2021 Reviewers With Distinction Award

The Journal of Mechanical Design Reviewers with Distinction Award is given to reviewers who have made a meritorious contribution to the journal in terms of the number, quality, and turnaround time of reviews completed during the past year.

Changing from mandatory to optional genotyping results in higher acceptance of pharmacist-guided warfarin dosing

Aim: We evaluated the clinical acceptance and feasibility of a pharmacist-guided personalized consult service following its transition from a mandatory (mPGx) to optional (oPGx) CYP2C9/ VKORC1/ CYP4F2 genotyping for warfarin. Methods: A total of 1105 patients were included. Clinical acceptance and feasibility outcomes were analyzed using bivariate and multivariable analyses. Results: After transitioning to optional genotyping, genotype testing was still ordered in a large segment of the eligible population (52.1%). Physician acceptance of pharmacist-recommended doses improved from 83.9% (mPGx) to 86.6% (oPGx; OR: 1.3; 95% CI: 1.1–1.5; p = 0.01) with a shorter median genotype result turnaround time (oPGX: 23.6 hr vs mPGX: 25.1 hr ; p < 0.01). Conclusion: Ordering of genotype testing and provider acceptance of dosing recommendations remained high after transitioning to optional genotyping.

Rapid syndromic PCR testing in patients with respiratory tract infections reduces time to results and improves microbial yield

Lack of rapid and comprehensive microbiological diagnosis in patients with community acquired pneumonia (CAP) hampers appropriate antimicrobial therapy. This study evaluates the real-world performance of the BioFire FilmArray Pneumonia panel plus (FAP plus) and explores the feasibility of evaluation in a randomised controlled trial. Patients presenting to hospital with suspected CAP were recruited in a prospective feasibility study. An induced sputum or an endotracheal aspirate was obtained from all participants. The FAP plus turnaround time (TAT) and microbiological yield were compared with standard diagnostic methods (SDs). 96/104 (92%) enrolled patients had a respiratory tract infection (RTI); 72 CAP and 24 other RTIs. Median TAT was shorter for the FAP plus, compared with in-house PCR (2.6 vs 24.1 h, p < 0.001) and sputum cultures (2.6 vs 57.5 h, p < 0.001). The total microbiological yield by the FAP plus was higher compared to SDs (91% (162/179) vs 55% (99/179), p < 0.0001). Haemophilus influenzae, Streptococcus pneumoniae and influenza A virus were the most frequent pathogens. In conclusion, molecular panel testing in adults with CAP was associated with a significant reduction in time to actionable results and increased microbiological yield. The impact on antibiotic use and patient outcome should be assessed in randomised controlled trials.

Molecular methods for diagnosing novel coronavirus infection: comparison of loop-mediated isothermal amplification and polymerase chain reaction

Introduction. Currently, the basis for molecular diagnostics of most infections is the use of reverse transcription polymerase chain reaction (RT-PCR). Technologies based on reverse transcription isothermal loop amplification (RT-LAMP) can be used as an alternative to RT-PCR for diagnostic purposes. In this study, we compared the RTLAMP and RT-PCR methods in order to analyze both the advantages and disadvantages of the two approaches.Material and methods. For the study, we used reagent kits based on RT-PCR and RT-LAMP. The biological material obtained by taking swabs from the mucous membrane of the oropharynx and nasopharynx in patients with symptoms of a new coronavirus infection was used.Results. We tested 381 RNA samples of the SARS-CoV-2 virus (Coronaviridae: Coronavirinae: Betacoronavirus; Sarbecovirus) from various patients. The obtained values of the threshold cycle (Ct) for RT-PCR averaged 20.0 ± 3.7 s (1530 ± 300 s), and for RT-LAMP 12.8 ± 3.7 s (550 ± 160 s). Proceeding from the theoretical assumptions, a linear relationship between values obtained in two kits was proposed as a hypothesis; the correlation coefficient was approximately 0.827. At the same time, for samples with a low viral load (VL), the higher Ct values in RT-LAMP did not always correlated with those obtained in RT-PCR.Discussion. We noted a significant gain in time for analysis using RT-LAMP compared to RT-PCR, which can be important in the context of testing a large number of samples. Being easy to use and boasting short turnaround time, RT-LAMP-based test systems can be used for mass screening in order to identify persons with medium and high VLs who pose the greatest threat of the spread of SARS-CoV-2, while RT-PCR-based diagnostic methods are also suitable for estimation of VL and its dynamics in patients with COVID-19.

RNA purification-free detection of SARS-CoV-2 using reverse transcription loop-mediated isothermal amplification (RT-LAMP)

Background Current diagnosis of SARS-CoV-2 infection relies on RNA purification prior to amplification. Typical extraction methods limit the processing speed and turnaround time for SARS-CoV-2 diagnostic testing. Methods Here, we applied reverse transcription loop-mediated isothermal amplification directly onto human clinical swabs samples to amplify the RNA from SARS-CoV-2 swab samples after processing with chelating resin. Results By testing our method on 64 samples, we managed to develop an RT-LAMP assay with 95.9% sensitivity (95% CI 86 to 99.5%) and 100% specificity (95% CI 78.2–100%). Conclusion The entire process including sample processing can be completed in approximately 50 min. This method has promising potential to be applied as a fast, simple and inexpensive diagnostic tool for the detection of SARS-CoV-2.

Clinical Performance of the Xpert® CT/NG Test for Detection of Chlamydia trachomatis and Neisseria gonorrhoeae: A Multicenter Evaluation in Chinese Urban Hospitals

BackgroundWe aimed to evaluate the clinical performance of the GeneXpert® (Xpert) CT/NG assay for the detection of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) using urine and cervical swabs collected from patients in China.MethodsThis study was conducted from September 2016 to September 2018 in three Chinese urban hospitals. The results from the Xpert CT/NG test were compared to those from the Roche cobas® 4800 CT/NG test. Discordant results were confirmed by DNA sequence analysis.ResultsIn this study, 619 first void urine (FVU) specimens and 1,042 cervical swab specimens were included in the final dataset. There were no statistical differences between the results of the two tests for the detection of CT/NG in urine samples (p &gt; 0.05), while a statistical difference was found in cervical swabs (p &lt; 0.05). For CT detection, the sensitivity and specificity of the Xpert test were 100.0% (95%CI = 96.8–99.9) and 98.3% (95%CI = 96.6–99.2) for urine samples and 99.4% (95%CI = 96.5–100.0) and 98.6% (95%CI 97.5–99.2) for cervical swabs, respectively. For NG detection, the sensitivity and specificity of the Xpert test were 99.2% (95%CI = 94.9–100.0) and 100.0% (95%CI = 99.0–100.0) for urine and 100% (95%CI = 92.8–100.0) and 99.7% (95%CI = 99.0–99.9) for cervical swabs, respectively.ConclusionThe Xpert CT/NG test exhibited high sensitivity and specificity in the detection of CT and NG in both urine and cervical samples when compared to the reference results. The 90-min turnaround time for CT and NG detection at the point of care using Xpert may enable patients to receive treatment promptly.

Clinical efficiency of simultaneous CNV-seq and whole-exome sequencing for testing fetal structural anomalies

Background Birth defects are responsible for approximately 7% of neonatal deaths worldwide by World Health Organization in 2004. Many methods have been utilized for examining the congenital anomalies in fetuses. This study aims to investigate the efficiency of simultaneous CNV-seq and whole-exome sequencing (WES) in the diagnosis of fetal anomaly based on a large Chinese cohort. Methods In this cohort study, 1800 pregnant women with singleton fetus in Hubei Province were recruited from 2018 to 2020 for prenatal ultrasonic screening. Those with fetal structural anomalies were transferred to the Maternal and Child Health Hospital of Hubei Province through a referral network in Hubei, China. After multidisciplinary consultation and decision on fetal outcome, products of conception (POC) samples were obtained. Simultaneous CNV-seq and WES was conducted to identify the fetal anomalies that can compress initial DNA and turnaround time of reports. Results In total, 959 couples were finally eligible for the enrollment. A total of 227 trios were identified with a causative alteration (CNV or variant), among which 191 (84.14%) were de novo. Double diagnosis of pathogenic CNVs and variants have been identified in 10 fetuses. The diagnostic yield of multisystem anomalies was significantly higher than single system anomalies (32.28% vs. 22.36%, P = 0.0183). The diagnostic rate of fetuses with consistent intra- and extra-uterine phenotypes (172/684) was significantly higher than the rate of these with inconsistent phenotypes (17/116, P = 0.0130). Conclusions Simultaneous CNV-seq and WES analysis contributed to fetal anomaly diagnosis and played a vital role in elucidating complex anomalies with compound causes.

Nanophotonics: An Emerging and Promising Approach for COVID-19 Diagnostic Technology

The public health crisis initiated by the emergence of the COVID-19 pandemic emphasizes the need for rapid and accurate diagnostic tests to monitor large populations through community mass testing. Many testing techniques have been implemented to prevent disease spread, critical to pandemic control. Polymerase chain reaction (PCR) tests for detecting viral RNA and immunoassay tests for detecting SARS-CoV-2 antibodies are currently used to diagnose COVID-19. PCR tests are time-consuming, with a 24–48 hours turnaround time. Samples undergoing PCR detection must also be sent to a laboratory to be processed by highly specialized workers, preventing a point-of-care diagnosis from being provided. Popular immunoassay tests have drawbacks as well. Enzyme-linked immunosorbent assays (ELISAs) are extremely labor-intensive and expensive, whereas lateral flow assays (LFAs) are primarily used for antigen detection. In this work, we propose a photonic SARS-CoV-2 detection method based on a ring resonator. We calculate the sensor performance using the finite-difference eigenmode (FDE) method. The sensor sensitivity in ring resonator resonance frequency is 29 nm/RIU, with an intrinsic detection level (iLOD) of 6.89 × 10-5 RIU. We envision ring resonator-based lab-on-chip devices being widely used for applications such as early diagnosis, with the added benefit of being ultra-compact and easily handled by non-specialists.

A Software Development Life Cycle Case Study Of Lean IT With Value Stream Mapping Analysis

Value Stream Mapping (VSM) is a useful tool for depicting the flow of materials and information in manufacturing and service processes. It is known as one of the most popular lean methods to identify bottlenecks, reduce cycle time, and improve current processes. Although VSM has been extensively used in manufacturing, there are limited studies that applied VSM in non-manufacturing environments. In this study, we present an application of VSM to improve Software Development Life Cycle (SDLC) process in an IT firm. The current process flows (as-is) are mapped to identify non-value-added activities as well as areas for improvement. Based on the analysis of the current state map, we propose recommendations, action plans, and a future state map (to-be-process). We estimate that, with the new process changes, IT project delivery time can be reduced from 210.5 days to 137.5 days – a 34.7% reduction in the software development life cycle process. This provides a powerful base for IT project management and enables the IT department to meet its expected project turnaround time.

Performance of the BinaxNOW COVID-19 Antigen Rapid Diagnostic Test for the Detection of SARS-CoV-2

Background: Diagnosis of COVID-19 disease primarily relies on nucleic acid amplification tests (NAAT) that amplify and detect viral RNA in specimens. These methods are expensive and time consuming. Antigen-based rapid diagnostic tests can substantially decrease turnaround time.Methods: We analyzed paired anterior nares swabs collected from symptomatic patients and asymptomatic healthcare workers being tested COVID-19. One swab was used for a direct RDT and the results were compared to NAAT.Results: 89 paired specimens were evaluated. The positive percent agreement (PPA) for the antigen RDT was 68.2%, and the negative percent agreement (NPA) was 98.5%. Despite a low PPA, the Κ statistic was 0.733 indicating substantial agreement with the NAAT result. The median cycle number in paired specimens with concordant results was significantly lower than in discordant specimens (21.3 versus 32.3; P=0.003).Conclusions: The RDT showed modest PPA and high NPA when compared to NAAT. The quick TAT and use of an inexpensive test more frequently could be useful in settings in which results from NAAT testing is delayed.