01/30/2024

Familial hypercholesterolemia

From the abstract: "A total of 21 studies evaluating 62 strategies were included in this review, most of the studies (95%) adopted a healthcare perspective in the base case, and majority were set in high-income countries. Strategies analysed included cascade screening (23 strategies), opportunistic screening (13 strategies), systematic screening (11 strategies) and population-wide screening (15 strategies). Most of the strategies relied on genetic diagnosis for case ascertainment. Based on reported willingness to pay thresholds for each setting, most CEA studies concluded that screening for FH compared with no screening was cost-effective, regardless of the screening strategy. Cascade screening resulted in the largest health benefits per person tested. "

Whole genome sequencing

From the abstract: "Is whole-genome sequencing (WGS) more cost-effective than whole-exome sequencing for children with suspected genetic disorders? The results of this economic evaluation of a cohort of 870 pediatric patients suggest that adopting WGS as a first-tier strategy would be cost-effective at a willingness-to-pay threshold of €30 000 to €50 000 (US $32?625-$54?375), specifically for the diagnosis of severely ill infants with suspected genetic disorders. ng These findings suggest that wider use of WGS may minimize diagnostic delays and facilitate timely implementation of appropriate treatments. "

Gene therapy

From the abstract: "Gene editing using clustered regularly interspaced short palindromic repeats (CRISPR) holds the promise to arrest or cure monogenic disease if it can be determined which genetic change to create without inducing unintended cellular dysfunction and how to deliver this technology to the target organ reliably and safely. Clinical trials for blood and liver disorders, for which delivery of CRISPR is not limiting, show promise, yet no trials have begun for central nervous system (CNS) indications. "

Sudden infant death

From the abstract: "In this case-control study, postmortem serum and/or cerebrospinal fluid (CSF) samples from 71 sudden infant death syndrome (SIDS) cases and 20 controls were screened for inflammatory markers. A subset of SIDS cases showed elevated levels of CSF neopterin; metagenomic next-generation sequencing identified human parechovirus 3 (HPeV3) in 1 case, and single-nucleus RNA sequencing revealed cell type–specific molecular signatures of brainstem neuroinflammation associated with HPeV3. Postmortem application of next-generation molecular approaches can reveal undiagnosed neuroinflammation, occult infection, and novel insights into pathophysiology in infants dying suddenly and unexpectedly. "

Artificial intelligence

From the article: "Little more than a year after ChatGPT’s public release, clinical applications of generative artificial intelligence and large language models (LLMs) are advancing rapidly. In the long term, LLMs may revolutionize much of clinical medicine, from patient diagnosis to treatment. In the short term, however, it is the everyday clinical tasks that LLMs will change most quickly and with the least scrutiny. Specifically, LLMs that summarize clinical notes, medications, and other forms of patient data are in advanced development and could soon reach patients. Summarization, though, is not as simple as it seems, and variation in LLM-generated summaries could exert important and unpredictable effects on clinician decision-making. "