A Human IgSF Cell-Surface Interactome Reveals a Complex Network of Protein-Protein Interactions.

Cell-surface protein-protein interactions (PPIs) mediate cell-cell communication, recognition, and responses. We executed an interactome screen of 564 human cell-surface and secreted proteins, most of which are immunoglobulin superfamily (IgSF) proteins, using a high-throughput, automated ELISA-based screening platform employing a pooled-protein strategy to test all 318,096 PPI combinations. Screen results, augmented by phylogenetic homology analysis, revealed ∼380 previously unreported PPIs. We validated a subset using surface plasmon resonance and cell binding assays. Observed PPIs reveal a large and complex network of interactions both within and across biological systems. We identified new PPIs for receptors with well-characterized ligands and binding partners for "orphan" receptors. New PPIs include proteins expressed on multiple cell types and involved in diverse processes including immune and nervous system development and function, differentiation/proliferation, metabolism, vascularization, and reproduction. These PPIs provide a resource for further biological investigation into their functional relevance and may offer new therapeutic drug targets.

Natural Killer Cells Control Tumor Growth by Sensing a Growth Factor.

Many tumors produce platelet-derived growth factor (PDGF)-DD, which promotes cellular proliferation, epithelial-mesenchymal transition, stromal reaction, and angiogenesis through autocrine and paracrine PDGFRß signaling. By screening a secretome library, we found that the human immunoreceptor NKp44, encoded by NCR2 and expressed on natural killer (NK) cells and innate lymphoid cells, recognizes PDGF-DD. PDGF-DD engagement of NKp44 triggered NK cell secretion of interferon gamma (IFN)-γ and tumor necrosis factor alpha (TNF-α) that induced tumor cell growth arrest. A distinctive transcriptional signature of PDGF-DD-induced cytokines and the downregulation of tumor cell-cycle genes correlated with NCR2 expression and greater survival in glioblastoma. NKp44 expression in mouse NK cells controlled the dissemination of tumors expressing PDGF-DD more effectively than control mice, an effect enhanced by blockade of the inhibitory receptor CD96 or CpG-oligonucleotide treatment. Thus, while cancer cell production of PDGF-DD supports tumor growth and stromal reaction, it concomitantly activates innate immune responses to tumor expansion.

An allosteric inhibitor of the human Cdc34 ubiquitin-conjugating enzyme.

In the ubiquitin-proteasome system (UPS), E2 enzymes mediate the conjugation of ubiquitin to substrates and thereby control protein stability and interactions. The E2 enzyme hCdc34 catalyzes the ubiquitination of hundreds of proteins in conjunction with the cullin-RING (CRL) superfamily of E3 enzymes. We identified a small molecule termed CC0651 that selectively inhibits hCdc34. Structure determination revealed that CC0651 inserts into a cryptic binding pocket on hCdc34 distant from the catalytic site, causing subtle but wholesale displacement of E2 secondary structural elements. CC0651 analogs inhibited proliferation of human cancer cell lines and caused accumulation of the SCF(Skp2) substrate p27(Kip1). CC0651 does not affect hCdc34 interactions with E1 or E3 enzymes or the formation of the ubiquitin thioester but instead interferes with the discharge of ubiquitin to acceptor lysine residues. E2 enzymes are thus susceptible to noncatalytic site inhibition and may represent a viable class of drug target in the UPS.

The actin nucleator Spir-1 is a virus restriction factor that promotes innate immune signalling.

Cellular proteins often have multiple and diverse functions. This is illustrated with protein Spir-1 that is an actin nucleator, but, as shown here, also functions to enhance innate immune signalling downstream of RNA sensing by RIG-I/MDA-5. In human and mouse cells lacking Spir-1, IRF3 and NF-κB-dependent gene activation is impaired, whereas Spir-1 overexpression enhanced IRF3 activation. Furthermore, the infectious virus titres and sizes of plaques formed by two viruses that are sensed by RIG-I, vaccinia virus (VACV) and Zika virus, are increased in Spir-1 KO cells. These observations demonstrate the biological importance of Spir-1 in the response to virus infection. Like cellular proteins, viral proteins also have multiple and diverse functions. Here, we also show that VACV virulence factor K7 binds directly to Spir-1 and that a diphenylalanine motif of Spir-1 is needed for this interaction and for Spir-1-mediated enhancement of IRF3 activation. Thus, Spir-1 is a new virus restriction factor and is targeted directly by an immunomodulatory viral protein that enhances virus virulence and diminishes the host antiviral responses.

Examining ethical issues that arise in providing ED/hospital care for patients experiencing elder mistreatment and approaches to address them.

Clinicians in the emergency department and hospital who treat patients experiencing elder mistreatment (EM) can expect to encounter challenging ethical dilemmas. Collaboration with ethics and EM consultation services offers teams an important opportunity to improve patient-centered outcomes and address value-based concerns when treating these patients. This article describes the role of a hospital clinical ethics consultation service and best practices for collaboration between ethics and EM consultation services. Illuminated via four case studies, the article presents several core ethical frameworks, including allowing patients the dignity of risk, considerations around a harm reduced discharge, involving abusers in surrogate decision making, and providers' experience of moral distress when dealing with patients experiencing EM. Increasing collaboration with ethics and elder mistreatment services can help teams more effectively respond to EM.

Differences in influenza vaccination by gender identity and state-level gender equity policies: Behavioral Risk Factor Surveillance System, 2015-2019.

BACKGROUND: It is estimated that there are one million transgender and over 340,000 gender non-conforming people in the United States, many of whom face significant health disparities including access to healthcare. Although previous studies have reported greater vaccine uptake in women compared to men, national-level estimates of influenza vaccine uptake among transgender and non-binary people are unknown. This study aims to characterize differences in influenza vaccine uptake by gender identity and examine associations between vaccination status and state-level gender equity policies. METHODS: We used cross-sectional data from adults participating in the 2015-2019 United States Behavioral Risk Factors Surveillance System surveys. Weighted prevalence differences (PDs) and associated confidence intervals (CIs) of being unvaccinated against influenza by self-reported gender identity were estimated using generalized linear regression models. RESULTS: Compared to cisgender women (unvaccinated prevalence = 57.3%), the prevalence of being unvaccinated was significantly higher among cisgender men (64.4%; PD = 7.0 per 100, 95% CI: 6.7-7.4), transgender women (65.4%; PD = 8.1 per 100, 95% CI 4.0-12.2), transgender men (64.6%; PD = 7.3 per 100, 95% CI: 2.7-11.8), and gender non-conforming individuals (64.6%; PD = 7.2 per 100, 95% CI: 1.3-13.2). This pattern was similar among individuals living in states with protective versus restrictive gender equity policies. CONCLUSIONS: Our results identified a disparity in influenza vaccine uptake among individuals across the gender spectrum. To improve vaccine equity, future research should explore barriers to and facilitators of vaccine uptake by gender identity, which could inform policies and health promotion interventions to improve uptake co-designed and implemented with the transgender and non-binary communities.

Incidence of SARS-CoV-2 infection and associated risk factors among staff and residents at homeless shelters in King County, Washington: an active surveillance study.

Homeless shelter residents and staff may be at higher risk of SARS-CoV-2 infection. However, SARS-CoV-2 infection estimates in this population have been reliant on cross-sectional or outbreak investigation data. We conducted routine surveillance and outbreak testing in 23 homeless shelters in King County, Washington, to estimate the occurrence of laboratory-confirmed SARS-CoV-2 infection and risk factors during 1 January 2020-31 May 2021. Symptom surveys and nasal swabs were collected for SARS-CoV-2 testing by RT-PCR for residents aged ≥3 months and staff. We collected 12,915 specimens from 2,930 unique participants. We identified 4.74 (95% CI 4.00-5.58) SARS-CoV-2 infections per 100 individuals (residents: 4.96, 95% CI 4.12-5.91; staff: 3.86, 95% CI 2.43-5.79). Most infections were asymptomatic at the time of detection (74%) and detected during routine surveillance (73%). Outbreak testing yielded higher test positivity than routine surveillance (2.7% versus 0.9%). Among those infected, residents were less likely to report symptoms than staff. Participants who were vaccinated against seasonal influenza and were current smokers had lower odds of having an infection detected. Active surveillance that includes SARS-CoV-2 testing of all persons is essential in ascertaining the true burden of SARS-CoV-2 infections among residents and staff of congregate settings.

Burden of long COVID among adults experiencing sheltered homelessness: a longitudinal cohort study in King County, WA between September 2020-April 2022.

BACKGROUND: People experiencing homelessness (PEH) are at increased risk for acquiring SARS-CoV-2, but the burden of long COVID in this population is unknown. METHODS: We conducted a matched prospective cohort study to assess the prevalence, characteristics, and impact of long COVID among sheltered PEH in Seattle, WA between September 2020-April 2022. Adults ≥ 18 years, residing across nine homeless shelters with active respiratory virus surveillance, were eligible to complete in-person baseline surveys and interval follow-up phone surveys. We included a subset of 22 COVID-19-positive cases who tested positive or inconclusive for SARS-CoV-2 and 44 COVID-19-negative controls who tested negative for SARS-CoV-2, frequency matched on age and sex. Among controls, 22 were positive and 22 were negative for one of 27 other respiratory virus pathogens. To assess the impact of COVID-19 on the risk of symptom presence at follow-up (day 30-225 post-enrollment test), we performed log-linear regression with robust standard errors, adjusting for confounding by shelter site and demographic variables determined a priori. RESULTS: Of 53 eligible COVID-19 cases, 22 (42%) completed ≥ 1 follow-up survey. While five (23%) cases reported ≥ 1 symptom at baseline, this increased to 77% (10/13) between day 30-59 and 33% (4/12) day 90 + . The most commonly reported symptoms day 30 + were fatigue (27%) and rhinorrhea (27%), with 8 (36%) reporting symptoms that interfered with or prevented daily activities. Four (33%) symptomatic cases reported receiving medical care outside of a medical provider at an isolation facility. Of 44 controls, 12 (27%) reported any symptoms day 90 + . Risk of any symptoms at follow-up was 5.4 times higher among COVID-19 cases compared to controls (95% CI: 2.7-10.5). CONCLUSIONS: Shelter residents reported a high prevalence of symptoms 30 + days after their SARS-CoV-2 detection, though few accessed medical care for persistent illness. The impact of COVID-19 extends beyond acute illness and may exacerbate existing challenges that marginalized populations face in maintaining their health and wellbeing.

The critical role of the specialized social worker as part of ED/hospital-based elder mistreatment response teams.

The emergency department and hospital provide a unique and important opportunity to identify elder mistreatment and offer intervention. To help manage these complex cases, multi-disciplinary response teams have been launched. In developing these teams, it quickly became clear that social workers play a critical role in responding to elder mistreatment. Their unique skillset allows them to establish close connections with community resources, collaborate with various hospital stakeholders, support patients/families/caregivers through challenging situations, navigate the legal and protective systems, and balance patient safety and quality of life in disposition decision-making. The role of the social worker on these multi-faceted teams includes conducting a comprehensive biopsychosocial assessment, helping to develop a safe discharge plan, and making appropriate referrals, among other responsibilities. Any institution considering developing a multi-disciplinary program should recognize the critical importance of social work.

The Clinical and Genomic Epidemiology of Rhinovirus in Homeless Shelters-King County, Washington.

BACKGROUND: Rhinovirus (RV) is a common cause of respiratory illness in all people, including those experiencing homelessness. RV epidemiology in homeless shelters is unknown. METHODS: We analyzed data from a cross-sectional homeless shelter study in King County, Washington, October 2019-May 2021. Shelter residents or guardians aged ≥3 months reporting acute respiratory illness completed questionnaires and submitted nasal swabs. After 1 April 2020, enrollment expanded to residents and staff regardless of symptoms. Samples were tested by multiplex RT-PCR for respiratory viruses. A subset of RV-positive samples was sequenced. RESULTS: There were 1066 RV-positive samples with RV present every month of the study period. RV was the most common virus before and during the coronavirus disease 2019 (COVID-19) pandemic (43% and 77% of virus-positive samples, respectively). Participants from family shelters had the highest prevalence of RV. Among 131 sequenced samples, 33 RV serotypes were identified with each serotype detected for ≤4 months. CONCLUSIONS: RV infections persisted through community mitigation measures and were most prevalent in shelters housing families. Sequencing showed a diversity of circulating RV serotypes, each detected over short periods of time. Community-based surveillance in congregate settings is important to characterize respiratory viral infections during and after the COVID-19 pandemic. CLINICAL TRIALS REGISTRATION: NCT04141917.

Human Parainfluenza Virus in Homeless Shelters before and during the COVID-19 Pandemic, Washington, USA.

To determine the epidemiology of human parainfluenza virus in homeless shelters during the COVID-19 pandemic, we analyzed data and sequences from respiratory specimens collected in 23 shelters in Washington, USA, during 2019-2021. Two clusters in children were genetically similar by shelter of origin. Shelter-specific interventions are needed to reduce these infections.

The value of decreasing the duration of the infectious period of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Finding medications or vaccines that may decrease the infectious period of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could potentially reduce transmission in the broader population. We developed a computational model of the U.S. simulating the spread of SARS-CoV-2 and the potential clinical and economic impact of reducing the infectious period duration. Simulation experiments found that reducing the average infectious period duration could avert a median of 442,852 [treating 25% of symptomatic cases, reducing by 0.5 days, reproductive number (R0) 3.5, and starting treatment when 15% of the population has been exposed] to 44.4 million SARS-CoV-2 cases (treating 75% of all infected cases, reducing by 3.5 days, R0 2.0). With R0 2.5, reducing the average infectious period duration by 0.5 days for 25% of symptomatic cases averted 1.4 million cases and 99,398 hospitalizations; increasing to 75% of symptomatic cases averted 2.8 million cases. At $500/person, treating 25% of symptomatic cases saved $209.5 billion (societal perspective). Further reducing the average infectious period duration by 3.5 days averted 7.4 million cases (treating 25% of symptomatic cases). Expanding treatment to 75% of all infected cases, including asymptomatic infections (R0 2.5), averted 35.9 million cases and 4 million hospitalizations, saving $48.8 billion (societal perspective and starting treatment after 5% of the population has been exposed). Our study quantifies the potential effects of reducing the SARS-CoV-2 infectious period duration.

Lives and Costs Saved by Expanding and Expediting Coronavirus Disease 2019 Vaccination.

BACKGROUND: With multiple coronavirus disease 2019 (COVID-19) vaccines available, understanding the epidemiologic, clinical, and economic value of increasing coverage levels and expediting vaccination is important. METHODS: We developed a computational model (transmission and age-stratified clinical and economics outcome model) representing the United States population, COVID-19 coronavirus spread (February 2020-December 2022), and vaccination to determine the impact of increasing coverage and expediting time to achieve coverage. RESULTS: When achieving a given vaccination coverage in 270 days (70% vaccine efficacy), every 1% increase in coverage can avert an average of 876 800 (217 000-2 398 000) cases, varying with the number of people already vaccinated. For example, each 1% increase between 40% and 50% coverage can prevent 1.5 million cases, 56 240 hospitalizations, and 6660 deaths; gain 77 590 quality-adjusted life-years (QALYs); and save $602.8 million in direct medical costs and $1.3 billion in productivity losses. Expediting to 180 days could save an additional 5.8 million cases, 215 790 hospitalizations, 26 370 deaths, 206 520 QALYs, $3.5 billion in direct medical costs, and $4.3 billion in productivity losses. CONCLUSIONS: Our study quantifies the potential value of decreasing vaccine hesitancy and increasing vaccination coverage and how this value may decrease with the time it takes to achieve coverage, emphasizing the need to reach high coverage levels as soon as possible, especially before the fall/winter.

Coronavirus Disease 2019 Outbreak in a San Francisco Homeless Shelter.

We report the public health response to a coronavirus disease 2019 (COVID-19) outbreak in a San Francisco shelter where 67% of residents and 17% of staff tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We describe the limited utility of case investigation, person-based contact tracing and symptom screening, and the benefits of mass testing in outbreak response.

Comparison of infection control strategies to reduce COVID-19 outbreaks in homeless shelters in the United States: a simulation study.

BACKGROUND: COVID-19 outbreaks have occurred in homeless shelters across the US, highlighting an urgent need to identify the most effective infection control strategy to prevent future outbreaks. METHODS: We developed a microsimulation model of SARS-CoV-2 transmission in a homeless shelter and calibrated it to data from cross-sectional polymerase chain reaction (PCR) surveys conducted during COVID-19 outbreaks in five homeless shelters in three US cities from March 28 to April 10, 2020. We estimated the probability of averting a COVID-19 outbreak when an exposed individual is introduced into a representative homeless shelter of 250 residents and 50 staff over 30 days under different infection control strategies, including daily symptom-based screening, twice-weekly PCR testing, and universal mask wearing. RESULTS: The proportion of PCR-positive residents and staff at the shelters with observed outbreaks ranged from 2.6 to 51.6%, which translated to the basic reproduction number (R0) estimates of 2.9-6.2. With moderate community incidence (~ 30 confirmed cases/1,000,000 people/day), the estimated probabilities of averting an outbreak in a low-risk (R0 = 1.5), moderate-risk (R0 = 2.9), and high-risk (R0 = 6.2) shelter were respectively 0.35, 0.13, and 0.04 for daily symptom-based screening; 0.53, 0.20, and 0.09 for twice-weekly PCR testing; 0.62, 0.27, and 0.08 for universal masking; and 0.74, 0.42, and 0.19 for these strategies in combination. The probability of averting an outbreak diminished with higher transmissibility (R0) within the simulated shelter and increasing incidence in the local community. CONCLUSIONS: In high-risk homeless shelter environments and locations with high community incidence of COVID-19, even intensive infection control strategies (incorporating daily symptom screening, frequent PCR testing, and universal mask wearing) are unlikely to prevent outbreaks, suggesting a need for non-congregate housing arrangements for people experiencing homelessness. In lower-risk environments, combined interventions should be employed to reduce outbreak risk.

The Potential Clinical and Economic Value of a Human Papillomavirus Primary Screening Test That Additionally Identifies Genotypes 31, 45, 51, and 52 Individually.

BACKGROUND: Although current human papillomavirus (HPV) genotype screening tests identify genotypes 16 and 18 and do not specifically identify other high-risk types, a new extended genotyping test identifies additional individual (31, 45, 51, and 52) and groups (33/58, 35/39/68, and 56/59/66) of high-risk genotypes. METHODS: We developed a Markov model of the HPV disease course and evaluated the clinical and economic value of HPV primary screening with Onclarity (BD Diagnostics, Franklin Lakes, NJ) capable of extended genotyping in a cohort of women 30 years or older. Women with certain genotypes were later rescreened instead of undergoing immediate colposcopy and varied which genotypes were rescreened, disease progression rate, and test cost. RESULTS: Assuming 100% compliance with screening, HPV primary screening using current tests resulted in 25,194 invasive procedures and 48 invasive cervical cancer (ICC) cases per 100,000 women. Screening with extended genotyping (100% compliance) and later rescreening women with certain genotypes averted 903 to 3163 invasive procedures and resulted in 0 to 3 more ICC cases compared with current HPV primary screening tests. Extended genotyping was cost-effective ($2298-$7236/quality-adjusted life year) when costing $75 and cost saving (median, $0.3-$1.0 million) when costing $43. When the probabilities of disease progression increased (2-4 times), extended genotyping was not cost-effective because it resulted in more ICC cases and accrued fewer quality-adjusted life years. CONCLUSIONS: Our study identified the conditions under which extended genotyping was cost-effective and even cost saving compared with current tests. A key driver of cost-effectiveness is the risk of disease progression, which emphasizes the need to better understand such risks in different populations.

Pressure injury and risk in the inpatient paediatric and neonatal populations: A single centre point-prevalence study.

INTRODUCTION: Prevention and management of pressure injury is a key nurse-sensitive quality indicator. From clinical insights, pressure injury effects hospitalised neonates and children, however it is unclear how prevalent this is. The aim of this study was to quantify prevalence of pressure injury, assess skin integrity risk level, and quantify preventive interventions in both neonatal and child inpatient populations at a large children's hospital in the UK. METHODS: A cross-sectional study was undertaken, assessing the skin integrity of all children allocated to a paediatric or neonatal bed in June/July 2020. A data collection tool was adapted from two established pressure ulcer point prevalence surveys (EUPAP and Medstrom pre-prevalence survey). Risk assessment was performed using the Braden QD scale. RESULTS: Eighty-eight participants were included, with median age of 0.85 years [range 0-17.5 years), with 32 (36%) of participants being preterm. Median length of hospital stay was 11 days [range 0-174 days]. Pressure ulcer prevalence was 3.4%. The majority of participants had at least two medical devices, with 16 (18.2%) having more than four. Having a medical device was associated with increased risk score of developing pressure injury (odds ratio [OR] 0.03, 95% Confidence Interval [CI] 0.01-0.05, p = 0.02). Most children (39 (44%)) were reported not having proposed preventive measures in place aligned to their risk assessment. However, for those that did, 2 to 4 hourly repositioning was associated with a risk reduction on pressure damage (OR 0.13, 95% CI 0.03-0.23, p = 0.01). CONCLUSION: Overall, we found a low prevalence of pressure injury across preterm infants, children and young people at a tertiary children's hospital. Accurate risk assessment as well as availability and implementation of preventive interventions are a priority for healthcare institutes to avoid pressure injury.

What If the Influenza Vaccine Did Not Offer Such Variable Protection?

BACKGROUND: The protection that an influenza vaccine offers can vary significantly from person to person due to differences in immune systems, body types, and other factors. The question, then, is what is the value of efforts to reduce this variability such as making vaccines more personalized and tailored to individuals. METHODS: We developed a compartment model of the United States to simulate different influenza seasons and the impact of reducing the variability in responses to the influenza vaccine across the population. RESULTS: Going from a vaccine that varied in efficacy (0-30%) to one that had a uniform 30% efficacy for everyone averted 16.0-31.2 million cases, $1.9-$3.6 billion in direct medical costs, and $16.1-$42.7 billion in productivity losses. Going from 0-50% in efficacy to just 50% for everyone averted 27.7-38.6 million cases, $3.3-$4.6 billion in direct medical costs, and $28.8-$57.4 billion in productivity losses. Going from 0-70% to 70% averted 33.6-54.1 million cases, $4.0-$6.5 billion in direct medical costs, and $44.8-$64.7 billion in productivity losses. CONCLUSIONS: This study quantifies for policy makers, funders, and vaccine developers and manufacturers the potential impact of efforts to reduce variability in the protection that influenza vaccines offer (eg, developing vaccines that are more personalized to different individual factors).

High-Throughput Screening at the Membrane Interface Reveals Inhibitors of Amyloid-ß.

Aggregation and the formation of oligomeric intermediates of amyloid-ß (Aß) at the membrane interface of neuronal cells are implicated in the cellular toxicity and pathology of Alzheimer's disease. Small molecule compounds have been shown to suppress amyloid aggregation and cellular toxicity, but often the presence of a lipid membrane negates their activity. A high-throughput screen of 1800 small molecules was performed to search for membrane active inhibitors, and 21 primary hits were discovered. Through the use of fluorescence-based assays, transmission electron microscopy, and dot blot assays, the initial 21 primary hits were narrowed down to five lead compounds. Nuclear magnetic resonance and circular dichroism experiments were used for further confirmation of amyloid inhibition at the membrane interface and to obtain insights into the secondary structure of amyloid-ß, while size exclusion chromatography was used to characterize the size of Aß species. Lastly, dye-leakage assays allowed us to understand how the addition of the five lead compounds affected amyloid-ß's ability to permeate the lipid bilayer. These results provide insights into small molecules that stabilize small amyloid species in the presence of membranes for the development of tool compounds for deeper investigations of these transient species.

Secure Delivery of HIV-Related and Tuberculosis Laboratory Results to Patient Cell Phones: A Pilot Comparative Study.

South Africa processes 5.1 million HIV CD4, viral load (VL), and tuberculosis (TB) tests annually. This pilot non-randomized trial in South Africa explored an intervention ("MatlaMobile") to deliver laboratory results via mobile phone. Adults completing CD4, VL, and/or TB laboratory tests were enrolled-either receiving results by returning to clinic (control, n = 174) or mobile phone (intervention, n = 226). Study staff instructed control participants to return within 6 days (standard-of-care). MatlaMobile instructed intervention participants with clinically actionable results requiring intervention or treatment change (i.e., < 200 CD4 cells per milliliter, ≥ 400 viral copies per milliliter, or TB positive) to return immediately. A greater proportion of intervention participants than controls saw their results within 7 days of enrollment (73% vs. 8.6%, p < 0.001). Among participants instructed to return, more intervention participants (20%, n = 14/70) returned than controls (8.6%, n = 15/174, p = 0.02). MatlaMobile demonstrated that patients can quickly receive and respond appropriately to digital delivery of health information.