Luminescent Platinum(II) Complexes with Stimuli-Responsive Flexible Lewis Pair Ligands: Spectroscopic and Computational Studies.

A series of new luminescent bimetallic platinum(II) complexes with stimuli-responsive flexible Lewis pair (FlexLP) ligands are described. The FlexLP ligands consist of a dimesitylboron Lewis acid and diphenylphosphine oxide Lewis base which are in equilibrium between the unbound open form and the Lewis adduct, controlled by the hydrogen bond donating strength of the solvent. Spectroscopic techniques and density functional theory (DFT) calculations were used to interpret the photophysics of the platinum(II) complexes. All complexes exhibit tunable absorption in the region of 300-500 nm and green to orange photoluminescence, depending on the ratio of weak (THF) to strong (MeOH) hydrogen bond donating solvent employed. Spectroscopic and computational data shows that phosphine and peripheral acetylide ligands on the platinum(II) centers have limited influence on the emission energy, indicating the emission originates from the FlexLP-dominated fluorescence. Using time-resolved transient absorption spectroscopy it is shown that the complexes undergo intersystem crossing (ISC) to the triplet-excited state upon photoexcitation, and the ISC efficiency is affected by the peripheral acetylide ligands. The triplet-excited state lifetime can also be manipulated by the state of the FlexLP ligand, with the closed form complexes having longer lifetimes than the open form complexes.

Managing medications among individuals with mild cognitive impairment and dementia: Patient-caregiver perspectives.

BACKGROUND: With changing cognitive abilities, individuals with mild cognitive impairment (MCI) and dementia face challenges in successfully managing multidrug regimens. We sought to understand how individuals with MCI or dementia and their family caregivers manage multidrug regimens and better understand patient-to-caregiver transitions in medication management responsibilities. METHODS: We conducted qualitative interviews among patient-caregiver dyads. Eligibility included: patients with a diagnosis of MCI, mild or moderate dementia, managing ≥3 chronic conditions, ≥5 prescription medications, who also had a family caregiver ≥18 years old. Semi-structured interview guides, informed by the Medication Self-Management model, ascertained roles and responsibilities for medication management and patient-to-caregiver transitions in medication responsibilities. RESULTS: We interviewed 32 patient-caregiver dyads. Older adults and caregivers favored older adult autonomy in medication management, and individuals with MCI and mild dementia largely managed their medications independently using multiple strategies (e.g., establishing daily routines, using pillboxes). Among individuals with moderate dementia, caregivers assumed all medication-related responsibilities except when living separately. In those scenarios, caregivers set up organizers and made reminder calls, but did not observe family members taking medications. Patient-to-caregiver transitions in medication responsibilities frequently occurred after caregivers observed older adults making errors with medications. As caregivers sought to assume greater responsibilities with family members' medicines, they faced multiple barriers. Most barriers were dyadic; they affected both the older adult and the caregiver and/or the relationship. Some barriers were specific to caregivers; these included caregivers' competing responsibilities or inaccurate perceptions of dementia, while other barriers were related to the healthcare system. CONCLUSIONS: To ease medication management transitions, balance must be sought between preservation of older adult autonomy and early family caregiver involvement. Clinicians should work to initiate conversations with family caregivers and individuals living with MCI or dementia about transitioning medication responsibilities as memory loss progresses, simplify regimens, and deprescribe, as appropriate.

Downregulation of the metalloproteinases ADAM10 or ADAM17 promotes osteoclast differentiation.

Bone resorption is driven through osteoclast differentiation by macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa-Β ligand (RANKL). We noted that a disintegrin and metalloproteinase (ADAM) 10 and ADAM17 are downregulated at the expression level during osteoclast differentiation of the murine monocytic cell line RAW264.7 in response to RANKL. Both proteinases are well known to shed a variety of single-pass transmembrane molecules from the cell surface. We further showed that inhibitors of ADAM10 or ADAM17 promote osteoclastic differentiation and furthermore enhance the surface expression of receptors for RANKL and M-CSF on RAW264.7 cells. Using murine bone marrow-derived monocytic cells (BMDMCs), we demonstrated that a genetic deficiency of ADAM17 or its required regulator iRhom2 leads to increased osteoclast development in response to M-CSF and RANKL stimulation. Moreover, ADAM17-deficient osteoclast precursor cells express increased levels of the receptors for RANKL and M-CSF. Thus, ADAM17 negatively regulates osteoclast differentiation, most likely through shedding of these receptors. To assess the time-dependent contribution of ADAM10, we blocked this proteinase by adding a specific inhibitor on day 0 of BMDMC stimulation with M-CSF or on day 7 of subsequent stimulation with RANKL. Only ADAM10 inhibition beginning on day 7 increased the size of developing osteoclasts indicating that ADAM10 suppresses osteoclast differentiation at a later stage. Finally, we could confirm our findings in human peripheral blood mononuclear cells (PBMCs). Thus, downregulation of either ADAM10 or ADAM17 during osteoclast differentiation may represent a novel regulatory mechanism to enhance their differentiation process. Enhanced bone resorption is a critical issue in osteoporosis and is driven through osteoclast differentiation by specific osteogenic mediators. The present study demonstrated that the metalloproteinases ADAM17 and ADAM10 critically suppress osteoclast development. This was observed for a murine cell line, for isolated murine bone marrow cells and for human blood cells by either preferential inhibition of the proteinases or by gene knockout. As a possible mechanism, we studied the surface expression of critical receptors for osteogenic mediators on developing osteoclasts. Our findings revealed that the suppressive effects of ADAM17 and ADAM10 on osteoclastogenesis can be explained in part by the proteolytic cleavage of surface receptors by ADAM10 and ADAM17, which reduces the sensitivity of these cells to osteogenic mediators. We also observed that osteoclast differentiation was associated with the downregulation of ADAM10 and ADAM17, which reduced their suppressive effects. We therefore propose that this downregulation serves as a feedback loop for enhancing osteoclast development.

Angiogenic potential in periodontal stem cells from upper and lower jaw: A pilot study.

BACKGROUND: Teeth and supporting oral tissues are attractive and accessible sources of stem cells. Periodontal ligament stem cells (PDLSC) are readily isolated from extracted third molars, and exhibit the ability to self-renew and differentiate into multiple mesodermal cell fates. Clinical experience suggests that the exact location of periodontal defects affects the oral bone remodeling and wound healing. Compared to the mandible, the maxilla heals quicker and more efficiently. Angiogenesis is key in tissue regeneration including dental tissues, yet few studies focus on the angiogenic potential of PDLSC, none of which considered the differences between upper and lower jaw PDLSC (u-PDLSC and l-PDLSC, respectively). METHODS: Here we studied the angiogenic potential of u-PDLSC and l-PDLSC and compared the results to well-established mesenchymal stem cells (MSC). Cells were characterized in terms of surface markers, proliferation, and vascular endothelial growth factor (VEGF) secretion, and angiogenic assays were performed. Newly formed capillaries were stained with CD31, and their expression of platelet endothelial cell adhesion molecule (PECAM-1), angiopoietin 2 (ANGPT2), and vascular endothelial growth factor receptor 1 and 2 (VEGFR-1, VEGFR-2) were measured. RESULTS: Periodontal stem cells from the upper jaw showed a higher proliferation capacity, secreted more VEGF, and formed capillary networks faster and denser than l-PDLSC. Gene expression of angiogenesis-related genes was significantly higher in u-PDLSC than in l-PDLSC or MSC, given that culture conditions were suitable. CONCLUSION: The oral cavity is a valuable source of stem cells, particularly PDLSC, which are promising for oral tissue engineering due to their robust growth, lifelong accessibility, low immunogenicity, and strong differentiation potential. Notably, u-PDLSC exhibit higher VEGF secretion and accelerate capillary formation compared to l-PDLSC or MSC. This study suggests a potential molecular mechanism in capillary formation, emphasizing the significance of precise location isolation of PDLSC.

Quality of orthodontic care-A multicenter cohort study in a German convenience sample : Part 2: Cross-sectional patient-reported outcomes after orthodontic treatment.

OBJECTIVES: In light of the growing interest in orthodontic care and its effectiveness in Germany, part 2 of this multicenter cohort study evaluated patient-reported outcomes such as oral health-related quality of life (OHRQoL), oral hygiene habits, oral health beliefs, and potential influencing factors. METHODS: Of 586 patients screened from seven German study centers, data from 343 patients were analyzed for this part of the study. At the end of their orthodontic treatment, study participants filled out a questionnaire of either the German long version of the Oral Health Impact Profile (OHIP-G 49) or the German short version of the Child Oral Health Impact Profile (COHIP-19), depending on their age, as well as questions about their oral hygiene behavior and beliefs. Patient-, treatment- and occlusion-related factors were analyzed to account for potential influencing factors with regard to patients' OHRQoL after orthodontic treatment. RESULTS: In all, 222 study participants filled out the OHIP-based and 121 the COHIP-based questionnaire. The mean OHIP-G 49 score was 12.68 and the mean OHIP-G 14 score was 3.09; the mean COHIP-19 score was 6.52 (inverted score 69.48). For OHIP-G 49 scores, a nonsignificant trend towards a higher score for male patients (14.45 vs 11.54; p = 0.061) was detected, while this trend was inverse for the COHIP-19 scores, i.e., female patients reported more impairment (total score 6.99 vs. 5.84; p = 0.099). Analyses suggested a trend towards better OHRQoL for patients who classified for the Peer Assessment Rating (PAR) Index improvement rate group 'greatly improved' as well as for nonsmokers. Oral hygiene habits and beliefs after orthodontic treatment were estimated to be good. CONCLUSION: In this German cohort, OHRQoL proved to be good and was rather unimpaired after orthodontic treatment. Furthermore, self-reported oral hygiene behavior and oral health beliefs represented good health awareness.

Behavioral Science: Enhancing Our Approach to the Development of Effective Additional Risk Minimization Strategies.

Additional risk minimization strategies may be required to assure a positive benefit-risk balance for some therapeutic products associated with serious adverse drug reactions/risks of use, without which these products may be otherwise unavailable to patients. The goals of risk minimization strategies are often fundamentally to influence the behavior of healthcare professionals (HCPs) and/or patients and can include appropriate patient selection, provision of education and counselling, appropriate medication use, adverse drug reaction monitoring, and adoption of other elements to assure safe use, such as pregnancy prevention. Current approaches to additional risk minimization strategy development rely heavily on information provision, without full consideration of the contextual factors and multi-level influences on patient and HCP behaviors that impact adoption and long-term adherence to these interventions. Application of evidence-based behavioral science methods are urgently needed to improve the quality and effectiveness of these strategies. Evidence from the fields of adherence, health promotion, and drug utilization research underscores the value and necessity for using established behavioral science frameworks and methods if we are to achieve clinical safety goals for patients. The current paper aims to enhance additional risk minimization strategy development and effectiveness by considering how a behavioral science approach can be applied, drawing from evidence in understanding of engagement with pharmaceutical medicines as well as wider public health interventions for patients and HCPs.

Antipsychotic Drug Prescription in Pediatric Intensive Care Units: A 10-Year U.S. Retrospective Database Study.

Delirium recognition during pediatric critical illness may result in the prescription of antipsychotic medication. These medications have unclear efficacy and safety. We sought to describe antipsychotic medication use in pediatric intensive care units (PICUs) contributing to a U.S. national database. This study is an analysis of the Pediatric Health Information System Database between 2008 and 2018, including children admitted to a PICU aged 0 to 18 years, without prior psychiatric diagnoses. Antipsychotics were given in 16,465 (2.3%) of 706,635 PICU admissions at 30 hospitals. Risperidone (39.6%), quetiapine (22.1%), and haloperidol (20.8%) were the most commonly used medications. Median duration of prescription was 4 days (interquartile range: 2-11 days) for atypical antipsychotics, and haloperidol was used a median of 1 day (1-3 days). Trend analysis showed quetiapine use increased over the study period, whereas use of haloperidol and chlorpromazine (typical antipsychotics) decreased ( p < 0.001). Compared with no antipsychotic administration, use of antipsychotics was associated with comorbidities (81 vs. 65%), mechanical ventilation (57 vs. 36%), longer PICU stay (6 vs. 3 days), and higher mortality (5.7 vs. 2.8%) in univariate analyses. In the multivariable model including demographic and clinical factors, antipsychotic prescription was associated with mortality (odds ratio [OR] = 1.09, 95% confidence interval [CI]: 1.02-1.18). Use of atypical antipsychotics increased over the 10-year period, possibly reflecting increased comfort with their use in pediatric patients. Antipsychotics were more common in patients with comorbidities, mechanical ventilation, and longer PICU stay, and associated with higher mortality in an adjusted model which warrants further study.

Systematic review on effects of experimental orthodontic tooth displacement on brain activation assessed by fMRI.

BACKGROUND: Orthodontic treatment is often accompanied by discomfort and pain in patients, which are believed to be a result of orthodontic tooth displacement caused by the mechanical forces exerted by the orthodontic appliances on the periodontal tissues. These lead to change blood oxygen level dependent response in related brain regions. OBJECTIVE: This systematic review aims to assess the impact of experimental orthodontic tooth displacement on alterations in central nervous system activation assessed by tasked based and resting state fMRI. MATERIALS AND METHODS: A literature search was conducted using online databases, following PRISMA guidelines and the PICO framework. Selected studies utilized magnetic resonance imaging to examine the brain activity changes in healthy participants after the insertion of orthodontic appliances. RESULTS: The initial database screening resulted in 791 studies. Of these, 234 were duplicates and 547 were deemed irrelevant considering the inclusion and exclusion criteria. Of the ten remaining potential relevant studies, two were excluded during full-text screening. Eight prospective articles were eligible for further analysis. The included studies provided evidence of the intricate interplay between orthodontic treatment, pain perception, and brain function. All of the participants in the included studies employed orthodontic separators in short-term experiments to induce tooth displacement during the early stage of orthodontic treatment. Alterations in brain activation were observed in brain regions, functional connectivity and brain networks, predominantly affecting regions implicated in nociception (thalamus, insula), emotion (insula, frontal areas), and cognition (frontal areas, cerebellum, default mode network). CONCLUSIONS: The results suggest that orthodontic treatment influences beyond the pain matrix and affects other brain regions including the limbic system. Furthermore, understanding the orthodontically induced brain activation can aid in development of targeted pain management strategies that do not adversely affect orthodontic tooth movement. Due to the moderate to serious risk of bias and the heterogeneity among the included studies, further clinical trials on this subject are recommended.

Patient factors associated with telehealth quality and experience among adults with chronic conditions.

Objective: To evaluate patient-reported experiences of telehealth and disparities in access, use, and satisfaction with telehealth during the COVID-19 pandemic. Materials and methods: We examined data from the fifth wave of the COVID-19 & Chronic Conditions (C3) study conducted between December 2020 and March 2021. Results: Of the 718 participants, 342 (47.6%) reported having a telehealth visit within the past 4 months. Participants who had a recent telehealth visit were younger, reported worse overall health and chronic illness burden, and living below poverty level. Among participants who had a telehealth visit, 66.7% reported telephone visits and most participants (57.6%) rated telehealth quality as better-or-equal-to in-person visits. Inadequate health literacy was associated with lower likelihood of reporting telehealth quality and usefulness. In multivariable analyses, lower patient activation (adjusted odds ratio (AOR) 0.19, 95% CI, 0.05-0.59) and limited English proficiency (AOR 0.12, 95% CI, 0.03-0.47) were less likely to report telehealth as being better than in-person visits; lower patient activation (AOR 0.06, 95% CI, 0.003-0.41) and income below poverty level (AOR 0.36, 95% CI, 0.13-0.98) were associated with difficulty remembering telehealth visit information. Discussion: Most participants reported usefulness and ease of navigating telehealth. Lower socioeconomic status, limited English proficiency, inadequate health literacy, lower educational attainment, and low patient activation are risks for poorer quality telehealth. Conclusion: The COVID pandemic has accelerated the adoption of telehealth, however, disparities in access and self-reported visit quality persist. Since telemedicine is here to stay, we identify vulnerable populations and discuss potential solutions to reduce healthcare disparities in telehealth use.

Protocol for a construct and clinical validation study of MyCog Mobile: a remote smartphone-based cognitive screener for older adults.

INTRODUCTION: Annual cognitive screening in older adults is essential for early detection of cognitive impairment, yet primary care settings face time constraints that present barriers to routine screening. A remote cognitive screener completed on a patient's personal smartphone before a visit has the potential to save primary care clinics time, encourage broader screening practices and increase early detection of cognitive decline. MyCog Mobile is a promising new remote smartphone-based cognitive screening app for primary care settings. We propose a combined construct and clinical validation study of MyCog Mobile. METHODS AND ANALYSIS: We will recruit a total sample of 300 adult participants aged 65 years and older. A subsample of 200 healthy adult participants and a subsample of 100 adults with a cognitive impairment diagnosis (ie, dementia, mild cognitive impairment, cognitive deficits or other memory loss) will be recruited from the general population and specialty memory care centres, respectively. To evaluate the construct validity of MyCog Mobile, the healthy control sample will self-administer MyCog Mobile on study-provided smartphones and be administered a battery of gold-standard neuropsychological assessments. We will compare correlations between performance on MyCog Mobile and measures of similar and dissimilar constructs to evaluate convergent and discriminant validity. To assess clinical validity, participants in the clinical sample will self-administer MyCog Mobile on a smartphone and be administered a Mini-Cog screener and these data will be combined with the healthy control sample. We will then apply several supervised model types to determine the best predictors of cognitive impairment within the sample. Area under the receiver operating characteristic curve, accuracy, sensitivity and specificity will be the primary performance metrics for clinical validity. ETHICS AND DISSEMINATION: The Institutional Review Board at Northwestern University (STU00214921) approved this study protocol. Results will be published in peer-reviewed journals and summaries provided to the study's funders.

Relationship Between Cognitive Impairment and Depression Among Middle Aged and Older Adults in Primary Care.

Objectives: To determine rates of previously undetected cognitive impairment among patients with depression in primary care. Methods: Patients ages 55 and older with no documented history of dementia or mild cognitive impairment were recruited from primary care practices in New York City, NY and Chicago, IL (n = 855). Cognitive function was assessed with the Montreal Cognitive Assessment (MoCA) and depression with the Patient Health Questionnaire-8. Results: The mean age was 66.8 (8.0) years, 45.3% were male, 32.7% Black, and 29.2% Latinx. Cognitive impairment increased with severity of depression: 22.9% in persons with mild depression, 27.4% in moderate depression and 41.8% in severe depression (p = .0002). Severe depression was significantly associated with cognitive impairment in multivariable analysis (standardized ß = -.11, SE = 0.33, p < .0001). Discussion: Depression was strongly associated with previously undetected cognitive impairment. Primary care clinicians should consider screening, or expand their screening, for both conditions.

Identifying Differences in Molecular Characteristics Relevant for Remodeling of Periodontal Ligament Stem Cells from the Upper and Lower Jaw.

Periodontal defects' localization affects wound healing and bone remodeling, with faster healing in the upper jaw compared to the lower jaw. While differences in blood supply, innervation, and odontogenesis contribute, cell-intrinsic variances may exist. Few studies explored cell signaling in periodontal ligament stem cells (PDLSC), overlooking mandible-maxilla disparitiesUsing kinomics technology, we investigated molecular variances in PDLSC. Characterization involved stem cell surface markers, proliferation, and differentiation capacities. Kinase activity was analyzed via multiplex kinase profiling, mapping differential activity in known gene regulatory networks. Upstream kinase analysis identified stronger EphA receptor expression in the mandible, potentially inhibiting osteogenic differentiation. The PI3K-Akt pathway showed higher activity in lower-jaw PDLSC. PDLSC from the upper jaw exhibit superior proliferation and differentiation capabilities. Differential activation of gene regulatory pathways in upper vs. lower-jaw PDLSC suggests implications for regenerative therapies.

Remote Self-Administration of Cognitive Screeners for Older Adults Prior to a Primary Care Visit: Pilot Cross-Sectional Study of the Reliability and Usability of the MyCog Mobile Screening App.

BACKGROUND: Routine cognitive screening is essential in the early detection of dementia, but time constraints in primary care settings often limit clinicians' ability to conduct screenings. MyCog Mobile is a newly developed cognitive screening system that patients can self-administer on their smartphones before a primary care visit, which can help save clinics' time, encourage broader screening practices, and increase early detection of cognitive decline. OBJECTIVE: The goal of this pilot study was to examine the feasibility, acceptability, and initial psychometric properties of MyCog Mobile. Research questions included (1) Can older adults complete MyCog Mobile remotely without staff support? (2) Are the internal consistency and test-retest reliability of the measures acceptable? and (3) How do participants rate the user experience of MyCog Mobile? METHODS: A sample of adults aged 65 years and older (N=51) self-administered the MyCog Mobile measures remotely on their smartphones twice within a 2- to 3-week interval. The pilot version of MyCog Mobile includes 4 activities: MyFaces measures facial memory, MySorting measures executive functioning, MySequences measures working memory, and MyPictures measures episodic memory. After their first administration, participants also completed a modified version of the Simplified System Usability Scale (S-SUS) and 2 custom survey items. RESULTS: All participants in the sample passed the practice items and completed each measure. Findings indicate that the Mobile Toolbox assessments measure the constructs well (internal consistency 0.73 to 0.91) and are stable over an approximately 2-week delay (test-retest reliability 0.61 to 0.71). Participants' rating of the user experience (mean S-SUS score 73.17, SD 19.27) indicated that older adults found the usability of MyCog Mobile to be above average. On free-response feedback items, most participants provided positive feedback or no feedback at all, but some indicated a need for clarity in certain task instructions, concerns about participants' abilities, desire to be able to contact a support person or use in-app technical support, and desire for additional practice items. CONCLUSIONS: Pilot evidence suggests that the MyCog Mobile cognitive screener can be reliably self-administered by older adults on their smartphones. Participants in our study generally provided positive feedback about the MyCog Mobile experience and rated the usability of the app highly. Based on participant feedback, we will conduct further usability research to improve support functionality, optimize task instructions and practice opportunities, and ensure that patients feel comfortable using MyCog Mobile. The next steps include a clinical validation study that compares MyCog Mobile to gold-standard assessments and tests the sensitivity and specificity of the measures for identifying dementia.

Differentiating primary and secondary FSGS using non-invasive urine biomarkers.

Background: Focal segmental glomerulosclerosis (FSGS) is divided into genetic, primary (p), uncertain cause, and secondary (s) forms. The subclasses differ in management and prognosis with differentiation often being challenging. We aimed to identify specific urine proteins/peptides discriminating between clinical and biopsy-proven pFSGS and sFSGS. Methods: Sixty-three urine samples were collected in two different centers (19 pFSGS and 44 sFSGS) prior to biopsy. Samples were analysed using capillary electrophoresis-coupled mass spectrometry. For biomarker definition, datasets of age-/sex-matched normal controls (NC, n = 98) and patients with other chronic kidney diseases (CKDs, n = 100) were extracted from the urinary proteome database. Independent specificity assessment was performed in additional data of NC (n = 110) and CKD (n = 170). Results: Proteomics data from patients with pFSGS were first compared to NC (n = 98). This resulted in 1179 biomarker (P < 0.05) candidates. Then, the pFSGS group was compared to sFSGS, and in a third step, pFSGS data were compared to data from different CKD etiologies (n = 100). Finally, 93 biomarkers were identified and combined in a classifier, pFSGS93. Total cross-validation of this classifier resulted in an area under the receiving operating curve of 0.95. The specificity investigated in an independent set of NC and CKD of other etiologies was 99.1% for NC and 94.7% for CKD, respectively. The defined biomarkers are largely fragments of different collagens (49%). Conclusion: A urine peptide-based classifier that selectively detects pFSGS could be developed. Specificity of 95%-99% could be assessed in independent samples. Sensitivity must be confirmed in independent cohorts before routine clinical application.

A diagnostic phase III/IV seamless design to investigate the diagnostic accuracy and clinical effectiveness using the example of HEDOS and HEDOS II.

The development process of medical devices can be streamlined by combining different study phases. Here, for a diagnostic medical device, we present the combination of confirmation of diagnostic accuracy (phase III) and evaluation of clinical effectiveness regarding patient-relevant endpoints (phase IV) using a seamless design. This approach is used in the Thyroid HEmorrhage DetectOr Study (HEDOS & HEDOS II) investigating a post-operative hemorrhage detector named ISAR-M THYRO® in patients after thyroid surgery. Data from the phase III trial are reused as external controls in the control group of the phase IV trial. An unblinded interim analysis is planned between the two study stages which includes a recalculation of the sample size for the phase IV part after completion of the first stage of the seamless design. The study concept presented here is the first seamless design proposed in the field of diagnostic studies. Hence, the aim of this work is to emphasize the statistical methodology as well as feasibility of the proposed design in relation to the planning and implementation of the seamless design. Seamless designs can accelerate the overall trial duration and increase its efficiency in terms of sample size and recruitment. However, careful planning addressing numerous methodological and procedural challenges is necessary for successful implementation as well as agreement with regulatory bodies.

Disparities in Patient Portal Use Among Adults With Chronic Conditions.

Importance: Disparities in patient access and use of health care portals have been documented. Limited research has evaluated disparities in portal use during and after the COVID-19 pandemic. Objective: To assess prevalence of health care portal use before, during, and after the most restrictive phase of the pandemic (2019-2022) among the COVID-19 & Chronic Conditions (C3) cohort and to investigate any disparities in use by sociodemographic factors. Design, Setting, and Participants: This cohort study uses data from the C3 study, an ongoing, longitudinal, telephone-based survey of participants with multiple chronic conditions. Participants were middle aged and older-adult primary care patients who had an active portal account, recruited from a single academic medical center in Chicago, Illinois, between 2019 and 2022. Data were analyzed between March and June 2022. Main Outcomes and Measures: Outcomes of portal use (ie, number of days of portal login by year) were recorded for all study participants by the electronic data warehouse. All parent studies had uniform sociodemographic data and measures of social support, self-efficacy, health literacy, and health activation. Results: Of 536 participants (mean [SD] age, 66.7 [12.0] years; 336 [62.7%] female), 44 (8.2%) were Hispanic or Latinx, 142 (26.5%) were non-Hispanic Black, 322 (60.1%) were non-Hispanic White, and 20 individuals (3.7%) identified as other race, including Asian, Native American or Alaskan Native, and self-reported other race. In multivariable analyses, portal login activity was higher during the 3 years of the COVID-19 pandemic compared with the 2019 baseline. Higher portal login activity was associated with adequate health literacy (incidence rate ratio [IRR], 1.51; 95% CI, 1.18-1.94) and multimorbidity (IRR, 1.38; 95% CI, 1.17-1.64). Lower portal activity was associated with older age (≥70 years: IRR, 0.69; 95% CI, 0.55-0.85) and female sex (IRR, 0.77; 95% CI, 0.66-0.91). Compared with non-Hispanic White patients, lower portal activity was observed among Hispanic or Latinx patients (IRR, 0.66; 95% CI, 0.49-0.89), non-Hispanic Black patients (IRR, 0.68; 95% CI, 0.56-0.83), and patients who identified as other race (IRR, 0.42; 95% CI, 0.28-0.64). Conclusions and Relevance: This cohort study using data from the C3 study identified changes in portal use over time and highlighted populations that had lower access to health information. The COVID-19 pandemic was associated with an increase in portal use. Sociodemographic disparities by sex and age were reduced, although disparities by health literacy widened. A brief validated health literacy measure may serve as a useful digital literacy screening tool to identify patients who need further support.

Missed Healthcare Visits During the COVID-19 Pandemic: A Longitudinal Study.

INTRODUCTION: Missed visits have been estimated to cost the U.S. healthcare system $50 billion annually and have been linked to healthcare inefficiency, higher rates of emergency department visits, and worse outcomes. COVID-19 disrupted existing outpatient healthcare utilization patterns. In our study, we sought to examine the frequency of missed outpatient visits over the course of the COVID-19 pandemic and to examine patient-level characteristics associated with non-attendance. METHODS: This study utilized data from a longitudinal cohort study (the Chicago COVID-19 Comorbidities (C3) study). C3 participants were enrollees in 1 of 4 active, "parent" studies; they were rapidly enrolled in C3 at the onset of the pandemic. Multiple waves of telephone-based interviews were conducted to collect experiences with the pandemic, as well as socio-demographic and health characteristics, health literacy, patient activation, and depressive and anxiety symptoms. For the current analysis, data from waves 3 to 8 (05/01/20-05/19/22) were analyzed. Participants included 845 English or Spanish-speaking adults with 1 or more chronic conditions. RESULTS: The percentage of participants reporting missed visits due to COVID-19 across study waves ranged from 3.1 to 22.4%. Overall, there was a decline in missed visits over time. No participant sociodemographic or health characteristic was consistently associated with missed visits across the study waves. In bivariate and multivariate analysis, only patient-reported anxiety was significantly associated with missed visits across all study waves. CONCLUSION: Findings reveal that anxiety was consistently associated with missed visits during the COVID-19 pandemic, but not sociodemographic or health characteristics. Results can inform future public health initiatives to reduce absenteeism by considering patients' emotional state during times of uncertainty.