TB in NYC prisons

This document lays out the reasons why QFT should be used in NYC correctional facilities,

Any more questions?

Fat cats have feelings, too.

Paul Krugman casts a wary eye over the goings on in Davos,

...............

MHLAMF in Davos

From the FT:

Governments around the world must stop banker-bashing and create the right environment for lenders to support economic growth, some of the world’s most powerful bankers will tell finance ministers on Saturday.

So “Ma! He’s looking at me funny!” is now at the core of the financial sector’s complaints. And the world’s top bankers feel that after bringing on a gigantic crisis that has left millions unemployed, being bailed out, and receiving huge paychecks all the while, they now have the right to demand that people stop saying critical things about them.

Oh, and substantively, they want interest rates to rise despite the persistence of high unemployment.

Update on CPT Code

CPT codes can vary from state to state (cost of doing business etc) and so the Centers for Medicare & Medicaid Services has released the 2011 clinical laboratory fee schedule (click on "ACCEPT" and download)

From the spreadsheet both 86480 and 86481 have the same fee ie $87.22.

A Spot of bother.

The October November 2010 edition of Intelligent Investor ran a piece on CST titled Cellestis passes the biotech test and someone recently commented that it contained a few factual errors, which rang more than just a few bells with me. For instance, take the issue of competition from T-Spot.TB which Intelligent Investor regard as a real threat. Recently the T-Spot people took great delight in proclaiming that in the US they now have their very own CPT code, which presumably would mean that there is now greater incentive to use their product. They mention that the reimbursement is a Category I code, 86481 but neglect to say how much that reimbursement is. A quick Google reveals that

New CPT code 86481 is priced at the same rate as CPT code 86480

and as we have been told CPT code 86480 is for QuantiFERON Gold and is for the amount of $69.27

So how much is a T-Spot test worth? It does take some digging around so lets look at this publication where Dr. Peter Wrighton-Smith, CEO of Oxford Immunotec says

As no reimbursement amount has yet been established in Switzerland for the TSPOT. TB test, a figure of CHF200 (EU129) was taken as an initial sum taken to estimate the costs of the test, associated consumables and labour required to perform the test both in the laboratory and the physician's office.

At today's exchange rate 129 euros is US$176.37 which would leave a shortfall of exactly $87.10. If these figures are correct then presumably either the provider or the customer will have to pick up the tab and therefore I just can't see any economic incentive to choose T-Spot.TB over QuantiFERON.

BBC - TB Vaccine - Kill or Cure

This was sent via Twitter by Professor Hazel M. Dockrell from the TuBerculosis Vaccine Initiative

"The threat of having an epedemic of drug resistant TB is really very frightening"

The market as a whole is always right.

Consider this statement,

The market factors all known information - and a lot of speculation as well, of course - in pricing stocks.

This is sounding very much like the Efficient Market Hypothesis, which asserts that financial markets are "informationally efficient".

Beyond the normal utility maximizing agents, the efficient-market hypothesis requires that agents have rational expectations; that on average the population is correct (even if no one person is) and whenever new relevant information appears, the agents update their expectations appropriately....Thus, any one person can be wrong about the market—indeed, everyone can be—but the market as a whole is always right.

Writing in the SMH Paul Hoffman from the Intelligent Investor said

Conventional economic theory tells us that people like Kerr Neilson and Warren Buffett are statistical flukes. But... their stock selections are based on a pre-defined philosophy. That should tell us something about the efficient market hypothesis (it's flawed) and the type of approach—the intellectual origin—these successful investors employ (it's successful).

And that is the nub of the EMH argument - that no matter how smart or intelligent or well informed you are, the market is always better at all these things so you may as well just give up now.

Warren Buffet refuted the EMH (you can read it all here) however the principle behind the EMH, that you don't need to think also needs to be thought about,

you really had the revealed truths, for a decade or so, saying it didn’t do any good to think. Investments presumably means businesses too. And once you say investments are all priced efficiently, you presumably have to go on and say businesses are priced efficiently, and you’re just throwing darts all the time. If this group were a bunch of chess players, or a bunch of bridge players, and they were all convinced that it did not pay to think about what to do, you’d have an enormous advantage. We’ve had tens of thousands of students in business schools taught that it’s [a waste of time to think].

Exactly, if the market is better at thinking than you can ever hope to be just what is it that they teach at business schools?

Denialism of biblical proportions.

Senator Abetz wades in to the discussion about the recent floods

“To imply climate change is responsible for flooding is to deny the World’s history from Noah and beyond.”

Senator Abetz is the current Leader of the Opposition in the Senate.

Simply the best

At the end of the day this is all that really matters,

PHMDC screens clients for TB with the Quantiferon Gold blood tests (QFT), a more accurate test than the TB skin test.

So what else is there to know?

PHMDC is shorthand for Public Health Madison & Dane County

The King is dead, long live the King!

Writing in the Murdoch rag Imre Salusinszy confidently pronounced

According to the Bureau of Meteorology, 2010 was Australia's coldest year since 2001. Since logic tells us the planet can't be getting hotter and colder at the same time, we can confidently pronounce global warming dead, buried and comprehensively beaten.

However, according to the Bureau of Meteorology 2010 was

Australia’s coolest year since 2001 and Australia’s warmest 10 years on record...

...The past 10 years have been the globe’s hottest on record with an anomaly of +0.46 °C. Increasing global mean temperatures derived from instrumental measurements are consistent with other independent indicators of climate change, such as reductions in ice and snow cover, and rises in global sea levels.

The BOM are referring to global, not local data which is surprisingly consistent and substantially in agreement.

One comment made is that the climate scenarios have been too conservative and that the reality is exceeding expectations,

A new analysis of the Northern Hemisphere's "albedo feedback" over a 30-year period concludes that the region's loss of reflectivity due to snow and sea ice decline is more than double what state-of-the-art climate models estimate.

Climate change is very much alive.

Changing the way the world looks at TB.

In this study of TB infection in HCWs in Malaysia the diagnostic used was not TST, it was Quantiferon TB Gold In Tube. Importantly, unlike other countries they did not use QFT to confirm a TST

a diagnosis of LTBI was made if the respondent was tested positive by Quantiferon TB Gold in-tube test (Cellestis Limited, Carnegie, Australia).

Testing low prevalence populations (with the TST) will statistically result in most reactors being false positives.

From the previous link in which doctors at the University of Miami discuss the pros and cons of using the tuberculin skin test to test for TB;

Any induration appearing at the injection site after 48–72 hours is considered a reaction and is measured in millimeters (mm) and recorded. The proper interpretation of skin test reactions depends on TST sensitivity and specificity as well as the positive predictive value of a reactive test. Tuberculin skin test sensitivity is estimated to be nearly 100% in those with LTBI and possessing normal immune responsiveness. False-positive tests can occur in persons infected with NTM or in those previously vaccinated with BCG, thereby resulting in a lower specificity and positive predictive value in those individuals who have a low probability of LTBI. Consequently, regardless of how high of specificity the TST may have, testing low prevalence populations will statistically result in most reactors being false positives.

The evidence just keeps piling up.

Showtime

More unnecessary treatment arising from a suspected false positive TST.

Link

We recently diagnosed a case of pleuropulmonary infection involving an unusual NTM, Mycobacterium interjectum (M. interjectum), in an immunocompromised man diagnosed 1 year after he had been treated for LTBI based on a reactive TST...

...Familiarity, availability, and low cost account for the current popularity and predominance of the TST for identification of LTBI. The QFT-GIT and T-SPOT assays offer distinct advantages over the TST. Substituting TSTs with IGRAs, as in our patient's case, may prevent patients from receiving unwarranted treatment for LTBI based on false-positive TSTs, either due to prior BCG vaccination or infection with NTM, although no information on the effect of infection with M. interjectum and IGRA test results exists. As knowledge and accessibility of this alternative diagnostic test continue to grow, the clinical practice of how we investigate MTB infection will hopefully evolve in a fashion benefiting the patients we serve.

Bringing clarity to muddy waters.

Writing in the Australian Prescriber Anastasios Konstantinos, Director of Queensland TB Control Centre made the following comment on the performance of interferon gamma release assays

many studies show that tuberculin skin testing and interferon gamma release assays perform similarly in non-BCG vaccinated people at high risk for recent tuberculosis infection, if an appropriate cut-off (for example 10 mm induration) is used for tuberculin skin testing.

The reference for this observation was the Pai Menzies Meta Analysis which clearly states that

the results of IGRAs and the TST were frequently discordant.

The latest Diel longitudinal study into the predictive value of IGRA for developing active TB clearly states

Many countries worldwide have adopted a higher TST cutoff for screening close contacts than the 5-mm cutoff recommended by bodies such as the U.S. Centers for Disease Control and Prevention (16) and the German Central Committee against Tuberculosis (17). Our results demonstrate that although the use of a greater than 10-mm cutoff may mitigate the specificity problems inherent with the greater than 5-mm TST cutoff, it introduces a dangerous compromise in terms of sensitivity. Nine of our 19 (47%) close contacts who progressed to active TB would have been overlooked if we had limited our concern to persons with indurations of 10 mm or more; resulting in an NPV for progression of only 98.7%. Clearly such information is highly relevant for policy makers who are considering replacing the TST with an IGRA.

TB skin test gets T-boned.

No doubt about it, anybody who continues to use the TB skin test during an immunosuppressive procedure needs to show good reason,

To conclude, our study shows that TST in patients on maintenance hemodialysis is an insensitive and nonspecific test to make a diagnosis of LTB infection and this should not be taken as the criterion to prescribe prophylaxis of TB in these patients.

Too often, too little and too late.

Another Pai/Menzies meta analysis, this one Interferon-gamma release assays for tuberculosis screening of healthcare workers: a systematic review.

Predictably they conclude

Further longitudinal research will be required to inform guidelines on serial testing using IGRAs.

As they say, been there done that

In contrast to the flood of recently published cross-sectional studies, longitudinal observations like the one performed by Diel and colleagues or by Leung and coworkers are needed to better define the role of novel immunodiagnostic tests in the prevention of tuberculosis.

Maybe Pai and Menzies are not getting the message, we don't need any more cross sectional studies.

One more time

..the current systematic review and meta-analysis on the accuracy of the IGRAs for LTBI diagnosis confirm the concept that the IGRAs are a valid alternative to the TST. The superior specificity and the good NPV make them the first choice, especially in BCG-vaccinated subjects..

..the predictive value for progression to active disease when testing positive is higher for the IGRAs as compared to the TST.

And this, from the much needed longitudinal study

Results suggest that QFT is more reliable than the TST for identifying those who will soon progress to active TB, especially in children.

It says it all.

The sensitivity of interferon-gamma release assays is not compromised in tuberculosis patients with diabetes

Link

Spotted Dick.

A study recently published in the Canadian Medical Association Journal raises some interesting issues regarding the treatment of latent tuberculosis in the general population

• 50% of active cases of tuberculosis in the United States occurred in patients over 45 years of age.

• this rate reflects the higher prevalence of many risk factors for reactivation of latent tuberculosis infection with older age

• the risk of hepatic adverse events increased significantly with age, with an approximate seven-fold increase among patients aged 50 to 65 years and a 35-fold increase among patients over age 65 years.

Obviously the risk-is-minimal crowd will have to take a back seat on this one. Two solutions to this situation spring easily to mind;

• Aim to diagnose and treat latent TB before the patient turns 45 years of age and

• Use QuantiFERON to eliminate false positive diagnoses and to reduce unnecessary therapy. 

More silliness from the Murdoch rag.

In it's haste to score points against central banking The Australian ran the following up the proverbial flagpole,

THE Reserve Bank sold most of the nation's gold reserves more than a decade ago because the board believed its price would remain flat

They believed also the commodity would not play a role in a future financial crisis.

The decision to sell 167 tonnes of the bank's reserves has cost the nation about $5 billion based on today's soaring price of almost $1400 an ounce.

Sharper minds dispute the claim

This analysis ignores two inconvenient facts. The gold was sitting on the RBA’s books at the Bretton Woods parity price, so the RBA booked a sizeable profit on the sale even at 1997 prices. The suggested $5 billion ‘loss’ ignores the return on the income producing assets the RBA purchased with the proceeds of the sale. It is likely these assets have underperformed gold recently, but historically, the real returns to gold have been negligible compared to other assets. As one of the world’s biggest producers, Australia is naturally long gold. There is no diversification value in relocating gold from the WA goldfields into vaults under Martin Place.

The 1997 RBA gold sale should give gold bugs pause. As we have noted previously, above ground gold stocks dwarf annual production, so the gold price is best viewed as a stock rather than a flow equilibrium. There is a certain irony in people who fear an over-supply of fiat money taking refuge in an asset in which central banks hold substantial stocks that could be dumped on the market at any time. At least one US think tank has advocated selling the US gold stock of 261.5m ounces to yield a quick and dirty profit for the US Treasury. The RBA was able to offload 167 tonnes without too much difficulty

.

Another peer reviewed study published.

This appears to be of significance, QFT-G was used before and during immunosuppressive therapy with some success,

Most patients with negative QFT-G tolerated anti-TNF therapy with no evidence of TB reactivation. Concomitant use of immunosuppressive therapy or anti-TNF did not seem to affect QFT-G results. One patient had an indeterminate QFT-G while on infliximab and later developed miliary TB. Concordance with TST is moderate.

The study was first released online in 10 May 2010 and has now been published in the January 2011 edition of Inflammatory Bowel Diseases Journal.

Going short on memory

More grumbling by the "what if" crowd, what if I bought in Feb 2005 for $4.00.. Nov 2005 for $3.00..HAD to sell on Monday you might get $2.40 to $2.45..What is wrong with saying "gee this mob hasn't done too well"

Comparing 2005 with 2011 is comparing apples with oranges, the 2007 Global Financial Crisis in which entire national and global financial and economic institutions were turned on their head has changed the world forever. The effect on the Australian equity markets can be best illustrated as thus;

















Here is CST compared with the all ordinaries index since that financial crisis

So what if you bought in Feb 2009 for $1.47 and had to sell on Monday for $2.40 to $2.45?

You would then expect to hear "gee this mob hasn't done too well has done well"

Of course I am only kidding, traders never give credit where credit is due - they only like to share their pain not their gain.

Moving on from meta and areas of uncertainty.

At the latest World Union Conference on Lung Health Pai, Menzies et al held a mini symposium (maximum 40 people) on meta analysis saying

Systematic reviews and meta-analyses are critical for evidence-based clinical and public health practice. They are a central component of policy and guideline development, especially with the widespread adoption of the GRADE system by WHO and other agencies.

The Pai Menzies meta analysis on IGRA identified "areas of uncertainty and recommendations for research" and recommended

New IGRAs show considerable promise and have excellent specificity. Additional studies are needed to better define their performance in high-risk populations and in serial testing. Longitudinal studies are needed to define the predictive value of IGRAs.

In the recent AJRCCM editorial Intention to Test Is Intention to Treat Christoph Lange and Hans L. Rieder write

In contrast to the flood of recently published cross-sectional studies, longitudinal observations like the one performed by Diel and colleagues or by Leung and coworkers are needed to better define the role of novel immunodiagnostic tests in the prevention of tuberculosis.

This is is why the latest Diel paper is so important - it is the longitudinal study "needed to better define" progression.

QFT News - Progression to Active TB

It's all here

Gerry Harvey looks down the chasm..

..doesn't like what he sees and jumps

Asked if he felt that it was poor judgment to launch the campaign in the post-Christmas sales period, he said: ''I agree with all that. It is bad timing in that respect.''

Mr Harvey said the launch of his own online store in the 1990s had been another example of bad timing. ''When I opened my site, I was doing $30,000 a week turnover, so I closed it and I opened it up again … I got the same turnover so I closed it again. Now I am opening another one as we speak because in this business it is as much about timing as anything else.

Geoffrey A. Moore on Crossing the Chasm

You could argue that the concept of chasms and crossing them is just some over hyped new age mumbo jumbo however the response to the author goes a long way to validating the theory,

the metaphor of the chasm and the recommendations for how to cross it struck a deep chord among experienced high-tech managers..

..it captured what had been for them scattered intuitions and rueful learnings and put them into a coherent set of frameworks that could be used for future decision making.

Remember, the author and publisher planned for an initial print run of 5,000...it is now over 300,000..

Full article below the fold, link here

Sceptics in denial.

Initially billionaire retailer Gerry Harvey was sceptical 

“I’ve got an online part of my business, but I definitely would not put more into it. That’d be a recipe for a disaster.”
“Online people do not make any money,” Harvey also told SmartCompany. “The whole world was conned with online retailing. People say I’m a dinosaur, and I’ve had people coming to me with sites and saying, ‘Oh, look at this, they have 10,000 or 20,000 hits!’ – but it’s a con, a complete con.”

His position of rejection could be summarised as thus

Two years later he hit the panic button

“There are a lot of retailers that are going to go broke between now and the next three months,” Harvey said. “This has been taken to the Productivity Commission, which will take nine months to look at it and then make a recommendation to the Government.

“We can’t wait that long. For the case of a lot of retailers this is a matter of life or death.”

Of course he is denying that it isnt just about the internet

Harvey told journalists in Sydney today, the issue had become “confused” and “out of control”, particularly as listeners had hit talkback radio to complain about Harvey Norman’s internet presence — or the lack of it.

“People come on, and they start talking about, oh these retailers are out of date, they haven’t got internet sites, or they should get on the internet more,” he said. “That’s not what we’re talking about. We have overseas retailers, that do not pay duties, that do not pay GST, and we have to compete with them.”

What's the bet that all the retailers, including Gerry Harvey, will be competing online in the very near future? Nobody wants to be left behind

Harvey had better get a move along otherwise he will too late;

Myer chief Bernie Brookes has said he could begin selling tax free as early as February, with Chinese-made clothing ordered from the company's website to be shipped from Shenzhen.

TB testing in Ireland, all bunged up?

This study is somewhat painful to read, after determining that Xrays are the best TB diagnostic for foreign HCWs they then spend an awful lot of time discussing how best to read them. But to me the interesting bit was how many foreign HCWs were BCG vaccinated; of the study group 96% (81/84 had BCG scars.)

So how many foreign HCWs are there in Ireland?

By 2006, 3,831 Filipinos worked as nurses in Ireland, making them the largest group of foreign nurses, roughly one-fifth larger than Indians, the next largest group.

I guess the important issue here is that you can expect that almost all foreign born HCWs are BCG vaccinated.

The value of CDC promotion of QuantiFERON.

In their newsletter the CDC advise of the following

New TB Testing Guidelines

In June 2010, CDC released Updated Guidelines for Using Interferon Gamma Release Assays to Detect Mycobacterium tuberculosis Infection—United States, 2010. This report updates CDC’s guidance on using interferon gamma release assays (IGRAs), which are whole-blood tests that can aid in diagnosing tuberculosis (TB) infection and can be used in place of the traditional tuberculin skin test (TST).

The IGRAs provide rapid results (in as little as 24 hours), do not boost responses measured by subsequent tests, and are unaffected by prior vaccination with Bacille Calmette-Guérin (BCG), a TB vaccine used most frequently outside the United States. IGRAs are preferred for testing some groups, such as those with historically low rates of return for TST reading, and for persons who have received BCG. This last group would include many foreign-born persons as well as certain cancer patients. In most circumstances requiring testing for TB infection, either a TST or an IGRA (but not both) can be used. A new IGRA fact sheet is available.

At the annual general meeting Cellestis said that this updated testing guideline from the CDC represented a quantum shift in thinking

Early adopters and early majority are terms used in describing technology adoption lifecycle

The concept was further developed by Geoffrey Moore who leads the Chasm Group

Crossing the Chasm is closely related to the technology adoption lifecycle where five main segments are recognized; innovators, early adopters, early majority, late majority and laggards. According to Moore, the marketer should focus on one group of customers at a time, using each group as a base for marketing to the next group. The most difficult step is making the transition between visionaries (early adopters) and pragmatists (early majority). This is the chasm that he refers to. If a successful firm can create a bandwagon effect in which enough momentum builds, then the product becomes a de facto standard.

The Chasm Group have some interesting ideas on marketing

Big Ideas – We don’t seek to “boil the ocean.” We have experienced first-hand that powerful business-building ideas, executed powerfully, beat a “by the numbers” approach (typically devoid of creativity) every day of the week. The antidote for complexity and ambiguity is to have a bigger cause in mind. We are accountable to this goal without reservation.

Treatment of latent TB is not to be taken lightly.

From the CDC

Monitoring of treatment. Clinical monitoring is indicated for all patients; this involves education of patients about the symptoms and signs that can result as adverse effects of the drug(s) being prescribed and the need for prompt cessation of treatment and clinical evaluation should symptoms occur. These include any of the following: unexplained anorexia, nausea, vomiting, dark urine, icterus, rash, persistent paresthesias of the hands and feet, persistent fatigue, weakness or fever lasting 3 or more days, abdominal tenderness (especially right upper quadrant discomfort), easy bruising or bleeding, and arthralgia (Table 8). Clinical monitoring begins at the first visit and should be repeated at each monthly visit. At monthly visits, patients should be instructed to interrupt therapy and contact their providers immediately upon the onset of such symptoms or any unexplained illness occurring during treatment.

Medical hypocrisy.

Medicos in Glasgow ask

It is well known that TST has poor sensitivity (particularly in immunocompromised groups) and poor specificity (due to cross-reaction with BCG and most mycobacteria...

...However, should T-SPOT testing be used as a screening tool in all patients? Does it have sufficient superiority to warrant its expense? Is it diagnostic of LTB in the absence of risk factors? Our audit demonstrates a relatively low diagnostic yield with the T-SPOT in our population. It is an expensive test, costing approximately £140 per sample, which occasionally needs repeating with no further diagnostic gain. Unnecessary treatment of false-positives is relatively inexpensive (∼£210), but delays early treatment with anti-TNF-α therapy. The risk of drug-induced hepatitis with chemoprophylaxis for TB is between 278 and 1766 per 100,0003.

It would seem that what is not well known is the Hippocratic Oath

I will apply, for the benefit of the sick, all measures [that] are required, avoiding those twin traps of overtreatment and therapeutic nihilism.

Another milestone met

The study is here and is the final peer reviewed version of the pre publication study

Negative and Positive Predictive Value of a Whole-Blood 

Interferon- Release Assay for Developing Active Tuberculosis: An Update

Now that it has been published it can be legitimately used as a marketing tool. And what a great piece of marketing it will be

To build on our initial study comparing the QuantiFERON-TB Gold in-tube assay (QFT) with the tuberculin skin test (TST) in close contacts of patients with TB and evaluating progression to active TB for up to 4 years..

..Results suggest that QFT is more reliable than the TST for identifying those who will soon progress to active TB, especially in children.

This calls for a celebratory drink, or two.

Time after time.

I don't envy the task that Forrest has set for himself, making sense out of nonsense seems like a next to impossible task. He is quite right in asserting that some investors make decisions which they are later unable to make proper account for and try to avoid accepting responsibility for their decision. The implication is that they were forced and/or coerced into making a decision, which is simply nonsense.