Bayesian inference is increasingly popular in clinical trial design and analysis. The subjective knowledge derived from an expert elicitation procedure may be useful to define a prior probability ...distribution when no or limited data is available. This work aims to investigate the state-of-the-art Bayesian prior elicitation methods with a focus on clinical trial research. A literature search on the Current Index to Statistics (CIS), PubMed, and Web of Science (WOS) databases, considering "prior elicitation" as a search string, was run on 1 November 2020. Summary statistics and trend of publications over time were reported. Finally, a Latent Dirichlet Allocation (LDA) model was developed to recognise latent topics in the pertinent papers retrieved. A total of 460 documents pertinent to the Bayesian prior elicitation were identified. Of these, 213 (45.4%) were published in the "Probability and Statistics" area. A total of 42 articles pertain to clinical trial and the majority of them (81%) reports parametric techniques as elicitation method. The last decade has seen an increased interest in prior elicitation and the gap between theory and application getting narrower and narrower. Given the promising flexibility of non-parametric approaches to the experts' elicitation, more efforts are needed to ensure their diffusion also in applied settings.
Background
We performed a systematic review and meta-analysis of studies assessing the end-expiratory occlusion test (EEXPO test)-induced changes in cardiac output (CO) measured by any haemodynamic ...monitoring device, as indicators of preload responsiveness.
Methods
MEDLINE, EMBASE and Cochrane Database were screened for original articles. Bivariate random-effects meta-analysis determined the Area under the Summary Receiver Operating Characteristic (AUSROC) curve of EEXPO test-induced changes in CO to detect preload responsiveness, as well as pooled sensitivity and specificity and the best diagnostic threshold.
Results
Thirteen studies (530 patients) were included. Nine studies were performed in the intensive care unit and four in the operating room. The pooled sensitivity and the pooled specificity for the EEXPO test-induced changes in CO were 0.85 0.77–0.91 and 0.88 0.83–0.91, respectively. The AUSROC curve was 0.91 0.86–0.94 with the best threshold of CO increase at 5.1 ± 0.2%. The accuracy of the test was not different when changes in CO were monitored through pulse contour analysis compared to other methods (AUSROC: 0.93 0.91–0.95 vs. 0.87 0.82–0.96, respectively,
p
= 0.62). Also, it was not different in studies in which the tidal volume was ≤ 7 mL/kg compared to the remaining ones (AUSROC: 0.96 0.92–0.97 vs. 0.89 0.82–0.95 respectively,
p
= 0.44). Subgroup analyses identified one possible source of heterogeneity.
Conclusions
EEXPO test-induced changes in CO reliably detect preload responsiveness. The diagnostic performance is not influenced by the method used to track the EEXPO test-induced changes in CO.
Trial registration
The study protocol was prospectively registered on PROSPERO: CRD42019138265.
To analyze the prevalence of homologous recombination deficiency (HRD) in patients with pancreatic ductal adenocarcinoma (PDAC).
We conducted a systematic review and meta-analysis of the prevalence ...of HRD in PDAC from PubMed, Scopus, and Cochrane Library databases, and online cancer genomic data sets. The main outcome was pooled prevalence of somatic and germline mutations in the better characterized HRD genes (
,
,
,
,
,
,
, and the
genes). The secondary outcomes were prevalence of germline mutations overall, and in sporadic and familial cases; prevalence of germline
mutations in Ashkenazi Jewish (AJ); and prevalence of HRD based on other definitions (ie, alterations in other genes, genomic scars, and mutational signatures). Random-effects modeling with the Freeman-Tukey transformation was used for the analyses. PROSPERO registration number: (CRD42020190813).
Sixty studies with 21,842 participants were included in the systematic review and 57 in the meta-analysis. Prevalence of germline and somatic mutations was
: 0.9%,
: 3.5%,
: 0.2%,
: 2.2%,
: 0.3%,
: 0.5%,
: 0.0%, and
: 0.1%. Prevalence of germline mutations was
: 0.9% (2.4% in AJ),
: 3.8% (8.2% in AJ),
: 0.2%,
: 2%,
: 0.3%, and
: 0.4%. No significant differences between sporadic and familial cases were identified. HRD prevalence ranged between 14.5%-16.5% through targeted next-generation sequencing and 24%-44% through whole-genome or whole-exome sequencing allowing complementary genomic analysis, including genomic scars and other signatures (surrogate markers of HRD).
Surrogate readouts of HRD identify a greater proportion of patients with HRD than analyses limited to gene-level approaches. There is a clear need to harmonize HRD definitions and to validate the optimal biomarker for treatment selection. Universal HRD screening including integrated somatic and germline analysis should be offered to all patients with PDAC.
Noninvasive respiratory support (NIRS) has been diffusely employed outside the intensive care unit (ICU) to face the high request of ventilatory support due to the massive influx of patients with ...acute respiratory failure (ARF) caused by coronavirus-19 disease (COVID-19). We sought to summarize the evidence on clinically relevant outcomes in COVID-19 patients supported by NIV outside the ICU.
We searched PUBMED®, EMBASE®, and the Cochrane Controlled Clinical trials register, along with medRxiv and bioRxiv repositories for pre-prints, for observational studies and randomized controlled trials, from inception to the end of February 2021. Two authors independently selected the investigations according to the following criteria: (1) observational study or randomized clinical trials enrolling ≥ 50 hospitalized patients undergoing NIRS outside the ICU, (2) laboratory-confirmed COVID-19, and (3) at least the intra-hospital mortality reported. Preferred Reporting Items for Systematic reviews and Meta-analysis guidelines were followed. Data extraction was independently performed by two authors to assess: investigation features, demographics and clinical characteristics, treatments employed, NIRS regulations, and clinical outcomes. Methodological index for nonrandomized studies tool was applied to determine the quality of the enrolled studies. The primary outcome was to assess the overall intra-hospital mortality of patients under NIRS outside the ICU. The secondary outcomes included the proportions intra-hospital mortalities of patients who underwent invasive mechanical ventilation following NIRS failure and of those with 'do-not-intubate' (DNI) orders.
Seventeen investigations (14 peer-reviewed and 3 pre-prints) were included with a low risk of bias and a high heterogeneity, for a total of 3377 patients. The overall intra-hospital mortality of patients receiving NIRS outside the ICU was 36% 30-41%. 26% 21-30% of the patients failed NIRS and required intubation, with an intra-hospital mortality rising to 45% 36-54%. 23% 15-32% of the patients received DNI orders with an intra-hospital mortality of 72% 65-78%. Oxygenation on admission was the main source of between-study heterogeneity.
During COVID-19 outbreak, delivering NIRS outside the ICU revealed as a feasible strategy to cope with the massive demand of ventilatory assistance.
PROSPERO, https://www.crd.york.ac.uk/prospero/ , CRD42020224788, December 11, 2020.
Awake prone position is an emerging rescue therapy applied in patients undergoing noninvasive ventilation (NIV) for acute hypoxemic respiratory failure (ARF) related to novel coronavirus disease ...(COVID-19). Although applied to stabilize respiratory status, in awake patients, the application of prone position may reduce comfort with a consequent increase in the workload imposed on respiratory muscles. Thus, we primarily ascertained the effect of awake prone position on diaphragmatic thickening fraction, assessed through ultrasound, in COVID-19 patients undergoing NIV.
We enrolled all COVID-19 adult critically ill patients, admitted to intensive care unit (ICU) for hypoxemic ARF and undergoing NIV, deserving of awake prone positioning as a rescue therapy. Exclusion criteria were pregnancy and any contraindication to awake prone position and NIV. On ICU admission, after NIV onset, in supine position, and at 1 h following awake prone position application, diaphragmatic thickening fraction was obtained on the right side. Across all the study phases, NIV was maintained with the same setting present at study entry. Vital signs were monitored throughout the entire study period. Comfort was assessed through numerical rating scale (0 the worst comfort and 10 the highest comfort level). Data were presented in median and 25th-75th percentile range.
From February to May 2021, 20 patients were enrolled and finally analyzed. Despite peripheral oxygen saturation improvement 96 (94-97)% supine vs 98 (96-99)% prone, p = 0.008, turning to prone position induced a worsening in comfort score from 7.0 (6.0-8.0) to 6.0 (5.0-7.0) (p = 0.012) and an increase in diaphragmatic thickening fraction from 33.3 (25.7-40.5)% to 41.5 (29.8-50.0)% (p = 0.025).
In our COVID-19 patients assisted by NIV in ICU, the application of awake prone position improved the oxygenation at the expense of a greater diaphragmatic thickening fraction compared to supine position. Trial registration ClinicalTrials.gov, number NCT04904731. Registered on 05/25/2021, retrospectively registered. https://clinicaltrials.gov/ct2/show/NCT04904731 .
We aimed to assess the perceived impact of the lockdown, imposed to control the spreading of COVID-19, on the adherence of Italian celiac disease (CD) subjects to the gluten-free diet by a web-based ...survey. A total of 1983 responses were analyzed, 1614 (81.4%) by CD adults and 369 (18.6%) by parents/caregivers of CD children/adolescents. The compliance with the GFD was unchanged for 69% of the adults and 70% of the children, and improved for 29% of both. The factors increasing the probability to report stricter compliance were the presence of CD symptoms in the last year before the lockdown (odds ratio (OR) 1.98, 95% confidence interval (CI) 1.46-2.26), a partial usual adherence to gluten-free diet (GFD) (OR 1.91, 95% CI 1.2-3.06), and having tried recipes with naturally gluten-free ingredients more than usual (OR 1.58, 95% CI 1.28-1.96) for adults; the presence of CD symptoms in the last year (OR 2.05, 95% CI 1.21-3.47), still positive CD antibodies (OR 1.89, 95% CI 1.14-3.13), and other family members with CD (OR 2.24, 95% CI 1.3-3.85) for children/adolescents. Therefore, the lockdown led to a reported improved adherence to the GFD in one-third of the respondents, in particular in those with previous worse disease control, offering the opportunity to avoid sources of contamination/transgression and increase the use of naturally gluten-free products.
The outbreak poses a relevant burden on hospital resources, with a marked increase in the intensive care unit (ICU) occupancy rates 1. SEE PDF These findings suggest that testing also ...asymptomatic/mild symptomatic patients would help reduce the proportion of most severe cases eventually requiring ICU and thus limiting the risk of saturation of ICU units. Regression modeling strategies with applications to linear models, logistic and ordinal regression and survival analysis (2nd Edition).
Cough variant asthma (CVA), a common asthma phenotype characterized by nonproductive cough and bronchial hyperreactivity (BHR), is usually detected by bronchial provocation tests (BPTs) which are ...time
consuming, expensive, and unsafe. The primary study objective was to provide proof of concept for the use of fractional exhaled nitric oxide (F
NO), eosinophil count percentage in induced sputum (sEOS%), forced expiratory flow between 25 and 75% of forced vital capacity (FEF
) % predicted value, and FEF
z-scores as surrogate markers predicting BHR in young adults with suspected CVA; the secondary objective was to compare the diagnostic performance of the various techniques. Three hundred and ten subjects (median age 24 years) were included in a cross-sectional study. Subjects were characterized as BHR positive (POS) (
= 147) or BHR negative (NEG) (n = 163) according to methacholine BPT. Classification accuracies were expressed as areas under the receiver operator characteristic curves (AUC). Compared with BHR NEG, FEF
% predicted value and FEF
z-scores were lower in the BHR POS group (
< 0.001), whereas F
NO (
< 0.001) and sEOS% were higher (
< 0.001). AUC values for detecting BHR were as follows: F
NO, 0.98 (SD = 0.02); sEOS%, 0.98 (SD = 0.02); FEF
% pred, 0.93 (SD = 0.05); FEF
z scores, 0.92 (SD = 0.05). Optimal cutoff values (OCV) for BHR prediction were as follows: F
NO, 32.7 ppb (sensitivity = 0.93, specificity = 0.96), sEOS%, 3.80% (sensitivity = 0.94, specificity = 0.94), FEF
% predicted value, 80.0% (sensitivity = 0.90, specificity = 0.87), and FEF
z-score, -0.87 (sensitivity = 0.89, specificity = 0.87). Non-invasive/semi-invasive airway inflammatory or small airway functional measures might be used as surrogate markers predicting BHR in young adults with suspected CVA.
Abstract
Background
Prone position is frequently used in patients with acute respiratory distress syndrome (ARDS), especially during the Coronavirus disease 2019 pandemic. Our study investigated the ...ability of pulse pressure variation (PPV) and its changes during a tidal volume challenge (TVC) to assess preload responsiveness in ARDS patients under prone position.
Methods
This was a prospective study conducted in a 25-bed intensive care unit at a university hospital. We included patients with ARDS under prone position, ventilated with 6 mL/kg tidal volume and monitored by a transpulmonary thermodilution device. We measured PPV and its changes during a TVC (ΔPPV TVC
6–8
) after increasing the tidal volume from 6 to 8 mL/kg for one minute. Changes in cardiac index (CI) during a Trendelenburg maneuver (ΔCI
TREND
) and during end-expiratory occlusion (EEO) at 8 mL/kg tidal volume (ΔCI EEO
8
) were recorded. Preload responsiveness was defined by both ΔCI
TREND
≥ 8% and ΔCI EEO
8
≥ 5%. Preload unresponsiveness was defined by both ΔCI
TREND
< 8% and ΔCI EEO
8
< 5%.
Results
Eighty-four sets of measurements were analyzed in 58 patients. Before prone positioning, the ratio of partial pressure of arterial oxygen to fraction of inspired oxygen was 104 ± 27 mmHg. At the inclusion time, patients were under prone position for 11 (2–14) hours. Norepinephrine was administered in 83% of cases with a dose of 0.25 (0.15–0.42) µg/kg/min. The positive end-expiratory pressure was 14 (11–16) cmH
2
O. The driving pressure was 12 (10–17) cmH
2
O, and the respiratory system compliance was 32 (22–40) mL/cmH
2
O. Preload responsiveness was detected in 42 cases. An absolute change in PPV ≥ 3.5% during a TVC assessed preload responsiveness with an area under the receiver operating characteristics (AUROC) curve of 0.94 ± 0.03 (sensitivity: 98%, specificity: 86%) better than that of baseline PPV (0.85 ± 0.05;
p
= 0.047). In the 56 cases where baseline PPV was inconclusive (≥ 4% and < 11%), ΔPPV TVC
6–8
≥ 3.5% still enabled to reliably assess preload responsiveness (AUROC: 0.91 ± 0.05, sensitivity: 97%, specificity: 81%;
p
< 0.01
vs.
baseline PPV).
Conclusion
In patients with ARDS under low tidal volume ventilation during prone position, the changes in PPV during a TVC can reliably assess preload responsiveness without the need for cardiac output measurements.
Trial registration:
ClinicalTrials.gov (NCT04457739). Registered 30 June 2020 —Retrospectively registered,
https://clinicaltrials.gov/ct2/show/record/NCT04457739
Free-text information is still widely used in emergency department (ED) records. Machine learning techniques are useful for analyzing narratives, but they have been used mostly for English-language ...data sets. Considering such a framework, the performance of an ML classification task of a Spanish-language ED visits database was tested. ED visits collected in the EDs of nine hospitals in Nicaragua were analyzed. Spanish-language, free-text discharge diagnoses were considered in the analysis. Five-hundred random forests were trained on a set of bootstrap samples of the whole data set (1,789 ED visits) to perform the classification task. For each one, after having identified optimal parameter value, the final validated model was trained on the whole bootstrapped data set and tested. The classification accuracies had a median of 0.783 (95% CI 0.779, 0.796). Machine learning techniques seemed to be a promising opportunity for the exploitation of unstructured information reported in ED records in low- and middle-income Spanish-speaking countries.
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