Background

Breast cancer is the most commonly diagnosed cancer among the rapidly growing population of Asian Americans; it is also the most common cause of cancer mortality among Filipinas. Asian women continue to have lower rates of mammographic screening than women of most other racial/ethnic groups. While prior studies have described the effects of sociodemographic and other characteristics of women on non-adherence to screening guidelines, they have not identified the distinct segments of the population who remain at highest risk of not being screened.

Methods

To better describe characteristics of Asian women associated with not having a mammogram in the last two years, we applied recursive partitioning to population-based data (N = 1521) from the 2001 California Health Interview Survey (CHIS), for seven racial/ethnic groups of interest: Chinese, Japanese, Filipino, Korean, South Asian, Vietnamese, and all Asians combined.

Results

We identified two major subgroups of Asian women who reported not having a mammogram in the past two years and therefore, did not follow mammography screening recommendations: 1) women who have never had a pap exam to screen for cervical cancer (68% had no mammogram), and 2) women who have had a pap exam, but have no women's health issues (osteoporosis, using menopausal hormone therapies, and/or hysterectomy) nor a usual source of care (62% had no mammogram). Only 19% of Asian women who have had pap screening and have women's health issues did not have a mammogram in the past two years. In virtually all ethnic subgroups, having had pap or colorectal screening were the strongest delineators of mammography usage. Other characteristics of women least likely to have had a mammogram included: Chinese non-U.S. citizens or citizens without usual source of health care, Filipinas with no health insurance, Koreans without women's health issues and public or no health insurance, South Asians less than age 50 who were unemployed or non-citizens, and Vietnamese women who were never married.

Conclusion

We identified distinct subgroups of Asian women at highest risk of not adhering to mammography screening guidelines; these data can inform outreach efforts aimed at reducing the disparity in mammography screening among Asian women.

Background and aims

To assess whether aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (AP) levels can predict the diagnosis of primary biliary cholangitis (PBC) or any other diagnoses and whether PBC occurs either simultaneously or independently of other liver diseases among antimitochondrial antibody (AMA)-positive patients.

Methods

Demographic and clinical variables were assessed in 90 AMA-positive patients with and without liver biopsies. These patients were further categorised as having a diagnosis of PBC, overlap syndrome or 'not established with a diagnosis of PBC'. Receiver operating characteristic curves were constructed to determine the thresholds of liver enzymes that predict these three diagnoses.

Results

The 48 patients with liver biopsies were more frequently female and had significantly higher AP levels compared with the non-liver biopsy group. Based on liver biopsy findings, 12, 12 and 22 patients were assigned a diagnosis of PBC, overlap syndrome with autoimmune hepatitis and PBC and 'not established diagnosis of PBC', respectively. Seven of 12 patients classified as PBC had AP level of ˂200 IU. AST, ALT and AP levels were significant predictors of a diagnosis of overlap syndrome compared with the rest of the patients; however, these tests were not discriminatory between diagnoses of PBC and 'not established with PBC'. Findings of fatty liver and bile duct injury on liver biopsies were not significantly associated with any liver test pattern.

Conclusions

As the liver test pattern did not correlate with the liver biopsy findings of PBC or other non-PBC diagnoses in AMA-positive patients at risk for other disease, a liver biopsy and/or non-invasive liver assessment along with serum liver tests should be interpreted to complete liver evaluation.

The potential role of enteric viral infections and the developing infant virome in affecting immune responses to the oral poliovirus vaccine (OPV) is unknown. Here we performed viral metagenomic sequencing on 3 serially collected stool samples from 30 Bangladeshi infants following OPV vaccination and compared findings to stool samples from 16 age-matched infants in the United States (US). In 14 Bangladeshi infants, available post-vaccination serum samples were tested for polio-neutralizing antibodies. The abundance (p = 0.006) and richness (p = 0.013) of the eukaryotic virome increased with age and were higher than seen in age-matched US infants (p < 0.001). In contrast, phage diversity metrics remained stable and were similar to those in US infants. Non-poliovirus eukaryotic virus abundance (3.68 log₁₀ vs. 2.25 log₁₀, p = 0.002), particularly from potential viral pathogens (2.78log₁₀ vs. 0.83log₁₀, p = 0.002), and richness (p = 0.016) were inversely associated with poliovirus shedding. Following vaccination, 28.6% of 14 infants tested developed neutralizing antibodies to all three Sabin types and also exhibited higher rates of poliovirus shedding (p = 0.020). No vaccine-derived poliovirus variants were detected. These results reveal an inverse association between eukaryotic virome abundance and poliovirus shedding. Overall gut virome ecology and concurrent viral infections may impact oral vaccine responsiveness in Bangladeshi infants.

Background

Remdesivir, a nucleotide analogue prodrug that inhibits viral RNA polymerases, has shown in vitro activity against SARS-CoV-2.

Methods

We provided remdesivir on a compassionate-use basis to patients hospitalized with Covid-19, the illness caused by infection with SARS-CoV-2. Patients were those with confirmed SARS-CoV-2 infection who had an oxygen saturation of 94% or less while they were breathing ambient air or who were receiving oxygen support. Patients received a 10-day course of remdesivir, consisting of 200 mg administered intravenously on day 1, followed by 100 mg daily for the remaining 9 days of treatment. This report is based on data from patients who received remdesivir during the period from January 25, 2020, through March 7, 2020, and have clinical data for at least 1 subsequent day.

Results

Of the 61 patients who received at least one dose of remdesivir, data from 8 could not be analyzed (including 7 patients with no post-treatment data and 1 with a dosing error). Of the 53 patients whose data were analyzed, 22 were in the United States, 22 in Europe or Canada, and 9 in Japan. At baseline, 30 patients (57%) were receiving mechanical ventilation and 4 (8%) were receiving extracorporeal membrane oxygenation. During a median follow-up of 18 days, 36 patients (68%) had an improvement in oxygen-support class, including 17 of 30 patients (57%) receiving mechanical ventilation who were extubated. A total of 25 patients (47%) were discharged, and 7 patients (13%) died; mortality was 18% (6 of 34) among patients receiving invasive ventilation and 5% (1 of 19) among those not receiving invasive ventilation.

Conclusions

In this cohort of patients hospitalized for severe Covid-19 who were treated with compassionate-use remdesivir, clinical improvement was observed in 36 of 53 patients (68%). Measurement of efficacy will require ongoing randomized, placebo-controlled trials of remdesivir therapy. (Funded by Gilead Sciences.).

Background

Ensovibep (MP0420) is a designed ankyrin repeat protein, a novel class of engineered proteins, under investigation as a treatment of SARS-CoV-2 infection.

Objective

To investigate if ensovibep, in addition to remdesivir and other standard care, improves clinical outcomes among patients hospitalized with COVID-19 compared with standard care alone.

Design

Double-blind, randomized, placebo-controlled, clinical trial. (ClinicalTrials.gov: NCT04501978).

Setting

Multinational, multicenter trial.

Participants

Adults hospitalized with COVID-19.

Intervention

Intravenous ensovibep, 600 mg, or placebo.

Measurements

Ensovibep was assessed for early futility on the basis of pulmonary ordinal scores at day 5. The primary outcome was time to sustained recovery through day 90, defined as 14 consecutive days at home or place of usual residence after hospital discharge. A composite safety outcome that included death, serious adverse events, end-organ disease, and serious infections was assessed through day 90.

Results

An independent data and safety monitoring board recommended that enrollment be halted for early futility after 485 patients were randomly assigned and received an infusion of ensovibep (n = 247) or placebo (n = 238). The odds ratio (OR) for a more favorable pulmonary outcome in the ensovibep (vs. placebo) group at day 5 was 0.93 (95% CI, 0.67 to 1.30; P = 0.68; OR > 1 would favor ensovibep). The 90-day cumulative incidence of sustained recovery was 82% for ensovibep and 80% for placebo (subhazard ratio [sHR], 1.06 [CI, 0.88 to 1.28]; sHR > 1 would favor ensovibep). The primary composite safety outcome at day 90 occurred in 78 ensovibep participants (32%) and 70 placebo participants (29%) (HR, 1.07 [CI, 0.77 to 1.47]; HR < 1 would favor ensovibep).

Limitation

The trial was prematurely stopped because of futility, limiting power for the primary outcome.

Conclusion

Compared with placebo, ensovibep did not improve clinical outcomes for hospitalized participants with COVID-19 receiving standard care, including remdesivir; no safety concerns were identified.

Primary funding source

National Institutes of Health.

Background

Levels of plasma SARS-CoV-2 nucleocapsid (N) antigen may be an important biomarker in patients with COVID-19 and enhance our understanding of the pathogenesis of COVID-19.

Objective

To evaluate whether levels of plasma antigen can predict short-term clinical outcomes and identify clinical and viral factors associated with plasma antigen levels in hospitalized patients with SARS-CoV-2.

Design

Cross-sectional study of baseline plasma antigen level from 2540 participants enrolled in the TICO (Therapeutics for Inpatients With COVID-19) platform trial from August 2020 to November 2021, with additional data on day 5 outcome and time to discharge.

Setting

114 centers in 10 countries.

Participants

Adults hospitalized for acute SARS-CoV-2 infection with 12 days or less of symptoms.

Measurements

Baseline plasma viral N antigen level was measured at a central laboratory. Delta variant status was determined from baseline nasal swabs using reverse transcriptase polymerase chain reaction. Associations between baseline patient characteristics and viral factors and baseline plasma antigen levels were assessed using both unadjusted and multivariable modeling. Association between elevated baseline antigen level of 1000 ng/L or greater and outcomes, including worsening of ordinal pulmonary scale at day 5 and time to hospital discharge, were evaluated using logistic regression and Fine-Gray regression models, respectively.

Results

Plasma antigen was below the level of quantification in 5% of participants at enrollment, and 1000 ng/L or greater in 57%. Baseline pulmonary severity of illness was strongly associated with plasma antigen level, with mean plasma antigen level 3.10-fold higher among those requiring noninvasive ventilation or high-flow nasal cannula compared with room air (95% CI, 2.22 to 4.34). Plasma antigen level was higher in those who lacked antispike antibodies (6.42 fold; CI, 5.37 to 7.66) and in those with the Delta variant (1.73 fold; CI, 1.41 to 2.13). Additional factors associated with higher baseline antigen level included male sex, shorter time since hospital admission, decreased days of remdesivir, and renal impairment. In contrast, race, ethnicity, body mass index, and immunocompromising conditions were not associated with plasma antigen levels. Plasma antigen level of 1000 ng/L or greater was associated with a markedly higher odds of worsened pulmonary status at day 5 (odds ratio, 5.06 [CI, 3.41 to 7.50]) and longer time to hospital discharge (median, 7 vs. 4 days; subhazard ratio, 0.51 [CI, 0.45 to 0.57]), with subhazard ratios similar across all levels of baseline pulmonary severity.

Limitations

Plasma samples were drawn at enrollment, not hospital presentation. No point-of-care test to measure plasma antigen is currently available.

Conclusion

Elevated plasma antigen is highly associated with both severity of pulmonary illness and clinically important patient outcomes. Multiple clinical and viral factors are associated with plasma antigen level at presentation. These data support a potential role of ongoing viral replication in the pathogenesis of SARS-CoV-2 in hospitalized patients.

Primary funding source

U.S. government Operation Warp Speed and National Institute of Allergy and Infectious Diseases.