Influences of resting-state intrinsic functional brain connectivity on the antidepressant treatment response in late-life depression.

BACKGROUND: Late-life depression (LLD) is characterized by differences in resting state functional connectivity within and between intrinsic functional networks. This study examined whether clinical improvement to antidepressant medications is associated with pre-randomization functional connectivity in intrinsic brain networks. METHODS: Participants were 95 elders aged 60 years or older with major depressive disorder. After clinical assessments and baseline MRI, participants were randomized to escitalopram or placebo with a two-to-one allocation for 8 weeks. Non-remitting participants subsequently entered an 8-week trial of open-label bupropion. The main clinical outcome was depression severity measured by MADRS. Resting state functional connectivity was measured between a priori key seeds in the default mode (DMN), cognitive control, and limbic networks. RESULTS: In primary analyses of blinded data, lower post-treatment MADRS score was associated with higher resting connectivity between: (a) posterior cingulate cortex (PCC) and left medial prefrontal cortex; (b) PCC and subgenual anterior cingulate cortex (ACC); (c) right medial PFC and subgenual ACC; (d) right orbitofrontal cortex and left hippocampus. Lower post-treatment MADRS was further associated with lower connectivity between: (e) the right orbitofrontal cortex and left amygdala; and (f) left dorsolateral PFC and left dorsal ACC. Secondary analyses associated mood improvement on escitalopram with anterior DMN hub connectivity. Exploratory analyses of the bupropion open-label trial associated improvement with subgenual ACC, frontal, and amygdala connectivity. CONCLUSIONS: Response to antidepressants in LLD is related to connectivity in the DMN, cognitive control and limbic networks. Future work should focus on clinical markers of network connectivity informing prognosis. REGISTRATION: ClinicalTrials.gov NCT02332291.

Structural MRI-Based Measures of Accelerated Brain Aging do not Moderate the Acute Antidepressant Response in Late-Life Depression.

OBJECTIVE: Late-life depression (LLD) is characterized by accelerated biological aging. Accelerated brain aging, estimated from structural magnetic resonance imaging (sMRI) data by a machine learning algorithm, is associated with LLD diagnosis, poorer cognitive performance, and disability. We hypothesized that accelerated brain aging moderates the antidepressant response. DESIGN AND INTERVENTIONS: Following MRI, participants entered an 8-week randomized, controlled trial of escitalopram. Nonremitting participants then entered an open-label 8-week trial of bupropion. PARTICIPANTS: Ninety-five individuals with LLD. MEASUREMENTS: A machine learning algorithm estimated each participant's brain age from sMRI data. This was used to calculate the brain-age gap (BAG), or how estimated age differed from chronological age. Secondary sMRI measures of aging pathology included white matter hyperintensity (WMH) volumes and hippocampal volumes. Mixed models examined the relationship between sMRI measures and change in depression severity. Initial analyses tested for a moderating effect of MRI measures on change in depression severity with escitalopram. Subsequent analyses tested for the effect of MRI measures on change in depression severity over time across trials. RESULTS: In the blinded initial phase, BAG was not significantly associated with a differential response to escitalopram over time. BAG was also not associated with a change in depression severity over time across both arms in the blinded phase or in the subsequent open-label bupropion phase. We similarly did not observe effects of WMH volume or hippocampal volume on change in depression severity over time. CONCLUSION: sMRI markers of accelerated brain aging were not associated with treatment response in this sequential antidepressant trial.

Placement of Subcutaneous Central Venous Ports in Breast Cancer Patients: Does Side Matter?

BACKGROUND: Central venous ports placed for breast cancer treatment have traditionally been placed contralateral to the disease. This is done out of concern for the possibility of an increased risk of complications with ipsilateral port placement. There have been only a few small studies evaluating complication rates between ports placed ipsilateral versus contralateral to the breast cancer. We sought to determine if there was a difference in port complications or lymphedema rates by location. METHODS: A single institution retrospective review was conducted of adult (aged >18 y) females undergoing central venous port placement for breast cancer treatment from 2012 to 2016. RESULTS: A total of 581 females were identified with a mean age of 52.9 ± 11.7 y. Ipsilateral ports were placed in 41 patients (7.1%). Ipsilateral ports were more likely to be placed via the internal jugular vein (56.1%), whereas contralateral ports were more likely to be placed in the subclavian vein (67.2%; P = 0.002). There was no difference between stage at diagnosis (P = 0.059), type of breast surgery (P = 0.999), axillary surgery (P = 0.087), or administration of radiation therapy (P = 0.684) between the groups. Ipsilateral ports were more likely to be on the right side, 73.2% versus 51.1% (P = 0.006). Port complications requiring intervention occurred in 3 patients (7.3%) with ipsilateral port and 33 patients (6.1%) with contralateral ports (P = 0.73). Lymphedema occurred in 8 patients (20%) with ipsilateral ports and 118 patients (21.9%) with contralateral ports (P = 0.639). On multivariable analysis, the type of axillary surgery (P = 0.003) was associated with upper extremity lymphedema, whereas port sidedness (P = 0.26) was not. CONCLUSIONS: There was no difference in port complications or lymphedema rates between patients who had ports placed on the ipsilateral side compared with the contralateral side for breast cancer treatment.

Safety and immunogenicity of Vi-diphtheria toxoid typhoid conjugate vaccine among children below 2 years: a systematic review and meta-analysis.

Background: The Vi-diphtheria toxoid typhoid conjugate vaccine (Vi-DT) has shown promising results in preventing typhoid fever in children under 2 years of age. However, a thorough assessment of its safety and immunogenicity is required to inform vaccination strategies. This systematic review and meta-analysis aimed to determine the safety and immunogenicity of Vi-DT in children below 2 years. Methods: We systematically searched multiple databases, including PubMed, Web of Science, and Scopus, for relevant studies published up to September 2023. We included studies reporting on the safety and immunogenicity outcomes of Vi-DT compared to the control or Vi-tetanus toxoid conjugated vaccine (Vi-TT) in children below 2 years. We applied a random-effects model for meta-analysis using RevMan 5.4. We expressed the results as risk ratio (RR) with a 95% confidence interval (95%CI). Results: In this analysis, five studies were selected, encompassing 1,292 children under 2 years who received the Vi-DT vaccine. No significant difference in immediate reactions was observed within 30 min post-vaccination between Vi-DT and control groups (RR: 0.99 [95% CI: 0.19, 5.26]), nor between Vi-DT and Vi-TT groups. For solicited adverse events within 4 weeks, the VI-DT group showed no significant increase in adverse events compared to control (RR: 0.93 [95% CI: 0.78, 1.12]) or Vi-TT (RR: 0.86 [95% CI: 0.69, 1.07]). Similarly, within 7 days post-vaccination, risk ratios indicated no significant differences in adverse events between the groups. The 4-week seroconversion rate was significantly higher in the Vi-DT group compared to the control (RR: 1.99 [95% CI: 1.07, 3.69]), but no difference was found between Vi-DT and Vi-TT. Adverse events associated with typhoid conjugate vaccines were predominantly non-serious, including fever and injection site reactions. Serious adverse events were rare but included conditions like pneumonia and gastroenteritis. Conclusion: This meta-analysis highlights Vi-DT safety and immunogenicity in six to 24-month-old children. The findings support the use of this Vi-DT to expand typhoid vaccination in endemic regions, in line with WHO's strategy.

Clinician use of data elements from cardiovascular implantable electronic devices in clinical practice.

Background: Cardiovascular implantable electronic devices (CIEDs) capture an abundance of data for clinicians to review and integrate into the clinical decision-making process. The multitude of data from different device types and vendors presents challenges for viewing and using the data in clinical practice. Efforts are needed to improve CIED reports by focusing on key data elements used by clinicians. Objective: The purpose of this study was to uncover the extent to which clinicians use the specific types of data elements from CIED reports in clinical practice and explore clinicians' perceptions of CIED reports. Methods: A brief, web-based, cross-sectional survey study was deployed using snowball sampling from March 2020 through September 2020 to clinicians who are involved in the care of patients with CIEDs. Results: Among 317 clinicians, the majority specialized in electrophysiology (EP) (80.1%), were from North America (88.6%), and were white (82.2%). Over half (55.3%) were physicians. Arrhythmia episodes and ventricular therapies rated the highest among 15 categories of data presented, and nocturnal or resting heart rate and heart rate variability were rated the lowest. As anticipated, clinicians specializing in EP reported using the data significantly more than other specialties across nearly all categories. A subset of respondents offered general comments describing preferences and challenges related to reviewing reports. Conclusion: CIED reports contain an abundance of information that is important to clinicians; however, some data are used more frequently than others, and reports could be streamlined for users to improve access to key information and facilitate more efficient clinical decision making.

Improving ascertainment of suicidal ideation and suicide attempt with natural language processing.

Methods relying on diagnostic codes to identify suicidal ideation and suicide attempt in Electronic Health Records (EHRs) at scale are suboptimal because suicide-related outcomes are heavily under-coded. We propose to improve the ascertainment of suicidal outcomes using natural language processing (NLP). We developed information retrieval methodologies to search over 200 million notes from the Vanderbilt EHR. Suicide query terms were extracted using word2vec. A weakly supervised approach was designed to label cases of suicidal outcomes. The NLP validation of the top 200 retrieved patients showed high performance for suicidal ideation (area under the receiver operator curve [AUROC]: 98.6, 95% confidence interval [CI] 97.1-99.5) and suicide attempt (AUROC: 97.3, 95% CI 95.2-98.7). Case extraction produced the best performance when combining NLP and diagnostic codes and when accounting for negated suicide expressions in notes. Overall, we demonstrated that scalable and accurate NLP methods can be developed to identify suicidal behavior in EHRs to enhance prevention efforts, predictive models, and precision medicine.

Organizational Models for Cardiac Implantable Electronic Device Remote Monitoring: Current and Future Directions.

This review provides an overview of the literature on the organization, staffing, and structure of remote monitoring (RM) clinics, primarily from countries in Western Europe and United States, as well as the challenges, considerations, and future directions for RM clinic models of care. Using a current case example of an RM clinic in the Midwestern United States, this document provides key information from the viewpoint of a clinic undergoing a shift in workflow. Finally, this review distills key considerations for RM management for electrophysiology clinics, vendors and industry, and policy makers.

Engaging Patients in Atrial Fibrillation Management via Digital Health Technology: The Impact of Tailored Messaging.

Patients with atrial fibrillation (AF) demonstrate persistent knowledge gaps regarding their condition and a substandard adherence to oral anticoagulant (OAC) medication, which contribute to thromboembolic stroke and other clot-related complications. Tailored patient education and medication reminders may help reduce these negative health outcomes. We sought to improve disease knowledge and medication adherence among a sample of AF patients using tailored education and nudges. The intervention leveraged three digital health technologies: a patient portal, an electronic-prescribing data feed, and a smart pill bottle. The content of the educational messaging, nudges, and cadence were tailored according to findings from our user-centered design studies and delivered via a patient portal (MyChart®; Epic Systems, Verona, WI, USA), with which participants were familiar. In a six-month randomized controlled trial with parallel groups, we used MyChart® to send educational messages and medication reminders according to a decision tree that emerged from our prior user-centered design studies. The intervention group demonstrated higher AF knowledge at study completion than the control group and more MyChart® logins throughout the trial, suggesting intervention uptake. Women were more adherent than men and patients diagnosed more than one year ago were more adherent than those with more recent diagnoses. The intervention and control group adherence rates were 93.1% and 89.5%, respectively; intervention effect was moderated by age, medication type, and prior MyChart® use. Within the intervention group, younger patients, those taking once-daily rivaroxaban, and those who were less active MyChart® users prior to the study benefited relative to their control group counterparts. Tailored educational and reminder messages contributed to increased adherence and disease knowledge among AF patients, though certain patient characteristics moderated the intervention's effectiveness. Technology-based health interventions can be useful for older adults with effective tailoring and training.

Involving patients as key stakeholders in the design of cardiovascular implantable electronic device data dashboards: Implications for patient care.

BACKGROUND: Data from remote monitoring (RM) of cardiovascular implantable electronic devices (CIEDs) currently are not accessible to patients despite demand. The typical RM report contains multiple pages of data for trained technicians to read and interpret and requires a patient-centered approach to be curated to meet individual user needs. OBJECTIVE: The purpose of this study was to understand which RM data elements are important to patients and to gain design insights for displaying meaningful data in a digital dashboard. METHODS: Adults with implantable cardioverter-defibrillators (ICDs) and pacemakers (PMs) participated in this 2-phase, user-centered design study. Phase 1 included a card-sorting activity to prioritize device data elements. Phase 2 included one-on-one design sessions to gather insights and feedback about a visual display (labels and icons). RESULTS: Twenty-nine adults (mean age 71.8 ± 11.6 years; 51.7% female; 89.7% white) participated. Priority data elements for both ICD and PM groups in phase 1 (n = 19) were related to cardiac episodes, device activity, and impedance values. Recommended replacement time for battery was high priority for the PM group but not the ICD group. Phase 2 (n = 10) revealed that patients would like descriptive, nontechnical terms to depict the data and icons that are intuitive and informative. CONCLUSION: This user-centered design study demonstrated that patients with ICDs and PMs were able to prioritize specific data from a comprehensive list of data elements that they had never seen before. This work contributes to the goal of sharing RM data with patients in a way that optimizes the RM feature of CIEDs for improving patient outcomes and clinical care.

Medication adherence for atrial fibrillation patients: triangulating measures from a smart pill bottle, e-prescribing software, and patient communication through the electronic health record.

OBJECTIVE: Our primary objectives were to examine adherence rates across two technologies (e-prescribing software and smart pill bottle) with cross-validation from alert-triggered messaging within the patient electronic health record (EHR) portal and to explore the benefits and challenges faced by atrial fibrillation (AF) patients in using a smart pill bottle. MATERIALS AND METHODS: We triangulated the rate of oral anticoagulant medication adherence among 160 AF patients over 6 months using an EHR in combination with data from the AdhereTech© Wireless Smart Pill Bottle and Surescripts©. In addition, we collected qualitative feedback on patients' Smart Pill Bottle usage through structured interviews with 153 participants. RESULTS: Patients maintained an average adherence rate of 90.0% according to the smart pill bottle; however, when dose misses were calibrated based on patient or provider feedback, the adjusted adherence was 93.6%. Surescripts adherence rates for refills were 92.2%. Participants generally found the bottle easy to operate but suggested that its size and functionality did not fit seamlessly into their existing routine, as many used weekly pill organizers to manage multiple medications. DISCUSSION: Though each method of tracking adherence has positive and negative attributes, combining them and seeking patient feedback may help capture a more accurate adherence rate than any single technological intervention. Technologies may have different design considerations for research and consumer use. CONCLUSION: Overall, these technologies provide useful but imperfect adherence data for research purposes, and smart pill bottles could be improved with patient-centered design. LAY SUMMARY: Medication adherence is very important for those with chronic health issues. For those with heart disease, medication adherence not only offers opportunities for improving quality of life, but it also can be life-saving. Nonetheless, many patients with heart disease, including those with atrial fibrillation (the target group for this study) do not take their medications regularly. As technologies advance, there is unprecedented opportunity to track patients' medication adherence through various methods, which might provide motivation and information to patients as they make daily choices about medication use. In this study, we cross-referenced the results of two of these measures over 6 months-a smart pill bottle, which we used to track pill bottle openings, and e-prescribing software, which we used to track medication refills. We also supplemented these measures with nurse-patient communication via the EHR messaging portal to record exceptions (eg, travel and medication changes) and interviewed patients about their medication use during the 6-month trial. Overall, the tracking technologies worked relatively well to track patient (n = 160) medication behavior; however, they did not capture exceptions. Hence, triangulating data from different sources, with a patient feedback loop, appears critical for gathering accurate data on medication adherence.

Untold Stories in User-Centered Design of Mobile Health: Practical Challenges and Strategies Learned From the Design and Evaluation of an App for Older Adults With Heart Failure.

BACKGROUND: User-centered design (UCD) is a powerful framework for creating useful, easy-to-use, and satisfying mobile health (mHealth) apps. However, the literature seldom reports the practical challenges of implementing UCD, particularly in the field of mHealth. OBJECTIVE: This study aims to characterize the practical challenges encountered and propose strategies when implementing UCD for mHealth. METHODS: Our multidisciplinary team implemented a UCD process to design and evaluate a mobile app for older adults with heart failure. During and after this process, we documented the challenges the team encountered and the strategies they used or considered using to address those challenges. RESULTS: We identified 12 challenges, 3 about UCD as a whole and 9 across the UCD stages of formative research, design, and evaluation. Challenges included the timing of stakeholder involvement, overcoming designers' assumptions, adapting methods to end users, and managing heterogeneity among stakeholders. To address these challenges, practical recommendations are provided to UCD researchers and practitioners. CONCLUSIONS: UCD is a gold standard approach that is increasingly adopted for mHealth projects. Although UCD methods are well-described and easily accessible, practical challenges and strategies for implementing them are underreported. To improve the implementation of UCD for mHealth, we must tell and learn from these traditionally untold stories.

Patient responses to daily cardiac resynchronization therapy device data: A pilot trial assessing a novel patient-centered digital dashboard in everyday life.

Background: Heart failure (HF) is a growing public health problem in the United States. Implantable cardiac resynchronization therapy (CRT) devices reduce mortality and morbidity, and remote monitoring (RM) of these devices improves outcomes. However, patient RM adherence is low, due in part to lack of access to their RM data. Providing these data to patients may increase engagement, but they must be appropriately tailored to ensure understanding. Objective: The purpose of this study was to examine patients' experiences interacting with their RM data through a novel digital dashboard as part of daily life. Methods: In this mixed-methods pilot study, 10 patients with implantable CRT defibrillators were given access to a patient-centered RM data dashboard, updated daily for 6-12 months. Pre- and post-health literacy, engagement, electronic portal (MyChart, Epic Systems Corporation) logins, and RM adherence were measured; system usability scores were collected at exit; and dashboard views were tracked. Exit interviews were conducted to elucidate patients' experiences. Results: Participants (100% white; 60% male; age 34-80 years [mean ± SD: 62.0 ± 13.4]) had adequate health literacy, increased MyChart logins (P = .0463), and nonsignificant increase in RM adherence. Participants viewed their dashboards 0-42 times (mean 14.9 ± 12.5). Interviews revealed participants generally appreciated access to their data, understood it, and responded to changes; however, questions and concerns remained regarding data interpretation and visualization. Conclusion: Preliminary findings support potential future integration of a CRT RM data dashboard in the daily care of HF patients. With appropriate informational support and personalization, sharing RM data with patients in a tailored dashboard may improve health engagement.

Visualization of Cardiac Implantable Electronic Device Data for Older Adults Using Participatory Design.

Patients with heart failure (HF) are commonly implanted with cardiac resynchronization therapy (CRT) devices as part of their treatment. Presently, they cannot directly access the remote monitoring (RM) data generated from these devices, representing a missed opportunity for increased knowledge and engagement in care. However, electronic health data sharing can create information overload issues for both clinicians and patients, and some older patients may not be comfortable using the technology (i.e., computers and smartphones) necessary to access this data. To mitigate these problems, patients can be directly involved in the creation of data visualization tailored to their preferences and needs, allowing them to successfully interpret and act upon their health data. We held a participatory design (PD) session with seven adult patients with HF and CRT device implants, who were presently undergoing RM, along with two informal caregivers. Working in three teams, participants used drawing supplies and design cards to design a prototype for a patient-facing dashboard with which they could engage with their device data. Information that patients rated as a high priority for the "Main Dashboard" screen included average percent pacing with alerts for abnormal pacing, other device information such as battery life and recorded events, and information about who to contact with for data-related questions. Preferences for inclusion in an "Additional Information" display included a daily pacing chart, health tips, aborted shocks, a symptom list, and a journal. These results informed the creation of an actual dashboard prototype which was later evaluated by both patients and clinicians. Additionally, important insights were gleaned regarding the involvement of older patients in PD for health technology.