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.

A Randomized Trial of Choice Architecture and Mailed Colorectal Cancer Screening Outreach in a Community Health Setting.

BACKGROUND & AIMS: Mailed outreach for colorectal cancer (CRC) screening increases uptake but it is unclear how to offer the choice of testing. We evaluated if the active choice between colonoscopy and fecal immunochemical test (FIT), or FIT alone, increased response compared with colonoscopy alone. METHODS: This pragmatic, randomized, controlled trial at a community health center included patients between ages 50 and 74 who were not up to date with CRC screening. Patients were randomized 1:1:1 to the following: (1) colonoscopy only, (2) active choice of colonoscopy or FIT, or (3) FIT only. Patients received an outreach letter with instructions for testing (colonoscopy referral and/or an enclosed FIT kit), a reminder letter at 2 months, and another reminder at 3 to 5 months via text message or automated voice recording. The primary outcome was CRC screening completion within 6 months. RESULTS: Among 738 patients in the final analysis, the mean age was 58.7 years (SD, 6.2 y); 48.6% were insured by Medicaid and 24.3% were insured by Medicare; and 71.7% were White, 16.9% were Black, and 7.3% were Hispanic/Latino. At 6 months, 5.6% (95% CI, 2.8-8.5) completed screening in the colonoscopy-only arm, 12.8% (95% CI, 8.6-17.0) in the active-choice arm, and 11.3% (95% CI, 7.4-15.3) in the FIT-only arm. Compared with colonoscopy only, there was a significant increase in screening in active choice (absolute difference, 7.1%; 95% CI, 2.0-12.2; P = .006) and FIT only (absolute difference, 5.7%; 95% CI, 0.8-10.6; P = .02). CONCLUSIONS: Both choice of testing and FIT alone increased response and may align with patient preferences. TRIAL REGISTRATION: clinicaltrials.gov NCT04711473.

A randomized trial of mailed outreach with behavioral economic interventions to improve liver cancer surveillance.

BACKGROUND: Surveillance rates for HCC remain limited in patients with cirrhosis. We evaluated whether opt-out mailed outreach increased uptake with or without a $20 unconditional incentive. METHODS: This was a pragmatic randomized controlled trial in an urban academic health system including adult patients with cirrhosis or advanced fibrosis, at least 1 visit to a specialty practice in the past 2 years and no surveillance in the last 7 months. Patients were randomized in a 1:2:2 ratio to (1) usual care, (2) a mailed letter with a signed order for an ultrasound, or (3) a mailed letter with an order and a $20 unconditional incentive. The main outcome was the proportion with completion of ultrasound within 6 months. RESULTS: Among the 562 patients included, the mean age was 62.1 (SD 11.1); 56.8% were male, 51.1% had Medicare, and 40.6% were Black. At 6 months, 27.6% (95% CI: 19.5-35.7) completed ultrasound in the Usual care arm, 54.5% (95% CI: 47.9-61.0) in the Letter + Order arm, and 54.1% (95% CI: 47.5-60.6) in the Letter + Order + Incentive arm. There was a significant increase in the Letter + Order arm compared to Usual care (absolute difference of 26.9%; 95% CI: 16.5-37.3; p<0.001), but no significant increase in the Letter + Order + Incentive arm compared to Letter + Order (absolute difference of -0.4; 95% CI: -9.7 to 8.8; p=0.93). CONCLUSIONS: There was an increase in HCC surveillance from mailed outreach with opt-out framing and a signed order slip, but no increase in response to the financial incentive.

Differential effects of integrin-linked kinase inhibitor Cpd22 on severe pulmonary hypertension in male and female rats.

Pulmonary arterial hypertension (PAH) is a progressive fatal disease with no cure. Inhibition of integrin-linked kinase (ILK) reverses experimental pulmonary hypertension (PH) in male mice, but its effect on severe experimental PH in either male or female animals is unknown. We examined effects of ILK inhibitor Cpd22 on rats with SU5416/hypoxia-induced PH; treatment was performed at six to eight weeks after PH initiation. Five weeks after PH initiation, male and female rats developed similar levels of PH. Eight weeks after PH induction, vehicle-treated male rats had more severe PH than females. Cpd22-treated males, but not females, showed complete suppression of phospho-Akt in small pulmonary arteries (PAs), significantly lower PA medial thickness and percentage of fully occluded arteries, decreased systolic right ventricle (RV) pressure, PA pressure, RV hypertrophy, RV end-diastolic pressure, and improved RV contractility index compared to vehicle-treated group. Cpd22 suppressed proliferation of human male and female PAH pulmonary artery vascular smooth muscle cell (PAVSMC). 17ß-estradiol had no effect as a single agent but significantly attenuated Cpd22-dependent inhibition of proliferation in female, but not male, PAH PAVSMC. Taken together, these data demonstrate that male rats develop more severe PH than females but respond better to Cpd22 treatment by reducing pulmonary vascular remodeling, PH, and RV hypertrophy and improving RV functional outcomes. 17ß-estradiol diminishes anti-proliferative effect of Cpd22 in female, but not male, human PAH PAVSMC. These findings suggest potential attractiveness of ILK inhibition to reduce established PH in males and suggest that the combination with estrogen-lowering drugs could be considered to maximize anti-proliferative and anti-remodeling effects of ILK inhibitors in females.

Inhibitory Antibodies against Activin A and TGF-ß Reduce Self-Supported, but Not Soluble Factors-Induced Growth of Human Pulmonary Arterial Vascular Smooth Muscle Cells in Pulmonary Arterial Hypertension.

Increased growth and proliferation of distal pulmonary artery vascular smooth muscle cells (PAVSMC) is an important pathological component of pulmonary arterial hypertension (PAH). Transforming Growth Factor-ß (TGF-ß) superfamily plays a critical role in PAH, but relative impacts of self-secreted Activin A, Gremlin1, and TGF-ß on PAH PAVSMC growth and proliferation are not studied. Here we report that hyper-proliferative human PAH PAVSMC have elevated secretion of TGF-ß1 and, to a lesser extent, Activin A, but not Gremlin 1, and significantly reduced Ser465/467-Smad2 and Ser423/425-Smad3 phosphorylation compared to controls. Media, conditioned by PAH PAVSMC, markedly increased Ser465/467-Smad2, Ser423/425-Smad3, and Ser463/465-Smad1/5 phosphorylation, up-regulated Akt, ERK1/2, and p38 MAPK, and induced significant proliferation of non-diseased PAVSMC. Inhibitory anti-Activin A antibody reduced PAH PAVSMC growth without affecting canonical (Smads) or non-canonical (Akt, ERK1/2, p38 MAPK) effectors. Inhibitory anti-TGF-ß antibody significantly reduced P-Smad3, P-ERK1/2 and proliferation of PAH PAVSMC, while anti-Gremlin 1 had no anti-proliferative effect. PDGF-BB diminished inhibitory effects of anti-Activin A and anti-TGF-ß antibodies. None of the antibodies affected growth and proliferation of non-diseased PAVSMC induced by PAH PAVSMC-secreted factors. Together, these data demonstrate that human PAH PAVSMC have secretory, proliferative phenotype that could be targeted by anti-Activin A and anti-TGF-ß antibodies; potential cross-talk with PDGF-BB should be considered while developing therapeutic interventions.

Prevalence and etiologic agents of female reproductive tract infection among in-patients and out-patients of a tertiary hospital in Benin city, Nigeria.

BACKGROUND: Reproductive tract infections are public health problems in women of reproductive age and can result in serious consequences if not treated. AIMS: To determine the prevalence and causes of reproductive tract infections among in-patients and out-patients attending a tertiary health institution in Benin City. The antimicrobial susceptibility profiles of bacterial agents will also be determined. PATIENTS AND METHODS: High vaginal swabs or endocervical swabs and blood were collected from 957 patients consisting of 755 out-patients and 202 in-patients. The swabs were processed and microbial isolates identified using standard technique. Disc susceptibility tests were also performed on microbial isolates. The blood samples were used for serological diagnosis of syphilis. RESULTS: There was no significant difference in the prevalence of female reproductive tract infections between in-patients (52.48%) and out-patients (47.02%), although in-patients showed a significantly higher risk of developing mixed infections (in-patients vs. out-patients; 34.91% vs. 22.25%, OR = 1.873 95% CI = 1.169, 3.001; P = 0.01). Candida albicans was the most prevalent etiologic agent among out-patients studied while Staphylococcus aureus was the most prevalent etiologic agent among in-patients. Trichomonas vaginalis was observed only among out-patients. Ceftriaxone, ciprofloxacin and ofloxacin were the most active antibacterial agents. Syphilis was not detected in any patient. CONCLUSION: An overall prevalence of 48.17% of female reproductive tract infection was observed among the study population. Although there was no significant difference between in-patients and out-patients, in-patients appeared to have 1-3-fold increase risk of developing mixed infections. The most prevalent etiologic agent differs between in-patients and out-patients. Despite the high activity of ceftriaxone, ciprofloxacin and ofloxacin against bacterial isolates from both in-patients and out-patients, prudent use of antibacterial agents is advocated.