Discontinuous Protocol Research Articles

Development of a Novel Protocol for Successful Discontinuation of Continuous Kidney Replacement Therapy: A Pilot Study

Development of a Novel Protocol for Successful Discontinuation of Continuous Kidney Replacement Therapy: A Pilot Study

Histodenz Separation of Lysosomal Subpopulations for Analysis of Chaperone-mediated Autophagy.

Chaperone-mediated autophagy (CMA) is the most selective form of lysosomal proteolysis, in which proteins are individually selected for lysosomal degradation. CMA degradation targets bear a pentapeptide consensus motif that is recognized by the cytosolic chaperone HSPA8 (Hsc70), which participates in the trafficking of the target to the lysosomal surface. From there, it is translocated into the lysosomal lumen, independent of vesicle fusion, in a process dependent upon the lysosomal transmembrane protein LAMP2A. There are limited tools for studying CMA in whole cells and tissues, and many of the best techniques for studying CMA rely on the preparation of lysosome enriched fractions. Such experiments include (1) the in vitro evaluation of CMA substrate uptake activity, (2) the characterization of changes to lysosomal resident and CMA regulatory proteins, and (3) lysosomal targetomics, i.e., the use of quantitative proteomics to characterize lysosomal degradation targets. Previous studies using discontinuous metrizamide gradients have shown that a subpopulation of liver lysosomes is responsible for the majority of CMA activity ("CMA+ "). These CMA+ lysosomes are low density and have higher levels of MTORC2 relative to the "CMA- " lysosomes, which are high density and have higher levels of MTORC1. Because of safety concerns surrounding metrizamide, however, this compound is difficult to obtain, and it is impractically expensive. Here, we have provided protocols for isolation of lysosomal subpopulations for CMA-related analyses from mouse liver using Histodenz, a safe and affordable alternative to metrizamide. Supplementary protocols show how to perform CMA activity assays with appropriate statistical analysis, and how to analyze for lysosomal breakage/membrane integrity. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol: Isolation of lysosomal subpopulations from mouse liver using discontinuous Histodenz gradients Alternate Protocol: Isolation of lysosomes from cultured cells using discontinuous Histodenz gradients Support Protocol 1: Verifying enrichment of lysosomal markers in lysosome-enriched fractions Support Protocol 2: Measuring in vitro uptake of CMA substrates Support Protocol 3: Measuring lysosomal membrane integrity by hexosaminidase assay.

Evaluation of a protocol for rifaximin discontinuation in critically ill patients with liver disease receiving broad-spectrum antibiotic therapy

BACKGROUND Rifaximin is frequently administered to critically ill patients with liver disease and hepatic encephalopathy, but patients currently or recently treated with antibiotics were frequently excluded from studies of rifaximin efficacy. Due to overlapping spectrums of activity, combination therapy with broad-spectrum antibiotics and rifaximin may be unnecessary. A pharmacist-driven protocol was piloted to reduce potentially overlapping therapy in critically ill patients with liver disease. It was hypothesized that withholding rifaximin during broad-spectrum antibiotic therapy would be safe and reduce healthcare costs. AIM To determine the clinical, safety, and financial impact of discontinuing rifaximin during broad-spectrum antibiotic therapy in critically ill liver patients. METHODS This was a single-center, quasi-experimental, pre-post study based on a pilot pharmacist-driven protocol. Patients in the protocol group were prospectively identified via the medical intensive care unit (ICU) (MICU) protocol to have rifaximin withheld during broad-spectrum antibiotic treatment. These were compared to a historical cohort who received combination therapy with broad-spectrum antibiotics and rifaximin. All data were collected retrospectively. The primary outcome was days alive and free of delirium and coma (DAFD) to 14 d. Safety outcomes included MICU length of stay, 48-h change in vasopressor dose, and ICU mortality. Secondary outcomes characterized rifaximin cost savings and protocol adherence. Multivariable analysis was utilized to evaluate the association between group assignment and the primary outcome while controlling for potential confounding factors. RESULTS Each group included 32 patients. The median number of delirium- and coma-free days was similar in the control and protocol groups [3 interquartile range (IQR 0, 8) vs 2 (IQR 0, 9.5), P = 0.93]. In multivariable analysis, group assignment was not associated with a reduced ratio of days alive and free of delirium or coma at 14 d. The protocol resulted in a reduced median duration of rifaximin use during broad-spectrum antibiotic therapy [6 d control (IQR 3, 9.5) vs 1 d protocol (IQR 0, 1); P < 0.001]. Rates of other secondary clinical and safety outcomes were similar including ICU mortality and 48-h change in vasopressor requirements. Overall adherence to the protocol was 91.4%. The median estimated total cost of rifaximin therapy per patient was reduced from $758.40 (IQR $379.20, $1200.80) to $126.40 (IQR $0, $126.40), P < 0.01. CONCLUSION The novel pharmacist-driven protocol for rifaximin discontinuation was associated with significant cost savings and no differences in safety outcomes including DAFD.

CURRENT ADVANCEMENTS AND COMPLICATIONS IN INTRATHECAL DRUG DELIVERY SYSTEM

Intrathecal drug delivery systems (IDDS) have emerged as a valuable treatment option for patients with chronic pain who have failed to achieve adequate relief with conventional therapies. These systems provide targeted delivery of medications directly to the cerebrospinal fluid, resulting in improved pain control and reduced systemic side effects. However, the use of IDDS is not without potential complications and considerations that must be addressed to ensure optimal patient outcomes. This comprehensive review examines the various complications associated with IDDS and the considerations that healthcare providers and patients need to be aware of. Surgical complications, such as infection, bleeding, spinal fluid leaks, and nerve damage, are discussed, along with strategies to minimize these risks. Device malfunctions, including pump failure, catheter issues, and electronic problems, are explored, highlighting the importance of regular monitoring and maintenance. Medication-related side effects, such as nausea, sedation, and respiratory depression, are addressed, emphasizing the need for close monitoring and appropriate dosage adjustments. Long-term considerations, including tolerance to medication, physical dependence, and withdrawal symptoms, are also examined, emphasizing the significance of gradual tapering and proper discontinuation protocols. The review underscores the importance of regular follow-up appointments to assess the system's functionality, medication dosages, and patient response to treatment. By proactively managing and addressing complications, healthcare providers can optimize pain relief and minimize adverse effects, ensuring the long-term effectiveness and safety of IDDS.

Standardized Opioid Counseling Is Underperformed Before and After Anterior Cruciate Ligament Reconstruction

To characterize contemporary pain management strategies after anterior cruciate ligament reconstruction (ACLR) within the US and international orthopaedic community. This was a cross-sectional survey-based study disseminated to a consortium of expert orthopaedic surgeons in the management of anterior cruciate ligament injuries. The survey was a 27-question, multiple choice-style questionnaire with question topics ranging from demographic characteristics and practice characteristics to surgeon-specific pain management strategies in the postoperative period after ACLR. Specific topics of interest included the use of preoperative opioid education and/or counseling sessions, implementation of standardized pain management regimens, use of pain tracking systems, and use of any adjunct non-narcotic analgesic modalities. A total of 34 completed surveys were collected, representing a 73.9% response rate. Over 85% of respondents reported prescribing opioids as a standardized postoperative regimen after ACLR. Surgeons reported prescribing 5- to 10-mg doses, with the tablet count ranging anywhere from fewer than 10 tablets to more than 20 tablets, often instructing their patients to stop opioid use 2 to 4 days postoperatively. Prescribed dosages remained stable or decreased over the past 6 months with increased use of non-narcotic adjuncts. Only one-third of respondents reported using standardized preoperative opioid counseling, with even fewer discussing postoperative discontinuation protocols. Over 85% of respondents prescribe opioids as a standardized postoperative regimen after ACLR, with only 15% providing non-narcotic pain regimens. However, prescribed dosages have remained stable or decreased over the past 6 months with increased use of non-narcotic adjuncts. Only one-third of respondents use standardized preoperative opioid counseling, with even fewer discussing postoperative discontinuation protocols. The ongoing opioid epidemic has created an urgent need to identify the most effective pain management strategies after orthopaedic procedures, especially ACLR. This study provides important information about current pain management practices for patients who have undergone ACLR.

Fully distributed finite-time adaptive robust time-varying formation-containment control for satellite formation

This paper investigates the finite-time time-varying formation-containment control problem for satellite formation flying under discontinuous control protocols based on nonsmooth analysis. The desired consequence is that the follower satellites can converge into a dynamic convex hull in finite time, which is spanned by leader satellites' time-varying formation according to the reference signal. Firstly, to accomplish this objective, a finite-time time-varying formation-containment control strategy is proposed for satellite formation system in present of the bounded disturbances and satellites' accelerations, which are known for each satellite. Then, considering the case that the information of disturbances may not be measured accurately and the accelerations of satellites may not be obtained globally in some practice application scenarios, a fully distributed adaptive control strategy is proposed by introducing the dynamic variables. The adaptive variables can compensate the unknown items and adjust with the evolution of neighbour satellites' states, which makes the controller more flexible. Moreover, the proposed control strategies are able to guarantee a fast dynamic response and also a suppression of disturbance. Finally, the performances of the proposed strategies are demonstrated by numerical simulations.

Feasibility of canakinumab withdrawal in colchicine-resistant familial Mediterranean fever.

There is no consensus on canakinumab treatment tapering and discontinuation strategies in colchicine-resistant familial Mediterranean fever (FMF) patients. In this study, we aimed to establish a treatment management and discontinuation protocol in pediatric FMF patients treated with canakinumab. Fifty-eight FMF patients treated with canakinumab were included. Since 2020, we have applied a protocol based on our experience that canakinumab is administered monthly at first six months, followed by bimonthly for six months, and a final period of every three months (for six months). The patients were divided into two groups as 2012-2019 (group A) and 2020-2022 (group B). In group A (n = 33), the median duration of canakinumab treatment was 2.5(1.9-3.7) years. Twenty-five out of 33 patients discontinued canakinumab after a median of 2.1 (1.8-3.4) years. In two patients, canakinumab was restarted because of relapse.In group B (n = 25), canakinumab was discontinued in 18 patients at the end of 18 months. After a median follow-up of 0.8 (0.6-1.1) years, two patients of them had a relapse and canakinumab treatment was re-initiated. The remaining 16 patients still have clinically inactive disease and are receiving only colchicine. When we compared the characteristics between groups A and B, there were no significant differences regarding demographic, clinical features, and outcomes. This is the largest study in the literature suggesting a protocol for discontinuing canakinumab in pediatric FMF patients. It was possible to discontinue canakinumab successfully in more than half of the patients in 18 months. Thus, we suggest that this protocol can be used in pediatric FMF patients.

Observer-Based Adaptive Time-Varying Formation-Containment Tracking for Multiagent System With Bounded Unknown Input

In this article, the time-varying formation (TVF)-containment tracking problem is investigated for linear multiagent systems (MASs), in which the input of tracking leader is unknown and bounded. A novel kind of adaptive discontinuous TVF-containment tracking protocol for linear MAS is proposed. Based on the Lyapunov stability theory, it is shown that under the appropriate assumptions the leaders can achieve an expected TVF and track the trajectory of the tracking leader, while the follower agents can move into the convex hull formed by leader agents. Furthermore, the continuous protocols are also presented to avoid undesirable chattering from the tracking leader’s nonzero input, under which the errors are uniformly ultimately bounded and the upper bound of errors can be made arbitrarily small. In the end, simulation example verifies the feasibility of the desired theoretical results.

Evaluation of a Multifaceted Protocol in Reducing Unnecessary Telemetry Monitoring across a Large Healthcare System.

Telemetry is frequently overused in hospitals. The goal of this study was to evaluate a telemetry protocol aimed at decreasing inappropriate telemetry utilization across four different hospitals within a large healthcare system by modifying the electronic telemetry order to incorporate the 2017 American Heart Association practice guidelines on the appropriate use of telemetry and using an electronic nursing screening task form to safely discontinue telemetry. We performed a retrospective analysis of telemetry utilization before and after we implemented a protocol across four hospitals within a large healthcare system. We compared the average number of days of telemetry monitoring and hospital length of stay during the preintervention period with the 6-month postintervention period. There were a total of 23,774 encounters evaluated. There was a statistically and clinically significant 24% decrease in telemetry duration between pre- and postintervention time periods (P < 0.0001). The mean (standard error) telemetry duration was 4.11 (0.17) and 2.36 (0.13) days in pre- and postintervention periods, respectively. The results of our study demonstrate a statistically significant decrease in overall duration of telemetry monitoring by nearly 1.75 days across each of the four hospitals with the implementation of a multifaceted telemetry protocol that included hardwiring the American Heart Association practice guidelines into the electronic order and using a nursing-driven discontinuation protocol.

Financial Impact of Imatinib Discontinuation in Brazil - a Real World Evidence Pharmacoeconomic Study in Chronic Myeloid Leukemia of a Private Institution

Introduction Recent studies showed that tyrosine kinase inhibitors (TKI) treatment could be safely discontinued in a selected group of chronic phase (CP) chronic myeloid leukemia (CML) patients that achieved deep molecular response (DMR), making treatment-free remission (TFR) a new goal of therapy. The discontinuation treatment in patients with sustained molecular response to MR4 or MR4.5, a practice that has been performed and consolidated since 2011 in other countries, is not feasible in Brazil outside clinical trials because of the lack of coverage for performing RQ-PCR as recommended by the international guidelines. For all these aspects, it seemed essential to us to analyze the financial impact of TKI discontinuation, following strict monitoring criteria, and perform a projection of economic costs in a population of CML patients treated in first-line with imatinib eligible for discontinuation. Aims: To demonstrate the feasibility of coverage of Q-PCR to perform discontinuation of imatinib treatment on eligible patients [ treatment free-response (TFR)] in Brazil based on the financial impact Material and Methods From 2020 -2021, 26 eligible patients from a single private institution in Brazil were invited to participate in a single-arm trial of Imatinib discontinuation (DIP). Inclusion criteria: age > 18 years, chronic phase, minimum of 04 years of Imatinib therapy, a deep molecular response sustained > or = 02 years (confirmed by 04 tests in the last two years, defined MR4.0 or MR 4.5 and a confirmatory exam at the moment of the screening). After discontinuation, patients were monitored by RT- PCR monthly in the first year, every two months in the second year, and every three months after the third year. Criteria for Imatinib re-initiation were the same of the Euro-Ski trial. Considering that US$ 1.00 are R$ 5.3 ( Brazilian currency- March /2022 ) for Branded Imatinib - 400 mg/d, the monthly cost has been estimated at R$ 16,933.90 or US$ 3,95.07 and the generic imatinib- 400mg/d monthly R$ 13,048.90 or US$ 2,462.05 ( CEMED- March/2022). The unitary value for the Q-PCR exam has been estimated, with a large price range at R$ 1,311.25 (R$790.00 to R$ 2,159.00) or US$ 247.40. Results Of 26 patients, 20 consent to discontinuation of imatinib. Six patients declined despite information because of their insecurity about TFR. Twelve patients (60%) presented MR4. The median age was 52.3, and 13 (65%) were female. Median time diagnosis to discontinuation of imatinib 8.5 (4.6-15.5) years. Twelve (60%) patients sustained TFR. . In this interim analysis, the median time of follow-up was 14.5 (2.7-18.8) months. During the follow-up, 244 RQ-PCR were performed. The cumulative time without treatment was 224.5 months. The costs with Q-PCR were R$ 319,945.00 or US$ 60,366.98 (244 exams during follow-up (median time 14,4 months). The average time of months without treatment was 224.5 months. The cost of treatment without discontinuation would be R$ 4,131,871.60 or US$ 779,598.41 (Branded Imatinib) or R$ 2,929,478.05 or US$ 552,731.70 (imatinib copies). The saving on median time of follow-up (14.4 months ) were R$ 3,811,926.60 or US$ 719,231.43 (Branded Imatinib) or R$ 2,609,533.05 or US$ 492,364.72 (imatinib copies). Discussion: Considering the methodology of Cost-Utility, the saving resulting from the discontinuation of treatment for 20 patients for 14.4 months despite the loss of MR of 40 % of patients were R$ 3,811,926.60 or US$ 719,231.43 (Branded Imatinib) or R$ 2,609,533.05 or US$ 492,364.72 (imatinib copies). The results show that if Q-PCR tests were available in clinical practice, within pre-established protocols, there would be equalization and adequacy with the international monitoring guidelines, and discontinuation protocols could be feasible in clinical practice. Conclusion: The possibility of discontinuation would have a huge financial impact on the Brazilian Health System, resulting in the economic viability of treating hundreds of patients and performing thousands of Q-PCR exams, creating a rational and balanced model of clinical efficacy coupled with basic sustainability premises of modern oncology.

Adaptive Discontinuous Control for Fixed-Time Consensus of Nonlinear Multi-Agent Systems

This paper mainly focuses on the fixed-time consensus (FXC) control problem for nonlinear multi-agent systems (MASs). For the cases of leader-following and leaderless, two adaptive discontinuous protocols are designed, respectively, to realize our control goals. Common adaptive control protocols always significantly increase the dimension of the considered system model, while the protocols presented here only require two adaptive update laws and are therefore simpler to apply in the engineering control. Moreover, no additional conditions are required to ensure that the system can achieve FXC successfully, except for some necessary assumptions. Simulation examples also illustrate that these two protocols are effective.

FINANCIAL IMPACT OF IMATINIB DISCONTINUATION IN BRAZIL – A PHARMACOECONOMIC STUDY IN CHRONIC MYELOID LEUKEMIA OF A PRIVATE INSTITUTION

Recent studies showed that tyrosine kinase inhibitors (TKI) treatment could be safely discontinued in a selected group of chronic phase (CP) chronic myeloid leukemia (CML) patients that achieved deep molecular response (DMR), making treatment-free remission (TFR) a new goal of therapy. The discontinuation of treatment in patients with sustained molecular response to MR4 or MR4.5, a practice that has been performed in other countries is not feasible in Brazil outside clinical trials because of the lack of coverage for performing RQ-PCR as recommended by the international guidelines. For all these aspects, it seemed essential to us to analyze the financial impact of TKI discontinuation, following strict monitoring criteria, and perform a projection of economic costs in a population of CML patients treated in first-line with imatinib eligible for discontinuation. To demonstrate the feasibility of coverage of Q-PCR to perform discontinuation of imatinib treatment on eligible patients [ treatment free-response (TFR)] in Brazil based on the financial impact. From 2020 -2021, 20 eligible patients from a single private institution in Brazil were invited to participate in a single-arm trial of Imatinib discontinuation (DIP). After discontinuation, patients were monitored by RT- PCR monthly in the first year, every two months in the second year, and every three months after the third year. Criteria for Imatinib re-initiation were the same of the Euro-Ski trial. Considering that US$ 1.00 are R$ 5.3 (Brazilian currency- March /2022) for Branded Imatinib – 400 mg/d, the monthly cost has been estimated at R$ 16,933.90 or US$ 3,95.07 and the generic imatinib- 400mg/d monthly R$ 13,048.90 or US$ 2,462.05 (CEMED- March/2022). The unitary value for the Q-PCR exam has been estimated, with a large price range at R$ 1,311.25 (R$790.00 to R$ 2,159.00) or US$ 247.40. Of 26 patients, 20 consent to discontinuation of imatinib. Twelve patients (60%) presented MR4. Median time diagnosis to discontinuation of imatinib 8.5 (4.6-15.5) years. Twelve (60%) patients sustained TFR. During the follow-up, 244 RQ-PCR were performed. The cumulative time without treatment was 224.5 months. The costs with Q-PCR were R$ 319,945.00 or US$ 60,366.98 (244 exams during follow-up (median time 14,4 months). The average time of months without treatment was 224.5 months. The cost of treatment without discontinuation would be R$ 4,131,871.60 or US$ 779,598.41 (Branded Imatinib) or R$ 2,929,478.05 or US$ 552,731.70 (imatinib copies). The saving on median time of follow-up (14.4 months) were R$ 3,811,926.60 or US$ 719,231.43 (Branded Imatinib) or R$ 2,609,533.05 or US$ 492,364.72 (imatinib copies). Considering the methodology of Cost-Utility, the saving resulting from the discontinuation of treatment for 20 patients for 14.4 months despite the loss of MR of 40 % of patients were R$ 3,811,926.60 or US$ 719,231.43 (Branded Imatinib) or R$ 2,609,533.05 or US$ 492,364.72 (imatinib copies). The results show that if Q-PCR tests were available in clinical practice, within pre-established protocols, there would be equalization and adequacy with the international monitoring guidelines, and discontinuation protocols could be feasible in clinical practice. The possibility of discontinuation would have a huge financial impact on the Brazilian Health System, resulting in the economic viability of treating hundreds of patients and performing thousands of Q-PCR exams, creating a rational and balanced model of clinical efficacy coupled with basic sustainability premises of modern oncology.

IMPACT OF TWICE-DAILY MULTIDISCIPLINARY ROUNDING IN DECREASING TIME TO EXTUBATION FROM MECHANICAL VENTILATION IN THE ICU

IMPACT OF TWICE-DAILY MULTIDISCIPLINARY ROUNDING IN DECREASING TIME TO EXTUBATION FROM MECHANICAL VENTILATION IN THE ICU

Impact of loading rate during hybrid simulation on seismic response of steel structures

AbstractThis study investigates the influence of loading rates on the seismic response of steel structures. A series of coupon tests under typical earthquake‐induced loading rates are carried out. In addition to the conventional monotonic tension test, the specimens are also tested under a discontinuous loading protocol that is analogous to the ramp‐and‐hold scheme employed in the pseudo‐dynamic hybrid simulations. The test results are used to develop a uniaxial steel material model to account for the strain rate effect and stress relaxation. The material model facilitates the reuse of existing steel hysteresis models and can be used to model different structural components, such as columns, beams, braces, etc. The material model is then used for a parametric study to evaluate the impact of various loading rates on the global seismic response of a single degree of freedom structural system with different structural periods, and types and intensities of ground motions. It is found that the impact of loading rates is more significant for structures with a period of 0.5 s or less and it thus requires a fast control of the physical specimen in pseudo‐dynamic hybrid testing. In addition, the material model is applied to a five‐storey buckling restrained braced frame (BRBF) building with a structural period of 1.2 s. It is found that the earthquake‐induced loading rates have a minor impact on the global response of the structure.

Implementing a Nurse-Driven Telemetry Discontinuation Protocol.

What is the best practice for implementing a nurse-driven telemetry discontinuation protocol?A Rayna Gorisek, MSN, RN, CCRN, CNL, replies:In the current climate of nurse staffing and supply shortages, nurses must take the lead in developing innovative ways to minimize waste and improve the quality of health care. Using a nurse-driven telemetry discontinuation protocol to optimize appropriate telemetry monitoring may decrease unnecessary monitoring, thereby reducing nurse workload, and it may promote patient flow through the hospital.The purpose of nursing protocols is to promote better patient outcomes, optimize patient safety, and improve quality of care. Nurse-driven protocols assist nurses in integrating evidence-based practices into patient settings, support nurses’ decision-making capacity, and increase their autonomy and accountability.1To begin developing a nurse-driven protocol for discontinuing telemetry, evaluate your organization’s existing process. Does a telemetry order set or protocol include steps to assess the need to continue telemetry? Next, conduct a comprehensive literature review, using more than one database to identify current evidence for developing a nurse-driven protocol for discontinuing telemetry. Also review any evidence-based guidelines for appropriate telemetry use, such as those from the American Heart Association, which identify 3 categories of patients and cardiac monitoring2: After reviewing the literature and guidelines, form an interdisciplinary task force that comprises all stakeholders—physicians, nurse managers, nurse directors, clinical nurse leaders, educators, risk management, and nursing staff—to produce a list of criteria for patients to be removed from telemetry. These criteria form the groundwork for developing the nurse-driven discontinuation protocol. As a team, the task force members develop a clinical research question using the PICOT (Patient, Intervention, Comparison, Outcome, and Time) method (see Table).3 Identify local problems specific to your unit or organization, such as delays in patient flow or limited availability of telemetry.Many organizations are challenged by transfer delays from emergency departments or intensive care units to acute care telemetry units. Specific metrics to consider evaluating include wait times for emergency department or intensive care unit patients to receive a bed on the telemetry unit and the total number of hours of telemetry monitoring. One opportunity for quality improvement is to assess alarm data on your unit. Nursing time and workload are impacted when nurses have to attend to unnecessary or nuisance telemetry alarms (eg, leads-off, poor connectivity, artifact, or battery failure alarms).4Initiating a 4-part iterative experiment by using the Plan-Do-Study-Act (PDSA) model offers a method of testing to achieve improvements on a small scale. With this model, a team performs a pilot to test a specific aim of improvement (see Figure).3 One of the benefits of using the PDSA model to test a nurse-driven protocol is that it does not require a lot of time or resources to fully execute the test for change. The PDSA model promotes simplicity by specifying who does what when and with what materials and supplies, ensuring that the stakeholders involved in the PDSA cycle have clear roles and responsibilities.4,5In the Plan phase of the PDSA cycle, the team establishes the specific aim or goal for change to be tested. Members of the interdisciplinary task force are assigned roles and responsibilities for the pilot, create a timetable for the pilot, and complete methods to measure and track data during the pilot. Frontline staff are given any necessary education or training during this phase. Consider ways to incorporate the nurse-driven protocol into nursing workflow, such as through the electronic health record or a checklist that would be used during nurse hand-offs or rounds.The Do phase of PDSA occurs when the pilot is implemented. Documentation is important in order to capture events—especially unanticipated ones—for future study. Listen to frontline staff and adjust the process on the basis of their feedback; making changes at this step reduces staff members’ anxiety and resistance to trying out a practice change.The Study phase is when data are analyzed. Ensure that an appropriate group and time interval are set for the comparison data that will be used to demonstrate the impact of the intervention or change. Evaluate and compare hypotheses and summarize the lessons learned.During the Act phase of PDSA, the task force decides, on the basis of the results, whether to implement, modify, or withdraw the change or idea. The team can continue the PDSA cycle if necessary.3–5Nurse-driven protocols can produce many positive outcomes. Implementing a protocol that decreases the amount of unnecessary telemetry monitoring may increase nurse autonomy, improve patient flow, and reduce costs. Using the PDSA cycle is one evidence-based way to systematically create improvement. Nurses need to be empowered and supported to lead in the development of innovations that improve processes and the outcomes of patients and the nursing profession.

Resilient fixed-time bipartite consensus of multi-agent systems with nonlinear dynamics and directed graphs

This article is concerned with the bipartite fixed-time consensus problem for a class of multi-agent systems with nonlinear dynamics and directed graphs. To achieve the fixed-time consensus, a discontinuous control protocol is proposed. Compared to the protocols with undirected graphs, the control parameters are designed using a new Laplacian matrix based on an underlying undirected graph. Besides, to apply the method to the multi-agent systems with malicious agents, the proposed controller is combined with the Weighted Mean Subsequence Reduced (WMSR) algorithm which is modified for signed graphs. Finally, some simulations are presented to demonstrate the performance of the proposed method.

Stochastic fixed‐time formation for nonlinear multi‐agent systems under a discontinuous protocol

AbstractThis article mainly studies the time‐varying fixed‐time formation (FTF) tracking control problem for stochastically disturbed nonlinear multi‐agent systems on detail balanced graphs. First, a novel sufficient condition for ensuring the fixed‐time stability in probability of stochastic differential equation is given. Then, using the neighboring information, a simple discontinuous control protocol is designed for achieving time‐varying FTF. By means of non‐smooth analysis techniques, our control objective is obtained and a proper upper bound for the expectation of the stochastic settling time is estimated. Finally, a numerical illustration demonstrates that the proposed control protocol is effective.

Fixed-time bipartite consensus of nonlinear multi-agent systems under directed signed graphs with disturbances

This paper considers the fixed-time bipartite consensus of nonlinear multi-agent systems (MASs) subjected to external disturbances. Under the directed signed networks, several sufficient conditions are proposed to guarantee the fixed-time bipartite consensus of MASs with or without leaders, respectively. Some discontinuous control protocols are developed to realize fixed-time tracking bipartite consensus of MASs with a leader. Moreover, the fixed-time leaderless bipartite consensus under directed signed graph are discussed as well. Two numerical examples are given to verify the effectiveness of the theoretical results.

Training status affects between-protocols differences in the assessment of maximal aerobic velocity

PurposeContinuous incremental protocols (CP) may misestimate the maximum aerobic velocity (Vmax) due to increases in running speed faster than cardiorespiratory/metabolic adjustments. A higher aerobic capacity may mitigate this issue due to faster pulmonary oxygen uptake (dot{V}O2) kinetics. Therefore, this study aimed to compare three different protocols to assess Vmax in athletes with higher or lower training status.MethodsSixteen well-trained runners were classified according to higher (HI) or lower (LO) dot{V}O2maxdot{V}O2-kinetics was calculated across four 5-min running bouts at 10 km·h−1. Two CPs [1 km·h−1 per min (CP1) and 1 km·h−1 every 2-min (CP2)] were performed to determine Vmaxdot{V}O2max, lactate-threshold and submaximal dot{V}O2/velocity relationship. Results were compared to the discontinuous incremental protocol (DP).ResultsVmax, dot{V}O2max, dot{V}CO2 and VE were higher [(P < 0.05,(ES:0.22/2.59)] in HI than in LO. dot{V}O2-kinetics was faster [P < 0.05,(ES:-2.74/ − 1.76)] in HI than in LO. dot{V}O2/velocity slope was lower in HI than in LO [(P < 0.05,(ES:-1.63/ − 0.18)]. Vmax and dot{V}O2/velocity slope were CP1 > CP2 = DP for HI and CP1 > CP2 > DP for LO. A lower [P < 0.05,(ES:0.53/0.75)] Vmax-difference for both CP1 and CP2 vs DP was found in HI than in LO. Vmax-differences in CP1 vs DP showed a large inverse correlation with Vmax, dot{V}O2max and lactate-threshold and a very large correlation with dot{V}O2-kinetics.ConclusionsHigher aerobic training status witnessed by faster dot{V}O2 kinetics led to lower between-protocol Vmax differences, particularly between CP2 vs DP. Faster kinetics may minimize the mismatch issues between metabolic and mechanical power that may occur in CP. This should be considered for exercise prescription at different percentages of Vmax.

Outcomes of a clinician-directed protocol for discontinuation of complement inhibition therapy in atypical hemolytic uremic syndrome

Terminal complement inhibition is the standard of care for atypical hemolytic uremic syndrome (aHUS). The optimal duration of complement inhibition is unknown, although indefinite therapy is common. Here, we present the outcomes of a physician-directed eculizumab discontinuation and monitoring protocol in a prospective cohort of 31 patients that started eculizumab for acute aHUS (and without a history of renal transplant). Twenty-five (80.6%) discontinued eculizumab therapy after a median duration on therapy of 2.37 (interquartile range: 1.06, 9.70) months. Eighteen patients discontinued per protocol and 7 because of nonadherence. Of these, 5 (20%) relapsed; however, relapse rate was higher in the case of nonadherence (42.8%) vs clinician-directed discontinuation and monitoring (11.1%). Four of 5 patients who relapsed were successfully retreated without a decline in renal function. One patient died because of recurrent aHUS and hypertensive emergency in the setting of nonadherence. Nonadherence to therapy (odds ratio, 8.25; 95% confidence interval, 1.02-66.19; P = .047) was associated with relapse, whereas the presence of complement gene variants (odds ratio, 1.39; 95% confidence interval, 0.39-4.87; P = .598) was not significantly associated with relapse. Relapse occurred in 40% (2 of 5) with a CFH or MCP variant, 33.3% (2 of 6) with other complement variants, and 0% (0 of 6) with no variants (P = .217). There was no decline in mean glomerular filtration rate from the date of stopping eculizumab until end of follow-up. In summary, eculizumab discontinuation with close monitoring is safe in most patients, with low rates of aHUS relapse and effective salvage with eculizumab retreatment in the event of recurrence.