Multimodal Quality Improvement Intervention With Dedicated Patient Flow Manager to Reduce Emergency Department Length of Stay and Occupancy: Interrupted Time Series Analysis.

INTRODUCTION: Crowding in the emergency department is a problem worldwide that can affect patient safety and clinical outcomes. The aim of this project was to evaluate a multimodal quality improvement intervention with a new patient flow manager to reduce ED length of stay and ED bed occupancy. METHODS: This single-site interrupted time-series analysis study was conducted in a tertiary hospital emergency department in South Korea. Interventions for a novel system load-balancing approach included a data-driven patient flow tracking informatics system, adding medical specialists, point-of-care creatinine testing (when required before diagnostic imaging) with dedicated imaging test slots for emergency patients, and introducing patient flow managers. Records of adult patients visiting the emergency department from January 2016 to March 2020 were included. Outcomes were ED length of stay and ED bed occupancy. Regression discontinuity analysis of an interrupted time series was used adjusting for seasonality and the number of patients per staff. RESULTS: A total of 46,494 patients in the preintervention period and 151,802 patients in the postintervention period were included. After the intervention, ED length of stay decreased by 4.07 hours, whereas the slope indicated a return to preintervention levels over time. Monthly average ED bed occupancy decreased by 34.6%, and the slope remained consistent over time. DISCUSSION: The multimodal quality improvement intervention that included a patient flow manager was an effective intervention to reduce the ED length of stay and the ED bed occupancy at the study site. The change for length of stay may not sustain over time without further intervention.

Exploratory study of VVZ-149, a novel analgesic molecule, in the affective component of acute postoperative pain after laparoscopic colorectal surgery.

STUDY OBJECTIVE: VVZ-149 is a small molecule that inhibits the glycine transporter type 2 and the serotonin receptor 5-hydroxytryptamine 2A. In the present study, we investigated the efficacy and safety of VVZ-149 as a single-use injectable analgesic for treating moderate to severe postoperative pain after colorectal surgery. DESIGN: Randomized, parallel group, double-blind Phase 2 clinical trial (NCT02489526). SETTING: 3 academic institutions in the United States. PATIENTS: 60 patients undergoing laparoscopic colorectal surgery. INTERVENTIONS: A continuous 8-h intravenous infusion of VVZ-149 Injections (n = 40) or placebo (n = 20) administered after emergence from anesthesia. MEASUREMENTS: The outcome measures included pain intensity (PI), opioid consumption via patient-controlled analgesia (PCA), and rescue dosing provided "as needed". Early rescue dosing with opioids postoperatively was associated with preoperative negative affect (anxiety, depression, and pain catastrophizing), enabling it to be used as an indirect measure of the affective component of pain. Efficacy outcomes were compared between treatment groups based on preoperative negative affect and early rescue dosing of opioids. MAIN RESULTS: Postoperative PI was non-significantly lower in patients receiving VVZ-149 compared to those receiving placebo. The VVZ-149 group had a 34.2% reduction in opioid consumption for 24 h post-dose, along with fewer PCA demands. Somnolence and headache was higher in the intervention group. For patients characterized by high levels of preoperative negative affect, the VVZ-149 group experienced a significant pain reduction and 40% less opioid use compared to the placebo group. CONCLUSIONS: VVZ-149 resulted in a non-significant reduction of postoperative pain during the first 8 h after surgery. Post hoc analysis indicates that VVZ-149 may benefit patients with negative affect who otherwise have higher postoperative opioid use. REGISTRATION NUMBER: www.clinicaltrials.gov, ID: NCT02489526.

Nursing staff factors influencing pain management in the emergency department: Both quantity and quality matter.

BACKGROUND: Abdominal pain is one of the most common symptoms for presentation to the emergency department (ED). However, administration of analgesics is often delayed and pain reassessment is often missed. We investigated the effect of several nursing staff factors on the time to administer analgesics and pain reassessment in ED. METHOD: This retrospective descriptive study was conducted in a tertiary hospital in Korea. The subjects were adult patients who visited the ED for abdominal pain and received analgesics in 2019. Nursing staff factors were defined as the nurse-to-patient ratio and the nurse's experience in the ED. Reassessment was classified into three groups: non-reassessment, reassessment in ≤ 1 h, and reassessment in ≥ 1 h. Patient characteristics and the analgesics' name were collected. The effect of nursing staff factors on the administration time was analyzed using a linear mixture model, and the differences in the nurse, and patient characteristics in the three reassessment groups were evaluated using generalized estimating equations. RESULTS: A total of 1428 cases were included, 54.1% of which received opioids. The median time from prescription to administration (TTA) was 16 min, and pain reassessment was conducted in 55.0%. TTA tended to increase as the nurse-to-patient ratio increased. Nurses in the two reassessment groups had more experience than those in the non-assessment group. CONCLUSION: Both the nurse-to-patient ratio and experience in the ED had a significant impact on pain management. Therefore, appropriate ED nurse staffing levels considering the unpredictable and fluctuating number of patients, and nurse retention strategies are needed.

Role of VVZ-149, a Novel Analgesic Molecule, in the Affective Component of Pain: Results from an Exploratory Proof-of-Concept Study of Postoperative Pain following Laparoscopic and Robotic-Laparoscopic Gastrectomy.

OBJECTIVE: VVZ-149 is a small molecule that both inhibits the glycine transporter type 2 and the serotonin receptor 5 hydroxytryptamine 2 A. In a randomized, parallel-group, and double-blind trial (NCT02844725), we investigated the analgesic efficacy and safety of VVZ-149 Injections, which is under clinical development as a single-use injectable product for treating moderate to severe postoperative pain. METHODS: Sixty patients undergoing laparoscopic and robotic-laparoscopic gastrectomy were randomly assigned to receive a 10-hour intravenous infusion of VVZ-149 Injections or placebo, initiated approximately 1 hour before completion of surgical suturing. Major outcomes included pain intensity and opioid consumption via patient-controlled analgesia and rescue analgesia provided "as needed." The treatment efficacy of VVZ-149 was further examined in a subpopulation requiring early rescue medication, previously associated with the presence of high levels of preoperative negative affect in a prior Phase 2 study (NCT02489526). RESULTS: Pain intensity was lower in the VVZ-149 (n = 30) than the placebo group (n = 29), reaching statistical significance at 4 hours post-emergence (P < .05), with a 29.5% reduction in opioid consumption for 24 hours and fewer demands for patient-controlled analgesia. In the rescued subgroup, VVZ-149 further reduced pain intensity (P < .05) with 32.6% less opioid consumption for 24 hours compared to placebo patients. CONCLUSIONS: VVZ-149 demonstrated effective analgesia with reduced postoperative pain and opioid requirements. Consistent with the results from the previous Phase 2 study, patients with early rescue requirement had greater benefit from VVZ-149, supporting the hypothesis that VVZ-149 may alleviate the affective component of pain and mitigate excessive use of opioids postoperatively.

Corrigendum: Correction of the Acknowledgment.Prevalence and management status of urologic disease in geriatric hospitals in South Korea: A population-based analysis.

[This corrects the article on p. 281 in vol. 58.].

Safety, Tolerability, and Pharmacokinetic Characteristics of a Novel Nonopioid Analgesic, VVZ-149 Injections in Healthy Volunteers: A First-in-Class, First-in-Human Study.

VVZ-149, a dual antagonist of GlyT2 and 5HT2 A receptors, is an investigational analgesic with a novel mechanism of action that is currently under early-stage clinical development as an injectable agent for the treatment of postoperative pain. Here, the safety, tolerability, and pharmacokinetics of VVZ-149 injections in healthy male volunteers were explored in a randomized, double-blind, single- and multiple-ascending-dose (SAD and MAD, respectively), placebo-controlled clinical study. Subjects randomly received a 4-hour intravenous infusion of 0.25-8 mg/kg VVZ-149 or placebo in the SAD study (n = 46) or a 4-hour intravenous infusion of 4-7 mg/kg VVZ-149 or placebo twice daily for 3 days in the MAD study (n = 20). Serial blood and urine samples were collected for the pharmacokinetic analysis of VVZ-149 and its active metabolite (VVZ-368). Noncompartmental and compartmental pharmacokinetic analyses were performed. Various dosing scenarios were simulated to identify the adequate dosing regimen for the subsequent trials. Plasma exposure to VVZ-149 and VVZ-368 showed a dose-proportional increase. VVZ-149 did not accumulate in the plasma, whereas the plasma concentration of VVZ-368 increased by 1.23- to 2.49-fold after the fifth and sixth doses, respectively, in the MAD trial. Among the simulated dosing regimens, a loading dose followed by a maintenance dose was found to be an optimal dosing regimen, yielding the effective concentration estimated from animal studies in rat models of neuropathic or inflammatory pain. Single- or multiple-dose administration of VVZ-149 was generally well tolerated. These results showed that 0.5-8 mg/kg VVZ-149 exhibited linear pharmacokinetic characteristics and can be safely administered in further clinical studies.

Prevalence and management status of urologic disease in geriatric hospitals in South Korea: A population-based analysis.

PURPOSE: This study aimed to investigate the prevalence and management status of urologic disease in geriatric hospitals in Korea. MATERIALS AND METHODS: We conducted population-based analyzed using cohort established by the National Health Insurance Service of Korea, which contains the medical insurance data of 1 million people from 2002 to 2013. The prevalence, prescription rate, and complication incidence of urologic disease in geriatric hospitals were compared with similar-sized general hospitals. We analyzed the changes that followed the adoption of the fixed sum medical fee per day for geriatric hospitals, which began in January 2008. Subgroup analysis was conducted in an elderly group and a propensity score matching (PSM) group. RESULTS: During this time, the number of geriatric hospitals exponentially increased over general hospitals (675.5%/y vs. 30.9%/y). The prevalence, prescription rate, and complication incidence of urologic disease was higher in geriatric hospitals than in general hospitals (2.1, 1.8, and 1.4 times higher). In the elderly group, the prevalence of urologic disorders was higher in geriatric hospitals than in general hospitals, but the prescription rate was lower (26.5% vs. 19.9% and 6.8% vs. 10.0%). This tendency also founded in the PSM analysis. After the medical fee system changed, diagnosis and prescription rates decreased in geriatric hospitals but increased in general hospitals. CONCLUSIONS: Urologic diseases are more prevalent yet management has some problem in geriatric hospitals. Lack of institutional urologists and changes in the medical payment system should be associated with this problem. Additional study and political support are needed to overcome this issue.

Prevalence and management status of urologic diseases in geriatric hospitals in South Korea: A field research.

PURPOSE: We aimed to investigate the current management status of urologic diseases in geriatric hospitals in South Korea. MATERIALS AND METHODS: Questionnaire surveys and in-depth person-to-person interviews were conducted at 13 hospitals within the Seoul and Incheon areas. RESULTS: The study was carried out from July to December 2014; 75.6% of patients (1,858/2,458) and 77.5% (779/1,031) of medical personnel responded to our survey. All surveys and interviews were performed by urology specialists, fellows, residents, or nurses. The hospitals included in the study had an average of 215.2 beds (range, 110-367), 189.1 patients (range, 90-345), and 40.2 nurses (range, 10-83). The average number of physicians was 6.2 (range, 3-11), but none of these were certified urologists. Only 4 hospitals provided consultation services for urological disorders. In total, 64% of patients had urological disorders, although only 20.7% of patients were receiving medication. Most patients were being treated using urological interventions; diapers (49.7%), indwelling catheters (19.5%), clean intermittent catheters (12.2%), and external collection urinary drainage (7.9%). However, most interventions were inadequately implemented, and only 17% of the patients had been examined by a certified urologist. Urological complications were found in 20.2% of patients, and secondary complications occurred in 18.8%. Excluding redundant cases, the total prevalence of urological complications was 39.0%. CONCLUSIONS: Urologic diseases are poorly managed, and no certified urologists work in geriatric hospitals. Therefore, more designated urologists are needed in geriatric hospitals.

Depressive-like behaviors in a rat model of chronic cerebral hypoperfusion.

The vascular depression hypothesis suggests that there is an association between cerebrovascular pathophysiology and depression in the elderly. We investigated depressive-like behaviors and perturbations in the hypothalamus-pituitary-adrenal (HPA) axis in a rat model of chronic cerebral hypoperfusion. We modeled chronic cerebral hypoperfusion by permanent occlusion of the bilateral common carotid arteries (BCCAo) in Wistar rats. Sucrose preference, forced swim, and social interaction tests were performed to measure depressive-like behaviors. The plasma levels of adrenocorticotropic hormone and corticosterone, and the hippocampal expression of the glucocorticoid receptor (GR) were assessed. Sucrose preference (P = 0.045) and social withdrawal (P = 0.038) were significantly enhanced in BCCAo rats. Increased plasma levels of corticosterone (P = 0.034) and impaired cytosolic-to-nuclear translocation of the GR protein were observed in the hippocampus (P = 0.038) of BCCAo rats. Our experimental results support the clinical hypothesis that vascular depression can be induced by chronic cerebral hypoperfusion. Increased HPA axis activity and perturbation of the GR signaling pathway in the hippocampus may be associated with depressive-like behaviors in rats with chronic cerebral hypoperfusion.

The Effects of Helicobacter pylori on the prognosis of patients with curatively resected gastric cancers in a population with high infection rate.

PURPOSE: The goal of this study was to assess the correlation between the Helicobacter pylori status of patients who underwent curative resection for gastric adenocarcinoma and their prognosis in Eastern societies where H. pylori infection is prevalent. METHODS: Between 2006 and 2007, 192 patients who had a curative resection for the treatment of gastric adenocarcinoma were enrolled in the study. Of these patients, 18 were excluded due to an inexact evaluation of the H. pylori status, thereby leaving 174 patients in the final analysis. Serologic testing for H. pylori was assessed using an enzyme-linked immunosorbent assay kit for immunoglobulin G, and the histological presence of H. pylori was identified using the Giemsa stain. RESULTS: Of the 174 patients, 111 patients (63.8%) were confirmed for H. pylori infection. H. pylori status did not correlate with the overall or disease-free survival. For patients with stage III or IV gastric cancer, a positive H. pylori status was a significant predictive factor for recurrence over that of a negative H. pylori status (P = 0.019). Negative H. pylori status was a predictive factor for recurrence in multivariable analysis (relative risk, 2.724; 95 confidence interval, 1.192 to 6.228). CONCLUSION: Helicobacter pylori status did not correlate with the clinicopathologic factors of gastric adenocarcinoma. However, a negative Helicobacter pylori status may be a predictive factor for recurrence in patients diagnosed with advanced gastric adenocarcinoma.

Minimally invasive treatment of gastric gastrointestinal stromal tumors: laparoscopic and endoscopic approach.

PURPOSE: This study aimed to verify the long-term outcome of a minimally invasive endoscopic or laparoscopic approach for the treatment of gastric gastrointestinal stromal tumor (GIST). METHODS: This single-center study involved a retrospective review of gastric tumors that were pathologically confirmed as GIST. A total of 84 patients who underwent minimally invasive endoscopic or laparoscopic resection for gastric GIST were enrolled from February 2002 to June 2007. These demographics, tumor characteristics, and outcomes were analyzed for identification of outcomes and feasibility of endoscopic or laparoscopic resection. RESULTS: Of 84 patients, 27 and 57 patients underwent endoscopic and laparoscopic resection, respectively. The average tumor size was 3.1 ± 1.7 cm. With a mean follow-up of 40.5 ± 20.7 months, 82 (97.7%) patients were disease free. Two patients, both of whom underwent laparoscopic resection, were alive with peritoneal recurrence. Two (7.4%) and 6 (10.5%) patients, respectively, had postoperative complications after endoscopic resection and laparoscopic resection. There was no significant difference in the operative morbidity according to tumor size. There was no postoperative mortality. CONCLUSIONS: Laparoscopic surgery for gastric GIST is safe and feasible, even in large (>5 cm) tumors. Because endoscopic resection showed good results without recurrence, this approach can be useful in selected cases with a high operative risk or a need for preservation of organ function.

Synergistic memory impairment through the interaction of chronic cerebral hypoperfusion and amlyloid toxicity in a rat model.

BACKGROUND AND PURPOSE: Vascular pathology and Alzheimer disease (AD) pathology have been shown to coexist in the brains of dementia patients. We investigated how cognitive impairment could be exacerbated in a rat model of combined injury through the interaction of chronic cerebral hypoperfusion and amyloid beta (Aß) toxicity. METHODS: In Wistar rats, chronic cerebral hypoperfusion was modeled by permanent occlusion of bilateral common carotid arteries (BCCAo). Further, AD pathology was modeled by bilateral intracerebroventricular Aß (Aß toxicity) using a nonphysiological Aß peptide (Aß 25 to 35). The experimental animals were divided into 4 groups, including sham, single injury (Aß toxicity or BCCAo), and combined injury (BCCAo-Aß toxicity) groups (n=7 per group) . Cerebral blood flow and metabolism were measured using small animal positron emission tomography. A Morris water maze task, novel object location and recognition tests, and histological investigation, including neuronal cell death, apoptosis, neuroinflammation, and AD-related pathology, were performed. RESULTS: Spatial memory impairment was synergistically exacerbated in the BCCAo-Aß toxicity group as compared to the BCCAo or Aß toxicity groups (P<0.05). Compared to the sham group, neuroinflammation with microglial or astroglial activation was increased both in multiple white matter lesions and the hippocampus in other experimental groups. AD-related pathology was enhanced in the BCCAo-Aß toxicity group compared to the Aß toxicity group. CONCLUSIONS: Our experimental results support a clinical hypothesis of the deleterious interaction between chronic cerebral hypoperfusion and Aß toxicity. Chronic cerebral hypoperfusion-induced perturbation in the equilibrium of AD-related pathology may exacerbate cognitive impairment in a rat model of combined injury.

Proximal-releasing stent insertion under transnasal endoscopic guidance in patients with postoperative esophageal leakage.

BACKGROUND: Covered metallic or plastic stent placement has become an important treatment for postoperative esophageal leakage; however, fluoroscopic guidance is also required. Here we present a novel stent insertion technique with a newly designed proximal-releasing, self-expanding metallic stent (PR-SEMS) and transnasal endoscope that can enable stent insertion without fluoroscopy as a new method to prevent stent migration. OBJECTIVE: To describe our experience with 7 patients who underwent PR-SEMS insertion with the direct-vision technique and our use of the transnasal endoscope without fluoroscopy. DESIGN: Prospective outcome study. SETTING: A tertiary-care referral university hospital. PATIENTS: This study involved all patients at our center who experienced postoperative esophageal leakage after esophagectomy, primary closure, or total gastrectomy. INTERVENTION: PR-SEMS insertion with the direct vision technique and use of transnasal endoscopy without fluoroscopy. MAIN OUTCOME MEASUREMENTS: Success rate of stent insertion, healing rate of postoperative esophageal leaks, and stent migration rate. RESULTS: All stents were placed at the expected location without complications. One patient had massive hematemesis and underwent surgery. The bleeding focus was the splenic artery, which was damaged during gastrectomy. A significant marginal ulcer occurred in one patient, and the stent was immediately retrieved with an endoscope. After stent removal, 4 postoperative leakages were completely healed, and 2 lesions were not occluded. The 2 remaining minimal lesions became completely occluded with conservative management after stent removal. Stent migration did not occur. LIMITATIONS: A small number of patients. Further prospective, randomized, controlled trials are needed. CONCLUSION: PR-SEMS insertion under transnasal endoscopic guidance is a feasible, safe, and effective treatment for postoperative esophageal leakage, and it can be performed as a bedside procedure. Our anchoring method is effective for the prevention of migration from nonobstructed lesions.

Cytosine deaminase-producing human mesenchymal stem cells mediate an antitumor effect in a mouse xenograft model.

BACKGROUND AND AIM: Stem cell transplantation offers potential gene therapy for brain tumors. However, this approach has received little attention as a treatment for gastrointestinal tumors. In the present study, we explored the possibility of human bone marrow-derived mesenchymal stem cells (hMSC) producing cytosine deaminase (CD), followed by systemic 5-fluorocytosine (5-FC) administration, showing an antitumor effect on a mouse gastric cancer xenograft. METHODS: We first explored the ability of hMSC, coated with fluorescent dye, to migrate to human gastric cancer MKN45 cells in vitro and in vivo. We then used hMSC in which a gene expressed the prodrug-activating enzyme CD, which can convert the prodrug 5-FC into the cytotoxic agent 5-fluorouracil (5-FU), and further investigated the potential of these cells to deliver the CD gene and to reduce tumor growth in nude mice. The migratory capacity of hMSC was confirmed by an in vitro migration assay, as well as in an in vivo model of nude mice bearing subcutaneous tumors of MKN45 cells when hMSC were injected. RESULTS: The migration ability of hMSC towards MKN45 cells was confirmed by migration assay. Effective conversion of 5-FC to 5-FU by hMSC transfected with the CD gene (CD-hMSC) showed therapeutic anticancer potential in a MKN45 cell co-culture system, as confirmed by thin layer chromatography. Nude mice bearing MKN45 tumors were intravenously injected with CD-hMSC, followed by systemic 5-FC treatment (500 mg/kg/day) for 7 days. Tumor volumes and weights of mice injected with CD-hMSC decreased significantly after treatment with 5-FC. However, the 5-FC-treated group without CD-hMSC injection showed neither a decrease in tumor volume nor bodyweight loss. CONCLUSION: The CD-hMSC system showed anticancer therapeutic potential, and minimized the side-effects of 5-FU.

Complications with laparoscopically assisted gastrectomy: multivariate analysis of 300 consecutive cases.

BACKGROUND: Complications associated with laparoscopically assisted gastrectomy (LAG) are not significantly different from those associated with open gastrectomy. However, additional risks related to abdominal access, pneumoperitoneum, and special electrosurgical instruments result in an increased incidence of complications with LAG. This study analyzed the causes and risk factors linked to postoperative morbidity. METHODS: A retrospective review analyzed the data of 300 patients who underwent consecutive LAG for gastric cancer in our department from May 2003 to October 2006. Among the 300 patients, total gastrectomy was performed for 42 patients, distal gastrectomy for 258 patients, and proximal gastrectomy for 3 patients. The clinical and operative data obtained included body mass index, medical comorbidities, history of previous abdominal surgery, operative time, type of surgery, extent of lymph node dissection according to the Japanese Guideline, number of retrieved lymph nodes and lymph node metastases, additional operative procedure, depth of tumor invasion, and disease stage. The outcome data consisted of mortality, major morbidities, and postoperative hospital stay. The 300 cases were divided into two periods: 50 cases in the first period and 250 cases in the second period. RESULTS: Postoperative complications developed in 61 cases (20.3%), wound infection in 21 cases (7%), intraabdominal abscess in 3 cases (1%), bleeding in 12 cases (4%), stenosis in 13 cases (4.3%), leakage in 3 cases (1%), acute pancreatitis in 2 cases (0.7%), pulmonary complication in 4 cases (1.3%), renal complication in 4 cases (1.3%), and cardiac complication in 2 cases (0.7%). The 30-day mortality rate was 0.7% (n=2). Univariate analysis proved that gender, operative period, comorbidity, and operative times were important risk factors. Multivariate analysis proved that cormobidity and operative period were important risk factors. CONCLUSION: The data suggest that LAG can be performed with acceptable perioperative complication rates. The surgeon's experience and careful patient selection determined optimal patient outcomes.