scholarly journals Addressing Uncertainty: The Emergence of the CRMS/CFSPID Diagnostic Category Following Newborn Screening for Cystic Fibrosis

OBM Genetics ◽  
2021 ◽  
Vol 05 (03) ◽  
pp. 1-1
Author(s):  
Michelle Lynne LaBonte ◽  
Keyword(s):  
Cystic Fibrosis ◽  
Newborn Screening ◽  
Diagnostic Category ◽  
Public Health Approach ◽  
Positive Screen ◽  
Early Twenty ◽  
Increased Risk ◽  
Wide Range ◽  
Long Term Follow Up ◽  
The Many

This article uses cystic fibrosis as a case study to examine how physicians and scientists have navigated uncertainty following newborn screening. Despite the many benefits of newborn screening, including earlier diagnosis, therapeutic intervention, and a reduced diagnostic odyssey, this public health approach also comes with challenges. For example, physicians began to document infants with indeterminate diagnoses - those with a positive screen who did not clearly fit into the cystic fibrosis or “normal” categories - by the early twenty first century. As a means of addressing this uncertainty and to facilitate long-term follow up of such infants, the U.S. Cystic Fibrosis Foundation recommended in 2009 that a new diagnostic term, CFTR-related metabolic syndrome (CRMS), be used. However, the CRMS label was not favored in Europe and a different term, cystic fibrosis screen positive, inconclusive diagnosis (CFSPID), was adopted in 2015 instead. Efforts to address the uncertainty associated with indeterminate diagnoses have been complicated, as stakeholders have held differing views about whether the screening algorithms should aim to maximize or minimize CRMS/CFSPID cases. Many who favor the identification of babies with CRMS/CFSPID note that they are at increased risk of developing symptoms and signs consistent with a cystic fibrosis diagnosis. In contrast, those who support algorithms that reduce CRMS/CFSPID cases point to iatrogenic harms associated with the medicalization of children who may remain healthy into adulthood. Furthermore, investigators have grappled with how best to ensure equity in newborn screening among different racialized groups while concomitantly attempting to minimize false positive results. These issues are applicable beyond the context of cystic fibrosis, especially as programs contemplate the incorporation or expanded use of next generation sequencing in algorithms for a wide range of diseases, and this history highlights how efforts to reduce uncertainty in one setting can lead to new and persistent sources of uncertainty in other areas.

scholarly journals Cystic fibrosis carriers are at increased risk for a wide range of cystic fibrosis-related conditions

2019 ◽  
Vol 117 (3) ◽  
pp. 1621-1627 ◽  
Author(s):  
Aaron C. Miller ◽  
Alejandro P. Comellas ◽  
Douglas B. Hornick ◽  
David A. Stoltz ◽  
Joseph E. Cavanaugh ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Failure To Thrive ◽  
Population Level ◽  
Population Based ◽  
Carrier State ◽  
Individual Level ◽  
Relative Odds ◽  
Increased Risk ◽  
Wide Range ◽  
Autosomal Recessive Diseases

Autosomal recessive diseases, such as cystic fibrosis (CF), require inheritance of 2 mutated genes. However, some studies indicate that CF carriers are at increased risk for some conditions associated with CF. These investigations focused on single conditions and included small numbers of subjects. Our goal was to determine whether CF carriers are at increased risk for a range of CF-related conditions. Using the Truven Health MarketScan Commercial Claims database (2001–2017), we performed a population-based retrospective matched-cohort study. We identified 19,802 CF carriers and matched each carrier with 5 controls. The prevalence of 59 CF-related diagnostic conditions was evaluated in each cohort. Odds ratios for each condition were computed for CF carriers relative to controls. All 59 CF-related conditions were more prevalent among carriers compared with controls, with significantly increased risk (P < 0.05) for 57 conditions. Risk was increased for some conditions previously linked to CF carriers (e.g., pancreatitis, male infertility, bronchiectasis), as well as some conditions not previously reported (e.g., diabetes, constipation, cholelithiasis, short stature, failure to thrive). We compared our results with 23,557 subjects with CF, who were also matched with controls; as the relative odds of a given condition increased among subjects with CF, so did the corresponding relative odds for carriers (P < 0.001). Although individual-level risk remained low for most conditions, because there are more than 10 million carriers in the US, population-level morbidity attributable to the CF carrier state is likely substantial. Genetic testing may inform prevention, diagnosis, and treatment for a broad range of CF carrier-related conditions.

scholarly journals Factors affecting the growth of infants diagnosed with cystic fibrosis by newborn screening

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
K. D. Patterson ◽  
T. Kyriacou ◽  
M. Desai ◽  
W. D. Carroll ◽  
F. J. Gilchrist
Keyword(s):  
Cystic Fibrosis ◽  
Birth Weight ◽  
Newborn Screening ◽  
Clinic Visit ◽  
Healthy Population ◽  
Z Score ◽  
Poor Growth ◽  
Increased Risk ◽  
Significant Difference ◽  
Future Growth

Abstract Background Newborn screening (NBS) for cystic fibrosis (CF) improves nutritional outcomes. Despite early dietetic intervention some children fail to grow optimally. We report growth from birth to 2 years in a cohort of children diagnosed with CF by NBS and identify the variables that influence future growth. Methods One hundred forty-four children were diagnosed with CF by the West Midlands Regional NBS laboratory between November 2007 and October 2014. All anthropometric measurements and microbiology results from the first 2 years were collated as was demographic and CF screening data. Classification modelling was used to identify the key variables in determining future growth. Results Complete data were available on 129 children. 113 (88%) were pancreatic insufficient (PI) and 16 (12%) pancreatic sufficient (PS). Mean birth weight (z score) was 3.17 kg (− 0.32). There was no significant difference in birth weight (z score) between PI and PS babies: 3.15 kg (− 0.36) vs 3.28 kg (− 0.05); p = 0.33. By the first clinic visit the difference was significant: 3.42 kg (− 1.39) vs 4.60 kg (− 0.48); p < 0.0001. Weight and height remained lower in PI infants in the first year of life. In the first 2 years of life, 18 (14%) infants failed to regain their birth weight z score. The median time to achieve a weight z score of − 2, − 1 and 0 was 18, 33 and 65 weeks respectively. The median times to reach the same z scores for height were 30, 51 and 90 weeks. Birth weight z score, change in weight z score from birth to first clinic, faecal elastase, isolation of Pseudomonas aeruginosa, isolation of Staphylococcus aureus and sweat chloride were the variables identified by the classification models to predict weight and height in the first and second year of life. Conclusions Babies with CF have a lower birth weight than the healthy population. For those diagnosed with CF by NBS, the weight difference between PI and PS babies was not significantly different at birth but became so by the first clinic visit. The presence of certain factors, most already identifiable at the first clinic visit can be used to identify infant at increased risk of poor growth.

scholarly journals Deaths from all causes in a long-term follow-up study of 11583 deliberate self-harm patients

2006 ◽  
Vol 36 (3) ◽  
pp. 397-405 ◽  
Author(s):  
K. HAWTON ◽  
L. HARRISS ◽  
D. ZAHL
Keyword(s):  
Deliberate Self Harm ◽  
Risk Of Death ◽  
Follow Up Study ◽  
Increased Risk ◽  
Wide Range ◽  
Long Term Follow Up ◽  
Physical Disorders ◽  
Self Harm ◽  
Care Costs

Background. Deliberate self-harm (DSH) may be associated with increased risk of death from a variety of causes, not just suicide.Method. A follow-up study of 11583 DSH patients who presented to a general hospital over a 20-year period was conducted to examine risk of death from a range of causes during a follow-up period of between 3 and 23 years. Deaths were identified through national death registries. Expected numbers of deaths were calculated from national death statistics.Results. The number of deaths (1185, 10·2%) was 2·2 times the expected number, the excess being significantly greater in males than females. Suicides were 17 times more frequent than expected and undetermined causes of death and accidental poisonings 15 times more frequent. Significantly more than expected numbers of deaths from most natural causes were found, including respiratory disease, circulatory, neurological, endocrine, digestive, skin and musculoskeletal and connective tissue disorders, and symptoms, signs and ill-defined conditions. Deaths due to accidents other than poisoning were more frequent than expected in both genders and homicides more frequent in males.Conclusions. In addition to increased risk of suicide, DSH patients are at increased risk of dying from a wide range of other causes. Possible explanations include lifestyle factors, physical disorders contributing to initial risk of DSH, and social disadvantage. The findings are relevant to clinical management and evaluation of outcome and health-care costs associated with DSH.

scholarly journals It All Depends What You Count—The Importance of Definitions in Evaluation of CF Screening Performance

2020 ◽  
Vol 6 (2) ◽  
pp. 47
Author(s):  
Natasha Heather ◽  
Dianne Webster
Keyword(s):  
Cystic Fibrosis ◽  
New Zealand ◽  
Newborn Screening ◽  
Quality Assessment ◽  
Key Factors ◽  
Meaningful Comparison ◽  
Screening Performance ◽  
Increased Risk ◽  
Screening Sensitivity ◽  
Quality Assessment And Improvement

Screening metrics are essential to both quality assessment and improvement, but are highly dependent on the way positive tests and cases are counted. In cystic fibrosis (CF) screening, key factors include how mild cases of late-presenting CF and CF screen positive, inconclusive diagnosis (CFSPID) are counted, whether those at prior increased risk of CF are excluded from the screened population, and which aspects of the screening pathway are considered. This paper draws on the New Zealand experience of almost forty years of newborn screening for CF. We demonstrate how different definitions impact the calculation of screening sensitivity. We suggest that, to enable meaningful comparison, CF screening reports should clarify what steps in the screening pathway are included in the assessment, as well as the algorithm used and screening target.

scholarly journals Long-term follow-up of cystic fibrosis newborn screening: Psychosocial functioning of adolescents and young adults

2014 ◽  
Vol 13 (2) ◽  
pp. 227-234 ◽  
Author(s):  
Audrey Tluczek ◽  
Anita Laxova ◽  
Adam Grieve ◽  
Anne Heun ◽  
Roger L. Brown ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Young Adults ◽  
Newborn Screening ◽  
Psychosocial Functioning ◽  
Adolescents And Young Adults ◽  
Long Term Follow Up

The Many Pasts of Detective Fiction

2020 ◽  
Vol 1 (2) ◽  
pp. 157-172
Author(s):  
Thomas Leitch
Keyword(s):  
Detective Fiction ◽  
Golden Age ◽  
Public History ◽  
Detective Novel ◽  
Sherlock Holmes ◽  
Detective Story ◽  
The Past ◽  
Wide Range ◽  
Detective Novels ◽  
The Many

Building on Tzvetan Todorov's observation that the detective novel ‘contains not one but two stories: the story of the crime and the story of the investigation’, this essay argues that detective novels display a remarkably wide range of attitudes toward the several pasts they represent: the pasts of the crime, the community, the criminal, the detective, and public history. It traces a series of defining shifts in these attitudes through the evolution of five distinct subgenres of detective fiction: exploits of a Great Detective like Sherlock Holmes, Golden Age whodunits that pose as intellectual puzzles to be solved, hardboiled stories that invoke a distant past that the present both breaks with and echoes, police procedurals that unfold in an indefinitely extended present, and historical mysteries that nostalgically fetishize the past. It concludes with a brief consideration of genre readers’ own ambivalent phenomenological investment in the past, present, and future each detective story projects.

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