834 hot topic(s) found with the query "Evidence"
Adherence to the Mediterranean diet can beneficially affect the gut microbiota composition: a systematic review
(Posted: Apr 19, 2024 10AM)
From the abstract: "Dietary patterns could have a notable role in shaping gut microbiota composition. Evidence confirms the positive impact of the Mediterranean diet (MD), as one of the most studied healthy dietary patterns, on the gut microbiota profile. We conducted this systematic review to investigate the results of observational studies and clinical trials regarding the possible changes in the gut microbiota composition, metabolites, and clinical outcomes following adherence to MD in healthy cases or patients suffering from metabolic disorders. "
Family cascade screening for equitable identification of familial hypercholesterolemia: study protocol for a hybrid effectiveness-implementation type III randomized controlled trial
(Posted: Apr 19, 2024 10AM)
From the abstract: " Familial hypercholesterolemia (FH) is a heritable disorder affecting 1.3 million individuals in the USA. Eighty percent of people with FH are undiagnosed, particularly minoritized populations including Black or African American people, Asian or Asian American people, and women across racial groups. Family cascade screening is an evidence-based practice that can increase diagnosis and improve health outcomes but is rarely implemented in routine practice, representing an important care gap. In pilot work, we leveraged best practices from behavioral economics and implementation science—including mixed-methods contextual inquiry with clinicians, patients, and health system constituents—to co-design two patient-facing implementation strategies to address this care gap..."
Lethal phenotypes in Mendelian disorder
P Cacheiro et al, GIM, April 15, 2024
(Posted: Apr 15, 2024 2PM)
From the abstract: "We queried Online Mendelian Inheritance in Man for terms related to lethality and classified all Mendelian genes according to the earliest age of death recorded for the associated disorders, from prenatal death to no reports of premature death. We characterised the genes across these lethality categories, examined the evidence on viability from mouse models and explored how this information could be used for novel gene discovery. "
Genomics reveals heterogeneous Plasmodium falciparum transmission and selection signals in Zambia.
Abebe A Fola et al. Commun Med (Lond) 2024 4 (1) 67
(Posted: Apr 10, 2024 8AM)
From the abstract: "We conducted genomic surveillance of Plasmodium falciparum parasites from the 2018 Malaria Indicator Survey in Zambia, a nationally representative household survey of children under five years of age. We whole-genome sequenced and analyzed 241?P. falciparum genomes from regions with varying levels of malaria transmission across Zambia and estimated genetic metrics that are informative about transmission intensity, genetic relatedness between parasites, and selection. We provide genomic evidence of widespread within-host polygenomic infections, regardless of epidemiological characteristics, underscoring the extensive and ongoing endemic malaria transmission in Zambia. Our analysis reveals country-level clustering of parasites from Zambia and neighboring regions, with distinct separation in West Africa. "
Clinical Effectiveness of Newborn Screening for Spinal Muscular Atrophy: A Nonrandomized Controlled Trial.
Oliver Schwartz et al. JAMA Pediatr 2024 4
(Posted: Apr 09, 2024 8AM)
From the abstract: " Is early diagnosis through newborn screening associated with improved outcomes in infants with spinal muscular atrophy compared to those diagnosed after onset of symptoms? In this nonrandomized controlled trial within the SMARTCARE registry, patients identified by newborn screening showed better motor development with disease-modifying treatments than those who were diagnosed after onset of symptoms. These results offer supporting evidence for the benefit of newborn screening for spinal muscular atrophy. "
How to support the transition to AI-powered healthcare.
et al. Nat Med 2024 3 (3) 609-610
(Posted: Mar 25, 2024 8AM)
From the article: "To make health systems more sustainable in the long-term, incentivize artificial intelligence (AI) and digital technologies that are grounded on careful testing and real-world validation. We are confident that this transition to ‘AI-powered’ healthcare will occur and that it has the potential to bring widespread public good. At the same time, we believe that these benefits will realize more steadily and more quickly with carefully designed clinical studies and evidence-based implementation of AI algorithms and devices in the real world."
PARP Inhibitors for Breast Cancer Treatment: A Review.
Stefania Morganti et al. JAMA Oncol 2024 3
(Posted: Mar 23, 2024 6AM)
From the abstract: "Poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitors have revolutionized the treatment of patients with germline BRCA1/2-associated breast cancer, representing the first targeted therapy capable of improving outcomes in patients with hereditary tumors. However, resistance to PARP inhibitors occurs in almost all patients. This narrative review summarizes the biological rationale behind the use of PARP inhibitors in breast cancer, as well as the available evidence, recent progress, and potential future applications of these agents. Recent studies have shown that the benefit of PARP inhibitors extends beyond patients with germline BRCA1/2-associated metastatic breast cancer to patients with somatic BRCA1/2 variants and to those with germline PALB2 alterations. "
Guidance on Use of Race, Ethnicity, and Geographic Origin as Proxies for Genetic Ancestry Groups in Biomedical Publications
G Feero et al, JAMA, March 12, 2024
(Posted: Mar 12, 2024 0PM)
From the article: "In March 2023, the National Academies of Sciences, Engineering, and Medicine (NASEM) released a consensus study report titled Using Population Descriptors in Genetics and Genomics Research.The report is more than a discussion of the use of terminology; the authors of the NASEM report suggest a tectonic shift away from current models that use race, ethnicity, and geographic origin as proxies for genetic ancestry groups (ie, a set of individuals who share more similar genetic ancestries) in genetic and genomic science. The recommendations are rooted in evidence that genetic variation in individuals falls, in general, on a continuum of variation not captured well by existing population descriptors and that the ongoing use of such descriptors as analytical variables jeopardizes the scientific validity of research."
Evidence for the additivity of rare and common variant burden throughout the spectrum of intellectual disability.
Lea Urpa et al. Eur J Hum Genet 2024 3
(Posted: Mar 12, 2024 0PM)
From the abstract: "Intellectual disability (ID) is a common disorder, yet there is a wide spectrum of impairment from mild to profoundly affected individuals. Mild ID is seen as the low extreme of the general distribution of intelligence, while severe ID is often seen as a monogenic disorder caused by rare, pathogenic, highly penetrant variants. To investigate the genetic factors influencing mild and severe ID, we evaluated rare and common variation in the Northern Finland Intellectual Disability cohort (n?=?1096 ID patients). Overall, we report evidence for the additivity of rare and common variant burden throughout the spectrum of intellectual disability. "
Being precise with anticoagulation to reduce adverse drug reactions: are we there yet?
Benjamin Cross et al. Pharmacogenomics J 2024 3 (2) 7
(Posted: Mar 12, 2024 0PM)
From the abstract: "This review seeks to highlight the genetic, environmental and clinical factors associated with variability in anticoagulant response, and review the current evidence base for tailoring the drug, dose, and/or monitoring decisions to identified patient subgroups to improve anticoagulant safety. Areas that would benefit from further research are also identified. Validated variants in VKORC1, CYP2C9 and CYP4F2 constitute biomarkers for differential warfarin response and genotype-informed warfarin dosing has been shown to reduce adverse clinical events. "
Dozens of precision cancer drugs tested at lower doses to reduce side effects and cut costs.
Sofia Moutinho et al. Nat Med 2024 3
(Posted: Mar 11, 2024 11AM)
From the abstract: "Growing evidence shows that lower doses or shorter treatments of precision cancer therapies could reduce toxicity and save money — but more clinical trials are needed. "
Spending on Targeted Therapies for Duchenne Muscular Dystrophy
L Bendicksen et al, JAMA, March 11, 2024
(Posted: Mar 11, 2024 11AM)
From the article: "Duchenne muscular dystrophy–targeted therapies with limited evidence of clinical efficacy have cost the US health care system more than $3 billion. Most of this spending was for eteplirsen, the efficacy of which has yet to be determined in a confirmatory trial more than 7 years after the drug’s accelerated approval. This analysis sheds light on controversies relating to drugs’ limited preapproval evidence of efficacy, high prices, and delayed confirmatory trials. "
Determining priority indicators of utility for genomic testing in rare disease: a Delphi study
Z Fehlberg et al, Genetics in Medicine, March 6, 2024
(Posted: Mar 07, 2024 8AM)
From the abstract: "This study obtained expert consensus on different utility indicators that are considered a priority in determining the value of genomic testing in rare disease. Twenty indicators reached consensus as a priority in value assessment, including those relating to prognostic information, timeliness of results, practical and health care outcomes, clinical accreditation, and diagnostic yield. Indicators may inform a standardized approach to evidence generation and assessment to guide future research, decision-making, and implementation efforts. "
Clinical impact of preemptive pharmacogenomic testing on antiplatelet therapy in a real-world setting
A Massman et al, EJHG, February 29, 2024
(Posted: Feb 29, 2024 8AM)
From the abstract: "CYP2C19 genotyping to guide antiplatelet therapy after patients develop acute coronary syndromes (ACS) or require percutaneous coronary interventions (PCIs) reduces the likelihood of major adverse cardiovascular events (MACE). Evidence about the impact of preemptive testing, where genotyping occurs while patients are healthy, is lacking. We found that preemptive genotyping had a strong impact on initial antiplatelet selection and a comparable impact on patient outcomes and healthcare utilization, compared to genotyping ordered after a need for antiplatelet therapy had been identified."
Evidence review and considerations for use of first line genome sequencing to diagnose rare genetic disorders.
Kristen M Wigby et al. NPJ Genom Med 2024 2 (1) 15
(Posted: Feb 29, 2024 8AM)
From the abstract: "Seventy-one studies met inclusion criteria, comprising over 13,000 patients who received GS in one of the following settings: hospitalized pediatric patients, pediatric outpatients, adult outpatients, or mixed. GS was the first-line test in 38% (27/71). The unweighted mean DY of first-line GS was 45% (12–73%), 33% (6–86%) in cohorts with prior genetic testing, and 33% (9–60%) in exome-negative cohorts. Clinical utility was reported in 81% of first-line GS studies in hospitalized pediatric patients. "
Selection, optimization and validation of ten chronic disease polygenic risk scores for clinical implementation in diverse US populations
NJ Lennon et al, Nature Medicine, February 19, 2024
(Posted: Feb 20, 2024 7AM)
From the abstract: " From an initial list of 23 conditions, ten were selected for implementation based on PRS performance, medical actionability and potential clinical utility, including cardiometabolic diseases and cancer. Standardized metrics were considered in the selection process, with additional consideration given to strength of evidence in African and Hispanic populations. We then developed a pipeline for clinical PRS implementation (score transfer to a clinical laboratory, validation and verification of score performance), and used genetic ancestry to calibrate PRS mean and variance, utilizing genetically diverse data from 13,475 participants of the All of Us Research Program cohort to train and test model parameters. "
We need to stand together on the shoulders of giants: consolidating effective approaches for translating genomics into practice with implementation science.
Stephanie Best et al. Public Health Genomics 2023 12
(Posted: Jan 22, 2024 8AM)
From the article: "Adopting a genomics learning implementation system approach would provide opportunities to bring together clinical and implementation data from observational studies and clinical trials, providing real-world evidence. These findings could be housed in the Digital Implementation Toolshed (DIT), an online bi-directional platform for resources generated from implementation science activity in genomics. The highly curated DIT (Fig. 1) would augment the Centers for Disease Control and Prevention Genomics and Precision Health Weekly Update. " "
Cost Effectiveness of Genomic Population Health Screening in Adults: A Review of Modeling Studies and Future Directions.
Robert S Wildin et al. J Appl Lab Med 2024 1 (1) 92-103
(Posted: Jan 09, 2024 9AM)
From the abstract: " Eight recent cost-effectiveness modeling studies for high penetrance monogenic dominant diseases that used input parameters from 3 different countries are reviewed. Results and their uses in refining implementations are analyzed and the roles for laboratory medicine in facilitating success are discussed. The reviewed studies generally found evidence for cost-effectiveness of genomic population health screening in at least a subset of their base case screening scenario. Sensitivity analyses identified opportunities for improving the likelihood of cost-effectiveness. On the whole, the modeling results suggest genomic population health screening is likely to be cost-effective for high penetrance disorders in younger adults."
Real-world diagnostic outcomes and cost-effectiveness of genome-wide sequencing for developmental and seizure disorders: evidence from Canada
DA Regier et al, Genetics in Medicine, January 8, 2024
(Posted: Jan 08, 2024 8AM)
From the abstract: "Based on medical records review, we estimated real-world costs and outcomes for 491 patients who underwent standard of care (SOC) diagnostic testing at BC Children’s Hospital. Results informed a state-transition Markov model examining cost-effectiveness of three competing diagnostic strategies: (1) SOC with last-tier access to ES; (2) streamlined ES access; (3) first-tier GS. We found earlier access to ES may yield more rapid genetic diagnosis of childhood developmental and seizure disorders and cost savings compared to current practice. "
Development of a human genetics-guided priority score for 19,365 genes and 399 drug indications
A Duffy et al, Nature Genetics, January 2, 2024
(Posted: Jan 03, 2024 8AM)
From the abstract: "Studies have shown that drug targets with human genetic support are more likely to succeed in clinical trials. Hence, a tool integrating genetic evidence to prioritize drug target genes is beneficial for drug discovery. We built a genetic priority score (GPS) by integrating eight genetic features with drug indications from the Open Targets and SIDER databases. The top 0.83%, 0.28% and 0.19% of the GPS conferred a 5.3-, 9.9- and 11.0-fold increased effect of having an indication, respectively. "
Systematic review and meta-analysis of AI-based conversational agents for promoting mental health and well-being
H Li, NPJ Digital Medicine, December 19, 2023
(Posted: Dec 20, 2023 9AM)
From the abstract: "Conversational artificial intelligence (AI), particularly AI-based conversational agents (CAs), is gaining traction in mental health care. Despite their growing usage, there is a scarcity of comprehensive evaluations of their impact on mental health and well-being. This systematic review and meta-analysis aims to fill this gap by synthesizing evidence on the effectiveness of AI-based CAs in improving mental health and factors influencing their effectiveness and user experience. "
Newborn Screening for Severe Combined Immunodeficiency: Lessons Learned from Screening and Follow-Up of the Preterm Newborn Population
A Gaviglio et al, IJNS, December 2023
(Posted: Dec 18, 2023 8AM)
From the abstract: " Newborn screening (NBS) for Severe Combined Immunodeficiency (SCID) by measurement of T-cell receptor excision circles (TRECs) successfully identifies newborns with SCID and severe T-cell lymphopenia, as intended. At the same time, NBS programs face the challenge of false positive results, with a disproportionately high number in the premature newborn population. This study evaluates TREC values and SCID screening outcomes in premature newborns and elucidates evidence-based SCID screening practices that reduce unnecessary follow-up activities in this population."
Population screening requires robust evidence-genomics is no exception.
Clare Turnbull et al. Lancet 2023 12
(Posted: Dec 12, 2023 2PM)
From the article: "We argue that the complexities and uncertainties inherent to genomic prediction (of future disease risk) mean that rigorous, independent, and expert evaluation is just as essential for proposed population-level genomic screening approaches as for conventional disease screening (ie, for the detection of disease presence today), for which such evaluation is standard. "
Psychological factors underlying attitudes toward AI tools.
Julian De Freitas et al. Nat Hum Behav 2023 11 (11) 1845-1854
(Posted: Nov 22, 2023 9AM)
From the abstract: "What are the psychological factors driving attitudes toward artificial intelligence (AI) tools, and how can resistance to AI systems be overcome when they are beneficial? Here we organize the main sources of resistance into five main categories: opacity, emotionlessness, rigidity, autonomy and group membership. We relate each of these barriers to fundamental aspects of cognition, then cover empirical studies providing correlational or causal evidence for how the barrier influences attitudes toward AI tools. "
The value of standards for health datasets in artificial intelligence-based applications.
Anmol Arora et al. Nat Med 2023 10
(Posted: Oct 27, 2023 9AM)
From the abstract: "Artificial intelligence as a medical device is increasingly being applied to healthcare for diagnosis, risk stratification and resource allocation. However, a growing body of evidence has highlighted the risk of algorithmic bias, which may perpetuate existing health inequity. This problem arises in part because of systemic inequalities in dataset curation, unequal opportunity to participate in research and inequalities of access. "
Rates and Classification of Variants of Uncertain Significance in Hereditary Disease Genetic Testing.
Elaine Chen et al. JAMA Netw Open 2023 10 (10) e2339571
(Posted: Oct 27, 2023 9AM)
From the abstract: " How are variants of uncertain significance (VUSs) distributed across genetic disorders and what evidence contributes to their resolution?
In this cohort study of 1?689?845 individuals who predominantly underwent multigene panel testing, 41% had VUSs (mostly missense changes), most often among those who underwent testing for disorders with incomplete penetrance or were identified as Asian or Shephardic Jewish individuals. Among unique VUSs, 7.3% were reclassified, with most reclassified as benign, often using clinical and experimental evidence."
Inborn errors of immunity: an expanding universe of disease and genetic architecture.
Yemsratch T Akalu et al. Nat Rev Genet 2023 10
(Posted: Oct 23, 2023 7PM)
From the abstract: "Inborn errors of immunity (IEIs) are generally considered to be rare monogenic disorders of the immune system that cause immunodeficiency, autoinflammation, autoimmunity, allergy and/or cancer. Here, we discuss evidence that IEIs need not be rare disorders or exclusively affect the immune system. Namely, an increasing number of patients with IEIs present with severe dysregulations of the central nervous, digestive, renal or pulmonary systems. "
Evidence from 2100 index cases supports genome sequencing as a first-tier genetic test
F Guo et al, Genetics in Medicine, October 12, 2023
(Posted: Oct 13, 2023 1PM)
From the abstract: "Genome sequencing (GS) is one of the most comprehensive assays that interrogate single nucleotide variants, copy number variants, mitochondrial variants, repeat expansions, and structural variants in one assay. Despite the clear technical superiority, the full clinical utility of GS has yet to be determined. The overall diagnostic yield was 28% (585/2100). The diagnostic yield for GS as the first-tier test was 26% (294/1146). Among cases with prior non-diagnostic genetic tests, GS provided a diagnosis for 27% (247/910) of cases. "
Prevalence and course of pregnancy symptoms using self-reported pregnancy app symptom tracker data
M Nissen et al, NPJ Digital Medicine, October 11, 2023
(Posted: Oct 11, 2023 4PM)
From the abstract: "We report real-world evidence from patient-reported outcomes that exceeds previous works: 1,549,186 tracked symptoms from 183,732 users of a smartphone pregnancy app symptom tracker are analyzed. The majority of users track symptoms on a single day. These data are generalizable to those users who use the tracker for at least 5 months. Week-by-week symptom report data are presented for each symptom. "
Relationship satisfaction in adults with phenylketonuria is positively associated with following recommended treatment, having a partner involved in management, and maintaining good health.
Rachel Sundstrom et al. J Community Genet 2023 10
(Posted: Oct 07, 2023 8AM)
From the abstract: " Phenylketonuria (PKU) is a metabolic condition that requires treatment for life. There is increasing evidence that chronic illnesses put strain on relationships and marriages. However, no studies have examined the unique factors that metabolic conditions have on affected individuals and their relationship satisfaction. We surveyed a population of adult patients with PKU and assessed how management, treatment, and lifestyle factors impact their relationship satisfaction."
Precision medicine for cardiometabolic disease: a framework for clinical translation
PW Franks et al, The Lancet Diabetes Endoc, October 4, 2023
(Posted: Oct 06, 2023 8AM)
From the abstract: "To contextualise precision medicine in both research and clinical settings, and to encourage the successful translation of discovery science into clinical practice, in this Series paper we outline a model (the EPPOS model) that builds on contemporary evidence-based approaches; includes precision medicine that improves disease-related predictions by stratifying a cohort into subgroups of similar characteristics, or using participants' characteristics to model treatment outcomes directly; "
Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine
DK Tobias et al, Nature Medicine, October 5, 2023
(Posted: Oct 05, 2023 9AM)
From the abstract: "This international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine. "
Participant characteristics in the prevention of gestational diabetes as evidence for precision medicine: a systematic review and meta-analysis
S Lim et al, Comm Medicine, October 5, 2023
(Posted: Oct 05, 2023 9AM)
From the abstract: "Precision prevention involves using the unique characteristics of a particular group to determine their responses to preventive interventions. This study aimed to systematically evaluate the participant characteristics associated with responses to interventions in gestational diabetes mellitus (GDM) prevention. GDM prevention through metformin or lifestyle differs according to some individual characteristics. Future research should include trials commencing preconception and provide results disaggregated by a priori defined participant characteristics including social and environmental factors, clinical traits, and other novel risk factors to predict GDM prevention through interventions. "
Genotype-stratified treatment for monogenic insulin resistance: a systematic review
RK Semple et al, Comm Medicine, October 5, 2023
(Posted: Oct 05, 2023 9AM)
From the abstract: " Systematic review using PubMed, MEDLINE and Embase (1 January 1987 to 23 June 2021). Studies reporting individual-level effects of pharmacologic and/or surgical interventions in monogenic IR were eligible. The evidence guiding genotype-specific treatment of monogenic IR is of low to very low quality. Metreleptin and Thiazolidinediones appear to improve metabolic markers in lipodystrophy, and rhIGF-1 appears to lower HbA1c in INSR-related IR. For other interventions, there is insufficient evidence to assess efficacy and risks in aggregated lipodystrophy or genetic subgroups. "
Utility and precision evidence of technology in the treatment of type 1 diabetes: a systematic review
LM Jacobsen et al, Comm Medicine, October 5, 2023
(Posted: Oct 05, 2023 9AM)
From the abstract: "The greatest change in the treatment of people living with type 1 diabetes in the last decade has been the explosion of technology assisting in all aspects of diabetes therapy, from glucose monitoring to insulin delivery and decision making. As such, the aim of our systematic review was to assess the utility of these technologies as well as identify any precision medicine-directed findings to personalize care. "
Emerging cancer risks in BRCA2 pathogenic germline variant carriers.
Patrick R Benusiglio et al. Eur J Hum Genet 2023 9
(Posted: Sep 28, 2023 11AM)
From the paper: "Carriers of pathogenic germline variants (PGV) in BRCA2 could soon be offered gastric cancer screening using gastroscopy. In the longer term, some might even take part in lung cancer screening programs. Indeed, while the risks of breast, ovarian, pancreatic and prostate cancer have been documented for years, recent data show an increased risk of gastric cancer, and suggest an association with lung cancer. This article focuses specifically on BRCA2, while sidelining its sister gene BRCA1, as evidence for a broad cancer spectrum is much stronger for the former."
Distinguishing features of Long COVID identified through immune profiling.
Jon Klein et al. Nature 2023 9
(Posted: Sep 27, 2023 8AM)
From the abstract: "Here, 273 individuals with or without LC were enrolled in a cross-sectional study that included multi-dimensional immune phenotyping and unbiased machine learning methods to identify biological features associated with LC. Marked differences were noted in circulating myeloid and lymphocyte populations relative to matched controls, as well as evidence of exaggerated humoral responses directed against SARS-CoV-2 among participants with LC. Further, higher antibody responses directed against non-SARS-CoV-2 viral pathogens were observed among individuals with LC, particularly Epstein-Barr virus. "
Germline Sequencing Analysis to Inform Clinical Gene Panel Testing for Aggressive Prostate Cancer.
Burcu F Darst et al. JAMA Oncol 2023 9
(Posted: Sep 22, 2023 2PM)
From the abstract: " Do rare pathogenic variants in genes beyond previously established prostate cancer risk genes contribute to risk of aggressive prostate cancer? In this exome-sequencing genetic association study of 17?546 men with aggressive and nonaggressive prostate cancer, an association between known genes BRCA2, ATM, and NBN with aggressive prostate cancer was found. Nominal association evidence was observed for MSH2, XRCC2, and MRE11A. The findings of this study suggest that DNA repair and cancer susceptibility genes can inform disease management in men with nonaggressive prostate cancer, as men carrying deleterious variants in these genes are likely to develop advanced disease."
Unequal global implementation of genomic newborn screening.
Ahmad N Abou Tayoun et al. Nat Rev Genet 2023 9
(Posted: Sep 20, 2023 7AM)
From the abstract: "Studies of genomic newborn screening are highly skewed towards populations in high-income countries. The evidence generated by these studies will be similarly biased and is likely to lead to disparate global implementation. Studies inclusive of historically under-represented populations are needed for equitable global access to genomic newborn screening. "
Barriers and facilitators to utilizing digital health technologies by healthcare professionals
I Junior et al, NPJDigital Medicine, September 18, 2023
(Posted: Sep 18, 2023 11AM)
From the abstract: "High-quality evidence suggested that infrastructure and technical barriers (Relative Frequency Occurrence [RFO] 6.4% [95% CI 2.9–14.1]), psychological and personal issues (RFO 5.3% [95% CI 2.2–12.7]), and concerns of increasing working hours or workload (RFO 3.9% [95% CI 1.5–10.1]) were common concerns reported by HPs. Likewise, high-quality evidence supports that training/educational programs, multisector incentives, and the perception of technology effectiveness facilitate the adoption of digital technologies by HPs. "
Future Forecasting for Research and Practice in Genetic Literacy
KA Kapingst, Public Health Genomics, September 13, 2023
(Posted: Sep 14, 2023 9AM)
From the abstract: "Available evidence highlights important gaps in genetic literacy throughout the population, limiting the potential use of these technologies to improve the health of individuals, their families, and their communities. Effective communication approaches are needed to meet the needs of individuals with varying levels of genetic literacy and from different communities. To achieve this goal, this piece highlights essential areas of research and practice in genetic literacy that are needed to inform public health translation of genomic discoveries. "
Viral genetic clustering and transmission dynamics of the 2022 mpox outbreak in Portugal.
Vítor Borges et al. Nat Med 2023 9
(Posted: Sep 12, 2023 7AM)
From the abstract: "Pathogen genome sequencing during epidemics enhances our ability to identify and understand suspected clusters and investigate their relationships. Here, we combine genomic and epidemiological data of the 2022 mpox outbreak to better understand early viral spread, diversification and transmission dynamics. By sequencing 52% of the confirmed cases in Portugal, we identified the mpox virus sublineages with the highest impact on case numbers and fitted them into a global context, finding evidence that several international sublineages probably emerged or spread early."
Systematic Evidence Review and Meta-Analysis of Outcomes associated with Cancer Genetic Counseling
JO Culver et al, Genetics in Medicine, September 6, 2023
(Posted: Sep 06, 2023 11AM)
From the abstract: "We conducted a systematic review and meta-analysis of 17 patient-reported and health services-related outcomes associated with pre- and post-test GC in GCRA in accordance with PRISMA guidelines and GRADE methodology. The true impact of GC on relevant outcomes is not known due to low quality or absent evidence. While a meta-analysis found that pre-test GC had beneficial effects on knowledge, worry and risk perception, the certainty of this evidence was low according to GRADE methodology. "
Epigenetics of Early-Life Socioeconomic Stressors and the Impact on Childhood Body Mass Index—Potential Mechanism and Biomarker?
UP Gujral et al, JAMA Pediatrics, September 5, 2023
(Posted: Sep 05, 2023 1PM)
From the paper: "a recent study indicates that salivary epigenetics, an easy measure to obtain in field or clinic, can be used to further explore the questions of pediatric obesity and related outcomes. Epigenetic and physiological BMI may be present at birth and remain stable throughout childhood and adolescence. These findings also add further evidence to a critical window, that of early life, at which to intervene to prevent childhood and adolescent obesity."
Older Patients With AML Less Likely to Receive Genomic Testing, Study Finds
P Steinzor, AJMC, August 29, 2023
(Posted: Sep 01, 2023 7AM)
From the article: "In a real-world setting of new and emerging targeted therapies, a study found that patients with acute myeloid leukemia (AML) had unmet needs that hindered their ability to receive genomic testing and treatment options, especially for older patients with AML. The analysis showed 13% of newly diagnosed patients with AML had evidence of a genomic sequencing report, which increased to 37% since 2016. Additionally, genomic testing was more likely to be performed in patients 60 years and younger compared with patients over 60 years."
Long-term cost-effectiveness of a melanoma prevention program using genomic risk information compared with standard prevention advice in Australia
CK Law et al, Genetics in Medicine, August 30, 2023
(Posted: Aug 31, 2023 7AM)
From the abstract: "Evidence indicates a melanoma prevention program using personalized genomic risk provision and genetic counselling, can impact prevention behaviors, including reducing sunburns in adults with no melanoma history. This analysis evaluated its longer-term cost-effectiveness from an Australian health system perspective. We found that genomic risk provision targeted to high-traditional melanoma risk individuals is likely a cost-effective strategy for reducing sunburns and will likely prevent future melanomas and keratinocyte carcinomas."
An Environmental Scan of Consumer-Initiated Germline Genetic Testing for Health Risks.
Hannah G Kirby et al. Mayo Clin Proc 2023 8
(Posted: Aug 29, 2023 11AM)
From the abstract: "An environmental scan was conducted to identify germline genetic testing companies that offer testing for at least one diagnosable health condition and are available for purchase by consumers in the US market without a visit to one's health care provider. We characterized variability in the content and processes used by 21 companies offering 74 distinct test products that met our inclusion and exclusion criteria. A minority (8 of 21 companies) offered tests that assessed the presence of at least 1 US Centers for Disease Control and Prevention Tier 1 condition for which detection can impact an individual's clinical care and for which evidence-based guidelines for detection and management exist."
Is Lipoprotein(a) Clinically Actionable with Today's Evidence? The Answer is Yes.
Gary S Ma et al. Curr Cardiol Rep 2023 8
(Posted: Aug 29, 2023 11AM)
From the abstract: "Lipoprotein(a) is an independent risk factor for cardiovascular disease. We review the ongoing shifts in consensus guidelines for the testing and management of Lp(a) and provide insight into whether current evidence suggests that awareness and testing of Lp(a) is clinically actionable."
Assessment of clinically actionable pharmacogenetic markers to stratify anti-seizure medications.
Debleena Guin et al. Pharmacogenomics J 2023 8
(Posted: Aug 28, 2023 1PM)
From the abstract: "A total of 270 articles were retrieved with PGx evidence associated with 19 ASMs including 178 variants across 93 genes, classifying 26 genetic variants as benign/ likely benign, fourteen as drug response markers and three as risk factors for drug response. Only seventeen of these were replicated, with accuracy (up to 95%) in predicting PGx outcomes specific to six ASMs. Eight out of seventeen variants have FDA-approved PGx drug labelling for clinical implementation."
Risk Assessment Summary for SARS CoV-2 Sublineage BA.2.86
CDC, August 23, 2023
(Posted: Aug 23, 2023 0PM)
Based on what CDC knows now, existing tests used to detect and medications used to treat COVID-19 appear to be effective with this variant. BA.2.86 may be more capable of causing infection in people who have previously had COVID-19 or who have received COVID-19 vaccines. Scientists are evaluating the effectiveness of the forthcoming, updated COVID-19 vaccine. CDC’s current assessment is that this updated vaccine will be effective at reducing severe disease and hospitalization. At this point, there is no evidence that this variant is causing more severe illness. That assessment may change as additional scientific data are developed. CDC will share more as we know more.
What to Know About EG.5, the Latest SARS-CoV-2 “Variant of Interest”
J Abbasi, JAMA, August 18, 2023
(Posted: Aug 18, 2023 5PM)
The Omicron descendant EG.5 is the latest to be labeled a “variant of interest” by the World Health Organization (WHO), joining the current ranks of XBB.1.16 and XBB.1.5. The new designation, made as part of an August 9 initial risk evaluation of the variant, reflects its “notable rise” in global prevalence during recent weeks. The report comes as the US is experiencing an increase in hospitalizations and deaths and as anticipation mounts for updated vaccines, expected to become available this fall. The EG.5 variant could contribute to a surge in cases, the report noted, although there’s no evidence to date that it causes more severe disease.
Metaplastic breast cancer and BRCA1: first strong evidence of a link
D Gareth et al, EJHG, August 17, 2023
(Posted: Aug 17, 2023 11AM)
Three of a Kind: CDC researchers find Cyclospora is not just a single species
CDC, August 2023
(Posted: Aug 14, 2023 1PM)
Over the last 10 years, CDC scientists in DPDM developed laboratory techniques specifically to extract a sufficient amount of DNA for analysis from this tiny organism and created a new typing tool to compare the pathogen’s genome. Over the course of three years, 2018-2020, researchers genotyped thousands of isolates. They uncovered evidence that the three Cyclospora populations do not reproduce with one another, meaning that they are not reproductively compatible. Without the genotyping data, these patterns—and their potential benefit for public health—would have remained undetected.
How are genetics, lifestyles, and cardiovascular and thromboembolic events associated following COVID-19 diagnosis?
TS Lomte, News Medical, August 2023
(Posted: Aug 11, 2023 11AM)
A recent study published in Nature Communications evaluated the associations between host genetics, lifestyle factors, and cardiovascular and thromboembolic events (CVEs) after coronavirus disease 2019 (COVID-19). Although prophylactic coagulation is recommended for hospitalized COVID-19 patients, mixed evidence exists for milder ambulatory and more critical COVID-19 patients. Polygenic risk scores (PRSs) have been proposed for early risk stratification and precision medicine. Whether genetic susceptibility to chronic CVD predisposes COVID-19 patients to CVE complications is unknown.
Converging evidence from exome sequencing and common variants implicates target genes for osteoporosis
S Zhou et al, Nature Genetics, August 9, 2023
(Posted: Aug 09, 2023 4PM)
We undertook a large-scale multiancestry exome-wide association study for estimated bone mineral density, which showed that the burden of rare coding alleles in 19 genes was associated with estimated bone mineral density (P<3.6×10–7). These genes were highly enriched for a set of known causal genes for osteoporosis (65-fold; P=2.5×10–5). Exome-wide significant genes had 96-fold increased odds of being the top ranked effector gene at a given GWAS locus (P=1.8×10–10). By integrating proteomics Mendelian randomization evidence, we prioritized CD109 (cluster of differentiation 109) as a gene for which heterozygous loss of function is associated with higher bone density.
Predictive evidence of the relevance of epigenetics to PTSD.
Leon Mutesa et al. Nat Rev Genet 2023 8
(Posted: Aug 09, 2023 4PM)
Post-traumatic stress disorder (PTSD) is a complex mental health condition that can occur after a life-threatening or otherwise traumatic event. Although its molecular causes are unclear, its development is thought to involve a range of biological, psychological and environmental factors. In 2009, Yehuda and Bierer posited that epigenetic modifications, such as DNA methylation, may occur in response to environmental influences such as trauma exposure, thus altering the functional expression of genes. These mechanisms may explain the intergenerational transmission of PTSD across affected families.
Genetic Architecture of Dilated Cardiomyopathy in Individuals of African and European Ancestry.
Elizabeth Jordan et al. JAMA 2023 8 (5) 432-441
(Posted: Aug 03, 2023 6PM)
Does the rare variant genetic architecture of dilated cardiomyopathy differ between patients of African and European ancestry? In this cross-sectional study of 1198 patients with dilated cardiomyopathy, significantly fewer patients of African ancestry (8.2%) than those European ancestry (25.5%) had variants classified as pathogenic or likely pathogenic, a difference due in part to fewer predicted loss-of-function variants and less case-based evidence to support pathogenicity for variants found only in patients of African ancestry.
Preliminary Evidence for Genetic Nurture in Depression and Neuroticism Through Polygenic Scores.
Justin D Tubbs et al. JAMA Psychiatry 2023 6 (8) 832-841
(Posted: Aug 03, 2023 6PM)
Is there evidence for parental genetic nurture in the risk of depression and neuroticism? In this cross-sectional study of 38?702 offspring, results from polygenic score (PGS) modeling provide limited preliminary evidence of genetic nurture in depression and neuroticism. Parental PGSs for depression were significantly associated with offspring neuroticism, with a regression estimate two-thirds that of the offspring’s own PGS, whereas results suggest that previous associations between cannabis use PGS and depression may be noticeably biased by parental genetic nurture.
Special Issue: “Genetic Counseling and Genetic Testing in Precision Medicine”
E Turbitt et al, J Per Med, July 27, 2023
(Posted: Jul 27, 2023 7AM)
Delivering on the promises of precision medicine comprehensively, equitably, and promptly depends on optimizing health service delivery to facilitate access to timely, evidence-based genetic and genomic testing. Improvements in access to genetic counseling and testing enable the delivery of the ‘right care to the right patient at the right time’. This Special Issue of the Journal of Personalized Medicine showcases the latest research on genetic counseling and genetic testing in precision medicine.
Roadmap on the use of artificial intelligence for imaging of vulnerable atherosclerotic plaque in coronary arteries.
Bernhard Föllmer et al. Nat Rev Cardiol 2023 7
(Posted: Jul 27, 2023 7AM)
Artificial intelligence (AI) is likely to revolutionize the way medical images are analysed and has the potential to improve the identification and analysis of vulnerable or high-risk atherosclerotic plaques in coronary arteries, leading to advances in the treatment of coronary artery disease. In this Roadmap, we review existing evidence on the application of AI to the imaging of vulnerable plaque in coronary arteries and provide consensus recommendations developed by an interdisciplinary group of experts on AI and non-invasive and invasive coronary imaging.
Persistent Underutilization of BRCA Testing for Breast and Ovarian Cancer in the United States: Implications for Health Disparities
L Shi et al, CDC Blog Post, July 25, 2023
(Posted: Jul 25, 2023 11AM)
Two recent studies document ongoing underutilization and disparities in genetic testing for patients with breast and ovarian cancer. The two studies demonstrate the importance of population-level data to track progress in implementation, outcomes, and disparities in genomic medicine. The studies also show how diverse data sources, such as state-based cancer registries, laboratory, EHR, administrative claims, and survey data, each with its own strengths and limitations, can be used to help build the evidence base on genetic testing utilization and disparities.
Transthyretin Cardiac Amyloidosis: Underrecognized in the Underrepresented.
Douglas J Leedy et al. J Am Heart Assoc 2023 7 e030802
(Posted: Jul 25, 2023 8AM)
Over the past decade, transthyretin cardiac amyloidosis (ATTR-CM) has rapidly emerged as an increasingly diagnosed cause of heart failure (HF) among older adults, predominantly those with HF with preserved ejection fraction. Although still frequently classified as a rare disease, there is mounting evidence that ATTR-CM is not as “rare” as it has been historically described. Because of the development of effective disease-modifying therapies, such as transthyretin stabilizers, early and accurate identification of ATTR-CM is essential.
The causal effects of education on adult health, mortality and income: evidence from Mendelian randomization and the raising of the school leaving age.
Neil M Davies et al. Int J Epidemiol 2023 7
(Posted: Jul 23, 2023 9AM)
On average, educated people are healthier, wealthier and have higher life expectancy than those with less education. Numerous studies have attempted to determine whether education causes differences in later health outcomes or whether another factor ultimately causes differences in education and subsequent outcomes. Previous studies have used a range of natural experiments to provide causal evidence. Here we compare two natural experiments: a policy reform, raising the school leaving age in the UK in 1972; and Mendelian randomization.
Still "on the Fence" About Universal Childhood Lipid Screening: The USPSTF Reaffirms an I Statement.
Sarah D de Ferranti et al. JAMA 2023 7 (3) 225-227
(Posted: Jul 21, 2023 9AM)
As in 2007 and in 2016, the task force again finds evidence insufficient to recommend for, or against, screening for lipid disorders in childhood, including both genetic conditions such as FH and secondary multifactorial lipid disorders—an I statement. This USPSTF recommendation is anchored in uncertainty about long-term benefits and safety of screening for, identifying, and treating childhood lipid disorders and uncertainty about the optimal age to start lipid-lowering therapy (ie, in childhood vs adulthood). At the crux of the controversy is the distinction between childhood screening for FH and general childhood lipid screening, as the latter will predominantly identify secondary lifestyle-related lipid abnormalities.
Screening for Lipid Disorders in Children and Adolescents: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.
Janelle M Guirguis-Blake et al. JAMA 2023 7 (3) 261-274
(Posted: Jul 21, 2023 9AM)
Lipid screening in childhood and adolescence can lead to early dyslipidemia diagnosis. The long-term benefits of lipid screening and subsequent treatment in this population are uncertain. We reviewed benefits and harms of screening and treatment of pediatric dyslipidemia due to familial hypercholesterolemia (FH) and multifactorial dyslipidemia. We found no direct evidence on the benefits or harms of pediatric lipid screening was identified. While multifactorial dyslipidemia is common, no evidence was found that treatment is effective for this condition. In contrast, FH is relatively rare; evidence shows that statins reduce lipid levels in children with FH, and observational studies suggest that such treatment has long-term benefit for this condition.
Rapid Genome Sequencing for Diagnosing Critically Ill Infants and Children: From Evidence to Equitable Implementation
CDC webinar, November 30, 2023
(Posted: Jul 21, 2023 9AM)
Dr. Stephen F. Kingsmore is president/CEO of Rady Children’s Institute for Genomic Medicine (RCIGM), where he leads a multidisciplinary team that is pioneering the use of rapid genome sequencing to diagnose critically ill children, implement precision medicine, and screen for approximately 500 genetic disorders. Dr. Kingsmore holds two Guinness World Records for achieving the fastest molecular diagnosis using whole genome sequencing.
Phenylalanine hydroxylase deficiency treatment and management: A systematic evidence review of the American College of Medical Genetics and Genomics (ACMG)
AD Adams et al, Genetics in Medicine, July 20, 2023
(Posted: Jul 20, 2023 7AM)
A total of 350 studies were included. Risk of bias was moderate. Lower Phe was consistently associated with better outcomes. Achieving Phe = 360 µmol/L before conception substantially lowered the risk of negative effect to offspring in pregnant individuals (odds ratio = 0.07, 95% CI = 0.04-0.14; P < .0001). Adverse events due to pharmacologic treatment were common, but medication reduced Phe levels, enabling dietary liberalization. Reduction of Phe levels to =360 µmol/L through diet or medication represents effective interventions to treat PAH deficiency.
Lipid Disorders in Children and Adolescents: Screening
USPSTF recommendation, July 18, 2023
(Posted: Jul 18, 2023 0PM)
Familial hypercholesterolemia (FH) and multifactorial dyslipidemia are 2 conditions that cause abnormally high lipid levels in children, which can lead to premature cardiovascular events (eg, myocardial infarction and stroke) and death in adulthood. The prevalence of FH in US children and adolescents ranges from 0.2% to 0.4% (1 of every 250 to 500 children and adolescents). Multifactorial dyslipidemia is much more common than FH, with prevalence in children and adolescents ranging from 7.1% to 9.4%. The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for lipid disorders in children and adolescents 20 years or younger.
The English National Lynch Syndrome Transformation Project
Brit Soc Gastro, July 14, 2023
(Posted: Jul 16, 2023 9AM)
Lynch syndrome (LS) affects approximately 1 in 400 individuals and predisposes to multiple cancers including colorectal, endometrial, gastric, small bowel, cholangiocarinoma and other tumors. Although a common condition, it is estimated that only 5% of patients with LS are known in the UK. There is consistent evidence of the cost-effectiveness and clinical benefit of a structured diagnostic pathway in patients with LS following a diagnosis of cancer linked to cascade testing in families. NICE DG27 and DG42 guidelines recommend universal testing of newly diagnosed colorectal and endometrial cancer for Lynch syndrome (LS), however there is strong evidence of variation in delivery of these guidelines by clinical services.
A new study of sick infants sees potential in DNA sequencing, but also a need for better ways to interpret the genome
J Wosen, Stat News, July 11, 2023
(Posted: Jul 12, 2023 9AM)
here’s growing evidence that DNA sequencing can help diagnose the health care system’s youngest patients — babies in their first year of life. But a new report resurfaces a thorny challenge in researchers’ quest to turn long strings of A’s, T’s, G’s, and C’s into information doctors and patients can use: Reading the genome is one challenge, interpreting it is another.
Randomized-controlled trial assessing a digital care program versus conventional physiotherapy for chronic low back pain
D Cui et al, NPJ Digital Medicine, July 7, 2023
(Posted: Jul 10, 2023 8AM)
This randomized controlled trial (RCT) aims to compare the clinical outcomes of patients with CLBP following a digital intervention versus evidence-based in-person physiotherapy. Our results demonstrate that patient satisfaction and adherence were high and similar between groups, although a significantly lower dropout rate is observed in the digital group (11/70, 15.7% versus 24/70, 34.3% in the conventional group; P?=?0.019). Both groups experience significant improvements in disability (primary outcome), with no differences between groups in change from baseline,
Mendelian randomization evidence for the causal effects of socio-economic inequality on human longevity among Europeans.
Chao-Jie Ye et al. Nat Hum Behav 2023 6
(Posted: Jul 03, 2023 8AM)
Here we performed two-sample Mendelian randomization analyses applying genetic instruments of education, income and occupation (n?=?248,847 to 1,131,881) to estimate their causal effects and consequences on parental lifespan and self-longevity (n?=?28,967 to 1,012,240) from the largest available genome-wide association studies in populations of European ancestry. Each 4.20 years of additional educational attainment were causally associated with a 3.23-year-longer parental lifespan independently of income and occupation and were causally associated with 30–59% higher odds of self-longevity.
Genomic newborn screening for rare diseases.
Zornitza Stark et al. Nat Rev Genet 2023 6
(Posted: Jun 30, 2023 10AM)
Incorporating genomic sequencing into newborn screening programs at the population scale holds the promise of substantially expanding the early detection of treatable rare diseases, with stored genomic data potentially benefitting health over a lifetime and supporting further research. As several large-scale newborn genomic screening projects launch internationally, we review the challenges and opportunities presented, particularly the need to generate evidence of benefit and to address the ethical, legal and psychosocial issues that genomic newborn screening raises.
Evolutionary implications of SARS-CoV-2 vaccination for the future design of vaccination strategies.
Igor M Rouzine et al. Commun Med (Lond) 2023 6 (1) 86
(Posted: Jun 24, 2023 10AM)
Once the first SARS-CoV-2 vaccine became available, mass vaccination was the main pillar of the public health response to the COVID-19 pandemic. It was very effective in reducing hospitalizations and deaths. Here, we discuss the possibility that mass vaccination might accelerate SARS-CoV-2 evolution in antibody-binding regions compared to natural infection at the population level. Using the evidence of strong genetic variation in antibody-binding regions and taking advantage of the similarity between the envelope proteins of SARS-CoV-2 and influenza, we assume that immune selection pressure acting on these regions of the two viruses is similar.
Tracking the Contributions of Implementation Science to the Population Health Impact of Genomics and Precision Health: A New Knowledge Base
M Clyne et al, CDC blog post, June 16, 2023
(Posted: Jun 19, 2023 1PM)
Successful implementation of evidence-based genomic and precision health interventions requires an understanding of what works and what doesn’t work within the context of various clinical and public health settings. Research and evaluation that incorporate implementation science tools and methods into the translation of these interventions facilitate this. Here we present a new CDC knowledge base, a collection of these implementation science studies, and a summary of their collective contributions to date.
BA.1 Bivalent COVID-19 Vaccine Use and Stroke in England.
Nick Andrews et al. JAMA 2023 6
(Posted: Jun 19, 2023 1PM)
This analysis showed no evidence of an increased risk of stroke in the 21 days immediately after vaccination with either of the 2 mRNA COVID-19 bivalent BA.1 vaccines in England, with similar results for ischemic and hemorrhagic stroke and for the subset aged 65 years and older given influenza vaccine on the same day as the bivalent COVID-19 vaccine. For ischemic stroke, the upper bounds of CIs for the RI were all below the point estimate of a relative risk of 1.47.
Cost-Effectiveness Analysis in Public Health Genomics and Precision Health: Recent Findings, Methodologic Issues, and the Path Forward
CDC Public Health Genomics Webinar, October 26, 2023
(Posted: Jun 09, 2023 8AM)
Dr David Veenstra from the University of Washington in Seattle will review the field as a whole and his research projects including evaluation of the cost-effectiveness of population-level genomic screening, pharmacogenomics in diverse populations, decision modeling techniques to assess evidence thresholds, and stakeholder preferences for precision medicine. He will address recent findings, methodologic issues and the path forward.
Severity Outcomes among Adult Patients with Primary Immunodeficiency and COVID-19 Seen in Emergency Departments, United States, April 2020–August 2021
CDC Visual Abstracts, June 2023
(Posted: Jun 09, 2023 8AM)
Severe COVID-19 outcomes, including hospitalization, IMV, ICU admission, and death, are more frequent in PI patients than in non-PI patients seen in emergency departments. These results provide real-world evidence that PI is a risk factor for adverse COVID-19 outcomes.
Rigorous and rapid evidence assessment in digital health with the evidence DEFINED framework
J Silberman et al, NPJ Digital Medicine, May 31, 2023
(Posted: May 31, 2023 7AM)
We propose a framework to assess Evidence in Digital health for EFfectiveness of INterventions with Evaluative Depth (Evidence DEFINED). Designed for real-world use, the Evidence DEFINED Quick Start Guide may help streamline DHI assessment. A checklist is provided summarizing high-priority evidence considerations in digital health. Evidence-to-recommendation guidelines are proposed, specifying degrees of adoption that may be appropriate for a range of evidence quality levels. Evidence DEFINED differs from prior frameworks in its inclusion of unique elements designed for rigor and speed.
When Is a High Lipoprotein (a) Concentration Too High?-The Need for Diverse Population-Based Samples.
Sadiya S Khan et al. JAMA Cardiol 2023 5
(Posted: May 27, 2023 6AM)
Preclinical, epidemiologic, and genomic studies identify lipoprotein (a) (Lp[a]) as a risk factor for atherosclerotic cardiovascular disease (ASCVD). Lp(a) is a low-density lipoprotein (LDL)–like particle that is bound to apolipoprotein(a) and is causally implicated in the pathogenesis of ASCVD. Despite growing evidence supporting the potential utility of Lp(a) in risk stratification for ASCVD, challenges remain in defining a cut point for what constitutes a high Lp(a) concentration. These include variation observed in Lp(a) concentrations across racial and ethnic groups, as well as differences in accuracy across various assays.
Genetic testing in monogenic early-onset atrial fibrillation.
Brandon Chalazan et al. Eur J Hum Genet 2023 5
(Posted: May 23, 2023 11AM)
We aim to determine the prevalence of likely pathogenic and pathogenic variants from AF genes with robust evidence in a well phenotyped early-onset AF population. We performed whole exome sequencing on 200 early-onset AF patients. Variants from exome sequencing in affected individuals were filtered in a multi-step process, prior to undergoing clinical classification using current ACMG/AMP guidelines. There was a 3.0% diagnostic yield for identifying a likely pathogenic or pathogenic variant across AF genes with robust gene-to-disease association evidence.
Digital interventions for genomics and genetics education, empowerment, and service engagement: A systematic review.
Norina Gasteiger et al. J Community Genet 2023 5
(Posted: May 21, 2023 8AM)
Patient-facing digital technologies may reduce barriers to and alleviate the burden on genetics services. However, no work has synthesised the evidence for patient-facing digital interventions for genomics/genetics education and empowerment, or to facilitate service engagement more broadly. It is also unclear which groups have been engaged by digital interventions. This systematic review found insufficient evidence related to empowering patients and engaging underserved communities or consanguineous couples. Future work should focus on co-developing content with end users and incorporating interactive features.
Feasibility and Value of Genomic-Profiling in Cancer of Unknown Primary: Real-World Evidence from Prospective Profiling Study.
Ryan W Huey et al. J Natl Cancer Inst 2023 5
(Posted: May 21, 2023 8AM)
Real-world evidence regarding the value of integrating genomic profiling (GP) in managing cancer of unknown primary (CUP) is limited. We assessed this clinical utility using a prospective trial of 158 patients with CUP (10/2016-09/2019) who underwent GP using next-generation sequencing designed to identify genomic alterations (GAs). Only 61 (38.6%) patients had sufficient tissue for successful profiling. GAs were seen in 55 (90.2%) patients; of which GAs with FDA approved genomically-matched therapy were seen in 25 (40.9%) cases
Information-Seeking Preferences in Diverse Patients Receiving a Genetic Testing Result in the Clinical Sequencing Evidence-Generating Research (CSER) Study
A Slavotinek et al, Genetics in Medicine, May 19, 2023
(Posted: May 19, 2023 2PM)
Accurate and understandable information following genetic testing is critical for patients, family members, and professionals alike. As part of a cross-site study from the Clinical Sequencing Evidence-Generating Research (CSER) consortium, we investigated the information-seeking practices among patients and family members at five to seven months after genetic testing results disclosure, assessing the perceived utility of a variety of information sources, such as family and friends, healthcare providers, support groups, and the internet.
Population Genomic Screening for Three Common Hereditary Conditions : A Cost-Effectiveness Analysis.
Gregory F Guzauskas et al. Ann Intern Med 2023 5
(Posted: May 09, 2023 5AM)
The cost-effectiveness of screening the U.S. population for Centers for Disease Control and Prevention (CDC) Tier 1 genomic conditions is unknown.
We estimated the cost-effectiveness of simultaneous genomic screening for Lynch syndrome (LS), hereditary breast and ovarian cancer syndrome (HBOC), and familial hypercholesterolemia (FH). We found that population genomic screening with a restricted panel of high-evidence genes is likely to be cost-effective in U.S. adults younger than 40 years if the testing cost is relatively low and probands have access to preventive interventions.
Considerations for integrating wearables into the everyday healthcare practice.
Dylan Powell et al. NPJ Digit Med (1) 70
(Posted: Apr 23, 2023 7AM)
Wearable technologies are becoming ever more popular as suggested tools for use in modern medicine. Studies evidence their growing pragmatism and provision of objective data for a more informative and personalized approach to patient care. Yet many wearables are one dimensional, despite the underlying technology being common across a large array of tools. That is primarily due to the accompanying software, unmodifiable or black box-based scripts that generally lack accessibility or modification.
Evaluation of Plasma Biomarkers for A/T/N Classification of Alzheimer Disease Among Adults of Caribbean Hispanic Ethnicity.
Lawrence S Honig et al. JAMA Netw Open (4) e238214
(Posted: Apr 21, 2023 6AM)
Can plasma biomarker analytes be used in a low-resource community to improve clinical accuracy in diagnosing Alzheimer disease (AD)? In this decision analytical modeling study of 746 Caribbean Hispanic individuals from the Dominican Republic and New York, a panel of plasma biomarkers, including phosphorylated tau181 (P-tau181) and the ratio of P-tau181 to amyloid-ß Aß42, identified biological evidence of AD. A proportion of asymptomatic individuals without dementia had biomarker evidence of AD and may be presymptomatic, while a proportion of affected individuals with dementia lacked biomarker evidence of AD and may have other dementia disorders.
Stroke, Myocardial Infarction, and Pulmonary Embolism after Bivalent Booster.
Marie-Joelle Jabagi et al. N Engl J Med 2023 3 (15) 1431-1432
(Posted: Apr 13, 2023 6AM)
At 21 days after the booster dose, we found no evidence of an increased risk of cardiovascular events among the recipients of the bivalent vaccine as compared with recipients of the monovalent vaccine. The evaluated events included ischemic stroke (hazard ratio, 0.86; 95% confidence interval [CI], 0.58 to 1.27), hemorrhagic stroke (hazard ratio, 0.86; 95% CI, 0.46 to 1.61), myocardial infarction (hazard ratio, 0.92; 95% CI, 0.62 to 1.36), pulmonary embolism (hazard ratio, 0.83; 95% CI, 0.49 to 1.40), and all four events combined (hazard ratio, 0.87; 95% CI, 0.69 to 1.09).
It Takes an Average of 17 Years for Evidence to Change Practice-the Burgeoning Field of Implementation Science Seeks to Speed Things Up.
Rita Rubin et al. JAMA 2023 4
(Posted: Apr 08, 2023 0PM)
Put simply, “implementation science is really trying to close that gap between what we know and what we do.” “Implementation science is about bringing the best possible care to everyone.” Chasm might be a better word to describe the gap between research and practice. A frequently cited estimate puts that gap at 17 years on average, and even then, only 1 in 5 evidence-based interventions make it to routine clinical practice. To some degree, the interventions do vary greatly in terms of their complexity. Some interventions may be easier to administer. In historically marginalized populations, the evidence-to-practice gap is often even more yawning.
Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction between CYP2D6, CYP3A4 and CYP1A2 and antipsychotics
L Beunk et al, EJHG, March 31, 2023
(Posted: Mar 31, 2023 7AM)
Even though evidence is limited, the DPWG recommends choosing an alternative drug to treat symptoms of depression or a dose reduction for other indications for quetiapine and CYP3A4 PMs. No therapy adjustments are recommended for the other CYP2D6 and CYP3A4 predicted phenotypes. In addition, no action is required for the gene-drug combinations CYP2D6 and clozapine, flupentixol, olanzapine or quetiapine and also not for CYP1A2 and clozapine or olanzapine.
Harnessing the Promise of Artificial Intelligence Responsibly.
David A Dorr et al. JAMA 2023 3
(Posted: Mar 28, 2023 6AM)
Recent reviews show that nearly all algorithms still fail to achieve substantial gains over human performance when implemented widely and are often based on limited evidence. The development and use of AI algorithms in health care require careful consideration of ethical frameworks relevant to health care and biomedicine, professional oaths and standards, and the systems in which they are implemented.
ACMG statement on clinical application of polygenic risk scores
L Blackburn, PHG Foundation Blog, March 2023
(Posted: Mar 27, 2023 7AM)
When it comes to implementing polygenic scores into routine healthcare, there are many questions yet to be answered - how polygenic scores are going to be used, is the intention to use them for all conditions or just specific ones, are they to answer questions around diagnosis or prediction? Or both? Only when answers to these and similar questions have been articulated can robust standards for evidence generation and assessment be developed.
Searching for SARS-CoV-2 origins: confidence versus evidence
Lancet Microbe editorial, March 20, 2023
(Posted: Mar 22, 2023 7AM)
Use of digital measurement of medication adherence and lung function to guide the management of uncontrolled asthma (INCA Sun): a multicentre, single-blinded, randomised clinical trial
EM Hale et al, Lancet Resp Medicine, March 21, 2023
(Posted: Mar 22, 2023 7AM)
The clinical value of using digital tools to assess adherence and lung function in uncontrolled asthma is not known. We aimed to compare treatment decisions guided by digitally acquired data on adherence, inhaler technique, and peak flow with existing methods. This RCT found that evidence-based care informed by digital data led to a modest improvement in medication adherence and a significantly lower treatment burden.
New Data Links Pandemic’s Origins to Raccoon Dogs at Wuhan Market
B Mueller, NY Times, March 16, 2023
(Posted: Mar 18, 2023 7PM)
An international team of virus experts said that they had found genetic data from a market in Wuhan, China, linking the coronavirus with raccoon dogs for sale there, adding evidence to the case that the worst pandemic in a century could have been ignited by an infected animal that was being dealt through the illegal wildlife trade.
Genetic association analysis of 77,539 genomes reveals rare disease etiologies.
Daniel Greene et al. Nature medicine 2023 3
(Posted: Mar 18, 2023 7PM)
We provide evidence that (1) loss-of-function variants in the Erythroblast Transformation Specific (ETS)-family transcription factor encoding gene ERG lead to primary lymphoedema, (2) truncating variants in the last exon of transforming growth factor-ß regulator PMEPA1 result in Loeys–Dietz syndrome and (3) loss-of-function variants in GPR156 give rise to recessive congenital hearing impairment. The Rareservoir provides a lightweight, flexible and portable system for synthesizing the genetic and phenotypic data required to study rare disease cohorts with tens of thousands of participants.
Early Detection and Prognostic Assessment of Cutaneous Melanoma Consensus on Optimal Practice and the Role of Gene Expression Profile Testing
MK Sabet et al, JAMA Dermatology, March 15, 2023
(Posted: Mar 15, 2023 5PM)
What are the recommended methods for early detection and prognostic assessment of cutaneous melanoma? In this consensus statement, via a modified Delphi method, melanoma experts supported a risk-stratified approach to various aspects of melanoma screening as well as the use of visual and dermoscopic examination, the interpretation of reflectance confocal microscopy, and some uses of epidermal tape stripping. They did not, based on available evidence, reach consensus on the role for gene expression profile testing in clinical decision-making.
Public Health and Diagnostic Approaches to Risk Stratification for Melanoma
AC Geller et al, JAMA Dermatology, March 15, 2023
(Posted: Mar 15, 2023 5PM)
Dermatologists and public health experts must remain open to evidence-based new diagnostics that can have a profound effect on practice. However, these important collaborations must be guided by rigorously designed studies and a body of evidence that carefully weighs the benefits and potential harms to patients. In doing so, we must ensure that our education, screening, and incorporation of new diagnostics considers populations and patients who are at greatest risk of fatal melanoma.
A non-antibiotic-disrupted gut microbiome is associated with clinical responses to CD19-CAR-T cell cancer immunotherapy
CKS Thoringer et al, Nature Medicine, March 13, 2023
(Posted: Mar 13, 2023 8PM)
Increasing evidence suggests that the gut microbiome may modulate the efficacy of cancer immunotherapy. In a B cell lymphoma patient cohort from five centers in Germany and the United States (Germany, n?=?66; United States, n?=?106; total, n?=?172), we demonstrate that wide-spectrum antibiotics treatment (‘high-risk antibiotics’) prior to CD19-targeted chimeric antigen receptor (CAR)-T cell therapy is associated with adverse outcomes, but this effect is likely to be confounded by an increased pretreatment tumor burden and systemic inflammation in patients pretreated with high-risk antibiotics. To resolve this confounding effect and gain insights into antibiotics-masked microbiome signals impacting CAR-T efficacy, we focused on the high-risk antibiotics non-exposed patient population.
The Progress and Pitfalls of Pharmacogenetics-Based Precision Medicine in Schizophrenia Spectrum Disorders: A Systematic Review and Meta-Analysis
Y Teng et al, J Per Med, March 4, 2023
(Posted: Mar 04, 2023 8AM)
The inadequate efficacy and adverse effects of antipsychotics severely affect the recovery of patients with schizophrenia spectrum disorders (SSD). We report the evidence for associations between pharmacogenetic (PGx) variants and antipsychotics outcomes, including antipsychotic response, antipsychotic-induced weight/BMI gain, metabolic syndrome, antipsychotic-related prolactin levels, antipsychotic-induced tardive dyskinesia (TD), clozapine-induced agranulocytosis (CLA), and drug concentration level (pharmacokinetics) in SSD patients.
