Performance Evaluation of the Microfluidic Antigen LumiraDx SARS-CoV-2 and Flu A/B Test in Diagnosing COVID-19 and Influenza in Patients with Respiratory Symptoms.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) and influenza share similar symptoms, which hampers diagnosis. Given that they require different containment and treatment strategies, fast and accurate distinction between the two infections is needed. This study evaluates the sensitivity and specificity of the microfluidic antigen LumiraDx SARS-CoV-2 and Flu A/B Test for simultaneous detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A/B from a single nasal swab. METHODS: Nasal samples were collected from patients as part of the ASPIRE (NCT04557046) and INSPIRE (NCT04288921) studies at point-of-care testing sites in the USA. ASPIRE study participants were included after developing COVID-19 symptoms in the last 14 days or following a positive SARS-CoV-2 test in the last 48 h. INSPIRE study participants were included after developing influenza symptoms in the last 4 days. Samples were extracted into proprietary buffer and analysed using the LumiraDx SARS-CoV-2 and Flu A/B Test. A reference sample was taken from each subject, placed into universal transport medium and tested using reference SARS-CoV-2 and influenza reverse transcription polymerase chain reaction (RT-PCR) tests. The test and reference samples were compared using the positive percent agreement (PPA) and negative percent agreement (NPA), together with their 95% confidence intervals (CIs). RESULTS: Analysis of the data from the ASPIRE (N = 124) and INSPIRE (N = 159) studies revealed high levels of agreement between the LumiraDx SARS-CoV-2 and Flu A/B Test and the reference tests in detecting SARS-CoV-2 (PPA = 95.5% [95% CI 84.9%, 98.7%]; NPA = 96.0% [95% CI 90.9%, 98.3%]), influenza A (PPA = 83.3% [95% CI 66.4%, 92.7%]; NPA = 97.7% [95% CI 93.4%, 99.2%]) and influenza B (PPA = 80.0% [95% CI 62.7%, 90.5%]; NPA = 95.3% [95% CI 90.2%, 97.9%]). CONCLUSIONS: The LumiraDx SARS-CoV-2 and Flu A/B Test shows a high agreement with the reference RT-PCR tests while simultaneously detecting and differentiating between SARS-CoV-2 and influenza A/B. TRIAL REGISTRATION: ClinicalTrials.gov identifiers NCT04557046 and NCT04288921.

Performance of the LumiraDx Microfluidic Immunofluorescence Point-of-Care SARS-CoV-2 Antigen Test in Asymptomatic Adults and Children.

OBJECTIVES: The LumiraDx SARS-CoV-2 Ag Test has previously been shown to accurately detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals symptomatic for coronavirus disease 2019 (COVID-19). This evaluation investigated the LumiraDx SARS-CoV-2 Ag Test as an aid in the diagnosis of SARS-CoV-2 infection in asymptomatic adults and children. METHODS: Asymptomatic individuals at high risk of COVID-19 infection were recruited in 5 point-of-care (POC) settings. Two paired anterior nasal swabs were collected from each participant, tested by using the LumiraDx SARS-CoV-2 Ag Test at the POC, and compared with results from reverse transcription-polymerase chain reaction (RT-PCR) assays (cobas 6800 [Roche Diagnostics] or TaqPath [Thermo Fisher Scientific]). We calculated positive percent agreement (PPA) and negative percent agreement (NPA), then stratified results on the basis of RT-PCR reference platform and cycle threshold. RESULTS: Of the 222 included study participants confirmed to be symptom-free for at least 2 weeks before testing, the PPA was 82.1% (95% confidence interval [CI], 64.4%-92.1%). The LumiraDx SARS-CoV-2 Ag Test correctly identified 95.8% (95% CI, 79.8%-99.3%) of the samples confirmed positive in fewer than 33 RT-PCR cycles and 100% (95% CI, 85.1%-100%) in fewer than 30 RT-PCR cycles while maintaining 100% NPA. CONCLUSIONS: This rapid, high-sensitivity test can be used to screen asymptomatic patients for acute SARS-CoV-2 infection in clinic- and community-based settings.

Performance Evaluation of the Quantitative Point-of-Care LumiraDx D-Dimer Test.

INTRODUCTION: Fibrin degradation product D-dimer can be a valuable indicator for venous thromboembolism (VTE). The use of D-dimer testing in primary care settings can be limited by restricted access to laboratory services. This performance evaluation compares a quantitative, point-of-care (POC) D-dimer assay (LumiraDx D-Dimer Test) with a reference laboratory-based D-dimer assay. METHODS: Plasma samples from patients presenting to secondary care in the UK, USA, and Germany were analyzed centrally using the LumiraDx D-Dimer Test and the reference test (bioMérieux VIDAS D-Dimer Exclusion II immunoassay). Method comparison used Passing-Bablok regression analysis with pre-specified equivalence criteria of r ≥ 0.9 and slope of 0.9-1.1. The NOVEL-3 study (NCT04375982) compared equivalency of fingerstick, venous blood (VB), and plasma samples from the same patient, tested at US primary care clinics next to the patient using the POC LumiraDx D-Dimer device. Measurements obtained from fingerstick and VB samples were compared with results from plasma samples, using Deming regression. The healthy reference range was determined using plasma samples of healthy volunteers, collected by commercial suppliers in Germany and the USA, which were analyzed centrally using the LumiraDx D-Dimer Test and the reference test. RESULTS: The LumiraDx D-Dimer Test demonstrated agreement with the bioMérieux VIDAS D-Dimer Exclusion II immunoassay for plasma samples (r = 0.923, slope of 1.016, n = 1767). There was good agreement between fingerstick/VB samples and plasma samples (r = 0.980-0.986, n = 93) measured using the LumiraDx D-Dimer Test. Overall error rates were 1.8%. The healthy reference range 90% percentile for D-dimer was calculated as 533 µg/l fibrinogen equivalent units (FEU). CONCLUSIONS: The quantitative LumiraDx D-Dimer Test is easy to use and can accurately measure D-dimer levels in a range of blood sample types, including fingerstick samples, which could improve assessment of VTE cases in community and hospital near-patient settings.

Oxygen levels are key to understanding "Anaerobic" protozoan pathogens with micro-aerophilic lifestyles.

Publications abound on the physiology, biochemistry and molecular biology of "anaerobic" protozoal parasites as usually grown under "anaerobic" culture conditions. The media routinely used are poised at low redox potentials using techniques that remove O2 to "undetectable" levels in sealed containers. However there is growing understanding that these culture conditions do not faithfully resemble the O2 environments these organisms inhabit. Here we review for protists lacking oxidative energy metabolism, the oxygen cascade from atmospheric to intracellular concentrations and relevant methods of measurements of O2, some well-studied parasitic or symbiotic protozoan lifestyles, their homeodynamic metabolic and redox balances, organism-drug-oxygen interactions, and the present and future prospects for improved drugs and treatment regimes.

Sequential classification of endocrine stages during reproductive aging in women: the FREEDOM study.

OBJECTIVE: Reproductive aging involves complex endocrine changes affecting women's fertility, health, and well-being; however, understanding of the specific changes involved is limited by the lack of detailed quantitative studies. We undertook a thorough study with the aim of characterizing the different endocrine stages involved in female reproductive aging. DESIGN: FREEDOM is a cohort study designed to determine the endocrine changes during reproductive aging in women. Here, we ascertained the different endocrine patterns in a representative population and developed a staging system. In this study, 112 women aged 30 to 58 years collected daily urine samples over a 6- to 18-month period and recorded their menstrual periods. A total of 36,786 samples were analyzed for follicle-stimulating hormone (FSH), luteinizing hormone, estrone 3-glucuronide, and pregnanediol 3-glucuronide. RESULTS: A classification of five sequential endocrine stages of reproductive aging was developed: stage 1, regular menstrual cycles with mean initial (day 1-5) FSH less than 5 IU/L; stage 2, regular cycles with FSH greater than 5 IU/L; stage 3, menstrual irregularity (with the appearance of "delayed-response cycles"); stage 4, acyclical ovarian activity with no evidence of ovulation and luteinization; and stage 5, ovarian quiescence and persistently raised gonadotropins. Distinct hormonal characteristics during the follicular and luteal phase were noted at each stage. CONCLUSION: This classification provides a detailed insight into the endocrinology of reproductive aging in women that could be useful for both clinical guidance and personal health care.

Levels of urinary human chorionic gonadotrophin (hCG) following conception and variability of menstrual cycle length in a cohort of women attempting to conceive.

OBJECTIVES: To define the variability of menstrual cycle length and contribution of follicular and luteal phases to overall cycle variability, and to examine the rise in urinary hCG in early pregnancy. METHODS: Menstrual cycle study. Urine samples from 101 women (recruited from two south-east counties in the UK) were assayed to determine day of luteinising hormone (LH) surge, lengths of follicular and luteal phases and correlations with total menstrual cycle length. HCG study. Daily urine samples collected from 86 women prior to conception until 43 days post-conception were assayed for hCG and examined versus time since LH surge, determined using fertility test kits. RESULTS: Mean menstrual cycle length was 27.7 +/- 3.4 days, mean follicular phase length was 14.5 +/- 3.4 days and mean luteal phase length was 13.2 +/- 1.9 days. Total cycle lengths varied between and within women. There was a significant correlation (r(2) = 0.70) between follicular phase length and total cycle length; luteal phase length was less variable and showed no association with total cycle length. Concentrations of hCG were significantly similar between women when referenced against the day since LH surge. Three thresholds were determined to indicate time since conception as 1-2 weeks, 2-3 weeks and 3+ weeks. CONCLUSIONS: Total cycle length variation is mainly determined by follicular phase variation and predicting menses onset to estimate time of pregnancy testing is unreliable. Evaluating concentrations of hCG relative to LH surge results in consistent increases between women up to 21 days after conception. Therefore, urinary hCG concentration can be used to accurately estimate time since conception.

Comparison of accuracy and certainty of results of six home pregnancy tests available over-the-counter.

BACKGROUND: The aim of the study was to determine the accuracy of home pregnancy tests (HPTs) in detecting human chorionic gonadotrophin (hCG) in human female urine and consumer certainty in reading the results. The Clearblue Digital Pregnancy Test (CBDPT) was compared with five alternative over-the-counter (OTC) brands of HPT. METHODS: HPTs (CBDPT [SPD, Geneva, Switzerland], Answer [Church & Dwight, Princeton, NJ], Predictor [Omega Teknika, Dublin, Ireland], Clearblue (non-digital) [SPD], EPT [McNeill, Fort Washington, PA], First Response [Church & Dwight]) were tested by study co-ordinators on samples of pooled urine containing hCG at 0 IU/l (negative control) or 25 IU/l (positive standard, typical of level found in early pregnancy), in a coded, randomised scheme. Results and level of certainty about the results were interpreted by 120 female volunteers. RESULTS: The CBDPT detected hCG in the 25 IU/l positive urine with 100% accuracy when read by volunteers. Accuracy of four alternative HPTs ranged from 65.8 to 87.5%, but was only 8.3% with the fifth test, Predictor. CBDPT was statistically significantly better than any of the alternative brands. All volunteers (100%) rated the results with the CBDPT as 'very certain' or 'certain' (score 1 or 2), whereas a score of 1 or 2 was recorded by only 40.3-58.3% for the other brands, except Predictor which was scored with certainty by 87.5%, although volunteers interpreted the result for the positive standard as not pregnant. A certainty score of 1 or 2 was recorded by a significantly (p<0.001) greater proportion of volunteers with CBDPT than any of the other HPTs. CONCLUSIONS: The CBDPT was significantly better in terms of accuracy and certainty than non-digital OTC HPTs tested at a low hCG concentration. These results demonstrate that a digital reading offers significant benefits to the consumer over traditional non-digital tests.

Mistiming of intercourse as a primary cause of failure to conceive: results of a survey on use of a home-use fertility monitor.

OBJECTIVE: To assess demographics, fecundity characteristics and fertility history of couples who successfully conceived using a home-use Fertility Monitor. STUDY DESIGN: This was a retrospective US observational study of couples who successfully conceived using a Fertility Monitor. Data were self-reported by volunteers using a questionnaire supplied and collected by mail. Of 276 surveys distributed, 196 (71.0%) were returned and evaluated. RESULTS: Length of time trying to conceive was < 12 months for 70% of women; proportions were similar across age groupings. After switching to the Fertility Monitor, 49.5% and 91.9% of women had conceived within first and third cycles, respectively. Prior to Fertility Monitor use, conception aids were used by 84.2% and 64.3% had consulted a physician to seek help in attempting to conceive. Average costs of prior treatment were (in US dollars) 6637 dollars; median costs for infertility evaluation were 1075 dollars per cycle. Fertility Monitor costs ranged from 250 dollars for one cycle to 550 dollars after 10 cycles. CONCLUSIONS: A probable cause for failure to conceive appeared to be mistiming of intercourse. The issue of early intervention with tests and medications were highlighted, resulting in escalating costs and strain on the couple. The use of a home Fertility Monitor that identifies all fertile days of the cycle and allows couples to target intercourse accordingly, should be considered as an alternative choice for couples seeking to conceive during the first year, before other attempts at infertility diagnosis are made, unless there are conflicting clinical reasons.

Increased pregnancy rate with use of the Clearblue Easy Fertility Monitor.

OBJECTIVE: To determine the effect on pregnancy rates through use of the Clearblue Easy Fertility Monitor (CEFM) in women trying to conceive. DESIGN: Prospective study, in which volunteers were randomly assigned either to use or not to use the CEFM. All participants could also use other aids to conception. Data were self-reported by volunteers using daily diaries, supplied and collected by mail. SETTING: Home use, under conditions normally experienced by over-the-counter purchasers of the marketed device. PATIENT(S): Women who were trying to conceive; 653 (CEFM 305, control 348) provided evaluable information. INTERVENTION(S): CEFM was used for two cycles. MAIN OUTCOME MEASURE(S): Cumulative pregnancy rates over two cycles of use. RESULT(S): The cumulative pregnancy rate for 2 cycles was significantly higher in the CEFM group (22.7%) compared with the control group (14.4%). More women who had been trying to conceive for <6 months became pregnant than women who had been trying to conceive for >6 months (odds ratio: 2.67). Previous pregnancy and younger age of partners were also significant prognostic factors, but use of other aids to conception was not. After adjustment for other factors, CEFM use remained a significant factor affecting the chance of conceiving within two cycles (odds ratio: 1.89). CEFM users found the device to be easy/very easy to use (90%) and convenient/very convenient (80%). CONCLUSION(S): Use of the CEFM increases the likelihood of getting pregnant during the first two cycles of use compared with its nonuse, in women who had been trying to conceive for up to 2 years.