Effect of Lean Processes on Surgical Wait Times and Efficiency in a Tertiary Care Veterans Affairs Medical Center.

Importance: There are an increasing number of veterans in the United States, and the current delay and wait times prevent Veterans Affairs institutions from fully meeting the needs of current and former service members. Concrete strategies to improve throughput at these facilities have been sparse. Objective: To identify whether lean processes can be used to improve wait times for surgical procedures in Veterans Affairs hospitals. Design, Setting, and Participants: Databases in the Veterans Integrated Service Network 11 Data Warehouse, Veterans Health Administration Support Service Center, and Veterans Information Systems and Technology Architecture/Dynamic Host Configuration Protocol were queried to assess changes in wait times for elective general surgical procedures and clinical volume before, during, and after implementation of lean processes over 3 fiscal years (FYs) at a tertiary care Veterans Affairs medical center. All patients evaluated by the general surgery department through outpatient clinics, clinical video teleconferencing, and e-consultations from October 2011 through September 2014 were included. Patients evaluated through the emergency department or as inpatient consults were excluded. Exposures: The surgery service and systems redesign service held a value stream analysis in FY 2013, culminating in multiple rapid process improvement workshops. Multidisciplinary teams identified systemic inefficiencies and strategies to improve interdepartmental and patient communication to reduce canceled consultations and cases, diagnostic rework, and no-shows. High-priority triage with enhanced operating room flexibility was instituted to reduce scheduling wait times. General surgery department pilot projects were then implemented mid-FY 2013. Main Outcomes and Measures: Planned outcome measures included wait time, clinic and telehealth volume, number of no-shows, and operative volume. Paired t tests were used to identify differences in outcome measures after the institution of reforms. Results: Following rapid process improvement workshop project rollouts, mean (SD) patient wait times for elective general surgical procedures decreased from 33.4 (8.3) days in FY 2012 to 26.0 (9.5) days in FY 2013 (P = .02). In FY 2014, mean (SD) wait times were half the value of the previous FY at 12.0 (2.1) days (P = .07). This was a 3-fold decrease from wait times in FY 2012 (P = .02). Operative volume increased from 931 patients in FY 2012 to 1090 in FY 2013 and 1072 in FY 2014. Combined clinic, telehealth, and e-consultation encounters increased from 3131 in FY 2012 to 3460 in FY 2013 and 3517 in FY 2014, while the number of no-shows decreased from 366 in FY 2012 to 227 in FY 2014 (P = .02). Conclusions and Relevance: Improvement in the overall surgical patient experience can stem from multidisciplinary collaboration among systems redesign personnel, clinicians, and surgical staff to reduce systemic inefficiencies. Monitoring and follow-up of system efficiency measures and the employment of lean practices and process improvements can have positive short- and long-term effects on wait times, clinical throughput, and patient care and satisfaction.

The novel use of different bupivacaine preparations with combined regional techniques for postoperative pain management in non-opioid-based laparoscopic inguinal herniorrhaphy.

Opioids are important for surgical pain control but may not be appropriate for patients with narcotic abuse histories or opioid intolerance. We describe a laparoscopic bilateral inguinal herniorrhaphy performed without perioperative or postoperative narcotics. Postoperative analgesia involves a novel technique using 2 different bupivacaine formulations that act synergistically to avoid lag time and provide extended pain relief during the acute surgical recovery phase.

Efficacy of Local Anesthetic With Dexamethasone on the Quality of Recovery Following Total Extraperitoneal Bilateral Inguinal Hernia Repair: A Randomized Clinical Trial.

Importance: Quality of recovery (directly associated with patient satisfaction) is an important clinical outcome measurement and a surrogate of anesthetic/surgical care quality. Objectives: To compare the efficacy of a transversus abdominis plane (TAP) block with dexamethasone sodium phosphate and preperitoneal instillation of local anesthetic (PILA) with dexamethasone vs control on postoperative quality of recovery following a bilateral total extraperitoneal inguinal hernia repair (TEP-IHR) (>24 hours). Secondary objectives included efficacy of this technique on postoperative opioid use, nausea and vomiting, and pain scores. Design, Setting, and Participants: Conducted from November 2013 to August 2015, this randomized, prospective, single-blinded study compared 2 groups (a TAP block and PILA) with a standard anesthetic technique with no regional technique (control) following bilateral TEP-IHR. This study at the Veterans Affairs Medical Center (Indianapolis, Indiana) included patients ages 18 to 80 years with an American Society of Anesthesiologists physical status of 1 to 3 scheduled for an outpatient bilateral TEP-IHR. Nurses assigning pain scores and administrating opioids for pain and staff anesthesiologists administering the Quality of Recovery-40 (QoR-40) questionnaire were blinded. Interventions: Patients randomized to receive a TAP block with local anesthetics and dexamethasone, PILA with dexamethasone, or no regional technique (3 groups). Main Outcomes and Measures: Patient's response to the QoR-40 questionnaire following a TEP-IHR surgery. Results: The mean (SD) ages in the TAP block (n = 19), PILA (n = 24), and control (n = 23) groups were 58.2 (9.4) years, 62.5 (8.1) years, and 62.9 (7.8) years, respectively. The global QoR-40 scores on postoperative day 1 for the TAP block group (median [interquartile range (IQR)], 178 [173-188]) were comparable with the control group (median [IQR], 174 [150-181]), while the PILA group had better global QoR-40 scores (median [IQR], 184 [175.5-190.75]) (P = .002). The effects of the TAP block and PILA on pain in the postoperative care unit (PACU) (median [IQR], 1 [0-5] and 3.5 [0-6.8], respectively), pain after discharge (median [IQR], 3 [2-5] and 3 [1-5.5], respectively), opiate use after discharge (median [IQR], 6.7 [5-10] and 6.7 [3.3-10], respectively), and incidence of nausea and vomiting in the PACU (4 of 19 [21.1%] and 6 of 24 [25%], respectively) were not significantly different from the control group (median [IQR], 4 [3-6] for pain scores in the PACU; 4 [3-7] for pain scores after discharge; 6.7 [3.3-10] for opioid use after discharge; and 6 of 23 [26.1%] for incidence of nausea/vomiting in the PACU). While there was a significant reduction of opioid use in the PACU in the TAP block group (median [IQR], 0 [0-1.3]) when compared with the control group (median [IQR], 4 [1.3-6.7]) (P = .001), this was not seen in the PILA group (median [IQR], 2 [0-6.4]). Conclusions and Relevance: This study demonstrates a better quality of recovery in patients' receiving PILA with dexamethasone compared with control for a TEP-IHR surgery. Trial Registration: clinicaltrials.gov Identifier: NCT02036983.

Proteomic analysis of neuroblastoma subtypes in response to mitogen-activated protein kinase inhibition: profiling multiple targets of cancer kinase signaling.

INTRODUCTION: Survival for high-risk neuroblastoma (NB) remains poor despite aggressive therapy. Novel therapies are vital for improving prognosis. We previously showed differential NB subtype sensitivity to p42/44 mitogen-activated protein kinase (ERK/MAPK) pathway inhibition. In this study, we investigated proteomic changes associated with resistance or sensitivity to MAPK kinase (MEK) inhibition in NB subtypes. MATERIALS AND METHODS: SH-SY5Y (N-type), BE(2)-C (I-type), and SK-N-AS (S-type) were treated with MEK inhibitor U0126 (10 microM) for 1 and 24 h. Proteins were extracted from untreated and treated cells and analyzed for differential expression by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). Selected polypeptides were extracted from the gel and identified by liquid chromatography-linked tandem mass spectrometry (LC-MS/MS). RESULTS: We identified 15 proteins that were decreased by 2.5-fold between untreated and 1 h treated cells and subsequently up-regulated 5-fold after 24 h drug treatment. N-type NB (MEK-resistant) showed the least altered proteomic profile whereas the I-type (MEK-sensitive) and S-type NB (MEK-intermediate) generated significant protein changes. The majority of proteins identified were induced by stress. CONCLUSIONS: Protein differences exist between MEK inhibitor-treated NB subtypes. Identified polypeptides all have roles in mediating cellular stress. These data suggest that inhibition of the ERK/MAPK in NB subtypes leads to an intracellular stress response. The most resistant NB cell line to MEK inhibitor treatment generated the least protective protein profile, whereas the intermediate and most sensitive NB cells produced the most stress response. These findings suggest stress related protein expression may be targeted in assessing a response to ERK/MAPK therapeutics.

Differential sensitivity of chemoresistant neuroblastoma subtypes to MAPK-targeted treatment correlates with ERK, p53 expression, and signaling response to U0126.

PURPOSE: Neuroblastoma tumors are comprised of neuroblastic (N), substrate-adherent (S), and intermediate (I) cells. Because cell growth and differentiation often involve p44/p42 mitogen-activated protein kinase (MAPK) pathway signaling, we explored MAPK signaling and growth response in three NB cell types after MAPK kinase (MEK) inhibition to evaluate the feasibility of MAPK-targeted treatment strategies. METHODS: Three human NB cell cultures, SH-SY5Y (N-type), BE(2)-C (I-type), and SK-N-AS (S-type), were treated in monolayer cultures with increasing concentrations of the MEK inhibitor U0126. MAPK pathway intermediates MEK and ERK, their activated (phosphorylated) forms p-MEK and p-ERK, and p53 expression were assessed by Western blot at 1 and 24 hours. At 72 hours, cell counts determined growth inhibition and DNA fragmentation ELISA assessed apoptosis. RESULTS: Among all three lines, total ERK and MEK expression were unaffected by U0126. However, constitutive total ERK and p53 expression were significantly greater in BE(2)-C (I-type) cells than in SH-SY5Y (N-type) and SK-N-AS (S-type). Active ERK (p-ERK) levels decreased in dose response to U0126 at 1 and 24 hours in all lines. Conversely, p-MEK levels increased with increasing U0126 concentrations at 1 hour in SH-SY5Y (N-type) and at 24 hours in all lines. BE(2)-C (I-type) cell counts decreased in concentration-dependent fashion with U0126, whereas SH-SY5Y (N-type) and SK-N-AS (S-type) showed a biphasic response with increased cell counts at 1 micromol/L U0126 and slightly decreased cell counts at 10 mumol/L U0126. CONCLUSION: This study demonstrates that BE(2)-C (I-type) cells exhibit greater constitutive total ERK and p53 expression than SH-SY5Y (N-type) and SK-N-AS (S-type). Although all three lines exhibit p-ERK decreases with MEK inhibition, only BE(2)-C (I-type) cells significantly decrease their proliferation with U0126 treatment. Although MEK inhibition holds promise in targeting I-type NB cells, successfully treating this heterogeneous tumor may require combining agents against N- and S-type cells.