Machine Learning and External Validation of the IDENTIFY Risk Calculator for Patients with Haematuria Referred to Secondary Care for Suspected Urinary Tract Cancer.

BACKGROUND: The IDENTIFY study developed a model to predict urinary tract cancer using patient characteristics from a large multicentre, international cohort of patients referred with haematuria. In addition to calculating an individual's cancer risk, it proposes thresholds to stratify them into very-low-risk (<1%), low-risk (1-<5%), intermediate-risk (5-<20%), and high-risk (≥20%) groups. OBJECTIVE: To externally validate the IDENTIFY haematuria risk calculator and compare traditional regression with machine learning algorithms. DESIGN, SETTING, AND PARTICIPANTS: Prospective data were collected on patients referred to secondary care with new haematuria. Data were collected for patient variables included in the IDENTIFY risk calculator, cancer outcome, and TNM staging. Machine learning methods were used to evaluate whether better models than those developed with traditional regression methods existed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The area under the receiver operating characteristic curve (AUC) for the detection of urinary tract cancer, calibration coefficient, calibration in the large (CITL), and Brier score were determined. RESULTS AND LIMITATIONS: There were 3582 patients in the validation cohort. The development and validation cohorts were well matched. The AUC of the IDENTIFY risk calculator on the validation cohort was 0.78. This improved to 0.80 on a subanalysis of urothelial cancer prevalent countries alone, with a calibration slope of 1.04, CITL of 0.24, and Brier score of 0.14. The best machine learning model was Random Forest, which achieved an AUC of 0.76 on the validation cohort. There were no cancers stratified to the very-low-risk group in the validation cohort. Most cancers were stratified to the intermediate- and high-risk groups, with more aggressive cancers in higher-risk groups. CONCLUSIONS: The IDENTIFY risk calculator performed well at predicting cancer in patients referred with haematuria on external validation. This tool can be used by urologists to better counsel patients on their cancer risks, to prioritise diagnostic resources on appropriate patients, and to avoid unnecessary invasive procedures in those with a very low risk of cancer. PATIENT SUMMARY: We previously developed a calculator that predicts patients' risk of cancer when they have blood in their urine, based on their personal characteristics. We have validated this risk calculator, by testing it on a separate group of patients to ensure that it works as expected. Most patients found to have cancer tended to be in the higher-risk groups and had more aggressive types of cancer with a higher risk. This tool can be used by clinicians to fast-track high-risk patients based on the calculator and investigate them more thoroughly.

Audit, Feedback, and Education to Improve Quality and Outcomes in Transurethral Resection and Single-Instillation Intravesical Chemotherapy for Nonmuscle Invasive Bladder Cancer Treatment: Protocol for a Multicenter International Observational Study With an Embedded Cluster Randomized Trial.

BACKGROUND: Nonmuscle invasive bladder cancer (NMIBC) accounts for 75% of bladder cancers. It is common and costly. Cost and detriment to patient outcomes and quality of life are driven by high recurrence rates and the need for regular invasive surveillance and repeat treatments. There is evidence that the quality of the initial surgical procedure (transurethral resection of bladder tumor [TURBT]) and administration of postoperative bladder chemotherapy significantly reduce cancer recurrence rates and improve outcomes (cancer progression and mortality). There is surgeon-reported evidence that TURBT practice varies significantly across surgeons and sites. There is limited evidence from clinical trials of intravesical chemotherapy that NMIBC recurrence rate varies significantly between sites and that this cannot be accounted for by differences in patient, tumor, or adjuvant treatment factors, suggesting that how the surgery is performed may be a reason for the variation. OBJECTIVE: This study primarily aims to determine if feedback on and education about surgical quality indicators can improve performance and secondarily if this can reduce cancer recurrence rates. Planned secondary analyses aim to determine what surgeon, operative, perioperative, institutional, and patient factors are associated with better achievement of TURBT quality indicators and NMIBC recurrence rates. METHODS: This is an observational, international, multicenter study with an embedded cluster randomized trial of audit, feedback, and education. Sites will be included if they perform TURBT for NMIBC. The study has four phases: (1) site registration and usual practice survey; (2) retrospective audit; (3) randomization to audit, feedback, and education intervention or to no intervention; and (4) prospective audit. Local and national ethical and institutional approvals or exemptions will be obtained at each participating site. RESULTS: The study has 4 coprimary outcomes, which are 4 evidence-based TURBT quality indicators: a surgical performance factor (detrusor muscle resection); an adjuvant treatment factor (intravesical chemotherapy administration); and 2 documentation factors (resection completeness and tumor features). A key secondary outcome is the early cancer recurrence rate. The intervention is a web-based surgical performance feedback dashboard with educational and practical resources for TURBT quality improvement. It will include anonymous site and surgeon-level peer comparison, a performance summary, and targets. The coprimary outcomes will be analyzed at the site level while recurrence rate will be analyzed at the patient level. The study was funded in October 2020 and began data collection in April 2021. As of January 2023, there were 220 hospitals participating and over 15,000 patient records. Projected data collection end date is June 30, 2023. CONCLUSIONS: This study aims to use a distributed collaborative model to deliver a site-level web-based performance feedback intervention to improve the quality of endoscopic bladder cancer surgery. The study is funded and projects to complete data collection in June 2023. TRIAL REGISTRATION: ClinicalTrials.org NCT05154084; https://clinicaltrials.gov/ct2/show/NCT05154084. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/42254.

Developing a Diagnostic Multivariable Prediction Model for Urinary Tract Cancer in Patients Referred with Haematuria: Results from the IDENTIFY Collaborative Study.

BACKGROUND: Patient factors associated with urinary tract cancer can be used to risk stratify patients referred with haematuria, prioritising those with a higher risk of cancer for prompt investigation. OBJECTIVE: To develop a prediction model for urinary tract cancer in patients referred with haematuria. DESIGN, SETTING, AND PARTICIPANTS: A prospective observational study was conducted in 10 282 patients from 110 hospitals across 26 countries, aged ≥16 yr and referred to secondary care with haematuria. Patients with a known or previous urological malignancy were excluded. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcomes were the presence or absence of urinary tract cancer (bladder cancer, upper tract urothelial cancer [UTUC], and renal cancer). Mixed-effect multivariable logistic regression was performed with site and country as random effects and clinically important patient-level candidate predictors, chosen a priori, as fixed effects. Predictors were selected primarily using clinical reasoning, in addition to backward stepwise selection. Calibration and discrimination were calculated, and bootstrap validation was performed to calculate optimism. RESULTS AND LIMITATIONS: The unadjusted prevalence was 17.2% (n = 1763) for bladder cancer, 1.20% (n = 123) for UTUC, and 1.00% (n = 103) for renal cancer. The final model included predictors of increased risk (visible haematuria, age, smoking history, male sex, and family history) and reduced risk (previous haematuria investigations, urinary tract infection, dysuria/suprapubic pain, anticoagulation, catheter use, and previous pelvic radiotherapy). The area under the receiver operating characteristic curve of the final model was 0.86 (95% confidence interval 0.85-0.87). The model is limited to patients without previous urological malignancy. CONCLUSIONS: This cancer prediction model is the first to consider established and novel urinary tract cancer diagnostic markers. It can be used in secondary care for risk stratifying patients and aid the clinician's decision-making process in prioritising patients for investigation. PATIENT SUMMARY: We have developed a tool that uses a person's characteristics to determine the risk of cancer if that person develops blood in the urine (haematuria). This can be used to help prioritise patients for further investigation.

The IDENTIFY study: the investigation and detection of urological neoplasia in patients referred with suspected urinary tract cancer - a multicentre observational study.

OBJECTIVE: To evaluate the contemporary prevalence of urinary tract cancer (bladder cancer, upper tract urothelial cancer [UTUC] and renal cancer) in patients referred to secondary care with haematuria, adjusted for established patient risk markers and geographical variation. PATIENTS AND METHODS: This was an international multicentre prospective observational study. We included patients aged ≥16 years, referred to secondary care with suspected urinary tract cancer. Patients with a known or previous urological malignancy were excluded. We estimated the prevalence of bladder cancer, UTUC, renal cancer and prostate cancer; stratified by age, type of haematuria, sex, and smoking. We used a multivariable mixed-effects logistic regression to adjust cancer prevalence for age, type of haematuria, sex, smoking, hospitals, and countries. RESULTS: Of the 11 059 patients assessed for eligibility, 10 896 were included from 110 hospitals across 26 countries. The overall adjusted cancer prevalence (n = 2257) was 28.2% (95% confidence interval [CI] 22.3-34.1), bladder cancer (n = 1951) 24.7% (95% CI 19.1-30.2), UTUC (n = 128) 1.14% (95% CI 0.77-1.52), renal cancer (n = 107) 1.05% (95% CI 0.80-1.29), and prostate cancer (n = 124) 1.75% (95% CI 1.32-2.18). The odds ratios for patient risk markers in the model for all cancers were: age 1.04 (95% CI 1.03-1.05; P < 0.001), visible haematuria 3.47 (95% CI 2.90-4.15; P < 0.001), male sex 1.30 (95% CI 1.14-1.50; P < 0.001), and smoking 2.70 (95% CI 2.30-3.18; P < 0.001). CONCLUSIONS: A better understanding of cancer prevalence across an international population is required to inform clinical guidelines. We are the first to report urinary tract cancer prevalence across an international population in patients referred to secondary care, adjusted for patient risk markers and geographical variation. Bladder cancer was the most prevalent disease. Visible haematuria was the strongest predictor for urinary tract cancer.

IDENTIFY: The investigation and detection of urological neoplasia in patients referred with suspected urinary tract cancer: A multicentre cohort study.

•IDENTIFY study: The largest prospective cohort study of haematuria in secondary care.•Contemporary urinary cancer detection rates and diagnostic strategies.•The effectiveness of diagnostic tests, e.g. ultrasound, in detecting urinary cancer.•Novel patient risk factors associated with bladder and upper tract urinary cancers.

Transperineal rectocele repair: a systematic review.

BACKGROUND: Transperineal rectocele repairs, either as isolated fascial repair or in combination with mesh augmentation, are hypothesized to reduce the risk of complications compared with alternative techniques. AIM: The aim of this study was to ascertain long-term success and complication rates following transperineal rectocele repairs. METHOD: A literature search of PubMed and Embase was performed using the terms 'transperineal rectocele', 'rectocele', 'transperineal' and 'repair'. Prospective studies, case series and retrospective case note analyses from 1 January 1994 to 1 December 2016 were included. Those that detailed outcomes of the transperineal approach or compared it to transanal/transvaginal approaches were included. The main outcome measures were reported complications and functional outcome scores. RESULTS: A total of 14 studies were included. Of 566 patients, 333 (58.8%) underwent a transperineal rectocele repair and 220 (41.2%) a transanal repair. Complications were identified in 27 (12.3%) of the 220 transanal repairs and in 41 (12.3%) of the 333 transperineal repairs. A significant complication following transperineal repair was noted in eight studies. There are not enough data to make a reliable comparison between mesh and non-mesh transperineal repairs or to compare biological and synthetic mesh use. LIMITATIONS: Outcome reporting differed between studies, precluding a full meta-analysis. CONCLUSION: Transperineal rectocele repair offers an effective method of symptom improvement and appears to have a similar complication rate as transanal rectocele repair. Concomitant use of synthetic and biological mesh augmentation is becoming more common; however, high-quality comparative data are lacking, so a direct comparison between surgical approaches is not yet possible.

Isolated preputial reconstruction in distal hypospadias.

OBJECTIVE: The aim of this single centre study was to determine: a) the outcome of isolated preputial reconstruction in distal hypospadias and b) overall parental satisfaction. METHODS: A retrospective analysis of case notes was performed to determine outcome. Postal parent-satisfaction questionnaires were devised to quantify subjective assessment of care and outcome. RESULTS: A total of 33 cases of isolated preputial reconstruction were identified between 2006 and 2012. Three sets of notes were untraceable. The median age of the 30 remaining patients at surgery was 23 months (range 11-119). At follow-up, 28 (94%) patients had retractile foreskins that had healed well. One patient (3%) had a foreskin fistula and the parents chose to proceed with circumcision rather than fistula closure. A second patient (3%) developed late phimosis secondary to balanitis xerotica obliterans and also underwent circumcision. Twelve follow-up questionnaires were returned. The median overall success rating of the operation was 4.7/5.0 (94%). All respondents reported that they would recommend the procedure to another parent whose child has a similar diagnosis. CONCLUSION: Isolated preputial reconstruction improves the cosmetic appearances in distal hypospadias, has a low complication rate and offers high parental satisfaction.

Ginkgo biloba for tinnitus.

BACKGROUND: This is an update of a Cochrane review first published in The Cochrane Library in Issue 2, 2004 and previously updated in 2007 and 2009.Tinnitus can be described as the perception of sound in the absence of external acoustic stimulation. At present no specific therapy for tinnitus is acknowledged to be satisfactory in all patients. There are a number of reports in the literature suggesting that Ginkgo biloba may be effective in the management of tinnitus. However, there also appears to be a strong placebo effect in tinnitus management. OBJECTIVES: To assess the effect of Ginkgo biloba in patients who are troubled by tinnitus. SEARCH METHODS: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; AMED; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the most recent search was 12 March 2012. SELECTION CRITERIA: Adults (18 years and over) complaining of tinnitus or adults with a primary complaint of cerebral insufficiency, where tinnitus forms part of the syndrome. DATA COLLECTION AND ANALYSIS: Both original authors independently extracted data and assessed trials for quality. For the 2012 update two authors determined trial eligibility, extracted data, analysed data and updated the contents of the review. MAIN RESULTS: Four trials with a total of 1543 participants were included in the review; we assessed all the included studies as having a low risk of bias. Three trials (1143 participants) included patients with a primary complaint of tinnitus and one (400 participants) included patients with mild to moderate dementia, some of whom had tinnitus.There was no evidence that Gingko biloba was effective in patients with a primary complaint of tinnitus. In the study of patients with dementia, mean baseline levels of tinnitus were low (1.7 to 2.5 on a 10-point subjective symptom rating scale). A small but statistically significant reduction of 1.5 and 0.7 points was seen in patients taking Gingko biloba with vascular dementia and Alzheimer's disease respectively. The practical clinical significance of this is unclear. The incidence of side effects was low. AUTHORS' CONCLUSIONS: The limited evidence does not demonstrate that Ginkgo biloba is effective for tinnitus when this is the primary complaint.

Modifications of the Epley (canalith repositioning) manoeuvre for posterior canal benign paroxysmal positional vertigo (BPPV).

BACKGROUND: Benign paroxsymal positional vertigo (BPPV) is a syndrome characterised by short-lived episodes of vertigo associated with rapid changes in head position. It is a common cause of vertigo presenting to primary care and specialist otolaryngology (ENT) clinics. BPPV of the posterior canal is a specific type of BPPV for which the Epley (canalith repositioning) manoeuvre is a verified treatment. A range of modifications of the Epley manoeuvre are used in clinical practice, including post-Epley vestibular exercises and post-Epley postural restrictions. OBJECTIVES: To assess whether the various modifications of the Epley manoeuvre for posterior canal BPPV enhance its efficacy in clinical practice. SEARCH METHODS: We searched the Cochrane ENT Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the search was 15 December 2011. SELECTION CRITERIA: Randomised controlled trials of modifications of the Epley manoeuvre versus a standard Epley manoeuvre as a control in adults with posterior canal BPPV diagnosed with a positive Dix-Hallpike test. Specific modifications sought were: application of vibration/oscillation to the mastoid region, vestibular rehabilitation exercises, additional steps in the Epley manoeuvre and post-treatment instructions relating to movement restriction. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies from the search results and the third author reviewed and resolved any disagreement. Two authors independently extracted data from the studies using standardised data forms. All authors independently assessed the trials for risk of bias. MAIN RESULTS: The review includes 11 trials involving 855 participants. A total of nine studies used post-Epley postural restrictions as their modification of the Epley manoeuvre. There was no evidence of a difference in the results for post-treatment vertigo intensity or subjective assessment of improvement in individual or pooled data. All nine trials included the conversion of a positive to a negative Dix-Hallpike test as an outcome measure. Pooled data identified a significant difference from the addition of postural restrictions in the frequency of Dix-Hallpike conversion when compared to the Epley manoeuvre alone. In the experimental group 88.7% (220 out of 248) patients versus 78.2% (219 out of 280) in the control group converted from a positive to negative Dix-Hallpike test (risk ratio (RR) 1.13, 95% confidence interval (CI) 1.05 to 1.22, P = 0.002). No serious adverse effects were reported, however three studies reported minor complications such as neck stiffness, horizontal BPPV, dizziness and disequilibrium in some patients.There was no evidence of benefit of mastoid oscillation applied during the Epley manoeuvre, or of additional steps in the Epley manoeuvre. No adverse effects were reported. AUTHORS' CONCLUSIONS: There is evidence supporting a statistically significant effect of post-Epley postural restrictions in comparison to the Epley manoeuvre alone. However, it important to note that this statistically significant effect only highlights a small improvement in treatment efficacy. An Epley manoeuvre alone is effective in just under 80% of patients with typical BPPV. The additional intervention of postural restrictions has a number needed to treat (NNT) of 10. The addition of postural restrictions does not expose the majority of patients to risk of harm, does not pose a major inconvenience, and can be routinely discussed and advised. Specific patients who experience discomfort due to wearing a cervical collar and inconvenience in sleeping upright may be treated with the Epley manoeuvre alone and still expect to be cured in most instances.There is insufficient evidence to support the routine application of mastoid oscillation during the Epley manoeuvre, or additional steps in an 'augmented' Epley manoeuvre. Neither treatment is associated with adverse outcomes. Further studies should employ a rigorous randomisation technique, blinded outcome assessment, a post-treatment Dix-Hallpike test as an outcome measure and longer-term follow-up of patients.