IGRA Use in the United States: San Francisco’s Experience

Masae Kawamura road tests QFT;

David Marder talks about replacing the skin test with Quantiferon

Link here

Neil Schluger talks the talk

Link here

Lee Reichman - the bottom line

Link here

Partnering with Quest Diagnostics for QuantiFERON™ Testing

Link here

The word is out

Clinical Lab Products (CLP) are running the CDC story;

New Guidelines Prefer Blood Tests to Diagnose Tuberculosis Infection in Certain Populations

....In these landmark guidelines, CDC advises that Interferon Gamma Release Assay (IGRA) blood tests are now preferred over the 100+-year-old tuberculin skin test (TST) for diagnosing TB infection in certain populations, including people who typically do not return for the necessary reading of TST results, and those who have received Bacille Calmette-Guerin (BCG) as a vaccine or for cancer therapy

CDC update their IGRA page

Available here

The value of peer reviewed studies

According to the latest Advance Publications edition of Laboratory Manager the CDC

identified relevant reports published through August 2008 by searching PubMed for articles written in English that listed "tuberculosis" as the major MeSH topic and included "QuantiFERON" or "T-Spot" in the title or abstract. The agency identified additional published reports by contacting test manufacturers and examining references listed in retrieved articles. These methods identified 152 potentially rel evant articles. The CDC reviewed methods in each study to select 96 primary reports that provided data related to: 

1) sensitivity or specificity of QFT-GIT or T-Spot, 

2) agreement of QFT-GIT and T-Spot results with each other or with TST results, 

3) association of QFT-GIT or T-Spot results with risk for M. tuberculosis infection or subsequent active tuberculosis and 

4) evaluation of QFT-GIT or T-Spot use in contact investigations, immunocompromised persons or children.

The CDC used the published reports, data submitted to the FDA, product package inserts and expert opinion related to QFT-GIT and T-Spot to prepare its guidelines. It coordinated development of these guidelines with the American Academy of Pediatrics, the American Thoracic Society and the Infectious Disease Society of America.

So there you go

Business as usual

Peter Sinclair grapples with the climate of denialism

Throwing the baby out with the bath water

Following the recent visits to Australia by high powered Chinese dignitaries Vice Premier Li Keqiang and Vice President Xi Jinping (Xi was once named by Time magazine as one of the top most influential people in the world) Professor Peter Drysdale* writes

Many of our international readers are perhaps justifiably baffled by the overthrow last week of former Australian Prime Minister, Kevin Rudd, by Australia’s new Prime Minister, Julia Gillard.

Rudd stood tall on the international stage. He led a government, alone among all the OECD countries, that steered Australia successfully through the Global Financial Crisis, without recession. He was among the most effective of the protagonists that influenced the launching of the G20, meeting this weekend in Toronto, a new group that has promise of providing a greater measure of international and political security because it is more representative of global power than its predecessor, the G8, and is more adept at dealing with the problems in global economic governance. He swiftly moved to have Australia sign the Kyoto Protocol. And Rudd, among all global leaders, had a surer grasp of Chinese affairs than any major political leader outside China, when that is a political commodity in drastic short supply at a time of great need. In dealings with China he communicated with dignity and uniquely in the Chinese language.

He had the correct strategic sense of how urgent it was to begin re-crafting arrangements in Asia and the Pacific to provide greater opportunity for dialogue on political as well as economic affairs in a way that comprehends the huge transformation of economic and political power that is taking place in our region.

These were impressive international political assets, and unquestionably huge assets for Australia. And, at home, he brought leadership to reconciliation with indigenous Australians and set in motion a substantial social and reform agenda. Rudd’s achievements in his short tenure in office were undoubtedly considerable.

Objective analysis suggests that Rudd was poised to win the next election, due within the next six months or so, despite a big drop in popular support driven by gaffs in the implementation of expansionary spending programs, a reversal of course on climate policy and questions of leadership style and process. The truth is that these questions provided the opening for factional powerbrokers within the governing Labor Party, in which Rudd had no permanent factional base, to settle scores. And amid the political uncertainties a sudden fracture of trust between Rudd and his Deputy led her to seize the unexpected prize.

Prime Minister Gillard is a very talented and polished political leader. There are likely to be few fundamental changes in Australian foreign policy direction. Rudd has chosen to continue in play. His foreign policy initiatives and big international diplomatic goals, in relation to China (of which Ms Gillard has a very sure grasp), climate change and regional architecture, are matters of deep foreign policy strategy that will not change and on which Rudd’s talents are likely deployed in some way.

The transfer of leadership has cut the Australian Prime Minister out of the G20 Summit in Toronto, where Rudd was also due to have important bilateral discussions with President Obama. That is a pity and an important cost to Australia’s national interests of the events of the last week in Canberra.

*Peter Drysdale is Emeritus Professor of Economics and a Visiting Fellow in the Crawford School of Economics and Government at The Australian National University. He is Head of Australia’s East Asia Forum. He is widely recognised as the leading intellectual architect of APEC. He is the author of a number of books and papers on international trade and economic policy in East Asia and the Pacific, including his prize-winning book, International Economic Pluralism: Economic Policy in East Asia and the Pacific. He is recipient of the Asia Pacific Prize, the Weary Dunlop Award, the Japanese Order of the Rising Sun with Gold Rays and Neck Ribbon, the Australian Centenary Medal and he is a member of the Order of Australia.

Radford on CNBC: Now is the Time

Source

Radford: Now is the Time for Heightened Focus on the TB Threat

 

Tony Radford

Founding CEO

of Cellestis Limited

While most people living in the United States might think tuberculosis (TB) is a disease that no longer affects this country, in reality, between nine and 14 million Americans are infected with the bacteria that cause TB. 

Consider the number of people you come in contact with every day – at the office, home, airports, trains, buses, restaurants, schools, hospitals, and shopping centers – it takes just one person with TB disease in any of these settings to pose a risk to all those around them. 

A contagious disease, TB is spread through the air when a person with TB disease of the lungs or throat coughs, sneezes, speaks, or sings, which may cause people in close proximity to become infected. TB usually attacks the lungs, but it often affects other organs, and if not treated properly, it can be fatal. Around one in every 10 TB-infected people will, without treatment, go on to develop potentially deadly TB disease. 

So why is TB still prevalent in the U.S.?

 

Giuseppe Ceschi | Workbook Stock | Getty Images

A key reason has to do with the very things that are supposed to help protect us from TB: the Bacille Calmette-Guérin (BCG) vaccine and the main method of TB testing traditionally used, the 110+-year-old tuberculin skin test (TST). 

The BCG vaccine is widely-adopted globally and its use engrained in TB control policies around the world.

However, it is recognized by many around the world that the BCG vaccine confounds the TST and leads to false-positive test results. 

This means that for the many foreign-born Americans who have been BCG-vaccinated, the usual method of TB testing will often indicate that they are positive for TB infection. With migration to the US (approximately one million per year, many from countries where TB is endemic), TB rates have been steadily growing in foreign-born individuals - in 2009 immigrants were nearly 11 times more likely than U.S.-born citizens to have TB.

Certain communities are also at higher risk: people with autoimmune conditions and those taking immunosuppressive therapies, the elderly, the homeless, and corrections facility inmates. As a consequence of frequent contact with high-risk individuals, doctors, nurses, and staff at hospitals and other group facilities are all at significant risk of TB. 

The major challenge for the U.S. is to modernize TB control.

 

The first hurdle will be for the nation to adopt new strategies for TB control and diagnosis. The U.S. Centers for Disease Control and Prevention (CDC) is taking steps to pave the way for change. 

In a landmark Public Health release issued last week, CDC is now championing the use of modern TB testing strategies. The CDC advises that IGRAs, simple blood tests known as interferon-gamma release assays, are now preferred over the TST for diagnosing TB infection in many groups of individuals. Further, the CDC in conjunction with the U.S. Department of Health and Human Services (Division of Global Migration and Quarantine) recently published new instructions for immigrant TB testing, which allow the blood tests to be used instead of the TST in certain immigration populations. 

Using these tests for immigration TB screening will prevent the large number of false-positive TST results in BCG-vaccinated immigrants and stem unnecessary (and expensive) evaluation and treatment. 

The distinct advantages of these blood tests, such as QuantiFERON®-TB Gold (QFT®), are greater accuracy over TST and not being confounded by BCG vaccination. 

These blood tests frequently show that fewer than a third of those previously thought TST-positive truly have TB and can provide more valuable information for physicians to diagnose TB infection. Economic studies show that, when staff time and evaluation of TST false-positives are included in cost comparisons, QFT reduces testing program costs by seven percent while providing superior medical outcomes.

Public health and TB control programs across the U.S. are also successfully beginning to implement change. 

At the forefront is the San Francisco Department of Public Health’s TB Control Health Program. The program’s switch from TST to QFT resulted in a more than 60 percent decline in the number of people testing positive for TB last year and, thus, a reduced number of follow-up visit costs. Despite this lower number of positive results, no cases of TB have been reported as missed in more than 45,000 people screened for TB in San Francisco since QFT was adopted. 

Switching for healthcare worker screening alone saved the program $101,648 in the course of one year.

The CDC’s announcement is a great move in the direction of tackling how TB is tested. Success will eventually be measured by local government and other groups’ adoption of these guidelines. Although TB is not on most Americans’ radar, it remains a significant public health threat in the U.S., with still much more to be done. 

More CEO's on the State of Health:

_________________________
Dr Tony Radford is the founding CEO of Cellestis Limited, a biotechnology company formed in 2000 in Melbourne, Australia, and listed on the Australian Stock Exchange (ASX). Dr. Radford was a senior member of Australia’s Commonwealth Scientific and Industrial Research Organization (CSIRO) team that invented the patented QuantiFERON® technology, which is used world-wide for testing for diseases such as tuberculosis. Cellestis develops and manufactures the QuantiFERON®-TB Gold (QFT) test, a breakthrough blood test for the detection and control of tuberculosis.

Myths and facts about TB

 "My TST test result was negative, so I do not have tuberculosis."

 

 "...more than 20 percent of people who are infected do not have a reaction to the (skin) test."

 

Source

--------------------------------------

 

TUBERCULOSIS (TB) MYTHS & FACTS

OH&S and TB

The US based Occupational Health & Safety Magazine, which in 2008 won an award from the American Society of Business Press Editors for magazines of 80,000 circulation or more, has the following news item

.....On Friday, CDC issued new and important guidelines on the detection of Mycobacterium tuberculosis infections, the causative agent of TB. In the guidelines, the agency advises that Interferon Gamma Release Assay (IGRA) blood tests are now preferred over the 100+-year-old tuberculin skin test (TST) for diagnosing TB infection in certain populations, including people who typically do not return for the necessary reading of TST results, and those who have received Bacille Calmette-Guérin (BCG) as a vaccine or for cancer therapy.

.....The populations specified by the new CDC guidelines represent a majority of those being screened for TB infection. Better, more reliable testing for TB infection is vital in order to efficiently identify the appropriate persons for treatment and thereby prevent its spread, the agency said

In most if not all developed countries worker safety is covered by Law, in the US it is the Occupational Safety and Health Act

Evidence-based Tuberculosis Diagnosis

The Stop TB Partnership's New Diagnostics Working Group has recently (August 2009) launched a new website resource called Evidence-based Tuberculosis Diagnosis. According to Madhukar Pai

Several agencies, groups and individuals contributed to the development of this comprehensive resource. These include the WHO, the Special Programme for Research and Training in Tropical Diseases (TDR), Foundation for Innovative New Diagnostics (FIND), the Global Laboratory Initiative, the Francis J Curry National TB Centre, McGill University and the Public Health Agency of Canada.

The section is IGRA has 7 reviews and was last updated 25 May 2010, the section on TST has 2 and was last updated 19 August 2009.

T-Spot and the guidelines

Never backward in coming forward Oxford Immunotec Inc welcomed the new guidelines saying;

Since obtaining premarket approval from the Food and Drug Administration (FDA) in July 2008, the T-SPOT.TB test has become widely utilized in hospitals, medical practices and public health facilities throughout the United States. The T-SPOT.TB test is backed by the clinical evidence of over 200 peer-reviewed publications, and is the only IGRA with both sensitivity and specificity exceeding 95% in FDA pivotal trials

The updated CDC guidelines do make mention of T-Spot;

The T-Spot interpretation criteria approved by FDA for use in the United States differ from those used in other countries. Also, the majority of published studies evaluating T-Spot have used criteria that differ from those approved by FDA.

What more can I say?

Nebraska LabLinc

Nebraska LabLinc did well to prepare for the updated CDC guidelines;
TB INTERFERON ANTIGEN (QuantiFERON-TB Gold) NLL Test# 99434.

The updated guidelines are now appearing all over the place eg PubMed,

For assistance in developing recommendations related to IGRA use, CDC convened a group of experts to review the scientific evidence and provide opinions regarding use of IGRAs. Data submitted to FDA, published reports, and expert opinion related to IGRAs were used in preparing these guidelines. Results of studies examining sensitivity, specificity, and agreement for IGRAs and TST vary with respect to which test is better. Although data on the accuracy of IGRAs and their ability to predict subsequent active tuberculosis are limited, to date, no major deficiencies have been reported in studies involving various populations.

Unlike most (if not all) other emerging 'biotechs' QuantiFERON is no longer just a 'good idea,' it has now gained official endorsement.

Be careful what you wish for

After being deposed in a coup the Rudd government's performance has since proved to be winnable;

So what % are BCG vaccinated?

For HCWs in Melbourne 88% and New York 54%, immigrants in Germany 43.5% and in the Nienhaus, Schablon and Diel study

the proportion of participants with BCG vaccination was 59% in the meta-analysis and 43% in our pooled population

For arguments sake lets say 50%. How many HCWs are there in the US? The US Dept of Labor says

• As one of the largest industries in 2008, healthcare provided 14.3 million jobs for wage and salary workers.
• Ten of the 20 fastest growing occupations are healthcare related.
• Healthcare will generate 3.2 million new wage and salary jobs between 2008 and 2018, more than any other industry, largely in response to rapid growth in the elderly population.
• Most workers have jobs that require less than 4 years of college education, but health diagnosing and treating practitioners are highly educated.

CDC guidelines - can it be summarised in 25 words or less?

Perhaps this;

For persons who have received BCG and who are not at increased risk for a poor outcome if infected (Box 2), TST reactions of <15 mm in size may reasonably be discounted as false positives when an IGRA is clearly negative.

This runs contrary to prior CDC instruction

TST reactions should be interpreted regardless of BCG vaccination history.

It appears that for those with a prior BCG vaccination the TST can now be discounted and for the CDC an IGRA is the preferred test in BCG vaccinated.

At last! updated CDC guidelines on IGRA

Source

Scary monsters invade Westminster

Paul Segal writes that

Politicians on the right love to scare us. George Osborne, in his Mansion House speech cited "fears" over government solvency and sovereign debt crises. David Cameron has declared the fiscal deficit a "threat" to "our whole way of life," and "a clear and present danger to the British economy". This is nonsense. The threat we face is ideologically driven cuts that risk causing a double-dip recession.

The fiscal deficit seems scary because it is debt. Cameron argues that within five years the national debt will rise to "some £22,000 for every man, woman and child in the country". This may be true, but what he doesn't tell us is that it is money the government owes to us – not money that we owe to anyone else. That's right: 80% of our government debt is owed to the British people. What is called "national debt" is our own savings, looked at from the other side of the balance sheet.

Professor Bill Mitchell calls them "flat earthers"

People get very confused about the concept of national saving. They assume that saving is spending less than you earn and then apply that to budget surpluses and conclude that the surpluses add to national saving. But this view is erroneous. A sovereign government does not save. What sense does it make to say that the government is saving in the currency that it issues? Households save to increase their capacity to spend in the future. How can this apply to the issuer of the currency who can spend at any time it chooses?

Bill concludes;

whatever the mainstream economists say the policy agendas they advocate cannot be justified in terms of the financial issues they hide behind – crowding out, inflation, sovereign insolvency etc.

Once you understand the way the monetary system operates their agendas become transparently ideological and intent on redistributing real output to the rich and way from the poor.

They might be clothed in the sophistry of the market and supported by mathematical models but when you distil the arguments down to their essentials you realise they just represent a crude and unsophisticated grab for wealth.

Bolt - screwed loose

Seasoned blabbermouth Andrew Bolt lets fly over one of his pet delusions; that global warming is a scam and the ABC is a willing participant;

How much longer will ABC management condone or ignore this disgracefully one-sided coverage of the global warming controversies by its flagship programs? This is treating the audience like fools. 

Most (if not all) of Bolt's references are from dubious sources, if not fake eg

- the citing of false information about the dangers to the Amazon

This allegation was later proved to be false and a retraction published

The article "UN climate panel shamed by bogus rainforest claim" (News, Jan 31) stated that the 2007 Intergovernmental Panel on Climate Change (IPCC) report had included an "unsubstantiated claim" that up to 40% of the Amazon rainforest could be sensitive to future changes in rainfall...

 
...In fact, the IPCC’s Amazon statement is supported by peer-reviewed scientific evidence.

Will Andrew Bolt correct his own "disgracefully one-sided coverage of the global warming controversies?" I doubt it.

Lee Reichman on hepatoxicity

The TB Working Group discuss INH and liver damage;

Over the last month, a few reports about new positive TB cases have surfaced from FL, involving students at a couple of high schools and at a college.

So what do you treat positive TB cases with - INH?

INH inhibits an enzynme, InhA, which is involved in fatty acid synthesis.  A recent Morbidity and Mortality Weekly Report (MMWR) published in the Journal of the American Medical Association (JAMA) by the CDC reports the incidence of severe liver toxicity in patients receiving INH treatment for LTBI.

Compliance presents a problem

9 months of INH therapy remains the mainstay of LTBI treatment.

Whilst INH therapy should be carefully monitored

No more than a 1-month supply of INH at a time should be prescribed, and treatment should be combined with careful clinical monitoring

monitoring is not 100% effective

despite adherence to current guidelines for monitoring, liver injury occurred

and symptoms of damage are not sufficient

In the absence of symptoms, isoniazid should be discontinued if aminotransferase values are five times the upper limit of normal.

Lee Reichman responds

It seems to me that the bottom line is that treatment of latent infection has always been toxic, that’s why we use targeted treatment, concentrating on those patients in whom treatment is necessary (contacts, immunosuppressed).

At our institute, we have been using Rifampin for 4 months [Reichman LB, Lardizabal A, Hayden: 2004 Am J Respir Crit Care Med 170 832-835;107. Lardizabal AA, Passannante M, Kojakali F, Hayden C, Reichman LB. 2006 Chest; 130:1712-1717.] with far less toxicity and far more compliance.

Also, the skin test is overly unspecific, consequently, many patients are treated who aren’t infected or at risk for TB. Exclusive use of IGRAS would obviate this immediately.

Exactly

The real culprit

Professor John Quiggin takes a look at the so called "European crisis" and finds fault with guess who - the banks;

Banks and other financial institutions lent too much money without worrying about the capacity of the borrowers to pay it back. Some of this money went to profligate governments, but most, as in the first round of crisis, went to stimulate booming real estate markets in Spain, Ireland, Iceland and elsewhere.

Which must make uncomfortable reading for those who profit out of speculation.

The main problem for the governments in this countries have arisen because they have been forced to bail out their domestic banks. As the losses are too big to be managed by the governments in question, their own solvency is called into question. 

So speculators can bring down governments? - perhaps

It remains to be seen whether the eurozone governments can manage this crisis, or whether the whole euro project will collapse. Whatever the outcome, the main policy lesson is that light-handed regulation of a ‘too big to fail’ financial sector is a recipe for disaster.

CDC guidelines - this week

Dr Dazmo catchs a Big One!

Preparation of updated guidelines

• Expert Committee
– Neil W. Schluger, Chair
– Representation from American Academy of Pediatrics, American Thoracic Society, ACET, Association of Public Health Laboratories, CDC, FDA, Infectious Disease Society of America, NTCA, Stop TB USA, US Army, US Air Force, and VA

• Final guidelines prepared by Gerald Mazurek, John Jereb, Andrew Vernon, Philip LoBue, Stefan Goldberg, and Ken Castro
– Development of guidelines coordinated with AAP, ATS, IDSA
– To be published in June 25, 2010 MMWR

I think that we are already familiar with the content;

• Situations in which IGRA is preferred but TST is acceptable
– An IGRA is preferred for testing persons from groups that historically have low rates of returning to have TSTs read
– An IGRA is preferred for testing persons who have received BCG (as a vaccine or for cancer therapy)

• Situations in which either IGRA or TST may be used, without preference
– An IGRA or a TST may be used without preference to test recent contacts of persons know or suspected to have active tuberculosis with special considerations for follow-up
– An IGRA or a TST may be used without preference for periodic screening of persons who might have occupational exposure to M. tuberculosis (e.g., surveillance programs for health-care workers) with special considerations regarding conversions and reversions

• Situations in which a TST is preferred but IGRA is acceptable
– A TST is preferred for testing children aged <5 years. Use of an IGRA in conjunction with TST has been advocated by some experts to increase diagnostic sensitivity in this age group. Recommendations regarding use of IGRAs in children have also been published by the American Academy of Pediatrics

Pole dancing media

Whilst much is being made of the latest Newspoll

Opposition Leader Tony Abbott closing the gap on Kevin Rudd as preferred prime minister.

..Mr Abbott is now the closest Liberal leader in the preferred prime minister stakes since Mr Rudd was elected

the reality is not that good for Mr Abbott

My word is my bond

Writing in WSJ Alan Greenspan notes;

An urgency to rein in budget deficits seems to be gaining some traction among American lawmakers. If so, it is none too soon. Perceptions of a large U.S. borrowing capacity are misleading.

Despite the surge in federal debt to the public during the past 18 months—to $8.6 trillion from $5.5 trillion—inflation and long-term interest rates, the typical symptoms of fiscal excess, have remained remarkably subdued. This is regrettable, because it is fostering a sense of complacency that can have dire consequences.

Which seems contradictory, with no evidence of fiscal excess there can be no case that fiscal excess exists.

Elsewhere he says

The U.S. government can create dollars at will to meet any obligation, and it will doubtless continue to do so. U.S. Treasurys are thus free of credit risk. But they are not free of interest rate risk. If Treasury net debt issuance were to double overnight, for example, newly issued Treasury securities would continue free of credit risk, but the Treasury would have to pay much higher interest rates to market its newly issued securities.

Good, so neither is there any evidence of fiscal excess there is also no risk of insolvency - there is no sovereign risk in the US.

Suspicion that Greenspan is acting for his clients is valid

Alan Greenspan, the former chairman of the US Federal Reserve and a well-known specialist on interest rate policy, has been roped in as a consultant by the operator of the world’s biggest bond fund, the Allianz-owned Pacific Investment Management, Pimco. In a major triumph for Pimco, whose bond portfolios are extremely sensitive to interest rate policy, Greenspan will communicate once a quarter with Pimco executives on economic issues, including offering his private outlook about interest rate policy at the US central bank.

Governments should act in the public interest - claims that governments have to embrace austerity measures to restore confidence in financial markets only serve the interests of traders who are deliberately undermining the general welfare of the people.

Taking the ill out of Illinois

They get straight down to business at the University of Illinois;

all new international students are screened for tuberculosis at McKinley Health Center. Screening consists of completion of a paper questionnaire and a Quantiferon TB Gold blood test for students who have lived in countries outside of the United States, Canada, Australia, New Zealand, or Western Europe.

More good stuff from the 2010 National TB Conference

Source

Collaborative Effort between TB Control Program and TB Laboratory Leads to Successful Implementation of Quantiferon Gold In-Tube Service

T.L. Elliott, P.E. Griffin, Kansas Department of Health and Environment, Topeka Kansas

Background and Objective: With the introduction of IGRAs, Kansas immediately began to consider the possibilities and impact on TB eliminations efforts in the state. Given that more than two-thirds of cases each were among person born outside of the US and many had contacts who were BCG vaccinated it was determined one area of use for the tests would be contacts. It was also observed that 15 – 20% of cases each year were among international students in our colleges and universities, thus establishing another use for the test. The objective was to establish a Quantiferon Gold In-Tube (QFT) service in a rural state that will meet Public Health best practice needs at an affordable cost to target audience.

Methods: Review of current literature to determine the most important target audiences. Market analysis conducted to determine current service availability and cost as well as realistic access to current services by the target audiences. Target audiences surveyed to establish a demand for the service that is not being met.

Results: The Kansas Public Health TB Laboratory became a validated provider of the QFT service. The Kansas TB Control Program targeted two populations for initial roll out of service, state universities screening high risk incoming students (generally international students with BCG vaccination) and high risk contacts identified in contact investigations statewide. In three years, the program has grown from processing less than two hundred tests in 2008 to an expected two thousand tests in 2010. Laboratory costs are neutral with reimbursement arrangements contracted with submitters. TB Control Program costs are decreased as a resulted of fewer required follow up expenditures for contacts that were BCG vaccinated and previously had questionable screening results.

Conclusions: In Kansas, a successful, cost effective and growing QFT service has been established. Such a service would not have been possible without a willing collaboration of the TB laboratory and TB program.

--00--

Implementation of a QuantiFERON-TB Gold Screening Program in a Public Health Clinic Setting

NiiAmah Stephens, MPH, CPH; Susan Dorman, MD; Sherry Ketemepi, MPH; Adena Greenbaum, MD, MPH; Nicketta Johnson, RN, BSN

Baltimore City Health Department (BCHD), Johns Hopkins Center for TB Research, Johns Hopkins Hospital

Background/Statement of Problem: For more than a century, the mainstay of latent tuberculosis detection has been the tuberculin skin test (TST). However, TST screening requires at least two interactions with a health worker, reading TSTs can be highly subjective, and result interpretation can be difficult among BCG-vaccinated individuals. Interferon-gamma release assays, such as the QuantiFERON-TB Gold (QFT-G) test, overcome these obstacles, may improve staff efficiency, and may be more cost-effective, but data on their use in public health clinic settings have been very limited.

Methods: The Baltimore City TB Control Program, BCHD’s BDC Laboratory, and Johns Hopkins partners met several times over 6 months to design a pilot program that would assess the feasibility of QuantiFERON-based screening in BCHD TB clinics; evaluate impact on contact investigation completion rates; evaluate impact on screening of BCG-vaccinated individuals; and costs and cost-effectiveness of implementation in a routine TB program setting.

Results: Health Department staff and Hopkins partners developed Standard Operating Procedures detailing eligibility criteria for QuantiFERON screening, how and when samples will be collected, and how often batches will be run at the laboratory. Background materials were developed to explain the new test to clinic patients, and the test manufacturer trained nurses and laboratory staff on appropriate phlebotomy and analysis techniques. Program evaluation will use a retrospective cohort approach that enables modeling of clinical efficiency, program effectiveness, and cost-effectiveness. TB screening using QFT-G began in Baltimore City’s Eastern District Health Center on March 1, 2010.

Conclusion: The initial implementation of QFT-G testing has been feasible in a local health department setting. Assessment of impact on patient-centered and program outcomes is underway. The data collected during this pilot program will be useful in determining the cost-effectiveness of broader QFT-G adoption.

QFT: the test of choice

The eagle eyes of thumbs up spotted this gem by San Francisco TB Control

Conclusions
• IGRAs in SF 2003 -2008: excellent track record  

• IGRAs are a significant advance because of its high specificity and operational advantages to the TST
 
• Sustainability: QFT pays for itself in SF and public demand comes from its convenience and specificity 

• IGRAs are the TB test of choice in SF

“Once you use them, you can’t go back”

How much is 2.5M barrels of oil?

About 9,464 cubic metres - or almost 4 Olympic sized swimming pools - of crude oil is leaking into the Gulf of Mexico per day. Shareholders may well ponder on the risks of their investment and the ability of their executives to manage that risk.

If the new range of flow estimates proves correct, and if BP is ultimately found guilty of gross negligence in actions it took that led to the Deepwater Horizon disaster, that would mean the company could be assessed fines of up to $258 million a day. Those fines could come on top of payments for cleanup costs and economic damage to Gulf Coast businesses.

WORKING GROUP on new TB drugs

Link

On Friday, June 11th, the Johns Hopkins University Center for Tuberculosis Research hosted their annual scientific meeting and the WGND was there to cover the event.  Approximately 100-200 people were present including persons from NIH and small pharmaceutical companies.  This annual meeting is an opportunity for the epidemiological, clinical and basic researchers to relate their most recent studies and results. Overall, the meeting was dynamic and informative.

The scientific method starts early

The meeting was organized into 3 general sections: Basic Science, Epidemiology and Clinical, and Drugs and Animal Models.  There were 23 speakers including the Keynote address by Andrew Nunn from the British Medical Research Council.  Andrew spoke about his training experiences in the background of the history of TB clinical trial development over the last 40 years.

The following is a list of all of the speakers with their talk titles.  Brief additional comments and/or links are included for most of the talks.

.......

Maunank Shah: ‘Interferon-gamma release assays for detection of M. tuberculosis infection in children exposed to TB in Soweto, South Africa’- IGRAs potentially more sensitive for detecting TB in the pediatric population.

Slippery slopes and greasy poles

Congressman Bart Stupak takes a look at Exxon's disaster management plan;

Maintain on camera skill proficiency

Stupak elaborates

My problem is that ExxonMobil has given far less attention to actually controlling a spill.  While ExxonMobil has 40 pages on its media response strategy, its plan for “Resource Protection” is only five pages long, and its plan for oil removal is just nine pages long.

We have all seen the horrible images of pelicans and other wildlife coated in oil from the recent spill.  ExxonMobil’s plan appears more concerned about public perception than wildlife protection given the fact that their media plan is five times longer than its plan for protecting wildlife.  And the canned pre-drafted “deeply sadden” press release rings hollow with the loss of 11 lives on the Deepwater Horizon!

ExxonMobil’s plan is a perfect metaphor for what is going wrong in the Gulf today.  The oil company response plans are great public relations.  They allow the oil companies to say they have a 500-page plan that shows they’re prepared for any contingency. 

But these plans are virtually worthless when an actual spill occurs. 

And that’s exactly the kind of misplaced priorities that led to this disaster.

Hillbilly Huntley

In May 2010 Ian Huntley writes;

I still consider this a major corrective market, the foothills, of a major Teens decade bull market

and he repeats his message in June

I continue to believe we are in the foothills ahead of the teen's decade bull market

He may well prove to be right however it will have to be by a new set of rules;

What is q?

q is the ratio between the value of companies according to the stock market and their net worth measured at replacement cost....

 Why is q Important?

q is one of the two valid methods of measuring the value of the stock market. The other is the cyclically adjusted P/E. As they are both valid measures they both give the same answer, subject to small variations arising from the differences in data sources.

Real dirty

Scott Steel puts ABS data into graphic form - it is no wonder that the big miners are keen to hang on to their profits and little wonder that this self interest is at odds with the national interest. Their claim that under an RSPT markets will go offshore just doesnt make sense - Australia has the resources that the world needs and miners would not walk away from making such large profits.

Going good now

I particularly liked this presentation from Kansas so have reproduced it in a text format; it was given at the 2010 National TB Conference

Lab Case Study of Implementing Interferon – Gamma Release Assays in Public Health

Thor Elliott, Microbiologist KDHE TB Lab

Setbacks
• Budgets cuts
• Courier cuts
• Manpower cuts
• Clear direction

Timeline
• Spring 2008 – Validation study
• Fall 2008 our first school, Emporia Sate University tested used IGRA testing to screen their international student population.
• Fall 2008 Our first use of IGRA testing in a case investigation.
• January 2009 What have we done!

Reorganization
• We are a PUBLIC HEALTH LAB!
• Did not want to be in competition with commercial labs.
• Defined our four areas of testing
• Began planning a “new order” (YES! see slide 1) to handle who we will test for, how we will bill them, and most importantly how we will train them.

4 types get in - Identifying the Criteria for Testing
The TB lab and the TB Program agreed it was important to maintain the role of public  health and to not enter into an area that would have us competing with the commercial labs for IGRA testing.

Four areas for testing were indentified:
• Post Secondary Educational Facilities that have entered into a contract for testing with KDHE
• Screening Purposes that would be done mainly by County Health Departments that have also contracted with the state.
• Contact Investigations paid for by the TB program as a contact investigation tool with pre approval by the lab and program.
• Refugees tested by county health departments involved in the KDHE Refugee Program and paid for by that program.

Logistics  

Option 1: Collect blood, transport @ RT, sample is good for 16 hours  

Option 2: Collect blood, incubate on transport @ RT, sample is good for 3 days Option 3: Collect blood, incubate on site, centrifuge on site, transport at 2--8C, sample is good for 28 days

Issues
• Incubators on site.
• Training
• Courier routes and Friday deliveries
• Pre-authorizations

Going good now
• We have implemented a successful screening tool for post secondary education facilities.
• We have many of our higher incidence health depts. using IGRA correctly.
• We have an important tool for the states refugee program.
• We have gone from testing a few hundred in ’08 to almost 2000 in ’09 and on track for 3000 or more in 2010.
• It’s not world dominance but I’m ok with that.

He who pays the piper calls the tune

According to the Murdoch rag our PM has few if any options left, the narrative of both Peter Van Onselen and Glenn Milne’s pieces is that Kevin Rudd has one more Newspoll left in him (or two, according to Milne, if reality fails to play to script and the bar needs to be moved). Milne holds Murdoch's Newspoll in high regard saying

The next two Newspolls will determine whether a pre-election Gillard leadership is an absurdity or not

The Oz also quotes former ALP insider Keith de Lacy as saying that the party should dump Prime Minister Kevin Rudd as leader as he had become an

"item of ridicule".

ASIC are not amused by the media antics of the miners saying that they need to ensure they comply with continuous disclosure rules;

"The rules require that ... the market is fully informed and that the market is not misled," she said.

"Now it's up to directors when they make statements about their companies, whether it's in relation to the resources tax, that their statements are accurate and that all material information is given to the market."

Undeterred by ASICs direction Keith de Lacy, now chairman of Macarthur Coal, said that

the Rudd government's 40 per cent resource super-profits tax would have dreadful consequences for the resources sector, the general economy "and Australia's reputation as an attractive investment destination".

and that with regards to Kevin Rudd there is an

"enormous gulf between word and deed, between spin and substance".

"This has led to the terminal loss of trust and respect that is reflected in the opinion polls,"

Well maybe, but a recent online poll in a Fairfax paper reflected a differing opinion

And there are others that also disagree

The superannuation industry is disputing the mining sector's assertion the proposed resources rent tax will hit super returns.

The mining industry has said in its advertising campaign, that the average superannuation investor would be worse off if the tax goes ahead.

The Association of Superannuation Funds estimates the tax would have an impact of less than 1 per cent on the superannuation account balances of an average worker. The association represents a range of corporate, industry and public sector funds.

Island in the sun

Over at guru Martin links to this fabulous holiday destination, all invitees are given a free medical including

Tuberculosis (TB) screening conducted via Quantiferon testing – the most accurate TB testing method available

So who's arguing?

Strining the friendship

Over on sharscene "alar" says

Western Australia is now using IGRA in preference to TST for immigrant screening

but that is just so not what they said;

Either a Mantoux test or a blood-based interferon–γ release assay (IGRA) may be used for screening.

Further on they are a little more expansive

At present, the Mantoux test remains the preferred method of investigation for LTBI pending further evaluation of IGRAs. However, it is recognised that IGRAs are currently used for LTBI screening in some jurisdictions and may be used more widely in the future. A patient with a positive IGRA test result should be referred to the local TB services for consideration of latent LTBI treatment. NTAC regularly reviews the use of IGRAs and publishes its Position Statements at www.health.gov.au/ntac.

So from this we know that NTAC are influencing the uptake of IGRAS in Australia. Now consider this;

Imagine the uptake if NTAC made QFT the preferred diagnostic.


.

Ian Verrender says enough is enough

Writing in the SMH he says

If one more person looks me in the eye and talks about sovereign risk and the new resources tax, I swear I'll strangle them.

Let's get it straight. Even by the loosest definition, modifying the tax system in the manner proposed by the federal government does not in any way endanger the national ability to repay debt.

Nor will it endanger the ability of resources companies to meet their commitments.

And that, dear reader, is the definition of sovereign risk.

I think he is being too kind, some of the actors in this drama have a history of loose talk;

TICKY FULLERTON: Joe Gutnick blames Forrest for the downfall of his company Centaur.

He claims Forrest reneged on a $20 million investment in his nickel project.

Gutnick won his case in court, the judge calling Forrest an 'untruthful' witness.

Anaconda is appealing, but it's not the only time judges have singled out Forrest.

In a litigious career, a judge said, he would achieve commercial ends even if it involved threats and falsehoods.

And just two weeks ago, another judge called him 'quite untruthful'.

ANDREW FORREST: People who know me very well, um -- would completely deny that.

But the hurt comes from, um -- the fact that those same commentators have ignored other judgments where I've been found to be very truthful and a very reliable witness.

TICKY FULLERTON: So as far as you're concerned -- I mean, the courts have -- have been wrong, have got -- have somehow seen a side of you which does not exist?

ANDREW FORREST: Well, the courts have been persuaded by a very clever Queen's Counsel acting for, say, Gutnick and, um, and have -- have reached a totally false conclusion.

TICKY FULLERTON: Forrest has also had fall-outs with some of his early business partners.

WARWICK GRIGOR: To put it simply, if you're his partner, you're running with the wolves and you don't know where the wolves are going to take you.

Andrew has a cavalier attitude that if he keeps running hard enough, nothing will catch up with him, so why worry?

A NICE trend

Even though April 2009 is over one year old, this audit of laboratories
/hospitals in the Merseyside, Lancashire and Cumbria regions has some pleasing aspects;

• Total number of laboratories in the region=15.
• Number of responses received =13

IV. Diagnosis of latent TB
1. Mantoux testing should be performed.
2. Interferon-gamma (IFN γ)– tests, if available, should be considered for those in whom Mantoux testing is positive or is less reliable.
 

Findings

Type of tests, Number of labs
Mantoux test = 7
Quantiferon test = 7
T-spot test = 2
Mantoux and IFNγ tests = 5*

*when chemoprophylaxis is indicated

Situations where IFNγ tests are recommended or performed, Number of labs

As evidence of exposure during a contact tracing exercise = 7
Diagnose latent TB in HCWs = 6
To rule out active TB as a possibility in smear negative cases = 2
To diagnose current active TB in smear negative cases = 2
Others = *
*Immunocompromised children, prior to start of immunosuppresive therapy, diagnose latent TB in immigrants.

IV. Diagnosis of latent tuberculosis
a. Increasing trend for the use of IFN-γ for a variety of situations.
b. 2 hospitals use it for diagnosis of active tuberculosis.

Agreed actions
NICE guidelines have considered the role of IFN-γ assays in the diagnosis of latent TB and have suggested its potential role in ruling out mycobacterial infection. Recent interim HPA guidance has also outlined certain situations when these assays can be performed, including diagnosis of active TB in exceptional circumstances.3 Hence, it was agreed that, in addition to having a regional centre, locally approved protocols would help streamline requests for IFN- γ testing, effecting better use of resources.

Conclusion
There is variable compliance with the NICE guidelines in the region. The only area where serious non-compliance was noted was in infection prevention and control of TB in hospitals, which will be addressed locally in each trust. The implementation will occur as soon as possible and will be undertaken by the respective Infection control teams. With respect to lab diagnosis including use of IFN-γ assays and molecular diagnostics, the protocols of testing have been adapted to suit the region, taking into account the incidence and prevalence of TB. However, there is need for optimum utilisation of resources and it was agreed that a locally approved protocol and a centralised service would be a best way forward, although a timescale would be difficult to predict. A re-audit has been planned in a year’s time unless an update to the guidelines is issued earlier.

EU - moving on IGRA Guidelines

From the International Symposium, Research and development of new tuberculosis vaccines - Spain 3 and 4 June, 2010

Dr. Emma Huitric is the Scientific Officer for Tuberculosis at the European Centre for Disease Prevention and Control (ECDC). She has a background in anti-TB drugs and resistance-development to these, having based her PhD-studies in this field of research. Currently at ECDC, Emma’s main focus of work is new tools for tuberculosis; an area which comprises new drugs, diagnostic tools and vaccines. Within this field and under the ECDC mandate, one of the key functions within the TB programme is to provide EU-Member States with the latest, most up-to-date scientific evidence as a support for developing and improving national TB programmes. For example, the TB programme is currently developing EU-adapted guidance on the use of Interferon-Gamma Release Assays (IGRAs) for the diagnosis of latent TB infection and active TB disease. Furthermore, the ECDC recently formed a European Reference Laboratory Network for TB (ERLN-TB), represented by all MS, which will play a further important role in assuring the optimal introduction of new tools for TB as they become available. Within the area of vaccination, the ECDC has focussed on the practices of BCG-vaccination having developed a model for determining BCG vaccination strategies, which it provided to countries in the process of reassessing their BCG vaccination strategies. The ECDC TB programme is represented in several international initiatives, as it is well known that TB control and elimination cannot be attained without a global effort. This includes the StopTBPartnership sub group Introducing New Approaches and Tools for TB (INAT), and the WHO Global Laboratory Initiative (GLI).

Breaking the drought

For a while there I thought that QFT had dropped off the map; from Holland and published in the Clinical and Vaccine Immunology, June 2010

Kinetics of a Tuberculosis-Specific Gamma Interferon Release Assay in Military Personnel with a Positive Tuberculin Skin Test

Sigrid E. van Brummelen,1, Anja M. Bauwens,1 Noël J. Schlösser,1 and Sandra M. Arend2*
 

Central Military Hospital, Department of Pulmonology, Utrecht, Netherlands,1 Leiden University Medical Center, Leiden, Netherlands2

Received 7 January 2010/ Returned for modification 11 March 2010/ Accepted 30 March 2010

Treatment of latent Mycobacterium tuberculosis infection on the basis of the tuberculin skin test (TST) result is inaccurate due to the false-positive TST results that occur after Mycobacterium bovis BCG vaccination or exposure to nontuberculous mycobacteria (NTM). Gamma interferon release assays (IGRAs) are based on M. tuberculosis-specific antigens. In a previous study among BCG-naïve military employees, a positive TST result after deployment was mostly associated with a negative IGRA result, suggesting exposure to NTM. Data regarding the kinetics of IGRAs are limited and controversial. The present study aimed to reassess the rate of false-positive TST results and to evaluate the kinetics of the Quantiferon TB Gold In-Tube assay (QFT-Git) in military personnel with a positive TST result. QFT-Git was performed at the time of inclusion in the study and was repeated after 2, 6, 12, and 18 or 24 months. Of 192 participants, 17 were recruits and 175 were screened after deployment (n = 169) or because of travel or health care work. Baseline positive QFT-Git results were observed in 7/17 (41.2%) and 12/174 (6.9%) participants, respectively. During follow-up, a negative QFT-Git result remained negative in 163/165 (98.8%) participants. Of 18 subjects with an initial positive QFT-Git result, reversion to a negative result occurred in 1/6 (16%) recruits, whereas it occurred in 8/12 (66%) subjects after deployment or with other risk factors (P = 0.046). The quantitative result was significantly lower in subjects with reversion than in those with consistent positive results (P = 0.017). This study confirmed a low rate of positive QFT-Git results among military personnel with a positive TST result after deployment, supporting the hypothesis of exposure to NTM. Reversion of the majority of initially low-positive QFT-Git results indicates that QFT-Git may be useful for the diagnosis of later reinfections.

Gut reaction

Tb Testing in IBD Patients - QuantiFeron vs. PPD

Jason Swoger, MD, Gastroenterology, 08:21PM Jun 1, 2010

The reactivation of infections due to encapsulated organisms, such as tuberculosis, has long been recognized as a potential risk of anti-TNF therapy.  Pre-treatment testing for Tb has long been recommended,  but studies are beginning to evaluate the best methods of testing.

A 2008 study published in the AJG by Schoepfer et al. reported a trial of the interferon-gamma release assay (Quantiferon) vs. Tuberculin skin test (TST) for screening patients with IBD.  The sensitivity of the TST was thought to be low in patients on immunosuppressive therapy, leading to false negative tests.  In addition, false positive tests, secondary to a history of BCG vaccination, or infection with non-tuberculous mycobacterium, could potentially decrease the specificity of the TST.  The Quantiferon test uses an enzyme-linked immunosorbent assay to measure antigen-specific production of interferon-gamma by T cells in blood exposed to M. Tuberculous antigens.  This was thought to increase both the specificity and sensitivity of the test, in comparison to the TST.  The genes encoding the antigens used in the assay are not present in the BCG vaccine or in non-tuberculous mycobacterium.  Cost and laboratory equipment are disadvantages of this assay, while an advantage is that it can be completed in one patient visit.

This study reported on 168 IBD patients and 44 controls (health-care workers, at higher risk of Tb exposure).  81% of IBD patients were on concomitant immunosuppressive therapy.  A positive quantiferon was found in 8.3% of IBD patients, compared to a positive TST in 18% of IBD patients.  The values among controls were 9% and 43%, respectively.  71% of study participants had received the BCG vaccine, which did not influence positive quantiferon results.  There was a negative correlation between the quantiferon assay and the TST in IBD patients, with a kappa value of -0.0297 (when BCG status not considered).  Kappa values were better in the non-IBD group (0.1302), and the agreement between the tests was significantly higher in controls vs. IBD patients (p=0.044).

Among immunosuppressed IBD patients, there were significantly lower rates of positive TST compared to non-immunosuppressed IBD patients, while quantiferon results were not influenced by the use of immunosuppressant medications.  In summary, there was less concordance between tests in the IBD patients compared to controls, quantiferon results seemed to be influenced less by prior BCG vaccination, and the quantiferon assay may be less affected by immunosuppression.

At the recent DDW, 2 abstracts added to the data regarding Tb testing in IBD patients.  Guidi et al. reported their experience with 101 Italian IBD patients.  55.4% were on immunosuppressive therapy.  4 patients had positive findings on both tests, 2 patients had positive quantiferon with negative TST (one on budesonide and one on AZA), and 1 previously vaccinated patient had a positive TST and a negative quantiferon.  They found a significant overall concordance between tests (p<0.0001), though this was a population at low risk for Tb, and with a low rate of BCG vaccination (only 1 patient).  The authors suggest combining the testing methods, especially in immunosuppressed patients, but there seemed to be general agreement overall.

However, Belard et al. evaluated the effect of corticosteroids in 265 patients with autoimmune diseases.  Patients underwent CXR, TST, and quantiferon.  There was a lower quantiferon response in patients on corticosteroids, or on other treatments.  Again, there was poor concordance between the 3 testing methods.  Kappa values for TST/quantiferon were 0.05, for TST/CXR were 0.145, and for quantiferon/CXR were -0.04.  The authors cautioned against the risk of false negative testing in patients on corticosteroids.

The quantiferon assay is not universally available, and a comprehensive cost/benefit analysis has not been carried out in the IBD population.  The data reviewed above does seem to show less false positive tests, due to BCG vaccination, with the quantiferon assay.  Data on testing results on immunosuppressive therapy are mixed, though the quantiferon assay may be superior to TST.  The level of Tb risk - due to prior vaccination, work exposure, or coming from a high-risk country - may play a role in individualizing our evaluation of Tb risk prior to anti-TNF use.  At our institution, we are beginning to test for Tb early on in the disease course, or immediately upon hospitalization, in order to attempt to diminish the influence of immunosuppressive therapy on the results.  Hopefully, as the Quantiferon test becomes more widely available, we may be able to better tailor testing recommendations based on individual patient risk factors, in order to optimize our cost/benefit ratios.

If others are using one or the other of these tests, or have experience to share in IBD patients, either receiving or not receiving immunosuppressants, we would like to hear your experience with these tesing methods.

--------

Jason Swoger
Jason Swoger, MD, MPH, is Assistant professor of Gastroenterology at University of Pittsburgh Medical Center (UPMC). Dr. Swoger completed his internal medicine residency at the Cleveland Clinic, and then went on to complete a fellowship in gastroenterology at Mayo Clinic, in Rochester, Minnesota. As a fellow, Dr. Swoger began to focus on inflammatory bowel disease and completed several clinical research projects aimed at the treatment of both ulcerative colitis and Crohn's disease. Dr. Swoger joined the faculty at UPMC in August 2009 and is seeing patients and conducting clinical research and clinical trials as part of the UPMC Inflammatory Bowel Disease Center.

Link

Spain to go down the drain

Maybe, the market thinks that their CDS are too risky;

According to this site Spain now joins the subgroup of Portugal and Greece ie almost bankrupt

There is also an election this year, this is what is drives the market, uncertainty and risk.

Crossing palms with silver

Billionaire miner Clive Palmer likes to keep everybody informed via his website and his very own whats on page. Of interest, to some, are items about his latest purchase of a resort, his favourite footy club, his enormous wealth and this

Queensland billionaire and mining magnate Clive Palmer has emerged as the largest political donor of the last financial year, tipping more than $800,000 into conservative parties' coffers.

Never mind the cheques, its the hyperbole that needs to be checked

In the heat of the public debate, Queensland billionaire and Liberal National Party (LNP) donor Clive Palmer admits he may have overstated the tax's impact on his projects in Western Australia's Pilbara region.

Mr Palmer owns one of the largest deposits of iron ore in the world, carved out in five separate projects.

The investment for the first development was secured before the super profits tax was announced.

When asked about one project Mr Palmer said was "canned", the chief geologist at Mineralogy, Mark Strizek, said the project was still going ahead.

"All approvals are done and we've also submitted the environmental approvals for the other three or four projects there, so they're all in train," he said.

Mr Palmer says he probably phrased it too strongly.

"It should have been ... slowing them down, waiting to see what happens," he said.

There's no business like show business

Rio has come out saying that it has

had its external auditor verify that its level of direct taxes paid in Australia is much higher than the government has been claiming in its attacks on the industry.

and

effective tax in the past 10 years has averaged more than 35 per cent - or $20 billion in corporate taxes and royalties.

What they didnt say was that royalties are deductible as an expense.

A quick look at their financials reveals

2009 Pre Tax Profit  10,295.46
2009 Tax Expense    (-2,213.18) = 21%

2008 Pre Tax Profit  24,238.24
2008 Tax Expense   (-6,826.28)  = 28%

2007 Pre Tax Profit  11,409.94
2007 Tax Expense   (-2,475.05)  = 22%

Stanford admissions

Whilst Stanford have been setting setting the pace for their HCWs their latest document needs to be read twice;

TB Skin Testing (please check which documentation you are submitting)

• 
  

  Documentation of 2 step TB skin testing withing the past three (3) months (TB Quantiferon Blood Test is required upon arrival @ SHC and LPCH) or

• 
  

  Documentation of Quantiferon test within past three (3) months

• 
  

  Chest Xray withinn three (3) months if Hx. of Positive skin test or QFT

Apparently on admission you must provide past record of TB testing plus have a QFT

I guess that is it, for Stanford Hospital & Clinics and Lucille Packard Children's Hospital it is QFT or nothing

What happens when you take the money off the table?

HT Peter Martin