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in times past it could have been worse. In the colonial times this would have almost certainly resulted in an “affair of honor with multiple potential parties demanding justice

Does anybody here remember Vera Lynn?
Remember how she said that
We would meet again
Some sunny day?
Vera, Vera
What has become of you
Does anybody else in here
Feel the way I do?

You won’t find anything current- any COVID + patient who dies while under treatment will be deemed COVID related.
Medication related deaths are far harder to prove

In fact the severe side effects that can occur in an acute setting- erythema multiforme, toxic epidermal necrolysis, prolonged QT syndrome, cardiomyopathy should be picked up by a provider (especially if the patient is hospitalized) with the patient immediately being taken off the hydroxycholorquine. All of the above conditions have been associated with death and you should look them up individually as opposed to the medication itself.

The bigger issue is if people to get a hold of this and use it without a physician monitoring (difficult though not impossible) and especially if they think they can use it without a concern as a preventative for months at a time as some here seem to be suggesting. Then other potentially issues arise, equally nasty, including aplastic anemia, hepatic necrosis and retinopathy, Not good.

My intention was not to show what it does but rather present the side effects for those who seem to argue that it is safer than water (not that water is safe when drunk in excess).

Many but not all— erythema multiforme, toxic epidermal necrolysis, cardiomyopathy, cardiac conduction abnormalities and hypoglycemia can all occur acutely along with the usual nuisance side effects.

A number of individuals on this forum are talking about using hydroxychloroquine as a preventative, however, and used like that the risks are far greater.

prolonged QT is associated with “a potentially fatal polymorphic ventricular tachycardia called torsades de pointes (TdP). Although usually self-limited, TdP may degenerate into ventricular fibrillation and cause sudden death”.

This is a list of side effects to hydroxychoroquine from UpToDate that I posted the other day on a different thread. I encourage you to read through them all.

Hydroxychloroquine may have some benefit for COVID-19 and is being used in this time of national emergency under medical supervision but definitive trials remain pending.

As a practicing neurologist (epileptologist) with over 30 years experience I have used my share of problematic medications (felbamate, ezogabine, valproate, lamotrigine, topiramate, everolimus) but even from my perspective this is not a list of side effects to consider lightly. Fortunately many of these are more likely to be a problem with long term use but while that is not an issue with treatment of COVID-19 it will be use for prevention is considered.

Adverse Reactions

1% to 10%: Ophthalmic: Retinopathy (4%; serum concentration dependent [Petri 2019]; early changes reversible [may progress despite discontinuation if advanced])

Frequency not defined:

Dermatologic: Acute generalized exanthematous pustulosis, alopecia, bullous rash, dyschromia (skin and mucosal), erythema multiforme, exacerbation of psoriasis, exfoliative dermatitis, hair discoloration, pruritus, skin photosensitivity, skin rash, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria

Endocrine & metabolic: Exacerbation of porphyria, severe hypoglycemia, weight loss

Gastrointestinal: Abdominal pain, decreased appetite, diarrhea, nausea, vomiting

Hematologic & oncologic: Agranulocytosis, anemia, aplastic anemia, bone marrow failure, hemolysis (in patients with glucose-6-phosphate deficiency), leukopenia, thrombocytopenia

Hepatic: Abnormal hepatic function tests, acute hepatic failure

Hypersensitivity: Angioedema

Immunologic: Drug reaction with eosinophilia and systemic symptoms

Nervous system: Ataxia, dizziness, emotional lability, fatigue, headache, irritability, nervousness, nightmares, psychosis, seizure, sensorineural hearing loss, suicidal tendencies, vertigo

Neuromuscular & skeletal: Myopathy (including palsy or neuromyopathy, leading to progressive weakness and atrophy of proximal muscle groups; may be associated with mild sensory changes and loss of deep tendon reflexes)

Ophthalmic: Corneal changes (corneal edema, corneal opacity, corneal sensitivity, corneal deposits, visual disturbance, blurred vision, photophobia), decreased visual acuity, macular degeneration, maculopathy, nystagmus disorder, retinal pigment changes, retinitis pigmentosa, scotoma, vision color changes, visual field defect

Otic: Deafness, tinnitus

Respiratory: Bronchospasm

Postmarketing:

Cardiovascular: Cardiomyopathy, prolonged QT interval on ECG, torsades de pointes, ventricular arrhythmia

Endocrine & metabolic: Hypoglycemia (can be severe; Cansu 2008; FDA Safety Alert, April 1, 2020; Unübol 2011)

Hematologic & oncologic: Neutropenia (FDA Safety Alert, April 1, 2020), pancytopenia (FDA Safety Alert, April 1, 2020)

Nervous system: Agitation (FDA Safety Alert, April 1, 2020), confusion (FDA Safety Alert, April 1, 2020), delirium (FDA Safety Alert, April 1, 2020), extrapyramidal reaction (FDA Safety Alert, April 1, 2020), hallucination (FDA Safety Alert, April 1, 2020)

Ophthalmic: Epithelial keratopathy (Dosso 2007)

Renal: Renal insufficiency (FDA Safety Alert, April 1, 2020)

Warnings/Precautions

Concerns related to adverse effects:

• Cardiovascular effects: Cardiomyopathy resulting in cardiac failure, sometimes fatal, has been reported (symptoms may present as atrioventricular block, pulmonary hypertension, sick sinus syndrome, or as cardiac complications), and may appear during acute or chronic therapy. Monitor for signs/symptoms of cardiac compromise; discontinue treatment promptly if signs and symptoms of cardiomyopathy occur. In a scientific statement from the American Heart Association, hydroxychloroquine has been determined to be an agent that may either cause direct myocardial toxicity or exacerbate underlying myocardial dysfunction (magnitude: major) (AHA [Page 2016]). Consider chronic toxicity if conduction disorders (eg, bundle branch block, atrioventricular heart block) as well as biventricular hypertrophy are diagnosed. May also be associated with QT interval prolongation; ventricular arrhythmia and torsades de pointes have been reported (monitor QT-prolonging effects during therapy in at-risk patients or if used in combination with other medications that prolong the QT interval).

• Dermatologic effects: Skin reactions to hydroxychloroquine may occur; use with caution in patients on concomitant medications with a propensity to cause dermatitis.

• Hematologic effects: Bone marrow suppression (eg, agranulocytosis, anemia, aplastic anemia, leukopenia, thrombocytopenia) have been reported; periodically monitor CBC during prolonged therapy. Discontinue treatment if signs/symptoms of severe blood disorder not attributable to the underlying disease occur.

• Hypoglycemia: Severe hypoglycemia, including life-threatening loss of consciousness, has been reported in patients with and without concomitant use of antidiabetic agents. Advise patients of risk of hypoglycemia and associated signs/symptoms; discontinue use in patients who develop severe hypoglycemia.

• Neuromuscular effects: Proximal myopathy or neuromyopathy, leading to progressive weakness, proximal muscle atrophy, depressed tendon reflexes, and abnormal nerve conduction may occur, especially with long-term therapy. Curvilinear bodies and muscle fiber atrophy with vacuolar changes have been noted on muscle or nerve biopsy. Muscle strength (especially proximal muscles) and reflexes should be assessed periodically during long term therapy.

• Psychiatric effects: Suicidal behavior has been reported rarely.

• Retinal toxicity: Retinal toxicity, potentially causing irreversible retinopathy, is predominantly associated with high daily doses and a duration of >5 years of use of chloroquine or hydroxychloroquine in the treatment of rheumatic diseases. One study suggested a correlation of higher serum concentrations of hydroxychloroquine with ocular toxicity (Petri 2019). Other major risk factors include concurrent tamoxifen use, renal impairment, lower body weight, and the presence of macular disease. Daily hydroxychloroquine (base) doses >5 mg/kg actual body weight were associated with an ~10% risk of retinal toxicity within 10 years of treatment and an almost 40% risk after 20 years of therapy. Risk is most accurately assessed on the basis of duration of use relative to daily dose/body weight (Marmor [AAO 2016]; Melles 2014). Based on these risks, the American Academy of Ophthalmology (AAO) recommends not exceeding a daily hydroxychloroquine dosage of 5 mg/kg using actual body weight in most patients. Previous recommendations to use ideal body weight are no longer advised; very thin patients in particular were at increased risk for retinal toxicity using this practice. Current AAO guidelines do not specifically address dosing in obese patients. AAO also recommends baseline screening for retinal toxicity and annual screening beginning after 5 years of use (or sooner if major risk factors are present) (Marmor [AAO 2016]). If ocular toxicity is suspected, discontinue and monitor closely; retinal changes and visual disturbances may progress after discontinuation. A baseline ocular exam is recommended within the first year of initiating hydroxychloroquine treatment.

I’m a bit concerned with the enthusiasm expressed here for hydroxychloroquine. The information thus far on it effectiveness in COVID-19 is largely anecdotal with no double blind placebo controlled date available. While I am a physician and spend about 50% of my time in the hospital I am not really on the front lines as a neurologist and cannot speak from personal experience about the drug’s efficacy. Still natural history is one possible confounding factor and placebo effect the other.

The potential side effects with hydroxychloroquine are definitely significant. This is not a safe drug like many here are touting. When used short-term under the care of a physician I think it is reasonable— many of the side effects are more long-term in nature, but if people start trying to use it as a preventative... not only is there no evidence to suggest that it would work but the risk of potentially severe side effects would escalate substantially.

Here is a current list of side effects from UpToDate for Hydroxychloroquine

Adverse Reactions

1% to 10%: Ophthalmic: Retinopathy (4%; serum concentration dependent [Petri 2019]; early changes reversible [may progress despite discontinuation if advanced])

Frequency not defined:

Dermatologic: Acute generalized exanthematous pustulosis, alopecia, bullous rash, dyschromia (skin and mucosal), erythema multiforme, exacerbation of psoriasis, exfoliative dermatitis, hair discoloration, pruritus, skin photosensitivity, skin rash, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria

Endocrine & metabolic: Exacerbation of porphyria, severe hypoglycemia, weight loss

Gastrointestinal: Abdominal pain, decreased appetite, diarrhea, nausea, vomiting

Hematologic & oncologic: Agranulocytosis, anemia, aplastic anemia, bone marrow failure, hemolysis (in patients with glucose-6-phosphate deficiency), leukopenia, thrombocytopenia

Hepatic: Abnormal hepatic function tests, acute hepatic failure

Hypersensitivity: Angioedema

Immunologic: Drug reaction with eosinophilia and systemic symptoms

Nervous system: Ataxia, dizziness, emotional lability, fatigue, headache, irritability, nervousness, nightmares, psychosis, seizure, sensorineural hearing loss, suicidal tendencies, vertigo

Neuromuscular & skeletal: Myopathy (including palsy or neuromyopathy, leading to progressive weakness and atrophy of proximal muscle groups; may be associated with mild sensory changes and loss of deep tendon reflexes)

Ophthalmic: Corneal changes (corneal edema, corneal opacity, corneal sensitivity, corneal deposits, visual disturbance, blurred vision, photophobia), decreased visual acuity, macular degeneration, maculopathy, nystagmus disorder, retinal pigment changes, retinitis pigmentosa, scotoma, vision color changes, visual field defect

Otic: Deafness, tinnitus

Respiratory: Bronchospasm

Postmarketing:

Cardiovascular: Cardiomyopathy, prolonged QT interval on ECG, torsades de pointes, ventricular arrhythmia

Endocrine & metabolic: Hypoglycemia (can be severe; Cansu 2008; FDA Safety Alert, April 1, 2020; Unübol 2011)

Hematologic & oncologic: Neutropenia (FDA Safety Alert, April 1, 2020), pancytopenia (FDA Safety Alert, April 1, 2020)

Nervous system: Agitation (FDA Safety Alert, April 1, 2020), confusion (FDA Safety Alert, April 1, 2020), delirium (FDA Safety Alert, April 1, 2020), extrapyramidal reaction (FDA Safety Alert, April 1, 2020), hallucination (FDA Safety Alert, April 1, 2020)

Ophthalmic: Epithelial keratopathy (Dosso 2007)

Renal: Renal insufficiency (FDA Safety Alert, April 1, 2020)

Warnings/Precautions

Concerns related to adverse effects:

• Cardiovascular effects: Cardiomyopathy resulting in cardiac failure, sometimes fatal, has been reported (symptoms may present as atrioventricular block, pulmonary hypertension, sick sinus syndrome, or as cardiac complications), and may appear during acute or chronic therapy. Monitor for signs/symptoms of cardiac compromise; discontinue treatment promptly if signs and symptoms of cardiomyopathy occur. In a scientific statement from the American Heart Association, hydroxychloroquine has been determined to be an agent that may either cause direct myocardial toxicity or exacerbate underlying myocardial dysfunction (magnitude: major) (AHA [Page 2016]). Consider chronic toxicity if conduction disorders (eg, bundle branch block, atrioventricular heart block) as well as biventricular hypertrophy are diagnosed. May also be associated with QT interval prolongation; ventricular arrhythmia and torsades de pointes have been reported (monitor QT-prolonging effects during therapy in at-risk patients or if used in combination with other medications that prolong the QT interval).

• Dermatologic effects: Skin reactions to hydroxychloroquine may occur; use with caution in patients on concomitant medications with a propensity to cause dermatitis.

• Hematologic effects: Bone marrow suppression (eg, agranulocytosis, anemia, aplastic anemia, leukopenia, thrombocytopenia) have been reported; periodically monitor CBC during prolonged therapy. Discontinue treatment if signs/symptoms of severe blood disorder not attributable to the underlying disease occur.

• Hypoglycemia: Severe hypoglycemia, including life-threatening loss of consciousness, has been reported in patients with and without concomitant use of antidiabetic agents. Advise patients of risk of hypoglycemia and associated signs/symptoms; discontinue use in patients who develop severe hypoglycemia.

• Neuromuscular effects: Proximal myopathy or neuromyopathy, leading to progressive weakness, proximal muscle atrophy, depressed tendon reflexes, and abnormal nerve conduction may occur, especially with long-term therapy. Curvilinear bodies and muscle fiber atrophy with vacuolar changes have been noted on muscle or nerve biopsy. Muscle strength (especially proximal muscles) and reflexes should be assessed periodically during long term therapy.

• Psychiatric effects: Suicidal behavior has been reported rarely.

• Retinal toxicity: Retinal toxicity, potentially causing irreversible retinopathy, is predominantly associated with high daily doses and a duration of >5 years of use of chloroquine or hydroxychloroquine in the treatment of rheumatic diseases. One study suggested a correlation of higher serum concentrations of hydroxychloroquine with ocular toxicity (Petri 2019). Other major risk factors include concurrent tamoxifen use, renal impairment, lower body weight, and the presence of macular disease. Daily hydroxychloroquine (base) doses >5 mg/kg actual body weight were associated with an ~10% risk of retinal toxicity within 10 years of treatment and an almost 40% risk after 20 years of therapy. Risk is most accurately assessed on the basis of duration of use relative to daily dose/body weight (Marmor [AAO 2016]; Melles 2014). Based on these risks, the American Academy of Ophthalmology (AAO) recommends not exceeding a daily hydroxychloroquine dosage of 5 mg/kg using actual body weight in most patients. Previous recommendations to use ideal body weight are no longer advised; very thin patients in particular were at increased risk for retinal toxicity using this practice. Current AAO guidelines do not specifically address dosing in obese patients. AAO also recommends baseline screening for retinal toxicity and annual screening beginning after 5 years of use (or sooner if major risk factors are present) (Marmor [AAO 2016]). If ocular toxicity is suspected, discontinue and monitor closely; retinal changes and visual disturbances may progress after discontinuation. A baseline ocular exam is recommended within the first year of initiating hydroxychloroquine treatment.

As others have said it tests for virus particles not antibodies but there is a bit of an unknown as to whether the presence of dead virus could cause a false positive. That is currently under investigation

No... he came in a distant third with 18%

The skeletal structure of a foot but enclosed in a fin. It had a skull tat was amphibian not fish like as a well as a neck and . Other transitional forms have been found... some thought to precede (Pandericthys, Eusthenopteron) and some forms suspected to be later (Icthyostega, Acanthostega).

They think that Tiktaalik did live in shallow water based on its structure and its location. and with its fin and pectoral girdle structure and
ventured onto land

How about Tiktaalik... sarcopterygian fish from the Devonian with limb anatomy analogous to amphibians and other tetrapods with limbs showing a one bone-two bone many bone structure encased in a fish fin.

https://en.wikipedia.org/wiki/Tiktaalik

https://www.youtube.com/watch?v=E8ttoKGxEKc

As an epileptologist I can tell you this is a real thing. Trials have been done showing its effectiveness in Dravet syndrome (and Lennox-Gastaut syndrome as well) and a pharmacologic product Epidiolex was recently approved by the FDA though it remains to be scheduled by the DEA- should happen in the next 3 months (if it happens at all).

Implicating Bush in the JFK assassination is ridiculous.

He was living in Houston at the time and that year had just been elected to his first political office- Chairman of the Harris County Republican party.

He wasn’t elected to congress until 1967 and he wasn’t involved in the CIA until 1976

When passed it will apply to 2017 tax year

Right now predominantly post mortum through autopsies by PET tau may very well also for identification in people before they die and possibly even in early stages of the disorder.

All of this will take time and further studies and comparisons to healthy “normals”

CTE is a the result of cumulative damage over years. There may be a genetic component (like so much else) with some individuals being more likely to develop CTE as a consequence of repeated impacts than others. The presence of an APOE genotype (also associated with Alzheimers) being one identified possible risk factor.

Good questions- not easily answered.

CTE is probably akin to dementia pugilistica which occurs in about 20% of professional boxers. Other sports have not been studied as well. Relative rates of concussive injuries may provide some guidance but not definitive.

Trauma certainly could have occurred earlier as well. There is some evidence to suggest that concussions occurring in the early teenage years or before may be more significant than those occurring later on

Possibly- anything reducing impacts on the skull and concussions would likely help.

My best guess- is Positron Emission Tomagraphy (PET) Tau- not something I can order in my neck of the woods and pretty cutting edge but clearly the way things are headed. They also have PET amyloid for Alzheimers- I am not able to order that either :(