Delayed post gadolinium MRI descriptors for Meniere's disease: a systematic review and meta-analysis.

OBJECTIVES: Delayed post-gadolinium magnetic resonance imaging (MRI) detects changes of endolymphatic hydrops (EH) within the inner ear in Meniere's disease (MD). A systematic review with meta-analysis was conducted to summarise the diagnostic performance of MRI descriptors across the range of MD clinical classifications. MATERIALS AND METHODS: Case-controlled studies documenting the diagnostic performance of MRI descriptors in distinguishing MD ears from asymptomatic ears or ears with other audio-vestibular conditions were identified (MEDLINE, EMBASE, Web of Science, Scopus databases: updated 17/2/2022). Methodological quality was evaluated with Quality Assessment of Diagnostic Accuracy Studies version 2. Results were pooled using a bivariate random-effects model for evaluation of sensitivity, specificity and diagnostic odds ratio (DOR). Meta-regression evaluated sources of heterogeneity, and subgroup analysis for individual clinical classifications was performed. RESULTS: The meta-analysis included 66 unique studies and 3073 ears with MD (mean age 40.2-67.2 years), evaluating 11 MRI descriptors. The combination of increased perilymphatic enhancement (PLE) and EH (3 studies, 122 MD ears) achieved the highest sensitivity (87% (95% CI: 79.92%)) whilst maintaining high specificity (91% (95% CI: 85.95%)). The diagnostic performance of "high grade cochlear EH" and "any EH" descriptors did not significantly differ between monosymptomatic cochlear MD and the latest reference standard for definite MD (p = 0.3; p = 0.09). Potential sources of bias were case-controlled design, unblinded observers and variable reference standard, whilst differing MRI techniques introduced heterogeneity. CONCLUSIONS: The combination of increased PLE and EH optimised sensitivity and specificity for MD, whilst some MRI descriptors also performed well in diagnosing monosymptomatic cochlear MD. KEY POINTS: • A meta-analysis of delayed post-gadolinium magnetic resonance imaging (MRI) for the diagnosis of Meniere's disease is reported for the first time and comprised 66 studies (3073 ears). • Increased enhancement of the perilymphatic space of the inner ear is shown to be a key MRI feature for the diagnosis of Meniere's disease. • MRI diagnosis of Meniere's disease can be usefully applied across a range of clinical classifications including patients with cochlear symptoms alone.

Association of dynamic contrast-enhanced MRI and 18F-Fluorodeoxyglucose PET/CT parameters with neoadjuvant therapy response and survival in esophagogastric cancer.

INTRODUCTION: Better predictive markers are needed to deliver individualized care for patients with primary esophagogastric cancer. This exploratory study aimed to assess whether pre-treatment imaging parameters from dynamic contrast-enhanced MRI and 18F-fluorodeoxyglucose (18F-FDG) PET/CT are associated with response to neoadjuvant therapy or outcome. MATERIALS AND METHODS: Following ethical approval and informed consent, prospective participants underwent dynamic contrast-enhanced MRI and 18F-FDG PET/CT prior to neoadjuvant chemotherapy/chemoradiotherapy ± surgery. Vascular dynamic contrast-enhanced MRI and metabolic 18F-FDG PET parameters were compared by tumor characteristics using Mann Whitney U test and with pathological response (Mandard tumor regression grade), recurrence-free and overall survival using logistic regression modelling, adjusting for predefined clinical variables. RESULTS: 39 of 47 recruited participants (30 males; median age 65 years, IQR: 54, 72 years) were included in the final analysis. The tumor vascular-metabolic ratio was higher in patients remaining node positive following neoadjuvant therapy (median tumor peak enhancement/SUVmax ratio: 0.052 vs. 0.023, p = 0.02). In multivariable analysis adjusted for age, gender, pre-treatment tumor and nodal stage, peak enhancement (highest gadolinium concentration value prior to contrast washout) was associated with pathological tumor regression grade. The odds of response decreased by 5% for each 0.01 unit increase (OR 0.95; 95% CI: 0.90, 1.00, p = 0.04). No 18F-FDG PET/CT parameters were predictive of pathological tumor response. No relationships between pre-treatment imaging and survival were identified. CONCLUSION: Pre-treatment esophagogastric tumor vascular and metabolic parameters may provide additional information in assessing response to neoadjuvant therapy.

Intraoperative bowel perfusion assessment methods and their effects on anastomotic leak rates: meta-analysis.

BACKGROUND: Anastomotic leak is one of the most feared complications of colorectal surgery, and probably linked to poor blood supply to the anastomotic site. Several technologies have been described for intraoperative assessment of bowel perfusion. This systematic review and meta-analysis aimed to evaluate the most frequently used bowel perfusion assessment modalities in elective colorectal procedures, and to assess their associated risk of anastomotic leak. Technologies included indocyanine green fluorescence angiography, diffuse reflectance spectroscopy, laser speckle contrast imaging, and hyperspectral imaging. METHODS: The review was preregistered with PROSPERO (CRD42021297299). A comprehensive literature search was performed using Embase, MEDLINE, Cochrane Library, Scopus, and Web of Science. The final search was undertaken on 29 July 2022. Data were extracted by two reviewers and the MINORS criteria were applied to assess the risk of bias. RESULTS: Some 66 eligible studies involving 11 560 participants were included. Indocyanine green fluorescence angiography was most used with 10 789 participants, followed by diffuse reflectance spectroscopy with 321, hyperspectral imaging with 265, and laser speckle contrast imaging with 185. In the meta-analysis, the total pooled effect of an intervention on anastomotic leak was 0.05 (95 per cent c.i. 0.04 to 0.07) in comparison with 0.10 (0.08 to 0.12) without. Use of indocyanine green fluorescence angiography, hyperspectral imaging, or laser speckle contrast imaging was associated with a significant reduction in anastomotic leak. CONCLUSION: Bowel perfusion assessment reduced the incidence of anastomotic leak, with intraoperative indocyanine green fluorescence angiography, hyperspectral imaging, and laser speckle contrast imaging all demonstrating comparable results.

Clinical utility of DaTscan in patients with suspected Parkinsonian syndrome: a systematic review and meta-analysis.

Images of DaTscan (ioflupane [123I] SPECT) have been used as an adjunct to clinical diagnosis to facilitate the differential diagnosis of neurodegenerative (ND) Parkinsonian Syndrome (PS) vs. non-dopamine deficiency aetiologies of Parkinsonism. Despite several systematic reviews having summarised the evidence on diagnostic accuracy, the impact of imaging results on clinical utility has not been systematically assessed. Our objective was to examine the available evidence on the clinical utility of DaTscan imaging in changing diagnosis and subsequent management of patients with suspected PS. We performed a systematic review of published studies of clinical utility from 2000 to 2019 without language restrictions. A meta-analysis of change in diagnosis and management rates reported from each study was performed using a random-effects model and logit transformation. Sub-group analysis, meta-regression and sensitivity analysis was performed to explore heterogeneity. Twenty studies met the inclusion criteria. Thirteen of these contributed to the meta-analyses including 950 and 779 patients with a reported change in management and change in diagnosis, respectively. The use of DaTscan imaging resulted in a change in management in 54% (95% CI: 47-61%) of patients. Change in diagnosis occurred in 31% (95% CI: 22-42%) of patients. The two pooled analyses were characterised by high levels of heterogeneity. Our systematic review and meta-analysis show that imaging with DaTscan was associated with a change in management in approximately half the patients tested and the diagnosis was modified in one third. Regardless of time from symptom onset to scan results, these changes were consistent. Further research focusing on specific patient subgroups could provide additional evidence on the impact on clinical outcomes.

Stereotactic ablative body radiotherapy in patients with oligometastatic cancers: a prospective, registry-based, single-arm, observational, evaluation study.

BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is increasingly being used to treat oligometastatic cancers, but high-level evidence to provide a basis for policy making is scarce. Additional evidence from a real-world setting is required. We present the results of a national study of patients with extracranial oligometastases undergoing SABR, representing the largest dataset, to our knowledge, on outcomes in this population so far. METHODS: In 2015, National Health Service (NHS) England launched a Commissioning through Evaluation scheme that funded a prospective, registry-based, single-arm, observational, evaluation study of patients with solid cancer and extracranial oligometastases treated with SABR. Prescribed doses ranged from 24-60 Gy administered in three to eight fractions. The study was done at 17 NHS radiotherapy centres in England. Patients were eligible for the scheme if aged 18 years or older with confirmed primary carcinoma (excluding haematological malignancies), one to three extracranial metastatic lesions, a disease-free interval from primary tumour development to metastases of longer than 6 months (with the exception of synchronous colorectal liver metastases), a WHO performance status of 2 or lower, and a life expectancy of at least 6 months. The primary outcome was overall survival at 1 year and 2 years from the start of SABR treatment. The study is now completed. FINDINGS: Between June 15, 2015, and Jan 30, 2019, 1422 patients were recruited from 17 hospitals in England. The median age of the patients was 69 years (IQR 62-76), and the most common primary tumour was prostate cancer (406 [28·6%] patients). Median follow-up was 13 months (IQR 6-23). Overall survival was 92·3% (95% CI 90·5-93·9) at 1 year and 79·2% (76·0-82·1) at 2 years. The most common grade 3 adverse event was fatigue (28 [2·0%] of 1422 patients) and the most common serious (grade 4) event was increased liver enzymes (nine [0·6%]). Notreatment-related deaths were reported. INTERPRETATION: In patients with extracranial oligometastatic cancer, use of SABR was associated with high overall survival and low toxicity. 'The study findings complement existing evidence from a randomised, phase 2 trial, and represent high-level, real-world evidence supporting the use of SABR in this patient cohort, with a phase 3 randomised, controlled trial to confirm these findings underway. Based on the selection criteria in this study, SABR was commissioned by NHS England in March, 2020, as a treatment option for patients with oligometastatic disease. FUNDING: NHS England Commissioning through Evaluation scheme.

A prospective cohort study of biopsychosocial factors associated with childhood urinary incontinence.

The objective of the study was to examine the association between biopsychosocial factors and developmental trajectories of childhood urinary incontinence (UI). We used developmental trajectories (latent classes) of childhood UI from 4-9 years including bedwetting alone, daytime wetting alone, delayed (daytime and nighttime) bladder control, and persistent (day and night) wetting (n = 8751, 4507 boys, 4244 girls). We examined whether biopsychosocial factors (developmental level, gestational age, birth weight, parental UI, temperament, behaviour/emotional problems, stressful events, maternal depression, age at initiation of toilet training, constipation) are associated with the trajectories using multinomial logistic regression (reference category = normative development of bladder control). Maternal history of bedwetting was associated with almost a fourfold increase in odds of persistent wetting [odds ratio and 95% confidence interval: 3.60 (1.75-7.40)]. In general, difficult temperament and behaviour/emotional problems were most strongly associated with combined (day and night) wetting, e.g. children with behavioural difficulties had increased odds of delayed (daytime and nighttime) bladder control [1.80 (1.59-2.03)]. Maternal postnatal depression was associated with persistent (day and night) wetting [2.09 (1.48-2.95)] and daytime wetting alone [2.38 (1.46-3.88)]. Developmental delay, stressful events, and later initiation of toilet training were not associated with bedwetting alone, but were associated with the other UI trajectories. Constipation was only associated with delayed bladder control. We find evidence that different trajectories of childhood UI are differentially associated with biopsychosocial factors. Increased understanding of factors associated with different trajectories of childhood UI could help clinicians to identify children at risk of persistent incontinence.

Psychosocial risks for constipation and soiling in primary school children.

To examine prospective associations between psychosocial problems and childhood constipation and soiling. We used latent classes of constipation and soiling ('constipation alone', 'soiling alone', 'constipation with soiling') extracted from longitudinal maternally reported data on constipation (4-10 years) and soiling (4-9 years) from 8435 children (4353 males, 4082 females) from the ALSPAC cohort. We examined the association between maternally reported psychosocial problems at 2-3 years (difficult temperament, behaviour/emotional problems, temper tantrums, behavioural sleep problems and stressful events) and the latent classes using multinomial logistic regression adjusted for a range of confounders relating to the child and family (reference category = normative latent class with very low probability of constipation/soiling). Difficult temperament and emotional/behaviour problems were associated with increased odds of constipation and soiling. Associations were generally strongest for 'constipation with soiling', e.g. difficult mood: 1.42 (1.23-1.64); behaviour problems: 1.48 (1.28-1.71); temper tantrums: 1.89 (1.34-2.65); lack of a regular sleep routine 2.09 (1.35-3.25). Stressful life events were associated with constipation alone [1.23 (1.12-1.36)] and constipation with soiling [1.32 (1.14-1.52)], but not soiling alone. Additional comparisons of the non-normative latent classes provided evidence for differential associations with the risk factors, e.g. frequent temper tantrums were associated with a greater than twofold increase in the odds of constipation with soiling versus constipation alone. Psychosocial problems in early childhood are risk factors for constipation and soiling at school age. An increased understanding of early risk factors for constipation and soiling could aid the identification of children who require treatment.

Examining the effectiveness of parental strategies to overcome bedwetting: an observational cohort study.

OBJECTIVE: To examine whether a range of common strategies used by parents to overcome bedwetting in 7½-year-old children (including lifting, restricting drinks before bedtime, regular daytime toilet trips, rewards, showing displeasure and using protection pants) are effective in reducing the risk of bedwetting at 9½ years. DESIGN: Prospective cohort study. SETTING: General community. PARTICIPANTS: The starting sample included 1258 children (66.7% boys and 33.2% girls) who were still bedwetting at 7½ years. OUTCOME MEASURE: Risk of bedwetting at 9½ years. RESULTS: Using propensity score-based methods, we found that two of the parental strategies used at 7½ years were associated with an increased risk of bedwetting at 9½ years, after adjusting the model for child and family variables and other parental strategies: lifting (risk difference=0.106 (95% CI 0.009 to 0.202), ie, there is a 10.6% (0.9% to 20.2%) increase in risk of bedwetting at 9½ years among children whose parents used lifting compared with children whose parents did not use this strategy) and restricting drinks before bedtime (0.123 (0.021 to 0.226)). The effect of using the other parental strategies was in either direction (an increase or decrease in the risk of bedwetting at 9½ years), for example, showing displeasure (-0.052 (-0.214 to 0.110)). When we re-analysed the data using multivariable regression analysis, the results were mostly consistent with the propensity score-based methods. CONCLUSION: These findings provide evidence that common strategies used to overcome bedwetting in 7½-year-olds are not effective in reducing the risk of bedwetting at 9½ years. Parents should be encouraged to seek professional advice for their child's bedwetting rather than persisting with strategies that may be ineffective.

Trajectories of urinary incontinence in childhood and bladder and bowel symptoms in adolescence: prospective cohort study.

OBJECTIVES: To identify different patterns (trajectories) of childhood urinary incontinence and examine which patterns are associated with bladder and bowel symptoms in adolescence. DESIGN: Prospective cohort study. SETTING: General community. PARTICIPANTS: The starting sample included 8751 children (4507 men and 4244 women) with parent-reported data on frequency of bedwetting and daytime wetting for at least three of five time points (4½, 5½, 6½, 7½ and 9½ years-hereafter referred to as 4-9 years). Study children provided data on a range of bladder and bowel symptoms at age 14 (data available for 5899 participants). OUTCOME MEASURES: Self-reported bladder and bowel symptoms at 14 years including daytime wetting, bedwetting, nocturia, urgency, frequent urination, low voided volume, voiding postponement, passing hard stools and low stool frequency. RESULTS: We extracted 5 trajectories of urinary incontinence from 4 to 9 years using longitudinal latent class analysis: (1) normative development of daytime and night-time bladder control (63.0% of the sample), (2) delayed attainment of bladder control (8.6%), (3) bedwetting alone (no daytime wetting) (15.6%), (4) daytime wetting alone (no bedwetting) (5.8%) and (5) persistent wetting (bedwetting with daytime wetting to age 9) (7.0%). The persistent wetting class generally showed the strongest associations with the adolescent bladder and bowel symptoms: OR for bedwetting at 14 years=23.5, 95% CI (15.1 to 36.5), daytime wetting (6.98 (4.50 to 10.8)), nocturia (2.39 (1.79 to 3.20)), urgency (2.10 (1.44 to 3.07)) and passing hard stools (2.64 (1.63 to 4.27)) (reference category=normative development). The association with adolescent bedwetting was weaker for children with bedwetting alone (3.69 (2.21 to 6.17)). CONCLUSIONS: Trajectories of childhood urinary incontinence are differentially associated with adolescent bladder and bowel symptoms. Children exhibiting persistent bedwetting with daytime wetting had the poorest outcomes in adolescence.

Effects of urinary incontinence on psychosocial outcomes in adolescence.

To examine whether daytime wetting and bedwetting urinary incontinence (UI) in childhood and adolescence are associated with psychosocial problems in adolescence. We used data from the Avon Longitudinal Study of Parents and Children to examine the association between trajectories of UI from 4 to 9 years and self-reported psychosocial problems in adolescence (13-14 years) including depressive symptoms, peer victimisation, poor self-image and school experiences (negative perception of school and teachers, problems with peer relationships). Sample sizes ranged from 5162 (perception of teachers) to 5887 (self-image). We also examined associations between self-reported UI at 14 years and psychosocial problems. Relative to normative development, adolescents who experienced delayed development of bladder control had poorer self-image [standardised mean difference = 0.18 (95% CI 0.04, 0.32)], more negative perceptions of school [0.18 (0.02, 0.34)] and more problems with peer relationships at school [0.25 (0.10, 0.40)]. Persistent wetting (bedwetting with daytime wetting) in childhood was associated with increased problems with peer relationships in adolescence [0.19 (0.03, 0.34)]. The strongest associations between adolescent UI and psychosocial problems were found for daytime wetting (reference = no UI at 14 years): depressive symptoms [OR = 3.04 (95% CI 1.91-4.84)], peer victimisation [2.14 (1.48-3.10)], poor self-image (t = -8.49, p < 0.001) and problems with peer relationships (t = -4.69, p < 0.001). Children with delayed development of bladder control and persistent wetting have increased psychosocial problems in adolescence. Adolescents with UI reported a range of psychosocial problems and clinicians should be aware that they might require support from psychological services.

Measuring standing balance in adults: reliability and minimal real difference of 14 instrumental measures.

The study provides estimates of reliability and minimal real difference (MRD) (i.e. the minimal change significantly different from zero, expressed in the original units) of 14 parameters obtained from six motor tasks of standing balance on the EquiTest (dynamic) and the Balance Master (static) force platforms. The different tasks and parameters allowed an assessment of balance in three domains: quiet standing, perturbed standing and multidirectional leaning. Fifteen healthy adults (eight men and seven women; age 22-42 years) were studied at baseline and retested 1 and 3 weeks later. The significance level was set at P-value less than 0.05 and adjusted for multiplicity within sets of tests reflecting the same balance domain (Bonferroni corrections). Repeated analysis of variance modelling revealed a moderate yet significant time trend across the three time points, suggesting a practice effect for the mean of one out of the 14 parameters. Changes across pairs of time points did not reach significance (Tukey's post-hoc test). Test-retest reliability across the three time points and across pairs of time points was estimated for each parameter using the intraclass correlation coefficients (ICCs) (model 3.1; range 0-1, none to perfect reliability). Across the three time points, the ICCs ranged from 0.21 to 0.85 (>0.60 in nine out of the 14 cases). The MRDs were computed from the ICCs. For all 14 parameters showing a time trend, absolute changes (root mean squares of differences) were minimal. Thus, albeit overestimated for one parameter, the MRDs provide useful thresholds for changes to be interpreted as dependent on therapeutic interventions.