Pregnancy Outcomes in the Ozanimod Clinical Development Program in Patients With Ulcerative Colitis, Crohn's Disease, and Relapsing Multiple Sclerosis.

This study evaluated pregnancy outcomes in patients with ulcerative colitis, Crohn's disease, or multiple sclerosis and in healthy volunteers treated with ozanimod. There was no increased incidence of fetal abnormalities or adverse pregnancy outcomes with ozanimod exposure during early pregnancy.

Predictors of Subspecialty Appointment Scheduling and Completion for Patients Referred From a Pediatric Primary Care Clinic.

Failure to complete subspecialty referrals decreases access to subspecialty care and may endanger patient safety. We conducted a retrospective analysis of new patient referrals made to the 14 most common referral departments at Boston Children's Hospital from January 1 to December 31, 2017. The sample included 2031 patient referrals. The mean wait time between referral and appointment date was 39.6 days. In all, 87% of referrals were scheduled and 84% of scheduled appointments attended, thus 73% of the original referrals were completed. In multivariate analysis, younger age, medical complexity, being a non-English speaker, and referral to a surgical subspecialty were associated with a higher likelihood of referral completion. Black and Hispanic/Latino race/ethnicity, living in a Census tract with Social Vulnerability Index (SVI) ≥ 90th percentile, and longer wait times were associated with a lower likelihood of appointment attendance. Future interventions should consider both health care system factors such as appointment wait times and community-level barriers to referral completion.

Understanding Caregiver Perspectives on an Electronic Consultation and Referral System.

This study examined caregiver impressions of an electronic consultation and referral (ECR) system. Participants included 56 caregivers of primary care patients referred through the ECR system. Semistructured interviews and surveys were conducted between August 2018 and April 2019. Transcripts were coded and themes developed using thematic content analysis. A total of 51% of caregivers stated that they would prefer to see their child's primary care provider (PCP) for a specialty issue if they could receive the same quality of care. All caregivers who received an electronic consult (n = 28) said that they would utilize that process again. Three themes emerged: (1) caregivers expect immediate action prior to or instead of a specialty referral; (2) caregiver preferences for PCP versus specialist are mediated by both child and provider characteristics; (3) caregiver attitudes toward the ECR system are influenced by external considerations and experiences with the system. Results suggest caregivers value enhanced communication and immediate access to specialty input facilitated by the ECR system.

Improving patient education for atopic dermatitis: A randomized controlled trial of a caregiver handbook.

BACKGROUND/OBJECTIVES: Patient education is important to families' ability to manage and cope with pediatric atopic dermatitis (AD). We evaluated whether an educational handbook could improve AD symptoms, caregiver confidence in AD management skills, and AD-related quality of life. METHODS: Caregivers of children with AD ages 1 month to 16 years were randomly assigned to the intervention arm (handbook in addition to standard AD management) or the control arm (standard management alone). Caregivers completed self-report outcome questionnaires prior to a clinical visit for AD and at 3-month follow-up. RESULTS: 175 caregivers completed questionnaires at baseline and follow-up. AD symptoms measured by the Patient-Oriented Eczema Measure (POEM) improved in both the handbook and control arms. However, the decrease in the mean POEM score in the handbook arm (-4.4, 95% CI [-5.8, -3.0]) did not differ from that in the control arm (-3.4, 95% CI [-4.8, -2.03]; P = .343). Change in quality of life did not differ between study arms. Among caregivers attending a new patient visit for AD, mean confidence scores (measured from 0 to 100) increased more in the handbook arm (67 [95% CI {60, 74}] to 83 [95% CI {77, 88}]) relative to the control arm (74 [95% CI {65, 82}] to 75 [95% CI {67, 83}]; P = .012). The majority of caregivers rated the handbook as helpful in managing the child's AD. CONCLUSIONS: Despite an adequate sample size, the handbook did not improve AD symptoms more than standard management alone. The handbook improved confidence in management skills for families attending new patient visits for AD.

Can Social Media Be Used as a Community-Building and Support Tool among Jewish Women Impacted by Breast and Ovarian Cancer? An Evidence-Based Observational Report.

About 1 in 40 Ashkenazi Jewish women carry a deleterious mutation in BRCA1/2 genes, predisposing them to hereditary breast/ovarian cancer (HBOC). Thus, efforts to prevent and control HBOC in the US must include sufficient outreach and education campaigns within and across the Jewish community. Social media (SM) is utilized in public health campaigns focused on cancer, but very little is known about the efficacy of those efforts when directed toward Jewish women at risk for ("previvors") and affected by ("survivors") HBOC. Here, we report on outcomes of a targeted SM campaign for this population, as led by a national not-for-profit HBOC advocacy organization. Mixed-methods data were obtained from n = 393 members of the community, including n = 20 key informants, and analyzed for engagement and satisfaction with its SM campaign and HBOC resources. Message recipients identified the SM campaign as helpful/meaningful (82%), of 'newsworthy' value (78%), and actionable/navigable (71%): interviews revealed that women were more likely to engage with SM if/when it featured stories relevant to their personal cancer experiences. SM is a valuable public health education tool to address the comprehensive cancer control and prevention needs of those previving and surviving with HBOC, including high-risk Jewish women.

An Innovative Model for Providing Dermatology Services Within Primary Care.

OBJECTIVE: Dermatologic complaints are common in outpatient pediatrics. However, pediatric dermatology specialty care can be difficult to access. We aimed to test the feasibility of co-locating dermatology services within primary care and increase the proportion of patients treated for basic skin complaints within the medical home while decreasing wait times. METHODS: The Rapid Assessment of Skin Health (RASH) clinic was created within a hospital-based primary care clinic in 11/2013. The clinic was staffed by 2 pediatricians trained in the dermatology department and supported with specialist advice as needed. Referral volume and wait times to dermatology and RASH clinic were tracked for visits between 11/1/12 and 10/31/18. A chart review was also conducted on a subset of RASH clinic visits. Primary care providers (PCPs) were surveyed about their experiences. RESULTS: Fifty-eight percent of patients referred for a dermatologic complaint were scheduled in RASH clinic. Wait times for new patient appointments in RASH clinic were significantly shorter than for new dermatology appointments in the previous 12 months (mean 36 days vs 65 days, P < .001). The monthly number of referrals to dermatology also decreased significantly after the RASH clinic opened (24/month vs 12/month, P < .001). Ten percent of RASH patients were referred on to dermatology. In a survey of PCPs (N = 67), 76% said the RASH clinic was "extremely/very helpful." CONCLUSIONS: Providing dermatologic care to low or moderate complexity patients within the medical home is feasible and leads to better access to care. This innovative model could be spread to other clinics and subspecialties.

Sucroferric Oxyhydroxide in Maintenance Hemodialysis: A Retrospective, Comparative Cohort Study.

RATIONALE & OBJECTIVE: High pill burden associates with reduced phosphate-binder adherence among dialysis patients, contributing to elevated serum phosphorus levels. We compared the real-world effectiveness of sucroferric oxyhydroxide (SO) versus other phosphate binders in hemodialysis patients over 2 years. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Adult in-center hemodialysis patients prescribed 2 years of uninterrupted SO therapy (maintenance SO; n = 222) compared with patients who discontinued SO therapy (discontinued SO; n = 596) within 90 days of first prescription and switched to other phosphate binder(s) for 2 years. EXPOSURES: Phosphate binders. OUTCOMES: Achievement of serum phosphorus levels ≤ 5.5 mg/dL, pill burden, and hospitalizations. ANALYTICAL APPROACH: Comparisons were made quarterly (Q1-Q8) between maintenance SO and discontinued SO using Poisson and mixed-effects linear regression. RESULTS: Patients achieving serum phosphorus levels ≤ 5.5 mg/dL increased from baseline in maintenance SO (46 [20.7%] to a maximum of 104 [46.8%; P < 0.001]) and discontinued SO (96 [16.1%] to a maximum of 201 [33.7%]; P < 0.001). 100 (45%) maintenance SO patients achieved target serum phosphorus levels at Q8 with 3.1 fewer pills per day from baseline (7.5 to 4.4 pills per day; P < 0.001), and 190 (31.9%) discontinued SO patients achieved serum phosphorus levels ≤ 5.5 mg/dL at Q8 with pill burden unchanged (9.1 to 9.3 pills per day; P = 0.3). Among all patients during 2 years, mean serum phosphorus levels decreased by -0.66 mg/dL and -0.45 mg/dL (maintenance SO vs discontinued SO; P = 0.014), and mean pill burden decreased in maintenance SO (8.5 to 5.1 pills per day; P < 0.001), but not in discontinued SO (11.6 to 10.9 pills per day; P = 0.2). The serum phosphorus level decrease with SO was confirmed in a sensitivity analysis including patients with SO therapy for 2 or fewer years. Compared with discontinued SO, maintenance SO patients had 35.6 fewer hospitalizations per 100 patient-years (incidence rate ratio, 0.75 [95% CI, 0.58-0.96]). LIMITATIONS: No data for treatment indication, tolerance, or adherence. CONCLUSIONS: Patients maintained on SO therapy were more likely to achieve target serum phosphorus levels, use 50% fewer phosphate-binder pills per day, and have fewer hospital admissions than patients switched to treatment with other binders.

Management of Acute Severe Ulcerative Colitis in a Pregnant Woman With COVID-19 Infection: A Case Report and Review of the Literature.

First detected in Wuhan, China, the novel 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped RNA beta-coronavirus responsible for an unprecedented, worldwide pandemic caused by COVID-19. Optimal management of immunosuppression in inflammatory bowel disease (IBD) patients with COVID-19 infection currently is based on expert opinion, given the novelty of the infection and the corresponding lack of high-level evidence in patients with immune-mediated conditions. There are limited data regarding IBD patients with COVID-19 and no data regarding early pregnancy in the era of COVID-19. This article describes a patient with acute severe ulcerative colitis (UC) during her first trimester of pregnancy who also has COVID-19. The case presentation is followed by a review of the literature to date on COVID-19 in regard to inflammatory bowel disease and pregnancy, respectively.

Neuronal ablation of mt-AspRS in mice induces immune pathway activation prior to severe and progressive cortical and behavioral disruption.

Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a rare, slowly progressive white matter disease caused by mutations in the mitochondrial aspartyl-tRNA synthetase (mt-AspRS, or DARS2). While patients show characteristic MRI T2 signal abnormalities throughout the cerebral white matter, brainstem, and spinal cord, the phenotypic spectrum is broad and a multitude of gene variants have been associated with the disease. Here, Dars2 disruption in CamKIIα-expressing cortical and hippocampal neurons results in slowly progressive increases in behavioral activity at five months, and culminating by nine months as severe brain atrophy, behavioral dysfunction, reduced corpus callosum thickness, and microglial morphology indicative of neuroinflammation. Interestingly, RNAseq based gene expression studies performed prior to the presentation of this severe phenotype reveal the upregulation of several pathways involved in immune activation, cytokine production and signaling, and defense response regulation. RNA transcript analysis demonstrates that activation of immune and cell stress pathways are initiated in advance of a behavioral phenotype and cerebral deficits. An understanding of these pathways and their contribution to significant neuronal loss in CamKII-Dars2 deficient mice may aid in deciphering mechanisms of LBSL pathology.

Escalation of Immunosuppressive Therapy for Inflammatory Bowel Disease Is Not Associated With Adverse Outcomes After Infection With Clostridium difficile.

BACKGROUND: Clostridium difficile infection (CDI) is common in patients with inflammatory bowel disease (IBD), often leading to diagnostic confusion and delays in IBD therapy escalation. This study sought to assess outcomes after CDI in IBD patients exposed to new or escalated immunosuppressive therapy. METHODS: This multicenter retrospective cohort study included IBD patients with documented CDI at 4 academic medical centers. Data were abstracted from clinical databases at each institution. Outcomes at 30 and 90 days were compared between patients undergoing new or intensified immunosuppressive therapy and those without therapy escalation. Continuous variables were compared using t tests, and proportions using chi-square tests. Multivariable logistic regression was used to determine the association of individual variables with severe outcomes (including death, sepsis, and/or colectomy) within 90 days. Secondary outcomes included CDI recurrence, rehospitalization, worsening of IBD, and severe outcomes within 30 days. RESULTS: A total of 207 adult patients with IBD and CDI were included, of whom 62 underwent escalation to biologic or corticosteroid therapy (median time to escalation, 13 days). Severe outcomes within 90 days occurred in 21 (15.6%) nonescalated and 1 (1.8%) therapy-escalated patients. Serum albumin <2.5 mg/dL, lactate >2.2 mg/dL, intensive care unit admission, hypotension, and comorbid disease were associated with severe outcomes. Likelihood of severe outcomes was decreased in patients undergoing escalation of IBD therapy after CDI (adjusted odds ratio [aOR], 0.12) and increased among patients aged >65 years (aOR, 4.55). CONCLUSIONS: Therapy escalation for IBD within 90 days of CDI was not associated with worse clinical outcomes. Initiation of immunosuppression for active IBD may therefore be appropriate in carefully selected patients after treatment of CDI.

Dendrimer-N-acetyl-L-cysteine modulates monophagocytic response in adrenoleukodystrophy.

OBJECTIVE: X-linked adrenoleukodystrophy (ALD) is a neurodegenerative disorder due to mutations in the peroxisomal very long-chain fatty acyl-CoA transporter, ABCD1, with limited therapeutic options. ALD may manifest in a slowly progressive adrenomyeloneuropathy (AMN) phenotype, or switch to rapid inflammatory demyelinating cerebral disease (cALD), in which microglia have been shown to play a pathophysiological role. The aim of this study was to determine the role of patient phenotype in the immune response of ex vivo monophagocytic cells to stimulation, and to evaluate the efficacy of polyamidoamine dendrimer conjugated to the antioxidant precursor N-acetyl-cysteine (NAC) in modulating this immune response. METHODS: Human monophagocytic cells were derived from fresh whole blood, from healthy (n = 4), heterozygote carrier (n = 4), AMN (n = 7), and cALD (n = 4) patients. Cells were exposed to very long-chain fatty acids (VLCFAs; C24:0 and C26:0) and treated with dendrimer-NAC (D-NAC). RESULTS: Ex vivo exposure to VLCFAs significantly increased tumor necrosis factor α (TNFα) and glutamate secretion from cALD patient macrophages. Additionally, a significant reduction in total intracellular glutathione was observed in cALD patient cells. D-NAC treatment dose-dependently reduced TNFα and glutamate secretion and replenished total intracellular glutathione levels in cALD patient macrophages, more efficiently than NAC. Similarly, D-NAC treatment decreased glutamate secretion in AMN patient cells. INTERPRETATION: ALD phenotypes display unique inflammatory profiles in response to VLCFA stimulation, and therefore ex vivo monophagocytic cells may provide a novel test bed for therapeutic agents. Based on our findings, D-NAC may be a viable therapeutic strategy for the treatment of cALD. Ann Neurol 2018;84:452-462.

Antioxidant Capacity and Superoxide Dismutase Activity in Adrenoleukodystrophy.

Importance: X-linked adrenoleukodystrophy (ALD) may switch phenotype to the fatal cerebral form (ie, cerebral ALD [cALD]), the cause of which is unknown. Determining differences in antioxidant capacity and superoxide dismutase (SOD) levels between phenotypes may allow for the generation of a clinical biomarker for predicting the onset of cALD, as well as initiating a more timely lifesaving therapy. Objective: To identify variations in the levels of antioxidant capacity and SOD activity between ALD phenotypes in patients with cALD or adrenomyeloneuropathy (AMN), heterozygote female carriers, and healthy controls and, in addition, correlate antioxidant levels with clinical outcome scores to determine a possible predictive value. Design, Setting, and Participants: Samples of monocytes and blood plasma were prospectively collected from healthy controls, heterozygote female carriers, and patients with AMN or cALD. We are counting each patient as 1 sample in our study. Because adrenoleukodystrophy is an X-linked disease, the affected group populations of cALD and AMN are all male. The heterozygote carriers are all female. The samples were assayed for total antioxidant capacity and SOD activity. The data were collected in an academic hospital setting. Eligibility criteria included patients who received a diagnosis of ALD and heterozygote female carriers, both of which groups were compared with age-matched controls. The prospective samples (n = 30) were collected between January 2015 to January 2016, and existing samples were collected from tissue storage banks at the Kennedy Krieger Institute (n = 30). The analyses were performed during the first 3 months of 2016. Main Outcome and Measures: Commercially available total antioxidant capacity and SOD assays were performed on samples of monocytes and blood plasma and correlated with magnetic resonance imaging severity score. Results: A reduction in antioxidant capacity was shown between the healthy controls (0.225 mmol trolox equivalent) and heterozygote carriers (0.181 mmol trolox equivalent), and significant reductions were seen between healthy controls and patients with AMN (0.102 mmol trolox equivalent; P < .01), as well as healthy controls and patients with cALD (0.042 mmol trolox equivalent; P < .01). Superoxide dismutase activity in human blood plasma mirrored these reductions between prospectively collected samples from healthy controls (2.66 units/mg protein) and samples from heterozygote female carriers (1.91 units/mg protein), patients with AMN (1.39 units/mg protein; P = .01), and patients with cALD (0.8 units/mg protein; P < .01). Further analysis of SOD activity in biobank samples showed significant reductions between patients with AMN (0.89 units/mg protein) and patients with cALD (0.18 units/mg protein) (P = .03). Plasma SOD levels from patients with cALD demonstrated an inverse correlation to brain magnetic resonance imaging severity score (R2 = 0.75, P < .002). Longitudinal plasma SOD samples from the same patients (n = 4) showed decreased activity prior to and at the time of cerebral diagnosis over a period of 13 to 42 months (mean period, 24 months). Conclusions and Relevance: Plasma SOD may serve as a potential biomarker for cerebral disease in ALD following future prospective studies.

Variable utilization patterns of computed tomography for rhinosinusitis in emergency departments.

OBJECTIVE: Computed tomography (CT) use among patients who present to emergency departments (EDs) with rhinosinusitis symptoms is not well described. We aim to: 1) describe sinus CT utilization patterns, and 2) identify predictors of use. We hypothesize that patient symptoms, socioeconomic factors, and gender may influence the decision to obtain a sinus CT scan. STUDY DESIGN: Retrospective review. METHODS: The Nationwide Emergency Department Sample (2009-2011) was queried for patient encounters with a primary diagnosis of sinusitis (International Classification of Diseases, Ninth Revision, Clinical Modification codes 461*, 473*). Patient demographics, comorbidities, and disposition were obtained. Factors associated with CT scan use were determined by univariable and multivariable logistic regression. RESULTS: A total of 2,297,830 visits were attributed to a primary diagnosis of sinusitis. The majority of patients were adult (age > 17) (80.8%) and female (63.7%). Computed tomography imaging was obtained in 56,088 patients (2.4%). In univariable analysis, many socioeconomic factors were predictive of imaging, including private insurance (P < 0.0001), metropolitan patient residence (P < 0.0001), and higher median household income quartile (P < 0.0001). The strongest predictors of CT use in multivariable analysis were history of injury (odds ratio [OR] = 2.82, 95% confidence interval [CI] = 2.43-3.29), headache (OR 2.11, 95% CI 1.02-2.34), Northeast hospital location (vs. Midwest) (OR 1.91, 95% CI 1.46-2.49), and male gender (OR 1.40, 95% CI 1.34-1.47). CONCLUSIONS: Several socioeconomic, demographic, and geographic factors are associated with sinus CT scan use in the ED for rhinosinusitis. This study has implications for CT imaging guidelines in the ED setting and demonstrates a need for further investigation of healthcare utilization disparities. LEVEL OF EVIDENCE: 2C. Laryngoscope, 127:537-543, 2017.

Establishing the feasibility of measuring performance in use of addiction pharmacotherapy.

This paper presents the rationale and feasibility of standardized performance measures for use of pharmacotherapy in the treatment of substance use disorders (SUD), an evidence-based practice and critical component of treatment that is often underused. These measures have been developed and specified by the Washington Circle, to measure treatment of alcohol and opioid dependence with FDA-approved prescription medications for use in office-based general health and addiction specialty care. Measures were pilot tested in private health plans, the Veterans Health Administration (VHA), and Medicaid. Testing revealed that use of standardized measures using administrative data for overall use and initiation of SUD pharmacotherapy is feasible and practical. Prevalence of diagnoses and use of pharmacotherapy vary widely across health systems. Pharmacotherapy is generally used in a limited portion of those for whom it might be indicated. An important methodological point is that results are sensitive to specifications, so that standardization is critical to measuring performance across systems.

Cost-effectiveness of conjugate pneumococcal vaccination in Singapore: comparing estimates for 7-valent, 10-valent, and 13-valent vaccines.

INTRODUCTION: Although multiple studies of cost-effectiveness of pneumococcal conjugate vaccines have been conducted, no such study has examined Singapore's situation nor compared the licensed conjugate vaccines in an Asian population. This paper estimates the costs and public health impacts of pneumococcal conjugate vaccine programs, varying estimates of serotype replacement and herd immunity effects as key parameters in the analysis. Based in part on a 2008 analysis also presented here, Singapore has approved the PCV-7, PHiD-10, and PCV-13 pneumococcal conjugate vaccines as part of its National Childhood Immunisation Programme. METHODS: An economic evaluation was performed using a Markov simulation model populated with Singapore-specific population parameters, vaccine costs, treatment costs, and disease incidence data. The vaccinated infant and child cohort of 226,000 was 6% of the Singapore resident population of 3.8 million. Vaccine efficacy estimates were constructed for PCV-7, PHiD-10, and PCV-13 vaccines based on their serotype coverage in Singapore and compared to 'no vaccination'. The model estimated impacts over a five-year time horizon with 3% per year discounting of costs and health effects. Costs were presented in 2010 U.S. dollars (USD) and Singapore dollars (SGD). Sensitivity analyses included varying herd immunity, serotype replacement rates, vaccine cost, and efficacy against acute otitis media. RESULTS: Under base case assumptions for the revised analysis (i.e., herd effects in the unvaccinated population equivalent to 20% of direct effects) PCV-13 prevented 834 cases and 7 deaths due to pneumonia, meningitis, and bacteremia in the vaccinated population, and 952 cases and 191 deaths in the unvaccinated population over the 5-year time horizon. Including herd effects, the cost-effectiveness ratio for PCV-13 was USD $37,644 (SGD $51,854) per QALY. Without herd effects, however, the ratio was USD $204,535 (SGD $281,743) per QALY. The PCV-7 cost per QALY including herd effects was USD $43,275 (SGD $59,610) and for PHiD-10 the ratios were USD $45,100 (SGD $62,125). The original 2008 analysis, which had higher estimates of pneumonia prevention due to herd immunity and lower estimates of cost per dose, had found a cost-effectiveness ratio of USD $5562 (SGD $7661) per QALY for PCV-7. CONCLUSIONS: When compared to cost-effectiveness thresholds recommended by the World Health Organization (WHO), our 2008 analysis found that vaccination of infants in Singapore with PCV-7 was very cost-effective if herd immunity effects were present. However, knowledge on herd immunity and serotype replacement that emerged subsequent to this analysis changed our expectations about indirect effects. Given these changed inputs, our current estimates of infant vaccination against pneumococcal disease in Singapore find such programs to be moderately cost-effective compared to WHO thresholds. The different findings from the 2008 and 2011 analyses suggest that the dynamic issue of serotype replacement should be monitored post-licensure and, as changes occur, vaccine effectiveness and cost-effectiveness analyses should be re-evaluated.