Postoperative Opioid Prescribing via Rule-Based Guidelines Derived from In-Hospital Consumption: An Assessment of Efficacy Based on Postdischarge Opioid Use.

BACKGROUND: Many institutions have developed operation-specific guidelines for opioid prescribing. These guidelines rarely incorporate in-hospital opioid consumption, which is highly correlated with consumption. We compare outcomes of several patient-centered approaches to prescribing that are derived from in-hospital consumption, including several experimental, rule-based prescribing guidelines and our current institutional guideline. STUDY DESIGN: We performed a retrospective, cohort study of all adults undergoing surgery at a single-academic medical center. Several rule-based guidelines, derived from in-hospital consumption (quantity of opioids consumed within 24 hours of discharge), were used to specify the theoretical quantity of opioid prescribed on discharge. The efficacy of the experimental guidelines was compared with 3 references: an approximation of our institution's tailored prescribing guideline; prescribing all patients the typical quantity of opioids consumed for patients undergoing the same operation; and a representative rule-based, tiered framework. For each scenario, we calculated the penalized residual sum of squares (reflecting the composite deviation from actual patient consumption, with 15% penalty for overprescribing) and the proportion of opioids consumed relative to prescribed. RESULTS: A total of 1,048 patients met inclusion criteria. Mean (SD) and median (interquartile range [IQR]) quantity of opioids consumed within 24 hours of discharge were 11.2 (26.9) morphine milligram equivalents and 0 (0 to 15) morphine milligram equivalents. Median (IQR) postdischarge consumption was 16 (0 to 150) morphine milligram equivalents. Our institutional guideline and the previously validated rule-based guideline outperform alternate approaches, with median (IQR) differences in prescribed vs consumed opioids of 0 (-60 to 27.25) and 37.5 (-37.5 to 37.5), respectively, corresponding to penalized residual sum of squares of 39,817,602 and 38,336,895, respectively. CONCLUSIONS: Rather than relying on fixed quantities for defined operations, rule-based guidelines offer a simple yet effective method for tailoring opioid prescribing to in-hospital consumption.

An Institutional Curriculum for Opioid Prescribing Education: Outcomes From 2017 to 2022.

INTRODUCTION: Prescription opioids, including those prescribed after surgery, have greatly contributed to the US opioid epidemic. Educating opioid prescribers is a crucial component of ensuring the safe use of opioids among surgical patients. METHODS: An annual opioid prescribing education curriculum was implemented among new surgical prescribers at our institution between 2017 and 2022. The curriculum includes a single 75-min session which is comprised of several components: pain medications (dosing, indications, and contraindications); patients at high risk for uncontrolled pain and/or opioid misuse or abuse; patient monitoring and care plans; and state and federal regulations. Participants were asked to complete an opioid knowledge assessment before and after the didactic session. RESULTS: Presession and postsession assessments were completed by 197 (89.6%) prescribers. Across the five studied years, the median presession score was 54.5%. This increased to 63.6% after completion of the curriculum, representing a median relative knowledge increase of 18.2%. The median relative improvement was greatest for preinterns and interns (18.2% for both groups); smaller improvements were observed for postgraduate year 2-5 residents (9.1%) and advanced practice providers (9.1%). On a scale of 1 to 10 (with 5 being comfortable), median (interquartile range) self-reported comfort in prescribing opioids increased from 3 (2-5) before education to 5 (4-6) after education (P < 0.001). CONCLUSIONS: Each year, the curriculum substantially improved provider knowledge of and comfort in opioid prescribing. Despite increased national awareness of the opioid epidemic and increasing institutional initiatives to improve opioid prescribing practices, there was a sustained knowledge and comfort gap among new surgical prescribers. The observed effects of our opioid education curriculum highlight the value of a simple and efficient educational initiative.

Retention of Knowledge After Opioid Education in Surgical Interns.

BACKGROUND: In many academic centers, opioid prescribing is managed primarily by residents with little or no formal opioid education. The present study evaluates intern knowledge and comfort with appropriate opioid prescribing 7 months after an organized opioid education effort. MATERIALS AND METHODS: A repeat knowledge and attitude survey was sent to surgical interns who had completed an initial opioid education training session 7 months before the study. Results were compared to post-education assessment results in the same cohort. SETTING: 16 general surgery and podiatric surgery interns at a single academic medical center. RESULTS: The mean percentage of correct answers on follow-up was 67.6% identical to the average post-session score of 67.6%. Interns reported comfort with opioid prescribing increased to a mean score of 5.9 (out of 10) on follow-up compared to post-session score of 5.19. CONCLUSIONS: Surgical interns have significant gaps in knowledge for optimal prescribing and management of opioid prescriptions. Targeted education demonstrates significant and lasting improvement in opioid assessment scores, but there remains room for improvement.

Machine learning nonresponse adjustment of patient-reported opioid consumption data to enable consumption-informed postoperative opioid prescribing guidelines.

Background: Post-discharge opioid consumption is a crucial patient-reported outcome informing opioid prescribing guidelines, but its collection is resource-intensive and vulnerable to inaccuracy due to nonresponse bias. Methods: We developed a post-discharge text message-to-web survey system for efficient collection of patient-reported pain outcomes. We prospectively recruited surgical patients at Beth Israel Deaconess Medical Center in Boston, Massachusetts from March 2019 through October 2020, sending an SMS link to a secure web survey to quantify opioids consumed after discharge from hospitalization. Patient factors extracted from the electronic health record were tested for nonresponse bias and observable confounding. Following targeted learning-based nonresponse adjustment, procedure-specific opioid consumption quantiles (medians and 75th percentiles) were estimated and compared to a previous telephone-based reference survey. Results: 6553 patients were included. Opioid consumption was measured in 44% of patients (2868), including 21% (1342) through survey response. Characteristics associated with inability to measure opioid consumption included age, tobacco use, and prescribed opioid dose. Among the 10 most common procedures, median consumption was only 36% of the median prescription size; 64% of prescribed opioids were not consumed. Among those procedures, nonresponse adjustment corrected the median opioid consumption by an average of 37% (IQR: 7, 65%) compared to unadjusted estimates, and corrected the 75th percentile by an average of 5% (IQR: 0, 12%). This brought median estimates for 5/10 procedures closer to telephone survey-based consumption estimates, and 75th percentile estimates for 2/10 procedures closer to telephone survey-based estimates. Conclusions: SMS-recruited online surveying can generate reliable opioid consumption estimates after nonresponse adjustment using patient factors recorded in the electronic health record, protecting patients from the risk of inaccurate prescription guidelines.

Who doesn't fit? A multi-institutional study using machine learning to uncover the limits of opioid prescribing guidelines.

BACKGROUND: Many U.S. institutions have adopted postsurgical opioid-prescribing guidelines to standardize prescribing practices, and yet there is inherent variability in patients' opioid consumption after surgery. The utility of these guidelines is limited by the fact that some patients' needs will inevitably exceed them, and yet there are no evidence-based tools to help providers identify these patients. In this study we aimed to maximize the value of these guidelines by training machine learning models to predict patients whose needs will be met by these smaller recommended prescriptions, and patients who may require an additional degree of personalization. The aim of the present study was to develop predictive models for determining whether a surgical patient's postdischarge opioid requirement will fall above or below common opioid prescribing guidelines. METHODS: We conducted a retrospective cohort study of surgical patients at one institution from 2017 to 2018. Patients were called after discharge to collect opioid consumption data. Machine learning models were used to identify outlier opioid consumers (ie, exceeding our institutional prescribing guidelines) using diagnosis codes, medical history, in-hospital opioid use, and perioperative factors as predictors. External validation was performed on opioid consumption data collected at a second institution from 2020 to 2021, and sensitivity analysis was performed using a third institution's prescribing guidelines. RESULTS: The development and external validation cohorts included 1,867 and 498 patients, respectively. Age, body mass index, tobacco use, preoperative opioid exposure, and in-hospital opioid consumption were the strongest predictors of postdischarge consumption. A lasso regression model exhibited an area under the receiver operating characteristic curve of 0.74 (95% confidence interval 0.67-0.81) in predicting postdischarge opioid consumption. External validation of a limited lasso model yielded an area under the receiver operating characteristic curve of 0.67 (0.60-0.74). Performance was preserved when evaluated on another institution's guidelines (area under the receiver operating characteristic curve 0.76 [0.72-0.80]). CONCLUSION: Patient characteristics reliably predict postdischarge opioid consumption in relation to prescribing guidelines for both opioid-naive and exposed populations. This model may be used to help providers confidently follow prescribing guidelines for patients with typical opioid responsiveness and correctly pursue more personalized prescribing for others.

Evaluation of U.S. state opioid prescribing restrictions using patient opioid consumption patterns from a single, urban, academic institution.

Background: Since 2017, states, insurers, and pharmacies have placed blanket limits on the duration and quantity of opioid prescriptions. In many states, overlapping duration and daily dose limits yield maximum prescription limits of 150-350 morphine milligram equivalents (MMEs). There is limited knowledge of how these restrictions compare with actual patient opioid consumption; while changes in prescription patterns and opioid misuse rates have been studied, these are, at best, weak proxies for actual pain control consumption. We sought to determine how patients undergoing surgery would be affected by opioid prescribing restrictions using actual patient opioid consumption data. Methods: We constructed a prospective database of post-discharge opioid consumption: patients undergoing surgery at one institution were called after discharge to collect opioid consumption data. Patients whose opioid consumption exceeded 150 and 350 MME were identified. Results: Two thousand nine hundred and seventy-one patients undergoing 54 common surgical procedures were included in our study. Twenty-one percent of patients consumed more than the 150 MME limit. Only 7% of patients consumed above the 350 MME limit. Typical (non-outlier) opioid consumption, defined as less than the 75th percentile of consumption for any given procedure, exceeded the 150 MME and 350 MME limits for 41 and 7% of procedures, respectively. Orthopedic, spinal/neurosurgical, and complex abdominal procedures most commonly exceeded these limits. Conclusions: While most patients undergoing surgery are unaffected by recent blanket prescribing limits, those undergoing a specific subset of procedures are likely to require more opioids than the restrictions permit; providers should be aware that these patients may require a refill to adequately control post-surgical pain. Real consumption data should be used to guide these restrictions and inform future interventions so the risk of worsened pain control (and its troublesome effects on opioid misuse) is minimized. Procedure-specific prescribing limits may be one approach to prevent misuse, while also optimizing post-operative pain control.

Comparing Clinician Consensus Recommendations to Patient-reported Opioid Use Across Multiple Hospital Systems.

OBJECTIVE: We compare consensus recommendations for 5 surgical procedures to prospectively collected patient consumption data. To address local variation, we combined data from multiple hospitals across the country. SUMMARY OF BACKGROUND DATA: One approach to address the opioid epidemic has been to create prescribing consensus reports for common surgical procedures. However, it is unclear how these guidelines compare to patient-reported data from multiple hospital systems. METHODS: Prospective observational studies of surgery patients were completed between 3/2017 and 12/2018. Data were collected utilizing post-discharge surveys and chart reviews from 5 hospitals (representing 3 hospital systems) in 5 states across the USA. Prescribing recommendations for 5 common surgical procedures identified in 2 recent consensus reports were compared to the prospectively collected aggregated data. Surgeries included: laparoscopic cholecystectomy, open inguinal hernia repair, laparoscopic inguinal hernia repair, partial mastectomy without sentinel lymph node biopsy, and partial mastectomy with sentinel lymph node biopsy. RESULTS: Eight hundred forty-seven opioid-naïve patients who underwent 1 of the 5 studied procedures reported counts of unused opioid pills after discharge. Forty-one percent did not take any opioid medications, and across all surgeries, the median consumption was 3 5 mg oxycodone pills or less. Generally, consensus reports recommended opioid quantities that were greater than the 75th percentile of consumption, and for 2 procedures, recommendations exceeded the 90th percentile of consumption. CONCLUSIONS: Although consensus recommendations were an important first step to address opioid prescribing, our data suggests that following these recommendations would result in 47%-56% of pills prescribed remaining unused. Future multi-institutional efforts should be directed toward refining and personalizing prescribing recommendations.

Telemedicine in Primary Care During the COVID-19 Pandemic: Provider and Patient Satisfaction Examined.

Introduction: During the COVID-19 pandemic telemedicine was rapidly expanded and incorporated into day-to-day practice by primary care providers to allow continued access to care for patients during this time. The quick adoption of telemedicine occurred out of necessity for social distancing, and evidence-based approaches are needed to determine the future utility of this approach to delivering care. The objective of this study was to identify factors associated with both provider and patient satisfaction with telemedicine visits in a primary care setting during the COVID-19 pandemic. Materials and Methods: This survey-based study was conducted in 2020. Surveys were distributed electronically by e-mail to providers and patients. Participants: Surveys related to satisfaction levels with telemedicine were distributed to 73 primary care providers and 6,626 patients. Main Outcomes and Measures: The primary measures of this study were satisfaction level with telemedicine in primary care. Results: Studies were completed by 23 primary care providers and 1,692 patients. Most patient participants were female (70.8%), white (89.7%), non-Hispanic or non-Latino (96.6%), and Massachusetts residents (96.9%). Variables that were found to be significantly associated with higher levels of satisfaction with telemedicine visits included: travel time saved >30 min (odds ratio [OR] 1.8), having an easy visit connection (OR = 3.2), use of Zoom© video visit over telephone only (OR = 2.8), and identifying as female (OR 1.8). Conclusions and Relevance: Patients and providers reported high levels of satisfaction with telemedicine visits in a primary care setting. Providers felt that telemedicine visits usually take the same amount or less time than in-person visits. Both providers and patients reported a desire to see telemedicine visits continued after the pandemic. Patients who saved more than 30 min of travel time found it easy to connect or those who were female were more likely to be satisfied with telemedicine visits, while those that had telephone visits were less likely to be satisfied than those that had Zoom© visits.

Patient and Provider Satisfaction with Telemedicine in a Comprehensive Weight Management Program.

Introduction: Telemedicine use became widespread at our weight management center in 2020 due to the coronavirus disease 2019 (COVID-19) pandemic. Objectives: The objective of this study was to determine patient and provider satisfaction with telemedicine visits at a community-based hospital in the United States. Methods: Patients and providers were electronically surveyed at the end of 2020 regarding telemedicine visit experiences. These visits took place throughout the majority of 2020 during the COVID-19 pandemic. Results: A total of 85.7% (6) of providers reported spending the same or less time on telemedicine visits compared with in-person visits. All providers were either somewhat or very satisfied with the interpersonal connections made in telemedicine visits. All providers wished to see telemedicine visits continued in the future. A total of 355 patients responded. Over 90% of participants reported feeling comfortable speaking to their provider about personal issues through telemedicine. Around 73.2% of patients were very satisfied with their telemedicine visit. Around 69.8% of patients report that they would like to use either primarily telemedicine visits or a combination of telemedicine and in-person visits when it is safe to return to in-person care. Conclusions: Patients and providers exhibited high levels of satisfaction with telemedicine use in a weight management center. They both wish to see these visit types offered in the future. Patients who saved more than 30 min of time traveling with a telemedicine visit were significantly more likely to show high levels of satisfaction. Patients who found it easier to connect with the virtual platforms also were significantly more likely to have higher satisfaction levels.

A Mixed-chimerism Protocol Utilizing Thymoglobulin and Belatacept Did Not Induce Lung Allograft Tolerance, Despite Previous Success in Renal Allotransplantation.

BACKGROUND: In kidney transplantation, long-term allograft acceptance in cynomolgus macaques was achieved using a mixed-chimerism protocol based on the clinically available reagents, rabbit anti-thymocyte globulin (ATG), and belatacept. Here, we have tested the same protocol in cynomolgus macaques transplanted with fully allogeneic lung grafts. METHODS: Five cynomolgus macaques underwent left orthotopic lung transplantation. Initial immunosuppression included equine ATG and anti-IL6RmAb induction, followed by triple-drug immunosuppression for 4 mo. Post-transplant, a nonmyeloablative conditioning regimen was applied, including total body and thymic irradiation. Rabbit ATG, belatacept, anti-IL6RmAb, and donor bone marrow transplantation (DBMT) were given, in addition to a 28-d course of cyclosporine. All immunosuppressant drugs were stopped on day 29 after DBMT. RESULTS: One monkey rejected its lung before DBMT due to AMR, after developing donor-specific antibodies. Two monkeys developed fatal post-transplant lymphoproliferative disorder, and both monkeys had signs of cellular rejection in their allografts upon autopsy. The remaining 2 monkeys showed severe cellular rejection on days 42 and 70 post-DBMT. Cytokine analysis suggested higher levels of pro-inflammatory markers in the lung transplant cohort, as compared to kidney recipients. CONCLUSION: Although the clinically applicable protocol showed success in kidney transplantation, the study did not show long-term survival in a lung transplant model, highlighting the organ-specific differences in tolerance induction.

A Comparison Between In-Person and Virtual Fellowship Interviews During the COVID-19 Pandemic.

IMPORTANCE: Traditional in-person fellowship interviews require great time and financial commitments. Here, we studied the response of program directors (PDs) and applicants to virtual interviews. Virtual interviews could decrease both financial and time commitments. OBJECTIVE: To determine if most applicants and PDs believed that virtual interviews should be used more widely in the future. DESIGN: After the 2020 cardiothoracic fellowship match, an e-mail survey was sent to 66 program directors and 107 applicants using the Qualtrics platform. SETTING: During the 2020 cardiothoracic fellowship interview cycle, the COVID-19 pandemic shut down travel for in-person interviews. This forced a transition to virtual interviews. PARTICIPANTS: Of 107 applicants emailed, 46 (44%) participated with a completion rate of 87%. sixty-six PDs were contacted and of those, 36 (55%) participated with a 92% survey completion rate. EXPOSURE: All survey participants were participants in the 2020 cardiothoracic match. MAIN OUTCOME(S) AND MEASURE(S): (1) The percent of participants who agree that virtual interviews should be continued in the future and the percent of participants who agree that virtual interviews could be replacements for in person interviews. (2) Were virtual interviews perceived to have a negative impact on one's ultimate match? (3) What is the current cost of an in-person interview in travel and lodging for an applicant? RESULTS: Fourty-six applicants (44% participation rate) and 36 PDs (55% participation rate) participated in the survey. Seventy-nine percent of program directors and 55% of applicants either agreed or strongly agreed that virtual interviews should be offered in the future. However, just 15% of PDs and 20% of applicants either agreed or strongly agreed that virtual interviews should be offered without the option of an in-person interview. Twenty-five percent of PDs and applicants agreed or strongly agreed that virtual interviews negatively impacted their chance of matching one of their top applicants/programs. The median cost of an in-person interview was $600 (interquatile range 500-725). CONCLUSIONS AND RELEVANCE: Most applicants and PDs agree that virtual interviews should be offered in the future. Twenty-five percent of participants reported that they believed virtual interviews negatively impacted their match. Given the overall acceptance of virtual interviews and the cost of in-person interviews, virtual interviews could be useful to incorporate into future interview seasons.

A retrospective cohort study of endoscopic therapy and esophagectomy for stage 1 esophageal cancer: less is more.

BACKGROUND AND AIMS: Current guidelines recommend consideration of endoscopic therapy (ET) when treating select stage I esophageal cancers. The proportion of esophageal cancers treated with ET compared with esophagectomy has increased over time. Overall and cancer-specific survival have not been shown to be superior with ET in prior population-based studies. We thus evaluated cancer-specific survival comparing patients treated with ET and esophagectomy. METHODS: We performed a retrospective cohort study using the Surveillance, Epidemiology, and End Results database from 2004 to 2015 of patients with node-negative, superficial (T1a/T1b), esophageal cancer treated with ET or esophagectomy. Competing-risks models were used to compare cancer-specific survival. Cox proportional hazards models were used to assess overall survival. Subgroup analysis was performed comparing time periods 2004 to 2009 and 2010 to 2015. RESULTS: Of 2133 included individuals, 772 (36.2%) underwent ET and 1361 (63.8%) underwent esophagectomy. Unadjusted 5-year survival for cancer-specific death was 87.7% (95% confidence interval [CI], 84.2-90.5) for ET and 82.4% (95% CI, 80.0- 84.5) for esophagectomy (P = .002). Within the adjusted competing-risk model, cancer-specific survival was superior in patients treated with ET compared with esophagectomy (subdistribution hazard ratio [SHR], 1.92; 95% CI, 1.35-2.74; P < .001). From 2004 to 2009, the SHR for esophagectomy was 1.68 (95% CI, 1.07-2.66; P = .024); whereas from 2010 to 2015, the SHR for esophagectomy was 2.02 (95% CI, 1.08-3.76; P = .027). CONCLUSIONS: ET was associated with improved cancer-specific survival compared with esophagectomy in stage I esophageal cancer. This advantage was more pronounced for patients treated after 2009, potentially because of increasing clinician expertise in performing ET and patient selection.

Opioid Consumption After Gender-Affirming Mastectomy and Two Other Breast Surgeries.

BACKGROUND: There are few studies that evaluate patient-reported opioid consumption after discharge from surgery. In addition, there has been a call for "special care in prescribing opioids" for lesbian, gay, bisexual, transgender, questioning patients. Here, we evaluate if patients undergoing gender-affirming mastectomy (GAM) require different amounts of opioids for pain management after discharge compared alongside two surgeries with similar surgical exposure. MATERIALS AND METHODS: From October 2017 to July 2018, patients undergoing oncologic mastectomy without reconstruction, mammoplasty reduction, or gender-affirming mastectomy at a single institution were enrolled in a phone survey study to quantify opioids consumed after discharge from surgery. Patient information was captured from the medical record. A total of 170 patients were called between 14 and 30 d after discharge and were asked to count unused pills from their opioid prescription. RESULTS: A total of 99 patients participated and provided pill counts. There were differences between prescribed and consumed opioids within each surgery. Patients who underwent oncologic mastectomy were prescribed and consumed the lowest amounts of opioids. There were significantly more opioids prescribed to patients with GAM than mammoplasty reduction, but consumption was not statistically different. Patients with oncologic mastectomy, mammoplasty reduction, and GAM consumed a median of 0, 10, and 15 five mg oxycodone equivalent tablets, respectively. CONCLUSIONS: Despite similar approaches, surgeries had different opioid prescribing and use profiles. Generally, all patients were overprescribed opioids. Overprescribing may be especially problematic in patients with known higher risk of misuse and substance abuse. Granular data on patient consumption, demographics, and preoperative risk factors for opioid misuse may improve prescribing practices.

Implementing and Evaluating a Multihospital Standardized Opioid Curriculum for Surgical Providers.

OBJECTIVE: (1) To identify gaps in providers knowledge on opioid medication and dosing, patient-specific characteristics that require alterations in dosing, and patient monitoring and treatment adjustments. (2) To evaluate an educational intervention aimed at minimizing these deficits. DESIGN: Observational prospective study. Providers took an anonymous paired pre-and posteducation knowledge assessment before and after participating in a 75-minute educational session. Results before and after the educational session were compared. SETTING: Surgical providers included nurse practitioners, physician assistants, preinterns, and general surgery residents across 4 quaternary care hospitals in Boston. Participants There were 194 participants and 174 completed both pre- and posteducation knowledge assessments. RESULTS: Average scores on the educational assessment increased from 59% before the course to 68% after the session. Posteducation, providers reported increased comfort in prescribing and 95% stated that the curriculum would impact their practice. CONCLUSIONS: Surgical providers at multiple hospitals have significant gaps in knowledge for optimal prescribing and management of opioid prescriptions. A 75-minute opioid education session increased prescriber knowledge as well as comfort in prescribing. This multicenter study demonstrates how an educational initiative can be implemented broadly and result in decreased knowledge gaps.

Maintaining T cell tolerance of alloantigens: Lessons from animal studies.

Achieving host immune tolerance of allogeneic transplants represents the ultimate challenge in clinical transplantation. It has become clear that different cells and mechanisms participate in acquisition versus maintenance of allograft tolerance. Indeed, manipulations which prevent tolerance induction often fail to abrogate tolerance once it has been established. Hence, elucidation of the immunological mechanisms underlying maintenance of T cell tolerance to alloantigens is essential for the development of novel interventions that preserve a robust and long lasting state of allograft tolerance that relies on T cell deletion in addition to intra-graft suppression of inflammatory immune responses. In this review, we discuss some essential elements of the mechanisms involved in the maintenance of naturally occurring or experimentally induced allograft tolerance, including the newly described role of antigen cross-dressing mediated by extracellular vesicles.

Airway pressure release ventilation and respiratory failure during pregnancy. A report of three cases.

BACKGROUND: Acute respiratory distress syndrome is a rare complication during pregnancy but remains dificult to manage, with a high incidence of maternal mortality. CASES: We present 3 cases of respiratory failure and severe pulmonary disease managed with airway pressure release ventilation, among other ventilatory modes, with improved ventilation. CONCLUSION: Airway pressure release ventilation may be an important option as a ventilatory mode for management of maternal respiratory failure during pregnancy.