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Drain Amylase level are routinely determined to diagnose pancreatic fistula after Pancreatocoduodenectomy. Consensus is lacking regarding the cut-off value of amylase to diagnosis clinically relevant postoperative pancreatic fistulae (POPF). The present study proposes a model based on Amylase Value in the Drain (AVD) measured in the first three postoperative days to predict a POPF. Amylase cut-offs were selected from a previous published systematic review and the accuracy were validated in a multicentre database from 12 centres in 2 countries. The present study defined POPF the 2016 ISGPS criteria (3 times the upper limit of normal serum amylase). A learning machine method was used to correlate AVD with the diagnosis of POPF. Overall, 454 (27%) of 1638 patients developed POPF. Machine learning excluded a clinically relevant postoperative pancreatic fistulae with an AUC of 0.962 (95% CI 0.940–0.984) in the first five postoperative days. An AVD at a cut-off of 270 U/L in 2 days in the first three postoperative days excluded a POPF with an AUC of 0.869 (CI 0.81–0.90, p < 0.0001). A single AVD in the first three postoperative days may not exclude POPF after pancreatoduodenectomy. The levels should be monitored until day 3 and have two negative values before removing the drain. In the group with a positive level, the drain should be kept in and AVD monitored until postoperative day five. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant therapy has several potential advantages over upfront surgery in patients with localized pancreatic cancer; more patients receive systemic treatment, fewer patients undergo futile surgery, and R0 resection rates are higher, thereby possibly improving overall survival (OS). Two recent randomized trials have suggested benefit of neoadjuvant chemoradiotherapy over upfront surgery, both including single-agent chemotherapy regimens. Potentially, the multi-agent FOLFIRINOX regimen (5-fluorouracil with leucovorin, irinotecan, and oxaliplatin) may further improve outcomes in the neoadjuvant setting for localized pancreatic cancer, but randomized studies are needed. The PREOPANC-2 trial investigates whether neoadjuvant FOLFIRINOX improves OS compared with neoadjuvant gemcitabine-based chemoradiotherapy and adjuvant gemcitabine in resectable and borderline resectable pancreatic cancer patients.Methods: This nationwide multicenter phase III randomized controlled trial includes patients with pathologically confirmed resectable and borderline resectable pancreatic cancer with a WHO performance score of 0 or 1. Resectable pancreatic cancer is defined as no arterial and ≤ 90 degrees venous involvement; borderline resectable pancreatic cancer is defined as ≤90 degrees arterial and ≤ 270 degrees venous involvement without occlusion. Patients receive 8 cycles of neoadjuvant FOLFIRINOX chemotherapy followed by surgery without adjuvant treatment (arm A), or 3 cycles of neoadjuvant gemcitabine with hypofractionated radiotherapy (36 Gy in 15 fractions) during the second cycle, followed by surgery and 4 cycles of adjuvant gemcitabine (arm B). The primary endpoint is OS by intention-to-treat. Secondary endpoints include progression-free survival, quality of life, resection rate, and R0 resection rate. To detect a hazard ratio of 0.70 with 80% power, 252 events are needed. The number of events is expected to be reached after inclusion of 368 eligible patients assuming an accrual period of 3 years and 1.5 years follow-up.Discussion: The PREOPANC-2 trial directly compares two neoadjuvant regimens for patients with resectable and borderline resectable pancreatic cancer. Our study will provide evidence on the neoadjuvant treatment of choice for patients with resectable and borderline resectable pancreatic cancer.Trial Registration: Primary registry and trial identifying number: EudraCT: 2017-002036-17 . Date of registration: March 6, 2018. Secondary identifying numbers: The Netherlands National Trial Register - NL7094 , NL61961.078.17, MEC-2018-004. [ABSTRACT FROM AUTHOR]

A correction to this paper has been published: https://doi.org/10.1007/s13304-021-01068-6 [ABSTRACT FROM AUTHOR]

Purpose: Shared decision-making (SDM) is crucial in pancreatic cancer treatment due to its choice-sensitive nature and limited prognosis. Treatment of pancreatic cancer is organized in a network approach. Several obstacles exist on different levels-patient, healthcare professional, organizational, societal-that impede integration of SDM. This study aims to identify barriers and facilitators to SDM implementation within a comprehensive cancer network., Methods: A qualitative research design was applied, involving interviews and focus groups on barriers and facilitators with healthcare professionals involved in the implementation of SDM. In one comprehensive cancer network in the Netherlands, including seven hospitals, a project was initiated with the goal of empowering patients and healthcare professionals in SDM throughout primary, secondary and tertiary healthcare settings. A total of 17 participants were assessed. Directed qualitative content analysis was performed by two researchers., Results: Main findings revealed barriers such as time constraints, lack of priority of physicians, little involvement of general practitioners, and insufficient social context of patients in referrals, alongside facilitators including learning communities with practical SDM examples, metro mapping, involvement of case manager in implementation and patient empowerment strategies., Conclusion: Addressing cultural, systemic barriers and developing innovative strategies are of importance to enhance SDM in pancreatic cancer treatment in a network approach. This study provides understanding of SDM implementation in complex healthcare settings and offers valuable guidance for future interventions seeking to improve decision-making processes in pancreatic cancer treatment and beyond., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background: This meta-analysis investigated the effects of enhanced recovery after surgery (ERAS) protocols compared to conventional care on postoperative outcomes in patients aged 70 years or older undergoing pancreatoduodenectomy (PD)., Methods: Five databases were systematically searched. Comparative studies with available individual patient data (IPD) were included. The main outcomes were postoperative morbidity, length of stay, readmission and postoperative functional recovery elements. To assess an age-dependent effect, the group was divided in septuagenarians (70-79 years) and older patients (≥80 years)., Results: IPD were obtained from 15 of 31 eligible studies comprising 1109 patients. The overall complication and major complication rates were comparable in both groups (OR 0.92 [95% CI: 0.65-1.29], p = .596 and OR 1.22 [95% CI: 0.61-2.46], p = .508). Length of hospital stay tended to be shorter in the ERAS group compared to the conventional care group (-0.14 days [95% CI: -0.29 to 0.01], p = .071) while readmission rates were comparable and the total length of stay including days in hospital after readmission tended to be shorter in the ERAS group (-0.28 days [95% CI: -0.62 to 0.05], p = .069). In the subgroups, the length of stay was shorter in octogenarians treated with ERAS (-0.36 days [95% CI: -0.71 to -0.004], p = .048). The readmission rate increased slightly but not significantly while the total length of stay was not longer in the ERAS group., Conclusion: ERAS in the elderly is safe and its benefits are preserved in the care of even in patients older than 80 years. Standardized care protocol should be encouraged in all pancreatic centers., (© 2024 Japanese Society of Hepato‐Biliary‐Pancreatic Surgery.)

Suboptimal patient education at discharge has been observed in many situations and is related to medication errors, complications and readmissions. The aim of this observational study was to improve patient education at the time of discharge and was performed in two academic hospitals in the United States. During a 14 month period 33 patients were observed during discharge conversation. The different domains that should be part of this patient education moment like self-management, changes in medication, reasons for contact were according to the researchers substandard. In this commentary we concluded that although this study has shortcomings, the situation and observations will probably be the same in the Netherlands. Research on personalized patient education at discharge should focus on relevant outcome parameters and interventions and this can only start in dialogue with patients.

Competing Interests: Competing interests: AMS and JR are board members of the not-for-profit Metro Mapping Foundation (no honorarium involved). JB is managing director of Design Studio Panton Deventer, who provide consultation in the use of Metro Mapping. The other authors declare no conflict of interest.

Digital images are becoming more readily available and possibilities for image processing are developing rapidly. This opens the possibility to use digital images to monitor and detect diseases in animals. In this paper we present 1) a generic facial feature scoring system based on seven facial features, 2) manual scores of images of Holstein Frisian heifers during foot-and-mouth disease vaccine efficacy trials and 3) automatic disease scores of the same animals. The automatic scoring system was based on the manual version and trained on annotated images from the manual scoring system. For both systems we found an increase in disease scores three days post infection, followed by a recovery. This temporal pattern matched with observations made by animal caretakers. Importantly, the automatic system was able to discern animals that were protected by the vaccine, and did not develop blisters at the feet, and animals that were not protected. Finally, automatic scores could be used to detect healthy and sick animals with a sensitivity and specificity of 0.94 on the second and third days following infection in an experimental setting. This generic facial feature disease scoring system could be further developed and extended to lactating Holstein Frisian dairy cows, other breeds and other infectious diseases. The system could be applied during animal experiments or, after further development, in a farm setting., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The necessity of the staging laparoscopy in patients with pancreatic cancer is still debated. The objective of this study was to assess the yield of staging laparoscopy for detecting occult metastases in patients with resectable or borderline resectable pancreatic cancer., Method: This was a post-hoc analysis of the randomized controlled PREOPANC trial in which patients with resectable or borderline resectable pancreatic cancer were randomized between preoperative chemoradiotherapy or immediate surgery. Patients assigned to preoperative treatment underwent a staging laparoscopy prior to preoperative treatment according to protocol, to avoid unnecessary chemoradiotherapy in patients with occult metastatic disease., Results: Of the 246 included patients, 7 did not undergo surgery. A staging laparoscopy was performed in 133 patients (55.6%) and explorative laparotomy in 106 patients (44.4%). At staging laparoscopy, occult metastases were detected in 13 patients (9.8%); 12 liver metastases and 1 peritoneal metastasis. At direct explorative laparotomy, occult metastases were found in 9 patients (8.5%); 6 with liver metastases, 1 with peritoneal metastases, and 2 with metastases at multiple sites. One patient had peritoneal metastases at exploration after a negative staging laparoscopy. Patients with occult metastases were more likely to receive palliative chemotherapy if found with staging laparoscopy compared to laparotomy (76.9% vs. 30.0%, p = 0.040)., Conclusions: Staging laparoscopy detected occult metastases in about 10% of patients with resectable or borderline resectable pancreatic cancer. These patients were more likely to receive palliative systemic chemotherapy compared to patients in whom occult metastases were detected with laparotomy. A staging laparoscopy is recommended before planned resection., (Copyright © 2022. Published by Elsevier Ltd.)

Background: The causal pathway between complications after pancreatic cancer resection and impaired long-term survival remains unknown. The aim of this study was to investigate the impact of complications after pancreatic cancer resection on disease-free interval and overall survival, with adjuvant chemotherapy as a mediator., Methods: This observational study included all patients undergoing pancreatic cancer resection in the Netherlands (2014-2017). Clinical data were extracted from the prospective Dutch Pancreatic Cancer Audit. Recurrence and survival data were collected additionally. In causal mediation analysis, direct and indirect effect estimates via adjuvant chemotherapy were calculated., Results: In total, 1071 patients were included. Major complications (hazards ratio 1.22 (95 per cent c.i. 1.04 to 1.43); P = 0.015 and hazards ratio 1.25 (95 per cent c.i. 1.08 to 1.46); P = 0.003) and organ failure (hazards ratio 1.86 (95 per cent c.i. 1.32 to 2.62); P < 0.001 and hazards ratio 1.89 (95 per cent c.i. 1.36 to 2.63); P < 0.001) were associated with shorter disease-free interval and overall survival respectively. The effects of major complications and organ failure on disease-free interval (-1.71 (95 per cent c.i. -2.27 to -1.05) and -3.05 (95 per cent c.i. -4.03 to -1.80) respectively) and overall survival (-1.92 (95 per cent c.i. -2.60 to -1.16) and -3.49 (95 per cent c.i. -4.84 to -2.03) respectively) were mediated by adjuvant chemotherapy. Additionally, organ failure directly affected disease-free interval (-5.38 (95 per cent c.i. -9.27 to -1.94)) and overall survival (-6.32 (95 per cent c.i. -10.43 to -1.99)). In subgroup analyses, the association was found in patients undergoing pancreaticoduodenectomy, but not in patients undergoing distal pancreatectomy., Conclusion: Major complications, including organ failure, negatively impact survival in patients after pancreatic cancer resection, largely mediated by adjuvant chemotherapy. Prevention or adequate treatment of complications and use of neoadjuvant treatment may improve oncological outcomes., (© The Author(s) 2023. Published by Oxford University Press on behalf of BJS Society Ltd.)

Background: Even during long-term combination antiretroviral therapy (cART), people living with HIV (PLHIV) have a dysregulated immune system, characterized by persistent immune activation, accelerated immune ageing and increased risk of non-AIDS comorbidities. A multi-omics approach is applied to a large cohort of PLHIV to understand pathways underlying these dysregulations in order to identify new biomarkers and novel genetically validated therapeutic drugs targets., Methods: The 2000HIV study is a prospective longitudinal cohort study of PLHIV on cART. In addition, untreated HIV spontaneous controllers were recruited. In-depth multi-omics characterization will be performed, including genomics, epigenomics, transcriptomics, proteomics, metabolomics and metagenomics, functional immunological assays and extensive immunophenotyping. Furthermore, the latent viral reservoir will be assessed through cell associated HIV-1 RNA and DNA, and full-length individual proviral sequencing on a subset. Clinical measurements include an ECG, carotid intima-media thickness and plaque measurement, hepatic steatosis and fibrosis measurement as well as psychological symptoms and recreational drug questionnaires. Additionally, considering the developing pandemic, COVID-19 history and vaccination was recorded. Participants return for a two-year follow-up visit. The 2000HIV study consists of a discovery and validation cohort collected at separate sites to immediately validate any finding in an independent cohort., Results: Overall, 1895 PLHIV from four sites were included for analysis, 1559 in the discovery and 336 in the validation cohort. The study population was representative of a Western European HIV population, including 288 (15.2%) cis -women, 463 (24.4%) non-whites, and 1360 (71.8%) MSM (Men who have Sex with Men). Extreme phenotypes included 114 spontaneous controllers, 81 rapid progressors and 162 immunological non-responders. According to the Framingham score 321 (16.9%) had a cardiovascular risk of >20% in the next 10 years. COVID-19 infection was documented in 234 (12.3%) participants and 474 (25.0%) individuals had received a COVID-19 vaccine., Conclusion: The 2000HIV study established a cohort of 1895 PLHIV that employs multi-omics to discover new biological pathways and biomarkers to unravel non-AIDS comorbidities, extreme phenotypes and the latent viral reservoir that impact the health of PLHIV. The ultimate goal is to contribute to a more personalized approach to the best standard of care and a potential cure for PLHIV., Competing Interests: All authors are part of the 2000HIV collaboration, which is supported by ViiV Healthcare. ViiV Healthcare funded this research and the included authors employed by the company contributed in the writing of the final manuscript. Although there is close collaboration, ViiV Healthcare did not have any role in data quality control, statistical analyses and final interpretation of the data.Author CR received grants from Gilead sciences, ViiV Healthcare, Janssen-Cilag, Health Holland, AIDSfonds, ErasmusMC, outside the submitted work. Authors EW, SVV, MK and JL are employed by ViiV healthcare. Authors QM and AJV received grants from Sysmex Corporation. Author TH is employed by Sysmex Corporation., (Copyright © 2022 Vos, Groenendijk, Blaauw, van Eekeren, Navas, Cleophas, Vadaq, Matzaraki, dos Santos, Meeder, Fröberg, Weijers, Zhang, Fu, ter Horst, Bock, Knoll, Aschenbrenner, Schultze, Vanderkerckhove, Hwandih, Wonderlich, Vemula, van der Kolk, de Vet, Blok, Brinkman, Rokx, Schellekens, de Mast, Joosten, Berrevoets, Stalenhoef, Verbon, van Lunzen, Netea and van der Ven.)

Background: Early recognition and management of postoperative complications, before they become clinically relevant, can improve postoperative outcomes for patients, especially for high-risk procedures such as pancreatic resection., Methods: We did an open-label, nationwide, stepped-wedge cluster-randomised trial that included all patients having pancreatic resection during a 22-month period in the Netherlands. In this trial design, all 17 centres that did pancreatic surgery were randomly allocated for the timing of the crossover from usual care (the control group) to treatment given in accordance with a multimodal, multidisciplinary algorithm for the early recognition and minimally invasive management of postoperative complications (the intervention group). Randomisation was done by an independent statistician using a computer-generated scheme, stratified to ensure that low-medium-volume centres alternated with high-volume centres. Patients and investigators were not masked to treatment. A smartphone app was designed that incorporated the algorithm and included the daily evaluation of clinical and biochemical markers. The algorithm determined when to do abdominal CT, radiological drainage, start antibiotic treatment, and remove abdominal drains. After crossover, clinicians were trained in how to use the algorithm during a 4-week wash-in period; analyses comparing outcomes between the control group and the intervention group included all patients other than those having pancreatic resection during this wash-in period. The primary outcome was a composite of bleeding that required invasive intervention, organ failure, and 90-day mortality, and was assessed by a masked adjudication committee. This trial was registered in the Netherlands Trial Register, NL6671., Findings: From Jan 8, 2018, to Nov 9, 2019, all 1805 patients who had pancreatic resection in the Netherlands were eligible for and included in this study. 57 patients who underwent resection during the wash-in phase were excluded from the primary analysis. 1748 patients (885 receiving usual care and 863 receiving algorithm-centred care) were included. The primary outcome occurred in fewer patients in the algorithm-centred care group than in the usual care group (73 [8%] of 863 patients vs 124 [14%] of 885 patients; adjusted risk ratio [RR] 0·48, 95% CI 0·38-0·61; p<0·0001). Among patients treated according to the algorithm, compared with patients who received usual care there was a decrease in bleeding that required intervention (47 [5%] patients vs 51 [6%] patients; RR 0·65, 0·42-0·99; p=0·046), organ failure (39 [5%] patients vs 92 [10%] patients; 0·35, 0·20-0·60; p=0·0001), and 90-day mortality (23 [3%] patients vs 44 [5%] patients; 0·42, 0·19-0·92; p=0·029)., Interpretation: The algorithm for the early recognition and minimally invasive management of complications after pancreatic resection considerably improved clinical outcomes compared with usual care. This difference included an approximate 50% reduction in mortality at 90 days., Funding: The Dutch Cancer Society and UMC Utrecht., Competing Interests: Declaration of interests CvdL is the Secretary of the Dutch Society of Interventional Radiology (unpaid position). CHvW's institution received payments from Pfizer, Biomerieux, Da Volterra, and MSD and he has a European Patent Application with Da Volterrra, University Antwerp, and University Medical Centre Utrecht Holdings. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: This individual-patient data meta-analysis investigated the effects of enhanced recovery after surgery (ERAS) protocols compared with conventional care on postoperative outcomes in patients undergoing pancreatoduodenectomy., Methods: The Cochrane Library, MEDLINE, Embase, Scopus, and Web of Science were searched systematically for articles reporting outcomes of ERAS after pancreatoduodenectomy published up to August 2020. Comparative studies were included. Main outcomes were postoperative functional recovery elements, postoperative morbidity, duration of hospital stay, and readmission., Results: Individual-patient data were obtained from 17 of 31 eligible studies comprising 3108 patients. Time to liquid (mean difference (MD) -3.23 (95 per cent c.i. -4.62 to -1.85) days; P < 0.001) and solid (-3.84 (-5.09 to -2.60) days; P < 0.001) intake, time to passage of first stool (MD -1.38 (-1.82 to -0.94) days; P < 0.001) and time to removal of the nasogastric tube (3.03 (-4.87 to -1.18) days; P = 0.001) were reduced with ERAS. ERAS was associated with lower overall morbidity (risk difference (RD) -0.04, 95 per cent c.i. -0.08 to -0.01; P = 0.015), less delayed gastric emptying (RD -0.11, -0.22 to -0.01; P = 0.039) and a shorter duration of hospital stay (MD -2.33 (-2.98 to -1.69) days; P < 0.001) without a higher readmission rate., Conclusion: ERAS improved postoperative outcome after pancreatoduodenectomy. Implementation should be encouraged., (© The Author(s) 2022. Published by Oxford University Press on behalf of BJS Society Ltd. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To quantify the impact of individual complications on mortality, organ failure, hospital stay, and readmission after pancreatoduodenectomy., Summary of Background Data: An initial complication may provoke a sequence of adverse events potentially leading to mortality after pancreatoduodenectomy. This study was conducted to aid prioritization of quality improvement initiatives., Methods: Data from consecutive patients undergoing pancreatoduodenectomy (2014-2017) were extracted from the Dutch Pancreatic Cancer Audit. Population attributable fractions (PAF) were calculated for the association of each complication (ie, postoperative pancreatic fistula, postpancreatectomy hemorrhage, bile leakage, delayed gastric emptying, wound infection, and pneumonia) with each unfavorable outcome [ie, in-hospital mortality, organ failure, prolonged hospital stay (>75th percentile), and unplanned readmission), whereas adjusting for confounders and other complications. The PAF represents the proportion of an outcome that could be prevented if a complication would be eliminated completely., Results: Overall, 2620 patients were analyzed. In-hospital mortality occurred in 95 patients (3.6%), organ failure in 198 patients (7.6%), and readmission in 427 patients (16.2%). Postoperative pancreatic fistula and postpancreatectomy hemorrhage had the greatest independent impact on mortality [PAF 25.7% (95% CI 13.4-37.9) and 32.8% (21.9-43.8), respectively] and organ failure [PAF 21.8% (95% CI 12.9-30.6) and 22.1% (15.0-29.1), respectively]. Delayed gastric emptying had the greatest independent impact on prolonged hospital stay [PAF 27.6% (95% CI 23.5-31.8)]. The impact of individual complications on unplanned readmission was smaller than 11%., Conclusion: Interventions focusing on postoperative pancreatic fistula and postpancreatectomy hemorrhage may have the greatest impact on in-hospital mortality and organ failure. To prevent prolonged hospital stay, initiatives should in addition focus on delayed gastric emptying., Competing Interests: The author reports no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

The emerging profile of blood flow and the cross-sectional distribution of blood cells have far reaching biological consequences in various diseases and vital internal processes, such as platelet adhesion. The effects of several essential blood flow parameters, such as red blood cell free layer width, wall shear rate, and hematocrit on platelet adhesion were previously explored to great lengths in straight geometries. In the current work, the effects of channel curvature on cellular blood flow are investigated by simulating the accurate cellular movement and interaction of red blood cells and platelets in a half-arc channel for multiple wall shear rate and hematocrit values. The results show significant differences in the emerging shear rate values and distributions between the inner and outer arc of the channel curve, while the cell distributions remain predominantly uninfluenced. The simulation predictions are also compared to experimental platelet adhesion in a similar curved geometry. The inner side of the arc shows elevated platelet adhesion intensity at high wall shear rate, which correlates with increased shear rate and shear rate gradient sites in the simulation. Furthermore, since the platelet availability for binding seems uninfluenced by the curvature, these effects might influence the binding mechanics rather than the probability. The presence of elongational flows is detected in the simulations and the link to increased platelet adhesion is discussed in the experimental results., (© 2021. The Author(s).)

An in silico trial simulates a disease and its corresponding therapies on a cohort of virtual patients to support the development and evaluation of medical devices, drugs, and treatment. In silico trials have the potential to refine, reduce cost, and partially replace current in vivo studies, namely clinical trials and animal testing. We present the design and implementation of an in silico trial for treatment of acute ischemic stroke. We propose an event-based modelling approach for the simulation of a disease and injury, where changes to the state of the system (the events) are assumed to be instantaneous. Using this approach we are able to combine a diverse set of models, spanning multiple time scales, to model acute ischemic stroke, treatment, and resulting brain tissue injury. The in silico trial is designed to be modular to aid development and reproducibility. It provides a comprehensive framework for application to any potential in silico trial. A statistical population model is used to generate cohorts of virtual patients. Patient functional outcomes are also predicted with a statistical model, using treatment and injury results and the patient's clinical parameters. We demonstrate the functionality of the event-based modelling approach and trial framework by running proof of concept in silico trials. The proof of concept trials simulate the same cohort of patients twice: once with successful treatment (successful recanalisation) and once with unsuccessful treatment (unsuccessful treatment). Ways to overcome some of the challenges and difficulties in setting up such an in silico trial are discussed, such as validation and computational limitations., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Older adults living with HIV (OALWH) are a growing population facing unique challenges to successful antiretroviral therapy. Objective: To assess efficacy and safety profiles of antiretroviral regimens, including those containing dolutegravir, in OALWH. Methods: Combined data from 6 phase III/IIIb trials in treatment-naive (ARIA, FLAMINGO, SINGLE, SPRING-2; N  = 2634) and treatment-experienced (DAWNING, SAILING; N  = 1339) participants receiving dolutegravir- or non-dolutegravir-based regimens were analyzed by age (<50, ≥50 to <65, and ≥65 years). Baseline data included comorbidities and numbers of concomitant medications. Week 48 efficacy outcomes included virologic response (HIV-1 RNA <50 copies/mL) and CD4+ cell count change from baseline. Safety outcomes included incidence of adverse events (AEs), serious AEs, and AE-related withdrawals. Results: Use of ≥5 concomitant medications was more frequently reported among treatment-naive and treatment-experienced participants aged ≥50 to <65 (30% [90/296] and 25% [57/227], respectively) and ≥65 years (43% [10/23] and 29% [4/14]) than among those aged <50 years (13% [310/2315] and 11% [118/1098]). Comorbidities were more prevalent in the older age groups. For dolutegravir-based regimens, Week 48 rates of virologic response and change in CD4+ cell count were similar across age groups (treatment naive, 80-87% and 234-251 cells/mm 3 ; treatment experienced, 70-100% and 105-156 cells/mm 3 , respectively). There were no major differences in safety outcomes in each age group. Conclusions: In these analyses of combined phase III/IIIb trial data, efficacy and safety of dolutegravir-based regimens were generally similar across age groups in treatment-naive or treatment-experienced participants. Polypharmacy and comorbidities were more common among OALWH than those aged <50 years.

Rationale, Aims and Objectives: Cardiac surgery (CS) is facilitated by multiple perioperative guidelines and protocols. Use of a clinical pathway (CP) may facilitate the care of these patients., Methods: This is a pre-post design study in the ICU of a tertiary referral centre. A CP for CS patients in the ICU was developed by ICU-nurses and enabled them to execute proactively predefined actions in accordance with and within the preset boundaries which were part of a variance report. A tailored implementation strategy was used. Primary outcome measure was protocol adherence above 80% on the domains of blood pressure control, action on chest tube blood loss and electrolyte control within the CP., Results: In a 4-month period, 84 consecutive CP patients were included and compared with 162 matched control patients admitted in the year before implementation; 3 patients were excluded. Propensity score was used as matching parameter. CP patients were more likely to receive early adequate treatment for derangements in electrolytes (96% vs 47%, P < .001), blood pressure (90% vs 49%, P < .001) and adequate treatment for chest tube blood loss (90% vs 10%, P < .001). We found no differences in hospital and ICU LOS, ICU readmission or mortality., Conclusion: Use of the CP improved postoperative ICU treatment for cardiac surgical patients. Implementation of a CP and the use of a special variance report could be a blueprint for the implementation and use of a CP in low-volume high complex surgery., (© 2017 John Wiley & Sons, Ltd.)

Introduction: Medical and nursing protocols in perioperative care for pancreaticoduodenectomy are mainly mono-disciplinary, limiting their integration and transparency in a continuous health care system. The aims of this study were to evaluate adherence to a multidisciplinary clinical pathway for all pancreaticoduodenectomy patients during their entire hospital stay and to determine if the use of this clinical pathway is associated with beneficial effects on clinical end points., Materials and Methods: A prospective cohort study was conducted in 95 pancreaticoduodenectomy patients treated according to a clinical pathway, including a variance report, compared to a historical control group (n = 52) with a traditional treatment regime., Results: Process evaluation of the clinical pathway group revealed that protocol adherence throughout all units was above 80%. Major complications according to Clavien-Dindo classification grade ≥3 decreased from 27 to 13%; p = 0.02. Hospital length of stay was significantly shorter in the clinical pathway group, median 10 days [IQR 8-15], compared with the control group, median 13 days [IQR 10-18]; p = 0.02., Conclusion: The use of a clinical pathway in pancreaticoduodenectomy patients was associated with high protocol adherence, improved outcome and shorter hospital length of stay. Variance report analysis and protocol adherence with a Prepare-Act-Reflect Cycle are essential in surveillance of outcome.

Background: Optimizing cardiac stroke volume during major surgery is of interest to many as a therapeutic target to decrease the incidence of postoperative complications. Because dynamic preload indicators are strongly correlated with stroke volume, it is suggested that these indices can be used for goal directed fluid therapy. However, threshold values of these indicators depend on many factors that are influenced by surgery, including opening of the abdomen. The aim of this study was therefore to assess the effect of opening the abdomen on arterial pressure variations in patients undergoing abdominal surgery., Methods: Blood pressure and bladder pressure were continuously recorded just before and after opening of the abdomen in patients undergoing elective laparotomy. Based on waveform analysis of the non-invasively derived blood pressure, the stroke volume index, pulse pressure variation (PPV) and stroke volume variation (SVV) were calculated off-line., Results: Thirteen patients were included. After opening the abdomen, PPV and SVV decreased from 11.5 ± 5.8% to 6.4 ± 2.9% (p < 0.005, a relative decrease of 40 ± 19%) and 12.7 ± 6.1% to 4.8 ± 1.6% (p < 0.05, a relative decrease of 53 ± 26%), respectively. Although mean arterial pressure and stroke volume index tended to increase (41 ± 6 versus 45 ± 4 ml/min/m2, p = 0.14 and 41 ± 6 versus 45 ± 4 ml/min/m2, p = 0.05), and heart rate tended to decrease (73 ± 15 versus 68 ± 11 1/min, p = 0.05), no significant change was found. No significant change was found in respiratory parameter (tidal volume, respiratory rate or inspiratory pressure; p = 0.36, 0.34 and 0.17, respectively) or bladder pressure (6.0 ± 3.7 versus 5.6 ± 2.7 mmHg, p = 0.6) either., Conclusions: Opening of the abdomen decreases PPV and SVV. During goal directed therapy, current thresholds for fluid responsiveness should be changed accordingly.