University HealthSystem Consortium

This work aimed to explore the use of gamma irradiation as a technique for the terminal sterilization of oligonucleotides. Since gamma irradiation can cause damage to oligonucleotides, several radioprotective factors were tested. Stabilizers such as glycerine, histidine, trehalose, and ascorbate, as well as the use of dry ice during irradiation, were evaluated. As representative oligonucleotides, homo-oligomers of deoxythymidine with base lengths between 5 and 45-mers were selected. The effect of gamma irradiation was evaluated in aqueous solutions. To quantify the extent of degradation, an ultra-high-performance liquid chromatography method with diode array detection, employing a HALO ES-C18 column and a mobile phase consisting of 0,1 M triethylammonium acetate (TEAA) in water and acetonitrile in gradient elution mode, was used. The method allowed accurate quantification of the oligonucleotides to a level of 0,156 to 0,270nmol/ml, sufficient to quantify up to 96,6-97,8% degradation, depending on the oligonucleotide. For a radiation dose of 25kGy, the best preserved integrity was observed in the samples without stabilizers, showing degradation levels between 5,2% and 13,2%. Samples containing histidine, trehalose, and ascorbate showed an increase in degradation, ranging from 9,5% to 24,2%. In contrast, samples with glycerin exhibited extensive degradation, with values between 78,8% and 96,8%, indicating a strong destabilizing effect. The use of dry ice during irradiation did not confer any protective benefit and slightly increased degradation across all samples. This study provides the first evidence of the potential suitability of gamma irradiation for the sterilization of oligonucleotides in aqueous solution, which surprisingly works best in the absence of radioprotective factors.

Abstract Recent evidence has shown a substantial RSV burden in healthy term-born children, but there is less data quantifying the relative burden compared to those with co-morbidity or prematurity. There is also limited primary care and emergency department (ED) data due to the lack of routine pathogen detection. These data are important for the development of RSV immunisation strategies. A prospective surveillance study of children < 3 years old, presenting with lower respiratory infection and a sub-study in primary care of upper respiratory infection was conducted. The primary endpoint was RSV prevalence by healthcare setting. Secondary endpoints included proportion of hospitalisations, level of ventilatory support and admission to higher levels of care. An economic analysis assessing the costs associated with healthcare utilisation was also conducted. The primary analysis revealed RSV prevalence was 50.4% in children admitted to hospital, 36.3% in ED discharges, 36.5% in primary care and 12.8% in primary care children with upper respiratory infection. Healthy term-born children accounted for 73.3% of medically-attended RSV cases and 70.1% of hospitalisations. Risk factors for severe disease included any level of prematurity, age < 3 months and congenital cardiac disease. RSV positive cases incurred a higher mean cost than RSV negative cases (mean = £1,706; incremental = £683) per illness. The findings revealed a substantial burden associated with RSV. Even moderate prematurity was a risk factor for severe disease, and these children may not benefit from the full maternal immune response to vaccination and would not be eligible for Nirsevimab under UK guidance, we therefore recommend broadening eligibility to include these children. What is already known on this topic Recent cohort studies have revealed a substantial healthcare and economic RSV burden from previously healthy term-born children which has supported the implementation of a maternal RSV vaccination programme in the UK, providing protection for infants from birth up to 6 months old. What this study adds We have shown that children born prematurely, including moderately preterm children, are at increased risk of severe RSV disease. These children may not benefit from full protection by maternal RSV vaccination, and may not be eligible for Nirsevimab, the long-acting monoclonal antibody, which is currently reserved for only the most high-risk children in the UK. How this study might affect research, practice or policy This data supports broadening eligibility for Nirsevimab, to include preterm children, who were born before full maternal protection from RSV vaccination may have developed, and to infants born to mothers not receiving maternal vaccination.

UTS ePRESS is the open access publishing arm of the University of Technology Sydney (UTS). Our aim is to remove barriers to knowledge by freely disseminating high quality scholarly works. Through this commitment to open knowledge, we contribute to scholarship that seeks to solve global challenges.

Interhospital transfer for patients with stroke due to large vessel occlusion for endovascular thrombectomy (EVT) has been associated with treatment delays. We analyzed data from Optimizing Patient Treatment in Major Ischemic Stroke With EVT, a quality improvement registry to support EVT implementation in Canada. We assessed for unadjusted differences in baseline characteristics, time metrics, and procedural outcomes between patients with large vessel occlusion transferred for EVT and those directly admitted to an EVT-capable center. Between January 1, 2018, and December 31, 2021, a total of 6803 patients received EVT at 20 participating centers (median age, 73 years; 50% women; and 50% treated with intravenous thrombolysis). Patients transferred for EVT (n=3376) had lower rates of M2 occlusion (22% versus 27%) and higher rates of basilar occlusion (9% versus 5%) compared with those patients presenting directly at an EVT-capable center (n=3373). Door-to-needle times were shorter in patients receiving intravenous thrombolysis before transfer compared with those presenting directly to an EVT center (32 versus 36 minutes). Patients transferred for EVT had shorter door-to-arterial access times (37 versus 87 minutes) but longer last seen normal-to-arterial access times (322 versus 181 minutes) compared with those presenting directly to an EVT-capable center. No differences in arterial access-to-reperfusion times, successful reperfusion rates (85% versus 86%), or adverse periprocedural events were found between the 2 groups. Patients transferred to EVT centers had a similar likelihood for good functional outcome (modified Rankin Scale score, 0-2; 41% versus 43%; risk ratio, 0.95 [95% CI, 0.88-1.01]; adjusted risk ratio, 0.98 [95% CI, 0.91-1.05]) and a higher risk for all-cause mortality at 90 days (29% versus 25%; risk ratio, 1.15 [95% CI, 1.05-1.27]; adjusted risk ratio, 1.14 [95% CI, 1.03-1.28]) compared with patients presenting directly to an EVT center. Patients transferred for EVT experience significant delays from the time they were last seen normal to the initiation of EVT.

• Data were obtained from 89 University HealthSystem Consortium hospitals for adult patients (age≥ 18) for 2011 using the Clinical Resource Manager Database. • Antibacterials were measured in Days of Therapy per 100 admissions. • Risk factors considered were case mix index (CMI), bed size (expressed as < or ≥ the median), the % of intensive care unit days, average length of stay (LOS), a marker for market competition (the Herfindahl Index: HHI), region (Northeast, South, Midwest, West), 4 clinical service lines ( surgery, medicine, transplant, and other; expressed as < or ≥ the median number of admissions per CSL). • Three forward stepwise regression models were conducted to identify factors associated with total antibacterial, total antipseudomonal, and anti-methicillin resistant S. aureus (MRSA) drug use. Methods

Existing surveillance mechanisms may underestimate the incidence of carbapenem-resistant gram-negative infections (CRGNIs). Although carbapenem resistance increases the risk of death, the trend in mortality over time is unknown. A retrospective cohort study was conducted at 40 academic medical centers using a discharge database to identify adult hospital admissions without cystic fibrosis in 2006-2012 and received intravenous colistin for >3 consecutive days or died during therapy (termed colistin cases). The primary outcomes were the number of colistin cases per 100,000 admissions per year and change in the hospital mortality rate over time compared with the rate of discharges to home. Secondary outcomes included median overall and intensive care unit lengths of stay. From 2006 to 2012, a total of 5011 unique patients were identified as colistin cases. The number per 100,000 admissions per year increased from 35.56 to 92.98 during the 7-year study (P < .001). The odds of in-hospital death among colistin cases (compared with discharge to home) decreased by a mean of 5.2%/y (P = .04), whereas discharge to an institution (P = .24) or hospice (P = .89) remained steady over time. The median overall and intensive care unit lengths of stay decreased by 7.5 and 6 days, respectively (P < .001). In a 4-hospital chart review, 81.6% of colistin cases were found to have culture-positive CRGNIs. Conversely, 53% of extensively drug-resistant bloodstream CRGNIs at 2 of these hospitals met colistin case criteria. Colistin cases represent a severely ill population with a high probability of having culture-confirmed CRGNIs. Colistin tracking is a novel strategy for monitoring the incidence and mortality of CRGNIs, particularly those caused by extensively drug-resistant bacteria. Although the incidence of colistin cases nearly tripled within 7 years, more of these patients are surviving hospitalization and going home.