An admittedly late notice. (The NYT report was published 5 days ago.)
But the paper provides an important insight into why some high-fee hospitals charge what they charge, especially when they claim that "the charges are irrelevant because virtually no one — private insurers, Medicare or even the uninsured — pays anywhere near those amounts."
The hospitals' defense begs an obvious follow-up: Then why charge such high fees for medical procedures or conditions, if the charges are irrelevant? The answer appears to be two-fold.
1) Uncollected hospital fees could be (or were) counted as tax-reducing charity. (Although this is no longer allowable, per the NYT, which cites the IRS.)
2) Also high-fee hospitals can maneuver to become "out-of-network," thereby allowing for the collection of relatively steeper, non-negotiated fees from insurers—particularly fees for emergency services.
The latter tactic I find to be particularly diabolical, since area patients are often required to seek care at high-fee hospitals on the basis of their proximity to the facility. It's easy for such patients to be angry with insurers in these cases, but it appears that high-fee hospitals are really the evil doers in this scenario.
But the paper provides an important insight into why some high-fee hospitals charge what they charge, especially when they claim that "the charges are irrelevant because virtually no one — private insurers, Medicare or even the uninsured — pays anywhere near those amounts."
The hospitals' defense begs an obvious follow-up: Then why charge such high fees for medical procedures or conditions, if the charges are irrelevant? The answer appears to be two-fold.
1) Uncollected hospital fees could be (or were) counted as tax-reducing charity. (Although this is no longer allowable, per the NYT, which cites the IRS.)
2) Also high-fee hospitals can maneuver to become "out-of-network," thereby allowing for the collection of relatively steeper, non-negotiated fees from insurers—particularly fees for emergency services.
The latter tactic I find to be particularly diabolical, since area patients are often required to seek care at high-fee hospitals on the basis of their proximity to the facility. It's easy for such patients to be angry with insurers in these cases, but it appears that high-fee hospitals are really the evil doers in this scenario.
Newly released data from the Center for Medicare and Medicaid Services show that the nation's hospitals charge wildly different fees for the same procedure. (See the NYT story here.) And while that information is really nothing new (or different from what was suspected), the fee differences are staggering and largely inexplicable. While some hospitals—particularly academic centers—justify their higher fees on the basis of a sicker (urban) patient population or higher bottom-line costs for teaching (pfft), I suspect these explanations are mostly BS. Generally I think these institutions charge what they charge because they can. And there's really no incentive to do otherwise, given that most patients—who are privately insured or covered by Medicare or Medicaid—aren't directly affected by the sticker shock. It's the uninsured or marginally insured who may be stuck with a staggering hospital bill.
In a healthcare system that remains largely free-market, greater accountability of hospitals to justify exorbitant fees can only be demanded by consumers. And that's unlikely to happen given the current structure of US healthcare and its financing. (Although I see no reason why ridiculously paid hospital administrators couldn't go the way of the dodo bird. That certainly would be one simple cost-containment measure that could save millions of dollars.)
Update: The raw data from the CMMS are provided here and can be manipulated and filtered with the online tools (after a little operant conditioning). For instance, you can determine what hospitals are charging for a specific procedure in your state or city. To download the data into one of the various offered formats (like Excel), it appears that you have to sign in with an account (which is free).
For instance, for a permanent cardiac pacemaker implant without CC/MCC (complications and comorbities/major complications and cormbidities; DRG 244), hospital charges in the United States ranged from $15,128.14 (at Peninsula Regional Medical Center in Salisbury, MD) to an astonishing $167,628.42 (at Vista Medical Center East in Waukegan, IL). The government reimbursed in the range of $10,000 to $27,000 (one outlier reimbursement exceeded $43,000). The government's reimbursement appeared to have little to do with the amount charged by the hospital.
In a healthcare system that remains largely free-market, greater accountability of hospitals to justify exorbitant fees can only be demanded by consumers. And that's unlikely to happen given the current structure of US healthcare and its financing. (Although I see no reason why ridiculously paid hospital administrators couldn't go the way of the dodo bird. That certainly would be one simple cost-containment measure that could save millions of dollars.)
Update: The raw data from the CMMS are provided here and can be manipulated and filtered with the online tools (after a little operant conditioning). For instance, you can determine what hospitals are charging for a specific procedure in your state or city. To download the data into one of the various offered formats (like Excel), it appears that you have to sign in with an account (which is free).
For instance, for a permanent cardiac pacemaker implant without CC/MCC (complications and comorbities/major complications and cormbidities; DRG 244), hospital charges in the United States ranged from $15,128.14 (at Peninsula Regional Medical Center in Salisbury, MD) to an astonishing $167,628.42 (at Vista Medical Center East in Waukegan, IL). The government reimbursed in the range of $10,000 to $27,000 (one outlier reimbursement exceeded $43,000). The government's reimbursement appeared to have little to do with the amount charged by the hospital.
Possibly the last immunotherapy hope in established Alzheimer disease, intravenous gamma globulin (aka IV Ig) failed to slow cognitive decline in a large, closely watched phase 3 trial. According to today's press release from Baxter, the trial sponsor, IV Ig* did not significantly alter cognitive decline or preserve functional abilities over 18 months, when compared with placebo, in patients with mild-moderate AD (total N = 390). Baxter provides a very handy data table here of the topline results.Like other commercial investigators of AD, however, Baxter remains interested in assessing outcomes of subgroups. Notably there was a numerically greater difference in cognitive decline between some patients** who received high-dose IV Ig and placebo-treated enrollees. But the phase 3 study was not statistically powered to validate these post-hoc analyses.
Generally IV Ig was well tolerated in the study with no new adverse-event signals. The most common side effects (in at least 5% of subjects) were rash and falls in hemoglobin levels. A total of 12 IV Ig-treated patients and 5 placebo-treated patients reportedly experienced serious adverse events.
According to Baxter, its studies of IV Ig in mild-moderate AD will be discontinued. The full study results will be presented at the AAIC in July.
* At doses of either 200 or 400 mg/kg every 2 weeks.
** Specifically those with moderate disease or ApoE4 carriers.
For those of us interested in writing about medical history, particularly early 20th-century medical history, a specific hurdle is encountered when attempting to quote, extract, or reprint text, figures, and photographs from early, relevant US medical journals—specifically those published between 1923 and 1963.* While the plea of "fair use" may be perfectly justified when using (and citing) brief excerpts from these articles in a scholarly (even for-profit) work, the issue of copyright protection and reprint permission can be a thorny one.
But a little online research suggests that many US medical journals published before 1950, even 1960, are in the public domain—including the preciously guarded journals of the AMA (eg, JAMA) and the Massachusetts Medical Society (ie, NEJM). While online access to remote back issues of these publications suggests that they remain copyrighted (even those published before 1923!), and both publishers charge not-inconsequential fees for downloading older articles, it appears that they should be freely and publicly available. (BTW, the Copyright Clearance Center is no help in this matter, at least not in my experience.)
The crux of maintaining copyright for these older issues was dependent on the 1909 copyright law, which was in effect at the time of anything published in the United States from 1923 to 1963. At the time of publication, copyright protection lasted for an automatic 28 years, at which time the copyright holder was obliged to renew the copyright (ultimately for another 67 years, thanks to subsequent copyright laws, for a total of 95 years). But many publishers, including apparently the AMA and the MMS, did not renew the copyright for their early 20th-century about-to-lapse issues. The answer as to whether they did or did not renew their copyright can be found by searching the online records of the US Copyright Office (here) and accessing links through the table here to digitized catalogs of US copyright records before January 1, 1978 (for instance, at archive.org).
As an example exercise to prove this point, let's say I want to quote extensively from a 1937 article in JAMA, but I'm not sure if an extensive quote qualifies as "fair use," and I'm not sure if the copyright for the article even remains in existence.** So I check the "1937 row" in the table here, which provides a link to copyright registrations, including the 28-year renewals, for 1965 (1937 + 28 = 1965). This drop-down link for "Periodicals" provides another link to the "Renewal Registrations" section of the digitized Catalog of Copyright Entries, 1965 (Periodicals Jan-Dec 3D Ser Vol 19 Pt 2) at archive.org. By scrolling through the section, it is readily apparent there is no entry for JAMA (or any possibly related entries). (It is also readily apparent how few periodicals, including medical journals, actually renewed their copyrights.) A search of surrounding years, 1964 and 1966, confirms the absence of JAMA in the copyright renewals section. Consequently it can be concluded with reasonable certainty that the copyright for JAMA issues of 1937 was not renewed and, therefore, automatically lapsed. These issues should therefore be in the public domain (although the online catalog warns that the catalog entries may not be complete).
So then the question becomes: When did the AMA and the MMS begin to renew the copyrights for the older issues of their journals? The answer is apparently found in the online copyright catalog. Renewals on copyrights for JAMA and many (possibly all) of the AMA's related Archives issues were apparently not registered until 1988—meaning 28 years after the 1960 issues were published. Copyright renewals on the NEJM did not begin until the January 3, 1957, issue. Therefore it may well be that older issues of these renowned medical journals are actually in the public domain, and I would argue (unless I'm presented with compelling, contrary data) that they are. See my table, for examples of relevant data from the online copyright database.
* Anything published before 1923 in the United States is public domain. And anything published after 1963 (save government works) is very likely to be copyrighted. See these excellent websites for reference: Public Domain Sherpa and US Catalog of Copyright Entries (Renewals).
** A major caveat. Some articles (although typically not medical articles) can remain under copyright independent of the journal in which they were originally published. However, this situation is more likely to be true for literature (eg, poetry, short stories) published in literature review periodicals.
But a little online research suggests that many US medical journals published before 1950, even 1960, are in the public domain—including the preciously guarded journals of the AMA (eg, JAMA) and the Massachusetts Medical Society (ie, NEJM). While online access to remote back issues of these publications suggests that they remain copyrighted (even those published before 1923!), and both publishers charge not-inconsequential fees for downloading older articles, it appears that they should be freely and publicly available. (BTW, the Copyright Clearance Center is no help in this matter, at least not in my experience.)
The crux of maintaining copyright for these older issues was dependent on the 1909 copyright law, which was in effect at the time of anything published in the United States from 1923 to 1963. At the time of publication, copyright protection lasted for an automatic 28 years, at which time the copyright holder was obliged to renew the copyright (ultimately for another 67 years, thanks to subsequent copyright laws, for a total of 95 years). But many publishers, including apparently the AMA and the MMS, did not renew the copyright for their early 20th-century about-to-lapse issues. The answer as to whether they did or did not renew their copyright can be found by searching the online records of the US Copyright Office (here) and accessing links through the table here to digitized catalogs of US copyright records before January 1, 1978 (for instance, at archive.org).
As an example exercise to prove this point, let's say I want to quote extensively from a 1937 article in JAMA, but I'm not sure if an extensive quote qualifies as "fair use," and I'm not sure if the copyright for the article even remains in existence.** So I check the "1937 row" in the table here, which provides a link to copyright registrations, including the 28-year renewals, for 1965 (1937 + 28 = 1965). This drop-down link for "Periodicals" provides another link to the "Renewal Registrations" section of the digitized Catalog of Copyright Entries, 1965 (Periodicals Jan-Dec 3D Ser Vol 19 Pt 2) at archive.org. By scrolling through the section, it is readily apparent there is no entry for JAMA (or any possibly related entries). (It is also readily apparent how few periodicals, including medical journals, actually renewed their copyrights.) A search of surrounding years, 1964 and 1966, confirms the absence of JAMA in the copyright renewals section. Consequently it can be concluded with reasonable certainty that the copyright for JAMA issues of 1937 was not renewed and, therefore, automatically lapsed. These issues should therefore be in the public domain (although the online catalog warns that the catalog entries may not be complete).
So then the question becomes: When did the AMA and the MMS begin to renew the copyrights for the older issues of their journals? The answer is apparently found in the online copyright catalog. Renewals on copyrights for JAMA and many (possibly all) of the AMA's related Archives issues were apparently not registered until 1988—meaning 28 years after the 1960 issues were published. Copyright renewals on the NEJM did not begin until the January 3, 1957, issue. Therefore it may well be that older issues of these renowned medical journals are actually in the public domain, and I would argue (unless I'm presented with compelling, contrary data) that they are. See my table, for examples of relevant data from the online copyright database.
|
US Journal |
Copyright Renewal Start Date |
Should Be Public Domain If Published Before… |
|
New England Journal of Medicine |
Jan 3, 1957 |
Jan 3, 1957 |
|
AMA journals |
||
|
JAMA |
Jan 1960 (vol. 172, no. 2) |
Jan 1960 |
|
Archives of
Dermatology |
Jan 1960 (vol. 81, no. 1) |
Jan 1960 |
|
Archives of
General Psychiatry |
Jul 1960 (vol. 3, no. 1) |
Jul 1960 |
|
Archives of Internal Medicine (now JAMA Internal Medicine) |
Jul 1960 (vol. 103, no. 1) |
Jul 1960 |
|
Archives of
Neurology |
Jan 1960 (vol. 2, no. 1) |
Jan 1960 |
|
Archives of Ophthalmology (now JAMA Ophthalmology) |
Jun 1960 (vol. 63, no. 6) |
Jun 1960 |
|
Archives of
Surgery |
Jan 1960 (vol. 80, no. 1) |
Jan 1960 |
* Anything published before 1923 in the United States is public domain. And anything published after 1963 (save government works) is very likely to be copyrighted. See these excellent websites for reference: Public Domain Sherpa and US Catalog of Copyright Entries (Renewals).
** A major caveat. Some articles (although typically not medical articles) can remain under copyright independent of the journal in which they were originally published. However, this situation is more likely to be true for literature (eg, poetry, short stories) published in literature review periodicals.
A new census-based study, published online in Neurology, indicates that the number of people with Alzheimer disease in 2010 was 4.7 million. This number is projected to increase to nearly 14 million (13.8 million) in 2050. The older elderly (85+)—meaning, the aging baby boomer population (who is expected to have good chances of longevity)—will account for about half of the AD cases in 40 years.
Of course, projections will change if any disease-modifying or preventive drug makes it to the market before then.
Of course, projections will change if any disease-modifying or preventive drug makes it to the market before then.
Despite the fact that Lilly's solanezumab failed in recent phase 3 trials (and despite vigorous attempts to pound out convincing clinical and biomarker data), the anti-amyloid MAb will be assessed in an upcoming prevention study in at-risk, nondemented elderly. The compound was likely selected over another failed anti-amyloid MAb, bapineuzumab, on the basis of more favorable safety data.
Notably the subjects for the new government-funded prevention trial will demonstrate amyloid build-up on brain images. In the phase 3 solanezumab trials, a substantial percentage of enrollees (~20%) did not demonstrate excessive amyloid on PET brain images—making the interpretation of biomarker results problematic.
MAb = monoclonal antibody; PET = positron emission tomography.
Notably the subjects for the new government-funded prevention trial will demonstrate amyloid build-up on brain images. In the phase 3 solanezumab trials, a substantial percentage of enrollees (~20%) did not demonstrate excessive amyloid on PET brain images—making the interpretation of biomarker results problematic.
MAb = monoclonal antibody; PET = positron emission tomography.
I concur with Richard Bazell, NBC's head science reporter, that information dispensed from the State Department about Hillary Clinton's medical condition is very confusing. The given and widely reported news is that Clinton suffered a "blood clot" "stemming from" her recent concussion, and that this blood clot is being treated with anticoagulants (eg, heparin or warfarin). However, the kind of blood clot most likely to occur in association with a concussion, a subdural hematoma (which is not really a "blood clot," that is, a vascular thrombosis) would not be treated with anticoagulants—because anticoagulants would increase the risk of further bleeding.The alternative explanation is that Clinton has suffered a deep venous thrombosis (DVT) in one of her legs—possibly as a result of prolonged sitting during extended and frequent plane rides and/or prolonged bed rest due to her recent (acknowledged) gastroenteritis. To reduce the risk of a pulmonary embolism as a result of the DVT, Clinton would, in this case, be treated with anticoagulants; however, this condition would not have occurred as a direct result of her concussion (which was reportedly due to fainting because of dehydration [which was due to the gastroenteritis]). Another alternative explanation is that Clinton was discovered to have a venous sinus thrombosis in the brain (possibly as a result of dehydration, and NOT a concussion) during her medical follow-up, and that this condition is being treated with anticoagulants. A third possibility is that the anticoagulants were prescribed to treat a stroke caused by an arterial thrombosis or embolism (in which case the anticoagulant might actually be tPA).
Until we receive a better a-to-b-to-c explanation about Clinton's condition and why she's receiving anticoagulants (and what kind), we're left grasping at more logical and medically sensible explanations than the State Department is currently willing to offer.
tPA = tissue plasminogen activator.
Update: Follow-up news reports indicate that Clinton will remain hospitalized (at New York Presbyterian) for 48 hours. The timing suggests that Clinton is being anticoagulated with IV heparin before the effects of oral warfarin can kick in. The forecasted brevity of her hospitalization also suggests that Clinton is being treated for a DVT, as opposed to a more severe "blood clot" or thrombosis, such as a venous sinus thrombosis or an arterial thrombosis in the brain. If true, then her "blood clot," as it was reported by the State Department, doesn't have anything directly to do with her concussion.
01/01/13 update: Surprise. News reports indicating that Clinton would be hospitalized for 48 hours were premature or simply incorrect. The LA Times now reports that Clinton has a thrombosis in the right transverse venous sinus. The thrombosis was discovered on Sunday, December 30th, after Clinton underwent a brain MRI as a follow-up study for her concussion. No one is reporting whether Clinton experienced persistent symptoms after her concussion, such as a prolonged headache, which might have warranted the follow-up imaging study; however, there is apparently no indication that she suffered a stroke as a result of the thrombosis (which would most likely be, if it occurred, a hemorrhagic stroke). The prescribed anticoagulant therapy is intended to reduce the risk that the thrombosis will propagate further and to allow the body to dissolve (more or less) the obstructing clot. Some doctors uninvolved with Clinton's care are offering that the concussion may have triggered the thrombosis; however, I find that explanation unlikely (but not impossible). While injury (eg, neurosurgical injury) has been epidemiologically linked to the formation of venous sinus thromboses, the relation of this condition to concussion is apparently confined to case reports (most of which are not in English). Given Clinton's history, it seems more likely that she was predisposed to thrombosis on the basis of some as-yet undetected hypercoagulable state, with or without the aggravating variable of dehydration. Alternatively the condition is idiopathic (meaning the idiots don't know what the pathology is). You can be sure, though, that her physicians are investigating with gusto the usual suspects for hypercoagulability (eg, protein C deficiency).
Despite tepid phase 3 results (see here and here), Lilly will continue late-phase development of its anti-amyloid MAb, solanezumab, in patients with mild AD. Today's company press release says that the new trial will begin "no later than Q3 2013." Market analysts expect the trial to complete in 2015 (the anticipated length of the trial is presumably the same as that of Lilly's EXPEDITION studies, 18 months). If successful, the drug would launch in 2017.Now set the teeth and stretch the nostril wide,
Hold hard the breath and bend up every spirit
To his full height.
Or don't.
MAb = monoclonal antibody.
Merck's recent announcement of the clinical development of its BACE1 inhibitor, MK-8931, into phase 2 study in Alzheimer disease met with head-scratching fanfare. Nevertheless the news provides an opportunity to survey the current landscape of AD drugs in development, and the results are particularly discouraging—at least when looking at drugs that are designed to attack amyloid beta (Aβ). In established AD, the field is littered with really unfortunate failures that have made it to late-stage clinical study; although there may be efficacy in earlier stages of AD or even prodromal disease. Here's my tabulation of the present state of affairs—which, no doubt, contains omissions or inaccuracies. So caveat...
The big challenges with BACE1 inhibitors, which are designed to block the initial production of Aβ, include 1) the hurdle of getting the drug through the blood-brain barrier and 2) the possibility that these molecules may interfere with the axonal integrity of some neurons [1]. Merck appears to have overcome the first obstacle with MK-8931. It's interesting to note that no mutations in BACE1 have been shown to cause AD, but enhanced activity of the enzyme has been observed in the brains of patients with sporadic AD. In addition, Icelandic investigators recently reported a BACE1-activity-reducing mutation in the gene encoding for amyloid precursor protein (APP) [2]. The mutation appears to lower the risk of AD and cognitive decline in the elderly.
Efforts to inhibit γ-secretase, another Aβ-producing enzyme, are hindered by the toxic effects of blocking other secretase functions—specifically cleavage of the Notch receptor, which otherwise regulates a number of important cellular functions. Current efforts to produce γ-secretase inhibitors for AD are aimed at creating compounds with "Notch-sparing" properties. The toxic effects of Lilly's now-discontinued γ-secretase inhbitor, semagacestat, were attributed to its inhibition of Notch-receptor cleavage.
Among the Aβ-targeting therapies in established AD, the most promising appears to be IV immunoglobulin. Investment in tau-targeting therapies is comparatively tiny; but TauRx has finally moved its potentially anti-aggregation candidate, a derivative of methylene blue, into phase 3.
Note: In a previous version of this table, I mistakenly placed Novartis's adjuvanted CAD106 vaccine under polyclonal Abs.
Abs = antibodies; BACE1 = β-site amyloid precursor protein–cleaving enzyme 1; GSK = glycogen synthase kinase 3β.
1. Rajapaksha TW et al. Mol Neurodegener. 2011;6:88.
2. Johsson T et al. Nature. 2012;488:96-99.
3. Treated patients demonstrated significantly worse cognition in phase 3 trials.
4. PMLive. BMS ends development of Alzheimer's candidate avagacestat.
5. Described as Notch-sparing.
6. Derivative compound of PBT1.
7. Parent compound is tramiprosate.
8. Except for SQ version.
9. Methylene blue derivative.
The big challenges with BACE1 inhibitors, which are designed to block the initial production of Aβ, include 1) the hurdle of getting the drug through the blood-brain barrier and 2) the possibility that these molecules may interfere with the axonal integrity of some neurons [1]. Merck appears to have overcome the first obstacle with MK-8931. It's interesting to note that no mutations in BACE1 have been shown to cause AD, but enhanced activity of the enzyme has been observed in the brains of patients with sporadic AD. In addition, Icelandic investigators recently reported a BACE1-activity-reducing mutation in the gene encoding for amyloid precursor protein (APP) [2]. The mutation appears to lower the risk of AD and cognitive decline in the elderly.
Efforts to inhibit γ-secretase, another Aβ-producing enzyme, are hindered by the toxic effects of blocking other secretase functions—specifically cleavage of the Notch receptor, which otherwise regulates a number of important cellular functions. Current efforts to produce γ-secretase inhibitors for AD are aimed at creating compounds with "Notch-sparing" properties. The toxic effects of Lilly's now-discontinued γ-secretase inhbitor, semagacestat, were attributed to its inhibition of Notch-receptor cleavage.
Among the Aβ-targeting therapies in established AD, the most promising appears to be IV immunoglobulin. Investment in tau-targeting therapies is comparatively tiny; but TauRx has finally moved its potentially anti-aggregation candidate, a derivative of methylene blue, into phase 3.
|
Target |
Investigational Molecule (Sponsor) |
Phase Completed |
|
Aβ |
||
|
BACE1 |
||
|
|
MK-8931 (Merck) |
1 (entering 2) |
|
|
CTS-21166 (CoMentis) |
1 |
|
γ-secretase |
||
|
|
Semagacestat (Lilly) |
3 (discontinued [3]) |
|
|
Tarenflurbil (Myriad Genetics) |
3 (discontinued) |
|
|
Avagacestat (BMS) |
2 (discontinued [4]) |
|
|
NIC5-15 (Humanetics) |
2 |
|
|
Begacestat [5] (Wyeth/Pfizer) |
1 |
|
Aggregation |
||
|
|
Tramiprosate (Bellus Health) |
3 (failed) |
|
|
Clioquinol/PBT1 (Prana Biotech) |
2 (discontinued) |
|
|
PBT2 [6] (Prana Biotech) |
2 |
|
|
BLU8499 [7] |
1 |
|
Build-up (eg, plaques) |
||
|
Active immunotherapy (vaccines) |
||
|
|
AN1792 (Pfizer/Janssen) |
2 (discontinued) |
|
|
ACC-001 (Pfizer/Janssen) |
2 (and ongoing) |
|
|
Affitope AD02 (Affiris AG) |
1 (2 ongoing) |
|
|
Adjuvanted CAD106 (Novartis) |
2 (active) |
|
Passive immunotherapy |
||
|
Monoclonal Abs |
||
|
|
Bapineuzumab (Pfizer/Janssen) |
3 (discontinued [8]) |
|
|
Solanezumab (Lilly) |
3 (status?) |
|
|
Ponezumab (Pfizer) |
2 (discontinued) |
|
|
Gantenerumab (Roche) |
1 (entering 3 for prodromal AD) |
|
|
Crenezumab (Roche) |
1 (entering 2 in AD; also in prodromal AD) |
|
|
GSK933776A (GSK) |
1 |
|
|
BAN2401 (Esai) |
1 |
|
Polyclonal Abs |
||
|
|
IV Ig (Baxter) |
2 (3 ongoing) |
|
|
IV Ig (Octapharma) |
2 |
|
|
IV Ig (Sutter Health) |
2 (active; in MCI) |
|
|
Albumin and Ig (Grifols Biologicals) |
3 (active) |
|
Tau |
||
|
Hyperphosphorylation (GSK-3 inhibitors) |
||
|
|
Lithium and divalproex (NIH) |
2 |
|
|
Nicotinamide (UC Irvine) |
1/2 (active) |
|
Aggregation |
TRx0014 [9] (TauRx) |
2 (entering 3) |
Note: In a previous version of this table, I mistakenly placed Novartis's adjuvanted CAD106 vaccine under polyclonal Abs.
Abs = antibodies; BACE1 = β-site amyloid precursor protein–cleaving enzyme 1; GSK = glycogen synthase kinase 3β.
1. Rajapaksha TW et al. Mol Neurodegener. 2011;6:88.
2. Johsson T et al. Nature. 2012;488:96-99.
3. Treated patients demonstrated significantly worse cognition in phase 3 trials.
4. PMLive. BMS ends development of Alzheimer's candidate avagacestat.
5. Described as Notch-sparing.
6. Derivative compound of PBT1.
7. Parent compound is tramiprosate.
8. Except for SQ version.
9. Methylene blue derivative.
Bolstering the idea that Alzheimer disease begins decades before clinical dementia is apparent, new data suggest that functional and structural brain changes as well as increased levels of amyloid beta (a hallmark of AD) are already present in at-risk young adults. In a cohort study from the Colombian Alzheimer's Prevention Initiative Registry, 18-26-year-old carriers of presenilin 1 (PSEN1), a deterministic gene for AD, were more likely to show greater activation (or less deactivation) of memory-critical parts of the brain, less gray matter in other parts of the brain (ie, "several parietal regions"), and elevated levels of amyloid beta 1-42 in the CSF and plasma than noncarriers.* The authors of the study, the results of which were published in the latest issue of Lancet Neurology, could not say whether the underlying brain changes were neurodegenerative or developmental.**
In a companion study, also published in Lancet Neurology, evidence of significantly increased amyloid deposition in the brain (as measured by florbetapir binding on PET images) was seen at a mean age of 28 years in PSEN1 carriers (vs noncarriers). By assessing older carriers (up to 56 years of age), the study authors found that amyloid deposition "rose steeply" during the next 9-10 years and plateaued thereafter—about 10-15 years before the typical onset of dementia in these cases of familial AD.
CSF = cerebrospinal fluid; PET = positron emission tomography.
* People who carry the PSEN1 gene in this extended Colombian family typically show clinical AD (eg, dementia) in their 40s and 50s.
** An underlying caveat of the study is that it was relatively small. There were 20 gene carriers and 24 noncarriers, and only 10 people in each cohort underwent lumbar puncture for CSF analysis.
In a companion study, also published in Lancet Neurology, evidence of significantly increased amyloid deposition in the brain (as measured by florbetapir binding on PET images) was seen at a mean age of 28 years in PSEN1 carriers (vs noncarriers). By assessing older carriers (up to 56 years of age), the study authors found that amyloid deposition "rose steeply" during the next 9-10 years and plateaued thereafter—about 10-15 years before the typical onset of dementia in these cases of familial AD.
CSF = cerebrospinal fluid; PET = positron emission tomography.
* People who carry the PSEN1 gene in this extended Colombian family typically show clinical AD (eg, dementia) in their 40s and 50s.
** An underlying caveat of the study is that it was relatively small. There were 20 gene carriers and 24 noncarriers, and only 10 people in each cohort underwent lumbar puncture for CSF analysis.
