Enfermedades raras en la infancia. Visión gastroenterológica / Rare Diseases in Childhood. Gastroenterological View

Introducción: Las enfermedades raras conforman las afecciones de baja prevalencia que asociadas a los medicamentos huérfanos representan un problema sanitario y social mundial. Objetivo: Revisar los aspectos más sobresalientes relacionados con las enfermedades raras, con una visión gastroenterológica, y su repercusión en la infancia. Métodos: Se realizaron búsquedas no estructuradas de publicaciones en español e inglés en PubMed, Google Scholar, Scimago, SciELO, desde enero 2010 hasta agosto 2021. Se usaron los términos: enfermedades raras, conceptualización, prevalencia, epidemiología, medicamentos huérfanos y ética. Análisis y síntesis de la información: Se revisaron las enfermedades raras en la infancia, criterios conceptuales, epidemiología global, enfermedades más reconocidas con énfasis en gastroenterología. Se destacó la prevalencia, vínculo genético, importancia social, dilema diagnóstico y categorías; repercusión de los tratamientos con medicamentos huérfanos, sus costos y problemas éticos. Se resaltó la incidencia de enfermedades digestivas y el valor de la endoscopia y la biopsia en el diagnóstico. Conclusiones: Se documentaron las enfermedades raras en la infancia, y se analizaron como problema mundial, sanitario y social. El desarrollo de la técnica y de la ciencia, resultaron contribuciones decisivas que variaron criterios sobre diferentes afecciones catalogadas como raras(AU)

Introduction: Rare diseases are the conditions of low prevalence associated with orphan drugs and they represent a global health and social problem. Objective: To review the most outstanding aspects related to rare diseases, with a gastroenterological view, and their impact on childhood. Methods: Unstructured searches for publications in Spanish and English in PubMed, Google Scholar, Scimago, SciELO were conducted, from January 2010 to August 2021. The terms rare diseases, conceptualization, prevalence, epidemiology, orphan drugs and ethics were used. Analysis and synthesis of information: Rare diseases in childhood, conceptual criteria, global epidemiology, and the most well-known diseases with emphasis on gastroenterology were reviewed. Prevalence, genetic link, social importance, diagnostic dilemma and categories, also the impact of orphan drug treatments, their costs and ethical problems were highlighted. The incidence of digestive diseases and the value of endoscopy and biopsy in diagnosis were highlighted. Conclusions: Rare diseases in childhood were documented and analyzed as a global health and social problem. The development of technique and science were decisive contributions that varied criteria on different conditions classified as rare(AU)

Endoscopic Management of Low-Grade Upper Tract Urothelial Carcinoma: Characterizing the Long-term Burden of Care in Comparison to Radical Nephroureterectomy.

OBJECTIVE: To compare procedure burden, oncologic, surgical and renal-function outcomes between patients with low-grade upper urothelial cancer (UTUC) who were referred for either radical management (RM) or kidney-sparing endoscopic management (EM). PATIENTS AND METHODS: We retrospectively reviewed data of all patients treated for UTUC at our tertiary medical center between 2000 and 2018 and selected patients diagnosed with unilateral low-grade UTUC. RESULTS: Twenty-four patients were treated with EM and 37 with RM. Surgical and oncologic risk factors were similar between the arms except for tumor size. Mean follow-up was 4.9 ± 3.4 years. The 5-year overall-survival rate was 85% with EM and 84% with RM (P = .707). Metastasis-free and cancer-specific survival were also similar (P = .994, P = .960). End-of-follow-up average glomerular filtration rates were 58.7 ± 21.5 and 49.2 ± 22.1 mL/min/1.73 m2, respectively (P = .12). Ninety-two percent of patients managed endoscopically had local recurrences, with an average of 3.2 recurrences per patient. Four (17%) patients underwent salvage radical nephroureterectomy. Procedure burden was higher with EM, having 6.5 ± 4.4 operations and 344 ± 272 minutes under anesthesia compared with 1.9 ± 0.4 operations (P <.0001) and 213 ± 84 minutes under anesthesia (P = .031) with RM. Cost-of-care analysis revealed higher costs for EM in both private and publicly funded medical insurance plans. CONCLUSION: Patients undergoing endoscopic management had an 83% chance of preserving their kidney and an 81% chance of 5-year metastasis-free survival at a cost of 6.5 ± 4.4 operations during a mean follow-up of 4.9 ± 3.4 years. Our findings support EM for low-grade UTUC as a valid option from oncological aspects but highlight the associated costs.

Variations in utilization and clinical outcomes for endoscopic sphenopalatine artery ligation and endovascular arterial embolization in a single multi-hospital network.

PURPOSE: Endoscopic sphenopalatine artery ligation (ESPAL) and endovascular arterial embolization (EAE) are increasingly common treatment options for patients with refractory epistaxis. The objective of this study was to compare the utilization pattern and clinical outcomes between these interventions within our single multi-hospital network. MATERIALS AND METHODS: A retrospective study of all patients undergoing ESPAL and/or EAE within any of the hospitals in a single healthcare network between 2008 and 2017 was conducted. We compared differences in procedure utilization with various hospital characteristics. Secondarily, we evaluated clinical outcomes and costs associated with each procedure. RESULTS: Forty-three ESPAL and 33 EAE procedures were performed across 7 hospitals, with the majority of procedures being performed at teaching institutions (65% and 91%, p = .013). The majority of both interventions were performed in larger hospitals and EAE patients were more likely to undergo inter-hospital transfer compared to ESPAL patients (48.5% and 16.3%, p = .02). Success rates for ESPAL and EAE were comparable (95% and 93%); however, the median direct cost of treatment for EAE was significantly higher than the cost for ESPAL ($12984.89 and $5002.02, p < .0001). CONCLUSIONS: The majority of both ESPAL and EAE interventions were performed at teaching and larger hospitals. Transfers occurring prior to EAE may have been due to the limited availability of interventional radiology services, and likely contributed to the increased cost of treatment. ESPAL is a known cost-effective management strategy and should be considered early in treatment algorithms of refractory epistaxis.

Endoscopic urethrotomy versus open urethroplasty for men with bulbar urethral stricture: the OPEN randomised trial cost-effectiveness analysis.

BACKGROUND: Bulbar urethral stricture is a common cause for urinary symptoms in men and its two main treatment options both have drawbacks with little evidence on their relative cost-effectiveness. Current guidelines on the management of recurrent bulbar urethral stricture have been predominantly based on expert opinion and panel consensus. OBJECTIVE: To assess the relative cost-effectiveness of open urethroplasty and endoscopic urethrotomy as treatment for recurrent urethral stricture in men. METHODS: Set in the UK National Health Service with recruitment from 38 hospital sites, a randomised controlled trial of open urethroplasty and endoscopic urethrotomy with 6-monthly follow-up over 24 months was conducted. Two hundred and twenty-two men requiring operative treatment for recurrence of bulbar urethral stricture and having had at least one previous intervention for stricture were recruited. Effectiveness was measured by quality- adjusted life years (QALYs) derived from EQ-5D 5L. Cost-effectiveness was measured by the incremental cost per QALY gained over 24 months using a within trial analysis and a Markov model with a 10-year time horizon. RESULTS: In the within trial, urethroplasty cost on average more than urethrotomy (cost difference: £2148 [95% CI 689, 3606]) and resulted in a similar number of QALYs on average (QALY difference: - 0.01 [95% CI - 0.17, 0.14)] over 24 months. The Markov model produced similar results. Sensitivity analyses using multiple imputation, suggested that the results were robust, despite observed missing data. CONCLUSIONS: Based on current practice and evidence, urethrotomy is a cost-effective treatment compared with urethroplasty. KEYPOINTS: Urethrotomy and urethroplasty both led to symptom improvement for men with bulbar urethral stricture-a common cause for urinary symptoms in men; Urethroplasty appeared unlikely to offer good value for money compared to urethrotomy based on current evidence. TRIAL REGISTRATION: ISRCTN: 98009168 (date: 29 November 2012) and it is also in the UK NIHR Portfolio (reference 13507). Trial protocol: The latest version (1.8) of the full protocol is available at: www.journalslibrary.nihr.ac.uk/programmes/hta/105723/ #/ and a published version is also available: Stephenson R, Carnell S, Johnson N, Brown R, Wilkinson J, Mundy A, et al. Open urethroplasty versus endoscopic urethrotomy-clarifying the management of men with recurrent urethral stricture (the OPEN trial): study protocol for a randomised controlled trial. Trials 2015;16:600. https://doi.org/10.1186/s13063-015-1120-4. Trial main clinical results publication: Goulao B, Carnell S, Shen J, MacLennan G, Norrie J, Cook J, et al. Surgical Treatment for Recurrent Bulbar Urethral Stricture: A Randomised Open-label Superiority Trial of Open Urethroplasty Versus Endoscopic Urethrotomy (the OPEN Trial), European Urology, Volume 78, Issue 4, 2020, Pages 572-580.

Cost-Effectiveness of Open Versus Endoscopic Carpal Tunnel Release.

BACKGROUND: Carpal tunnel syndrome is the most common upper-extremity nerve compression syndrome. Over 500,000 carpal tunnel release (CTR) procedures are performed in the U.S. yearly. We estimated the cost-effectiveness of endoscopic CTR (ECTR) versus open CTR (OCTR) using data from published meta-analyses comparing outcomes for ECTR and OCTR. METHODS: We developed a Markov model to examine the cost-effectiveness of OCTR versus ECTR for patients undergoing unilateral CTR in an office setting under local anesthesia and in an operating-room (OR) setting under monitored anesthesia care. The main outcomes were costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). We modeled societal (modeled with a 50-year-old patient) and Medicare payer (modeled with a 65-year-old patient) perspectives, adopting a lifetime time horizon. We performed deterministic and probabilistic sensitivity analyses (PSAs). RESULTS: ECTR resulted in 0.00141 additional QALY compared with OCTR. From a societal perspective, assuming 8.21 fewer days of work missed after ECTR than after OCTR, ECTR cost less across all procedure settings. The results are sensitive to the number of days of work missed following surgery. From a payer perspective, ECTR in the OR (ECTROR) cost $1,872 more than OCTR in the office (OCTRoffice), for an ICER of approximately $1,332,000/QALY. The ECTROR cost $654 more than the OCTROR, for an ICER of $464,000/QALY. The ECTRoffice cost $107 more than the OCTRoffice, for an ICER of $76,000/QALY. From a payer perspective, for a willingness-to-pay threshold of $100,000/QALY, OCTRoffice was preferred over ECTROR in 77% of the PSA iterations. From a societal perspective, ECTROR was preferred over OCTRoffice in 61% of the PSA iterations. CONCLUSIONS: From a societal perspective, ECTR is associated with lower costs as a result of an earlier return to work and leads to higher QALYs. Additional research on return to work is needed to confirm these findings on the basis of contemporary return-to-work practices. From a payer perspective, ECTR is more expensive and is cost-effective only if performed in an office setting under local anesthesia. LEVEL OF EVIDENCE: Economic and Decision Analysis Level I. See Instructions for Authors for a complete description of levels of evidence.

Cost Utility Analysis of Dupilumab Versus Endoscopic Sinus Surgery for Chronic Rhinosinusitis With Nasal Polyps.

OBJECTIVE: Both endoscopic sinus surgery (ESS) and biologic therapies have shown effectiveness for medically-refractory chronic rhinosinusitis with nasal polyps (CRSwNP) without severe asthma. The objective was to evaluate cost-effectiveness of dupilumab versus ESS for patients with CRSwNP. STUDY DESIGN: Cohort-style Markov decision-tree economic model with a 36-year time horizon. METHODS: A cohort of 197 CRSwNP patients who underwent ESS were compared with a matched cohort of 293 CRSwNP patients from the SINUS-24 and SINUS-52 Phase 3 studies who underwent treatment with dupilumab 300 mg every 2 weeks. Utility scores were calculated from the SNOT-22 instrument in both cohorts. Decision-tree analysis and a 10-state Markov model utilized published event probabilities and primary data to calculate long-term costs and utility. The primary outcome measure was incremental cost per quality-adjusted life year (QALY), which is expressed as an Incremental Cost Effectiveness Ratio. One-way and probabilistic sensitivity analyses were performed. RESULTS: The ESS strategy cost $50,436.99 and produced 9.80 QALYs. The dupilumab treatment strategy cost $536,420.22 and produced 8.95 QALYs. Because dupilumab treatment was more costly and less effective than the ESS strategy, it is dominated by ESS in the base case. One-way sensitivity analyses showed ESS to be cost-effective versus dupilumab regardless of the frequency of revision surgery and at any yearly cost of dupilumab above $855. CONCLUSIONS: The ESS treatment strategy is more cost effective than dupilumab for upfront treatment of CRSwNP. More studies are needed to isolate potential phenotypes or endotypes that will benefit most from dupilumab in a cost-effective manner. LEVEL OF EVIDENCE: 2C Laryngoscope, 131:E26-E33, 2021.

Cost-effectiveness analysis of SARS-CoV-2 infection prevention strategies including pre-endoscopic virus testing and use of high risk personal protective equipment.

BACKGROUND: Infection prevention strategies to protect healthcare workers in endoscopy units during the post-peak phase of the COVID-19 pandemic are currently under intense discussion. In this paper, the cost-effectiveness of routine pre-endoscopy testing and high risk personal protective equipment (PPE) is addressed. METHOD: A model based on theoretical assumptions of 10 000 asymptomatic patients presenting to a high volume center was created. Incremental cost-effectiveness ratios (ICERs) and absolute costs per endoscopy were calculated using a Monte Carlo simulation. RESULTS: ICER values for universal testing decreased with increasing prevalence rates. For higher prevalence rates (≥ 1 %), ICER values were lowest for routine pre-endoscopy testing coupled with use of high risk PPE, while cost per endoscopy was lowest for routine use of high risk PPE without universal testing. CONCLUSION: In general, routine pre-endoscopy testing combined with high risk PPE becomes more cost-effective with rising prevalence rates of COVID-19.

Cost-effectiveness of palliative emergent surgery versus endoscopic stenting for acute malignant colonic obstruction.

BACKGROUND: Endoscopic stenting has demonstrated value over emergent surgery as a palliative intervention for patients with acute large bowel obstruction due to advanced colorectal cancer. However, concerns regarding high reintervention rates and the risk of perforation have brought into question its cost-effectiveness. METHODS: A decision tree analysis was performed to analyze costs and survival in patients with unresectable or metastatic colorectal cancer who present with acute large bowel obstruction. The model was designed with two treatment arms: self-expanding metallic stent (SEMS) placement and emergent surgery. Costs were derived from medicare reimbursement rates (US$), while effectiveness was represented by quality-adjusted life years (QALYs). The primary outcome measure was the incremental cost-effectiveness ratio (ICER). The model was tested for validation using one-way, two-way, and probabilistic sensitivity analyses. RESULTS: Endoscopic stenting resulted in an average cost of $43,798.06 and 0.68 QALYs. Emergent surgery cost $5865.30 more, while only yielding 0.58 QALYs. This resulted in an ICER of - $58,653.00, indicating that SEMS placement is the dominant strategy. One-way and two-way sensitivity analyses demonstrated that emergent surgery would require an improved survival rate in comparison to endoscopic stenting to become the favored treatment modality. In 100,000 probabilistic simulations, endoscopic stenting was favored 96.3% of the time. CONCLUSIONS: In patients with acute colonic obstruction in the presence of unresectable or metastatic disease, endoscopic stenting is a more cost-effective palliative intervention than emergent surgery. This recommendation would favor surgery over SEMS placement with improved surgical survival, or if the majority of patients undergoing stenting required reintervention.

Robot-assisted sialolithotomy with sialoendoscopy: a review of safety, efficacy and cost.

OBJECTIVE: Review the safety, efficacy and cost of robot-assisted sialolithotomy with sialoendoscopy (RASS) for large submandibular gland hilar sialoliths. STUDY DESIGN: Retrospective case series. METHODS: Patients ≥18 years diagnosed with submandibular hilar sialolithiasis between 1/1/2015 and 7/31/2018 who underwent RASS were identified. Procedure success, post-operative complications, procedure duration, and costs associated with the procedure were reviewed. RESULTS: 33 patients fit inclusion criteria. 94% of patients had successful sialolith removal. Mean sialolith size was 8.9 mm. 15.1% had transient tongue paresthesia. 0% had permanent tongue paresthesia compared to a 2% rate of lingual nerve damage cited in the literature for combined approach sialolithotomy (CAS). The average total cost was $16,921. Insurance paid 100%, 90-99%, 70-89.9%, and 40-69.9% of the expected reimbursement in 43.8%, 18.7%, 18.7% and 12.5% of patients respectively. 6% of patients self-paid. Compared to CAS, the cost of reusable robotic arms and drapes totaled $475, though these costs were included in the standardized operative cost per minute and were not forwarded to the patient. The mean procedure time was 62 minutes. Compared to published mean procedure times for CAS, the reduced operative time may account for a savings of $3332-$6069. CONCLUSION: RASS is a safe modality for submandibular hilar sialolith removal with a high success rate, low risk for temporary tongue paresthesia, and lower rate of permeant lingual nerve damage compared to CAS. Compared with CAS, RASS may result in a net reduction of operative room costs given its shorter procedure time.

Drivers of In-Hospital Costs Following Endoscopic Transphenoidal Pituitary Surgery.

OBJECTIVE: To characterize the patient and clinical factors that determine variability in hospital costs following endoscopic transphenoidal pituitary surgery. METHODS: All endoscopic transphenoidal pituitary surgeries performed from January 1, 2015, to October 24, 2017, with complete data were evaluated in this retrospective single-institution study. The electronic medical record was reviewed for patient factors, tumor characteristics, and cost variables during each hospital stay. Multivariate linear regression was performed using Stata software. RESULTS: The analysis included 190 patients and average length of stay was 4.71 days. Average total in-hospital cost was $28,624 (95% confidence interval $25,094-$32,155) with average total direct cost of $19,444 ($17,136-$21,752) and total indirect cost of $9181 ($7592-$10,409). On multivariate regression, post-operative cerebrospinal fluid (CSF) leak was associated with a significant increase in all cost variables, including a total cost increase of $40,981 ($15,474-$66,489, P = .002). Current smoking status was associated with an increased total cost of $20,189 ($6,638-$33,740, P = .004). Self-reported Caucasian ethnicity was associated with a significant decrease in total cost of $6646 (-$12,760 to -$532, P = .033). Post-operative DI was associated with increased costs across all variables that were not statistically significant. CONCLUSIONS: Post-operative CSF leak, current smoking status, and non-Caucasian ethnicity were associated with significantly increased costs. Understanding of cost drivers of endoscopic transphenoidal pituitary surgery is critical for future cost control and value creation initiatives. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:760-764, 2021.

Percutaneous Transforaminal Endoscopic Discectomy Versus Open Microdiscectomy for Lumbar Disc Herniation: A Systematic Review and Meta-analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: To give a systematic overview of effectiveness of percutaneous transforaminal endoscopic discectomy (PTED) compared with open microdiscectomy (OM) in the treatment of lumbar disk herniation (LDH). SUMMARY OF BACKGROUND DATA: The current standard procedure for the treatment of sciatica caused by LDH, is OM. PTED is an alternative surgical technique which is thought to be less invasive. It is unclear if PTED has comparable outcomes compared with OM. METHODS: Multiple online databases were systematically searched up to April 2020 for randomized controlled trials and prospective studies comparing PTED with OM for LDH. Primary outcomes were leg pain and functional status. Pooled effect estimates were calculated for the primary outcomes only and presented as standard mean differences (SMD) with their 95% confidence intervals (CI) at short (1-day postoperative), intermediate (3-6 months), and long-term (12 months). RESULTS: We identified 2276 citations, of which eventually 14 studies were included. There was substantial heterogeneity in effects on leg pain at short term. There is moderate quality evidence suggesting no difference in leg pain at intermediate (SMD 0.05, 95% CI -0.10-0.21) and long-term follow-up (SMD 0.11, 95% CI -0.30-0.53). Only one study measured functional status at short-term and reported no differences. There is moderate quality evidence suggesting no difference in functional status at intermediate (SMD -0.09, 95% CI -0.24-0.07) and long-term (SMD -0.11, 95% CI -0.45-0.24). CONCLUSION: There is moderate quality evidence suggesting no difference in leg pain or functional status at intermediate and long-term follow-up between PTED and OM in the treatment of LDH. High quality, robust studies reporting on clinical outcomes and cost-effectiveness on the long term are lacking.Level of Evidence: 2.

Comparative study of endoscopic and microscopic tympanoplasty performed by a single experienced surgeon.

PURPOSE: The use of endoscopes in otologic procedures has been increasing worldwide. This study aimed to compare the efficacy of microscopic tympanoplasty (MT) and endoscopic tympanoplasty (ET) for tympanic membrane and middle ear surgery. MATERIALS AND METHODS: We retrospectively analyzed 81 patients who underwent MT (n = 44) and ET (n = 37) for chronic otitis media with tympanic membrane perforation performed by a single surgeon between January 2013 and September 2019. The hearing outcomes, graft success rate, complications, operation time and hospital stay, and cost-effectiveness were recorded and compared between groups. Hearing outcomes were determined by pure tone audiometry. Cost-effectiveness was determined by the operation cost and total cost. RESULTS: There was no significant difference between the MT and ET groups regarding demographic characteristics, with the exception of the male:female ratio. There was no significant difference in the pre- and postoperative air conduction, bone conduction thresholds, and air-bone gap values between the two groups, but a significant audiologic improvement was observed in both groups (p < 0.05). In terms of recurrence of tympanic membrane perforation, postoperative otorrhea, and discomfort symptoms, there was no significant difference between groups (p > 0.05). The operation time and hospital stay were shorter in the ET group than in the MT group (p < 0.05). There were no significant differences in operation cost between the two groups (p > 0.05), but the total cost was significantly lower in the ET group than the MT group (p < 0.05). CONCLUSION: ET is as safe and medically efficacious as conventional MT, shortens the operation time and hospital stay, and is cost-effective.

Early Career Challenges in Setting Up an Endoscopic Spine Surgery Practice.

After the completion of an endoscopic spinal surgery fellowship, the next challenge for the newly minted consultant is to set up a viable and sustainable endoscopic practice. A successful practice of endoscopic spine surgery is dependent on several factors, such as anesthetic support; surgical expertise; support for provision and maintenance of endoscopic equipment; cost of equipment; administrative and nursing support; postoperative care services to optimize patients' outcome and satisfaction; patients' ideas, concerns, and expectations, as well as continuing medical education. In this article, a perspective is given on the early career challenges that a fellowship-trained endoscopic surgeon may encounter in the period leading to first successful endoscopic spinal surgery.

Open urethroplasty versus endoscopic urethrotomy for recurrent urethral stricture in men: the OPEN RCT.

BACKGROUND: Men who suffer recurrence of bulbar urethral stricture have to decide between endoscopic urethrotomy and open urethroplasty to manage their urinary symptoms. Evidence of relative clinical effectiveness and cost-effectiveness is lacking. OBJECTIVES: To assess benefit, harms and cost-effectiveness of open urethroplasty compared with endoscopic urethrotomy as treatment for recurrent urethral stricture in men. DESIGN: Parallel-group, open-label, patient-randomised trial of allocated intervention with 6-monthly follow-ups over 24 months. Target sample size was 210 participants providing outcome data. Participants, clinicians and local research staff could not be blinded to allocation. Central trial staff were blinded when needed. SETTING: UK NHS with recruitment from 38 hospital sites. PARTICIPANTS: A total of 222 men requiring operative treatment for recurrence of bulbar urethral stricture who had received at least one previous intervention for stricture. INTERVENTIONS: A centralised randomisation system using random blocks allocated participants 1 : 1 to open urethroplasty (experimental group) or endoscopic urethrotomy (control group). MAIN OUTCOME MEASURES: The primary clinical outcome was control of urinary symptoms. Cost-effectiveness was assessed by cost per quality-adjusted life-year (QALY) gained over 24 months. The main secondary outcome was the need for reintervention for stricture recurrence. RESULTS: The mean difference in the area under the curve of repeated measurement of voiding symptoms scored from 0 (no symptoms) to 24 (severe symptoms) between the two groups was -0.36 [95% confidence interval (CI) -1.78 to 1.02; p = 0.6]. Mean voiding symptom scores improved between baseline and 24 months after randomisation from 13.4 [standard deviation (SD) 4.5] to 6 (SD 5.5) for urethroplasty group and from 13.2 (SD 4.7) to 6.4 (SD 5.3) for urethrotomy. Reintervention was less frequent and occurred earlier in the urethroplasty group (hazard ratio 0.52, 95% CI 0.31 to 0.89; p = 0.02). There were two postoperative complications requiring reinterventions in the group that received urethroplasty and five, including one death from pulmonary embolism, in the group that received urethrotomy. Over 24 months, urethroplasty cost on average more than urethrotomy (cost difference £2148, 95% CI £689 to £3606) and resulted in a similar number of QALYs (QALY difference -0.01, 95% CI -0.17 to 0.14). Therefore, based on current evidence, urethrotomy is considered to be cost-effective. LIMITATIONS: We were able to include only 69 (63%) of the 109 men allocated to urethroplasty and 90 (80%) of the 113 men allocated to urethrotomy in the primary complete-case intention-to-treat analysis. CONCLUSIONS: The similar magnitude of symptom improvement seen for the two procedures over 24 months of follow-up shows that both provide effective symptom control. The lower likelihood of further intervention favours urethroplasty, but this had a higher cost over the 24 months of follow-up and was unlikely to be considered cost-effective. FUTURE WORK: Formulate methods to incorporate short-term disutility data into cost-effectiveness analysis. Survey pathways of care for men with urethral stricture, including the use of enhanced recovery after urethroplasty. Establish a pragmatic follow-up schedule to allow national audit of outcomes following urethral surgery with linkage to NHS Hospital Episode Statistics. TRIAL REGISTRATION: Current Controlled Trials ISRCTN98009168. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 61. See the NIHR Journals Library website for further project information.

The urethra carries urine from the bladder to the tip of the penis. Men can develop a condition called urethral stricture when part of the urethra narrows due to scarring. This can lead to difficulties in passing urine and can recur. There are two operations for urethral stricture. The standard approach is endoscopic urethrotomy. The alternative is open urethroplasty. This study wanted to find out which operation was preferable in terms of symptom control, time before further surgery and which operation was best value for the NHS. All aspects of the study were informed by patients. Two hundred and twenty-two men who had received at least one previous operation for stricture took part. The choice of operation was decided by chance (randomisation). Of these men, 113 were randomised to urethrotomy and 109 were randomised to urethroplasty. Following their operation, the men filled in questionnaires every 3­6 months for 2 years about their symptoms and if any further surgery was needed. The two groups were then compared. Of the 222 men who took part, 159 provided enough information for inclusion in the comparison (90 were in the urethrotomy group and 69 were in the urethroplasty group). The improvement over time in urinary symptoms was similar for the two groups. Men in the urethrotomy group were twice as likely to need a further operation over the 2-year study period. Very few men experienced serious complications. This study showed that both operations led to symptom improvement for men with recurrent urethral stricture. Urethroplasty, however, appears unlikely to offer good value for money for the NHS. Men needing treatment for recurrent urethral stricture can use this information to weigh up the pros and cons of each operation to decide with their clinical team which one to undergo.

Evaluating the Use of microRNA Blood Tests for Gastric Cancer Screening in a Stratified Population-Level Screening Program: An Early Model-Based Cost-Effectiveness Analysis.

OBJECTIVES: To evaluate cost-effectiveness of a novel screening strategy using a microRNA (miRNA) blood test as a screen, followed by endoscopy for diagnosis confirmation in a 3-yearly population screening program for gastric cancer. METHODS: A Markov cohort model has been developed in Microsoft Excel 2016 for the population identified to be at intermediate risk (Singaporean men, aged 50-75 years with Chinese ethnicity). The interventions compared were (1) initial screening using miRNA test followed by endoscopy for test-positive individuals and a 3-yearly follow-up screening for test-negative individuals (proposed strategy), and (2) no screening with gastric cancer being diagnosed clinically (current practice). The model was evaluated for 25 years with a healthcare perspective and accounted for test characteristics, compliance, disease progression, cancer recurrence, costs, utilities, and mortality. The outcomes measured included incremental cost-effectiveness ratios, cancer stage at diagnosis, and thresholds for significant variables. RESULTS: The miRNA-based screening was found to be cost-effective with an incremental cost-effectiveness ratio of $40 971/quality-adjusted life-year. Key drivers included test costs, test accuracy, cancer incidence, and recurrence risk. Threshold analysis highlights the need for high accuracy of miRNA tests (threshold sensitivity: 68%; threshold specificity: 77%). A perfect compliance to screening would double the cancer diagnosis in early stages compared to the current practice. Probabilistic sensitivity analysis reported the miRNA-based screening to be cost-effective in >95% of iterations for a willingness to pay of $70 000/quality-adjusted life-year (approximately equivalent to 1 gross domestic product/capita) CONCLUSIONS: The miRNA-based screening intervention was found to be cost-effective and is expected to contribute immensely in early diagnosis of cancer by improving screening compliance.

Endoscopy Used as Provocative Testing in Bariatric Surgery: An Analysis of the Texas Public Use Data File.

BACKGROUND: Many bariatric surgeons test the anastomosis and staple lines with some sort of provocative test. This can take the form of an air leak test with a nasogastric tube with methylene blue dye or with an endoscopy. The State Department of Health Statistics in Texas tracks outcomes using the Texas Public Use Data File (PUDF). METHODS: We queried the Texas Inpatient and Outpatient PUDFs for 2013 to 2017 to examine the number of bariatric surgeries with endoscopy performed at the same time. We used the International Classification of Diseases Clinical Modification Version 9 (ICD-9-CM) and ICD-10 procedure codes and Current Procedural Terminology for Sleeve Gastrectomy (SG) and laparoscopic Roux-en-Y gastric bypass (LRYGB) and endoscopy, and the ICD-9-CM and ICD-10 diagnosis codes for morbid obesity. RESULTS: There were 74,075 SG reported in the Texas Inpatient and Outpatient PUDF for the years 2013-2017. Of the SG performed, 5,521 (7.4%) had an intraoperative endoscopy. For the 19,192 LRYGB reported, 1640 (8.6%) underwent LRYGB + endoscopy. This was broken down by SG only vs SG + endoscopy and LRYGB only vs LRYGB + endoscopy. Overall, SG + endoscopy had a significantly shorter length of stay (LOS) vs LRYGB + endoscopy at 1.74 d vs 2.34 d (P < .001) and a significantly less cost of $71,685 vs $91,093 (P < .001). CONCLUSIONS: A small percentage of SG and LRYGB patients underwent endoscopy for provocative testing over the study period. Provocative testing with endoscopy costs more for SG and LRYGB and was associated with a shorter LOS.

Surgical Treatment for Recurrent Bulbar Urethral Stricture: A Randomised Open-label Superiority Trial of Open Urethroplasty Versus Endoscopic Urethrotomy (the OPEN Trial).

BACKGROUND: Urethral stricture affects 0.9% of men. Initial treatment is urethrotomy. Approximately, half of the strictures recur within 4 yr. Options for further treatment are repeat urethrotomy or open urethroplasty. OBJECTIVE: To compare the effectiveness and cost-effectiveness of urethrotomy with open urethroplasty in adult men with recurrent bulbar urethral stricture. DESIGN, SETTING, AND PARTICIPANTS: This was an open label, two-arm, patient-randomised controlled trial. UK National Health Service hospitals were recruited and 222 men were randomised to receive urethroplasty or urethrotomy. INTERVENTION: Urethrotomy is a minimally invasive technique whereby the narrowed area is progressively widened by cutting the scar tissue with a steel blade mounted on a urethroscope. Urethroplasty is a more invasive surgery to reconstruct the narrowed area. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the profile over 24 mo of a patient-reported outcome measure, the voiding symptom score. The main clinical outcome was time until reintervention. RESULTS AND LIMITATIONS: The primary analysis included 69 (63%) and 90 (81%) of those allocated to urethroplasty and urethrotomy, respectively. The mean difference between the urethroplasty and urethrotomy groups was -0.36 (95% confidence interval [CI] -1.74 to 1.02). Fifteen men allocated to urethroplasty needed a reintervention compared with 29 allocated to urethrotomy (hazard ratio [95% CI] 0.52 [0.31-0.89]). CONCLUSIONS: In men with recurrent bulbar urethral stricture, both urethroplasty and urethrotomy improved voiding symptoms. The benefit lasted longer for urethroplasty. PATIENT SUMMARY: There was uncertainty about the best treatment for men with recurrent bulbar urethral stricture. We randomised men to receive one of the following two treatment options: urethrotomy and urethroplasty. At the end of the study, both treatments resulted in similar and better symptom scores. However, the urethroplasty group had fewer reinterventions.

A handheld flexible manipulator system for frontal sinus surgery.

PURPOSE: Draf drainage is the standard treatment procedure for frontal sinus diseases. In this procedure, rigid angled endoscopes and rigid curved instruments are used. However, laterally located pathologies in the frontal sinus cannot be reached with rigid instrumentation. In order to assist surgeons with such complicated cases, we propose a novel handheld flexible manipulator system. METHODS: A cross section of 3 mm × 4.6 mm enables transnasal guiding of a flexible endoscope with 1.4 mm diameter and a standard flexible surgical instrument with up to 1.8 mm diameter into the frontal sinus with increased reachability. The developed system consists of an electrical discharge-machined flexure hinge-based nitinol manipulator arm and a purely mechanical handheld control unit. The corresponding control unit enables upward and left-right bending of the manipulator arm, translation, rolling, actuation and also quick exchange of the surgical instrument. In order to verify the fulfillment of performance requirements, tests regarding reachability and payload capacity were conducted. RESULTS: Reachability tests showed that the manipulator arm can be inserted into the frontal sinus and reach its lateral regions following a Draf IIa procedure. The system can exert forces of at least 2 N in the vertical direction and 1 N in the lateral direction which is sufficient for manipulation of frontal sinus pathologies. CONCLUSION: Considering the fact that the anatomical requirements of the frontal sinus are not addressed satisfactorily in the development of prospective flexible instruments, the proposed system shows great potential in terms of therapeutic use owing to its small cross section and dexterity.

Network Meta-analysis for the Diagnostic Approach to Pathologic Nipple Discharge.

Pathologic nipple discharge (PND) is one of the most common breast-related complaints for referral because of its supposed association with breast cancer. The aim of this network meta-analysis (NMA) was to compare the diagnostic efficacy of ultrasound, mammogram, cytology, magnetic resonance imaging (MRI), and ductoscopy in patients with PND, as well as to determine the best diagnostic strategy to assess the risk of malignancy as cause for PND. Cochrane Library, PubMed, and Embase were searched to collect relevant literature from the inception of each of the diagnostic methods until January 27, 2020. The search yielded 1472 original citations, of which 36 studies with 3764 patients were finally included for analysis. Direct and indirect comparisons were performed using an NMA approach to evaluate the combined odd ratios and to determine the surface under the cumulative ranking curves (SUCRA) of the diagnostic value of different imaging methods for the detection of breast cancer in patients with PND. Additionally, a subgroup meta-analysis comparing ductoscopy to MRI when conventional imaging was negative was also performed. According to this NMA, sensitivity for detection of malignancy in patients with PND was highest for MRI (83%), followed by ductoscopy (58%), ultrasound (50%), cytology (38%), and mammogram (22%). Specificity was highest for mammogram (93%) followed by ductoscopy (92%), cytology (90%), MRI (76%), and ultrasound (69%). Diagnostic accuracy was the highest for ductoscopy (88%), followed by cytology (82%), MRI (77%), mammogram (76%), and ultrasound (65%). Subgroup meta-analysis (comparing ductoscopy to MRI when ultrasound and mammogram were negative) showed no significant difference in sensitivity, but ductoscopy was statistically significantly better with regard to specificity and diagnostic accuracy. The results from this NMA indicate that although ultrasound and mammogram may remain low-cost useful first choices for the detection of malignancy in patients with PND, ductoscopy outperforms most imaging techniques (especially MRI) and cytology.

COVID-19 polymerase chain reaction testing before endoscopy: an economic analysis.

BACKGROUND AND AIMS: The novel coronavirus disease 2019 (COVID-19) pandemic has limited endoscopy utilization, causing significant health and economic losses. We aim to model the impact of polymerase chain reaction (PCR) testing into resuming endoscopy practice. METHODS: We performed a retrospective review of endoscopy utilization during the COVID-19 pandemic for a baseline reference. A computer model compared 3 approaches: strategy 1, endoscopy for urgent indications only; strategy 2, testing for semiurgent indications; and strategy 3, testing all patients. Analysis was made under current COVID-19 prevalence and projected prevalence of 5% and 10%. Primary outcomes were number of procedures performed and/or canceled. Secondary outcomes were direct costs, reimbursement, personal protective equipment used, and personnel infected. Disease prevalence, testing accuracy, and costs were obtained from the literature. RESULTS: During the COVID-19 pandemic, endoscopy volume was 12.7% of expected. Strategies 2 and 3 were safe and effective interventions to resume endoscopy in semiurgent and elective cases. Investing 22 U.S. dollars (USD) and 105 USD in testing per patient allowed the completion of 19.4% and 95.3% of baseline endoscopies, respectively. False-negative results were seen after testing 4700 patients (or 3 months of applying strategy 2 in our practice). Implementing PCR testing over 1 week in the United States would require 13 and 64 million USD, with a return of 165 and 767 million USD to providers, leaving 65 and 325 healthcare workers infected. CONCLUSIONS: PCR testing is an effective strategy to restart endoscopic practice in the United States. PCR screening should be implemented during the second phase of the pandemic, once the healthcare system is able to test and isolate all suspected COVID-19 cases.