61 Matching Annotations
  1. Nov 2020
    1. Samples(n)True positiveFalsepositiveTrue negativeFalse negativeePlex SARS-CoV-2 Test2251012*1241**TheePlex SARS-CoV-2 testdemonstrated the following assay performance:Sensitivity 99.02% (94.66 –99.98%; 95% CI)Specificity 98.41% (94.38 –99.81%; 95% CI)

      Results showing high but not perfect PPA (sensitivity) and NPA (specificity).

    2. TCID50/mL

      This is not an SI unit. We need to stop using this.

    3. The evaluation sample panel totalled 230 specimens, including respiratory clinical specimens negative (n= 120) and positive (n=93) for SARS-CoV-2 as determined by the in-house PHE PCR assay.

      Samples used in characterisation

    1. if reaction inhibition is a significant source of false negative results, a control material capable of detecting the inhibition.

      Requirement for materials to detect inhibition of test

    2. At least once each day patient specimens are assayed or examined perform the following for - (i) Each quantitative procedure, include two control materials of different concentrations; (ii) Each qualitative procedure, include a negative and positive control material;

      Minimum control procedures

    1. No mentions of the limitations of the study:

      Inconclusive results, missing data, variable adherence, patient-reported findings on home tests, no blinding, and no assessment of whether masks could decrease disease transmission from mask wearers to others.

    2. randomised controlled trial – making it the highest quality scientific evidence.

      Wrong. It's not double blinded so it is not the highest quality (as it doesn't say it's paired either so...). The behaviour of participants is likely having a significant and unknown effect. When you're wearing a mask maybe you go out more. Maybe you get closer to others. This study does not control for those potential confounding factors.

    1. This is a disadvantage for laboratories, whichmust make decisions and investments in reagents and in-struments without complete knowledge of test accuracy.

      EUA disadvantage

    2. some degree of variation in the performance of theseassays

      could also read "some degree of variation in assessment of the performance of these assays"

    1. Senator Rand Paul introduced the Verified Innovative Testing in American Laboratories Act of 2020

      VITAL Act of 2020

    2. The clinical laboratory community rapidly provided widely available H1N1 influenza molecular testing, facilitating a swift pandemic response.2Jernigan D.B. Lindstrom S.L. Johnson J.R. Miller J.D. Hoelscher M. Humes R. Shively R. Brammer L. Burke S.A. Villanueva J.M. Balish A. Uyeki T. Mustaquim D. Bishop A. Handsfield J.H. Astles R. Xu X. Klimov A.I. Cox N.J. Shaw M.W. Detecting 2009 pandemic influenza A (H1N1) virus infection: availability of diagnostic testing led to rapid pandemic response.Clin Infect Dis. 2011; 52: S36-S43Crossref PubMed Scopus (65) Google Scholar,  3Crawford J.M. Stallone R. Zhang F. Gerolimatos M. Korologos D.D. Sweetapple C. De Geronimo M. Dlugacz Y. Armellino D.M. Ginocchio C.C. Laboratory surge response to pandemic (H1N1) 2009 outbreak, New York City metropolitan area, USA.Emerg Infect Dis. 2010; 16: 8-13Crossref PubMed Scopus (31) Google Scholar,  4Meltzer M.I. McNeill K.M. Miller J.D. Laboratory surge capacity and pandemic influenza.Emerg Infect Dis. 2010; 16: 147-148Crossref PubMed Scopus (8) Google Scholar,  5van der Vries E. Jonges M. Herfst S. Maaskant J. Van der Linden A. Guldemeester J. Aron G.I. Bestebroer T.M. Koopmans M. Meijer A. Fouchier R.A.M. Osterhaus A.D.M.E. Boucher C.A. Schutten M. Evaluation of a rapid molecular algorithm for detection of pandemic influenza A (H1N1) 2009 virus and screening for a key oseltamivir resistance (H275Y) substitution in neuraminidase.J Clin Virol. 2010; 47: 34-37Crossref PubMed Scopus (67) Google Scholar,  6

      References for H1N1 pandemic response

    3. AMP member peer-to-peer listserv communications have been robust as colleagues rapidly shared concerns, challenges, knowledge, experience, and solutions to support the clinical laboratory community's COVID-19 testing response

      Private peer to peer "expert crowdsourced" intelligence

    1. The EUA template also streamlined submission paperwork. A typical submission seeking full FDA approval for a test is about 1000 pages for laboratories and about 2000 pages for commercial manufacturers that distribute tests. The template reduced commercial manufacturers’ EUA submissions to 100 to 200 pages and laboratory submissions to about 40 pages, of which only about half were generated solely to meet FDA requirements, and most of those consisted of data rather than text.

      Traditional submission process versus EUA templates

    1. Food and Drug Administration ("FDA") will not require premarket review of laboratory developed tests ("LDT") absent notice-and-comment rulemaking, as opposed to through guidance documents, compliance manuals, website statements, or other informal issuances

      This change was summarised in this article.

    1. assure that samples mimic actual patient specimens when possible and that samples are homogeneous

      Call for similarity to real patient specimens

    2. White blood cell differential Target ±3SD based on the percentage of different types of white blood cells in the samples. Erythrocyte count Target ±6%. Hematocrit (Excluding spun hematocrits) Target ±6%. Hemoglobin Target ±7%. Leukocyte count Target ±15%. Platelet count Target ±25%.

      Differences in accuracy that can be expected from lab analysis.

    3. 820
    4. 640
    1. (F) Testing results The Secretary shall establish a system to make the results of the proficiency testing programs subject to the standards established by the Secretary under subparagraph (A) available, on a reasonable basis, upon request of any person. The Secretary shall include with results made available under this subparagraph such explanatory information as may be appropriate to assist in the interpretation of such results.

      PT results are made available

    1. GPS system malfunctions when the battery dies

      GPS uses a tiny amount of energy versus the energy needed to move a vehicle. If the GPS stops working when the battery is flat you have much much bigger problems and could use the last known location to send a rescue team to the dysfunctional vehicle.

    2. This mainly happens because the signals will also be affected by the changes in the weather.

      There are so many problems with this statement.

      Firstly climate is not the same as weather.

      Secondly, what weather patterns interfere with GPS? It seems to work in icy winter, in the middle or storms, during rain, when it's cloudy or sunny, when it's a heatwave. So I don't understand why, when or how the signals will be affected.

      Thirdly, why would the signals stop working forever. Surely they would be useful for most of the time?

    1. essential vitamins such as Vitamin D and A are also broken down into microscopic particles

      Is there a reference for this statement? It sounds like patent nonsense. Vitamin D and A are molecules... they're already far smaller than "microscopic" and I would be very surprised if mechanical action breaks chemical bonds in them.

    1. It is inappropriate to describe a test with these properties as “less accurate”— a description that has allowed some companies to launch suboptimal products,12 possibly encouraged by the magnitude of government contracts, low levels of government scrutiny, and the lack of an effective regulatory process for diagnostic tests.13

      Is this test actually allowed to be sold?

    1. commonsense

      commonsense is not common. I'd suggest putting this explicitly and clearly in guidelines or regulations.

    2. We have made note of this QC issue previously in this journal (9), and we argue that this is yet an additional reason that reliability needs to be established during the initial AST

      Related to original authors post.

    3. the cited variability in agar medium should be detected by QC testing.

      QC testing is claimed to be adequate for this failure mode.

    1. QC ranges are typically much lower than the clinical breakpoint. For example, the meropenem-vaborbactam QC ranges span from 0.008 to 0.5 μg/ml for Enterobacterales QC organisms. The Enterobacterales clinical breakpoints are ≤4 μg/ml (susceptible), 8 μg/ml (intermediate), and ≥16 μg/ml (resistant), several dilutions away from these QC ranges (4).

      Inappropriate QC ranges should be updated.

      Related to agreement in rebuttal

    2. QC testing was within acceptable limits

      In this scenario it sounds like QC might be improved to be more sensitive to this class of error: i.e. its improved because it includes more failure modes.

    3. QC does not evaluate all aspects of testing (i.e., preanalytical, analytical, and postanalytical components)

      Seems like a power example to champion expanding the remit of QC to catch more errors.

    1. The establishment of an independent, third party reviewer to develop and verify quality and accuracy of claims prior to review by FDA and the federal CLIA-regulating agencies would enhance the transparency of the process. This entity would be not-for-profit, non-governmental, non-ac-crediting, non-industry, and entirely neutral. Both public health and patient safety would be best served by imple-menting a centralized third party review system rather than a peer review model.

      call for third party independent reviewer

    1. ãþâ»ÄôçÍÑãÑüÑ°üÑĐÄ÷аĐÄ»ÄÄã÷Äüþñ÷ñļÑķ¼°ÝÝēüç¼ççôÀÑã°üÄefforts and resources from makers towards COVID-19 challenges, such as GetusPPE in the US and the HelpfulEngineers open-source group setup by Project Open Air which has more than 3,000+ members looking for different COVID-19 solutions (www.getusppe.org, 2020),(www.app.jogl.io, 2020),(www.projectopenair.org, 2020)
    1. Abortion should be

      Percentage of all voters:

      • Legal + Trump == 12% (24% * 51%)
      • Illegal + Trump == 32% (75% * 42%)
      • Legal + Biden == 37% (72% * 51%)
      • Illegal + Biden == 10% (23% * 42%)
    2. Do you think climate change, also known as global warming, is a serious problem?

      Percentage of all voters:

      • Yes + Trump == 19% (29% * 66%)
      • No + Trump == 26% (84% * 31%)
      • Yes + Biden == 45% (68% * 66%)
      • No + Biden == 5% (15% * 31%)
    3. What is your level of education?

      Percentage of all voters:

      • College + Trump == 18% (42% * 44%)
      • No college + Trump == 27% (49% * 56%)
      • College + Biden == 24% (55% * 44%)
      • No college + Biden == 27% (49% * 56%)
    4. Are you a white evangelical or white born-again Christian?

      Terms:

      • Christian == White evangelical or white born-again Christian
      • Others == All others

      Percentage of all voters:

      • Christian + Trump == 21% (76% * 27%)
      • Others + Trump == 27% (37% * 73%)
      • Christian + Biden == 6% (23% * 27%)
      • Others + Biden == 44% (60% * 73%)

      (sanity check: 21 + 27 + 6 + 44 == 98%)

    1. CMS’ CLIA program does not address the clinical validity of any test

      See bottom paragraph of next page for fuller explanation of this sentence.

      42 CFR 493.1253(b)(2) requires LDTs be assessed on:

      (i) Accuracy.

      (ii) Precision.

      (iii) Analytical sensitivity.

      (iv) Analytical specificity to include interfering substances.

      (v) Reportable range of test results for the test system.

      (vi) Reference intervals (normal values).

      (vii) Any other performance characteristic required for test performance.

    2. 42 CFR 493.1253(b)(2
    1. The origin of the crack was located practically in the centre of slot No 10 (Figure 17), around 14 cm (5.6 inches) behind the front face of the hub and 1.4 mm (0.055 inches) below the surface of the slot bottom. No material quality (composition, microstructure) or manufacturing related anomaly was found.

      Origin of failure

    1. adeno-associated virus vector-based gene therapyindicated for the treatment of patients with confirmed biallelic RPE65mutation-associated retinal dystrophy

      gene therapy

    1. The negatives will be fresh samples, transported within 48 hours, the positives will be frozen. This follows recent work at PHE Porton Down to support the development of this protocol which found there to be no discernible difference in performance when using frozen samples.

      claim that frozen samples are similar to unfrozen samples. New questions: what temperature, what freezing profile, any additives?

    1. continually consult the open databases of SARS-CoV-2 genome sequences to ensure their tests remain up-to-date and that false negatives do not arise because of genome variation

      continuous monitoring needed to avoid mutation enabled false negatives

    1. we do have a whole lot of applications

      referring to FDA EUA backlog

    1. while the ID Now had an LOD of 20,000 copies/ml (9), well above the limit of detection stated in the Abbott ID Now COVID-19 package insert (125 genome equivalents/ml)

      claimed discrepancy between package insert / EUA and third party evaluation.

    1. Senator Rand Paulintroduced the Verified Innovative Testing in AmericanLaboratories Act of 2020

      VITAL Act of 2020

    1. PAHPRA also enhances the authority of the U.S. Food and Drug Administration to support rapid responses to public health emergencies.

      PAHPRA and FDA

  2. Oct 2020
    1. There were a number of science-based options that politicians could have followed in this outbreak. If they chose the wrong ones, then we need to be clear that this was because of broken politics, not broken scientific advice.

      This article is an oxymoron. It claims "The idea that government advisers can separate science and politics is bogus" and then says "science-based options" and "if they chose the wrong ones [blame] politics"... so then the options can [obviously] be independent of politics.

      When approaching any complex area, unless there is insufficient time or resources, then all the (scientific) strategies can be laid out. And the politicians can make their assessment of the political value / cost of each and view the scientific assessment through this political lens.

    1. To ascertain whether this decrease in confidence was as a result of the Cummings events (a Cummings effect), we carried out analyses using two types of comparisons. First, we compared the responses for people living in England to those of people living in the devolved nations of Scotland and Wales who were asked to rate their confidence in their own devolved governments. There was no evidence of a similar large decrease in confidence in the governments of the devolved nations either descriptively (appendix p 1–3) or statistically

      Trust in government

    1. There is some evidence that in care homes where staff receive sick pay, there are lower levels of infection in residents.

      Will be interesting to see how this hypothesis evolves

    1. offered two nasal swabs

      Was the order random or consistent? If consistent, in which order, Antigen then PCR or vice versa? And does this introduce variability?

  3. Sep 2020
    1. Poorly timed testing, if conducted infrequently, could lead to false positives or false negatives,

      A "false negative" can be made more likely if testing too soon or too late. Though also if there's no virus in the specimen but it is in the human it's arguable if you can even call it a false negative.

      But false positives and the timing of a test makes no sense. False positives are inherently independent of when someone is infected... because they're not infected but the test comes back positive. So it's meaningless to say false positives depend on the time of a test.

    1. at the peak of infection

      No, at the peak of infectivity which may be before the peak of infection as when at the peak of infection, symptoms may be causing the person lethargy and they are staying at home, effectively isolating themselves.

    2. PCR may actually be too sensitive in some settings, picking up on scraps of innocuous coronavirus genetic material in patients who are no longer sick; antigen testing could circumvent this.

      Either you want a sensitive test or you don't. If you don't you can circumvent the "sensitive problem" of PCR because almost all are quantitative so just set the threshold lower for what is a positive result. There will still be antigens floating around too.

    3. advertised accuracy rates will almost certainly drop when used at home,

      Some tests are validated in "at home" settings to avoid this uncertainty

    4. antigen tests aren’t great at sussing out small amounts of the coronavirus, which means they’re far more likely to miss a case that a technique like PCR would catch

      No references to support this.

  4. Jun 2019
    1. The division of the base line of facts is indeed worrying but it is already occurring all over the world, in each country, across different social, economic, cultural, demographic, etc lines, even between people who are very close to each other.