Characterization of a novel mouse platelet transfusion model.

BACKGROUND AND OBJECTIVES: Platelet transfusions are increasing with medical advances. Based on FDA criteria, platelet units are assessed by in vitro measures; however, it is not known how platelet processing and storage duration affect function in vivo. Our study's aim was to develop a novel platelet transfusion model stored in mouse plasma that meets FDA criteria adapted to mice, and transfused fresh and stored platelets are detectable in clots in vivo. STUDY DESIGN AND METHODS: Platelet units stored in mouse plasma were prepared using a modified platelet-rich plasma (PRP) collection protocol. Characteristics of fresh and stored units, including pH, cell count, in vitro measures of activity, including activation and aggregation, and post-transfusion recovery (PTR), were determined. Lastly, a tail transection assay was conducted using mice transfused with fresh or stored units, and transfused platelets were identified by confocal imaging. RESULTS: Platelet units had acceptable platelet and white cell counts and were negative for bacterial contamination. Fresh and 1-day stored units had acceptable pH; the platelets were activatable by thrombin and adenosine diphosphate, agreeable with thrombin, had acceptable PTR, and were present in vivo in clots of recipients after tail transection. In contrast, 2-day stored units had clinically unacceptable quality. CONCLUSION: We developed mouse platelets for transfusion analogous to human platelet units using a modified PRP collection protocol with maximum storage of 1 day for an 'old' unit. This provides a powerful tool to test how process modifications and storage conditions affect transfused platelet function in vivo.

Predictors of Episode-of-Care Costs for Ankle Fractures.

Ankle fractures are one of the most resource-consuming traumatic orthopedic injuries. Few studies have successfully evaluated the episode-of-care costs (EOCC) of common traumatic orthopedic injuries. The objective of this study was to determine the EOCC associated with the surgical management of ankle fractures. A retrospective cohort study of 105 consecutive patients who underwent open reduction internal fixation of an isolated ankle fracture at a Canadian Level-1 trauma center was conducted. Episode-of-care costs were generated using an activity-based costing framework. The median global episode-of-care cost for ankle fracture surgeries performed at the studied institution was $3,487 CAD [IQR 880] ($2,685 USD [IQR 616]). Patients aged 60 to 90 years had a significantly higher median EOCC than younger patients (p = .01). Supination-adduction injuries had a significantly higher median EOCC than other injury patterns (p = .01). The median EOCC for patients who underwent surgery within 10 days of their injury ($3,347 CAD [582], $2,577 USD [448]) was significantly lower than the cost for patients who had their surgery delayed 10 days or more after the injury ($3,634 CAD [776], $2,798 USD [598]) (p = .03). Patient sex, anesthesia type, ASA score and surgeon's fellowship training did not affect the EOCC. This study provides valuable data on predictors of EOCC in the surgical management of ankle fractures. Delaying simple ankle fracture cases due to operating time constraints can increase the total cost and burden of these fractures on the healthcare system. In addition, this study provides a framework for future episode-of-care cost analysis studies in orthopedic surgery.

Congenital Tuberculosis After In Vitro Fertilization: A Case for Tuberculosis Screening of Women Evaluated for Infertility.

We report a case of multidrug-resistant congenital tuberculosis (TB) in an infant conceived by in vitro fertilization and review 22 additional infant-mother pairs in the literature. Females evaluated for infertility should be screened for TB risk, and those at risk require a TB-specific diagnostic evaluation before receiving assisted reproductive treatment.

Multicenter Evaluation of the BIOFIRE Blood Culture Identification 2 Panel for Detection of Bacteria, Yeasts, and Antimicrobial Resistance Genes in Positive Blood Culture Samples.

Diagnostic tools that can rapidly identify and characterize microbes growing in blood cultures are important components of clinical microbiology practice because they help to provide timely information that can be used to optimize patient management. This publication describes the bioMérieux BIOFIRE Blood Culture Identification 2 (BCID2) Panel clinical study that was submitted to the U.S. Food & Drug Administration. Results obtained with the BIOFIRE BCID2 Panel were compared to standard-of-care (SoC) results, sequencing results, PCR results, and reference laboratory antimicrobial susceptibility testing results to evaluate the accuracy of its performance. Results for 1,093 retrospectively and prospectively collected positive blood culture samples were initially enrolled, and 1,074 samples met the study criteria and were included in the final analyses. The BIOFIRE BCID2 Panel demonstrated an overall sensitivity of 98.9% (1,712/1,731) and an overall specificity of 99.6% (33,592/33,711) for Gram-positive bacteria, Gram-negative bacteria and yeast targets which the panel is designed to detect. One hundred eighteen off-panel organisms, which the BIOFIRE BCID2 Panel is not designed to detect, were identified by SoC in 10.6% (114/1,074) of samples. The BIOFIRE BCID2 Panel also demonstrated an overall positive percent agreement (PPA) of 97.9% (325/332) and an overall negative percent agreement (NPA) of 99.9% (2,465/2,767) for antimicrobial resistance determinants which the panel is designed to detect. The presence or absence of resistance markers in Enterobacterales correlated closely with phenotypic susceptibility and resistance. We conclude that the BIOFIRE BCID2 Panel produced accurate results in this clinical trial.

A case of novel, rapidly-growing Mycolicibacter kumamotonensis infection in a patient with severe pulmonary disease treated in New York City.

INTRODUCTION: Mycolicibacter kumamotonensis is a slowly growing, non-chromogenic non-tuberculous mycobacteria (NTM) that was initially distinguished from the M. terrae complex in 2006. Since then it has been rarely reported as the cause of pulmonary and soft-tissue infections in both immunocompromised and immunocompetent patients. CASE PRESENTATION: We present a case of severe pulmonary disease due to Mycolicibacter kumamotonensis in a 57-year-old male who was immunocompetent at time of diagnosis, with a history of interstitial lung disease and a prior diagnosis of tuberculosis (TB). After initial treatment for TB in 2017, his condition stabilized until a recurrence in September 2021, leading to an evaluation for lung transplant in the setting of pulmonary fibrosis and emphysema which led to the identification of Mycolicibacter kumamotonensis. A lung transplant was completed, and the patient was successfully treated with a combination of Ethambutol, Azithromycin, and Rifabutin. CONCLUSIONS: This represents the first case reported of M. kumamotonensis in a patient undergoing lung transplant, and the first case with rapid culture growth during identification of the organism (4 days). This report highlights the need for consideration of M. kumamotonensis as a pathogen in humans, with the potential for rapid growth in liquid media, and the importance of early identification to inform empiric therapy.

Strategies to prevent long-term opioid use following trauma: a Canadian practice survey.

PURPOSE: To evaluate how Canadian clinicians involved in trauma patient care and prescribing opioids perceive the use and effectiveness of strategies to prevent long-term opioid therapy following trauma. Barriers and facilitators to the implementation of these strategies were also assessed. METHODS: We conducted a web-based cross-sectional survey. Potential participants were identified by trauma program managers and directors of the targeted departments in three Canadian provinces. We designed our questionnaire using standard health survey research methods. The questionnaire was administered between April 2021 and November 2021. RESULTS: Our response rate was 47% (350/744), and 52% (181/350) of participants completed the entire survey. Most respondents (71%, 129/181) worked in teaching hospitals. Multimodal analgesia (93%, 240/257), nonsteroidal anti-inflammatory agents (77%, 198/257), and physical stimulation (75%, 193/257) were the strategies perceived to be the most frequently used. Several preventive strategies were perceived to be very effective by over 80% of respondents. Of these, some that were reported as not being frequently used were perceived to be among the most effective ones, including guidelines or protocols, assessing risk factors for opioid misuse, physical health follow-up by a professional, training for clinicians, patient education, and prescription monitoring systems. Staff shortages, time constraints, and organizational practices were identified as the main barriers to the implementation of the highest ranked preventive strategies. CONCLUSIONS: Several strategies to prevent long-term opioid therapy following trauma are perceived as being effective by those prescribing opioids in this population. Some of these strategies appear to be commonly used in everyday practice and others less so. Future research should focus on which preventive strategies should be given higher priority for implementation before assessing their effectiveness.

RéSUMé: OBJECTIF: Évaluer comment les cliniciens canadiens impliqués dans les soins aux patients traumatisés et prescrivant des opioïdes perçoivent l'utilisation et l'efficacité des stratégies visant à prévenir le traitement prolongé par opioïde après un traumatisme. Les obstacles et facilitateurs de la mise en œuvre de ces stratégies ont aussi été analysés. MéTHODES: Nous avons réalisé une enquête transversale via le Web. Les participants potentiels ont été identifiés par les gestionnaires et directeurs de programmes de traumatologie des départements ciblés dans trois provinces canadiennes. Nous avons conçu notre questionnaire en utilisant la méthodologie de recherche usuelle des enquêtes de santé. Le questionnaire a été administré entre avril 2021 et novembre 2021. RéSULTATS: Notre taux de réponse a été de 47 % (350/744) et 52 % (181/350) des participants ont complété l'enquête dans sa totalité. La majorité des personnes interrogées (71 %, 129/181) travaillait dans des hôpitaux universitaires. L'analgésie multimodale (93 %, 240/257), les anti-inflammatoires non stéroïdiens (77 %, 198/257) et la stimulation physique (75 %, 193/257) étaient les stratégies perçues comme étant le plus fréquemment utilisées. Plusieurs stratégies préventives étaient perçues comme étant très efficaces par plus de 80 % des répondants. Parmi celles-ci, certaines étaient signalées comme n'étant pas utilisées très souvent, mais perçues comme étant les plus efficaces, notamment les lignes directrices et protocoles évaluant les facteurs de risque d'utilisation abusive des opioïdes, le suivi de la santé physique par un professionnel, la formation des cliniciens, l'éducation des patients et les systèmes de suivi des prescriptions. La pénurie de personnels, les contraintes de temps et les pratiques de l'établissement ont été identifiées comme étant les principaux obstacles à la mise en place des stratégies préventives classées parmi les premières. CONCLUSIONS: Plusieurs stratégies de prévention du traitement par opioïdes à long terme après un traumatisme sont perçues comme efficaces par ceux qui les prescrivent à cette population de patients. Certaines de ces stratégies apparaissent comme couramment utilisées dans la pratique quotidienne et d'autres moins souvent. La recherche future devrait se concentrer sur la détermination des stratégies préventives auxquelles il faudrait accorder la plus grande priorité de mise en œuvre avant d'évaluer leur efficacité.

Bacterial Pneumonia and Respiratory Culture Utilization among Hospitalized Patients with and without COVID-19 in a New York City Hospital.

COVID-19 is associated with prolonged hospitalization and a high risk of intubation, which raises concern for bacterial coinfection and antimicrobial resistance. Previous research has shown a wide range of bacterial pneumonia rates for COVID-19 patients in a variety of clinical and demographic settings, but none have compared hospitalized COVID-19 patients to patients testing negative for severe acute respiratory syndrome coronavirus (SARS-CoV-2) in similar care settings. We performed a retrospective cohort study on hospitalized patients with COVID-19 testing from March 10th, 2020 to December 31st, 2020. A total of 19,219 patients were included, of which 3,796 tested positive for SARS-CoV-2. We found a 2.6-fold increase (P < 0.001) in respiratory culture ordering in COVID-19 patients. On a per-patient basis, COVID-19 patients were 1.5-fold more likely than non-COVID patients to have positive respiratory cultures (46.8% versus 30.9%, P < 0.001), which was primarily driven by patients requiring intubation. Among patients with pneumonia, a significantly higher proportion of COVID-19 patients had ventilator-associated pneumonia (VAP) relative to non-COVID patients (86.3% versus 70.8%, P < 0.001), but a lower proportion had community-acquired (11.2% vs 25.5%, P < 0.01) pneumonia. There was also a significantly higher proportion of respiratory cultures positive for methicillin-resistant Staphylococcus aureus, Klebsiella pneumoniae, and antibiotic-resistant organisms in COVID-19 patients. Increased rates of respiratory culture ordering for COVID-19 patients therefore appear to be clinically justified for patients requiring intubation, but further research is needed to understand how SARS-CoV-2 increases the risk of VAP.

Multicenter Evaluation of the BioFire Respiratory Panel 2.1 (RP2.1) for Detection of SARS-CoV-2 in Nasopharyngeal Swab Samples.

As the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) begins to overlap with the traditional respiratory season in the Northern Hemisphere, simultaneous testing for SARS-CoV-2 and the other common causes of respiratory infections is imperative. This has led to the development of multiplex respiratory assays that include SARS-CoV-2 as a target. One such assay is the BioFire respiratory panel 2.1 (RP2.1), which is an expansion of the original BioFire FilmArray respiratory panel 2 (RP2) to include SARS-CoV-2. In this multicenter evaluation, we assessed the performance characteristics of the BioFire RP2.1 for the detection of SARS-CoV-2. One or more targets on the panel were detected in 19.3% (101/524) of specimens tested, with SARS-CoV-2 detected in 12.6% (66/524) of specimens. Human rhinovirus/enterovirus was also detected in 32.7% (33/101) and adenovirus in 3.0% (3/101) of positive specimens, with one dual positive for both SARS-CoV-2 and adenovirus being detected. A further breakdown of pathogens by age revealed a 4-fold predominance of human rhinovirus/enterovirus in subjects 0 to 18 years of age, whereas in all other age groups, SARS-CoV-2 was clearly the predominant pathogen. Overall, SARS-CoV-2 results obtained from the BioFire RP2.1 were highly concordant with the composite result, exhibiting 98.4% (61/62) positive percent agreement (95% confidence interval [CI], 91.4 to 99.7%) and 98.9% (457/462) negative percent agreement (95% CI, 97.5 to 99.5%) with further analysis of discordant results suggesting that the concentration of SARS-CoV-2 in the specimens was near the limit of detection (LoD) for both the BioFire RP2.1 and the comparator assays. Overall, the BioFire RP2.1 exhibited excellent performance in the detection of SARS-CoV-2.

Partial ORF1ab Gene Target Failure with Omicron BA.2.12.1.

Mutations in the genome of SARS-CoV-2 can affect the performance of molecular diagnostic assays. In some cases, such as S-gene target failure, the impact can serve as a unique indicator of a particular SARS-CoV-2 variant and provide a method for rapid detection. Here, we describe partial ORF1ab gene target failure (pOGTF) on the cobas SARS-CoV-2 assays, defined by a ≥2-thermocycle delay in detection of the ORF1ab gene compared to that of the E-gene. We demonstrate that pOGTF is 98.6% sensitive and 99.9% specific for SARS-CoV-2 lineage BA.2.12.1, an emerging variant in the United States with spike L452Q and S704L mutations that may affect transmission, infectivity, and/or immune evasion. Increasing rates of pOGTF closely mirrored rates of BA.2.12.1 sequences uploaded to public databases, and, importantly, increasing local rates of pOGTF also mirrored increasing overall test positivity. Use of pOGTF as a proxy for BA.2.12.1 provides faster tracking of the variant than whole-genome sequencing and can benefit laboratories without sequencing capabilities.

Cancellations and delays of emergent orthopedic operations at a Canadian level 1 trauma centre.

BACKGROUND: Day-of surgery cancellation (DOSC) is considered to be a very inefficient use of hospital resources and results in emotional stress for the patient. To examine opportunities to minimize the incidence of preventable cancellations - an indicator of quality of care - we assessed the incidence of and reasons for DOSCs over 3 months among inpatients and outpatients at a trauma orthopedic service. METHODS: This was a prospective study of 2 cohorts of patients, inpatients and outpatients, scheduled for emergent orthopedic surgery at a Canadian tertiary level 1 trauma centre from Jan. 1 to Mar. 31, 2020. Patient demographic characteristics, injury characteristics, delays until surgery and reasons for DOSCs were recorded. RESULTS: A total of 185 patients (100 males and 85 females with a mean age of 54 yr) were included in the study. There were 98 outpatients and 87 inpatients. Seventy-five (40%) of the scheduled procedures in the outpatient group and 34 (30%) of those in the inpatient group were cancelled. In both groups, more than 85% of the cancellations were because of prioritization of a more urgent orthopedic or nonorthopedic surgical case. The average operative delay for the outpatient group was 11.4 days, compared to 3.8 days for the inpatient group (p < 0.001). CONCLUSION: High DOSC rates were observed among both outpatients and inpatients. The main reason for delaying surgery was prioritization of a more urgent surgical case. Providing the orthopedic trauma service with a dedicated OR opened 6 days per week, along with extended hours of OR services to 1700 daily, might be effective at minimizing DOSCs.

3-Dimensional Printed Alternative to the Standard Synthetic Flocked Nasopharyngeal Swabs Used for Coronavirus Disease 2019 Testing.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), can be detected in respiratory samples by real-time reverse transcriptase polymerase chain reaction (RT-PCR) or other molecular methods. Accessibility of diagnostic testing for COVID-19 has been limited by intermittent shortages of supplies required for testing, including flocked nasopharyngeal (FLNP) swabs. METHODS: We developed a 3-dimensional printed nasopharyngeal (3DP) swab as a replacement of the FLNP swab. The performance of 3DP and FLNP swabs were compared in a clinical trial of symptomatic patients at 3 clinical sites (n = 291) using 3 SARS-CoV-2 emergency use authorization tests: a modified version of the Centers for Disease Control and Prevention (CDC) RT-PCR Diagnostic Panel and 2 commercial automated formats, Roche Cobas and NeuMoDx. RESULTS: The cycle threshold-C(t)-values from the gene targets and the RNase P gene control in the CDC assay showed no significant differences between swabs for both gene targets (P = .152 and P = .092), with the RNase P target performing significantly better in the 3DP swabs (P < .001). The C(t) values showed no significant differences between swabs for both viral gene targets in the Roche cobas assay (P = .05 and P = .05) as well as the NeuMoDx assay (P = .401 and P = .484). The overall clinical correlation of COVID-19 diagnosis between all methods was 95.88% (Kappa 0.901). CONCLUSIONS: The 3DP swabs were equivalent to standard FLNP in 3 testing platforms for SARS-CoV-2. Given the need for widespread testing, 3DP swabs printed onsite are an alternate to FLNP that can rapidly scale in response to acute needs when supply chain disruptions affect availability of collection kits.

Multicenter Evaluation of the Cepheid Xpert Xpress SARS-CoV-2/Flu/RSV Test.

With the approach of respiratory virus season in the Northern Hemisphere, clinical microbiology and public health laboratories will need rapid diagnostic assays to distinguish severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from influenza virus and respiratory syncytial virus (RSV) infections for diagnosis and surveillance. In this study, the clinical performance of the Xpert Xpress SARS-CoV-2/Flu/RSV test (Cepheid, Sunnyvale, CA, USA) for nasopharyngeal swab specimens was evaluated in four centers: Johns Hopkins Medical Microbiology Laboratory, Northwell Health Laboratories, NYC Public Health Laboratory, and Los Angeles County/University of Southern California (LAC+USC) Medical Center. A total of 319 nasopharyngeal swab specimens, positive for SARS-CoV-2 (n = 75), influenza A virus (n = 65), influenza B virus (n = 50), or RSV (n = 38) or negative (n = 91) by the standard-of-care nucleic acid amplification tests at each site, were tested using the Cepheid panel test. The overall positive percent agreement for the SARS-CoV-2 target was 98.7% (n = 74/75), and the negative agreement was 100% (n = 91), with all other analytes showing 100% total agreement (n = 153). Standard-of-care tests to which the Cepheid panel was compared included the Cepheid Xpert Xpress SARS-CoV-2, Cepheid Xpert Xpress Flu/RSV, GenMark ePlex respiratory panel, BioFire respiratory panel 2.1 and v1.7, DiaSorin Simplexa COVID-19 Direct, and Hologic Panther Fusion SARS-CoV-2 assays. The Xpert Xpress SARS-CoV-2/Flu/RSV test showed high sensitivity and accuracy for all analytes included in the test. This test will provide a valuable clinical diagnostic and public health solution for detecting and differentiating SARS-CoV-2, influenza A and B virus, and RSV infections during the current respiratory virus season.

Low-value injury care in the adult orthopaedic trauma population: A systematic review.

OBJECTIVES: Fifteen potentially low value practices in adult orthopaedic trauma care were previously identified in a scoping review. The aim of this study was to synthesise the evidence on these practices. METHODS: We searched four databases for systematic reviews, randomised controlled trials (RCTs), cohort studies and case series that assessed the effectiveness of selected practices. Methodological quality was evaluated using the Measurement Tool to Assess Systematic Reviews version 2 (AMSTAR-2) for systematic reviews and the Critical Appraisal Checklist for Case Series. We evaluated risk of bias with the Cochrane revised tool for RCTs and the risk of bias in non-randomised studies of interventions tool for observational studies. We summarised findings with measures of frequency and association for primary outcomes. RESULTS: Of the 30,670 records screened, 70 studies were retained. We identified high-level evidence of lack of effectiveness or harm for routine initial imaging of ankle injury, orthosis for A0-A3 thoracolumbar burst fracture in patients <60 years of age, cast or splint immobilisation for suspected scaphoid fracture negative on MRI or confirmed fifth metacarpal neck fracture, and routine follow-up imaging for distal radius and ankles fractures. However, evidence was mostly based on studies of low methodological quality or high risk of bias. CONCLUSION: In this review, we identified clinical practices in orthopaedic injury care which are not supported by current evidence and whose use may be questioned. In future research, we should measure their frequency, assess practice variations and evaluate root causes to identify practices that could be targeted for de-implementation.

Rapid Emergence of SARS-CoV-2 in the Greater New York Metropolitan Area: Geolocation, Demographics, Positivity Rates, and Hospitalization for 46 793 Persons Tested by Northwell Health.

BACKGROUND: In March 2020, the greater New York metropolitan area became an epicenter for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The initial evolution of case incidence has not been well characterized. METHODS: Northwell Health Laboratories tested 46 793 persons for SARS-CoV-2 from 4 March through 10 April. The primary outcome measure was a positive reverse transcription-polymerase chain reaction test for SARS-CoV-2. The secondary outcomes included patient age, sex, and race, if stated; dates the specimen was obtained and the test result; clinical practice site sources; geolocation of patient residence; and hospitalization. RESULTS: From 8 March through 10 April, a total of 26 735 of 46 793 persons (57.1%) tested positive for SARS-CoV-2. Males of each race were disproportionally more affected than females above age 25, with a progressive male predominance as age increased. Of the positive persons, 7292 were hospitalized directly upon presentation; an additional 882 persons tested positive in an ambulatory setting before subsequent hospitalization, a median of 4.8 days later. Total hospitalization rate was thus 8174 persons (30.6% of positive persons). There was a broad range (>10-fold) in the cumulative number of positive cases across individual zip codes following documented first caseincidence. Test positivity was greater for persons living in zip codes with lower annual household income. CONCLUSIONS: Our data reveal that SARS-CoV-2 incidence emerged rapidly and almost simultaneously across a broad demographic population in the region. These findings support the premise that SARS-CoV-2 infection was widely distributed prior to virus testing availability.

Clinical Evaluation of Three Sample-to-Answer Platforms for Detection of SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now spread across the globe. As part of the worldwide response, many molecular diagnostic platforms have been granted emergency use authorization (EUA) by the Food and Drug Administration (FDA) to identify SARS-CoV-2 positive patients. Our objective was to evaluate three sample-to-answer molecular diagnostic platforms (Cepheid Xpert Xpress SARS-CoV-2 [Xpert Xpress], Abbott ID NOW COVID-19 [ID NOW], and GenMark ePlex SARS-CoV-2 Test [ePlex]) to determine analytical sensitivity, clinical performance, and workflow for the detection of SARS-CoV-2 in nasopharyngeal swabs from 108 symptomatic patients. We found that Xpert Xpress had the lowest limit of detection (100% detection at 100 copies/ml), followed by ePlex (100% detection at 1,000 copies/ml), and ID NOW (20,000 copies/ml). Xpert Xpress also had highest positive percent agreement (PPA) compared to our reference standard (98.3%) followed by ePlex (91.4%) and ID NOW (87.7%). All three assays showed 100% negative percent agreement (NPA). In the workflow analysis, ID NOW produced the lowest time to result per specimen (∼17 min) compared to Xpert Xpress (∼46 min) and ePlex (∼1.5 h), but what ID NOW gained in rapid results, it lost in analytical and clinical performance. ePlex had the longest time to results and showed a slight improvement in PPA over ID NOW. Information about the clinical and analytical performance of these assays, as well as workflow, will be critical in making informed and timely decisions on testing platforms.

Comparison of Four Molecular In Vitro Diagnostic Assays for the Detection of SARS-CoV-2 in Nasopharyngeal Specimens.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel human coronavirus that causes coronavirus disease 2019 (COVID-19), was first discovered in December 2019 as the cause of an outbreak of pneumonia in the city of Wuhan, Hubei province, China. The clinical presentation of COVID-19 is fairly nonspecific, and symptoms overlap those of other seasonal respiratory infections concurrently circulating in the population. Furthermore, it is estimated that up to 80% of infected individuals experience mild symptoms or are asymptomatic, confounding efforts to reliably diagnose COVID-19 empirically. To support infection control measures, there is an urgent need for rapid and accurate molecular diagnostics to identify COVID-19-positive patients. In the present study, we evaluated the analytical sensitivity and clinical performance of the following four SARS-CoV-2 molecular diagnostic assays granted emergency use authorization by the FDA using nasopharyngeal swabs from symptomatic patients: the New York SARS-CoV-2 Real-time Reverse Transcriptase (RT)-PCR Diagnostic Panel (modified CDC) assay, the Simplexa COVID-19 Direct (Diasorin Molecular) assay, GenMark ePlex SARS-CoV-2 (GenMark) assay, and the Hologic Panther Fusion SARS-CoV-2 (Hologic) assay. This information is crucial for both laboratories and clinical teams as decisions on which testing platform to implement are made.

Analytical and Clinical Comparison of Three Nucleic Acid Amplification Tests for SARS-CoV-2 Detection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in December 2019 and has quickly become a worldwide pandemic. In response, many diagnostic manufacturers have developed molecular assays for SARS-CoV-2 under the Food and Drug Administration (FDA) Emergency Use Authorization (EUA) pathway. This study compared three of these assays, the Hologic Panther Fusion SARS-CoV-2 assay (Fusion), the Hologic Aptima SARS-CoV-2 assay (Aptima), and the BioFire Defense COVID-19 test (BioFire), to determine analytical and clinical performance as well as workflow. All three assays showed similar limits of detection (LODs) using inactivated virus, with 100% detection, ranging from 500 to 1,000 genome equivalents/ml, whereas use of a quantified RNA transcript standard showed the same trend but had values ranging from 62.5 to 125 copies/ml, confirming variability in absolute quantification of reference standards. The clinical correlation found that the Fusion and BioFire assays had a positive percent agreement (PPA) of 98.7%, followed by the Aptima assay at 94.7%, compared to the consensus result. All three assays exhibited 100% negative percent agreement (NPA). Analysis of discordant results revealed that all four samples missed by the Aptima assay had cycle threshold (Ct ) values of >37 by the Fusion assay. In conclusion, while all three assays showed similar relative LODs, we showed differences in absolute LODs depending on which standard was employed. In addition, the Fusion and BioFire assays showed better clinical performance, while the Aptima assay showed a modest decrease in overall PPA. These findings should be kept in mind when making platform testing decisions.

The Promise of Smartphone Applications in the Remote Monitoring of Postsurgical Wounds: A Literature Review.

OBJECTIVE: To review the clinical and scientific literature on remote monitoring and management of postsurgical wounds using smartphone applications (apps). DATA SOURCES: MEDLINE, PubMed, EMBASE, and Cochrane libraries were searched for relevant articles on patients who received surgery and were monitored postdischarge via an app. STUDY SELECTION: Articles were selected with the terms "mobile phones," "smartphones," "wounds," "monitor," and "patient preference." DATA EXTRACTION: The authors found 276 review articles related to telemedicine in wound care. Investigators reviewed the titles and abstracts of the search results and selected 83 articles that were relevant to the remote monitoring of wounds using smartphone apps. DATA SYNTHESIS: The topics explored in selected literature included smartphone app importance to telemedicine, benefits (medical and financial), app examples, and challenges in the context of wound monitoring and management. The authors identified several challenges and limitations that future studies in the field need to address. CONCLUSIONS: Remote monitoring and management of wounds using smartphone apps is a valuable technique to enhance the quality of and access to healthcare. However, although some patients may prefer this technology, some lack technological competence, limiting telemedicine's applicability. In addition, issues remain with the reliable interpretation of data collected through apps.

Comparison of the Panther Fusion and BD MAX Group B Streptococcus (GBS) Assays for Detection of GBS in Prenatal Screening Specimens.

Streptococcus agalactiae or group B Streptococcus (GBS) is the cause of early- and late-onset GBS disease in neonates and can present as septicemia, meningitis, and pneumonia. Our objective was to compare the performance of two FDA-approved nucleic acid amplification tests (NAATs), the Panther Fusion and BD MAX systems, for detection of GBS in vaginal-rectal screening specimens. A total of 510 vaginal-rectal prepartum specimens were tested simultaneously in both NAATs following broth enrichment. Assay agreement was calculated using kappa statistics. Overall agreement between assays was 99.0% (505/510; 95% confidence interval, 0.951 to 0.997; kappa = 0.974). Discordant results were retested with both assays and by standard culture. The assays were also compared for workflow characteristics, including time to first results (TFR), total turnaround time (TAT), number of return visits to load additional specimens, and hands-on time (HoT). Using a standard run size of 60 specimens/day, the Panther Fusion assay had a longer TFR (2.4 versus 2.0 h) but showed a shorter overall TAT for all 60 samples (3.98 versus 7.18 h) due to an increased initial sample loading capacity, and it required less labor (35.0 versus 71.3 s/sample) and fewer return visits for loading additional specimens (0 versus 2). The Panther Fusion system also had a larger sample loading capacity (120 versus 24 samples) and greater 8-h throughput (335 versus 96 samples). In summary, the Panther Fusion GBS assay has clinical performance comparable to that of the BD MAX GBS assay but provides a faster TAT, less HoT, and higher throughput.

Comparison of the Alere i Strep A Test and the BD Veritor System in the Detection of Group A Streptococcus and the Hypothetical Impact of Results on Antibiotic Utilization.

Rapid detection of group A Streptococcus (GAS) is an integral component of treatment decisions in the clinic, especially in the pediatric population. We prospectively collected 216 specimens from symptomatic, predominantly pediatric patients and evaluated the performance of the Alere i Strep A test (Alere i; Alere Inc., Scarborough, ME) and the BD Veritor system (BD Veritor; Becton, Dickinson and Company, Sparks, MD), with culture results being used as a comparator. Real-time PCR (RT-PCR) was performed as an arbiter in discordant cases. Comprehensive chart review was also done to determine the hypothetical impact of the results on antibiotic use. Alere i had a sensitivity and a specificity of 100% and 91.3%, respectively, and BD Veritor had a sensitivity and a specificity of 76.2% and 93.6%, respectively, when the results were compared to those of GAS culture. Further analysis of discordant results using RT-PCR revealed that while BD Veritor missed 13 confirmed positive cases, Alere i detected 100% (n = 13) of the same cases. Analysis of assay agreement showed that Alere i and BD Veritor had only moderate agreement (agreement = 0.888 [95% confidence interval {CI}, 0.838 to 0.927]; kappa index = 0.689 [95% CI, 0.91 to 0.974]). We also found both the underutilization and the overutilization of antibiotics based on the results of molecular testing. Overall, Alere i showed superior performance over BD Veritor in the detection of GAS pharyngitis and could potentially assist in better antibiotic utilization.