Apples with oranges = bananas

When confronted by evidence that the TST may/is less than perfect the Australian Tuberculosis Review resort to their default position;

The major limitation is that we don't have a gold standard

The lack of a gold standard does not diminish the science. QuantiFERON uses antigens that are specific only to Tuberculosis and therefore must be more accurate than the TST, which uses a broad range of antigens not specific to Tuberculosis. The lack of a gold standard has not stopped other doctors appreciating the science and acting accordingly eg San Jose

..The Student Health Center will no longer be offering PPD skin tests.

..The Quantiferon Gold test is more accurate than the PPD

Off the rails.

Ex Communications Minister Helen Coonan is determined to maintain relevancy

Infrastructure is clearly falling behind world standards because the government does not see it as a priority. Talk of productivity gains is hollow if building Australia's capacity for efficient transport of people and goods is not in the equation.

Sydney, Melbourne and Brisbane would already have high-speed rail connections if Canberra policymakers spent as much time on trains as they do in the air

So what is the difference between a government funded very fast train and a government funded NBN? Not much, both are examples of modern high speed communication networks.

NBN nets a big fish.

From The Fairfax SMH, according to a

study, prepared by the British telecommunications consultant Robert Kenny and Charles Kenny from the US Centre for Global Development

which

found the claimed benefits of a national broadband network have been "grossly overstated", and accuses the federal government of misusing research to build the case for it.

This is the same Charles Kenny that previously advocated that

Overcoming the "digital divide" in terms of public access to the Internet should probably not be a priority of governments or development agencies.

As Professor John Quiggin points out,

so far, betting against the idea that people will want faster and more powerful communications and computers has not had a good track record.

And he has the facts to prove it.

Macro to micro - Paul Krugman.

Link here.

But economists were bound to push at the dividing line between micro and macro – which in practice has meant trying to make macro more like micro, basing more and more of it on optimization and market-clearing. And if the attempts to provide “microfoundations” fell short? Well, given human propensities, plus the law of diminishing disciples, it was probably inevitable that a substantial part of the economics profession would simply assume away the realities of the business cycle, because they didn’t fit the models.

....there was bound to be a shock, sooner or later, too big for the central bankers to handle without help from broader fiscal policy. Also, sooner or later the barbarians were going to go after the monasteries too; and as the current furor over quantitative easing shows, the invading hordes have arrived

.

Head turning

The Australian Tuberculosis Review has never been particularly enamoured with IGRA and QuantiFERON however the following comment by Dr John Thompson indicates a sea change in opinion

In wealthy countries like Australia, we should be using both tests to detect LTBI.  If the tuberculin test (PPD 10units) is less than 15 mm induration,  then a QuantiFERON –TB gold in tube is called for .  This should considerably reduce the number of people treated unnecessarily

The obvious question would be, why bother with the TST in the first place? Perhaps it is time for the NTAC to also review their position.

iPhone, therefore iAm

Smart phones are taking over the world, from Damn You Auto Correct!

Brad DeLong on macro stuff

I would confidently lecture only three short years ago that the days when governments could stand back and let the business cycle wreak havoc were over in the rich world. No such government today, I said, could or would tolerate any prolonged period in which the unemployment rate was kissing 10% and inflation was quiescent without doing something major about it.

I was wrong. That is precisely what is happening.

More here

TB testing for all HCWs

The UN, WHO and ILO have produced guidelines on TB and HIV for the approximately 60M HCWs.

According to VOA

United Nations agencies say millions of health workers around the world are at risk of becoming infected with HIV and tuberculosis while treating the sick. New guidelines developed by the International Labor Organization, World Health Organization and UNAIDS aim to protect health workers from these occupational hazards.

There are more than 60 million health workers throughout the world whose job it is to care for the sick.  They play an important role during epidemics in delivering services to the public.  

Sophia Kisting is Director of the International Labor Organization's Global Program on HIV/AIDS and the World of Work.  While health workers provide vital services to others, she says very often their own conditions of work, occupational safety and health are overlooked.

"We find that health workers are on the frontline in providing prevention and treatment and care for people living with HIV and TB throughout the world," says Kisting. "They are at risk of occupational exposure to HIV and TB and now in the context of MDR and XDR [multi-drug resistant and Extreme Drug Resistant] TB, it is even a much higher risk.  But, so often, they, themselves, lack adequate access to protection or to treatment."  

The new guidelines are aimed at overcoming these concerns. They are based on international consultations and an assessment of current practices in 21 country-based studies.

The 14-point guidelines are inter-related and can be effectively implemented as one package.  They ensure priority access for health workers and their families to prevention and treatment services for HIV and TB.

Other provisions include strengthening occupational health services for the entire health workforce, the provision of free HIV and TB treatment for health workers, policies to prevent discrimination against health workers with HIV and TB, and adequate compensation for health workers who become sick on the job.

Technical Officer in WHO's Occupational and Environmental Health Division, Susan Wilburn, says health workers are exposed to many illnesses, such as HIV, TB, hepatitis and Avian influenza.  

"We know that there are at least 1,000 new infections, work-related infections with HIV every year globally as a result of health worker exposures," Wilburn says. "Those are estimates of the burden of disease.  And among health workers who are infected with hepatitis, 40 percent of those infections are work-related infections."  

Many countries suffer critical shortages of health workers.  The problem is most acute in Africa.  The United Nations notes Africa has 11 percent of the global population and 25 percent of the global health burden, with only three percent of the health workforce.

A NICE irony

Two points of interest in this study of latent tuberculosis infection in immigrants to the UK; firstly it is the NICE guidelines that decide who should and should not be tested and it is the NICE guidelines that prevent screening of all at risk immigrants.

The rationale underpinning these guidelines remains unclear particularly as there are little data on the prevalence of LTBI in immigrants to the UK from regions with different TB incidence rates

And secondly, whilst the diagnostic used is QuantiFERON the inventor of T.Spot TB, Ajit Lalvani, co-authored the study.

Medicare data update

Can the sales performance of QFT in Australia be replicated in the US?

Absolutely!

Public transport of TB

They tested public transport workers in Lima, Peru for ltbi and found 76.6% to be positive to the TB skin test. That's a lot of TB in storage, ready to become active.

More of the same.

From the Pediatric Infectious Disease Journal

The performance of QuantiFERON-tuberculosis (TB) Gold-In-Tube assay was compared with the tuberculin skin test for the diagnosis of TB among children. It was shown that among non Bacille Calmette Guerin immunized children, agreement between tests was excellent both in those with TB disease and in TB contacts. Among Bacille Calmette Guerin immunized children, agreement was fair in those with active disease and poor among TB contacts. It is concluded that QuantiFERON-TB Gold-In-Tube compares with the tuberculin skin test in the diagnosis of TB disease and latent tuberculosis infection in TB contacts among children and has enhanced specificity

.

Clayton Utz on share registry access

Article by John Elliott, Ron Smooker and David Landy

Clayton Utz 

New controls on access to share registers received the green light from Parliament last Thursday.


Although aimed primarily at "low-ball" unsolicited share offers, the Corporations Amendment (No 1) Bill will also restrict access to registers for a far wider range of users.


On the other side of the coin, companies will now have considerable power to control who gets to look at their list of shareholders.

BioTechnologyNews

Cellestis gets a mention in BioTechnologyNews (BTN)

Market Pulse: It's a brand new day

CDC OSH TB guidelines

Available here

Busting IP myths

By Jack Redfern and Matthew Ward via mondaq.com

There are quite a few common misconceptions regarding patenting. Here, we address a selection of myths which are observed on an all-too-regular basis, and provide some tips on how to better work with the system.

A NICE backflip

When the 2006 NICE TB Guidelines were published Professor Peter Ormerod, a member of the NICE Guideline Development Group, had this to say

The sooner TB is diagnosed, the easier it is to treat. This guideline is not about pointing the finger at the non-UK born who are disproportionately affected by TB, but is about making sure those who have active TB are identified as soon as possible so they can be offered access to treatment as quickly as possible, which both treats their TB and breaks the cycle of transmission between people.”

He also advised that the Guidelines, which were essentially cost based, found economic limitations with IGRA

IGRA testing alone is ONLY cost effective if LTBI rate 40% or greater

Then came the volte-face

Adapting Corporations to the internet

Benefits and pitfalls of social media for your business - do you have all the right policies in place?

You can have too many happy customers?

---

Title: Quantiferon TB Gold Test Question
Post by: phildinftlaudy on September 24, 2010, 06:29:35 PM

---

So, I got my lab requisition emailed to me today from my ID doc for my next labs which I will go for on Dec. 1.  I noticed that in addition to metabolic panel, lipid panel, CBC, T-Cell panel, and HIV Viral Load, she also ordered a Quantiferon TB Gold test -

So, I looked it up and it says it is to detect TB - latent or manifest.  Is this normal?  I usually get that llittle arm prick (tb test) thing (starts with an "M") every couple years, but I think this is the first time I have had this test done.

I did tell her that I have been having pretty bad fatigue lately -

Just trying to see if this is a normal test to have or if I should go into panic mode   LOL

Correlation and causation

The UK health system has adopted a reactive approach to TB - their priority is to treat active TB and sometimes vaccinate with BCG - which doesnt seem to be working

Cases of tuberculosis in the UK have reached 9,040 in 2009 - the highest number in the UK for nearly 30 years while the number of new drug resistant TB has nearly doubled in the past 10 years, from 206 cases in 2000 to 389 cases in 2009. 

Compare this with the USA

A total of 11,545 TB cases (a rate of 3.8 cases per 100,000 persons) were reported in the United States in 2009.  Both the number of TB cases reported and the case rate decreased; this represents a 10.5% and 11.3% decline, respectively, compared to 2008.  The TB rate in 2009 was the lowest recorded rate since national reporting began in 1953.

reports from London here and here indicate that they are still dragging their feet

While good progress has been made on compliance with NICE guidance, some issues are still being addressed.
The sector needs to work on ensuring that Gamma Interferon Testing is available at all Chest Clinics and ideally provided by a laboratory within SWL.

Somebody in the UK needs to get a grip

Footnote; using a population figure of 62M for the UK and 311M for the US gives us 1 per 6,858 people in the UK and 1 per 26,851 for the US with active TB - the disease rate is almost 4 times that in the UK as in the US.

Featherdusters

More on game theory

..in two of Plato's texts, the Laches and the Symposium, Socrates recalls an episode from the Battle of Delium that some commentators have interpreted (probably anachronistically) as involving the following situation. Consider a soldier at the front, waiting with his comrades to repulse an enemy attack. It may occur to him that if the defense is likely to be successful, then it isn't very probable that his own personal contribution will be essential. But if he stays, he runs the risk of being killed or wounded—apparently for no point. On the other hand, if the enemy is going to win the battle, then his chances of death or injury are higher still, and now quite clearly to no point, since the line will be overwhelmed anyway. Based on this reasoning, it would appear that the soldier is better off running away regardless of who is going to win the battle. Of course, if all of the soldiers reason this way—as they all apparently should, since they're all in identical situations—then this will certainly bring about the outcome in which the battle is lost. Of course, this point, since it has occurred to us as analysts, can occur to the soldiers too. Does this give them a reason for staying at their posts? Just the contrary: the greater the soldiers' fear that the battle will be lost, the greater their incentive to get themselves out of harm's way. And the greater the soldiers' belief that the battle will be won, without the need of any particular individual's contributions, the less reason they have to stay and fight. If each soldier anticipates this sort of reasoning on the part of the others, all will quickly reason themselves into a panic, and their horrified commander will have a rout on his hands before the enemy has even fired a shot.

Once people start thinking like chickens it is easy to make them lay.

Are you feeling game?

I was wondering how best to describe the current share trading in Cellestis; as Forrest postulates only 5% of the available stock is in play (traded) whilst 95% is being held back. Take for instance today, AGM +1 when 216,686 shares were traded, what exactly can be deduced from this action?

Nothing useful really* as only a minority are actively involved and that minority could be playing a game that is quite removed from the main game - because the vast majority are not actively participating the prices are distorted and bear little or no relation to the real value. John Keynes had something to say on those who like to figure out the average opinion of the average opinion

Professional investment may be likened to those newspaper competitions in which the competitors have to pick out the six prettiest faces from a hundred photographs, the prize being awarded to the competitor whose choice most nearly corresponds to the average preferences of the competitors as a whole; so that each competitor has to pick, not the faces which he himself finds the prettiest, but those which he thinks likeliest to catch the fancy of the other competitors, all of whom are looking at the problem from the same point of view. It is not a case of choosing those which, to the best of one's judgment, are really the prettiest, nor even those which average opinion genuinely thinks the prettiest. We have reached the third degree when we devote our intelligences to anticipating what average opinion expects the average opinion to be. And there are some, I believe, who practise the fourth, fifth and higher degrees.

And that is what they call game theory.  In the game involving Cellestis the seller is at a particular disadvantage as the average opinion appears to be...to not sell.

* correction; someone is keenly buying everything that is being offered, at their price.

It's the steak not the sizzle.

From the self promoting Intelligent Investor;

Stocks in Brief | High Stakes

Cellestis
16 Nov 10 | Issue 309
   
By James Greenhalgh

At its 2010 annual meeting yesterday, Cellestis put some stakes in the ground. After selling 1.9m QFT tests in 2010, the company expects to sell between 2.6m and 2.9m this financial year. Subject to the usual ‘unforeseen events’ caveat, this should translate into at least 30% growth in operating profit in 2011. Management is hoping for similar growth in 2012 and, if achieved, then Cellestis’s PER of 26 will fall quickly.

Of course, growth of this magnitude is required to justify Cellestis’s current share price. But it’s reassuring that management feels confident enough to provide a forecast (it hasn’t previously). But even this strong growth rate disappointed some shareholders, and the stock is down 4% since we commenced coverage in Cellestis passes the biotech test on 2 Nov 10 (Speculative Buy – $2.35).

We’ve been unable to determine the intricacies of Cellestis’s patent protection. At the meeting, management mentioned that generic competition was expected from 2017, but we understand patent protection on the main QFT product runs until 2023. By highlighting this is a one-product company, we believe management is signalling it will step up investment in its product pipeline.

Overall, the meeting confirmed our thesis on Cellestis. Sales growth, if anything, looks to be accelerating this year and management was optimistic. We’re sticking with SPECULATIVE BUY.

Pressed for an opinion

Mr Denmore continues to find fault with the media business and this time his ally is Ted Koppel

The transition of news from a public service to a profitable commodity is irreversible. Legions of new media present a vista of unrelenting competition. Advertisers crave young viewers, and these young viewers are deemed to be uninterested in hard news, especially hard news from abroad. This is felicitous, since covering overseas news is very expensive. On the other hand, the appetite for strongly held, if unsubstantiated, opinion is demonstrably high. And such talk, as they say, is cheap.

Broadcast news has been outflanked and will soon be overtaken by scores of other media options. The need for clear, objective reporting in a world of rising religious fundamentalism, economic interdependence and global ecological problems is probably greater than it has ever been. But we are no longer a national audience receiving news from a handful of trusted gatekeepers; we're now a million or more clusters of consumers, harvesting information from like-minded providers.

Ignorance more frequently begets confidence than does knowledge.

Forrest has a good post up, by "lab rat" and everybody should do themselves a favour and read it.

I used to work for a biotech company that received much mainstream press coverage and it always was inaccurate, sometimes grossly so. Certainly, the New Yorker article on TB contains multiple inaccurate details

It is disappointing that after all this time and after all the information and discussion there are still shareholders who don't appear to understand the difference between active and latent TB and that latent TB has no symptoms.

During latent TB, a patient does not have the bacteria in their sputum and therefore the Xpert method is unlikely to be informative (the NEJM study did not examine latent TB, but this conclusion is reasonable). The Xpert method cannot be performed on another sample type, such as blood, because the TB bacterium is not present in the blood of an infected individual.

There should be no excuse for this ignorance.

A state of mind.

Much has been made of Cellestis' perceived lack of engagement with the media. Some say that the media needs to be alerted and better informed to the TB story and in particular the story of Cellestis and that this lack of communication with the Fourth Estate has impacted on sales.

But can you trust the media to report the news properly? Following the now forgotten Monckton/Plimer Climate Change Tour the ABC ran a forum asking

Thundering heads

Shareholders (some) continue to vent their spleen at the shareprice of Cellestis; consider the comments of "bigmumma"

Most people in the world don't have a [email="#$@*ing"]#$@*ing[/email] clue about Cellestis & TB, except investors, and even they are kept in the dark.

He may have some support there

Radford on Biosecurity

Tuberculosis: threatening Australia’s borders

Cellestis offers a solution to curb influx of tuberculosis brought in by immigrants and refugees.

Australian Life Scientist

By Tony Radford, CEO of Cellestis

Tuberculosis (TB) is regarded by many as a disease of the past, but as a recent tuberculosis outbreak in Australian’s customs offices shows, there is a case for modernising testing for TB in developed nations, and Melbourne-based company Cellestis offers a way to do so.

Roaring mice

Shareholders are still maintaining their rage, "where's my share of the loot?" they collectively cry, "we wus robbed!"

Well hardly, if they had participated in the Cellestis float @25c they would still be doing OK.  And if they bought their share of the capital from another party, well that is obviously an arrangement between themselves and the seller and absolutely nothing to do with the Company. Consenting adults, willing seller and buyer and all that stuff.

Presently there appears to be more selling than buying of shares between shareholders and this has put pressure on the share price - ultimately it is the shareholders who determine the share price.

So why is the Company to be held responsible for the performance of transactions conducted between other parties?

All very strange and no doubt part of this global spread of denialism.

NICE, damned by faint praise

In a recent article

In a letter obtained by Pharmafocus NICE chief executive Andrew Dillon said even he was ‘taken by surprise’ by the sudden speculation over NICE’s future in the last couple of weeks.

Writing to NICE’s appraisal committee members Dillon said: “I am sorry that speculation on the future of the appraisal programme has appeared without me being able to forewarn you. We were also taken by surprise.”

What is also surprising is that internal and presumably confidential communications are being published, NICE has sprung a leak.


Think tank Stockholm Network warn against throwing the baby out with the bathwater

“..it would be a shame if the NICE experiment was replaced by an equally unpredictable and misguided means of allocating resources.”

More deluded nonsense

The falling shareprice has enraged some holders to produce comments along the line of;

Our management team's job is to run the business in our best interests etc etc

So when did shareholders get to own management?

The reality is that all that the shareholder owns....is a share of the capital. That doesnt mean that you own any portion of the business, a shareholder is just a stakeholder.

And that's it, take it or leave it.

News syndication

The Hecht article, originally published in the Philadelphia Inquirer, is still bouncing around the traps.

Times Leader (Dallas)

McClatchy Tribune (Michigan)

Apria Healthcare (just everywhere)

Get Quantiferon - update

According to the website there are now 146 US and Canadian institutions which have agreed to provide QFT testing services to outside physicians and laboratories.

Wrong

Some Occupational Health workers were discussing QuantiFERON;

--------
1.  Do the IGRA tests stay positive for life, even after treatment?
2.  For post exposure work up, after baseline what is the time frame for the follow up test (3 months)? 

Watson Clinic
--------
1. Yes
2. Yes

Dr. G Lantos
University of Toronto

IFN-y levels do increase and decrease over time and can be influenced by treatment and these changes can be called conversion and reversion.

For example, 59 soldiers with newly diagnosed active TB were tested at 1, 3 and 6 months after initiating the standard TB treatment of isoniazid (INH), rifampicin (RMP), ethambutol (EMB), and pyrazinamide (PZA).

After treatment, 53 (89.8%) had a positive QFT-GIT result at 1 month; 42 (71.2%), at 3 months; and 39 (66.1%), at 6 months.

Then there was the Lee study of latent TB following a contact investigation where only rifampicin (RMP) was used;

IFN-γ levels decreased in 97.3% (72/74) of the subjects and QFT-GIT test reversion (positive to negative) was achieved in 31 subjects (41.9%).

Clearly the evidence does not support the statement that IGRA tests stay positive for life, even after treatment.

Cleveland Clinic endorses and promotes the use of QFT

Last September the Cleveland Clinic Journal of Medicine published the following article, Interferon-gamma-release assays: Better than tuberculin skin testing?

Extracts;

In our experience, contact investigation has been more efficient and easier to conduct with the use of the QFT-GIT than with the tuberculin skin test..

..This case illustrates how the assays are useful in diagnosing latent tuberculosis in foreign-born health care workers. Whereas this patient’s previous positive skin tests may have been falsely positive because of her childhood BCG vaccination, BCG vaccination does not affect the results of interferon- gamma-release assays, and thus a positive QFT-GIT test is likely to indicate latent tuberculosis.

So we are left with the cautious message

Given the wide availability of interferon-gamma-release assays and laboratories that process them, more tuberculosis control programs will probably start using them rather than tuberculin skin testing.

The Editor of the CCJM was also cautiously positive

In this issue of the Journal, Drs. Cyndee Miranda, J. Walton Tomford, and Steven
M. Gordon describe the relatively new ex vivo interferon-gamma-release assays, which have received the full support of the US Centers for Disease Control and Prevention and are beginning to supplant the tuberculin skin test..

..These tests are not perfect. There are challenges with the interpretation of some results, the assay kits are relatively costly, and laboratory technicians must handle the samples and assay kits with great care. Nonetheless, I believe that these tests are a positive step towards accurate recognition and treatment of patients with latent tuberculosis.

This article was no. 4 on the "most read" list.

Known knowns, unknown knowns and unknown unknowns

I bet Donald Rumsfeld must be regretting that phrase, what he didn't know then was that he just plain didn't know.

Similarly with TB and Cellestis, you only have to spend a few minutes on their website to know that there is a lot we just don't know about TB

Ignorance breeds TB

Following outbreaks of TB in the Irish counties of Cork and Kerry came the usual chattering and the finger pointing

When folks immigrate, they bring diseases with them that are not under control in their home countries. TB is on the rise worldwide

and

What the Irish newspapers won´t tell you--but what I know to be true from personal contacts in the area--is that this outbreak resulted when some children who had spent the summer in their native East Africa came to school in Ireland. Would Fianna Fail and Sinn Fein supporters care to explain why Irish children should be exposed to dangerous infectious diseases in order to further the settlement of foreigners in Ireland?

Just shows how wrong folk can be, according to a report in the Irish Times

“Using DNA techniques, we can see that most of the tuberculosis bacteria spread between people in Cork and Kerry are local strains presumably persisting from the days when tuberculosis was common,”

As Charles Darwin famously noted

Ignorance more frequently begets confidence than does knowledge: it is those who know little, not those who know much, who so positively assert that this or that problem will never be solved by science.

What, then, could go wrong?

asks Intelligent Investor.

Cellestis faces many known and unknown threats; in time, one could destroy it.

Sounds pretty dire, what about the known threats?

TB vaccines superior to the existing one are under development which, if approved, could eventually eliminate the need for a test altogether. 

This is where most people get unstuck and telling them over and over again doesnt seem to make any difference.

Intelligent Investor - Cellestis passes the biotech test

In a world of biotech failures, Cellestis has developed a successful test for tuberculosis. The market’s response has been, ‘so what?’

link

Recommendation guide
Speculative Buy    Up to $2.60
Hold    Up to $5.00
Sell    Above $5.00

Medical Center Occupational and Enviromental Health

In a private list run by Boston University and the Boston Medical Center Department of Occupational and Environmental Medicine the issue of IGRA was raised

We are considering using IGRAs at our institution and would like to collect some additional information from those of you use these tests in lieu of the TST.  I would appreciate if you would reply to the questions below.  I would be happy to summarize the results and share with all.

Not so nice - for some

According to the beeb

The medicines watchdog, NICE, is to lose its power to turn down new medicines for use on the NHS.

It will give advice on which drugs are effective, but will not decide whether patients should be given treatments their doctor recommends, the Department of Health has confirmed.

Instead, groups of GPs will decide whether a drug should be funded or not.

This follows on from other news

The U.K.'s National Institute for Clinical Excellence (NICE) will likely no longer have any role in drug cost-effectiveness decisions after 2013, according to officials.

Instead, a new value-based pricing system will set drug prices to reflect a product's value at the outset, without the need for NICE to carry out its assessment once a drug already is available.

Whilst the Minister, Earl Howe, said that NICE work remained very very important he also said that NICE cost-effectiveness decisions would be 

“somewhat redundant,”

There is the smell of gunpowder in the air..

Transport costs going off the rails

The QLD Bligh Government's proposed sale of QR freight rail, for an estimated $15B, has attracted plenty of attention, mostly negative.  Premier Bligh announced that a portion of the proceeds would go to updating the Brisbane-Cairns link which currently requires a $265 per passenger subsidy to break even. Says Premier Bligh

“There is no public transport system anywhere in the world that is not subsidised,”