Genetic and phenotypic characterization of Parkinson's disease at the clinic-wide level.

Observational studies in Parkinson's disease (PD) deeply characterize relatively small numbers of participants. The Molecular Integration in Neurological Diagnosis Initiative seeks to characterize molecular and clinical features of every PD patient at the University of Pennsylvania (UPenn). The objectives of this study are to determine the feasibility of genetic characterization in PD and assess clinical features by sex and GBA1/LRRK2 status on a clinic-wide scale. All PD patients with clinical visits at the UPenn PD Center between 9/2018 and 12/2022 were eligible. Blood or saliva were collected, and a clinical questionnaire administered. Genotyping at 14 GBA1 and 8 LRRK2 variants was performed. PD symptoms were compared by sex and gene groups. 2063 patients were approached and 1,689 (82%) were enrolled, with 374 (18%) declining to participate. 608 (36%) females were enrolled, 159 (9%) carried a GBA1 variant, and 44 (3%) carried a LRRK2 variant. Compared with males, females across gene groups more frequently reported dystonia (53% vs 46%, p = 0.01) and anxiety (64% vs 55%, p < 0.01), but less frequently reported cognitive impairment (10% vs 49%, p < 0.01) and vivid dreaming (53% vs 60%, p = 0.01). GBA1 variant carriers more frequently reported anxiety (67% vs 57%, p = 0.04) and depression (62% vs 46%, p < 0.01) than non-carriers; LRRK2 variant carriers did not differ from non-carriers. We report feasibility for near-clinic-wide enrollment and characterization of individuals with PD during clinical visits at a high-volume academic center. Clinical symptoms differ by sex and GBA1, but not LRRK2, status.

Disparities in Genetic Testing for Neurologic Disorders.

BACKGROUND AND OBJECTIVES: Genetic testing is now the standard of care for many neurologic conditions. Health care disparities are unfortunately widespread in the US health care system, but disparities in the utilization of genetic testing for neurologic conditions have not been studied. We tested the hypothesis that access to and results of genetic testing vary according to race, ethnicity, sex, socioeconomic status, and insurance status for adults with neurologic conditions. METHODS: We analyzed retrospective data from patients who underwent genetic evaluation and testing through our institution's neurogenetics program. We tested for differences between demographic groups in 3 steps of a genetic evaluation pathway: (1) attending a neurogenetic evaluation, (2) completing genetic testing, and (3) receiving a diagnostic result. We compared patients on this genetic evaluation pathway with the population of all neurology outpatients at our institution, using univariate and multivariable logistic regression analyses. RESULTS: Between 2015 and 2022, a total of 128,440 patients were seen in our outpatient neurology clinics and 2,540 patients underwent genetic evaluation. Black patients were less than half as likely as White patients to be evaluated (odds ratio [OR] 0.49, p < 0.001), and this disparity was similar after controlling for other demographic factors in multivariable analysis. Patients from the least wealthy quartile of zip codes were also less likely to be evaluated (OR 0.67, p < 0.001). Among patients who underwent evaluation, there were no disparities in the likelihood of completing genetic testing, nor in the likelihood of a diagnostic result after adjusting for age. Analyses restricted to specific indications for genetic testing supported these findings. DISCUSSION: We observed unequal utilization of our clinical neurogenetics program for patients from marginalized and minoritized demographic groups, especially Black patients. Among patients who do undergo evaluation, all groups benefit similarly from genetic testing when it is indicated. Understanding and removing barriers to accessing genetic testing will be essential to health care equity and optimal care for all patients with neurologic disorders.

Elevating Voices, Addressing Depression, Toxic Stress, and Equity Through Group Prenatal Care: A Pilot Study.

Introduction: Elevating Voices, Addressing Depression, Toxic Stress and Equity (EleVATE) is a group prenatal care (GC) model designed to improve pregnancy outcomes and promote health equity for Black birthing people. This article outlines the foundational community-engaged process to develop EleVATE GC and pilot study results. Methods: We used community-based participatory research principles and the Ferguson Commission Report to guide creation of EleVATE GC. The intervention, designed by and for Black birthing people, centers trauma-informed care, antiracism, and integrates behavioral health strategies into group prenatal care to address unmet mental health needs. Using a convenience sample of patients seeking care at one of three safety-net health care sites, we compared preterm birth, small for gestational age, depression scores, and other pregnancy outcomes between patients in individual care (IC), CenteringPregnancy™ (CP), and EleVATE GC. Results: Forty-eight patients enrolled in the study (n=11 IC; n=14 CP; n=23 EleVATE GC) and 86% self-identified as Black. Patients participating in group prenatal care (EleVATE GC or CP) were significantly less likely to experience a preterm birth <34 weeks. Rates of small for gestational age, preterm birth <37 weeks, depression scores, and other pregnancy outcomes were similar across groups. Participants in CP and EleVATE GC were more likely to attend their postpartum visit and breastfeed at hospital discharge than those in IC. Discussion: Our findings model a systematic approach to design a feasible, patient-centered, community-based, trauma-informed, antiracist intervention. Further study is needed to determine whether EleVATE GC improves perinatal outcomes and promotes health equity.

Genetic testing in adults with neurologic disorders: indications, approach, and clinical impacts.

The role of genetic testing in neurologic clinical practice has increased dramatically in recent years, driven by research on genetic causes of neurologic disease and increased availability of genetic sequencing technology. Genetic testing is now indicated for adults with a wide range of common neurologic conditions. The potential clinical impacts of a genetic diagnosis are also rapidly expanding, with a growing list of gene-specific treatments and clinical trials, in addition to important implications for prognosis, surveillance, family planning, and diagnostic closure. The goals of this review are to provide practical guidance for clinicians about the role of genetics in their practice and to provide the neuroscience research community with a broad survey of current progress in this field. We aim to answer three questions for the neurologist in practice: Which of my patients need genetic testing? What testing should I order? And how will genetic testing help my patient? We focus on common neurologic disorders and presentations to the neurology clinic. For each condition, we review the most current guidelines and evidence regarding indications for genetic testing, expected diagnostic yield, and recommended testing approach. We also focus on clinical impacts of genetic diagnoses, highlighting a number of gene-specific therapies recently approved for clinical use, and a rapidly expanding landscape of gene-specific clinical trials, many using novel nucleotide-based therapeutic modalities like antisense oligonucleotides and gene transfer. We anticipate that more widespread use of genetic testing will help advance therapeutic development and improve the care, and outcomes, of patients with neurologic conditions.

The Association between Mode of Transportation Support and Research Study Visit Attendance among Pregnant Patients.

OBJECTIVE: This study aimed to examine the association between transportation assistance and study visits, and explore differences by transportation modality. STUDY DESIGN: This was a secondary analysis of prospective cohort study. We identified patients requesting transportation support for research ultrasound visits and identified controls (1:2 ratio) who did not request support matched for age, race, and insurance type. Conditional logistic regression examined the association between transportation support and mode of transportation with study visit attendance. RESULTS: Transportation support was requested by 57/1,184 (4.8%) participants. Participants that requested transportation support were three times more likely to attend visits than their matched controls (adjusted odds ratio [aOR] 3.16, 95% confidence interval [CI]: 1.76-5.68). Among visits with transportation support, those supported by a ridesharing service had five-fold higher odds of attendance than visits supported with taxi service (aOR 5.06, 95% CI: 1.50-16.98). CONCLUSION: Transportation support, especially a ridesharing service, is associated with improved attendance at research study visits in a sample of predominantly low-income, Black, pregnant participants. Implementing transportation support may be a promising strategy to improve engagement in research studies. KEY POINTS: · Participants utilizing transportation assistance were more likely to attend study appointments.. · Participants using ridesharing had higher likelihood of attendance than those using taxi service.. · Transportation assistance may improve research engagement for historically marginalized people..

Diabetes Group Prenatal Care: A Systematic Review and Meta-analysis.

OBJECTIVE: To estimate the effect of diabetes group prenatal care on rates of preterm birth and large for gestational age (LGA) among patients with diabetes in pregnancy compared with individual diabetes prenatal care. DATA SOURCES: We searched Ovid Medline (1946-), Embase.com (1947-), Scopus (1823-), Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov. METHODS OF STUDY SELECTION: We searched electronic databases for randomized controlled trials (RCTs) and observational studies comparing diabetes group prenatal care with individual care among patients with type 2 diabetes mellitus or gestational diabetes mellitus (GDM). The primary outcomes were preterm birth before 37 weeks of gestation and LGA (birth weight at or above the 90th percentile). Secondary outcomes were small for gestational age, cesarean delivery, neonatal hypoglycemia, neonatal intensive care unit admission, breastfeeding at hospital discharge, long-acting reversible contraception (LARC) uptake, and 6-week postpartum visit attendance. Secondary outcomes, limited to the subgroup of patients with GDM, included rates of GDM requiring diabetes medication (A2GDM) and completion of postpartum oral glucose tolerance testing (OGTT). Heterogeneity was assessed with the Cochran Q test and I2 statistic. Random-effects models were used to calculate pooled relative risks (RRs) and weighted mean differences. TABULATION, INTEGRATION, AND RESULTS: Eight studies met study criteria and were included in the final analysis: three RCTs and five observational studies. A total of 1,701 patients were included in the pooled studies: 770 (45.3%) in diabetes group prenatal care and 931 (54.7%) in individual care. Patients in diabetes group prenatal care had similar rates of preterm birth compared with patients in individual care (seven studies: pooled rates 9.5% diabetes group prenatal care vs 11.5% individual care, pooled RR 0.77, 95% CI, 0.59-1.01), which held for RCTs and observational studies. There was no difference between diabetes group prenatal care and individual care in rates of LGA overall (four studies: pooled rate 16.7% diabetes group prenatal care vs 20.2% individual care, pooled RR 0.93, 95% CI, 0.59-1.45) or by study type. Rates of other secondary outcomes were similar between diabetes group prenatal care and individual care, except patients in diabetes group prenatal care were more likely to receive postpartum LARC (three studies: pooled rates 46.1% diabetes group prenatal care vs 34.1% individual care, pooled RR 1.44, 95% CI, 1.09-1.91). When analysis was limited to patients with GDM, there were no differences in rates of A2GDM or postpartum visit attendance, but patients in diabetes group prenatal care were significantly more likely to complete postpartum OGTT (five studies: pooled rate 74.0% diabetes group prenatal care vs 49.4% individual care, pooled RR 1.58, 95% CI, 1.19-2.09). CONCLUSION: Patients with type 2 diabetes and GDM who participate in diabetes group prenatal care have similar rates of preterm birth, LGA, and other pregnancy outcomes compared with those who participate in individual care; however, they are significantly more likely to receive postpartum LARC, and those with GDM are more likely to return for postpartum OGTT. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42021279233.

Mi Vida Saludable: Content Validity and Reliability of The Preferences and Self-Efficacy of Diet and Physical Activity Behaviors Questionnaire for Latina Women (PSEDPALW) for Cancer Survivors.

The purpose of this study is to conduct validity and reliability testing of a new instrument, the Preferences and Self-Efficacy of Diet and Physical Activity Behaviors Questionnaire for Latina Women (PSEDPALW), which is for women who identify as Latina and are breast cancer survivors. PSEDPALW measures preferences and self-efficacy for four behaviors: physical activity (PA), fruit and vegetable (FV) intake, dietary fat (DF) intake, and added sugar (AS) intake (eight scales in total). Validity testing was conducted through an expert panel review and a cognitive interviewing focus group (n = 4). Reliability was tested via internal consistency reliability (n = 118) and test-retest reliability (n = 30). Validity testing was used to refine PSEDPALW. Reliability testing was conducted on three versions with 104, 47, and 41 items. PA scales had acceptable Cronbach's α (>0.70) but low ICC (NS). FV and DF scales had acceptable Cronbach's α (>0.70), with preferences for the shorter (47- and 41-item) versions (Cronbach's α < 0.70), and all scales had moderate ICC (p < 0.05, except the FV scale on the 104-item version (p = 0.07)). The AS preferences scale had Cronbach's α < 0.70, with self-efficacy > 0.70 for all versions and ICC moderate for all versions (p ≤ 0.01). PSEDPALW may be useful to assess diet and physical activity preferences and self-efficacy in theory-based diet and physical activity interventions in women who identify as Latina and are breast cancer survivors.

Women's preferences for a new contraceptive under development: an exploratory study.

Objective: Currently available contraceptive methods do not meet the needs of all users. We sought to explore preferences of potential end-users regarding an on-demand, non-hormonal female contraceptive currently under development, using a web-based survey. Study design: We recruited respondents for an exploratory survey via web link on Amazon Mechanical Turk (MTurk). Individuals were eligible if they were 18-44 years of age, identified as cis-gender female, were English-speaking, not pregnant, and had used barrier contraception previously. Respondents provided demographic characteristics and a basic reproductive history. We then provided a brief description of the potential contraceptive. Respondents were asked about their interest in the proposed contraceptive and preferences for method attributes. Results: A total of 500 respondents completed the survey. Three-quarters of respondents were <35 years of age and 48.2% were currently using a barrier contraceptive method. Three-fourths of respondents (73.8%) expressed interest in using the contraceptive under development. The majority wanted the method to be small (≤2 inches), rod-shaped, and low cost (<$5 per use). More than half (59.4%) said it was important to be able to use the method without partners' knowledge. The most reported potential concerns were vaginal irritation (51.6%) and lack of effectiveness (46.4%). Sixty percent of respondents were confident they could use the method correctly. Discussion: Available contraceptive methods lack attributes preferred by some users. Development of new contraceptives frequently does not involve end-user input early in the development process. Individuals in this sample displayed interest in the proposed contraceptive and expressed preferences that can inform the further development of this method.

Preimplantation Genetic Testing for Adult-Onset Neurodegenerative Disease: Considerations for Access, Utilization, and Counseling.

Preimplantation genetic testing for monogenic conditions (PGT-M), formerly called preimplantation genetic diagnosis, is a specialized assisted reproduction technique that aims to reduce the risk of a pregnancy inheriting a monogenic condition. Despite calls to increase awareness and prepare neurologists for discussing PGT-M with patients and their families, no guidelines currently exist. When introducing PGT-M to those who may be interested in using it, there are major factors for discussion, including (1) genetic considerations (e.g., requirement for a confirmed genetic diagnosis; timing of genetic test results); (2) practical considerations (e.g., access to PGT-M and genetic services); (3) technical considerations (e.g., factors that can affect the success rate of PGT-M); and (4) psychosocial and ethical considerations (e.g., predictive testing for asymptomatic family members; family dynamics and values). Here, our team of neurologists and specialized genetic counselors discusses the current state of genetic characterization in adult-onset neurodegenerative conditions and highlights the major factors that should be considered when discussing PGT-M with families.

Clinical Reasoning: A 48-Year-Old Man With Spasticity and Progressive Ataxia.

A 48-year-old man was referred to the movement disorders clinic for 10 years of progressive slurred speech, spasticity, limb incoordination, and wide-based gait. Extensive neurologic workup was inconclusive, including serum and CSF testing, neuroimaging, EMG/NCS, exome sequencing, and mitochondrial testing. An ataxia repeat expansion panel ultimately revealed the final diagnosis. In this report, we review the clinical characteristics of a rare, late-onset, autosomal recessive cerebellar ataxia and discuss the importance of pursuing targeted gene testing to avoid diagnostic delays, especially as new treatments for this and other genetic diseases become available.

Comparison of interpersonal quality of contraceptive counseling delivered via telehealth versus in person.

OBJECTIVES: This study aimed to compare the interpersonal quality of contraceptive counseling between telehealth and in-person visits. STUDY DESIGN: Patients at a single Title X-funded clinic selected their preferred counseling modality (in person or telehealth via video or telephone) when scheduling an appointment for contraception. After counseling, we invited patients to complete a survey and recorded their desired contraceptive method. We assessed the quality of counseling using the Interpersonal Quality in Family Planning scale. We reviewed the electronic medical record to identify any subsequent clinician visit. We performed between-group comparisons using Mann-Whitney U, χ2, and Fisher exact tests. RESULTS: From March 2021 to June 2022, 360 patients were eligible to participate, and 296 (82%) completed the survey and were included in the analysis; 150 (51%) completed counseling in person, and 146 (49%) completed counseling via telehealth. In the telehealth group, 102 (70%) chose telephone, and 44 (30%) chose video. Respondent characteristics were similar between groups. The majority of respondents in both groups reported high quality of counseling, defined as a top score on the Interpersonal Quality in Family Planning scale (75.0% telehealth respondents and 80.0% in person, p = 0.30). Compared to respondents completing in-person counseling, telehealth respondents were less likely to have a subsequent clinician visit (89.0% versus 100.0%, p < 0.001). CONCLUSIONS: The majority of respondents reported high-quality contraceptive counseling without significant difference between the modalities. However, respondents choosing telehealth were less likely to have a subsequent clinician visit. Given the higher uptake of telephone compared to video, telehealth via telephone may be more accessible or acceptable to some patients. IMPLICATIONS: Contraceptive counseling via telehealth has similar high interpersonal quality when compared to traditional, in-person visits. However, barriers may exist for patients who choose telehealth contraceptive counseling to access subsequent in-person care. Utilization of telehealth for contraceptive visits may provide opportunities for more equitable health care and to expand contraceptive access.

Improvement in contraceptive knowledge after using an online educational resource.

OBJECTIVES: To measure the change in contraceptive knowledge after interaction with a web-based contraception education resource in an online cohort of potential users. STUDY DESIGN: We conducted a cross-sectional online survey of reproductive-aged, biologically female respondents using Amazon Mechanical Turk. Respondents provided demographic characteristics and responded to 32 contraceptive knowledge questions. We assessed contraceptive knowledge before and after interaction with the resource and compared the number of correct answers using Wilcoxon signed-rank test. We used univariate and multivariable logistic regression to identify respondent characteristics associated with an increase in the number of correct answers. We calculated System Usability Scale scores to assess ease of use. RESULTS: A convenience sample of 789 respondents were included in our analysis. Prior to resource use, respondents had a median of 17/32 correct contraceptive knowledge responses (interquartile range [IQR] 12-22). The number of correct answers increased to 21/32 (IQR 12-26, p < 0.001) after viewing the resource; 556 (70.5%) had an increase contraceptive knowledge. In adjusted analyses, respondents who were never married (adjusted odds ratio [aOR] 1.47, 95% CI 1.01-2.15), or thought decisions about birth control should be made by themselves (aOR 1.95, 95% CI 1.17-3.26) or in conjunction with a clinician (aOR 2.09, 95% CI 1.20-3.64) were more likely to have an increase in contraceptive knowledge. Respondents reported a median system usability score of 70 out of 100 (IQR 50-82.5). CONCLUSIONS: These results support the effectiveness and usability of this online contraception education resource among this sample of online respondents. The educational resource could effectively augment contraceptive counseling in the clinical setting. IMPLICATIONS: Use of an online contraception education resource improved contraceptive knowledge among reproductive-age users.

A Micro-evolutionary Change in Target Binding Sites as a Key Determinant of Ultrabithorax Function in Drosophila.

Hox genes encode Homeodomain-containing transcription factors, which specify segmental identities along the anterior-posterior axis. Functional changes in Hox genes have been directly implicated in the evolution of body plans across the metazoan lineage. The Hox protein Ultrabithorax (Ubx) is expressed and required in developing third thoracic (T3) segments in holometabolous insects studied so far, particularly, of the order Coleoptera, Lepidoptera and Diptera. Ubx function is key to specify differential development of the second (T2) and T3 thoracic segments in these insects. While Ubx is expressed in the third thoracic segment in developing larvae of Hymenopteran Apis mellifera, the morphological differences between T2 and T3 are subtle. To identify evolutionary changes that are behind the differential function of Ubx in Drosophila and Apis, which are diverged for more than 350 million years, we performed comparative analyses of genome wide Ubx-binding sites between these two insects. Our studies reveal that a motif with a TAAAT core is a preferred binding site for Ubx in Drosophila, but not in Apis. Biochemical and transgenic assays suggest that in Drosophila, the TAAAT core sequence in the Ubx binding sites is required for Ubx-mediated regulation of two of its target genes studied here; CG13222, a gene that is normally upregulated by Ubx and vestigial (vg), whose expression is repressed by Ubx in T3. Interestingly, changing the TAAT site to a TAAAT site was sufficient to bring an otherwise unresponsive enhancer of the vg gene from Apis under the control of Ubx in a Drosophila transgenic assay. Taken together, our results suggest an evolutionary mechanism by which critical wing patterning genes might have come under the regulation of Ubx in the Dipteran lineage.

Outcomes of the "BRCA Quality Improvement Dissemination Program": An initiative to improve patient receipt of cancer genetics services at five health systems.

OBJECTIVE: A quality improvement initiative (QII) was conducted with five community-based health systems' oncology care centers (sites A-E). The QII aimed to increase referrals, genetic counseling (GC), and germline genetic testing (GT) for patients with ovarian cancer (OC) and triple-negative breast cancer (TNBC). METHODS: QII activities occurred at sites over several years, all concluding by December 2020. Medical records of patients with OC and TNBC were reviewed, and rates of referral, GC, and GT of patients diagnosed during the 2 years before the QII were compared to those diagnosed during the QII. Outcomes were analyzed using descriptive statistics, two-sample t-test, chi-squared/Fisher's exact test, and logistic regression. RESULTS: For patients with OC, improvement was observed in the rate of referral (from 70% to 79%), GC (from 44% to 61%), GT (from 54% to 62%) and decreased time from diagnosis to GC and GT. For patients with TNBC, increased rates of referral (from 90% to 92%), GC (from 68% to 72%) and GT (81% to 86%) were observed. Effective interventions streamlined GC scheduling and standardized referral processes. CONCLUSION: A multi-year QII increased patient referral and uptake of recommended genetics services across five unique community-based oncology care settings.

Neonatal Intensive Care Unit Latent Profiles of Maternal Distress: Associations With 5-Year Maternal and Child Mental Health Outcomes.

OBJECTIVE: To examine profiles of distress of mothers of preterm infants in the neonatal intensive care unit (NICU) and relate profiles to maternal and child outcomes at child age 5 years. METHOD: A racially and economically diverse sample of mothers (n = 94; 39% African American, 52% White) of preterm infants (≤30 weeks of gestation) completed validated questionnaires assessing depression, anxiety (state and trait), NICU stress, and life stress at NICU discharge of their infant. Mothers reported on their own and their children's symptomatology at child age 5. A latent profile analysis was conducted to categorize maternal symptomatology. RESULTS: Latent profile analysis yielded 4 distinct maternal profiles: low symptomatology, high NICU stress, high depression and anxiety, and high state anxiety. Social determinants of health factors including age, education, neighborhood deprivation, and infant clinical risk distinguished the profiles. Mothers in the high depression and anxiety profile reported more anxiety and life stress at follow-up and reported their children experienced more anxious/depressed symptoms. CONCLUSION: Existing literature has gaps related to examining multiple dimensions of NICU distress and understanding how patterns of mood/affective symptoms, life stressors, and related social determinants of health factors vary across mothers. In this study, one specific profile of maternal NICU distress demonstrated enduring risks for poorer maternal and child mental health outcomes. This new knowledge underscores sources of disparate health outcomes for mothers of preterm infants and the infants themselves. Universal screening is needed to identify at-risk dyads for poor health outcomes in need of individualized interventions that address both maternal and child well-being. DIVERSITY & INCLUSION STATEMENT: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list.

Comparison of Early Pregnancy Loss Management Between States With Restrictive and Supportive Abortion Policies.

INTRODUCTION: Mifepristone-misoprostol and office uterine aspiration used for abortion care are also evidence-based, cost-effective strategies for early pregnancy loss management. We aimed to compare the provision of mifepristone-misoprostol and office uterine aspiration for early pregnancy loss between states with restrictive and supportive abortion policies. METHODS: We conducted a cross-sectional, internet-based survey regarding early pregnancy loss management among obstetrician-gynecologists (OBGYNs) at academic medical centers. We assessed management offered along with facilitators and barriers to implementation of mifepristone-misoprostol and office uterine aspiration. We used χ2 and multivariable logistic regression to compare practice patterns. RESULTS: We analyzed responses from 350 physicians, 56% from states with restrictive abortion policies. OBGYNs in states with restrictive abortion policies were less likely than those in states with supportive abortion policies to offer both mifepristone-misoprostol and office uterine aspiration (33.2% vs. 51.3%; p = .001), to report having received induced abortion training (67.3% vs. 89.6%; p < .001), and to report perceived institutional support for abortion care (49.0% vs. 85.0%; p < .001). After adjusting for confounders, restrictive state policy was no longer associated with providing both mifepristone-misoprostol and office uterine aspiration for early pregnancy loss (adjusted odds ratio, 1.19; 95% confidence interval [CI], 0.58-2.45). However both prior induced abortion training and institutional support for abortion care remained significantly associated (adjusted odds ratio, 2.06; 95% CI, 1.07-3.97 and adjusted odds ratio, 3.91; 95% CI, 2.08-7.38, respectively). CONCLUSIONS: OBGYNs practicing in states with restrictive abortion policies are less likely than those in states with supportive abortion policies to have received abortion training or perceive institutional support for abortion care, and they are less likely to offer mifepristone-misoprostol and office uterine aspiration for early pregnancy loss.

The Impact of Group Prenatal Care on Interpregnancy Interval.

OBJECTIVE: To evaluate whether participation in CenteringPregnancy group prenatal care is associated with decreased risk of an interpregnancy interval (IPI) ≤6 months. STUDY DESIGN: We conducted a retrospective cohort study of women enrolled in Missouri Medicaid from 2007 to 2014 using maternal Medicaid data linked to infant birth certificate records. Inclusion criteria were women ≥11 years old, ≥1 viable singleton delivery during the study period, residency in St. Louis city or county, and ≥2 prenatal visits. The primary outcome was an IPI ≤6 months. Secondary outcomes included IPI ≤12 months, IPI ≤18 months, postpartum long-acting reversible contraception (LARC) uptake, and postpartum LARC or depot medroxyprogesterone acetate (DMPA) uptake. Data were analyzed using descriptive statistics and logistic regression. Backward stepwise logistic regression was used to adjust for potential confounders including maternal age, race, obesity, nulliparity, marital status, diabetes, hypertension, prior preterm birth, and maternal education. RESULTS: Of the 54,968 pregnancies meeting inclusion criteria, 1,550 (3%) participated in CenteringPregnancy. CenteringPregnancy participants were less likely to have an IPI ≤6 months (adjusted odds ratio [aOR]: 0.61; 95% confidence interval [CI]: 0.47-0.79) and an IPI ≤12 months (aOR: 0.74; 95% CI: 0.62-0.87). However, there was no difference for an IPI ≤18 months (aOR: 0.89; 95% CI: 0.77-1.13). Women in CenteringPregnancy were more likely to use LARC for postpartum contraception (aOR: 1.37; 95% CI: 1.20-1.57). CONCLUSION: Participation in CenteringPregnancy is associated with a significant decrease in an IPI ≤6 and ≤12 months and a significant increase in postpartum LARC uptake among women enrolled in Missouri Medicaid compared with women in traditional prenatal care. KEY POINTS: · CenteringPregnancy is associated with a significant decrease in interpregnancy intervals ≤6 and ≤12 months.. · LARC uptake is significantly higher among patients participating in CenteringPregnancy.. · CenteringPregnancy participation enhances self-efficacy in making contraception decisions and promotes healthy pregnancy spacing..

One-Step Compared With Two-Step Gestational Diabetes Screening and Pregnancy Outcomes: A Systematic Review and Meta-analysis.

OBJECTIVE: To estimate short-term maternal and neonatal outcomes with one-compared with two-step testing for gestational diabetes mellitus (GDM). DATA SOURCES: A systematic review of randomized controlled trials (RCTs) and observational studies comparing one-step and two-step GDM testing strategies before September 2021 was conducted. We searched Ovid Medline (1946-), EMBASE (1947-), Scopus (1960-), Cochrane Central, and ClinicalTrials.gov . The primary outcome was rate of large-for-gestational age (LGA) neonates. Secondary outcomes were clinically relevant outcomes for GDM that were selected a priori. METHODS OF STUDY SELECTION: Titles, abstracts, and manuscripts were screened, selected, and reviewed by the first two authors. Four RCTs (24,966 patients) and 13 observational studies (710,677 patients) were analyzed. TABULATION, INTEGRATION, AND RESULTS: Pooled relative risks (RRs) were calculated with 95% CIs using random-effects models and were plotted graphically with forest plots. Study heterogeneity was evaluated using Cochran Q and Higgins I 2 tests. The quality of studies that met the inclusion criteria was evaluated with the Downs and Black checklist. Publication bias was assessed by using asymmetry of funnel plots and Harbord's test. There was no difference in the rate of LGA neonates (pooled RR 0.95; 95% CI 0.88-1.04) by testing strategy among RCTs, but patients who underwent one-step testing were more likely to be diagnosed with GDM (pooled RR 2.13; 95% CI 1.61-2.82) and treated with diabetes medications (pooled RR 2.24; 95% CI 1.21-4.15). One-step testing was associated with higher rates of neonatal intensive care unit (NICU) admission (pooled RR 1.12; 95% CI 1.00-1.26) and neonatal hypoglycemia (pooled RR 1.23; 95% CI 1.13-1.34). In analysis of high-quality RCTs and observational studies, one-step testing was associated with a lower rate of LGA neonates (pooled RR 0.97; 95% CI 0.95-0.98), but higher rates of GDM diagnosis, treatment, NICU admission, and neonatal hypoglycemia. CONCLUSION: Despite a significant increase in GDM diagnosis and treatment with one-step testing, there is no difference in rate of LGA neonates compared with two-step testing among RCTs. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42021252703.

Developing a Diet and Physical Activity Intervention for Hispanic/Latina Breast Cancer Survivors.

OBJECTIVES: There is limited guidance on how to effectively educate cancer survivors to adopt and maintain specific diet and physical activity recommendations, especially among underserved and under-resourced populations. Here, the objective is to present the development of a behavioral and theoretically-based multi-modal diet and physical activity intervention program for Hispanic/Latina breast cancer survivors, Mi Vida Saludable (My Healthy Life). METHODS: The development process was based on the 6 steps of the Nutrition Education DESIGN Procedure: (1). Decide behaviors; (2). Explore determinants; (3). Select theory-based model; (4). Indicate objectives; (5). Generate plans; and (6). Nail down evaluation. The theoretical framework for the intervention is Social Cognitive Theory. RESULTS: The resulting behavioral intervention consists of 2 components. The first component is in-person group education consisting of 4 lessons over 1 month. Each 4-hour group lesson includes a hands-on cooking component, a physical activity component, and facilitator-led nutrition education and discussion, with 2 field trips to a local grocery store and farmers' market. The second component is an e-Health program that includes weekly text messages, biweekly emailed newsletters, and ongoing website access. CONCLUSION: The systematic DESIGN Procedure provided practical guidance for developing a behaviorally-focused, theory-based, and culturally sensitive program that addresses both dietary and physical activity behaviors for delivery both in-person education and through eHealth. The Procedure may be useful for developing other behaviorally focused and theory-based interventions.

IRE1α overexpression in malignant cells limits tumor progression by inducing an anti-cancer immune response.

IRE1α is one of the three ER transmembrane transducers of the Unfolded Protein Response (UPR) activated under endoplasmic reticulum (ER) stress. IRE1α activation has a dual role in cancer as it may be either pro- or anti-tumoral depending on the studied models. Here, we describe the discovery that exogenous expression of IRE1α, resulting in IRE1α auto-activation, did not affect cancer cell proliferation in vitro but resulted in a tumor-suppressive phenotype in syngeneic immunocompetent mice. We found that exogenous expression of IRE1α in murine colorectal and Lewis lung carcinoma cells impaired tumor growth when syngeneic tumor cells were subcutaneously implanted in immunocompetent mice but not in immunodeficient mice. Mechanistically, the in vivo tumor-suppressive effect of overexpressing IRE1α in tumor cells was associated with IRE1α RNAse activity driving both XBP1 mRNA splicing and regulated IRE1-dependent decay of RNA (RIDD). We showed that the tumor-suppressive phenotype upon IRE1α overexpression was characterized by the induction of apoptosis in tumor cells along with an enhanced adaptive anti-cancer immunosurveillance. Hence, our work indicates that IRE1α overexpression and/or activation in tumor cells can limit tumor growth in immunocompetent mice. This finding might point toward the need of adjusting the use of IRE1α inhibitors in cancer treatments based on the predominant outcome of the RNAse activity of IRE1α.