Impact of the COVID-19 Pandemic on the Management of Juvenile Idiopathic Arthritis: Analysis of United States Commercial Insurance Data.

BACKGROUND/OBJECTIVE: Given limited information on health care and treatment utilization for juvenile idiopathic arthritis (JIA) during the pandemic, we studied JIA-related health care and treatment utilization in a commercially insured retrospective US cohort. METHODS: We studied rates of outpatient visits, new disease-modifying antirheumatic drug (DMARD) initiations, intra-articular glucocorticoid injections (iaGC), dispensed oral glucocorticoids and opioids, DMARD adherence, and DMARD discontinuation by quarter in March 2018-February 2021 (Q1 started in March). Incident rate ratios (IRR, pandemic vs prepandemic) with 95% confidence intervals (CIs) were estimated using multivariable Poisson or Quasi-Poisson models stratified by diagnosis recency (incident JIA, <12 months ago; prevalent JIA, ≥12 months ago). RESULTS: Among 1294 children diagnosed with JIA, total and in-person outpatient visits for JIA declined during the pandemic (IRR, 0.88-0.90), most markedly in Q1 2020. Telemedicine visits, while higher during the pandemic, declined from 21% (Q1) to 13% (Q4) in 2020 to 2021. During the pandemic, children with prevalent JIA, but not incident JIA, had lower usage of iaGC (IRR, 0.60; 95% CI, 0.34-1.07), oral glucocorticoids (IRR, 0.47; 95% CI, 0.33-0.67), and opioids (IRR, 0.44; 95% CI, 0.26-0.75). Adherence to and discontinuation of DMARDs was similar before and during the pandemic. CONCLUSIONS: In the first year of the pandemic, visits for JIA dropped by 10% to 12% in commercially insured children in the United States, declines partly mitigated by use of telemedicine. Pandemic-related declines in intra-articular glucocorticoids, oral glucocorticoids, and opioids were observed for children with prevalent, but not incident, JIA. These changes may have important implications for disease control and quality of life.

Injury to Cone Synapses by Retinal Detachment: Differences from Rod Synapses and Protection by ROCK Inhibition.

Attachment of a detached retina does not always restore vision to pre-injury levels, even if the attachment is anatomically successful. The problem is due in part to long-term damage to photoreceptor synapses. Previously, we reported on damage to rod synapses and synaptic protection using a Rho kinase (ROCK) inhibitor (AR13503) after retinal detachment (RD). This report documents the effects of detachment, reattachment, and protection by ROCK inhibition on cone synapses. Conventional confocal and stimulated emission depletion (STED) microscopy were used for morphological assessment and electroretinograms for functional analysis of an adult pig model of RD. RDs were examined 2 and 4 h after injury or two days later when spontaneous reattachment had occurred. Cone pedicles respond differently than rod spherules. They lose their synaptic ribbons, reduce invaginations, and change their shape. ROCK inhibition protects against these structural abnormalities whether the inhibitor is applied immediately or 2 h after the RD. Functional restoration of the photopic b-wave, indicating cone-bipolar neurotransmission, is also improved with ROCK inhibition. Successful protection of both rod and cone synapses with AR13503 suggests this drug will (1) be a useful adjunct to subretinal administration of gene or stem cell therapies and (2) improve recovery of the injured retina when treatment is delayed.

Prevalence and Disparities in the Detection of Autism Without Intellectual Disability.

BACKGROUND: Intellectual ability predicts functional outcomes for children with autism spectrum disorder (ASD). It is essential to classify ASD children with and without intellectual disability (ID) to aid etiological research, provide services, and inform evidence-based educational and health planning. METHODS: Using a cross-sectional study design, data from 2000 to 2016 active ASD surveillance among 8-year-olds residing in the New York-New Jersey Metropolitan Area were analyzed to determine ASD prevalence with and without ID. Multivariable Poisson regression models were used to identify trends for ASD with ID (ASD-I) and without ID (ASD-N). RESULTS: Overall, 4661 8-year-olds were identified with ASD. Those that were ASI-I were 1505 (32.3%) and 2764 (59.3%) were ASD-N. Males were 3794 (81.4%), 946 (20.3%) were non-Hispanic Black (Black), 1230 (26.4%) were Hispanic, and 2114 (45.4%) were non-Hispanic white (white). We observed 2-fold and 5-fold increases in the prevalence of ASD-I and ASD-N, respectively, from 2000-2016. Black children were 30% less likely to be identified with ASD-N compared with white children. Children residing in affluent areas were 80% more likely to be identified with ASD-N compared with children in underserved areas. A greater proportion of children with ASD-I resided in vulnerable areas compared with children with ASD-N. Males had higher prevalence compared with females regardless of ID status; however, male-to-female ratios were slightly lower among ASD-I compared with ASD-N cases. CONCLUSIONS: One-in-3 children with ASD had ID. Disparities in the identification of ASD without ID were observed among Black and Hispanic children as well as among children residing in underserved areas.

Disparities in Early Intervention Program Participation by Children With Autism Spectrum Disorder in a US Metropolitan Area, 2006 to 2016.

Importance: Multiple studies have shown the value of early interventions for autism spectrum disorder (ASD). In the US, the Early Intervention Program (EIP) is mandated by law (Part C of the Individuals With Disabilities Education Act [IDEA]) to provide services to all young children with delays or disabilities. However, the extent to which children with ASD participate in this key service system is unknown. Objectives: To evaluate EIP use by children with ASD from 2006 to 2016 and to describe the factors associated with EIP participation. Design, Setting, and Participants: This cross-sectional study used repeated data collected from 2006 to 2016 by active ASD surveillance of the New York-New Jersey metropolitan area as reported in the New Jersey Autism Study. The New Jersey Autism Study identified 4050 children aged 8 years with ASD from 2006 to 2016. Demographic and clinical data were collected and participation in an EIP was assessed through active surveillance. Data were analyzed from June to December 2021. Exposure: Sociodemographic factors associated with the outcome of EIP participation. Main Outcomes and Measures: Participation in an EIP assessed at age 8 years. Demographic, ecological, and clinical factors, as well as temporal patterns, were examined by using standard and multilevel logistic regression models. Results: Among 4050 children aged 8 years with ASD by active surveillance, 1887 (46.6%) received EIP services. Of these children, 3303 (81.6%) were boys; 1105 (27.3%) were Hispanic, 801 (19.8%) were non-Hispanic Black, 1816 (44.8%) were non-Hispanic White, and 328 (8.1%) were non-Hispanic other (included Alaska Native or American Indian and Asian or Pacific Islander). In adjusted regression models, non-Hispanic Black children with ASD had lower odds of EIP participation (adjusted odds ratio [AOR], 0.67; 95% CI, 0.54-0.84) compared with their non-Hispanic White peers, and children residing in affluent areas had higher odds of receiving EIP services (AOR, 1.71; 95% CI, 1.36-2.15) compared with children residing in underserved areas. Children with ASD born in 2008 had higher odds of EIP participation than children born in 1998 (AOR, 2.64; 95% CI, 2.07-3.36). Conclusions and Relevance: Early identification of ASD is an important public health priority and receipt of EIP services may improve ASD outcomes. Approximately half of the population of children aged 8 years with ASD received EIP services between 2006 and 2016, and EIP participation by children with ASD increased during the 10-year period. However, receipt of EIP services was marked by strong socioeconomic status- and race and ethnicity-based disparities. Universal ASD screening and additional strategies are needed to address disparities and to increase access to EIP services.

Antibody Seroprevalence, Infection and Surveillance for SARS-CoV-2 in Residents and Staff of New Jersey Long-Term Care Facilities.

Early in the pandemic, New Jersey (NJ) long-term care facilities (LTCFs) witnessed severe COVID-19 illness. With limited surveillance to characterize the scope of infection, we estimated the prevalence of antibody to the SARS-CoV-2 nucleocapsid protein among residents and staff, to describe the epidemiology, and to measure antibody distribution by prior PCR/antigen status and symptomatology. 10 NJ LTCFs of 20 solicited with diverse geography and bed-capacities were visited between October 2020 and March 2021. A single serum was tested for total N-antibody (ELISA) by the state laboratory. Residents' demographics and clinical history were transcribed from the patient record. For staff, this information was solicited directly from employees, supplemented by prior PCR/antigen results from facilities. 62% of 332 residents and 46% of 661 staff tested N-antibody positive. In a multivariable logistic regression in residents, odds ratios for older age and admission prior before March 1, 2020 were significant. Among the staff, odds ratios for older age, ethnic-racial group, nursing-related job, and COVID-19 symptoms were significantly associated with N-antibody positivity. In a sub-analysis in five better record-keeping LTCFs, 90% of residents and 85% of staff with positive PCR/antigen results were seropositive for N-antibody, yet 25% of residents and 22% of staff were N-antibody positive but PCR/antigen and symptoms negative. The high rate of clinically unsuspected infections likely contributed to the spread. These findings argue for robust surveillance, regular screening of asymptomatic individuals, and vaccinating both residents and staff to abate the pandemic. The data also provide guidance to prevent future outbreaks.

Prevalence of autism spectrum disorder in a large, diverse metropolitan area: Variation by sociodemographic factors.

Autism spectrum disorder (ASD) prevalence estimates have varied by region. In this study, ASD prevalence, based on active case finding from multiple sources, was determined at the county and school district levels in the New Jersey metropolitan area. Among children born in 2008, residing in a four-county area and enrolled in public school in 2016, ASD prevalence was estimated to be 36 per 1000, but was significantly higher in one region-54 per 1000 and greater than 70 per 1000, in multiple school districts. Significant variation in ASD prevalence by race/ethnicity, socioeconomic status (SES), and school district size was identified. Highest prevalence was in mid-SES communities, contrary to expectation. Prevalence among Hispanic children was lower than expected, indicating a disparity in identification. Comprehensive surveillance should provide estimates at the county and town levels to appreciate ASD trends, identify disparities in detection or treatment, and explore factors influencing change in prevalence. LAY SUMMARY: We found autism prevalence to be 3.6% in New Jersey overall, but higher in one region (5.4%) and in multiple areas approaching 7.0%. We identified significant variation in autism spectrum disorder (ASD) prevalence by race/ethnicity, socioeconomic status (SES) and school district size. Mapping prevalence in smaller, well-specified, regions may be useful to better understand the true scope of ASD, disparities in ASD detection and the factors impacting ASD prevalence estimation.

Poisonings After a Hurricane: Lessons From the New Jersey Poison Information and Education System (NJPIES) During and Following Hurricane Sandy.

OBJECTIVE: Hurricane Sandy made landfall in New Jersey on October 29, 2012, resulting in widespread power outages and gasoline shortages. These events led to potentially toxic exposures and the need for information related to poisons/toxins in the environment. This report characterizes the New Jersey Poison Information and Education System (NJPIES) call patterns in the days immediately preceding, during, and after Hurricane Sandy to identify areas in need of public health education and prevention. METHODS: We examined NJPIES case data from October through December 2012. Most Sandy-related calls had been coded as such by NJPIES staff. Additional Sandy-related cases were identified by performing a case narrative review. Descriptive analyses were performed for timing, case frequencies, exposure substances, gender, caller site, type of information requests, and other data. RESULTS: The most frequent Sandy-related exposures were gasoline and carbon monoxide (CO). Gasoline exposure cases were predominantly males and CO exposure cases, females (P < 0.0001). Other leading reasons for Sandy-related calls were poison information, food poisoning/spoilage information, and water contamination. CONCLUSIONS: This analysis identified the need for enhanced public health education and intervention to improve the handling of gasoline and encourage the proper use of gasoline-powered generators and cleaning and cooking equipment, thus reducing toxic exposures.

Adaptation of the Flu-FIT Program for Patient-Aligned Care Teams: A Quality Improvement Project.

The Flu-FIT program aims to increase colorectal cancer screening rates by offering a home fecal immunochemical test (FIT) at the time of annual influenza immunization. This program was piloted at a VA campus in New Jersey during the 2018-2019 influenza season, with a 9% increase in colorectal cancer screening rates. In the 2019-2020 season, the program was implemented in 6 primary care teams; 6 additional teams maintaining standard of care served as a comparison group. A total of 816 patients aged 50 to 75 years were eligible for participation; 509 patients were available for analysis, 242 in the Flu-FIT group and 267 in the comparison group. The Flu-FIT group patients were 2.4 times more likely to accept FIT kits (95% confidence interval: 1.6-3.6, P = .001). The colorectal cancer screening rates increased 77.0% to 81.9% in the Flu-FIT group and 77.0% to 79.8% in the comparison group (P > .05).

ROCK inhibition reduces morphological and functional damage to rod synapses after retinal injury.

Retinal detachment (RD) causes damage, including disjunction, of the rod photoreceptor-bipolar synapse, which disrupts vision and may contribute to the poor visual recovery observed after retinal reattachment surgery. We created a model of iatrogenic RD in adult female pigs to study damage to the rod-bipolar synapse after injury and the ability of a highly specific Rho-kinase (ROCK) inhibitor to preserve synaptic structure and function. This model mimics procedures used in humans when viral vectors or cells are injected subretinally for treatment of retinal disease. Synaptic disjunction by retraction of rod spherules, quantified by image analysis of confocal sections, was present 2 h after detachment and remained 2 days later even though the retina had spontaneously reattached by then. Moreover, spherule retraction occurred in attached retina 1-2 cms from detached retina. Synaptic damage was significantly reduced by ROCK inhibition in detached retina whether injected subretinally or intravitreally. Dark-adapted full-field electroretinograms were recorded in reattached retinas to assess rod-specific function. Reduction in synaptic injury correlated with increases in rod-driven responses in drug-treated eyes. Thus, ROCK inhibition helps prevent synaptic damage and improves functional outcomes after retinal injury and may be a useful adjunctive treatment in iatrogenic RD and other retinal degenerative diseases.

Increased frequency of canine distemper virus-specific antibodies in multiple sclerosis.

BACKGROUND AND PURPOSE: Canine distemper virus (CDV) is a candidate agent in the etiology of multiple sclerosis (MS). Elevated anti-CDV levels were previously found in the sera from MS patients compared with controls. We now investigated whether there was an age-related association with the presence of antibodies specific to CDV-hemagglutinin (H) protein in MS. METHODS: Sera from patients with MS, other neurological diseases, and inflammatory and/or autoimmune diseases, and healthy individuals were screened for anti-CDV in an ELISA using linear peptides of the CDV-H protein as antigen. Antibody levels to measles and varicella-zoster virus were measured and served as controls. RESULTS: Analysis of the new cohort of MS patients and controls confirmed our initial finding of elevated anti-CDV-H levels in MS patients. An increase in measles but not varicella-zoster virus antibody levels was found in MS patients compared with healthy controls. Data from the new cohort of patients and controls were combined with data from the original study and analyzed with respect to age distribution of anti-CDV IgG. Mean CDV antibody levels were significantly elevated in each decade from 20 to 50 years of age in MS compared with healthy and disease controls. Antibody levels to measles virus were not consistently elevated during this age span. A striking relationship (p < .0001, odds ratio = 5.0) was observed between elevated anti-CDV-H levels and diagnosis of MS. CONCLUSIONS: The finding that anti-CDV levels are elevated in MS patients of all ages provides substantial evidence of a strong association between elevated anti-CDV and MS.

The Impact of HIV Infection on TB Disparities Among US-Born Black and White Tuberculosis Patients in the United States.

BACKGROUND/OBJECTIVES: US-born non-Hispanic black persons (blacks) (12% of the US population) accounted for 41% of HIV diagnoses during 2008-2014. HIV infection significantly increases TB and TB-related mortality. TB rate ratios were 6 to 7 times as high in blacks versus US-born non-Hispanic whites (whites) during 2013-2016. We analyzed a sample of black and white TB patients to assess the impact of HIV infection on TB racial disparities. METHODS: In total, 552 black and white TB patients with known HIV/AIDS status were recruited from 10 US sites in 2009-2010. We abstracted data from the National TB Surveillance System, medical records, and death certificates and interviewed 477 patients. We estimated adjusted odds ratios (AORs) with 95% confidence intervals (CIs) for associations of TB with HIV infection, late HIV diagnosis (≤3 months before or any time after TB diagnosis), and mortality during TB treatment. RESULTS: Twenty-one percent of the sample had HIV/AIDS infection. Blacks (AOR = 3.4; 95% CI, 1.7-6.8) and persons with recent homelessness (AOR = 2.5; 95% CI, 1.5-4.3) had greater odds of HIV infection than others. The majority of HIV-infected/TB patients were diagnosed with HIV infection 3 months or less before (57%) or after (4%) TB diagnosis. Among HIV-infected/TB patients, blacks had similar percentages to whites (61% vs 57%) of late HIV diagnosis. Twenty-five percent of HIV-infected/TB patients died, 38% prior to TB diagnosis and 62% during TB treatment. Blacks did not have significantly greater odds of TB-related mortality than whites (AOR = 1.1; 95% CI, 0.6-2.1). CONCLUSIONS: Black TB patients had greater HIV prevalence than whites. While mortality was associated with HIV infection, it was not significantly associated with black or white race.

Revisiting John Snow to Meet the Challenge of Nontuberculous Mycobacterial Lung Disease.

Nontuberculous mycobacteria (NTM) are ubiquitous components of the soil and surface water microbiome. Disparities by sex, age, and geography demonstrate that both host and environmental factors are key determinants of NTM disease in populations, which predominates in the form of chronic pulmonary disease. As the incidence of NTM pulmonary disease rises across the United States, it becomes increasingly evident that addressing this emerging human health issue requires a bold, multi-disciplinary research framework that incorporates host risk factors for NTM pulmonary disease alongside the determinants of NTM residence in the environment. Such a framework should include the assessment of environmental characteristics promoting NTM growth in soil and surface water, detailed evaluations of water distribution systems, direct sampling of water sources for NTM contamination and species diversity, and studies of host and bacterial factors involved in NTM pathogenesis. This comprehensive approach can identify intervention points to interrupt the transmission of pathogenic NTM species from the environment to the susceptible host and to reduce NTM pulmonary disease incidence.

Intraarticular Glucocorticoid Injection as Second-line Treatment for Lyme Arthritis in Children.

OBJECTIVE: To determine whether second-line intraarticular glucocorticoid (IAGC) injection improves outcomes in children with persistently active Lyme arthritis after initial antibiotics. METHODS: We conducted an observational comparative effectiveness study through chart review within 3 pediatric rheumatology centers with distinct clinical approaches to second-line treatment of Lyme arthritis. We primarily compared children receiving second-line IAGC to children receiving a second course of antibiotics alone. We evaluated the risk of developing antibiotic-refractory Lyme arthritis (ARLA) using logistic regression and the time to clinical resolution of Lyme arthritis using Cox regression. RESULTS: Of 112 children with persistently active Lyme arthritis after first-line antibiotics, 18 children received second-line IAGC (13 with concomitant oral antibiotics). Compared to children receiving second-line oral antibiotics alone, children treated with IAGC had similar baseline characteristics but lower rates of ARLA (17% vs 44%; OR 0.3, 95% CI 0.1-0.95; p = 0.04) and faster rates of clinical resolution (HR 2.2, 95% CI 1.2-3.9; p = 0.01). Children in IAGC and oral antibiotic cohorts did not differ in treatment-associated adverse events. Among children receiving second-line IAGC, outcomes appeared similar irrespective of use of concomitant antibiotics. Outcomes were also similar between intravenous (IV) and oral antibiotic-treated cohorts, but older children seemed to respond more favorably to IV therapy. IV antibiotics were also associated with higher rates of toxicity. CONCLUSION: IAGC injection appears to be an effective and safe second-line strategy for persistent Lyme arthritis in children, associated with rapid clinical resolution and reduced need for additional treatment.

Pediatric Antibiotic-refractory Lyme Arthritis: A Multicenter Case-control Study.

OBJECTIVE: Few factors have consistently been linked to antibiotic-refractory Lyme arthritis (ARLA). We sought to identify clinical and treatment factors associated with pediatric ARLA. METHODS: We performed a case-control study in 3 pediatric rheumatology clinics in a Lyme-endemic region (2000-2013). Eligible children were aged ≤ 18 years with arthritis and had positive testing for Lyme disease by Western blot. Cases were 49 children with persistently active arthritis despite ≥ 8 weeks of oral antibiotics or ≥ 2 weeks of parenteral antibiotics; controls were 188 children whose arthritis resolved within 3 months of starting antibiotics. We compared preselected demographic, clinical, and treatment factors between groups using logistic regression. RESULTS: Characteristics positively associated with ARLA were age ≥ 10 years, prolonged arthritis at diagnosis, knee-only arthritis, and worsening after starting antibiotics. In contrast, children with fever, severe pain, or other signs of systemic inflammation were more likely to respond quickly to treatment. Secondarily, low-dose amoxicillin and treatment nonadherence were also linked to higher risk of ARLA. Greater antibiotic use for children with ARLA was accompanied by higher rates of treatment-associated adverse events (37% vs 15%) and resultant hospitalization (6% vs 1%). CONCLUSION: Older children and those with prolonged arthritis, arthritis limited to the knees, or poor initial response to antibiotics are more likely to have antibiotic-refractory disease and treatment-associated toxicity. Children with severe symptoms of systemic inflammation have more favorable outcomes. For children with persistently active Lyme arthritis after 2 antibiotic courses, pediatricians should consider starting antiinflammatory treatment and referring to a pediatric rheumatologist.

HIV virologic response better with single-tablet once daily regimens compared to multiple-tablet daily regimens.

BACKGROUND: Single-tablet regimens are preferred prescription choices for HIV treatment, but there are limited outcomes data comparing single-tablet regimens to multiple-tablet regimens. METHODS: We retrospectively assessed treatment-naïve patients at a single urban HIV clinic in the United States for viral load suppression at 6 and 12 months after initiating either single-tablet or multiple-tablet regimens. Multivariate regression was performed to obtain relative risks and adjust for potential confounders. RESULTS: Of 218 patients, 47% were on single-tablet regimens and 53% on multiple-tablet regimens; 77% of single-tablet regimen patients had undetectable viral load at 6 months compared to 61% of multiple-tablet regimen patients (p = 0.012). At 12 months, 82% on single-tablet regimens and 66% on multiple-tablet regimens (p = 0.019) had undetectable viral load. Relative risk of any detectable viral load was 1.6 (95% confidence interval: 1.1-2.5) for patients on multiple-tablet regimens compared to single-tablet regimens at 6 months, and 2.2 (95% confidence interval: 1.2-4.0) at 12 months. CONCLUSION: Single-tablet regimens may provide better virologic control than multiple-tablet regimens in urban HIV-infected persons.

Active Tuberculosis Is Characterized by Highly Differentiated Effector Memory Th1 Cells.

Despite advances in diagnosing latent Mycobacterium tuberculosis infection (LTBI), we still lack a diagnostic test that differentiates LTBI from active tuberculosis (TB) or predicts the risk of progression to active disease. One reason for the absence of such a test may be the failure of current assays to capture the dynamic complexities of the immune responses associated with various stages of TB, since these assays measure only a single parameter (release of IFN-γ) and rely on prolonged (overnight) T cell stimulation. We describe a novel, semi-automated RNA flow cytometry assay to determine whether immunological differences can be identified between LTBI and active TB. We analyzed antigen-induced expression of Th1 cytokine mRNA after short (2- and 6-h) stimulation with antigen, in the context of memory T cell immunophenotyping. IFNG and TNFA mRNA induction was detectable in CD4+ T cells after only 2 h of ex vivo stimulation. Moreover, IFNG- and TNFA-expressing CD4+ T cells (Th1 cells) were more frequent in active TB than in LTBI, a difference that is undetectable with conventional, protein-based cytokine assays. We also found that active TB was associated with higher ratios of effector memory to central memory Th1 cells than LTBI. This effector memory phenotype of active TB was associated with increased T cell differentiation, as defined by loss of the CD27 marker, but not with T cell exhaustion, as determined by PD-1 abundance. These results indicate that single-cell-based, mRNA measurements may help identify time-dependent, quantitative differences in T cell functional status between latent infection and active tuberculosis.

Tuberculosis Mortality in the United States: Epidemiology and Prevention Opportunities.

Rationale: More information on risk factors for death from tuberculosis in the United States could help reduce the tuberculosis mortality rate, which has remained steady for more than a decade.Objective: To identify risk factors for tuberculosis-related death in adults.Methods: We performed a retrospective study of 1,304 adults with tuberculosis who died before treatment completion and 1,039 frequency-matched control subjects who completed tuberculosis treatment in 2005 to 2006 in 13 states reporting 65% of U.S. tuberculosis cases. We used in-depth record abstractions and a standard algorithm to classify deaths in persons with tuberculosis as tuberculosis-related or not. We then compared these classifications to causes of death as coded in death certificates. We used multivariable logistic regression to calculate adjusted odds ratios for predictors of tuberculosis-related death among adults compared with those who completed tuberculosis treatment.Results: Of 1,304 adult deaths, 942 (72%) were tuberculosis related, 272 (21%) were not, and 90 (7%) could not be classified. Of 847 tuberculosis-related deaths with death certificates available, 378 (45%) did not list tuberculosis as a cause of death. Adjusting for known risks, we identified new risks for tuberculosis-related death during treatment: absence of pyrazinamide in the initial regimen (adjusted odds ratio, 3.4; 95% confidence interval, 1.9-6.0); immunosuppressive medications (adjusted odds ratio, 2.5; 95% confidence interval, 1.1-5.6); incomplete tuberculosis diagnostic evaluation (adjusted odds ratio, 2.2; 95% confidence interval, 1.5-3.3), and an alternative nontuberculosis diagnosis before tuberculosis diagnosis (adjusted odds ratio, 1.6; 95% confidence interval, 1.2-2.2).Conclusions: Most persons who died with tuberculosis had a tuberculosis-related death. Intensive record review revealed tuberculosis as a cause of death more often than did death certificate diagnoses. New tools, such as a tuberculosis mortality risk score based on our study findings, may identify patients with tuberculosis for in-hospital interventions to prevent death.

Effect of a Rapid Test Algorithm on Linkage to Medical Care and Viral Suppression Among New Jersey Residents, 2007 to 2015.

BACKGROUND: Efforts to identify and link human immunodeficiency virus-infected persons to medical care are the first steps to achieving viral suppression. In the United States, the goals are to link 85% of newly diagnosed persons to medical care in 30 days or less and for 80% to become virally suppressed by 2020. Among newly diagnosed residents from 2007 to 2015, in New Jersey, we evaluated the impact of a rapid testing algorithm (RTA) on linkage to medical care and viral suppression. METHODS: This is a retrospective review of data from New Jersey's Enhanced HIV/AIDS Reporting System for residents, newly diagnosed at 13 years or older, from 2007 to 2015. We used survival analysis methods to estimate the proportion of residents and time to linkage to medical care and viral suppression. RESULTS: Of 8508 newly diagnosed residents, 60.3% and 72.3% were linked to medical care in 30 days or less and 90 days or less, respectively; 45.7% achieved viral suppression in 365 days or less. Linkage to medical care in 90 days or less and viral suppression in 365 days or less were more likely among those tested by RTA than laboratory testing. The adjusted hazard ratios for linkage to medical care, in clinical sites were 1.41, (95% confidence interval [CI], 1.22-1.63 and 1.08, 95% CI, 0.97-1.2 in community sites. The adjusted hazard ratios for viral suppression in clinical sites were 1.25 (95% CI, 1.05-1.47 and 1.16, 95% CI, 1.01-1.32, in community sites. CONCLUSIONS: Implementation of a RTA may eliminate barriers to linkage to medical care and viral suppression leading to decreased morbidity, mortality, and transmission.

Depot medroxyprogesterone acetate administration alters immune markers for HIV preference and increases susceptibility of peripheral CD4+ T cells to HIV infection.

Depot medroxyprogesterone acetate (Depo-Provera) has been associated with an increased risk of HIV acquisition. In a longitudinal study, we investigated the impact of Depo-Provera use by healthy women on expression of immune markers for HIV preference and on HIV infection ex vivo at baseline (visit 1), one month (visit 2) and three months (visit 3) after Depo-Provera treatment. We found a significant increase in the frequency and expression of integrin α4ß7 on CD4+ T cells at visit 2. Interestingly, Hispanic but not black women exhibited a significant increase in integrin α4ß7 cell numbers and expression levels at visit 2, whereas, black but not Hispanic women exhibited a significant change in CCR5 and CD38 expression levels between visit 2 and visit 3. The frequency of terminal effector memory CD4+ T cells decreased significantly in black women from visit 1 to visit 3. Virus production following ex vivo HIV infection of PBMCs was increased at visit 3 compared to visit 1. In black women, the frequency of HIV p24+CD4+ T cells was higher at visit 3 than at visit 1. Expression of integrin α4ß7 on HIV p24+CD4+ T cells following ex vivo infection at visit 2 was significantly less than at visit 1. These results demonstrate that Depo-Provera alters the immune profile of peripheral CD4+ T cells and increases susceptibility to HIV infection ex vivo. The observation that these effects differed between women of different ethnicities has implications for developing effective and targeted strategies for HIV prevention.

Impact of the black triangle label on prescribing of new drugs in the United Kingdom: lessons for the United States at a time of deregulation.

PURPOSE: Newly approved novel drugs in Europe receive a black triangle label to promote pharmacovigilance. With growing momentum for earlier drug approvals and reliance on real-world evidence, we studied if the black triangle label promotes more judicious prescribing. METHODS: We examined whether general practitioners prescribed escitalopram, tadalafil, and vardenafil with a black triangle more cautiously than the same or similar drugs without a black triangle in The Health Improvement Network (UK). We performed interrupted time-series analyses to estimate changes in new prescription rates and nested case-control studies to compare characteristics of new users before and after removal of a black triangle. RESULTS: Prescribing rates to the 33 441 new users of these new drugs were highest shortly after initial approval and declined subsequently; there were no increases in rates of new prescriptions after a black triangle's removal (new prescriptions/million/month postlabel: escitalopram -1.5 [95% CI, -1.9 to -1.2]; tadalafil and vardenafil: -0.1 [95% CI, -0.6 to 0.4]). Among drugs in the same class, loss of a patent had more impact on prescribing rates than loss of a black triangle. People who began taking black triangle drugs were less likely to be young or to have multiple comorbidities or recent hospitalization compared with those starting the same drugs after the label's removal. However, these differences generally reflected secular trends seen also in similar, unlabeled medicines. CONCLUSIONS: Accelerated drug approvals could cause more uncertainty about drug effectiveness and safety, but specific labeling of newly approved medicines is unlikely to promote more judicious prescribing.