Prenatal exposure to particulate matter and infant birth outcomes: Evidence from a population-wide database.

There are growing concerns about the impact of pollution on maternal and infant health. Despite an extensive correlational literature, observational studies which adopt methods that seek to address potential biases due to unmeasured confounders draw mixed conclusions. Using a population database of births in Northern Ireland (NI) linked to localized geographic information on pollution in mothers' postcodes (zipcodes) of residence during pregnancy, we examine whether prenatal exposure to PM2.5 is associated with a comprehensive range of birth outcomes, including placental health. Overall, we find little evidence that particulate matter is related to infant outcomes at the pollution levels experienced in NI, once we implement a mother fixed effects approach that accounts for time-invariant factors. This contrasts with strong associations in models that adjust for observed confounders but without fixed effects. While reducing ambient air pollution remains an urgent public health priority globally, our results imply that further improvements in short-run levels of prenatal PM2.5 exposure in a relatively low-pollution, higher-income country context, are unlikely to impact on birth outcomes at the population level.

A trans-Canadian positive deviance seminar for paraesophageal hernia surgery: Reporting national postoperative outcomes and consensus recommendations.

BACKGROUND: The incidence of adverse events (AEs) and length of stay (LOS) varies significantly following paraesophageal hernia surgery. We performed a Canadian multicenter positive deviance (PD) seminar to review individual center and national level data and establish holistic perioperative practice recommendations. METHODS: A national virtual PD seminar was performed in October 2021. Recent best evidence focusing on AEs and LOS was presented. Subsequently, anonymized center-level AE and LOS data collected between 01/2017 and 01/2021 from a prospective, web-based database that tracks postoperative outcomes was presented. The top two performing centers with regards to these metrics were chosen and surgeons from these hospitals discussed elements of their treatment pathways that contributed to these outcomes. Consensus recommendations were then identified with participants independently rating their level of agreement. RESULTS: Twenty-eight surgeons form 8 centers took part in the seminar across 5 Canadian provinces. Of the 680 included patients included, Clavien-Dindo grade I and II/III/IV/V complications occurred in 121/39/12/2 patients (17.8%/5.7%/1.8%/0.3%). Respiratory complications were the most common (effusion 12/680, 1.7% and pneumonia 9/680, 1.3%). Esophageal and gastric perforation occurred in 7 and 4/680, (1.0% and 0.6% respectively). Median LOS varied significantly between institutions (1 day, range 1-3 vs. 7 days, 3-8, p < 0.001). A strong level of agreement was achieved for 10/12 of the consensus statements generated. CONCLUSION: PD seminars provide a supportive forum for centers to review best evidence and experience and generate recommendations based on expert opinion. Further research is ongoing to determine if this approach effectively accomplishes this objective.

Nurses' decision-making around gastric residual volume measurement in UK adult intensive care: A four-centre survey.

BACKGROUND: Despite increasing evidence of the potential inaccuracy and unwarranted practice of regular GRV measurement in critically in adults, this practice persists within the United Kingdom. AIM: To explore adult intensive care nurses' decision-making around the practice of GRV measurement to guide enteral feeding. METHODS: A cross-sectional 16 item electronic survey in four adult intensive care units (ICUs) in England and Wales. RESULTS: Two hundred and seventy-three responses were obtained across four ICUs with acceptable response rates for most [Unit 1 74 /127 = 58.2%; Unit 2 87/129 = 67.4%; Unit 3 77/120 = 64.1%; Unit 4 35/168 = 20.8%]. Most (243/273 (89%) reported measuring GRV 4-6 hourly, with most (223/273 82%) reporting that the main reason was to assess feed tolerance or intolerance and 37/273 (13.5%) saying their unit protocol required it. In terms of factors affecting decision-making, volume obtained was the most important factor, followed by the condition of the patient, with aspirate colour and appearance less important. When asked how they would feel about not measuring GRV routinely, the majority (78.2%) of nurses felt worried (140/273 = 51.2%) or very worried (74/273 = 27%). CONCLUSIONS: Factors affecting the nurses' decision-making around GRV were based largely on fear of risk (around vomiting and pulmonary aspiration) and compliance with unit protocols. RELEVANCE TO CLINICAL PRACTICE: Despite increasing evidence suggesting it is unnecessary, nurses' beliefs around the value of this practice persist and it continues to be embedded into unit protocols around feeding.

Antithrombotic Therapy and Hematoma Risk during Image-guided Core-Needle Breast Biopsy.

Background For image-guided core-needle breast biopsy (CNBB), it remains unclear whether antithrombotic medication should be withheld because of hematoma risk. Purpose To determine hematoma risk after CNBB in patients receiving antithrombotic medication and to stratify risk by antithrombotic type. Materials and Methods This HIPAA-compliant retrospective study included US-, stereotactic-, or MRI-guided CNBBs performed across six academic and six private practices between April 2019 and April 2021. Patients were instructed to continue antithrombotic medications, forming two groups: antithrombotic and nonantithrombotic. Hematomas were defined as new biopsy-site masses with a diameter of 2 cm or larger on postprocedure mammograms. Hematomas were considered clinically significant if management involved an intervention other than manual compression. Patient age, type of antithrombotic medication, practice type, image guidance modality, needle gauge and type, and outcome of pathologic analysis were recorded. Multivariable logistic regression analysis was used to analyze variables associated with hematomas. Results A total of 3311 biopsies were performed in 2664 patients (median age, 60 years; IQR, 48-70 years; 2658 women). The nonantithrombotic group included 2788 biopsies, and the antithrombotic group included 523 biopsies (328 low-dose aspirin, 73 full-dose antiplatelet drugs, 51 direct oral anticoagulants, 36 warfarin, 32 daily nonsteroidal anti-inflammatory drugs, three heparin or enoxaparin). The antithrombotic group had a higher overall hematoma rate (antithrombotic group: 49 of 523 biopsies [9.4%], nonantithrombotic group: 172 of 2788 biopsies [6.2%]; P = .007), but clinically significant hematoma rates were not different (antithrombotic group: two of 523 biopsies [0.4%], nonantithrombotic group: one of 2788 biopsies [0.04%]; P = .07). At multivariable analysis, age (odds ratio [OR], 1.02; 95% CI: 1.01, 1.03; P < .001), 9-gauge or larger needles (OR, 2.1; 95% CI: 1.28, 3.3; P = .003), and full-dose antiplatelet drugs (OR, 2.5; 95% CI: 1.29, 5.0; P = .007) were associated with higher hematoma rates. US guidance (OR, 0.26; 95% CI: 0.17, 0.40; P < .001) and 10-14-gauge needles (OR, 0.53; 95% CI: 0.36, 0.79; P = .002) were predictive of no hematoma. Conclusion Because clinically significant hematomas were uncommon, withholding antithrombotic medications before core-needle breast biopsy may be unnecessary. Postbiopsy hematomas were associated with full-dose antiplatelet drugs, patient age, and 9-gauge or larger needles. No association was found with other types of antithrombotic medication. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Chang and Yoen in this issue.

Exposure to weak opioids and risk of gastrointestinal tract cancers: A series of nested case-control studies.

AIMS: There is evidence gastrointestinal (GI) motility may play a role in the development of GI cancers. Weak opioids (codeine and dihydrocodeine) decrease GI motility, but their effect on GI cancer risk has not been assessed. We aim to assess the association between weak opioids and cancers of the GI tract. METHODS: A series of nested case-control studies was conducted using Scottish general practice records from the Primary Care Clinical Informatics Unit Research database. Oesophageal (n = 2432), gastric (n = 1443) and colorectal cancer (n = 8750) cases, diagnosed between 1999 and 2011, were identified and matched with up to five controls. Weak opioid use was identified from prescribing records. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression, adjusting for relevant comorbidities and medication use. RESULTS: There was no association between weak opioids and colorectal cancer (adjusted OR = 0.96, CI 0.90, 1.02, P = 0.15). There was an increased risk of oesophageal (adjusted OR = 1.16, CI 1.04, 1.29, P = 0.01) and gastric cancer (adjusted OR = 1.26, CI 1.10, 1.45, P = 0.001). The associations for oesophageal cancer, but not gastric cancer, were attenuated when weak opioid users were compared with users of another analgesic (adjusted OR = 1.03 CI 0.86, 1.22, P = 0.76 and adjusted OR = 1.29 CI 1.02, 1.64, P = 0.04 respectively). CONCLUSIONS: In this large population-based study, there was no consistent evidence of an association between weak opioids and oesophageal or colorectal cancer risk, but a small increased risk of gastric cancer. Further investigation is required to determine whether this association is causal or reflects residual confounding or confounding by indication.

Who to escalate during a pandemic? A retrospective observational study about decision-making during the COVID-19 pandemic in the UK.

BACKGROUND: Optimal decision-making regarding who to admit to critical care in pandemic situations remains unclear. We compared age, Clinical Frailty Score (CFS), 4C Mortality Score and hospital mortality in two separate COVID-19 surges based on the escalation decision made by the treating physician. METHODS: A retrospective analysis of all referrals to critical care during the first COVID-19 surge (cohort 1, March/April 2020) and a late surge (cohort 2, October/November 2021) was undertaken. Patients with confirmed or high clinical suspicion of COVID-19 infection were included. A senior critical care physician assessed all patients regarding their suitability for potential intensive care unit admission. Demographics, CFS, 4C Mortality Score and hospital mortality were compared depending on the escalation decision made by the attending physician. RESULTS: 203 patients were included in the study, 139 in cohort 1 and 64 in cohort 2. There were no significant differences in age, CFS and 4C scores between the two cohorts. Patients deemed suitable for escalation by clinicians were significantly younger with significantly lower CFS and 4C scores compared with patients who were not deemed to benefit from escalation. This pattern was observed in both cohorts. Mortality in patients not deemed suitable for escalation was 61.8% in cohort 1 and 47.4% in cohort 2 (p<0.001). CONCLUSIONS: Decisions who to escalate to critical care in settings with limited resources pose moral distress on clinicians. 4C score, age and CFS did not change significantly between the two surges but differed significantly between patients deemed suitable for escalation and those deemed unsuitable by clinicians. Risk prediction tools may be useful in a pandemic to supplement clinical decision-making, even though escalation thresholds require adjustments to reflect changes in risk profile and outcomes between different pandemic surges.

Intestinal Persistence of Colonizing Escherichia coli Strains, Especially ST131-H30, in Relation to Bacterial and Host Factors.

BACKGROUND: Superior gut colonization may underlie the pandemic emergence of the resistance-associated H30 subclone of Escherichia coli sequence type 131 (ST131-H30). Little is known about the associated host and bacterial characteristics, or the comparative persistence of non-ST131 intestinal E. coli. METHODS: Generic and fluoroquinolone-resistant E. coli isolates from volunteers' serial fecal samples underwent clonal analysis and extensive polymerase chain reaction (PCR)-based characterization (phylogroup, selected sequence types, virulence genes). Kaplan-Meier survival analysis and Cox proportional hazards survival analysis using penalized regression (a machine-learning method) were used to identify correlates of strain persistence. RESULTS: Screening of 2005 subjects at the Minneapolis VA Medical Center identified 222 subjects (117 veterans, 105 human and animal household members) for longitudinal fecal surveillance. Analysis of their 585 unique-by-subject fecal E. coli strains identified multiple epidemiological, ecological, and bacterial correlates of strain persistence. ST131-H30, a strong univariable correlate of persistence, was superseded in multivariable analysis by outpatient status, fluoroquinolone resistance, and diverse (predominantly iron uptake-related) virulence genes. CONCLUSIONS: ST131-H30 exhibits exceptional intestinal persistence, possibly due to a combination of fluoroquinolone resistance and virulence factors, which may be primarily colonization factors. This identifies both likely contributors to the ST131-H30 pandemic and potential targets for interventions against it.

Management of new onset atrial fibrillation in critically unwell adult patients: a systematic review and narrative synthesis.

BACKGROUND: New onset atrial fibrillation (NOAF) is the most common arrhythmia affecting critically unwell patients. NOAF can lead to worsening haemodynamic compromise, heart failure, thromboembolic events, and increased mortality. The aim of this systematic review and narrative synthesis is to evaluate the non-pharmacological and pharmacological management strategies for NOAF in critically unwell patients. METHODS: Of 1782 studies, 30 were eligible for inclusion, including 4 RCTs and 26 observational studies. Efficacy of direct current cardioversion, amiodarone, ß-adrenergic receptor antagonists, calcium channel blockers, digoxin, magnesium, and less commonly used agents such as ibutilide are reported. RESULTS: Cardioversion rates of 48% were reported for direct current cardioversion; however, re-initiation of NOAF was as high as 23.4%. Amiodarone was the most commonly reported intervention with cardioversion rates ranging from 18% to 96% followed by ß-antagonists with cardioversion rates from 40% to 92%. Amiodarone was more effective than diltiazem (odds ratio [OR]=1.91, P=0.32) at cardioversion. Short-acting ß-antagonists esmolol and landiolol were more effective compared with diltiazem for cardioversion (OR=3.55, P=0.04) and HR control (OR=3.2, P<0.001). CONCLUSION: There was significant variation between studies with regard to the definition of successful cardioversion and heart rate control, making comparisons between studies and interventions difficult. Future RCTs comparing individual anti-arrhythmic agents, in particular magnesium, amiodarone, and ß-antagonists, and studying the role of anticoagulation in critically unwell patients are required. There is also an urgent need for a core outcome dataset for studies of new onset atrial fibrillation to allow comparisons between different anti-arrhythmic strategies. CLINICAL TRIAL REGISTRATION: PROSPERO CRD42019121739.

Operationalizing a patient engagement plan for health research: Sharing a codesigned planning template from a national clinical trial.

INTRODUCTION: Engaging with patients about their lived experience of health and illness and their experience within the healthcare system can help inform the provision of care, health policies and health research. In the context of health research, however, operationalizing the levels of patient engagement is not straightforward. We suggest that a key challenge to the routine inclusion of patients as partners in health research is a lack of tangible guidance regarding how this can be accomplished. METHODS: In this article, we provide guidance on how to codesign and operationalize a concrete patient engagement plan for any health research project. RESULTS: We illustrate a seven-step approach using the example of a national clinical trial in Canada and provide a patient engagement planning template for use in any health research project. CONCLUSION: Such concrete guidance should improve the design and reporting of patient engagement in health research. PATIENT OR PUBLIC CONTRIBUTION: The De-Implementing Wisely Research group is informed by a national 9-member patient partner council (PPC). The research team includes three lead patient partners who are coinvestigators on the grant that funds the program of research. Members of the council advise on all aspects of the study design and implementation. The ideas presented in this paper were informed by regular communication and planning with the PPC; specific contributions of lead patient partner authors are outlined as follows: Brian Johnston, Susan Goold and Vanessa Francis are patient partners with a wide breadth of experience in the healthcare system and health research projects. The guidance in this article draws on their lived and professional expertise. All patient partner authors contributed to the planning of the manuscript, participated in meetings to develop content and provided critical manuscript edits and comments on drafts.

Core Genome Multilocus Sequence Typing and Prediction of Antimicrobial Susceptibility Using Whole-Genome Sequences of Escherichia coli Bloodstream Infection Isolates.

In total, 50 Escherichia coli bloodstream isolates from the clinical laboratory and 12 E. coli isolates referred for pulsed-field gel electrophoresis (PFGE) were sequenced, assessed for clonality using core genome multilocus sequence typing (cgMLST), and evaluated for genomic susceptibility predictions using ARESdb. Results of sequence typing using whole-genome sequencing (WGS)-based MLST and sequence type (ST)-specific PCR were identical. Overall categorical agreement between genotypic (ARESdb) and phenotypic susceptibility testing for 62 isolates and 11 antimicrobial agents was 91%. Among the referred isolates, high major error rates were found for ceftazidime, cefepime, and piperacillin-tazobactam.

Circulating Sex Hormones Are Associated With Gastric and Colorectal Cancers but Not Esophageal Adenocarcinoma in the UK Biobank.

INTRODUCTION: Gastrointestinal cancers show an unexplained male predominance, but few prospective studies have investigated sex hormones and gastrointestinal cancer risk. This study aimed to determine the impact of circulating sex hormones on risk of esophageal, gastric, and colorectal cancers in men and women. METHODS: We included 219,425 men and 147,180 women from the UK Biobank. Sex hormones were quantified using chemiluminescent immunoassay. Gastrointestinal cancers were identified from cancer registry linkages. Sex hormone concentrations and risk of gastrointestinal cancers were investigated using Cox proportional hazards regression. RESULTS: During the 10 years of follow-up, 376 esophageal adenocarcinoma, 108 esophageal squamous cell carcinoma, and 333 gastric and 2,868 colorectal cancer cases were identified. Increased hazard ratios (HRs) were found for sex hormone-binding globulin (SHBG) and risk of gastric cancer in men (Q4 vs Q1 HR 1.43, 95% confidence interval [CI] 0.95-2.17, Ptrend = 0.01). Free testosterone was inversely associated with esophageal squamous cell carcinoma in women (Q4 vs Q1 HR 0.32, 95% CI 0.11-0.98, Ptrend = 0.05). For colorectal cancer, SHBG was associated with a reduced risk among men (Q4 vs Q1 HR 0.89, 95% CI 0.77-1.03, Ptrend = 0.04) and free testosterone concentrations was associated with a reduction in risk among women (Q4 vs Q1 HR 0.80, 95% CI 0.66-0.97, Ptrend = 0.01). No associations were found for esophageal adenocarcinoma. DISCUSSION: In this large prospective investigation of prediagnostic sex hormones and risk of gastrointestinal cancers, men with higher SHBG concentrations had higher gastric, yet lower colorectal, cancer risks, whereas women with higher free testosterone levels had a lower risk of esophageal squamous cell carcinoma and colorectal cancer.

Activity of plazomicin against carbapenem-intermediate or -resistant Escherichia coli isolates from the United States and international sites in relation to clonal background, resistance genes, co-resistance, and region.

BACKGROUND: Emerging carbapenem resistance in Escherichia coli, including sequence type 131 (ST131), threatens therapeutic efficacy. Plazomicin (PLZ), a semisynthetic aminoglycoside approved by the FDA in 2018, overcomes the most common aminoglycoside resistance mechanisms and maintains activity against many carbapenem-intermediate or -resistant (CIR) E. coli strains. OBJECTIVES: To assess plazomicin susceptibility among CIR E. coli in relation to region and multiple bacterial characteristics. METHODS: We determined broth microdilution MICs for plazomicin and 11 comparators against 343 CIR clinical E. coli isolates, then compared susceptibility results by bacterial characteristics and region. The collection comprised 203 US isolates (2002-17) and 141 isolates from 17 countries in Europe, Latin America, and the Asia-West Pacific region (2003-17). Isolates were characterized for phylogenetic group, resistance-associated sequence types (STs) and subsets thereof, and relevant ß-lactamase-encoding genes. RESULTS: Plazomicin exhibited the highest percentage susceptible (89%) after tigecycline (99%). The percentage susceptible to plazomicin varied significantly by phylogroup (63%, group B1; versus >93%, others) and ST131 subclone (92%, H30Rx; versus 87%-89%, H30R1 and non-H30), but not ST. It also varied by resistance genotype [higher with Klebsiella pneumoniae carbapenemase (KPC), lower with metallo-ß-lactamases], global region [highest for Latin America (94%), lowest for Asia-West Pacific (69%)], and US region (80%, South, versus 96%-100%, others). Although reduced susceptibility to comparators often predicted reduced susceptibility to plazomicin, even among comparator-intermediate or -resistant isolates the plazomicin-susceptible fraction was ≥77%, except for amikacin (53%). CONCLUSIONS: The likely utility of plazomicin against CIR E. coli is high overall, but varies with region and multiple bacterial characteristics.

Molecular Characteristics, Ecology, and Zoonotic Potential of Escherichia coli Strains That Cause Hemorrhagic Pneumonia in Animals.

Hemorrhagic pneumonia (HP) is a rare but highly lethal disease, mainly of dogs and cats, caused by hemolytic Escherichia coli strains that contain cnf1 (encoding cytotoxic necrotizing factor 1). After encountering fatal HP in two dogs, we used contemporary molecular methods, including multilocus sequence typing and whole-genome sequencing, to compare the corresponding case isolates with published HP clinical isolates and newly obtained fecal E. coli isolates from 20 humans and animals in the index HP case household. We also compared the aggregated HP clinical isolates, which represented 13 discrete strains, by pulsotype with a large, private pulsotype library of diverse-source E. coli. The HP clinical isolates represented a narrow range of phylogenetic group B2 lineages (mainly sequence types 12 and 127), O types (mainly O4 and O6), and H types (mainly H5 and H31), but diverse fimH alleles (type-1 fimbriae adhesin). Their extensive, highly conserved virulence genotypes, which qualified as extraintestinal pathogenic E. coli (ExPEC), encoded diverse adhesins, toxins, iron uptake systems, and protectins. Household surveillance identified multiple HP-like fecal strains, plus abundant between-host strain sharing, including of the household's index HP strain. The pulsotype library search identified, for five HP clinical strains, same-pulsotype human and animal fecal and clinical (predominantly urine) isolates, from diverse locales and time periods. Thus, E. coli strains that cause HP derive from a narrow range of ExPEC lineages within phylogroup B2, contain multiple virulence genes other than cnf1, are shared extensively between hosts, and likely function in nature mainly as intestinal colonizers and uropathogens. IMPORTANCE This study clarifies the clonal background and extensive virulence genotypes of the E. coli strains that cause hemorrhagic pneumonia in domestic animals (mainly dogs and cats), shows that such strains circulate among animals and humans, identifies a substantial intestinal colonization component to their lifestyle, and extends their known clinical manifestations to include bacteremia and urinary tract infection. The findings place these strains better into context vis-à-vis current understandings of E. coli phylogeny, ecology, and pathogenesis; identify questions for future research; and may prove relevant for surveillance and prevention efforts.

Investigating the physical activity, health, wellbeing, social and environmental effects of a new urban greenway: a natural experiment (the PARC study).

BACKGROUND: Evidence for the health benefits of urban green space tends to stem from small, short-term quasi-experimental or cross-sectional observational research, whilst evidence from intervention studies is sparse. The development of an urban greenway (9 km running along 3 rivers) in Northern Ireland provided the opportunity to conduct a natural experiment. This study investigated the public health impact of the urban greenway on a range of physical activity, health, wellbeing, social, and perceptions of the environment outcomes. METHODS: A repeated cross-sectional household survey of adult residents (aged ≥16 years) who lived ≤1-mile radius of the greenway (intervention sample) and > 1-mile radius of the greenway (control sample) was conducted pre (2010/2011) and 6-months post implementation (2016/2017). We assessed changes in outcomes pre- and post-intervention follow-up including physical activity behaviour (primary outcome measure: Global Physical Activity Questionnaire), quality of life, mental wellbeing, social capital and perceptions of the built environment. Linear regression was used to calculate the mean difference between post-intervention and baseline measures adjusting for age, season, education, car ownership and deprivation. Multi-level models were fitted using a random intercept at the super output area (smallest geographical unit) to account for clustering within areas. The analyses were stratified by distance from the greenway and deprivation. We assessed change in the social patterning of outcomes over time using an ordered logit to make model-based outcome predictions across strata. RESULTS: The mean ages of intervention samples were 50.3 (SD 18.9) years at baseline (n = 1037) and 51.7 (SD 19.1) years at follow-up (n = 968). Post-intervention, 65% (adjusted OR 0.60, 95% CI 0.35 to 1.00) of residents who lived closest to the greenway (i.e., ≤400 m) and 60% (adjusted OR, 0.64 95% CI 0.41 to 0.99) who lived furthest from the greenway (i.e.,≥1200 m) met the physical activity guidelines - 68% of the intervention sample met the physical activity guidelines before the intervention. Residents in the most deprived quintiles had a similar reduction in physical activity behaviour as residents in less deprived quintiles. Quality of life at follow-up compared to baseline declined and this decline was significantly less than in the control area (adjusted differences in mean EQ5D: -11.0 (95% CI - 14.5 to - 7.4); - 30.5 (95% CI - 37.9 to - 23.2). Significant change in mental wellbeing was not observed despite improvements in some indicators of social capital. Positive perceptions of the local environment in relation to its attractiveness, traffic and safety increased. CONCLUSIONS: Our findings illustrate the major challenge of evaluating complex urban interventions and the difficulty of capturing and measuring the network of potential variables that influence or hinder meaningful outcomes. The results indicate at this stage no intervention effect for improvements in population-level physical activity behaviour or mental wellbeing. However, they show some modest improvements for secondary outcomes including positive perceptions of the environment and social capital constructs. The public health impact of urban greenways may take a longer period of time to be realised and there is a need to improve evaluation methodology that captures the complex systems nature of urban regeneration.

Comparative activity of plazomicin against extended-spectrum cephalosporin-resistant Escherichia coli clinical isolates (2012-2017) in relation to phylogenetic background, sequence type 131 subclones, blaCTX-M genotype, and resistance to comparator agents.

Extended-spectrum cephalosporin-resistant Escherichia coli (ESCREC) are a growing threat. Leading ESCREC lineages include sequence type ST131, especially its (blaCTX-M-15-associated) H30Rx subclone and (blaCTX-M-27-associated) C1-M27 subset within the H30R1 subclone. The comparative activity against such strains of alternative antimicrobial agents, including the recently developed aminoglycoside plazomicin, is undefined, so was investigated here. We assessed plazomicin and 11 comparators for activity against 216 well-characterized ESCREC isolates (Minnesota, 2012-2017) and then compared broth microdilution MICs with phylogenetic and clonal background, beta-lactamase genotype (blaCTX-M; group 1 and 9 variants), and co-resistance. Percent susceptible was > 99% for plazomicin, meropenem, imipenem, and tigecycline; 96-98% for amikacin and ertapenem; and ≤ 75% for the remaining comparators. For most comparators, MICs varied significantly in relation to multiple bacterial characteristics, in agent-specific patterns. By contrast, for plazomicin, the only bacterial characteristic significantly associated with MICs was ST131 subclone: plazomicin MICs were lowest among O16 ST131 isolates and highest among ST131-H30R1 C1-M27 subclone isolates. Additionally, plazomicin MICs varied significantly in relation to resistance vs. susceptibility to comparator agents only for amikacin and levofloxacin. For most study agents, antimicrobial activity against ESCREC varied extensively in relation to multiple bacterial characteristics, including clonal background, whereas for plazomicin, it varied only by ST131 subclone (C1-M27 isolates least susceptible, O16 isolates most susceptible). These findings support plazomicin as a reliable alternative for treating ESCREC infections and urge continued attention to the C1-M27 ST131 subclone.

Global molecular epidemiology of carbapenem-resistant Escherichia coli (2002-2017).

The emergence of carbapenem-resistant (CR) Escherichia coli obliges an assessment of such strains' molecular epidemiology. Accordingly, we characterized in detail a globally distributed collection of CR E. coli isolates, then explored for associations between geographical origin and bacterial traits, and between different bacterial traits. We used established PCR-based assays and broth microdilution MIC determinations to characterize 343 global CR (i.e., non-susceptible to ≥ 1 carbapenem) extraintestinal E. coli isolates (2002-2017) for diverse molecular traits-including phylogroups, sequence types (STs), beta-lactamase genes, and 51 virulence genes-and susceptibility to 12 relevant antimicrobial agents. The study population was tremendously diverse according to all assessed variables. Nonetheless, certain geographically aligned, unifying themes emerged. These included an association of an Asia/West Pacific origin with non-B2/D/F phylogroups and STs, lower molecularly inferred virulence, more extensive resistance, and specific resistance genes (notably, metallo-beta-lactamases). Likewise, U.S. isolates from the central region, vs. other regions, were more virulent-appearing and more often from phylogroup B2 and ST131, but less extensively resistant and more often carbapenemase-gene negative. The global CR E. coli population is highly diverse according to multiple characteristics and varies significantly by geographical region. This predictably will pose challenges for prevention and management, and obliges ongoing surveillance.

Esophageal Columnar Metaplasia in Childhood: A Population-Based Case Series Analysis.

BACKGROUND: Adults with Barrett's esophagus (BE) are often entered into surveillance for esophageal adenocarcinoma (EAC), although cancer risk is relatively low. BE can be detected in children (< 16 years). Little is known about the epidemiology of pediatric BE, and it is unclear what the optimal surveillance regimes are in children. AIM: To evaluate the demographic and clinical characteristics, and future neoplastic progression risk in all pediatric BE patients diagnosed in Northern Ireland between 1993 and 2010. METHODS: Data from the population-based Northern Ireland BE register were matched to the Northern Ireland Cancer Registry for EAC outcomes until end 2013. Age-adjusted incidence of pediatric BE was calculated, and characteristics between pediatric and adult BE patients compared using Chi-square tests. RESULTS: Over 18 years, 42 pediatric BE patients (< 16 years) were identified, equivalent to an age-adjusted incidence of < 2 per 100,000 children. There was a clear age differential, with BE incidence increasing with age within the pediatric population. The majority (85.7%) of patients were male, a significantly higher male/female ratio than adult BE patients (p < 0.001). No pediatric BE patients progressed to high-grade dysplasia (HGD) or EAC, although the eldest patient was aged 34 years by the end of follow-up. CONCLUSIONS: This is the largest series of pediatric BE ever reported. It demonstrates that pediatric BE is rare. The male preponderance of this condition is more apparent in childhood compared with adult cases. No children developed HGD/EAC during follow-up, suggesting that regular surveillance is not required, at least until adulthood.

Does Risk of Progression from Barrett's Esophagus to Esophageal Adenocarcinoma Change Based on the Number of Non-dysplastic Endoscopies?

BACKGROUND: There is a large Barrett's esophagus patient population undergoing endoscopic surveillance. Methods to stratify patients into higher and lower risk groups may enable more varied surveillance intervals for patients with non-dysplastic Barrett's esophagus that could optimize use of endoscopy resources. OBJECTIVE: We aimed to assess whether risk of progression to esophageal adenocarcinoma differed in patients with multiple endoscopic biopsies negative for dysplasia. METHODS: We conducted a retrospective cohort study among individuals from the population-based Northern Ireland Barrett's register with a histologically confirmed diagnosis of non-dysplastic Barrett's esophagus (with intestinal metaplasia) between 1993 and 2010, who had at least one endoscopic biopsy conducted at least 12 months after diagnosis. We used Poisson regression to estimate incidence rate ratios (IRR) and 95% confidence intervals (CI) for the association between number of successive endoscopies showing non-dysplastic Barrett's esophagus and risk of esophageal adenocarcinoma alone, and combined with high-grade dysplasia, at the next endoscopy. RESULTS: We identified 1761 individuals who met our eligibility criteria. Subsequent risk of progression to esophageal adenocarcinoma was lower at the next endoscopy following two endoscopies showing non-dysplastic Barrett's esophagus (IRR 0.26, 95% CI 0.10-0.66) than following one endoscopy showing non-dysplastic Barrett's esophagus. Similar findings were apparent for risk of progression to esophageal adenocarcinoma or high-grade dysplasia (IRR 0.41, 95% CI 0.22-0.79). CONCLUSION: The lower risk of malignant progression in individuals with persistent non-dysplastic Barrett's esophagus over two consecutive endoscopic biopsies but not for longer term persistence does not support hypotheses of persistence being an indicator of less biologically aggressive lesions. Instead, the initial difference may be attributable to post-endoscopy cancers and support the necessity of adhering to robust quality standards for endoscopic procedures.

Feasibility and Acceptability of a Telephone-Based Intervention for Hispanic Children to Promote Treatment Adherence After Traumatic Brain Injury: A Pilot Study.

OBJECTIVE: To assess the feasibility and acceptability of a telephone-based education and navigation program for Hispanic parents of children hospitalized with traumatic brain injury (TBI). SETTING: Level I trauma hospital and pediatric inpatient rehabilitation unit in the Northwestern United States. PARTICIPANTS: Fourteen Hispanic parent-child dyads. Parents were 85% female, with a mean age of 35 years. Children were 58% male, with a mean age of 9.7 years, and had been hospitalized for complicated mild/moderate (n = 5) or severe (n = 9) TBI. DESIGN: Pilot prospective cohort design. MAIN MEASURES: Feasibility measures include recruitment, retention, and intervention adherence rates. Acceptability of intervention was measured by parents' use of educational materials and satisfaction with navigation program. We also evaluated study processes, including completion of baseline, 3, 6, and 12 months functional assessments of the child; assessment of parental health literacy and self-efficacy; and adherence to follow-up rehabilitation appointments. RESULTS: Eighty-two percent of approached potential participants were recruited into the study. One hundred percent of participants completed the intervention, and 85% had 1-year follow-up. Intervention acceptability was high: 90% reported satisfaction with navigator, and 92% used the educational manual. Assessments demonstrated significant improvement in parents' TBI caregiving and community self-efficacy; 92% attendance to follow-up rehabilitation appointments; and improvement in the child's functional measures, except communication skills. CONCLUSIONS: Findings support feasibility and acceptability of a culturally relevant program to facilitate transitions of care for Hispanic children with TBI. A future randomized trial is warranted to determine the efficacy of the intervention on long-term treatment adherence and the child's post-TBI function.

Bringing Physical Exam Skills Back from the Dead.

Physical examination education begins early for medical learners. A hindrance to physical exam competency is lack of exposure to pathology in standardized patient settings. This research focuses on improving medical education through the utilization of cadavers that have undergone a soft-embalming technique: the Thiel method. Three scenarios were created in four Thiel cadavers: anterior cruciate ligament (ACL) tear, posterior cruciate ligament (PCL) tear, and sham incision. Students were asked to diagnose ACL tears using the Lachman exam. A total of 54 learners participated in the study. Post-surveys indicated most learners: (1) prefer to use standardized patients (SPs) and soft-embalmed cadavers in their physical examination courses, (2) increased their confidence in performing the Lachman exam on real patients, and (3) enhanced their Lachman technique. SPs ultimately cannot volitionally reproduce the physical exam findings of ACL deficiency. Consequently, learners cannot accurately identify positive versus negative examination findings. Thiel-embalmed cadavers are a valuable resource for physical examination education. (Journal of Surgical Orthopaedic Advances 30(2):112-115, 2021).