COVID-19 Vaccine Safety Surveillance in Early Pregnancy in the United States: Design Factors Affecting the Association Between Vaccine and Spontaneous Abortion.

In the Vaccine Safety Datalink (VSD), we previously reported no association between coronavirus disease 2019 (COVID-19) vaccination in early pregnancy and spontaneous abortion (SAB). The present study aims to understand how time since vaccine rollout or other methodological factors could affect results. Using a case-control design and generalized estimating equations, we estimated the odds ratios (ORs) of COVID-19 vaccination in the 28 days before a SAB or last date of the surveillance period (index date) in ongoing pregnancies and occurrence of SAB, across cumulative 4-week periods from December 2020 through June 2021. Using data from a single site, we evaluated alternative methodological approaches: increasing the exposure window to 42 days, modifying the index date from the last day to the midpoint of the surveillance period, and constructing a cohort design with a time-dependent exposure model. A protective effect (OR = 0.78, 95% confidence interval: 0.69, 0.89), observed with 3-cumulative periods ending March 8, 2021, was attenuated when surveillance extended to June 28, 2021 (OR = 1.02, 95% confidence interval: 0.96, 1.08). We observed a lower OR for a 42-day window compared with a 28-day window. The time-dependent model showed no association. Timing of the surveillance appears to be an important factor affecting the observed vaccine-SAB association.

Household Income, Cortisol, and Obesity During Early Childhood: A Prospective Longitudinal Study.

OBJECTIVE: To prospectively evaluate the relationship between household income, children's cortisol, and body mass index (BMI) trajectories over a 3-year period in early childhood. STUDY DESIGN: Household income, child hair cortisol levels, and BMI were measured at baseline, 12-, 24-, and 36-month follow-up visits in the Now Everybody Together for Amazing and Healthful Kids (NET-Works) Study (n = 534, children ages 2-4 years, and household income <$65 000/year at baseline). Relationships were examined between very low household income (<$25 000/year) at baseline, income status over time (remained <$25 000/year or had increasing income), cortisol accumulation from hair samples, and BMI percent of the 95th percentile (BMIp95) trajectories using adjusted linear growth curve modeling. Households with baseline income between $25 000 and $65 000/year were the reference group for all analyses. RESULTS: Children from very low-income households at baseline had annual changes in BMIp95 that were higher (P < .001) than children from reference group households (0.40 vs -0.62 percentage units/year). Annual increases in BMIp95 were also greater among children from households that remained very low income (P < .01, .34 percentage units/year) and among those with increasing income (P = .01, .51 percentage units/year) compared with the reference group (-0.61 percentage units/year). Children from households that remained very low income had higher hair cortisol accumulations (0.22 pg/mg, P = .02) than reference group children, whereas hair cortisol concentrations of children from households with increasing income (0.03 pg/mg) did not differ significantly from the reference group. Cortisol was not related to BMIp95. CONCLUSIONS: The economic circumstances of families may impact children's BMI trajectories and their developing stress systems, but these processes may be independent of one another.

Clinician perceptions of a clinical decision support system to reduce cardiovascular risk among prediabetes patients in a predominantly rural healthcare system.

BACKGROUND: The early detection and management of uncontrolled cardiovascular risk factors among prediabetes patients can prevent cardiovascular disease (CVD). Prediabetes increases the risk of CVD, which is a leading cause of death in the United States. CVD clinical decision support (CDS) in primary care settings has the potential to reduce cardiovascular risk in patients with prediabetes while potentially saving clinicians time. The objective of this study is to understand primary care clinician (PCC) perceptions of a CDS system designed to reduce CVD risk in adults with prediabetes. METHODS: We administered pre-CDS implementation (6/30/2016 to 8/25/2016) (n = 183, 61% response rate) and post-CDS implementation (6/12/2019 to 8/7/2019) (n = 131, 44.5% response rate) independent cross-sectional electronic surveys to PCCs at 36 randomized primary care clinics participating in a federally funded study of a CVD risk reduction CDS tool. Surveys assessed PCC demographics, experiences in delivering prediabetes care, perceptions of CDS impact on shared decision making, perception of CDS impact on control of major CVD risk factors, and overall perceptions of the CDS tool when managing cardiovascular risk. RESULTS: We found few significant differences when comparing pre- and post-implementation responses across CDS intervention and usual care (UC) clinics. A majority of PCCs felt well-prepared to discuss CVD risk factor control with patients both pre- and post-implementation. About 73% of PCCs at CDS intervention clinics agreed that the CDS helped improve risk control, 68% reported the CDS added value to patient clinic visits, and 72% reported they would recommend use of this CDS system to colleagues. However, most PCCs disagreed that the CDS saves time talking about preventing diabetes or CVD, and most PCCs also did not find the clinical domains useful, nor did PCCs believe that the clinical domains were useful in getting patients to take action. Finally, only about 38% reported they were satisfied with the CDS. CONCLUSIONS: These results improve our understanding of CDS user experience and can be used to guide iterative improvement of the CDS. While most PCCs agreed the CDS improves CVD and diabetes risk factor control, they were generally not satisfied with the CDS. Moreover, only 40-50% agreed that specific suggestions on clinical domains helped patients to take action. In spite of this, an overwhelming majority reported they would recommend the CDS to colleagues, pointing for the need to improve upon the current CDS. TRIAL REGISTRATION: NCT02759055 03/05/2016.

Infants exposed to antibiotics after birth have altered recognition memory responses at one month of age.

BACKGROUND: Neonatal exposure to antibiotics, in the absence of infection, results in abnormal learning and memory in animals and is linked to changes in gut microbes. The relevance of early-life antibiotic exposure to brain function in humans is not known. METHODS: Recognition memory was assessed at 1 month of age in 15 term-born infants exposed to antibiotics (with negative cultures) and 57 unexposed infants using event-related potentials (ERPs). Linear regression analysis, adjusting for covariates, was employed to compare groups with respect to ERP features representing early stimulus processing (P2 amplitude) and discrimination between mother and stranger voices. RESULTS: Infants exposed to antibiotics exhibited smaller P2 amplitudes for both voice conditions (p = 0.001), with greatest reductions observed for mother's voice in frontal and central scalp regions (p < 0.04). Infants exposed to antibiotics showed larger P2 amplitudes to stranger's as compared to mother's voice, a reversal of the typical response exhibited by unexposed infants. Abnormal ERP responses did not consistently correlate with increased inflammatory cytokines within the antibiotic-exposed group. CONCLUSIONS: Otherwise healthy infants exposed to antibiotics soon after birth demonstrated altered auditory processing and recognition memory responses, supporting the possibility of a microbiota-gut-brain axis in humans during early life. IMPACT: Infants exposed to antibiotics after birth demonstrate altered auditory processing and recognition memory responses at 1 month of age. Preclinical models support a role for gut microbiomes in modulating brain function and behavior, particularly in developing brains. This study is one of the first to explore the relevance of these findings for human infants. The findings of this study have implications for the management and follow-up of at-risk infants with exposure to gut-microbiome disrupting factors and lay foundation for future studies to further characterize the short- and long-term effects of gut microbiome perturbation on brain development.

Relationships between Early Nutrition, Illness, and Later Outcomes among Infants Born Preterm with Hyperglycemia.

OBJECTIVE: To evaluate the effects of hyperglycemia on body composition and neurodevelopment, and how early nutrition and illness modify these relationships in infants born preterm. STUDY DESIGN: Prospective data were collected from infants born <32 weeks of gestational age (N = 97), including inpatient days of hyperglycemia (blood glucose >150 mg/dL) and nutrient intake. Body composition was measured at discharge and 4 months' postmenstrual age (PMA). Bayley Scales of Infant Development III (BSID-III) were administered at 12 months' PMA. Linear regression analysis was performed, adjusting for birth gestational age. Associations between hyperglycemia, body composition, and BSID-III were analyzed in models accounting for first-week nutrition and early illness severity via Score for Neonatal Acute Physiology-II. RESULTS: Mean birth gestational age was 27.8 (SD 2.4) weeks. Hyperglycemia occurred in 48.5% of infants. Hyperglycemia for ≥5 days was negatively associated with fat mass and fat free mass z scores at discharge, and fat free mass z score at 4 months' PMA (P < .05 all). Hyperglycemia for ≥5 days was negatively associated with cognition, language, and motor scores on the BSDI at 12 months (P ≤ .01 all). Associations with body composition and BSID-III were diminished when models included first week nutrition yet remained unchanged when illness severity was included. CONCLUSIONS: In infants <32 weeks, ≥5 days of hyperglycemia is associated with decreased lean mass at 4 months' PMA and poorer neurodevelopmental outcome at 12 months' PMA. These associations may be mediated by decreased first week nutrition, potentially related to reduced glucose infusion rate for management of hyperglycemia.

The dose of behavioral interventions to prevent and treat childhood obesity: a systematic review and meta-regression.

BACKGROUND: A better understanding of the optimal "dose" of behavioral interventions to affect change in weight-related outcomes is a critical topic for childhood obesity intervention research. The objective of this review was to quantify the relationship between dose and outcome in behavioral trials targeting childhood obesity to guide future intervention development. METHODS: A systematic review and meta-regression included randomized controlled trials published between 1990 and June 2017 that tested a behavioral intervention for obesity among children 2-18 years old. Searches were conducted among PubMed (Web-based), Cumulative Index to Nursing and Allied Health Literature (EBSCO platform), PsycINFO (Ovid platform) and EMBASE (Ovid Platform). Two coders independently reviewed and abstracted each included study. Dose was extracted as intended intervention duration, number of sessions, and length of sessions. Standardized effect sizes were calculated from change in weight-related outcome (e.g., BMI-Z score). RESULTS: Of the 258 studies identified, 133 had sufficient data to be included in the meta-regression. Average intended total contact (# sessions x length of sessions) was 27.7 (SD 32.2) hours and average duration was 26.0 (SD 23.4) weeks. When controlling for study covariates, a random-effects meta-regression revealed no significant association between contact hours, intended duration or their interaction and effect size. CONCLUSIONS: This systematic review identified wide variation in the dose of behavioral interventions to prevent and treat pediatric obesity, but was unable to detect a clear relationship between dose and weight-related outcomes. There is insufficient evidence to provide quantitative guidance for future intervention development. One limitation of this review was the ability to uniformly quantify dose due to a wide range of reporting strategies. Future trials should report dose intended, delivered, and received to facilitate quantitative evaluation of optimal dose. TRIAL REGISTRATIONS: The protocol was registered on PROSPERO (Registration # CRD42016036124 ).

Protocol of a patient randomized clinical trial to improve medication adherence in primary care.

BACKGROUND: Enhanced awareness of poor medication adherence could improve patient care. This article describes the original and adapted protocols of a randomized trial to improve medication adherence for cardiometabolic conditions. METHODS: The original protocol entailed a cluster randomized trial of 28 primary care clinics allocated to either (i) medication adherence enhanced chronic disease care clinical decision support (eCDC-CDS) integrated within the electronic health record (EHR) or (ii) usual care (non-enhanced CDC-CDS). Enhancements comprised (a) electronic interfaces printed for patients and clinicians at primary care encounters that encouraged discussion about specific medication adherence issues that were identified, and (b) pharmacist phone outreach. Study subjects were individuals who at an index visit were aged 18-74 years and not at evidence-based care goals for hypertension (HTN), diabetes mellitus (DM), or lipid management, along with low medication adherence (proportion of days covered [PDC] <80%) for a corresponding medication. The primary study outcomes were improved medication adherence and clinical outcomes (BP and A1C) at 12 months. Protocol adaptation became imperative in response to major implementation challenges: (a) the availability of EHR system-wide PDC calculations that superseded our ability to limit PDC adherence information solely to intervention clinics; (b) the unforeseen closure of pharmacies committed to conducting the pharmacist outreach; and (c) disruptions and clinic closures due to the Covid-19 pandemic. CONCLUSION: This manuscript details the protocol of a study to assess whether enhanced awareness of medication adherence issues in primary care settings could improve patient outcomes. The need for protocol adaptation arose in response to multiple implementation challenges.

Cumulative environmental stress and emerging cardiometabolic risk during childhood.

OBJECTIVE: To prospectively evaluate the relationship between cumulative environmental stress and cardiometabolic risk in middle childhood, and to examine whether hair cortisol, a measure of hypothalamic pituitary adrenal-axis activity, mediates this relationship. METHODS: In a cohort of children from low-income households (n = 320; 59% Hispanic, 23% Black, body mass index (BMI) percentile >50th at enrollment), environmental stressors including family and neighbourhood factors representing disadvantage/deprivation, and cortisol concentrations from hair samples, were measured over five timepoints beginning when children were 2-4 years old. Cardiometabolic risk factors (i.e., BMI, blood pressure, lipids, blood sugar, C-reactive protein) were measured at the final timepoint when children were 7-11 years of age. RESULTS: In adjusted logistic regression models, greater cumulative environmental stress was associated with a higher likelihood of elevated cardiometabolic risk in middle childhood (p = 0.01). Children from minoritized racial/ethnic groups had a higher prevalence of both stressors and cardiometabolic risk factors. Cumulative environmental stress was associated with higher hair cortisol concentrations (p < 0.01). However, hair cortisol was not directly associated with cardiometabolic risk factors and did not explain the association between environmental stress and cardiometabolic risk in causal mediation analysis. CONCLUSIONS: The influence of cumulative stress on cardiometabolic health can be observed in middle childhood and may contribute to cardiometabolic health disparities, highlighting the importance of public health interventions to mitigate disadvantage.

Maternal oral probiotic use is associated with decreased breastmilk inflammatory markers, infant fecal microbiome variation, and altered recognition memory responses in infants-a pilot observational study.

Introduction: Early life gut microbiomes are important for brain and immune system development in animal models. Probiotic use has been proposed as a strategy to promote health via modulation of microbiomes. In this observational study, we explore if early life exposure to probiotics via the mother during pregnancy and lactation, is associated with decreased inflammation in breastmilk, maternal and infant microbiome variation, and altered infant neurodevelopmental features. Methods: Exclusively breastfeeding mother-infant dyads were recruited as part of the "Mothers and Infants Linked for Healthy Growth (MILk) Study." Probiotic comparison groups were defined by exposure to maternal probiotics (NO/YES) and by timing of probiotic exposure (prenatal, postnatal, total). C-reactive protein (CRP) and IL-6 levels were determined in breastmilk by immunoassays, and microbiomes were characterized from 1-month milk and from 1- and 6-month infant feces by 16S rDNA sequencing. Infant brain function was profiled via electroencephalogram (EEG); we assessed recognition memory using event-related potential (ERP) responses to familiar and novel auditory (1 month) and visual (6 months) stimuli. Statistical comparisons of study outcomes between probiotic groups were performed using permutational analysis of variance (PERMANOVA) (microbiome) and linear models (all other study outcomes), including relevant covariables as indicated. Results: We observed associations between probiotic exposure and lower breastmilk CRP and IL-6 levels, and infant gut microbiome variation at 1- and 6-months of age (including higher abundances of Bifidobacteria and Lactobacillus). In addition, maternal probiotic exposure was associated with differences in infant ERP features at 6-months of age. Specifically, infants who were exposed to postnatal maternal probiotics (between the 1- and 6-month study visits) via breastfeeding/breastmilk, had larger differential responses between familiar and novel visual stimuli with respect to the late slow wave component of the EEG, which may indicate greater memory updating potential. The milk of mothers of this subgroup of infants had lower IL-6 levels and infants had different 6-month fecal microbiomes as compared to those in the "NO" maternal probiotics group. Discussion: These results support continued research into "Microbiota-Gut-Brain" connections during early life and the role of pre- and postnatal probiotics in mothers to promote healthy microbiome-associated outcomes in infants.

Do Children's Health Behaviors Buffer the Impact of Cumulative Environmental Stress on Emerging Cardiometabolic Risk?

BACKGROUND: Previous studies have found that exposure to childhood environmental stress is associated with cardiometabolic risk. However, it is not known whether individual health behaviors disrupt this relationship. This study prospectively evaluated the relationship between cumulative environmental stress in a low-income sample and cardiometabolic risk in middle childhood and examined whether child health behaviors attenuated this relationship. METHODS AND RESULTS: In a cohort of children (n=338; 57% Hispanic children; 25% Black children), environmental stressors (family and neighborhood factors representing disadvantage/deprivation) and child health behaviors (accelerometry measured physical activity; parent-reported screen time and diet recalls) were measured over 5 time points beginning when children were aged 2 to 4 years and ending when they were aged 7 to 11 years. Children's cardiometabolic risk factors (body mass index, blood pressure, triglyceride/high-density lipoprotein ratio, glucose, hemoglobin A1c, C-reactive protein) were measured at 7 to 11 years. Emerging cardiometabolic risk was defined as having ≥1 elevations that exceeded clinical thresholds. In adjusted path analyses, greater cumulative environmental stress was associated with higher likelihood of emerging cardiometabolic risk in middle childhood (P<0.001). Higher levels of moderate to vigorous physical activity and fewer sedentary minutes attenuated the positive relationship between stress and cardiometabolic risk (P<0.05). Children with >2 hours of average daily screen time had a higher likelihood of elevated cardiometabolic risk (P<0.01), but screen time did not moderate the stress-cardiometabolic risk relationship. Dietary intake was not related to cardiometabolic risk. CONCLUSIONS: Interventions that promote moderate to vigorous physical activity and limit sedentary behavior may have particular importance for the cardiometabolic health of children exposed to high levels of cumulative environmental stress.

Cervical Total Disc Replacement and Anterior Cervical Discectomy and Fusion: Comparison of 30-Day Population Comorbidities and Perioperative Complications Using 6 Years of American College of Surgeons National Surgical Quality Improvement Program Participant Use File Data.

OBJECTIVE: American College of Surgeons National Surgical Quality Improvement Program Participant Use File data from 2014 through 2019 were used to compare 1- and 2-level anterior cervical discectomy and fusion (ACDF) and cervical total disc replacement (cTDR) with respect to: patient demographics, comorbidities, adverse events, and 30-day morbidity rates. METHODS: One- and 2-level ACDF and cTDR patients were identified by current procedural terminology codes. Demographics, comorbidities, and adverse events were summarized. Unmatched cohorts were compared using Wilcoxon Rank Sum test for continuous variables, Pearson χ2 test for categorical variables, and 30-day morbidity using inverse probability of treatment weighted log-binomial regression. RESULTS: American College of Surgeons National Surgical Quality Improvement Program 2014 through 2019 Participant Use File datasets represent 4,862,497 unique patients, identifying 13,347 1-level, 6933 2-level ACDF, 3114 1-level, and 862 2-level cTDR patient cohorts. Statistically significant differences between cohorts are extensive: age, sex, race, admission status, patient origin, discharge disposition, emergent surgery, surgical specialty, American Society of Anesthesiologists classification, wound class, operative time, hospital LOS, BMI, functional status, smoking, diabetes, dyspnea, chronic obstructive pulmonary disease, congestive heart failure, hypertension, renal failure, dialysis, cancer, steroid use, anemia, bleeding disorders, systemic sepsis, and number of concurrent comorbid conditions. Inverse probability of treatment weighted log-binomial models, demonstrated increased risk of deep venous thrombosis/thrombophlebitis, pulmonary embolism, deep incisional surgical site infection, pneumonia, and unplanned return to operating room associated with ACDF while increased risk of cerebral vascular accident/stroke with neurological deficit and myocardial infarction associated with cTDR. The composite complications outcome favors cTDR over ACDF for 30-day morbidity. No mortalities occurred within the cTDR cohort. CONCLUSIONS: Adjusting for demographics and comorbidities; ACDF has a higher average risk of adverse event. When ACDF and cTDR are equipoise, consideration for cTDR may be indicated in populations with higher rates of comorbid conditions.

Preterm infant body composition, working memory, and temperament.

Altered body composition in preterm infants is associated with risks to cognitive development, but the effect specific to prefrontal cortex (PFC) development is unknown. We were interested in the impact of fat mass (FM) and fat free mass (FFM) gains out to 4 months corrected gestational age (CGA) on PFC development, as indexed by working memory and temperament. This is a prospective observational pilot study recruiting 100 preterm (<33 weeks gestation), appropriate for gestational age, and very low birth weight infants, of which 49 infants met inclusion criteria. Body composition was measured using air displacement plethysmography at hospital discharge and 4 months CGA. Questionnaire based temperament assessments were completed at 12 and 24 months CGA and a working memory assessment was completed at 24 months CGA. Associations between developmental tests and body composition obtained at term and 4 months were analyzed. Increased FM at discharge was associated with increased fear and decreased soothability at 12 months. Increased FM at 4 months was associated with increased activity level, increased distress from limitations at 12 months and decreased attentional shifting, decreased frustration, and decreased inhibitory control at 24 months. Increased FFM at 4 months was associated with increased activity level at 12 months and increased impulsivity and decreased low intensity pleasure at 24 months. In this exploratory pilot study, increased FM out to 4 months and increased FFM after discharge are associated with negative markers of infant temperament. Infant temperament may be sensitive to body composition status at least to 4 months CGA.

Survey-based Evaluation of a Fish Consumption Information Dissemination Campaign Within an Integrated Health System: Learnings From ChooseYourFish.

INTRODUCTION/OBJECTIVES: Safe fish consumption is important for people who are or could become pregnant. A health system in Minnesota partnered with the Minnesota Department of Health to develop and disseminate messages to promote safe fish consumption for this population via the ChooseYourFish initiative. The ChooseYourFish message was delivered through 5 channels: the Healthy Pregnancy Program (HPP) with phone-based coaching, a clinic brochure, in the clinic after visit summary (AVS), direct mailing of the brochure with a letter, and in images on clinic waiting room monitors. METHODS: We designed a pragmatic evaluation to understand the likelihood that each channel would result in awareness of the message and increase a recipient's intent to act on the information. We surveyed 1050 women aged 18 to 40 in March-May 2020. Results are reported with descriptive statistics. RESULTS: The survey was completed by 524 respondents (51%). Respondents receiving the ChooseYourFish message through any channel except clinic monitors reported a higher awareness of recommendations about eating fish (42%-56%) than respondents in the no-message comparison group (21%). The after visit summary and Healthy Pregnancy Program channels had more confidence in following recommendations (50%-54%) and showed more intention to eat fish (61%-62%) compared to lower-intensity channels (24%-31% and 19%-32%, respectively). CONCLUSIONS: Messages delivered by an often-trusted source (eg, healthcare provider) were more likely to increase confidence and intent. Despite the trend toward online health information, physical brochures still have large reach. Repetition of exposure may be important. Because all communication channels have advantages and drawbacks, using multiple delivery channels is appropriate in communication campaigns.

30-year Cardiovascular Disease Risk for Young Adults with Serious Mental Illness.

Objective: To estimate 30-year CVD risk and modifiable risk factors in young adults with serious mental illness (SMI) versus those without, and assess variations in CVD risk by race, ethnicity, and sex. Method: In this cross-sectional study, we estimated and compared the Framingham 30-year CVD risk score and individual modifiable CVD risk factors in young adult (20-39 years) primary care patients with and without SMI at two US healthcare systems (January 2016-Septemeber 2018). Interaction terms assessed whether the SMI-risk association differed across demographic groups. Results: Covariate-adjusted 30-year CVD risk was significantly higher for those with (n=4228) versus those without (n=155,363) SMI (RR 1.28, 95% CI [1.26, 1.30]). Patients with SMI had higher rates of hypertension (OR 2.02 [1.7, 2.39]), diabetes (OR 3.14 [2.59, 3.82]), obesity (OR 1.93 [1.8, 2.07]), and smoking (OR 4.94 [4.6, 5.36]). The increased 30-year CVD risk associated with SMI varied significantly by race and sex: there was an 8% higher risk in Black compared to White patients (RR 1.08, [1.04, 1.12]) and a 9% lower risk in men compared to women (RR 0.91 [0.88, 0.94]). Conclusions: Young adults with SMI are at increased 30-year risk of CVD, and further disparities exist for Black individuals and women.

The potential impact of clinical decision support on nonwaivered primary care clinicians' prescribing of buprenorphine.

Elimination of the X-waiver increased potential buprenorphine prescribers 13-fold, but growth in prescribing will likely be much lower. We explored self-assessments of nonwaivered primary care clinicians (PCCs) for factors affecting their likelihood to prescribe buprenorphine were the X-waiver eliminated (since realized January 2023) and the potential impacts of a clinical decision-support (CDS) tool for opioid use disorder (OUD). Cross-sectional survey data were obtained between January 2021 and March 2022 from 305 nonwaivered PCCs at 3 health systems. Factors explored were patient requests for buprenorphine, PCC access to an OUD-CDS, and PCC confidence and abilities for 5 OUD-care activities. Relationships were described using descriptive statistics and odds ratios. Only 26% of PCCs were more likely to prescribe buprenorphine upon patient request, whereas 63% were more likely to prescribe with the OUD-CDS. PCC confidence and abilities for some OUD-care activities were associated with increased prescribing likelihood from patient requests, but none were associated with the OUD-CDS. The OUD-CDS may increase buprenorphine prescribing for PCCs less likely to prescribe upon patient request. Future research is needed to develop interventions that increase PCC buprenorphine prescribing. Clinical trial registration: ClinicalTrials.gov. Identifier: NCT04198428. Clinical trial name: Clinical Decision Support for Opioid Use Disorders in Medical Settings (Compute 2.0).

Medically Attended Acute Adverse Events in Pregnant People After Coronavirus Disease 2019 (COVID-19) Booster Vaccination.

In this multisite, observational, matched cohort study of more than 80,000 pregnant people, receipt of an mRNA monovalent coronavirus disease 2019 (COVID-19) booster vaccination in pregnancy was not associated with increased risk for thrombocytopenia, myocarditis, venous thromboembolism, ischemic stroke, or other serious adverse events within 21 or 42 days after booster vaccination. The mRNA monovalent COVID-19 booster in pregnancy was associated with an increased risk for medically attended malaise or fatigue within 7 days of vaccination (adjusted rate ratio [aRR] 3.64, 95% CI 2.42-5.48) and lymphadenopathy or lymphadenitis within 21 days (aRR 3.25, 95% CI 1.67-6.30) or 42 days (aRR 2.18, 95% CI 1.33-3.58) of vaccination. Our findings are consistent with prior evaluations of the primary COVID-19 vaccine series and are reassuring with respect to COVID-19 booster vaccination in pregnancy.

COVID-19 Booster Vaccination in Early Pregnancy and Surveillance for Spontaneous Abortion.

Importance: Adherence to COVID-19 booster vaccine recommendations has lagged in pregnant and nonpregnant adult populations. One barrier to booster vaccination is uncertainty regarding the safety of booster doses among pregnant people. Objective: To evaluate whether there is an association between COVID-19 booster vaccination during pregnancy and spontaneous abortion. Design, Setting, and Participants: This observational, case-control, surveillance study evaluated people aged 16 to 49 years with pregnancies at 6 to 19 weeks' gestation at 8 health systems in the Vaccine Safety Datalink from November 1, 2021, to June 12, 2022. Spontaneous abortion cases and ongoing pregnancy controls were evaluated during consecutive surveillance periods, defined by calendar time. Exposure: Primary exposure was receipt of a third messenger RNA (mRNA) COVID-19 vaccine dose within 28 days before spontaneous abortion or index date (midpoint of surveillance period in ongoing pregnancy controls). Secondary exposures were third mRNA vaccine doses in a 42-day window or any COVID-19 booster in 28- and 42-day windows. Main Outcomes and Measures: Spontaneous abortion cases and ongoing pregnancy controls were identified from electronic health data using a validated algorithm. Cases were assigned to a single surveillance period based on pregnancy outcome date. Eligible ongoing pregnancy time was assigned to 1 or more surveillance periods as an ongoing pregnancy-period control. Generalized estimating equations were used to estimate adjusted odds ratios (AOR) with gestational age, maternal age, antenatal visits, race and ethnicity, site, and surveillance period as covariates and robust variance estimates to account for inclusion of multiple pregnancy periods per unique pregnancy. Results: Among 112 718 unique pregnancies included in the study, the mean (SD) maternal age was 30.6 (5.5) years. Pregnant individuals were Asian, non-Hispanic (15.1%); Black, non-Hispanic (7.5%); Hispanic (35.6%); White, non-Hispanic (31.2%); and of other or unknown (10.6%); and 100% were female. Across eight 28-day surveillance periods, among 270 853 ongoing pregnancy-period controls, 11 095 (4.1%) had received a third mRNA COVID-19 vaccine in a 28-day window; among 14 226 cases, 553 (3.9%) had received a third mRNA COVID-19 vaccine within 28 days of the spontaneous abortion. Receipt of a third mRNA COVID-19 vaccine was not associated with spontaneous abortion in a 28-day window (AOR, 0.94; 95% CI, 0.86-1.03). Results were consistent when using a 42-day window (AOR, 0.97; 95% CI, 0.90-1.05) and for any COVID-19 booster in a 28-day (AOR, 0.94; 95% CI, 0.86-1.02) or 42-day (AOR, 0.96; 95% CI, 0.89-1.04) exposure window. Conclusions and Relevance: In this case-control surveillance study, COVID-19 booster vaccination in pregnancy was not associated with spontaneous abortion. These findings support the safety of recommendations for COVID-19 booster vaccination, including in pregnant populations.

Design of a pragmatic clinical trial to improve screening and treatment for opioid use disorder in primary care.

BACKGROUND: Opioid-related deaths continue to rise in the U.S. A shared decision-making (SDM) system to help primary care clinicians (PCCs) identify and treat patients with opioid use disorder (OUD) could help address this crisis. METHODS: In this cluster-randomized trial, primary care clinics in three healthcare systems were randomized to receive or not receive access to an OUD-SDM system. The OUD-SDM system alerts PCCs and patients to elevated risk of OUD and supports OUD screening and treatment. It includes guidance on OUD screening and diagnosis, treatment selection, starting and maintaining patients on buprenorphine for waivered clinicians, and screening for common comorbid conditions. The primary study outcome is, of patients at high risk for OUD, the percentage receiving an OUD diagnosis within 30 days of index visit. Additional outcomes are, of patients at high risk for or with a diagnosis of OUD, (a) the percentage receiving a naloxone prescription, or (b) the percentage receiving a medication for OUD (MOUD) prescription or referral to specialty care within 30 days of an index visit, and (c) total days covered by a MOUD prescription within 90 days of an index visit. RESULTS: The intervention started in April 2021 and continues through December 2023. PCCs and patients in 90 clinics are included; study results are expected in 2024. CONCLUSION: This protocol paper describes the design of a multi-site trial to help PCCs recognize and treat OUD. If effective, this OUD-SDM intervention could improve screening of at-risk patients and rates of OUD treatment for people with OUD.