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Background Postoperative pain after complex revision spine surgery, especially for the treatment of persistent spinal pain syndrome (PSPS), is frequently severe and can be debilitating, requiring the use of intravenous and oral opioids. To the best of our knowledge, the present study is the first to evaluate the effectiveness and safety of a continuous infusion regional anesthesia pump placed after thoracopelvic fusion for the treatment of PSPS. Methods We performed a retrospective comparative study of consecutive patients who had undergone thoracopelvic fusion for PSPS. The patients included in the present study had either had a continuous infusion regional anesthesia pump placed during surgery or had not (control). Demographics, use of preoperative and postoperative opioids, postoperative adverse events, length of hospital stay, and 90-day readmission were recorded. Results The patients in the pump group (n = 14) had used fewer opioids during their hospital stay compared with the control group (n = 12; P = 0.6). This difference was greater for postoperative days 1 and 2 (P = 0.3 and P = 0.2, respectively). No significant difference was found in opioid usage during the first 14 days after surgery (P = 0.8) or at the 3-month postoperative follow-up evaluation (P = 0.8). Furthermore, no significant difference was found between the 2 groups in terms of postoperative complications. The pump group had a 1.4-day shorter hospital stay (P = 0.7). The control group had more 90-day readmissions than did the pump group (P = 0.2). Conclusions Despite showing a trend toward less usage of opioids during the first 2 days after surgery and a shorter hospital stay with no increased complications in the pump group, the study data failed to demonstrate a statistically significant difference between the two groups.

Transfusion of red blood cell (RBC) concentrates is a common procedure to restore blood volume and tissue oxygen delivery in patients with trauma. Although RBC warmers may prevent hypothermia, some warming or infusion equipment may lead to haemolysis and patient injury.The aim of this study was to test the effect of (i) RBC warming and (ii) administration via manual vs. pump infusion on haemolysis.This experimental ex vivo study studied haemolysis markers of RBC injury. The sample consisted of 90 RBC infusions in two simulations, randomly, 45 warmed RBC infusions and 45 nonwarmed RBC infusions, in two or three stages: before the intervention (baseline-warming, N= 45; nonwarming, N= 45), after water bath warming at 42 °C (warmed, N= 45), and then after the warmed or nonwarmed RBCs were infused by manual or pump infusion at a rate of 100 mL/h (infusion-warming, N= 45; nonwarming, N= 45).Warmed RBCs showed significantly lower total haemoglobin (Hb) and haematocrit levels and increase in free Hb levels, haemolysis levels, and lactate dehydrogenase (LDH) activity (all p0.05) than baseline RBCs. Pump infusion RBCs were associated with reduced total Hb and increased free Hb, haemolysis, and potassium (K) levels (all p0.05) compared with warmed RBCs. In contrast, manual infusion of warmed RBCs resulted in significantly reduced total Hb levels and increased LDH activity (both0.05). After infusion, total Hb, free Hb, haematocrit, haemolysis, and LDH values were significantly different for warmed vs. nonwarmed RBCs (p0.05).Haemolysis biomarkers increase with RBC warming and infusion, especially when using infusion pumps. Critically ill patients should be carefully monitored for possible complications during and after RBC infusion.

Rapid infusion pumps employing filters, roller pumps, and heat exchangers for the administration of blood products are not approved for platelets or cryoprecipitate. This technology may decrease platelet count and degrade coagulation proteins. The effect of rapid infusers on the hemostatic potential of whole blood is unknown.Five units of low titer O+ whole blood were obtained from anonymous donors. Each unit was subjected to infusion by five different techniques: (1) gravity infusion without a filter, (2) gravity infusion with a filter, (3) Belmont rapid infuser at 70 mL/min, (4) Belmont at 100 mL/min, and (5) pressurized infusion with a pneumatic pressure bag and filter. After infusion, platelet count, platelet function, thrombin generation, and hemostatic potential were measured for each aliquot. Infusion techniques were compared, using gravity infusion without a filter as the control.There was a significant decrease in platelet count from baseline (168,000) in the BELMONT70 (97,000) and BELMONT100 (94,000) groups (P 0.05). However, there were no differences in platelet function (all P 0.20). While there were no differences in thromboelastography parameters between control and infusion models (all P 0.20), there were significant increases in thrombin generation parameters by CAT in both the BELMONT70 and BELMONT100 groups (all P 0.05).The use of a rapid infuser decreases the platelet count of WB but does not decrease platelet function or overall hemostatic potential. In fact, thrombin generation and thrombin potential are actually increased. Rapid infusers are safe for the transfusion of WB.

Objectives Alternative dosing strategies for β-lactams – the most common antibiotics used to treat critically ill patients with respiratory tract infections – have been recommended to maximize the duration of exposure and reduce drug resistance. The objective of this study was to evaluate whether extended infusion of antipseudomonal β-lactams improves mortality and clinical efficacy. Methods Two independent authors identified eligible trials by searching the PubMed, Cochrane Library, Scopus, and ICHUSHI databases, in both English and Japanese, up to June 2019. Data were extracted from both randomized controlled and observational trials comparing extended infusion (≥3 h) with intermittent infusion in critically ill patients. The primary outcome was all-cause mortality. Risk differences (RD) and 95% confidential intervals (CI) were calculated using a random-effects model and subgroup analyses were performed. Sensitivity and heterogeneity were also evaluated. Results Nine studies involving 1508 participants were included in the meta-analysis. Mortality was lower for extended infusion than for intermittent infusion (RD −0.10; 95% CI −0.15 to −0.04). However, no significant between-group differences in clinical success, length of ICU stay, length of hospital stay, and antibiotic duration were observed. Conclusions Extended infusions of β-lactams were associated with reduced mortality rates but not with clinical success.

Background Neuronal ceroid lipofuscinosis type 2 or CLN2 disease is a rare, autosomal recessive, neurodegenerative lysosomal storage disorder caused by tripeptidyl peptidase 1 deficiency. Cerliponase alfa, a recombinant human tripeptidyl peptidase 1 enzyme, is the first and only approved treatment for CLN2 disease and the first approved enzyme replacement therapy administered via intracerebroventricular infusion. Methods A meeting of health care professionals from US institutions with experience in cerliponase alfa treatment of children with CLN2 disease was held in November 2018. Key common practices were identified, and later refined during the drafting of this article, that facilitate safe chronic administration of cerliponase alfa. Results Key practices include developing a multidisciplinary team of clinicians, pharmacists, and coordinators, and institution-specific processes. Infection risk may be reduced through strict aseptic techniques and minimizing connections and disconnections during infusion. The impact of intracerebroventricular device design on port needle stability during extended intracerebroventricular infusion is a critical consideration in device selection. Monitoring for central nervous system infection is performed at each patient contact, but with flexibility in the degree of monitoring. Although few institutions had experienced positive cerebrospinal fluid test results, the response to a positive cerebrospinal fluid culture should be determined on a case-by-case basis, and the intracerebroventricular device should be removed if cerebrospinal fluid infection is confirmed. Conclusions The key common practices and flexible practices used by institutions with cerliponase alfa experience may assist other institutions in process development. Continued sharing of experiences will be essential for developing standards and patient care guidelines.

Advanced age is an important risk factor for adverse events (AEs) during propofol sedation for endoscopic procedures. This study aimed to evaluate the safety and efficacy of nonanesthesiologist-administered propofol (NAAP) sedation with a target-controlled infusion (TCI) system in elderly patients during ERCP.This study retrospectively analyzed 482 patients who underwent ERCP under propofol sedation with a TCI system at Iwakuni Medical Center between January 2014 and October 2016. Patients were divided into 3 groups according to their age: group A, 70 years (n = 130); group B, ≥70 and 85 years (n = 224); and group C, ≥85 years (n = 125). We compared the propofol dose and AEs during ERCP.The median total infusion dose and minimum and maximum target blood concentrations of propofol were 336 mg, 2.2 μg/mL, and 2.2 μg/mL in group A; 184 mg, 1.0 μg/mL, and 1.4 μg/mL in group B; and 99 mg, .6 μg/mL, and 1.0 μg/mL in group C, respectively, with older groups requiring a lower dose (P .0001). Hypotension was observed in 23 patients (4.8%), with no significant difference between groups (group A, 2.3%; group B, 6.3%; group C, 4.8%; P = .24). Hypoxemia was observed in 16 patients (3.3%), with no significant difference between groups (group A, 3.1%; group B, 4.9%; group C, .8%; P = .17). All AEs were immediately resolved, and no procedures were aborted.NAAP sedation with a TCI system during ERCP may be acceptable in elderly patients with a lower dose of propofol than that used in younger patients.

This guideline will inform physicians, nurses, dieticians, pharmacists, caregivers and other home parenteral nutrition (HPN) providers, as well as healthcare administrators and policy makers, about appropriate and safe HPN provision. This guideline will also inform patients requiring HPN. The guideline is based on previous published guidelines and provides an update of current evidence and expert opinion; it consists of 71 recommendations that address the indications for HPN, central venous access device (CVAD) and infusion pump, infusion line and CVAD site care, nutritional admixtures, program monitoring and management. Meta-analyses, systematic reviews and single clinical trials based on clinical questions were searched according to the PICO format. The evidence was evaluated and used to develop clinical recommendations implementing Scottish Intercollegiate Guidelines Network methodology. The guideline was commissioned and financially supported by ESPEN and members of the guideline group were selected by ESPEN.

Purpose Meropenem and vaborbactam is an intravenous beta-lactam/beta-lactamase inhibitor combination antibiotic active against multidrug resistant gram-negative bacteria. It may be a suitable treatment for inpatient and outpatient management of infections, and the intravenous admixture stability is therefore important for optimal utilization. The purpose of this study was to determine the stability of meropenem and vaborbactam in polyvinyl chloride (PVC) infusion bags and elastomeric pumps at room and refrigerated temperatures. Methods Meropenem and vaborbactam vials were reconstituted according to manufacturer instructions and diluted in PVC infusion bags to final concentrations of 4, 8, and 16 mg/mL and in elastomeric pumps to 11.4 mg/mL (n = 5 replicates per concentration and per temperature). PVC bags and elastomeric pumps were stored at room temperature (~24 °C) or in the refrigerator (~4 °C) and sampled over 12 and 144 h, respectively. Stability was defined as the duration that meropenem and vaborbactam concentrations remained ≥90% of the original concentrations. Findings All room temperature replicates across the tested concentrations retained meropenem and vaborbactam stability over 12 h and displayed concentration-dependent degradation. Refrigerated studies resulted in meropenem and vaborbactam stability at all tested concentrations up to 120 h. Implications Meropenem and vaborbactam in PVC bags (4, 8, and 16 mg/mL) and elastomeric pumps (11.4 mg/mL) were stable for 12 h at room temperature and 120 h when refrigerated. These stability data allow for enhanced flexibility in the preparation, storage, wastage, and administration of meropenem and vaborbactam in the hospital and outpatient setting. (Clin Ther. 2020; 42:XXX–XXX) © 2020 Elsevier HS Journals, Inc.

This protocol describes the materials and approaches for administering liquid incentives to human participants during fMRI scanning. We first describe preparation of the liquid solutions (e.g., neutral solution and saltwater) and liquid delivery setups. We then detail steps to connect the setups to the computer-controlled syringe pump in the MRI control room, followed by procedures for testing the syringe pump dispensing a liquid bolus during the task. Description of custom software and required adapters for implementing the liquid setup are included. For complete details on the use and execution of this protocol, please refer to Yee et al. (2021).

The main goal of this study was to use state-of-the-art instruments for nanoparticle (nanoparticle tracking analysis and resonant mass measurement) and microparticle counting (flow imaging) to assess the effects of peristaltic filling pump operation on particle formation in formulations of intravenous immunoglobulin. Microparticle levels were also measured with light obscuration. Postpumping agitation was studied as an accelerated degradation method, 3 different commercial peristaltic tubing types were tested, and the effects of formulation pH and inclusion of polysorbate 80 were determined. Overall, the results documented that nanoparticle measurements, as well as microparticle determinations with flow imaging, were essential to gain rigorous insights into impacts of processing and formulation parameters on pumping- and agitation-induced particle formation. In addition, light obscuration was a relatively insensitive method and failed to detect large increases in protein particles caused by pumping and postpumping agitation. Formulation studies showed that the presence of polysorbate 80 or increasing protein colloidal stability with appropriate choice of buffer generally reduced particle formation. The results highlight the need for filling pump assessments in formulation development studies. Combining such assessments with appropriate analytical methods should help assure that particle levels are controlled during filling pump operation and that the highest quality products are manufactured.

Background Although adoption of "smart" infusion pumps has improved intravenous medication administration safety, pump integration with electronic health records (EHRs) remains rare. Early-adopter hospitals have recently implemented intravenous clinical integration (IVCI) to allow bidirectional communication between their EHRs and infusion pumps. However, the challenges and strategies involved in IVCI implementation have not been described. Methods A qualitative description of one hospital's IVCI implementation was conducted. The research team interviewed 33 pharmacists, technologists, clinicians, nurse managers, educators, and organizational leaders; observed nurses on five units using EHR–integrated pumps; and attended nurse training. Interview notes and transcripts were analyzed to describe IVCI implementation, highlighting its effects on clinicians and the organization. Results Motivations for implementation included a culture of innovation, simultaneous pump and EHR upgrades, and belief that IVCI would improve patient safety. Proactive planning included a simultaneous go-live across selected units, financial investment, multidisciplinary planning teams, and clinical training. Challenges included lack of direct communication between EHR and pump vendors, nonstandardized unit-specific drug libraries, and unit- and nurse-specific variation in workflows for administering infusions. Mitigation strategies included serving as messenger between vendors, conducting hospitalwide efforts to standardize drug libraries and workflows, and standardizing organizational policies. Lessons learned included that IVCI adoption was as much a nursing workflow and organizational policy intervention as a technological implementation. Conclusion Integrating infusion pumps and EHRs involves much more than installing new technologies. Hospitals considering IVCI should prepare to undertake significant simultaneous changes to organizational policies and clinician workflows.

Reducing the frequency of drug administration in the treatment of exotic pets is advantageous because it may decrease handling frequency and thus potential stress and injury risk for the animal, increase owner compliance with the prescribed treatment, and decrease need for general anesthesia in patients that cannot be handled safely. Increasing efficient drug plasma concentration using sustained-released delivery systems is an appealing solution. Potential candidates that could provide a promising solution have been investigated in exotic pets. In this article, the technologies that are the closest to being integrated in exotic pet medicine are reviewed: osmotic pumps, nanoparticles, and hydrogels.

Background The Institute for Safe Medication Practices (ISMP) describes high alert medications (HAM) as medications that represent a heightened risk of patient harm when used in error. IV smart pumps with dose error reduction systems (DERS) were created to help address medication administration errors. Compliance with DERS provides a measure of how accurately a hospital uses smart pump technology to reduce IV medication error. Objective The primary purpose of this research was to use the REMEDI dataset, an aggregate, multi-hospital database inclusive of smart pump analytics, to improve the current understanding of clinical practices for IV HAM administration. Methods Descriptive analyses and analysis of variance (ANOVA) were used to test for differences in the mean DERS alert override rate, and mean DERS alert override to reprogram ratio between non-HAM and HAM overall, by hospital system, and by pump type. Results High mean override rates for non-HAM (73.8%) and HAM (75.8%) and high override to reprogram ratios for both non-HAM (7.30) and HAM (9.92) were seen. No significant differences were found in override rates (p = 0.23) and override to reprogram ratios (p = 0.06) between non-HAM and HAM. By hospital system, significant variability in override rates and override to reprogram ratios were seen. By pump type, there were no significant differences in the mean override rates (Baxter: p = 0.09; BD p = 0.34; ICU Medical p = 0.18) and the mean override to reprogram ratios (Baxter p = 0.84; BD p = 0.03; ICU Medical p = 0.63) between non-HAM and HAM. Conclusions These findings indicate that the majority of alerts generated are bypassed by clinicians at the point of care, a symptom of alert fatigue. Given the potential for significant patient harm with HAM and the high DERS alert override rates that routinely occur during IV medication administration, this study provides further support for clinician-driven IV smart pump innovation to improve alert fatigue.

AIM To evaluate the efficacy and safety of the uterine artery embolisation (UAE) in combination with methotrexate (MTX) for conservative management of placental adhesive disorders. MATERIAL AND METHODS Patients with placental adhesive disorders (including accreta, increta, and percreta lesions) that were treated with UAE in combination with MTX were identified and were followed prospectively for outcomes including uterine preservation and complications. RESULTS Twenty-six patients were identified who had the diagnosis of abnormal placenta implantation during this study. Fourteen patients were excluded because they were treated by a caesarean hysterectomy. Among remaining 12 patients, the successful uterine preservation observed in seven (58%) cases. Menstruation cycles returned in all successfully treated patients, although they did not have desire to get pregnant. Five (42%) patients underwent primary or delayed hysterectomy due to severe post-partum haemorrhage in three cases, and intestinal adhesion/peritonitis and secondary post-partum haemorrhage/sepsis in two patients, respectively. CONCLUSION Although this interventional method is relatively successful in uterine preservation, the possibility of treatment failure cannot be ignored. Given that there are too few data regarding its efficacy and safety, this method should be reserved to patients who have a strong desire to maintain the uterus and their fertility, or if it is technically difficult to perform hysterectomy due to the extent of the invasion.

Characterization of dissolution of solid suspended drug particles in vivo is important for developing biopredictive in vitro tests. Therefore, methods to gain deeper insights into particle dissolution in vivo are needed. The soft Bioperm intubation method, a well established tool for investigation of permeability, absorption, metabolism, and drug interactions at predefined locations in the gastroinstinal tract, was modified. The novel intubation method involved pump-controlled infusion of pharmaceutical suspensions as well as simultaneous pH monitoring. This technique was used in a proof of concept study in healthy humans. Plasma sampling and non-compartmental analysis allowed comparison of three different ibuprofen drug products, a solution and two suspensions with different particle size distribution, as well as two different infusion rates. Both a particle size effect and an effect of altering infusion rates on pharmacokinetic parameters were shown. Moreover, it was possible to monitor intestinal pH changes after intestinal infusion. Infusion of ibuprofen resulted in a pH drop that was quantified by the concept of Area Between Curves (ABC).

Since a micro-infusion pump continuously pumps drugs at a low speed, it has the risk of complications including venous blood return, indwelling needle blockage, and the lack of regular delivery of drugs. This study aimed to investigate venous blood return and indwelling needle blockage after cardiac surgery when a micro-infusion pump was used at a very low flow rate of only 2 ml/h without any accompanying fluid.A total of 215 patients, who were hospitalized at the Second Hospital of Shandong University between May and December 2020, received a continuous intravenous administration of drugs via a micro-infusion pump at 2 ml/h without or with accompanying fluid. These patients were randomly divided into an observation group (108 patients) and a control group (107 patients). In the observation group, drugs were administered at 2 ml/h without any additional fluid. In contrast, the control group received drugs also at 2 ml/h but with a normal saline through an intravenous drip. The venous backflow, blockage of the indwelling needle and catheter, and other adverse reactions were evaluated In addition, the volume of an accompanying fluid as well as the mean of nursing work time and additional costs were calculated.The main finding of this analysis showed no statistically significant differences in the number of complications such as venous backflow, blockage of the indwelling needle or catheter, or any adverse reactions between the observational and control groups (P 0.05). Compared to the control group, the observation group had significantly reduced the amount of fluid intake (P 0.001). In addition, the 2 ml/h infusion tempo without any additional fluid shortened nursing hours (P 0.001), and thus reduced costs for the observation group vs. the control group.It is feasible and safe to administer drugs via a micro-infusion pump at the slow 2 ml/h tempo without any accompanying fluid to patients after surgery requiring minimal volume of fluids.

Critical care transport is an essential component of care system. Inadequacies in equipment, during the interhospital transport can lead to adverse event.To verify the influence of physical transport conditions in the infusion pumps (IPs) performance and alarm activation.Simulation-based study about IPs use during interhospital ground transportation. There were 54 simulations (18 flowmetric, 18 volumetric, 18 syringe IPs). The equipment were tested at 01, 05 and 50mL/h infusion flow. Descriptive and inferential statistical analysis, with a 5% significance level was performed.The effectively infused volume was lower than the expected volume for the 3 IPs types. Vibration was the variable with highest correlation in volume difference. Flowmetric IPs showed higher alarm frequency (50.0%), followed by syringe IPs (27.8%). Free flow predominated in flowmetric IP and airline and occlusion alarms in volumetric and syringe IP. Error percentage of delivered fluid ranged from 2.8% to 25.9% being more evident in flowmeter IPs.The infusion pumps showed infusion misfunctioning when subjected to physical transport conditions. Syringe IPs were more accurate for low flow administration, while for the administration of solutions at higher flow rate, the volumetric IP showed the highest accuracy.

Inhibition of histone deacetylase (HDAC) suppresses inflammation of pancreatic islets and apoptosis of β-cells. However, the underlying molecular mechanism is unclear. In the present study, we demonstrate that MGCD0103 (MGCD), an HDAC inhibitor, protects the pancreas from streptozotocin (STZ)-induced oxidative stress and cell death. Sprague-Dawley rats were intraperitoneally injected with STZ (40 mg/kg) to induce type I diabetes. MGCD (10 μg/day) was infused with osmotic mini-pump for 4 weeks. Pancreatic insulin and macrophage infiltration were analyzed by immunohistochemistry. Cellular level of reactive oxygen species (ROS) was evaluated with fluorescence-activated cell sorting. Tetramethylrhodamine ethyl ester was used to analyze mitochondrial membrane potential. Activation of caspase-3 was analyzed by western blotting. Chromatin immunoprecipitation was performed to investigate the binding affinity of specificity protein 1 (SP1) on the promoters of target genes. mRNA expression was analyzed by quantitative real-time polymerase chain reaction. As a result, we found that MGCD infusion ameliorated STZ-induced hyperglycemia, islet deformation, decreased insulin level, and macrophage infiltration. STZ injection promoted the production of ROS, which induced caspase activity and β-cell death. 4-Hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPOL), a mimetic of superoxide dismutase (SOD), reduced STZ-induced caspase activity and β-cell death. MGCD treatment increased SOD expression and histone acetylation level on promoters. Infusion of MGCD promoted acetylation of SP1 and its enrichment on SOD promoters. Thus, MGCD protects pancreatic β-cells from STZ-induced oxidative stress and cell death through the induction of antioxidant enzymes such as SODs.

Some infectious diseases, such as infective endocarditis, osteomyelitis, and abscesses, require treatment with long-term intravenous antimicrobial treatment. Therefore, the patient is required to stay in the hospital to receive therapy, which lowers their quality of life. Establishing an outpatient parenteral antimicrobial therapy (OPAT) by continuous infusion pump is desired in Japan to overcome these issues. However, the 24-h stability of antimicrobial agents dissolved in infusion solutions is unclear. Thus, we investigated the stability of antimicrobial agents in five different infusion solutions in a clinical setting. Benzylpenicillin potassium (PCG) and ampicillin (ABPC) were dissolved separately in five different infusion solutions and kept at 25 or 31.1 °C for 24 h. The residual ratios were determined by high-performance liquid chromatography (HPLC). Dissolved PCG in acetate ringer solution remained stable for 24 h at temperatures of 25 and 31.1 °C (101.7 ± 1.4% and 92.9 ± 1.3%, respectively). In addition, the PCG solution did not adsorb onto the elastomeric infusion pump after 24 h at 31.1 °C. PCG dissolved in acetate ringer solution was also stable for 10 days after being kept in an elastomeric infusion pump at 4 °C (99.7 ± 0.5%). ABPC was unstable in all of the tested infusion solutions and temperatures. Based on our results, PCG in acetate ringer solution can be used in OPAT with continuous infusion pumps.

Background Prolonged infusion of beta-lactam antibiotics is broadly recognized as a strategy to optimize antibiotic therapy by achieving a higher percentage of time that concentrations remain above the minimal inhibitory concentration (% fT>MIC), i.e. the pharmacokinetic/pharmacodynamic (PK/PD) index. However, %fT>MIC may not be the PK/PD index of choice for inhibition of resistance emergence and it is therefore unsure what impact prolonged infusion of beta-lactam antibiotics may have on the emergence of resistance. Methods A retrospective cohort study including 205 patients receiving either intermittent (101 patients) or continuous (104 patients) infusion of piperacillin/tazobactam or meropenem was conducted in the ICU of the Ghent University Hospital. Logistic regression analysis was used to develop a prediction model and to determine whether the mode of infusion was a predictor of emergence of antimicrobial resistance. Results Resistant strains emerged in 24 out of the 205 patients (11.7%). The mode of infusion was no predictor of emergence of antimicrobial resistance. Infection with Pseudomonas aeruginosa was associated with a significantly higher risk for emergence of resistance. Conclusions In this retrospective cohort study, the emergence of antimicrobial resistance to piperacillin/tazobactam or meropenem was not related to the mode of infusion.

Currently, EA is supported by high-level evidence, specifically in liver surgery, to be the most effective analgesic modality for pain control after HPB surgery. Additional high-level evidence for superior analgesic modalities after pancreatectomies is required. Subsequent randomized controlled trials are required to elucidate the effectiveness and safety of new strategies such as a TAP block compared to EA for both hepatectomies and pancreatectomies in the setting of ER. Beyond adequate pain control and total opiate consumption, PRO tools and the ability to RIOT in cancer patients should be secondary outcome measure in all future studies.

Although smart infusion pumps were built to eliminate medication errors, new types of usability errors have arisen. The purposes of this study were to determine potential risks when using smart pumps during secondary medication administration and to identify opportunities for design improvements. We observed and analyzed nurses when they interacted with smart pumps and heuristically evaluated the smart pump to identify usability problems. Forty-three usability problems were identified with the smart pump. The usability problems have the potential to create high cognitive burden on nurses and to increase the likelihood of mistakes. We discuss design and process improvement recommendations for each major finding from this study.

Recognition memory can rely on three components: “what”, “where” and “when”. Recently we demonstrated that the anterior retrosplenial cortex (aRSC), like the perirhinal cortex (PRH) and unlike the hippocampus (HP), is required for consolidation of the “what” component. Here, we aimed at studying which brain structures interact with the aRSC to process object recognition (OR) memory in rats. We studied the interaction of six brain structures that are connected to the aRSC during OR memory processing: PRH, medial prefrontal cortex (mPFC), anteromedial thalamic nuclei (AM), medial entorhinal cortex (MEC), anterior cingulate cortex (ACC) and the dorsal HP (dHP). We previously described the role of the PRH and dHP, so we first studied the participation of the mPFC, AM, MEC and ACC in OR memory consolidation by bilateral microinfusions of the GABAA receptor agonist muscimol. We observed an impairment in OR long-term memory (LTM) when inactivating the mPFC, the AM and the MEC, but not the ACC. Then, we studied the functional connections by unilateral inactivation of the aRSC and each one of the six structures in the same (ipsilateral) or the opposite (contralateral) hemisphere. Our results showed an amnesic LTM effect in rats with ipsilateral inactivations of aRSC-PRH, aRSC-mPFC, aRSC-AM, or aRSC-MEC. On the other hand, we observed memory impairment when aRSC-ACC were inactivated in opposite hemispheres, and no effect when the aRSC-dHP connection was inactivated. Thus, our ipsilateral inactivation findings reveal that the aRSC and, at least one brain region required in OR LTM processing are essential to consolidate OR memory. In conclusion, our results show that several cortico-cortical and cortico-thalamic pathways are important for OR memory consolidation.

Background Effective treatment for advanced Parkinson disease (PD) uncontrolled with oral medication includes device-aided therapies such as deep brain stimulation (DBS) and continuous levodopa-carbidopa infusion to the duodenum via a portable pump. Objective Our objective was to quantify patient preferences for attributes of these device-aided treatments. Methods We administered a Web-enabled survey to 401 patients in the United States. A discrete-choice experiment (DCE) was used to evaluate patients' willingness to accept tradeoffs among efficacy, tolerability, and convenience of alternative treatments. DCE data were analyzed using random-parameters logit. Best-worst scaling (BWS) was used to elicit the relative importance of device-specific attributes. Conditional logit was used to analyze the BWS data. We tested for differences in preferences among subgroups of patients. Results Improving ability to think clearly was twice as important as a 6-hour-per-day improvement in control of movement symptoms. After controlling for efficacy, treatment delivered via portable infusion pump was preferred over DBS, and both devices were preferred to oral therapy with poor symptom control. Patients were most concerned about device attributes relating to risk of stroke, difficulty thinking, and neurosurgery. Avoiding surgery to insert a wire in the brain was more important than avoiding surgery to insert a tube into the small intestine. Some differences in preferences among subgroups were statistically, but not qualitatively, significant. Conclusions This study clarifies the patient perspective in therapeutic choices for advanced PD. These findings may help improve communication between patients and providers and also provide evidence on patient preferences to inform regulatory and access decisions.

The ALARIS MSIII Infusion Pump (CareFusion, San Diego, CA) uses 3 separate alarms designed to prevent air emboli: "check air sensor," "air in lower tubing," and "air in line." It is assumed that ambient pressure changes cause air emboli that lead to pump failure although evidence to support this is limited. In this small study, the MSIII proved to be highly resilient and able to maintain function even after large repetitive emboli. Although unproven, it is more likely that these alarms are usually caused by loosening of the intravenous tubing within the pump's collar. This disjointing of the tubing and the ultrasonic sensor can be perceived as an air embolus leading to severe consequences. If the user attempts the clear air function, the pump will not resume function. Problems such as this may have been related to at least 1 reported patient death. More research is needed to determine the cause of these alarms and determine the exact cause. Patient safety can potentially be improved at all levels including manufacturer modifications and operator training. It seems reasonable that the manufacturer should design a mode ("transport mode") that allows the pump to function even with air emboli.

Syringe drivers are medical devices that are critical for end of life care. They deliver continuous medication over extended periods of time. Their design contributes to the quality of experience for both patients and healthcare professionals. Little research has been published about the factors that influence the usability of this type of equipment for frontline users (i.e. those in direct contact with patients) and how equipment gets introduced. Understanding how syringe drivers are used in practice can help improve the design of equipment. 27 semi-structured interviews were conducted across acute hospitals, community hospitals and hospices (4 organisations in total). All participating organisations used the same type of syringe driver. It was found that frontline staff needed to adapt this equipment to fit the circumstances of use. The analysis provided examples of this happening for aspects relating to the appearance of the device (bags), accessories (batteries) and security (the lockable box).

Study objective The glass vial of acetaminophen as an intravenous preparation (Acelio®, Terumo, Japan) has a strong internal negative pressure. The aim of our study was to determine if this negative pressure could result in medication administration errors if not released prior to connecting to the IV set. Design Questionnaire survey and simulation study. Setting University hospital and its affiliated hospitals. Subjects Fifty-two anesthesiologists in 6 different hospitals in Yokohama. Measurements A questionnaire on current practice was sent to the subjects. The authors then first calculated the internal pressure of the Acelio® vial followed by a simulation set-up. This set-up measured the amount of saline that could be aspirated from a syringe loaded on a syringe pump connected via a secondary IV line when the Acelio® vial was attached to the primary line without prior release of the internal pressure. The volume of aspiration was tested with two syringe sizes and with a fully open IV clamp vs partially closed. Main results Twenty-nine (56.9%) of 51 anesthesiologists who responded to the survey had connected the Acelio® vial at least once without releasing the internal negative pressure, and 21 experienced consequences such as backflow of the venous blood. The pressure inside the Acelio® vial was 81.8±19.6Torr. With the clamp of the simulated IV line fully open, the amount of saline aspirated before the alarm of the syringe pump went off was 1.5±0.1ml and 3.2±0.3ml when 20ml and 50ml syringes were used, respectively. When the clamp was partially closed to allow 2 drops per second, this value was 1.3±0.1ml and 2.3±0.1ml, respectively. After removing the plunger from the holder of the syringe pump, an additional 7ml (clamp partially closed) or 15–18ml (clamp fully open) was aspirated in the subsequent 1min. Conclusions A considerable number of anesthesiologists experienced consequences caused by the negative pressure inside the Acelio® vial. This can also cause aspiration of the contents of the syringe pump.

Study Objective To determine after knee arthroplasty surgery the feasibility of discharging patients home on postoperative day 1 with continuous adductor canal blocks. Design Retrospective case series. Setting Outpatient setting after hospital discharge. Patients Patients undergoing knee arthroplasty surgery from October 2013 to August 2014. Interventions All patients received continuous adductor canal catheters for postoperative analgesia and were discharged to home on postoperative day 1. Continuous catheters were intended to remain intact in the ambulatory setting through postoperative day 3. Measurements Data obtained included demographic information, duration of hospital stay, resting and active pain scores, opioid utilization, opioid-induced adverse effects, complications relating to the perineural catheter, and hospital readmissions. Main Results Sixty-nine of 582 patients (11.9%) were discharged to home on postoperative day 1. The median numerical pain score after discharge with a continuous adductor canal block was ≤2 at rest and ≤4 with activity. After block discontinuation on postoperative day 4, median pain scores were the same. No patients reported any unintentional catheter dislodgements, falls, or dysesthesias. There were no readmissions of any patient in this cohort within 90 days of surgery. Conclusions Ambulatory adductor canal catheters are a feasible analgesic modality after knee arthroplasty surgery as pain scores remained low and adverse events were minimal.

Postdural puncture headache (PDPH) is the most common symptom of accidental dural puncture, a frequent complication of intraspinal anesthesia. We developed a postoperative intervention technique to prevent and treat PDPH in accidental dural puncture patients, including epidural pumping of saline. This retrospective study aimed to retrospectively evaluate this new technique for PDPH prevention and treatment.Retrospective study.Beijing Obstetrics and Gynecology Hospital affiliated to the Capital Medical University, between January 2006 and December 2012.Eighty-seven cases undergoing intraspinal anesthesia were assessed.Of these patients, 68 cases had successful repuncture and were assigned to group A (epidural filling group, n=68), receiving continuous epidural pumping of 0.9% NS (150mL) at a rate of 6mL/h; the remaining cases were assigned to group B (conservative therapy group, n=19).Age, height, and body weight were collected, and postoperative headache was assessed using a visual analog scale.Of 68 patients in group A, 49 (72.1%) developed PDPH, whereas all in group B developed PDPH (P=.009). In addition, all patients showed PDPH within 3days after surgery regardless of treatment group. However, a statistically significant difference was obtained for PDPH duration between groups A and B (P.001). Multivariate logistic regression analysis showed that frequency of epidural puncture and continuous epidural pumping of saline were significant risk factors for PDPH.Our data indicated that application of 6mL/h saline effectively contributes to PDPH management, and its clinical application should be broadened.

Nicotine's effect on food intake and body weight has been well documented; however, the relevant receptors underlying these effects have not been firmly established. The purpose of the present study was to: (1) identify the nicotinic acetylcholine receptor (nAChR) subtype involved in food intake and body weight; (2) establish whether food intake and body weight reduction produced by nicotinic drugs are due to activation or desensitization of nAChRs; and, (3) assess the role of the melanocortin system in nicotinic drug effects on food intake and body weight. To identify the nAChR, we tested the effect of sazetidine-A (SAZ-A), a relatively selective ligand of β2-containing nAChRs, on food intake and body weight in obese mice. SAZ-A (3 mg/kg; SC) administered twice-daily significantly decreased food intake and body weight. To assess whether these effects involved desensitization, SAZ-A was administered to non-obese mice via osmotic pump, which, due to its slow sustained drug delivery method, causes prolonged desensitization. SAZ-A via osmotic pump delivery significantly decreased the gain in body weight and reduced food intake. In contrast, body weight was unaffected by SAZ-A in β2−/− mice or in mice lacking the melanocortin 4 receptor (MC4R). These results indicate that β2 containing nAChRs are essential to SAZ-A's inhibitory effect on body weight and food intake and engage the melanocortin system.

Programmed intermittent bolus injection of epidural anesthetic solution results in decreased anesthetic consumption and better patient satisfaction compared with continuous infusion, presumably by better spread of the anesthetic solution in the epidural space. It is not known whether the delivery speed of the bolus injection influences analgesia outcomes. The objective of this in vitro study was to determine the pressure generated by a programmed intermittent bolus pump at 4 infusion delivery speeds through open-ended, single-orifice and closed-end, multiorifice epidural catheters.In vitro observational study.Not applicable.Not applicable.A CADD-Solis Pain Management System v3.0 with Programmed Intermittent Bolus Model 2110 was connected via a 3-way adapter to an epidural catheter and a digital pressure transducer. Pressures generated by delivery speeds of 100, 175, 300, and 400 mL/h of saline solution were tested with 4 epidural catheters (2 single orifice and 2 multiorifice). These runs were replicated on 5 pumps. Analysis of variance was used to compare the mean peak pressures of each delivery speed within each catheter group (single orifice and multiorifice).Thirty runs at each delivery speed were performed with each type of catheter for a total of 240 experimental runs. Peak pressure increased with increasing delivery speeds in both catheter groups (P.001). Peak pressures were higher with the multiorifice catheter compared with the single-orifice catheter at all delivery speeds (P.001, for all).Using a pump designed for programmed intermittent infusion boluses, the delivery speed of saline solution through epidural catheters was directly related to the peak pressures. Future work should evaluate whether differences in the delivery speed of anesthetic solution into the epidural space correlate with differences in the duration and quality of analgesia during programmed intermittent epidural bolus delivery.

Background: Target-controlled infusion (TCI) systems allow the administration of drug to achieve a target blood or site-effect concentration. We determine induction and recovery times and the amount of drug used with TCI systems vs. manual induction. Objective: To determine whether the induction of propofol TCI and manual infusion are two comparable techniques. Methods: A retrospective observational study was conducted in which sixty-two ASA I-II patients scheduled for elective surgery received induction using TCI or manually. Anaesthetic induction was achieved with remifentanil (0.25 μg/kg/min) and propofol (manual bolus injection: 2 mg/kg, or target blood concentration: 5 μg/ml with the TCI system [Marsh model]) with maintenance doses of remifentanil (0.15 μg/kg/min) and propofol (manually 0.10 mg/kg/min or 2.5-4 μg/ml using the TCI system). In both groups, rocuronium bromide was used (induction and maintenance doses: 0.6 and 0.3 mg/kg, respectively) as was morphine (0.1 mg/kg) 45 min before the end of the surgery. We measured: induction, operative and recovery mean times; bispectral index, heart rate, blood pressure, costs, haemodynamic instability, and intraoperative awareness. A telephone questionnaire was administered 1 month later. Results: The mean induction time was longer in the TCI than the manual group (1.76 ± 0.94 vs. 0.9 ±0.4 min; p < 0.001), but the total dose of propofol (TCI: 112.4 ±60.9 vs. manual: 133.8 ± 80.3 ml, p = 0.241) tended to be smaller and the recovery time was significantly shorter (TCI: 7.48 ±3.1 vs. manual: 10.3 ± 4.9 min) (p = 0.008). Condusions: Induction with propofol using TCI is similar to manually delivered propofol. Antecedentes: los sistemas de infusión controlada por objetivo (TCI) permiten la administración de fármacos para lograr una concentración en sangre de destino o sitio-efecto. Determinamos los tiempos de inducción y recuperación y la cantidad de fármacos que se usa con los sistemas TCI vs inducción manual. Objetivo: comprobar si la inducción de propofol en TCI y la infusión manual son dos técnicas comparables. Métodos: Estudio observacional retrospectivo en el que sesenta y dos pacientes ASA I-II programados para cirugía electiva recibieron inducción manualmente o usando TCI. La inducción de anestesia se logró con remifentanilo (0,25 μg/kg/min) y propofol (inyección de bolo Manual: 2 mg/kg, o concentración en sangre: 5 μg/ml con el sistema TCI [modelo de Marsh]) con dosis de mantenimiento de remifentanilo (0,15 μg/kg/min) y propofol (0,10 manualmente mg/kg/min o 2.5-1 μg/ml utilizando el sistema de TCI). En ambos grupos, se utilizó bromuro de rocuronio (dosis de inducción y mantenimiento: 0,6 y 0,3 mg/kg, respectivamente) así como la morfina (0,1 mg/kg) 45 minutos antes del final de la cirugía. Medimos: tiempos medios de inducción, mantenimiento y de recuperación; índice biespectral, la frecuencia cardíaca, la presión arterial, los costes, la inestabilidad hemodinámica y el despertar intraoperatorio. Un cuestionario telefónico se administró 1 mes después. Resultados: La media de tiempo de inducción fue mayor en el grupo TCI que en el grupo manual (1,76 ±0,94 vs. 0,9 ±0,4 min; p< 0,001), pero la dosis total de propofol (TCI: 112,4 ±60,9 vs Manual: 133,8 ± 80,3 ml, p = 0,241) tendía a ser más pequeña y el tiempo de recuperación fue significativamente más corto (TCI: 7,48 ±3,1 vs. manual de: 10,3 ± 4,9 min) (p = 0,008) en el grupo TCI. Conclusiones: inducción de propofol en TCI es comparable a la infusión manual.

The emergence of bacterial resistance and the lack of new antibiotics in the pipeline represent a public health priority. Maximizing the quality of antibiotic prescriptions is therefore of major importance in terms of adequate preparation and administration modalities. Adequate preparation prevents the inactivation of antibiotics and is a prerequisite to maximizing their efficacy (taking into account the pharmacokinetic/pharmacodynamic relationship) and to minimizing their toxicity. Many antibiotic guidelines address the choice of drugs and treatment duration but none of them exclusively address preparation and administration modalities. These guidelines are based on the available literature and offer essential data for a proper antibiotic preparation and administration by physicians and nurses. They may lead to a better efficacy and to a reduced antibiotic resistance. Such guidelines also contribute to a proper use of drugs and improve the interaction between inpatient and outpatient care for a better overall management of patients.

ResumenIntroducciónLa administración de remifentanil y propofol con el uso de perfusores TCI ha mostrado beneficios en la práctica anestésica, sin embargo, su disponibilidad es limitada.ObjetivoBasados en modelos farmacocinéticos, diseñar un algoritmo capaz de calcular esquemas de infusión manual para alcanzar concentraciones en plasma y sitio efecto que puedan ser utilizados en bombas de infusión volumétricas. Adicionalmente, comparar la diferencia entre concentraciones deseadas y predichas mediante simulación farmacocinética.MétodosSiguiendo modelos de Minto y Schnider para remifentanil y propofol, respectivamente, el algoritmo se implementó en una aplicación llamada interactive TIVA (iTIVA) para los sistemas operativos iOS y Android. El desempeño del algoritmo se evaluó calculando esquemas de infusión para obtener distintas concentraciones en sitio efecto en la inducción y mantenimiento en 34 pacientes teóricos durante 240 min.ResultadosLos esquemas de infusión obtenidos para remifentanil y propofol presentaron una desviación sistemática promedio menor al 5% respecto a las concentraciones en sitio efecto objetivo en la inducción y mantenimiento. En la inducción una única infusión fue requerida para el remifentanil y propofol. Durante el mantenimiento, una única tasa de infusión fue requerida para el remifentanil y entre 2 y 5 cambios de tasa de infusión para el propofol para mantener una concentración estable. El algoritmo implementado en iTIVA calcula concentraciones similares que el software TivaTrainer®.ConclusionesEl desempeño del algoritmo para alcanzar concentraciones en sitio efecto durante la inducción y mantenimiento para remifentanil y propofol fue excelente con una desviación sistemática baja con respecto a las concentraciones objetivo deseadas.AbstractIntroductionRemifentanil and propofol infusion using TCI pumps has proven to be beneficial for the practice of anesthesia but the availability of these systems is limited.ObjectiveDesigning a pharmacokinetic model-based algorithm for calculating manual infusion regimens to achieve plasma and effect-site concentrations that may be used in volume infusion pumps, and to compare the difference between the desired and the forecasted concentrations via pharmacokinetic simulation.MethodsUsing the Minto & Schnider models for remifentanil and propofol respectively, the algorithm was implemented on an iTIVA application (interactive TIVA) for iOS and Android operating systems. The performance of the algorithm was evaluated estimating the infusion regimens for achieving different effect-site concentrations for induction and maintenance in 34 theoretical patients for 240minutes.ResultsThe infusion regimens obtained for remifentanil and propofol resulted in less than 5% average systemic deviation versus the target effect-site concentrations during induction and maintenance. Only one induction infusion was required for remifentanil and propofol. Just one infusion rate was required for remifentanil during maintenance, and between 2 to 5 infusion rate changes for propofol to maintain a stable concentration. The iTIVA-based algorithm estimates concentrations similar to the TivaTrainer® software.ConclusionsThe performance of the algorithm to achieve effect-site concentrations during induction and maintenance for remifentanil and propofol was excellent, with a low systemic deviation versus the desired target concentrations.

The aim of this study was to quantify culturable microorganisms on needleless connectors (NCs) attached to peripheral intravenous catheters in hospitalized adult medical patients. Half (50%) of 40 NCs were contaminated with microorganisms commonly found on the skin or mouth. Staphylococcus capitis and Staphylococcus epidermidis were most commonly isolated. Emergency department insertion and higher patient dependency were statistically associated with positive NC microorganism growth. These results reaffirm the need for NC decontamination prior to access.

Objective Subcutaneous immunoglobulin (SCIg) administered through infusion pump has been reported as effective in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) patients. In this study we evaluate an alternative technique of SCIg administration, based on the delivery of lower volumes administered daily using manual push technique (MPT) in 10 CIDP patients. Methods In this randomized, controlled, two-arm, crossover clinical trial, CIDP patients were randomly assigned 1:1 to receive SCIg either by MPT or pumps for 4 consecutive months with crossover to the other. The primary objective was to assess whether MPT had the same effectiveness as pumps. The secondary objectives were to assess whether MPT resulted in greater plasma IgG levels and improved quality of life (QoL). Results Ten patients (mean age = 48.3) were enrolled. No significant changes were observed in the efficacy parameters (INCAT, MRC, R-ODS, and GS scales). A positive mean variation of 5.4 % in plasma IgG levels in the group treated with MPT was observed at the end of MPT periods. Treatment interference, which is one of the dimensions of the Life Quality Index, showed a significant improvement in the MPT periods. Conclusion In CIDP patients, the MPT technique was as effective as pump infusion, allowed comparable, slightly increases plasma IgG levels, and also improved the QoL.

Background and Objective The main aim of this work is to present an optimal and robust controller design in order to improve the drug infusion to the automatic control of mean arterial blood pressure in conditions like critically-ill or post-operative or anaesthesia administration. The physiological systems also have uncertainty issues such as parameter variations with time or external disturbances and noise. Therefore, a controlled drug administration is necessary to regulate the mean arterial blood pressure of a person during surgery/observation. Over the years, the proportional-integral-derivative (PID) controller is the most commonly used controller in industries due to its easy structure and simplicity. However, this controller does not meet the desired performance with the complex and uncertain plants. Therefore, a robust controller is required to regulate the physiological variables that are uncertain in nature and can affect the human life. Methods In this work, a hybrid control scheme consisting of an interval type-2-fuzzy logic controller which acts as pre-compensator to the traditional PID controller is presented, to regulate the mean arterial blood pressure of a patient by administering the drug sodium nitroprusside in a controlled manner. An effective and well-established nature-inspired optimization technique namely cuckoo search algorithm is employed for obtaining the optimal parameters for the presented scheme. Results Simulation results are presented to show the effectiveness and robustness of proposed interval type-2-fuzzy logic controller based PID controller scheme, for maintaining the mean arterial pressure to 100 mmHg within considerable limit through SNP infusion. The results are further compared with other two controllers namely type-1 fuzzy logic based PID and traditional PID controllers for the parameter variations and external noise. Conclusion In this study, the proposed interval type-2-fuzzy logic controller pre-compensator based PID controller provides an effective control than traditional type-1 fuzzy logic based control scheme and PID controller in terms of overshoot, settling-time and error which are the prime performance objectives of the closed-loop controlled drug delivery of human blood pressure. The presented study provides a firm base for initial design considerations for development of a low-cost closed-loop drug delivery system for blood pressure regulation.

Intragastric (IG) flavor conditioning studies in rodents indicate that isocaloric sugar infusions differ in their reinforcing actions, with glucose and sucrose more potent than fructose. Here we determined if the sugars also differ in their ability to maintain operant self-administration by licking an empty spout for IG infusions. Food-restricted C57BL/6J mice were trained 1 h/day to lick a food-baited spout, which triggered IG infusions of 16% sucrose. In testing, the mice licked an empty spout, which triggered IG infusions of different sugars. Mice shifted from sucrose to 16% glucose increased dry licking, whereas mice shifted to 16% fructose rapidly reduced licking to low levels. Other mice shifted from sucrose to IG water reduced licking more slowly but reached the same low levels. Thus IG fructose, like water, is not reinforcing to hungry mice. The more rapid decline in licking induced by fructose may be due to the sugar's satiating effects. Further tests revealed that the Glucose mice increased their dry licking when shifted from 16% to 8% glucose, and reduced their dry licking when shifted to 32% glucose. This may reflect caloric regulation and/or differences in satiation. The Glucose mice did not maintain caloric intake when tested with different sugars. They self-infused less sugar when shifted from 16% glucose to 16% sucrose, and even more so when shifted to 16% fructose. Reduced sucrose self-administration may occur because the fructose component of the disaccharide reduces its reinforcing potency. FVB mice also reduced operant licking when tested with 16% fructose, yet learned to prefer a flavor paired with IG fructose. These data indicate that sugars differ substantially in their ability to support IG self-administration and flavor preference learning. The same post-oral reinforcement process appears to mediate operant licking and flavor learning, although flavor learning provides a more sensitive measure of sugar reinforcement.

Tumor necrosis factor-α (TNF-α) is one of the key players in stroke progression and can interfere with brain functioning. We previously documented an impairment of experience-dependent plasticity in the cortex neighboring the stroke-induced lesion, which was accompanied with an upregulation of Tnf-α level in the brain of ischemic mice 1 week after the stroke. Because TNF receptor 1 (TnfR1) signaling is believed to be a major mediator of the cytotoxicity of Tnf-α through activation of caspases, we used an anti-inflammatory intervention aimed at Tnf-α R1 pathway, in order to try to attenuate the detrimental effect of post-stroke inflammation, and investigated if this will be effective in protecting plasticity in the infarct proximity. Aged mice (12-14 months) were subjected to the photothrombotic stroke localized near somatosensory cortex, and immediately after ischemia sensory deprivation was introduced to induce plasticity. Soluble TNF-α R1 (sTNF-α R1), which competed for TNF-α with receptors localized in the brain, was delivered chronically directly into the brain tissue for the whole period of deprivation using ALZET Micro-Osmotic pumps. We have shown that such approach undertaken simultaneously with the stroke reduced the level of TNF-α in the peri-ischemic tissue and was successful in preserving the post-stroke deprivation-induced brain plasticity.

International audience; Alternatives to DEHP plasticizers are used in various PVC medical devices (MD) for infusion. As they are able to migrate from these MDs into infused solutions, they may come into contact with patient. Different and specific clinical parameters influence their migration in at-risk situations such as infusion. In contrast to the regulations for Food Contact Materials (MCDA), there is currently no acceptable migration limits for the use of these plasticizers in clinical situations. In order to assess their migration, and thus control the risks linked to these MDs, we developed a migration model for the plasticizers in MDs. To this end, we applied a cross-disciplinary methodological process similar to that used in the food-processing industry, taking into account the MDs' conditions of use in clinical practice. The simulation model is simple and includes the following conditions: MD should be tested with a dynamic method that respects our established clinical assumption (2 L of infused solutions via 13 dm(2) of plasticized PVC), at a temperature of 25 °C and during 24 h of contact, using a 50/50 (v/v) ethanol/water simulant. This model could be proposed as a tool for the safety evaluation of the patients' exposure risk to plasticizers from PVC medical devices for infusions.

Previous work by our laboratory has shown that tacrine can produce long-lasting reductions in cocaine-reinforced behavior, when administered to rats as daily intravenous infusions over four days. Tacrine causes dose-related liver toxicity in different species, and its manufacture for human use was recently discontinued. This study was conducted to further characterize its actions on cocaine reward. Cocaine-experienced animals that had no contact with drug over one week resumed self-administration at levels similar to their initial baseline. When tacrine was administered over four days which were preceded and followed by washout periods to allow elimination of cocaine and tacrine respectively, subsequent cocaine self-administration was attenuated by more than one-half. Tacrine administered at 10 mg/kg-day as a chronic infusion by osmotic pump did not modify cocaine-induced increases in locomotor activity or conditioned-place preference. In rats that exhibited persistent attenuation of cocaine-self-administration after receiving tacrine, cocaine-induced reinstatement was also attenuated. No changes in plasma measures of renal or hepatic function were observed in rats receiving tacrine. In conclusion, pretreatment with tacrine can decrease cocaine-motivated behavior measured by self-administration or reinstatement, but not conditioned-place preference. Reductions in cocaine self-administration following pretreatment with tacrine do not require direct interaction with cocaine and are not secondary to either liver or kidney toxicity.

Here we introduce a novel method of transplanting human fetal kidneys into adult rats. To overcome the technical challenges of fetal-to-adult organ transplantation, we devised an arterial flow regulator (AFR), consisting of a volume adjustable saline-filled cuff, which enables low-pressure human fetal kidneys to be transplanted into high-pressure adult rat hosts. By incrementally withdrawing saline from the AFR over time, blood flow entering the human fetal kidney was gradually increased until full blood flow was restored 30 days after transplantation. Human fetal kidneys were shown to dramatically increase in size and function. Moreover, rats which had all native renal mass removed 30 days after successful transplantation of the human fetal kidney were shown to have a mean survival time of 122 days compared to 3 days for control rats that underwent bilateral nephrectomy without a prior human fetal kidney transplant. These in vivo human fetal kidney models may serve as powerful platforms for drug testing and discovery.

Context Pain is a common and significant symptom experienced by children with advanced malignant disease. There is limited research on pain management of these children at home. Objectives To describe and review the indications for using patient-controlled analgesia (PCA) in the form of a Computerized Ambulatory Drug Delivery device (CADD ® ) in the home setting. Methods A retrospective chart review was conducted in children discharged home with opioid infusions using a CADD. Charts from January 2008 to February 2012 were surveyed. Results Thirty-seven CADDs were dispensed during the study period, and of these, 33 were prescribed for patients with cancer-related pain. A third of the CADDs were commenced at home and almost all PCA CADDs were used for end-of-life care. Hydromorphone was the most commonly prescribed opioid. Patients remained at home and pain control was achieved by either increasing the opioid dose or switching the opioid and using adjuvant therapy. Sixteen patients were readmitted to hospital from home and three admissions were related to pain. The median duration on a PCA CADD at home was 33.7 days (range, 1–150 days), and the mean morphine equivalent dose was 2.13 mg/kg/day. Conclusion PCA with a CADD can be used to manage pain in the home setting. Dose adjustments and opioid switches were performed with no adverse incidents.

In a typical manufacturing setup for biopharmaceutical drug products, the fill and dosing pump is placed after the final sterile filtration unit in order to ensure adequate dispensing accuracy and avoid backpressure peaks. Given the sensitivity of protein molecules, peristaltic pumps are often preferred over piston pumps. However, particles may be shed from the silicone tubing employed. In this study, particle shedding and a potential turbidity increase during peristaltic pumping of water and buffer were investigated using three types of commercially available silicone tubing. In the recirculates, mainly particles of around 200 nm next to a very small fraction of particles in the lower micrometer range were found. Using 3D laser scanning microscopy, surface roughness of the inner tubing surface was found to be a determining factor for particle shedding from silicone tubing. As the propensity toward particle shedding varied between tubing types and also cannot be concluded from manufacturer's specifications, individual testing with the presented methods is recommended during tubing qualification. Choosing low abrasive tubing can help to further minimize the very low particle counts to be expected in pharmaceutical drug products.

Determining the physiological mechanisms underpinning life-history decisions is essential for understanding the constraints under which life-history strategies can evolve. In long-lived species, where the residual reproductive value of breeders is high, adult survival is a key contributor to lifetime reproductive success. We therefore expect that when adult survival is compromised during reproduction, mechanisms will evolve to redirect resources away from reproduction, with implications for reproductive hormones, adult body mass, nest attendance behaviour and breeding success. We investigated whether manipulating corticosterone, to simulate exposure to an environmental stressor, affected the secretion of prolactin and breeding success in the black-legged kittiwake Rissa tridactyla. We used implanted Alzet® osmotic pumps to administer corticosterone to incubating kittiwakes at a constant rate over a period of approximately eight days. Manipulated birds were compared with sham implanted birds and control birds, which had no implants. There was no significant difference in the body mass of captured individuals at the time of implantation and implant removal. Corticosterone-implanted males showed lower nest attendance during the chick rearing period compared to sham-implanted males; the opposite pattern was found in females. Corticosterone treated birds showed a marginally significant reduction in breeding success compared to sham-implanted individuals, with all failures occurring at least one week after implant removal. However, prolactin concentrations at implant removal were not significantly different from initial values. We were unable to measure the profile of change in corticosterone during the experiment. However, our results suggest a delayed effect of elevated corticosterone on breeding success rather than an immediate suppression of prolactin concentrations causing premature failure.

Patient safety and error reduction are essential to improve patient care, and new technology is expected to contribute to such improvements while reducing costs and increasing care efficiency in health care organizations. The purpose of this study was to assess the relationships among pediatric nurses' perceptions of smart infusion pump (SIP) technology, patient safety, and error reduction. Findings revealed that RNs' perceptions of SIP correlated with patient safety. No significant relationship was found between RNs' perceptions of SIP and error reduction, but data retrieved from the pumps revealed 93 manipulations of the pumps, of which error reduction was captured 65 times.

Objective To analyze the cost effectiveness of implementing smart infusion pump technology in a pediatric intensive care unit (PICU). Material and methods An observational, prospective, intervention study with analytical components was carried out. A drug library was developed and integrated into the Carefusion Alaris Guardrails ® infusion systems. A systematic analysis of all the data stored on the devices during use was performed by the data processing program Guardrails ® CQI v4.1 Event Reporter. Intercepted errors were classified in terms of their potential severity and probability of causing an adverse effect (PAE) had they reached the patient. Knowing the estimated cost of a preventable adverse effect (AE), we analyzed costs saved and the profit/cost ratio resulting from the implementation process. Results Compliance with the drug library was 92% and during the study period 92 infusion-related programming errors were intercepted, leading to a saving of 172,279 euros by preventing AEs. This means that 2.15 euros would be obtained for each euro invested in hiring a pharmacist to implement this technology. Discussion The high percentage of use of safety software in our study compared to others allowed for the interception of 92 errors. The estimation of the potential impact of these errors is based on clinical judgment. The cost saved might be underestimated because the cost of an AE is usually higher in pediatrics, indirect and intangible costs were not considered and pharmacists involved do not spend the whole day on this task. Conclusions Smart pumps have shown to be profitable in a PICU because they have the ability to intercept potentially serious medication errors and reduce costs associated with such errors.

Chronic pain poses a major concern to modern medicine and is frequently undertreated, causing suffering and disability. Patient-controlled analgesia, although successful, does have limitations. Transdermal delivery is the pivot to which analgesic research in drug delivery has centralized, especially with the confines of needle phobias and associated pain related to traditional injections, and the existing limitations associated with oral drug delivery. Highlighted within is the possibility of further developing transdermal drug delivery for chronic pain treatment using iontophoresis-based microneedle array patches. A concerted effort was made to review critically all available therapies designed for the treatment of chronic pain. The drug delivery systems developed for this purpose and nondrug routes are elaborated on, in a systematic manner. Recent developments and future goals in transdermal delivery as a means to overcome the individual limitations of the aforementioned delivery routes are represented as well. The approval of patch-like devices that contain both the microelectronic-processing mechanism and the active medicament in a small portable device is still awaited by the pharmaceutical industry. This anticipated platform may provide transdermal electro-activated and electro-modulated drug delivery systems a feasible attempt in chronic pain treatment. Iontophoresis has been proven an effective mode used to administer ionized drugs in physiotherapeutic, diagnostic, and dermatological applications and may be an encouraging probability for the development of devices and aids in the treatment of chronic pain.