Reducing overdiagnosis by polygenic risk-stratified screening: findings from the Finnish section of the ERSPC

Background:

We derived estimates of overdiagnosis by polygenic risk groups and examined whether polygenic risk-stratified screening for prostate cancer reduces overdiagnosis.

Methods:

We calculated the polygenic risk score based on genotypes of 66 known prostate cancer loci for 4967 men from the Finnish section of the European Randomised Study of Screening for Prostate Cancer. We stratified the 72 072 men in the trial into those with polygenic risk below and above the median. Using a maximum likelihood method based on interval cancers, we estimated the mean sojourn time (MST) and episode sensitivity. For each polygenic risk group, we estimated the proportion of screen-detected cancers that are likely to be overdiagnosed from the difference between the observed and expected number of screen-detected cancers.

Results:

Of the prostate cancers, 74% occurred among men with polygenic risk above population median. The sensitivity was 0.55 (95% confidence interval (CI) 0.45–0.65) and MST 6.3 (95% CI 4.2–8.3) years. The overall overdiagnosis was 42% (95% CI 37–52) of the screen-detected cancers, with 58% (95% CI 54–65) in men with the lower and 37% (95% CI 31–47) in those with higher polygenic risk.

Conclusion:

Targeting screening to men at higher polygenic risk could reduce the proportion of cancers overdiagnosed.     

Preparation of factor IX deficient human plasma by immunoaffinity chromatography using a monoclonal antibody

A murine hybridoma clone is described that grows continuously in culture and produces a monoclonal antibody we have called Royal Free Monoclonal Antibody to factor IX No. 1 (RFF-IX/1). This has high affinity for a coagulation site on factor IX. RFF-IX/1 immobilised on sepharose can be used to deplete factor IX from normal human plasma. This immunoaffinity depleted plasma is indistinguishable from severe Christmas disease plasma and can be used as the substrate in a one stage coagulation assay for factor IX. The affinity column has high capacity and can be regenerated so that large scale production from normal plasma of factor IX deficient plasma as a diagnostic reagent is now feasible.     

The effect of hemodialysis and C5a des arg on neutrophil subpopulations

Alterations in neutrophil subpopulations during human hemodialysis or following injection of C5a des arg into rabbits were studied. Whereas baseline peripheral blood neutrophils contained approximately 80% of cells that formed rosettes with IgG-sensitized erythrocytes, neutrophils harvested at the granulocyte nadir (20 min after initiating hemodialysis or the injection of C5a des arg) were markedly depleted of this population. This was seen in a change in ratio of rosette-forming neutrophils (RFN) to non-rosette-forming neutrophils (non-RFN) from 4:1 at 0 time to 1:2 at 20 min. Since non-RFN are less active in assays of adherence and chemotaxis, these alterations in circulating neutrophil populations were reflected in abnormal functional capacity of neutrophils harvested at 20 min. To study the mechanism of RFN depletion, we investigated the ability of C5a des arg to aggregate various human neutrophil suspensions. Unfractionated neutrophils and RFN demonstrated prompt in vitro aggregation in response to C5a des arg, whereas this activated complement fragment induced little aggregation in a population enriched for non-RFN. These results may explain the alterations in neutrophil adherence, chemotaxis, phagocytosis, and bactericidal activity, which have been reported to accompany clinical disorders characterized by in vivo complement activation (i.e., hemodialysis or gram-negative sepsis).     

Smoking intensity and severity of specific symptom clusters in posttraumatic stress disorder

Smoking prevalence among patients with posttraumatic stress disorder (PTSD) is over 40%. Baseline data from the VA Cooperative Studies Program trial of integrated versus usual care for smoking cessation in veterans with PTSD (N = 863) were used in multivariate analyses of PTSD and depression severity, and 4 measures of smoking intensity: cigarettes per day (CPD), Fagerström Test for Nicotine Dependence (FTND), time to first cigarette, and expired carbon monoxide. Multivariate regression analysis showed the following significant associations: CPD with race (B = ?7.16), age (B = 0.11), and emotional numbing (B =0 .16); FTND with race (B = ?0.94), education (B = ?0.34), emotional numbing (B = 0.04), significant distress (B = ?0.12), and PHQ‐9 (B = 0.04); time to first cigarette with education (B = 0.41), emotional numbing (B = ?0.03), significant distress (B = 0.09), and PHQ‐9 (B = ?0.03); and expired carbon monoxide with race (B = ?9.40). Findings suggest that among veterans with PTSD, White race and emotional numbing were most consistently related to increased smoking intensity and had more explanatory power than total PTSD symptom score. Results suggest specific PTSD symptom clusters are important to understanding smoking behavior in patients with PTSD.     

Optic Neuritis Diagnosed by Bedside Emergency Physician−Performed Ultrasound: A Case Report

Background

Optic neuritis is an inflammatory demyelinating condition of the optic nerve that causes subacute visual loss. It is often the result of an underlying systemic condition, such as multiple sclerosis. Due to the possible long-term morbidity associated with this condition, it is essential that the emergency physician recognizes the diagnosis and expedites treatment.

Objective

This case report describes optic neuritis diagnosed at the bedside by emergency physician−performed ultrasound.

Case Report

This is a case report of a young man presenting with unilateral painful vision loss. Optic neuritis must be considered in the differential diagnosis of any young patient who presents with visual complaints without any other neurologic findings. This report is unique because there are very few cases describing the findings of optic neuritis on emergency physician−performed bedside ultrasound in the literature.

Conclusions

This article presents the case, describes diagnostic modalities, especially the use of ultrasound in its diagnosis, and the course of treatment for this particular condition.     

Pediatric Program Directors Should Have an Active Presence on Twitter

For academic pediatricians, social media has become an important avenue for professional development through continuing education, professional networking, and academic collaboration. Pediatric residency program directors have recognized additional benefits of social media engagement via program promotion and resident recruitment. The novel coronavirus disease 2019 (COVID-19) pandemic and subsequent move to virtual interviews for the 2020–2021 residency interview season have created a new urgency for pediatric program directors to establish an active social media presence, primarily as a means to engage applicants and provide them with information in lieu of cancelled away rotations and in-person interviews. Twitter is a free microblogging and social networking platform that allows real-time engagement among academic pediatricians. Here, we make the case that all pediatric program directors should have an active presence on Twitter.     

MRI diagnosis of thoracic ossification of posterior longitudinal ligament with concomitant disc herniation

Summary Ossification of the posterior longitudinal ligament is a potentially curable cause of thoracic myelopathy. As this case illustrates, MRI can confirm the diagnosis, demonstrate other concomitant pathology such as disc herniation, and help assess the clinical significance of OPLL by showing spinal word compression.