Care partners and consumer health information technology: A framework to guide systems-level initiatives in support of digital health equity.

Introduction: Consumer-oriented health information technologies (CHIT) such as the patient portal have a growing role in care delivery redesign initiatives such as the Learning Health System. Care partners commonly navigate CHIT demands alongside persons with complex health and social needs, but their role is not well specified. Methods: We assemble evidence and concepts from the literature describing interpersonal communication, relational coordination theory, and systems-thinking to develop an integrative framework describing the care partner's role in applied CHIT innovations. Our framework describes pathways through which systematic engagement of the care partner affects longitudinal work processes and multi-level outcomes relevant to Learning Health Systems. Results: Our framework is grounded in relational coordination, an emerging theory for understanding the dynamics of coordinating work that emphasizes role-based relationships and communication, and the Systems Engineering Initiative for Patient Safety (SEIPS) model. Cross-cutting work systems geared toward explicit and purposeful support of the care partner role through CHIT may advance work processes by promoting frequent, timely, accurate, problem-solving communication, reinforced by shared goals, shared knowledge, and mutual respect between patients, care partners, and care team. We further contend that systematic engagement of the care partner in longitudinal work processes exerts beneficial effects on care delivery experiences and efficiencies at both individual and organizational levels. We discuss the utility of our framework through the lens of an illustrative case study involving patient portal-mediated pre-visit agenda setting. Conclusions: Our framework can be used to guide applied embedded CHIT interventions that support the care partner role and bring value to Learning Health Systems through advancing digital health equity, improving user experiences, and driving efficiencies through improved coordination within complex work systems.

Emergency department visits and hospital readmissions after a deprescribing intervention among hospitalized older adults.

BACKGROUND: Deprescribing is the planned/supervised method of dose reduction or cessation of medications that might be harmful, or no longer be beneficial. Though benefits of deprescribing are debatable in improving clinical outcomes, it has been associated with decreased number of potentially inappropriate medications, which may potentially reduce the risk of adverse events among hospitalized older adults. With unclear evidence for deprescribing in this population, this study aimed to examine time-to-first unplanned healthcare utilization, which included 90-day emergency department (ED) visits or hospital readmission and associated predictors, during a deprescribing intervention. METHODS: A secondary data analysis of a clinical trial (Shed-MEDS NCT02979353) was performed. Cox regression was used to compare the time-to-first 90-day ED visit/readmission/death from hospital discharge for the intervention and control groups. Additionally, we performed exploratory analysis of predictors (comorbidities, functional health status, drug burden index (DBI), hospital length of stay, health literacy, food insecurity, and financial burden) associated with the time-to-first 90-day ED visit/readmission/death. RESULTS: The hazard of first 90-day ED visits/readmissions/death was 15% lower in the intervention versus the control group (95% CI: 0.61-1.19, p = 0.352, respectively); however, this difference was not statistically significant. For every additional number of comorbidities (Hazard ratio (HR): 1.12, 95% CI: 1.04-1.21) and each additional day of hospital length of stay (HR: 1.04, 95% CI: 1.01-1.07) were significantly associated with a higher hazard of 90-day ED visit/readmission/death in the intervention group; whereas for each unit of increase in pre-hospital DBI score (HR: 1.08 and HR 1.16, respectively) was significantly associated with a higher hazard of 90-day ED visit/readmission/death in the control group. CONCLUSIONS: The intervention and control groups had comparable time-to-first 90-day ED visit/readmission/death during a deprescribing intervention. This finding suggests that deprescribing did not result in a higher risk of ED visit/readmission/death during the 90-day period following hospital discharge.

EPAS1 expression contributes to maintenance of the primordial follicle pool in the mouse ovary.

Oxygen availability can have profound effects on cell fate decisions and survival, in part by regulating expression of hypoxia-inducible factors (HIFs). In the ovary, HIF expression has been characterised in granulosa cells, however, any requirement in oocytes remains relatively undefined. Here we developed a Hif2a/Epas1 germline-specific knockout mouse line in which females were fertile, however produced 40% fewer pups than controls. No defects in follicle development were detected, and quality of MII oocytes was normal, as per assessments of viability, intracellular reactive oxygen species, and spindle parameters. However, a significant diminishment of the primordial follicle pool was evident in cKO females that was attributed to accelerated follicle loss from postnatal day 6 onwards, potentially via disruption of the autophagy pathway. These data demonstrate the importance of HIF signalling in oocytes, particularly at the primordial follicle stage, and lend to the importance of controlling oxygen tension in the development of in vitro growth and maturation approaches for assisted reproduction.

The effect of unloading and ejection conditions on the properties of pharmaceutical tablets.

This study investigates decompression and ejection conditions on tablet characteristics by comparing compact densities and tensile strengths made using regular rigid dies and custom-built die systems that enable triaxial decompression. Die-wall pressure evolution during decompression and ejection stresses did not meaningfully impact the density and tensile strength of the materials tested: microcrystalline cellulose, crystalline lactose monohydrate, and mannitol. Furthermore, the apparent differences in tensile strength between rectangular cuboids and cylindrical compacts are unrelated to decompression and ejection conditions, but rather a consequence of their shapes and of the test configurations. This suggests that elastic and plastic deformations that may occur during decompression and ejection are not significantly influenced by die-wall pressure evolution. We thus conclude that while triaxial decompression and constraint-free ejection may allow the production of defect-free compacts for materials that otherwise are defect prone using a rigid die, they seem to pose no benefits when the materials already produce defect-free compacts using a rigid die.

Pharmacist-led telehealth deprescribing for people living with dementia and polypharmacy in primary care: A pilot study.

BACKGROUND: People living with dementia (PLWD) have complex medication regimens, exposing them to increased risk of harm. Pragmatic deprescribing strategies that align with patient-care partner goals are needed. METHODS: A pilot study of a pharmacist-led intervention to optimize medications with patient-care partner priorities, ran May 2021-2022 at two health systems. PLWD with ≥7 medications in primary care and a care partner were enrolled. After an introductory mailing, dyads were randomized to a pharmacist telehealth intervention immediately (intervention) or delayed by 3 months (control). Feasibility outcomes were enrollment, intervention completion, pharmacist time, and primary care provider (PCP) acceptance of recommendations. To refine pragmatic data collection protocols, we assessed the Medication Regimen Complexity Index (MRCI; primary efficacy outcome) and the Family Caregiver Medication Administration Hassles Scale (FCMAHS). RESULTS: 69 dyads enrolled; 27 of 34 (79%) randomized to intervention and 28 of 35 (80%) randomized to control completed the intervention. Most visits (93%) took more than 20 min and required multiple follow-up interactions (62%). PCPs responded to 82% of the pharmacists' first messages and agreed with 98% of recommendations. At 3 months, 22 (81%) patients in the intervention and 14 (50%) in the control had ≥1 medication discontinued; 21 (78%) and 12 (43%), respectively, had ≥1 new medication added. The mean number of medications decreased by 0.6 (3.4) in the intervention and 0.2 (1.7) in the control, reflecting a non-clinically meaningful 1.0 (±12.4) point reduction in the MRCI among intervention patients and a 1.2 (±12.9) point increase among control. FCMAHS scores decreased by 3.3 (±18.8) points in the intervention and 2.5 (±14.4) points in the control. CONCLUSION: Though complex, pharmacist-led telehealth deprescribing is feasible and may reduce medication burden in PLWD. To align with patient-care partner goals, pharmacists recommended deprescribing and prescribing. If scalable, such interventions may optimize goal-concordant care for PLWD.

Responsive parenting and Black mothers' postpartum sleep: Secondary analysis of a randomized controlled trial.

OBJECTIVE: To determine if an intervention designed to enhance early responsive parenting (RP) practices (e.g., reading infant cues, establishing bedtime routines) and promote infant sleep and soothing among Black families has secondary benefits for mothers' postpartum sleep. METHOD: This preregistered secondary analysis of the Sleep Strong African American Families randomized controlled trial investigated effects of an RP intervention versus a safety control condition on self-reported maternal sleep difficulties at 8 and 16 weeks postpartum and on actigraph-measured maternal sleep at 8 weeks postpartum. RESULTS: The 212 randomized mothers were Black/African American (100%) and non-Hispanic (98.6%) and averaged 22.7 years (SD = 4.5) of age. Among 138 mothers with useable actigraph data, RP mothers had a mean 20 [95% CI: 2, 37] minutes longer actigraph-measured total sleep time than controls at 8 weeks postpartum, after adjusting for age and other covariates likely to influence mothers' sleep (p = .04). Participation in the RP intervention did not significantly impact self-reported sleep difficulties or other actigraph-measured sleep parameters (e.g., efficiency) in either unadjusted or adjusted models, although RP effects on sleep difficulties and sleep efficiency were in the hypothesized directions. CONCLUSIONS: Interventions supporting responsive sleep parenting practices to increase infant sleep may also help first-time Black mothers get more sleep themselves during the postpartum period, even without an explicit focus on maternal sleep strategies. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Enhanced recovery after cesarean from the patient perspective: a prospective study of the ERAC Questionnaire (ERAC-Q).

OBJECTIVES: To evaluate the impact of an Enhanced Recovery After Cesarean (ERAC) protocol on the post-cesarean recovery experience using a validated ten-item questionnaire (ERAC-Q). METHODS: This is a prospective cohort study of patients completing ERAC quality-of-life questionnaires (ERAC-Q) during inpatient recovery after cesarean delivery (CD) between October 2019 and September 2020, before and after the implementation of our ERAC protocol. Patients with non-Pfannenstiel incision, ICU admission, massive transfusion, bowel injury, existing chronic pain disorders, acute postpartum depression, or neonatal demise were excluded. The ERAC-Q was administered on postoperative day one and day of discharge to the pre- and post-ERAC implementation cohorts, rating aspects of their recovery experience on a scale of 0 (best) to 10 (worst). The primary outcome was ERAC-Q scores. Statistical analysis was performed with SAS software. RESULTS: There were 196 and 112 patients in the pre- and post-ERAC cohorts, respectively. The post-ERAC group reported significantly lower total ERAC-Q scores compared to the pre-ERAC group, reflecting fewer adverse symptoms and greater perceived recovery on postoperative day one (1.6 [0.7, 2.8] vs. 2.7 [1.6, 4.3]) and day of discharge (0.8 [0.3, 1.5] vs. 1.4 [0.7, 2.2]) (p<0.001). ERAC-Q responses did not predict the time to achieve objective postoperative milestones. However, worse ERAC-Q pain and total scores were associated with higher inpatient opiate use. CONCLUSIONS: ERAC implementation positively impacts patient recovery experience. The administration of ERAC-Q can provide real-time feedback on patient-perceived recovery quality and how healthcare protocol changes may impact their experience.

Creation of Novel Sensitive Probe Substrate and Moderate Inhibitor Models for a Comprehensive Prediction of CYP2C8 Interactions for Tucatinib.

A physiologically-based pharmacokinetic (PBPK) model was developed to simulate plasma concentrations of tucatinib (TUKYSA®) after single-dose or multiple-dose administration of 300 mg b.i.d. orally. This PBPK model was subsequently applied to support evaluation of drug-drug interaction (DDI) risk as a perpetrator resulting from tucatinib inhibition of CYP3A4, CYP2C8, CYP2C9, P-gp, or MATE1/2-K. The PBPK model was also applied to support evaluation of DDI risk as a victim resulting from co-administration with CYP3A4 or CYP2C8 inhibitors, or a CYP3A4 inducer. After refinement with clinical DDI data, the final PBPK model was able to recover the clinically observed single and multiple-dose plasma concentrations for tucatinib when tucatinib was administered as a single agent in healthy subjects. In addition, the final model was able to recover clinically observed plasma concentrations of tucatinib when administered in combination with itraconazole, rifampin, or gemfibrozil as well as clinically observed plasma concentrations of probe substrates of CYP3A4, CYP2C8, CYP2C9, P-gp, or MATE1/2-K. The PBPK model was then applied to prospectively predict the potential perpetrator or victim DDIs with other substrates, inducers, or inhibitors. To simulate a potential interaction with a moderate CYP2C8 inhibitor, two novel PBPK models representing a moderate CYP2C8 inhibitor and a sensitive CYP2C8 substrate were developed based on the existing PBPK models for gemfibrozil and rosiglitazone, respectively. The simulated population geometric mean area under the curve ratio of tucatinib with a moderate CYP2C8 inhibitor ranged from 1.98- to 3.08-fold, and based on these results, no dose modifications were proposed for moderate CYP2C8 inhibitors for the tucatinib label.

Characterization of Common Genetic Variants in P2RX7 and Their Contribution to Chronic Pain Conditions.

The adenosine triphosphate (ATP)-gated channel P2X7 is encoded by a gene enriched for common nonsynonymous variants. Many of these variants have functional cellular effects, and some have been implicated in chronic pain. In this study, we first systematically characterized all 17 common nonsynonymous variants using whole-cell patch clamp electrophysiology. Then, we analyzed these variants for statistical association with chronic pain phenotypes using both individual P2RX7 variants as predictors and cumulative allele counts of same-direction cellular effect in univariate models. Association and validation analyses were conducted in the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) cohort (N = 3260) and in the Complex Persistent Pain Conditions (CPPC) cohort (N = 900), respectively. Our results showed an association between allele A of rs7958311 and an increased risk of chronic pelvic pain, with convergent evidence for contribution to fibromyalgia and irritable bowel syndrome, confirmed in a meta-analysis. This allelic variant produced a unique cellular phenotype: a gain-of-function in channel opening, and a loss-of-function in pore opening. A computational study using a 12-state Markov model of ATP binding to the P2X7 receptor suggested that this cellular phenotype arises from an increased ATP binding affinity and an increased open channel conductance combined with a loss of sensitization. Cumulative allele count analysis did not provide additional insights. In conclusion, our results go beyond reproducing association for rs7958311 with chronic pain and suggest that its unique combination of gain-of-function in channel and loss-of-function in pore activity may explain why it is likely the only common P2RX7 variant with contribution to chronic pain. PERSPECTIVE: This study characterizes all common P2RX7 variants using cellular assays and statistical association analyses with chronic pain, with Markov state modeling of the most robustly associated variant.

Evaluating the Safety of an Educational Deprescribing Intervention: Lessons from the Optimize Trial.

BACKGROUND: Patients, family members, and clinicians express concerns about potential adverse drug withdrawal events (ADWEs) following medication discontinuation or fears of upsetting a stable medical equilibrium as key barriers to deprescribing. Currently, there are limited methods to pragmatically assess the safety of deprescribing and ascertain ADWEs. We report the methods and results of safety monitoring for the OPTIMIZE trial of deprescribing education for patients, family members, and clinicians. METHODS: This was a pragmatic cluster randomized trial with multivariable Poisson regression comparing outcome rates between study arms. We conducted clinical record review and adjudication of sampled records to assess potential causal relationships between medication discontinuation and outcomes. This study included adults aged 65+ with dementia or mild cognitive impairment, one or more additional chronic conditions, and prescribed 5+ chronic medications. The intervention included an educational brochure on deprescribing that was mailed to patients prior to primary care visits, a clinician notification about individual brochure mailings, and an educational tip sheets was provided monthly to primary care clinicians. The outcomes of the safety monitoring were rates of hospitalizations and mortality during the 4 months following brochure mailings and results of record review and adjudication. The adjudication process was conducted throughout the trial and included classifications: likely, possibly, and unlikely. RESULTS: There was a total of 3012 (1433 intervention and 1579 control) participants. There were 420 total hospitalizations involving 269 (18.8%) people in the intervention versus 517 total hospitalizations involving 317 (20.1%) people in the control groups. Adjusted risk ratios comparing intervention to control groups were 0.92 [95% confidence interval (CI) 0.72, 1.16] for hospitalization and 1.19 (95% CI 0.67, 2.11) for mortality. Both groups had zero deaths "likely" attributed to a medication change prior to the event. A total of 3 out of 30 (10%) intervention group hospitalizations and 7 out of 35 (20%) control group hospitalizations were considered "likely" due to a medication change. CONCLUSIONS: Population-based deprescribing education is safe in the older adult population with cognitive impairment in our study. Pragmatic methods for safety monitoring are needed to further inform deprescribing interventions. TRIAL REGISTRATION: NCT03984396. Registered on 13 June 2019.

Identifying Optimal Acute Care Comparators to Inform the Evaluation of an Advanced Care at Home Pilot Program.

BACKGROUND: Hospital at Home (H@H) programs-which seek to deliver acute care within a patient's home-have become more prevalent over time. However, existing literature exhibits heterogeneity in program structure, evaluation design, and target population size, making it difficult to draw generalizable conclusions to inform future H@H program design. OBJECTIVE: The objective of this work was to develop a quality improvement evaluation strategy for a H@H program-the Kaiser Permanente Advanced Care at Home (KPACAH) program in Northern California-leveraging electronic health record data, chart review, and patient surveys to compare KPACAH patients with inpatients in traditional hospital settings. METHODS: The authors developed a 3-step recruitment workflow that used electronic health record filtering tools to generate a daily list of potential comparators, a manual chart review of potentially eligible comparator patients to assess individual clinical and social criteria, and a phone interview with patients to affirm eligibility and interest from potential comparator patients. RESULTS: This workflow successfully identified and enrolled a population of 446 comparator patients in a 5-month period who exhibited similar demographics, reasons for hospitalization, comorbidity burden, and utilization measures to patients enrolled in the KPACAH program. CONCLUSION: These initial findings provide promise for a workflow that can facilitate the identification of similar inpatients hospitalized at traditional brick and mortar facilities to enhance outcomes evaluations for the H@H programs, as well as to identify the potential volume of enrollees as the program expands.

Ethical Aspects of Physician Decision-Making for Deprescribing Among Older Adults With Dementia.

Importance: Physicians endorse deprescribing of risky or unnecessary medications for older adults (aged ≥65 years) with dementia, but there is a lack of information on what influences decisions to deprescribe in this population. Objective: To understand how physicians make decisions to deprescribe for older adults with moderate dementia and ethical and pragmatic concerns influencing those decisions. Design, Setting, and Participants: A cross-sectional national mailed survey study of a random sample of 3000 primary care physicians from the American Medical Association Physician Masterfile who care for older adults was conducted from January 15 to December 31, 2021. Main Outcomes and Measures: The study randomized participants to consider 2 clinical scenarios in which a physician may decide to deprescribe a medication for older adults with moderate dementia: 1 in which the medication could cause an adverse drug event if continued and the other in which there is no evidence of benefit. Participants ranked 9 factors related to possible ethical and pragmatic concerns through best-worst scaling methods (from greatest barrier to smallest barrier to deprescribing). Conditional logit regression quantified the relative importance for each factor as a barrier to deprescribing. Results: A total of 890 physicians (35.0%) returned surveys; 511 (57.4%) were male, and the mean (SD) years since graduation was 26.0 (11.7). Most physicians had a primary specialty in family practice (50.4% [449 of 890]) and internal medicine (43.5% [387 of 890]). A total of 689 surveys were sufficiently complete to analyze. In both clinical scenarios, the 2 greatest barriers to deprescribing were (1) the patient or family reporting symptomatic benefit from the medication (beneficence and autonomy) and (2) the medication having been prescribed by another physician (autonomy and nonmaleficence). The least influential factor was ease of paying for the medication (justice). Conclusions and Relevance: Findings from this national survey study of primary care physicians suggests that understanding ethical aspects of physician decision-making can inform clinician education about medication management and deprescribing decisions for older adults with moderate dementia.

Interpretive Qualitative Evaluation Informs Research Participation and Advocacy Training Program for Seniors: A Pilot Study.

Background: An 8-week educational intervention co-taught by medical students and faculty was designed to foster communication between clinical researchers and populations of interest to ultimately increase participation in clinical research by older adults, including underrepresented groups. Weekly topics focused on age-related changes and health conditions, socio-contextual factors impacting aging populations, and wellness strategies. Objectives: To evaluate the successes and weaknesses of an educational intervention aimed at increasing the participation of older adults in clinical research. Design: A focus group was assembled after an 8-week educational intervention, titled DREAMS, to obtain participants' feedback on the program, following a pre-formulated interview guide. Settings: Participants were interviewed in a health center office environment in the United States of America in April of 2016. Participants: A post-intervention focus group was conducted with a group of eight older adults (mean age = 75.8 ± 11.4 years) from 51 total participants who completed the intervention. Methods: The focus group was interviewed loosely following a pre-formed question guide. Participants were encouraged to give honest feedback. The conversation was recorded, transcribed verbatim, and analyzed using thematic analyses. Results: While participants viewed most aspects of the study as a success and stated that it was a productive learning experience, most participants had suggestions for improvements in the program content and implementation. Specifically, the composition of and direction to small breakout groups should be carefully considered and planned in this population, and attention should be paid to the delivery of sensitive topic such as death and dementia. A clear main benefit of this programmatic approach is the development of a rapport amongst participants and between participants and clinical researchers. Conclusions: The results provide useful insights regarding improving participation among hard-to-reach and historically underrepresented groups of older adults in clinical research. Future iterations of this program and similar educational interventions can use these findings to better achieve the programmatic objectives.

Assessing the Feasibility of an Empathic Inquiry Approach to Social Needs Screening in 10 Federally Qualified Health Centers.

OBJECTIVES: Despite an increasing emphasis from health care organizations on patients' social health, there is debate about how best to screen patients for social health needs in practice. Empathic Inquiry is a patient-centered approach to asking about patients' social needs that incorporates motivational interviewing and trauma-informed care techniques to increase patient experience of trustworthiness and safety with their care teams. The purpose of this brief report is to describe the feasibility and acceptability of implementing an Empathic Inquiry-informed approach to social needs screening in 10 federally qualified health centers. METHODS: Clinical staff at community health centers implemented Empathic Inquiry as part of an 8-month learning collaborative. Patients completed surveys about their experience with Empathic Inquiry after screening conversations took place. Qualitative data on organizational implementation experience were collected monthly during 2018. FINDINGS: Eight of 10 organizations completed the learning collaborative and implemented Empathic Inquiry in practice. Of 132 patient surveys received, patients agreed (64% strongly agree, 28% somewhat agree) that being screened for social needs strengthened their relationship with their care team and 83% strongly agreed the conversation was a good use of time. Most patients (54%) indicated social health screening was appropriate at every visit, and 27% answered once every 6 months. CONCLUSIONS: The Empathic Inquiry approach to understanding patients' social needs was feasible for implementation in community settings. Patients said the conversations were worthwhile, built trust with their care teams, and should be conducted every 6 months or more frequently.

Effect of Tucatinib on Cardiac Repolarization in Healthy Volunteers.

BACKGROUND AND OBJECTIVE: Tucatinib is a selective tyrosine kinase inhibitor of the human epidermal growth factor receptor 2 (HER2) approved to treat metastatic HER2-positive breast and colorectal cancers. The International Council for Harmonisation of Technical Requirements for Human Use (ICH) E14 guideline mandates that new drugs are assessed for potential effects on cardiac repolarization through electrocardiogram (ECG) evaluation in a QT/corrected QT (TQT) study. METHODS: We evaluated the effect of tucatinib on cardiac repolarization in healthy volunteers in a phase I, randomized, partially double-blind, placebo-and positive-controlled three-period crossover study. The primary endpoint was the placebo-corrected change from baseline in QT interval values, corrected for heart rate using Fridericia's method (ΔΔQTcF). RESULTS: After achieving steady-state tucatinib exposures with 300 mg twice daily, the observed ΔΔQTcF ranged from -2.9 msec at 2 hours post-dose to 0 msec at 4 hours post-dose. The upper bound of the 90% confidence interval (CI) was below 5 ms at all post-dose timepoints. Assay sensitivity was confirmed as the lower bound of the 90% CI and was >5 ms following moxifloxacin dosing. As the mean ΔΔQTcF of tucatinib was predicted to be -  1.80 ms (90% CI -  3.90, 0.30) at clinically relevant tucatinib concentrations (511 ng/mL), an effect of tucatinib on QTcF exceeding 10 ms was excluded within observed ranges of tucatinib (up to ~1000 ng/mL). Tucatinib had no clinically relevant effect on heart rate or cardiac conduction. The safety profile of tucatinib was manageable after multiple doses. CONCLUSION: Tucatinib had no clinically relevant effects on studied ECG parameters. This study constitutes a clearly negative TQT study per ICH E14 guidance. CLINICAL TRIAL REGISTRATION: This trial (NCT03777761) was registered on 17 December 2018.

Barriers and facilitators to deprescribing before surgery: A qualitative study of providers and older adults.

INTRODUCTION: Deprescribing, the collaborative process between providers and patients to streamline medication regimen, may reduce the risk of adverse events following surgery among older adults with multimorbidity. However, barriers and facilitators to deprescribing for surgery has not been explored. METHODS: We conducted a qualitative study of Primary Care Providers (PCP) and patients aged 65 and older who were scheduled for surgery. We used the Theoretical Domains Framework, which informed the interview guide and analysis. RESULTS: A total of 16 participants (n=8 providers, n=8 patients) were included. Themes were regarding: 1) attitudes towards deprescribing before surgery, 2) perceived benefits of deprescribing before surgery, 3) patient-provider relationship and shared decision-making, 4) hope for surgery, 5) barriers to deprescribing before surgery, and 6) preferences for deprescribing follow-up. CONCLUSION: Our study findings regarding provider- and patient-related barriers and facilitators for deprescribing and desired processes before surgery may inform future deprescribing intervention targets before surgery.

A Phase-I pharmacokinetic, safety and food-effect study on flubentylosin, a novel analog of Tylosin-A having potent anti-Wolbachia and antifilarial activity.

BACKGROUND: The parasitic filariae responsible for onchocerciasis and lymphatic filariasis are host to an endosymbiotic bacterium, Wolbachia, which is essential to the fertility and development of the parasites. We performed a Phase-I pharmacokinetic, safety and food-effect study on single and multiple ascending doses of flubentylosin (ABBV-4083), a macrolide antibacterial with activity against Wolbachia, intended to sterilize and eliminate the parasites. METHODS: Seventy-eight healthy adults were exposed to flubentylosin; 36 were exposed to single ascending 40, 100, 200, 400 or 1000 mg doses; 12 received 1000 mg in the food-effect part; and 30 received multiple ascending daily doses of 100 mg for 7 days, 200 mg for 7 or 14 days, or 400 mg for 7 or 14 days. Twenty-two subjects received placebo. RESULTS: Maximum concentrations (Cmax) of flubentylosin were reached after 1-2 hours, with a half-life < 4 hours at doses ≤ 400 mg. Cmax and AUC increased in a more than dose-proportional manner, with similar exposure after multiple dose administration. The most frequently reported adverse events were nausea (8/78, 10%) and headache (6/78, 8%). Two subjects given a single dose of flubentylosin 1000 mg in the food-effect part experienced reversible asymptomatic ALT and AST elevations at Grade 2 or Grade 4, with no elevation in bilirubin, deemed related to study drug. The effect of food on exposure parameters was minimal. No treatment-related serious adverse events were reported. DISCUSSION: Flubentylosin 400 mg for 14 days was the maximum tolerated dose in this first-in-human, Phase-I study in healthy adults. Based on preclinical pharmacokinetic/pharmacodynamic modeling, flubentylosin 400 mg once daily for 7 or 14 days is expected to be an effective dose. A Phase-II, proof-of-concept study with flubentylosin using these regimens is currently ongoing in patients with onchocerciasis in Africa.

Tracking the Uneven Outcomes of COVID-19 on Racial and Ethnic Groups: Implications for Health Policy.

The socioeconomic shocks of the first COVID-19 pandemic wave disproportionately affected vulnerable groups. But did that trend continue to hold during the Delta and Omicron waves? Leveraging data from the Johns Hopkins Coronavirus Resource Center, this paper examines whether demographic inequalities persisted across the waves of COVID-19 infections. The current study utilizes fixed effects regressions to isolate the marginal relationships between socioeconomic factors with case counts and death counts. Factors include levels of urbanization, age, gender, racial distribution, educational attainment, and household income, along with time- and state-specific COVID-19 restrictions and other time invariant controls captured via fixed effects controls. County-level health outcomes in large metropolitan areas show that despite higher incidence rates in suburban and exurban counties, urban counties still had disproportionately poor outcomes in the latter COVID-19 waves. Policy makers should consider health disparities when developing long-term public health regulatory policies to help shield low-income households from the adverse effects of COVID-19 and future pandemics.