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Introduction: As new treatments have become established, more frail pre-ICU patients are being admitted to intensive care units (ICUs); this is creating new challenges to provide adequate care and to ensure that resources are allocated in an ethical and economical manner. This systematic review evaluates the current standard for assessing frailty on the ICU, including methods of assessment, time point of measurements, and cut-offs. Methods: A systematic search was conducted on MEDLINE, Clinical Trials, Cochrane Library, and Embase. Randomized and non-randomized controlled studies were included that evaluated diagnostic tools and ICU outcomes for frailty. Exclusion criteria were the following: studies without baseline assessment of frailty on ICU admission, studies in paediatric patients or pregnant women, and studies that targeted very narrow populations of ICU patients. Eligible articles were included until January 31, 2021. Methodological quality was assessed using the Newcastle-Ottawa Scale. No meta-analysis was performed, due to heterogeneity. Results: N = 57 articles (253,376 patients) were included using 19 different methods to assess frailty or a surrogate. Frailty on ICU admission was most frequently detected using the Clinical Frailty Scale (CFS) (n = 35, 60.3%), the Frailty Index (n = 5, 8.6%), and Fried’s frailty phenotype (n = 6, 10.3%). N = 22 (37.9%) studies assessed functional status. Cut-offs, time points, and manner of baseline assessment of frailty on ICU admission varied widely. Frailty on ICU admission was associated with short- and long-term mortality, functional and cognitive impairment, increased health care dependency, and impaired quality of life post-ICU discharge. Conclusions: Frailty assessment on the ICU is heterogeneous with respect to methods, cut-offs, and time points. The CFS may best reflect frailty in the ICU. Frailty assessments should be harmonized and performed routinely in the critically ill.

Long-duration surgery requires repeated administration of antimicrobial prophylaxis (amp). Amp “redosing” reduces incidence of surgical site infections (SSI) but is frequently omitted. Clinical relevance of redosing timing needs to be investigated. Here, we evaluated the effects of compliance with amp redosing and its timing on SSI incidence in prolonged duration surgery. Data from >9000 patients undergoing visceral, trauma, or vascular surgery with elective or emergency treatment in two tertiary referral Swiss hospitals were analyzed. All patients had to receive amp preoperatively and redosing, if indicated. Antibiotics used were cefuroxime (1.5 or 3 g, if weight >80 kg), or cefuroxime and metronidazole (1.5 and 0.5 g, or 3 and 1 g doses, if weight >80 kg). Alternatively, in cases of known or suspected allergies, vancomycin (1 g), gentamicin (4 mg/Kg), and metronidazole or clindamycin (300 mg) with or without ciprofloxacin (400 mg) were used. Association of defined parameters, including wound class, ASA scores, and duration of operation, with SSI incidence was explored. In the whole cohort, SSI incidence significantly correlated with duration of surgery (ρ = 0.73, p = 0.031). In 593 patients undergoing >240 min long interventions, duration of surgery was the only parameter significantly (p

Background: Bevacizumab combined with chemotherapy has been shown to improve response rate and progression free survival in metastatic breast cancer. The aim of the health economic analysis (HEA) of this study was to demonstrate that the combination regimen of bevacizumab with cyclophosphamide and capecitabine (metronomic chemotherapy) compared to bevacizumab and paclitaxel treatment decreases overall treatment costs in patients with breast cancer without suffering any losses in effectiveness. Methods: In this multicenter, randomized phase III trial, we compared bevacizumab (10 mg/kg i.v. q 2 weeks) with either paclitaxel (90 mg/m2) i.v. on days 1, 8, and 15 of a 4 week cycle (arm A) or daily oral capecitabine (3x500 mg) and cyclophosphamide (50 mg, arm B) as first-line treatment in patients with HER2-negative advanced breast cancer. Primary endpoint of the health economic analysis was the total incurred treatment costs until patients stopped trial treatment (time to trial treatment stop (TTS)). TTS was defined as treatment stop due to progressive disease, symptom deterioration, unacceptable adverse events, patient refusal, death or other reasons for withdrawal. The HEA adopted a health system perspective including all substantial direct medical costs incurred in the treatment of the patient. Health-related quality of life was measured by means of the EQ-5D utility instrument. Statistical differences between costs in the treatment arms were tested by the Wilcoxon rank-sum test. A global multivariable linear model, with a gamma distribution and a logarithmic cost transformation was used to analyze the costs for the two arms controlled for age. Results: Between September 2010 and December 2012, 147 patients were included at 22 centers in Switzerland, 73 (intention to treat (ITT) n=71) in arm A and 74 (ITT n=68) in arm B. The clinical study results will be presented at ASCO 2014. In January 2014, 66 patients in arm A and 63 in arm B of the ITT patients had reached TTS and were analyzed. Mean TTS was 7.3 month in arm A (95%CI 6.3–8.2, median 5.9; quality adjusted mean 5.9, median 5.1) versus 8.5 month (95%CI 6.7–10.2, median 6.8; quality adjusted mean 6.5, median 5.0) in arm B. Total incurred mean costs per patient were CHF 69’474 in arm A (95%CI 60’624–78’324, median CHF 61’815; mean cost per month CHF 10’044) versus CHF 80’324 in arm B (95%CI 62’975–97’672, median CHF 61’751; mean cost per month CHF 10’229). There were no significant differences in costs between the treatment arms and age had no significant effect on the results. Conclusion: Metronomic chemotherapy plus bevacizumab compared to bevacizumab and paclitaxel treatment showed no substantial reductions in treatment costs. In view of the clinical results the HEA does not favor the metronomic approach. An incremental cost-utility analysis is planned. Citation Format: Klazien W Matter-Walstra, Martin Bigler, Matthias Schwenkglenks, Daniela Bertschi, Jörg Brechbühl, Ursula Hasler-Strub, Roger von Moos, Andreas Müller, Ralph Winterhalder, Christoph Rochlitz. Health economic evaluation of: Bevacizumab plus paclitaxel vs. bevacizumab plus metronomic cyclophosphamide and capecitabine as first-line therapy in patients with HER2-negative advanced breast cancer: A multicenter, randomized phase III trial - SAKK 24/0 [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-10-06.

ObjectiveRecent studies have shown that mechanically unloading a failing heart may induce reverse remodeling and functional improvement. However, these benefits may be balanced by an unloading-related remodeling including myocardial atrophy that might lead to decrease in function. Using a model of heterotopic heart transplantation, we aimed to characterize the myocardial changes induced by long-term unloading.Material and MethodsMacroscopic as well as cellular and functional changes were followed in normal hearts unloaded for a 3-month period. Microscopic parameters were evaluated with stereologic methodology. Myocardial contractile function was quantified with a Langendorff isolated, perfused heart technique.ResultsAtrophy was macroscopically obvious and accompanied by a 67% reduction of the myocyte volume and a 43% reduction of the interstitial tissue volume, thus accounting for a shift of the myocyte/connective tissue ratio in favor of noncontractile tissue. The absolute number of cardiomyocyte nuclei decreased from 64.7 ± 5.1 × 107 in controls to 22.6 ± 3.7 × 107 (30 days) and 21.6 ± 3.1 × 107 (90 days) after unloading (P < .05). The numeric nucleic density in the unloaded myocardium, as well as the mean cardiomyocyte volume per cardiomyocyte nucleus, remained constant throughout the 90 days of observation. Functional data indicated an increase in ventricular stiffness, although contractile function was preserved, as confirmed by unaltered maximal developed pressure and increased contractility (maximum rate of left ventricular pressure development) and relaxation (minimum rate of left ventricular pressure development).ConclusionAtrophic remodeling involves both the myocyte and interstitial tissue compartment. These data suggest that although there is decreased myocardial volume and increased stiffness, contractile capacity is preserved in the long-term unloaded heart.