ARGNet: using deep neural networks for robust identification and classification of antibiotic resistance genes from sequences.

BACKGROUND: Emergence of antibiotic resistance in bacteria is an important threat to global health. Antibiotic resistance genes (ARGs) are some of the key components to define bacterial resistance and their spread in different environments. Identification of ARGs, particularly from high-throughput sequencing data of the specimens, is the state-of-the-art method for comprehensively monitoring their spread and evolution. Current computational methods to identify ARGs mainly rely on alignment-based sequence similarities with known ARGs. Such approaches are limited by choice of reference databases and may potentially miss novel ARGs. The similarity thresholds are usually simple and could not accommodate variations across different gene families and regions. It is also difficult to scale up when sequence data are increasing. RESULTS: In this study, we developed ARGNet, a deep neural network that incorporates an unsupervised learning autoencoder model to identify ARGs and a multiclass classification convolutional neural network to classify ARGs that do not depend on sequence alignment. This approach enables a more efficient discovery of both known and novel ARGs. ARGNet accepts both amino acid and nucleotide sequences of variable lengths, from partial (30-50 aa; 100-150 nt) sequences to full-length protein or genes, allowing its application in both target sequencing and metagenomic sequencing. Our performance evaluation showed that ARGNet outperformed other deep learning models including DeepARG and HMD-ARG in most of the application scenarios especially quasi-negative test and the analysis of prediction consistency with phylogenetic tree. ARGNet has a reduced inference runtime by up to 57% relative to DeepARG. CONCLUSIONS: ARGNet is flexible, efficient, and accurate at predicting a broad range of ARGs from the sequencing data. ARGNet is freely available at https://github.com/id-bioinfo/ARGNet , with an online service provided at https://ARGNet.hku.hk . Video Abstract.

Daily COVID-19 employee attestations at a large quaternary hospital in Melbourne, Australia - Limitations and lessons learnt.

BACKGROUND: As one of the many measures to limit the potentially infectious persons entering healthcare settings, the Victorian Department of Health (DH) introduced a daily attestation between 2020 and 2022. Upon entry to a health service, employees were required to confirm they were free from symptoms related to COVID-19 and did not have contact with a confirmed COVID-19 case in the previous 7-14 days. METHODS: We performed a retrospective analysis of employee attestations and SARS-CoV-2 tests performed between 1/6/2021 and 14/2/2022 at the main campus of the Royal Melbourne Hospital. RESULTS: We found the proportion of SARS-CoV-2 positive employees identified through workplace attestation was low (1.3%). Most SARS-CoV-2 positive employees analysed in this study (94%) were asymptomatic. DISCUSSION: Although the proportion of SARS-CoV-2 positive employees identified was low, attestations may have deterred unwell employees from presenting to work. Proactively monitoring employee attestations, such as measuring and reporting the number of symptomatic attestations, may make this a more useful tool.

Concurrent Validation of MI-CAT(V), a Clinical Metrology Instrument for Veterinarians Assessing Osteoarthritis Pain in Cats, through Testing for Firocoxib Analgesic Efficacy in a Prospective, Randomized, Controlled, and Blinded Study.

Veterinarians face the lack of a rapid, reliable, inexpensive, and treatment-sensitive metrological instrument reflecting feline osteoarthritis (OA) pain. The Montreal Instrument for Cat Arthritis Testing, for Use by Veterinarians (MI-CAT(V)) has been refined in 4 sub-sections, and we proposed its concurrent validation. Cats naturally affected by OA (n = 32) were randomly distributed into 4 groups of firocoxib analgesic (Gr. A: 0.40; B: 0.25; C: 0.15, and P: 0.00 mg/kg bodyweight). They were assessed during Baseline, Treatment, and Recovery periods using MI-CAT(V) and objective outcomes (effort path, stairs assay compliance, and actimetry). The MI-CAT(V) total score correlated to the effort path and actimetry (RhoS = -0.501 to -0.453; p < 0.001), also being sensitive to treatment responsiveness. The pooled treatment group improved its total, gait, and body posture scores during Treatment compared to the Baseline, Recovery, and placebo group (p < 0.05). The MI-CAT(V) suggested a dose-(especially for Gr. B) and cluster-response. Cats in the moderate and severe MI-CAT(V) clusters responded to firocoxib with a remaining analgesic effect, while the mild cluster seemed less responsive and experienced a negative rebound effect. The MI-CAT(V) was validated for its OA pain severity discriminatory abilities and sensitivity to firocoxib treatment, providing a new perspective for individualized care.

Using whole genome sequencing to characterize Clostridioides difficile isolates at a tertiary center in Melbourne, Australia.

Objective: Clostridioides difficile infection (CDI) is the commonest cause of healthcare-associated diarrhea and undergoes standardized surveillance and mandatory reporting in most Australian states and territories. Historically attributed to nosocomial spread, local and international whole genome sequencing (WGS) data suggest varied sources of acquisition. This study describes C. difficile genotypes isolated at a tertiary center in Melbourne, Australia, their likely source of acquisition, and common risk factors. Design: Retrospective observational study. Setting: The Royal Melbourne Hospital (RMH), a 570-bed tertiary center in Victoria, Australia. Methods: Short-read whole genome sequencing was performed on 75 out of 137 C. difficile isolates obtained from 1/5/2021 to 28/2/2022 and compared to previous data from 8/11/2015 to 1/11/2016. Existing data from infection control surveillance and electronic medical records were used for epidemiological and risk factor analysis. Results: Eighty-five (62.1%) of the 137 cases were defined as healthcare-associated from epidemiological data. On genome sequencing, 33 different multi-locus sequence type (MLST) subtypes were identified, with changes in population structure compared to the 2015-16 period. Risk factors for CDI were present in 130 (94.9%) cases, including 108 (78.8%) on antibiotics, 86 (62.8%) on acid suppression therapy, and 25 (18.2) on chemotherapy. Conclusion: In both study periods, most C. difficile isolates were not closely related, suggesting varied sources of acquisition and that spread of C. difficile within the hospital was unlikely. Current infection control precautions may therefore warrant review. Underlying risk factors for CDI were common and may contribute to the proportion of healthcare-associated infections in the absence of proven hospital transmission.

Preclinical Application of CEST MRI to Detect Early and Regional Tumor Response to Local Brain Tumor Treatment.

Treating glioblastoma and monitoring treatment response non-invasively remain challenging. Here, we developed a robust approach using a drug-loaded liposomal hydrogel that is mechanically compatible with the brain, and, simultaneously, we successfully monitored early tumor response using Chemical Exchange Saturation Transfer (CEST) MRI. This CEST-detectable liposomal hydrogel was optimized based on a sustainable drug release and a soft hydrogel for the brain tumor, which is unfavorable for tumor cell proliferation. After injecting the hydrogel next to the tumor, three distinctive CEST contrasts enabled the monitoring of tumor response and drug release longitudinally at 3T. As a result, a continuous tumor volume decrease was observed in the treatment group along with a significant decrease in CEST contrasts relating to the tumor response at 3.5 ppm (Amide Proton Transfer; APT) and at -3.5 ppm (relayed Nuclear Overhauser Effect; rNOE) when compared to the control group (p < 0.05). Interestingly, the molecular change at 3.5 ppm on day 3 (p < 0.05) was found to be prior to the significant decrease in tumor volume on day 5. An APT signal also showed a strong correlation with the number of proliferating cells in the tumors. This demonstrated that APT detected a distinctive decrease in mobile proteins and peptides in tumors before the change in tumor morphology. Moreover, the APT signal showed a regional response to the treatment, associated with proliferating and apoptotic cells, which allowed an in-depth evaluation and prediction of the tumor treatment response. This newly developed liposomal hydrogel allows image-guided brain tumor treatment to address clinical needs using CEST MRI.

Rebound in community antibiotic consumption after the observed decrease during the COVID-19 pandemic, EU/EEA, 2022.

We observed a rebound in consumption of antibacterials for systemic use (ATC J01) in the community sector in the European Union/European Economic Area during 2021 and 2022, after an observed decrease between 2019 and 2020. The rates in 2022 returned to pre-COVID-19-pandemic levels and were exceeded in 13 countries. Although these patterns could partly be a result of changes in disease transmission during the study period, it could also reflect a lost opportunity to strengthen and reinforce prudent antibiotic use.

Superior immunogenicity of mRNA over adenoviral vectored COVID-19 vaccines reflects B cell dynamics independent of anti-vector immunity: Implications for future pandemic vaccines.

Both vector and mRNA vaccines were an important part of the response to the COVID-19 pandemic and may be required in future outbreaks and pandemics. The aim of this study was to validate whether immunogenicity differs for adenoviral vectored (AdV) versus mRNA vaccines against SARS-CoV-2, and to investigate how anti-vector immunity and B cell dynamics modulate immunogenicity. We enrolled SARS-CoV-2 infection-naïve health care workers who had received two doses of either AdV AZD1222 (n = 184) or mRNA BNT162b2 vaccine (n = 274) between April and October 2021. Blood was collected at least once, 10-48 days after vaccine dose 2 for antibody and B cell analyses. Median ages were 42 and 39 years, for AdV and mRNA vaccinees, respectively. Surrogate virus neutralization test (sVNT) and spike binding antibody titres were a median of 4.2 and 2.2 times lower, respectively, for AdV compared to mRNA vaccinees (p < 0.001). Median percentages of memory B cells that recognized fluorescent-tagged spike and RBD were 2.9 and 8.3 times lower, respectively for AdV compared to mRNA vaccinees. Titres of IgG reactive with human adenovirus type 5 hexon protein rose a median of 2.2-fold after AdV vaccination but were not correlated with anti-spike antibody titres. Together the results show that mRNA induced substantially more sVNT antibody than AdV vaccine, which reflected greater B cell expansion and targeting of the RBD rather than an attenuating effect of anti-vector antibodies. ClinicalTrials.gov Identifier: NCT05110911.

Lessons Learned from the Connecticut Response to COVID-19 in Nursing Homes during the First 2 Years of the Pandemic.

Nearly half of all SARS-CoV-2-related deaths in the United States occurred in long-term care facilities during the early pandemic. In Connecticut, statewide mitigation of this impact involved a collaboration between the Connecticut Department of Public Health and the Yale School of Public Health, alongside existing relationships with the long-term care industry and individual facilities. This close government-academic-industry collaboration facilitated the creation of a robust COVID-19 surveillance system that allowed for real-time analysis and identification of nursing homes where outbreak support was needed. The collaboration further facilitated vaccine and booster deployment to Connecticut nursing homes at a speed that outpaced much of the country. The impact of these interventions is demonstrated through COVID-19 case and death burdens among nursing home residents and the greater Connecticut population during each wave of the pandemic. We outline the evolution and impact of these alliances and how they enabled us to prioritize facilities, interventions, and the distribution of limited resources and training throughout the pandemic. We further detail lessons learned over the first 2 years of the pandemic. Such partnerships strengthen our ability to respond effectively to public health crises and should be created and/or maintained in the face of continued pandemic threats.

Literature Review of Ascorbic Acid, Cranberry, and D-mannose for Urinary Tract Infection Prophylaxis in Older People.

Background Urinary tract infections (UTIs) are the most prevalent infections in older patients with the potential for morbidity and mortality. Antibiotics are not generally recommended for UTI prophylaxis in this population. There is interest among the public and health providers to try over-the-counter products, such as cranberry, D-mannose, and vitamin C. The objective of this analysis was to review the literature for the efficacy and tolerability of these supplements in older individuals. Methods A literature review was conducted on PubMed using the search terms urinary tract infection or UTI, prevention/prophylaxis, cranberry, D-mannose, vitamin C/ascorbic acid. Few studies were conducted among older people; therefore, the authors included studies of all adults who had recurrent UTIs or were at increased risk of UTIs. Level (quality) of evidence were determined using the ACC/AHA Clinical Practice Guideline Recommendation Classification System. Results A total of 24 studies were included. This review captured all studies in previous reviews as well as recent publications. The authors determined that there were limited data for D-mannose and vitamin C, and randomized data for cranberry as defined by the classification system. Conclusions The three supplements reviewed appear not to be strongly supported by clinical data. For those who are interested in trying these products despite the lack of robust evidence for clinical efficacy, it may be helpful to know that the studies included in this review did not identify any clinically important signs of harm, to the extent that safety data were documented and reported.

Comparative B cell and antibody responses induced by adenoviral vectored and mRNA vaccines against COVID-19.

Both vector and mRNA vaccines were an important part of the response to the COVID-19 pandemic and may be required in future outbreaks and pandemics. However, adenoviral vectored (AdV) vaccines may be less immunogenic than mRNA vaccines against SARS-CoV-2. We assessed anti-spike and anti-vector immunity among infection-naïve Health Care Workers (HCW) following two doses of AdV (AZD1222) versus mRNA (BNT162b2) vaccine. 183 AdV and 274 mRNA vaccinees enrolled between April and October 2021. Median ages were 42 and 39 years, respectively. Blood was collected at least once, 10-48 days after vaccine dose 2. Surrogate virus neutralization test (sVNT) and spike binding antibody titres were a median of 4.2 and 2.2 times lower, respectively, for AdV compared to mRNA vaccinees (p<0.001). Median percentages of memory B cells that recognized fluorescent-tagged spike and RBD were 2.9 and 8.3 times lower, respectively for AdV compared to mRNA vaccinees. Titres of IgG reactive with human Adenovirus type 5 hexon protein rose a median of 2.2-fold after AdV vaccination but were not correlated with anti-spike antibody titres. Together the results show that mRNA induced substantially more sVNT antibody than AdV vaccine due to greater B cell expansion and targeting of the RBD. Pre-existing AdV vector cross-reactive antibodies were boosted following AdV vaccination but had no detectable effect on immunogenicity.

Design of a Nursing Home Infection Control Peer Coaching Program.

OBJECTIVE: To pilot test and refine an infection control peer coaching program, Infection Control Amplification in Nursing Centers (ICAN), in partnership with providers. DESIGN: Intervention design and pilot test. SETTING AND PARTICIPANTS: Infection preventionists (IPs) from 7 Connecticut nursing homes (NHs). METHODS: We codesigned and pilot tested the ICAN program with NH IPs. The initial program involved designating peer coaches to provide real-time feedback on infection control practices to coworkers and targeting coaches' observations using data from both observations shared by coaches in daily huddles and weekly audit data about hand hygiene, masking, and transmission-based precautions. IPs tested the initial program while providing feedback to the research team during weekly calls. We used information from the calls, participant surveys, and the pilot process to update the program. RESULTS: Despite IPs reporting that the initial program was highly aligned with facility priorities and needs, their weekly call attendance dropped as they dealt with short staffing and COVID-19-related outbreaks and none implemented all of the program's components as intended. Most IPs described making changes to increase feasibility and reduce burden on staff amid short staffing and other ongoing issues exacerbated by the SARS-CoV-2 pandemic. We used information from the IPs and the pilot to update the program, including shifting from having IPs lead implementation solo to using a team-based approach. The updated program retains peer coaches and audit data, while broadening the mode of feedback from huddles only to communication using one-on-one meetings or emails, huddles, or other strategies. It also provides NH staff with flexibility to tailor implementation of each to their needs and constraints. CONCLUSIONS AND IMPLICATIONS: Working with staff, we developed an infection control peer coaching program that may be of use to NH leaders seeking strategies to strengthen infection control practices. Future work should involve implementing and evaluating the updated program.

Piezo1 regulates cholesterol biosynthesis to influence neural stem cell fate during brain development.

Mechanical forces and tissue mechanics influence the morphology of the developing brain, but the underlying molecular mechanisms have been elusive. Here, we examine the role of mechanotransduction in brain development by focusing on Piezo1, a mechanically activated ion channel. We find that Piezo1 deletion results in a thinner neuroepithelial layer, disrupts pseudostratification, and reduces neurogenesis in E10.5 mouse embryos. Proliferation and differentiation of Piezo1 knockout (KO) mouse neural stem cells (NSCs) isolated from E10.5 embryos are reduced in vitro compared to littermate WT NSCs. Transcriptome analysis of E10.5 Piezo1 KO brains reveals downregulation of the cholesterol biosynthesis superpathway, in which 16 genes, including Hmgcr, the gene encoding the rate-limiting enzyme of the cholesterol biosynthesis pathway, are downregulated by 1.5-fold or more. Consistent with this finding, membrane lipid composition is altered, and the cholesterol levels are reduced in Piezo1 KO NSCs. Cholesterol supplementation of Piezo1 KO NSCs partially rescues the phenotype in vitro. These findings demonstrate a role for Piezo1 in the neurodevelopmental process that modulates the quantity, quality, and organization of cells by influencing cellular cholesterol metabolism. Our study establishes a direct link in NSCs between PIEZO1, intracellular cholesterol levels, and neural development.

Opposing Effects of Prior Infection versus Prior Vaccination on Vaccine Immunogenicity against Influenza A(H3N2) Viruses.

Prior vaccination can alternately enhance or attenuate influenza vaccine immunogenicity and effectiveness. Analogously, we found that vaccine immunogenicity was enhanced by prior A(H3N2) virus infection among participants of the Ha Nam Cohort, Viet Nam, but was attenuated by prior vaccination among Australian Health Care Workers (HCWs) vaccinated in the same year. Here, we combined these studies to directly compare antibody titers against 35 A(H3N2) viruses spanning 1968-2018. Participants received licensed inactivated vaccines containing A/HongKong/4801/2014 (H3N2). The analysis was limited to participants aged 18-65 Y, and compared those exposed to A(H3N2) viruses circulating since 2009 by infection (Ha Nam) or vaccination (HCWs) to a reference group who had no recent A(H3N2) infection or vaccination (Ha Nam). Antibody responses were compared by fitting titer/titer-rise landscapes across strains, and by estimating titer ratios to the reference group of 2009-2018 viruses. Pre-vaccination, titers were lowest against 2009-2014 viruses among the reference (no recent exposure) group. Post-vaccination, titers were, on average, two-fold higher among participants with prior infection and two-fold lower among participants with 3-5 prior vaccinations compared to the reference group. Titer rise was negligible among participants with 3-5 prior vaccinations, poor among participants with 1-2 prior vaccinations, and equivalent or better among those with prior infection compared to the reference group. The enhancing effect of prior infection versus the incrementally attenuating effect of prior vaccinations suggests that these exposures may alternately promote and constrain the generation of memory that can be recalled by a new vaccine strain.

Hospital Readmissions Among Infants Diagnosed With Early-Onset Neonatal Sepsis in Connecticut.

BACKGROUND: Early-onset neonatal sepsis, defined as sepsis within 72 hours of birth, results in significant infant morbidity and mortality. Readmissions associated with neonatal sepsis have not previously been well described. Early-onset neonatal sepsis is a mandatory reportable condition in Connecticut, allowing for expanded data collection through public health surveillance to evaluate readmissions. METHODS: Infants with early-onset neonatal sepsis born in Connecticut during 2007-2016 were identified from statewide surveillance data and matched with a statewide hospital discharge database. We describe readmission rates, causes and timing of readmissions, and demographic and clinical factors associated with readmission among this group. RESULTS: Among 241 infants with early-onset neonatal sepsis matched to discharge data, 203 (84.2%) infants survived their initial hospitalization at birth. During the first year of life, 47 (23.2%) infants were readmitted, most often in the first 3 months after birth (n = 29, 42.6%). The most frequent reasons for readmissions were pulmonary complications (19%), infections (17%), and gastrointestinal illness (13%). Infants with initial hospitalizations lasting longer than 30 days after birth were associated with higher rates of readmission compared with those discharged within 30 days after birth (35% vs 19%, P = .02). CONCLUSIONS: A substantial proportion of infants diagnosed with early-onset neonatal sepsis are readmitted within the first year of life. Those with prolonged hospitalizations after birth are at the highest risk. Further efforts and intensified strategies are needed to prevent readmissions among this vulnerable patient population.

Longitudinal Changes in Structural Connectivity in Young People at High Genetic Risk for Bipolar Disorder.

OBJECTIVE: Recent studies of patients with bipolar disorder or at high genetic risk reveal structural dysconnections among key brain networks supporting cognitive and affective processes. Understanding the longitudinal trajectories of these networks across the peak age range of bipolar disorder onset could inform mechanisms of illness onset or resilience. METHODS: Longitudinal diffusion-weighted MRI and phenotypic data were acquired at baseline and after 2 years in 183 individuals ages 12-30 years in two cohorts: 97 unaffected individuals with a first-degree relative with bipolar disorder (the high-risk group) and 86 individuals with no family history of mental illness (the control group). Whole-brain structural networks were derived using tractography, and longitudinal changes in these networks were studied using network-based statistics and mixed linear models. RESULTS: Both groups showed widespread longitudinal changes, comprising both increases and decreases in structural connectivity, consistent with a shared neurodevelopmental process. On top of these shared changes, high-risk participants showed weakening of connectivity in a network encompassing the left inferior and middle frontal areas, left striatal and thalamic structures, the left fusiform, and right parietal and occipital regions. Connections among these regions strengthened in the control group, whereas they weakened in the high-risk group, shifting toward a cohort with established bipolar disorder. There was marginal evidence for even greater network weakening in those who had their first manic or hypomanic episode before follow-up. CONCLUSIONS: Neurodevelopment from adolescence into early adulthood is associated with a substantial reorganization of structural brain networks. Differences in these maturational processes occur in a multisystem network in individuals at high genetic risk of bipolar disorder. This may represent a novel candidate to understand resilience and predict conversion to bipolar disorder.

Tolerating clear fluids diet on postoperative day 0 predicts early recovery of gastrointestinal function after laparoscopic colectomy.

INTRODUCTION: A high proportion of colorectal surgery patients within an enhanced recovery pathway (ERP) do not experience complications but remain hospitalized mainly waiting for gastrointestinal (GI) recovery. Accurate identification of these patients may allow discharge prior to the return of GI function. Therefore, the objective of this study is to determine if tolerating clear fluid (CF) on postoperative day (POD) 0 was associated with uncomplicated return of GI function after laparoscopic colorectal surgery. METHODS: Pooled data from three prospective studies from a single specialist colorectal referral center were analyzed (2013-2019). The present study included adult patients that underwent elective laparoscopic colectomy without stoma. Postoperative GI symptoms were collected daily in all three datasets. The main exposure variable, whether CF diet was tolerated on POD0, was defined as patients drinking at least 300 mL of CF without any nausea, anti-emetics, or vomiting (CF+ vs CF-). The main outcome measure was time to GI-3 (tolerating solid diet and passage of gas or stools). RESULTS: A total of 221 patients were included in this study, including 69% CF+ and 31% CF-. The groups were similar in age, gender, and comorbidities, but the CF- patients were more likely to have surgery for inflammatory bowel disease. CF+ patients had faster time to GI-3 (mean 1.6d (SD 0.7) vs. 2.3d (SD 1.5), p < 0.001). The CF+ group also experienced fewer complications (19% vs. 35%, p = 0.009), shorter mean LOS (mean 3.6d (SD 2.9) vs. 6.2d (SD 9.4), p = 0.002), and were more likely to be discharged by the target LOS (66% vs. 50%, p = 0.024). CONCLUSION: Toleration of CF on POD0 was associated with faster return of GI function, fewer complications, and shorter LOS. This may be used as a criteria for potential discharge prior to full return of GI function after laparoscopic colectomy within an ERP.

Intrahepatic Injection of Sodium Pentobarbital as an Alternative to Intraperitoneal Injection for the Euthanasia of Rats (Rattus norvegicus).

The most commonly accepted method of rat euthanasia in North America is intraperitoneal injection of sodium pentobarbital (PB). However, misinjection can occur, and intraperitoneal PB may cause pain and distress. The objective of this study was to test an alternative method of euthanasia: intrahepatic injection of PB. A pilot study was conducted to develop a method of intrahepatic injections (evaluated using CT scans and test injections), followed by a full study comparing intraperitoneal (n = 14) and intrahepatic PB injections (n = 66) in adult rats. Full study outcomes were: 1) time from injection to loss of right- ing reflex (LORR), 2) time from injection to cessation of heartbeat (CHB), 3) number of failed euthanasia attempts, and 4) confirmation of successful intrahepatic injection or misinjection via necropsy. All injections were performed by a veterinary student. CT revealed that intrahepatic injections were feasible. Times (median [range]) to LORR and CHB were faster after successful intrahepatic injections (LORR, 3 s [1 to 5 s]; CHB, 8 s [2 to 242 s]) than after intraperitoneal injections (LORR, 89.5 s [73 to 110 s], CHB: 284.5 s [237 to 423 s]). The misinjection rate was higher with intrahepatic injections (59%) than with intraperitoneal injections (29%), but intrahepatic misinjection still resulted in fast and successful euthanasia (LORR, 29 s [1 to 96 s]; CHB, 216 s [12 to 330 s]), with the injectate distributed between the intraperitoneal and intrahepatic locations. The number of failed euthanasia attempts with intrahepatic injections was low (n = 2). Intrahepatic injections show potential as an alternative to intraperitoneal injections for rat euthanasia.

Performance of hospital-based contact tracing for COVID-19 during Australia's second wave.

BACKGROUND: Hospital-based contact tracing aims to limit spread of COVID-19 within healthcare facilities. In large outbreaks, this can stretch resources and workforce due to quarantine of uninfected staff. We analysed the performance of a manual contact tracing system for healthcare workers (HCW) at a multi-site healthcare facility in Melbourne, Australia, from June-September 2020, during an epidemic of COVID-19. METHODS: All HCW close contacts were quarantined for 14 days, and tested around day 11, if not already diagnosed with COVID-19. We examined the prevalence and timing of symptoms in cases detected during quarantine, described this group as proportions of all close contacts and of all cases, and used logistic regression to assess factors associated with infection. RESULTS: COVID-19 was diagnosed during quarantine in 52 furloughed HCWs, from 483 quarantine episodes (11%), accounting for 19% (52/270) of total HCW cases. In 361 exposures to a clear index case, odds of infection were higher after contact with an infectious patient compared to an infectious HCW (aOR: 4.69, 95% CI: 1.98-12.14). Contact with cases outside the workplace increased odds of infection compared to workplace contact only (aOR: 7.70, 95% CI: 2.63-23.05). We estimated 30%, 78% and 95% of symptomatic cases would develop symptoms by days 3, 7, and 11 of quarantine, respectively. CONCLUSION: In our setting, hospital-based contact tracing detected and contained a significant proportion of HCW cases, without excessive quarantine of uninfected staff. Effectiveness of contact tracing is determined by a range of dynamic factors, so system performance should be monitored in real-time.

Excess respiratory mortality and hospitalizations associated with influenza in Australia, 2007-2015.

BACKGROUND: Influenza is the most common vaccine-preventable disease in Australia, causing significant morbidity and mortality. We assessed the burden of influenza across all ages in terms of influenza-associated mortality and hospitalizations using national mortality, hospital-discharge and influenza surveillance data. METHODS: Influenza-associated excess respiratory mortality and hospitalization rates from 2007 to 2015 were estimated using generalized additive models with a proxy of influenza activity based on syndromic and laboratory surveillance data. Estimates were made for each age group and year. RESULTS: The estimated mean annual influenza-associated excess respiratory mortality was 2.6 per 100 000 population [95% confidence interval (CI): 1.8, 3.4 per 100 000 population]. The excess annual respiratory hospitalization rate was 57.4 per 100 000 population (95% CI: 32.5, 82.2 per 100 000 population). The highest mortality rates were observed among those aged ≥75 years (35.11 per 100 000 population; 95% CI: 19.93, 50.29 per 100 000 population) and hospitalization rates were also highest among older adults aged ≥75 years (302.95 per 100 000 population; 95% CI: 144.71, 461.19 per 100 000 population), as well as children aged <6 months (164.02 per 100 000 population; 95% CI: -34.84, 362.88 per 100 000 population). Annual variation was apparent, ranging from 1.0 to 3.9 per 100 000 population for mortality and 24.2 to 94.28 per 100 000 population for hospitalizations. Influenza A contributed to almost 80% of the average excess respiratory hospitalizations and 60% of the average excess respiratory deaths. CONCLUSIONS: Influenza causes considerable burden to all Australians. Expected variation was observed among age groups, years and influenza type, with the greatest burden falling to older adults and young children. Understanding the current burden is useful for understanding the potential impact of mitigation strategies, such as vaccination.

Trajectory of gastrointestinal function after laparoscopic colorectal surgery within an enhanced recovery pathway.

BACKGROUND: Early identification of colorectal surgery patients predicted to have uneventful gastrointestinal recovery may allow for early discharge. Our objective was to identify trajectories of gastrointestinal recovery within a colorectal surgery enhanced recovery pathway. METHODS: Data from 2 prospective studies enrolling adult patients undergoing elective laparoscopic colorectal resection at a specialist colorectal referral center were analyzed (2013-2019). All patients were managed according to a mature enhanced recovery pathway with a 3-day target length of stay. Postoperative gastrointestinal symptoms were collected daily and expressed using the validated I-FEED score. Latent-class growth curve (trajectory) analysis was used to identify different I-FEED trajectories over the first 3 postoperative days. RESULTS: A total of 192 patients were analyzed. Trajectory analysis identified 3 distinct trajectories: trajectory 1 had no gastrointestinal symptoms (41%); trajectory 2 had mild early symptoms with improvement over time (48%); and trajectory 3 had gastrointestinal symptoms that significantly worsened between postoperative days 1 and 2 (11%). I-FEED score ≤1 on postoperative day 1 predicted trajectory 1. Trajectory 1 had the best clinical outcomes, whereas trajectory 3 had the worst. CONCLUSION: I-FEED trajectory over postoperative days 1-3 was associated with clinical outcomes and may be used to predict gastrointestinal recovery. Findings from this study may inform clinical decision making regarding early hospital discharge within colorectal enhanced recovery pathways.