An Effective Program to Resolve Ambiguous Results from State Newborn Hemoglobinopathy Screening.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3563-3563 ◽  
Author(s):  
Carolyn Hoppe ◽  
Mahin Azimi ◽  
Sharon Aslanian ◽  
Bertram Lubin ◽  
Elliott Vichinsky ◽  
...  
Keyword(s):  
Newborn Screening ◽  
Diagnostic Testing ◽  
Screening Programs ◽  
Resource Center ◽  
Life Threatening ◽  
Effective Program ◽  
Hb S ◽  
Clinically Significant ◽  
One Year ◽  
Conclusive Diagnosis

Abstract Newborn screening (NBS) for hemoglobinopathies is an important mechanism for identification of affected individuals so that prophylactic treatment and comprehensive care are delivered before life-threatening complications occur. Whilst more common Hb variants, such as Hb S and Hb C, are readily identified, many children with other potentially significant Hb variants never have a conclusive diagnosis made by state newborn screening programs. In conjunction with the National Newborn Screening and Genetics Resource Center (NNSGRC), we investigated whether unconfirmed or ambiguous samples could be rapidly diagnosed and reported, using only a portion of the original dried blood spot (DBS) specimen. State NBS programs were approached about sending DBS samples from newborns with ambiguous Hb results for further testing. Using a single 6 mm hole punch from the original DBS, the primary screening results were first confirmed with HPLC, IEF and citrate agar electrophoresis. With the same sample, genotyping for Hb S, C, E, Knossos, D-LA, and O-Arab, and > 95% of the most common β-thalassemia mutations, was performed using a novel linear array platform. Samples revealing Bart’s Hb were tested for common deletional and non-deletional α-thalassemia mutations using gap-PCR or DNA sequencing. The test results, along with a clinical interpretation, were reported back to the NBS programs within 2 weeks. During a one-year period (08/03–08/04), a total of 309 newborn samples from 30 participating states were received for definitive diagnostic testing. Of these, 115 (37%) revealed a clinically significant genotype. Specifically, 102 newborns had sickle cell disease (55 HbSS, 27 HbSC, 16 HbS/β-thal, 3 HbSE, 1 HbS/O-Arab); 6 newborns had β-thalassemia (2 β0-thal, 4 E/β-thal); and 7 had α-thalassemia (5 HbH, 1 HbH-CS, 2 α-triplication). Compound heterozygosity for 2 Hb variants was found in 15 cases and interpreted as clinically insignificant. Another 14 samples revealed a clinically benign HbEE genotype. A Hb variant trait was identified in 124 samples and 41 samples had a normal Hb genotype. This NNSGRC-sponsored pilot study demonstrates that a centralized referral laboratory providing definitive diagnostic testing for hemoglobinopathies is not only feasible, but a much needed resource for many state newborn screening programs. Using rapid and efficient molecular methods, our laboratory identified a clinically significant sickling of thalassemic disorder in 37% of previously unconfirmed newborn samples. Based on these results, the implementation of a referral laboratory to provide prompt definitive diagnosis of clinically relevant hemoglobin variants would be an invaluable extension of existing newborn screening programs.

Newborn Screening for Sickle Cell Disease: Effect on Mortality

PEDIATRICS ◽  
1989 ◽  
Vol 83 (5) ◽  
pp. 834-834
Author(s):  
Elliott Vichinsky ◽  
Deborah Hurst ◽  
Ann Earles ◽  
Klara Kleman ◽  
Bertram Lubin
Keyword(s):  
Sickle Cell Disease ◽  
Mortality Rate ◽  
Newborn Screening ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Comprehensive Treatment ◽  
Cell Disease ◽  
Screening Programs ◽  
Hb S ◽  
Overall Mortality

Newborn screening for sickle cell disease has been recommended as a method of decreasing patient mortality. However, its effectiveness in accomplishing this has not been reliably measured. To help determine the effectiveness, 10 years of experience in newborn screening have been summarized. The effects of early patient enrollment in a comprehensive treatment program on long-term morbidity and mortality are reported. From 1975 to 1985, 84,663 newborns were screened regardless of race or ethnic background. Hb Bait's was present in 5%, hemoglobin AS in 2.6%, and hemoglobin AC in 0.75%. Excluding Bart's, approximately 3.6% of all newborns were carriers for hemoglobinopathy. Sickle cell disease occurred in 1:951 births (58 Hb 55, 25 Hb FSC, three Hb S-β+-thalassemia, and three Hb S-β°-thalassemia). In addition, one in every 4,233 newborns had a clinically significant thalassemia syndrome (eight Hb FE, ten Hb F only, two Hb H). Compared with other newborn screening programs in California (congenital hypothyroidism, 1:3,849; phenylketonuria, 1:22,474; galactosemia, 1:74,103), hemoglobinopathies are the most prevalent congenital disease. Eighty-one newborns with sickle cell disease were followed up for 7.2 years. Patients experienced 513 hospitalizations, including 13 episodes of sepsis with or without meningitis and ten acute sequestration crises. The overall mortality rate for patients with sickle cell anemia diagnosed in the newborn period was 1.8%. In comparison, the clinical course of 64 patients with sickle cell anemia diagnosed after 3 months of age and followed up for an average of 9.4 years was analyzed. Five of these patients died. In two of these, sickle cell anemia was diagnosed at the time of the death. Overall mortality rate in this group was 8%. In summary, the data indicate that newborn screening, when coupled with extensive follow-up and education, will significantly decrease patient mortality.

scholarly journals 1114. Utility of a Bedside Diagnostic Testing Algorithm to Screen for Hospital-Onset Clostridium difficile Infection

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S334-S334
Author(s):  
Ramesh V Nathan ◽  
Amy Lenz ◽  
Genevieve Davis
Keyword(s):  
Diagnostic Testing ◽  
Cost Effective ◽  
Major Elements ◽  
Clinical Change ◽  
Marked Rise ◽  
Clinically Significant ◽  
One Year ◽  
Definition Of ◽  
Testing Algorithm ◽  
Simple Bedside

Abstract Background Molecular assays have improved C. difficile detection in hospitalized patients. However, asymptomatic carriers have been misclassified as hospital onset C. difficile infection (HO-CDI), which has implications for management and infection prevention programs. At our facility, we implemented robust antibiotic stewardship policies in 2016 and had an SIR for HO-CDI of 0.73 for the year. In Q1 2017, this increased to 1.88. These cases revealed that nearly all tests, found positive for C. difficile, did not meet the standard definition of clinically significant diarrhea (CSD). Moreover, many patients did not have a clinical change in condition that supported a diagnosis of C. difficile. We reasoned that an algorithm for appropriate testing for C. difficile would significantly reduce our perceived rates of HO-CDI. We also reasoned that this tool could efficiently be used at the bedside during a clinical assessment. Methods To determine which patients had CSD, we designed, educated on and implemented an algorithm to screen for appropriate testing. It required three major elements: three or more loose stools in 24 hours, no gastric motility agents 48 hours prior, and a clinical change in condition (e.g., leukocytosis, fever, abdominal cramping). The completed algorithm accompanied the stool specimen and was required for testing. We evaluated each submitted algorithm for method validation. From this, we determined testing appropriateness and algorithm tool selectivity. Results One year pre- and post-algorithm periods (PR-A and PO-A, respectively) were defined. Following its introduction, we noted a 57% decline in rates of HO-CDI (23 cases PR-A vs. 10 cases PO-A), and a 44% reduction in tests sent for C. difficile (average of 41 tests/month PR-A vs. 23 tests/month PO-A). We only used NAAT testing. We also noted a marked rise in adherence to the algorithm as time elapsed. The PDSA tool was used to refine the algorithm, with improved utilization by providers. Conclusion A simple bedside algorithm leads to more appropriate testing of patients for HO-CDI. A significant decline in reported rates of HO-CDI was noted. There is an additional benefit of diagnostic stewardship, as fewer tests are sent. This tool can be used immediately and independent of an electronic health record, is very cost effective, and is applicable to hospitals with low rates of HO-CDI. Disclosures R. V. Nathan, Merck, Allergan, The Medicines Co.: Speaker’s Bureau, Speaker honorarium.

scholarly journals Value of Newborn Screening Programs for Severe Combined Immunodeficiency

2021 ◽  
Author(s):  
Elisa Pirozzi
Keyword(s):  
Newborn Screening ◽  
Screening Program ◽  
Severe Combined Immunodeficiency ◽  
Positive Family History ◽  
Cell Receptor ◽  
Screening Tests ◽  
Combined Immunodeficiency ◽  
Medical Progress ◽  
Screening Programs ◽  
Life Threatening

Severe Combined Immunodeficiency Disease (SCID) is life-threatening disease of infancy and childhood characterized by recurrent infections and failure to thrive. Given the modern medical progress made available for treating SCID, early identification of these children is paramount to their wellbeing and overall survival into adulthood. Newborn screening (NBS) programs provide the opportunity to identify SCID patients before life-threatening infections can manifest. The T-cell receptor excision circles (TRECs) assay currently used for SCID screening has been shown to satisfy all parameters of an effective screening test.  Its widespread use is indicated by the time-sensitive nature of the disease, its efficacy in reducing morbidity and mortality in these patients, and the cost-effectiveness of prompt recognition versus long-term management. While immensely beneficial, screening tests still hold limitations that require analyzing. Follow-up measures for SCID identification programs have identified ambiguity and inconsistency among testing algorithms across facilities and technical errors that have causes inaccurate results. Considering fewer than 20% of SCID patients report a positive family history and the lethal consequences of disease if left untreated, a screening program is a highly valuable tool for early diagnosis and prompt intervention.

Renal Phosphate Handling in Antiretroviral-naïve HIV-infected Patients

2020 ◽  
Vol 20 ◽  
Author(s):  
Tewogbade Adeoye Adedeji ◽  
Simeon Adelani. Adebisi ◽  
Nife Olamide Adedeji ◽  
Olusola Akanni Jeje ◽  
Rotimi Samuel Owolabi
Keyword(s):  
Hiv Infection ◽  
Plasma Phosphate ◽  
Cross Sectional ◽  
Phosphate Retention ◽  
Significant Difference ◽  
Immunodeficiency Virus ◽  
Life Threatening ◽  
Moderate Chronic Kidney Disease ◽  
One Year ◽  
Sectional Analysis

Background: Human immunodeficiency virus (HIV) infection impairs renal function, thereby affecting renal phosphate metabolism. Objectives: We prospectively estimated the prevalence of phosphate abnormalities (mild, moderate to life-threatening hypophosphataemia, and hyperphosphataemia) before initiating antiretroviral therapy (ART). Methods: A cross-sectional analysis was performed on 170 consecutive newly diagnosed ART-naïve, HIV-infected patients attending our HIV/AIDS clinics over a period of one year. Fifty (50) screened HIV-negative blood donors were used for comparison (controls). Blood and urine were collected simultaneously for phosphate and creatinine assay to estimate fractional phosphate excretion (FEPi %) and glomerular filtration rate (eGFR). Results: eGFR showed significant difference between patients’ and controls’ medians (47.89ml/min/1.73m2 versus 60ml/min/1.73m2, p <0.001); which denotes a moderate chronic kidney disease in the patients. Of the 170 patients, 78 (45.9%) had normal plasma phosphate (0.6-1.4 mmol/L); 85 (50%) had hyperphosphataemia. Grades 1, 2 and 3 hypophosphataemia was observed in 3 (1.8%), 3 (1.8%), and 1(0.5%) patient(s) respectively. None had grade 4 hypophosphataemia. Overall, the patients had significantly higher median of plasma phosphate than the controls, 1.4 mmol/L (IQR: 1.0 – 2.2) versus 1.1 mmol/L (IQR: 0.3 – 1.6), p <0.001, implying hyperphosphataemia in the patients; significantly lower median urine phosphate than the controls, 1.5 mmol/L (IQR: 0.7 -2.1) versus 8.4 mmol/L (IQR: 3.4 – 16), p <0.001), justifying the hyperphosphataemia is from phosphate retention; but a non-significantly lower median FEPi% than the controls, 0.96 % (IQR: 0.3 -2.2) versus 1.4% (IQR: 1.2 -1.6), p > 0.05. Predictors of FEPi% were age (Odds ratio, OR 0.9, p = 0.009); weight (OR 2.0, p < 0.001); CD4+ cells count predicted urine phosphate among males (p = 0.029). Conclusion: HIV infection likely induces renal insufficiency with reduced renal phosphate clearance. Thus, hyperphosphataemia is highly prevalent, and there is mild to moderate hypophosphataemia but its life-threatening form (grade 4) is rare among ART-naïve HIV patients.

A Serological Storm

1970 ◽  
Vol 9 (2) ◽  
Author(s):  
Bertha Wong MD ◽  
Maria Bagovich MD ◽  
Ivan Blasutig PhD ◽  
Simon Carette MD MPhil
Keyword(s):  
Differential Diagnosis ◽  
Hepatitis C Virus ◽  
Immune System ◽  
Hepatitis C ◽  
Hcv Infection ◽  
Clinical Context ◽  
Autoantibody Profile ◽  
Life Threatening ◽  
Clinically Significant ◽  
Sensory Polyneuropathy

This article describes a patient presenting with a sensory polyneuropathy and multiple autoantibodies, leading to the diagnosis of hepatitis C virus (HCV) infection. His widely positive autoantibody profile in the absence of clinically significant rheumatic disease illustrates the importance of interpreting autoimmune serology in the appropriate clinical context and the concept of HCV being a non-specific activator of the immune system. In addition, it highlights the importance of considering untreated HCV infection in the differential diagnosis of rheumatic complaints, particularly if the workup reveals multiple autoantibodies, as HCV is a potentially severe and life-threatening disease, which can be appropriately managed with effective antiviral therapy.

scholarly journals Adrenoleukodystrophy Newborn Screening in California Since 2016: Programmatic Outcomes and Follow-Up

2021 ◽  
Vol 7 (2) ◽  
pp. 22
Author(s):  
Jamie Matteson ◽  
Stanley Sciortino ◽  
Lisa Feuchtbaum ◽  
Tracey Bishop ◽  
Richard S. Olney ◽  
...  
Keyword(s):  
Newborn Screening ◽  
Program Implementation ◽  
Screening Program ◽  
Birth Prevalence ◽  
Variant Of Uncertain Significance ◽  
Implementation Challenges ◽  
Screening Programs ◽  
Uncertain Significance ◽  
Long Term Follow Up

X-linked adrenoleukodystrophy (ALD) is a recent addition to the Recommended Uniform Screening Panel, prompting many states to begin screening newborns for the disorder. We provide California’s experience with ALD newborn screening, highlighting the clinical and epidemiological outcomes observed as well as program implementation challenges. In this retrospective cohort study, we examine ALD newborn screening results and clinical outcomes for 1,854,631 newborns whose specimens were received by the California Genetic Disease Screening Program from 16 February 2016 through 15 February 2020. In the first four years of ALD newborn screening in California, 355 newborns screened positive for ALD, including 147 (41%) with an ABCD1 variant of uncertain significance (VUS) and 95 males diagnosed with ALD. After modifying cutoffs, we observed an ALD birth prevalence of 1 in 14,397 males. Long-term follow-up identified 14 males with signs of adrenal involvement. This study adds to a growing body of literature reporting on outcomes of newborn screening for ALD and offering a glimpse of what other large newborn screening programs can expect when adding ALD to their screening panel.

scholarly journals Newborn Screening for Congenital Hypothyroidism in Japan

2021 ◽  
Vol 7 (3) ◽  
pp. 34
Author(s):  
Kanshi Minamitani
Keyword(s):  
Birth Weight ◽  
Low Birth Weight ◽  
Newborn Screening ◽  
Congenital Hypothyroidism ◽  
Failure To Thrive ◽  
Thyroid Stimulating Hormone ◽  
Low Birth Weight Infants ◽  
Term Infants ◽  
Screening Programs ◽  
Screening Strategies

Congenital hypothyroidism (CH) is the most common preventable cause of intellectual impairment or failure to thrive by early identification and treatment. In Japan, newborn screening programs for CH were introduced in 1979, and the clinical guidelines for newborn screening of CH were developed in 1998, revised in 2014, and are currently undergoing further revision. Newborn screening strategies are designed to detect the elevated levels of thyroid stimulating hormone (TSH) in most areas of Japan, although TSH and free thyroxine (FT4) are often measured simultaneously in some areas. Since 1987, in order not to observe the delayed rise in TSH, additional rescreening of premature neonates and low birth weight infants (<2000 g) at four weeks of life or when their body weight reaches 2500 g has been recommended, despite a normal initial newborn screening. Recently, the actual incidence of CH has doubled to approximately 1:2500 in Japan as in other countries. This increasing incidence is speculated to be mainly due to an increase in the number of mildly affected patients detected by the generalized lowering of TSH screening cutoffs and an increase in the number of preterm or low birth weight neonates at a higher risk of having CH than term infants.

scholarly journals The bowel and beyond: extracolonic findings from CT colonography

2021 ◽  
Author(s):  
Gerard Lambe ◽  
Peter Hughes ◽  
Louise Rice ◽  
Caoimhe McDonnell ◽  
Mark Murphy ◽  
...  
Keyword(s):  
Ct Colonography ◽  
Surgical Intervention ◽  
Potential Significance ◽  
Age And Gender ◽  
Abdominal Aortic ◽  
Life Threatening ◽  
Extracolonic Findings ◽  
The Difference ◽  
Clinically Significant ◽  
And Gender

AbstractCT colonography has emerged as the investigation of choice for suspected colorectal cancer in patients when a colonoscopy in incomplete, is deemed high risk or is declined because of patient preference. Unlike a traditional colonoscopy, it frequently reveals extracolonic as well as colonic findings. Our study aimed to determine the prevalence, characteristics and potential significance of extracolonic findings on CT colonography within our own institution. A retrospective review was performed of 502 patients who underwent CT colonography in our institution between January 1, 2010 and January 4, 2015. Of 502 patients, 60.63% had at least one extracolonic finding. This was close to other similar-sized studies (Kumar et al. Radiology 236(2):519–526, 2005). However, our rate of E4 findings was significantly higher than that reported in larger studies at 5.3%(Pooler et al. AJR 206:313–318, 2016). The difference may be explained by our combination of symptomatic/screening patients or by the age and gender distribution of our population. Our study lends support to the hypothesis that CT colonography may be particularly useful in identifying clinically significant extracolonic findings in symptomatic patients. CT colonography may allow early identification of extracolonic malignancies and life-threatening conditions such as an abdominal aortic aneurysm at a preclinical stage when they are amenable to medical or surgical intervention. However, extracolonic findings may also result in unnecessary investigations for subsequently benign findings.

scholarly journals Consequences of antepartum hemorrhage and its maternal and perinatal outcome

2019 ◽  
Vol 8 (4) ◽  
pp. 1480
Author(s):  
Himang Jharaik ◽  
Bishan Dhiman ◽  
S. K. Verma ◽  
Aditi Sharma
Keyword(s):  
Perinatal Outcome ◽  
Placenta Previa ◽  
Developed Countries ◽  
Perinatal Morbidity ◽  
Antepartum Haemorrhage ◽  
High Risk Factors ◽  
Fetal Complications ◽  
Life Threatening ◽  
One Year ◽  
Life Threatening Event

Background: Antepartum haemorrhage, a life-threatening event, is defined as bleeding per vaginum occurring after the fetus has reached the period of viability, considered to be 20 weeks in developed countries and 28 weeks in countries with low resource settings. We evaluated the consequences of antepartum haemorrhage, their maternal and perinatal outcome so as to outline the proper management of patient in order to improve both maternal and perinatal morbidity and mortality.Methods: This one-year prospective study totaled 133 cases of APH fulfilling the inclusion criteria were studied. Data was recorded on the MS excel sheet for further analysis and processing.Results: Total 6693 deliveries were conducted out of which 133 presented as APH and incidence of APH was found out to be 1.98%. Placenta previa was most common. APH was commonly associated with multigravida and most cases were in age group of 26-30 years. Most of the PP and abruption cases were admitted at 34-37 weeks and 31-33 weeks respectively. High risk factors included previous LSCS and D and C, hypertension, multiple pregnancies and malpresentations. Most of the patients underwent preterm LSCS. Most fetal complications were due to prematurity. 58.6% patients were transfused blood. Overall perinatal mortality was 20.1% and maternal mortality was zero.Conclusions: Early diagnoses, timely referrals and transfusion facilities along with trained team of doctors with well-equipped ICU facility goes a long way in avoiding APH related maternak and fetal complications.

scholarly journals Bedside examination of the vestibular and ocular motor system in patients with acute vertigo or dizziness

2019 ◽  
Vol 3 (2) ◽  
pp. 2514183X1988615
Author(s):  
Alexander A Tarnutzer ◽  
Marianne Dieterich
Keyword(s):  
Diagnostic Testing ◽  
Initial Assessment ◽  
Head Impulse Test ◽  
Motor Deficits ◽  
Ocular Motor ◽  
Bedside Examination ◽  
Life Threatening ◽  
Ocular Motor System ◽  
Bedside Tests ◽  
The Brain

In the initial assessment of the patient with acute vertigo or dizziness, both structured history-taking and a targeted bedside neuro-otological examination are essential for distinguishing potentially life-threatening central vestibular causes from those of benign, self-limited peripheral labyrinthine origin and thus for deciding on further diagnostic testing. In this article, the key elements of the vestibular and ocular motor examination, which should be obtained at the bedside in these acutely dizzy patients, will be discussed. Specifically, this will include the following five domains: ocular stability for (I) nystagmus and for (II) eye position (skew deviation), (III) the head-impulse test (HIT), (IV) postural stability, and (V) ocular motor deficits of saccades, smooth pursuit eye movements, and optokinetic nystagmus. We will also discuss the diagnostic accuracy of specific combinations of these bedside tests (i.e. HIT, testing for nystagmus and vertical divergence, referred to as the H.I.N.T.S. three-step examination), emphasizing that the targeted neuro-otological bedside examination is more sensitive for identifying central causes in acute prolonged vertigo and dizziness than early MRI of the brain.

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