Systematic literature review of the somatic comorbidities experienced by adults with phenylketonuria.

BACKGROUND: Phenylketonuria (PKU) is an inborn error of phenylalanine (Phe) metabolism that, if untreated, causes Phe accumulation in the brain leading to neurophysiologic alterations and poor outcomes. Lifelong management centers on dietary Phe restriction, yet long-term complete metabolic control is unachievable for many adults. High blood Phe levels or chronic Phe and intact protein restriction in the diet may lead to somatic comorbidities. A systematic literature review was conducted to evaluate somatic comorbidities experienced by adults with PKU. METHODS: Clinical and observational studies reporting somatic comorbidities experienced by individuals with PKU aged ≥ 16 years (or classified as adults) evaluating a Phe-restricted diet with or without pharmacologic therapy versus no therapeutic intervention (including healthy controls), or pharmacologic therapy versus a Phe-restricted diet alone, were identified. PubMed® was searched (February 1, 2022 and updated November 1, 2023), using a pre-defined search strategy, followed by two-stage screening and data extraction. Included studies were grouped by PKU population comparison. RESULTS: 1185 records were screened; 51 studies across 12,602 individuals were extracted. Bone-related abnormalities were the most reported outcome (n = 21); several outcome measures were used. Original study groupings included: Phe-restricted diet versus healthy controls or reference values (n = 40); treatment-adherent versus those non-adherent (n = 12). Additional groups added as part of a protocol amendment included: different Phe-restricted diets (n = 4); severe versus less severe disease (n = 5). Vote counting indicated a higher burden of ≥ 1 comorbidity (or outcome measure) for the Phe-restricted diet group by 37 of 38 studies included in the analysis of Phe-restricted diet versus healthy controls; higher burden in healthy controls was reported in 12 studies. Vote counting was similar between those treatment adherent (n = 7) versus non-adherent (n = 10). CONCLUSIONS: Adults with PKU have a higher comorbidity burden than a non-PKU population. More robust studies are needed to better understand the relationship between effective metabolic control and comorbidity burden, using consistent outcome measures. This SLR was supported by BioMarin Pharmaceutical Inc., Novato, CA, and is registered with the Research Registry (reviewregistry1476).

Understanding the Economic Burden of Treating Low-Grade Upper Tract Urothelial Cancer in the United States.

INTRODUCTION: Low grade upper tract urothelial cancer is an uncommon urothelial tumor for which treatment involves multiple ureteroscopic interventions and potentially radical nephroureterectomy. Given the burden of these procedures, there is growing interest in determining how the utilization, complications and morbidities associated with treatment contribute to the burden of care for upper tract urothelial cancer. The aim of this study was to conduct a systematic literature review to understand the economic burden of treating low grade upper tract urothelial cancer. METHODS: The systematic literature review captured publications from January 1, 2009 to March 11, 2019 in MEDLINE®, Embase®, Evidence-Based Medicine Reviews, PsycINFO and EconLit. Conference proceedings from 7 different conferences were also searched. RESULTS: We identified 15 studies that reported on the economic burden associated with treatment interventions in upper tract urothelial cancer. Treatment costs associated with radical nephroureterectomy were the greatest cost component contributing to expenditures including initial procedural costs (ranging from $11,793 to $23,235 per patient), readmission/retreatment costs ($31,697 per patient) and long-terms costs up to 5 years associated with end stage renal disease and chronic kidney disease ($41,474 to $385,464 per patient). Kidney-sparing management was identified as a cost saving alternative to radical nephroureterectomy, with $252,272 per patient saved through 5 years. CONCLUSIONS: The economic burden of low grade upper tract urothelial cancer is high due to costs incurred by patient comorbidities, multiple episodes of care and complications associated with radical nephroureterectomy. Therefore, there is a need for a paradigm shift towards cost-effective, minimally invasive, kidney-sparing treatments.