Association of Chronic Kidney Disease and End-Stage Renal Disease with Procedural Complications and Inpatient Outcomes of Leadless Pacemaker Implantations Across the United States.

BACKGROUND: Leadless pacemakers have emerged as a promising alternative to transvenous pacemakers in patients with kidney disease. However, studies investigating leadless pacemaker outcomes and complications based on kidney dysfunction are limited. OBJECTIVE: To evaluate the association of chronic kidney disease (CKD) and end-stage renal disease (ESRD) with inpatient complications and outcomes of leadless pacemaker implantations. METHODS: National Inpatient Sample and International Classification of Diseases, Tenth Revision codes were used to identify CKD and ESRD patients who underwent leadless pacemaker implantations in the U.S. from 2016-2020. Study endpoints assessed included inpatient complications, outcomes and resource utilization of leadless pacemaker implantations. RESULTS: A total of 29,005 leadless pacemaker placements were identified. Patients with CKD (n=5,245, 18.1%) and ESRD (n=3,790, 13.1%) were younger and had higher prevalence of important comorbidities than patients without CKD. In crude analysis, ESRD was associated with higher prevalence of major complications, peripheral vascular complications, and inpatient mortality. After multivariable adjustment, CKD and ESRD were associated with inpatient mortality (aOR 1.62, 95% CI 1.40 - 1.86; aOR 1.38, 95% CI 1.18 - 1.63) and prolonged length of stay (aOR 1.55, 95% CI 1.46 - 1.66; aOR 1.81, 95% CI 1.67 - 1.96). ESRD was also associated with higher hospitalization costs (aOR 1.63, 95% CI 1.50 - 1.77) and major complications (aOR 1.62, 95% CI 1.40 - 1.86) after leadless pacemaker implantation. CONCLUSIONS: Approximately one-third of patients undergoing leadless pacemaker implantation had CKD or ESRD. CKD and ESRD were associated with greater length and cost of stay, and inpatient mortality.

Far-red and sensitive sensor for monitoring real time H2O2 dynamics with subcellular resolution and in multi-parametric imaging applications.

H2O2 is a key oxidant in mammalian biology and a pleiotropic signaling molecule at the physiological level, and its excessive accumulation in conjunction with decreased cellular reduction capacity is often found to be a common pathological marker. Here, we present a red fluorescent Genetically Encoded H2O2 Indicator (GEHI) allowing versatile optogenetic dissection of redox biology. Our new GEHI, oROS-HT, is a chemigenetic sensor utilizing a HaloTag and Janelia Fluor (JF) rhodamine dye as fluorescent reporters. We developed oROS-HT through a structure-guided approach aided by classic protein structures and recent protein structure prediction tools. Optimized with JF635, oROS-HT is a sensor with 635 nm excitation and 650 nm emission peaks, allowing it to retain its brightness while monitoring intracellular H2O2 dynamics. Furthermore, it enables multi-color imaging in combination with blue-green fluorescent sensors for orthogonal analytes and low auto-fluorescence interference in biological tissues. Other advantages of oROS-HT over alternative GEHIs are its fast kinetics, oxygen-independent maturation, low pH sensitivity, lack of photo-artifact, and lack of intracellular aggregation. Here, we demonstrated efficient subcellular targeting and how oROS-HT can map inter and intracellular H2O2 diffusion at subcellular resolution. Lastly, we used oROS-HT with the green fluorescent calcium indicator Fluo-4 to investigate the transient effect of the anti-inflammatory agent auranofin on cellular redox physiology and calcium levels via multi-parametric, dual-color imaging.

Introduction to the Special Issue: International Responses to Prevention Intervention Research During Human Ecosystem Disruptions.

For decades, human ecosystem disruptions (HEDs), including pandemics, natural disasters, and socio-economic crises, have shaped national and international responses affecting everyday life. These disruptions present challenges and opportunities for prevention science to address emerging behavioral and mental health research questions, intervention strategies, methodologies, analyses, and research collaboration. This paper introduces a special issue that aims to document examples of how prevention science research teams had (1) globally improved health and well-being through swift, scientifically based responses during HED events and (2) advanced our understanding of the conduct and outcomes of prevention intervention research during crises such as pandemics, natural disasters, and socio-economic crises. The issue presents six research studies conducted in over ten different countries (e.g., Australia, Mexico, China). This issue includes original empirical and descriptive work that addressed HED implications for preventive interventions at within-country and cross-national levels. The findings hold potential applications for responses during current and future pandemics and natural disasters. Participants reflected on methodological and contextual considerations during HEDs, such as navigating travel restrictions, adapting ongoing research efforts to accommodate scientific learning during disruptions, and assessing the impact of policies redistributing preventive resources during and after a HED.

A Cost Analysis of Phosphodiesterase Type 5 Inhibitors in the United States.

OBJECTIVE: To perform a cost analysis of generic and brand-name Phosphodiesterase Type 5 (PDE5) inhibitors at different dosages and pharmacies across the US. METHODS: Using an all-payer retail pharmacy-claims database, we analyzed prescription drug data for three generic and six brand-name oral PDE5 inhibitors at different dosages across US chain and independent pharmacies in 2019. RESULTS: We obtained cash price data from 60,186 pharmacies (35,976 chain and 24,210 independent). The nationwide mean cash price per unit (PPU) ranged from $8.6 ± 5.2 (sildenafil 20 mg at chain pharmacies) to $107.1 ± 71 (Adcirca 20 mg at independent pharmacies) equal to 1145.3% difference. Chain pharmacies provided significantly lower average prices for one brand-name and six generic PDE5 inhibitors. Tadalafil PPU was cheaper at higher quantities, however, PPU increased with quantity prescribed for sildenafil. Looking at the top 10 metropolitan statistical areas, the highest PPUs were observed for tadalafil (Cialis) 10 mg and sildenafil (Viagra) 50 mg in Atlanta ($67.4 ± 8.7) and Los Angeles ($50.3 ± 24.0), while New York ($9.7 ± 2.6) and Miami ($27.9 ± 16.4) had the lowest PPUs for tadalafil (Cialis) 5 mg and sildenafil (Viagra) 100 mg, respectively. CONCLUSION: A substantial variability in PDE5 inhibitor cash prices exists across manufacturer, dosage, quantity, pharmacy type, and location. In addition, the pricing does not necessarily correlate with the regional socioeconomic factors. This highlights the importance of provider awareness and patient counseling on drug price including potentially assisting patients in identifying opportunities for cost savings.

Evaluating Adherence to Guideline-based Injury Grading in Pediatric Renal Trauma: How Are Patients Being Worked Up Prior to Transfer to a Level 1 Trauma Center?

OBJECTIVE: To determine whether children with renal trauma who are transferred to a level I trauma center (TC) receive appropriate imaging studies before transfer and whether this impacts care. The American Urologic Association (AUA) Urotrauma guidelines state clinicians should perform IV contrast-enhanced CT with immediate and delayed images when renal trauma is suspected. Adherence to these guidelines in pediatric patients is unknown. METHODS: Children treated for renal trauma at our TC between 2005 and 2019 were identified. Comparisons between patients with initial imaging at a transferring hospital (TH) and patients with initial imaging at our TC were performed using logistic regression. RESULTS: Of the included 293 children, 67% (197/293) were transferred into our TC and 61% (180/293) received initial imaging at the TH. Patients with initial imaging at the TH were more likely to have higher-grade renal injuries (P = .001) and were less likely to have guideline-recommended imaging (31% vs 82%, P < .001). Of patients who were imaged at the TH, 28% (50/180) underwent an additional CT imaging shortly after transfer. When imaging was incomplete at the TH, having an additional scan upon transfer was associated with emergent urologic surgery (P = .004). CONCLUSION: Adherence to the AUA Urotrauma guidelines is low, with most pediatric renal trauma patients not receiving complete staging with delayed-phase imaging before transfer to a TC. Furthermore, patients initially imaged at THs were more likely to receive more CT scans per admission and were exposed to higher amounts of radiation. There is a need to improve imaging protocols for complete staging of renal trauma in children before transfer.

Perspectives of researchers engaging in majority world research to promote diverse and global psychological science.

Journal analyses have documented the historical neglect of research pertaining to the Majority World in psychological science, and the need for inclusivity is clearly articulated to ensure a science that is comprehensive and globally applicable. However, no systematic efforts have explored the perspectives of researchers working with Majority World communities regarding the challenges they experience in conducting and disseminating research and ways to address them. Our aim was to explore these challenges from the perspective of these researchers using an embedded mixed-methods design. Based on responses of 232 researchers who engage in psychological research with Majority World communities (68.1% from Africa, Asia, or Latin America, remaining from the Minority World), we identified challenges in three areas: (a) stemming from an inherent bias against Majority World research, (b) experienced by all researchers, which nonetheless are heightened for those engaging in research with Majority World populations, and (c) specific to researchers affiliated with Majority World institutions. Based on the findings, we recommend journal editorial teams and funding agencies: (a) acknowledge and address the bias inherent in the publication and funding process, (b) recruit editorial team members, program officers, and reviewers from the Majority World, (c) train editorial team members, program officers, and reviewers from the Minority World to thoughtfully evaluate Majority World research, and (d) provide resources for researchers affiliated with Majority World institutions. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

DASH-HF Study: A Pragmatic Quality Improvement Randomized Implementation Trial for Patients With Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Heart failure is a prevailing diagnosis of hospitalization and readmission within 6 months, and nearly a quarter of these patients die within a year. Guideline-directed medication therapies reduce risk of mortality by 73% over 2 years; however, the implementation of these therapies to their target dose in clinical practice continues to be challenging. In 2020, the Veterans Affairs (VA) Health Care System developed a HF dashboard to monitor and improve outpatient HF management. The DASH-HF (Dashboard Activated Services and Telehealth for Heart Failure) study is a randomized, pragmatic clinical trial to evaluate proactive dashboard-directed telehealth clinics to improve the use and dosing of guideline-directed medication therapy for patients with heart failure with reduced ejection fraction not on optimal guideline-directed medication therapy within the VA. METHODS: Three hundred veterans with heart failure with reduced ejection fraction met inclusion criteria with an optimization potential score (OPS) of 5 or less out of 10, representing nonoptimal guideline-directed medication therapy. The primary outcome was a composite score of guideline-directed medical therapy, the OPS, 6 months after the end of the intervention. Secondary outcomes included active prescriptions for each individual guideline-directed medical therapy class, HF-related hospitalizations, deaths, and clinician time per patient during the intervention clinics. RESULTS: There was no significant difference between the intervention arm and usual care group in the primary outcome (OPS, 2.9; SD=2.1 versus OPS, 2.6, SD=2.1); adjusted mean difference 0.3 (95% CI, -0.1 to 0.7) or in the prespecified secondary outcomes for hospitalization and all-cause mortality for the intervention of proactive dashboard-based clinics. CONCLUSIONS: A dashboard-based clinic intervention did not improve the OPS or secondary outcomes of hospitalization and all-cause mortality. There remains a larger opportunity to better target patients and provide more intensive follow-up to further evaluate the utility of proactive dashboard-based clinics for HF management and quality improvement. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT05001165.

Preschool- and childcare center-based interventions to increase fruit and vegetable intake in preschool children in the United States: a systematic review of effectiveness and behavior change techniques.

BACKGROUND: Fruit and vegetable (FV) consumption in children in the United States (US) is very low. Adequate FV consumption is required for proper development during childhood, and dietary habits are established during preschool-age and tend to persist into adulthood. As most U.S. preschool-aged children attend childcare or preschool, this may be an opportune time and setting to conduct interventions to improve FV intake. These interventions should be based in theory and use behavior change techniques (BCTs) to explain mechanisms for expected change. To date, no published reviews have examined the effectiveness of childcare- or preschool-based FV interventions in preschoolers and their use of theoretical frameworks and BCTs. METHODS: This systematic review was completed adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria were randomized controlled trials (RCTs) published between 2012 and 2022 of interventions to improve diet or FV intake in preschoolers (aged 2-5 years) in childcare or preschool-settings. A search of four databases was conducted between in September 2022 using search terms pertaining to the study's primary aim (FV consumption), age group (preschool-aged), settings (US childcare or preschool settings), and study design (RCT). Additional criteria were objective measures of FV consumption or skin carotenoids, as a proxy for FV intake. Included studies were narratively synthesized based on intervention type, measured effect, and use of theory and BCTs. RESULTS: The search resulted in six studies that reported on nine interventions. Overall, six interventions increased FV intake, of which five used nutrition education and one manipulated the feeding environment. Among the three interventions with no measured effect, two manipulated the feeding environment and one used peer modeling. Effective studies used at least three BCTs, though no pattern was observed between use of theory or BCTs and intervention effect. CONCLUSIONS: While several studies have shown promising results, the limited number of studies identified in this review highlights key gaps in this field: there is a need for studies to test FV interventions in US childcare settings that use objective measures of FV intake, directly compare intervention components and BCTs, are theory-based, and assess long-term behavior change.

Development and Piloting of a Mental Health Prevention and Referral Program for Veterans and Their Families in Ukraine.

BACKGROUND: While growing evidence exists for the effectiveness of mental health interventions in global mental health, the evidence base for psychosocial supports is lacking despite the need for a broader range of supports that span the prevention-treatment continuum and can be integrated into other service systems. Following rigorous evaluation of the Common Elements Treatment Approach (CETA) in Ukraine, this article describes the development and feasibility testing of CETA Psychosocial Support (CPSS), a brief psychosocial prevention and referral program for Ukrainian veterans and their families. CPSS DEVELOPMENT: CPSS development used evidence-based CETA intervention components and was informed by a stakeholder needs analysis incorporating feedback from veterans and their families, literature review, and expert consultations. The program includes psychoeducation, cognitive coping skill development, and a self-assessment tool that identifies participants for potential referral. After initial development of the program, the intervention underwent: (1) initial implementation by skilled providers focused on iterative refinement; (2) additional field-testing of the refined intervention by newly trained providers in real-world conditions; and (3) a formal pilot evaluation with collection of pre-post mental health assessments and implementation ratings using locally validated instruments. RESULTS: Fifteen CPSS providers delivered 14 group sessions to 109 participants (55 veterans, 39 family members, and 15 providers from veterans' service organizations). After incorporating changes related to content, process, and group dynamics, data from the pilot evaluation suggest the refined CPSS program is an acceptable and potentially effective brief psychosocial prevention and promotion program that can be implemented by trained veteran providers. Forty percent of participants required safety or referral follow-ups. CONCLUSION: The iterative, inclusive development process resulted in an appropriate program with content and implementation strategies tailored to Ukrainian veterans and their families. Brief psychosocial programs can fit within a larger multitiered mental health and psychosocial continuum of care that supports further referral.

Predictors of arrhythmia during pregnancy in adults with congenital heart disease.

BACKGROUND: Risk prediction of arrhythmia during pregnancy in adult congenital heart disease (ACHD) patients is currently lacking, and the impact of preconception catheter ablation on future antepartum arrhythmia has not been studied. METHODS: We conducted a single-center, retrospective cohort study of pregnancies in ACHD patients. Clinically significant arrhythmia events during pregnancy were described, predictors of arrhythmia were analyzed, and a risk score devised. The impact of preconception catheter ablation on antepartum arrhythmia was assessed. RESULTS: The study included 172 pregnancies in 137 patients. Arrhythmia events occurred in 25 (15%) of pregnancies, with 64% of events occurring in the second trimester and sustained supraventricular tachycardia being the most common rhythm. Univariate predictors of arrhythmia were history of tachyarrhythmia (OR 20.33, 95% CI 6.95-59.47, p < 0.001, Fontan circulation (OR 11.90, 95% CI 2.60-53.70, p < 0.001), baseline physiologic class C/D (OR 3.72, 95% CI 1.54-9.01, p = 0.002) and history of multiple valve interventions (OR 3.10, 95% CI 1.20-8.20, p = 0.017). Three risk factors (excluding multiple valve interventions) were used to formulate a risk score, with a cutoff of ≥2 points predicting antepartum arrhythmia with sensitivity and specificity of 84%. While recurrence of the index arrhythmia was not observed following successful catheter ablation, preconception ablation did not impact odds of antepartum arrhythmia. CONCLUSIONS: We provide a novel risk stratification scheme for predicting antepartum arrhythmia in ACHD patients. The role of contemporary preconception catheter ablation in risk reduction needs further refinement with multicenter investigation.

Chest Wall Keloids Depicted by 18 F-Piflufolastat PET/CT Imaging.

ABSTRACT: Keloids are pathological scars from exuberant fibroproliferative collagen response and excessive extracellular matrix production usually extending beyond the original wound margins. Although keloids are mostly of dermatological concern, they could be incidentally depicted on scintigraphic planar and PET/CT imaging and could mimic other types of skin diseases. The authors present a case of chest wall keloids documented on 18 F-piflufolastat PET/CT during the evaluation of prostate cancer recurrence.

Psychosocial support interventions in the context of forced displacement: A systematic review and meta-analysis.

Background: Forced displacement is associated with elevated risk for poor psychosocial wellbeing, yet there remains a lack of clarity around the effectiveness of commonly implemented psychosocial support interventions focused on preventing disorder and promoting wellbeing. This study aimed to synthesize the literature on evaluations of psychosocial support interventions for populations affected by forced displacement. Methods: We searched for peer reviewed and gray literature in seven databases (PubMed, Embase, Global Health, CINAHL, SocIndex, PsychInfo, PILOTS), fifteen organizational websites, and via solicitation through multiple networks. Various study designs were included, with the criteria that they report an evaluation of a psychosocial intervention delivered to populations affected by forced displacement, and included quantitative or qualitative data on psychosocial outcomes. Records were screened independently by two reviewers at both title/abstract and full-text review; data was double-extracted and study quality assessed, with discrepancies resolved by consensus. Meta-analyses for seven outcomes were conducted on a subset of 33 studies. Results: We identified 162 reports. Over half (55%) used a single-group study design, with fewer using non-random (19%) or randomized (21%) comparisons. Study designs incorporating comparison conditions were less likely to report positive findings than single-group studies. In the meta-analyses, a moderately strong overall effect was found for psychosocial wellbeing (ES: -0.534, 95% CI: [-0.870, -0.197], p=.005); small effects on both internalizing (ES: -0.152, 95% CI: [-0.310, 0.005], p= .057) and externalizing (ES: -0.249, 95% CI: [-0.515, 0.016], p=.064) problems were promising but not conclusive. Subgroup analysis suggested differential impacts on internalizing problems for adults (improvement; ES: -0.289, 95% CI: [-0.435, -0.143], p=.001) and children (worsening; ES: 0.129, 95% CI: [.054, 0.204], p=.002). Other subgroup analyses showed little meaningful variation by context, population, or intervention characteristics. Conclusion: Pragmatic, field-driven program evaluations are dominated by single-group designs with significant risk of bias. Findings from controlled studies are promising but highlight a need for more rigorous research to support causal inference, align outcomes with theories of change, improve measurement of more positive or wellbeing-focused outcomes, examine subgroup differences, and report potentially negative impacts.

'I feel hopeless': Exploring the psychosocial impacts of caring for mentally ill relatives in Cambodia.

BACKGROUND: There is growing recognition of the psychosocial burden of caregiving on relative caregivers of the mentally ill in low-and middle-income countries. Yet there remains limited formal research examining the challenges and psychosocial support needs of these relative caregivers, particularly with sensitivity to understanding caregiver experiences across diverse cultures and contexts. The purpose of this study was to study caregiver burden to inform potential intervention approaches among relative caregivers of treatment-engaged mentally ill patients in Cambodia. METHODS: Participants were all relative caregivers identified through their connection to a non-governmental organization providing psychiatric care. Five focus group discussions were held with 37 participants to explore challenges experienced by relative caregivers. A total of 115 caregivers then completed a mental health assessment consisting of the Patient Health Questionnaire - 9 item scale, Generalized Anxiety Disorder - 7-item scale, and 21-item Depression, Anxiety, and Stress Scale. Internal consistencies ranged from α = .81 to .87 across scales. RESULTS: Five themes emerged from the focus group discussions: financial burden, erratic behavior of patients, social alienation, somatic and emotional symptoms, and barriers to help-seeking. Assessment data indicated the sample was highly symptomatic. Women and those with no employment appeared to be at higher risk of distress, as were those caregivers with a biological relationship to the patient (parents, children, and siblings; relative to spouses or other relationships). DISCUSSION: Findings suggest a need for regular screening and greater psychosocial support for relative caregivers. It is notable that the needs identified within the current study remain prominent even as this is a treatment-engaged sample.

Geospatial Analysis of Access to Health Care and Internet Services in the US.

This cross-sectional study examines internet access in areas of the US with limited health care services.

Short term reoperation rates after artificial urinary sphincter placement in pediatric patients.

INTRODUCTION: Artificial urinary sphincters (AUS) have demonstrated good functional outcomes in pediatric populations. We sought to examine the nationwide short term reoperation rates in pediatric patients after AUS placement. MATERIALS AND METHODS: An observational cohort study was designed utilizing claims from the Truven MarketScan Commercial Claims and Encounters database from 2007 to 2018. Patients under 18 years of age undergoing an AUS procedure were identified using CPT and ICD9/10 codes. Reoperations included any removal, replacement, or AUS placement codes which occurred after the initially identified placement code. Follow up time was the amount of time between AUS placement and the end of MarketScan enrollment. RESULTS: From 2007-2018, we identified 57 patients under the age of 18 who underwent AUS placement and after excluding 8 for concurrent AUS complication procedure codes and 4 for follow up < 60 days, the final cohort included 45 patients. The median age was 13 years (IQR 9-16 years) at the time of AUS placement, and the median follow up time after AUS placement was 787 days (IQR 442-1562 days), approximately 2.2 years. Total reoperation rate was 22%. Reoperations included 40% device removals (4/10) and 60% replacements (6/10). Neither gender (p = 0.70) nor age (p = 0.23) was associated with need for reoperation. Patients who had a concurrent bladder surgery had a higher rate of undergoing reoperation (50% vs. 12%, p = 0.007). CONCLUSIONS: The rate of reoperation after AUS placement approached 1 in 4 in pediatric patients. These data may be instrumental for providers and parents in counseling and decision-making regarding risks of prosthetic implantation.

Inhibition of itch by neurokinin 1 receptor (Tacr1) -expressing ON cells in the rostral ventromedial medulla in mice.

The rostral ventromedial medulla (RVM) is important in descending modulation of spinal nociceptive transmission, but it is unclear if the RVM also modulates spinal pruriceptive transmission. RVM ON cells are activated by noxious algesic and pruritic stimuli and are pronociceptive. Many RVM-spinal projection neurons express the neurokinin-1 receptor (Tacr1), and ON-cells are excited by local administration of substance P (SP). We hypothesized that Tacr1-expressing RVM ON cells exert an inhibitory effect on itch opposite to their pronociceptive action. Intramedullary microinjection of SP significantly potentiated RVM ON cells and reduced pruritogen-evoked scratching while producing mild mechanical sensitization. Chemogenetic activation of RVM Tacr1-expressing RVM neurons also reduced acute pruritogen-evoked scratching. Optotagging experiments confirmed RVM Tacr1-expressing neurons to be ON cells. We conclude that Tacr1-expressing ON cells in RVM play a significant role in the modulation of pruriceptive transmission.

Independently paced Ca2+ oscillations in progenitor and differentiated cells in an ex vivo epithelial organ.

Cytosolic Ca2+ is a highly dynamic, tightly regulated and broadly conserved cellular signal. Ca2+ dynamics have been studied widely in cellular monocultures, yet organs in vivo comprise heterogeneous populations of stem and differentiated cells. Here, we examine Ca2+ dynamics in the adult Drosophila intestine, a self-renewing epithelial organ in which stem cells continuously produce daughters that differentiate into either enteroendocrine cells or enterocytes. Live imaging of whole organs ex vivo reveals that stem-cell daughters adopt strikingly distinct patterns of Ca2+ oscillations after differentiation: enteroendocrine cells exhibit single-cell Ca2+ oscillations, whereas enterocytes exhibit rhythmic, long-range Ca2+ waves. These multicellular waves do not propagate through immature progenitors (stem cells and enteroblasts), of which the oscillation frequency is approximately half that of enteroendocrine cells. Organ-scale inhibition of gap junctions eliminates Ca2+ oscillations in all cell types - even, intriguingly, in progenitor and enteroendocrine cells that are surrounded only by enterocytes. Our findings establish that cells adopt fate-specific modes of Ca2+ dynamics as they terminally differentiate and reveal that the oscillatory dynamics of different cell types in a single, coherent epithelium are paced independently.

Psychometric performance of the Mental Health Implementation Science Tools (mhIST) across six low- and middle-income countries.

BACKGROUND: Existing implementation measures developed in high-income countries may have limited appropriateness for use within low- and middle-income countries (LMIC). In response, researchers at Johns Hopkins University began developing the Mental Health Implementation Science Tools (mhIST) in 2013 to assess priority implementation determinants and outcomes across four key stakeholder groups-consumers, providers, organization leaders, and policy makers-with dedicated versions of scales for each group. These were field tested and refined in several contexts, and criterion validity was established in Ukraine. The Consumer and Provider mhIST have since grown in popularity in mental health research, outpacing psychometric evaluation. Our objective was to establish the cross-context psychometric properties of these versions and inform future revisions. METHODS: We compiled secondary data from seven studies across six LMIC-Colombia, Myanmar, Pakistan, Thailand, Ukraine, and Zambia-to evaluate the psychometric performance of the Consumer and Provider mhIST. We used exploratory factor analysis to identify dimensionality, factor structure, and item loadings for each scale within each stakeholder version. We also used alignment analysis (i.e., multi-group confirmatory factor analysis) to estimate measurement invariance and differential item functioning of the Consumer scales across the six countries. RESULTS: All but one scale within the Provider and Consumer versions had Cronbach's alpha greater than 0.8. Exploratory factor analysis indicated most scales were multidimensional, with factors generally aligning with a priori subscales for the Provider version; the Consumer version has no predefined subscales. Alignment analysis of the Consumer mhIST indicated a range of measurement invariance for scales across settings (R2 0.46 to 0.77). Several items were identified for potential revision due to participant nonresponse or low or cross- factor loadings. We found only one item, which asked consumers whether their intervention provider was available when needed, to have differential item functioning in both intercept and loading. CONCLUSION: We provide evidence that the Consumer and Provider versions of the mhIST are internally valid and reliable across diverse contexts and stakeholder groups for mental health research in LMIC. We recommend the instrument be revised based on these analyses and future research examine instrument utility by linking measurement to other outcomes of interest.

The effects of xeno-free cryopreservation on the contractile properties of human iPSC derived cardiomyocytes.

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have advanced our ability to study the basic function of the heart and model cardiac diseases. Due to the complexities in stem cell culture and differentiation protocols, many researchers source their hiPSC-CMs from collaborators or commercial biobanks. Generally, the field has assumed the health of frozen cardiomyocytes is unchanged if the cells adhere to the substrate and commence beating. However, very few have investigated the effects of cryopreservation on hiPSC-CM's functional and transcriptional health at the cellular and molecular level. Here we review methods and challenges associated with cryopreservation, and examine the effects of cryopreservation on the functionality (contractility and calcium handling) and transcriptome of hiPSC-CMs from six healthy stem cell lines. Utilizing protein patterning methods to template physiological cell aspect ratios (7:1, length:width) in conjunction with polyacrylamide (PA) hydrogels, we measured changes in force generation and calcium handling of single hiPSC-CMs. We observed that cryopreservation altered the functionality and transcriptome of hiPSC-CMs towards larger sizes and contractile force as assessed by increased spread area and volume, single cell traction force microscopy and delayed calcium dynamics. hiPSC-CMs are broadly used for basic science research, regenerative medicine, and testing biological therapeutics. This study informs the design of experiments utilizing hiPSC-CMs to avoid confounding functional changes due to cryopreservation with other treatments.

The Impact of Job and Insurance Loss on Prescription Drug use: A Panel Data Approach to Quantifying the Health Consequences of Unemployment During the Covid-19 Pandemic.

Due to the nature of health insurance in the United States, health care utilization is often tied to economic conditions, at both the individual and aggregate levels. This article examines how loss of employment may reduce medication adherence through the subsequent loss of insurance and income. At the individual level, the loss of employer-sponsored insurance is shown to be associated with lower prescription drug use and higher out-of-pocket expenditures. The rapid increase in unemployment during the COVID-19 pandemic provides a natural experiment to estimate the causal relationship between unemployment and prescription drug use at the aggregate level. In total, the growth in unemployment during the pandemic resulted in a 2.6% reduction in medication adherence and 57.5 million fewer prescriptions filled in 2020, with prescriptions declining for many chronic conditions. Unemployment-related reductions in prescription fills and medication adherence were highest in states without expanded Medicaid eligibility, further underscoring the importance of social safety nets such as Medicaid during times of economic hardship.