Muirstefansen9285

This revealed a mismatch between the optimal temperatures for resistance and for egg production in immigrating females. Increasing global temperatures could reduce the effectiveness of anti-herbivore resistance in rice and other crops where such mismatches occur.

Cytochrome P450 2D6 (CYP2D6) genotype-guided opioid prescribing is limited. The purpose of this type 2 hybrid implementation-effectiveness trial was to evaluate the feasibility of clinically implementing CYP2D6-guided postsurgical pain management and determine that such an approach did not worsen pain control.

Adults undergoing total joint arthroplasty were randomized 21 to genotype-guided or usual pain management. For participants in the genotype-guided arm with a CYP2D6 poor (PM), intermediate (IM), or ultrarapid (UM)metabolizer phenotype, recommendations were to avoid hydrocodone, tramadol, codeine, and oxycodone. The primary endpoints were feasibility metrics and opioid use; pain intensity was a secondary endpoint. Effectiveness outcomes were collected 2 weeks postsurgery.

Of 282 patients approached, 260 (92%) agreed to participate. In the genotype-guided arm, 20% had a high-risk (IM/PM/UM) phenotype, of whom 72% received an alternative opioid versus 0% of usual care participants (p < 0.001). In an exploratory analysis, there was less opioid consumption (200 [104-280] vs. 230 [133-350] morphine milligram equivalents; p = 0.047) and similar pain intensity (2.6 ± 0.8 vs. 2.5 ± 0.7; p = 0.638) in the genotype-guided vs. usual care arm, respectively.

Implementing CYP2D6 to guide postoperative pain management is feasible and may lead to lower opioid use without compromising pain control.

Implementing CYP2D6 to guide postoperative pain management is feasible and may lead to lower opioid use without compromising pain control.

Pharmacogenomic biomarkers are increasingly listed on medication labels and authoritative guidelines but pharmacogenomic-guided prescribing is not yet common. Our objective was to assess the potential for incorporating knowledge of patients' genomic characteristics into prescribing practices.

We performed a retrospective analysis of claims data for 2,096,971 beneficiaries with pharmacy coverage from a national, commercial health insurance plan between January 2017 and December 2019. Children between 0 and 17 years comprised 21% of the cohort. Adults were age 18 to 64. Medications with actionable pharmacogenomic biomarkers (MAPBs) were identified using public information from the US Food and Drug Administration (FDA), Clinical Pharmacogenomics Implementation Consortium (CPIC), and PharmGKB.

MAPBs were dispensed to 63% of the adults and 29% of the children in the cohort. Most frequently dispensed were ibuprofen, ondansetron, codeine, and oxycodone. Most common were medications with CYP2D6, G6PD, or CYPC19 pharmacogenomic biomarkers. Ten percent of the cohort were codispensed more than one MAPB for at least 30 days.

The number of people who might benefit from pharmacogenomic-guided prescribing is substantial. Future work should address obstacles to integrating genomic data into prescriber workflows, complex factors contributing to the magnitude of benefit, and the clinical availability of reliable on-demand or pre-emptive pharmacogenomic testing.

The number of people who might benefit from pharmacogenomic-guided prescribing is substantial. Future work should address obstacles to integrating genomic data into prescriber workflows, complex factors contributing to the magnitude of benefit, and the clinical availability of reliable on-demand or pre-emptive pharmacogenomic testing.

To identify novel genes associated with intellectual disability (ID) in four unrelated families.

Here, through exome sequencing and international collaboration, we report eight individuals from four unrelated families of diverse geographic origin with biallelic loss-of-function variants in UBE4A.

Eight evaluated individuals presented with syndromic intellectual disability and global developmental delay. Other clinical features included hypotonia, short stature, seizures, and behavior disorder. Characteristic features were appreciated in some individuals but not all; in some cases, features became more apparent with age. We demonstrated that UBE4A loss-of-function variants reduced RNA expression and protein levels in clinical samples. Mice generated to mimic patient-specific Ube4a loss-of-function variant exhibited muscular and neurological/behavioral abnormalities, some of which are suggestive of the clinical abnormalities seen in the affected individuals.

These data indicate that biallelic loss-of-function variants in UBE4A cause a novel intellectual disability syndrome, suggesting that UBE4A enzyme activity is required for normal development and neurological function.

These data indicate that biallelic loss-of-function variants in UBE4A cause a novel intellectual disability syndrome, suggesting that UBE4A enzyme activity is required for normal development and neurological function.

Patient care involving genetics is challenging for nongenetics health-care providers. Hedgehog inhibitor Clinical decision support (CDS) tools are a potential solution because they provide patient-specific risk assessments and/or management recommendations. This systematic review synthesized evidence on whether using CDS tools resulted in appropriate changes in genetics-related patient management made by nongenetics health-care providers.

A comprehensive search in MEDLINE, Embase, and CINAHL yielded 2,239 unique articles. Two independent reviewers screened abstracts and full texts for quantitative, qualitative, and mixed-methods articles on management changes by nongenetics clinicians using a CDS tool as part of patient care. Effect sizes were calculated for quantitative studies and all articles were analyzed together using narrative synthesis. Twenty articles were included.

In 12/16 quantitative studies, CDS tools slightly increased appropriate changes in management, but study design appeared to affect the statistical significance of the effect. The qualitative data in the four remaining studies reaffirmed that CDS tools facilitated management decisions but raised questions about their effect on patient outcomes.

Our review assessed clinical utility of CDS tools, finding that they slightly increase appropriate management changes by nongenetics providers. Future studies on CDS tools should explicitly evaluate decision making and patient outcomes.

Our review assessed clinical utility of CDS tools, finding that they slightly increase appropriate management changes by nongenetics providers. Future studies on CDS tools should explicitly evaluate decision making and patient outcomes.