Livestream, group movement program for people living with cognitive impairment and care partners: A randomized clinical trial.

INTRODUCTION: There are few widely-available, evidence-based options to support quality of life (QOL) for people living with Alzheimer's disease and related dementias. METHODS: We performed a randomized, controlled trial with a Waitlist control group to determine whether an online, livestream, mind-body, group movement program (Moving Together, 1 hour, 2 days/week, 12 weeks) improves QOL in people with cognitive impairment (PWCI) or care partners (CPs) and explore mechanisms of action. The primary outcome for both participants was self-reported QOL. Secondary outcomes and potential mediators included mobility, isolation, well-being, cognitive function, and sleep in PWCI and burden, positive emotions, caregiver self-efficacy, stress management, and sleep in CPs. Blinded assessors collected outcome data at baseline, 12, and 24 weeks. We assessed adverse events including falls through monthly check-in surveys and collected qualitative data through evaluation surveys. Intention-to-treat analyses used linear mixed models to compare mean change over time between groups and calculated standardized effect sizes (ESs). RESULTS: Ninety-seven dyads enrolled (PWCI: age 76 ± 11 years, 43% female, 80% non-Hispanic White; CPs: age 66 ± 12 years, 78% female, 71% non-Hispanic White); 15% withdrew before 12 weeks and 22% before 24 weeks. PWCI self-reported significantly better QOL from baseline to 12 weeks in the Moving Together group compared to the Waitlist group (ES = 0.474, p = 0.048) and CPs self-reported improved ability to manage stress (ES = 0.484, p = 0.021). Improvements in participant self-reported QOL were mediated by improvements in their self-reported well-being and CP-reported ability to manage stress. Results were similar when the Waitlist group participated in the program (QOL ES = 0.663, p = 0.006; stress management ES = 0.742, p = 0.002) and were supported by qualitative data. Exploratory analyses suggested possible fall reduction in PWCI. There were no study-related serious adverse events. DISCUSSION: Online programs such as Moving Together offer a scalable strategy for supporting high QOL for PWCI and helping CPs manage stress. TRIAL REGISTRATION: ClinicalTrials.gov NCT04621448. Highlights: The approval of new medications that slow cognitive decline in people living with Alzheimer's disease and related disorders (ADRD) has raised hope and excitement. However, these medications do not appear to impact quality of life, which is often considered by patients and care partners to be the most important outcome.In this randomized clinical trial, we found that an evidence-based, online, livestream, mind-body, group movement program significantly and meaningfully improves self-rated quality of life in people with ADRD and helps care partners manage stress. Mediation analyses revealed that the key drivers of improvements in participants' quality of life were improvements in their feelings of well-being and care partners' ability to manage stress. Exploratory analyses also suggested a 30% reduction in falls.These results are important because they suggest that an online program, which is available now and can be performed by people from the comfort of home or other location of choice, could be recommended as a complement or alternative to new therapies to help maximize quality of life for people living with ADRD and their care partners.

Four-factor Prothrombin Complex Concentrate During Liver Transplantation: A Retrospective Cohort Study.

Background: Four-factor prothrombin complex concentrate (PCC) is a plasma product that contains factors II, VII, IX, X, protein C, and protein S. PCC can be used off-label to treat coagulopathy during orthotopic liver transplantation (OLT). However, its use comes with safety concerns regarding thrombosis. The purpose of our study is to determine the safety of PCC in OLT. Methods: We conducted a retrospective cohort study of patients who received 4-factor PCC during OLT at our institution from January 1, 2018, to May 1, 2022, with a 1:1 match of 83 patients who received PCC and 83 patients who did not. We evaluated 30-d mortality, 1-y mortality, prevalence of thrombotic complications (portal vein thrombosis, deep venous thrombosis, myocardial infarction, and pulmonary embolus), and postoperative intensive care (ICU) length of stay (LOS). Results: There was no significant difference in 30-d mortality (odds ratio [OR] 5; 95% confidence interval [CI], 0.58-42.8; P = 0.14), 1-y mortality (OR 3; 95% CI, 0.61-14.86; P = 0.18), or ICU LOS (OR -13.8; 95% CI, -39.2 to 11.6; P = 0.29). There was no increased incidence of thrombotic complications among patients receiving PCC 90 d after surgery, including portal vein thrombosis (OR 1.5; 95% CI, 0.42-5.32; P = 0.53), pulmonary embolus (OR 1; 95% CI, 0.14-7.1; P = 0.99), deep venous thrombosis (OR 0.67; 95% CI, 0.11-3.99; P = 0.66), and myocardial infarction (OR 1.67; 95% CI, 0.4-6.97; P = 0.48). Conclusions: Although there was a statistically insignificant increase in mortality after PCC administration during OLT, we did not see a significant increase in perioperative complications, including thrombotic events and increased ICU LOS.

Adherence to caregiver-administered intravenous immunosuppressant medications in pediatric hematopoietic stem cell transplant.

BACKGROUND: The purpose of this study was to describe taking, timing, and dosing adherence to home caregiver-administered intravenous (IV) immunosuppressants in a sample of pediatric hematopoietic stem cell transplant (HCT) recipients. PROCEDURES: Sixteen children who had undergone HCT, ages 3 months to 15 years, and their caregivers participated. All caregivers were biological mothers. Caregivers completed a demographic questionnaire as part of a larger study and brought in portable infusion pumps to download the pump data at the time of their child's post-HCT clinic visit. Pump data were then examined for dose taking, timing, and amount for 30 days following discharge. RESULTS: Despite the importance of the precise timing of IV immunosuppressants, adherence taking, dosing, and timing varied widely in this sample. The mean percentage of doses administered was 98.72%, and 81.3% of children received all doses of immunosuppressant. However, only 62% of doses were given on time and the mean difference between the prescribed and actual administration time was 67.03 minutes. CONCLUSIONS: Although taking adherence was high, the timing and dosing adherence to IV immunosuppressants in the home was poor. Additional support to promote adherence should be provided including assisting caregivers to identify and use adherence strategies specific to their child's IV immunosuppressant regimen in the home.

Development of a comprehensive cardiovascular disease genetic risk assessment test.

Background: Despite monogenic and polygenic contributions to cardiovascular disease (CVD), genetic testing is not widely adopted, and current tests are limited by the breadth of surveyed conditions and interpretation burden. Methods: We developed a comprehensive clinical genome CVD test with semi-automated interpretation. Monogenic conditions and risk alleles were selected based on the strength of disease association and evidence for increased disease risk, respectively. Non-CVD secondary findings genes, pharmacogenomic (PGx) variants and CVD polygenic risk scores (PRS) were assessed for inclusion. Test performance was modeled using 2,594 genomes from the 1000 Genomes Project, and further investigated in 20 previously tested individuals. Results: The CVD genome test is composed of a panel of 215 CVD gene-disease pairs, 35 non-CVD secondary findings genes, 4 risk alleles or genotypes, 10 PGx genes and a PRS for coronary artery disease. Modeling of test performance using samples from the 1000 Genomes Project revealed ~6% of individuals with a monogenic finding in a CVD-associated gene, 6% with a risk allele finding, ~1% with a non-CVD secondary finding, and 93% with CVD-associated PGx variants. Assessment of blinded clinical samples showed complete concordance with prior testing. An average of 4 variants were reviewed per case, with interpretation and reporting time ranging from 9-96 min. Conclusions: A genome sequencing based CVD genetic risk assessment can provide comprehensive genetic disease and genetic risk information to patients with CVD. The semi-automated and limited interpretation burden suggest that this testing approach could be scaled to support population-level initiatives.

COVID-19 vaccination safety and associated health care utilization among adults with inflammatory bowel disease - a population-based self-controlled case series analysis.

BACKGROUND AND AIMS: There is an incomplete understanding of the full safety profiles of repeated COVID-19 vaccinations in patients with inflammatory bowel disease (IBD). Among individuals with IBD, we assessed whether COVID-19 vaccines were associated with serious adverse events of special interest (AESI) and health care utilization [all-cause hospitalizations, Emergency Department (ED) visits, gastroenterology visits, IBD-related visits]. METHODS: Using comprehensive administrative health data from Ontario, Canada, adults with IBD who received at least one COVID-19 vaccine from December 2020-January 2022 were included. Self-controlled case series analyses were conducted to evaluate the relative incidence rates of AESI and health care utilization outcomes across post-vaccination risk and control periods. RESULTS: Among 88,407 IBD patients, 99.7% received mRNA vaccines and 75.9% received ≥ 3 doses. Relative to control periods, we did not detect an increase in AESI. IBD patients had fewer all-cause hospitalizations during post-vaccination risk periods. Patients experienced more all-cause ED visits after dose 2 [Relative Incidence (RI):1.08(95%CI:1.04-1.12)] but fewer visits after doses 3 [RI:0.85 (95%CI:0.81-0.90)] and 4 [RI:0.73 (95%CI:0.57-0.92)]. There was no increase in gastroenterologist visits or IBD-related health care utilization post-vaccination. There were fewer IBD-related hospitalizations after dose 1 [RI:0.84 (95%CI:0.72-0.98)] and 3 [RI:0.63 (95%CI:0.52-0.76)], fewer IBD-related ED visits after dose 3 [RI:0.81 (95%CI:0.71-0.91)] and 4 [RI:0.55 (95%CI:0.32-0.96)], and fewer outpatient visits after dose 2 [RI:0.91 (95%CI:0.90-0.93)] and 3 [RI:0.87 (95%CI:0.86-0.89)]. CONCLUSION: This population-based study did not detect increased AESI, all-cause or IBD-related health care utilization following COVID-19 vaccination, suggesting a lack of association between vaccination and increased disease activity.

Commitment to inclusion: The importance of collaboration in gender equity work.

Despite decades of faculty professional development programs created to prepare women for leadership, gender inequities persist in salary, promotion, and leadership roles. Indeed, men still earn more than women, are more likely than women to hold the rank of professor, and hold the vast majority of positions of power in academic medicine. Institutions demonstrate commitment to their faculty's growth by investing resources, including creating faculty development programs. These programs are essential to help prepare women to lead and navigate the highly matrixed, complex systems of academic medicine. However, data still show that women persistently lag behind men in their career advancement and salary. Clearly, training women to adapt to existing structures and norms alone is not sufficient. To effectively generate organizational change, leaders with power and resources must commit to gender equity. This article describes several efforts by the Office of Faculty in the Johns Hopkins University School of Medicine to broaden inclusivity in collaborative work for gender equity. The authors are women and men leaders in the Office of Faculty, which is within the Johns Hopkins University School of Medicine dean's office and includes Women in Science and Medicine. Here, we discuss potential methods to advance gender equity using inclusivity based on our institutional experience and on the findings of other studies. Ongoing data collection to evaluate programmatic outcomes in the Johns Hopkins University School of Medicine will be reported in the future.

Insufficient Sleep and Behavioral Health in the Military: A 5-Country Perspective.

PURPOSE OF REVIEW: The goal of this paper was to highlight the degree to which sleep, behavioral health, and leader involvement were interrelated using data from militaries in five English-speaking countries: Australia, Canada, New Zealand, the UK, and the United States. RECENT FINDINGS: Many service members reported sleeping fewer than the recommended 7 h/night: 34.9%, 67.2%, and 77.2% of respondents from New Zealand, Canada, and the United States, respectively. Countries reporting shorter sleep duration also reported fewer insomnia-related difficulties, likely reflecting higher sleep pressure from chronic sleep loss. Across all countries, sleep problems were positively correlated with behavioral health symptoms. Importantly, leader promotion of healthy sleep was positively correlated with more sleep and negatively correlated with sleep problems and behavioral health symptoms. Insufficient sleep in the military is ubiquitous, with serious implications for the behavioral health and functioning of service members. Leaders should attend to these risks and examine ways to promote healthy sleep in service members.

Drug retention of biologic and targeted synthetic disease-modifying antirheumatic drugs in Korean patients with seropositive rheumatoid arthritis.

Background/Aims: The aim of this study was to compare the short- and long-term retention rates of biologic and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) in Korean patients with seropositive rheumatoid arthritis. Methods: This study was conducted with 1,538 treatment courses of 1,063 patients, including adalimumab (n = 332), etanercept (n = 369), infliximab (n = 146), abatacept (n = 152), tocilizumab (n = 299), tofacitinib (n = 136), and baricitinib (n = 104), in patients with seropositive rheumatoid arthritis who started b/tsDMARD treatment between 2008 and 2020 at Seoul St. Mary's Hospital. Discontinuation 1 and 3 years after the first prescription of each drug was investigated. Kaplan- Meier estimates of time to discontinuation were calculated to compare the difference in drug retention rate for each drug. Patient-level predictors of drug discontinuation were evaluated using a Cox proportional hazards model. Results: The overall 1-year drug retention rate was from 60.1% for adalimumab to 90.0% for tofacitinib in the b/tsDMARD-naïve group, and from 55.2% for infliximab to 84.8% for tofacitinib in the b/tsDMARD-experienced group. The 3-year drug retention rate was from 36.9% for infliximab to 86.5% for tofacitinib in the b/tsDMARD-naïve group, and from 31.0% for infliximab to 65.4% for tocilizumab in the b/tsDMARD-experienced group. Drug discontinuation appeared to be affected by specific types of b/tsDMARDs. Conclusions: Tocilizumab and tofacitinib are less commonly discontinued compared to tumor necrosis factor-α inhibitors at 1 and 3 years. Specifically, tofacitinib in the b/tsDMARD-naïve group and tocilizumab in the b/tsDMARD-experienced group showed the highest 3-year retention rates.

Disruption of G-quadruplex dynamicity by BRCA2 abrogation instigates phase separation and break-induced replication at telomeres.

Dynamic interaction between BRCA2 and telomeric G-quadruplexes (G4) is crucial for maintaining telomere replication homeostasis. Cells lacking BRCA2 display telomeric damage with a subset of these cells bypassing senescence to initiate break-induced replication (BIR) for telomere synthesis. Here we show that the abnormal stabilization of telomeric G4 following BRCA2 depletion leads to telomeric repeat-containing RNA (TERRA)-R-loop accumulation, triggering liquid-liquid phase separation (LLPS) and the assembly of Alternative Lengthening of Telomeres (ALT)-associated promyelocytic leukemia (PML) bodies (APBs). Disruption of R-loops abolishes LLPS and impairs telomere synthesis. Artificial engineering of telomeric LLPS restores telomere synthesis, underscoring the critical role of LLPS in ALT. TERRA-R-loops also recruit Polycomb Repressive Complex 2 (PRC2), leading to tri-methylation of Lys27 on histone H3 (H3K27me3) at telomeres. Half of paraffin-embedded tissue sections from human breast cancers exhibit APBs and telomere length heterogeneity, suggesting that BRCA2 mutations can predispose individuals to ALT-type tumorigenesis. Overall, BRCA2 abrogation disrupts the dynamicity of telomeric G4, producing TERRA-R-loops, finally leading to the assembly of telomeric liquid condensates crucial for ALT. We propose that modulating the dynamicity of telomeric G4 and targeting TERRA-R-loops in telomeric LLPS maintenance may represent effective therapeutic strategies for treating ALT-like cancers with APBs, including those with BRCA2 disruptions.

Raman spectroscopy in the study of amyloid formation and phase separation.

Neurodegenerative diseases, such as Alzheimer's and Parkinson's, share a common pathological feature of amyloid structure accumulation. However, the structure-function relationship between these well-ordered, ß-sheet-rich, filamentous protein deposits and disease etiology remains to be defined. Recently, an emerging hypothesis has linked phase separation, a process involved in the formation of protein condensates, to amyloid formation, suggesting that liquid protein droplets serve as loci for amyloid initiation. To elucidate how these processes contribute to disease progression, tools that can directly report on protein secondary structural changes are needed. Here, we review recent studies that have demonstrated Raman spectroscopy as a powerful vibrational technique for interrogating amyloid structures; one that offers sensitivity from the global secondary structural level to specific residues. This probe-free technique is further enhanced via coupling to a microscope, which affords structural data with spatial resolution, known as Raman spectral imaging (RSI). In vitro and in cellulo applications of RSI are discussed, highlighting studies of protein droplet aging, cellular internalization of fibrils, and Raman imaging of intracellular water. Collectively, utilization of the myriad Raman spectroscopic methods will contribute to a deeper understanding of protein conformational dynamics in the complex cellular milieu and offer potential clinical diagnostic capabilities for protein misfolding and aggregation processes in disease states.

Predicting clinical outcomes of SARS-CoV-2 infection during the Omicron wave using machine learning.

The Omicron SARS-CoV-2 variant continues to strain healthcare systems. Developing tools that facilitate the identification of patients at highest risk of adverse outcomes is a priority. The study objectives are to develop population-scale predictive models that: 1) identify predictors of adverse outcomes with Omicron surge SARS-CoV-2 infections, and 2) predict the impact of prioritized vaccination of high-risk groups for said outcome. We prepared a retrospective longitudinal observational study of a national cohort of 172,814 patients in the U.S. Veteran Health Administration who tested positive for SARS-CoV-2 from January 15 to August 15, 2022. We utilized sociodemographic characteristics, comorbidities, and vaccination status, at time of testing positive for SARS-CoV-2 to predict hospitalization, escalation of care (high-flow oxygen, mechanical ventilation, vasopressor use, dialysis, or extracorporeal membrane oxygenation), and death within 30 days. Machine learning models demonstrated that advanced age, high comorbidity burden, lower body mass index, unvaccinated status, and oral anticoagulant use were the important predictors of hospitalization and escalation of care. Similar factors predicted death. However, anticoagulant use did not predict mortality risk. The all-cause death model showed the highest discrimination (Area Under the Curve (AUC) = 0.903, 95% Confidence Interval (CI): 0.895, 0.911) followed by hospitalization (AUC = 0.822, CI: 0.818, 0.826), then escalation of care (AUC = 0.793, CI: 0.784, 0.805). Assuming a vaccine efficacy range of 70.8 to 78.7%, our simulations projected that targeted prevention in the highest risk group may have reduced 30-day hospitalization and death in more than 2 of 5 unvaccinated patients.

It's Not Just: Evaluation of a Media Campaign to Motivate Action Around Targeting of Menthol Tobacco in Black Communities.

Introduction: For more than 60 years, tobacco companies have aggressively marketed menthol tobacco products in Black communities. In 2021, New York State Department of Health-funded grantees launched a media campaign aimed toward civically engaged New York adults to educate and mobilize community action to prevent targeted marketing of menthol tobacco. This study examined audience reactions to the campaign and associations between campaign awareness and key outcomes. Methods: Following campaign implementation, we administered 2 online, cross-sectional surveys to 2,000 civically engaged New York adults to assess campaign awareness, audience reactions, and campaign-related attitudes and behaviors. We examined sociodemographic differences in audience reactions and assessed multivariate associations between campaign awareness and key outcomes. Results: Overall, 40% of respondents were aware of the campaign. Perceived advertisement (ad) effectiveness was higher among Black, Hispanic, and nonsmoking respondents and those aware of the campaign. Negative reactions to ads were higher at wave 1, among non-Hispanic White and male respondents, and among current smokers. Campaign awareness was positively associated with campaign-related beliefs. The association between campaign awareness and support for a menthol ban varied by survey wave and race, with positive associations at wave 2 and among non-Hispanic White respondents only. Among wave 2 respondents only, campaign awareness was positively associated with actions to reduce the targeting of menthol in Black communities. Conclusion: Media campaigns can play an important role in raising awareness of menthol tobacco product targeting in Black communities and building public support for local and statewide menthol restrictions that may be implemented before federal product standards are in place.

Rosacea in Older Adults and Pharmacologic Treatments.

Rosacea is a chronic inflammatory skin condition that is often more severe in older patients. The main clinical features are erythema, telangiectasia, and inflammatory lesions of the face. The pathogenesis of this condition is not fully understood but certainly multifaceted. Immune and inflammatory dysregulation, genetics, neurogenic dysregulation, microbiome dysbiosis, and systemic disease have all been implicated in rosacea pathogenesis. As we better understand the various pathways that lead to rosacea, we acknowledge that the different symptoms may have unique underlying triggers and mechanisms. Aging also impacts rosacea diagnosis and treatment. Older adults have more severe rosacea symptoms while also having more sensitive and fragile skin than younger patients; therefore, rosacea treatments for older patients require a balance between delivering adequate potency while also minimizing skin irritation and other adverse effects. Until recently, rosacea diagnoses were based on concrete subtypes that did not necessarily capture each patient's manifestation of rosacea. There is now an emphasis on more personalized phenotype-based diagnoses and treatments, which allows for more emphasis on treating individual symptoms and accounting for the unique characteristics of older patients. Centrofacial erythema is best treated with brimonidine and oxymetazoline, while phymatous change and telangiectasia are best treated with surgery and laser ablation. Treatment for rosacea papules and pustules ranges from topicals, such as azelaic acid, ivermectin, metronidazole, minocycline, and encapsulated benzoyl peroxide, to systemics, such as doxycycline and isotretinoin. It is important to understand these treatments in relation to adverse effects and drug interactions that may specifically arise in older populations to provide optimal care. As we advance in understanding rosacea's pathogenesis and adopt personalized phenotype-based approaches, optimizing care for older patients becomes crucial. Continued research into novel treatments is essential to address their unique needs.

When Should I Get My Next COVID-19 Vaccine? Data From the Surveillance of Responses to COVID-19 Vaccines in Systemic Immune-Mediated Inflammatory Diseases (SUCCEED) Study.

OBJECTIVE: To determine how serologic responses to coronavirus disease 2019 (COVID-19) vaccination and infection in immune-mediated inflammatory disease (IMID) are affected by time since last vaccination and other factors. METHODS: Post-COVID-19 vaccination, data, and dried blood spots or sera were collected from adults with rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis and spondylarthritis, and psoriasis and psoriatic arthritis. The first sample was collected at enrollment, then at 2 to 4 weeks and 3, 6, and 12 months after the latest vaccine dose. Multivariate generalized estimating equation regressions (including medications, demographics, and vaccination history) evaluated serologic response, based on log-transformed anti-receptor-binding domain (RBD) IgG titers; we also measured antinucleocapsid (anti-N) IgG. RESULTS: Positive associations for log-transformed anti-RBD titers were seen with female sex, number of doses, and self-reported COVID-19 infections in 2021 to 2023. Negative associations were seen with prednisone, anti-tumor necrosis factor agents, and rituximab. Over the 2021-2023 period, most (94%) of anti-N positivity was associated with a self-reported infection in the 3 months prior to testing. From March 2021 to February 2022, anti-N positivity was present in 5% to 15% of samples and was highest in the post-Omicron era, with antinucleocapsid positivity trending to 30% to 35% or higher as of March 2023. Anti-N positivity in IMID remained lower than Canada's general population seroprevalence (> 50% in 2022 and > 75% in 2023). Time since last vaccination was negatively associated with log-transformed anti-RBD titers, particularly after 210 days. CONCLUSION: Ours is the first pan-Canadian IMID assessment of how vaccine history and other factors affect serologic COVID-19 vaccine responses. These findings may help individuals personalize vaccination decisions, including consideration of additional vaccination when > 6 months has elapsed since last COVID-19 vaccination/infection.

Predicting state level suicide fatalities in the united states with realtime data and machine learning.

Digital trace data and machine learning techniques are increasingly being adopted to predict suicide-related outcomes at the individual level; however, there is also considerable public health need for timely data about suicide trends at the population level. Although significant geographic variation in suicide rates exist by state within the United States, national systems for reporting state suicide trends typically lag by one or more years. We developed and validated a deep learning based approach to utilize real-time, state-level online (Mental Health America web-based depression screenings; Google and YouTube Search Trends), social media (Twitter), and health administrative data (National Syndromic Surveillance Program emergency department visits) to estimate weekly suicide counts in four participating states. Specifically, per state, we built a long short-term memory (LSTM) neural network model to combine signals from the real-time data sources and compared predicted values of suicide deaths from our model to observed values in the same state. Our LSTM model produced accurate estimates of state-specific suicide rates in all four states (percentage error in suicide rate of -2.768% for Utah, -2.823% for Louisiana, -3.449% for New York, and -5.323% for Colorado). Furthermore, our deep learning based approach outperformed current gold-standard baseline autoregressive models that use historical death data alone. We demonstrate an approach to incorporate signals from multiple proxy real-time data sources that can potentially provide more timely estimates of suicide trends at the state level. Timely suicide data at the state level has the potential to improve suicide prevention planning and response tailored to the needs of specific geographic communities.

Long-term HIV care outcomes under universal HIV treatment guidelines: A retrospective cohort study in 25 countries.

BACKGROUND: While national adoption of universal HIV treatment guidelines has led to improved, timely uptake of antiretroviral therapy (ART), longer-term care outcomes are understudied. There is little data from real-world service delivery settings on patient attrition, viral load (VL) monitoring, and viral suppression (VS) at 24 and 36 months after HIV treatment initiation. METHODS AND FINDINGS: For this retrospective cohort analysis, we used observational data from 25 countries in the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium's Asia-Pacific, Central Africa, East Africa, Central/South America, and North America regions for patients who were ART naïve and aged ≥15 years at care enrollment between 24 months before and 12 months after national adoption of universal treatment guidelines, occurring 2012 to 2018. We estimated crude cumulative incidence of loss-to-clinic (CI-LTC) at 12, 24, and 36 months after enrollment among patients enrolling in care before and after guideline adoption using competing risks regression. Guideline change-associated hazard ratios of LTC at each time point after enrollment were estimated via cause-specific Cox proportional hazards regression models. Modified Poisson regression was used to estimate relative risks of retention, VL monitoring, and VS at 12, 24, and 36 months after ART initiation. There were 66,963 patients enrolling in HIV care at 109 clinics with ≥12 months of follow-up time after enrollment (46,484 [69.4%] enrolling before guideline adoption and 20,479 [30.6%] enrolling afterwards). More than half (54.9%) were females, and median age was 34 years (interquartile range [IQR]: 27 to 43). Mean follow-up time was 51 months (standard deviation: 17 months; range: 12, 110 months). Among patients enrolling before guideline adoption, crude CI-LTC was 23.8% (95% confidence interval [95% CI] 23.4, 24.2) at 12 months, 31.0% (95% CI [30.6, 31.5]) at 24 months, and 37.2% (95% [CI 36.8, 37.7]) at 36 months after enrollment. Adjusting for sex, age group, enrollment CD4, clinic location and type, and country income level, enrolling in care and initiating ART after guideline adoption was associated with increased hazard of LTC at 12 months (adjusted hazard ratio [aHR] 1.25 [95% CI 1.08, 1.44]; p = 0.003); 24 months (aHR 1.38 [95% CI 1.19, 1.59]; p < .001); and 36 months (aHR 1.34 [95% CI 1.18, 1.53], p < .001) compared with enrollment before guideline adoption, with no before-after differences among patients with no record of ART initiation by end of follow-up. Among patients retained after ART initiation, VL monitoring was low, with marginal improvements associated with guideline adoption only at 12 months after ART initiation. Among those with VL monitoring, VS was high at each time point among patients enrolling before guideline adoption (86.0% to 88.8%) and afterwards (86.2% to 90.3%), with no substantive difference associated with guideline adoption. Study limitations include lags in and potential underascertainment of care outcomes in real-world service delivery data and potential lack of generalizability beyond IeDEA sites and regions included in this analysis. CONCLUSIONS: In this study, adoption of universal HIV treatment guidelines was associated with lower retention after ART initiation out to 36 months of follow-up, with little change in VL monitoring or VS among retained patients. Monitoring long-term HIV care outcomes remains critical to identify and address causes of attrition and gaps in HIV care quality.

Using Initial Biopsies and Vertical Sections to Improve Trainees' Confidence in Performing Mohs Surgery.

BACKGROUND: Tissue preservation and tumor clearance are hallmarks of Mohs micrographic surgery, but no standardized method currently exists to guide trainees on how to balance the two. OBJECTIVE: The authors provided residents and fellows with additional histologic information to enhance their surgical decision-making without changing the standard methodology of Mohs surgery. METHODS AND MATERIALS: Trainees were provided initial biopsy slides (IS) and frozen vertical sections (VS) of the first Mohs layer. All Mohs layers were excised in standard fashion, and vertically oriented sections were taken from the layer without disturbing the surgical margins to obtain VS. Surveys were used to assess trainees' confidence in performing Mohs surgery with and without these tools. RESULTS: Trainees reported increased confidence in performing Mohs surgery when they reviewed IS before surgery and viewed VS of the first layer. CONCLUSION: Reviewing IS and VS improved trainees' confidence in performing Mohs surgery. This additional histological information was obtained while maintaining the usual steps of Mohs surgery. Objective information obtained from IS and VS may explain why trainees' confidence increased using this technique. Both IS and VS can be valuable teaching tools that may enhance trainees' ability to perform Mohs surgery.

Cell-Free Protein Expression in Polymer Materials.

While synthetic biology has advanced complex capabilities such as sensing and molecular synthesis in aqueous solutions, important applications may also be pursued for biological systems in solid materials. Harsh processing conditions used to produce many synthetic materials such as plastics make the incorporation of biological functionality challenging. One technology that shows promise in circumventing these issues is cell-free protein synthesis (CFPS), where core cellular functionality is reconstituted outside the cell. CFPS enables genetic functions to be implemented without the complications of membrane transport or concerns over the cellular viability or release of genetically modified organisms. Here, we demonstrate that dried CFPS reactions have remarkable tolerance to heat and organic solvent exposure during the casting processes for polymer materials. We demonstrate the utility of this observation by creating plastics that have spatially patterned genetic functionality, produce antimicrobials in situ, and perform sensing reactions. The resulting materials unlock the potential to deliver DNA-programmable biofunctionality in a ubiquitous class of synthetic materials.