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Background Empiric antifungal therapy is considered the standard of care for high-risk neutropenic patients with persistent fever. The impact of a preemptive, diagnostic-driven approach based on galactomannan screening and chest computed tomography scan on demand on survival and on the risk of invasive fungal disease (IFD) during the first weeks of high-risk neutropenia is unknown. Methods Patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) and allogeneic hematopoietic cell transplant recipients were randomly assigned to receive caspofungin empirically (arm A) or preemptively (arm B), while receiving fluconazole 400 mg daily prophylactically. The primary end point of this noninferiority study was overall survival (OS) 42 days after randomization. Results Of 556 patients recruited, 549 were eligible: 275 in arm A and 274 in arm B. Eighty percent of the patients had AML or MDS requiring high-dose chemotherapy, and 93% of them were in the first induction phase. At day 42, the OS was not inferior in arm B (96.7%; 95% confidence interval [CI], 93.8%–98.3%) when compared with arm A (93.1%; 95% CI, 89.3%–95.5%). The rates of IFDs at day 84 were not significantly different, 7.7% (95% CI, 4.5%–10.8%) in arm B vs 6.6% (95% CI, 3.6%–9.5%) in arm A. The rate of patients who received caspofungin was significantly lower in arm B (27%) than in arm A (63%; P < .001). Conclusions The preemptive antifungal strategy was safe for high-risk neutropenic patients given fluconazole as prophylaxis, halving the number of patients receiving antifungals without excess mortality or IFDs. Clinical Trials Registration. NCT01288378; EudraCT 2010-020814-27.

Jingmin Zhang,1,2 Guangzhao Qi,1,2 Chao Han,1,2 Yubing Zhou,1,2 Yongjie Yang,1 Xinru Wang,1,2 Suna Liu,3 Xiaojian Zhang1,2 1Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Henan Key Laboratory for Precision Clinical Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 3Newborn Screening Center, Department of Pediatrics, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of ChinaCorrespondence: Guangzhao Qi; Xiaojian Zhang Tel +86-37166295269Email qiguangzhao1223@sina.com; zhangxiaojian15@126.comPurpose: Pharmacogenetic testing is recognized as the major method for the individualized pharmacotherapy in clinical pharmacy practice, but information about the clinical implementation of pharmacogenetic testing in China is limited. The present study aimed to determine the situation of clinical implementation for pharmacogenetic testing in central China.Methods: The study is conducted in the department of clinical pharmacy in The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. We collected and analyzed pharmacogenetic testing results from November 1, 2013 to November 2, 2018 in our hospital, which were checked in the electronic medical record system. The main outcome measures were the number and type of pharmacogenetic testing across five years.Results: A total of 47,265 (56.9% male, mean age = 51.5 years) pharmacogenetic testing results were obtained with an average annual rate of growth of 63.0% across five years. A 50.2% (23,748/47,265) of all the pharmacogenetic testing results were for the determination of cytochrome P450 2C19 (CYP2C19) &ast;2, &ast;3 genotypes, and 41.7% were for the methylene tetrahydrofolate reductase (MTHFR) C677T genotype. The number of departments performing the pharmacogenetic testing was 35, 63, 55, 52, 52 and 39 for 2013– 2018, respectively, and the main top five departments were cardiology, psychiatry, ICU, cardiac surgery and intervention.Conclusion: Clinical implementation of pharmacogenetic testing in China is growing rapidly, but the types and implementing departments of pharmacogenetic testing were limited. Our present study reported the real-world implementation modality of pharmacogenomic tests in China. It will help us to understand the testing of pharmacogenetics in China in order to promote the rational development of pharmacogenetics.Keywords: clinical implementation, pharmacogenomics, pharmacogenetics, China, preemptive

Jingmin Zhang,1,2 Guangzhao Qi,1,2 Chao Han,1,2 Yubing Zhou,1,2 Yongjie Yang,1 Xinru Wang,1,2 Suna Liu,3 Xiaojian Zhang1,2 1Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Henan Key Laboratory for Precision Clinical Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 3Newborn Screening Center, Department of Pediatrics, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of ChinaCorrespondence: Guangzhao Qi; Xiaojian Zhang Tel +86-37166295269Email qiguangzhao1223@sina.com; zhangxiaojian15@126.comPurpose: Pharmacogenetic testing is recognized as the major method for the individualized pharmacotherapy in clinical pharmacy practice, but information about the clinical implementation of pharmacogenetic testing in China is limited. The present study aimed to determine the situation of clinical implementation for pharmacogenetic testing in central China.Methods: The study is conducted in the department of clinical pharmacy in The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. We collected and analyzed pharmacogenetic testing results from November 1, 2013 to November 2, 2018 in our hospital, which were checked in the electronic medical record system. The main outcome measures were the number and type of pharmacogenetic testing across five years.Results: A total of 47,265 (56.9% male, mean age = 51.5 years) pharmacogenetic testing results were obtained with an average annual rate of growth of 63.0% across five years. A 50.2% (23,748/47,265) of all the pharmacogenetic testing results were for the determination of cytochrome P450 2C19 (CYP2C19) &ast;2, &ast;3 genotypes, and 41.7% were for the methylene tetrahydrofolate reductase (MTHFR) C677T genotype. The number of departments performing the pharmacogenetic testing was 35, 63, 55, 52, 52 and 39 for 2013– 2018, respectively, and the main top five departments were cardiology, psychiatry, ICU, cardiac surgery and intervention.Conclusion: Clinical implementation of pharmacogenetic testing in China is growing rapidly, but the types and implementing departments of pharmacogenetic testing were limited. Our present study reported the real-world implementation modality of pharmacogenomic tests in China. It will help us to understand the testing of pharmacogenetics in China in order to promote the rational development of pharmacogenetics.Keywords: clinical implementation, pharmacogenomics, pharmacogenetics, China, preemptive

CPU scheduling algorithms have a significant function in multiprogramming operating systems. When the CPU scheduling is effective a high rate of computation could be done correctly and also the system will maintain in a stable state. As well as, CPU scheduling algorithms are the main service in the operating systems that fulfill the maximum utilization of the CPU. This paper aims to compare the characteristics of the CPU scheduling algorithms towards which one is the best algorithm for gaining a higher CPU utilization. The comparison has been done between ten scheduling algorithms with presenting different parameters, such as performance, algorithm’s complexity, algorithm’s problem, average waiting times, algorithm’s advantages-disadvantages, allocation way, etc. The main purpose of the article is to analyze the CPU scheduler in such a way that suits the scheduling goals. However, knowing the algorithm type which is most suitable for a particular situation by showing its full properties.

Objective: The aim of this study is to investigate the effect of the preemptive use of plerixafor in patients with lymphoma and multiple myeloma which was administered as a preemptive single dose to the patients who were determined to have a CD34+ cell count of

Purpose Abdominal myomectomy can be a challenging procedure, with elevated intraoperative blood loss and post-operative complications such as the need for blood transfusion and hemostasis with sometimes hysterectomy. Previous studies suggested that preemptive uterine artery embolization (PUAE) might reduce intraoperative blood loss. Materials and methods We reviewed all cases of abdominal myomectomy in our institution between January 2016 and June 2018. Out of 119 cases, 16 patients had PUAE and 103 did not. The objective of our study was to determine whereas PUAE reduced blood loss and post-operative complication rate. Results In our study, there was no difference between the two groups in regard to average blood loss (128 vs 192 mL, OR 1,00 [0.99;1,01], p = 0,73), difference between pre- and post-operative hemoglobin level (− 1,15 g/dL vs − 1,32 g/dL, OR 0,91 [0.47;1,73], p = 0,79), and post-operative complications (need for transfusion, surgical revision, post-operative embolization, hysterectomy). Conclusion Our findings could not conclude that PUAE is effective in reducing intraoperative blood loss during abdominal myomectomy, but it should still be considered an option for patients with large or multiple myomas, with a specific situation or previously operated, who wish to preserve their uterus.

Çalışmamızda mastektomi uygulanan hastalarda preemptif ve postoperatif tenoksikam kullanımının postoperatif ağrı üzerine etkilerinin karşılaştırılması amaçlandı. Haziran 2009-Eylül 2010 tarihleri arasında mastektomi uygulanan 75 hasta çalışmaya dahil edildi. Preemptif tenoksikam grubundaki (Grup CÖ-T, n=25) hastalara cerrahi başlangıcından 30 dk önce tenoksikam 20 mg iv (2 ml), cerrahi bitiminde serum fizyolojik (SF) 2 ml iv verildi. Cerrahi sonrası tenoksikam uygulanan gruptaki (Grup CB-T, n=25) hastalara ise cerrahi başlangıcından 30 dk önce SF, cerrahi bitiminde tenoksikam uygulandı. Kontrol grubundaki (Grup Kontrol, n=25) hastalara ise cerrahi başlangıcından 30 dk önce ve cerrahi bitiminde SF uygulandı. Postoperatif hasta kontrollü analjezi başlandı. Postoperatif Görsel Analog Skala (VAS) değerleri, bulantı kusma şiddeti ve morfin kullanım miktarları ile postoperatif ilk analjezik gereksinim ve mobilizasyon zamanları, hastanede kalış süreleri, 24 saatlik morfin tüketimleri, postoperatif komplikasyonlar, hasta ve hemşire memnuniyetleri kaydedildi. Postoperatif derlenme ünitesinde yapılan ilk değerlendirme (0. saat) VAS değeri Grup CÖ-T ve Grup CB-T’de benzer, Grup-Kontrol’de yüksek bulundu. (p

With the continuous development of intelligent manufacturing technology, the intelligent production line for the Industrial Internet of Things occupies an important position in the field of industrial intelligence. OPC UA is a standard for communication data exchange between intelligent production line devices. OPC UA can establish a unified information model for production line devices and improve the connectivity of heterogeneous networks. However, in industrial wireless network application scenarios, there are various types of sensing information and large amounts of data to be transmitted. Each type of data has different requirements for real-time. The traditional OPC UA communication method is difficult to achieve real-time and reliable transmission in intelligent production lines and can’t meet the transmission requirements of time-sensitive data. In this paper, we propose a real-time communication model of the OPC UA wireless network for intelligent production lines (UAMPDS). IEEE 802.15.4e TSCH is used as the wireless communication infrastructure, and OPC UA protocols are fused to this model. Meanwhile, we design a load-aware time-slot scheduling algorithm to dynamically allocate and schedule time slots according to the network topology and traffic load of each node. We also implement a dynamic preemptive resource scheduling strategy based on service differentiation to ensure real-time transmission of time-sensitive data. The experimental results show that this model achieves differentiated services based on data with different latency tolerance and effectively reduces the transmission latency of real-time service data under the constrained network resources. It can avoid the starvation phenomenon of low priority queues, and improves the overall quality of service of intelligent production line communication networks.

As an emerging measure of data freshness, the age of information (AoI) is receiving extensive attention. Many methods using AoI have been proposed for communication scheduling in the Internet of Things (IoT). However, most of them are aimed at constant channel conditions in the ideal state, and the utilization of link resources is not sufficient. In addition, only the optimization of AoI is considered, without considering whether the sample is extruded. Sample extrusion refers to the scenario in which the transmission of the remaining untransmitted sample of the source node cannot be completed within the transmission time interval (TTI) before the arrival of the new sampling period of the source node. Thus, sample extrusion is a phenomenon that occurs when the new sample arrives while the old sample has not yet been completely transmitted. This scenario has a serious impact on delay-sensitive IoT applications. Therefore, under dynamic channel conditions and limited link resources, this paper establishes two mathematical models for AoI and sample extrusion. The influence of the scheduling algorithm on these two target values is analyzed and proven. Based on a greedy strategy, we propose a preemptive online algorithm for link resource allocation that considers two objectives: to give full play to the value of link resources and to minimize sample extrusion. The simulation results show that the proposed strategy can achieve better comprehensive performance in both scenarios where the sample variance between source nodes is small or large.

Background Pancreaticoduodenectomy is a technically demanding operation, with reported morbidity rates of approximately 40%-50%. A novel idea is to use endoscopic vacuum therapy (EVT) in a preemptive setting to prevent anastomotic leakage and pancreatic fistulas. In a recent case series, EVT was proven to be effective in preventing leaks in patients with anastomotic ischemia. There have been no previous reports on preemptive EVT after pancreaticoduodenectomy. Case summary We describe the case of a 71-year-old woman with hypertension and diabetes who was admitted to the emergency room with jaundice, choluria, fecal acholia, abdominal pain, and fever. Admission examinations revealed leukocytosis and hyperbilirubinemia (total: 13 mg/dL; conjugated: 12.1 mg/dL). Abdominal ultrasound showed cholelithiasis and dilation of the common bile duct. Magnetic resonance imaging demonstrated a stenotic area, and a biopsy confirmed cholangiocarcinoma. Considering the high risk of leaks after pancreatico-duodenectomy, preemptive endoluminal vacuum therapy was performed. The system comprised a nasogastric tube, gauze, and an antimicrobial incise drape. The negative pressure was 125 mmHg, and no adverse events occurred. The patient was discharged on postoperative day 5 without any symptoms. Conclusion Preemptive endoluminal vacuum therapy may be a safe and feasible technique to reduce leaks after pancreaticoduodenectomy.

For allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients, preemptive interferon-α (IFN-α) therapy is considered as a useful method to eliminate the minimal residual disease (MRD). Our purpose is to assess the long-term efficacy of preemptive IFN-α therapy in acute myeloid leukemia (AML) patients following allo-HSCT based on two registry studies (#NCT02185261 and #NCT02027064). We would present the final data and unpublished results of long-term clinical outcomes with extended follow-up. We adopted polymerase chain reaction (PCR) and multiparameter flow cytometry (MFC) to monitor MRD, and a positive result of bone marrow specimen examined by either of them would be identified as the MRD-positive status. Subcutaneous injections of recombinant human IFN-α-2b were performed for 6 cycles, and prolonged IFN-α therapy could be permitted at the request of patients. The median cycles were 3.5 (range, 0.5–30.5) cycles. A total of 9 patients suffered from grade ≥3 toxicities (i.e., infectious: n = 6; hematologic: n = 3). The 6-year cumulative incidences of relapse and non-relapse mortality following IFN-α therapy were 13.0% (95% confidence interval [CI], 5.4–20.6%) and 3.9% (95%CI, 0.0–17.6%), respectively. The probability of disease-free survival at 6 years following IFN-α therapy was 83.1% (95%CI, 75.2–91.9%). The probability of overall survival at 6 years following IFN-α therapy was 88.3% (95%CI, 81.4–95.8%). The cumulative incidences of total chronic graft-versus-host disease (cGVHD) and severe cGVHD at 6 years following IFN-α therapy were 66.2% (95%CI, 55.5–77.0%) and 10.4% (95%CI, 3.6–17.2%), respectively. Multivariable analysis showed that an alternative donor was associated with a lower risk of relapse and the better disease-free survival. Thus, preemptive IFN-α therapy could clear MRD persistently, prevent relapse truly, and improve long-term survival in AML patients following allo-HSCT.

Millions of people suffer from heart failure worldwide. The need for heart donations started the development of mechanical circulatory support systems. A suction phenomenon can occur in the artificial heart when not enough blood is available. Due to occlusion, suction in the artificial heart can cause the arteries to collapse and have fatal consequences. This thesis is in collaboration with Scandinavian Real Heart AB and follows the implementation of a preemptive atrial suction detection algorithm for the total artificial heart (TAH) developed by Realheart. The main limitation is the number of sensors available to collect data from, restricted to a pressure and current sensor. The data used in the thesis is collected on a mock loop that simulates the pressures in the human body. The implementation follows an iterative process where different Artificial Intelligence algorithms are tested and evaluated. The final algorithm uses a recurrent neural network (RNN) for classification and is evaluated based on the accuracy and the number of seconds before suction occurs. The results show that the RNN can preemptively classify the data one second before it occurs. The algorithm assumes suction to happen one second before it occurs, preemptively detecting suction. The results from this thesis enable a continuation that can improve the development of TAHs. Future work includes an addition of features for a more accurate and robust algorithm, a more diverse dataset, an improved labelling process and the addition of a time axis to the RNN to improve the time before suction is detected.

BackgroundInvasive fungal infections (IFIs) are complications that lead to mortality and morbidity in hematologic malignancies. The time of starting antifungal therapy is vital. Preemptive antifungal therapy has appeared recently as a new policy for the management of IFIs based on noninvasive ways in neutropenic patients.MethodsWe enrolled leukemia patients with neutropenia after chemotherapy in Imam Khomeini Hospital Complex, Tehran, Iran. Patients who entered the neutropenic phase were divided into two categories (empirical and preemptive) for receiving antifungal agents. The patients were clinically examined in the preemptive group every day to find IFIs. As soon as clinical evidence of IFIs was observed, antifungal was prescribed. The empirical group patients received antifungals based on the ward protocol. Based on the data in each group, the diagnostic and therapeutic results of cases are followed-up to 3 months. To compare percentages between the two groups, the chi-squared test was used. And to compare two means between the two groups, the independent t-test was used. All the statistical analyses were done in the Statistical Package for the Social Sciences (SPSS) version 24 software (IBM Corporation, Armonk, New York, USA).ResultsWe assessed 132 leukemic patients with inclusion and exclusion criteria. Eventually, 80 patients were enrolled. The mean age was 35.52 years. Demographics data and distribution of leukemia type show no significant differences between the two groups. Despite a higher percentage of IFIs discovered in the preemptive group than the empirical group (25 vs. 18.75%, respectively), but data show no significant differences. The average days of IFIs diagnosis since the beginning of neutropenia in the empirical group were 9.5 days while in the preemptive group, the average days were 5.4 days (p < 0.05). Totally, there were 15 patients with a proven IFI in each group (40% in the empirical group and 60% in the preemptive group). Results significantly show an increase in surgical sinus debridement in the empirical groups (83.3%) vs. the preemptive groups (55.5%), (p < 0.05). The mortality rate differed significantly among the two groups; it was 7.5% in the preemptive group and 25% in the empirical group (p < 0.05).ConclusionDaily oral and nasal cavities examination to find the symptoms of IFIs and then start preemptive antifungal agents may be able to lead to accurate diagnosis, earlier treatment, and decreasing sinus surgery debridement in leukemia patients with neutropenia.

In patients with t(8;21) acute myeloid leukemia (AML), recurrent minimal residual disease (MRD) measured by RUNX1-RUNX1T1 transcript levels can predict relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study aimed to compare the efficacy of preemptive interferon (IFN)-α therapy and donor lymphocyte infusion (DLI) in patients with t(8;21) AML following allo-HSCT. We also evaluated the appropriate method for patients with different levels of RUNX1-RUNX1T1 transcripts. In this retrospective study, consecutive patients who had high-risk t(8;21) AML and received allo-HSCT were enrolled. The inclusion criteria were as follows: (1) age ≤65 years; (2) regained MRD positive following allo-HSCT. MRD positive was defined as the loss of a ≥4.5-log reduction and/or RUNX1-RUNX1T1 transcripts, and high-level, intermediate-level, and low-level MRDs were, respectively, defined as RUNX1-RUNX1T1 could receive preemptive IFN-α therapy or DLI, which was primarily based on donor availability and the intentions of physicians and patients. The patients received recombinant human IFN-α-2b therapy by subcutaneous injection twice a week every 4 weeks. IFN-α therapy was scheduled for six cycles or until the RUNX1-RUNX1T1 transcripts were negative for at least two consecutive tests. The rates of MRD turning negative for patients with low-level, intermediate-level, and high-level RUNX1-RUNX1T1 receiving IFN-α were 87.5%, 58.1%, and 22.2%, respectively; meanwhile, for patients with intermediate-level and high-level RUNX1-RUNX1T1 receiving DLI, the rates were 50.0% and 14.3%, respectively. For patients with low-level and intermediate-level RUNX1-RUNX1T1, the probability of overall survival at 2 years was higher in the IFN-α group than in the DLI group (87.6% vs. 55.6%; p = 0.003). For patients with high levels of RUNX1-RUNX1T1, the probability of overall survival was comparable between the IFN-α and DLI groups (53.3% vs. 83.3%; p = 0.780). Therefore, patients with low-level and intermediate-level RUNX1-RUNX1T1 could benefit more from preemptive IFN-α therapy compared with DLI. Clinical outcomes were comparable between preemptive IFN-α therapy and DLI in patients with high-level RUNX1-RUNX1T1; however, they should be further improved.

The paper introduces foundational response-time analysis (RTA) as a means to produce strong and independently checkable evidence of temporal correctness. In a foundational RTA, each response-time bound calculated comes with an auto-generated certificate of correctness - a short and human-inspectable sequence of machine-checked proofs that formally show the claimed bound to hold. In other words, a foundational RTA yields explainable results that can be independently verified (e.g., by a certification authority) in a rigorous manner (with an automated proof checker). Consequently, the analysis tool itself does not need to be verified nor trusted. As a proof of concept, the paper presents POET, the first foundational RTA tool. POET generates certificates based on Prosa, the to-date largest verified framework for schedulability analysis, which is based on Coq. The trusted computing base is hence reduced to the Coq proof checker and its dependencies. POET currently supports two scheduling policies (earliest-deadline-first, fixed-priority), two preemption models (fully preemptive, fully non-preemptive), arbitrary deadlines, periodic and sporadic tasks, and tasks characterized by arbitrary arrival curves. The paper describes the challenges inherent in the development of a foundational RTA tool, discusses key design choices, and reports on its scalability., LIPIcs, Vol. 231, 34th Euromicro Conference on Real-Time Systems (ECRTS 2022), pages 19:1-19:25

This artifact provides the means to validate and reproduce the results of the associated paper “Foundational Response-Time Analysis as Explainable Evidence of Timeliness”. The artifact demonstrates how to (i) generate task sets needed to run the experiments, (ii) prepare and run POET on the generated input, (iii) plot the figures presented in the paper, and (iv) visually inspect the generated certificates., DARTS, Vol. 8, Special Issue of the 34th Euromicro Conference on Real-Time Systems (ECRTS 2022), pages 7:1-7:2

Many factors have been described to contribute to voriconazole (VCZ) interpatient variability in plasma concentrations, especially CYP2C19 genetic variability. In 2014, Hicks et al. presented data describing the correlation between VCZ plasma concentrations and CYP2C19 diplotypes in immunocompromised pediatric patients and utilized pharmacokinetic modeling to extrapolate a more suitable VCZ dose for each CYP2C19 diplotype. In 2017, in our hospital, a clinical protocol was developed for individualization of VCZ in immunocompromised patients based on preemptive genotyping of CYP2C19 and dosing proposed by Hicks et al., Clinical Pharmacogenetics Implementation Consortium (CPIC) clinical guidelines, and routine therapeutic drug monitoring (TDM). We made a retrospective review of a cohort of 28 immunocompromised pediatric patients receiving VCZ according to our protocol. CYP2C19 gene molecular analysis was preemptively performed using PharmArray®. Plasma trough concentrations were measured by immunoassay analysis until target concentrations (1–5.5 μg/ml) were reached. Sixteen patients (57.14%) achieved VCZ trough target concentrations in the first measure after the initial dose based on PGx. This figure is similar to estimations made by Hicks et al. in their simulation (60%). Subdividing by phenotype, our genotyping and TDM-combined strategy allow us to achieve target concentrations during treatment/prophylaxis in 90% of the CYP2C19 Normal Metabolizers (NM)/Intermediate Metabolizers (IM) and 100% of the Rapid Metabolizers (RM) and Ultrarapid Metabolizers (UM) of our cohort. We recommended modifications of the initial dose in 29% (n = 8) of the patients. In RM ≥12 years old, an increase of the initial dose resulted in 50% of these patients achieving target concentrations in the first measure after initial dose adjustment based only on PGx information. Our experience highlights the need to improve VCZ dose predictions in children and the potential of preemptive genotyping and TDM to this aim. We are conducting a multicenter, randomized clinical trial in patients with risk of aspergillosis in order to evaluate the effectiveness and efficiency of VCZ individualization: VORIGENIPHARM (EudraCT: 2019-000376-41).

In this paper, we consider two single server queueing systems to which customers of two distinct priorities (P1 and P2) arrive according to a Marked Markovian arrival process (MMAP). They are served according to two distinct phase type distributions. The probability of a P1 customer to feedback is θ on completion of his service. The feedback (P1) customers, as well as P2 customers, join the low priority queue. Low priority (P2) customers are taken for service from the head of the line whenever the P1 queue is found to be empty at the service completion epoch. We assume a finite waiting space for P1 customers and infinite waiting space for P2 customers. Two models are discussed in this paper. In model I, we assume that the service of P2 customers is according to a non-preemptive service discipline and in model II, the P2 customers service follow a preemptive policy. No feedback is permitted to customers in the P2 line. In the steady state these two models are compared through numerical experiments which reveal their respective performance characteristics.

Background: Pregabalin provides good postoperative analgesia in nociceptive stimuli. Various studies show that preemptive oral pregabalin reduces acute postoperative pain. We conducted a study to evaluate the efficacy of two different doses of pregabalin and its effect on onset and duration of spinal anesthesia and postoperative pain. Methods: In prospective, double-blind and randomized study, 60 patients posted for vaginal hysterectomy under spinal anesthesia were randomly allocated to two groups recieving cap. Pregabalin 75 mg (group 1) and cap pregabalin 150 mg (group 2) orally, 90 min prior to surgery. Onset and duration of motor and sensory blockade were observed. Postoperative pain was assessed by VAS for 24 hrs. Injection paracetamol 1 gm. was given intravenously as rescue analgesic. Time of first rescue analgesic and total dose of rescue analgesics was noted. Results: Group 2 patients had better postoperative analgesia in terms of prolonged sensory and motor blockade which correlated well with the time of first request for rescue analgesia (504±123.2 min) as compared to group 1 patients (304.9±37.6 min). Also the total dose of rescue analgesic (paracetamol) was significantly less with 150mg pregabalin (p = 0.0001). Conclusion: Pregabalin 150 mg prolongs the duration of spinal anesthesia and has better analgesic profile without significant side effects. Thus we conclude that 150 mg pregabalin given preemptively optimizes spinal anesthesia well in patients for vaginal hysterectomy.

Preemptive pharmacogenetic testing aims to optimize medication use by having genetic information at the point of prescribing. Payers’ decisions influence implementation of this technology. We investigated US payers’ knowledge, awareness, and perspectives on preemptive pharmacogenetic testing. A qualitative study was conducted using semistructured interviews. Participants were screened for eligibility through an online survey. A blended inductive and deductive approach was used to analyze the transcripts. Two authors conducted an iterative reading process to code and categorize the data. Medical or pharmacy directors from 14 payer organizations covering 122 million US lives were interviewed. Three concept domains and ten dimensions were developed. Key findings include clinical utility concerns and limited exposure to preemptive germ-line testing, continued preference for outcomes from randomized controlled trials, interest in guideline development, importance of demonstrating an impact on clinical decision making, concerns of downstream costs and benefit predictability, and the impact of public stakeholders such as the Food and Drug Administration and Centers for Medicare and Medicaid Services. Both barriers and potential facilitators exist to developing cohesive reimbursement policy for pharmacogenetics, and there are unique challenges for the preemptive testing model. Prospective outcome studies, more precisely defining target populations, and predictive economic models are important considerations for future research.

Objective: The main objectives of this article were to assess the effect of preoperative transdermal fentanyl patch (TFP) on interleukin (IL)-6 and IL-8 levels and pain after laparoscopic cholecystectomy. Materials and Methods: Patients received a TFP (25 μg/h) (patch group, n=30) or a placebo patch (control group, n=30) applied 14 hours before operation. After surgery, control group received intravenous continuous fentanyl (25 μg/h) with loading dose (25 μg). IL-6 and IL-8 levels were measured at admission and 1, 6, 12, 24, and 48 hours postoperatively. Pain score and consumption of rescue analgesic were evaluated too. Results: At 24 hours postoperatively, IL-6 and IL-8 reached a peak and then decreased. The peak IL-6 levels were 21.92(±6.22) and 24.91(±6.81) pg/mL in the patch and control group. The significant differences of IL-6 between groups were shown at 6 and 12 hours postoperatively (P=0.032, 0.0001). There were no significant differences in IL-8 levels and pain score. Conclusions: Preoperative TFP attenuated the increase in IL-6 levels after surgery and provided similar analgesia to continuous fentanyl infusion. Preemptive TFP may have influence on proinflammatory reactions and pain control after surgery.

Background: Lumbar spine surgery is associated with moderate-to-severe postoperative pain. Adequate pain management during the postoperative period facilitates rehabilitation. Recently, preemptive analgesia has been considered among the important analgesic methods for reducing postoperative pain. However, its efficacy in postoperative pain relief after lumbar spine surgery remains unclear. This study aimed to evaluate the effects of preemptive analgesia on lumbar spine surgery. Methods: We searched for randomized controlled trials in PubMed (1996 to May 2020), Embase (1980 to May 2020), and Cochrane Library (CENTRAL, May 2020). We included seven studies that evaluated the preemptive analgesic efficacy in lumbar spine surgeries. Results: Seven studies, including 509 patients, met the inclusion criteria. Pooled data revealed that preemptive analgesia is effective for lumbar spine surgeries with respect to the visual analog scale score (P

The thriving globalization conditions fostered the emergence of distributed manufacturing over the past decades, covering almost all of the industries, regions, and economies. The international and complex network of manufacturers, sub-manufacturers, and integrated logistics companies organized the industrial throughput to an almost perfect extent. Nevertheless, the disruptive event of the COVID-19 pandemic appearing in 2020 changed the rules of the game. This pandemic took most of the countries and organisations by surprise, with the tragic consequences of 120 million infections and almost 3 million deaths worldwide until March 2021. This thesis starts off with a brief introduction of the history of distributed manufacturing and economic internationalization. Then, an overview of the various pandemics of the past centuries is presented, with special focus on their economic consequences. Special attention of the analysis is put on the challenges from the current COVID-19 pandemic. Generally, the risks and challenges that arise in this crisis are manifold and range from immediate health risks, isolation risks as well as disruptive changes in the supply chain and manufacturing setups. This thesis focusses on suggesting and analysing a broad range of mitigation action that can be implemented to meet, solve or ease them. Resilience, redundancy and flexibility are the factors of robustness that play an important role in crisis management. Building up robustness and resilience is proposed by applying corrective and preparative action for a wide range of production factors (people, material, processes, supply chain etc.) and a variety of risk classes (health, isolation, lockdown). In order to exemplify the approach, two case scenarios with corrective actions are analysed and presented. The thesis closes with an outlook on how the mitigation actions can tactically serve as a set of corrective and preventive actions in order to improve the economic position. Focus is given on how to prepare for future challenges by a strong emphasis on resilience and robustness of the supply and value chains in distributed manufacturing. h

Because of the high incidence of cytomegalovirus (CMV) seropositivity in the population, CMV infection is a common and severe complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Taiwan. Here we propose a CMV management strategy for patients undergoing allo-HSCT from the Taiwanese perspective, which focuses on the epidemiology, diagnosis, monitoring, prophylaxis, and treatment of CMV infection after allo-HSCT. In terms of CMV monitoring, weekly CMV monitoring with the COBAS® AmpliPrep system is the standard approach because the pp65 CMV antigenemia assay has a lower sensitivity than CMV monitoring with the COBAS® AmpliPrep system. However, pp65 CMV antigenemia assay has a better correlation with clinical symptoms in immunocompromised patients. A 14-week prophylactic course of letermovir is recommended for allo-HSCT recipients in Taiwan, especially for recipients of hematopoietic stem cells from mismatched unrelated and haploidentical donors. Preemptive ganciclovir therapy should be initiated when the CMV viral load exceeds 1000 copies/mL, and should not be discontinued until CMV DNA is no longer detected in the blood. For allo-HSCT recipients who have CMV-related diseases, ganciclovir with or without CMV-specific intravenous immunoglobulin is the standard of care. The limited availability of foscarnet, an alternative for patients who are not responsive to or cannot tolerate ganciclovir, is a crucial issue in Taiwan. For pediatric allo-HSCT recipients, more data are needed to propose a CMV management recommendation.

A multimodal analgesic method was known to avoid the high-dose requirements and dose-dependent adverse events of opioids, and to achieve synergistic effects. The purpose of this study was to compare the efficacy of our multimodal analgesia (MMA) regimen with that of the patient-controlled analgesia (PCA) method for acute postoperative pain management. Patients who underwent one or two-level posterior lumbar fusion (PLF) followed by either MMA or PCA administration at our hospital were compared for pain score, additional opioid and non-opioid consumption, side effects, length of hospital stay, cost of pain control, and patient satisfaction. From 2016 through 2017, a total 146 of patients were screened. After propensity score matching, 66 remained in the PCA and 34 in the MMA group. Compared with the PCA group, the MMA group had a shorter length of hospital stay (median (interquartile range): 7 days (5&ndash, 8) vs. 8 (7&ndash, 11), P = 0.001) and lower cost of pain control (70.6 &plusmn, 0.9 USD vs. 173.4 &plusmn, 3.3, P &lt, 0.001). Baseline data, clinical characteristics, pain score, additional non-opioid consumption, side effects, and patient subjective satisfaction score were similar between the two groups. The MMA seems to be a good alternative to the PCA after one or two-level PLF.

This artifact provides the means to validate and reproduce the results of the associated paper "Abstract Response-Time Analysis: A Formal Foundation for the Busy-Window Principle". In this artifact we demonstrate how to compile the source code and automatically check the proofs of each theorem. We also provide references to all key results claimed to be proven in the paper (including Abstract RTA and all eight instantiations), so that readers may confirm that no proofs have been omitted., DARTS, Vol. 6, Issue 1, Special Issue of the 32nd Euromicro Conference on Real-Time Systems (ECRTS 2020), pages 3:1-3:2

This paper introduces the first general and rigorous formalization of the classic busy-window principle for uniprocessors. The essence of the principle is identified as a minimal set of generic, high-level hypotheses that allow for a unified and general abstract response-time analysis, which is independent of specific scheduling policies, workload models, and preemption policy details. From this abstract core, the paper shows how to obtain concrete analysis instantiations for specific uniprocessor schedulers via a sequence of refinement steps, and provides formally verified response-time bounds for eight common schedulers and workloads, including the widely used fixed-priority (FP) and earliest-deadline first (EDF) scheduling policies in the context of fully, limited-, and non-preemptive sporadic tasks. All definitions and proofs in this paper have been mechanized and verified with the Coq proof assistant, and in fact form the common core and foundation for verified response-time analyses in the Prosa open-source framework for formally proven schedulability analyses.

International audience; PURPOSE:The waiting list period for kidney transplantation can be lengthy and associated with a deteriorated health-related quality of life (HRQoL). It might also be experienced differently depending on the experience of renal replacement therapy (preemptive or dialyzed patients), and the type of dialysis. The main objective of this study is to measure and compare HRQoL changes in preemptive, hemodialysis (HD), and peritoneal dialysis (PD) patients during the waiting list period for kidney transplantation.METHODS:A sample of adult patients on kidney transplant waiting list from three French University Hospital centers was recruited. HRQoL was measured using the SF-36 and a specific questionnaire (ReTransQol), which were collected every 6 months before transplantation in preemptive, HD, and PD patients. Mixed-effects models taking into account time and possible confounding factors were used to compare HRQoL changes between the three groups.RESULTS:Preemptive (n = 230), HD (n = 177), and PD patients (n = 39) were enrolled. The renal replacement therapy modalities, time (time on waiting list and age at registration), and gender were associated with HRQoL changes. The HD and PD patients had a significantly lower perceived HRQoL on Role Physical, Social Functioning, and Role Emotional dimensions than the preemptive patients, with lower scores for PD compared to HD patients. The HRQoL scores of all patients were lower compared to the French general population for all dimensions.CONCLUSIONS:A better understanding of pre-transplantation patients' experience can help improving patient care with adapted educational programs and psychological support depending on the type of renal replacement therapy.

Background: The aim of this study is to evaluate the impact of preemptive adding topical Ketorolac to Tetracaine drop on pain intensity and hemodynamic parameters during and after cataract surgery. Materials and Methods: Eighty patients scheduled for elective cataract surgery under sedation and topical anesthesia, were randomly allocated to two equal groups: group T received Tetracaine 0.5%, and group TK received Tetracaine with ketorolac eye drops. One drop of each ophthalmic drug was applied every 10 minutes from 30 minutes before surgery. Pain intensity and hemodynamic parameters were assessed just before starting the operation and 5, 10, 15and 20 minutes during the operation, and then 0, 5, 10, 15 and 20 minutes after arrival of the patient to the recovery room. Results: Mean pain intensity was significantly lower in TK group (1 ± 0.128) compared with T group (2 ± 1.54) during the surgery (p = 0.003), but there was no significant difference between the two groups in this regard during the recovery time (p =0.157). The number of patients requiring additional analgesic was not significantly different between the groups. There was no significant difference between the two groups regarding hemodynamic parameters except at 20th minutes and 15th and 20th minutes (heart rate and respiratory rate) after arrival to the recovery room. Conclusion: Preemptive adding topical Ketorolac to Tetracaine drop is more effective than Tetracaine alone to reduce pain during cataract surgery.

The aim of a multi-mode resource-constrained project scheduling problem (MRCPSP) is to assign resource(s) with the restricted capacity to an execution mode of activities by considering relationship constraints, to achieve pre-determined objective(s). These goals vary with managers or decision makers of any organization who should determine suitable objective(s) considering organization strategies. We also introduce the preemptive extension of the problem which allows activity splitting. In this paper the preemption multi-mode resource-constrained project scheduling problem (P-MMRCPSP) with Minimum makespan and the maximization of net present value (NPV) has been considered. Since the considered model is NP-Hard, The performance of our proposed model is evaluated by comparison with two well-known algorithms; non-dominated sorting genetic algorithm (NSGA II), multi-objective imperialist competitive algorithm (MOICA). These metaheuristics have been compared on the basis of a computational experiment performed on a set of instances obtained from standard test problems constructed by the ProGen project generator, where, additionally, cash flows were generated randomly with the uniform distribution. Since the effectiveness of most meta-heuristic algorithms significantly depends on choosing the proper parameters. A Taguchi experimental design method (DOE) was applied to set and estimate the proper values of GAs parameters for improving their performances. The computational results show that the proposed MOICA outperforms the NSGA-II.

This paper introduces a preemptive rank offloading scheduling framework for joint ultra-reliable low-latency communications (URLLC) and enhanced mobile broadband (eMBB) traffic in 5G new radio (NR). Proposed scheduler dynamically adapts the overall system optimization among the network-centric ergodic capacity and the user-centric URLLC one-way latency, based on the instantaneous traffic and radio resources availability. The spatial degrees of freedom, offered by the transmit antenna array, are fully exploited to maximize the overall spectral efficiency. However, when URLLC traffic buffering is foreseen, proposed scheduler immediately enforces scheduling pending URLLC payloads through preemption-aware subspace projection. Compared to the state-of-the-art schedulers from industry and academia, proposed scheduler framework shows significant scheduling flexibility in terms of the overall ergodic capacity and URLLC latency performance. The presented results therefore offer valuable insights of how to most efficiently multiplex joint URLLC-eMBB traffic over the 5G NR spectrum.

Background: Currently, the administration of non-opioid analgesics as a preemptive treatment has been approved by the surgeons of jaw due to lack of side effects of opioids in jaw surgery. However, which medicine as a pre-medication has a good result, is a controversy. Therefore, the aim of this study was to investigate the effect of preemptive therapy by pre-gabalin single dose on opioid consumption rate after surgery on mandibular fractures. Methods: This double-blind clinical trial was conducted in Tabriz Imam Hospital in 2012 on 60 patients who were undergoing mandibular fracture surgery. Patients were classified as intervention and control groups and the intervention group consumed one pregabalin capsule 300 milligrams with 50 ml of water half an hour before surgery. The amount of opioid use in the first eight hours after surgery was measured and recorded in both groups. Results: Opioid use in both groups was decreased with time- spending. There was also a significant relationship between opioid use in both intervention and control groups (P

International audience; Cryptococcal antigen (CrAg) screening and targeted preemptive fluconazole in antiretroviral-naive human immunodeficiency virus-infected adults with CD4 cell counts

Background There is wide variation in referral for kidney transplant and preemptive kidney transplant (PKT). Patient characteristics such as age, race, sex and geographic location have been cited as contributing factors to this disparity. We hypothesize that the characteristics of nephrologists interplay with the patients' characteristics to influence the referral decision. In this study, we used hypothetical case scenarios to assess nephrologists' decisions regarding transplant referral. Methods A total of 3180 nephrologists were invited to participate. Among those interested, 252 were randomly selected to receive a survey in which nephrologists were asked whether they would recommend transplant for the 25 hypothetical patients. Logistic regression models with single covariates and multiple covariates were used to identify patient characteristics associated with likelihood of being referred for transplant and to identify nephrologists' characteristics associated with likelihood of referring for transplant. Results Of the 252 potential participants, 216 completed the survey. A nephrologist's affiliation with an academic institution was associated with a higher likelihood of referral, and being ‘>10 years from fellowship’ was associated with lower likelihood of referring patients for transplant. Patient age

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In this paper, we propose a null-space-based preemptive scheduling framework for cross-objective optimization to always guarantee robust URLLC performance, while extracting the maximum possible eMBB capacity. The proposed scheduler perpetually grants incoming URLLC traffic a higher priority for instant scheduling. In case that radio resources are not immediately schedulable, proposed scheduler forcibly enforces an artificial spatial user separation, for the URLLC traffic to get instantly scheduled over shared resources with ongoing eMBB transmissions. A pre-defined reference spatial subspace is constructed for which scheduler instantly picks the active eMBB user whose precoder is the closest possible. Then, it projects the eMBB precoder on-the-go onto the reference subspace, in order for its paired URLLC user to orient its decoder matrix into one possible null space of the reference subspace. Hence, a robust decoding ability is always preserved at the URLLC user, while cross-maximizing the ergodic capacity. Compared to the state-of-the-art proposals from industry and academia, proposed scheduler shows extreme URLLC latency robustness with significantly improved overall spectral efficiency. Analytical analysis and extensive system level simulations are presented to support paper conclusions.

International audience; The impact of preemptive second kidney transplantation (2KT) on graft and patient survival is poorly established. The association between preemptive 2KT (p2KT, N = 93) and outcomes was estimated in a multicenter French cohort of 2KT (N = 1314) recipients using propensity score methods. During the follow-up, there were 274 returns to dialysis and 134 deaths. p2KT was associated with lower death-censored graft loss (HR = 0.39 [0.18-0.88], P = 0.024) and graft failure from any cause including death (HR = 0.42 [0.22-0.80], P = 0.008). Similar associations were observed for death with a functioning graft, although not reaching statistical significance (HR = 0.47 [0.17-1.26], P = 0.13). There was a significant interaction between donor type and p2KT (P for interaction = 0.016). Indeed, p2KT was not significantly associated with the risk of graft failure from any cause including death in living donor 2KT (P = 0.39), whereas the association was substantial in the deceased donor subset (HR = 0.30 [0.14-0.64], P = 0.002). Of note, the adjusted graft survival of p2KT with deceased donor paralleled that of 2KT with living donor, either preemptive or not (93.8% vs. 88.6% at 4 years and 76.1% vs. 70.5% at 8 years, P = 0.13). This large French multicenter study analyzed using propensity scores suggests that p2KT is associated with better graft prognosis.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES Post-operative pain is one of the main complications and its control is essential to increase well-being and facilitate patient recovery. One of the most effective means of pain control is preemptive analgesia and the most commonly used analgesic is tramadol hydrochloride. The aim of this study was to evaluate the preemptive effect of tramadol hydrochloride at a dose of 6 mg / kg. For that, 29 female dogs with no defined breed, of different ages and average weight of 10 kg were selected, which were submitted to elective ovariohysterectomy. Randomly distributed into three groups, the first group (CT-MPA) received tramadol hydrochloride only on preanesthetic medication (MPA), the second group (CT-6) received one dose of the drug 6 hours before MPA and the third group (CT-24) every 6 hours, for 24 hours before MPA. Postoperative pain assessment was performed with the Glasgow Scales and Visual Analogue Scale (EVA) by two observers at one hour intervals, starting one hour after the animal extubation. For salvage analgesia, 6 mg / kg of intramuscular tramadol and 1 mg / kg of ketoprofen were used subcutaneously, six hours after extubation or when EVA reached 33%, indicating pain. The CT-6 and CT-24 groups had the lowest pain rates, presenting a greater analgesic effect due to repeated administration. However, at the end of the evaluation, the CT-24 group remained constant, with no decrease in pain indexes, because repeated administration of tramadol led to the development of tolerance of its effect, and the CT-6 group received only one dose before of MPA had its effect enhanced. With this, it was concluded that the use of tramadol hydrochloride preemptively with only one dose prior to pre-anesthetic medication results in a greater analgesic effect in the immediate postoperative period. A dor no pós-operatório é uma das principais complicações e seu controle é essencial para aumentar o bem-estar e facilitar a recuperação do paciente. Um dos meios mais eficazes no controle da dor é a analgesia preemptiva e o analgésico mais utilizado é o cloridrato de tramadol. Neste estudo objetivou-se avaliar o efeito preemptivo do cloridrato de tramadol na dose de 6 mg/kg. Para tal, foram selecionadas 29 cadelas sem raça definida, de idades variadas e peso médio de 10 kg, as quais foram submetidas a ovariohisterectomia eletiva. Distribuídas aleatoriamente em três grupos, o primeiro grupo (CT-MPA) recebeu Cloridrato de tramadol apenas na medicação pré-anestésica (MPA), segundo grupo (CT-6) recebeu uma dose do fármaco 6 horas antes da MPA e o terceiro grupo (CT-24) a cada 6 horas, durante 24 horas antes da MPA. A avaliação álgica pós-operatória foi realizada com as escalas de Glasgow e Escala Visual Analógica (EVA), por dois observadores, em intervalos de uma hora, iniciando-se uma hora após a extubação do animal. Para analgesia resgate foi utilizado 6 mg/kg de tramadol por via intramuscular e 1 mg/kg de Cetoprofeno por via subcutânea, seis horas após extubação ou quando a EVA atingia 33%, indicando dor. Os grupos CT-6 e CT-24 obtiveram os menores índices de dor, apresentando um maior efeito analgésico devido a administração repetida. Entretanto, no final da avaliação o grupo CT-24 se manteve constante, não apresentondo diminuição dos índices de dor, devido a administração repetida de tramadol levou ao desenvolvimento da tolerância de seu efeito, e o grupo CT-6 que recebeu apenas uma dose antes da MPA teve seu efeito potencializado. Com isso concluiu-se que o uso de Cloridrato de tramadol de forma preemptiva, com apenas uma dose anterior à medicação pré-anestésica, resulta em maior efeito analgésico no período pós-operatório imediato.

Scheduling in datacenters is an important, yet challenging problem. Datacenters are composed of a large number, typically tens of thousands, of commodity computers running a variety of data-parallel jobs. The role of the scheduler is to assign cluster resources to jobs, which is not trivial due to the large scale of the cluster, as well as the high scheduling load (tens of thousands of scheduling decisions per second). Additionally to scalability, modern datacenters face increasingly heterogeneous workloads composed of long batch jobs, e.g., data analytics, and latency-sensitive short jobs, e.g., operations of user-facing services. In such workloads, and especially if the cluster is highly utilized, it is challenging to avoid short running jobs getting stuck behind long running jobs, i.e. head-of-line blocking. Schedulers have evolved from being centralized (one single scheduler for the entire cluster) to distributed (many schedulers that take scheduling decisions in parallel). Although distributed schedulers can handle the large-scale nature of datacenters, they trade scheduling latency for accuracy. The complexity of scheduling in datacenters is exacerbated by the data-parallel nature of the jobs. That is, a job is composed of multiple tasks and the job completes only when all of its tasks complete. A scheduler that takes into account this fact, i.e. job-aware, could use this information to provide better scheduling decisions. Furthermore, to improve the quality of their scheduling decisions, most of datacenter schedulers use job runtime estimates. Obtaining accurate runtime estimates is, however, far from trivial, and erroneous estimates may lead to sub-optimal scheduling decisions. Considering these challenges, in this dissertation we argue the following: (i) that a hybrid centralized/distributed design can get the best of both worlds by scheduling long jobs in a centralized way and short jobs in a distributed way; (ii) such a hybrid scheduler can avoid head-of-line blocking and provide job-awareness by dynamically partitioning the cluster for short and long jobs and by executing a job to completion once it started; (iii) a scheduler can dispense with runtime estimates by sharing the resources of a node with preemption, and load balancing jobs among the nodes.

Objective To investigate the efficacy of the preemptive analgesic effect of low dose ketamine versus MgSO 4 on potentiating postoperative analgesia when compared to placebo in patients undergoing cesarean section under general anesthesia. Methods This prospective randomized blind study included 60 parturient females scheduled for cesarean section under general anesthesia. They were randomized into three equal groups [20 patients each ]: group I [ Control ]: received 20 ml normal saline 0.9%, group II [ Ketamine ]: received ketamine 0.3 mg/kg in 20 ml normal saline and group III [MgSO 4 ]: received MgSO 4 , 30 mg/kg in 20 ml normal saline. Investigated medications infused over 10 min before induction of anesthesia. Fentanyl requirement, mean BP and HR were measured intraoperatively. Pain, sedation and nausea and vomiting were assessed at 2, 6, 12 and 24 h postoperatively. Total postoperative pethidine dose over 24 h was calculated. Results MBP and HR showed statistically significantly lower value in group (K) and (M) compared to group (C) at postintubation and postincision readings. Intraoperative fentanyl requirement was statistically higher in (C) groups compared to (K) and (M) groups. The time for first request for postoperative analgesia was longer and the total postoperative pethidine dose over 24 h was lower in (K) group compared to (C) and (M) groups. Postoperative VAS scores at 2 and 6 h postoperatively showed statistically highly significantly lower values in (K) group compared to (C) and (M) groups. Apgar, postoperative sedation and PONV scores showed no statistically significant differences among the three groups. Conclusions Preemptive dose of either ketamine (0.3 mg/kg) or MgSO 4 (30 mg/kg) in patients undergoing cesarean section under general anesthesia could suppress the pressor response to endotracheal intubation and skin incision and decreased the intraoperative fentanyl requirement. Ketamine showed a significant preemptive analgesic effect compared to MgSO 4 at 2 and 6 h postoperatively.

Background End-stage liver disease is associated with marked hemodynamic disturbances that are further deteriorated during liver transplantation and is aggressively represented in the form of postreperfusion syndrome (PRS). Aim The aim was to test the hypothesis that preemptive ephedrine administration pre-reperfusion targeting a rational level of mean arterial blood pressure (MAP) of 85–100 mmHg, may reduce the incidence of PRS. Patient and methods One hundred recipients for adult living donor liver transplantation (ALDLT) were prospectively randomized into 2 groups; group C, control group and group E, who received ephedrine 2.5–5 mg/min starting 5 min before reperfusion till mean arterial blood pressure (MAP) reached 85–100 mmHg. Hemodynamic parameters including MAP, heart rate (HR), Transesophageal Doppler (TED) parameters including corrected flow time (FTc), systemic vascular resistance (SVR), and cardiac output (COP) were measured; just predrug administration, just before reperfusion, just after reperfusion, 5 min after reperfusion and at the end of surgery. Cold and warm ischemia times (C/WIT), duration of anhepatic phase and total duration of surgery were recorded. The incidence of PRS, the need of rescue vasoconstrictor for hemodynamic instability at time of reperfusion, need for postreperfusion vasoconstrictor infusions, over shooting of hemodynamics, postreperfusion fibrinolysis indicated by fibrinogen level and maximum lysis parameter of rotational thromboelastometry (ROTEM) were compared between both groups. Results The mean dose of ephedrine required was (12.5 ± 7.5 mg). Group E had statistically significant increase in MAP, SVR, and COP; just before reperfusion, just after reperfusion and 5 min after reperfusion readings. There were no statistical significant differences between the 2 groups at the end of surgery. The incidence of PRS and the need of rescue adrenaline at the time of reperfusion, and the postreperfusion need for vasoconstrictor infusion decreased significantly in group E when compared to group C. Also postoperative mechanical ventilation decreased significantly in group E. Conclusion The preemptive goal directed titration of ephedrine against a target MAP pre-reperfusion could decrease the incidence of PRS by 40%, attenuated the hypotensive response to reperfusion and decreased the need for postreperfusion vasoconstrictor support without over shooting of any of the monitored hemodynamic indices.

Introduction: Postoperative pain management of high quality is important and in majority of post surgical cases pain is not treated adequately. We have evaluated the efficacy and safety of pregabalin and gabapentine as preemptive analgesic for post operative pain management in patients undergoing lower abdominal and lower limb surgery under spinal anesthesia. Materials and Methods: In a randomized double blind study, 90 patients were divided into three groups. Group G received tab gabapentin 900 mg, Group P received tab pregabalin 300 mg and Group C received placebo tablet orally 1 hour prior to surgery. All patients underwent surgery under spinal anesthesia using 0.5% Bupivacaine. Assessment of postoperative pain was made with visual Analogue Scale (VAS) score at 1, 2, 4, 6, 8, 12, 18, and 24 hours post operatively. Injection tramadol 100 mg was given as rescue analgesic intramuscularly when VAS score was > 7 in all the groups. Time to first rescue analgesics and number of rescue analgesics received were noted in all groups. The occurrences of side effects were noted in all groups. Results: The tramadol as rescue analgesia consumption was less in pregabalin and gabapentin groups compared to control and was statistically significant (P < 0.001). Initial VAS scores were lower in pregabalin (3.2 ± 0.4) and gabapentin (3.63 ± 0.32) groups compared to control (6.60 ± 0.77) and was statistically significant (P < 0.001). Time to first rescue analgesia was significantly longer for pregabalin (24.6 hours) followed by gabapentin (20.76 hours) and control (4.93 hours) groups. Conclusion: Pregabalin 300 mg single dose given 1 hour prior to surgery is superior to 900 mg gabapentin and placebo in attenuating post operative in patients undergoing lower abdominal and lower limb surgery. Both drugs are better than placebo.

Introduction Preemptive (P) living donor kidney transplantation (LDKT) provides better survival rates, quality of life and economic saving. However, the extent of these advantages over those with a short period of pre-LDKT dialysis is not known. Objectives Evaluation of the patients’ characteristics and short-term outcomes of PLDKT and LDKT after a pre-transplant period of hemodialysis (HD) not >6 months. Patient and methods This study was conducted between June 2010 and June 2012 and included two groups. Group-I included recipients without HD before operation. Group-II included those who had a period of HD ≤6 months. Recipients and donors were evaluated according to the classic work up. Follow-up for 12 months was scheduled. Results Group-I included 30 recipients and group-II included 15 recipients. Demographic and clinical characteristics were similar except for mean recipient age (44 versus 34.3 years; p = 0.024), recipient donor age difference ( p = 0.03), job categories ( p = 0.047) and ABO distribution ( p = 0.01). Cumulative graft (0.88 versus 0.93) and recipient (0.92 versus 0.100) survival rates were non-significantly different. Graft function and mean serum creatinine level were within normal up to 12 months. Acute graft rejection (AGR) was significantly higher in group-II (16.7% versus 46.7%; p = 0.03). However, lymphoceles were significantly more common in group-I (40% versus 6.7%; p = 0.02). There was no delayed graft function (DGF), major urinary or vascular complications. Conclusion PLDKT has a lower rate of AGR. Despite it has a higher rate of lymphoceles, it saves the patient the morbidities of vascular access and inconveniences of HD. Hence, PLDKT is recommended as the first choice for each KT-candidate.

Background and Objectives: Using opioid alone for postoperative pain relief is usually inadequate, and higher doses can cause a multitude of complications. A drug, which has anxiolytic property without the adverse effects of traditional analgesics mentioned, may be an attractive choice for postoperative analgesia. This study was done to compare analgesic efficacy of different nonopioid drugs on early postoperative pain and thus opioid-sparing effect. Materials and Methods: It was a randomized controlled trial. Sixty patients scheduled to undergo elective abdominal surgery under general anesthesia were assessed in the study. Primary Objective: The primary objective of this study was to observe the effect of preemptive pregabalin and pregabalin with intravenous (IV) ketamine on Cumulative analgesic requirement postoperatively. Secondary Objective: The secondary objective of this study was to observe the effect of preemptive pregabalin and pregabalin with IV ketamine on (1) analgesia and (2) adverse effects. Patients were randomly divided into two groups each containing 30 patients. Group P received 150 mg of oral pregabalin, 2 h before induction of anesthesia. Group PK received 150 mg of oral pregabalin, 2 h before induction of anesthesia, and injection ketamine 0.15 mg/kg intravenously just before induction of anesthesia. Heart rate and mean blood pressure (MBP) were observed and recorded at different time intervals during surgery. Heart rate, MBP, time to first analgesic demand, visual analog scale (VAS) score, total postoperative analgesic requirement, sedation score, and side effects were recorded in postoperative period. Results: In Group P, the mean total analgesia requirement in postoperative period was 44.47 ± 5.06 mg, whereas in Group PK, it was 41.8 ± 2.34 mg (P = 0.006). VAS score and time to first analgesic demand were insignificantly higher in Group P. No statistically significant difference was found in side effect profile among the two groups. Conclusion: From our study, it could be concluded that a combination of oral pregabalin and IV ketamine when administered preoperatively can decrease opioid consumption while providing good pain control.

Objectives: To evaluate the effectiveness of preoperative intramuscular diclofenac for pain relief after total abdominal hysterectomy.Methods: A prospective double-blind, randomized study was conducted in 37 patients who underwent total abdominal hysterectomy at our institution between September 2012 and January 2013. The patients were randomly allocated into two groups to receive either single intramuscular 75 mg diclofenac (treatment group; n = 18) or normal saline (control group; n = 19) 20 min before surgery. Total consumption of meperidine over a 24-h period were recorded. The degrees of postoperative pain were assessed at 4, 8, 12, and 24 h postoperatively by using a numeric rating scale and the adverse events relevant to diclofenac were observe. Results: The mean 24-h postoperative meperidine consumption in the treatment group was insignificantly lower compared to that in the control group (46.11+24.77 mg and 68.42+44.63 mg, respectively, p=0.069). Mean pain scores at 4, 8, 12, and 24 h postoperatively in the treatment group were lower than those in the control group (2.83 vs 4.53, p=0.052; 2.83 vs 4.89, p=0.031; 2.78 vs 4.68, p=0.044; 1.28 vs 1.89, p=0.296, respectively). No serious adverse events were observed in both groups.Conclusion: Preoperative intramuscular diclofenac significantly reduced pain scores at 8 and 12 h(while insignificantly decreased 24-h meperidine consumption) after total abdominal hysterectomy.

Burak Sayin, Turan Colak, Emre Tutal, Siren SezerDepartment of Nephrology, Baskent University Faculty of Medicine, Ankara, TurkeyBackground: For suitable patients with end-stage renal disease, kidney transplantation (KT) is the best renal replacement therapy, resulting in lower morbidity and mortality rates and improved quality of life. Preemptive kidney transplantation (PKT) is defined as transplantation performed before initiation of maintenance dialysis and reported to be associated with superior outcomes of graft and patient survival. In our study, we aimed to compare the 5-year outcomes of PKT and nonpreemptive kidney transplantation (NPKT) patients who received KT in our center, to define the differences according to complications, comorbidities, adverse effects, clinical symptoms, periodical laboratory parameters, rejection episodes, graft, and patient survival.Methods: One hundred kidney transplantation (37 PKT, 63 NPKT) recipients were included in our study. All patients were evaluated for adverse effects, complications, comorbidities, clinical symptoms, monthly laboratory parameters, acute rejection episodes, graft, and patient survival.Results: Acute rejection episodes were found to be significantly correlated with graft loss in both groups (P = 0.02 and P = 0.01, respectively). Hypertension after transplantation was diagnosed by ambulatory blood pressure measurement in 74 of 100 patients. Twenty-five of 37 (67.6%) of Group 1 (PKT) recipients had hypertension while 54 of 63 (85.4%) of Group 2 (NPKT) had hypertension. The incidence of hypertension between two groups was statistically significant (P = 0.03), but this finding was not correlated to graft survival (P = 0.07). Some patients had serious infections, requiring hospitalization, and were treated immediately. Infection rates between the two groups were 10.8% for Group 1 patients and 31.7% for Group 2 patients and were statistically significant (P = 0.02). Infection, requiring hospitalization, was found to be statistically correlated to graft loss in only NPKT patients (P = 0.00).Conclusion: While the comparison of PKT and graft and patient survival with NPKT is poorer than we expected, lower morbidity rates of hypertension and infection are similar with recent data. Avoidance of dialysis-associated comorbidities, diminished immune response, and cardiovascular complications are the main benefits of PKT.Keywords: transplantation, preemptive, hypertension, infection, graft, survival

Background: The purpose of the present study was to determine the post-operative analgesic effects of preemptive intravenous (iv) paracetamol and the amount of reduction in tramadol (Contramal® ) consumption. Materials and Methods: Following local research ethics committee approval, ASAI-II, 300 patients were assigned in a randomized manner into three groups: Group I (preemptive) received iv paracetamol 1 g/100 mL 10 min before skin inscision and 100 mL of saline solution at the end of the operation, Group II (post-operative) received 100 mL of saline solution 10 min before skin inscision and iv paracetamol 1 g/100 mL at the end of the operation and Group III (placebo) received 100 mL of saline solution 10 min before skin insicision and 100 mL of saline solution at the end of the operation as well. The time to first analgesic requirement use and 24 h total analgesic consumption were recorded. Visual analog scale (VAS) pain scores were obtained from all patients at 15, 30, min 1, 2, 4, 6, 8, 12 and 24 h after the end of the operation. Results: Time to first analgesic requirement was significantly longer in Group I and Group II, compared to Group III (P < 0.05). Time to first analgesic requirement was significantly longer in Group I compared to Group II (P < 0.05). Total analgesic consumption and postoperative VAS pain scores recorded were significantly lower in Group I and II, compared to Group III. Total analgesic consumption and postoperative VAS pain scores recorded were significantly lower in Group I compared to Group II (P < 0.05). Conclusion: In conclusion, preemptive iv paracetamol provided effective and reliable pain control after cholecystectomy surgeries and reduced post-operative pain scores, the need for and use of supplementary opioids and the time to first request of analgesics.