Clinical Path Research Articles

PCV47 - Extended Thromboprophylaxis With Betrixaban Is Cost-Effective In Acutely ILL Medical Patients

The APEX trial demonstrated that prophylaxis of venous thromboembolism (VTE) with betrixaban from hospital admission through post-discharge (35-42 days) in acutely ill medical patients reduced VTE events without significant increase in major bleeding vs standard-duration prophylaxis (6-14 days) with enoxaparin. Here, we analyzed the cost-effectiveness of this new thromboprophylaxis regimen with betrixaban versus standard-duration enoxaparin. We adopted our previously published decision-tree model to compare two thromboprophylaxis strategies from a US health care provider perspective among a hypothetical cohort of 10,000 acutely ill medical patients who are at risk of VTE: betrixaban (160 mg loading dose followed by 80 mg once daily for 35 days; $396) versus enoxaparin (40 mg daily for 9 days; $284). To estimate VTE-related deaths within 35 days that might have been averted by thromboprophylaxis, the model incorporated a clinical care path, including primary and secondary VTE prophylaxis as well as treatment of thromboprophylaxis-related adverse events. Parameter values and costs were estimated for each node in the decision tree based on publically available health data. All costs were converted to 2017 USD based on the US medical care consumer index. For the base-case scenario, among a hypothetical cohort of 10,000 acutely ill medical patients at increased VTE risk, betrixaban was estimated to reduce risk of death by 0.16% and save nearly $1.8M (or $178.27 per patient treated). One-way sensitivity analyses indicated that betrixaban would dominate enoxaparin assuming: a) the cost of 35-day betrixaban was <$15.94 per dose (<$574 per 36 doses); b) the clinically relevant recognized bleeding rate was ≤3.8% or c) the VTE rate was ≤7.2%. Based on the rates of clinical events reported in the APEX study, thromboprophylaxis with betrixaban from admission through post-discharge in acutely ill medical patients is likely to prevent additional deaths and reduce costs compared with standard-duration thromboprophylaxis with enoxaparin.

Robotic-assisted surgery in ophthalmology.

Provide an overview of the current landscape of robotics in ophthalmology, including the pros and cons of system designs, the clinical development path, and the likely future direction of the field. Robots designed for eye surgery should meet certain basic requirements. Three designs are currently being developed: smart surgical tools such as the steady hand, comanipulation devices and telemanipulators using either a fixed or virtual remote center of motion. Successful human intraocular surgery is being performed using the Preceyes surgical system. Another telemanipulation robot, the da Vinci Surgical System, has been used to perform a pterygium repair in humans and was successful in ex-vivo corneal surgery despite its nonophthalmic design. Apart from Preceyes' BV research platform, none of the currently eye-specific systems has reached a commercial stage. Systems are likely to evolve from robotic assistance during specific procedural steps to semiautonomous surgery, as smart sensors are introduced to enhance the basic functionalities of robotic systems. Robotics is still in its infancy in ophthalmology but is rapidly reaching a stage wherein it will be introduced into everyday ophthalmic practice. It will most likely be introduced first for demanding vitreo-retinal procedures, followed by anterior segment applications.

The Integrated Case Management Program: Essential for Today's Case Manager.

I thought that most health care professionals, and ertainly case managers, were beyond segregating physical health, mental health, and behavioral health. However, I was mistaken. As recently as last week, I overheard a hospital case manager tell her manager that she was not trained in mental health

Abstract 135: Extended Thromboprophylaxis With Betrixaban is Cost-effective in Acutely Ill Medical Patients

Objectives: The APEX trial demonstrated that prophylaxis of venous thromboembolism (VTE) with betrixaban from hospital admission through post-discharge (35-42 days) in acutely ill medical patients reduced VTE events, including symptomatic VTEs, without significant increase in major bleeding versus standard-duration prophylaxis (6-14 days) with enoxaparin. Based on these data, betrixaban has been approved by the FDA for prophylaxis of VTE in adult patients hospitalized for an acute medical illness who are at risk for thromboembolic complications. Here, we analyzed the cost-effectiveness of this new thromboprophylaxis regimen with betrixaban versus standard-duration thromboprophylaxis with enoxaparin. Methods: We adopted our previously published decision-tree model to compare two thromboprophylaxis strategies from a US health care provider perspective among a hypothetical cohort of 10,000 acutely ill medical patients who are at risk of VTE: betrixaban (160 mg loading dose followed by 80 mg once daily for 35 days; $396) versus enoxaparin (40 mg daily for 9 days; $284). To estimate VTE-related deaths within 35 days that might have been averted by thromboprophylaxis, the model incorporated a clinical care path, including primary and secondary VTE prophylaxis as well as treatment of thromboprophylaxis-related adverse events. Parameter values and costs were estimated for each node in the decision tree based on publically available health data. All costs were converted to 2017 USD based on the US medical care consumer index. Results: For the base-case scenario, among a hypothetical cohort of 10,000 acutely ill medical patients at increased VTE risk, betrixaban was estimated to reduce risk of death by 0.16% and save nearly $1.8M (or $178.27 per patient treated). One-way sensitivity analyses indicated that betrixaban would dominate enoxaparin assuming: a) the cost of 35-day betrixaban was &lt;$15.94 per dose (&lt;$574 per 36 doses); b) the clinically relevant recognized bleeding rate was ≤3.8% or c) the VTE rate was ≤7.2%. Conclusions: Based on the rates of clinical events reported in the APEX study, extended-duration thromboprophylaxis with betrixaban from hospital admission through post-discharge in acutely ill medical patients is likely to prevent additional deaths and reduce costs compared with standard-duration thromboprophylaxis with enoxaparin.

Risk factors for post-colorectal endoscopic submucosal dissection (ESD) coagulation syndrome: a multicenter, prospective, observational study.

Background and study aims Colorectal cancer (CRC) is one of the most common neoplasms and endoscopic submucosal dissection (ESD) is an effective treatment for early-stage CRC. However, it has been observed that patients undergoing ESD often complain of pain, even if ESD has been successfully performed. Risk factors for such pain still remain unknown. The aim of this study was to explore the risk factors for post-colorectal ESD coagulation syndrome (PECS). Patients and methods This was a prospective multicenter observational trial (UMIN000016781) conducted in 106 of 223 patients who underwent ESD between March 2015 and April 2016. We investigated age, sex, tumor location, ESD operation time, lesion size, duration of hospitalization, and frequency of PECS. We defined PECS as local abdominal pain (evaluated on a visual analogue scale) in the region corresponding to the site of the ESD that occurred within 4 days of the procedure. Results PECS occurred in 15/106 (14.2 %), and 10 were women ( P = 0.01, OR: 7.74 [1.6 – 36.4]), 7 had lesions in the cecum ( P < 0.001, OR: 20.6 [3.7 – 115.2]), and 9 in whom ESD operation time was > 90 min ( P = 0.002, OR: 10.3 [2.4 – 44.6]). Frequency of deviation from the prescribed clinical path was significantly higher (47 % [7/15] vs. 2 % [2/91], P < 0.001, OR: 38.9 [6.9 – 219.6]), and hospital stay was significantly longer in the PECS group. Conclusions Female gender, location of lesion in the cecum, and ESD operation time > 90 minutes were significant risk factors independent of PECS. These findings are important to management of PECS.

Effects of clinical nursing pathway on postoperative rehabilitation and compliance of parturients undergoing cesarean section

Objective To analyze the effect of clinical nursing pathway on postoperative rehabilitation and compliance of parturients who had undergone cesarean section. Methods A total of 70 parturients who had undergone cesarean section in our hospital from September to December 2016 were selected as the research objects.This study was approved by the ethics committee of the hospital.All these parturients were divided into two groups according to the random table method, with 35 cases in each group.Patients in the control group received routine nursing, whereas those in the observation group was given routine nursing plus clinical nursing pathway.The conditions before and after nursing, cesarean section, compliance to rehabilitation and nursing satisfaction of the parturients in the two groups were compared. Results The SAS and SDS scores of the two groups were not statistically significant (P>0.05) .The SAS and SDS score of the control group were higher than those of the observation group, and the differences were statistically significant (P<0.05). In the control group, the amount of bleeding, postoperative exhaust time, lower bed activity time and lactation time were longer than the observation group, and the difference was statistically significant (P<0.05). In the control group, the recovery compliance and nursing satisfaction were lower than those in the observation group, and the difference was statistically significant (P<0.05). Conclusions Giving clinical care path mode to cesarean delivery puerperae plays an important role in improving postoperative rehabilitation and compliance. Meanwhile, it's conducive to reducing the influence of unhealthy emotion on puerperae, and promoting puerperae to have prognosis recovery, which is worth having popularization for clinical application. Key words: Clinical nursing pathway; Cesarean delivery; Postoperative rehabilitation; Compliance

A synthetic combinatorial approach to disabling deviant Hedgehog signaling

Mutations in components of the Hedgehog (HH) signal transduction pathway are found in the majority of basal cell carcinoma (BCC) and medulloblastoma incidents. Cancerous cells with intrinsic or acquired resistance to antagonists targeting the seven transmembrane effector Smoothened (SMO) frequently invoke alternative mechanisms for maintaining deviant activity of the GLI DNA binding proteins. Here we introduce a chemical agent that simultaneously achieves inhibition of SMO and GLI activity by direct targeting of the SMO heptahelical domain and the GLI-modifying enzymes belonging to the histone deacetylase (HDAC) family. We demonstrate a small molecule SMO-HDAC antagonist (IHR-SAHA) retains inhibitory activity for GLI transcription induced by SMO-dependent and -independent mechanisms frequently associated with cancer biogenesis. Synthetic combinatorial therapeutic agents such as IHR-SAHA that a priori disable cancer drivers and anticipated mechanisms of drug resistance could extend the duration of disease remission, and provide an alternative clinical development path for realizing combinatorial therapy modalities.

Clinical Path Based Simulations to Estimate the Necessary Working Hours for Hospital Ward Nurses and to Make the Hours Distributed Reduction. Applications to The Cases Composed of Five Usual Cardiac Catheter Tests and One Additional Urgent Test

Clinical Path Based Simulations to Estimate the Necessary Working Hours for Hospital Ward Nurses and to Make the Hours Distributed Reduction. Applications to The Cases Composed of Five Usual Cardiac Catheter Tests and One Additional Urgent Test

Nursing and patient education in clinical path of carotid artery stenting

Nursing and patient education in clinical path of carotid artery stenting

Measurement and Comparison of Costs of Hypertensive Patients Aged 40-89 Years Treated with Lisinopril and Perindopril

Summary A cross-sectional study was carried out in 2016 in the research project No 4/2016. We selected 98 patients aged 40-89 and diagnosed with hypertension. The patients were admitted to Cardiology Clinic One of the University Hospital in Pleven. The study aimed to measure and compare direct and indirect costs of hypertensive patients aged 40-89 years, who were treated with lisinopril and perindopril. We estimated the total and average costs of 50 (51.0%) patients treated with lisinopril and 48 (49.0%) treated with perindopril. Males were 46.4%, and the mean age of the sample was 65.9.0±11.2 years. Data were processed by Statistical Package for Social Science version 19.0 (SPSS.v.19.0). Total costs exceeded amount reimbursed for the clinical path (BGN 420.00) in 64.6% of the patients treated with perindopril and 48.0% of the patients treated with lisinopril. We found that treatment costs within 6-months after discharge were BGN 673.82 in patients treated with lisinopril, as compared to BGN 171.92 reimbursed by the National Health Insurance Fund (NHIF), and BGN 781.18 for those treated with perindopril, compared to BGN 216.33 reimbursed by NHIF. The NHIF reimbursement rate for antihypertensive treatment is insufficient to cover all direct costs. Increased hospital costs and out-of-pocket payments present a significant restriction on access to treatment for arterial hypertension.

Guidelines for standardizedmanagement of neutropenia induced by chemotherapy and radiotherapy

Neutropenia is the most common hematologic toxicity of myelosuppressive chemotherapy and radiotherapy. The degree and duration of neutropenia are directly related to the risk of infection and even death, which can also affect the relative dose intensity of chemotherapy and the prognosis of patients. At present, clinicians tend to underestimate the harm of neutropenia, and are in lack of knowledge on granulocyte colony-stimulating factor(G-CSF), especially on prevention and treatment of neutropenia. Based on clinical evidence, the Chinese Society of Clinical Oncology (CSCO) develops guidelines on the assessment, prevention and treatment of neutropenia and the application of G-CSF. It suggests a hierarchical management concept for neutropenia and establishes a clinical path of prevention and treatment, in order to provide guidance for standardized management of neutropenia and the rational use of G-CSF.

Automated multimodal spectral histopathology for quantitative diagnosis of residual tumour during basal cell carcinoma surgery.

Multimodal spectral histopathology (MSH), an optical technique combining tissue auto-fluorescence (AF) imaging and Raman micro-spectroscopy (RMS), was previously proposed for detection of residual basal cell carcinoma (BCC) at the surface of surgically-resected skin tissue. Here we report the development of a fully-automated prototype instrument based on MSH designed to be used in the clinic and operated by a non-specialist spectroscopy user. The algorithms for the AF image processing and Raman spectroscopy classification had been first optimised on a manually-operated laboratory instrument and then validated on the automated prototype using skin samples from independent patients. We present results on a range of skin samples excised during Mohs micrographic surgery, and demonstrate consistent diagnosis obtained in repeat test measurement, in agreement with the reference histopathology diagnosis. We also show that the prototype instrument can be operated by clinical users (a skin surgeon and a core medical trainee, after only 1-8 hours of training) to obtain consistent results in agreement with histopathology. The development of the new automated prototype and demonstration of inter-instrument transferability of the diagnosis models are important steps on the clinical translation path: it allows the testing of the MSH technology in a relevant clinical environment in order to evaluate its performance on a sufficiently large number of patients.

Reverse and Forward Translational Neuropharmacology in Psychiatric Drug Discovery.

The probability of achieving marketing approval of a novel therapeutic for psychiatric indications is extremely low due largely to the inability to demonstrate durable and reproducible efficacy in phase II trials and beyond. These failures are often attributed to the lack of translation of the underlying neuropharmacology from animal model(s) to the disease population. However, how assured is such a conclusion considering the clinical efficacy path rarely meticulously parallels the preclinical experiment(s) that underwrote it?

N-(Pivaloyloxy)alkoxy-carbonyl Prodrugs of the Glutamine Antagonist 6-Diazo-5-oxo-l-norleucine (DON) as a Potential Treatment for HIV Associated Neurocognitive Disorders.

Aberrant excitatory neurotransmission associated with overproduction of glutamate has been implicated in the development of HIV-associated neurocognitive disorders (HAND). The glutamine antagonist 6-diazo-5-oxo-l-norleucine (DON, 14) attenuates glutamate synthesis in HIV-infected microglia/macrophages, offering therapeutic potential for HAND. We show that 14 prevents manifestation of spatial memory deficits in chimeric EcoHIV-infected mice, a model of HAND. 14 is not clinically available, however, because its development was hampered by peripheral toxicities. We describe the synthesis of several substituted N-(pivaloyloxy)alkoxy-carbonyl prodrugs of 14 designed to circulate inert in plasma and be taken up and biotransformed to 14 in the brain. The lead prodrug, isopropyl 6-diazo-5-oxo-2-(((phenyl(pivaloyloxy)methoxy)carbonyl)amino)hexanoate (13d), was stable in swine and human plasma but liberated 14 in swine brain homogenate. When dosed systemically in swine, 13d provided a 15-fold enhanced CSF-to-plasma ratio and a 9-fold enhanced brain-to-plasma ratio relative to 14, opening a possible clinical path for the treatment of HAND.

Supportive care pathway functionalities of EHR system in a Saudi Arabian hospital

BackgroundElectronic health record (EHR) is a data management system used in healthcare services. The stored medical information in EHR can be accessed and utilized by authorized users, which helps clinicians in making clinical decisions. Therefore, this study aims at comparing the embedded clinical guidelines or the supportive pathway functions as well as their compliance level in the two EMR systems, i.e. QuadraMed (QCPR) and BestCare. MethodsA test vignette was used to evaluate the features, functions, performance, and output to assess the EHR clinical path way functionality of the QCPR and BestCare. The study was based on interview and discussion, followed by actual system testing. ResultsThe results of the evaluation showed that the overall total score of QuadraMed and BESTCare systems supportive care pathway functions were 44.4% and 68.9%, respectively. BestCare is set to replace QCPR in all King Abdulaziz Medical City (KAMCS) hospitals. ConclusionsEmbedding clinical decision support system into EMRs improved clinician performance and facilitated quality of care. However, further investigation of the BESTCare is highly recommended to utilize and fulfill the basic demands of the supportive care pathway functions in King Abdulaziz Medical City (KAMC) hospitals.

Vital pulp therapy of damaged dental pulp

The development of an expert consensus on vital pulp therapy can provide practical guidance for the improvement of pulp damage care in China. Dental pulp disease is a major type of illness that adversely affects human oral health. Pulp capping and pulpotomy are currently the main methods for vital pulp therapy. Along with the development of minimal invasion cosmetic dentistry, using different treatment technologies and materials reasonably, preserving healthy tooth tissue, and extending tooth save time have become urgent problems that call for immediate solution in dental clinics. This paper summarizes the experiences and knowledge of endodontic experts. We develop a clinical path of vital pulp therapy for clinical work by utilizing the nature, approach, and degree of pulp damage as references, defense and self-repairing ability of pulp as guidance, and modern technologies of diagnosis and treatment as means.

A rare but life-threatening complication of aortic surgery: iliac appendiceal fistula

Aortoenteric fistulas are rare (<1%) but disastrous complications after open and endovascular aortic surgery. The most frequently involved anatomical sites are abdominal aorta and duodenum. Surgery is the only possible treatment and consists, in most of cases, in an axillobifemoral bypass, a very invasive procedure with a high rate of complications. In the literature, less than 10 cases of direct communication between the right iliac artery and the appendix are described. In this paper, we discuss our experience of a case of iliac appendiceal fistula. We go through clinical presentation, diagnostic path and treatment with a brief look at the literature. Our conclusion is that in some cases a less invasive surgical approach could lead to good results, but the long-term outcomes need to be studied. Iliac appendiceal fistulas are rare variations of aortoenteric fistulas with similar onset. In cases like ours, a less invasive surgical approach could lead to good results.

Abstract 4178: The novel PLK1 inhibitor, CYC140: Identification of pharmacodynamic markers, sensitive target indications and potential combinations

Abstract Introduction: CYC140 is a selective and potent ATP-competitive inhibitor of PLK1, which has completed IND-enabling studies. The aim of this translational project was to inform the clinical development path of CYC140. Esophageal cancer was investigated as a potential target indication based on unmet medical need and the observation that PLK1 is frequently overexpressed in esophageal tumors and carries a poor prognosis. Experimental procedures: The anticancer activity of CYC140 was examined across multiple tumor types to identify sensitive target indications or tumor subsets. 6 h pulse exposure to CYC140 was used to determine sensitivity in a panel of over 250 cancer cell lines, including 15 esophageal cancer cell lines, using CellTiter Glo and resazurin-based assays. Candidate pharmacodynamic markers were examined in malignant and non-malignant cells. Drug combination testing was undertaken in several esophageal cell lines using approved and targeted agents. Solid tumor and leukemia xenograft models were performed to assess CYC140 dosing schedules and efficacy. Summary: Inhibition of PLK1 by CYC140 perturbs the entry into and exit from mitosis. In malignant cells, CYC140 treatment leads to the appearance of mitotic cells with monopolar spindles and a persistent increase in the proportion of cells in G2 and M phase, resulting in complete growth inhibition and induction of cell death. In non-malignant cells, the growth arrest is transient, and cells resume cycling once compound is removed. Short (6 h) pulse treatments of CYC140 maximise the difference in cellular response between malignant esophageal cell lines and cells of a non-malignant origin. In the esophageal cell line panel, CYC140 cellular IC50 correlates with induction of apoptosis. The effect of CYC140 on pharmacodynamic markers of PLK-1 activity such as phospho-nucleophosmin and phospho-histone H3 was characterized in malignant and non-malignant cells. Several promising combinations of CYC140 with targeted agents were identified, including EGFR inhibitors, HDAC inhibitors and PI3K pathway inhibitors, and CYC140 can also be combined with cytotoxic agents approved for use in esophageal cancer, such as cisplatin or irinotecan. CYC140 anti-tumor efficacy was demonstrated in solid tumor and leukemic xenograft models with responses including tumor regression and tumor-free cures. Conclusions: CYC140 is a promising anti-cancer agent with potent anti-proliferative activity and therapeutic potential in a variety of cancers, including esophageal cancer and acute leukemia. The mode of action of CYC140 is consistent with PLK1 inhibition and cell death is preferentially triggered in sensitive malignant cells. Suitable pharmacodynamic markers and several promising combinations have been identified that could assist clinical development of CYC140. Citation Format: Sylvie Moureau, Craig MacKay, Chiara Saladino, Elizabeth Pohler, Karin Kroboth, Jonathan Hollick, Daniella Zheleva, Sheelagh Frame, David Blake. The novel PLK1 inhibitor, CYC140: Identification of pharmacodynamic markers, sensitive target indications and potential combinations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4178. doi:10.1158/1538-7445.AM2017-4178

The Application of an Evidence-Based Clinical Nursing Path for Improving the Preoperative and Postoperative Quality of Care of Pediatric Retroperitoneal Neuroblastoma Patients: A Randomized Controlled Trial at a Tertiary Medical Institution.

A clinical nursing path (CNP) that encourages patients and their families to become actively involved in healthcare decision-making processes may improve outcomes of pediatric retroperitoneal neuroblastoma (NB) patients. The aim of this study was to evaluate the utility and value of an evidence-based CNP provided to pediatric retroperitoneal NB patients undergoing resection surgery. One hundred twenty NB cases were assigned to a control group or a CNP group. The control group was provided with standard nursing care. The CNP group was provided with nursing care in accordance with an evidence-based CNP. The utility and value of the CNP were compared with standard nursing care. Outcome measures included rates of postoperative complications, lengths of hospital stay, and cost of hospitalization, as well as preoperative and postoperative quality of care and patient satisfaction with care. The rates of postoperative complications, length of preoperative hospitalization, total length of hospital stay, and costs of hospitalization were significantly lower for patients receiving the CNP compared with the control group. Preoperative and postoperative quality of care and patient satisfaction with care were significantly higher in patients receiving the CNP compared with the control group. Adoption of a CNP for preoperative and postoperative care of pediatric retroperitoneal NB patients undergoing resection surgery improves clinical outcomes and patient satisfaction with care. A CNP can increase families' participation in a patient's recovery process, enhance nurses' understanding of the services they are providing, and improve the quality of healthcare received by patients.

EFFECTS OF IMPLEMENTING CLINICAL PATHWAY ON PAIN AND ANXIETY FOR PATIENTS UNDERGOING CARDIAC SURGERY

Background :Vulvular heart replacement surgery is an increasingly important in cardiac valve disease management .VHRS tends to be suitable for clinical pathway development because high volume , high cost of the surgery and predictable course of events that occur during hospitalization .The aim of this study was to determine the effects of implementing clinical pathway on pain and anxiety for patients undergoing cardiac surgery . Subject and methods, this is a randomized controlled design was utilized . This study was carried out in cardiothoracic surgery unit at the Mansoura University Hospital . A Purposeful sample of 50 adult patients of both sexes scheduled for vulvular heart replacement surgery was included in the study (25 clinical path group and 25 control group ). Two tools used for data collection pain scale tool and State trait anxiety inventory .The clinical pathway for cardiac surgery patients conducted in four phases : Phase one : patients assessment , Phase two :cardiac valve surgery clinical pathway establishment and jury . Phase three: implementation and tracking variances . Phase four :Evaluation .The main results of study demonstrated no statistical significant differences in basic data on admission ,.the CP group had significantly lower level of anxiety and pain than the control group before and after surgery . All of the patients in CP group had no variance from VHRS pathway which prove the preset hypothesis of the study