019 and the second year of the COVID-19 pandemic, Black individuals, Hispanic individuals, and individuals of other racial groups continued to have fewer total visits than White individuals. Conclusions and Relevance: The results of this cross-sectional study of US Medicare enrollees suggest that although nationally, Black individuals, Hispanic individuals, and individuals of other racial groups received more telemedicine visits during the pandemic and disproportionately lived in geographic regions with higher telemedicine use, after controlling for geographic region, Black individuals, Hispanic individuals, and individuals of other racial groups received fewer telemedicine visits than White individuals.

Patient Safety Indicators During the Initial COVID-19 Pandemic Surge in the United States.

OBJECTIVE: The COVID-19 pandemic presented a challenge to inpatient safety. It is unknown whether there were spillover effects due to COVID-19 into non-COVID-19 care and safety. We sought to evaluate the changes in inpatient Agency for Healthcare Research and Quality patient safety indicators (PSIs) in the United States before and during the first surge of the pandemic among patients admitted without COVID-19. METHODS: We analyzed trends in PSIs from January 2019 to June 2020 in patients without COVID-19 using data from IBM MarketScan Commercial Database. We included members of employer-sponsored or Medicare supplemental health plans with inpatient, non-COVID-19 admissions. The primary outcomes were risk-adjusted composite and individual PSIs. RESULTS: We analyzed 1,869,430 patients admitted without COVID-19. Among patients without COVID-19, the composite PSI score was not significantly different when comparing the first surge (Q2 2020) to the prepandemic period (e.g., Q2 2020 score of 2.46 [95% confidence interval {CI}, 2.34-2.58] versus Q1 2020 score of 2.37 [95% CI, 2.27-2.46]; P = 0.22). Individual PSIs for these patients during Q2 2020 were also not significantly different, except in-hospital fall with hip fracture (e.g., Q2 2020 was 3.42 [95% CI, 3.34-3.49] versus Q4 2019 was 2.45 [95% CI, 2.40-2.50]; P = 0.01). CONCLUSIONS: The first surge of COVID-19 was not associated with worse inpatient safety for patients without COVID-19, highlighting the ability of the healthcare system to respond to the initial surge of the pandemic.

Long chain capsaicin analogues synthetized by CALB-CLEAs show cytotoxicity on glioblastoma cell lines.

Glioblastoma is one of the most lethal tumors, displaying striking cellular heterogeneity and drug resistance. The prognosis of patients suffering from glioblastoma after 5 years is only 5%. In the present work, capsaicin analogues bearing modifications on the acyl chain with long-chain fatty acids showed promising anti-tumoral activity by its cytotoxicity on U-87 and U-138 glioblastoma multiforme cells. The capsaicin analogues were enzymatically synthetized with cross-linked enzyme aggregates of lipase B from Candida antarctica (CALB). The catalytic performance of recombinant CALB-CLEAs was compared to their immobilized form on a hydrophobic support. After 72 h of reaction, the synthesis of capsaicin analogues from linoleic acid, docosahexaenoic acid, and punicic acid achieved a maximum conversion of 69.7, 8.3 and 30.3% with CALB-CLEAs, respectively. Similar values were obtained with commercial CALB, with conversion yields of 58.3, 24.2 and 22% for capsaicin analogues from linoleic acid, DHA and punicic acid, respectively. Olvanil and dohevanil had a significant cytotoxic effect on both U-87 and U-138 glioblastoma cells. Irrespective of the immobilization form, CALB is an efficient biocatalyst for the synthesis of anti-tumoral capsaicin derivatives. KEY POINTS: • This is the first report concerning the enzymatic synthesis of capsaicin analogues from docosahexaenoic acid and punicic acid with CALB-CLEAs. • The viability U-87 and U-138 glioblastoma cells was significantly affected after incubation with olvanil and dohevanil. • Capsaicin analogues from fatty acids obtained by CALB-CLEAs are promising candidates for therapeutic use as cytotoxic agents in glioblastoma cancer cells.

Development of a rapid assay for ß-etherase activity using a novel chromogenic substrate.

Biocatalytic processes play a crucial role in the valorization of lignin; therefore, methods enabling the monitoring of enzymes such as ß-etherases, capable of breaking ß-O-4 aryl-ether bonds, are of significant biotechnological interest. A novel method for quantifying ß-etherase activity was developed based on the ß-ester bond formation between a chromophore and acetovainillone. The chromogenic substrate ß-(ρ-nitrophenoxy)-α-acetovanillone (PNPAV), was chemically synthesized. Kintetic monitoring of ρ-nitrophenolate release at 410 nm over 10 min, using recombinant LigF from Sphingobium sp SYK-6, LigF-AB and LigE-AB from Althererytrobacter sp B11, yielded enzimatic activities of 404. 3 mU/mg, 72 mU/mg, and 50 mU/mg, respectively. This method is applicable in a pH range of 7.0-9.0, with a sensitivity of up to 50 ng of enzyme, exhibiting no interference with lipolytic, glycolytic, proteolytic, and oxidoreductase enzymes.

Assessing the potential of GPT-4 to perpetuate racial and gender biases in health care: a model evaluation study.

BACKGROUND: Large language models (LLMs) such as GPT-4 hold great promise as transformative tools in health care, ranging from automating administrative tasks to augmenting clinical decision making. However, these models also pose a danger of perpetuating biases and delivering incorrect medical diagnoses, which can have a direct, harmful impact on medical care. We aimed to assess whether GPT-4 encodes racial and gender biases that impact its use in health care. METHODS: Using the Azure OpenAI application interface, this model evaluation study tested whether GPT-4 encodes racial and gender biases and examined the impact of such biases on four potential applications of LLMs in the clinical domain-namely, medical education, diagnostic reasoning, clinical plan generation, and subjective patient assessment. We conducted experiments with prompts designed to resemble typical use of GPT-4 within clinical and medical education applications. We used clinical vignettes from NEJM Healer and from published research on implicit bias in health care. GPT-4 estimates of the demographic distribution of medical conditions were compared with true US prevalence estimates. Differential diagnosis and treatment planning were evaluated across demographic groups using standard statistical tests for significance between groups. FINDINGS: We found that GPT-4 did not appropriately model the demographic diversity of medical conditions, consistently producing clinical vignettes that stereotype demographic presentations. The differential diagnoses created by GPT-4 for standardised clinical vignettes were more likely to include diagnoses that stereotype certain races, ethnicities, and genders. Assessment and plans created by the model showed significant association between demographic attributes and recommendations for more expensive procedures as well as differences in patient perception. INTERPRETATION: Our findings highlight the urgent need for comprehensive and transparent bias assessments of LLM tools such as GPT-4 for intended use cases before they are integrated into clinical care. We discuss the potential sources of these biases and potential mitigation strategies before clinical implementation. FUNDING: Priscilla Chan and Mark Zuckerberg.

Protocol to Induce the Temporary Opening of the Blood-Brain Barrier with Short-Time Focused Ultrasound in Rats.

Brain neurodegenerative diseases are central nervous system (CNS) affections typically common in older adults. A new therapeutic approach for them consists of providing specific drugs to the CNS through blood circulation; however, the Blood-Brain Barrier (BBB) prevents almost 100% of neurotherapeutics from reaching the brain. There are indications that Focused Ultrasound (FUS), temporarily placed in the BBB, can achieve a controlled increase in temperature at its focus, allowing temporary, localized, and reversible opening of this barrier, which facilitates the temporary delivery of specific drugs. This work presents a FUS-based protocol for the local, temporary, and reversible opening of the BBB in Wistar rats. The proposed protocol specifies certain power, treatment times, and duty cycle to controllably increase the temperature at the region of interest, i.e., the substantia nigra. Numerical simulations using commercial software based on the finite element method were carried out to determine the optimal size of the craniotomies for nearly full-acoustic transmission. Experiments in rats were performed with the parameters used during computational simulations to determine the adequate opening of the BBB. For this, craniotomies of different sizes were made at coordinates of the substantia nigra, and FUS was applied from the exterior. The opening of the BBB was evaluated using Evans Blue (EB) as an indicator of the crossing of the dye from the blood vessels to brain tissue. Numerical simulations demonstrated a major distance reached by the ultrasound focus with a bigger diameter. Experimental results show the local, temporary, and reversible opening of the BBB through a 10 mm diameter craniotomy, which effectively allowed placing the ultrasound focus over the substantia nigra, unlike a 6 mm diameter craniotomy in which there is a deviation of the focus through that window. Moreover, from these results, it was also determined that the disruption of the BBB was reversible, with an opening duration of 6 h after FUS application. The experimental work developed in this study resulted in a minimally invasive method for the temporary opening of the BBB.