maudit

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  1. Hydroxychloroquine can be dangerous regardless of indication because it can prolong QT interval and cause sudden cardiac death. There is a slightly higher risk of this side effect when taking HCQ for covid-19 vs other indications such as for lupus as: i) the dose used is higher for covid, ii) it may be taken at the same time as another drug with prolongs QT (e.g. azithromycin), iii) the risk factors (age, pre-existing heart problems) for drug induced QT prolongation coincide with the target population at risk of covid-19, and iv) if patients self-medicate they are not screened for vulnerability to QT prolongation. Many drugs can cause QT prolongation which is why TQT studies are required for nearly all new compounds (ICH E14, 2005), before this the risk was often not known until post-marketing pharmacovigilance detected a signal for sudden death or TdP. Despite this HCQ may be a good treatment, all drugs have side effects and the potential benefit vs harm should be evaluated for each patient. The MSM should not have been claiming it does not work before we have results from well designed RCTs - a neutral position would be more appropriate.
  2. Varespladib has action on IL6 and sPLA2, I wonder if it could help in covid patients. Interesting drug in terms of the biomarkers but they went for the wrong indication with ACS (which we advised based on the Phase 2 results)
  3. CMMID github https://github.com/cmmid/covid-uk For equivalent paper https://cmmid.github.io/topics/covid19/reports/uk_scenario_modelling_preprint_2020_04_01.pdf code better documented, NPI paper clear assumptions, limitations. They were also advising the government and I suspect influenced initial elderly shielding + herd immunity plan as they found even with fairly severe interventions there is limited gain over the long term when looking over years rather than the immediate first few months. They estimated with no interventions 370 k dead (95% prediction interval 250 k–470 k). Only by spending >50% of 2020 in lockdown was total number of deaths brought below 100k (looking at 2020 only, there would probably be further deaths the following year) - and this likely would have been considered to have too many negative impacts to be a sensible policy. FWIW behind closed doors epidemiologists were saying back in Jan/Feb that the cure would be worse than the disease if we went for a lockdown. Given the timings the government did not change policy because of the Ferguson paper, it provided a convenient narrative that their decision making was guided "by the science".
  4. It is probably nothing to worry about but viruses can cause myocarditis and pericarditis - check for description of the chest pain to see if either fit. My colleague went running with a cold and ended up with heart problems from virus getting into the heart.
  5. Not quite true, the government had similar numbers from other modelling groups earlier. Change in policy likely driven by the actions of other European countries: https://uk.reuters.com/article/uk-health-coronavirus-britain-path-speci/special-report-johnson-listened-to-his-scientists-about-coronavirus-but-they-were-slow-to-sound-the-alarm-idUKKBN21P1X8?il=0
  6. Probability of showing symptoms given infection is dependent on age
  7. You have to be very careful when looking at stopping early for benefit. Ime it is more common to continue the trial but with option for clinician to switch patients to active treatment if they are not doing well on their assigned treatment (this is especially common in cancer trials); this too causes problems when you come to do the primary ITT analysis, indeed this was part of the motivation behind development of estimand framework. If stopping early for benefit consider: i) multiple testing - if we have multiple interim analyses using unadjusted sig level then probability of significant result by chance will exceed selected sig level. We have adjustments to the significance level to deal with this (eg O'Brien-Fleming, alpha-spending, Peto-Haybittle) where much smaller p-value limit used at each interim to preserve the overall type 1 error. ii) overestimation of treatment benefit even with the adjusted stopping rules we may stop trial early where a random fluctuation in trt effect was observed, this would lead to to estimate of trt effect size being misleading. We do not yet have a solution to deal with this risk of overestimation. Stopping early for benefit therefore is a great risk for introducing bias.
  8. Problem with this trial is waiting until patients are hospitalised before starting treatment: Given the proposed mechanism of action of hydroxychloroquine we should be giving in to patients at the onset of symptoms/upon +ve test result and follow up with hospitalisation as one of the endpoints. It is likely too late to get the benefit (should there be one) if you wait until the virus has been multiplying within the patient for many days already. Once the patient is hospitalised we need to be looking at the anti inflammatory treatments like toclizumab. Lots of the US RCTs are doing it right (inclusion criteria being recent infection, start trt asap) and they also have some RCTs giving it as post-exposure prophylaxis or giving as a preventative measure to high risk groups like healthcare workers.
  9. France requested the numbers dead in the Ehpads (nursing homes) across the country, as they receive the numbers they are being added to the totals but represent deaths from the last few weeks, until they have more data with dates of deaths may be able to go back to correct previous day counts but I expect this is an issue in many countries to include the community deaths. From today numbers 588 died in hospital:
  10. You cannot claim it is nothing based on deaths observed with extreme lockdown. The question is what would the deaths have been with no action, the unmitigated epidemic. In Italy now if no action had been taken we would probably be looking at around 52,000 deaths (counterfactual) rather than the 12400 observed yesterday. https://www.imperial.ac.uk/media/imperial-college/medicine/sph/ide/gida-fellowships/Imperial-College-COVID19-Europe-estimates-and-NPI-impact-30-03-2020.pdf
  11. was referring to my original post - by more recent data I mean more recent time period rather than data updated for period up to 16 Mar. up to 16 Mar lower nationally. Deaths for week 16-22 Mar show higher mortality at national level compared with previous years.
  12. France stats on mortality for 01-16 March compared to previous years https://www.insee.fr/fr/information/4470857 Summary: no excess yet at national level [however more recent time periods eg week 16-22 March French director general of health Jerome Salomon claimed 9% excess compared to that expected]. Departement level shows areas where covid19 epidemic started in France already have significant higher mortality compared to same time 2019 - notably Haut-Rhin 38 % (Mulhouse evangelical church super spreading event).
  13. 12 year old girl died from covid19 in Belgium https://www.lefigaro.fr/flash-actu/coronavirus-deces-d-une-adolescente-de-12-ans-en-belgique-20200331
  14. We had BCG at school but were one of the last cohort to do so - they stopped universal BCG here in 2005. It is also effective as immunotherapy treatment for bladder cancer https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4427258/