Disseminating Research on Null, Inconclusive, and Confirmatory Findings in Cardiovascular Science

Our fucking failures of stroke associations  should report on all stroke research that falls into these categories. BUT THEY ARE SO FUCKING INCOMPETENT THEY WILL DO NOTHING!

 Disseminating Research on Null, Inconclusive, and Confirmatory Findings in Cardiovascular Science

 

Brahmajee K. Nallamothu

,

Jonathan Schultz

,

Sandra Petty

Originally published1 Oct 2020https://doi.org/10.1161/CIRCOUTCOMES.120.007448Circulation: Cardiovascular Quality and Outcomes. ;0

"True Negatives." Circulation: Cardiovascular Quality and Outcomes, , pp. –

Footnotes

The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.

This article is part of the Null Hypothesis Collection, a collaborative effort between CBMRT, AHA Journals, and Wolters Kluwer. For more information, visit https://www.ahajournals.org/null-hypothesis

Brahmajee K. Nallamothu, MD, MPH, University of Michigan Medical School, Internal Medicine-Cardiovascular Medicine North Campus Research Complex, 2800 Plymouth Rd, Bldg 16, Ann Arbor, MI 48109. Email bnallamo@umich.edu

The Hazard of Negative (Not Neutral) Trials on Treatment of Acute Stroke

And since we have fucking failures of stroke associations with NO database of all stroke research, you have to hope like hell your doctors and stroke hospital are competent enough to keep up with and implement stroke research. I think I've proven thousands of times they are not competent.  So you may as well go back to the blood letting practice. 

“In the treatment of apoplexy, the most important point is the employment of bleeding; the judicious use of which powerful remedy the cure greatly depends.” (Bright 1831, p 334)

The Hazard of Negative (Not Neutral) Trials on Treatment of Acute Stroke

Philip M. Bath, FMedSci^1,2; Jason P. Appleton, MRCP(UK)^1,2; Timothy England, FRCP³

Author Affiliations

JAMA Neurol. Published online December 2, 2019. doi:https://doi.org/10.1001/jamaneurol.2019.4107

Abstract

Importance  While there are a limited number of beneficial treatments for acute stroke (eg, stroke units, reperfusion, aspirin, hemicraniectomy), there are more negative (as opposed to neutral) interventions spanning multiple different mechanisms of action. To reduce the risk of future negative studies, it is vital to understand why previous interventions appeared to cause harm.
Observations  The limited number of beneficial treatments for acute ischemic stroke are far outnumbered by negative (not neutral) interventions that worsened outcomes in randomized clinical trials (RCTs), including those with putative neuroprotectant, anticoagulant, anti-inflammatory, free radical–scavenging, hemorrhagic, or vasoactive activity. Other agents reduced thrombolytic efficiency or exhibited neuropsychiatric or cardiac toxicity. In intracerebral hemorrhage, platelet transfusion was hazardous. Although reperfusion treatments should be given as soon as possible, very early intervention with other strategies may instead be hazardous, as has been seen with physical therapy and vasodepressors.
Conclusions and Relevance  The lessons learned from negative stroke RCTs are vital for designing future studies. Multicenter preclinical studies are necessary, and animals that die must be included in analyses. Randomized clinical trials must assess multiple neurological, vascular, cardiac, and general safety effects, whether these are on target or off target. All preclinical trials and RCTs must be published in full. Learning from the past will help to reduce the number of negative stroke RCTs in the future.

Full Text

Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage (TICH-2): An international randomised, placebo-controlled, phase 3 superiority trial

So it didn't really help. Nice to see a negative research finding being published.
https://www.mdlinx.com/journal-summaries/tranexamic-acid-hematoma-stroke-intracerebral-hemorrhage/2018/05/21/7521061/?

The Lancet — Sprigg N, et al. | May 21, 2018

An international, randomized placebo-controlled trial was performed to evaluate if tranexamic acid lessens hematoma expansion and improves outcomes in adults with stroke due to intracerebral hemorrhage. Despite a decrease in early deaths and serious adverse events, functional status 90 days following intracerebral hemorrhage did not differ significantly among patients who received tranexamic acid vs those who received placebo.

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Methods

• This trial was conducted on adults with intracerebral hemorrhage from acute stroke units at 124 hospital sites in 12 countries.
• Members were randomized (1:1) to receive 1g intravenous tranexamic acid bolus followed by an 8-hour infusion of 1g tranexamic acid or a matching placebo, within 8 hours of symptom onset.
• Randomization happened centrally in real time via a secure website, with stratification by country and minimization on key prognostic factors.
• Treatment allocation was hidden from patients, outcome assessors, and all other health-care workers involved in the trial.
• Using ordinal logistic regression with adjustment for stratification and minimization criteria, the primary outcome was functional status at day 90, measured by shift in the modified Rankin Scale.
• All examinations were done on an intention-to-treat basis.

Results

• Between March 1, 2013, and Sept 30, 2017, 2,325 participants were recruited.
• One 1,161 patients received tranexamic acid and 1,164 received placebo; the treatment groups were well balanced at baseline.
• For 2,307 (99%) participants, the primary outcome was assessed.
• They observed that the primary outcome did not differ significantly between the groups (adjusted odds ratio [aOR] 0.88, 95% CI 0.76–1.03, p=0.11).
• Findings revealed that, although there were fewer deaths by day 7 in the tranexamic acid group(Except for this positive) (101 [9%] deaths in the tranexamic acid group vs 123 [11%] deaths in the placebo group; aOR 0.73, 0.53–0.99, p=0.0406), there was no difference in case fatality at 90 days (250 [22%] vs 249 [21%]; adjusted hazard ratio 0.92, 95% CI 0.77–1.10, p=0·37).
• It was observed in the findings that fewer patients had serious adverse events after tranexamic acid vs after placebo by days 2 (379 [33%] patients vs 417 [36%] patients)(Except for this positive), 7 (456 [39%] vs 497 [43%]), and 90 (521 [45%] vs 556 [48%]).

Read the full article on The Lancet