Pharmacogenetic testing and monitoring of complete blood counts among Veterans newly prescribed thiopurine treatments: a retrospective cohort study.

Pharmacogenetic (PGx) testing before initiation of thiopurine treatment and CBC monitoring post-initiation helps avoid adverse events and ensure patient safety. This study aims to evaluate trends in PGx testing and CBC monitoring among Veterans prescribed azathioprine, thioguanine, or mercaptopurine to demonstrate VA's efforts to improve medication safety after an adverse event. To assess testing patterns, we used VA electronic health report data to identify 20,524 Veterans who first began thiopurine treatment between January 1, 2010, to December 31, 2021. Aggregate monthly counts of thiopurine prescriptions and associated lab tests were tabulated, and the trend in the proportion of patients tested was analyzed using the Mann-Kendall test. The proportion of patients undergoing PGx testing rose from 30.0% in 2010 to 47.5% in late 2014 (July-December). However, PGx testing and overall testing only increased slightly after the sentinel event, and orders levelled off over time at slightly lower levels than before the sentinel event. Very little change was seen in the overall proportion of individuals receiving any testing across all patients with new prescriptions from the time of the sentinel event in 2014 to the end of 2021. A large portion of patients prescribed thiopurine drugs did not receive testing that could help prevent the development of potential adverse events, leading to a predominantly reactive approach. Increased PGx testing may result in a more proactive approach to the prevention of adverse events due to genetic interaction.

Assessing Pathogen Transmission Opportunities: Variation in Nursing Home Staff-Resident Interactions.

OBJECTIVES: The Centers for Disease Control and Prevention (CDC) recommends implementing Enhanced Barrier Precautions (EBP) for all nursing home (NH) residents known to be colonized with targeted multidrug-resistant organisms (MDROs), wounds, or medical devices. Differences in health care personnel (HCP) and resident interactions between units may affect risk of acquiring and transmitting MDROs, affecting EBP implementation. We studied HCP-resident interactions across a variety of NHs to characterize MDRO transmission opportunities. DESIGN: 2 cross-sectional visits. SETTING AND PARTICIPANTS: Four CDC Epicenter sites and CDC Emerging Infection Program sites in 7 states recruited NHs with a mix of unit care types (≥30 beds or ≥2 units). HCP were observed providing resident care. METHODS: Room-based observations and HCP interviews assessed HCP-resident interactions, care type provided, and equipment use. Observations and interviews were conducted for 7-8 hours in 3-6-month intervals per unit. Chart reviews collected deidentified resident demographics and MDRO risk factors (eg, indwelling devices, pressure injuries, and antibiotic use). RESULTS: We recruited 25 NHs (49 units) with no loss to follow-up, conducted 2540 room-based observations (total duration: 405 hours), and 924 HCP interviews. HCP averaged 2.5 interactions per resident per hour (long-term care units) to 3.4 per resident per hour (ventilator care units). Nurses provided care to more residents (n = 12) than certified nursing assistants (CNAs) and respiratory therapists (RTs) (CNA: 9.8 and RT: 9) but nurses performed significantly fewer task types per interaction compared to CNAs (incidence rate ratio (IRR): 0.61, P < .05). Short-stay (IRR: 0.89) and ventilator-capable (IRR: 0.94) units had less varied care compared with long-term care units (P < .05), although HCP visited residents in these units at similar rates. CONCLUSIONS AND IMPLICATIONS: Resident-HCP interaction rates are similar across NH unit types, differing primarily in types of care provided. Current and future interventions such as EBP, care bundling, or targeted infection prevention education should consider unit-specific HCP-resident interaction patterns.

Hand hygiene and the sequence of patient care.

OBJECTIVE: To determine whether the order in which healthcare workers perform patient care tasks affects hand hygiene compliance. DESIGN: For this retrospective analysis of data collected during the Strategies to Reduce Transmission of Antimicrobial Resistant Bacteria in Intensive Care Units (STAR*ICU) study, we linked consecutive tasks healthcare workers performed into care sequences and identified task transitions: 2 consecutive task sequences and the intervening hand hygiene opportunity. We compared hand hygiene compliance rates and used multiple logistic regression to determine the adjusted odds for healthcare workers (HCWs) transitioning in a direction that increased or decreased the risk to patients if healthcare workers did not perform hand hygiene before the task and for HCWs contaminating their hands. SETTING: The study was conducted in 17 adult surgical, medical, and medical-surgical intensive care units. PARTICIPANTS: HCWs in the STAR*ICU study units. RESULTS: HCWs moved from cleaner to dirtier tasks during 5,303 transitions (34.7%) and from dirtier to cleaner tasks during 10,000 transitions (65.4%). Physicians (odds ratio [OR]: 1.50; P < .0001) and other HCWs (OR, 2.15; P < .0001) were more likely than nurses to move from dirtier to cleaner tasks. Glove use was associated with moving from dirtier to cleaner tasks (OR, 1.22; P < .0001). Hand hygiene compliance was lower when HCWs transitioned from dirtier to cleaner tasks than when they transitioned in the opposite direction (adjusted OR, 0.93; P < .0001). CONCLUSIONS: HCWs did not organize patient care tasks in a manner that decreased risk to patients, and they were less likely to perform hand hygiene when transitioning from dirtier to cleaner tasks than the reverse. These practices could increase the risk of transmission or infection.

The impact of workload on hand hygiene compliance: Is 100% compliance achievable?

Hand hygiene compliance decreased significantly when opportunities exceeded 30 per hour. At higher workloads, the number of healthcare worker types involved and the proportion of hand hygiene opportunities for which physicians and other healthcare workers were responsible increased. Thus, care complexity and risk to patients may both increase with workload.

Hand Hygiene Compliance at Critical Points of Care.

BACKGROUND: Most articles on hand hygiene report either overall compliance or compliance with specific hand hygiene moments. These moments vary in the level of risk to patients if healthcare workers (HCWs) are noncompliant. We assessed how task type affected HCWs' hand hygiene compliance. METHODS: We linked consecutive tasks individual HCWs performed during the Strategies to Reduce Transmission of Antimicrobial Resistant Bacteria in Intensive Care Units (STAR*ICU) study into care sequences and identified task pairs-2 consecutive tasks and the intervening hand hygiene opportunity. We defined tasks as critical and/or contaminating. We determined the odds of critical and contaminating tasks occurring, and the odds of hand hygiene compliance using logistic regression for transition with a random effect adjusting for isolation precautions, glove use, HCW type, and compliance at prior opportunities. RESULTS: Healthcare workers were less likely to do hand hygiene before critical tasks than before other tasks (adjusted odds ratio [aOR], 0.97 [95% confidence interval {CI}, .95-.98]) and more likely to do hand hygiene after contaminating tasks than after other tasks (aOR, 1.12 [95% CI, 1.10-1.13]). Nurses were more likely to perform both critical and contaminating tasks, but nurses' hand hygiene compliance was better than physicians' (aOR, 0.94 [95% CI, .91-.97]) and other HCWs' compliance (aOR, 0.87 [95% CI, .87-.94]). CONCLUSIONS: Healthcare workers were more likely to do hand hygiene after contaminating tasks than before critical tasks, suggesting that habits and a feeling of disgust may influence hand hygiene compliance. This information could be incorporated into interventions to improve hand hygiene practices, particularly before critical tasks and after contaminating tasks.

Oral ß-Lactam Antibiotics vs Fluoroquinolones or Trimethoprim-Sulfamethoxazole for Definitive Treatment of Enterobacterales Bacteremia From a Urine Source.

Importance: Oral ß-lactam antibiotics are traditionally not recommended to treat Enterobacterales bacteremia because of concerns over subtherapeutic serum concentrations, but there is a lack of outcomes data, specifically after initial treatment with parenteral antibiotics. Given the limited data and increasing limitations of fluoroquinolones or trimethoprim-sulfamethoxazole (TMP-SMX), oral ß-lactam antibiotics may be a valuable additional treatment option. Objective: To compare definitive therapy with oral ß-lactam antibiotics vs fluoroquinolones or TMP-SMX for Enterobacterales bacteremia from a suspected urine source. Design, Setting, and Participants: A retrospective cohort study was conducted from January 1, 2007, to September 30, 2015, at 114 Veterans Affairs hospitals among 4089 adults with Escherichia coli, Klebsiella spp, or Proteus spp bacteremia and matching urine culture results. Additional inclusion criteria were receipt of active parenteral antibiotic(s) followed by conversion to an oral antibiotic. Exclusion criteria were previous Enterobacterales bacteremia, urologic abscess, or chronic prostatitis. Data were analyzed from April 15, 2019, to July 26, 2020. Exposures: Conversion of therapy to an oral ß-lactam antibiotic vs fluoroquinolones or TMP-SMX after 1 to 5 days of parenteral antibiotics. Main Outcomes and Measures: The main outcome was a composite of either 30-day all-cause mortality or 30-day recurrent bacteremia. Propensity-based overlap weights were used to adjust for differences between groups. Log binomial regression models were used to estimate adjusted relative risks (aRRs) and adjusted risk differences (aRDs). Results: Of the 4089 eligible patients (3731 men [91.2%]; median age, 71 years [interquartile range, 63-81 years]), 955 received an oral ß-lactam antibiotic, and 3134 received fluoroquinolones or TMP-SMX. The primary outcome occurred for 42 patients (4.4%) who received ß-lactam antibiotics and 94 patients (3.0%) who received fluoroquinolones or TMP-SMX (aRD, 0.99% [95% CI, -0.42% to 2.40%]; aRR, 1.31 [95% CI, 0.87-1.95]). Mortality rates were 3.0% (n = 29) for patients receiving ß-lactam antibiotics vs 2.6% (n = 82) for those receiving fluoroquinolones or TMP-SMX (aRD, 0.06% [95% CI, -1.13% to 1.26%]; aRR, 1.02 [95% CI, 0.67-1.56]). Recurrent bacteremia rates were 1.5% (n = 14) among those receiving ß-lactam antibiotics vs 0.4% (n = 12) among those receiving fluoroquinolones or TMP-SMX (aRD, 1.03% [95% CI, 0.24%-1.82%]; aRR, 3.43 [95% CI, 0.42-27.90]). Conclusions and Relevance: In this cohort study of adults with E coli, Klebsiella spp, or Proteus spp bacteremia from a suspected urine source, the relative risk of recurrent bacteremia was not significantly higher with ß-lactam antibiotics compared with fluoroquinolones or TMP-SMX, and the absolute risk and risk difference were small (ie, <3%). No significant difference in mortality was observed. Oral ß-lactam antibiotics may be a reasonable step-down treatment option, primarily when alternative options are limited by resistance or adverse effects. Further study is needed because statistical power was limited owing to a low number of recurrent bacteremia events.

"The role as a champion is to not only monitor but to speak out and to educate": the contradictory roles of hand hygiene champions.

BACKGROUND: Implementation science experts define champions as "supporting, marketing, and driving through an implementation, overcoming indifference or resistance that the intervention may provoke in an organization." Many hospitals use designated clinical champions-often called "hand hygiene (HH) champions"-typically to improve hand hygiene compliance. We conducted an ethnographic examination of how infection control teams in the Veterans Health Administration (VHA) use the term "HH champion" and how they define the role. METHODS: An ethnographic study was conducted with infection control teams and frontline staff directly involved with hand hygiene across 10 geographically dispersed VHA facilities in the USA. Individual and group semi-structured interviews were conducted with hospital epidemiologists, infection preventionists, multi-drug-resistant organism (MDRO) program coordinators, and quality improvement specialists and frontline staff from June 2014 to September 2017. The team coded the transcripts using thematic content analysis content based on a codebook composed of inductive and deductive themes. RESULTS: A total of 173 healthcare workers participated in interviews from the 10 VHA facilities. All hand hygiene programs at each facility used the term HH champion to define a core element of their hand hygiene programs. While most described the role of HH champions as providing peer-to-peer coaching, delivering formal and informal education, and promoting hand hygiene, a majority also included hand hygiene surveillance. This conflation of implementation strategies led to contradictory responsibilities for HH champions. Participants described additional barriers to the role of HH champions, including competing priorities, staffing hierarchies, and turnover in the role. CONCLUSIONS: Healthcare systems should consider narrowly defining the role of the HH champion as a dedicated individual whose mission is to overcome resistance and improve hand hygiene compliance-and differentiate it from the role of a "compliance auditor." Returning to the traditional application of the implementation strategy may lead to overall improvements in hand hygiene and reduction of the transmission of healthcare-acquired infections.

Association between universal gloving and healthcare-associated infections: A systematic literature review and meta-analysis.

OBJECTIVE: Healthcare-associated infections (HAIs) are a significant burden on healthcare facilities. Universal gloving is a horizontal intervention to prevent transmission of pathogens that cause HAI. In this meta-analysis, we aimed to identify whether implementation of universal gloving is associated with decreased incidence of HAI in clinical settings. METHODS: A systematic literature search was conducted to find all relevant publications using search terms for universal gloving and HAIs. Pooled incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated using random effects models. Heterogeneity was evaluated using the Woolf test and the I2 test. RESULTS: In total, 8 studies were included. These studies were moderately to substantially heterogeneous (I2 = 59%) and had varied results. Stratified analyses showed a nonsignificant association between universal gloving and incidence of methicillin-resistant Staphylococcus aureus (MRSA; pooled IRR, 0.94; 95% CI, 0.79-1.11) and vancomycin-resistant enterococci (VRE; pooled IRR, 0.94; 95% CI, 0.69-1.28). Studies that implemented universal gloving alone showed a significant association with decreased incidence of HAI (IRR, 0.77; 95% CI, 0.67-0.89), but studies implementing universal gloving as part of intervention bundles showed no significant association with incidence of HAI (IRR, 0.95; 95% CI, 0.86-1.05). CONCLUSIONS: Universal gloving may be associated with a small protective effect against HAI. Despite limited data, universal gloving may be considered in high-risk settings, such as pediatric intensive care units. Further research should be performed to determine the effects of universal gloving on a broader range of pathogens, including gram-negative pathogens.

Acquired somatic TP53 or PIK3CA mutations are potential predictors of when polyps evolve into colorectal cancer.

Colorectal cancer (CRC) develops from accumulated mutations. However, which gene determines the malignant transformation from adenoma to carcinoma is still uncertain. Fifty-three formalin fixed paraffin-embedded polyps that had pathological findings from patients with hyperplasia, adenomatous, and tubular adenoma < 1 cm (non-neoplasia polyps, NNP, n = 27) or tubular adenoma ≥ 1 cm, tubulovillous and villous adenoma (neoplastic polyps, NP, n = 26) were recruited. Six paired synchronous polyps and cancer tissues and 50 independent fresh CRC tumors were also collected. All tissues were analyzed for their mutation genomes using next generation sequencing with a 50-gene panel. There were 40 types of somatic variants found in 7 genes, APC (43%), KRAS (28%), TP53 (11%), FBXW7 (8%), GNAS (4%), SMAD4 (2%), and BRAF (2%), and they were detected in 32 (60%) polyps. If combined with the mutation spectrum found in CRC tissues, a significant increase in the mutation rate in TP53 and PIK3CA from NNP, NP, early and late stage carcinoma (7%, 15%, 33.3% and 65% for TP53, p < 0.001; 0%, 0%, 23.3% and 25% for PIK3CA, p = 0.002) were noticed. Furthermore, distinct molecular features can be found in five pairs of synchronous polyps and tumors. However, TP53 or PIK3CA mutations can be found in tumor tissues but not in polyps. By systematically investigating the genome from polyps to tumor tissues, we demonstrated that acquired TP53 or PIK3CA somatic mutations are potential predictors for malignancy development. These results may aid in the identification of high risk individuals with tissues harboring mutations in these two genes.

Nonsynonymous variants in MYH9 and ABCA4 are the most frequent risk loci associated with nonsyndromic orofacial cleft in Taiwanese population.

BACKGROUND: Nonsyndromic orofacial cleft is a common birth defect with a complex etiology, including multiple genetic and environmental risk factors. Recent whole genome analyses suggested associations between nonsyndromic orofacial cleft and up to 18 genetic risk loci (ABCA4, BMP4, CRISPLD2, GSTT1, FGF8, FGFR2, FOXE1, IRF6, MAFB, MSX1, MTHFR, MYH9, PDGFC, PVRL1, SUMO1, TGFA, TGFB3, and VAX1), each of which confers a different relative risk in different populations. We evaluate the nonsynonymous variants in these 18 genetic risk loci in nonsyndromic orofacial clefts and normal controls to clarify the specific variants in Taiwanese population. METHODS: We evaluated these 18 genetic risk loci in 103 cases of nonsyndromic orofacial clefts and 100 normal controls using a next-generation sequencing (NGS) customized panel and manipulated a whole-exon targeted-sequencing study based on the NGS system of an Ion Torrent Personal Genome Machine (IT-PGM). IT-PGM data processing, including alignment with the human genome build 19 reference genome (hg19), base calling, trimming of barcoded adapter sequences, and filtering of poor signal reads, was performed using the IT platform-specific pipeline software Torrent Suite, version 4.2, with the plug-in "variant caller" program. Further advanced annotation was facilitated by uploading the exported VCF file from Variant Caller to the commercial software package Ion Reporter; the free online annotation software Vanno and Mutation Taster. Benign or tolerated amino acid changes were excluded after analysis using sorting intolerant from tolerant and polymorphism phenotyping. Sanger sequencing was used to validate the significant variants identified by NGS. Furthermore, each variant was confirmed in asymptomatic controls using the Sequenom MassARRAY (San Diego, CA, USA). RESULTS: We identified totally 22 types of nonsynonymous variants specific in nonsyndromic orofacial clefts, including 19 single nucleotide variants, 2 deletions, and 1 duplication in 10 studied genes(ABCA4, MYH9, MTHFR, CRISPLD2, FGF8, PVRL1, FOXE1, VAX1, FGFR2, and IRF6). Nonsynonymous variants in MYH9 and ABCA4, which were detected in 6 and 5 individuals, respectively, were identified to be the most frequent risk loci in nonsyndromic orofacial clefts in the Taiwanese population. CONCLUSIONS: Nonsynonymous variants in MYH9 and ABCA4 were identified to be the most frequent risk loci in nonsyndromic orofacial clefts in the Taiwanese population. These findings in our study have provided additional information regarding specific variants associated with nonsyndromic orofacial clefts in different population and demonstrate the power of our customized NGS panel, which is clinically useful for the simultaneous detection of multiple genes associated with nonsyndromic orofacial clefts.

Feasibility of monitoring compliance to the My 5 Moments and Entry/Exit hand hygiene methods in US hospitals.

We compared the ability to observe hand hygiene opportunities using the World Health Organization My 5 Moments method to the Entry/Exit method. Under covert direct observation, Entry/Exit method opportunities were observed at all times. My 5 Moments were observable in 32.3% of episodes, with a lower rate in wards versus intensive care units (28.0% vs 39.4%; P < .01). In US hospitals, the Entry/Exit method appears to be more feasible for directly observed hand hygiene compliance monitoring due to line-of-sight issues and other barriers.

NRAS germline variant G138R and multiple rare somatic mutations on APC in colorectal cancer patients in Taiwan by next generation sequencing.

Colorectal cancer (CRC) arises from mutations in a subset of genes. We investigated the germline and somatic mutation spectrum of patients with CRC in Taiwan by using the AmpliSeq Cancer Hotspot Panel V2. Fifty paired freshly frozen stage 0-IV CRC tumors and adjacent normal tissue were collected. Blood DNA from 20 healthy donors were used for comparison of germline mutations. Variants were identified using an ion-torrent personal genomic machine and subsequently confirmed by Sanger sequencing or pyrosequencing. Five nonsynonymous germline variants on 4 cancer susceptible genes, CDH1, APC, MLH1, and NRAS, were observed in 6 patients with CRC (12%). Among them, oncogene NRAS G138R variant was identified as having a predicted damaging effect on protein function, which has never been reported by other laboratories. CDH1 T340A variants were presented in 3 patients. The germline variants in the cancer patients differed completely from those found in asymptomatic controls. Furthermore, a total of 56 COSMIC and 21 novel somatic variants distributed in 20 genes were detected in 44 (88%) of the CRC samples. High inter- and intra-tumor heterogeneity levels were observed. Nine rare variants located in the ß-catenin binding region of the APC gene were discovered, 7 of which could cause amino acid frameshift and might have a pathogenic effect. In conclusion, panel-based mutation detection by using a high-throughput sequencing platform can elucidate race-dependent cancer genomes. This approach facilitates identifying individuals at high risk and aiding the recognition of novel mutations as targets for drug development.