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Newborn screening for congenital adrenal hyperplasia (CAH) caused by 21-hydroxylase deficiency is mandated throughout the US. Filter paper blood specimens are assayed for 17-hydroxyprogesterone (17OHP). Prematurity, low birth weight, or critical illness cause falsely elevated results. The purpose of this report is to highlight differences in protocols among US state laboratories. We circulated a survey to state laboratory directors requesting qualitative and quantitative information about individual screening programs. Qualitative and quantitative information provided by 17 state programs were available for analysis. Disease prevalence ranged from 1:9941 to 1:28,661 live births. Four state laboratories mandated a second screen regardless of the initial screening results; most others did so for infants in intensive care units. All but one program utilized birthweight cut-points, but cutoffs varied widely: 17OHP values of 25 to 75 ng/mL for birthweights >2250-2500 g. The positive predictive values for normal birthweight infants varied from 0.7% to 50%, with the highest predictive values based in two of the states with a mandatory second screen. Data were unavailable for negative predictive values. These data imply differences in sensitivity and specificity in CAH screening in the US. Standardization of newborn screening protocols could improve the positive predictive value.

Alopecia areata is a T cell-mediated autoimmune disease characterized phenotypically by hair loss and, histologically, by infiltrating T cells surrounding the hair follicle bulb (reviewed in ref. 1). Previous studies [...], Alopecia areata (AA) is a common autoimmune disease resulting from damage of the hair follicle by T cells. The immune pathways required for autoreactive T cell activation in AA are not defined limiting clinical development of rational targeted therapies (1). Genome-wide association studies (GWAS) (2) implicated ligands for the NKG2D receptor (product of the KLRK1 gene) in disease pathogenesis. Here, we show that cytotoxic [CD8.sup.+][NKG2D.sup.+] T cells are both necessary and sufficient for the induction of AA in mouse models of disease. Global transcriptional profiling of mouse and human AA skin revealed gene expression signatures indicative of cytotoxic T cell infiltration, an interferon-γ (IFN-γ) response and upregulation of several γ-chain (γc) cytokines known to promote the activation and survival of IFN-γ-producing [CD8.sup.+][NKG2D.sup.+] effector T cells. Therapeutically, antibody-mediated blockade of IFN-γ, interleukin-2 (IL-2) or interleukin-15 receptor β (IL-15Rb) prevented disease development, reducing the accumulation of [CD8.sup.+][NKG2D.sup.+] T cells in the skin and the dermal IFN response in a mouse model of AA. Systemically administered pharmacological inhibitors of Janus kinase (JAK) family protein tyrosine kinases, downstream effectors of the IFN-γ and [γ.sub.c] cytokine receptors, eliminated the IFN signature and prevented the development of AA, while topical administration promoted hair regrowth and reversed established disease. Notably, three patients treated with oral ruxolitinib, an inhibitor of JAK1 and JAK2, achieved near-complete hair regrowth within 5 months of treatment, suggesting the potential clinical utility of JAK inhibition in human AA.

Purpose: Describe the process of obtaining the best possible medication history (BPMH) by Certified Pharmacy Technicians (CPhTs) on hospital admission to identify medication discrepancies. Methods: Cross-sectional, descriptive study conducted between December 2016 and June 2017 at a quaternary center in New York, including all patients 18 years and older admitted to the medicine service through the Emergency Department (ED) and seen by a CPhT. CPhTs obtained the BPMH using a systematic approach involving a standardized interview, checking medications with secondary sources and updating the electronic health record (EHR). Medication discrepancies were identified and categorized by type and risk. Summary statistics were provided as average and standard deviation (SD) for continuous variables, and as frequencies and percentages for categorical variables. Multivariable regression was used to test for associations between patient factors and presence of a medication discrepancy. Results: Of the 3,087 patient visits, the average age was 69 (SD 17.8), 54% were female (n = 1652) and 65% white (n = 2017); comorbidity score breakdown was: 0 (25%, n = 757), 1-2 (33%, n = 1023), 3-4 (23%, n = 699), > 4 (20%, n = 608). The average number of home and discharge medications were 10 (SD 6.1) and 10 (SD 5.4), respectively. The average time spent obtaining the BPMH was 30.6 minutes (SD 12.9). 69% of patients (n = 2130) had at least 1 discrepancy with an average of 4.2 (SD 4.6), of which 43% (n = 920) included high-risk medications. Having a medication discrepancy was associated with a higher number of home medications (p < 0.0001) comorbidities (p < 0.0001), and source of information (p < 0.04). Conclusion: Obtaining the BPMH by CPhTs on hospital admission frequently identifies medication discrepancies. Further studies are needed to evaluate the association between obtaining the BPMH and clinical outcomes. [ABSTRACT FROM AUTHOR]

Objective: To evaluate racial and ethnic differences in mortality among patients hospitalized with coronavirus disease 2019 (COVID-19) after adjusting for baseline characteristics and comorbidities. Methods: This retrospective cohort study at 13 acute care facilities in the New York City metropolitan area included sequentially hospitalized patients between March 1, 2020, and April 27, 2020. Last day of follow up was July 31, 2020. Patient demographic information, including race/ethnicity and comorbidities, were collected. The primary outcome was in-hospital mortality. Results: A total of 10 869 patients were included in the study (median age, 65 years [interquartile range (IQR) 54–77; range, 18–107 years]; 40.5% female). In adjusted time-to-event analysis, increased age, male sex, insurance type (Medicare and Self-Pay), unknown smoking status, and a higher score on the Charlson Comorbidity Index were significantly associated with higher in-hospital mortality. Adjusted risk of hospital mortality for Black, Asian, Hispanic, multiracial/other, and unknown race/ethnicity patients were similar to risk for White patients. Conclusions: In a large diverse cohort of patients hospitalized with COVID-19, patients from racial/ethnic minorities experienced similar mortality risk as White patients. [ABSTRACT FROM AUTHOR]

Objectives Immunosuppressed paediatric patients with rheumatic disease (RD) may be at risk for severe or critical disease related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Data remain scarce on coronavirus disease 2019 (COVID-19) outcomes in paediatric RD patients. The aim of this study was to determine the seroprevalence of SARS-CoV-2 IgG and to describe COVID-19 outcomes in immunosuppressed paediatric RD patients. Methods Patients diagnosed with RD before age 18 years and treated with at least one immunosuppressive medication for at least 3 months were enrolled from a tertiary paediatric rheumatology practice in New York and also underwent routine SARS-CoV-2 IgG testing from May to November 2020. A total of 571 patients were screened and 262 were enrolled. SARS-CoV-2 IgG-positive subjects were assessed for symptoms of COVID-19 infection. SARS-CoV-2 PCR results were recorded where available. Demographic, diagnostic, medication and outcome data were collected. Results Of 262 subjects (186 female), 35 (13%) were SARS-CoV-2 IgG positive; 17 (49%) had symptoms suggestive of COVID-19. Of the 17 patients who had SARS-CoV-2 PCR testing, 11 (65%) were PCR positive, 7 of whom were IgG positive. Most SARS-CoV-2 IgG-positive subjects were not PCR tested. The most common symptoms in IgG- and/or PCR-positive subjects were fever, fatigue and cough. No SARS-CoV-2 IgG- or PCR-positive subject developed severe or critical COVID-19 or required hospitalization. Conclusions This is the first report of clinical outcomes of SARS-CoV-2 infection and seroprevalence of SARS-CoV-2 IgG in a large cohort of paediatric RD patients. Most SARS-CoV-2 IgG-positive subjects had no symptoms of COVID-19 infection. Symptomatic subjects all had mild COVID-19 symptoms, suggesting that the risk of severe or critical COVID-19 in immunosuppressed paediatric RD patients is minimal. [ABSTRACT FROM AUTHOR]

Background: Airway dysbiosis in premature infants may be associated with bronchopulmonary dysplasia (BPD). Early oropharyngeal colostrum (OPC) administration alters the oral microbiome, which may impact the lung microbiome. We aim to compare the oral and tracheal microbiota during the first week of life, and to determine whether early OPC administration affects microbial diversity or leukocyte inflammatory activity in the lung.Methods: Intubated premature infants (n = 42) were evaluated. The oral microbiome was characterized on day of life (DOL) 3, and the tracheal microbiome on DOL 3 and DOL 7, using 16S ribosomal DNA sequencing. Gene expression for inflammatory markers was quantified in airway leukocytes by real-time q-PCR.Results: The oral and tracheal microbiota were significantly different on DOL 3, but the tracheal microbiome on DOL 7 was more similar to the oral from DOL 3. Tracheal bacterial diversity decreased from DOL 3 to DOL 7. Longer time to first OPC administration tended to be associated with lower bacterial diversity in the airways.Conclusions: The tracheal microbiome in intubated premature infants in the first week is likely determined, in part, by the composition of the oral microbiome. Bacterial diversity in intubated babies decreases during the first week of life, a pattern that could be consistent with risk for BPD. Decreased bacterial diversity and increased inflammatory activity in the lung may also be associated with delayed administration of OPC. [ABSTRACT FROM AUTHOR]

Background: Thousands of patients annually receive treatment for advanced non‐small cell lung cancer (NSCLC), but little is known about their views on the decision to receive that treatment, or regret. This trial prospectively evaluated the incidence of regret and whether baseline characteristics, patient decision‐making parameters, or clinical progress early in the treatment course predicts regret. Materials and Methods: Patients receiving systemic treatment for advanced NSCLC completed every 3‐week patient reported outcome (PRO) assessment using the electronic Lung Cancer Symptom Scale (eLCSS‐QL), including the 3‐Item Global Index (3‐IGI; assessing overall distress, activities, and quality of life [QL]). A prespecified secondary aim was to determine the frequency of regret evaluated at 3 months after starting treatment. Patients were randomized to usual care or enhanced care (which included use of the DecisionKEYS decision aid). Results: Of 164 patients entered, 160 received treatment and 142 were evaluable for regret. In total, 11.5% of patients and 9% of their supporters expressed regret. Baseline characteristics did not predict regret; regret was rarely expressed by those who had a less than 20% decline or improvement in the 3‐IGI PRO score after two treatment cycles. In contrast, when asked if they would make the same decision again, only 1% not having a 20% 3‐IGI decline expressed regret, versus 14% with a 3‐IGI decline (p =.01). Conclusion: The majority of patients having regret were identified early using the PRO 3‐IGI of the eLCSS‐QL measure. Identifying patients at risk for regret allows for interventions, including frank discussions of progress and goals early in the treatment course, which could address regret in patients and their supporters. Implications for Practice: This report documents prospectively, for the first time, the incidence of treatment‐related regret in patients with advanced lung cancer and outlines that risk of regret is associated with patient‐determined worsening health status early in the course of treatment. Identifying patients at risk for regret early in treatment (before the third cycle of treatment) appears to be crucial. Counseling at that time should include a discussion of consideration of treatment change and the reason for this change. Considering that most patients are unlikely to have a major response treatment for advanced non‐small cell lung cancer, efforts should be made to avoid or reduce patient regret associated with treatment decision making. This article focuses on frequency of regret, prospectively evaluated in patients at 3 months after starting systemic treatment for advanced lung cancer. [ABSTRACT FROM AUTHOR]

Alopecia areata (AA) is a highly prevalent autoimmune disease that attacks the hair follicle and leads to hair loss that can range from small patches to complete loss of scalp and body hair. Our previous linkage and genome‐wide association studies (GWAS) generated strong evidence for aetiological contributions from inherited genetic variants at different population frequencies, including both rare mutations and common polymorphisms. Additionally, we conducted gene expression (GE) studies on scalp biopsies of 96 patients and controls to establish signatures of active disease. In this study, we performed an integrative analysis on these two datasets to test the hypothesis that rare CNVs in patients with AA could be leveraged to identify drivers of disease in our AA GE signatures. We analysed copy number variants (CNVs) in a case‐control cohort of 673 patients with AA and 16 311 controls independent of the case‐control cohort of 96 research participants used in our GE study. Using an integrative computational analysis, we identified 14 genes whose expression levels were altered by CNVs in a consistent direction of effect, corresponding to gene expression changes in lesional skin of patients. Four of these genes were affected by CNVs in three or more unrelated patients with AA, including ATG4B and SMARCA2, which are involved in autophagy and chromatin remodelling, respectively. Our findings identified new classes of genes with potential contributions to AA pathogenesis. [ABSTRACT FROM AUTHOR]