Estimate of Increase in Colorectal Cancer Diagnoses with Expansion of Fecal Immunochemical Testing in an Urban Safety-Net Population.

BACKGROUND: Fecal immunochemical test (FIT) is less effective in detecting advanced adenomas (AA) than colonoscopy. Increase in FIT for colorectal cancer (CRC) screening may lead to an increased number of undetected AAs which may develop into future CRCs. AIM: We determined the potential impact of FIT expansion on missed AAs and future CRC diagnoses in an urban, tertiary-care, safety-net hospital. METHODS: CRC and AA diagnoses were identified in patients undergoing colonoscopy for average-risk CRC screening or positive FIT between 2017 and 2019 at Boston Medical Center. Poisson regression modeling was used to estimate the frequency of AAs per year by age group using data from 2017 to 2019, assuming average outpatient volume and proportion of screening colonoscopies. Total number of patients who received FIT was extrapolated from those who underwent colonoscopy for positive FIT. We estimated AAs per year if 'one-time' FIT was used for screening in 75% and 100% of the population and subtracted this from the estimated AAs per year under the Poisson model to determine missed AAs. We used previously described, age and gender specific estimates of the annual progression of AA to CRC. RESULTS: The estimated number of CRCs detected per year is 4.6/1785 males and 4.6/2086 females screened. With 75% FIT expansion, we estimate an additional 3.5 (95% CI 1.3, 9.5) and 2.2 (95% CI 0.64, 7.6) CRCs; with 100% FIT expansion, we estimate an additional 7.4 (95% CI 3.7, 14.9) and 4.2 (95% CI 1.7, 10.5) CRCs, in 5 years, in males and females, respectively. CONCLUSION: Expansion of FIT may substantially increase CRC incidence.

Patient Satisfaction with the Hybrid Telemedicine Model for Ophthalmology.

Background: The purpose of this research was to compare patient satisfaction between hybrid ophthalmology telemedicine and standard-of-care in-person visits. A retrospective, cross-sectional, case-control analysis of patient satisfaction based on survey data was used. Methods: Responses to the National Research Council Health Patient Survey were retrieved for randomly sampled hybrid ophthalmology telemedicine and in-person visits between March 11, 2020 and December 31, 2021 at a hospital-based eye clinic in Boston, Massachusetts. The primary outcome was based on the question "How likely would you be to recommend this provider to your family and friends?" (0-10 scale) with a score of 9 or 10 coded as satisfied. Two-sample t-tests, Pearson's chi-square tests, and bivariate logistic regressions were used to compare patient satisfaction scores between the hybrid and in-person cohorts. Demographic data, including age, sex, language, and self-reported race and ethnicity, were used as potential predictors of patient satisfaction in a multivariable logistic regression model. Results: There were 49 surveys from hybrid visits and 3,390 surveys from in-person visits. Hybrid visit patients reported high satisfaction scores without significant differences compared to in-person visit patients (hybrid 79% satisfied, in-person 82% satisfied, p = 0.728). Age was significantly associated with satisfaction in the hybrid cohort with the 65+ age group reporting lower satisfaction (below 65 years 100% satisfied, 65+ years 60% satisfied, p = 0.003). No association with age was observed in the in-person cohort. Conclusions: The hybrid ophthalmology telemedicine model can provide effective care without sacrificing patient satisfaction. Older patients may benefit from targeted interventions in future telemedicine models.

Dairy Foods, Weight Change, and Risk of Obesity During the Menopausal Transition.

BACKGROUND: Weight gain during the menopausal transition is common. Dairy consumption may impact weight change during this critical period, and different dairy foods may have different effects. OBJECTIVES: This study aimed to investigate the associations of different types of dairy foods with weight gain and risk of obesity in perimenopausal women from the Nurses' Health Study II cohort. METHODS: The examination at menopause was selected as the exam closest to the reported age at menopause. Weight change during 12 y surrounding menopause was derived from self-reported weight data for 3 exams before and 3 after menopause. The mean age of the first weight measure was 45.8 y and the average BMI was 25.0 kg/m2. Dairy food intakes were estimated as mean intakes over the same 12 y. Generalized linear models were used to assess the association between dairy foods and annualized weight change. Cox proportional hazard models were used to estimate the adjusted relative risks for becoming obese over 12 y surrounding menopause. RESULTS: In longitudinal analyses, those with the highest yogurt intakes had the lowest weight gain at every exam. This was not the case for other forms of dairy. After adjusting for potential covariates, those consuming ≥2.0 servings/wk of yogurt (compared with <1.0 serving/month) had a 31% (RR: 0.69; 95% CI: 0.64, 0.74) lower risk of obesity. The highest total dairy intake (≥2.0 servings/d compared with <1.0) was associated with only a 12% (RR: 0.88; 95% CI: 0.82, 0.95) reduction in obesity risk. Higher activity levels and alternative healthy eating index scores were independently associated with statistically significant reductions in risk of obesity, but higher intakes of yogurt strengthened these beneficial associations. CONCLUSION: Yogurt intake was associated with less weight gain and lower obesity risk in women during the menopausal transition.

ZB-06, a vaginal film containing an engineered human contraceptive antibody (HC4-N), demonstrates safety and efficacy in a phase 1 postcoital test and safety study.

BACKGROUND: With an unplanned pregnancy rate of 50% or more in many countries, there is an urgent need for contraceptives that are more accessible and acceptable. To meet the growing demand for new contraceptives, ZabBio developed ZB-06, a vaginal film containing HC4-N, a human contraceptive antibody that inactivates sperm. OBJECTIVE: This study aimed to assess the potential contraceptive activity of the ZB-06 film using a surrogate assessment for contraceptive efficacy, the postcoital test. We also assessed clinical safety of film use among healthy heterosexual couples. Serum, cervical mucus, and vaginal fluid HC4-N antibody concentrations and sperm agglutination potency were determined after single film use. Changes in the concentration of soluble proinflammatory cytokines and vaginal Nugent score after film use were measured as subclinical safety endpoints. STUDY DESIGN: This was a phase 1, first-in-woman, open-label, proof-of-concept, postcoital test and safety study. RESULTS: A total of 20 healthy women were enrolled in the study, and 8 heterosexual couples completed all study visits. The product was safe for both female participants and their male sexual partners. The postcoital test performed on ovulatory cervical mucus at baseline (no product use) revealed a mean of 25.9 (±30.6) progressively motile sperm per high-power field. After use of a single ZB-06 film before intercourse, this number dropped to 0.04 (±0.06) progressively motile sperm per high-power field (P<.0001). At the follow-up postcoital test visit approximately 1 month later (no product use), a mean of 47.4 (±37.4) progressively motile sperm per high-power field was observed, indicating contraceptive reversibility. CONCLUSION: A single dose of the ZB-06 film applied before intercourse was safe and met efficacy surrogate benchmarks of excluding progressively motile sperm from ovulatory cervical mucus. These data indicate that ZB-06 is a viable contraceptive candidate warranting further development and testing.

Depression and PTSD among Houston Residents who Experienced Hurricane Harvey and COVID-19: Implications for Urban Areas Affected by Multiple Disasters.

Little is known about the combined impact of the COVID-19 pandemic and other major disasters on mental health. Hurricane Harvey hit the Gulf Coast in 2017, resulting in substantial costs, significant levels of displacement, and approximately 100 deaths, and was followed in 2020 by the COVID-19 pandemic. We randomly sampled 1167 Houstonians from 88 designated super-neighborhoods and surveyed them about their demographics, event-specific traumas and stressors, and symptoms of current depression and post-traumatic stress disorder (PTSD). We estimated the prevalence of depression (5.8%) and PTSD (12.6%) more than three years after Hurricane Harvey, and assessed the relative influence of event-specific stressors and traumas on current mental health. Overall, we observed evidence for two key findings that are salient for residents of urban environments in the context of multiple disasters. First, stressors were primary influences on depression, whereas both stressors and traumas influenced PTSD. Second, the influences of stressors and traumas on depression and PTSD symptoms faded with time.

Stressful life events and incident depression among U.S. military personnel.

PURPOSE: Although stressful life events (i.e., stressors) and depression are often assumed to be linked, the relation between stressors and incident depression is rarely studied, particularly in the military. The National Guard is a part-time subset of the U.S. military for whom civilian life stressors may be particularly salient, due to the soldiers' dual roles and frequent transitions between military and civilian life. METHODS: We used a dynamic cohort study of National Guard members from 2010 to 2016 to investigate the relationship between recent stressful experiences (e.g., divorce) and incident depression, with an exploratory analysis of effect modification by income. RESULTS: Respondents endorsing at least one of nine past-year stressful events (a time-varying exposure, lagged by 1 year) had almost twice the adjusted rate of incident depression compared to those with no stressful events (HR = 1.8; 95% CI 1.4, 2.4). This association may be modified by income: among individuals making under $80,000 per year, those with past-year stressors had twice the rate of depression compared to those with no stressors, but among those making over $80,000, past-year stressors were associated with only 1.2 times the rate of depression. CONCLUSION: Stressful life events outside of deployment are important determinants of incident depression among National Guard servicemembers, but the effect of these events may be buffered by higher income.

The Black women first initiative: using implementation science to examine bundled interventions to improve care and treatment coordination for Black women with HIV.

BACKGROUND: Black cisgender and transgender women are disproportionately affected by the HIV epidemic compared to women of other racial and ethnic identities. Twelve demonstration sites across the United States are adapting, implementing and evaluating a comprehensive bundle of two or more evidence informed interventions to improve health and outcomes and quality of life for Black women with HIV. METHODS: Guided by Greenhalgh's Conceptual Model of Diffusion of Innovations in Health Service Organizations and Proctor's model for use of implementation strategies and evaluating implementation, service and client outcomes, this mixed methods study documents outcomes at the client, organization, and system level. Participant eligibility for the bundled interventions includes: individuals who are 18 years or older, identify as Black or African-American, identify as cisgender or transgender female and have a diagnosis of HIV. Qualitative data are collected systematically through a series of annual site visits and a standardized monthly call form to assess the barriers and facilitators to the implementation process and the key determinants impacting the intervention uptake and implementation strategies. Quantitative data collection for the implementation, service and client outcomes is conducted through a pre-post prospective study to examine the impact on Black women's health and well-being. Implementation outcomes include: the reach to Black women with HIV, adoption of interventions across the sites and their community; the fidelity to the components of the bundled interventions; the costs of the intervention; and the sustainability of the intervention in the organization and community. Primary service and client outcomes are improved linkage to and retention in HIV care and treatment, increased and sustained viral suppression, improved quality of life and resilience, and stigma reduction. DISCUSSION: The study protocol presented is specifically designed to advance the evidence for adopting culturally responsive and relevant care into clinic and public health settings to improve the health and well-being for Black women with HIV. In addition the study may advance the implementation science field by furthering what is known about the ways in which bundled interventions can address barriers to care and facilitate the uptake of organizational practices to improve health.

Pre-Paid Phone Distribution: A Tool for Improving Healthcare Engagement for People with Substance Use Disorder.

BACKGROUND: The COVID-19 pandemic drove significant disruptions in access to substance use disorder (SUD) treatment and harm reduction services. Healthcare delivery via telemedicine has increasingly become the norm, rendering access to a phone essential for engagement in care. METHODS: Adult patients with SUD who lacked phones (n = 181) received a free, pre-paid phone during encounters with inpatient and outpatient SUD programs. We evaluated changes in healthcare engagement including completed in-person and telemedicine outpatient visits and telephone encounters 30 days before and after phone receipt. We used descriptive statistics, where appropriate, and paired t-tests to assess the change in healthcare engagement measures. RESULTS: Patients were predominantly male (64%) and white (62%) with high rates of homelessness (81%) and opioid use disorder (89%). When comparing 30 days before to 30 days after phone receipt, there was a significant increased change in number of telemedicine visits by 0.3 (95% CL [0.1,0.4], p < 0.001) and telephone encounters by 0.2 (95% CL [0.1,0.3], p = 0.004). There was no statistically significant change in in-person outpatient visits observed. CONCLUSIONS: Pre-paid phone distribution to patients with SUD was associated with an increased healthcare engagement including telemedicine visits and encounters.

Polycystic ovary syndrome and risk of adverse pregnancy outcomes: a registry linkage study from Massachusetts.

STUDY QUESTION: Do women with polycystic ovary syndrome (PCOS) have a greater risk of adverse pregnancy complications (gestational diabetes, preeclampsia, cesarean section, placental abnormalities) and neonatal outcomes (preterm birth, small for gestational age, prolonged delivery hospitalization) compared to women without a PCOS diagnosis and does this risk vary by BMI, subfertility and fertility treatment utilization? SUMMARY ANSWER: Deliveries to women with a history of PCOS were at greater risk of complications associated with cardiometabolic function, including gestational diabetes and preeclampsia, as well as preterm birth and prolonged length of delivery hospitalization. WHAT IS KNOWN ALREADY: Prior research has suggested that women with PCOS may be at increased risk of adverse pregnancy outcomes. However, findings have been inconsistent possibly due to lack of consistent adjustment for confounding factors, small samples size and other sources of bias. STUDY DESIGN, SIZE, DURATION: Massachusetts deliveries among women ≥18 years old during 2013-2017 from state vital records linked to hospital discharges, observational stays and emergency department visits were linked to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) and the Massachusetts All-Payers Claims Database (APCD). PARTICIPANTS/MATERIALS, SETTING, METHODS: PCOS was identified by ICD9 and ICD10 codes in APCD prior to index delivery. Relative risks (RRs) and 95% CI for pregnancy and delivery complications were modeled using generalized estimating equations with a log link and a Poisson distribution to take multiple cycles into account and were adjusted a priori for maternal age, BMI, race/ethnicity, education, plurality, birth year, chronic hypertension and chronic diabetes. Tests for homogeneity investigated differences between maternal pre-pregnancy BMI categories (<30, ≥30, <25 and ≥25 kg/m2) and between non-infertile deliveries and deliveries that used ART or had a history of subfertility (defined by birth certificates, SART CORS records, APCD or hospital records). MAIN RESULTS AND THE ROLE OF CHANCE: Among 91 825 deliveries, 3.9% had a history of PCOS. Women with a history of PCOS had a 51% greater risk of gestational diabetes (CI: 1.38-1.65) and a 25% greater risk of preeclampsia (CI: 1.15-1.35) compared to women without a diagnosis of PCOS. Neonates born to women with a history of PCOS were more likely to be born preterm (RR: 1.17, CI: 1.06-1.29) and more likely to have a prolonged delivery hospitalization after additionally adjusting for gestational age (RR: 1.23, CI: 1.09-1.40) compared to those of women without a diagnosis of PCOS. The risk for gestational diabetes for women with PCOS was greater among women with a pre-pregnancy BMI <30 kg/m2. LIMITATIONS, REASONS FOR CAUTION: PCOS was defined by ICD documentation prior to delivery so there may be women with undiagnosed PCOS or PCOS diagnosed after delivery included in the unexposed group. The study population is limited to deliveries within Massachusetts among most private insurance payers and inpatient or observational hospitalization in Massachusetts during the follow-up window, therefore there may be diagnoses and or deliveries outside of the state or outside of our sample that were not captured. WIDER IMPLICATIONS OF THE FINDINGS: In this population-based study, women with a history of PCOS were at greater risk of pregnancy complications associated with cardiometabolic function and preterm birth. Obstetricians should be aware of patients' PCOS status and closely monitor for potential pregnancy complications to improve maternal and infant perinatal health outcomes. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the NIH (R01HD067270). S.A.M. receives grant funding from NIH, AbbVie and the Marriot Family Foundation; payment/honoraria from the University of British Columbia, World Endometriosis Research Foundation and Huilun Shanghai; travel support for attending meetings for ESHRE 2019, IASP 2019, National Endometriosis Network UK meeting 2019; SRI 2022, ESHRE 2022; participates on the data safety monitoring board/advisory board for AbbVie, Roche, Frontiers in Reproductive Health; and has a leadership role in the Society for Women's Health Research, World Endometriosis Research Foundation, World Endometriosis Society, American Society for Reproductive Medicine and ESHRE. The other authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Medicaid Expansion and Change in Federally Qualified Health Center Accessibility From 2008 to 2016.

BACKGROUND: The Affordable Care Act expanded health coverage for low-income residents through Medicaid expansion and increased funding for Health Center Program New Access Points from 2009 to 2015, improving federally qualified health center (FQHC) accessibility. The extent to which these provisions progressed synergistically as intended when states could opt out of Medicaid expansion is unknown. OBJECTIVE: To compare change in FQHC accessibility among census tracts in Medicaid expansion and nonexpansion states. RESEARCH DESIGN: Tract-level FQHC accessibility scores for 2008 and 2016 were estimated applying the 2-step floating catchment area method to American Community Survey and Health Resources and Services Administration data. Multivariable linear regression compared changes in FQHC accessibility between tracts in Medicaid expansion and nonexpansion states, adjusting for sociodemographic and health system factors and accounting for state-level clustering. SUBJECTS: In total, 7058 census tracts across 10 states. RESULTS: FQHC accessibility increased comparably among tracts in Medicaid expansion and nonexpansion states (coef: 0.3; 95% CI: -0.3, 0.8; P -value: 0.36). FQHC accessibility increased more in tracts with higher poverty and uninsured rates, and those with lower proportions of non-English speakers and Black or African American residents. CONCLUSION: Similar gains in FQHC accessibility across Medicaid expansion and nonexpansion states indicate improvements progressed independently from Medicaid expansion, rather than synergistically as expected. Accessibility increases appeared consistent with HRSA's goal to improve access for individuals experiencing economic barriers to health care but not for those experiencing cultural or language barriers to health care.

Pregnancy outcomes among women with endometriosis and fibroids: registry linkage study in Massachusetts.

BACKGROUND: Endometriosis and uterine fibroids are common gynecologic conditions associated with a greater risk for infertility. Previous research has suggested that these conditions are associated with adverse pregnancy outcomes, potentially because of increased utilization of fertility treatments. OBJECTIVE: Our objective was to investigate whether women with a history of endometriosis or fibroids had a greater risk for adverse pregnancy outcomes and whether this risk varied by infertility history and fertility treatment utilization. STUDY DESIGN: Deliveries (2013-2017) recorded in Massachusetts' vital records were linked to assisted reproductive technology data, hospital stays, and all-payer claims database. We identified endometriosis and fibroids diagnoses via the all-payer claims database before index delivery. Adjusted relative risks for pregnancy complications were modeled using generalized estimating equations with a log link and Poisson distribution. The influence of subfertility or infertility and assisted reproductive technology was also investigated. RESULTS: Among 91,825 deliveries, 1560 women had endometriosis and 4212 had fibroids. Approximately 30% of women with endometriosis and 26% of women with fibroids experienced subfertility or infertility without utilizing assisted reproductive technology, and 34% of women with endometriosis and 21% of women with fibroids utilized assisted reproductive technology for the index delivery. Women with a history of endometriosis or fibroids were at a greater risk for pregnancy-induced hypertension, preeclampsia, or eclampsia (endometriosis relative risk, 1.17; fibroids relative risk, 1.08), placental abnormalities (endometriosis relative risk, 1.65; fibroids relative risk, 1.38), and cesarean delivery (endometriosis relative risk, 1.22; fibroids relative risk, 1.17) than women with no history of those conditions. Neonates born to women with a history of endometriosis or fibroids were also at a greater risk for preterm birth (endometriosis relative risk, 1.24; fibroids relative risk, 1.17). Associations between fibroids and low birthweight varied by fertility status or assisted reproductive technology (P homogeneity=.01) and were stronger among noninfertile women. CONCLUSION: Endometriosis or fibroids increased the risk for adverse pregnancy outcomes, possibly warranting differential screening or treatment.

Calculating power for the Finkelstein and Schoenfeld test statistic for a composite endpoint with two components.

The Finkelstein and Schoenfeld (FS) test is a popular generalized pairwise comparison approach to analyze prioritized composite endpoints (eg, components are assessed in order of clinical importance). Power and sample size estimation for the FS test, however, are generally done via simulation studies. This simulation approach can be extremely computationally burdensome, compounded by increasing number of composite endpoints and with increasing sample size. Here we propose an analytical solution to calculate power and sample size for commonly encountered two-component hierarchical composite endpoints. The power formulas are derived assuming underlying distributions in each of the component outcomes on the population level, which provide a computationally efficient and practical alternative to the standard simulation approach. Monte Carlo simulation results demonstrate that performance of the proposed power formulas are consistent with that of the simulation approach, and have generally desirable objective properties including robustness to mis-specified distributional assumptions. We demonstrate the application of the proposed formulas by calculating power and sample size for the Transthyretin Amyloidosis Cardiomyopathy Clinical Trial.

Reducing Readmission of Hospitalized Patients With Depressive Symptoms: A Randomized Trial.

PURPOSE: To determine if hospitalized patients with depressive symptoms will benefit from post-discharge depression treatment with care transition support. METHODS: This is a randomized controlled trial of hospitalized patients with patient health questionnaire-9 score of 10 or more. We delivered the Re-Engineered Discharge (RED) and randomized participants to groups receiving RED-only or RED for Depression (RED-D), a 12-week post-discharge telehealth intervention including cognitive behavioral therapy, self-management support, and patient navigation. Primary outcomes were hospital readmission and reutilization rates at 30 and 90 days post discharge. RESULTS: We randomized 709 participants (353 RED-D, 356 RED-only). At 90 days, 265 (75%) intervention participants had received at least 1 RED-D session (median 4). At 30 days, the intention-to-treat analysis showed no differences between RED-D vs RED-only in hospital readmission (9% vs 10%, incidence rate ratio [IRR] 0.92 [95% CI, 0.56-1.52]) or reutilization (27% vs 24%, IRR 1.14 [95% CI, 0.85-1.54]). The intention-to-treat analysis also showed no differences at 90 days in readmission (28% vs 21%, IRR 1.30 [95% CI, 0.95-1.78]) or reutilization (70% vs 57%, IRR 1.22 [95% CI, 1.01-1.49]). In the as-treated analysis, each additional RED-D session was associated with a decrease in 30- and 90-day readmissions. At 30 days, among 104 participants receiving 3 or more sessions, there were fewer readmissions (3% vs 10%, IRR 0.30 [95% CI, 0.07-0.84]) compared with the control group. At 90 days, among 109 participants receiving 6 or more sessions, there were fewer readmissions (11% vs 21%, IRR 0.52 [95% CI, 0.27-0.92]). Intention-to-treat analysis showed no differences between study groups on secondary outcomes. CONCLUSIONS: Care transition support and post-discharge depression treatment can reduce unplanned hospital use with sufficient uptake of the RED-D intervention.

Does HIV Stigma Predict Social Networks Over Time: A Latent Growth Curve Analysis.

Persons living with HIV (PLWH) with socio-economic vulnerabilities are especially vulnerable to HIV stigma and adverse HIV outcomes. Stigma related to HIV may intersect with marginalized socio-economic conditions to negatively affect social networks. HIV stigma may limit the ability of individuals to sustain social relationships. This study examined the potential cross-sectional and longitudinal associations between HIV stigma and the quality and quantity of social networks for PLWH. PLWH (n = 1,082) who were experiencing housing, employment, and medical care-related difficulties were recruited to participate in a one-year navigation and system coordination intervention to improve housing stability and employment. Neither stigma reduction nor social networks were the main components of the intervention. A series of latent growth curves were estimated to assess the cross-sectional and longitudinal relationships among internalized and anticipated HIV stigma and social networks. Anticipated HIV stigma predicted social networks both cross-sectionally and longitudinally. Internalized HIV stigma predicted social networks cross-sectionally but not longitudinally in this population. These data support the HIV Stigma Framework and suggest that anticipated stigma seems to have a strong association with social networks. As anticipated stigma decreases over time, social network scores increase. Interventions to decrease anticipated HIV stigma as a mechanism of improving social networks warrants further investigation.

Outcomes from the Adaptation of an Evidence-Based Peer Linkage & Re-Engagement Intervention for Women of Color with HIV in Three Urban Clinics.

Peer interventions have demonstrated efficacy with improving HIV health outcomes. Yet, little is known about factors associated with their uptake into the clinic setting. Three urban sites in the US were funded to adapt, implement and evaluate a peer intervention to improve HIV health outcomes for 173 out of care and newly diagnosed women of color. Peers worked with cis and transgender women of color for four months to achieve the goals of linkage and retention in HIV case management and medical care. Results were 96% of women were linked to medical care, 73% were retained in care and 81% were virally suppressed post 12 months. The average duration of the peer intervention was seven months. Women who received four peer encounters had a 10% increase in retention in care and viral suppression. The findings highlight key elements such as dose and duration of client interaction for peer staff as part of the health care team.

Using community-engaged methods to develop a study protocol for a cost analysis of a multi-site patient navigation intervention for breast cancer care.

BACKGROUND: Patient navigation is an evidence-based intervention for reducing delays in oncology care among underserved populations. In order to address the financial sustainability of this intervention, information is needed on the cost of implementing patient navigation in diverse healthcare settings. Because patient navigation programs and care settings are highly variable, this paucity of cost data creates difficulties in identifying best practices and decisions about the feasibility of implementing navigation programs within a health care system. One barrier to collecting these cost data is the lack of assessment tools available to support patient navigation programs. These tools must be relevant to the wide variety of navigation activities that exist in health care settings, and be flexible enough to collect cost data important to stakeholders in fee-for-service and value-based care environments. METHODS AND RESULTS: We present a novel approach and methods for assessing the cost of a patient navigation program implemented across six hospital systems to enhance timely entry and uptake of breast cancer care and treatment. These methods and tools were developed in partnership with breast oncology patient navigators and supervisors using principles of stakeholder engagement, with the goal of increasing usability and feasibility in the field. CONCLUSIONS: This methodology can be used to strengthen cost analysis and assessment tools for other navigation programs for improving care and treatment for patients with chronic conditions. TRIAL REGISTRATION: NCT03514433.

History of cancer and fertility treatment outcomes: a registry linkage study in Massachusetts.

PURPOSE: To investigate assisted reproductive technology (ART) outcomes among adolescent and young-adult female cancer survivors. METHODS: The Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) data were linked to the Massachusetts Cancer Registry for 90,928 ART cycles in Massachusetts to women ≥ 18 years old from 2004 to 2013. To estimate relative risks (RR) and 95% confidence intervals (CI), we used generalized estimating equations with a log link that accounted for multiple cycles per woman and a priori adjusted for maternal age and cycle year. The main outcomes of interest were ART treatment patterns; number of autologous oocytes retrieved, fertilized, and transferred; and rates of implantation, clinical intrauterine gestation (CIG), live birth, and pregnancy loss. RESULTS: We saw no difference in number of oocytes retrieved (aRR: 0.95 (0.89-1.02)) or proportion of autologous oocytes fertilized (aRR: 0.99 (0.95-1.03)) between autologous cycles with and without a history of cancer; however, cancer survivors required a higher total FSH administered (aRR: 1.12 (1.06-1.19)). Among autologous cycle starts, cycles in women with a history of cancer were less likely to result in CIG compared to no history of cancer (aRR: 0.73 (0.65-0.83)); this relationship was absent from donor cycles (aRR: 1.01 (0.85-1.20)). Once achieving CIG, donor cycles for women with a history of cancer were two times more likely to result in pregnancy loss (aRR: 1.99 (1.26-3.16)). CONCLUSIONS: Our analysis suggests that cancer may influence ovarian stimulation response, requiring more FSH and resulting in lower CIG among cycle starts.

Safety, acceptability, and pharmacokinetics of a monoclonal antibody-based vaginal multipurpose prevention film (MB66): A Phase I randomized trial.

BACKGROUND: MB66 film is a multipurpose prevention technology (MPT) product with monoclonal antibodies (mAbs) against HIV-1 (VRC01-N) and HSV-1 and 2 (HSV8-N). The mAbs were produced by transient expression in Nicotiana benthamiana (N). We conducted a Phase I clinical trial to assess the safety, pharmacokinetics (PK), and ex vivo efficacy of single and repeated doses of MB66 when used intravaginally. METHODS AND FINDINGS: The clinical trial enrolled healthy reproductive-aged, sexually abstinent women. In Segment A, 9 women received a single MB66 film which was inserted into the vaginal posterior fornix by a clinician. In Segment B, 29 women were randomly assigned to MB66 (Active) or Placebo film groups and were instructed to insert 1 film vaginally for 7 consecutive days. Visits and clinical sampling occurred predose and at various time points after single and repeated film doses. The primary endpoint was number of adverse events (AEs) Grade 2 or higher related to product use. Secondary endpoints included film dissolution rate, Nugent score (a Gram stain scoring system to diagnose bacterial vaginosis), vaginal pH, post-use survey results, cytokine concentrations in cervicovaginal lavage (CVL) specimens (assessed by Luminex assay), mAb concentrations in vaginal fluid collected from 4 sites (assessed by ELISA), and HIV and HSV neutralization activity of CVL samples ex vivo (assessed by TZM-bl and plaque reduction assay, respectively). The product was generally safe and well tolerated, with no serious AEs recorded in either segment. The AEs in this study were primarily genitourinary in nature with the most commonly reported AE being asymptomatic microscopic hematuria. There were no differences in vaginal pH or Nugent scores or significant increases in levels of proinflammatory cytokines for up to 7 days after film insertion in either segment or between Active and Placebo groups. Acceptability and willingness to use the product were judged to be high by post-use surveys. Concentrations of VRC01-N and HSV8-N in vaginal secretions were assessed over time to generate pharmacokinetic curves. Antibody levels peaked 1 hour postdosing with Active film (median: 35 µg/mL) and remained significantly elevated at 24 hours post first and seventh film (median: 1.8 µg/mL). Correcting for sample dilution (1:20), VRC01-N concentrations ranged from 36 to 700 µg/mL at the 24-hour time point, greater than 100-fold the IC50 for VRC01 (0.32 µg/mL); HSV8-N concentrations ranged from 80 to 601 µg/mL, well above the IC50 of 0.1 µg/m. CVL samples collected 24 hours after MB66 insertion significantly neutralized both HIV-1 and HSV-2 ex vivo. Study limitations include the small size of the study cohort, and the fact that no samples were collected between 24 hours and 7 days for pharmacokinetic evaluation. CONCLUSIONS: Single and repeated intravaginal applications of MB66 film were safe, well tolerated, and acceptable. Concentrations and ex vivo bioactivity of both mAbs in vaginal secretions were significantly elevated and thus could provide protection for at least 24 hours postdose. However, further research is needed to evaluate the efficacy of MB66 film in women at risk for HIV and HSV infection. Additional antibodies could be added to this platform to provide protection against other sexually transmitted infections (STIs) and contraception. TRIAL REGISTRATION: ClinicalTrials.gov NCT02579083.

Early-life cancer, infertility, and risk of adverse pregnancy outcomes: a registry linkage study in Massachusetts.

PURPOSE: Investigate the relationship between history of cancer and adverse pregnancy outcomes according to subfertility/fertility treatment. METHODS: Deliveries (2004-2013) from Massachusetts (MA) Registry of Vital Records and Statistics were linked to MA assisted reproductive technology data, hospital discharge records, and Cancer Registry. The relative risks (RR) and 95% confidence intervals of adverse outcomes (gestational diabetes (GDM), gestational hypertension (GHTN), cesarean section (CS), low birth weight (LBW), small for gestational age (SGA), preterm birth (PTB), neonatal mortality, and prolonged neonatal hospital stay) were modeled with log-link and Poisson distribution generalized estimating equations. Differences by history of subfertility/fertility treatment were investigated with likelihood ratio tests. RESULTS: Among 662,630 deliveries, 2,983 had a history of cancer. Women with cancer history were not at greater risk of GDM, GHTN, or CS. However, infants born to women with prior cancer had higher risk of LBW (RR: 1.19 [1.07-1.32]), prolonged neonatal hospital stay (RR: 1.16 [1.01-1.34]), and PTB (RR: 1.19 [1.07-1.32]). We found clinically and statistically significant differences in the relationship between cancer history and SGA by subfertility/fertility treatment (p value, test for heterogeneity = 0.02); among deliveries with subfertility or fertility treatment, those with a history of cancer experienced a greater risk of SGA (RRsubfertile: 1.36 [1.02-1.83]). CONCLUSIONS: Women with a history of cancer had greater risk of some adverse pregnancy outcomes; this relationship varied by subfertility and fertility treatment.

Embryo biopsy and maternal and neonatal outcomes following cryopreserved-thawed single embryo transfer.

BACKGROUND: Contemporary embryo biopsy in the United States involves the removal of several cells from a blastocyst that would become the placenta for preimplantation genetic testing. Embryos are then cryopreserved while patients await biopsy results, with transfers occurring in a subsequent cycle as a single frozen-thawed embryo transfer, if euploid. OBJECTIVE: We sought to determine if removal of these cells for preimplantation genetic testing was associated with adverse obstetrical or neonatal outcomes after frozen-thawed single embryo transfer. STUDY DESIGN: We linked assisted reproductive technology surveillance data from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System to birth certificates and maternal and neonatal hospitalization discharge diagnoses in Massachusetts from 2014 to 2017, considering only singleton births after frozen-thawed single embryo transfers. We compared outcomes of cycles having embryo biopsy (n=585) to those having no biopsy (n=2191) using chi-square for categorical and binary variables and logistic regression for adjusted odds ratios and 95% confidence intervals, adjusting for mother's age, race, education, parity, body mass index, birth year, insurance, and all infertility diagnoses. RESULTS: Considering no biopsy as the reference, there was no difference between groups with respect to preeclampsia (adjusted odds ratio, 0.82; 95% confidence interval, 0.42-1.61; P=.5685); pregnancy-induced hypertension (adjusted odds ratio, 0.85; 95% confidence interval, 0.46-1.59; P=.6146); placental disorders, including placental abruption, placenta previa, placenta accreta, placenta increta, and placenta percreta (adjusted odds ratio, 1.16; 95% confidence interval, 0.60-2.24; P=.6675); preterm birth (adjusted odds ratio, 1.22; 95% confidence interval 0.73-2.03; P=.4418); low birthweight (adjusted odds ratio, 1.12; 95% confidence interval, 0.58-2.15; P=.7355); cesarean delivery (adjusted odds ratio, 1.04; 95% confidence interval, 0.79-1.38; P=.7762); or gestational diabetes mellitus (adjusted odds ratio, 0.83; 95% confidence interval, 0.50-1.38; P=.4734). In addition, there was no difference between the groups for prolonged hospital stay for mothers (adjusted odds ratio, 1.23; 95% confidence interval, 0.83-1.80; P=.3014) or for infants (95% confidence interval, 1.29; 95% confidence interval, 0.72-2.29; P=.3923). CONCLUSION: Embryo biopsy for preimplantation genetic testing does not increase the odds for diagnoses related to placentation (preeclampsia, pregnancy-related hypertension, placental disorders, preterm delivery, or low birthweight), maternal conditions (gestational diabetes mellitus), or maternal or infant length of stay after delivery.