The Improved Kidney Risk Score in ANCA-Associated Vasculitis for Clinical Practice and Trials.

SIGNIFICANCE STATEMENT: Reliable prediction tools are needed to personalize treatment in ANCA-associated GN. More than 1500 patients were collated in an international longitudinal study to revise the ANCA kidney risk score. The score showed satisfactory performance, mimicking the original study (Harrell's C=0.779). In the development cohort of 959 patients, no additional parameters aiding the tool were detected, but replacing the GFR with creatinine identified an additional cutoff. The parameter interstitial fibrosis and tubular atrophy was modified to allow wider access, risk points were reweighted, and a fourth risk group was created, improving predictive ability (C=0.831). In the validation, the new model performed similarly well with excellent calibration and discrimination ( n =480, C=0.821). The revised score optimizes prognostication for clinical practice and trials. BACKGROUND: Reliable prediction tools are needed to personalize treatment in ANCA-associated GN. A retrospective international longitudinal cohort was collated to revise the ANCA renal risk score. METHODS: The primary end point was ESKD with patients censored at last follow-up. Cox proportional hazards were used to reweight risk factors. Kaplan-Meier curves, Harrell's C statistic, receiver operating characteristics, and calibration plots were used to assess model performance. RESULTS: Of 1591 patients, 1439 were included in the final analyses, 2:1 randomly allocated per center to development and validation cohorts (52% male, median age 64 years). In the development cohort ( n =959), the ANCA renal risk score was validated and calibrated, and parameters were reinvestigated modifying interstitial fibrosis and tubular atrophy allowing semiquantitative reporting. An additional cutoff for kidney function (K) was identified, and serum creatinine replaced GFR (K0: <250 µ mol/L=0, K1: 250-450 µ mol/L=4, K2: >450 µ mol/L=11 points). The risk points for the percentage of normal glomeruli (N) and interstitial fibrosis and tubular atrophy (T) were reweighted (N0: >25%=0, N1: 10%-25%=4, N2: <10%=7, T0: none/mild or <25%=0, T1: ≥ mild-moderate or ≥25%=3 points), and four risk groups created: low (0-4 points), moderate (5-11), high (12-18), and very high (21). Discrimination was C=0.831, and the 3-year kidney survival was 96%, 79%, 54%, and 19%, respectively. The revised score performed similarly well in the validation cohort with excellent calibration and discrimination ( n =480, C=0.821). CONCLUSIONS: The updated score optimizes clinicopathologic prognostication for clinical practice and trials.

Fecal Urgency in Ulcerative Colitis: Impact on Quality of Life and Psychological Well-Being in Active and Inactive Disease States.

Ulcerative colitis (UC) is a chronic, relapsing-and-remitting, potentially progressive form of inflammatory bowel disease (IBD) with multidimensional and often negative effects on patients' lives. Fecal urgency, the sudden and compelling desire to defecate, often accompanied by impaired bowel control leading to frequent and urgent trips to the bathroom, is a distressing symptom, experienced by more than 50% of patients with UC.1 Physicians frequently underestimate the burden of fecal urgency on patients' lives, with ramifications ranging from disruption in daily activities, social interactions, and emotional distress with resultant impairment in quality of life (QoL).2,3.

Risk Stratification to Predict Renal Survival in Anti-Glomerular Basement Membrane Disease.

SIGNIFICANCE STATEMENT: Most patients with anti-glomerular basement membrane (GBM) disease present with rapidly progressive glomerulonephritis, and more than half develop ESKD. Currently, no tools are available to aid in the prognostication or management of this rare disease. In one of the largest assembled cohorts of patients with anti-GBM disease (with 174 patients included in the final analysis), the authors demonstrated that the renal risk score for ANCA-associated vasculitis is transferable to anti-GBM disease and the renal histology is strongly predictive of renal survival and recovery. Stratifying patients according to the percentage of normal glomeruli in the kidney biopsy and the need for RRT at the time of diagnosis improves outcome prediction. Such stratification may assist in the management of anti-GBM disease. BACKGROUND: Prospective randomized trials investigating treatments and outcomes in anti-glomerular basement membrane (anti-GBM) disease are sparse, and validated tools to aid prognostication or management are lacking. METHODS: In a retrospective, multicenter, international cohort study, we investigated clinical and histologic parameters predicting kidney outcome and sought to identify patients who benefit from rescue immunosuppressive therapy. We also explored applying the concept of the renal risk score (RRS), currently used to predict renal outcomes in ANCA-associated vasculitis, to anti-GBM disease. RESULTS: The final analysis included 174 patients (out of a total of 191). Using Cox and Kaplan-Meier methods, we found that the RRS was a strong predictor for ESKD. The 36-month renal survival was 100%, 62.4%, and 20.7% in the low-risk, moderate-risk, and high-risk groups, respectively. The need for renal replacement therapy (RRT) at diagnosis and the percentage of normal glomeruli in the biopsy were independent predictors of ESKD. The best predictor for renal recovery was the percentage of normal glomeruli, with a cut point of 10% normal glomeruli providing good stratification. A model with the predictors RRT and normal glomeruli ( N ) achieved superior discrimination for significant differences in renal survival. Dividing patients into four risk groups led to a 36-month renal survival of 96.4% (no RRT, N ≥10%), 74.0% (no RRT, N <10%), 42.3% (RRT, N ≥10%), and 14.1% (RRT, N <10%), respectively. CONCLUSIONS: These findings demonstrate that the RRS concept is transferrable to anti-GBM disease. Stratifying patients according to the need for RRT at diagnosis and renal histology improves prediction, highlighting the importance of normal glomeruli. Such stratification may assist in the management of anti-GBM disease. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/JASN/2023_02_27_JASN0000000000000060.mp3.

Mobile audiometry for hearing threshold assessment: A systematic review and meta-analysis.

OBJECTIVES: Technological advancements in mobile audiometry (MA) have enabled hearing assessment using tablets and smartphones. This systematic review (PROSPERO ID: CRD42021274761) aimed to identify MA options available to health providers, assess their accuracy in measuring hearing thresholds, and explore factors that might influence their accuracy. DESIGN AND SETTING: A systematic search of online databases including PubMed, Embase, Cochrane, Evidence Search and Dynamed was conducted on 13th December 2021, and repeated on 30th October 2022, using appropriate Medical Subject Headings (MeSH) terms. Eligible studies reported the use of MA to determine hearing thresholds and compared results to conventional pure-tone audiometry (CA). Studies investigating MA for hearing screening (i.e. reporting just pass/fail) were ineligible for inclusion. Two authors independently reviewed studies, extracted data, and assessed methodological quality and risk of bias using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. PARTICIPANTS: Adults and children, with and without diagnosis of hearing impairment. MAIN OUTCOME MEASURES: A meta-analysis was performed to obtain the mean difference between thresholds measured using MA and CA in dB HL. RESULTS: Searches returned 858 articles. After systematic review, 17 articles including 1032 participants were analysed. The most used software application was ShoeboxTM (6/17) followed by Hearing TestTM (3/17), then HearTestTM (2/17). Tablet computers were used in ten studies, smartphones in six, and a computer in one. The mean difference between MA and CA thresholds was 1.36 dB (95% CI, 0.07-2.66, p = 0.04). Significant differences between mobile audiometry (MA) and conventional audiometry (CA) thresholds were observed in thresholds measured at 500Hz, in children, when MA was conducted in a sound booth, and when MA was self-administered. However, these differences did not exceed the clinically significant threshold of 10 decibels (dB). Included studies exhibited high levels of heterogeneity, high risk of bias and low concerns about applicability. CONCLUSIONS: MA compares favourably to CA in measuring hearing thresholds and has role in providing access to hearing assessment in situations where CA is not available or feasible. Future studies should prioritize the integration of pure-tone threshold assessment with additional tests, such as Speech Recognition and Digits-in-Noise, for a more rounded evaluation of hearing ability, assesses acceptability and feasibility, and the cost-effectiveness of MA in non-specialist settings.

Risk factors associated with the development of chronic suppurative otitis media in children: Systematic review and meta-analysis.

OBJECTIVES: Chronic suppurative otitis media (CSOM) is defined as persistent discharge through a tympanic membrane perforation for greater than 2 weeks. It is associated with a significant disease burden, including hearing loss, and reducing its incidence could significantly improve short- and long-term health. We aimed to identify risk factors associated with the development of CSOM in children. DESIGN AND SETTING: Systematic review and meta-analysis of studies set in community, primary and secondary care settings, identified from Medline, Embase and Cochrane databases from 2000 to 2022. PARTICIPANTS: Children 16 years old and below. MAIN OUTCOME MEASURES: Clinical diagnosis of CSOM. RESULTS: In total, 739 papers were screened, with 12 deemed eligible for inclusion in the systematic review, of which, 10 were included in the meta-analysis. Risk factors examined included perinatal, patient, dietary, environmental and parental factors. Meta-analysis results indicate that atopy (RR = 1.18, 95% CI [1.01-1.37], p = .04, 2 studies); and birth weight <2500 g (RR = 1.79 [1.27-2.50], p < .01, 2 studies) are associated with an increased risk of CSOM development. Factors not associated were male sex (RR = 0.96 [0.82-1.13], p = .62, 8 studies); exposure to passive smoking (RR = 1.27 [0.81-2.01], p = .30, 3 studies); and parental history of otitis media (RR = 1.14 [0.59-2.20], p = .69, 2 studies). CONCLUSION: Optimal management of risk factors associated with CSOM development will help reduce the burden of disease and prevent disease progression or recurrence. The current quality of evidence in the literature is variable and heterogeneous. Future studies should aim to use standardised classification systems to define risk factors to allow meta-analysis.

Rethinking Blood Eosinophils for Assessing ICS Response in COPD: A Post-Hoc Analysis from FLAME.

BACKGROUND: The varied treatment response to inhaled corticosteroids (ICS) in COPD, and the increased risk of pneumonia necessitate a personalised ICS therapeutic approach. This is informed by blood eosinophil count (BEC), which predicts ICS treatment response. However, BEC appears to change in response to ICS treatment. RESEARCH QUESTION: Does BEC measured on or off ICS treatment or the change in BEC during ICS treatment, best predict treatment response to ICS in COPD? STUDY DESIGN AND METHODS: FLAME, a 52-week, double-blind RCT compared LABA/LAMA versus LABA/ICS. Corticosteroids were prohibited during a 4-week run-in period. We chose patients previously on ICS, thereby allowing pre- and post-run-in period BEC to represent BEC on and off ICS, respectively. In this post-hoc analysis, we revisited outcome data, exploring how the three BEC biomarkers interacted with treatment response to the ICS containing regimen. RESULTS: Our study confirms that LABA/LAMA combination is superior, or at least non-inferior, to LABA/ICS in curbing exacerbations for most FLAME participants. However, higher BEC off and BEC on ICS and significant BEC suppression during ICS treatment corresponded to superior response to LABA/ICS in terms of exacerbation rate, time-to-first exacerbation, and time-to-first pneumonia. In a subgroup, including 9% of participants, BEC changed significantly during ICS treatment (≥200 cells/µL), and higher BEC on ICS did not predict ICS treatment response. For these patients, BEC off ICS and BEC change proved more predictive. Excess pneumonia risk associated with ICS appeared to be confined to patients who do not benefit from this treatment. BEC were not predictive of treatment effects on lung function and health status. INTERPRETATION: This exploratory analysis advocates preferentially using BEC off ICS or BEC change during ICS treatment for guiding ICS treatment decisions. BEC measured on ICS is less predictive of treatment response. CLINICAL TRIAL REGISTRATION: NCT01782326.

External Validation of Prognostic Models in Critical Care: A Cautionary Tale From COVID-19 Pneumonitis.

OBJECTIVES BACKGROUND: To externally validate clinical prediction models that aim to predict progression to invasive ventilation or death on the ICU in patients admitted with confirmed COVID-19 pneumonitis. DESIGN: Single-center retrospective external validation study. DATA SOURCES: Routinely collected healthcare data in the ICU electronic patient record. Curated data recorded for each ICU admission for the purposes of the U.K. Intensive Care National Audit and Research Centre (ICNARC). SETTING: The ICU at Manchester Royal Infirmary, Manchester, United Kingdom. PATIENTS: Three hundred forty-nine patients admitted to ICU with confirmed COVID-19 Pneumonitis, older than 18 years, from March 1, 2020, to February 28, 2022. Three hundred two met the inclusion criteria for at least one model. Fifty-five of the 349 patients were admitted before the widespread adoption of dexamethasone for the treatment of severe COVID-19 (pre-dexamethasone patients). OUTCOMES: Ability to be externally validated, discriminate, and calibrate. METHODS: Articles meeting the inclusion criteria were identified, and those that gave sufficient details on predictors used and methods to generate predictions were tested in our cohort of patients, which matched the original publications' inclusion/exclusion criteria and endpoint. RESULTS: Thirteen clinical prediction articles were identified. There was insufficient information available to validate models in five of the articles; a further three contained predictors that were not routinely measured in our ICU cohort and were not validated; three had performance that was substantially lower than previously published (range C-statistic = 0.483-0.605 in pre-dexamethasone patients and C = 0.494-0.564 among all patients). One model retained its discriminative ability in our cohort compared with previously published results (C = 0.672 and 0.686), and one retained performance among pre-dexamethasone patients but was poor in all patients (C = 0.793 and 0.596). One model could be calibrated but with poor performance. CONCLUSIONS: Our findings, albeit from a single center, suggest that the published performance of COVID-19 prediction models may not be replicated when translated to other institutions. In light of this, we would encourage bedside intensivists to reflect on the role of clinical prediction models in their own clinical decision-making.

Treating Tobacco Dependency in National Health Service Workers in Greater Manchester: An Evaluation of a Bespoke Digital Service.

Introduction: Treating tobacco dependency in National Health Service (NHS) workers delivers substantial benefits at an individual, population, and health care system level. We report the outcomes from the Greater Manchester Integrated Care Partnership's tobacco dependency treatment program for NHS workers which includes 6-months' access to behavioral support and 12 weeks of treatment through a digital application. Methods: Aggregate results for all participants across the program from January 1, 2022, to September 1, 2023, are reported including a deep-dive evaluation of 300 participants recruited to provide chemically validated outcomes. Results: A total of 1567 NHS workers participated in the program within the evaluation period, completing 24,048 sessions with specialist advisors within the application, ordering 18,710 nicotine vape liquids, 6927 nicotine patches, and 297 short-acting nicotine products. Users reported achieving 89,464 smoke-free days, 1,258,069 less cigarettes smoked, and a financial saving of £622,231. The deep-dive evaluation revealed a CO-verified 12-week abstinence rate of 37% (111 of 300). Conclusion: This evaluation provides assurance of clinical effectiveness within a bespoke digital tobacco dependency treatment program for NHS workers across an Integrated Care Partnership.

The prevalence and burden of Rome IV faecal incontinence in ulcerative colitis: A cross-sectional study.

BACKGROUND: Despite advances in ulcerative colitis (UC) therapies, a relatively undefined proportion of patients experience faecal incontinence (FI) in the absence of active inflammation. For this group, there remains a significant unmet need with a limited evidence base. AIMS: We aimed to estimate the prevalence and impact of FI in UC. METHODS: In a prospective cross-sectional study, patients with UC completed a series of validated questionnaires, including Rome IV FI criteria, an inflammatory bowel disease (IBD)-specific FI questionnaire (ICIQ-IBD), Hospital Anxiety and Depression Scale and IBD-Control. UC remission was defined as faecal calprotectin (FCP) ≤250 µg/g, or IBD-control 8 score ≥13 and IBD-Control-VAS ≥ 85. RESULTS: Of 255 patients with UC, overall, 20.4% fulfilled Rome IV criteria for FI. Rome IV FI prevalence did not differ between active and quiescent UC regardless of whether disease activity was defined by IBD-Control scores ± FCP (p = 0.25), or objectively with FCP thresholds of 250 µg/g (p = 0.86) and 100 µg/g (p = 0.95). Most patients (75.2%) reported FI when in 'remission' and during 'relapse' (90.6%) according to ICIQ-IBD. Those who reported FI according to both ICIQ-IBD and Rome IV definitions had higher anxiety, depression and worse quality-of-life (QoL) scores (p < 0.05). In those with Rome IV FI, there was a strong correlation between FI symptom severity and impaired QoL (r = 0.809, p < 0.001). CONCLUSIONS: The prevalence of FI in UC is high, even in remission, and associated with significant psychological distress, symptom burden and impaired QoL. These findings highlight the urgent need for further research and development of evidence-based treatments for FI in UC.

PLA2R Antibody Does Not Outperform Conventional Clinical Markers in Predicting Outcomes in Membranous Nephropathy.

Introduction: The prognostic value of PLA2R antibody (Ab) test in clinical practice remains unclear. We aimed to evaluate its ability in predicting hard outcomes in primary membranous nephropathy (PMN) after adjustments to conventional markers of disease activity. Methods: A total of 222 patients diagnosed with PMN from January 2003 to July 2019 having had a serum PLA2R Ab test, were included from 3 centers in the north of England. Baseline conventional markers, PLA2R-Ab-status (positive vs. negative), Ab-titer (high vs. low), and time of testing (pre-PLA2R era vs. PLA2R era) were evaluated for association with outcomes. Primary outcome was time to progression (composite of doubling of creatinine, stage 5 chronic kidney disease, or death). Secondary outcomes were time to partial remission (PR) and time to immunosuppression. Cox proportional hazard testing was used. Results: During a median follow-up of 5.26 years, progression was seen in 65 (29.3%) and PR in 179 of 222 patients (80.6%). There was a clear association of estimated glomerular filtration rate (eGFR) (standardized hazard ratio [HRZ] = 0.767, P < 0.05) and urine protein-to-creatinine ratio (uPCR) (HRZ = 1.44, P < 0.005) with time to progression among all patients, and eGFR (HRZ = 0.606, P < 0.005) in Ab-positive patients. Baseline Ab-positivity was not associated with time to progression (adjusted hazard ratio [aHR] = 0.93, P = 0.71) or time to PR (aHR = 0.84, P = 0.13). Similarly, baseline high Ab-titer was not associated with time to progression (aHR = 1.07, P = 0.77) or time to PR (aHR = 0.794, P = 0.08). Conclusion: Once adjusted to conventional markers of disease activity, baseline PLA2R Ab-positivity or Ab-titer do not predict disease progression or time to PR. Further studies are needed to harness the utility of PLA2R Ab test in prognostication in PMN.

Evaluating the impact of an enhanced triage process on the performance and diagnostic yield of oesophageal physiology studies post COVID-19.

OBJECTIVES: The COVID-19 pandemic significantly impacted on the provision of oesophageal physiology investigations. During the recovery phase, triaging tools were empirically recommended by national bodies for prioritisation of referrals amidst rising waiting lists and reduced capacity. We evaluated the performance of an enhanced triage process (ETP) consisting of telephone triage combined with the hierarchical 'traffic light system' recommended in the UK for prioritising oesophageal physiology referrals. DESIGN: In a cross-sectional study of patients referred for oesophageal physiology studies at a tertiary centre, data were compared between patients who underwent oesophageal physiology studies 6 months prior to the COVID-19 pandemic and those who were investigated within 6 months after service resumption with implementation of the ETP. OUTCOME MEASURES: Adjusted time from referral to investigation; non-attendance rates; the detection of Chicago Classification (CC) oesophageal motility disorders on oesophageal manometry and severity of acid reflux on 24 hours pH/impedance monitoring. RESULTS: Following service resumption, the ETP reduced non-attendance rates from 9.1% to 2.8% (p=0.021). Use of the 'traffic light system' identified a higher proportion of patients with CC oesophageal motility disorders in the 'amber' and 'red' triage categories, compared with the 'green' category (p=0.011). ETP also reduced the time to test for those who were subsequently found to have a major CC oesophageal motility diagnosis compared with those with minor CC disorders and normal motility (p=0.004). The ETP did not affect the yield or timing of acid reflux studies. CONCLUSION: ETPs can effectively prioritise patients with oesophageal motility disorders and may therefore have a role beyond the current pandemic.