Critical Errors Research Articles

P-521 Importance of full clinical presentation for precise diagnosis by WES: a clinical geneticist’s viewpoint

Abstract Study question To what extent is the fullness and detail of the description of a patient’s clinical presentation necessary to ensure the precise diagnosis by WES? Summary answer A full clinical presentation and description of a patient’s phenotype are critical to reduce the incidence of false-negative results at the WES bioinformatics processing stage. What is known already Whole Exome Sequencing (WES) is a powerful method of genetic testing. However, genetic laboratory business models have created conditions where doctors of any specialty or patients themselves can send a biosample for testing. That being said, the lack of understanding by doctors and patients of the testing principles and the testing accessibility creates a misconception regarding the simplicity of the diagnosis and can lead to critical errors when conducting bioinformatics processing. Errors may include the derivation of an excessive number of variants without clinical significance which will make genetic counseling too difficult, can lead to false-negative results and/or misdiagnosis. Study design, size, duration Retrospective bioinformatics reanalysis of raw sequencing data (RAW data) for patients seeking genetic counseling to clinically interpret WES results in case of negative results (no mutations identified) (2020-2021). Group A – patients (24 cases, full clinical information collection, patient phenotyping, HPO-coding when referring to WES). Group B – patients (12) who underwent WES only with a diagnosis. Group C – patients (15) who underwent WES with clinical information, but without a description of the phenotype. Participants/materials, setting, methods The study included cases of negative WES results in the case of examinations of children with undifferentiated neuropsychiatric retardation aged 1 to 5 years for whom clinical interpretation of WES results was performed independently of the WES implementing laboratory. For all negative results, RAW data bioinformatics re-processing was performed in an independent laboratory. For groups B and C – after full clinical information collection, phenotype description, and HPO coding. Main results and the role of chance Bioinformatics re-analysis in an independent laboratory in the group with a full patient description (A) allowed to identify 2 positive cases out of 24 previously negative ones (8.3%). In group B – 5 cases out of 12 (41.7%) after full clinical information collection, phenotype description, and HPO-coding. In group C, with full phenotype description and HPO coding, – 3 cases out of 15 (20%). Overall chi-sq (2;N=51)=5.64 p = 0.059 Group A vs B: chi-sq (1;N=36)=5.67 p = 0.017 (significant at p ≤ 0.05) Group A vs C: chi-sq (1;N=39)=1.12 p = 0.28 (not significant at p ≤ 0.05) Group B vs C: chi-sq (1;N=27)=1.05 p = 0.22 (not significant at p ≤ 0.05) Limitations, reasons for caution The study results and the evaluation of statistical significance criteria are limited to a small sample with negative WES results, and also apply only to children with undifferentiated neuropsychiatric retardation aged 1 to 5 years. Wider implications of the findings The study results may serve as a basis for modifying the requirements of genetic laboratories for the description of a clinical case during referral for diagnosis by WES. Such modifications will allow geneticists to find a precise diagnosis and provide reproductive family planning and PGT procedures Trial registration number -

The impact of using different add-on devices to pressurized metered-dose-inhalers containing salbutamol in healthy adult volunteers: An in-vivo study

BackgroundImproper handling of pMDIs results in suboptimal delivery of the drug to the lungs and poor clinical outcomes in adult asthmatics. Forceful inhalation is one of the most critical errors in the pMDI inhalation technique. Using advanced tools to optimize the inhalation technique is required to enhance the inhalation flow and hence the drug delivery to the lungs. MethodsTwo newly adopted add-on devices; the Clip-Tone and the Flo-Tone CR, along with their respective smartphone applications were tested and compared to the normal pMDI inhalation. 12 healthy volunteers (6 females) were trained to use the pMDI alone, pMDI + Clip-Tone, and pMDI + Flo-Tone CR in a cross-over study design. Using the urinary salbutamol excretion pharmacokinetic model, urine samples of 30 min (USAL0.5) and collective urine of 24 h (USAL24) were collected for each experiment; the first represents the lung deposition and the latter represents the systemic bioavailability. Samples were solid-phase extracted and then assayed using HPLC to determine the amount of salbutamol in urine. Since subjects were trained to perform through 2 different add-on tools in addition to the pMDI alone, they reported their personal preference regarding the delivery method. Also, a correlation between inhalation time to USAL 0.5 was determined. ResultsComparing means (SD) of USAL0.5 among the 3 groups, pMDI + Clip-Tone, 22.2 (8.21), and pMDI + Flo-Tone CR, 19.83 (9.94), showed a significant increase (p < 0.01) compared to using pMDI alone, 10.68 (5.82). Comparing means (SD) of USAL24, no significant difference was found among salbutamol amounts in the urine of the pMDI + Clip-Tone group, 54.77 (20.18), and pMDI + Flo-Tone CR group, 49.76 (25.30), and pMDI sole use group, 56.48 (24.42). Studying the associations between the inhalation duration measured and the amount of salbutamol in urine after 30 min, there was a significantly high positive correlation (r = 0.72) (p < 0.001). 50% of the subjects preferred training using the Clip-Tone add-on tool while the other half felt comfortable using both add-on tools. ConclusionUsing advanced training tools that provide audio-visual feedback improved the inhalation technique compared to the sole use of pMDI, which was translated into improved lung deposition of salbutamol. The more preferred add-on tool by subjects, the Clip-Tone device, has not shown significant superiority to the Flo-Tone CR in terms of lung deposition of salbutamol.

A Survey of Prescription Errors in Paediatric Outpatients in Multi-Primary Care Settings: The Implementation of an Electronic Pre-Prescription System.

BackgroundPrescription errors impact the safety and efficacy of therapy and are considered to have a higher impact on paediatric populations. Nevertheless, information in paediatrics is still lacking, particularly in primary care settings. There exists a need to investigate the prevalence and characteristics of prescription errors in paediatric outpatients to prevent such errors during the prescription stage.MethodsA cross-sectional study to evaluate paediatric prescription errors in multi-primary care settings was conducted between August 2019 and July 2021. Prescriptions documented within the electronic pre-prescription system were automatically reviewed by the system and then, potentially inappropriate prescriptions would be reconciled by remote pharmacists via a regional pharmacy information exchange network. The demographics of paediatric patients, prescription details, and types/rates of errors were assessed and used to identify associated factors for prescription using logistic regression.ResultsA total of 39,754 outpatient paediatric prescriptions in 13 community health care centres were reviewed, among which 1,724 prescriptions (4.3%) were enrolled in the study as they met the inclusion criteria. Dose errors were the most prevalent (27%), with the predominance of underdosing (69%). They were followed by errors in selection without specified indications (24.5%), incompatibility (12.4%), and frequency errors (9.9%). Among critical errors were drug duplication (8.7%), contraindication (.9%), and drug interaction (.8%) that directly affect the drug's safety and efficacy. Notably, error rates were highest in medications for respiratory system drugs (50.5%), antibiotics (27.3%), and Chinese traditional medicine (12.3%). Results of logistic regression revealed that specific drug classification (antitussives, expectorants and mucolytic agents, anti-infective agents), patient age (<6 years), and prescriber specialty (paediatrics) related positively to errors.ConclusionOur study provides the prevalence and characteristics of prescription errors of paediatric outpatients in community settings based on an electronic pre-prescription system. Errors in dose calculations and medications commonly prescribed in primary care settings, such as respiratory system drugs, antibiotics, and Chinese traditional medicine, are certainly to be aware of. These results highlight an essential requirement to update the rules of prescriptions in the pre-prescription system to facilitate the delivery of excellent therapeutic outcomes.

Safety Rules of Heuristic Behavior Algorithms as a Prototype of the "Morality" of Robotic Systems

The relevance of choosing the subject of research, as the use of autonomous robotic systems for various purposes and the object of research, which are algorithmic problems arising in terms of algorithm security control, is determined by the existing contradiction between the need for autonomous robotic systems and the complexity of the software implementation of this requirement. The study was conducted on the example of the application of robotics in the field of autonomous transport systems. The implementation of trends of autonomization in this area generates certain legal and technological problems related to the security of algorithmic support of autonomous systems. The manifestation of such problems are critical application errors that are problematic to identify at the development stage. In robotics, the main potential cause of these errors is the functioning of the software of autonomous robotic systems outside the framework of deterministic algorithms that were tested during their development. And if for conventional technical systems the consequences of application errors are predictable, and responsibility for their results is determined, then for the case of autonomous robots, the situation requires a solution. In the article, using general scientific methods of analysis and synthesis, the main aspects of the current state and prospects of the problem of algorithmization of the use of autonomous systems are investigated. Based on a review analysis of algorithmic problems of using autonomous robots, possible consequences and causes of algorithmic errors arising from their use, the formulation of the scientific problem of solving the problem of developing heuristic algorithms that determine their application using a dynamically formed system of predicate behavior similar to human morality is synthesized.

Peer review quality assurance in stereotactic body radiotherapy planning: the impact of case volume

Abstract Purpose: Peer review is an essential quality assurance component of radiation therapy planning. A growing body of literature has demonstrated substantial rates of suggested plan changes resulting from peer review. There remains a paucity of data on the impact of peer review rounds for stereotactic body radiation therapy (SBRT). We therefore aim to evaluate the outcomes of peer review in this specific patient cohort. Methods and materials: We conducted a retrospective review of all SBRT cases that underwent peer review from July 2015 to June 2018 at a single institution. Weekly peer review rounds are grouped according to cancer subsite and attended by radiation oncologists, medical physicists and medical radiation technologists. We prospectively compiled ‘learning moments’, defined as cases with suggested changes or where an educational discussion occurred beyond routine management, and critical errors, defined as errors which could alter clinical outcomes, recorded prospectively during peer review. Plan changes implemented after peer review were documented. Results: Nine hundred thirty-four SBRT cases were included. The most common treatment sites were lung (518, 55%), liver (196, 21%) and spine (119, 13%). Learning moments were identified in 161 cases (17%) and translated into plan changes in 28 cases (3%). Two critical errors (0.2%) were identified: an inadequate planning target volume margin and an incorrect image set used for contouring. There was a statistically significantly higher rate of learning moments for lower-volume SBRT sites (defined as ≤30 cases/year) versus higher-volume SBRT sites (29% vs 16%, respectively; p = 0.001). Conclusions: Peer review for SBRT cases revealed a low rate of critical errors, but did result in implemented plan changes in 3% of cases, and either educational discussion or suggestions of plan changes in 17% of cases. All SBRT sites appear to benefit from peer review, though lower-volume sites may require particular attention.

Adequacy of Serial Self-performed SARS-CoV-2 Rapid Antigen Detection Testing for Longitudinal Mass Screening in the Workplace

Longitudinal mass testing using rapid antigen detection tests (RADT) for serial screening of asymptomatic persons has been proposed for preventing SARS-CoV-2 community transmission. The feasibility of this strategy relies on accurate self-testing. To quantify the adequacy of serial self-performed SARS-CoV-2 RADT testing in the workplace, in terms of the frequency of correct execution of procedural steps and accurate interpretation of the range of possible RADT results. This prospective repeated cross-sectional study was performed from July to October 2021 at businesses with at least 2 active cases of SARS-CoV-2 infection in Montreal, Canada. Participants included untrained persons in their workplace, not meeting Public Health quarantine criteria (ie, required quarantine for 10 days after a moderate-risk contact with someone infected with SARS-CoV-2). Interpretation and performance were compared between participants who received instructions provided by the manufacturer vs those who received modified instructions that were informed by the most frequent or most critical errors we observed. Data were analyzed from October to November 2021. RADT testing using a modified quick reference guide compared with the original manufacturer's instructions. The main outcome was the difference in correctly interpreted RADT results. Secondary outcomes included difference in proportions of correctly performed procedural steps. Additional analyses, assessed among participants with 2 self-testing visits, compared the second self-test visit with the first self-test visit using the same measures. Overall, 1892 tests were performed among 647 participants, of whom 278 participants (median [IQR] age, 43 [31-55] years; 156 [56.1%] men) had at least 1 self-testing visit. For self-test visit 1, significantly better accuracy in test interpretation was observed among participants using the modified quick reference guide than those using the manufacturer's instructions for reading results that were weak positive (64 of 115 participants [55.6%] vs 20 of 163 participants [12.3%]; difference, 43.3 [95% CI, 33.0-53.8] percentage points), positive (103 of 115 participants [89.6%] vs 84 of 163 participants [51.5%]; difference, 38.1 [95% CI, 28.5-47.5] percentage points), strong positive (219 of 229 participants [95.6%] vs 274 of 326 participants [84.0%]; difference, 11.6 [95% CI, 6.8-16.3] percentage points), and invalid (200 of 229 participants [87.3%] vs 252 of 326 participants [77.3%]; difference, 10.0 [95% CI, 3.8-16.3] percentage points). Use of the modified guide was associated with improvements on self-test visit 2 for results that were weak positive (difference, 15.4 [95% CI, 0.7-30.1] percentage points), positive (difference, 19.0 [95% CI, 7.2-30.9] percentage points), and invalid (difference, 8.0 [95% CI, 0.8-15.4] percentage points). For procedural steps identified as critical for test validity, adherence to procedural testing steps did not differ meaningfully according to instructions provided or reader experience. In this cross-sectional study of self-performed SARS-CoV-2 RADT in an intended-use setting, a modified quick reference guide was associated with significantly improved accuracy in RADT interpretations.

Intraoperative robotic-assisted low anterior rectal resection performance assessment using procedure-specific binary metrics and a global rating scale.

BackgroundThis study aimed to evaluate the use of binary metric-based (proficiency-based progression; PBP) performance assessments and global evaluative assessment of robotic skills (GEARS) of a robotic-assisted low anterior rectal resection (RA-LAR) procedure.MethodA prospective study of video analysis of RA-LAR procedures was carried out using the PBP metrics with binary parameters previously developed, and GEARS. Recordings were collected from five novice surgeons (≤30 RA-LAR previously performed) and seven experienced surgeons (>30 RA-LAR previously performed). Two consultant colorectal surgeons were trained to be assessors in the use of PBP binary parameters to evaluate the procedure phases, surgical steps, errors, and critical errors in male and female patients and GEARS scores. Novice and experienced surgeons were categorized and assessed using PBP metrics and GEARS; mean scores obtained were compared for statistical purpose. Also, the inter-rater reliability (IRR) of these assessment tools was evaluated.ResultsTwenty unedited recordings of RA-LAR procedures were blindly assessed. Overall, using PBP metric-based assessment, a subgroup of experienced surgeons made more errors (20 versus 16, P = 0.158) and critical errors (9.2 versus 7.8, P = 0.417) than the novice group, although not significantly. However, during the critical phase of RA-LAR, experienced surgeons made significantly fewer errors than the novice group (95% CI of the difference, Lower = 0.104 – Upper = 5.155, df = 11.9, t = 2.23, p = 0.042), and a similar pattern was observed for critical errors. The PBP metric and GEARS assessment tools distinguished between the objectively assessed performance of experienced and novice colorectal surgeons performing RA-LAR (total error scores with PBP metrics, P = 0.019–0.008; GEARS scores, P = 0.029–0.025). GEARS demonstrated poor IRR (mean IRR 0.49) and weaker discrimination between groups (15–41 per cent difference). PBP binary metrics demonstrated good IRR (mean 0.94) and robust discrimination particularly for total error scores (58–64 per cent).ConclusionsPBP binary metrics seem to be useful for metric-based training for surgeons learning RA-LAR procedures.

MP41-13 DOES QUALITY ASSURED ELEARNING PROVIDE ADEQUATE PREPARATION FOR ROBOTIC SURGICAL SKILLS; A PROSPECTIVE, RANDOMIZED AND MULTI-CENTER STUDY

You have accessJournal of UrologyCME1 May 2022MP41-13 DOES QUALITY ASSURED ELEARNING PROVIDE ADEQUATE PREPARATION FOR ROBOTIC SURGICAL SKILLS; A PROSPECTIVE, RANDOMIZED AND MULTI-CENTER STUDY Stefano Puliatti, Marco Amato, Rui Farinha, Artur Paludo, Giuseppe Rosiello, Ruben De Groote, Andrea Mari, Lorenzo Bianchi, Pietro Piazza, Ben Van Cleynenbreugel, Elio Mazzone, Simon Meganck, Léonore Maertens, Louise Callens, Filippo Migliorini, Saverio Forte, Bernardo Rocco, Salvatore Micali, Alexandre Mottrie, and Anthony Gallagher Stefano PuliattiStefano Puliatti More articles by this author , Marco AmatoMarco Amato More articles by this author , Rui FarinhaRui Farinha More articles by this author , Artur PaludoArtur Paludo More articles by this author , Giuseppe RosielloGiuseppe Rosiello More articles by this author , Ruben De GrooteRuben De Groote More articles by this author , Andrea MariAndrea Mari More articles by this author , Lorenzo BianchiLorenzo Bianchi More articles by this author , Pietro PiazzaPietro Piazza More articles by this author , Ben Van CleynenbreugelBen Van Cleynenbreugel More articles by this author , Elio MazzoneElio Mazzone More articles by this author , Simon MeganckSimon Meganck More articles by this author , Léonore MaertensLéonore Maertens More articles by this author , Louise CallensLouise Callens More articles by this author , Filippo MiglioriniFilippo Migliorini More articles by this author , Saverio ForteSaverio Forte More articles by this author , Bernardo RoccoBernardo Rocco More articles by this author , Salvatore MicaliSalvatore Micali More articles by this author , Alexandre MottrieAlexandre Mottrie More articles by this author , and Anthony GallagherAnthony Gallagher More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002607.13AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: In particular after the onset of the COVID-19 pandemic, there was a precipitous rush to implement virtual and online learning strategies in surgery and medicine. It is essential to understand whether this approach is sufficient and adequate to allow the development of robotic basic surgical skills. The main aim of the authors was to verify if the quality assured eLearning is sufficient to prepare individuals to perform a basic surgical robotic task. METHODS: A prospective, randomized and multi-center study conducted in September 2020 in the ORSI Academy, International surgical robotic training center. 47 participants with no experience but a special interest in robotic surgery, were matched and randomized into 4 groups who underwent a didactic preparation with different formats before carrying out a robotic suturing and anastomosis task. Didactic preparation methods, ranged from a complete eLearning path to peer-reviewed published manuscripts describing the suturing, knot tying and task assessment metrics. RESULTS: The primary outcome was the percentage of trainees who demonstrated the quantitatively defined proficiency benchmark after learning to complete an assisted but unaided robotic vesico-urethral anastomosis task. The quantitatively defined benchmark was based on the objectively assessed performance (i.e., procedure steps completed, errors and critical errors) of experienced robotic surgeons for a proficiency based progression (PBP) training course. None of the trainees in this study demonstrated the proficiency benchmarks in completing the robotic surgery task (Figure 1a-c). CONCLUSIONS: Quality assured online learning is insufficient preparation for robotic suturing and knot tying anastomosis skills. Source of Funding: No © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e724 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Stefano Puliatti More articles by this author Marco Amato More articles by this author Rui Farinha More articles by this author Artur Paludo More articles by this author Giuseppe Rosiello More articles by this author Ruben De Groote More articles by this author Andrea Mari More articles by this author Lorenzo Bianchi More articles by this author Pietro Piazza More articles by this author Ben Van Cleynenbreugel More articles by this author Elio Mazzone More articles by this author Simon Meganck More articles by this author Léonore Maertens More articles by this author Louise Callens More articles by this author Filippo Migliorini More articles by this author Saverio Forte More articles by this author Bernardo Rocco More articles by this author Salvatore Micali More articles by this author Alexandre Mottrie More articles by this author Anthony Gallagher More articles by this author Expand All Advertisement PDF DownloadLoading ...

Vulnerability evaluation on 16 nm FinFET Ultrascale+ MPSoC using fault injection and proton irradiation

The SEE vulnerability in two ways bitstream loading implementations on a dynamic partial reconfiguration (DPR) design is examined using fault injections and proton irradiations on a Xilinx 16 nm FinFET Ultrascale+ MPSoC. During fault injection, two kinds of soft errors are detected, they are system halt (SH) and calculation result error (CRE). In comparison, the detected errors are only SHs in the 100 and 80 MeV proton irradiations. Also, the critical bit error and cross sections are calculated in the fault injection and proton irradiation, respectively. The results signify that there is almost no difference in SEE vulnerability between the two ways of bitstream loading in DPR design.

Evaluating the evaluators - Developing evidence of quality oversight effectiveness for clinical trial monitoring: Source data verification, source data review, statistical monitoring, key risk indicators, and direct measure of high risk errors

BackgroundDetailed information about clinical trial quality typically is not published in primary publications. This is a significant issue for physicians, advisory groups, and regulators. In addition, the efficacy of methods to find critical errors that affect trial integrity has not been tested. For more than 20 years, visits to research sites for source data verification (SDV) have been the gold standard method for oversight by pharmaceutical, biotech, device, and vaccine manufacturers. However, there is no evidence of its effectiveness and significant evidence of its lack of effectiveness. GapsWe consulted documents from the Food and Drug Administration (FDA), European Medicines Association (EMA), and International Council for Harmonization (ICH) to break down components of this pivotal issue into gaps in monitoring, oversight cost, and test validation and effectiveness. RecommendationsWe recommend that the pharma, biotech, academic, and publishing communities develop and provide reference datasets with defined errors for trials similar to the reference standards for analytic tests; systematically test the different monitoring methods using the reference datasets as well as provide sensitivity, specificity, positive and negative predictive values, and time to critical finding for each methodology for different types of trial errors; and publish the details of trial quality in each publication, including the number of major deviations. ConclusionsThis will allow the scientific community to improve measurements of research quality, evaluate new methods, and compare the effectiveness of different oversight approaches in the same environment.

Changes in critical inhaler technique errors in inhaled COPD treatment – A one-year follow-up study in Sweden

BackgroundCritical inhaler technique errors have been associated with lower treatment efficacy in chronic obstructive pulmonary disease (COPD). We aimed to assess and follow-up critical inhaler technique errors, and to investigate their association with COPD symptoms and exacerbations. MethodsCOPD-diagnosed primary and secondary care outpatients (n = 310) demonstrated inhaler technique with inhaler devices they were currently using. Critical errors in opening, positioning and loading the inhaler device, and exhalation through dry-powder inhalers were assessed and corrected, and the assessment was repeated one year later. COPD Assessment Test, the modified Medical Research Council dyspnoea scale and history of exacerbations were collected at both visits. ResultsThe proportion of patients making ≥1 critical inhaler technique error was lower at follow-up in the total population (46% vs 37%, p = 0.01) and among patients with unchanged device models (46% vs 35%, p = 0.02), but not among patients with a new inhaler device model (46% vs 41%, p = 0.56). Not positioning the device correctly was the most common critical error at both visits (30% and 22%). Seventy-four percent of the patients had unchanged COPD treatment from baseline to follow-up. Treatment escalation, de-escalation, and switch was observed in 14%, 11%, and 1% of the patients, respectively. No association was found between critical errors and COPD symptoms or exacerbations. ConclusionsAssessment and correction of inhaler technique was associated with a decrease in critical inhaler technique errors. This effect was most pronounced in patients using the same device models throughout the follow-up period.

Leukocytes identification using augmentation and transfer learning based convolution neural network

Most haematological diseases can be diagnosed using the morphological analysis of the microscopic blood image. The basic routine of the morphological analysis can be performed using the microscopic device which requires the skills and experiences of the haematologists. An inexperienced haematologist can lead to critical human errors. Therefore, this paper aims to propose an automated classification system used to classify different types of leukocytes based on the convolution neural network (CNN) algorithm. CNN has achieved robust performance in various fields especially in medical applications. A dataset of microscopic blood cells images of the conforming tags (basophil, eosinophil, erythroblast, lymphocyte, monocyte, neutrophil, and platelet) was used to train and test the proposed algorithm. The augmentation and deep transfer approaches were used to improve and enhance the performance of the CNN algorithm. The overall accuracy of the proposed classifier was 98% with Visual Geometry Group-19 (VGG-19). The obtained accuracy was higher than the state-of-art algorithms. To conclude that using the augmentation and deep transfer approaches with VGG-19 can obtain better classification results.

Indicators for implementation outcome monitoring of reporting and learning systems in hospitals: an underestimated need for patient safety

ObjectiveWe aimed to investigate the perception of the implementation success of reporting and learning systems in German hospitals, the perceived relevance of the implementation outcomes and whether and how these...

Is Inhaler Technique Adequately Assessed and Reported in Clinical Trials of Asthma and Chronic Obstructive Pulmonary Disease Therapy? A Systematic Review and Suggested Best Practice Checklist

Inhaled medications are central to treating asthma and chronic obstructive pulmonary disease (COPD), yet critical inhaler technique errors are made by up to 90% of patients. In the clinical research setting, recruitment of subjects with poor inhaler technique may give a false impression of both the benefits and the necessity of add-on treatments such as biologic therapies. To assess the frequency with which inhaler technique is assessed and reliably optimized before and during patient enrollment into randomized controlled trials (RCTs) addressing the efficacy of topical therapy, and the escalation of therapy for asthma and COPD. Systematic searches were conducted of PubMed and Embase for RCTs published in the past 10 years involving patients with a diagnosis of asthma or COPD undergoing escalation of baseline inhaled therapy (stepping up, changing, adding, switching, increasing, etc) or the introduction of biologic agents. Searches highlighted 1,014 studies, 118 of which were eligible after the removal of duplicates as well as screening and full text review. Of these, only 14 (11.9%) included accessible information in the methods section or referred to such information in online supplements or protocols concerning assessment of participants' inhaler technique. We therefore developed the proposed Best Practice Inhaler Technique Assessment and Reporting Checklist. Our study identifies a concerning lack of checking and correcting inhaler technique, or at least reporting that this was undertaken, before enrollment in asthma and COPD RCTs, which may affect the conclusions drawn. Mandating the use of a standardized checklist in RCT protocols and ensuring all published RCTs report checking and correcting inhaler technique before enrollment are important next steps.

Development of a Mobile Application for Smart Clinical Trial Subject Data Collection and Management

Wearable devices and digital health technologies have enabled the exchange of urgent clinical trial information. We developed an application to improve the functioning of decentralized clinical trials and performed a heuristic evaluation to reflect the user demands of existing clinical trial workers. The waterfall model of the software life cycle was used to guide the development. Focus group interviews (N = 7) were conducted to reflect the needs of clinical research professionals, and Wizard of Oz prototyping was performed to ensure high usability and completeness. Unit tests and heuristic evaluation (N = 11) were used. Thematic analysis was performed using the focus group interview data. Based on this analysis, the main menu was designed to include health management, laboratory test results, medications, concomitant medications, adverse reactions, questionnaires, meals, and My Alarm. Through role-playing, the functions and configuration of the prototype were adjusted and enhanced, and a heuristic evaluation was performed. None of the heuristic evaluation items indicated critical usability errors, suggesting that the revised prototype application can be practically applied to clinical trials. The application is expected to increase the efficiency of clinical trial management, and the development process introduced in this study will be helpful for researchers developing similar applications in the future.

Analyzing Reduced Precision Triple Modular Redundancy Under Proton Irradiation

This work analyzes the performance of the reduced precision redundancy (RPR) error mitigation technique using the fast Fourier transform (FFT) as a case study. To this purpose, several configurations of an FFT IP design were implemented in field-programmable gate array (FPGA) using reduced precision triple modular redundancy (RP-TMR) and tested under proton irradiation and fault injection. The cross section, the sensitivity to common-mode failures (CMFs), and the signal-to-noise ratio of these configurations were evaluated. The results of the radiation experiments and fault injection campaigns are in agreement and show that the RP-TMR technique may be used as an alternative to triple modular redundancy (TMR) if small errors can be tolerated, as it has a good performance in terms of error correction capabilities, area usage, and sensitivity to critical errors.

Development of a method for checking vulnerabilities of a corporate network using Bernstein transformations

One of the leading areas of cybersecurity of communication networks is considered – the introduction of preventive mechanisms, among which the most promising are the methods of active security analysis. These methods allow, in addition to timely detection of vulnerabilities of the target system (analyzed system), to confirm the possibility of their implementation, that is, to validate vulnerabilities by simulating the real actions of a potential attacker. The urgent need to validate vulnerabilities out of the many identified is caused by the fact that some of them can only be theoretical, while others are exploited using malicious scripts (exploits). At the same time, the process of validating vulnerabilities is practically not studied. That is why the work carried out an experimental study of the functioning of modern tools for exploiting vulnerabilities. Based on the observations, general quantitative characteristics of the vulnerability validation process were identified. A mathematical model for the analysis of the above characteristics based on Bernstein polynomials has been developed. It is the polynomial representation of the procedure for confirming the possibility of implementing the identified vulnerabilities that makes it possible to describe the dynamics of this process, taking into account the complex and volatile nature of the environment. Analytical dependencies are obtained for the number of cases of successful and negative confirmation of vulnerabilities. In particular, negative validation cases include simply failed attempts to validate vulnerabilities, as well as attempts that resulted in critical errors on the target system during the rational cycle of validating the identified vulnerabilities. The proposed dependencies make it possible to construct the probability distribution laws for the above characteristics of the vulnerability testing process.

At-home medical student simulation: achieving knot-tying proficiency using video-based assessment.

PurposeDue to the pandemic, we restructured our medical student knot-tying simulation to a virtual format. This study evaluated curriculum feasibility and effectiveness.MethodsOver 4 weeks, second-year medical students (n = 229) viewed a video tutorial (task demonstration, errors, scoring) and self-practiced to proficiency (no critical errors, < 2 min) using at-home suture kits (simple interrupted suture, instrument tie, penrose drain model). Optional virtual tutoring sessions were offered. Students submitted video performance for proficiency verification. Two sets of 14 videos were viewed by two surgeons until inter-rater reliability (IRR) was established. Students scoring “needs remediation” attended virtual remediation sessions. Non-parametric statistics were performed using RStudio.ResultsAll 229 medical students completed the curriculum within 1–4 h; 1.3% attended an optional tutorial. All videos were assessed: 4.8% “exceeds expectations”, 60.7% “meets expectations”, and 34.5% “needs remediation.” All 79 needing remediation due to critical errors achieved proficiency during 1-h group sessions. IRR Cohen’s κ was 0.69 (initial) and 1.0 (ultimate). Task completion time was 56 (47–68) s (median [IQR]); p < 0.01 between all pairs. Students rated the overall curriculum (79.2%) and overall curriculum and video tutorial effectiveness (92.7%) as “agree” or “strongly agree”. No definitive preference emerged regarding virtual versus in-person formats; however, 80.2% affirmed wanting other at-home skills curricula. Comments supported home practice as lower stress; remediation students valued direct formative feedback.ConclusionsA completely virtual 1-month knot-tying simulation is feasible and effective in achieving proficiency using video-based assessment and as-needed remediation strategies for a large student class.

Towards smart monitored AM: Open source in-situ layer-wise 3D printing image anomaly detection using histograms of oriented gradients and a physics-based rendering engine

This study presents an open source method for detecting 3D printing anomalies by comparing images of printed layers from a stationary monocular camera with G-code-based reference images of an ideal process generated with Blender, an open source free physics rendering engine. Recognition of visual deviations was accomplished by analyzing the similarity of histograms of oriented gradients (HOG) of local image areas. The developed technique requires preliminary modeling of the working environment to achieve the best match for orientation, color rendering, lighting, and other parameters of the printed part. The output of the algorithm is a level of mismatch between printed and synthetic reference layers. Twelve similarity and distance measures were implemented and compared for their effectiveness at detecting 3D printing errors on six different representative failure types (local infill defects, presence of a foreign body in the layer, spaghetti problem, separation and shift of the printing part from the working surface, defects in thin walls, and layer shift) and their control error-free print images. The results show that although Kendall’s tau, Jaccard, and Sorensen similarities are the most sensitive, Pearson's r, Spearman's rho, cosine, and Dice similarities produce the more distinguishable results. This open source method allows the program to notice critical errors in the early stages of their occurrence and either pause manufacturing processes for further investigation by an operator or in the future intelligent automatic error correction. The implementation of this novel method does not require preliminary data for training, and the greatest efficiency can be achieved with the mass production of parts by either additive or subtractive manufacturing of the same geometric shape. This open-source method has the potential means of enabling smart distributed recycling for additive manufacturing in challenging environments.

A prospective study of switching asthma patients from a Fixed-Dose Combination (FDC) Inhaled Corticosteroid [ICS]/Long-Acting Beta Agonist [LABA] therapy delivered by Dry Powder Inhaler (DPI) to ICS/LABA delivered by pressurised Metered Dose Inhaler (pMDI)

BackgroundPrevious real-world studies have suggested that in comparison to a dry powder inhaler (DPI), the rate of critical errors is lower with a pressurised metered dose inhaler (pMDI), and inhaled corticosteroid/long-acting bronchodilator (ICS/LABA) delivered by pMDI is more likely to achieve asthma control. ObjectivesTo evaluate the acceptability, efficacy, safety and cost-effectiveness of switching asthma patients from an ICS/LABA DPI to an ICS/LABA pMDI in a real-world population in Kuwait. MethodsThis was a 12-month, observational, nonblinded, prospective, real world study. Patients with asthma for ≥1 year with 2 or more asthma exacerbations in the last year were assigned to either switch to ICS/LABA pMDI, or to continue with ICS/LABA DPI. ResultsA total of 239 patients were treated with either ICS/LABA pMDI (Switch cohort; n = 119) or ICS/LABA DPI (Maintenance cohort; n = 120). The majority of patients (99/119; 83.2%) in the Switch cohort remained on ICS/LABA pMDI over 12 months of follow-up. Both cohorts experienced an improvement in their FEV1 levels, with mean values in the Switch group reaching normal levels (>80% predicted). On average, at 3 and 12 months, the Switch cohort had significantly better FEV1 values than patients in the Maintenance cohort (p = 0.001). At 12 months, the proportion of patients with controlled asthma increased in the Switch group, but did not change significantly in the Maintenance group. ConclusionsIn patients with asthma symptoms that are not well controlled with an ICS/LABA DPI, switching to an ICS/LABA pMDI provides an alternative choice that may improve asthma control.