Sickle cell disease (SCD) is a group of inherited disorders caused by mutations in HBB, which encodes haemoglobin subunit β. The incidence is estimated to be between 300,000 and 400,000 neonates globally each year, the majority in sub-Saharan Africa. Haemoglobin molecules that include mutant sickle β-globin subunits can polymerize; erythrocytes that contain mostly haemoglobin polymers assume a sickled form and are prone to haemolysis. Other pathophysiological mechanisms that contribute to the SCD phenotype are vaso-occlusion and activation of the immune system. SCD is characterized by a remarkable phenotypic complexity. Common acute complications are acute pain events, acute chest syndrome and stroke; chronic complications (including chronic kidney disease) can damage all organs. Hydroxycarbamide, blood transfusions and haematopoietic stem cell transplantation can reduce the severity of the disease. Early diagnosis is crucial to improve survival, and universal newborn screening programmes have been implemented in some countries but are challenging in low-income, high-burden settings.

Sickle cell disease

Current status of newborn screening worldwide: 2015

https://zenodo.org/record/1259489/files/article.pdf

Phenylketonuria Scientific Review Conference: state of the science and future research needs.

Newborn dried blood spot screening (NBS) is a core public health service and is the largest application of genetic testing in the United States. NBS is conducted by state public health departments to identify infants with certain genetic, metabolic, and endocrine disorders. Screening is performed in the first few days of life through blood testing. Several drops of blood are taken from the baby's heel and placed on a filter paper card. The dried blood, on the filter cards, is sent from the newborn nursery to the state health department laboratory, or a commercial partner, where the blood is analyzed. Scientific and technological advances have lead to a significant expansion in the number of tests-from an average of 6 to more than 50--and there is a national trend to further expand the NBS program. This rapid expansion has created significant ethical, legal, and social challenges for the health care system and opportunity for scholarly inquiry to address these issues. The purpose of this chapter is to provide an overview of the NBS programs and to provide an in-depth examination of two significant concerns raised from expanded newborn screening, specifically false-positives and lack of information for parents. Implications for nursing research in managing these ethical dilemmas are discussed.

Newborn screening: ethical, legal, and social implications.

A Kwan, RS Abraham, R Currier. JAMA. 2014;312(7):729–738

To assess the results of a spectrum of state-based newborn screening programs using the T-cell receptor excision (TREC) testing approach to develop more accurate population-based incidence of severe combined immunodeficiency (SCID) and other conditions associated with T-cell lymphopenia and document the effectiveness of early intervention in those newborns found to have a significant immunologic abnormality.

Cumulative TREC newborn screening data were evaluated from 10 states plus the Navajo Nation involving ∼3 million newborns.

This was an epidemiologic and retrospective observational study based on states invited to submit SCID screening algorithms, test performance data, and deidentified clinical and laboratory information regarding infants screened and cases with nonnormal results. The data evaluated were collected from January 2008 through …

https://pediatrics.aappublications.org/content/pediatrics/136/Supplement_3/S275.full.pdf

Newborn Screening for Severe Combined Immunodeficiency in 11 Screening Programs in the United States

Newborn screening in North America dates to the early work of Bob Guthrie in the USA. Screening programmes in both the USA and Canada began in the early 1960s, with documented programmes in both countries as early as 1962. Throughout the 1960s and 1970s, many of the screening tests that later became part of routine screening around the world were developed in US and Canadian laboratories, including tests for phenylketonuria, other inborn errors of metabolism, congenital hypothyroidism, congenital adrenal hyperplasia, and haemoglobinopathies. An automated punching machine developed in the USA facilitated screening expansion by significantly reducing sample preparation time and effort. US and Canadian programmes were leaders in applying computerized data management to newborn screening in the 1980s. In the 1990s, DNA and tandem mass spectrometry testing protocols were developed in the USA and applied to newborn screening. US programmes have continually expanded over time, while most Canadian programmes have not. With impetus from private laboratories and professional and consumer groups, many US programmes now screen for more than 50 conditions and there is increased expansion activity in Canada. NBS research in the USA is focused on improving system efficiency and translating other genetic testing to NBS, particularly where new technologies and treatment therapies exist. Although national newborn screening policies do not exist in either Canada or the USA, there are intense efforts to provide uniform access to screening nationwide in both countries. New partnerships between health professionals, consumers and politicians are benefiting the overall screening systems in both countries.

Newborn screening in North America

Background Methods to diagnose prostate cancer (PCa), a highly prevalent disease, remain inadequate in terms of accuracy, cost, and logistical constraints for both patients and providers. Early and accurate detection of PCa is crucial to patient management, most notably in increasing quality of life and lowering cost burdens when considering the associated treatment and follow-up pathways. This article aims to discuss the impact to care pathways for nine patients whose PCa was detected by a novel Food and Drug Administration-cleared low-field magnetic resonance imager (MRI) for transperineal PCa interventions but was missed by standard-of-care systematic transrectal ultrasound (TRUS). Methodology From December 2020 to March 2022, 41 men with elevated prostate-specific antigen (PSA) levels, positive digital rectal exam findings, and Prostate Imaging Reporting & Data System scores of three or higher were enrolled. Patients first underwent targeted transperineal biopsy guided by a low-field MRI (MRIgTBx) and co-registered with T2-weighted images from a pre-procedural 3-T MRI with suspicious lesions annotated by a board-certified radiologist. Following this procedure, patients underwent standard-of-care systematic transrectal ultrasound-guided biopsy (TRUSgSBx). The entire procedure was supervised by a board-certified urologist. Results Of the 41 enrolled patients, both MRIgTBx and TRUSgSBx biopsies detected PCa in 20 patients. MRIgTBx detected PCa in an additional nine patients that were missed by TRUSgSBx. Five of the nine patients elected to pursue immediate treatment. Patients with suspected PCa and a negative biopsy return to the clinic every three to six months for PSA tests, with additional biopsies performed every year for cases with increasing PSA levels. Conclusions Early detection of PCa in nine of the 41 patients using a novel MRIgTBx method has allowed for change management resulting in an improved quality of life and cost saving for those who opted for immediate treatment. Early intervention in cases where the standard-of-care TRUSgSBx treatment was falsely negative ultimately led to a decrease in additional screening procedures, biopsies, associated tests, and an improved pathway for patient management.

/pdf/advantageous-detection-of-significant-prostate-cancer-using-29rkxsjk.pdf

Advantageous Detection of Significant Prostate Cancer Using a Low-Field, Office-Based MRI System

http://www.endocrinepractice.org/article/S1530891X22002506/pdf

Abstract #1183829: COVID-19 Outcomes and Mortality in Patients with Metabolic Syndrome in a County-Based Hospital Setting in a Primarily Hispanic Population

Abstract In Hispanic populations, rates of metabolic comorbidities such as obesity are higher than that of non-Hispanic White in the United States. Despite having higher comorbidity rates, Hispanic populations have a lower total risk of mortality compared to non-Hispanic counterparts. In this study, we explore whether this paradox exists for COVID-19 related deaths in Hispanic patients with Metabolic Syndrome (MetS). MetS is defined by the WHO as having at least 3 of the following 5 criteria: obesity, hypertension, diabetes, hypertriglyceridemia, and low levels of HDL. A retrospective study was conducted of patients hospitalized for COVID-19 between January 1, 2020 and May 1, 2021 at a regional county hospital in Southern California. In this cohort of 269 patients, 55.4% were male, mean age was 58.4 (IQR, 48-68) years, 63.9% had obesity, 42.4% had hypertension, 40.1% had diabetes, 18.2% had hypertriglyceridemia, and 32.3% had low HDL levels, and 30.9% fit the criteria for MetS. The racial demographic of this cohort was 78.8% Hispanic, 6.32% African American, 4.46% White and 3.72% Asian. Odds ratios and confidence intervals for the relationship between MetS and mortality were calculated separately among patients who were either Hispanic or non-Hispanic. Multivariable logistic regressions accounting for interactions between MetS and Hispanic patients were assessed. In our cohort, 49 (18.2%) patients died of COVID-19. Hispanic patients had a lower probability of mortality (16.0%; 95% CI 11.1-21.0) than non-Hispanic patients (26.3%; 95% Cl 14.9-37.7). Hispanic patients with MetS had a higher risk of mortality from COVID-19 ([OR] 1.57; 95% Cl 0.74-3.33) compared to Hispanic patients without MetS. Non-Hispanic patients with MetS also had a higher risk of mortality from COVID-19 ([OR] 4.38; 95% Cl 1.19-16.03) compared to non-Hispanic patients without MetS. The MetS effect on mortality in Hispanic was 64% lower than that in non-Hispanic patients, although this result did not reach statistical significance (p value=0.18.) Our data suggests that MetS is a risk factor for COVID-19 mortality and MetS may have a lower impact on COVID-19 related death in the Hispanic population than non-Hispanic counterparts. Studies with larger sample sizes will be required to confirm these relationships. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

/pdf/psun148-disparities-in-covid-19-mortality-in-hispanic-and-2gohh8uf.pdf

John Adams

Papers

Current status of newborn screening worldwide: 2015

Newborn screening in North America

Advantageous Detection of Significant Prostate Cancer Using a Low-Field, Office-Based MRI System

Abstract #1183829: COVID-19 Outcomes and Mortality in Patients with Metabolic Syndrome in a County-Based Hospital Setting in a Primarily Hispanic Population

PSUN148 Disparities in COVID-19 Mortality in Hispanic and Non-Hispanic Patients with Metabolic Syndrome in a Community-Based Hospital