Long-term safety of intraluminal spring-mediated bowel lengthening.

PURPOSE: The purpose of the study is to examine the long-term safety of an endoluminal bowel lengthening device prior to its use in the first human trial. In addition, device performance and natural passage will be evaluated. METHODS: Endoluminal lengthening springs were surgically placed into the jejunum of Yucatan minipigs using the Eclipse XL1 device. A matching internal control segment of jejunum was marked at the time of operation. Weekly weights and fluoroscopic studies were obtained to evaluate spring deployment and position until devices passed. Animals were euthanized at 28, 60, 90, and 180 days. At necropsy, length measurements were recorded, and histopathologic analysis was performed. RESULTS: There were no bowel obstructions or overt perforations attributable to the device. All surviving animals gained weight and were clinically thriving. All devices passed out of the rectum by 180 days. Bowel lengthening was seen in all experimental segments, and minimal fibrosis was observed by 180 days. CONCLUSION: Jejunal lengthening persisted after device had passed through the intestinal tract after 180 days. Early histopathologic changes of the jejunum during distraction enterogenesis normalized over time.

Hospital Variation in Surgical Technique for Repair of Uncomplicated Gastroschisis.

Practices in surgical repair of uncomplicated gastroschisis are varied. Data regarding hospital volume, surgical technique, clinical outcomes, and costs remain limited. Neonatal patients with uncomplicated gastroschisis were identified using the 2015-2019 National Readmissions Database. Hospital volume tertiles were determined, and sutureless or fascial repair techniques were enumerated. High volume centers (HVC) comprised the top tertile. Hospital-level variability in surgical technique was determined. Adjusted multivariable analysis was performed to compare clinical outcomes and costs among HVC and lower-volume centers and among repair techniques. Of an estimated 2903 hospitalizations meeting inclusion criteria, 23.5% occurred at HVC. There was 42.4% variation among sutureless and fascial repair techniques across all hospitals. Among HVC and lower-volume centers, there were no significant differences in rates of 30-day readmission or complication; however, HVC were associated with greater cost and length of stay. Those with codes for fascial repair technique experienced greater lengths of stay, costs, and rates of complication. Codes for surgical repair technique for uncomplicated gastroschisis vary widely, while outcomes are equivalent across strata of hospital volume. Those with codes for sutureless technique were associated with favorable clinical outcomes, irrespective of hospital volume. Guidelines for management of uncomplicated gastroschisis should account for hospital volume, variation in technique, outcomes, and resource utilization.

Unintended Perioperative Hypothermia and Surgical Site Infection in Children.

INTRODUCTION: Unintended perioperative hypothermia is associated with surgical site infection (SSI) in adults, prompting exhaustive efforts to maintain perioperative normothermia. Although these efforts are also made for pediatric patients, the association between hypothermia and SSI has not been demonstrated in children. We sought to determine whether perioperative hypothermia and other risk factors and clinical outcomes are associated with SSI in the pediatric population. MATERIALS AND METHODS: This case-control study took place from January 2014 through December 2016 and included patients at a National Surgical Quality Improvement Program-participant academic children's hospital. All surgical patients were included in this retrospective analysis. SSI rates were determined. A univariate analysis was performed to determine clinical factors associated with SSI. A multivariate regression analysis was then performed to determine the predictive effect of minimum perioperative temperature for SSI. RESULTS: This study included 3541 patients, of which 92 (2.6%) developed SSI. A univariate analysis showed associations among SSI and higher perioperative temperatures, surgical specialty of otolaryngology and general surgery, and wound classification (American Society of Anesthesiologists [ASA] classification III and IV). A multivariate analysis determined the odds of SSI increased by a factor of 1.6 for every 1°C increase in minimum perioperative temperature. CONCLUSIONS: Unintended perioperative hypothermia in our pediatric patients was inversely associated with SSI. This finding suggests that pediatric SSI prevention may not require the efforts made for adult patients to maintain normothermia.

Association of research timing with surgery resident perceptions of operative autonomy and satisfaction: A multi-institutional study.

BACKGROUND: General surgery residents commonly engage in research years after the second (Post-postgraduate year 2 [PostPGY2]) or third (PostPGY3) clinical training year. The impact of dedicated research training timing on training experience is unknown. Our aim was to examine the progression of residents' perceived meaningful operative autonomy and evaluate career satisfaction, in relation to research timing. METHODS: Categorical surgery residents with 2-year research requirements were surveyed regarding perceived autonomy for laparoscopic appendectomy, laparoscopic cholecystectomy, and right hemicolectomy and satisfaction with the impact of dedicated research training on professional development. Meaningful operative autonomy was defined as Zwisch scores ≥3 (passive help or supervision only). RESULTS: Residents from 17 programs participated (n = 233, 30.6%); 48% were PostPGY2. PostPGY3 residents were more likely to perceive meaningful operative autonomy when starting dedicated research training (laparoscopic appendectomy: 98% vs 74%, P < .001; laparoscopic cholecystectomy: 87% vs 48%, P < .001; right hemicolectomy: 27% vs 3%, P < .001). Meaningful operative autonomy declined during dedicated research training but was still higher for PostPGY3 residents for laparoscopic appendectomy (84% vs 42%, P < .001) and laparoscopic cholecystectomy (68% vs 30%, P < .001). By PGY4, PostPGY2 residents reported rates of meaningful operative autonomy comparable to PostPGY3 through training completion. A higher proportion of PostPGY3 residents reported dedicated research training satisfaction (90% vs 78%, P = .01). Training at PostPGY3 programs (odds ratio, 3.06, 95% confidence interval, 1.38-6.80) and postresearch training stage (compared with preresearch residents, odds ratio, 3.25, 95% confidence interval, 1.06-10.0) were independently associated with satisfaction. CONCLUSION: Significant differences existed in the progression of perceived operative autonomy and dedicated research training satisfaction between PostPGY2 and PostPGY3 residents. These results could help surgical educators make individualized decisions regarding research timing to promote surgical skill acquisition and resident well-being.

Persistence of Gender Bias Over Four Decades of Surgical Training.

OBJECTIVE: Female surgeons face gender-specific obstacles during residency training, yet longitudinal data on gender bias experienced by female surgery residents are lacking. We aimed to investigate the evolution of gender bias, identify obstacles experienced by female general surgery residents, and discuss approaches to supporting female surgeons during residency training. METHODS: Between August 2019 and January 2021, we conducted a retrospective cohort study using structured telephone interviews of female graduates of the UCLA General Surgery Residency training program. Responses of early graduates (1981-2009) were compared with those of recent graduates (2010-2020). Quantitative data were compared with Fisher's exact tests and Chi-squared tests. Interview responses were reviewed to catalog gender bias, obstacles experienced by female surgeons, and advice offered to training programs to address women's concerns. RESULTS: Of 61 female surgery residency graduates, 37 (61%) participated. Compared to early graduates (N = 20), recent graduates (N = 17) were significantly more likely to pursue fellowship training (100% vs. 65%, p < 0.01) and have children before or during residency (65% vs. 25%, p = 0.02). A substantial proportion in each cohort experienced some form of gender bias (71% vs. 85%, p = 0.43). Compared to early graduates, recent graduates were significantly less likely to report experiencing explicit gender bias (12% vs. 50%, p = 0.02) but equally likely to report implicit gender bias (71% vs. 55%, p = 0.50). Female graduates across the decades advocated for specific measures to champion work-life balance in residency (51%), strengthen female mentorship (49%), increase childcare support (41%), and promote women into leadership positions (32%). CONCLUSIONS: While having children during residency has become more common and accepted over the decades, female surgery residents continue to experience implicit gender bias in the workplace. Female surgeons advocate for targeted interventions to establish systems for parental leave, address gender bias, and strengthen female mentorship.

Paint and wait management of giant omphaloceles.

Management of the very large defect or those in patients with severe comorbidities has evolved to the use of methods that result in escharification and eventual skin coverage over the viscera. This treatment strategy employs principles that were described in the early 20th century. This review will describe the history, principles, methods, and outcomes from the so called 'paint and wait' management of omphalocele.

Use of Entrustable Professional Activities in the Assessment of Surgical Resident Competency.

Importance: Competency-based assessments of surgical resident performance require metrics of entrustable autonomy. Objectives: To designate entrustable professional activities (EPAs) in global performance and in specific operations, and to identify differences in perceived capability, autonomy, and expectations between surgical faculty and residents. Design, Setting, and Participants: This survey study was conducted from August 9, 2016, through August 24, 2016, in the Department of Surgery at the UCLA David Geffen School of Medicine. The survey instrument consisted of 5-point Likert scales for assessing perceptions of entrustability for 5 global and 5 operative EPAs. Faculty members were surveyed regarding resident capabilities and expected capabilities by postgraduate year. Residents were surveyed regarding their own capabilities, actual autonomy entrusted in the last EPA performed, and expected capabilities. Main Outcomes and Measures: Differences in mean ratings were assessed across 7 comparison domains. Results: Among 78 total faculty members, 31 (40%) participated in the survey. Among 49 residents, 39 (80%) participated in the survey. Residents generally rated their global EPA performance higher than the faculty did (mean, 3.7 vs 2.8; P < .01), but operative EPA performance ratings were equivalent (mean, 2.7 vs 2.4; P < .12). Faculty members perceived senior residents as underperforming expectations in operative EPAs. Most faculty members (80%) expected residents not to be independently capable of performing complex operations by graduation. Faculty members perceived residents in postgraduate years 4 and 5 to have greater operative capability than the level of autonomy entrusted to those residents (95% CI, 3.3-3.5 vs 1.9-2.2). Conclusions and Relevance: Global and operative EPAs are practical for developing competency-based curricula. Graduated autonomy should be granted to improve the operative experience for residents.

Web-Based Video Assessments of Operative Performance for Remote Telementoring.

INTRODUCTION: Performance-based feedback is critical to surgical skills acquisition. Barriers of geography and time limit trainees' access to expert mentorship. In this study, we hypothesized that telementoring using an asynchronous, web-based video interface would allow trainees to receive systematic feedback from expert mentors despite these barriers. MATERIALS AND METHODS: Between October 2014 and October 2016, 18 surgeons in Brazil, Dominican Republic, Haiti, and Paraguay underwent in-person training in Lichtenstein for hernioplasty or laparoscopic total extraperitoneal inguinal hernia repair. After initial training, surgeons submitted 6- to 12-month interval operative videos for expert review. Expert surgeons reviewed each video using the Surgus web platform with performance metrics adapted from the Operative Performance Rating Scale (OPRS). The time required to perform video review, number of freeform comments, mean OPRS scores, and variance of OPRS scores among telementors was assessed. RESULTS: A total of 18 surgeons submitted 20 operative videos, and three expert surgeons reviewed each video using the Surgus platform. The median time to perform video review was 20 minutes. Median number of freeform verbal comments was eight. Mean OPRS overall performance scores were 3.9 ± 0.9 (scale of five). Mean variance in scoring among telementors for overall performance was 0.25 (maximum 5.29), suggesting a high degree of concordance. CONCLUSIONS: Video-based assessments had a high degree of concordance among expert raters. Asynchronous performance reviews by telementors offer opportunities for longitudinal feedback that overcome geographical, material, and temporal disparities. This platform offers a means of sharing expertise in surgical training, continuing education, credentialing, and global health.

Centralized, capacity-building training of Lichtenstein hernioplasty in Brazil.

BACKGROUND: In Brazil, access to healthcare varies widely by community. Options for repair of surgically correctable conditions, such as inguinal hernias, are limited. A training program was instituted to expand access to Lichtenstein hernioplasty. METHODS: Between September, 2014 and September, 2015, 3 orders of training series took place in São Paulo, Brazil. Participating surgeons received training and assessments from expert trainers using the Operative Performance Rating Scale (OPRS). Those who completed training successfully were invited to become trainers. OPRS scores were compared between training series. Outcomes were documented up to 6 months post-training. RESULTS: The 3 orders of training series resulted in 45 surgeons trained and 213 hernias repaired. Eleven trainees subsequently became trainers. Mean post-training OPRS scores were 4.4 (scale of 5) and did not vary significantly between training series. The overall complication rate was 4.7%, with no hernia recurrences or reoperations at 6 months. CONCLUSIONS: Competency-based training generates a regional network of surgeons proficient in Lichtenstein hernioplasty. Each training session progressively expands patient access to high quality operations in underserved communities in Brazil.

Global Outreach Using a Systematic, Competency-Based Training Paradigm for Inguinal Hernioplasty.

Importance: Sustainable, capacity-building educational collaborations are essential to address the global burden of surgical disease. Objective: To assess an international, competency-based training paradigm for hernia surgery in underserved countries. Design, Setting, and Participants: In this prospective, observational study performed from November 1, 2013, through October 31, 2015, at 16 hospitals in Brazil, Ecuador, Haiti, Paraguay, and the Dominican Republic, surgeons completed initial training programs in hernia repair, underwent interval proficiency assessments, and were appointed regional trainers. Competency-based evaluations of technical proficiency were performed using the Operative Performance Rating Scale (OPRS). Maintenance of proficiency was evaluated by video assessments 6 months after training. Certified trainees received incentives to document independent surgical outcomes after training. Main Outcomes and Measures: An OPRS score of 3.0 (scale of 1 [poor] to 5 [excellent]) indicated proficiency. Secondary outcomes included initial vs final scores by country, scores among surgeons trained by the regional trainers (second-order trainees), interval scores 6 months after training, and postoperative complications. Results: A total of 20 surgeon trainers, 81 local surgeons, and 364 patients (343 adult, 21 pediatric) participated in the study (mean [SD] age, 47.5 [16.3] years; age range, 16-83 years). All 81 surgeons successfully completed the program, and all 364 patients received successful operations. Mean (SD) OPRS scores improved from 4.06 (0.87) before the initial training program to 4.52 (0.57) after training (P < .001). No significant variation was found by country in final scores. On trainee certification, 20 became regional trainers. The mean (SD) OPRS score among 53 second-order trainees was 4.34 (0.68). After 6-month intervals, the mean (SD) OPRS score among participating surgeons was 4.34 (0.55). The overall operative complication rate during training series was 1.1%. Conclusions and Relevance: Competency-based training helps address the global burden of surgical disease. The OPRS establishes an international standard of technical assessment. Additional studies of long-term surgeon trainer proficiency, community-specific quality initiatives, and expansion to other operations are warranted.

Mouse model of endoscopically ablated enteric nervous system.

BACKGROUND: Current transgenic animal models of Hirschsprung disease are restricted by limited survival and need for special dietary care. We used small animal colonoscopy to produce chemically ablated enteric nervous system in the distal colon and rectum of normal mice. MATERIALS AND METHODS: Adult C57BL/6 mice underwent colonoscopy with submucosal injection of 75-100 µL of saline (n = 2) or 0.002% (n = 2), 0.02% (n = 15), or 0.2% (n = 2) benzalkonium chloride (BAC). Each mouse received 1-3 injections in the distal colon and rectum. Mice were sacrificed on postprocedure day 7 or 28. Injection sites were analyzed histologically and with immunostaining for ß-tubulin III. RESULTS: Submucosal injection of 0.02% BAC resulted in megacolon and obliteration of 82 ± 8.8% of myenteric ganglia at the injection site on postprocedure day 7 compared with normal colon. This effect was sustained until day 28. Injection of 0.002% BAC had little effect on the myenteric neuronal network at these time points. Multiple injections of 0.002% or 0.02% BAC (up to three injections per mouse) were well tolerated. Injection of 0.2% BAC caused acute toxicity or death. CONCLUSIONS: A novel model of chemically ablated enteric nervous system in the mouse colon and rectum is introduced. This model can be valuable in evaluating targeted cell delivery therapies for Hirschsprung disease.

Wearable Technology for Global Surgical Teleproctoring.

OBJECTIVE: In underserved communities around the world, inguinal hernias represent a significant burden of surgically-treatable disease. With traditional models of international surgical assistance limited to mission trips, a standardized framework to strengthen local healthcare systems is lacking. We established a surgical education model using web-based tools and wearable technology to allow for long-term proctoring and assessment in a resource-poor setting. This is a feasibility study examining wearable technology and web-based performance rating tools for long-term proctoring in an international setting. METHODS: Using the Lichtenstein inguinal hernia repair as the index surgical procedure, local surgeons in Paraguay and Brazil were trained in person by visiting international expert trainers using a formal, standardized teaching protocol. Surgeries were captured in real-time using Google Glass and transmitted wirelessly to an online video stream, permitting real-time observation and proctoring by mentoring surgeon experts in remote locations around the world. A system for ongoing remote evaluation and support by experienced surgeons was established using the Lichtenstein-specific Operative Performance Rating Scale. RESULTS: Data were collected from 4 sequential training operations for surgeons trained in both Paraguay and Brazil. With continuous internet connectivity, live streaming of the surgeries was successful. The Operative Performance Rating Scale was immediately used after each operation. Both surgeons demonstrated proficiency at the completion of the fourth case. CONCLUSIONS: A sustainable model for surgical training and proctoring to empower local surgeons in resource-poor locations and "train trainers" is feasible with wearable technology and web-based communication. Capacity building by maximizing use of local resources and expertise offers a long-term solution to reducing the global burden of surgically-treatable disease.

Innovation in Pediatric Surgical Education for General Surgery Residents: A Mobile Web Resource.

BACKGROUND/OBJECTIVES: General surgery residents lack a standardized educational experience in pediatric surgery. We hypothesized that the development of a mobile educational interface would provide general surgery residents broader access to pediatric surgical education materials. METHODS: We created an educational mobile website for general surgery residents rotating on pediatric surgery, which included a curriculum, multimedia resources, the Operative Performance Rating Scale (OPRS), and Twitter functionality. Residents were instructed to consult the curriculum. Residents and faculty posted media using the Twitter hashtag, #UCLAPedSurg, and following each surgical procedure reviewed performance via the OPRS. Site visits, Twitter posts, and OPRS submissions were quantified from September 2013 to July 2014. RESULTS: The pediatric surgery mobile website received 257 hits; 108 to the homepage, 107 to multimedia, 28 to the syllabus, and 19 to the OPRS. All eligible residents accessed the content. The Twitter hashtag, #UCLAPedSurg, was assigned to 20 posts; the overall audience reach was 85 individuals. Participants in the mobile OPRS included 11 general surgery residents and 4 pediatric surgery faculty. CONCLUSION: Pediatric surgical education resources and operative performance evaluations are effectively administered to general surgery residents via a structured mobile platform.

Repeated mechanical lengthening of intestinal segments in a novel model.

PURPOSE: Currently, animal models used for mechanical intestinal lengthening utilize a single lengthening procedure prior to analysis or restoration back into continuity. Here we developed a novel surgical model to examine the feasibility of repeated lengthening of intestinal segments. METHODS: A Roux-en-Y jejunojejunostomy with a blind Roux limb was created in rats. An encapsulated polycaprolactone spring was placed into a 1cm segment of the Roux limb. After 4 weeks, a second encapsulated PCL spring was inserted into a 1cm portion of the lengthened segment. After another 4 weeks, the repeatedly lengthened segments were retrieved for histological analyses. RESULTS: Jejunal segments of the Roux limb were successfully lengthened from 1.0 cm to 2.6 ± 0.7 cm. Four weeks after the second PCL spring placement, 1.0 cm of the previously lengthened segment increased to 2.7 ± 0.8 cm. Stronger mechanical force was required to achieve subsequent re-lengthening. Lengthened and re-lengthened segments had increased smooth muscle thickness and crypt depth when compared to normal jejunal mucosa. CONCLUSION: Using the Roux-en-Y model, previously lengthened segments of intestine can be successfully re-lengthened. Intestinal segments may be subjected to multiple lengthening procedures to achieve clinically significant length for the treatment of short bowel syndrome.

A real-time mobile web-based module promotes bidirectional feedback and improves evaluations of the surgery clerkship.

BACKGROUND: We implemented a real-time mobile web-based reporting module for students in our surgery clerkship and evaluated its effect on student satisfaction and perceived abuse. METHODS: Third-year medical students in the surgery clerkship received surveys regarding intimidation, perceived abuse, satisfaction with clerkship resources, and interest in a surgical career. Survey data were analyzed to assess differences after implementing the mobile reporting system and to identify independent predictors of perceived abuse. RESULTS: With the reporting module, students perceived less intimidation by residents (P < .001) and by faculty (P = .008), greater satisfaction reporting feedback (P < .001), and greater interest in surgical careers (P = .003). Perceived abuse decreased without reaching statistical significance (P = .331). High ratings of intimidation by faculty independently predicted perceived abuse (odds ratio = 1.3), and satisfaction with anonymous reporting was a negative predictor (odds ratio = .2). CONCLUSIONS: A mobile web-based system for real-time reporting fosters open communication and bidirectional feedback and promotes greater satisfaction with the surgery clerkship and interest in a surgical career.

Intestinal lengthening in an innovative rodent surgical model.

PURPOSE: Current animal models of mechanical lengthening separate intestinal segments from enteric continuity. Such models are difficult to use for repeated lengthening procedures and result in intestinal tissue loss during restoration into continuity. We sought to create a novel surgical model to allow multiple lengthening procedures for the purpose of maximizing the net increase in tissue after intestinal lengthening. METHODS: A Roux-en-y jejunojejunostomy with a 6-cm blind-ended Roux limb was created in the proximal jejunum of rats. Encapsulated 1-cm polycaprolactone springs were placed into the closed end of the roux limb and secured with a vessel loop. After 4weeks, lengthened segments and normal jejunum were retrieved for histologic analysis. RESULTS: Jejunal segments were lengthened from 1.0cm to 3.0cm. Lengthened segments had increased smooth muscle thickness, fewer submucosal ganglia, and similar numbers of myenteric ganglia compared to normal intestine. When compared to normal jejunal mucosa, lengthened segments demonstrated unchanged villus height and increased crypt depth. CONCLUSIONS: We created an innovative surgical model for intestinal lengthening and successfully lengthened jejunal segments with a degradable spring. The Roux-en-y model may allow the use of a degradable spring for the treatment of short bowel syndrome.

Skin-derived precursors generate enteric-type neurons in aganglionic jejunum.

PURPOSE: Skin-derived precursor cells (SKPs) may regenerate the enteric nervous system in Hirschsprung's disease. SKPs migrate and differentiate into myenteric ganglia in aganglionic intestine. We sought to characterize the time-course of SKP gangliogenesis and enteric neurotransmitter synthesis in vivo. METHODS: Adult Lewis rat jejunal segments were isolated and denervated with benzalkonium chloride (BAC). Denervation was evaluated by immunohistochemical (IHC) stains for markers of mature neuronal and glial cells. Green fluorescent protein (GFP)-expressing neonatal rat SKPs were cultured in neuroglial-selective medium. SKPs were transplanted into aganglionic segments 65-85days after BAC treatment. IHC was performed to identify glia, neurons, and neurotransmitter synthesis in GFP+cells between post-transplant days 1 and 28. RESULTS: Aganglionosis was confirmed by IHC. On post-transplant days 1 and 2, GFP+cells were detected near injection sites within the muscularis propria. GFP+cell clusters were evident only between longitudinal and circular smooth muscle layers at post-transplant days 14, 21, and 28. These structures co-expressed markers of mature neurons and gliocytes. Several markers of neurotransmitter synthesis were detected in GFP+clusters at days 21 and 28. CONCLUSION: SKPs are capable of enteric neuroglial differentiation in vivo. SKPs migrate to the intermuscular layer of aganglionic intestine within days of transplantation. Our observations suggest that SKPs are capable of generating enteric ganglia in aganglionic intestine.

A durable model of Hirschsprung's colon.

INTRODUCTION: Hirschsprung's disease is characterized by colonic aganglionosis, curable only by surgical correction. Stem cells may offer regenerative benefits while preventing surgical risks. Existing Hirschsprung's model systems are limited by alimentary compromise and spontaneous ganglionic reconstitution. We endeavored to generate a model of permanent colonic aganglionosis to support longitudinal cell therapy studies. METHODS: Among adult female Lewis rats (n=11), laparotomy was performed and one-centimeter segments of descending colon were isolated from continuity and denervated by trans-serosal benzalkonium chloride (BAC) exposure. Postoperative weights were plotted. The colon segments were retrieved after 50 or 100days. Immunohistochemical staining (IHC) for beta-III tubulin (TUJ1) and glial fibrillary acid protein (GFAP) revealed colonic ganglia. Muscle layer diameter and the presence of ganglia were contrasted between normal and denervated segments. RESULTS: All animals survived, experienced 5% weight loss after one week, and then consistently gained weight. Isolated segments had significantly hypertrophied smooth muscle layers compared to normal colon. Ganglia were identified by IHC in normal colonic segments, and denervated colonic segments had no IHC evidence of myenteric ganglia. CONCLUSION: Colonic segmental isolation and denervation result in an effective model of irreversible colonic aganglionosis. Animals retain alimentary function. Muscularis hypertrophy, myenteric denervation, and normal animal longevity are suitable for long-term studies of cell therapy.