Association Between Local Anesthetic Dosing, Postoperative Opioid Requirement, and Pain Scores After Lumpectomy and Sentinel Lymph Node Biopsy with Multimodal Analgesia.

BACKGROUND: Multimodal analgesia (MMA) during breast surgery reduces postoperative pain and opioid requirements, but the relative contribution of local anesthetic dosing as a component of MMA is not well defined among patients undergoing lumpectomy and sentinel lymph node biopsy (SLNB). PATIENTS AND METHODS: We identified consecutive patients who underwent lumpectomy and SLNB with MMA from 1/2019 to 4/2020. Univariable and multivariable linear and logistic regression were used to examine associations between local anesthetics, opioid requirements in the post-anesthesia care unit (PACU), and pain scores in the PACU and on postoperative day (POD) 1. RESULTS: In total, 1603 patients [median tumor size, 14 mm (interquartile range 8-20 mm)] were included. The median PACU opioid requirement was 0 morphine milligram equivalents (interquartile range 0-5). PACU maximum pain was none or mild in 58% of patients and moderate to severe in 42%; among 420 survey respondents, 56% reported no or mild pain and 44% reported moderate to severe pain on POD 1. On multivariable analysis that adjusted for routine components of MMA, increasing doses of 0.5% bupivacaine were associated with reduced PACU opioid requirements (ß -0.04, 95% confidence interval -0.07 to -0.01, p = 0.011) and lower odds of moderate to severe pain (odds ratio 0.98, 95% confidence interval 0.97-0.99, p < 0.001). Local anesthetics were not associated with pain scores on POD 1. CONCLUSIONS: Higher amounts of local anesthetics reduce acute postoperative pain and opioid requirement after lumpectomy and SLNB. Maximizing dosing within weight-based limits is a low-risk, cost-effective pain control strategy that can be used in diverse practice settings.

Enhanced Recovery Programs in an Ambulatory Surgical Oncology Center.

BACKGROUND: We describe the implementation of enhanced recovery after surgery (ERAS) programs designed to minimize postoperative nausea and vomiting (PONV) and pain and reduce opioid use in patients undergoing selected procedures at an ambulatory cancer surgery center. Key components of the ERAS included preoperative patient education regarding the postoperative course, liberal preoperative hydration, standardized PONV prophylaxis, appropriate intraoperative fluid management, and multimodal analgesia at all stages. METHODS: We retrospectively reviewed data on patients who underwent mastectomy with or without immediate reconstruction, minimally invasive hysterectomy, thyroidectomy, or minimally invasive prostatectomy from the opening of our institution on January 2016 to December 2018. Data collected included use of total intravenous anesthesia (TIVA), rate of PONV rescue, time to first oral opioid, and total intraoperative and postoperative opioid consumption. Compliance with ERAS elements was determined for each service. Quality outcomes included time to first ambulation, postoperative length of stay (LOS), rate of reoperation, rate of transfer to acute care hospital, 30-day readmission, and urgent care visits ≤30 days. RESULTS: We analyzed 6781 ambulatory surgery cases (2965 mastectomies, 1099 hysterectomies, 680 thyroidectomies, and 1976 prostatectomies). PONV rescue decreased most appreciably for mastectomy (28% decrease; 95% confidence interval [CI], -36 to -22). TIVA use increased for both mastectomies (28%; 95% CI, 20-40) and hysterectomies (58%; 95% CI, 46-76). Total intraoperative opioid administration decreased over time across all procedures. Time to first oral opioid decreased for all surgeries; decreases ranged from 0.96 hours (95% CI, 2.1-1.4) for thyroidectomies to 3.3 hours (95% CI, 4.5 to -1.7) for hysterectomies. Total postoperative opioid consumption did not change by a clinically meaningful degree for any surgery. Compliance with ERAS measures was generally high but varied among surgeries. CONCLUSIONS: This quality improvement study demonstrates the feasibility of implementing ERAS at an ambulatory surgery center. However, the study did not include either a concurrent or preintervention control so that further studies are needed to assess whether there is an association between implementation of ERAS components and improvements in outcomes. Nevertheless, we provide benchmarking data on postoperative outcomes during the first 3 years of ERAS implementation. Our findings reflect progressive improvement achieved through continuous feedback and education of staff.

Association Between Electronic Patient Symptom Reporting With Alerts and Potentially Avoidable Urgent Care Visits After Ambulatory Cancer Surgery.

Importance: Increasingly complex surgical procedures are being performed in the outpatient setting, increasing the burden on patients and caregivers to manage their postoperative symptoms. Electronic patient-reported symptom tracking may reduce this burden and help patients distinguish between expected symptoms and those requiring intervention. Objective: To determine whether electronic symptom reporting with clinical alerts for 10 days after ambulatory cancer surgery is associated with a reduction in potentially avoidable urgent care visits, defined as a visit not leading to admission. Design, Setting, and Participants: This retrospective cohort study was conducted at the Josie Robertson Surgery Center (JRSC), Memorial Sloan Kettering Cancer Center's ambulatory surgery center with overnight stay capacity from September 20, 2016, to December 31, 2018. Patients undergoing prostatectomy, nephrectomy, mastectomy with or without immediate reconstruction, hysterectomy, or thyroidectomy at the surgery center before (n = 4195) and after (n = 2970) implementation of the Recovery Tracker (RT) electronic postoperative symptom survey were included. Data analyses were conducted from February 1 to November 24, 2020. Exposures: A short electronic survey assessing symptoms daily for 10 days after surgery, administered via the patient portal, with alerts to the clinical team and follow-up for concerning responses. Main Outcomes and Measures: The main outcome was Memorial Sloan Kettering urgent care center visits with and without readmission and any readmission within 30 days after surgery. Nursing workload was measured by patient phone calls, emails, and secure messages as documented in the electronic medical record. Results: A total of 7165 patients were analyzed, including 4195 (median age, 53 [interquartile range (IQR), 44-63] years; 3490 women [83%]) from the pre-RT implementation period and 2970 (median age, 56 [IQR, 46-65] years; 2221 women [75%]) from after full implementation. On multivariable, intent-to-treat analysis by study period, having surgery in the post-RT period was associated with a 22% decrease in the odds of an urgent care center visit without readmission (OR, 0.78; 95% CI, 0.60-1.00; P = .047). Having responded to at least 1 survey was associated with a 42% reduction in the odds of an urgent care center visit without readmission (OR, 0.58; 95% CI, 0.39-0.87; P = .007). There was no change in the risk of admission. Nursing calls increased by a mean of 0.86 (95% CI, 0.75-0.98) calls per patient after RT implementation (P < .001), a 34% increase. Conclusions and Relevance: In this cohort study, electronic symptom reporting with nursing follow-up for clinical alerts was associated with a reduction in potentially avoidable urgent care visits. The low risk and high benefit of this intervention suggest that these systems should be more broadly implemented.

Intraoperative Ketorolac is Associated with Risk of Reoperation After Mastectomy: A Single-Center Examination.

BACKGROUND: Although ketorolac is an effective adjunct for managing pain in the perioperative period, it is associated with a risk of postoperative bleeding. This study retrospectively investigated the association between ketorolac use and both reoperation and postoperative opioid use among mastectomy patients. METHODS: The study identified all women undergoing mastectomy (unilaterally or bilaterally) at our ambulatory surgery cancer center from January 2016 to June 2019. The primary outcome was reoperation for bleeding on postoperative day 0 or 1, and the secondary outcome was postoperative opioid use. The association between ketorolac and outcomes was assessed using multivariable regression models. The covariates were age, body mass index, breast reconstruction, bilateral surgery, peripheral nerve block, and preoperative antiplatelet and/or anticoagulation medication. RESULTS: A cohort of 3469 women were identified. Ketorolac was given to 1549 (45%) of the women, with 922 women (60%) receiving 30 mg and 627 women (40%) receiving 15 mg. The overall reoperation rate for bleeding was 3.1% (1.8% without ketorolac vs 4.8% with ketorolac). In the multivariable analysis, ketorolac was associated with a higher risk of reoperation [odds ratio (OR) 2.43; 95% confidence interval (CI) 1.60-3.70; P < 0.0001]. Ketorolac also was associated with a lower proportion of patients receiving any postoperative narcotic within 24 h (15 mg: OR 0.73; 95% CI 0.57-0.94; P = 0.014 vs 30 mg: OR 0.52; 95% CI 0.42-0.66; P < 0.0001). CONCLUSIONS: Ketorolac use decreased postoperative opioid use, but this benefit was outweighed by the increased risk of bleeding requiring reoperation. This finding led to a change in practice at the authors' center, with ketorolac no longer administered in the perioperative care of the mastectomy patient.

Routine Opioid Prescriptions Are Not Necessary After Breast Excisional Biopsy or Lumpectomy Procedures.

BACKGROUND: Opioid analgesics are overprescribed after surgery. In August 2018, the authors replaced routine discharge opioid prescription with a nonsteroidal anti-inflammatory drug (NSAID) for patients who had a lumpectomy or excisional biopsy (lump/ex). This study compared patient-reported post-discharge pain scores for patients treated before and after the change in routine discharge medication. METHODS: Patients were categorized based on treatment before and after a change in discharge medication as follows: study period 1 (routine opioids), study period 2 (routine NSAID). Pain severity was assessed with an electronic survey on postoperative days (PODs) 1 to 5. Multivariable generalized estimating equations tested the association between pain severity and discharge in the first versus the second study period. RESULTS: Lump/ex was performed for 1606 patients between December 2017 and June 2019. Of these patients, 789 (49%) reported pain scores and were analyzed (328 in study period 1, 461 in study period 2). Opioid prescription at discharge decreased from 96% in period 1 to 14% (95% confidence interval [CI], 11-18%) in period 2. Only 1% of the patients discharged with NSAID were later prescribed an opioid. The maximum reported pain score on any POD for all the patients was severe for 30 patients (3.8%), moderate for 217 patients (28%), mild for 430 patients (54%), and none for 112 patients (14%). The estimated risk for moderate or greater pain on POD 1 was 36% for period 1 and 34% for period 2. The proportion of patients reporting moderate or greater pain was nonsignificantly lower for the patients treated in period 2 (odds ratio [OR], 0.91; 95% CI 0.67-1.22; P = 0.5). CONCLUSIONS: For patients undergoing lump/ex, a clinically meaningful difference in reported post-discharge pain scores can be excluded with a change to routine NSAID at discharge. Patients undergoing lump/ex should not be routinely discharged with opioids.

Standardizing Opioid Prescriptions to Patients After Ambulatory Oncologic Surgery Reduces Overprescription.

BACKGROUND: Overprescribing of opioids after surgery contributes to long-term abuse. Evaluating opioid prescription patterns and patient-reported opioid use offers an evidence-based method to identify potential overprescription. This quality improvement initiative aimed to reduce and standardize opioid prescriptions upon discharge from an ambulatory oncologic surgery center and evaluate the effect of this change on patients' subsequent opioid use and reported pain. METHODS: Between March 2018 and January 2019, consecutive opioid-naïve patients aged ≥ 18 years who underwent robotic or laparoscopic hysterectomy, radical prostatectomy, or partial nephrectomy, or total mastectomy with or without immediate reconstruction were surveyed 7-10 days postoperatively. Data collected in the pre- (n = 551) and post-standardization (n = 480) cohorts included perception of pain relief, opioids prescribed (verified by electronic medical record review) and consumed, and refills received. RESULTS: Pre-standardization, the median opioid prescription at discharge was 20 pills (interquartile range [IQR] 20-28) or 140 oral morphine milligram equivalents (MME) (IQR 100-150). Median opioid consumption was 2 pills (IQR 0-7) or 10 MME (IQR 0-40) among all services. Opioid prescriptions were later standardized to 7, 8, and 10 pills (35, 40, and 75 MME), in the gynecology, urology, and breast services, respectively. The change was not associated with an increase in reported pain. Refill requests increased postintervention across all surgeries from 4.4% to 7.7%, with the largest increase among patients who underwent breast surgery. CONCLUSION: The number of opioid pills given at discharge to patients undergoing ambulatory or short-stay cancer surgery can safely be reduced.

Complex Cancer Surgery in the Outpatient Setting: The Josie Robertson Surgery Center.

Minimally invasive operative techniques and enhanced recovery after surgery (ERAS) protocols have transformed clinical practice and made it possible to perform increasingly complex oncologic procedures in the ambulatory setting, with recovery at home after a single overnight stay. Capitalizing on these changes, Memorial Sloan Kettering Cancer Center's Josie Robertson Surgery Center (JRSC), a freestanding ambulatory surgery facility, was established to provide both outpatient procedures and several surgeries that had previously been performed in the inpatient setting, newly transitioned to this ambulatory extended recovery (AXR) model. However, the JRSC core mission goes beyond rapid recovery, aiming to be an innovation center with a focus on superlative patient experience and engagement, efficiency, and data-driven continuous improvement. Here, we describe the JRSC genesis, design, care model, and outcome tracking and quality improvement efforts to provide an example of successful, patient-centered surgical care for select patients undergoing relatively complex procedures in an ambulatory setting.

Impact of intraoperative remifentanil on postoperative pain and opioid use in thyroid surgery.

BACKGROUND AND OBJECTIVES: Remifentanil infusion is used as an intraoperative anesthetic for thyroidectomy, but has been associated with acute opioid tolerance and hyperalgesia. A national shortage of remifentanil provided an opportunity to study postoperative pain in patients undergoing thyroidectomy. METHODS: Retrospective review of prospectively collected data from an outpatient surgery center. Primary analysis compared patients treated before and after remifentanil shortage. RESULTS: Median postoperative opioid consumption was 20 morphine milligram equivalents (MMEs) among those treated in the high-dose period and 15 MMEs in the low-dose period. Remifentanil/weight received was a significant predictor of requiring a postoperative narcotic (P = .006). Total non-remifentanil narcotics administered were equivalent but patients in the low dose period received higher amounts of intraoperative long-acting narcotics. CONCLUSIONS: Remifentanil infusion for thyroid surgery is associated with higher postoperative pain and postoperative narcotics requirement. While a hyperalgesia state is possible, shifting of longer-acting narcotics from intraoperative to postoperatively is also supported.

Effects of Midazolam on Postoperative Nausea and Vomiting and Discharge Times in Outpatients Undergoing Cancer-Related Surgery.

Midazolam, a short-acting benzodiazepine used for preoperative anxiolysis, may also have pharmacologic properties that could further reduce the incidence of postoperative nausea and vomiting (PONV) in high-risk patients when included in a multimodal antiemetic protocol. However, concerns remain that the sedating properties of midazolam will delay discharge after short outpatient procedures. A retrospective data analysis (N = 4,057) investigated effects of midazolam on postoperative antiemetic administration and length of stay following cancer-related outpatient procedures over 15 months. Following initial univariate analysis, a multivariable model adjusting for Apfel score, surgical service, age, length of surgery, and type of anesthesia was created to test these associations. The multivariable analysis demonstrated that midazolam was associated with reduced need for postoperative antiemetic medications (3.2% lower than no-midazolam group; 95% confidence interval = 0.03%-6.0%, P = .032). Furthermore, the multivariable analysis demonstrated no clinically significant effect on postoperative length of stay (7.9 minutes shorter in midazolam group; 95% confidence interval = -20 to 4.4, P = .2). In patients for whom midazolam is not otherwise indicated, evidence is insufficient to warrant midazolam administration solely to prevent PONV. Randomized trials are needed to provide an accurate estimation of the effect size of midazolam for PONV in these patients.

Suitability of outpatient or ambulatory extended recovery cancer surgeries for obese patients.

STUDY OBJECTIVE: An increasing number of overweight and obese patients are presenting for ambulatory surgical procedures and may be at risk of complications including longer surgeries, longer length of stay (LOS), and possible increase in unanticipated return visits or hospital admissions. DESIGN: Observational study using prospectively-collected data. SETTING: Freestanding and hospital-based ambulatory surgery facilities. PATIENTS AND INTERVENTIONS: 13,957 patients underwent ambulatory cancer surgery procedures at the Josie Robertson Surgery Center (JRSC) since opening in 2016, and 4591 patients eligible for ambulatory surgery at JRSC underwent surgery at the main hospital during the same timeframe. MEASUREMENTS: We assessed whether BMI was associated with increased operative time, post-operative LOS, hospital transfer after surgery, or hospital readmission or urgent care center visits within 30 days. Using multivariable logistic regression, we assessed whether BMI was associated with decision to do surgery at JRSC controlling for age, ASA score and surgical service. MAIN RESULTS: While higher BMI was associated with a higher rate of transfer out of JRSC (p = 0.014), the difference in rate was small (mean risk 0.8% for BMI 25 vs 1.3% for BMI 40, difference in risk 0.52%, 95% CI 0.05%, 1.0%). We found no evidence that higher BMI increased the risk of urgent care visits or readmissions within 30 days or outpatient LOS (p = 0.7 for all). There was a statistically but not clinically significant difference in operative time for outpatient procedures (p = <0.0001), with a mean operative time of 59 vs 63 min for BMI 25 vs 40. Ambulatory extended recovery patients with higher BMI had shorter operative times (p < 0.0001). Patients with higher BMI were not significantly less likely to undergo surgery at JRSC (84% vs 83% vs 82% probability of treatment at JRSC for BMI 25, BMI 40 or BMI 50, respectively, p = 0.089). CONCLUSIONS: Ambulatory cancer surgeries can be performed safely among clinically eligible patients. Patients with BMI up to 50 or more can be treated safely in an ambulatory setting if they otherwise meet eligibility criteria.

Enhanced Recovery Programs in Outpatient Surgery.

Although enhanced recovery pathways were initially implemented in inpatients, their principles are relevant in the ambulatory setting. Opioid minimization and addressing pain and nausea through multimodal analgesia, regional anesthesia, and robust preoperative education programs are integral to the success of ambulatory enhanced recovery programs. Rather than measurements of length of stay as in traditional inpatient programs, the focus of enhanced recovery programs in ambulatory surgery should be on improved quality of recovery, pain management, and early ambulation.

Outcomes and Safety Among Patients With Obstructive Sleep Apnea Undergoing Cancer Surgery Procedures in a Freestanding Ambulatory Surgical Facility.

BACKGROUND: Patients with obstructive sleep apnea (OSA) may be at increased risk for serious perioperative complications. The suitability of ambulatory surgery for patients with OSA remains controversial, and several national guidelines call for more evidence that assesses clinically significant outcomes. In this study, we investigate the association between OSA status (STOP-BANG risk, or previously diagnosed) and short-term outcomes and safety for patients undergoing cancer surgery at a freestanding ambulatory surgery facility. METHODS: We conducted a retrospective analysis of all patients having surgery at the Josie Robertson Surgery Center, a freestanding ambulatory surgery facility of the Memorial Sloan Kettering Cancer Center. Surgeries included more complex ambulatory extended recovery procedures for which patients typically stay overnight, such as mastectomy, thyroidectomy, and minimally invasive hysterectomy, prostatectomy, and nephrectomy, as well as typical outpatient surgeries. Both univariate and multivariable analyses were used to assess the association between OSA risk and transfer to the main hospital, urgent care center visit, and hospital readmission within 30 days postoperatively (primary outcomes) and length of stay and discharge time (secondary outcomes). Multivariable models were adjusted for age, American Society of Anesthesiologists score, robotic surgery, and type of anesthesia (general or monitored anesthesia care) and also adjusted for surgery start time for length of stay and discharge time outcomes. χ tests were used to assess the association between OSA risk and respiratory events and device use. RESULTS: Of the 5721 patients included in the analysis, 526 (9.2%) were diagnosed or at moderate or high risk for OSA. We found no evidence of a difference in length of stay when comparing high-risk or diagnosed patients with OSA to low- or moderate-risk patients whether they underwent outpatient (P = .2) or ambulatory extended recovery procedures (P = .3). Though a greater frequency of postoperative respiratory events were reported in high-risk or diagnosed patients with OSA compared to moderate risk (P = .004), the rate of hospital transfer was not significantly different between the groups (risk difference, 0.78%; 95% CI, -0.43% to 2%; P = .2). On multivariable analysis, there was no evidence of increased rate of urgent care center visits (adjusted risk difference, 1.4%; 95% CI, -0.68% to 3.4%; P = .15) or readmissions within 30 days (adjusted risk difference, 1.2%; 95% CI, -0.40% to 2.8%; P = .077) when comparing high-risk or diagnosed OSA to low- or moderate-risk patients. Based on the upper bounds of the CIs, a clinically relevant increase in transfers, readmissions, and urgent care center visits is unlikely. CONCLUSIONS: Our results contribute to the body of evidence supporting that patients with moderate-risk, high-risk, or diagnosed OSA can safely undergo outpatient and advanced ambulatory oncology surgery without increased health care burden of extended stay or hospital admission and avoiding adverse postoperative outcomes. Our results support the adoption of several national OSA guidelines focusing on preoperative identification of patients with OSA and clinical pathways for perioperative management and postoperative monitoring.

Assessing Rapidity of Recovery After Cancer Surgeries in a Single Overnight Short-Stay Setting.

BACKGROUND: In the short-stay surgery setting, where patients remain in hospital for a single overnight at most, it is unclear as to whether postoperative length of stay is a good surrogate for assessing rapidity of recovery. We hypothesized that length of stay would be a function of time of surgery and would be a poorer marker of recovery than time of discharge. METHODS: A cohort of 891 mastectomy and 538 prostatectomy patients had a planned single overnight stay after surgery at an ambulatory surgical hospital during 2016. The relationship between surgical start time and postoperative length of stay or discharge time was assessed. RESULTS: For both mastectomy and prostatectomy patients, 75% of patients were discharged between 10 AM and 12 noon and the median postoperative length of stay was 20 hours. There was a strong association between time of surgery and calculated length of stay. For mastectomies, having a surgery which begins at 6 PM vs 8 AM results in an estimated decrease of 8.8 hours (95% CI, 8.3-9.3) in postoperative length of stay but only 1.2 hours (95% CI, 0.77-1.6) later time of discharge. For prostatectomies, the estimated difference is a decrease of 6.9 hours (95% CI, 6.4-7.4) for postoperative length of stay and 2.5 hours (95% CI, 2.0-3.0) later discharge time. CONCLUSIONS: Postoperative length of stay is a poor outcome measure in a short-stay setting. When assessing rapidity of recovery for single overnight stay patients, we advocate the use of discharge time with adjustment for surgery start time. The effect of surgery start time on both postoperative length of stay and discharge time should be investigated to ascertain which is best to assess rapidity of recovery in other ambulatory care settings where recovery involves a single overnight stay.

Evaluating Patient-Centered Outcomes in Clinical Trials of Procedural Sedation, Part 2 Safety: Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research Recommendations.

The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research, established by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks, a public-private partnership with the US Food and Drug Administration, convened a second meeting of sedation experts from a variety of clinical specialties and research backgrounds to develop recommendations for procedural sedation research. The previous meeting addressed efficacy and patient- and/or family-centered outcomes. This meeting addressed issues of safety, which was defined as "the avoidance of physical or psychological harm." A literature review identified 133 articles addressing safety measures in procedural sedation clinical trials. After basic reporting of vital signs, the most commonly measured safety parameter was oxygen saturation. Adverse events were inconsistently defined throughout the studies. Only 6 of the 133 studies used a previously validated measure of safety. The meeting identified methodological problems associated with measuring infrequent adverse events. With a consensus discussion, a set of core and supplemental measures were recommended to code for safety in future procedural clinical trials. When adopted, these measures should improve the integration of safety data across studies and facilitate comparisons in systematic reviews and meta-analyses.

Evaluating Patient-Centered Outcomes in Clinical Trials of Procedural Sedation, Part 1 Efficacy: Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research Recommendations.

The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research, established by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks public-private partnership with the US Food and Drug Administration, convened a meeting of sedation experts from a variety of clinical specialties and research backgrounds with the objective of developing recommendations for procedural sedation research. Four core outcome domains were recommended for consideration in sedation clinical trials: (1) safety, (2) efficacy, (3) patient-centered and/or family-centered outcomes, and (4) efficiency. This meeting identified core outcome measures within the efficacy and patient-centered and/or family-centered domains. Safety will be addressed in a subsequent meeting, and efficiency will not be addressed at this time. These measures encompass depth and levels of sedation, proceduralist and patient satisfaction, patient recall, and degree of pain experienced. Consistent use of the recommended outcome measures will facilitate the comprehensive reporting across sedation trials, along with meaningful comparisons among studies and interventions in systematic reviews and meta-analyses.