J Pers Med. 2021 Aug 27;11(9):851. doi: 10.3390/jpm11090851.

ABSTRACT

The management of neuropsychiatric disorders involves different pharmacological treatments. In order to perform efficacious drug treatments, the metabolism of CYP genes can help to foresee potential drug-drug interactions. The NeuroPGx software is an open-source web-based tool for genotype/diplotype/phenotype interpretation for neuropharmacogenomic purposes. The software provides information about: (i) the genotypes of evaluated SNPs (single nucleotide polymorphisms); (ii) the main diplotypes in CYP genes and corresponding metabolization phenotypes; (iii) the list of neuropsychiatric drugs with recommended dosage adjustment (according to CPIC and DPWG guidelines); (iv) the list of possible (rare) diplotypes and corresponding metabolization phenotypes. The combined application of NeuroPGx software to the OpenArray technology results in an easy, quick, and highly automated device ready to be used in routine clinical practice.

PMID:34575628 | DOI:10.3390/jpm11090851

J Pers Med. 2021 Aug 27;11(9):848. doi: 10.3390/jpm11090848.

ABSTRACT

Autism Spectrum Disorder (ASD) comprises a heterogeneous group of neurodevelopmental disorders with a strong heritable genetic component. At present, ASD is diagnosed solely by behavioral criteria. Advances in genomic analysis have contributed to numerous candidate genes for the risk of ASD, where rare mutations and s common variants contribute to its susceptibility. Moreover, studies show rare de novo variants, copy number variation and single nucleotide polymorphisms (SNPs) also impact neurodevelopment signaling. Exploration of rare and common variants involved in common dysregulated pathways can provide new diagnostic and therapeutic strategies for ASD. Contributions of current innovative molecular strategies to understand etiology of ASD will be explored which are focused on whole exome sequencing (WES), whole genome sequencing (WGS), microRNA, long non-coding RNAs and CRISPR/Cas9 models. Some promising areas of pharmacogenomic and endophenotype directed therapies as novel personalized treatment and prevention will be discussed.

PMID:34575625 | DOI:10.3390/jpm11090848

Pharmaceutics. 2021 Sep 14;13(9):1466. doi: 10.3390/pharmaceutics13091466.

ABSTRACT

Oxycodone is a widely used opioid for the management of chronic pain. Analgesic effects observed following the administration of oxycodone are mediated mostly by agonistic effects on the μ-opioid receptor. Wide inter-subject variability observed in oxycodone efficacy could be explained by polymorphisms in the gene coding for the μ-opioid receptor (OPRM1). In humans, oxycodone is converted into several metabolites, particularly into oxymorphone, an active metabolite with potent μ-opioid receptor agonist activity. The CYP2D6 enzyme is principally responsible for the conversion of oxycodone to oxymorphone. The CYP2D6 gene is highly polymorphic with encoded protein activities, ranging from non-functioning to high-functioning enzymes. Several pharmacogenetic studies have shown the importance of CYP2D6-mediated conversion of oxycodone to oxymorphone for analgesic efficacy. Pharmacogenetic testing could optimize oxycodone therapy and help achieve adequate pain control, avoiding harmful side effects. However, the most recent Clinical Pharmacogenetics Implementation Consortium guidelines fell short of recommending pharmacogenomic testing for oxycodone treatment. In this review, we (1) analyze pharmacogenomic and drug-interaction studies to delineate the association between CYP2D6 activity and oxycodone efficacy, (2) review evidence from CYP3A4 drug-interaction studies to untangle the nature of oxycodone metabolism and its efficacy, (3) report on the current knowledge linking the efficacy of oxycodone to OPRM1 variants, and (4) discuss the potential role of CYP2D6 brain expression on the local formation of oxymorphone. In conclusion, we opine that pharmacogenetic testing, especially for CYP2D6 with considerations of phenoconversion due to concomitant drug administration, should be appraised to improve oxycodone efficacy.

PMID:34575542 | DOI:10.3390/pharmaceutics13091466

J Clin Med. 2021 Sep 9;10(18):4079. doi: 10.3390/jcm10184079.

ABSTRACT

Anthracyclines are one of the most widely used and effective chemotherapies in oncology, but their most important side effect is the cumulative, dose-related cardiotoxicity leading to congestive heart failure in ~5% of individuals. Methodology and pharmacogenetic studies for predicting which individuals are at high risk and subsequently the development of targeted and individualized cardioprotective plans are beginning to make progress. Here, we review current putative risk genes and variants, the strength of evidence for each genetic association and the interaction between risk genes, in the context of known clinical risk factors and potential novel cardioprotective strategies.

PMID:34575190 | DOI:10.3390/jcm10184079

Foods. 2021 Aug 30;10(9):2037. doi: 10.3390/foods10092037.

ABSTRACT

Nutritional knowledge, attitudes and practice (KAP) may guide healthy meal choices. Here, nutritional KAP was compared across school students in Sabah based on locality and gender. A cross-sectional survey of students aged 15-19 years was conducted using multistage sampling. Nutritional KAP was measured via questionnaire. Anthropometric measures of weight and height were taken in person to calculate body mass index (BMI). Among the 994 participants, 80% were urban and 60% were female (mean age 16.5 ± 0.6 yr). Most were of Kadazan-Dusun (23%) ethnicity. Measured height for age Z score (HAZ) and BMI for age Z score (BAZ) differed between urban and rural students (-1.2 ± 0.8 versus -1.5 ± 0.7 for HAZ; p < 0.001; 0.2 ± 1.4 versus -0.1 ± 1.3; p = 0.02, respectively). No difference in nutritional knowledge was found, although urban students prioritized having a healthy/balanced diet (59.55% versus 48.50%, p = 0.03) and ate daily breakfast (57.4% versus 10.2%, p < 0.001) compared to rural. Females scored higher on nutritional knowledge than males (18.9 ± 2.8 vs. 18.1 ± 3.4, respectively, p = 0.0001), yet males selected more healthy/balanced foods (63.3% versus 53.3%, p = 0.041). The gap remains between nutritional KAP and translating this to healthy eating among adolescents, related to locality and gender.

PMID:34574147 | DOI:10.3390/foods10092037

Genes (Basel). 2021 Sep 15;12(9):1419. doi: 10.3390/genes12091419.

ABSTRACT

P-glycoprotein encoded by the ABCB1 gene constitutes a molecular barrier in the small and large bowel epithelium, and its different expression may influence susceptibility to inflammatory bowel disease (IBD). We aimed to assess the contribution of the C3435T polymorphism to disease risk in the Polish population. A total of 100 patients (50 Crohn's disease (CD), 50 ulcerative colitis (UC)) and 100 healthy controls were genotyped for the single nucleotide polymorphism (SNP) C3435T by using the PCR-RFLP method. Patients were classified on the basis of disease phenotype and the specific treatment used. A meta-analysis was carried out of our results and those from previously published Polish studies. There was no significant difference in allele and genotype frequencies in IBD patients compared with controls. For CD patients, a lower frequency of TT genotype in those with colonic disease, a lower frequency of T allele, and a higher frequency of C allele in those with luminal disease were observed, whereas for UC patients, a lower frequency of CT genotype was observed in those with left-sided colitis. A meta-analysis showed a tendency towards higher prevalence of CC genotype in UC cases. These results indicate that the C3435T variants may confer a risk for UC and influence disease behaviour.

PMID:34573401 | DOI:10.3390/genes12091419

Genes (Basel). 2021 Sep 10;12(9):1398. doi: 10.3390/genes12091398.

ABSTRACT

Pharmacogenomic studies allowed the reasons behind the different responses to treatments to be understood. Its clinical utility, in fact, is demonstrated by the reduction in adverse drug reaction incidence and the improvement of drug efficacy. Pharmacogenomics is an important tool that is able to improve the drug therapy of different disorders. In particular, this review will highlight the current pharmacogenomics knowledge about biologics and small-molecule treatments for psoriasis. To date, studies performed on genes involved in the metabolism of biological drugs (tumor necrosis factor inhibitors and cytokines inhibitors) and small molecules (apremilast, dimethyl fumarate, and tofacitinib) have provided conflicting results, and further investigations are necessary in order to establish a set of biomarkers to be introduced into clinical practice.

PMID:34573380 | DOI:10.3390/genes12091398

Antioxidants (Basel). 2021 Sep 20;10(9):1495. doi: 10.3390/antiox10091495.

ABSTRACT

Inflammation and oxidative stress after hypoxic-ischemic brain injury may be modified by genetic variability in addition to therapeutic hypothermia. The aim of our study was to evaluate the association between the polymorphisms in genes of antioxidant and inflammatory pathways in newborns treated with therapeutic hypothermia and the development of epilepsy or CP at two years follow-up. The DNA of 55 subjects was isolated from buccal swabs. Genotyping using competitive allele-specific PCR was performed for polymorphisms in antioxidant (SOD2 rs4880, CAT rs1001179, GPX1 rs1050450) and inflammatory (NLRP3 rs35829419, CARD8 rs2043211, IL1B rs1143623, IL1B rs16944, IL1B rs10716 76, TNF rs1800629) pathways. Polymorphic CARD8 rs2043211 T allele was less frequent in patients with epilepsy, but the association was not statistically significant. The interaction between CARD8 rs2043211 and IL1B rs16944 was associated with epilepsy after HIE: CARD8 rs2043211 was associated with lower epilepsy risk, but only in carriers of two normal IL1B rs16944 alleles (ORadj = 0.03 95% CI = 0.00-0.55; padj = 0.019). Additionally, IL1B rs16944 was associated with higher epilepsy risk only in carriers of at least one polymorphic CARD8 rs2043211 (ORadj = 13.33 95% CI = 1.07-166.37; padj = 0.044). Our results suggest that gene-gene interaction in inflammation pathways might contribute to the severity of brain injury in newborns with HIE treated with therapeutic hypothermia.

PMID:34573127 | DOI:10.3390/antiox10091495

Antioxidants (Basel). 2021 Sep 15;10(9):1467. doi: 10.3390/antiox10091467.

ABSTRACT

Methionine is an aliphatic, sulfur-containing, essential amino acid that has been demonstrated to have crucial roles in metabolism, innate immunity, and activation of endogenous antioxidant enzymes, including methionine sulfoxide reductase A/B and the biosynthesis of glutathione to counteract oxidative stress. Still, methionine restriction avoids altered methionine/transmethylation metabolism, thus reducing DNA damage and possibly avoiding neurodegenerative processes. In this study, we wanted to study the preventive effects of methionine in counteracting 6-hydroxydopamine (6-OHDA)-induced injury. In particular, we analyzed the protective effects of the amino acid L-methionine in an in vitro model of Parkinson's disease and dissected the underlying mechanisms compared to the known antioxidant taurine to gain insights into the potential of methionine treatment in slowing the progression of the disease by maintaining mitochondrial functionality. In addition, to ascribe the effects of methionine on mitochondria and oxidative stress, methionine sulfoxide was used in place of methionine. The data obtained suggested that an L-methionine-enriched diet could be beneficial during aging to protect neurons from oxidative imbalance and mitochondrial dysfunction, thus preventing the progression of neurodegenerative processes.

PMID:34573099 | DOI:10.3390/antiox10091467

Cancers (Basel). 2021 Sep 21;13(18):4714. doi: 10.3390/cancers13184714.

ABSTRACT

BRCA1/2-associated hereditary breast and ovarian cancer is the most common form of hereditary breast and ovarian cancer and occurs in all ethnicities and racial populations. Different BRCA1/BRCA2 pathogenic variants (PVs) have been reported with a wide variety among populations. In this study, we retrospectively analyzed prevalence and geographic distribution of pathogenic germline BRCA1/2 variants in families from Apulia in southern Italy and evaluated the genotype-phenotype correlations. Data were collected from Oncogenetic Services present in Apulian hospitals and a shared database was built containing Apulian native probands (n = 2026) that had undergone genetic testing from 2004 to 2019. PVs were detected in 499 of 2026 (24.6%) probands and 68.5% of them (342 of 499) were in the BRCA1 gene. We found 65 different PVs in BRCA1 and 46 in BRCA2. There were 10 most recurrent PVs and their geographical distribution appears to be significantly specific for each province. We have assumed that these PVs are related to the historical and geopolitical changes that occurred in Apulia over time and/or to a "founder effect". Broader knowledge of BRCA1/2 prevalence and recurring PVs in specific geographic areas could help establish more flexible genetic testing strategies that may enhance our ability to detect high-risk subjects.

PMID:34572941 | DOI:10.3390/cancers13184714

Cancers (Basel). 2021 Sep 13;13(18):4589. doi: 10.3390/cancers13184589.

ABSTRACT

The clinical influence of the neutrophil-to-lymphocyte ratio (NLR) in predicting outcomes in patients with locally advanced rectal cancer (LARC) who achieve a pathological complete response (pCR) to neoadjuvant chemoradiotherapy (NACRT) has seldom been investigated. We retrospectively recruited 102 patients with LARC who achieved a pCR to NACRT and the association of NLR status with survival and tumor recurrence in the patients was analyzed. Thirteen patients (12.7%) developed tumor recurrence. A high NLR (≥3.2) was significantly associated with tumor recurrence (p = 0.039). The 5-year OS rates in patients with a low NLR and patients with a high NLR were 95.1% and 77.7%, respectively (p = 0.014); the 5-year DFS rates in patients with low NLR and patients with a high NLR were 90.6% and 71.3%, respectively (p = 0.031). The Cox proportional hazards model indicated that an NLR of ≥3.2 was an independent poor prognostic factor for DFS (hazard ratio [HR] = 3.12, 95% confidence interval [CI] = 1.06-9.46, p = 0.048) and OS (HR = 6.96, 95% CI = 1.53-35.51, p = 0.013). A pretreatment high NLR (≥3.2) was a promising predictor of reduced OS and DFS in patients with LARC who achieved a pCR to NACRT.

PMID:34572816 | DOI:10.3390/cancers13184589

Cancers (Basel). 2021 Sep 10;13(18):4550. doi: 10.3390/cancers13184550.

ABSTRACT

Hepatocellular carcinoma (HCC) is one of the deadliest cancers. HCC is associated with multiple risk factors and is characterized by a marked tumor heterogeneity that makes its molecular classification difficult to apply in the clinics. The lack of circulating biomarkers for the diagnosis, prognosis, and prediction of response to treatments further undermines the possibility of developing personalized therapies. Accumulating evidence affirms the involvement of cancer stem cells (CSCs) in tumor heterogeneity, recurrence, and drug resistance. Owing to the contribution of CSCs to treatment failure, there is an urgent need to develop novel therapeutic strategies targeting, not only the tumor bulk, but also the CSC subpopulation. Clarification of the molecular mechanisms influencing CSC properties, and the identification of their functional roles in tumor progression, may facilitate the discovery of novel CSC-based therapeutic targets to be used alone, or in combination with current anticancer agents, for the treatment of HCC. Here, we review the driving forces behind the regulation of liver CSCs and their therapeutic implications. Additionally, we provide data on their possible exploitation as prognostic and predictive biomarkers in patients with HCC.

PMID:34572776 | DOI:10.3390/cancers13184550

Cancers (Basel). 2021 Sep 8;13(18):4524. doi: 10.3390/cancers13184524.

ABSTRACT

The purpose of this study was to determine the frequency of clinically actionable treatment-relevant germline pharmacogenomic variants in patients with cancer and assess the real-world clinical utility of universal screening using whole-exome sequencing in this population. Cancer patients underwent research-grade germline whole-exome sequencing as a component of sequencing for somatic variants. Analysis in a clinical bioinformatics pipeline identified clinically actionable pharmacogenomic variants. Clinical Pharmacogenetics Implementation Consortium guidelines defined clinical actionability. We assessed clinical utility by reviewing electronic health records to determine the frequency of patients receiving pharmacogenomically actionable anti-cancer agents and associated outcomes. This observational study evaluated 291 patients with cancer. More than 90% carried any clinically relevant pharmacogenetic variant. At least one disease-relevant variant impacting anti-cancer agents was identified in 26.5% (77/291). Nine patients with toxicity-associated pharmacogenomic variants were treated with a relevant medication: seven UGT1A1 intermediate metabolizers were treated with irinotecan, one intermediate DPYD metabolizer was treated with 5-fluorouracil, and one TPMT poor metabolizer was treated with mercaptopurine. These individuals were more likely to experience treatment-associated toxicities than their wild-type counterparts (p = 0.0567). One UGT1A1 heterozygote died after a single dose of irinotecan due to irinotecan-related adverse effects. Identifying germline pharmacogenomic variants was feasible using whole-exome sequencing. Actionable pharmacogenetic variants are common and relevant to patients undergoing cancer treatment. Universal pharmacogenomic screening can be performed using whole-exome sequencing data originally obtained for quality control purposes and could be considered for patients who are candidates for irinotecan, 5-fluorouracil, capecitabine, and mercaptopurine.

PMID:34572750 | DOI:10.3390/cancers13184524

Antibiotics (Basel). 2021 Sep 1;10(9):1061. doi: 10.3390/antibiotics10091061.

ABSTRACT

The emergence of multidrug-resistant H. pylori poses a public healthcare threat, particularly in low- and middle-income countries. Recently, the World Health Organization has classified clarithromycin-resistant H. pylori as high priority in the research and discovery of novel antibiotics. This study was aimed to systematically review the prevalence of primary antibiotic resistance in H. pylori in Southeast Asian countries (SEAC) and to review current studies of antimicrobial peptides against H. pylori. We systematically searched through electronic databases of studies conducted on antimicrobial resistance of H. pylori in SEA countries. Furthermore, we searched articles that conducted studies on antimicrobial peptides, naturally occurring host's defense molecules, against H. pylori. After a series of screening processes, 15 studies were included in our systematic review. Our analysis revealed that primary resistance of H. pylori to metronidazole, clarithromycin, and levofloxacin were high in SEAC, although the primary resistance to amoxicillin and tetracycline remains low. Multidrug-resistant H. pylori are emerging in SE Asian countries. The antimicrobial peptides show promising antibacterial and antibiofilm activity against drug-resistant H. pylori. The research and discovery of antimicrobial peptides against H. pylori in SEAC will help in limiting the spread of antimicrobial resistance of H. pylori.

PMID:34572643 | DOI:10.3390/antibiotics10091061

Biomolecules. 2021 Aug 25;11(9):1272. doi: 10.3390/biom11091272.

ABSTRACT

Metalloproteinases (MMPs) have an important role in tissue remodeling and have been shown to have an effect on tumor progression, invasion, metastasis formation, and apoptosis in several tumors, including mesothelioma. Mesothelioma is a rare tumor arising from pleura and peritoneum and is frequently associated with asbestos exposure. We have performed a systematic search of PubMed.gov and ClinicalTrials.gov databases to retrieve and review three groups of studies: studies of MMPs expression in tumor tissue or body fluids in patients with mesothelioma, studies of MMPs genetic variability, and studies of MMPs as potential novel drug targets in mesothelioma. Several studies of MMPs in mesothelioma tissues reported a link between higher expression levels of commonly studied MMPs and clinical parameters, such as overall survival. Fewer studies have investigated genetic variability of MMP genes. Nevertheless, these studies suggested that certain genetic variants in MMP genes can have either protective or tumor-promoting effects on mesothelioma patients. MMPs have been also reported as novel drug targets, but so far no clinical trials of MMP inhibitors are registered in mesothelioma. In conclusion, MMPs play an important role in mesothelioma, but further studies are needed to elucidate the potentials of MMPs as biomarkers and drug targets in mesothelioma.

PMID:34572485 | DOI:10.3390/biom11091272

Biomedicines. 2021 Sep 12;9(9):1202. doi: 10.3390/biomedicines9091202.

ABSTRACT

Although studies show an annual trend for immunosuppressive drugs, particularly during different seasons, no data are available for antiretroviral drugs exposures in different periods of the year. For this reason, the aim of this study was to investigate an association between seasonality and antiretroviral drugs plasma concentrations. Antiretroviral drugs exposures were measured with liquid chromatography validated methods. A total of 4148 human samples were analysed. Lopinavir, etravirine and maraviroc levels showed seasonal fluctuation. In detail, maraviroc and etravirine concentrations decreased further in summer than in winter. In contrast, lopinavir concentrations had an opposite trend, increasing more in summer than in winter. The etravirine efficacy cut-off value of 300 ng/mL seems to be affected by seasonality: 77.1% and 22.9% of samples achieved this therapeutic target, respectively, in winter and summer, whereas 30% in winter and 70% in summer did not reach this value. Finally, age over 50 years and summer remained in the final multivariate regression model as predictors of the etravirine efficacy cut-off. This study highlights the seasonal variation in antiretroviral drugs plasma concentrations during the year, leading to a better understanding of inter-individual variability in drug exposures. Studies are required in order to confirm these data, clarifying which aspects may be involved.

PMID:34572388 | DOI:10.3390/biomedicines9091202

Cells. 2021 Sep 17;10(9):2461. doi: 10.3390/cells10092461.

ABSTRACT

The ATP-binding cassette (ABC) transporter superfamily consists of several proteins with a wide repertoire of functions. Under physiological conditions, ABC transporters are involved in cellular trafficking of hormones, lipids, ions, xenobiotics, and several other molecules, including a broad spectrum of chemical substrates and chemotherapeutic drugs. In cancers, ABC transporters have been intensely studied over the past decades, mostly for their involvement in the multidrug resistance (MDR) phenotype. This review provides an overview of ABC transporters, both related and unrelated to MDR, which have been studied in osteosarcoma and Ewing's sarcoma. Since different backbone drugs used in first-line or rescue chemotherapy for these two rare bone sarcomas are substrates of ABC transporters, this review particularly focused on studies that have provided findings that have been either translated to clinical practice or have indicated new candidate therapeutic targets; however, findings obtained from ABC transporters that were not directly involved in drug resistance were also discussed, in order to provide a more complete overview of the biological impacts of these molecules in osteosarcoma and Ewing's sarcoma. Finally, therapeutic strategies and agents aimed to circumvent ABC-mediated chemoresistance were discussed to provide future perspectives about possible treatment improvements of these neoplasms.

PMID:34572110 | DOI:10.3390/cells10092461

Brief Bioinform. 2021 Sep 24:bbab386. doi: 10.1093/bib/bbab386. Online ahead of print.

ABSTRACT

Cancer stem cells (CSCs) actively reprogram their tumor microenvironment (TME) to sustain a supportive niche, which may have a dramatic impact on prognosis and immunotherapy. However, our knowledge of the landscape of the gastric cancer stem-like cell (GCSC) microenvironment needs to be further improved. A multi-step process of machine learning approaches was performed to develop and validate the prognostic and predictive potential of the GCSC-related score (GCScore). The high GCScore subgroup was not only associated with stem cell characteristics, but also with a potential immune escape mechanism. Furthermore, we experimentally demonstrated the upregulated infiltration of CD206+ tumor-associated macrophages (TAMs) in the invasive margin region, which in turn maintained the stem cell properties of tumor cells. Finally, we proposed that the GCScore showed a robust capacity for prediction for immunotherapy, and investigated potential therapeutic targets and compounds for patients with a high GCScore. The results indicate that the proposed GCScore can be a promising predictor of prognosis and responses to immunotherapy, which provides new strategies for the precision treatment of GCSCs.

PMID:34571533 | DOI:10.1093/bib/bbab386

J Mol Neurosci. 2021 Sep 27. doi: 10.1007/s12031-021-01913-8. Online ahead of print.

ABSTRACT

Cluster headache (CH) is a primary headache disorder with a complex genetic background. Several studies indicate a potential link between iron homeostasis and the pathophysiology of primary headaches. The HFE gene encodes for a protein involved in iron metabolism, while genetic variants in HFE have been associated with hereditary hemochromatosis (HH), an iron overload disorder. The objective of the current study was to examine the association of the more common HFE H63D variant, with the susceptibility to develop CH and diverse clinical phenotypes in a population of Southeastern European Caucasian (SEC) origin. Genomic DNA samples from 128 CH patients and 294 neurologically healthy controls were genotyped for the HFE rs1799945 (H63D) variant. H63D genotypic and allelic frequency distribution did not differ significantly between patients and controls (p > 0.05). Subgroup analysis revealed a significantly more frequent occurrence of the variant G allele in chronic compared to episodic CH patients, indicative for a possible correlation of the HFE gene with the susceptibility for disease chronification. Although homozygosity for the less prevalent H63D variant G allele was minimal in the CH cohort, the results of the present study are in accordance with previous studies in CH and migraine patients, suggesting that HFE H63D variant modifies the disease clinical characteristics. Hence, despite the absence of a per se association with CH susceptibility in the current SEC cohort, variability in HFE gene may be potentially regarded as a disease modifier genetic factor in CH.

PMID:34570359 | DOI:10.1007/s12031-021-01913-8

Pharmacogenet Genomics. 2021 Sep 23. doi: 10.1097/FPC.0000000000000455. Online ahead of print.

ABSTRACT

OBJECTIVES: Integration of pharmacogenomics into clinical care is being studied in multiple disciplines. We hypothesized that understanding attitudes and perceptions of anesthesiologists, critical care and pain medicine providers would uncover unique considerations for future implementation within perioperative care.

METHODS: A survey (multiple choice and Likert-scale) was administered to providers within our Department of Anesthesia and Critical Care prior to initiation of a department-wide prospective pharmacogenomics implementation program. The survey addressed knowledge, perceptions, experiences, resources and barriers.

RESULTS: Of 153 providers contacted, 149 (97%) completed the survey. Almost all providers (92%) said that genetic results influence drug therapy, and few (22%) were skeptical about the usefulness of pharmacogenomics. Despite this enthusiasm, 87% said their awareness about pharmacogenomic information is lacking. Feeling well-informed about pharmacogenomics was directly related to years in practice/experience: only 38% of trainees reported being well-informed, compared to 46% of those with 1-10 years of experience, and nearly two-thirds with 11+ years (P < 0.05). Regarding barriers, providers reported uncertainty about availability of testing, turnaround time and whether testing is worth financial costs.

CONCLUSIONS: Anesthesiology, critical care and pain medicine providers are optimistic about the potential clinical utility of pharmacogenomics, but are uncertain about practical aspects of testing and desire clear guidelines on the use of results. These findings may inform future institutional efforts toward greater integration of genomic results to improve medication-related outcomes.

PMID:34570085 | DOI:10.1097/FPC.0000000000000455