Pioneering Just-in-Time (JIT) Strategy for Accelerating Raman Method Development and Implementation for Biologic Continuous Manufacturing.

Raman spectroscopy is a popular process analytical technology (PAT) tool that has been increasingly used to monitor and control the monoclonal antibody (mAb) manufacturing process. Although it allows the characterization of a variety of quality attributes by developing chemometric models, a large quantity of representative data is required, and hence, the model development process can be time-consuming. In recent years, the pharmaceutical industry has been expediting new drug development in order to achieve faster delivery of life-changing drugs to patients. The shortened development timelines have impacted the Raman application, as less time is allowed for data collection. To address this problem, an innovative Just-in-Time (JIT) strategy is proposed with the goal of reducing the time needed for Raman model development and ensuring its implementation. To demonstrate its capabilities, a proof-of-concept study was performed by applying the JIT strategy to a biologic continuous process for producing monoclonal antibody products. Raman spectroscopy and online two-dimensional liquid chromatography (2D-LC) were integrated as a PAT analyzer system. Raman models of antibody titer and aggregate percentage were calibrated by chemometric modeling in real-time. The models were also updated in real-time using new data collected during process monitoring. Initial Raman models with adequate performance were established using data collected from two lab-scale cell culture batches and subsequently updated using one scale-up batch. The JIT strategy is capable of accelerating Raman method development to monitor and guide the expedited biologics process development.

National trends in the treatment of adult diffuse midline gliomas: a rare clinical scenario.

PURPOSE: Diffuse midline gliomas (DMG) include all midline gliomas with a point mutation to the histone H3 gene resulting in the substitution of a lysine with a methionine (K27M). These tumors are classified as World Health Organization grade 4 with a mean survival between 9- and 19-months following diagnosis. There is currently no standard of care for DMG, and palliative radiation therapy has been proven to only extend survival by months. Our current study aims to report current treatment trends and predictors of the overall survival of DMG. METHODS: We searched the National Cancer Database for adult patients treated for DMG from 2016 to 2020. Patients were required to have been treated with primary radiation directed at the brain with or without concurrent chemotherapy. Univariable and multivariable Cox regressions were used to determine predictors of overall survival. RESULTS: Of the 131 patients meeting the inclusion criteria, 113 (86%) received radiation and chemotherapy. Based on multivariable Cox regression, significant predictors of survival were Charlson-Deyo comorbidity index and race. Patients with a Charlson-Deyo score of 1 had 2.72 times higher odds of mortality than those with a score of 0. Patients not identifying as White or Black had 2.67 times higher odds of mortality than those identifying as White. The median survival for all patients was 19 months. CONCLUSIONS: Despite being considered ineffective, chemotherapy is still administered in most adult patients diagnosed with DMG. Significant predictors of survival were Charlson-Deyo comorbidity index and race.

Birth Prevalence of Sickle Cell Disease and County-Level Social Vulnerability - Sickle Cell Data Collection Program, 11 States, 2016-2020.

Sickle cell disease (SCD) remains a public health priority in the United States because of its association with complex health needs, reduced life expectancy, lifelong disabilities, and high cost of care. A cross-sectional analysis was conducted to calculate the crude and race-specific birth prevalence for SCD using state newborn screening program records during 2016-2020 from 11 Sickle Cell Data Collection program states. The percentage distribution of birth mother residence within Social Vulnerability Index quartiles was derived. Among 3,305 newborns with confirmed SCD (including 57% with homozygous hemoglobin S or sickle ß-null thalassemia across 11 states, 90% of whom were Black or African American [Black], and 4% of whom were Hispanic or Latino), the crude SCD birth prevalence was 4.83 per 10,000 (one in every 2,070) live births and 28.54 per 10,000 (one in every 350) non-Hispanic Black newborns. Approximately two thirds (67%) of mothers of newborns with SCD lived in counties with high or very high levels of social vulnerability; most mothers lived in counties with high or very high levels of vulnerability for racial and ethnic minority status (89%) and housing type and transportation (64%) themes. These findings can guide public health, health care systems, and community program planning and implementation that address social determinants of health for infants with SCD. Implementation of tailored interventions, including increasing access to transportation, improving housing, and advancing equity in high vulnerability areas, could facilitate care and improve health outcomes for children with SCD.

Preoperative Depression Status and 5 Year Metabolic and Bariatric Surgery Outcomes in the PCORnet Bariatric Study Cohort.

OBJECTIVE: To examine whether depression status before metabolic and bariatric surgery (MBS) influenced 5-year weight loss, diabetes, and safety/utilization outcomes in the PCORnet Bariatric Study. SUMMARY OF BACKGROUND DATA: Research on the impact of depression on MBS outcomes is inconsistent with few large, long-term studies. METHODS: Data were extracted from 23 health systems on 36,871 patients who underwent sleeve gastrectomy (SG; n=16,158) or gastric bypass (RYGB; n=20,713) from 2005-2015. Patients with and without a depression diagnosis in the year before MBS were evaluated for % total weight loss (%TWL), diabetes outcomes, and postsurgical safety/utilization (reoperations, revisions, endoscopy, hospitalizations, mortality) at 1, 3, and 5 years after MBS. RESULTS: 27.1% of SG and 33.0% of RYGB patients had preoperative depression, and they had more medical and psychiatric comorbidities than those without depression. At 5 years of follow-up, those with depression, versus those without depression, had slightly less %TWL after RYGB, but not after SG (between group difference = 0.42%TWL, P = 0.04). However, patients with depression had slightly larger HbA1c improvements after RYGB but not after SG (between group difference = - 0.19, P = 0.04). Baseline depression did not moderate diabetes remission or relapse, reoperations, revision, or mortality across operations; however, baseline depression did moderate the risk of endoscopy and repeat hospitalization across RYGB versus SG. CONCLUSIONS: Patients with depression undergoing RYGB and SG had similar weight loss, diabetes, and safety/utilization outcomes to those without depression. The effects of depression were clinically small compared to the choice of operation.

Challenges in the Clinical Recognition of Acute Flaccid Myelitis and its Implications.

OBJECTIVES: To explore the challenges in diagnosing acute flaccid myelitis (AFM) and evaluate clinical features and treatment paradigms associated with under recognition. STUDY DESIGN: This was a retrospective multicenter study of pediatric patients (≤18 years) who were diagnosed with AFM from 2014 to 2018 using the Centers for Disease Control and Prevention's case definition. RESULTS: In 72% of the cases (126 of 175), AFM was not considered in the initial differential diagnosis (n = 108; 61.7%) and/or the patient was not referred for acute care (n = 90; 51.4%) at the initial clinical encounter, and this did not improve over time. Although many features of the presentation were similar in those initially diagnosed with AFM and those who were not; preceding illness, constipation, and reflexes differed significantly between the 2 groups. Patients with a non-AFM initial diagnosis more often required ventilatory support (26.2% vs 12.2%; OR, 0.4; 95% CI, 0.2-1.0; P = .05). These patients received immunomodulatory treatment later (3 days vs 2 days after neurologic symptom onset; 95% CI, -2 to 0; P = .05), particularly intravenous immunoglobulin (5 days vs 2 days; 95% CI, -4 to -2; P < .001). CONCLUSIONS: Delayed recognition of AFM is concerning because of the risk for respiratory decompensation and need for intensive care monitoring. A non-AFM initial diagnosis was associated with delayed treatment that could have a clinical impact, particularly as new treatment options emerge.

Acute flaccid myelitis: cause, diagnosis, and management.

Acute flaccid myelitis (AFM) is a disabling, polio-like illness mainly affecting children. Outbreaks of AFM have occurred across multiple global regions since 2012, and the disease appears to be caused by non-polio enterovirus infection, posing a major public health challenge. The clinical presentation of flaccid and often profound muscle weakness (which can invoke respiratory failure and other critical complications) can mimic several other acute neurological illnesses. There is no single sensitive and specific test for AFM, and the diagnosis relies on identification of several important clinical, neuroimaging, and cerebrospinal fluid characteristics. Following the acute phase of AFM, patients typically have substantial residual disability and unique long-term rehabilitation needs. In this Review we describe the epidemiology, clinical features, course, and outcomes of AFM to help to guide diagnosis, management, and rehabilitation. Future research directions include further studies evaluating host and pathogen factors, including investigations into genetic, viral, and immunological features of affected patients, host-virus interactions, and investigations of targeted therapeutic approaches to improve the long-term outcomes in this population.

Lack of clinically relevant differences in safety and pharmacokinetics after second-dose administration of intranasal diazepam within 4 h for acute treatment of seizure clusters: A population analysis.

OBJECTIVE: Current diazepam nasal spray labeling requires waiting 4 h before administering a second dose. The objective of the current analyses was to examine safety and pharmacokinetic profiles of second doses of diazepam nasal spray given 0-4 h after the first dose. METHODS: Two datasets were analyzed. The first, a long-term, repeat-dose safety study of diazepam nasal spray, compared rates of treatment-emergent adverse events (TEAEs), serious TEAEs, and treatment-related TEAEs for patients receiving ≥1 second dose ≤4 h versus all second doses >4 h after the first. The second was a population pharmacokinetic analysis using data from three phase 1 studies to model drug exposure when a second dose of diazepam nasal spray was administered across multiple time points (1 min-4 h) following the first dose. RESULTS: In the repeat-dose safety study, a second dose of diazepam nasal spray was administered ≤24 h after the first to treat 485 seizure clusters in 79 patients. Rates of TEAEs were similar between patients receiving ≥1 second dose in ≤4 h (89.5%, n = 38) compared with >4-24 h only (80.5%, n = 41). The most common treatment-related TEAEs were associated with nasal discomfort, which was mild or moderate and transient. There were no reports of respiratory or cardiac depression. The pharmacokinetic simulations of second doses predicted comparable elevations of plasma diazepam concentrations with administrations across a range of intervals after the first dose (1 min-4 h). SIGNIFICANCE: These data indicate that the safety and pharmacokinetic profiles of a second dose of diazepam nasal spray administered within 4 h of the first dose are consistent with those associated with current labeling. This is potentially important for patients with seizure clusters who have a recurrent seizure within 4 h of first treatment and might benefit from immediate retreatment to reduce the risk of progression to status epilepticus.

Using advanced racial and ethnic identity demographics to improve surveillance of work-related conditions in an occupational clinic setting.

BACKGROUND: Although racial and ethnic identities are associated with a multitude of disparate medical outcomes, surveillance of these subpopulations in the occupational clinic setting could benefit enormously from a more detailed and nuanced recognition of racial and ethnic identity. METHODS: The research group designed a brief questionnaire to capture several dimensions of this identity and collected data from patients seen for work-related conditions in four occupational medicine clinics from May 2019 through March 2020. Responses were used to calculate the sensitivity and specificity of extant racial/ethnic identity data within our electronic health records system, and were compared to participants' self-reported industry and occupation, coded according to North American Industry Classification System and Standard Occupational Classification System listings. RESULTS: Our questionnaire permitted collection of data that defined our patients' specific racial/ethnic identity with far greater detail, identified patients with multiple ethnic identities, and elicited their preferred language. Response rate was excellent (94.2%, n = 773). Non-White participants frequently selected a racial/ethnic subcategory (78.1%-92.2%). Using our race/ethnicity data as a referent, the electronic health record (EHR) had a high specificity (>87.1%), widely variable sensitivity (11.8%-82.2%), and poorer response rates (75.1% for race, 82.5% for ethnicity, as compared to 93.8% with our questionnaire). Additional analyses revealed some industries and occupations disproportionately populated by patients of particular racial/ethnic identities. CONCLUSIONS: Our project demonstrates the usefulness of a questionnaire which more effectively identifies racial/ethnic subpopulations in an occupational medicine clinic, permitting far more detailed characterization of their occupations, industries, and diagnoses.

Assessing the implementation of a clinical decision support tool in primary care for diabetes prevention: a qualitative interview study using the Consolidated Framework for Implementation Science.

BACKGROUND: In this paper we describe the use of the Consolidated Framework for Implementation Research (CFIR) to study implementation of a web-based, point-of-care, EHR-linked clinical decision support (CDS) tool designed to identify and provide care recommendations for adults with prediabetes (Pre-D CDS). METHODS: As part of a large NIH-funded clinic-randomized trial, we identified a convenience sample of interview participants from 22 primary care clinics in Minnesota, North Dakota, and Wisconsin that were randomly allocated to receive or not receive a web-based EHR-integrated prediabetes CDS intervention. Participants included 11 clinicians, 6 rooming staff, and 7 nurse or clinic managers recruited by study staff to participate in telephone interviews conducted by an expert in qualitative methods. Interviews were recorded and transcribed, and data analysis was conducted using a constructivist version of grounded theory. RESULTS: Implementing a prediabetes CDS tool into primary care clinics was useful and well received. The intervention was integrated with clinic workflows, supported primary care clinicians in clearly communicating prediabetes risk and management options with patients, and in identifying actionable care opportunities. The main barriers to CDS use were time and competing priorities. Finally, while the implementation process worked well, opportunities remain in engaging the care team more broadly in CDS use. CONCLUSIONS: The use of CDS tools for engaging patients and providers in care improvement opportunities for prediabetes is a promising and potentially effective strategy in primary care settings. A workflow that incorporates the whole care team in the use of such tools may optimize the implementation of CDS tools like these in primary care settings. Trial registration Name of the registry: Clinicaltrial.gov. TRIAL REGISTRATION NUMBER: NCT02759055. Date of registration: 05/03/2016. URL of trial registry record: https://clinicaltrials.gov/ct2/show/NCT02759055 Prospectively registered.

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.

"We will do whatever it takes": Understanding Socioecological Level Influences on Hmong-American Adolescents and Parents' Perceptions of the Human Papillomavirus Vaccine.

Human papillomavirus (HPV) vaccination completion rates in Asian-American populations are substantially lower than most White Americans. Our objective was to identify the knowledge, perceptions, and decision-making processes about HPV vaccinations in the Hmong population, an Asian-American group with increased risks of HPV-related cancers. We conducted eight focus groups with Hmong adolescents (n = 12) and parents (n = 13) to learn about barriers, facilitators, and decision-making processes regarding general vaccinations and the HPV vaccine. The focus group results were analyzed using thematic analysis, informed by the socioecological model and asset lens. Findings showed that at the individual level, Hmong adolescents and parents had low HPV and HPV vaccine awareness levels (barrier) and strong desires to learn about HPV and the HPV vaccine (facilitator). Community-level barriers included salient narratives about traumatic experiences with vaccines and vaccine research, while facilitators included strong community connections. At the institutional level, barriers included structural constraints in health care settings, while facilitators included ease of obtaining vaccines at school-based clinics and provider authoritative decision-making. Additionally, a range of decision-making processes between parents, adolescents, and providers were present, with parents expressing a strong appeal to engage in more shared decision-making with providers. A linguistically and culturally specific HPV educational program for Hmong adolescents and parents could address the barriers and build on facilitators and assets to promote HPV vaccine uptake in this growing Asian-American community.

Final results from a Phase 3, long-term, open-label, repeat-dose safety study of diazepam nasal spray for seizure clusters in patients with epilepsy.

OBJECTIVE: A Phase 3 open-label safety study (NCT02721069) evaluated long-term safety of diazepam nasal spray (Valtoco) in patients with epilepsy and frequent seizure clusters. METHODS: Patients were 6-65 years old with diagnosed epilepsy and seizure clusters despite stable antiseizure medications. The treatment period was 12 months, with study visits at Day 30 and every 60 days thereafter, after which patients could elect to continue. Doses were based on age and weight. Seizure and treatment information was recorded in diaries. Treatment-emergent adverse events (TEAEs), nasal irritation, and olfactory changes were recorded. RESULTS: Of 163 patients in the safety population, 117 (71.8%) completed the study. Duration of exposure was ≥12 months for 81.6% of patients. There was one death (sudden unexpected death in epilepsy) and one withdrawal owing to a TEAE (major depression), both considered unlikely to be related to treatment. Diazepam nasal spray was administered 4390 times for 3853 seizure clusters, with 485 clusters treated with a second dose within 24 h; 53.4% of patients had monthly average usage of one to two doses, 41.7% two to five doses, and 4.9% more than five doses. No serious TEAEs were considered to be treatment related. TEAEs possibly or probably related to treatment (n = 30) were most commonly nasal discomfort (6.1%); headache (2.5%); and dysgeusia, epistaxis, and somnolence (1.8% each). Only 13 patients (7.9%) showed nasal irritation, and there were no relevant olfactory changes. The safety profile of diazepam nasal spray was generally similar across subgroups based on age, monthly usage, concomitant benzodiazepine therapy, or seasonal allergy/rhinitis. SIGNIFICANCE: In this large open-label safety study, the safety profile of diazepam nasal spray was consistent with the established profile of rectal diazepam, and the high retention rate supports effectiveness in this population. A second dose was used in only 12.6% of seizure clusters.

Evaluation of diazepam nasal spray in patients with epilepsy concomitantly using maintenance benzodiazepines: An interim subgroup analysis from a phase 3, long-term, open-label safety study.

OBJECTIVE: Diazepam nasal spray (Valtoco), indicated for acute treatment of frequent seizure activity (seizure clusters) in patients with epilepsy ≥6 years of age, is designed to be a rapid, noninvasive, socially acceptable route of administration. This interim analysis evaluated the safety profile of diazepam nasal spray in patients with and without concomitant use of benzodiazepines, with use of a second dose for a seizure cluster as a proxy for effectiveness. METHODS: A long-term, phase 3, open-label safety study enrolled patients with epilepsy who had seizures despite a stable antiseizure medication regimen. RESULTS: Among 175 patients enrolled by October 31, 2019, a total of 158 were treated with diazepam nasal spray (aged 6-65 years; 53.8% female). Of those, 119 (75.3%) received concomitant benzodiazepines (60, chronic; 59, intermittent); 39 (24.7%) did not. Use of a second dose was similar in patients using chronic concomitant benzodiazepines (second dose in 11.1% [144/1299]) and those with no concomitant benzodiazepines (second dose in 10.3% [41/398]). Treatment emergent adverse events (TEAEs) occurred for 80.0% with chronic use of concomitant benzodiazepines and 61.5% without. Cardiorespiratory depression was not reported, and no serious TEAEs were treatment related. Study retention was high: 83.3% in the chronic benzodiazepine group and 76.9% in the no-benzodiazepine group. Findings were similar in a sub-analysis of patients who were (n = 44) or were not (n = 75) taking clobazam. SIGNIFICANCE: This analysis of patients from a long-term study shows a similar safety profile of diazepam nasal spray in patients with and without concomitant benzodiazepines, and consistent with the established profile for diazepam. Use of a single dose of diazepam nasal spray and high study retention rates suggest the effectiveness of diazepam nasal spray in patients irrespective of chronic daily benzodiazepine use. Results were similar in the clobazam sub-analysis. These results support the safety and effectiveness of diazepam nasal spray in patients with concomitant benzodiazepine use.

Lack of observed impact of history or concomitant treatment of seasonal allergies or rhinitis on repeated doses of diazepam nasal spray administered per seizure episode in a day, safety, and tolerability: Interim results from a phase 3, open-label, 12-month repeat-dose safety study.

Intranasal formulations are commonly used for drug delivery, and the literature has shown that seasonal allergies do not affect nasal administration of some agents. Diazepam nasal spray (Valtoco®) is a proprietary intranasal formulation with n-dodecyl-beta-d-maltoside (Intravail® A3) that is indicated for acute treatment of seizure clusters in patients with epilepsy aged 6 years and older. The analysis presented here is from an interim cutoff of a phase 3 open-label study evaluating the safety and tolerability of diazepam nasal spray. This analysis assessed whether seasonal allergies alter control of seizures with an intranasal formulation, using administration of a second dose as a surrogate efficacy endpoint. Of 158 evaluated patients with epilepsy having seizures despite a stable anti-seizure regimen, 62 patients had medical histories that included seasonal allergies or rhinitis. The results of this analysis show that seasonal allergies did not appear to influence use of a second dose; the groups of patients with and without a history of seasonal allergies both presented with low rates of seizure episodes for which a second dose was used, which suggests that there is not a major difference in pattern of use. Diazepam nasal spray demonstrated a similar safety and tolerability profile in patients with and without a history of seasonal allergies.

Lack of observed tolerance to diazepam nasal spray (Valtoco®) after long-term rescue therapy in patients with epilepsy: Interim results from a phase 3, open-label, repeat-dose safety study.

OBJECTIVE: Tolerance is a known consideration for maintenance use of benzodiazepines and other antiseizure drugs; however, clinical experience suggests that tolerance may not be anticipated with long-term intermittent use of benzodiazepines as rescue therapy. Diazepam nasal spray (Valtoco®) is a proprietary intranasal formulation approved for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity (ie, seizure clusters, acute repetitive seizures) in patients with epilepsy aged ≥6 years. Reported here are exploratory analyses investigating whether there was evidence of development of tolerance in an interim analysis of a long-term, phase 3, open-label safety study of diazepam nasal spray. METHODS: Patients and care partners were trained to administer 5, 10, 15, or 20 mg of diazepam nasal spray (age- and weight-based dosing), with a second dose administered 4-12 hours later if needed. A series of analyses were performed to assess evidence of tolerance using 2 equal, adjacent time periods and data for each patient to compare the proportion of events for which second doses of diazepam nasal spray (as a proxy for effectiveness) were administered in period 1 compared with period 2. RESULTS: A total of 175 patients were enrolled at interim cutoff, and 158 were treated with diazepam nasal spray for 3370 seizure-cluster events. For 73.4% of patients, duration of exposure to diazepam nasal spray was ≥12 months. A total of 191 analyses were conducted; the proportion of analyses in which second doses in period 2 were lower than in period 1 was 72.8%. Only 5 analyses showed nominally statistically significant changes (P < 0.05); this is fewer than expected by chance, and these differences were not directionally consistent. There was no safety signal with continued use. CONCLUSIONS: These analyses found no statistical evidence of tolerance with the use of diazepam nasal spray over time based on use of a second dose in an initial period of the study compared with a subsequent period for each patient. These results are in agreement with prior studies of benzodiazepine rescue therapy.

Management and short-term outcomes of neonates born to mothers with active perinatal SARS-CoV-2 infection.

OBJECTIVE: We report here on the management and outcomes of neonates born to mothers with active perinatal SARS-CoV-2 infection. STUDY DESIGN: In this prospective study, eligible neonates were enrolled in a database to track in-hospital outcomes and followed up outpatient periodically till 2 months of age to assess for late onset symptoms of infection. RESULTS: From April 2020 to February 2021, 67 mothers with perinatal SARS-CoV-2 infection and 70 at-risk neonates were included. Two neonates (3%) tested positive for SARS-CoV-2 within 48 h of life but remained asymptomatic during hospitalization and at all follow-up periods. Three infants were reported to have a febrile illness in 2 months follow up period, none of which was attributable to SARS-CoV-2. CONCLUSION: Our data supports the emerging evidence which describes a probable low risk of vertical transmission of SARS-CoV-2. We also demonstrate a low risk of post-natal transmission or late-onset symptomatic infection with SARS-CoV-2.

The effects of financial incentives on diabetes prevention program attendance and weight loss among low-income patients: the We Can Prevent Diabetes cluster-randomized controlled trial.

BACKGROUND: Penetration and participation of real life implementation of lifestyle change programs to prevent type 2 diabetes has been challenging. This is particularly so among low income individuals in the United States. The purpose of this study is to examine the effectiveness of financial incentives on attendance and weight loss among Medicaid beneficiaries participating in the 12-month Diabetes Prevention Program (DPP). METHODS: This is a cluster-randomized controlled trial with two financial incentive study arms and an attention control study arm. Medicaid beneficiaries with prediabetes from 13 primary care clinics were randomly assigned to individually earned incentives (IND; 33 groups; n = 309), a hybrid of individual- and group-earned incentives (GRP; 30 groups; n = 259), and an attention control (AC; 30 groups; n = 279). Up to $520 in incentives could be earned for attaining attendance and weight loss goals over 12 months. Outcomes are percent weight loss from baseline, achieving 5% weight loss from baseline, and attending 75% of core and 75% of maintenance DPP sessions. Linear mixed models were used to examine weight change and attendance rates over the 16 weeks and 12 months. RESULTS: The percent weight change at 16 weeks for the IND, GRP, and AC participants were similar, at - 2.6, - 3.1%, and - 3.4%, respectively. However, participants achieving 5% weight loss in the IND, GRP, and AC groups was 21.5, 24.0% (GRP vs AC, P < 0.05), and 15.2%. Attendance at 75% of the DPP core sessions was significantly higher among IND (60.8%, P < 0.001) and GRP (64.0%, P < 0.001) participants than among AC (38.6%) participants. Despite substantial attrition over time, attendance at 75% of the DPP maintenance sessions was also significantly higher among IND (23.0%, P < 0.001) and GRP (26.1%, P < 0.001) participants than among AC (11.0%) participants. CONCLUSIONS: Financial incentives can improve the proportion of Medicaid beneficiaries attending the 12-month DPP and achieving at least 5% weight loss. TRIAL REGISTRATION: ClinicalTrials.gov NCT02422420 ; retrospectively registered April 21, 2015.

Locations and Mucosal Lesions Responsible for Major Gastrointestinal Bleeding in Patients on Warfarin or Dabigatran.

BACKGROUND AND AIM: Different oral anticoagulants may be associated with gastrointestinal bleeding (GIB) from different locations or mucosal lesions. We aimed to test this hypothesis. METHODS: Two blinded gastroenterologists independently analyzed source documents from the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial of dabigatran 150 mg BID (D150), dabigatran 110 mg BID (D110) versus warfarin in non-valvular atrial fibrillation (NVAF). RESULTS: Major GIB events (total n = 546) and life-threatening GIB events (n = 258) were more common with D150 versus warfarin (RR 1.57 [1.28-1.92] and RR 1.62 [1.20-2.18], respectively) and similar for D110 compared to warfarin (RR 1.11 [0.89-1.38] and RR 1.16 [0.84-1.61], respectively). Fatal bleeding was similarly rare across treatment groups. Lower GI major bleeding and life-threatening bleeding were more common with D150 compared to warfarin (RR 2.23 [1.47, 3.38] and RR 2.64 [1.36, 5.13], respectively) and with D110 compared to warfarin (RR 1.78 [1.16, 2.75] and RR 2.00 [1.00, 4.00], respectively). MGIB from colonic angiodysplasia was increased with dabigatran versus warfarin (P < 0.01 for both dose comparisons). Subacute and chronic MGIB events were more common with D150 than with warfarin (RR 1.72 [1.06, 2.78] and RR 1.66 [1.12, 2.45], respectively), as were hematochezia or melena (RR 1.67 [1.18, 2.36] and RR 1.72 [1.20, 2.47], respectively). CONCLUSIONS: In a chronic NVAF population, D150 but not D110 is associated with increased major and life-threatening GI bleeding in comparison with warfarin. At both dabigatran doses, increased bleeding from the colorectum, in particular from angiodysplasia, is seen.

Male Undergraduates' HPV Vaccination Behavior: Implications for Achieving HPV-Associated Cancer Equity.

Despite the availability of the human papillomavirus (HPV) vaccine for males, uptake of the vaccine has been low, particularly among young adult males. This study aimed to investigate the levels of HPV vaccination and predictors of HPV vaccine completion in college men ages 18-26. We analyzed data from the 2015 College Student Health Survey, which was administered at 17 post-secondary institutions in Midwest areas. We included only responses from male participants who were ages 18-26 years old, resulting in a sample size of 2516. We used Andersen's Behavioral Model of Health Services Utilization to guide our study design. Multivariate logistic regression was used to examine predictors of HPV vaccine receipt. College-aged males in our sample had a HPV vaccine completion rate of 50.0%. Male students who were younger, had at least one parent who held a graduate degree, had initiated sex, and were enrolled at a private 4-year institution were more likely to have been vaccinated. These findings suggest that HPV vaccination in college-aged men are low. Efforts are needed to increase HPV vaccination in male students who are older, from lower socioeconomic statuses, have not initiated sex, and enrolled at public institutions. Findings also indicate important gender disparities in vaccine uptake that must be addressed in order to achieve optimal vaccine uptake in college-aged males.

Understanding Primary Care Provider Attitudes and Behaviors Regarding Cardiovascular Disease Risk and Diabetes Prevention in the Northern Midwest.

IN BRIEF We sought to fill critical gaps in understanding primary care providers' (PCPs') beliefs regarding diabetes prevention and cardiovascular disease risk in the prediabetes population, including through comparison of attitudes between rural and non-rural PCPs. We used data from a 2016 cross-sectional survey sent to 299 PCPs practicing in 36 primary clinics that are part of a randomized control trial in a predominately rural northern Midwestern integrated health care system. Results showed a few significant, but clinically marginal, differences between rural and non-rural PCPs. Generally, PCPs agreed with the importance of screening for prediabetes and thoroughly and clearly discussing CV risk with high-risk patients.