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[podcast] Ronda Greaves: e-Learning

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Dr Ronda Greaves is the Senior Lecturer in Clinical Biochemistry at RMIT University, Bundoora West Campus. She is the Head of the Clinical Biochemistry Mass Spectrometry Laboratory and is also an Honorary Research Fellow at the Murdoch Children’s Research Institute (MCRI).

Dr Greaves’ main interests focus on specialised paediatric clinical biochemistry, which encompasses endocrinology, gastroenterology and respiratory medicine. She is involved in projects which have an emphasis on harmonisation and standardisation of mass spectrometry measurement procedures. Specific paediatric analytical interests include serum and urine steroids for the investigation of disorders of sex development, environmental and genetic influences of vitamins, and sweat chloride as a function test to diagnose cystic fibrosis. These interests are enhanced through collaborative projects with the Murdoch Children’s Research Institute in Melbourne, and the National Hospital of Pediatrics in Hanoi Vietnam.

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Satellites Predict a Cholera Outbreak Weeks in Advance

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Orbiting satellites can warn us of bad weather and help us navigate to that new taco joint. Scientists are also using data satellites to solve a worldwide problem: predicting cholera outbreaks.

Cholera infects millions of people each year, leading to thousands of deaths. Often communities do not realize an epidemic is underway until infected individuals swarm hospitals. Advanced warning for impending epidemics could help health workers prepare for the onslaught—stockpiling rehydration supplies, medicines and vaccines—which can save lives and quell the disease’s spread. Back in May 2017 a team of scientists used satellite information to assess whether an outbreak would occur in Yemen, and they ended up predicting an outburst that spread across the country in June.

Testing the waters

Cholera is a waterborne bacterial disease that causes intestinal distress and dehydration. The illness can progress rapidly, peaking within hours or days. An overwhelming majority of cases occur in developing countries, exasperated by poor sanitation, urban slums and refugee camps.

Cholera can spread two ways: endemically or epidemically. Coastal communities are hot spots for endemic episodes. Ocean-dwelling cholera flourish in dry and hot seasons, and can be carried ashore by high tides. Coastal towns and villages become infected, but in many locales the process happens regularly and residents are reasonably prepared for these waves of infection.

Epidemic contamination is much less predictable, and can take inland communities by surprise. “They are not prepared—they don’t have vaccines, they don’t have dehydration solutions,” says Antarpreet Jutla, a hydrologist and civil engineer at West Virginia University who led the Yemen study. Cholera can spread easily via water, and with a burst of warm temperatures, high precipitation and poor water infrastructure, an epidemic can blossom quickly.

Disease in real time

Quickly collecting ground data about these kinds of events can be challenging, especially in chaotic locations. Yemen is a textbook case. “Yemen has massive civil unrest, people are moving around, [there is] political instability—there’s no way for us to get a single data point,” Jutla says. But satellites gave his team a way to assess the disease risk from the sky, and without being in the country.

At the American Geophysical Union annual meeting in December, Jutla presented the group’s prediction model of cholera for Yemen. The team used a handful of satellites to monitor temperatures, water storage, precipitation and land around the country. By processing that information in algorithms they developed, the team predicted areas most at risk for an outbreak over the upcoming month.

Weeks later an epidemic occurred that closely resembled what the model had predicted. “It was something we did not expect,” Jutla says, because they had built the algorithms—and calibrated and validated them—on data from the Bengal Delta in southern Asia as well as parts of Africa. They were unable to go into war-torn Yemen directly, however. For those reasons, the team had not informed Yemen officials of the predicted June outbreak.

The successful prediction did give the team confidence that their model, built on a variety of data types, is on the right track. “One of the things I like,” says Michael Wimberly, an ecologist at South Dakota State University, is that they are not looking “only at correlation to rainfall.” Wimberly uses remote-sensing technologies to monitor diseases like West Nile virus, and was not involved in the study. He says the cholera model is well grounded in hydrology and epidemiology. “They have an understanding of different types of epidemics that occur in different seasons; it’s very sophisticated.”

Helping the sick

With a fast-moving disease like cholera, advanced warnings matter, especially in remote places. They offer a major advantage, says study co-author Rita Colwell, a microbiologist at the University of Maryland, College Park, and a former director of the National Science Foundation. Colwell has been studying global infectious diseases for decades, and says their model for cholera is highly predictive. “This is a mechanism that will help preparation with medical supplies and vaccinations.”

Wimberly agrees. “That’s the value of disease forecasting: to be able to anticipate the right place, a little bit ahead of time, so we can get those tools out there.”

The team is cautious about broadcasting disease forecasts, not wanting to create public panic. They are working with several international agencies on the best way to communicate future predictions. They are also developing a platform that uses hydrologic and societal conditions to determine the probability of cholera outbreaks globally—with a goal of providing warnings that offer four weeks of lead time.

Author: Sarah Derouin

Source: scientificamerican.com

Evidence Based Guidelines to Eliminate Repetitive Laboratory Testing

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Interventions based on educating clinicians about appropriated indications and costs of laboratory testing had mixed results. Decreased test ordering following education was not sustained. A randomized clinical trial revealed no significant effect on clinicians ordering practices after displaying Medicare fees for 30 different laboratory tests in the EMR.

Several studies that audited physician test ordering practices and provided individual and group feedback of their results reported a significant reduction in laboratory testing per patient day. The biggest impact occurred with high utilizers.

May EMR interventions that limited the ability of providers to repeat laboratory tests led to a consistent and sustainable reduction in blood draws. In one example, clinicians were limited to ordering 5 common laboratory tests only once or with an expiration of 24 hours. EMR based strategies were consistent and sustainable.

Studies that combined education, audit and feedback and EMR restrictions yielded the best results.  Several studies confirmed reducing repetitive laboratory testing was not associated with an increase in adverse patient outcomes.

The authors of the JAMA paper provided a blueprint for a multimodal approach to reducing repetitive laboratory testing.

  • Collectively outline and standardize best practice. Data should be provided by those with authority and responsibility to implement institutional change.
  • Target a multidisciplinary audience across all departments and services that care for hospitalized patients.
  • Tailor educational material for each specialty.
  • Include all health care professional levels to foster culture change.
  • Engage senior leadership and respected professional leaders in each department to deliver the lectures or at least be present at educational events.
  • Focus educational materials on the appropriate indication for various laboratory tests for high utilizers. Consider including laboratory costs.
  • Emphasize education on potential adverse effects of repetitive testing, including patient discomfort, hospital-acquired anemia, cost, and resultant downstream testing.
  • Provide evidence-based reassurance that less laboratory testing does not lead to delayed diagnosis or misdiagnosis.Encourage daily discussions on rounds to specify the clinical rationale for laboratory testing.
  • Provide ordering clinicians with real-time data on their personal ordering patterns with an institutional benchmark. Provide anonymized, specialty-specific comparison data at routine intervals that include peer comparisons on laboratory utilization.
  • Encourage high utilizers to develop a personalized, educative approach to reduce unnecessary ordering practices.
  • Leverage the EMR to restrict the ability to order repetitive daily laboratory tests.
  • Identify and remove repetitive laboratory testing options from all order sets.
  • If this is not feasible, begin by limiting preordered, repeated daily laboratory tests to a short, defined period, such as 48 to 72 hours.
  • Create alerts that display prior normal or stable results for the test being ordered.
  • Encourage clinicians to engage in reflective ordering patterns based on clinical indication review. The goal is to increase targeted testing rather than decrease laboratory testing overall.

Reference: Eaton KP, et al. Evidence-based Guidelines to Eliminate Repetitive Laboratory Testing. JAMA Intern Med, doi:10.1001/jamainternmed.2017.5152 , published online October 16, 2017.

Sourceclinlabnavigator.com

FDA Warns that Biotin May Affect Some Lab Test Results

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But biotin may interfere with some laboratory testing, causing results of tests to be either falsely high or falsely low. These inaccurate test results can cause healthcare practitioners to misdiagnose and mistreat their patients.

Laboratory professionals have known about this potential problem for some time. In late November 2017, the Food and Drug Administration (FDA) published a safety alert to make the public and healthcare practitioners more aware that biotin can “significantly interfere with certain lab tests and cause incorrect test results…” According to the safety alert, there has been “an increase in the number of reported adverse events [injuries associated with medical care], including one death, related to biotin interference with lab tests.” The one death occurred when a patient taking high doses of biotin had falsely low troponin results from a troponin test known to have interference from biotin. Troponin is a biomarker that helps diagnose heart attacks.

Excess biotin in patients’ blood samples can interfere with types of tests called immunoassays because many use biotin as part of the testing methodology. For example, some immunoassays use biotin to bind chemicals and other substances in the blood to the test tube so they can be measured. Excess biotin in the blood from supplements can block that binding and the substance won’t be measured accurately.

Most of the published research on biotin interference covers hormone tests, such as parathyroid hormone (PTH), thyroid stimulating hormone (TSH), T4 and T3 tests, as well as tests for troponin. However, because biotin is used in so many immunoassays, scientists say it could interfere with many others.

In its Safety Communication, the FDA advises healthcare practitioners to ask their patients if they are taking any biotin supplements and inform the testing laboratory if interference from biotin is a possibility. They should also consider biotin interference as a potential reason for lab results not matching with a patient’s signs and symptoms and/or suspected health condition.

One important way people can protect themselves from biotin interference with their lab tests, according to the FDA, is to know exactly what is in the supplements they are taking. It’s not always obvious that a supplement contains biotin—for example, vitamins labeled for healthier hair, nails, and skin may only list biotin as an ingredient on the back label, in small print.

The FDA urges the general public to that know that biotin is found in many over-the-counter supplements in levels that may interfere with laboratory tests. Examples include:

  • B-complex vitamins
  • Coenzyme R
  • Dietary supplements for hair, skin, or nail growth
  • Multivitamins
  • Prenatal vitamins
  • Vitamin B7 supplements
  • Vitamin H

Patients should tell their healthcare practitioners if they are taking or plan to take biotin or a supplement containing biotin, and consider the possibility that biotin was the cause of test results that don’t seem to make sense. Healthcare practitioners may advise their patients to discontinue taking biotin supplements a few days before having lab tests done.

The FDA will continue to monitor reports of adverse events of biotin interference with immunoassays and will update the public if significant new information becomes available.

Source: LTO

70th AACC Annual Scientific Meeting & Clinical Lab Expo

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JOIN THE GLOBAL LABORATORY MEDICINE COMMUNITY

July 29 – August 2, 2018. McCormick Place. Chicago, Illinois

The 70th AACC Annual Scientific Meeting & Clinical Lab Expo is the largest global scientific conference and tradeshow in the field of laboratory medicine. At this dynamic meeting, you’ll have the opportunity to:

  • Connect with global leaders in clinical chemistry, molecular diagnostics, mass spectrometry, translational medicine, lab management, and other areas of breaking science in laboratory medicine.
  • Learn about cutting edge technology. The AACC Clinical Lab Expo has more than 200 new product introductions each year.
  • Hear vital research and learn about important changes in the field. With more than 200 educational and scientific sessions, you can design an educational experience that meets your need to stay ahead of changes in the field.

Web page: aacc.org/2018-annual-meeting

No more information is available on infobioquimica.org.
For further requests, you can contact the organizers of the event.

Reprogramming bacteria instead of killing them could be the answer to antibiotic resistance

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Author: Yu-Hsuan Tsai. Lecturer in Organic Chemistry, Cardiff University

That means we can affect the genetic instructions that get sent to an organism’s body by changing its environment or with drugs.

This field of “epigenetics” is already helping doctors understand how certain diseases work, why exercise can be so beneficial, and how we might be able to alter the aging process. But my colleagues and I are trying to investigate the role of epigenetics in bacteria.

We recently studied a possible way to affect bacterial epigenetics that might be able to stop infections without using antibiotic drugs. And given that many bacteria are becoming resistant to existing antibiotics, that could open up a vital new way of treating disease.

Our study looked at the bacterium Acinetobacter baumannii, which is a major cause of the infections people can catch in hospitals and which kills up to 70% of people who are infected with it. Antibiotics no longer work on some strains of A. baumannii – and the World Health Organization recently ranked it as the greatest bacterial threat to human health.

We do already have some so-called antivirulence drugs that don’t kill bacteria but make them harmless so that the body’s immune system can clear them out without leaving any behind to become resistant to the drug. Coming up with a way to affect bacteria’s epigenetics rendering the bugs harmless could help us create new antivirulence drugs that would make a huge contribution to medicine.

To start this process this we first turned to human epigenetics. The most common way of affecting our epigenetics is to add a small molecular tag to our genetic material that turns on or off a related gene. In particular, we can add a tag known as an acetyl group to an important protein called histone .

Histone organises our 2m-long DNA molecules so that they can fit neatly inside our 100 micrometre-long cells. Adding the acetyl tag is a natural mechanism used by cells to change the way histone interacts with DNA. Adding the acetyl tags normally activates certain genes, meaning they change the way the cell behaves. Failures in this histone modification process are linked to cancers, cardiovascular diseases and many neurodegenerative disorders.

Bacterial cells have their own version of histone known as HU, which organises their DNA and is involved in making all its functions work. Bacteria that are referred to as “Gram-positive”, such as the ones in our digestive system that help us break down food, can’t survive without working HU. And “Gram-negative bacteria”, which are typically the ones that make us ill such as Salmonella enterica, become much less harmful without HU.

New drugs

In our study, we found that adding an acetyl tag to HU significantly affected the way it interacted with the DNA. This means it’s highly likely that such modification makes epigenetic changes, affecting how the bacteria grow and infect other organisms. So if we can create drugs that make these changes to bacterial proteins in this way, we could have a new way of stopping infections.

This is a really important challenge in medicine right now, because bacteria that are resistant to antibiotics kill 700,000 people a year worldwide. If we don’t find new treatments, the annual death toll could rise to 10 million by 2050.

Once we verify the link between specific epigenetic changes and bacterial infection, we can begin looking for substances that alter bacteria’s epigenetics in this way to make it less harmful. There are already several molecules targeting human epigenetics in a similar way under preclinical development or in clinical trials. So a drug that “turns off” bacteria’s ability to cause infections may not be too far away.

This article was amended on 15 December 2017 to state that the annual death toll from antibiotic-resistant bactaeria coud rise to 10 million by 2050, not 2025 as originally stated.

Source: theconversation.com

Recent Advances in Syphilis Testing

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Especially in light of these incidence figures, healthcare providers need to screen populations at-risk, recognize signs and symptoms of disease, and provide timely treatment. For example, the U.S. Preventive Services Task Force recommends syphilis screening every 3 months for persons who are at increased risk for infection, including HIV-positive men and men who have sex with men. This rising tide of new cases and frequent screening for at-risk populations definitely will culminate in increased testing demands, and laboratories should expect to see more specimens for screening.

Direct Versus Serologic Methods

Syphilis can be diagnosed using direct detection (dark field microscopy, direct fluorescence assay, or polymerase chain reaction) or serologic methods. Direct methods help detect early stages of the disease, but are rarely used nowadays. T. pallidum cannot be cultured in vitro using standard microbiology media. However, this microorganism elicits in vivo production of both treponemal (IgM, IgG, IgA) and non-treponemal (IgM, IgG, and rapid plasma reagin or RPR) antibodies. Therefore serology testing remains the mainstay of syphilis diagnostics and can be accomplished via three algorithms: traditional, reverse, and European.

Established Algorithms, New Technologies

Both the traditional and reverse algorithms rely on assays that detect non-treponemal and treponemal antibodies. The traditional algorithm involves screening with a non-treponemal antibody assay and confirming reactive samples with a treponemal antibody assay. In contrast, the reverse algorithm calls for screening with a treponemal assay and confirming reactive samples with a non-treponemal antibody assay. This algorithm resolves discordant results (a reactive treponemal and negative non-treponemal) by testing with another treponemal assay. The European algorithm utilizes two different treponemal assays, one for screening and a second for confirmation.

Most laboratories in the U.S. follow the traditional algorithm; however, many high-volume operations have transitioned to the reverse algorithm approach. Several factors prompted this shift, including the high-throughput and laboratory information system connectivity offered by automated testing platforms, as well as the opportunity to reduce manual labor and costs.

In the U.S., almost all non-treponemal assays are manual, including RPR and the Venereal Disease Research Laboratory test, and offered by multiple manufacturers. The exception is Gold Standard Diagnostics’ AIX1000 RPR automated test, which last year received Food and Drug Administration (FDA) clearance. Other automated RPR assays will be available in the near future.

The opposite is true for treponemal assays; just a few are manual, including fluorescent treponemal antibody absorption, T. pallidum hemagglutination assay, and T. pallidum particle agglutination (TP-PA). Many automated treponemal immunoassays are available from multiple manufacturers. Examples include CAPTIA Syphilis-G, Advia Centaur Syphilis, Architect Syphilis TP, Trep-Sure Syphilis Total Antibody EIA, TREP-SURE Anti-Treponema EIA Screen, LIAISON Treponema Assay, Elecsys Syphilis, BioPlex 2200 Syphilis IgG, and BioPlex 2200 Syphilis Total & RPR. Automated TP-PA assays will become available in the future in the U.S.

The most recently FDA-cleared assay for syphilis, the BioPlex 2200 Syphilis Total & RPR, could be a game-changer in syphilis diagnostics. This automated, dual assay simultaneously detects and differentiates both treponemal antibodies (IgG/IgM) and non-treponemal RPR antibodies, and provides RPR titer determination up to 1:64. Laboratories that implement this assay will be able to utilize either the traditional or reverse testing algorithm, and still have both tests automated with faster turnaround times, increased throughput, and improved workflows. Additional studies are needed to assess the performance of this and other new assays in the pipeline.

Reliable and timely detection of acute syphilis infection is a necessity, especially in community testing programs and in sexually transmitted infection clinics where loss of patient follow-up is a major concern. CDC issued a call-to-action to develop sensitive screening tests that would enhance detection of primary syphilis and speed treatment for this age-old contagion. Hopefully, additional clinical experience with the novel assays described here and others coming on the market will lead to more patients being diagnosed and managed, ultimately improving syphilis prevention and control.

Author: Vera Tesic, MD, MS, D(ABMM), M(ASCP)  // Date: DEC.1.2017  //

Source: AACC

IFCC eNews: November-December edition

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En esta edición:

  • The retrospectoscope: a look back at WorldLab 2017 Durban
  • Record number of travel scholarships contribute to success of WorldLab Durban 2017
  • Young Scientists Symposium at WorldLab Durban
  • IFCC Regional Representatives 2018-2020 elected
  • Let us join together to achieve excellence in lab medicine!
  • Opinion: our common home and the laboratory
  • IFCC Working Group on CSF Proteins & EC-JRC Alzheimer Video on EuroNews
  • IFCC standardisation of Carbohydrate Deficient Transferrin (CDT)
    IFCC welcomes a new Affiliate Member: LMC, China
  • IFCC is seeking an eAcademy coordinator
  • IFCC electronic journal (eJIFCC) and IFCC app
  • Season’s greetings from IFCC
  • NEWS FROM REGIONAL FEDERATIONS AND MEMBER SOCIETIES
    • News from the Spanish Society of Laboratory Medicine (SEQCML)
    • Experts produce a Spanish consensus on recommended values for the lipid profile
    • Presentation of the SEQCML POCT online database
    • News from Paraguay: evaluation of patients with kidney diseases
    • News from the Chilean Society of Clinical Chemistry
    • 13th EFLM Symposium for Balkan Region
    • News from Croatia: research integrity workshop
    • VLP Report from COLABIOCLI Congress
    • Updates of the EFLM publication list
    • EFLM recommendation for venous blood sampling: call for comments
  • IFCC PROFESSIONAL SCIENTIFIC EXCHANGE PROGRAMME (PSEP)
    • My experience at Mayo Clinic

THE IFCC ENEWS IS AVAILABLE IN DIFFERENT FORMATS: FLIP Page & PDF! 

Urine lipoarabinomannan glycan in HIV-negative patients with pulmonary tuberculosis correlates with disease severity

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Using hydrogel “nanocage” nanoparticles and a chemical bait with high affinity for LAM, Paris et al. showed that patients negative for HIV with active tuberculosis infections had detectably higher concentrations of LAM in their urine than patients without active tuberculosis infections. Nanocages could also be used to detect cytokines and other antigens present in low concentrations in urine, demonstrating the versatility of the technology as a method to detect and monitor infections.

Abstract

An accurate urine test for pulmonary tuberculosis (TB), affecting 9.6 million patients worldwide, is critically needed for surveillance and treatment management. Past attempts failed to reliably detect the mycobacterial glycan antigen lipoarabinomannan (LAM), a marker of active TB, in HIV-negative, pulmonary TB–infected patients’ urine (85% of 9.6 million patients). We apply a copper complex dye within a hydrogel nanocage that captures LAM with very high affinity, displacing interfering urine proteins. The technology was applied to study pretreatment urine from 48 Peruvian patients, all negative for HIV, with microbiologically confirmed active pulmonary TB. LAM was quantitatively measured in the urine with a sensitivity of >95% and a specificity of >80% (n = 101) in a concentration range of 14 to 2000 picograms per milliliter, as compared to non-TB, healthy and diseased, age-matched controls (evaluated by receiver operating characteristic analysis; area under the curve, 0.95; 95% confidence interval, 0.9005 to 0.9957). Urinary LAM was elevated in patients with a higher mycobacterial burden (n = 42), a higher proportion of weight loss (n = 37), or cough (n = 50). The technology can be configured in a variety of formats to detect a panel of previously undetectable very-low-abundance TB urinary analytes. Eight of nine patients who were smear-negative and culture-positive for TB tested positive for urinary LAM. This technology has broad implications for pulmonary TB screening, transmission control, and treatment management for HIV-negative patients.

Authors: Luisa Paris1, Ruben Magni1, Fatima Zaidi1, Robyn Araujo2, Neal Saini1, Michael Harpole1, Jorge Coronel3, Daniela E. Kirwan4, Hannah Steinberg5, Robert H. Gilman5, Emanuel F. Petricoin III1, Roberto Nisini6, Alessandra Luchini1,* and Lance Liotta1

  1. George Mason University, Manassas, VA 20110, USA.
  2. Queensland University of Technology, Brisbane, Queensland 4000, Australia.
  3. Universidad Peruana Cayetano Heredia, Lima 31, Peru.
  4. St. George’s Hospital, London SW17 0QT, UK.
  5. Johns Hopkins University, Baltimore, MD 21205, USA.
  6. Istituto Superiore di Sanità, Rome 00161, Italy.

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