The effect of a bundle intervention for ambulatory otorhinolaryngology procedures on same-day case cancellation rate and associated costs.

Cancellations within 24 h of planned elective surgical procedures reduce operating theatre efficiency, add unnecessary costs and negatively affect patient experience. We implemented a bundle intervention that aimed to reduce same-day case cancellations. This consisted of communication tools to improve patient engagement and new screening instruments (automated estimation of ASA physical status and case cancellation risk score plus four screening questions) to identify patients in advance (ideally before case booking) who needed comprehensive pre-operative risk stratification. We studied patients scheduled for ambulatory surgery with the otorhinolaryngology service at a single centre from April 2021 to December 2022. Multivariable logistic regression and interrupted time-series analyses were used to analyse the effects of this intervention on case cancellations within 24 h and costs. We analysed 1548 consecutive scheduled cases. Cancellation within 24 h occurred in 114 of 929 (12.3%) cases pre-intervention and 52 of 619 (8.4%) cases post-intervention. The cancellation rate decreased by 2.7% (95%CI 1.6-3.7%, p < 0.01) during the first month, followed by a monthly decrease of 0.2% (95%CI 0.1-0.4%, p < 0.01). This resulted in an estimated $150,200 (£118,755; €138,370) or 35.3% cost saving (p < 0.01). Median (IQR [range]) number of days between case scheduling and day of surgery decreased from 34 (21-61 [0-288]) pre-intervention to 31 (20-51 [1-250]) post-intervention (p < 0.01). Patient engagement via the electronic health record patient portal or text messaging increased from 75.9% at baseline to 90.8% (p < 0.01) post-intervention. The primary reason for case cancellation was patients' missed appointment on the day of surgery, which decreased from 7.2% pre-intervention to 4.5% post-intervention (p = 0.03). An anaesthetist-driven, clinical informatics-based bundle intervention decreases same-day case cancellation rate and associated costs in patients scheduled for ambulatory otorhinolaryngology surgery.

Olanzapine With or Without Fosaprepitant for Preventing Chemotherapy Induced Nausea and Vomiting in Patients Receiving Highly Emetogenic Chemotherapy: A Phase III Randomized, Double-Blind, Placebo-Controlled Trial (ALLIANCE A221602).

PURPOSE: A protocol was developed to evaluate the value of an NK-1 receptor antagonist for preventing nausea and vomiting resulting from highly emetogenic chemotherapy when an olanzapine-based antiemetogenic regimen was used. MATERIALS AND METHODS: A221602, a prospective double-blind, placebo-controlled clinical trial, was developed to compare 2 -olanzapine-containing antiemetic regimens, one with an NK-1 receptor antagonist (aprepitant or fosaprepitant) and one without. Trial patients had a malignant disease for which they received intravenous highly emetogenic chemotherapy (single day cisplatin ≥ 70 mg/m2 or doxorubicin plus cyclophosphamide on 1 day). Patients on both arms received commonly administered doses of a 5-HT3 receptor antagonist, dexamethasone, and olanzapine. Additionally, patients were randomized to receive an NK-1 receptor antagonist (fosaprepitant 150 mg IV or aprepitant 130 mg IV) or a corresponding placebo. The primary objective was to compare the proportion of patients with no nausea for 5 days following chemotherapy between the 2 study arms. This trial was designed to test for the noninferiority of deleting the NK-1 receptor antagonist, with noninferiority defined as a decrease in freedom from nausea by less than 10%. RESULTS: A total of 690 patients were entered on this trial, 50% on each arm. The proportion of patients without nausea for the complete 5-day study period was 7.4% lower (upper limit of the one-sided 95% confidence interval was 13.5%) in the arm without an NK-1 receptor antagonist compared with the arm with an NK-1 receptor antagonist. CONCLUSION: This trial did not provide sufficient evidence to support that deletion of the NK-1 receptor antagonist was as good as keeping it, as a part of a 4-drug antiemetic regimen for highly emetogenic chemotherapy (ClinicalTrials.gov Identifier: NCT03578081).

2023 updated MASCC/ESMO consensus recommendations: prevention of nausea and vomiting following multiple-day chemotherapy, high-dose chemotherapy, and breakthrough nausea and vomiting.

PURPOSE: This review is an update of the MASCC/ESMO 2015 recommendations for the prophylaxis of acute and delayed nausea and vomiting induced by multiple-day chemotherapy, high-dose chemotherapy, and breakthrough nausea and vomiting. METHODS: A systematic literature search was conducted using PubMed from June 1, 2015, through February 1, 2023. RESULTS: We identified 56 references (16 were duplications or invalid), leaving 40 manuscripts for this search. The panel classified level I evidence (three manuscripts) and level II evidence (14 manuscripts). High-dose chemotherapy and stem cell transplant were discussed in four of these manuscripts, and multiple-day chemotherapy treatment in 15. Some manuscripts covered both topics. Additionally, a search for breakthrough nausea and vomiting resulted in 12 "hits." No new relevant studies were identified. CONCLUSIONS: The recommendations for patients receiving high-dose chemotherapy with stem cell transplants and patients undergoing multiple-day cisplatin were updated. For patients receiving high-dose chemotherapy for stem cell transplant, a combination of a 5-HT3 receptor antagonist with dexamethasone and aprepitant is recommended. Olanzapine could be considered part of the antiemetic regimen. Patients receiving multiple-day cisplatin should receive a 5-HT3 receptor antagonist plus dexamethasone plus aprepitant plus olanzapine. For patients experiencing breakthrough nausea and vomiting, the available evidence suggests using a single dose of olanzapine daily for 3 days.

Work loss and activity impairment due to extended nausea and vomiting in patients with breast cancer receiving CINV prophylaxis.

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV)'s impact on work loss remains poorly described. We evaluated associations between the duration of CINV episodes, CINV-related work loss (CINV-WL), and CINV-related activity impairment (CINV-AI) in patients with breast cancer receiving highly emetogenic chemotherapy. METHODS: We analyzed data from a prospective CINV prophylaxis trial of netupitant/palonestron and dexamethasone for patients receiving an anthracycline and cyclophosphamide (AC) for breast cancer (NCT0340371). Over the observed CINV duration (0-5 days), we analyzed patient-reported CINV-WL and CINV-AI for the first two chemotherapy cycles. We categorized patients as having either extended (≥ 3 days) or short (1-2 days) CINV duration and quantified its impact on work using the Work Productivity and Activity Impairment Questionnaire (WPAI). RESULTS: Overall, we captured data for 792 cycles in 402 women, including 136 (33.8%) employed patients with 35.3% reporting CINV. Of those with CINV, patients reported CINV-WL in 26 cycles and CINV-AI in 142 cycles. Of those with CINV, 55.3% of extended CINV cycles experienced CINV-WL compared to 16.7% of short CINV cycles (p < 0.001). The relative risk of CINV-WL between extended and short CINV was 3.32 (p < 0.01) for employed patients. The mean difference in CINV-AI scores (higher = worse) between extended and short duration CINV was 5.0 vs. 3.0 (p < 0.001). CONCLUSION: Extended (≥ 3 days) CINV was associated with more than triple the risk of CINV-WL and higher CINV-AI compared with short CINV.

Avoidable Acute Care Use Associated with Nausea and Vomiting Among Patients Receiving Highly Emetogenic Chemotherapy or Oxaliplatin.

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) contributes to avoidable acute care, a metric now tracked in Medicare's oncology outcome measure. CINV is preventable, yet guidelines are often not followed. We sought to quantify acute care involving CINV and other avoidable toxicities after highly emetogenic chemotherapy (HEC) to identify excess risk and assess clinician adherence to antiemesis guidelines for HEC. MATERIALS AND METHODS: We retrospectively evaluated U.S. electronic health records (2012-2018) using Medicare's OP-35 outcome measure to identify avoidable acute care involving any of 10 toxicities, including CINV, after HEC regimens relative to non-HEC. Antiemetic guideline adherence was defined as use ofneurokinin-1 (NKl) receptor antagonists Q5 (RAs) plus 5-hydroxytryptamine type 3 RA+ dexamethasone at HEC initiation. RESULTS: Among 17,609 patients receiving HEC, acute care rates associated with HEC chemotherapy included 32% cisplatin, 31% carboplatin, and 21% anthracycline/cyclosphospharnide (AC), with 76% meeting the criteria as avoidable events. Oxaliplatin rates were 29%. Avoidable acute care occurred 1.83 times (95% confidence interval, 1.76-1.91, p < .0001) as often after HEC versus non-HEC excluding oxaliplatin; CINV-related acute care occurred 2.29 times as often. Nonadherence to antiemesis guidelines occurred in 34% and 24% of cisplatin and AC courses, respectively, because of omission of a NKl RA. CONCLUSIONS: Patients treated with HEC regimens experienced high avoidable acute care use, 1.8 times the risk seen for other chemotherapy. Nonadherence to guideline-directed antiemetic prophylaxis highlights the need to ensure adherence to antiemetic guidelines, including the use of NKl RA in HEC. IMPLICATIONS FOR PRACTICE: After survival, perhaps the most important goal in oncology is limiting avoidable acute care, a goal now used by Medicare to impact cancer reimbursement. This study found that patients treated with highly emetogenic chemotherapy (HEC) regimens had high rates of avoidable acute care use, 1.8 times the risk seen for other chemotherapy. A substantial proportion of the avoidable acute care involved chemotherapy-induced nausea and vomiting. Results showed that incomplete adherence to national antiemetic guidelines for HEC regimens primarily driven by omission of upfront neurokinin-1 receptor antagonist use, suggesting that improved adherence can meaningfully resolve this gap in quality and cost of care.

Single-dose netupitant/palonosetron versus 3-day aprepitant for preventing chemotherapy-induced nausea and vomiting: a pooled analysis.

Aim: In the absence of comparative studies, guidelines consider neurokinin 1 receptor antagonists (RAs) as interchangeable. We evaluated the pooled efficacy from three cisplatin registration trials, each with arms containing netupitant/palonosetron (NEPA), a fixed neurokinin 1 RA (netupitant)/serotonin Type 3 (5-HT3) RA (palonosetron) combination, and an aprepitant (APR) regimen. Materials & methods: Efficacy data were pooled for rates of complete response (CR: no emesis/no rescue medication), complete protection (CR + no significant nausea), total control (CR + no nausea) and no significant nausea during acute (0-24 h), delayed (>24-120 h) and overall (0-120 h) phases post chemotherapy. Results: Among 621 NEPA and 576 APR patients, response rates were similar for the acute phase, and generally favored NEPA during delayed and overall phases. CR rates for NEPA versus APR were 88.4 versus 89.2%, 81.8 versus 76.9% (p < 0.05) and 78.4 versus 75.0% during the acute, delayed and overall phases, respectively. Conclusion: Oral NEPA administered on day 1 was more effective than a 3-day APR regimen in preventing delayed nausea and vomiting associated with cisplatin.

Lay abstract Oral netupitant/palonosetron (NEPA) is an innovative product that combines two drugs (netupitant and palonosetron) in a single capsule to prevent nausea and vomiting associated with certain types of chemotherapy. In this paper we pooled together the results of three studies comparing the efficacy of NEPA to two drugs from the same classes administered separately (aprepitant regimen) in patients with various solid tumors receiving cisplatin, a type of chemotherapy with a high likelihood of causing nausea and vomiting. In summary, NEPA was more effective than the aprepitant regimen in preventing nausea and vomiting in the later days (days 3­5) following chemotherapy.

Cost-effectiveness analysis of olanzapine-containing antiemetic therapy for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV) in highly emetogenic chemotherapy (HEC) patients.

PURPOSE: Olanzapine-containing regimens have been reported to be effective in preventing CINV following highly emetogenic chemotherapy (HEC), but it is unsure whether it is cost-effective. There has been no cost-effectiveness analysis conducted for olanzapine using costs from the USA. The aim of this study is to determine whether olanzapine-containing antiemetic regimens are cost-effective in patients receiving HEC. METHODS: A decision tree model was constructed to evaluate the cost and health outcomes associated with olanzapine-containing antiemetic regimens and otherwise-identical regimens. One-way sensitivity analyses were conducted to individually investigate the effect of (i) lower complete response (CR) rates of olanzapine, closer to non-olanzapine-containing regimens; (ii) higher FLIE scores for patients who achieved no/incomplete response, closer to FLIE scores of patients achieving a complete response; (iii) differing costs of olanzapine to reflect different costs per hospitals, globally, due to different insurance systems and drug costs; and (iv) varying costs for uncontrolled CINV, to account for varying durations of chemotherapy and accompanying uncontrolled CINV. RESULTS: Olanzapine regimens have an expected cost of $325.24, compared with $551.23 for non-olanzapine regimens. Meanwhile, olanzapine regimens have an expected utility/index of 0.89, relative to 0.87 for non-olanzapine regimens. Olanzapine-containing regimens dominate non-olanzapine-containing regimens even if CR of olanzapine-containing regimens fall to 0.63. Only when CR is between 0.60 and 0.62 is olanzapine both more effective and more costly. CONCLUSION: Olanzapine-containing regimens are both cheaper and more effective in the prophylaxis of CINV in HEC patients, compared with non-olanzapine-containing regimens. Future CINV trial resources should be allocated to understand newer antiemetics and compare them to olanzapine-containing regimens as the control arm. Further analysis should use nationally representative data to examine medication costs by payer type.

Olanzapine for the prophylaxis and rescue of chemotherapy-induced nausea and vomiting: a systematic review, meta-analysis, cumulative meta-analysis and fragility assessment of the literature.

INTRODUCTION: The aim of this study is to rigorously review the efficacy and safety of olanzapine in defined hematology oncology settings including (1) the setting of highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC) settings (2) at 5 mg and 10 mg doses, and (3) for response rates for use in the acute, delayed, and overall settings post-MEC and HEC. METHODS: Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were searched through April 23, 2020. The primary efficacy endpoints were the rate of complete response, in the acute (0-24 h post-chemotherapy), delayed (24-120 h post-chemotherapy), and overall (0-120 h post-chemotherapy) phases. The secondary efficacy endpoints were the rates of no nausea and no emesis, for each phase. Safety endpoints were the rate of no serious adverse events (i.e., no grade 3 or 4 toxicities), as assessed by Common Terminology Criteria for Adverse Events (CTCAE) criteria. The Mantel-Haenszel, random-effects analysis model was used to compute risk ratios and accompanying 95% confidence intervals for each endpoint. For endpoints that statistically favored one arm, absolute risk differences were computed to assess whether there is a 10% or greater difference, used as the threshold for clinical significance by MASCC/ESMO. Fragility indices were also calculated for each statistically significant endpoint, to quantitatively assess the robustness of the summary estimate. A cumulative meta-analysis was conducted for each efficacy meta-analysis with more than 5 studies, also using the Mantel-Haenszel random-effects analysis model. RESULTS: Three studies reported on olanzapine for the rescue of breakthrough chemotherapy-induced nausea and vomiting (CINV); 22 studies reported on olanzapine in the prophylactic setting. For studies reporting on HEC patients, olanzapine-containing regimens were statistically and clinically superior in seven of nine efficacy endpoints in the prophylaxis setting. When olanzapine is administered at a 10-mg dose, it is statistically and clinically superior to control patients in eight of nine endpoints among adults. Olanzapine may be effective in the MEC setting and when administered at 5-mg doses, but the paucity of data leads to notable uncertainty. CONCLUSION: Further RCTs are needed in the setting of MEC patients and administration of olanzapine at a lower 5-mg dose, which may be given to reduce the sedative effect of olanzapine at 10 mg.

Tuning Magnetic Properties of a Carbon Nanotube-Lanthanide Hybrid Molecular Complex through Controlled Functionalization.

Molecular magnets attached to carbon nanotubes (CNT) are being studied as potential candidates for developing spintronic and quantum technologies. However, the functionalization routes used to develop these hybrid systems can drastically affect their respective physiochemical properties. Due to the complexity of this systems, little work has been directed at establishing the correlation between the degree of functionalization and the magnetic character. Here, we demonstrate the chemical functionalization degree associated with molecular magnet loading can be utilized for controlled tuning the magnetic properties of a CNT-lanthanide hybrid complex. CNT functionalization degree was evaluated by interpreting minor Raman phonon modes in relation to the controlled reaction conditions. These findings were exploited in attaching a rare-earth-based molecular magnet (Gd-DTPA) to the CNTs. Inductively coupled plasma mass spectrometry, time-of-flight secondary ion mass spectrometry and super conducting quantum interference device (SQUID) measurements were used to elucidate the variation of magnetic character across the samples. This controlled Gd-DTPA loading on the CNT surface has led to a significant change in the nanotube intrinsic diamagnetism, showing antiferromagnetic coupling with increase in the Weiss temperature with respect to increased loading. This indicates that synthesis of a highly correlated spin system for developing novel spintronic technologies can be realized through a carbon-based hybrid material.

What the HEC? Clinician Adherence to Evidence-Based Antiemetic Prophylaxis for Highly Emetogenic Chemotherapy.

BACKGROUND: Clinician adherence to antiemetic guidelines for preventing chemotherapy-induced nausea and vomiting (CINV) caused by highly emetogenic chemotherapy (HEC) remains poorly characterized. The primary aim of this study was to evaluate individual clinician adherence to HEC antiemetic guidelines. PATIENTS AND METHODS: A retrospective analysis of patients receiving HEC was conducted using the IBM Watson Explorys Electronic Health Record Database (2012-2018). HEC antiemetic guideline adherence was defined as prescription of triple prophylaxis (neurokinin-1 receptor antagonist [NK1 RA], serotonin type-3 receptor antagonist, dexamethasone) at initiation of cisplatin or anthracycline + cyclophosphamide (AC). Clinicians who prescribed ≥5 HEC courses were included and individual guideline adherence was assessed, noting the number of prescribing clinicians with >90% adherence. RESULTS: A total of 217 clinicians were identified who prescribed 2,543 cisplatin and 1,490 AC courses. Patients (N=4,033) were primarily women (63.3%) and chemotherapy-naïve (92%) with a mean age of 58.6 years. Breast (36%) and thoracic (19%) cancers were the most common tumor types. Guideline adherence rates of >90% were achieved by 35% and 58% of clinicians using cisplatin or AC, respectively. Omission of an NK1 RA was the most common practice of nonadherence. Variation in prophylaxis guideline adherence was considerable for cisplatin (mean, 71%; SD, 29%; coefficient of variation [CV], 0.40) and AC (mean, 84%; SD, 26%; CV, 0.31). CONCLUSIONS: Findings showed substantial gaps in clinician adherence to HEC CINV guidelines, including a high variability across clinicians. Clinicians should review their individual clinical practices and ensure adherence to evidence-based CINV guidelines to optimize patient care.

Nausea and Vomiting in Advanced Cancer.

OPINION STATEMENT: Nausea and vomiting is a common clinical issue in the advanced cancer patient. The etiology may be related to treatment (chemotherapy, radiation, surgery) or non-treatment clinical issues related to the advanced cancer. A very detailed initial assessment of nausea/vomiting is indicated including frequency, duration, intensity, associated activities, and the presence of anorexia or cachexia and is necessary in order to determine a specific etiology which may allow a potentially specific successful intervention. Various international antiemetic guidelines have been developed for the successful prevention of chemotherapy- and radiotherapy-induced nausea and emesis but the treatment of post-chemotherapy nausea/vomiting and of radiation-induced nausea/vomiting has been less successful. Chronic nausea/vomiting in the advanced cancer patient unrelated to treatment remains a significant clinical problem with few successful treatments and interventions. NCCN and ASCO palliative care guidelines provide various treatment suggestions but these are based on empiric evidence with very few clinical trials available to provide demonstrated effective treatments. Recent randomized clinical trials have demonstrated that olanzapine may be an effective agent for the prevention and treatment of chemotherapy-induced nausea and emesis as well as treatment of chronic nausea and vomiting unrelated to treatment.

Unscheduled hydrations: redefining complete response in chemotherapy-induced nausea and vomiting studies.

Breakthrough chemotherapy-induced nausea and vomiting (CINV) is nausea and/or vomiting occurring within 5 days of chemotherapy administration despite using guideline-directed prophylactic antiemetic agents. It is highly prevalent (30-40%), usually requiring immediate treatment or "rescue" medication. If breakthrough CINV occurs, antiemetic guidelines recommend using an antiemetic agent from a different class not used in prophylaxis, along with intravenous hydration and/or dexamethasone. Data supporting these guideline recommendations are limited. Importantly, costs associated with breakthrough CINV can be substantial (i.e., unscheduled hydrations). Two retrospective analyses evaluating guideline-adherent CINV prophylaxis suggest that the initial antiemetic selection may decrease breakthrough CINV. Here we review optimal CINV prophylactic strategies and introduce unscheduled hydration as a potential important surrogate for breakthrough CINV aligning with cost-effective cancer care.

Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting.

BACKGROUND: We examined the efficacy of olanzapine for the prevention of nausea and vomiting in patients receiving highly emetogenic chemotherapy. METHODS: In a randomized, double-blind, phase 3 trial, we compared olanzapine with placebo, in combination with dexamethasone, aprepitant or fosaprepitant, and a 5-hydroxytryptamine type 3-receptor antagonist, in patients with no previous chemotherapy who were receiving cisplatin (≥70 mg per square meter of body-surface area) or cyclophosphamide-doxorubicin. The doses of the three concomitant drugs administered before and after chemotherapy were similar in the two groups. The two groups received either 10 mg of olanzapine orally or matching placebo daily on days 1 through 4. Nausea prevention was the primary end point; a complete response (no emesis and no use of rescue medication) was a secondary end point. RESULTS: In the analysis, we included 380 patients who could be evaluated (192 assigned to olanzapine, and 188 to placebo). The proportion of patients with no chemotherapy-induced nausea was significantly greater with olanzapine than with placebo in the first 24 hours after chemotherapy (74% vs. 45%, P=0.002), the period from 25 to 120 hours after chemotherapy (42% vs. 25%, P=0.002), and the overall 120-hour period (37% vs. 22%, P=0.002). The complete-response rate was also significantly increased with olanzapine during the three periods: 86% versus 65% (P<0.001), 67% versus 52% (P=0.007), and 64% versus 41% (P<0.001), respectively. Although there were no grade 5 toxic effects, some patients receiving olanzapine had increased sedation (severe in 5%) on day 2. CONCLUSIONS: Olanzapine, as compared with placebo, significantly improved nausea prevention, as well as the complete-response rate, among previously untreated patients who were receiving highly emetogenic chemotherapy. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT02116530.).

HTX-019: polysorbate 80- and synthetic surfactant-free neurokinin 1 receptor antagonist for chemotherapy-induced nausea and vomiting prophylaxis.

Chemotherapy-induced nausea and vomiting (CINV) may occur during the acute (0-24 h) or delayed (25-120 h) phase following chemotherapy administration. The addition of a neurokinin 1 receptor antagonist to antiemetic regimens containing a 5-hydroxytryptamine type 3 receptor antagonist and dexamethasone has resulted in improved CINV prophylaxis. Due to numerous adverse events and hypersensitivity reactions associated with fosaprepitant, a commonly used neurokinin 1 receptor antagonist, there remains an unmet need for better-tolerated formulations. HTX-019, the US FDA-approved polysorbate 80- and synthetic surfactant-free aprepitant injectable emulsion, is bioequivalent to and better tolerated (fewer treatment-emergent adverse events) than fosaprepitant. HTX-019 represents a valuable alternative to fosaprepitant for CINV prophylaxis.

Water-saving strategies in the mining industry - The potential of mineral processing simulators as a tool for their implementation.

As the mining industry is facing an increasing number of issues related to its fresh water consumption, water-saving strategies are progressively being implemented in the mineral processing plants, often leading to variations in the process water chemistry. However, the impact of water chemistry variations on the process performance is rarely known beforehand, thus creating an obstacle to the implementation of those water-saving strategies. To tackle this problem, the effect the different dissolved species present in the process water have on the processing plant performance must be quantified, and this information must be digitalized in a practical and suitable form to be used in mineral processing simulators. To achieve this goal, a methodology to digitalize the influence of the process water composition on the flotation performance is presented in this paper. Using the flotation of a fluorite ore as case study, the relationship between process water composition and the flotation kinetics of that fluorite ore was determined. This relationship was digitalized in HSC Sim, a mineral processing simulator, turning it into a tool capable of simulating the flotation performance under a variety of process water compositions. Finally, the potential of this new tool to help implementing water-saving strategies on the mine site is discussed, and the challenges that need to be overcome in order to apply this tool at industrial scale are being addressed.

A hedgehog pathway-dependent gene signature is associated with poor clinical outcomes in Luminal A breast cancer.

PURPOSE: High expression of glioma-associated oncogene homolog-1 (GLI1) is associated with poor prognosis in estrogen receptor (ER) positive breast cancers. We sought to define a GLI1-dependent gene signature in ER-positive tumors that could further stratify patients at higher risk for disease recurrence and potentially lead to novel combination therapies. METHODS: We identified an inverse correlation between GLI1 expression and distant disease-free survival (DFS) using a dataset developed at MD Anderson Cancer Center (Hatzis dataset) containing clinical data from 508 breast cancer patients. Using a qPCR-based microarray platform, we identified genes differentially regulated by GLI1 in MCF7 cells and then determined if expression of these genes correlated with GLI1 expression in patient tumor samples. Statistical comparison between the groups was performed by ANOVA. Direct comparison of two groups was done by a two-tailed t test. Correlations between variables were done by Pearson's method. RESULTS: Expression of GLI1 and its target genes correlated significantly with worse distant DFS in breast cancer patients with Luminal A molecular subtype. Particularly, co-expression of GLI1 with EGFR and/or SNAI1, two of the identified GLI1 targets, was predictive of worse distant DFS in this subtype. Furthermore, patients with Luminal A tumors with a high GLI1 signature had a shorter distant DFS compared to the Luminal B subtype and the outcome for this group was comparable to patients with HER2-positive or basal-like tumors. CONCLUSION: We have identified a novel GLI1 gene signature that is associated with worse clinical outcomes among the patients with Luminal A subtype of breast cancer.

Managing Nausea and Vomiting in Patients With Cancer: What Works.

The approach to the treatment of nausea and vomiting in a cancer patient should begin with a complete assessment, including the frequency, duration, and intensity of the nausea/vomiting; associated activities; and whether anorexia or cachexia is present. It is important to determine whether the nausea and vomiting is related to treatment (chemotherapy, radiation) or is independent of cancer treatment. Nausea/vomiting unrelated to chemotherapy and/or radiation may have an etiology for which there is a specific and potentially successful intervention. Various national and international antiemetic guidelines have been developed for the prevention of chemotherapy- and radiotherapy-induced nausea and emesis. The antiemetics recommended in these guidelines (5-hydroxytryptamine type 3 receptor antagonists, neurokinin-1 receptor antagonists, dexamethasone) have significantly reduced emesis but not nausea. Recent randomized clinical trials have demonstrated that olanzapine may be an effective agent for the prevention and treatment of chemotherapy-induced nausea as well as emesis.

Should palonosetron be a preferred 5-HT3 receptor antagonist for chemotherapy-induced nausea and vomiting? An updated systematic review and meta-analysis.

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) continues to be a common side effect of systemic anticancer therapy, decreasing quality of life and increasing resource utilization. The aim of this meta-analysis was to investigate the comparative efficacy and safety of palonosetron relative to other 5-HT3RAs. METHODS: A literature search was carried out in Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials. Full-text references were then screened and included in this meta-analysis if they were an RCT and had adequate data regarding one of the five primary endpoints-complete response (CR), complete control (CC), no emesis, no nausea, or no rescue medications. RESULTS: A total of 24 RCTs were included in this review. Palonosetron was statistically superior to other 5-HT3RAs for 10 of the 19 assessed endpoints. Only one endpoint-emesis in the overall phase-had noticeable more favorable data for palonosetron to the point that it approached the 10% risk difference (RD) threshold as specified by the MASCC/ESMO antiemetic panel; another two endpoints (CR in the overall phase and nausea in the delayed phase) approached the 10% threshold. CONCLUSIONS: Palonosetron seems to be more efficacious and safe than other 5-HT3RAs-statistically superior in 10 of 19 endpoints. It is, however, only clinically significant in one endpoint and approached clinically significant difference in another two endpoints. Within the limits of this meta-analysis, our results indicate that palonosetron may not be as superior in efficacy and safety as reported in a previous meta-analysis, and supports the recent MASCC/ESMO, ASCO, and NCCN guidelines in not generally indicating palonosetron as the 5-HT3RA of choice.

Implementation of a new strategy to improve the peri-operative management of neuromuscular blockade and its effects on postoperative pulmonary complications.

Inappropriate dosing of neostigmine for antagonism of neuromuscular blockade has been associated with postoperative pulmonary complications. We evaluated the effects of a quality improvement initiative tailored to optimise the use of neostigmine in antagonising neuromuscular blockade on postoperative pulmonary complications, costs and duration of hospital stay. The quality improvement initiative consisted of: a reduction in available neostigmine aliquot sizes; a cognitive aid; an educational component; and a financial incentive for the intra-operative documentation of train-of-four measurement before administration of neostigmine. We conducted a pre-specified analysis of data obtained in our quality improvement study. Additional analyses were conducted in a propensity-matched cohort. An interrupted time series design was used to discriminate between the intervention and a counterfactual scenario. We analysed 12,025 consecutive surgical cases performed in 2015. Postoperative pulmonary complications occurred in 220 (7.5%) of 2937 cases pre-intervention and 568 (6.3%) of 9088 cases post-intervention. Adjusted regression analyses showed significantly a lower risk of postoperative pulmonary complications (OR 0.73 (95%CI 0.61-0.88); p = 0.001), lower costs (incidence rate ratio 0.95 (95%CI 0.93-0.97); p < 0.001) and shorter duration of hospital stay (incidence rate ratio 0.91 (95%CI 0.87-0.94); p < 0.001) after implementation of the quality improvement initiative. Analyses in a propensity-matched sample (n = 2936 per group) and interrupted time series analysis (n = 27,202 cases) confirmed the findings. Our data show that a local, multifaceted quality improvement initiative can enhance the quality of intra-operative neuromuscular blocking agent utilisation, thereby reducing the incidence of postoperative pulmonary complications.

Early infant adipose deposition is positively associated with the n-6 to n-3 fatty acid ratio in human milk independent of maternal BMI.

BACKGROUND/OBJECTIVES: Excessive infant weight gain in the first 6-month of life is a powerful predictor of childhood obesity and related health risks. In mice, omega-6 fatty acids (FAs) serve as potent ligands driving adipogenesis during early development. The ratio of omega-6 relative to omega-3 (n-6/n-3) FA in human milk (HM) has increased threefold over the last 30 years, but the impact of this shift on infant adipose development remains undetermined. This study investigated how maternal obesity and maternal dietary FA (as reflected in maternal red blood cells (RBCs) composition) influenced HM n-6 and n-3 FAs, and whether the HM n-6/n-3 ratio was associated with changes in infant adipose deposition between 2 weeks and 4 months postpartum. SUBJECTS/METHODS: Forty-eight infants from normal weight (NW), overweight (OW) and obese (OB) mothers were exclusively or predominantly breastfed over the first 4 months of lactation. Mid-feed HM and maternal RBC were collected at either transitional (2 weeks) or established (4 months) lactation, along with infant body composition assessed using air-displacement plethysmography. The FA composition of HM and maternal RBC was measured quantitatively by lipid mass spectrometry. RESULTS: In transitional and established HM, docosahexaenoic acid (DHA) was lower (P=0.008; 0.005) and the arachidonic acid (AA)/DHA+eicosapentaenoic acid (EPA) ratio was higher (P=0.05; 0.02) in the OB relative to the NW group. Maternal prepregnancy body mass index (BMI) and AA/DHA+EPA ratios in transitional and established HM were moderately correlated (P=0.018; 0.001). Total infant fat mass was increased in the upper AA/DHA+EPA tertile of established HM relative to the lower tertile (P=0.019). The amount of changes in infant fat mass and percentage of body fat were predicted by AA/EPA+DHA ratios in established HM (P=0.038; 0.010). CONCLUSIONS: Perinatal infant exposures to a high AA/EPA+DHA ratio during the first 4 months of life, which is primarily reflective of maternal dietary FA, may significantly contribute to the way infants accumulate adipose.