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Objectives: Hemorrhage in osteoporotic pelvic ring fractures is a rare, but serious complication. Most bleeding comes from the bone or venous plexuses, but arterial injury does occur. The purpose of this study was to characterize a large geriatric pelvic fracture cohort and determine the prevalence of pelvic CT angiography (CTA) and subsequent need for arterial embolization., Methods: A cohort of geriatric pelvic fracture patients at two level 1 trauma centers was reviewed. Many epidemiologic and patient factors were collected for cohort characterization. The primary outcome was if patients underwent a CTA of the pelvis and subsequently underwent arterial embolization., Results: There were 457 patients included and mean age was 83.1 years (range 65-100). Most patients had a low energy mechanism (91.4 %). In-hospital mortality was recorded for 30 cases (6.6 %). Of these deaths, two received a pelvic CTA and two had an embolization procedure. Pelvic CTA was performed on 33 patients (7.2 %). Fourteen patients (3.0 %) had an arterial embolization procedure. A high energy mechanism of injury was associated with receiving a pelvic CTA (p = 0.0067). Mechanism of injury was not associated with undergoing an embolization procedure (p = 0.685)., Discussion: In the geriatric population, even patients with stable pelvic fractures can present with life-threatening arterial bleeding. A non-insignificant percentage of patients will require CTA for suspected bleeding (7.2 %) and embolization to treat confirmed arterial bleeding (3.0 %)., Conclusions: Bleeding events in geriatric pelvic ring injuries is a previously under researched area of orthopedic trauma. Further research is needed to elucidate the exact pathomechanisms of arterial injury and what patients or injury patterns are most significantly associated. Specifically, larger cohort sizes and evaluating our existing cohort with different injury classification systems may yield useful results., Competing Interests: Declaration of competing interest None of the authors have any conflicts of interest related to this manuscript to disclose., (Copyright © 2024. Published by Elsevier Ltd.)

Background: To establish the feasibility and safety of multimodal prehabilitation (MP), and to obtain pilot data on the change in quality of life, functional walking capacity, and the need for surgery for a full-scale trial., Methods: Pilot randomized controlled trial that included patients older than 50 years old suffering from moderate to severe intermittent claudication and who were candidates for endovascular revascularization (ER). Participants were excluded if they presented with ischemic rest pain, gangrene or ulceration of the index leg, significant lesions in the iliac vessels, planned surgical bypass, comorbidities in which exercise was contraindicated or if they were unable to speak English or French. Participants were randomized in a 1:1 ratio to 12 weeks of MP or institutional standard of care (unsupervised walking advice). MP consisted of i)1 weekly supervised exercise session; ii) home-based exercise prescription; iii) nutritional counseling and supplementation; iv) smoking cessation therapy; and v) psychosocial support. Feasibility and safety were measured with recruitment and retention rates, as well as the occurrence of any adverse events. In addition, barriers to attend supervised sessions and compliance to each component were assessed. Change in functional walking capacity, health-related quality of life, and the rates of patients deciding not to undergo ER were collected and analyzed throughout the follow-up period of 12 months., Results: Of the 37 patients referred for eligibility, 27 (73%) accepted to participate in the trial and were randomized. Of the 27 patients included, 24 completed the 12-week program. Adherence to each prehabilitation component was 83% interquartile range [72,93] for supervised exercise, 90% [83,96] for home-based exercise and 69% [45,93] for nutritional sessions. Fifty percent of patients were referred for and underwent psychosocial intervention and 40% of the active smokers enrolled in the smoking cessation program. No adverse events were observed during the program. The 2 main barriers for not fully adhering to the intervention were excessive pain while performing the exercises and the difficulty to keep up with the prescribed exercises. A statistically significant mean change (standard deviation (SD)) was seen in the MP group versus standard of care for functional capacity, mean (SD) 6 Min Walk Test 60 (74) vs. -11 (40) meters P < 0.05, and quality of life mean (SD) VascuQol 1.15 (0.54) vs. -0.3 (1.09) points P < 0.05. There was no statistically significant difference between groups in the rates of patients deciding to undergo ER during the 1-year follow-up period., Conclusions: The results of this pilot trial demonstrate that MP is safe and feasible. A 12-week MP program seems to improve quality of life and functional walking capacity to a greater extent than unsupervised walking advice. There is a need for a large-scale trial to investigate the effectiveness of MP at improving quality of life and assessing its impact on the rates of patients deciding not to undergo or delay ER. The long-term functional and quality of life outcomes of the patients deciding to undergo ER after prehabilitation also need to be assessed., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Objective: Real-world evidence (RWE) can complement and fill knowledge gaps from randomized controlled trials to assist in health-technology assessment (HTA) for regulatory decision-making. However, the generation of RWE is an intricate process with many sequential decision points, and different methods and approaches may impact the quality and reliability of evidence. Standardization and transparency in reporting these decisions is imperative to appraise RWE and incorporate it into HTA decision-making. A partnership between Canadian health system stakeholders, namely, Health Canada and Canada's Drug Agency (formerly the Canadian Agency for Drugs and Technologies in Health), was established to develop guidance for the standardization of reporting of RWE for regulatory and HTA decision-making in Canada., Study Design and Setting: A collaborative initiative to create structured guidance for RWE reporting in the context of regulatory and HTA decision-making., Results: The developed guidance aims to standardize and ensure transparent reporting of RWE to improve its reliability and usefulness in regulatory and HTA processes., Conclusion: This guidance can be adapted for other jurisdictions and will have future extensions to incorporate emerging issues with RWE and HTA decision-making., Competing Interests: Declaration of competing interest M. T. received financial support from the Canadian Agency for Drugs and Technologies in Health. M. T., T. A., and K. N. H. report a relationship with Canadian Agency for Drugs and Technologies in Health that includes consulting or advisory. N. M., L. L., and F. H. are employed with the Canadian Agency for Drugs and Technologies in Health. There are no competing interests for any other author., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This ISPOR Good Practices report provides a framework for assessing the suitability of electronic health records data for use in health technology assessments (HTAs). Although electronic health record (EHR) data can fill evidence gaps and improve decisions, several important limitations can affect its validity and relevance. The ISPOR framework includes 2 components: data delineation and data fitness for purpose. Data delineation provides a complete understanding of the data and an assessment of its trustworthiness by describing (1) data characteristics; (2) data provenance; and (3) data governance. Fitness for purpose comprises (1) data reliability items, ie, how accurate and complete the estimates are for answering the question at hand and (2) data relevance items, which assess how well the data are suited to answer the particular question from a decision-making perspective. The report includes a checklist specific to EHR data reporting: the ISPOR SUITABILITY Checklist. It also provides recommendations for HTA agencies and policy makers to improve the use of EHR-derived data over time. The report concludes with a discussion of limitations and future directions in the field, including the potential impact from the substantial and rapid advances in the diffusion and capabilities of large language models and generative artificial intelligence. The report's immediate audiences are HTA evidence developers and users. We anticipate that it will also be useful to other stakeholders, particularly regulators and manufacturers, in the future., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2024. Published by Elsevier Inc.)

Background: Obesity is prevalent in patients with abdominal aortic aneurysms (AAA). There is an association between increasing body mass index (BMI) and increased overall cardiovascular mortality and morbidity. This study aims to assess the difference in mortality and complication rates between normal weight (NW), overweight (OW), and obese patients undergoing endovascular aneurysm repair (EVAR) for infrarenal AAA., Methods: This is a retrospective analysis of consecutive patients undergoing EVAR for AAA between January 1998 and December 2019. Weight classes were defined as: BMI<18.5 kg/m 2 , underweight; BMI 18.5-24.9 kg/m 2 , NW; BMI 25.0-29.9 kg/m 2 , OW; BMI 30.0-39.9 kg/m 2 , obese; BMI>39.9 kg/m 2 morbidly obese. Primary outcomes were long-term all-cause mortality and freedom from reintervention. Secondary outcome was aneurysm sac regression (defined as a reduction in sac diameter of 5 mm or more). Kaplan-Meier survival estimates and mixed model analysis of variance were used., Results: The study included 515 patients (83% males, mean age 77 ± 8 years) with a mean follow-up of 3.8 ± 2.8 years. In terms of weight class, 2.1% (n = 11) were underweight, 32.4% (167) were NW, 41.6% (n = 214) were OW, 21.2% (n = 109) were obese, and 2.7% (n = 14) were morbidly obese. Obese patients were younger (mean difference -5.0 years) but had a higher prevalence of diabetes mellitus (33.3% vs. 10.6% for NW) and dyslipidemia (82.4% vs. 60.9% for NW). Obese patients had similar freedom from all-cause mortality (88%) compared to OW (78%) and NW (81%) patients. The same findings were evident for freedom from reintervention where obese (79%) was similar to OW (76%) and NW (79%). At a mean follow-up of 5.1 ± 0.4 years, sac regression was observed similarly across weight classes at 49.6%, 50.6%, and 51.8% for NW, OW, and obese, respectively (P = 0.501). There was a significant difference in mean AAA diameter pre- and post-EVAR [F(2,318) = 24.37, P < 0.001] across weight classes. NW [mean reduction 4.8 mm (2.0-7.6 mm, P < 0.001)], OW [mean reduction 3.9 mm (1.5-6.3 mm, P < 0.001)], and obese [mean reduction 5.7 mm (2.3-9.1 mm, P < 0.001)] achieved similar reductions., Conclusions: Obesity was not associated with increased mortality or reintervention in patients undergoing EVAR. Obese patients achieved similar rates of sac regression on imaging follow-up., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: In the present review, we assessed the effect of obesity on clinical outcomes for patients with peripheral arterial disease who had undergone endovascular or open lower extremity revascularization surgery., Methods: A systematic search strategy of MEDLINE, EMBASE, CINAHL, Web of Science, and Cochrane Library was conducted. The included studies had compared obese and nonobese cohorts with peripheral arterial disease who had undergone endovascular or open lower extremity revascularization. The outcomes included mortality, major adverse cardiovascular events, major adverse limb events, surgical site infections, endovascular access site complications, and perioperative complications., Results: Eight studies were included with 171,648 patients. The obese patients (body mass index ≥30 kg/m 2 ) were more likely to be women, to have diabetes, and to have more cardiovascular comorbidities despite being younger. No association was found between obesity and peripheral arterial disease severity. Obesity was associated with an overall 22% decreased mortality risk after lower extremity revascularization (risk ratio [RR], 0.78; 95% confidence interval [CI], 0.71-0.85; P < .001; I 2  = 0%; GRADE (grading of recommendations assessment, development, evaluation), very low quality). A subgroup analysis by intervention type showed similar findings (endovascular: RR, 0.79; 95% CI, 0.71-0.87; P < .001; I 2  = 0%; open: RR, 0.70; 95% CI, 0.51-0.95; P = .024; I 2  = 43%). Obesity was associated with a 14% decreased risk of major adverse cardiovascular events for open surgery only (RR, 0.86; 95% CI, 0.76-0.98; P = .021; I 2  = 0%; GRADE, very low quality). Obesity was associated with an increased risk of surgical site infections pooled across intervention types (RR, 1.69; 95% CI, 1.34-2.14; P < .001; I 2  = 78%; GRADE, very low quality). No association was found between obesity and major adverse limb events (RR, 1.02; 95% CI, 0.93-1.11; P = .73; I 2  = 15%; GRADE, very low quality) or endovascular access site complications (RR, 1.11; 95% CI, 0.76-1.63; P = .58; I 2  = 86%; GRADE, very low quality). Pooled perioperative complications did not differ between the obese and nonobese cohorts (RR, 1.04; 95% CI, 0.84-1.28; P = .73; I 2  = 92%; GRADE, very low quality)., Conclusions: Obesity was associated with reduced mortality risk with both endovascular and open surgery, although a reduction in major adverse cardiovascular events was only observed with open surgery. In addition, obese patients had an increased risk of surgical site infections. Obesity was not associated with major adverse limb events, endovascular access site complications, or perioperative complications. The GRADE quality of evidence was very low. The findings from the present review suggest a survival advantage for obese patients with peripheral arterial disease. Future studies could focus on prospectively investigating the effect of obesity on peripheral arterial disease outcomes. A nuanced evaluation of body mass index as a preoperative risk factor is warranted., (Copyright © 2022 Society for Vascular Surgery. All rights reserved.)

Objective: In the present study, we evaluated the effects of inframalleolar (IM) disease on the occurrence of major adverse limb events (MALE) in patients undergoing endovascular revascularization for chronic limb-threatening ischemia (CLTI)., Methods: Patients who had undergone endovascular revascularization for CLTI between January 2015 and December 2019 at two university-affiliated hospitals were reviewed retrospectively. Patients with severe IM disease (pedal score of 2) were compared with those with mild to moderate IM disease (score of 0 or 1) using the Global Vascular Guidelines. The primary outcome was MALE (open revascularization, acute leg ischemia, major amputation). The secondary outcomes were mortality, reintervention, major adverse cardiac events, and perioperative complications ≤30 days after endovascular revascularization, primary limb-based patency, and the occurrence of any limb event (defined as any amputation, acute leg ischemia, or open revascularization). Kaplan-Meier estimates were used to compare the primary outcome, and the Cox proportion hazard model was used to assess the effects of IM disease., Results: The study included 167 limbs in 149 patients (36% female; mean age, 74 ± 12 years). Severe IM disease was identified in 71 limbs (43%). No differences were found in the baseline characteristics, except for a higher prevalence of dyslipidemia in the patients with severe IM disease (66% vs 43%; P = .003). Most patients in both groups had had a WIfI (Wound, Ischemia, foot Infection) score of 4 (severe IM disease, 64%; vs mild to moderate IM disease, 57%; P = .462) and GLASS (global limb anatomic severity scale) III anatomy (severe IM disease, 54%; vs mild to moderate IM disease, 48%; P = .752). The Kaplan-Meier estimates showed that severe IM disease was associated with lower freedom from MALE (69% vs 82%; P = .026). The Cox proportion hazard regression model showed that severe IM disease was an independent predictor of increased MALE and amputation risk (hazard ratio, 1.715; 95% confidence interval, 1.015-2.896; P = .044) after adjusting for covariates. During follow-up, patients with severe IM disease had had mortality (27% vs 31%; P = .567) and reintervention (42% vs 38%; P = .608) similar to those for patients with mild to moderate IM disease. Primary limb-based patency was also similar (79% vs 84%; P = .593) at a mean follow-up of 3.8 ± 0.8 years., Conclusions: Severe IM disease was prevalent in 43% of limbs that had undergone endovascular revascularization for CLTI and was associated with lower freedom from MALE. Severe IM disease also independently increased the hazard of adverse limb outcomes and amputations in patients with CLTI by >70%, highlighting its importance as a measure of foot perfusion., (Copyright © 2022 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Depression is a significant risk factor for death in coronary artery disease. Conversely, the research surrounding depression and peripheral arterial disease is limited. This review aimed to systematically evaluate the available literature on the impact of comorbid depression on adverse outcomes in peripheral arterial disease., Data Sources: A systematic review and meta-analysis were performed using the following databases MEDLINE, EMBASE, CINAHL, PsycINFO, and Cochrane Library from inception until July 2021., Review Methods: Included studies compared depressed and non-depressed patients with peripheral arterial disease. The outcomes included death, major adverse cardiovascular events, and major adverse limb events., Results: A total of 9 297 articles were searched. Of these, seven studies were identified. Depressed patients were more likely to be women, diabetic, have a history of smoking, and have chronic limb threatening ischaemia, despite being younger than non-depressed patients. There was a 20% increase in major adverse limb events in depressed patients (RR 1.20, 95% CI 1.11 - 1.31, z = 3.9, p < .001, GRADE strength: very low) but no increased risk of death (RR 1.03, 95% CI 0.72 - 1.40, z = 0.06, p = .95, GRADE strength: very low) or major adverse cardiovascular events (RR 1.16, 95% CI 0.67 - 2.01, z = 0.54, p = .59, GRADE strength: very low). A follow up meta-regression of various comorbidities and demographic variables did not demonstrate a significant contribution to the observed risk ratio for major adverse limb events., Conclusion: Depression was reported in 13% of patients with peripheral arterial disease, associated with more medical comorbidity, and a 20% increased risk of major adverse limb events. Although the strength of this evidence is very low, the current state of the literature remains limited. Future studies should prospectively assess the impact of depression and its relationship to medical comorbidities and high risk health behaviours., (Copyright © 2022 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Genome integrity is essential for life and, as a result, DNA repair systems evolved to remove unavoidable DNA lesions from cellular DNA. Many forms of life possess the capacity to remove interstrand DNA cross-links (ICLs) from their genome but the identity of the naturally-occurring, endogenous substrates that drove the evolution and retention of these DNA repair systems across a wide range of life forms remains uncertain. In this review, we describe more than a dozen chemical processes by which endogenous ICLs plausibly can be introduced into cellular DNA. The majority involve DNA degradation processes that introduce aldehyde residues into the double helix or reactions of DNA with endogenous low molecular weight aldehyde metabolites. A smaller number of the cross-linking processes involve reactions of DNA radicals generated by oxidation., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aldehyde dehydrogenase 9A1 (ALDH9A1) is a human enzyme that catalyzes the NAD + -dependent oxidation of the carnitine precursor 4-trimethylaminobutyraldehyde to 4-N-trimethylaminobutyrate. Here we show that the broad-spectrum ALDH inhibitor diethylaminobenzaldehyde (DEAB) reversibly inhibits ALDH9A1 in a time-dependent manner. Possible mechanisms of inhibition include covalent reversible inactivation involving the thiohemiacetal intermediate and slow, tight-binding inhibition. Two crystal structures of ALDH9A1 are reported, including the first of the enzyme complexed with NAD + . One of the structures reveals the active conformation of the enzyme, in which the Rossmann dinucleotide-binding domain is fully ordered and the inter-domain linker adopts the canonical β-hairpin observed in other ALDH structures. The oligomeric structure of ALDH9A1 was investigated using analytical ultracentrifugation, small-angle X-ray scattering, and negative stain electron microscopy. These data show that ALDH9A1 forms the classic ALDH superfamily dimer-of-dimers tetramer in solution. Our results suggest that the presence of an aldehyde substrate and NAD + promotes isomerization of the enzyme into the active conformation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Interstrand DNA-DNA cross-links (ICLs) are generated by endogenous processes, drugs, and environmental toxins. Understanding the cellular pathways by which various ICLs are repaired is critical to understanding their biological effects. Recent studies showed that replication-dependent repair of an ICL derived from the reaction of an abasic (AP) site with an adenine residue (dA) on the opposing strand of duplex DNA proceeds via a novel mechanism in which the DNA glycosylase NEIL3 unhooks the ICL. Here we examined the ability of the glycosylase domain of murine NEIL3 (MmuNEIL3-GD) to unhook dA-AP ICLs. The enzyme selectively unhooks the dA-AP ICL located at the duplex/single-strand junction of splayed duplexes that model the strand-separated DNA at the leading edge of a replication fork. We show that the ability to unhook the dA-AP ICL is a specialized function of NEIL3 as this activity is not observed in other BER enzymes. Importantly, NEIL3 only unhooks the dA-AP ICL when the AP residue is located on what would be the leading template strand of a model replication fork. The same specificity for the leading template strand was observed with a 5,6-dihydrothymine monoadduct, demonstrating that this preference is a general feature of the glycosylase and independent of the type of DNA damage. Overall, the results show that the glycosylase domain of NEIL3, lacking the C-terminal NPL4 and GRF zinc finger motifs, is competent to unhook the dA-AP ICL in splayed substrates and independently enforces important substrate preferences on the repair process., (Copyright © 2019. Published by Elsevier B.V.)

Background: Randomized controlled trials of long-term survival for infrarenal abdominal aortic aneurysms have compared open surgical repair (OSR) with endovascular aneurysm repair (EVAR) in patients with suitable aortic anatomy for EVAR. However, in clinical practice, patients who do not meet instructions for use (IFU) criteria are often still treated by EVAR despite that some studies show higher graft-related adverse events. The goal of this study was to compare the long-term survival of EVAR and OSR in patients with anatomy outside IFU criteria for EVAR., Methods: This multicenter retrospective cohort study included patients with at least one anatomic IFU violation for EVAR undergoing either elective EVAR or elective OSR for abdominal aortic aneurysm. Demographics, anatomic data, and follow-up data of patients were collected from three academic centers from 2003 to 2016. Device-specific IFU were used for EVAR patients, whereas generic IFU for EVAR were applied to the OSR patients. The primary outcomes were 30-day mortality and long-term all-cause mortality. Secondary outcomes were aneurysm-related mortality and perioperative complications at 30 days. Kaplan-Meier survival and Cox proportional hazards modeling were performed. Inverse propensity score weights were used to adjust for differences in treatment selection., Results: The study population included 202 EVAR patients and 224 OSR patients with at least one anatomic IFU violation for EVAR. EVAR patients were older (78.1 ± 7.3 vs 70.9 ± 7.0 years; P < .001) and less likely to be hypertensive (69.3% vs 79.0%; P = .02) compared with OSR patients. OSR patients were more likely to have proximal aortic neck IFU violations (75.0% vs 47.1%; P < .001) and were less likely to have iliac IFU violations (65.2% vs 79.2%; P < .001). All-cause mortality was 37.6% in the EVAR group and 24.1% in the OSR group with a median follow-up time of 5.2 (3.5-7.2) and 5.4 (2.8-9.3) years, respectively (P < .002). Kaplan-Meier survival analysis revealed a significant association between patients undergoing OSR and increased long-term survival (log-rank P < .0001). When adjusted for possible confounders and weighted for propensity for treatment through Cox hazard modeling, the association remained significant (hazard ratio, 0.6; 95% confidence interval, 0.4-0.9). Aneurysm-related mortality was 3.5% in the EVAR group and 2.2% in the OSR group during long-term follow-up (P < .001)., Conclusions: Our study identified that patients with IFU violations have higher overall long-term survival with open surgery compared with EVAR. Caution should be applied in considering standard EVAR for patients with anatomy outside of IFU., (Copyright © 2019. Published by Elsevier Inc.)

Background: Late-stage isolated medial knee osteoarthritis can be treated with total knee replacement (TKR) or partial knee replacement (PKR). There is high variation in treatment choice and little robust evidence to guide selection. The Total or Partial Knee Arthroplasty Trial (TOPKAT) therefore aims to assess the clinical effectiveness and cost-effectiveness of TKR versus PKR in patients with medial compartment osteoarthritis of the knee, and this represents an analysis of the main endpoints at 5 years., Methods: Our multicentre, pragmatic randomised controlled trial was done at 27 UK sites. We used a combined expertise-based and equipoise-based approach, in which patients with isolated osteoarthritis of the medial compartment of the knee and who satisfied general requirements for a medial PKR were randomly assigned (1:1) to receive PKR or TKR by surgeons who were either expert in and willing to perform both surgeries or by a surgeon with particular expertise in the allocated procedure. The primary endpoint was the Oxford Knee Score (OKS) 5 years after randomisation in all patients assigned to groups. Health-care costs (in UK 2017 prices) and cost-effectiveness were also assessed. This trial is registered with ISRCTN (ISRCTN03013488) and ClinicalTrials.gov (NCT01352247)., Findings: Between Jan 18, 2010, and Sept 30, 2013, we assessed 962 patients for their eligibility, of whom 431 (45%) patients were excluded (121 [13%] patients did not meet the inclusion criteria and 310 [32%] patients declined to participate) and 528 (55%) patients were randomly assigned to groups. 94% of participants responded to the follow-up survey 5 years after their operation. At the 5-year follow-up, we found no difference in OKS between groups (mean difference 1·04, 95% CI -0·42 to 2·50; p=0·159). In our within-trial cost-effectiveness analysis, we found that PKR was more effective (0·240 additional quality-adjusted life-years, 95% CI 0·046 to 0·434) and less expensive (-£910, 95% CI -1503 to -317) than TKR during the 5 years of follow-up. This finding was a result of slightly better outcomes, lower costs of surgery, and lower follow-up health-care costs with PKR than TKR., Interpretation: Both TKR and PKR are effective, offer similar clinical outcomes, and result in a similar incidence of re-operations and complications. Based on our clinical findings, and results regarding the lower costs and better cost-effectiveness with PKR during the 5-year study period, we suggest that PKR should be considered the first choice for patients with late-stage isolated medial compartment osteoarthritis., Funding: National Institute for Health Research Health Technology Assessment Programme., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Carotid endarterectomy (CEA) is a well-established surgical intervention for stroke prevention in patients with carotid stenosis of all ages. However, the decision to proceed to operate in the elderly involves a more complicated risk-benefit assessment due in part to increased comorbidities and reduced life expectancy. Some studies suggest that CEA is more risky in the elderly with worse outcomes, whereas others have found no difference. Our objective was to evaluate and compare outcomes of CEA between elderly and younger patients at our institution., Methods: All hospital charts were reviewed for consecutive patients undergoing CEA from the Jewish General Hospital and the Royal Victoria Hospital from October 2009 to December 2015. Primary outcomes were ipsilateral stroke, death, and restenosis at 30 days and 1 year. Secondary outcomes were cranial nerve injury, myocardial infarction (MI), hematoma, wound infection, cerebral hyperperfusion, and transient ischemic attacks within 30 days. Primary and secondary outcomes were compared between patients aged ≥80 years and <80 years., Results: A total of 361 patients were included in this study with a mean age of 70.2 ± 9.5 years (n = 247 [68.4%] male and n = 272 [75.8%] symptomatic). Elderly patients were more often symptomatic (93.8% vs. 71.6%, P < 0.0001) and had an increased length of stay (2.8 ± 5.3 vs. 1.6 ± 1.8, P = 0.001). There was no statistically significant difference in primary outcomes between patients aged <80 years and ≥80 years, including 30-day stroke (1.7% vs. 0%), death (no deaths in either group), restenosis (8.8% vs. 12.3%), 1-year stroke (1.7% vs. 0%), death (0.7% vs. 0%), or restenosis (14.9% vs. 13.8%). However, elderly patients had significantly increased MI risk postoperatively (4.6% vs. 0.7%, P = 0.01). Other complications, including cranial nerve injury (3.7% in <80 years vs. 4.6% in the elderly group), were similar between the groups., Conclusions: We found that CEA in the elderly does not have an increased risk of stroke or death up to one year postoperatively. However, the postoperative length of stay is increased and complicated by significantly more MIs, which should weigh into the decision of whether to perform CEA on an elderly patient., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Statin-based treatments reduce cardiovascular disease (CVD) risk in patients with non-dialysis chronic kidney disease (CKD), but it is unclear which regimen is the most cost-effective. We used the Study of Heart and Renal Protection (SHARP) CKD-CVD policy model to evaluate the effect of statins and ezetimibe on quality-adjusted life years (QALYs) and health care costs in the United States (US) and the United Kingdom (UK). Net costs below $100,000/QALY (US) or £20,000/QALY (UK) were considered cost-effective. We investigated statin regimens with or without ezetimibe 10 mg. Treatment effects on cardiovascular risk were estimated per 1-mmol/L reduction in low-density lipoprotein (LDL) cholesterol as reported in the Cholesterol Treatment Trialists' Collaboration meta-analysis, and reductions in LDL cholesterol were estimated for each statin/ezetimibe regimen. In the US, atorvastatin 40 mg ($0.103/day as of January 2019) increased life expectancy by 0.23 to 0.31 QALYs in non-dialysis patients with stages 3B to 5 CKD, at a net cost of $20,300 to $78,200/QALY. Adding ezetimibe 10 mg ($0.203/day) increased life expectancy by an additional 0.05 to 0.07 QALYs, at a net cost of $43,600 to $91,500/QALY. The cost-effectiveness findings and policy implications in the UK were similar. In summary, in patients with non-dialysis-dependent CKD, the evidence suggests that statin/ezetimibe combination therapy is a cost-effective treatment to reduce the risk of CVD., (Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: Several low-profile grafts have been created for use in endovascular aneurysm repair in patients with small or difficult to access vessels. Our objective was to evaluate the outcomes of patients undergoing endovascular aneurysm repair with the INCRAFT device in a real-world North American setting., Methods: Consecutive patients undergoing INCRAFT implantation between March 2015 and December 2016 at two McGill University teaching hospitals were enrolled in a prospectively maintained registry. Clinical characteristic and perioperative outcomes were entered into the registry. Two authors performed anatomic measurements from preoperative and postoperative computed tomography angiograms and intraoperative angiograms independently. In cases of disagreement a consensus was reached., Results: We included 61 patients with a median follow-up of 363 days (mean, 344 ± 244 days). Minimum left and right access vessel sizes were 7.5 ± 1.7 mm and 7.4 ± 1.5 mm, respectively. More than 90% of grafts were implanted for aneurysm size or growth. Vessel access was percutaneous in 95% of cases. We had a mean length of stay of 0.88 ± 1.8 days with 57.3% of patients discharged the same day. There were 14 procedural type II endoleaks, 10 new type II leaks that were discovered during follow-up, and 11 that resolved for 77% of patients remaining endoleak free during follow-up. There were no 30-day mortalities. Three cancer-related deaths occurred during follow-up. Early complications included one access site repair for bleeding, one access site repair for dissection, and two aortounilateral conversions with femoral-femoral bypass owing to inadvertent ipsilateral gate cannulation. Long-term complications included one graft limb thrombosis, one intervention for type II endoleak with sac expansion that subsequently became infected and was explanted, and one intervention for a type III endoleak for an intervention. During follow-up, 95% of patients remained reintervention free., Conclusions: Use of the INCRAFT device in a real-world North American setting is relatively safe and effective, and is associated with a low rate of perioperative complications. However, we experienced early issues with inadvertent cannulation and deployment of the contralateral limb in the ipsilateral gate. Therefore, we recommend deploying the entire ipsilateral limb before cannulating the contralateral limb. Data with additional follow-up are needed to assess the long-term effectiveness of the INCRAFT device., (Copyright © 2018. Published by Elsevier Inc.)

Parenteral nutrition (PN) is a complex therapeutic modality provided to neonates, children, and adults for various indications. Surveys have shown that current electronic health record (EHR) systems are in need of functionality enhancement for safe and optimal delivery of PN. This is a consensus statement from the American Society for Parenteral and Enteral Nutrition, the Academy of Nutrition and Dietetics, and the American Society of Health-System Pharmacists outlining some of the key challenges to prescribing, order review/verification, compounding, and administration of PN using EHRs today and is a call to action for clinicians and vendors to optimize their EHRs regarding the PN build and workflow., (Copyright © 2018 American Society of Health-System Pharmacists Inc, American Society for Parenteral and Enteral Nutrition, and the Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Tissue-resident memory (T RM ) CD8 T cells survey a range of non-lymphoid mucosal tissues where they rapidly mediate clearance of viral infections at the entry portals. Vaccines that establish CD8 T RM cells in the cervicovaginal mucosa hold promise for effective immunity against sexually transmitted HIV. We demonstrate that HIV-specific CD8 T RM cells can be established in the murine vaginal mucosa using a combined intranasal and intravaginal mucosal immunization with recombinant influenza-HIV vectors. Using in situ tetramer immunofluorescence microscopy, we found that this mucosally administered prime-boost immunization also resulted in the durable seeding of CD8 T cells in the frontline vaginal epithelial compartment as opposed to the vaginal submucosa. Upon cognate antigen recognition within the vaginal mucosa, these HIV-specific CD8 T RM cells rapidly initiated a tissue-wide state of immunity. The activation of HIV-specific CD8 T RM cells resulted in the upregulation of endothelial vessel addressin expression and substantial recruitment of both adaptive and innate immune cells in the vaginal mucosa. These findings suggest that the epithelial localization of HIV-specific CD8 T RM cell populations and their capacity to rapidly activate both arms of the immune system could significantly augment frontline defenses against vaginal HIV infection.

In 2015, the US Preventive Services Task Force updated their hypertension recommendations to advise that adults with elevated office blood pressure (BP) undergo out-of-office BP measurement to exclude white coat hypertension before diagnosis. Our goal was to determine the most important barriers to primary care providers' ordering ambulatory and home BP monitoring in the United States. We enrolled 63 primary care providers into nominal group panels in which participants iteratively listed and ranked barriers to ambulatory and home BP monitoring. Top-ranked barriers to ambulatory BP monitoring were challenges in accessing testing, costs of testing, concerns about the willingness or ability of patients to successfully complete tests, and concerns about the accuracy and benefits of testing. Top-ranked barriers to home BP monitoring were concerns about compliance with the correct test protocol, accuracy of tests results, out-of-pocket costs of home BP devices, and time needed to instruct patients on home BP monitoring protocol. Efforts to increase the use of ambulatory and home BP monitoring by primary care providers in the United States should prioritize increasing the financial and personnel resources available for testing and addressing provider concerns about patients' ability to conduct high-quality tests., (Copyright © 2017 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

Interstrand DNA-DNA cross-links are highly toxic lesions that are important in medicinal chemistry, toxicology, and endogenous biology. In current models of replication-dependent repair, stalling of a replication fork activates the Fanconi anemia pathway and cross-links are "unhooked" by the action of structure-specific endonucleases such as XPF-ERCC1 that make incisions flanking the cross-link. This process generates a double-strand break, which must be subsequently repaired by homologous recombination. Recent work provided evidence for a new, incision-independent unhooking mechanism involving intrusion of a base excision repair (BER) enzyme, NEIL3, into the world of cross-link repair. The evidence suggests that the glycosylase action of NEIL3 unhooks interstrand cross-links derived from an abasic site or the psoralen derivative trioxsalen. If the incision-independent NEIL3 pathway is blocked, repair reverts to the incision-dependent route. In light of the new model invoking participation of NEIL3 in cross-link repair, we consider the possibility that various BER glycosylases or other DNA-processing enzymes might participate in the unhooking of chemically diverse interstrand DNA cross-links., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Study Objective: To demonstrate a possible alternative treatment for postdural puncture headache (PDPH)., Design: Postdural puncture headache is a common complication associated with neuraxial anesthesia and unintentional dural puncture. Epidural blood patch (EBP) is the standard therapy for PDPH but has risks including pain, dural puncture, and infection. Transnasal sphenopalatine ganglion block (SPGB) has been successfully used to treat migraine, cluster headache, and trigeminal neuralgia. This is a small case series in which SPGB was used to treat PDPH in 3 obstetric patients., Setting: Labor and delivery suite., Patients: Three postpartum patients with PDPH were studied. One patient was American Society of Anesthesiologists physical status 1, and the other 2 were American Society of Anesthesiologists physical status 2., Interventions: Transnasal SPGB using cotton-tipped applicators and 2% viscous lidocaine was performed on all 3 patients., Measurements: Height, weight, and vital signs were measured on all patients. In addition, the numeric rating scale (0-10) was used to quantify the pain level while in the sitting position preprocedure, immediately postprocedure, 24 hours postprocedure, and 48 hours postprocedure., Main Results: All 3 patients had significant pain relief following the SPGB without the need for EBP., Conclusions: When comparing the risks of a transnasal SPGB, which include bleeding and temporary discomfort, against those of an EBP, which are documented as dural puncture, neurologic complications, bleeding, and infection, it seems reasonable to offer the SPGB before EBP., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: Mucormycosis is a rare but serious sequelae of penetrating trauma [1-5]. In spite of aggressive management, mortality remains high due to dissemination of infection. We completed a review of literature to determine the most optimal treatment of cutaneous mucormycosis which occurs secondary to penetrating trauma., Methods: We completed a review regarding the management of mucormycosis in trauma patients. We selected a total of 36 reports, of which 18 were case-based, for review., Results: Surgical debridement is a primary predictor of improved outcomes in the treatment of mucormycosis [3,6,7]. Anti-fungal therapy, especially lipid soluble formulation of Amphotericin B, is helpful as an adjunct or when surgical debridement has been maximally achieved. Further research is needed to fully evaluate the impact of topical dressings; negative pressure wound therapy is helpful., Conclusion: An aggressive and early surgical approach, even at the expense of disfigurement, is necessary to reduce mortality in the setting of cutaneous mucormycosis that results from penetrating trauma [4,8,9]. Anti-fungal therapy and negative pressure wound therapy are formidable adjuncts., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: This survey aims to explore trainees' perspectives on how Canadian vascular surgery training programs are using simulation in teaching and assessing technical skills through a cross-sectional national survey., Methods: A 10-min online questionnaire was sent to Program Directors of Canada's Royal College of Physicians and Surgeons' of Canada approved training programs in vascular surgery. This survey was distributed among residents and fellows who were studying in the 2013-2014 academic year., Results: Twenty-eight (58%) of the 48 Canadian vascular surgery trainees completed the survey. A total of 68% of the respondents were part of the 0 + 5 integrated vascular surgery training program. The use of simulation in the assessment of technical skills at the beginning of training was reported by only 3 (11%) respondents, whereas 43% reported that simulation was used in their programs in the assessment of technical skills at some time during their training. Training programs most often provided simulation as a method of teaching and learning endovascular abdominal aortic or thoracic aneurysm repair (64%). Furthermore, 96% of trainees reported the most common resource to learn and enhance technical skills was dialog with vascular surgery staff., Conclusions: Surveyed vascular surgery trainees in Canada report that simulation is rarely used as a tool to assess baseline technical skills at the beginning of training. Less than half of surveyed trainees in vascular surgery programs in Canada report that simulation is being used for skills acquisition. Currently, in Canadian training programs, simulation is most commonly used to teach endovascular skills., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: This study determined the outcome of the contralateral internal iliac artery (IIA) in patients undergoing aortouni-iliac (AUI) endovascular abdominal aortic aneurysm repair (EVAR) with a femorofemoral bypass., Methods: This retrospective study evaluated 131 consecutive patients undergoing AUI EVAR with femorofemoral bypass at the McGill University Health Center from October 2001 to November 2010. One hundred patients with preoperatively patent contralateral IIA met inclusion criteria for the study. Preoperative demographics and preoperative and postoperative contrast-enhanced computed tomography (CT) scans with multiplanar reconstruction were reviewed for all patients. The last available postoperative CT imaging for all patients was identified and evaluated for contralateral IIA patency. Patency in preoperative and postoperative CT scans was defined as contrast enhancement of the IIA in continuity with the external iliac artery and absence of >50% stenosis at the origin of the IIA. Clinical outcome focused on postoperative pelvic ischemia and reported symptoms of buttock claudication., Results: Mean age at the time of operation was 77.6 ± 6.7 years, and 78% were male. Mean clinical follow-up was 29.2 months after surgery, and mean follow-up of imaging with intravenous contrast was 30.6 months. The last imaging follow-up showed 67 patients (67%) had a patent contralateral IIA and that the IIAs in 33 patients (33%) were occluded (25 [76%]) or stenotic (8 [24%]). Of the patients with IIA occlusion, 80% (20 of 25) were occluded on the first postoperative imaging (median, 8.5 days). Buttock claudication was reported in 18% (6 of 33 patients) with an occluded IIA compared with only 3% (2 of 67 patients) of patients with a patent contralateral IIA on final imaging follow-up (18% vs 3%; P = .014). There were no observed cases of buttock necrosis, spinal ischemia, or colonic ischemia., Conclusions: Our findings suggest that AUI EVAR with femorofemoral bypass is associated with a significant incidence of contralateral IIA malperfusion on postoperative CT imaging. Occlusion appears to occur early in the postoperative period in most patients, and patient-reported buttock claudication is observed significantly more frequently in patients with an occluded IIA compared with those with a patent IIA. More serious pelvic ischemic complications were not seen in this series. Further study is required to determine whether modification of the procedure can prevent contralateral IIA occlusion and the development of buttock claudication., (Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Fever has been recognized as an important symptom of disease since ancient times. For many years, fever was treated as a putative life-threatening phenomenon. More recently, it has been recognized as an important part of the body's defense mechanisms; indeed at times it has even been used as a therapeutic agent. The knowledge of the functional role of the central nervous system in the genesis of fever has greatly improved over the last decade. It is clear that the febrile process, which develops in the sick individual, is just one of many brain-controlled sickness symptoms. Not only will the sick individual appear "feverish" but they may also display a range of behavioral changes, such as anorexia, fatigue, loss of interest in usual daily activities, social withdrawal, listlessness or malaise, hyperalgesia, sleep disturbances and cognitive dysfunction, collectively termed "sickness behavior". In this review we consider the issue of whether fever and sickness behaviors are friend or foe during: a critical illness, the common cold or influenza, in pregnancy and in the newborn. Deciding whether these sickness responses are beneficial or harmful will very much shape our approach to the use of antipyretics during illness., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Heparin-induced thrombocytopenia (HIT) is an immune-mediated thrombocytopenia resulting from prior heparin exposure. It can be associated with limb- or life-threatening thrombotic events. Patients undergoing any vascular procedures including endovascular procedures that require heparin administration are at risk. There is very little reported in the literature with regards to thrombosis associated with HIT after endovascular aortic aneurysm repair. All reported cases of HIT thrombosis presented as acute arterial lower limb ischemia or deep vein thrombosis. In this report, we present a case of HIT complicated by stent graft thrombosis and bowel ischemia., (Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Standards of Excellence in Nutrition and Dietetics for an Organization is a self-assessment tool to measure and evaluate an organization's program, services, and initiatives that identify and distinguish the Registered Dietitian Nutritionist (RDN) brand as the professional expert in food and nutrition. The Standards of Excellence will serve as a road map to recognize RDNs as leaders and collaborators. Standards of Excellence criteria apply to all practice segments of nutrition and dietetics: health care, education and research, business and industry, and community nutrition and public health. Given the membership's call to action to be recognized for their professional expertise, the Academy of Nutrition and Dietetics Quality Management Committee developed four Standards of Excellence in Nutrition and Dietetics for Organizations: Quality of Leadership, Quality of Organization, Quality of Practice, and Quality of Outcomes. Within each standard, specific indicators provide strategies for an organization to demonstrate excellence. The Academy will develop a self-evaluation scoring tool to assist the organization in applying and implementing one or more of the strategies in the Standards of Excellence indicators. The organization can use the self-assessment tool to establish itself as a Center of Excellence in Nutrition and Dietetics. The role examples illustrate initiatives RDNs and organizations can take to identify themselves as a Center of Excellence in Nutrition and Dietetics. Achieving the Excellence level is an important collaborative initiative between nutrition and dietetics organizations and the Academy to provide increased autonomy, supportive management, respect within peers and community, opportunities for professional development, support for further education, and compensation for the RDN. For purposes of the Standards, "organization" means workplace or practice setting., (Copyright © 2014 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Objective: The risk of endoleak and reintervention after endovascular abdominal aortic aneurysm repair necessitates lifelong surveillance, which has associated costs, radiation exposure, and risk of nephrotoxicity. The best imaging method and timing of surveillance remain controversial. We sought to determine if a negative result of first postoperative imaging by computed tomography (CT) scan was predictive of decreased need for reintervention. We hypothesized that initial negative postoperative imaging could identify a low-risk cohort of patients who could be observed less frequently., Methods: Retrospective review of prospectively collected institutional outcomes data (2004-2009) included stratification according to postoperative imaging results. Baseline characteristics and aneurysm morphology were compared between the two groups. Cox regression analysis was used to identify risk factors predictive for endoleak-related reintervention. Kaplan-Meier survival curves were used to plot freedom from all-cause reintervention and endoleak-related reintervention for the two groups., Results: A total of 134 patients were included in the analysis. A total of 107 patients (80%) had negative initial postoperative imaging, whereas 27 patients (20%) had evidence of an endoleak. There were no significant differences between the two groups in terms of comorbidities or anticoagulation status. Kaplan-Meier survival curves showed that there was a significant difference between those patients who had a negative initial CT scan and those who had a positive scan for endoleak in terms of both overall reintervention rates and leak-related reintervention rates. Endoleak on the first postoperative CT scan was associated with a hazard ratio of 6.37 (confidence interval, 2.02-20.10; P = .002) for leak-related reintervention and a hazard ratio of 6.01 (confidence interval, 2.24-16.17; P < .001) for all-cause reintervention., Conclusions: Patients with negative initial postoperative imaging were significantly less likely to require repeated interventions. These data suggest that these patients are candidates for less rigorous screening protocols., (Copyright © 2014 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

In mice a 50% calorie restriction (CR) for 28days attenuates sickness behavior after lipopolysaccharide (LPS) and these mice demonstrate a central anti-inflammatory bias. This study examined the dose-dependent effect of CR on sickness behavior (fever, anorexia, cachexia) and peripheral immune markers post-LPS. Male Sprague-Dawley rats fed ad libitum or CR by 50% for 14, 21, or 28days were injected on day 15, 22, or 29 with 50μg/kg of LPS or saline (1mL/500g). Changes in body temperature (Tb), locomotor activity, body weight, and food intake were determined. A separate cohort of rats was fed ad libitum or CR by 50% for 28days and serum levels of corticosterone (CORT), interleukin 6 (IL-6), and IL-10 were determined at 0, 2, and 4h post-LPS. The rats CR for 28days demonstrated the largest attenuation of sickness behavior: no fever, limited reduction in locomotor activity, no anorexia, and reduced cachexia following LPS. Rats CR for 14 and 21days demonstrated a partial attenuation of sickness behavior. Rats CR for 14days demonstrated a larger increase in Tb, larger reduction in locomotor activity, and larger weight loss compared to rats CR for 21days. Serum CORT was increased at 2h post-LPS in ad libitum and CR groups; however it was two times larger in the CR animals. Levels of IL-6 were significantly attenuated at 2h post-LPS in the CR animals. IL-10 levels were similar post-LPS. CR results in an enhanced anti-inflammatory response in the form of increased CORT and diminished pro-inflammatory signals., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Calorie restriction (CR) has been shown to increase longevity and elicit many health promoting benefits including delaying immunosenescence and attenuating neurodegeneration in animal models of Alzheimer's disease and Parkinson's disease. CR also suppresses microglial activation following cortical injury and aging. We previously demonstrated that CR attenuates lipopolysaccharide (LPS)-induced fever and shifts hypothalamic signaling pathways to an anti-inflammatory bias; however, the effects of CR on LPS-induced microglial activation remain largely unexplored. The current study investigated regional changes in LPS-induced microglial activation in mice exposed to 50% CR for 28days. Immunohistochemistry was conducted to examine changes in ionized calcium-binding adapter molecule-1 (Iba1), a protein constitutively expressed by microglia, in a total of 27 brain regions involved in immunity, stress, and/or thermoregulation. Exposure to CR attenuated LPS-induced fever, and LPS-induced microglial activation in a subset of regions: the arcuate nucleus (ARC) and ventromedial nucleus of the hypothalamus (VMH) and the subfornical organ (SFO). Microglial activation in the ARC and VMH was positively correlated with body temperature. These data suggest that CR exerts effects on regionally specific populations of microglia; particularly, in appetite-sensing regions of the hypothalamus, and/or regions lacking a complete blood brain barrier, possibly through altered pro- and anti-inflammatory signaling in these regions., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Road traffic crashes are responsible for a vast amount of death and disability in developing countries. This study uses a bottom up, micro-costing approach to determine the cost of road traffic related crashes in South Africa., Methods: Using the data from one hundred consecutive RTC related admissions to a regional hospital in South Africa we performed a bottom up costing study. To calculate costs patients were reviewed every 48 h and all interventions were recorded for each individual patient. Prices of interventions were obtained from hospital pricelists. A total cost was calculated on an individual basis., Results: The total cost of in-patient care for these patients was US $6,98,850. Upper limb injuries were the most expensive, and the total cost increased with the number of body regions injured. The biggest expenditure was on ward overheads ($2,81,681). Ninety operations were performed - the total cost of theatre time was $1,48,230 and the cost of orthopaedic implants was $1,26,487., Conclusion: The cost of care of a RTC victim is significant. In light of the high numbers of RTC victims admitted over the course of the year this is a significant cost burden for a regional hospital to bear. This cost must be taken into account when allocating hospital budgets., (Copyright © 2013 Elsevier Ltd. All rights reserved.)