To assess the benefit of Enhanced Recovery After Surgery (ERAS) on length of stay (LOS), postoperative complications, 30-day readmission, and cost in gynecologic oncology.
A systematic literature ...search was performed in MEDLINE, EMBASE, Cochrane Register of Controlled Trials, and Web of Science for all peer-reviewed cohort studies and controlled trials on ERAS involving gynecologic oncology patients. Abstracts, commentaries, non-controlled studies, and studies without specific data on gynecologic oncology patients were excluded. Meta-analysis was performed on the primary endpoint of LOS. Subgroup analyses were performed based on risk of bias of the studies included, number of ERAS elements, and ERAS compliance. Secondary endpoints were readmission rate, complications, and cost.
A total of 31 studies (6703 patients) were included: 5 randomized controlled trials, and 26 cohort studies. Meta-analysis of 27 studies (6345 patients) demonstrated a decrease in LOS of 1.6 days (95% confidence interval, CI 1.2–2.1) with ERAS implementation. Meta-analysis of 21 studies (4974 patients) demonstrated a 32% reduction in complications (OR 0.68, 95% CI 0.55–0.83) and a 20% reduction in readmission (OR 0.80, 95% CI 0.64–0.99) for ERAS patients. There was no difference in 30-day postoperative mortality (OR 0.61, 95% CI 0.23–1.6) for ERAS patients compared to controls. No difference in the odds of complications or reduction in LOS was observed based on number of included ERAS elements or reported compliance with ERAS interventions. The mean cost savings for ERAS patients was $2129 USD (95% CI $712 - $3544).
ERAS protocols decrease LOS, complications, and cost without increasing rates of readmission or mortality in gynecologic oncology surgery. This evidence supports implementation of ERAS as standard of care in gynecologic oncology.
•Enhanced Recovery After Surgery (ERAS) is a global surgical quality improvement initiative.•ERAS protocols decrease length of stay, complications, and cost without increasing readmission in gynecologic oncology.•Meta-analysis of evidence supports implementation of ERAS as standard of care in gynecologic oncology.
Enhanced recovery pathways have been shown to reduce length of stay without increasing readmission or complications in numerous areas of surgery. Uptake of gynecologic oncology ERAS guidelines has ...been limited. We describe the effect of ERAS guideline implementation in gynecologic oncology on length of stay, patient outcomes, and economic impact for a province-wide single-payer system.
We compared pre- and post-guideline implementation outcomes in consecutive staging and debulking patients at two centers that provide the majority of surgical gynecologic oncology care in Alberta, Canada between March 2016 and April 2017. Clinical outcomes and compliance were obtained using the ERAS Interactive Audit System. Patients were followed until 30 days after discharge. Negative binomial regression was employed to adjust for patient characteristics.
We assessed 152 pre-ERAS and 367 post-ERAS implementation patients. Mean compliance with ERAS care elements increased from 56% to 77.0% after implementation (p < 0.0001). Median length of stay for all surgeries decreased from 4.0 days to 3.0 days post-ERAS (p < 0.0001), which translated to an adjusted LOS decrease of 31.4% (95% CI = 21.7% - 39.9%, p < 0.0001). In medium/high complexity surgery median LOS was reduced by 2.0 days (p = 0.0005). Complications prior to discharge decreased from 53.3% to 36.2% post-ERAS (p = 0.0003). There was no significant difference in readmission (p = 0.6159), complications up to 30 days (p = 0.6274), or mortality (p = 0.3618) between the cohorts. The net cost savings per patient was $956 (95%CI: $162 to $1636).
Systematic implementation of ERAS gynecologic oncology guidelines across a healthcare system improves patient outcomes and saves resources.
•Implementation of ERAS gynecologic oncology guidelines results in significant clinical improvements and cost savings.•Use of an audit system allows measurement of compliance to the individual ERAS recommendations.•ERAS teams should strive to improve compliance to guidelines as this translates into improved outcomes.
Despite evidence supporting its use, many Enhanced Recovery After Surgery (ERAS) recommendations remain poorly adhered to and barriers to ERAS implementation persist. In this second updated ERAS® ...Society guideline, a consensus for optimal perioperative care in gynecologic oncology surgery is presented, with a specific emphasis on implementation challenges.
Based on the gaps identified by clinician stakeholder groups, nine implementation challenge topics were prioritized for review. A database search of publications using Embase and PubMed was performed (2018–2023). Studies on each topic were selected with emphasis on meta-analyses, randomized controlled trials, and large prospective cohort studies. These studies were then reviewed and graded by an international panel according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system.
All recommendations on ERAS implementation challenge topics are based on best available evidence. The level of evidence for each item is presented accordingly.
The updated evidence base and recommendations for stakeholder derived ERAS implementation challenges in gynecologic oncology are presented by the ERAS® Society in this consensus review.
•Despite best efforts, many of the ERAS recommendations remain poorly adhered to and barriers to ERAS implementation persist.•This guideline update summarizes evidence investigating ERAS implementation challenges highlighted by stakeholder groups.•Overcoming implementation barriers will increase ERAS uptake and improve clinical outcomes for patients.
We demonstrate the negative effect of depth-dependent spherical aberration on femtosecond laser written waveguides fabricated in the high pulse repetition rate regime (1 MHz). Writing inside ...borosilicate Eagle 2000 glass, we show that, even in the cumulative heating regime, the focal distortion encountered at greater depths prevents the formation of single-mode waveguides. A liquid crystal spatial light modulator was incorporated for adaptive optics aberration correction, enabling low-loss single-mode waveguides to be written at various depths up to 1 mm. This result allows the accurate fabrication of 3D photonic devices consisting of uniform waveguides located at different depths.
IntroductionIron-deficiency anaemia is common in gynaecological oncology patients. Blood transfusions are immunosuppressive and carry immediate and long-term risks. Oral iron replacement remains the ...standard of care but requires prolonged treatment courses associated with gastrointestinal side effects, poor compliance and variable absorption in cancer patients. Intravenous iron has been shown to decrease the need for allogeneic blood transfusion in gynaecological oncology patients undergoing chemotherapy, but the efficacy of this treatment in the preoperative period is unknown. The goal of this pilot study is to determine the effect of intravenous ferric derisomaltose on preoperative haemoglobin in patients undergoing surgery for gynaecological malignancy.Methods and analysisWe will conduct a pilot single-centre, parallel-arm randomised controlled trial of intravenous ferric derisomaltose versus placebo among consenting patients with iron-deficiency anaemia having elective major surgery on the gynaecological oncology service. Patients, clinicians and outcome assessors will be blinded. The intervention consists of a single infusion of 500–1000 mg of intravenous ferric derisomaltose administered a minimum of 21 days prior to the planned operation. The primary outcome is mean preoperative haemoglobin concentration measured 0–3 days prior to surgery in patients receiving intravenous ferric derisomaltose compared with those receiving placebo. Secondary outcomes include the following: change in haemoglobin concentration, postoperative haemoglobin concentration, perioperative blood transfusion rates, patient-reported quality of life scores (Quality of Recovery 15, Modified Short Form 36 v1, EuroQol 5-dimension 5-level and Functional Assessment of Cancer Therapy – Anaemia), surgical site infection, complication rates, length of hospital stay and readmission rate. Analyses will follow intention-to-treat principles for all randomised participants. All patients will be followed up to 60 days following surgery.Ethics and disseminationEthical approval has been granted by Health Research Ethics Board of Alberta (Project ID: HREBA.CC-22–0187) and Health Canada (HC6-024-c264013). Results will be disseminated through presentation at scientific conferences, peer-reviewed publication and social and traditional media.Trial registration numberNCT05407987.
Inclisiran inhibits hepatic synthesis of proprotein convertase subtilisin-kexin type 9. Previous studies suggest that inclisiran might provide sustained reductions in low-density lipoprotein (LDL) ...cholesterol levels with infrequent dosing.
We enrolled patients with atherosclerotic cardiovascular disease (ORION-10 trial) and patients with atherosclerotic cardiovascular disease or an atherosclerotic cardiovascular disease risk equivalent (ORION-11 trial) who had elevated LDL cholesterol levels despite receiving statin therapy at the maximum tolerated dose. Patients were randomly assigned in a 1:1 ratio to receive either inclisiran (284 mg) or placebo, administered by subcutaneous injection on day 1, day 90, and every 6 months thereafter over a period of 540 days. The coprimary end points in each trial were the placebo-corrected percentage change in LDL cholesterol level from baseline to day 510 and the time-adjusted percentage change in LDL cholesterol level from baseline after day 90 and up to day 540.
A total of 1561 and 1617 patients underwent randomization in the ORION-10 and ORION-11 trials, respectively. Mean (±SD) LDL cholesterol levels at baseline were 104.7±38.3 mg per deciliter (2.71±0.99 mmol per liter) and 105.5±39.1 mg per deciliter (2.73±1.01 mmol per liter), respectively. At day 510, inclisiran reduced LDL cholesterol levels by 52.3% (95% confidence interval CI, 48.8 to 55.7) in the ORION-10 trial and by 49.9% (95% CI, 46.6 to 53.1) in the ORION-11 trial, with corresponding time-adjusted reductions of 53.8% (95% CI, 51.3 to 56.2) and 49.2% (95% CI, 46.8 to 51.6) (P<0.001 for all comparisons vs. placebo). Adverse events were generally similar in the inclisiran and placebo groups in each trial, although injection-site adverse events were more frequent with inclisiran than with placebo (2.6% vs. 0.9% in the ORION-10 trial and 4.7% vs. 0.5% in the ORION-11 trial); such reactions were generally mild, and none were severe or persistent.
Reductions in LDL cholesterol levels of approximately 50% were obtained with inclisiran, administered subcutaneously every 6 months. More injection-site adverse events occurred with inclisiran than with placebo. (Funded by the Medicines Company; ORION-10 and ORION-11 ClinicalTrials.gov numbers, NCT03399370 and NCT03400800.).
Enhanced Recovery After Surgery (ERAS) is a global surgical quality improvement program that started in colorectal surgery and has now expanded to numerous specialties, including gynecologic ...oncology. ERAS guidelines comprise multidisciplinary, evidence-based recommendations in the preoperative, intraoperative, and postoperative period; these interventions broadly encompass patient education, anesthetic choice, multimodal pain control, avoidance of unnecessary drains, maintenance of nutrition, and prevention of emesis. Implementation of ERAS has been shown to be associated with improved clinical outcomes (length of hospital stay, complications, readmissions) and cost. Marx and colleagues first demonstrated the feasibility of ERAS in gynecologic oncology in 2003; since then, over 30 comparative studies and 4 guidelines have been published encompassing major gynecologic surgery, cytoreductive surgery, and vulvar/vaginal surgery. Implementation of ERAS in gynecologic oncology has been demonstrated to provide improvements in length of stay, complications, cost, opioid use, and patient satisfaction. Increased compliance with ERAS guidelines has been associated with greater improvement in outcomes.
The worldwide pandemic involving the novel respiratory syndrome (COVID-19) has forced health care systems to delay elective operations, including abdominal aortic aneurysm (AAA) repair, to conserve ...resources. This study provides a structured analysis of the decision to delay AAA repair and quantify the potential for harm.
A decision tree was constructed modeling immediate repair of AAA relative to an initial nonoperative (delayed repair) approach. Risks of COVID-19 contraction and mortality, aneurysm rupture, and operative mortality were considered. A deterministic sensitivity analysis for a range of patient ages (50 to >80), probability of COVID-19 infection (0.01%-30%), aneurysm size (5.5 to >7 cm), and time horizons (3-9 months) was performed. Probabilistic sensitivity analyses were conducted for three representative ages (60, 70, and 80). Analyses were conducted for endovascular aortic aneurysm repair (EVAR) and open surgical repair (OSR).
Patients with aneurysms 7 cm or greater demonstrated a higher probability of survival when treated with immediate EVAR or OSR, compared with delayed repair, for patients under 80 years of age. When considering EVAR for aneurysms 5.5 to 6.9 cm, immediate repair had a higher probability of survival except in settings with a high probability of COVID-19 infection (10%-30%) and advanced age (70-85+ years). A nonoperative strategy maximized the probability of survival as patient age or operative risk increased. Probabilistic sensitivity analyses demonstrated that patients with large aneurysms (>7 cm) faced a 5.4% to 7.7% absolute increase in the probability of mortality with a delay of repair of 3 months. Young patients (60-70 years) with aneurysms 6 to 6.9 cm demonstrated an elevated risk of mortality (1.5%-1.9%) with a delay of 3 months. Those with aneurysms 5 to 5.9 cm demonstrated an increased survival with immediate repair in young patients (60); however, this was small in magnitude (0.2%-0.8%). The potential for harm increased as the length of surgical delay increased. For elderly patients requiring OSR, in the context of endemic COVID-19, delay of repair improves the probability of survival.
The decision to delay operative repair of AAA should consider both patient age and local COVID-19 prevalence in addition to aneurysm size. EVAR should be considered when possible due to a reduced risk of harm and lower resource utilization.
Dorsal-ventral patterning of the
Drosophila
embryo depends on the NFκB superfamily transcription factor Dorsal (Dl). Toll receptor activation signals for degradation of the IκB inhibitor Cactus ...(Cact), leading to a ventral-to-dorsal nuclear Dl gradient. Cact is critical for Dl nuclear import, as it binds to and prevents Dl from entering the nuclei. Quantitative analysis of
cact
mutants revealed an additional Cact function to promote Dl nuclear translocation in ventral regions of the embryo. To investigate this dual Cact role, we developed a predictive model based on a reaction-diffusion regulatory network. This network distinguishes non-uniform Toll-dependent Dl nuclear import and Cact degradation, from the Toll-independent processes of Cact degradation and reversible nuclear-cytoplasmic Dl flow. In addition, it incorporates translational control of Cact levels by Dl. Our model successfully reproduces wild-type data and emulates the Dl nuclear gradient in mutant
dl
and
cact
allelic combinations. Our results indicate that the dual role of Cact depends on the dynamics of Dl-Cact trimers along the dorsal-ventral axis: In the absence of Toll activation, free Dl-Cact trimers retain Dl in the cytoplasm, limiting the flow of Dl into the nucleus; in ventral-lateral regions, Dl-Cact trimers are recruited by Toll activation into predominant signaling complexes and promote Dl nuclear translocation. Simulations suggest that the balance between Toll-dependent and Toll-independent processes are key to this dynamics and reproduce the full assortment of Cact effects. Considering the high evolutionary conservation of these pathways, our analysis should contribute to understanding NFκB/c-Rel activation in other contexts such as in the vertebrate immune system and disease.
To characterize the effect of transversus abdominis plane (TAP) blocks on post-operative outcomes in patients undergoing laparotomy for gynecologic malignancy.
This retrospective cohort study ...assessed patients undergoing laparotomy in 2016–2017 and 2020 in Alberta, Canada. The primary outcome was opioid consumption in oral morphine milligram equivalent (MME). Secondary outcomes included maximum pain scores, length of stay, and patient-controlled analgesia (PCA) use. Outcomes were compared using t-test with subgroup analysis by NSAID use. Multivariate regression modelling was performed for potential confounders.
Data was collected on 956 patients; 828 received a TAP block, 128 did not. Opioid use in the first 24 h was lower in the TAP block group (35.9 mg MME vs 44.5 mg MME, p = 0.0294), without any increase in pain scores, this did not remain significant after regression analysis. Patients with TAP blocks had significant reduced mean length of stay (3.2 days vs. 5.0 days, p < 0.0001), and PCA use (19.9% vs. 56.25%, p < 0.0001). On subgroup analysis of patients that did not receive NSAIDs (n = 160), mean opioid use was decreased in those patients with TAP blocks compared to those without TAP blocks in the first 24 h (36.1 mg vs. 61.2 mg, p = 0.0017), and at 24 to 48 h (16.3 mg vs. 51.0 mg, p < 0.0001).
Surgeon-administered TAP blocks were associated with decreased length of stay and post-operative opioid use in patients not receiving scheduled NSAIDs. This decrease in opioid use was not associated with any increase in average or maximum pain scores.
•Transversus abdominis plane (TAP) blocks associated with shorter length of stay in patients undergoing laparotomy.•In patients not receiving scheduled NSAIDs, TAP blocks are associated with reduction in post-operative opioid use.•This decrease in opioid use was not associated with any increase in pain scores.
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