Effectiveness and safety of measures to prevent infections and other complications associated with peripheral intravenous catheters: A systematic review and meta-analysis.

BACKGROUND: Peripheral intravenous catheters (PIVCs) contribute substantially to the global burden of infections. This systematic review assessed 24 infection prevention and control (IPC) interventions to prevent PIVC-associated infections and other complications. METHODS: We searched Ovid MEDLINE, Embase, Cochrane Library, WHO Global Index Medicus, CINAHL and reference lists for controlled studies, from January 1, 1980-March 16, 2023. We dually selected studies, assessed risk of bias, extracted data, and rated the certainty of evidence (COE). For outcomes with three or more trials, we conducted Bayesian random-effects meta-analyses. RESULTS: 105 studies met our prespecified eligibility criteria, addressing 16 of the 24 research questions; no studies were identified for eight research questions.Based on findings of low to high COE, wearing gloves reduced the risk for overall adverse events related to insertion compared to no gloves (one non-randomised controlled trial [RCT]; adjusted risk ratio [RR]: 0.52, 95% confidence interval 0.33-0.85), and catheter removal based on defined schedules potentially resulted in a lower phlebitis/thrombophlebitis incidence (10 RCTs; RR: 0.74, 95% credible interval 0.49-1.01) compared to clinically indicated removal in adults. In neonates, chlorhexidine reduced the phlebitis score compared to non-chlorhexidine-containing disinfection (one RCT; 0.14 versus 0.68, p = 0.003). No statistically significant differences were found for other measures. CONCLUSIONS: Despite their frequent use and concern about PIVC-associated complications, this review underscores the urgent need for more high-quality studies on effective IPC methods regarding safe PIVC management. In the absence of valid evidence, adherence to standard precaution measures and documentation remain the most important principles to curb PIVC complications.

The Utilization of Preoperative Steroids Safely Decreases the Risk of Postoperative Delirium in Geriatric Patients After Hip Fracture Surgery: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVES: Postoperative delirium is an acute neurocognitive complication that can have adverse effects on outcomes of geriatric patients after undergoing hip fracture surgery. The objective of this study was to examine the efficacy of preoperative steroids in preventing postoperative delirium after hip fracture surgery. DATA SOURCES: A systematic review and meta-analysis was performed using PubMed, SPORTDiscus, CINAHL, MEDLINE, and Web of Science from database inception until September 28, 2023. STUDY SELECTION: Inclusion criteria were randomized controlled trials of patients who underwent surgical intervention for hip fracture, were examined for postoperative delirium, and used preoperative steroids. DATA EXTRACTION: Data included the risk of postoperative delirium, postoperative all-cause infection, and postoperative hyperglycemia. Articles were graded via the Cochrane Collaboration's tool. DATA SYNTHESIS: Statistical analysis included a random-effects binary model with relative risk, 95% confidence intervals along with a defined "number needed to treat" threshold (number needed to treat). RESULTS: Four randomized controlled trials were included from 128 articles initially retrieved. Patients (n = 416; average age: 82.2 ± 2.2 years) underwent surgical intervention for hip fracture after receiving either preoperative steroids (n = 209) or control interventions (n = 207). There was a statistically significant decrease in the incidence of postoperative delirium among patients who received preoperative steroids (12.9%; 27 cases) as compared with patients who received control interventions (26.7%; 55 cases) after hip fracture surgery ( P < 0.001; RR: 0.84). The absolute risk difference was 13.8%, and the number needed to treat was 7.2 patients. There was no statistically significant difference in the risk of postoperative all-cause infection among patients who received preoperative steroids as compared with patients who received normal saline as placebo after hip fracture surgery ( P = 0.850; RR: 0.96). CONCLUSIONS: The utilization of preoperative steroids seems to decrease the risk of postoperative delirium after hip fracture surgery in elderly adults. Furthermore, this decreased risk of postoperative delirium was not associated with a significant increase in postoperative infection, indicating possible safety of preoperative steroid administration. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Socioeconomic Status and Race Are Rarely Reported in Randomized Controlled Trials for Achilles Tendon Pathology in the Top 10 Orthopaedic Journals: A Systematic Review.

Background: Randomized controlled trials (RCTs) are crucial in comparative research, and a careful approach to randomization methodology helps minimize bias. However, confounding variables like socioeconomic status (SES) and race are often underreported in orthopaedic RCTs, potentially affecting the generalizability of results. This study aimed to analyze the reporting trends of SES and race in RCTs pertaining to Achilles tendon pathology, considering 4 decades of data from top-tier orthopaedic journals. Methods: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and used PubMed to search 10 high-impact factor orthopaedic journals for RCTs related to the management of Achilles tendon pathology. The search encompassed all articles from the inception of each journal until July 11, 2023. Data extraction included year of publication, study type, reporting of SES and race, primary study location, and intervention details. Results: Of the 88 RCTs identified, 68 met the inclusion criteria. Based on decade of publication, 6 articles (8.8%) reported on SES, whereas only 2 articles (2.9%) reported on race. No RCTs reported SES in the pre-1999 period, but the frequency of reporting increased in subsequent decades. Meanwhile, all RCTs reporting race were published in the current decade (2020-2030), with a frequency of 20%. When considering the study location, RCTs conducted outside the United States were more likely to report SES compared with those within the USA. Conclusion: This review revealed a concerning underreporting of SES and race in Achilles tendon pathology RCTs. The reporting percentage remains low for both SES and race, indicating a need for comprehensive reporting practices in orthopaedic research. Understanding the impact of SES and race on treatment outcomes is critical for informed clinical decision making and ensuring equitable patient care. Future studies should prioritize the inclusion of these variables to enhance the generalizability and validity of RCT results.

Mode of carbon and energy metabolism shifts lipid composition in the thermoacidophile Acidianus.

The degree of cyclization, or ring index (RI), in archaeal glycerol dibiphytanyl glycerol tetraether (GDGT) lipids was long thought to reflect homeoviscous adaptation to temperature. However, more recent experiments show that other factors (e.g., pH, growth phase, and energy flux) can also affect membrane composition. The main objective of this study was to investigate the effect of carbon and energy metabolism on membrane cyclization. To do so, we cultivated Acidianus sp. DS80, a metabolically flexible and thermoacidophilic archaeon, on different electron donor, acceptor, and carbon source combinations (S0/Fe3+/CO2, H2/Fe3+/CO2, H2/S0/CO2, or H2/S0/glucose). We show that differences in energy and carbon metabolism can result in over a full unit of change in RI in the thermoacidophile Acidianus sp. DS80. The patterns in RI correlated with the normalized electron transfer rate between the electron donor and acceptor and did not always align with thermodynamic predictions of energy yield. In light of this, we discuss other factors that may affect the kinetics of cellular energy metabolism: electron transfer chain (ETC) efficiency, location of ETC reaction components (cytoplasmic vs. extracellular), and the physical state of electron donors and acceptors (gas vs. solid). Furthermore, the assimilation of a more reduced form of carbon during heterotrophy appears to decrease the demand for reducing equivalents during lipid biosynthesis, resulting in lower RI. Together, these results point to the fundamental role of the cellular energy state in dictating GDGT cyclization, with those cells experiencing greater energy limitation synthesizing more cyclized GDGTs.IMPORTANCESome archaea make unique membrane-spanning lipids with different numbers of five- or six-membered rings in the core structure, which modulate membrane fluidity and permeability. Changes in membrane core lipid composition reflect the fundamental adaptation strategies of archaea in response to stress, but multiple environmental and physiological factors may affect the needs for membrane fluidity and permeability. In this study, we tested how Acidianus sp. DS80 changed its core lipid composition when grown with different electron donor/acceptor pairs. We show that changes in energy and carbon metabolisms significantly affected the relative abundance of rings in the core lipids of DS80. These observations highlight the need to better constrain metabolic parameters, in addition to environmental factors, which may influence changes in membrane physiology in Archaea. Such consideration would be particularly important for studying archaeal lipids from habitats that experience frequent environmental fluctuations and/or where metabolically diverse archaea thrive.

Weightbearing Imaging Assessment of Midfoot Instability in Patients with Confirmed Hallux Valgus Deformity: A Systematic Review of the Literature.

Hallux valgus deformity (HVD) involves subluxation of the first metatarsophalangeal joint. While HVD is primarily considered a forefoot condition, midfoot instability may play a significant role in its development and severity. However, very few studies have placed a heavy emphasis on studying this phenomenon. Therefore, this review had a particular focus on understanding midfoot instability based on weightbearing imaging assessments of the TMT joint. This review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and searched five databases for studies on midfoot instability in HVD patients. The severity of HVD was defined by hallux valgus angle (HVA) and distal metatarsal articular angle (DMAA). Data was extracted, and articles were graded using the Methodological Index for Non-Randomized Studies (MINORS). Of 547 initially retrieved articles, 23 met the inclusion criteria. Patients with HVD showed higher HVA and DMAA on weightbearing radiographs (WBRG) and weightbearing computed tomography (WBCT) compared to healthy individuals. Midfoot instability was assessed through intermetatarsal angle (IMA) and tarsometatarsal angle (TMT angle). Patients with HVD exhibited greater IMA and TMT angles on both WBRG and WBCT. This review highlights the importance of weightbearing imaging assessments for midfoot instability in HVD. IMA and TMT angles can differentiate between healthy individuals and HVD patients, emphasizing the significance of midfoot assessment in understanding HVD pathology. These findings validate the limited evidence thus far in the literature pertaining to consistent midfoot instability in HVD patients and are able to provide ample reasoning for physicians to place a larger emphasis on midfoot imaging when assessing HVD in its entirety.

Weightbearing Computed Tomography vs Conventional Tomography for Examination of Varying Degrees of Lisfranc Injures: A Systematic Review of the Literature.

Background: Lisfranc injuries, if not accurately diagnosed, can result in chronic pain and instability. Previous studies have examined ultrasonographs, radiographs, magnetic resonance imaging (MRI), and conventional computed tomography (CT) scan to differentiate Lisfranc instability, but they focused on a healthy/injured scale without differentiating subtle injury. Weightbearing CT (WBCT) has emerged as a diagnostic tool for detecting subtle Lisfranc injuries. This systematic review aimed to compare WBCT with conventional CT in diagnosing Lisfranc injury, and the ability to differentiate injuries of varying severities. Methods: The review encompassed PubMed, CINAHL, MEDLINE, SPORTDiscus, and Web of Science databases from inception until July 5, 2023. Inclusion criteria involved studies on CT and/or WBCT for Lisfranc injuries and nonoperative studies. Exclusion criteria composed case reports, commentaries, postoperative imaging studies, pediatric patients, studies with nonobjective radiographic measurements, studies exclusively focused on injury classification, and studies with fewer than 5 patients because of poor statistical power. Data extraction focused on radiographic measurements of the Lisfranc complex, categorized into conventional CT, partial WBCT, and total WBCT. Results: Out of the initially retrieved 489 articles, 9 met the inclusion criteria. Several studies consistently demonstrate that WBCT provides a higher level of accuracy in measuring the Lisfranc area, offering enhanced sensitivity to detect subtle alterations in joint structure. Moreover, WBCT exhibits superior sensitivity in distinguishing between healthy Lisfranc joints and those with injuries, particularly when identifying dorsal ligament damage. This imaging modality allows for the detection of significant variations in critical measurements like first-second metatarsal (M1-M2) distance, first cuneiform (C1)-M2 distance, and joint volumes, enabling a more comprehensive assessment of Lisfranc joint health especially with subtle instability. Conclusion: This review evaluates the extant literature on WBCT's utility in diagnosing Lisfranc injuries and compares its effectiveness to CT in distinguishing between injuries of varying severity. WBCT, with reliable measurement techniques, appears more adept at detecting subtle Lisfranc instability compared to CT, likely by allowing the assessment of injury under load.

Higher Risk of Reoperation after Total Knee Arthroplasty in Young and Elderly Patients.

As outcomes and survivorship improve, total knee arthroplasty (TKA) has expanded into broader age groups. The purpose of this study is to analyze the impact of age on TKA outcomes using the National Surgical Quality Improvement Program (NSQIP) database from 2015 to 2020. Patients were categorized into young (40-49 years), middle (50-79 years), and elderly (80-89 years) groups. Findings reveal notable differences across age groups. The young cohort had the highest BMI, smoking incidence, and steroid use, while the elderly group exhibited a higher prevalence of comorbidities. Young patients experienced shorter hospital stays (p < 0.001) but longer operative times (p < 0.001), and outpatient surgery was most common in the middle age group. Multivariable regression demonstrated that the elderly group faced increased risks of pneumonia (p < 0.001), acute renal failure (p < 0.001), stroke (p < 0.001), cardiac arrest (p < 0.001), and transfusions (p < 0.001), while both young and elderly patients had higher 30-day reoperation risks (youngest cohort, 1.4% and elderly cohort 1.3% (p < 0.001)). In summary, elderly patients undergoing TKA are at the highest risk for medical complications, while young patients are more likely to undergo inpatient surgery, experience reoperations, and have longer operative times. This study underscores the importance of age-specific counseling for TKA patients and contributes valuable insights into the evolving landscape of knee replacement surgery.

Evaluating the Biomechanical Integrity of Various Constructs Utilized for First Metatarsophalangeal Joint Arthrodesis: A Systematic Review.

The first metatarsophalangeal (MTP) joint is a frequently loaded joint, handling loads up to 90% of bodyweight. First MTP arthrodesis is a frequently performed procedure designed to improve pain in patients with degenerative MTP joint disease. There are a wide variety of fixation constructs for this procedure without consensus on the most effective method. The purpose of this study was to compare the biomechanical integrity of various constructs utilized for first MTP arthrodesis. A systematic review of the literature was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, CINAHL, MEDLINE, and Web of Science databases were searched from inception to 18 June 2023. Articles discussing the biomechanics of first MTP arthrodesis constructs were included. A total of 168 articles were retrieved. A total of 20 articles involving 446 cadaveric and synthetic bone constructs were included in the final review. Of the six articles comparing dorsal plating with compression screws to crossed interfragmentary screws, five found that dorsal plating had significantly higher stiffness. All three studies assessing shape-memory staples found them to be significantly less stable than crossed screws or dorsal plates alone. Both studies evaluating fully threaded screws found them to be stronger than crossed cancellous screws. Wedge resections have been shown to be 10 times stronger than standard planar or conical excision. Dorsal plating with compression screws is the gold standard for MTP arthrodesis. However, more research into newer methods such as fully threaded screws and wedge resections with an increased focus on translation to clinical outcomes is needed.

Diabetes Research and Resource Sharing During the COVID-19 Pandemic: A Systematic Review and Experience from an Academic/Non-Profit Resource Website.

BACKGROUND: The magnitude of the response of the diabetes professional community to the COVID-19 pandemic is not known. We aimed to examine diabetes technology research trends and resources offered by professional organizations during this period. METHODS: We explored patterns of the response from the professional diabetes community to the pandemic by (1) systematically searching for articles related to diabetes, COVID-19, and diabetes technologies; (2) examining publication trends of research protocols (clinicaltrials.gov) and preprints (medRxiv); and (3) reviewing online resources from professional organizations including our website (COVIDinDiabetes.org; an Emory University-Diabetes Technology Society collaboration). RESULTS: We identified 492 articles published between December 2019 and December 2022 meeting our inclusion criteria. Telemedicine and continuous glucose monitoring were the most common reported technologies from most parts of the world. The largest number of preprint articles was published in 2020, with a decline in 2021 and 2022. The number of research protocols related to COVID-19 was the highest in 2020 and declined in 2021 and 2022. Resources from organizations included protocols adapted to treat patients with diabetes and COVID-19, training programs, emergency preparedness, and literature on diabetes and COVID-19. On our website (COVIDinDiabetes.org), there were 12 236 visits and 18 149 pageviews, with 1.6 actions per visits, with most visits coming from North America (N = 7233, 54.2%), South America (N = 2663, 21.8%), and Europe (N = 1219). CONCLUSIONS: We conclude that the COVID-19 pandemic promoted unprecedented global research productivity related to diabetes and COVID-19 and that the transition to the use of technology resources has been evident during this period.

Australian Donation and Transplantation Biobank: A Research Biobank Integrated Within a Deceased Organ and Tissue Donation Program.

We aimed to facilitate the donation of tissue samples for research by establishing a centralized system integrated in the organ donation program for collection, storage, and distribution of samples (the Australian Donation and Transplantation Biobank [ADTB]). Methods: Feasibility of a research biobank integrated within the deceased organ and tissue donation program was assessed. DonateLife Victoria sought consent for ADTB donation after consent was received for organ donation for transplantation from the donor's senior available next of kin. ADTB samples were collected during donation surgery and distributed fresh to researchers or stored for future research. The main outcome measures were ADTB donation rates, ADTB sample collection, ADTB sample use, and to identify ethical considerations. Results: Over 2 y, samples were collected for the ADTB from 69 donors (28% of 249 donors). Samples were obtained from the spleen (n = 59, 86%), colon (n = 57, 83%), ileum (n = 56, 82%), duodenum (n = 55, 80%), blood (n = 55, 80%), bone marrow (n = 55, 80%), skin (n = 54, 78%), mesenteric lymph nodes (n = 56, 81%), liver (n = 21, 30%), lung (n = 29, 42%), and lung-draining lymph node (n = 29, 42%). Heart (n = 20), breast (n = 1), and lower urinary tract (n = 1) samples were obtained in the second year. Five hundred fifty-six samples were used in 19 ethics-approved research projects spanning the fields of immunology, microbiology, oncology, anatomy, physiology, and surgery. Conclusions: The integration of routine deceased donation and transplantation activities with a coordinated system for retrieval and allocation of donor samples for use in a range of research projects is feasible and valuable.

Using thermodynamics to obtain geochemical information from genomes.

Thermodynamic characterization of the relative stabilities of chemical compounds is a pillar of conceptual models in various fields of geosciences. Analogous models applied to genomes can yield new information about the relationship between genomes and their geochemical environments. In this perspective article, we present a chemical and thermodynamic analysis of prokaryotic lineages that have been the target of previous phylogenomic studies of evolutionary adaptation to varying redox conditions. The thermodynamic model development begins by quantifying the effects of hydrogen activity (aH2 ) and temperature on the relative stabilities of organic compounds with different carbon oxidation state. When applied to proteins instead of metabolites, the same techniques can be used to identify combinations of aH2 and temperature at which reference proteomes for Class I or Class II methanogens are relatively stable. The calculated aH2 values are compatible with reported measurements for habitats of methanogens ranging from highly reducing submarine hydrothermal systems to less reducing environments including methanogenic sediments. In contrast to the transition between the two classes of methanogenic archaea, that between basal and terrestrial groups of Thaumarchaeota (denoting the origin of ammonia-oxidizing archaea) occurs at a less-reducing redox boundary. These examples reveal the consequences of energy minimization driving evolution and show how geochemical calculations involving biomolecules can be used to quantify and better understand the coevolution of the geosphere and biosphere.

Examining the Dimensions of the Bicipital Groove: A Human Cadaveric Study.

Introduction Understanding the mechanisms and risk factors associated with bicipital groove (BG) morphology is essential for optimizing patient outcomes. Despite interest in the topic of BG morphology, there remains a lack of clarity and consensus on the parameters of BG morphology due to significant methodological limitations in the existing research. The purpose of this study is to explore the dimensions of BG morphology with a methodology rooted in recent research findings to better understand the human anatomy, potentially underpinning various shoulder pathologies.  Methods The right shoulders of seventeen cadavers (nine male and eight female; median age of death: 88.0 years; age of death range: 66.0 - 97.0 years) were included in this cadaveric study. Dissection was done by removing the deltoid musculature and reflecting the long head of the biceps tendon to expose the BG. Measurements for BG morphology included BG width (millimeters, mm), depth (mm), and length (mm). Statistical comparisons were done between male and female measurements using the independent-samples Mann-Whitney U test due to the small sample size.  Results The median width of the BG at the narrowest point was 4.3 mm (mean: 4.7 ± 1.4 mm; range: 3.0 - 7.7 mm) with male cadavers having a significantly wider BG as compared to female cadavers (median: 5.0 mm versus 3.7 mm; p=0.006). The median depth of the BG was 5.1 mm (mean: 5.0 ± 0.7 mm; range: 3.8 - 6.3 mm) with no statistically significant difference between male and female cadavers (median: 4.8 mm versus 5.3 mm; p=0.370). The median length of the BG was 25.1 mm (mean: 25.1 ± 3.3 mm; range: 18.1 - 31.3 mm) with no statistically significant difference between male and female cadavers (median: 25.4 mm versus 23.9 mm; p=0.673). Conclusion The width of the BG at the narrowest point was significantly larger in male cadavers as compared to female cadavers in this study. However, there was no difference between male and female cadavers in terms of depth and length of the BG. This study contributes to the understanding of BG morphology by exploring the dimensions for width, depth, and length of the BG, which may contribute to biceps tendon pathology in clinical practice. Future research should focus on reducing measurement variability and exploring the possible relationship between BG morphology and biceps tendon conditions to further enhance the understanding of this complex relationship.

Multi-site implementation of whole genome sequencing for hospital infection control: A prospective genomic epidemiological analysis.

Background: Current microbiological methods lack the resolution to accurately identify multidrug-resistant organism (MDRO) transmission, however, whole genome sequencing can identify highly-related patient isolates providing opportunities for precision infection control interventions. We investigated the feasibility and potential impact of a prospective multi-centre genomics workflow for hospital infection control. Methods: We conducted a prospective genomics implementation study across eight Australian hospitals over 15 months (2017,2018), collecting all clinical and screening isolates from inpatients with vanA VRE, MRSA, ESBL Escherichia coli (ESBL-Ec), or ESBL Klebsiella pneumoniae (ESBL-Kp). Genomic and epidemiologic data were integrated to assess MDRO transmission. Findings: In total, 2275 isolates were included from 1970 patients, predominantly ESBL-Ec (40·8%) followed by MRSA (35·6%), vanA VRE (15·2%), and ESBL-Kp (8·3%).Overall, hospital and genomic epidemiology showed 607 patients (30·8%) acquired their MDRO in hospital, including the majority of vanA VRE (266 patients, 86·4%), with lower proportions of ESBL-Ec (186 patients, 23·0%), ESBL-Kp (42 patients, 26·3%), and MRSA (113 patients, 16·3%). Complex patient movements meant the majority of MDRO transmissions would remain undetected without genomic data.The genomics implementation had major impacts, identifying unexpected MDRO transmissions prompting new infection control interventions, and contributing to vanA VRE becoming a notifiable condition. We identified barriers to implementation and recommend strategies for mitigation. Interpretation: Implementation of a multi-centre genomics-informed infection control workflow is feasible and identifies many unrecognised MDRO transmissions. This provides critical opportunities for interventions to improve patient safety in hospitals. Funding: Melbourne Genomics Health Alliance (supported by State Government of Victoria, Australia), and National Health and Medical Research Council (Australia).

Lung-resident memory B cells established after pulmonary influenza infection display distinct transcriptional and phenotypic profiles.

Recent studies have established that memory B cells, largely thought to be circulatory in the blood, can take up long-term residency in inflamed tissues, analogous to widely described tissue-resident T cells. The dynamics of recruitment and retention of memory B cells to tissues and their immunological purpose remains unclear. Here, we characterized tissue-resident memory B cells (BRM) that are stably maintained in the lungs of mice after pulmonary influenza infection. Influenza-specific BRM were localized within inducible bronchus-associated lymphoid tissues (iBALTs) and displayed transcriptional signatures distinct from classical memory B cells in the blood or spleen while showing partial overlap with memory B cells in lung-draining lymph nodes. We identified lung-resident markers, including elevated expression of CXCR3, CCR6, and CD69, on hemagglutinin (HA)- and nucleoprotein (NP)-specific lung BRM. We found that CCR6 facilitates increased recruitment and/or retention of BRM in lungs and differentiation into antibody-secreting cells upon recall. Although expression of CXCR3 and CCR6 was comparable in total and influenza-specific memory B cells isolated across tissues of human donors, CD69 expression was higher in memory B cells from lung and draining lymph nodes of human organ donors relative to splenic and PBMC-derived populations, indicating that mechanisms underpinning BRM localization may be evolutionarily conserved. Last, we demonstrate that human memory B cells in lungs are transcriptionally distinct to populations in lung-draining lymph nodes or PBMCs. These data suggest that BRM may constitute a discrete component of B cell immunity, positioned at the lung mucosa for rapid humoral response against respiratory viral infections.

Optimising genomic approaches for identifying vancomycin-resistant Enterococcus faecium transmission in healthcare settings.

Vancomycin-resistant Enterococcus faecium (VREfm) is a major nosocomial pathogen. Identifying VREfm transmission dynamics permits targeted interventions, and while genomics is increasingly being utilised, methods are not yet standardised or optimised for accuracy. We aimed to develop a standardized genomic method for identifying putative VREfm transmission links. Using comprehensive genomic and epidemiological data from a cohort of 308 VREfm infection or colonization cases, we compared multiple approaches for quantifying genetic relatedness. We showed that clustering by core genome multilocus sequence type (cgMLST) was more informative of population structure than traditional MLST. Pairwise genome comparisons using split k-mer analysis (SKA) provided the high-level resolution needed to infer patient-to-patient transmission. The more common mapping to a reference genome was not sufficiently discriminatory, defining more than three times more genomic transmission events than SKA (3729 compared to 1079 events). Here, we show a standardized genomic framework for inferring VREfm transmission that can be the basis for global deployment of VREfm genomics into routine outbreak detection and investigation.

Staff to staff transmission as a driver of healthcare worker infections with COVID-19.

BACKGROUND: High rates of healthcare worker (HCW) infections due to COVID-19 have been attributed to several factors, including inadequate personal protective equipment (PPE), exposure to a high density of patients with COVID-19, and poor building ventilation. We investigated an increase in the number of staff COVID-19 infections at our hospital to determine the factors contributing to infection and to implement the interventions required to prevent subsequent infections. METHODS: We conducted a single-centre retrospective cohort study of staff working at a tertiary referral hospital who tested positive for SARS-CoV-2 between 25 January 2020 and 25 November 2020. The primary outcome was the source of COVID-19 infection. RESULTS: Of 45 staff who returned a positive test result for SARS-CoV-2, 19 were determined to be acquired at our hospital. Fifteen (15/19; 79% [95% CI: 54-94%]) of these were identified through contact tracing and testing following exposures to other infected staff and were presumed to be staff-to-staff transmission, including an outbreak in 10 healthcare workers (HCWs) linked to a single ward that cared for COVID-19 patients. The staff tearoom was identified as the likely location for transmission, with subsequent reduction in HCW infections and resolution of the outbreak following implementation of enhanced control measures in tearoom facilities. No HCW contacts (0/204; 0% [95% CI: 0-2%]) developed COVID-19 infection following exposure to unrecognised patients with COVID-19. CONCLUSION: Unrecognised infections among staff may be a significant driver of HCW infections in healthcare settings. Control measures should be implemented to prevent acquisition from other staff as well as patient-staff transmission.

Pilot study of a combined genomic and epidemiologic surveillance program for hospital-acquired multidrug-resistant pathogens across multiple hospital networks in Australia.

OBJECTIVES: To conduct a pilot study implementing combined genomic and epidemiologic surveillance for hospital-acquired multidrug-resistant organisms (MDROs) to predict transmission between patients and to estimate the local burden of MDRO transmission. DESIGN: Pilot prospective multicenter surveillance study. SETTING: The study was conducted in 8 university hospitals (2,800 beds total) in Melbourne, Australia (population 4.8 million), including 4 acute-care, 1 specialist cancer care, and 3 subacute-care hospitals. METHODS: All clinical and screening isolates from hospital inpatients (April 24 to June 18, 2017) were collected for 6 MDROs: vanA VRE, MRSA, ESBL Escherichia coli (ESBL-Ec) and Klebsiella pneumoniae (ESBL-Kp), and carbapenem-resistant Pseudomonas aeruginosa (CRPa) and Acinetobacter baumannii (CRAb). Isolates were analyzed and reported as routine by hospital laboratories, underwent whole-genome sequencing at the central laboratory, and were analyzed using open-source bioinformatic tools. MDRO burden and transmission were assessed using combined genomic and epidemiologic data. RESULTS: In total, 408 isolates were collected from 358 patients; 47.5% were screening isolates. ESBL-Ec was most common (52.5%), then MRSA (21.6%), vanA VRE (15.7%), and ESBL-Kp (7.6%). Most MDROs (88.3%) were isolated from patients with recent healthcare exposure.Combining genomics and epidemiology identified that at least 27.1% of MDROs were likely acquired in a hospital; most of these transmission events would not have been detected without genomics. The highest proportion of transmission occurred with vanA VRE (88.4% of patients). CONCLUSIONS: Genomic and epidemiologic data from multiple institutions can feasibly be combined prospectively, providing substantial insights into the burden and distribution of MDROs, including in-hospital transmission. This analysis enables infection control teams to target interventions more effectively.

Cure of Limb-Threatening XDR Pseudomonas aeruginosa Infection: Combining Genome Sequencing, Therapeutic Drug Level Monitoring, and Surgical Debridement.

We describe a case of limb-threatening osteomyelitis and metalware infection with carbapenemase-producing extensively drug-resistant Pseudomonas aeruginosa successfully cured with aggressive surgical debridement and combined intravenous fosfomycin and colistin. Real-time therapeutic drug monitoring was used to maximize probability of efficacy and minimize potential for toxicity.

The NeST (Neoadjuvant systemic therapy in breast cancer) study: National Practice Questionnaire of United Kingdom multi-disciplinary decision making.

BACKGROUND: Neoadjuvant systemic therapy (NST) is increasingly used in the treatment of breast cancer, yet it is clear that there is significant geographical variation in its use in the UK. This study aimed to examine stated practice across UK breast units, in terms of indications for use, radiological monitoring, pathological reporting of treatment response, and post-treatment surgical management. METHODS: Multidisciplinary teams (MDTs) from all UK breast units were invited to participate in the NeST study. A detailed questionnaire assessing current stated practice was distributed to all participating units in December 2017 and data collated securely usingREDCap. Descriptive statistics were calculated for each questionnaire item. RESULTS: Thirty-nine MDTs from a diverse range of hospitals responded. All MDTs routinely offered neoadjuvant chemotherapy (NACT) to a median of 10% (range 5-60%) of patients. Neoadjuvant endocrine therapy (NET) was offered to a median of 4% (range 0-25%) of patients by 66% of MDTs. The principal indication given for use of neoadjuvant therapy was for surgical downstaging. There was no consensus on methods of radiological monitoring of response, and a wide variety of pathological reporting systems were used to assess tumour response. Twenty-five percent of centres reported resecting the original tumour footprint, irrespective of clinical/radiological response. Radiologically negative axillae at diagnosis routinely had post-NACT or post-NET sentinel lymph node biopsy (SLNB) in 73.0 and 84% of centres respectively, whereas 16% performed SLNB pre-NACT. Positive axillae at diagnosis would receive axillary node clearance at 60% of centres, regardless of response to NACT. DISCUSSION: There is wide variation in the stated use of neoadjuvant systemic therapy across the UK, with general low usage of NET. Surgical downstaging remains the most common indication of the use of NAC, although not all centres leverage the benefits of NAC for de-escalating surgery to the breast and/or axilla. There is a need for agreed multidisciplinary guidance for optimising selection and management of patients for NST. These findings will be corroborated in phase II of the NeST study which is a national collaborative prospective audit of NST utilisation and clinical outcomes.

Key parameters for genomics-based real-time detection and tracking of multidrug-resistant bacteria: a systematic analysis.

BACKGROUND: Pairwise single nucleotide polymorphisms (SNPs) are a cornerstone of genomic approaches to the inference of transmission of multidrug-resistant (MDR) organisms in hospitals. However, the impact of many key analytical approaches on these inferences has not yet been systematically assessed. This study aims to make such a systematic assessment. METHODS: We conducted a 15-month prospective study (2-month pilot phase, 13-month implementation phase), across four hospital networks including eight hospitals in Melbourne, VIC, Australia. Patient clinical and screening samples containing one or more isolates of meticillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, and extended-spectrum ß-lactamase-producing Escherichia coli and Klebsiella pneumoniae were collected and underwent whole genome sequencing. Using the genome data from the top four most numerous sequence types from each species, 16 in total, we systematically assessed the: (1) impact of sample and reference genome diversity through multiple core genome alignments using different data subsets and reference genomes, (2) effect of masking of prophage and regions of recombination in the core genome alignments by assessing SNP distances before and after masking, (3) differences between a cumulative versus a 3-month sliding-window approach to sample genome inclusion in the dataset over time, and (4) the comparative effects each of these approaches had when applying a previously defined SNP threshold for inferring likely transmission. FINDINGS: 2275 samples were collected (397 during the pilot phase from April 4 to June 18, 2017; 1878 during the implementation phase from Oct 30, 2017, to Nov 30, 2018) from 1870 patients. Of these 2275 samples, 1537 were identified as arising from the four most numerous sequence types from each of the four target species of MDR organisms in this dataset (16 sequence types in total: S aureus ST5, ST22, ST45, and ST93; E faecium ST80, ST203, ST1421, and ST1424; K pneumoniae ST15, ST17, ST307, and ST323; and E coli ST38, ST131, ST648, and ST1193). Across the species, using a reference genome of the same sequence type provided a greater degree of pairwise SNP resolution, compared with species and outgroup-reference alignments that mostly resulted in inflated SNP distances and the possibility of missed transmission events. Omitting prophage regions had minimal effect; however, omitting recombination regions had a highly variable effect, often inflating the number of closely related pairs. Estimated SNP distances between isolate pairs over time were more consistent using a sliding-window than a cumulative approach. INTERPRETATION: We propose that the use of a closely related reference genome, without masking of prophage or recombination regions, and of a sliding-window approach for isolate inclusion is best for accurate and consistent MDR organism transmission inference, when using core genome alignments and SNP thresholds. These approaches provide increased stability and resolution, so SNP thresholds can be more reliably applied for putative transmission inference among diverse MDR organisms, reducing the chance of incorrectly inferring the presence or absence of close genetic relatedness and, therefore, transmission. The establishment of a broadly applicable and standardised approach, as proposed here, is necessary to implement widespread prospective genomic surveillance for MDR organism transmission. FUNDING: Melbourne Genomics Health Alliance, and National Health and Medical Research Council of Australia.