Insurance Type and Area Deprivation Are Associated With Worse Overall Mortality for Patients With Muscle-invasive Bladder Cancer.

OBJECTIVE: To examine the association of area-level socioeconomic status, rural-urban residence, and type of insurance with overall and cancer-specific mortality among patients with muscle-invasive bladder cancer. METHODS: Using the Pennsylvania Cancer Registry, which collects demographic, insurance, and clinical information on every patient with cancer within the state, we identified all patients diagnosed with non-metastatic muscle-invasive bladder cancer between 2010 and 2016 based on clinical and pathologic staging. We used the Area Deprivation Index (ADI) as a surrogate for socioeconomic status and Rural-Urban Commuting Area codes to classify urban, large town, and rural communities. ADI was reported in quartiles, with 4 representing the lowest socioeconomic status. We fit multivariable logistic regression and Cox models to assess the relationship of these social determinants with overall and cancer-specific survival adjusting for age, sex, race, stage, treatment, rural-urban classification, insurance and ADI. RESULTS: We identified 2597 patients with non-metastatic muscle-invasive bladder cancer. On multivariable analysis, Medicare (hazards ratio [HR] 1.15), Medicaid (HR 1.38), ADI 3 (HR 1.16) and ADI 4 (HR 1.21) were independent predictors of greater overall mortality (all P < 0.05). Female sex and receipt of non-standard treatment were associated with increased overall mortality and bladder cancer-specific mortality. There was no significant difference in both overall and cancer-specific survival between patients who were non-Hispanic White compared to non-White or between those from urban areas, large towns, or rural locations. CONCLUSION: Lower socioeconomic status and Medicare and Medicaid insurance were associated with a greater risk of overall mortality while rural residence was not a significant factor. Implementation of public health programs may help reduce the gap in mortality for low SES at-risk populations.

Clinical validity assessment of genes frequently tested on intellectual disability/autism sequencing panels.

PURPOSE: Neurodevelopmental disorders (NDDs), such as intellectual disability (ID) and autism spectrum disorder (ASD), exhibit genetic and phenotypic heterogeneity, making them difficult to differentiate without a molecular diagnosis. The Clinical Genome Resource Intellectual Disability/Autism Gene Curation Expert Panel (GCEP) uses systematic curation to distinguish ID/ASD genes that are appropriate for clinical testing (ie, with substantial evidence supporting their relationship to disease) from those that are not. METHODS: Using the Clinical Genome Resource gene-disease validity curation framework, the ID/Autism GCEP classified genes frequently included on clinical ID/ASD testing panels as Definitive, Strong, Moderate, Limited, Disputed, Refuted, or No Known Disease Relationship. RESULTS: As of September 2021, 156 gene-disease pairs have been evaluated. Although most (75%) were determined to have definitive roles in NDDs, 22 (14%) genes evaluated had either Limited or Disputed evidence. Such genes are currently not recommended for use in clinical testing owing to the limited ability to assess the effect of identified variants. CONCLUSION: Our understanding of gene-disease relationships evolves over time; new relationships are discovered and previously-held conclusions may be questioned. Without periodic re-examination, inaccurate gene-disease claims may be perpetuated. The ID/Autism GCEP will continue to evaluate these claims to improve diagnosis and clinical care for NDDs.

Health Supervision for Children With Neurofibromatosis Type 1.

Neurofibromatosis type 1 (NF1) is a multisystem disorder that primarily involves the skin and peripheral nervous system. Its population prevalence is approximately 1 in 3000. The condition is usually recognized in early childhood, when pigmentary manifestations emerge. Although NF1 is associated with marked clinical variability, most children affected follow patterns of growth and development within the normal range. Some features of NF1 can be present at birth, but most manifestations emerge with age, necessitating periodic monitoring to address ongoing health and developmental needs and minimize the risk of serious medical complications. In this report, we provide a review of the clinical criteria needed to establish a diagnosis, the inheritance pattern of NF1, its major clinical and developmental manifestations, and guidelines for monitoring and providing intervention to maximize the health and quality of life of a child affected.

A prospective assessment of the Y402H variant in complement factor H, genetic variants in C-reactive protein, and risk of age-related macular degeneration.

PURPOSE: Two biologically related factors, complement factor H (CFH) and C-reactive protein (CRP), have been associated with AMD. The Y402H variant of CFH is located within the binding site of CFH for CRP. Although plasma CRP levels have been related to AMD and plasma CRP levels are partly determined by genetic variation, there is no information on whether genetic variants in CRP are associated with AMD. METHODS: A prospective analysis was performed of 111 men who eventually developed AMD and 401 men who remained free of AMD, all participants in the Physicians' Health Study. Genotypes were determined for the common T-->C single nucleotide polymorphism (SNP) in exon 9 of CFH (rs1061170; protein Y402H), as well as seven previously described CRP SNPs (rs3093059, rs2794521, rs3091244, rs1417938, rs1800947, rs1130864, and rs1205). Logistic regression analysis was used to evaluate individual SNPs, as well as six CRP haplotypes for association with AMD. RESULTS: The high-risk C allele of CFH was present in 45% of cases and 34% of controls. An odds ratio (OR) of 1.46 was observed for AMD (95% confidence interval [CI]: 1.05-2.04) for TC heterozygotes and an OR of 2.13 (95% CI: 1.10-4.16) for CC homozygotes, assuming a multiplicative (log-additive) model and attributable fraction of 25% (95% CI: 1% to 44%) was calculated. For CRP, single-marker or haplotype-based analysis failed to reveal any significant associations with a risk of AMD. CONCLUSIONS: These prospective data confirmed an association between the Y402H variant of CFH and a risk of AMD. In contrast, although a biologically plausible, genetic variation in CRP does not appear to be associated with a risk of AMD. Further prospective studies of a larger number of subjects are needed to substantiate available information on the genetic epidemiology of AMD.