Plasma metabolites are altered before and after diagnosis of preeclampsia or fetal growth restriction.

Metabolomics is the study of small molecules (metabolites), within cells, tissues and biofluids. Maternal metabolites can provide important insight into the health and development of both mother and fetus throughout pregnancy. This study assessed metabolic profiles in the maternal circulation prior to and at the time of diagnosis of preeclampsia and fetal growth restriction. Maternal plasma samples were collected from two independent cohorts: (1) Established disease cohort: 50 participants diagnosed with early-onset preeclampsia (< 34 weeks' gestation), 14 with early-onset fetal growth restriction, and 25 gestation-matched controls. (2) Prospective cohort, collected at 36 weeks' gestation before diagnosis: 17 participants later developed preeclampsia, 49 delivered infants with fetal growth restriction (birthweight < 5th centile), and 72 randomly selected controls. Metabolic evaluation was performed by Metabolomics Australia on the Agilent 6545 QTOF Mass Spectrometer. In the established disease cohort, 77 metabolites were altered in circulation from participants with preeclampsia - increased L-cysteine (3.73-fold), L-cystine (3.28-fold), L-acetylcarnitine (2.57-fold), and carnitine (1.53-fold) (p < 0.05). There were 53 metabolites dysregulated in participants who delivered a fetal growth restriction infant-including increased levulinic acid, citric acid (1.93-fold), and creatine (1.14-fold) (p < 0.05). In the prospective cohort, 30 metabolites were altered in participants who later developed preeclampsia at term - reduced glutaric acid (0.85-fold), porphobilinogen (0.77-fold) and amininohippuric acid (0.82-fold) (p < 0.05) was observed. There were 5 metabolites altered in participants who later delivered a fetal growth restriction infant - including reduced 3-methoxybenzenepropanoic acid (p < 0.05). Downstream pathway analysis revealed aminoacyl-tRNA biosynthesis to be most significantly altered in the established cohort in preeclampsia (13/48 hits, p < 0.001) and fetal growth restriction (7/48 hits, p < 0.001). The predictive cohort showed no significant pathway alterations. This study observed altered metabolites in maternal plasma collected before and after diagnosis of a preeclampsia or fetal growth restriction. While a significant number of metabolites were altered with established disease, few changes were observed in the predictive cohort. Thus, metabolites measured in this study may not be useful as predictors of preeclampsia or fetal growth restriction.

Bridging an Education Gap: Ultrasound-guided Peripheral IVs.

PURPOSE: To provide ultrasound (US) education to anesthesia providers to increase usage for peripheral intravascular (IV) cannulation on difficult IV access patients. DESIGN: This project reflects a qualitative descriptive quality improvement project with outcomes measured. Data in this project include the overall knowledge and competency scores from the provider's US survey before and after education and training were provided. METHODS: A presentation was developed and provided to 38 certified registered nurse anesthetists (CRNA) via the hospital's online platform. Next, in-person simulations were conducted to facilitate the skills of US utilization. Each CRNA participating in simulations successfully performed the skill. The impact and success of the education bundle were collected via the disbursement of a Likert-scale survey via an automated data collection software. FINDINGS: Seventeen of the 38 (45%) participants responded to the survey. Of these respondents, 88% of providers indicated that their US skills and confidence had increased following the intervention, and 100% of participants stated that the intervention was helpful in learning US-guided peripheral IV insertion. CONCLUSIONS: Education and hands-on skills sessions increased provider confidence in US use. While this project focused on educational training of CRNAs, this is applicable to all health care providers who are responsible for IV cannulation. The project team members will disseminate these findings and plan to improve perioperative nurses' confidence in US-guided peripheral IV insertions; thus, improving efficiency in the operative setting.

Providers' experiences discussing care for patients with kidney failure who forgo kidney replacement therapy: A national qualitative study.

BACKGROUND: Many nephrology providers express difficulty in discussing care options for patients who forgo kidney replacement therapy (KRT), which hampers their ability to help patients make decisions about their current and future treatment of kidney disease. METHODS: We conducted a qualitative study using interviews with a national sample of nephrology providers (i.e., physicians and advanced practice providers) who participated in US professional societies between July and December 2022. We performed a thematic analysis of interviews to identify emergent themes reflecting providers' experiences discussing care for patients who forgo KRT. RESULTS: There were 21 providers (age 54±13years, female 81%, White 32%) who participated in interviews, of which 43% were physicians and most (57%) practiced in academic settings. Three dominant themes emerged from interviews: 1) Inconsistent terminology: while providers sought to use terms to describe care for patients who forgo KRT that affirmed patients' decision, clearly conveyed that KRT would not be pursued, and were familiar to patients and other providers, they disagreed about which terms satisfied these priorities; 2) Blurred distinctions between KRT and its alternative: providers' descriptions of their care practices suggested that differences in their approaches to caring for patients who forgo KRT and those who are planning to pursue KRT could be opaque; and, 3) Deciphering patients' decision to forgo KRT: providers did not readily accept patients' expressed preferences to forgo KRT at face value and described using a variety of methods to assess whether patients would follow through with their decision. CONCLUSIONS: Providers used different, inconsistent terms to describe care for patients who forgo KRT. They disagreed about what this care entailed and were uncertain about what patients might mean when they express not wanting to undergo KRT.

Evaluating the Phenotypic Patterns of Post-Traumatic Headache: A Systematic Review of Military Personnel.

INTRODUCTION: Mild traumatic brain injury (TBI) affects a significant number of military personnel, primarily because of physical impact, vehicle incidents, and blast exposure. Post-traumatic headache (PTH) is the most common symptom reported following mild TBI and can persist for several years. However, the current International Classification of Headache Disorders lacks phenotypic characterization for this specific headache disorder. It is important to appropriately classify the headache sub-phenotypes as it may enable more targeted management approaches. This systematic review seeks to identify the most common sub-phenotype of headaches in military personnel with PTH attributed to mild TBI. METHODS: We conducted a systematic search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines, focusing on the military population. PubMed, Web of Science, Cochrane, and Clinicaltrials.gov databases were searched. Abstracts and full texts were independently reviewed by two authors using predefined inclusion and exclusion criteria. Data extraction was performed using a standardized form. The risk of bias was assessed using the Newcastle-Ottawa Scale. RESULTS: Eight papers related to the military population were included in this review. Migraine was the most commonly reported headache sub-phenotype, with a prevalence ranging from 33 to 92%. Additionally, one military study identified tension-type headaches as the most prevalent headache phenotype. Although not the primary phenotype, one military cohort reported that approximately one-third of their cohort experienced trigeminal autonomic cephalalgias, which were associated with exposure to blast injuries and prior concussions. CONCLUSION: This systematic review demonstrated that PTH in the military population frequently exhibit migraine-like features. Tension-type headache and trigeminal autonomic cephalalgias also occur, although less commonly reported. Sub-phenotyping PTH may be important for initiating effective treatment since different phenotypes may respond differently to medications. The study populations analyzed in this systematic review display heterogeneity, underscoring the necessity for additional research features, more stringent criteria and comprehensive recording of baseline characteristics. Characterizing headaches following injury is crucial for an accurate diagnosis to enable effective management and rehabilitation planning for our armed forces.

Sex differences and immune correlates of Long COVID development, persistence, and resolution.

Sex differences have been observed in acute COVID-19 and Long COVID (LC) outcomes, with greater disease severity and mortality during acute infection in males and a greater proportion of females developing LC. We hypothesized that sex-specific immune dysregulation contributes to the pathogenesis of LC. To investigate the immunologic underpinnings of LC development and persistence, we used single-cell transcriptomics, single-cell proteomics, and plasma proteomics on blood samples obtained during acute SARS-CoV-2 infection and at 3 and 12 months post-infection in a cohort of 45 patients who either developed LC or recovered. Several sex-specific immune pathways were associated with LC. Specifically, males who would develop LC at 3 months had widespread increases in TGF-ß signaling during acute infection in proliferating NK cells. Females who would develop LC demonstrated increased expression of XIST, an RNA gene implicated in autoimmunity, and increased IL1 signaling in monocytes at 12 months post infection. Several immune features of LC were also conserved across sexes. Both males and females with LC had reduced co-stimulatory signaling from monocytes and broad upregulation of NF-κB transcription factors. In both sexes, those with persistent LC demonstrated increased LAG3, a marker of T cell exhaustion, reduced ETS1 transcription factor expression across lymphocyte subsets, and elevated intracellular IL-4 levels in T cell subsets, suggesting that ETS1 alterations may drive an aberrantly elevated Th2-like response in LC. Altogether, this study describes multiple innate and adaptive immune correlates of LC, some of which differ by sex, and offers insights toward the pursuit of tailored therapeutics.

Assessment of the Quality, Accountability, and Readability of Online Patient Education Materials for Optic Neuritis.

Most cases of optic neuritis (ON) occur in women and in patients between the ages of 15 and 45 years, which represents a key demographic of individuals who seek health information using the internet. As clinical providers strive to ensure patients have accessible information to understand their condition, assessing the standard of online resources is essential. To assess the quality, content, accountability, and readability of online information for optic neuritis. This cross-sectional study analyzed 11 freely available medical sites with information on optic neuritis and used PubMed as a gold standard for comparison. Twelve questions were composed to include the information most relevant to patients, and each website was independently examined by four neuro-ophthalmologists. Readability was analyzed using an online readability tool. Journal of the American Medical Association (JAMA) benchmarks, four criteria designed to assess the quality of health information further were used to evaluate the accountability of each website. Freely available online information. On average, websites scored 27.98 (SD ± 9.93, 95% CI 24.96-31.00) of 48 potential points (58.3%) for the twelve questions. There were significant differences in the comprehensiveness and accuracy of content across websites (p < .001). The mean reading grade level of websites was 11.90 (SD ± 2.52, 95% CI 8.83-15.25). Zero websites achieved all four JAMA benchmarks. Interobserver reliability was robust between three of four neuro-ophthalmologist (NO) reviewers (ρ = 0.77 between NO3 and NO2, ρ = 0.91 between NO3 and NO1, ρ = 0.74 between NO2 and NO1; all p < .05). The quality of freely available online information detailing optic neuritis varies by source, with significant room for improvement. The material presented is difficult to interpret and exceeds the recommended reading level for health information. Most websites reviewed did not provide comprehensive information regarding non-therapeutic aspects of the disease. Ophthalmology organizations should be encouraged to create content that is more accessible to the general public.

Vision Threatening Raised Intracranial Pressure Associated with Recreational Nitrous Oxide Use.

Nitrous oxide is used as an anaesthetic and analgesic agent in the medical setting and is known to cause raised intracranial pressure. The use of nitrous oxide recreationally for the drug's euphoric and relaxant properties has been linked to multiple neurological and psychiatric sequelae including neuropathy, myelopathy, and psychosis. We describe a case of a young person who declared heavy nitrous oxide use resulting in vision-threatening papilloedema secondary to raised intracranial pressure. He underwent emergency lumbar drainage alongside high-dose acetazolamide and parenteral vitamin B12 injections. To our knowledge, there have yet to be other reports of cases where heavy nitrous oxide use has caused secondary pseudotumor cerebri syndrome.

Integrating Genetic and Transcriptomic Data to Identify Genes Underlying Obesity Risk Loci.

Genome-wide association studies (GWAS) have identified numerous body mass index (BMI) loci. However, most underlying mechanisms from risk locus to BMI remain unknown. Leveraging omics data through integrative analyses could provide more comprehensive views of biological pathways on BMI. We analyzed genotype and blood gene expression data in up to 5,619 samples from the Framingham Heart Study (FHS). Using 3,992 single nucleotide polymorphisms (SNPs) at 97 BMI loci and 20,692 transcripts within 1 Mb, we performed separate association analyses of transcript with BMI and SNP with transcript (PBMI and PSNP, respectively) and then a correlated meta-analysis between the full summary data sets (PMETA). We identified transcripts that met Bonferroni-corrected significance for each omic, were more significant in the correlated meta-analysis than each omic, and were at least nominally associated with BMI in FHS data. Among 308 significant SNP-transcript-BMI associations, we identified seven genes (NT5C2, GSTM3, SNAPC3, SPNS1, TMEM245, YPEL3, and ZNF646) in five association regions. Using an independent sample of blood gene expression data, we validated results for SNAPC3 and YPEL3. We tested for generalization of these associations in hypothalamus, nucleus accumbens, and liver and observed significant (PMETA<0.05 & PMETA

Point-of-care urine tenofovir test predicts future HIV pre-exposure prophylaxis discontinuation among young users.

BACKGROUND: Young men who have sex with men and transgender women (YMSM/TGW) have disproportionately high HIV incidence and lower PrEP adherence. Point-of-care (POC) urine tenofovir (TFV) rapid assay (UTRA) testing permits real-time monitoring for nonadherence within clinical settings. We performed UTRA testing among PrEP users to examine the relationship between low PrEP adherence and future PrEP discontinuation, and the accuracy of POC testing compared to gold-standard liquid chromatography tandem mass spectrometry (LC/MS/MS). METHODS: YMSM/TGW participants (n = 100) were recruited during a daily PrEP visit. Logistic regression models analyzed the relationship between the primary predictor of urine POC assay results (cutoff 1,500 ng/mL) and the primary outcome of PrEP discontinuation, defined as no PrEP follow-up or prescription within 120 days. RESULTS: Overall, 19% of participants had low urine TFV and 21% discontinued PrEP, while 11% of participants self-reported low PrEP adherence (< 4 pills per week), which was only 43% sensitive/84% specific in predicting low TFV levels and was not associated with PrEP discontinuation. Low urine TFV level predicted PrEP discontinuation (AOR 6.1; 95% CI: 1.4-11; p = 0.005) and was 71% sensitive/90% specific for discontinuation after 120 days. Compared to LC/MS/MS, UTRA testing had a 98% positive and 100% negative predictive value. CONCLUSIONS: In a sample of YMSM/TGW on daily PrEP, POC UTRA testing predicted PrEP discontinuation more accurately than self-reported adherence, with high predictive values compared to LC/MS/MS. UTRA testing may be a clinical tool for directing preventive interventions towards those likelier to discontinue PrEP despite ongoing HIV vulnerability.

Does metformin prolong pregnancy in preterm pre-eclampsia? A study protocol for a South African, hospital-based double-blind, randomised, placebo-controlled trial.

INTRODUCTION: Preterm pre-eclampsia is a leading cause of maternal morbidity and mortality. The Pre-eclampsia Intervention 2 (PI 2) trial suggested that metformin sustained release (XR) may prolong gestation by a week in pregnant women undergoing expectant management (7.6 days, geometric mean ratio 1.39, 95% CI 0.99 to 1.95; p=0.057). These findings should be confirmed with a larger sample size, and we need to know if such a prolongation improves neonatal outcome. Here, we describe the protocol for such a follow-up trial. METHODS: The PI 3 trial is a phase III, intention-to-treat, double-blind, placebo-controlled randomised clinical trial to assess if metformin XR can prolong gestation and improve neonatal outcomes in women undergoing expectant management for preterm pre-eclampsia. We will recruit women who are between 26+0 and 31+6 weeks pregnant. Women will be randomised to receive either 3 g metformin XR or an identical placebo in divided daily doses. The primary outcome is prolongation of pregnancy. Secondary outcomes are neonatal birth weight and length of neonatal care admission (an indicator of neonatal health at birth). All other outcomes will be exploratory. We will record tolerability and adverse events. We plan a sample size of 500 participants to be powered for the primary and secondary outcomes. ETHICS AND DISSEMINATION: PI 3 has ethical approval (Health Research Ethics Committee 2, Stellenbosch University, Protocol number M21/03/007, Project ID 21639, Federal Wide Assurance Number 00001372, Institutional Review Board Number IRB0005239), and is registered with the Pan African Clinical Trial Registry (PACTR202104532026017) and the South African Medicine Control Council (20211211). Data will be presented at international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: PACTR202104532026017).

ACR Appropriateness Criteria® Imaging of Invasive Breast Cancer.

As the proportion of women diagnosed with invasive breast cancer increases, the role of imaging for staging and surveillance purposes should be determined based on evidence-based guidelines. It is important to understand the indications for extent of disease evaluation and staging, as unnecessary imaging can delay care and even result in adverse outcomes. In asymptomatic patients that received treatment for curative intent, there is no role for imaging to screen for distant recurrence. Routine surveillance with an annual 2-D mammogram and/or tomosynthesis is recommended to detect an in-breast recurrence or a new primary breast cancer in women with a history of breast cancer, and MRI is increasingly used as an additional screening tool in this population, especially in women with dense breasts. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Depends on whom you ask: Discordance in reporting spousal care between older women and men across European welfare states.

PURPOSE: We aim to investigate systematic differences in reporting spousal care between caregivers and cared-for persons and their possible effects for the analysis of care regimes and correlation of care with health. MATERIALS AND METHODS: Using information on care provided/received from the Survey on Health, Ageing and Retirement in Europe (SHARE), we estimate the prevalence of spousal care and discordance between caregivers and cared-for persons in the reporting of care among caregiving dyads. Multinomial regressions are used to estimate systematic differences in reporting spousal care. We then use multivariable logistic regressions to assess the association between discordance in reporting informal care and carer's self-rated health (SRH) and depression using the EURO-D scale. RESULTS: Only 53.9 % of dyads report care that is confirmed by both spouses. Multinomial regressions show that agreement on care being provided/received is more common when women are caregivers, while men are likely to underreport when providing or receiving personal care. Prevalence of spousal care across care regimes is sensitive to who reports care. There is no effect on the association of care with SRH regardless of who identifies the carer, while the magnitude and statistical significance of the association between depression symptoms and care varies according to the choice of respondent. CONCLUSIONS: Informal care may be understated across Europe when relying solely on carer self-identification through description of tasks in surveys. From a policy standpoint, relying on self-identification of carers to access support or social benefits may potentially reduce the take-up of such benefits or support.

Pediatric immunotherapy and HIV control.

PURPOSE OF REVIEW: Highlighting opportunities/potential for immunotherapy by understanding dynamics of HIV control during pediatric HIV infection with and without antiretroviral therapy (ART), as modeled in Simian immunodeficiency virus (SIV) and Simian-human immunodeficiency virus (SHIV)-infected rhesus macaques and observed in clinical trials. This review outlines mode of transmission, pathogenesis of pediatric HIV, unique aspects of the infant immune system, infant macaque models and immunotherapies. RECENT FINDINGS: During the earliest stages of perinatal HIV infection, the infant immune system is characterized by a unique environment defined by immune tolerance and lack of HIV-specific T cell responses which contribute to disease progression. Moreover, primary lymphoid organs such as the thymus appear to play a distinct role in HIV pathogenesis in children living with HIV (CLWH). Key components of the immune system determine the degree of viral control, targets for strategies to induce viral control, and the response to immunotherapy. The pursuit of highly potent broadly neutralizing antibodies (bNAbs) and T cell vaccines has revolutionized the approach to HIV cure. Administration of HIV-1-specific bNAbs, targeting the highly variable envelope improves humoral immunity, and T cell vaccines induce or improve T cell responses such as the cytotoxic effects of HIV-1-specific CD8+ T cells, both of which are promising options towards virologic control and ART-free remission as evidenced by completed and ongoing clinical trials. SUMMARY: Understanding early events during HIV infection and disease progression in CLWH serves as a foundation for predicting or targeting later outcomes by harnessing the immune system's natural responses. The developing pediatric immune system offers multiple opportunities for specific long-term immunotherapies capable of improving quality of life during adolescence and adulthood.

2024 HRS expert consensus statement on arrhythmias in the athlete: Evaluation, treatment, and return to play.

Youth and adult participation in sports continues to increase, and athletes may be diagnosed with potentially arrhythmogenic cardiac conditions. This international multidisciplinary document is intended to guide electrophysiologists, sports cardiologists, and associated health care team members in the diagnosis, treatment, and management of arrhythmic conditions in the athlete with the goal of facilitating return to sport and avoiding the harm caused by restriction. Expert, disease-specific risk assessment in the context of athlete symptoms and diagnoses is emphasized throughout the document. After appropriate risk assessment, management of arrhythmias geared toward return to play when possible is addressed. Other topics include shared decision-making and emergency action planning. The goal of this document is to provide evidence-based recommendations impacting all areas in the care of athletes with arrhythmic conditions. Areas in need of further study are also discussed.

Abbreviated Breast MRI for Supplemental Screening in Patients With Dense Breasts: Comparison of Baseline Versus Subsequent-Round Examinations.

Background: Abbreviated breast MRI (AB-MR) achieves a higher cancer detection rate (CDR) versus digital breast tomosynthesis when applied for baseline (i.e. first-round) supplemental screening in individuals with dense breasts. Limited literature has evaluated subsequent (i.e., sequential) AB-MR screening rounds. Objectives: This study aimed to compare outcomes between baseline and subsequent rounds of screening AB-MR in individuals with dense breasts at otherwise average risk of breast cancer. Methods: This retrospective study included patients with dense breasts and at otherwise average breast-cancer risk who underwent AB-MR for supplemental screening between December 20, 2016 and May 10, 2023. Clinical interpretations and results of recommended biopsies for AB-MR examinations were extracted from the EMR. Baseline and subsequent-round AB-MR examinations were compared. Results: The final sample included 2585 AB-MR examinations (2007 baseline, 578 subsequent-round) performed for supplemental screening in 2007 women (mean age, 57.1 years) with dense breasts. Among baseline examinations, 1658 (82.6%) were assessed as BI-RADS category 1 or 2, 171 (8.5%) as category 3, and 178 (8.9%) as category 4 or 5. Among subsequent-round examinations, 533 (92.2%) were assessed as BI-RADS category 1 or 2, 20 (3.5%) as category 3, and 25 (4.3%) as category 4 or 5 (p<.001). Abnormal interpretation rate (AIR) was 17.4% (349/2007) among baseline examinations, versus 7.8% (45/578) among subsequent-round examinations (p<.001). Among baseline examinations, PPV2 was 21.3% (38/178), PPV3 was 26.6% (38/143), and CDR was 18.9 per 1000 (38/2007). Among subsequent-round examinations PPV2 was 28.0% (7/25) (p=.45), PPV3 was 29.2% (7/24) (p=.81), and CDR was 12.1 per 1000 (7/578) (p=.37). All 45 cancers diagnosed by baseline or subsequent-round AB-MR were stage 0 or 1. Seven cancers diagnosed by subsequent-round AB-MR had a mean interval since prior AB-MR of 872 days, size of 0.3-1.2 cm, and node-negative status at surgical axillary evaluation. Conclusion: Subsequent rounds of AB-MR screening in individuals with dense breasts had lower AIR compared to baseline examinations while maintaining high CDR. All cancers detected by subsequent-round examinations were early-stage node-negative cancers. Clinical Impact: The findings support sequential AB-MR for supplemental screening in individuals with dense breasts. Further investigations are warranted to optimize the screening interval.

Pediatric and Familial Genetic Arrhythmia Syndromes-Evaluation of Prolonged QTc-Differential Diagnosis and what You Need to Know.

The case series reviews differential diagnosis of a genetic arrhythmia syndrome when evaluating a patient with prolonged QTc. Making the correct diagnosis requires: detailed patient history, family history, and careful review of the electrocardiogram (ECG). Signs and symptoms and ECG characteristics can often help clinicians make the diagnosis before genetic testing results return. These skills can help clinicians make an accurate and timely diagnosis and prevent life-threatening events.

Behavioral Interventions to Improve Breast Cancer Screening Outreach: Two Randomized Clinical Trials.

Importance: Despite public health efforts, breast cancer screening rates remain below national goals. Objective: To evaluate whether bulk ordering, text messaging, and clinician endorsement increase breast cancer screening rates. Design, Setting, and Participants: Two concurrent, pragmatic, randomized clinical trials, each with a 2-by-2 factorial design, were conducted between October 25, 2021, and April 25, 2022, in 2 primary care regions of an academic health system. The trials included women aged 40 to 74 years with at least 1 primary care visit in the past 2 years who were eligible for breast cancer screening. Interventions: Patients in trial A were randomized in a 1:1 ratio to receive a signed bulk order for mammogram or no order; in a factorial design, patients were concurrently randomized in a 1:1 ratio to receive or not receive text message reminders. Patients in trial B were randomized in a 1:1 ratio to receive a message signed by their primary care clinician (clinician endorsement) or from the organization (standard messaging); in a factorial design, patients were concurrently randomized in a 1:1 ratio to receive or not receive text message reminders. Main Outcomes and Measures: The primary outcome was the proportion of patients who completed a screening mammogram within 3 months. Results: Among 24 632 patients included, the mean (SD) age was 60.4 (7.5) years. In trial A, at 3 months, 15.4% (95% CI, 14.6%-16.1%) of patients in the bulk order arm and 12.7% (95% CI, 12.1%-13.4%) in the no order arm completed a mammogram, showing a significant increase (absolute difference, 2.7%; 95% CI, 1.6%-3.6%; P < .001). In the text messaging comparison arms, 15.1% (95% CI, 14.3%-15.8%) of patients receiving a text message completed a mammogram compared with 13.0% (95% CI, 12.4%-13.7%) of those in the no text messaging arm, a significant increase (absolute difference of 2.1%; 95% CI, 1.0%-3.0%; P < .001). In trial B, at 3 months, 12.5% (95% CI, 11.3%-13.7%) of patients in the clinician endorsement arm completed a mammogram compared with 11.4% (95% CI, 10.3%-12.5%) of those in the standard messaging arm, which was not significant (absolute difference, 1.1%; 95% CI, -0.5% to 2.7%; P = .18). In the text messaging comparison arms, 13.2% (95% CI, 12.0%-14.4%) of patients receiving a text message completed a mammogram compared with 10.7% (95% CI, 9.7%-11.8%) of those in the no text messaging arm, a significant increase (absolute difference, 2.5%; 95% CI, 0.8%-4.0%; P = .003). Conclusions and Relevance: These findings show that text messaging women after initial breast cancer screening outreach via either electronic portal or mailings, as well as bulk ordering with or without text messaging, can increase mammogram completion rates. Trial Registration: ClinicalTrials.gov Identifier: NCT05089903.

Premature skewing of T cell receptor clonality and delayed memory expansion in HIV-exposed infants.

While preventing vertical HIV transmission has been very successful, HIV-exposed uninfected infants (iHEU) experience an elevated risk to infections compared to HIV-unexposed and uninfected infants (iHUU). Here we present a longitudinal multimodal analysis of infant immune ontogeny that highlights the impact of HIV/ARV exposure. Using mass cytometry, we show alterations in T cell memory differentiation between iHEU and iHUU being significant from week 15 of life. The altered memory T cell differentiation in iHEU was preceded by lower TCR Vß clonotypic diversity and linked to TCR clonal depletion within the naïve T cell compartment. Compared to iHUU, iHEU had elevated CD56loCD16loPerforin+CD38+CD45RA+FcεRIγ+ NK cells at 1 month postpartum and whose abundance pre-vaccination were predictive of vaccine-induced pertussis and rotavirus antibody responses post 3 months of life. Collectively, HIV/ARV exposure disrupted the trajectory of innate and adaptive immunity from birth which may underlie relative vulnerability to infections in iHEU.