EAES and SAGES 2018 consensus conference on acute diverticulitis management:evidence-based recommendations for clinical practice

Background Acute diverticulitis (AD) presents a unique diagnostic and therapeutic challenge for general surgeons. This collaborative project between EAES and SAGES aimed to summarize recent evidence and draw statements of recommendation to guide our members on comprehensive AD management. Methods Systematic reviews of the literature were conducted across six AD topics by an international steering group including experts from both societies. Topics encompassed the epidemiology, diagnosis, management of non-complicated and complicated AD as well as emergency and elective operative AD management. Consensus statements and recommendations were generated, and the quality of the evidence and recommendation strength rated with the GRADE system. Modified Delphi methodology was used to reach consensus among experts prior to surveying the EAES and SAGES membership on the recommendations and likelihood to impact their practice. Results were presented at both EAES and SAGES annual meetings with live re-voting carried out for recommendations with < 70% agreement. Results A total of 51 consensus statements and 41 recommendations across all six topics were agreed upon by the experts and submitted for members’ online voting. Based on 1004 complete surveys and over 300 live votes at the SAGES and EAES Diverticulitis Consensus Conference (DCC), consensus was achieved for 97.6% (40/41) of recommendations with 92% (38/41) agreement on the likelihood that these recommendations would change practice if not already applied. Areas of persistent disagreement included the selective use of imaging to guide AD diagnosis, recommendations against antibiotics in non-complicated AD, and routine colonic evaluation after resolution of non-complicated diverticulitis. Conclusion This joint EAES and SAGES consensus conference updates clinicians on the current evidence and provides a set of recommendations that can guide clinical AD management practice

Phase II Feasibility and Biomarker Study of Neoadjuvant Trastuzumab and Pertuzumab With Chemoradiotherapy for Resectable Human Epidermal Growth Factor Receptor 2-Positive Esophageal Adenocarcinoma:TRAP Study

PURPOSE: Approximately 15% to 43% of esophageal adenocarcinomas (EACs) are human epidermal growth factor receptor 2 (HER2) positive. Because dual-agent HER2 blockade demonstrated a survival benefit in breast cancer, we conducted a phase II feasibility study of trastuzumab and pertuzumab added to neoadjuvant chemoradiotherapy (nCRT) in patients with EAC. PATIENTS AND METHODS: Patients with resectable HER2-positive EAC received standard nCRT with carboplatin and paclitaxel and 41.4 Gy of radiotherapy, with 4 mg/kg of trastuzumab on day 1, 2 mg/kg per week during weeks 2 to 6, and 6 mg/kg per week during weeks 7, 10, and 13 and 840 mg of pertuzumab every 3 weeks. The primary end point was feasibility, defined as ≥ 80% completion of treatment with both trastuzumab and pertuzumab. An exploratory comparison of survival with a propensity score-matched cohort receiving standard nCRT was performed, as were exploratory pharmacokinetic and biomarker analyses. RESULTS: Of the 40 enrolled patients (78% men; median age, 63 years), 33 (83%) completed treatment with trastuzumab and pertuzumab. No unexpected safety events were observed. R0 resection was achieved in all patients undergoing surgery, with pathologic complete response in 13 patients (34%). Three-year progression-free and overall survival (OS) were 57% and 71%, respectively (median follow-up, 32.1 months). Compared with the propensity score-matched cohort, a significantly longer OS was observed with HER2 blockade (hazard ratio, 0.58; 95% CI, 0.34 to 0.97). Results of pharmacokinetic analysis and activity on [18F]fluorodeoxyglucose positron emission tomography scans did not correlate with survival or pathologic response. Patients with HER2 3+ overexpression or growth factor receptor-bound protein 7 (Grb7) -positive tumors at baseline demonstrated significantly better survival (P = .007) or treatment response (P = .016), respectively. CONCLUSION: Addition of trastuzumab and pertuzumab to nCRT in patients with HER2-positive EAC is feasible and demonstrates potentially promising activity compared with historical controls. HER2 3+ overexpression and Grb7 positivity are potentially predictive for survival and treatment response, respectively

Molecular signatures for CCN1, p21 and p27 in progressive mantle cell lymphoma

Mantle cell lymphoma (MCL) is a comparatively rare non-Hodgkin’s lymphoma characterised by overexpression of cyclin D1.Many patients present with or progress to advanced stage disease within 3 years. MCL is considered an incurable disease withmedian survival between 3 and 4 years. We have investigated the role(s) of CCN1 (CYR61) and cell cycle regulators inprogressive MCL. We have used the human MCL cell lines REC1 G519 > JVM2 cells by RQ-PCR, depicting a decrease in CCN1expression with disease progression. Investigation of CCN1 isoform expression by western blotting showed that whilst expres-sion of full-length CCN1 was barely altered in the cell lines, expression of truncated forms (18–20 and 28–30 kDa) decreasedwith disease progression. We have then demonstrated that cyclin D1 and cyclin dependent kinase inhibitors (p21CIP1and p27KIP1)are also involved in disease progression. Cyclin D1 was highly expressed in REC1 cells (OD: 1.0), reduced to one fifth in G519cells (OD: 0.2) and not detected by western blotting in JVM2 cells. p27KIP1followed a similar profile of expression as cyclin D1.Conversely, p21CIP1was absent in the REC1 cells and showed increasing expression in G519 and JVM2 cells. Subcellularlocalization detected p21CIP1/p27KIP1primarily within the cytoplasm and absent from the nucleus, consistent with altered roles in treatment resistance. Dysregulation of the CCN1 truncated forms are associated with MCL progression. In conjunction withreduced expression of cyclin D1 and increased expression of p21, this molecular signature may depict aggressive disease andtreatment resistance

Cost estimation of redispensing unused medicines that are returned to the pharmacy: A micro-costing study

Background and Objective: Redispensing of unused medicines returned to the pharmacy by patients may optimise the use of health care resources and reduce medication waste. Little is known about the costs associated with the pharmacy proceedings for redispensing, and which medicines might be eligible for redispensing from a cost-perspective. The objective of this study was to estimate the cost of the redispensing process in the pharmacy and the minimal economic value (MEV) of unused medicines that are eligible for redispensing. Setting and Method: A micro-costing study was performed in four outpatient pharmacies in the Netherlands in 2016. First, all proceedings and resources needed for redispensing were identified from pharmacist reviews. Second, the time required to redispense unused medicines was measured by simulating the proceedings in each pharmacy. Third, time measurements were quantified into costs using salary scales and purchasing prices. Lastly, a model was made to calculate the MEV for medicines requiring room or cold storage. Influence of assumptions (market prices, proportion of dispensed medicines returned to the pharmacy and proportion of medicines eligible for redispensing) was assessed using sensitivity analysis. Main outcome measures: Measured time and related costs associated with performing the proceedings of redispensing medicines in the pharmacy, and the MEV for medicines requiring room or cold storage. Results: Redispensing medicines in the pharmacy require that an (electronic) system is dispensed with the medicines that assure proper home storage. This requires extra handling, which takes approximately 6.30 min for medicines requiring room temperature storage and 8.05 min for medicines requiring storage between 2 and 8 °C. Estimated costs amounted to respectively €5.95 and € 106.00 (due to additional resources needed for quality control like temperature chips). The MEV for room temperature stored medicines eligible for redispensing is €94 and for cooled stored medicines €201. Sensitivity analysis showed that the proportion of dispensed medicines returned to the pharmacy has the strongest influence on the MEV. Conclusion: Redispensing unused medicines in the pharmacy is not time consuming, however, only expensive medicines are eligible for redispensing from a cost perspective. Most costs are made with medicines' dispensing as only a small proportion of dispensed medicines are returned to the pharmacy

Conflicting Guidelines: A Systematic Review on the Proper Interval for Colorectal Cancer Treatment

Background: Timely treatment for colorectal cancer (CRC) is a quality indicator in oncological care. However, patients with CRC might benefit more from preoperative optimization rather than rapid treatment initiation. The objectives of this study are (1) to determine the definition of the CRC treatment interval, (2) to study international recommendations regarding this interval and (3) to study whether length of the interval is associated with outcome. Methods: We performed a systematic search of the literature in June 2020 through MEDLINE, EMBASE and Cochrane databases, complemented with a web search and a survey among colorectal surgeons worldwide. Full-text papers including subjects with CRC and a description of the treatment interval were included. Results: Definition of the treatment interval varies widely in published studies, especially due to different starting points of the interval. Date of diagnosis is often used as start of the interval, determined with date of pathological confirmation. The end of the interval is rather consistently determined with date of initiation of any primary treatment. Recommendations on the timeline of the treatment interval range between and within countries from two weeks between decision to treat and surgery, to treatment within seven weeks after pathological diagnosis. Finally, there is no decisive evidence that a longer treatment interval is associated with worse outcome. Conclusions: The interval from diagnosis to treatment for CRC treatment could be used for prehabilitation to benefit patient recovery. It may be that this strategy is more beneficial than urgently proceeding with treatment

Pharmacists' Activities to Reduce Medication Waste : An International Survey

Aim: To identify activities that pharmacists undertake to reduce medication waste, and to assess the extent to which these activities are implemented, their importance for waste-reduction and feasibility for broad implementation. Methods: A two-phase survey was conducted among community and hospital pharmacists working in different developed countries. Phase one used an open-ended questionnaire to identify activities undertaken by pharmacists. Answers were thematically analysed to construct a list of medication waste-reducing activities. In phase two, a questionnaire was disseminated among pharmacists from different countries, to assess if these activities are implemented (yes/no), their importance and feasibility (1 to 5 ranking scale). Results: In phase one, 53 pharmacists participated and 14 activities were identified. These were categorized into the pharmaceutical supply chain: prescribing, dispensing (pharmacy/patient-related) and leftover stage. In phase two, 89 pharmacists participated. Most activities were implemented by a minority of pharmacists. Reducing medication amounts in stock was most frequently implemented (dispensing stage pharmacy-related; 86%), followed by collecting unused medications (leftover stage; 77%) and performing a medication review (dispensing stage; 68%). Waste-reducing activities in the dispensing stage activities were both considered most important and feasible (ranked 4). Overall, most activities scored higher on importance than on feasibility. Conclusions: Pharmacists have various opportunities to reduce medication waste throughout the pharmaceutical supply chain, however, not all are broadly implemented. Pharmacists consider waste-reducing activities important, but they are less certain about the feasibility for implementation in practice

What does it cost to redispense unused medications in the pharmacy? A micro-costing study

Abstract Background Redispensing unused medications that have been returned to outpatient pharmacies by patients may reduce waste and healthcare costs. However, little is known regarding the extra costs associated with this process, nor the price level of medications for which this is economically beneficial. The objective of this study was to assess costs associated with redispensing unused medications in the pharmacy and the price level at which redispensing becomes cost-beneficial. Methods A micro-costing study was conducted in four Dutch outpatient pharmacies for medications requiring room-temperature storage and requiring refrigeration. First, the pharmacy’s necessary additional process steps and resources for redispensing were identified. Second, time required for each process step was simulated. Third, required resources were quantified by calculating labour, purchasing and overhead costs. Lastly, a model with different scenarios was constructed to calculate the price of a medication package at which redispensing becomes cost-beneficial. Results Three main additional process steps for redispensing were identified: (1) pack medications with product quality indicators before dispensing, (2) assess quality of medications returned to the pharmacy (temperature storage, package integrity, expiry date) and (3a) restock medications fulfilling quality criteria or (3b) dispose of medications not fulfilling criteria. Total time required for all steps up to restock one medication package was on average 5.3 (SD ±0.3) and 6.8 (SD ±0.3) minutes for medications stored at room-temperature and under refrigeration, respectively, and associated costs were €5.54 and €7.61. Similar outcomes were found if a medication package would ultimately be disposed of. The price level primarily depended upon the proportion of dispensed packages returned unused to the pharmacy and fulfilling the quality criteria: if 5% is returned, of which 60% fulfils quality criteria, the price level was €101 per package for medications requiring room-temperature storage and €215 per package for those requiring refrigeration. However, if 10% is returned, of which 60% fulfils the quality criteria, the price level decreases to €53 and €109, respectively (arbitrary proportions). Conclusions Redispensing unused medications in the pharmacy is at least cost-beneficial if applied to expensive medications

Estimating VO2peak in 18-90 Year-Old Adults:Development and Validation of the FitMáx©-Questionnaire

PURPOSE: Cardiorespiratory fitness (CRF) plays an essential role in health outcomes and quality of life. However, it is often not assessed nor estimated. Objective CRF assessment is costly, labour intensive and not widely available. Patient-reported outcome measures estimate CRF more cost-efficiently, but current questionnaires lack accuracy. The aim of this study is to develop a new self-reported questionnaire to estimate CRF. MATERIALS AND METHODS: The FitMáx©-questionnaire, consisting of only three questions assessing walking, stair climbing, and cycling capacity, was compared with the commonly used Duke Activity Status Index (DASI) and Veterans Specific Activity Questionnaire (VSAQ). These questionnaires were compared to peak oxygen uptake (VO(2peak)) as measured with cardiopulmonary exercise testing. This study included 759 cardiac, pulmonary and oncologic patients and healthy persons aged 18‒90. RESULTS: FitMáx© strongly correlated (r = 0.94 (0.92‒0.95) SEE = 4.14 mL∙kg(−1)∙min(−1)) with measured VO(2peak). Bias between predicted and measured VO(2peak) was −0.24 (−9.23‒8.75; 95% limits of agreement) mL·kg(−1)·min(−1). The FitMáx© scored superiorly on correlation and SEE compared with the DASI and VSAQ, r = 0.75 (0.68‒0.80) SEE = 4.62 mL∙kg(−1)∙min(−1) and r = 0.87 (0.83‒0.90) SEE = 6.75 mL∙kg(−1)∙min(−1), respectively. CONCLUSION: FitMáx© is a valid and accessible questionnaire to estimate CRF expressed as VO(2peak) in clinical practice and shows substantial improvement compared to currently used questionnaires