27 Matching Annotations
  1. Mar 2024
  2. Jan 2024
  3. Aug 2022
  4. Jan 2022
  5. Aug 2021
  6. Jul 2021
    1. case-driven trial was planned 205to accrue 130case

      What was the rationale for accrual of 130 cases has not been explained here. Would be nice to have that explanation. When the study parameters (95% confidence interval, 60% vaccine efficacy, 1% baseline attack rate) were applied to the WHO calculator obtained from here, the sample size turned out to be 86000, and when 80% confidence interval, 60% vaccine efficacy, and 1% baseline rate among unvaccinated) was used to assess sample size, it turned out to be 21000; in any case, the study then would be underpowered unless the rationale of 130 case accrual is made.<br> Why was not the WHO sample size estimator used?

    2. at least two of the following symptoms:

      This means that by design the trial would MISS asymptomatic COVID19 cases that nevertheless make up a substantial proportion (about 60% of covid cases). But this was mitigated by taking monthly swabs for Category 2 participants.

    3. The master randomisation list, containing the randomisation 120number and intended treatment allocation, as well as the kit code, was sent to the IWRSand121kits were despatched to the sites according to the IWRSby an unblinded statistician from the 122CRO

      This opens up the possibility of bias in the analysis if the same statistician was involved in the data analysis of the efficacy. How was that mitigated?

    4. per-protocol population

      Why was the decision of per-protocol taken if the study was blinded to the participants and the study personnel BUT unblinded to the analysts?

    5. Participants, investigators, study coordinators, 126study-related personnel, and the sponsor were masked to the treatment group allocation, and 127masked study nursesat each site were responsible for vaccine preparation and administration

      That still leaves open the role of unblinded data analysts. Why were they not blinded as well or at least made agnostic as to the status of the allocation. How was allocation concealment achieved and why was this not described here?

    6. adult volunteers 18 years

      How did they mitigate self-report bias?

    7. blinded

      ??What does blinding mean here? Double blinded or single blinded?

  7. May 2021
  8. Mar 2021
  9. Feb 2021
  10. Jun 2020
  11. Apr 2020
    1. REE decreased approximately 15% when TSH increased between 0.1 and 10 mU/L.

      The individual change in REE to a given change in dose varied radically. The dose change was only 50 mcg, which seemed to change TSH about half what they've calculated for 15% REE change. That is to say, it looks like a 50 mcg dose reduction will only raise TSH from 1.0 to 5.0, not to 10.0. This is my personal guesstimate, and will need to be properly calculated from other studies. My point is merely that 50 mcg will not cause the full 15% REE increase. Additionally, the response to 50 mcg may depend on initial TSH.

      It looks like TSH changes that remained hyperthyroid (i.e. bellow 1.0) had little effect on REE. This might be because the body is maintaining thyroid status, or that REE is more like an on/off switch. However, this only covers relatively small changes in thyroxine dose.

      It is unclear how supraphysiological doses effect REE. It seems likely that the ten times greater dose (500 mcg) used for depression would significantly increase REE.

  12. Mar 2020
    1. The addition of supraphysiologic doses of L-T4 (300 mcg per day) to an otherwise stable medication regimen of standard treatments resulted in a significant decline in depression scores during the 6-week, double-blind treatment phase. At endpoint (week 6), the mean HamD score showed a group difference of 3.7 points in favor of L-T4. Such difference is generally considered to be clinically meaningful in a short-term treatment trial for major depression. NICE used a 3.0-point difference in HamD change scores as a criterion of clinical significance.27

      This is consistent with the open label data. The dose is also similar. Combining this placebo-controlled trial with the three open-label supraphysiological thyroxine studies that I've seen, that is sufficient for me to conclude efficacy. Namely, combining with Pfeiffer et al (350 mcg), Rudas et al (235 mcg) and Bauer et al (482 mcg)

      I would like to see if this study mentions nonresponders. Those three other studies found roughly a 50% response rate. Thus, the effect size in responders may be twice as significant.

  13. Jan 2020
    1. The authors demonstrated an inverse correlation between TSH and REE with a change of 15% for a TSH ranging from 0.1 to 10 μIU/mL. Of interest, free T4 remained within the normal range in all of the study volunteers. Nonetheless, the changes in REE with different LT4 doses were demonstrated in every patient [46].

      Thus, a 15% expected increase would be reasonable for a euthyroid subject such as myself. However, since T3 reduces weight compared to T4, it is possible the weight loss indicates greater energy expenditure.

    1. 22.3 per cent (−10.7; 95% CI, −15.6 to −5.7) in the diet group

      Interesting that the diet group worked better. I'd like to see if it's statistically significantly better than the drug group. It's also worth asking whether sodium was the only important dietary change, or if avoiding sodium caused many other dietary improvements.

    2. Sleepiness and neck circumference were significantly reduced only in the diet group (p = .007 and p < .001 for the time × group interactions, respectively).

      Fascinating. Neck circumference suggests that sodium intake may indeed be the significant dietary factor. The recommended diet wasn't even very restricted in sodium.

    1. CONCLUSION: This randomized double-blind, placebo-controlled clinical trial demonstrated that Amla could reduce frequencies of heartburn and regurgitation and improve heartburn and regurgitation severity in patients with NERD.

      Is there anything it can't do? I have noted, however, that larger doses cause nausea for me. That is, 3 or more grams on an empty stomach. I just vomited after taking 7.5 grams before my meal, but I have not yet established the causal link. It is the largest amount I've ever taken at one time. I suspect that it may have contributed significantly, but that it was also one out of half a dozen factors.

  14. Dec 2018
  15. May 2017
    1. Excellent Piece Dr Malerba. I would remind everyone reading that Homeopathy has been found efficacious in all methodologically rigorous meta analysis. Furthermore trials of individualised Homeopathy, when sorted by Cochrane criterea, show a positive result that becomes more positive with higher quality of evidence. Please seehttps://www.ncbi.nlm.nih.gov/pubmed/25480654 for more details.

      This comment didn't get through moderation:

      Paul Theriault said:

      “I would remind everyone reading that Homeopathy has been found efficacious in all methodologically rigorous meta analysis.”

      Which ones are they? Can you provide a link to them?

      “Furthermore trials of individualised Homeopathy, when sorted by Cochrane criterea, show a positive result that becomes more positive with higher quality of evidence. Please seehttps://www.ncbi.nlm.nih.gov/pubmed/25480654 for more details.”

      It’s interesting that you should cite that Mathie et al. paper. He didn’t find very much high quality reliable evidence at all, did he? He found no trials that had low risk of bias in all seven domains they assessed. In the next lower category, he identified just 12 that had uncertain risk of bias in some domains and low risk of bias in all other domains. The rest were identified as having a high risk of bias in some domains. Of the 12 with uncertain risk of bias, he singled out just three that he concluded were of ‘reliable evidence’.

      The number of participants in these three trials were 81, 75 and 62. One self-describes as ‘preliminary’ and another as ‘a pilot study’. It is difficult to understand why he chose to categorise as being ‘reliable evidence’, or why you cited it.

      But it’s interesting to read what Mathie concluded: “Medicines prescribed in individualised homeopathy may have small, specific treatment effects. Findings are consistent with sub-group data available in a previous ‘global’ systematic review. The low or unclear overall quality of the evidence prompts caution in interpreting the findings. New high-quality RCT research is necessary to enable more decisive interpretation.” Moreover, he emphasised:

      “The overall quality of the evidence was low or unclear, preventing decisive conclusions.”

      Is that the best then?