Recent Developments
Two-Drug Combination May Treat Cocaine Addiction
A Naltrexone and buprenorphine combination (low dose) has made laboratory rats at The Scripps Research Institute less likely to take cocaine compulsively. This is a standard preclinical test that generally comes before human trials. This is exciting for scientists as there are currently no FDA-approved medications which treat cocaine addiction. Many drugs have been tried for this but all have failed to show significant efficacy in treating people addicted to cocaine, according to Scripps Research Professor George Koob, chair of the Scripps Research Committee on the Neurobiology of Addictive Disorders and team leader for the research, which appears in last week’s Science Translational Medicine journal.
“Combining drugs with multiple actions may be a useful approach that has not been utilised extensively.” (Koob)
“These findings potentially represent a huge bridge from basic research to the establishment of a new and effective medication for cocaine addiction.” (Senior Research Associate Leandro F. Vendruscolo, a co-author on the study with Scripps Research Colleagues Assistant Professor Sunmee Wee (first author), former Research Associate Kaushik Misra, and Research Associate Joel Schlosburg)
Cocaine abuse is a massive problem in the United States. In 2008, approximately 1.9 million Americans had used cocaine in one month and about a quarter of all drug-related emergency room visits are linked to cocaine use (482, 188 in 2008) according to the National Institute on Drug Abuse. Doctors have reached a better understanding of how cocaine affects the brain’s physiology. The focus for treatment used to be solely on therapy, counselling and other forms of social support, but today doctors are looking at issuing anti-stress medications and other pharmaceuticals as well as traditional therapies to address long-term physiological effects of a drug on the body.
When cocaine is snorted, injected or smoked, the chemical enters the bloodstream and crosses the blood-brain barrier, accumulating rapidly in areas linked to the so-called motivational/pleasure circuits of the brain;
“There, the cocaine molecules interfere with the normal regulation of dopamine by binding to dopamine transporters and blocking them from recycling the neurotransmitter.” (ScienceDaily)
The build-up of dopamine in the brain’s motivational systems produces a euphoric feeling in the user, a rush that comes seconds after taking the drug and lasts for several minutes. An opponent process then takes place; the physiological action triggers opposing actions in the brain, one of which increases in a neuropeptide dynorphin that results in stress/aversive-like effects.
Koob and his colleagues have demonstrated that excessive and long-term cocaine use changes the point at which euphoria is achieved, in part by activating the stress/aversive systems in the brain. Prolonged usage results in more of the drug being needed by the user to achieve the same effect, and after cocaine use increases, stress and aversion remain elevated.
In 2009, Koob’s team found that two different systems (kappa opioid system and mu receptor) had different effects on the cocaine intake or rats with short versus extended access to the drug. The findings can be observed in a paper in Psychopharmacology;
“This finding gave us a firm idea that, during extended access to cocaine, the positive brain reward function becomes attenuated while the negative brain stress/aversive systems get involved.” (Wee)
This resetting can result in the withdrawal and cravings addicts experience when they quit cocaine use. These effects drive relapse because drug use can temporarily alleviate their negative symptoms.
Using pharmaceuticals to treat drug addiction has the potential to result in the restoration of the brain’s reward and stress/aversive systems to normal. This new study explored the combination of two existing pharmaceuticals to treat cocaine addiction – one that does not work by itself and one that works but is addictive so it is not prescribed.
Naltrexone is already approved by the FDA for treating alcohol and tobacco addiction. Buprenorphine is an opiate and has been used by heroin and cocaine addicts to help them gradually quit the illegal addictive drugs rather than stopping immediately or going “cold turkey”. Buprenorphine has mu opioid partial antagonist effects which moderately produces the pleasurable effects of opioids. It also has kappa opioid antagonist effects which reverse the stress/aversive-like effects of opioid withdrawal by blocking the actions of dynorphin. However, addiction to buprenorphine can occur, and if used to treat cocaine addiction it has the possibility to just become a substitute and then patients would suffer from buprenorphine withdrawal instead of cocaine withdrawal.
The Scripps Research team have developed a solution to this problem; they have combined buprenorphine with a low dose of naltrexone and showed that by administering this combination to rats in the laboratory, it effectively blocked compulsive cocaine self-administration without causing the physical opioid withdrawal syndrome observed in rats treated with only buprenorphine.
References
Wee. S., Vendruscolo, L.F., Misra, K.K., Schlosburg, J.E. & Koob, G.F. (2012) A Combination of Buprenorphine and Naltrexone Blocks Compulsive Cocaine Intake in Rodents Without Producing Dependence. Science Translational Medicine; 4:146
stm.sciencemag.org/content/4/146/146ra110
Serious Side-Effects Reduced in Trials of New Targeted Drugs
Patients in early clinical trials of new-style targeted cancer therapies appear to have a much lower risk of the most serious side-effects than with traditional chemotherapy, according to a new analysis.
Researchers at The Institute of Cancer Research London, and The Royal Marsden NHS Foundation Trust analysed data from 36 Phase I trials run by the organisations’ joint Drug Development Unit.
The study, published today in August’s Annals of Oncology, found the overall risk to patients of suffering a life-threatening side-effect was around seven times less than for traditional cytotoxic agents.
Most new cancer drugs developed over recent years are targeted agents, which attack the specific genetic or molecular faults driving cancer growth, rather than one-size-fits-all chemotherapeutics, which kill all rapidly dividing cells.
Recent studies have shown that patient response rates in Phase I trials of new-generation targeted drugs are approximately two-fold higher than for old-style drugs. But until now, the risk of side-effects to patients taking part in early stage trials of new-style drugs has been unclear.
Senior author Dr Rhoda Molife, a medical oncologist and senior investigator in Phase I clinical trials in the Drug Development Unit of The Institute of Cancer Research and The Royal Marsden, said: “Our study found that the risk of developing a serious side-effect in a Phase I trial of a targeted drug was relatively low, compared with previous analyses of similar trials of old-style chemotherapies.
“The theory behind targeted drugs is that they should affect only cancer cells that have a specific fault and spare healthy cells, which we hoped would lead to higher rates of efficacy and lower rates of side-effects. It’s very pleasing that our study seems to back this up, at least in the context of Phase I trials.”
“Importantly, we also identified characteristics that put patients at higher risk of these toxicities, including if they were sicker when joining the trial. This will help doctors make the right choices about who should be given new drugs in early stage clinical trials.”
Scientists retrospectively analysed data from 687 patients treated at the Drug Development Unit of The Institute of Cancer Research and The Royal Marsden between January 2005 and December 2009. They had a range of cancer types, with gastrointestinal, gynaecological and sarcoma the most common.
The Drug Development Unit of The Institute of Cancer Research and The Royal Marsden is supported by the National Institute for Health Research Biomedical Research Centre for Cancer, and also receives funding from Cancer Research UK and the Experimental Cancer Medicine Centre network.
For targeted drugs, the most common toxicities were gastrointestinal – such as loss of appetite, diarrhoea and vomiting – and fatigue, while side-effects for cytotoxic drugs are generally haematological or cardiovascular in nature
Patients were more likely to suffer side-effects if they were given a higher dose than that which the trial later found to be optimal, or if they were sicker when they joined the trial. The findings should help guide researchers in selecting patients for trials and improving trial design.
Professor Alan Ashworth, Chief Executive of The Institute of Cancer Research, said: “The discovery of targeted therapies is revolutionising the way we treat cancer, and is a key focus of our research here at The Institute of Cancer Research. Many of these drugs have individually transformed the care of certain cancers, but the strength of this study is that it helps confirm the validity of the overall approach.”
Reference
Anti-Angina Drug could Protect against Carbon Monoxide Poisoning
An international research team, led by the University of Leeds, has discovered that a common anti-angina drug could help protect the heart against carbon monoxide poisoning. The drug “ranolazine” can significantly reduce the number of deaths from such heart difficulties as arrhythmias brought on by exposure to carbon monoxide.
This discovery could have a positive impact on those who have been exposed to toxic levels of the gas as the drug can be developed into a protective treatment.
“When patients are admitted to hospital with carbon monoxide poisoning, the main problem doctors face is preventing damage to the body whilst the body slowly removes the chemical. We’ve shown that ranolazine can rapidly protect the heart and prevent the kind of cardiac events which threaten patients long after their exposure to the gas.” (Professor Peers from University of Leeds, leader of the research)
1.6 million deaths occur worldwide each year due to carbon monoxide poisoning. The biochemical mechanisms which cause damage to the heart have not been fully understood, until now. Ranolazine (sold under the trade name “Ranexa”) was approved in the United States in 2006 for the treatment of angina. It targets a sodium channel in the heart which is the same channel that can induce irregular heartbeats.
To understand why carbon monoxide can trigger arrhythmias, researchers at University of Leeds examined the effect of the drug in single cardiac cells. The results showed that exposure to carbon monoxide caused a key membrane channel carrying sodium ions through the heart to stay open for longer. This then caused calcium to build up within cells resulting in an alteration in the heart’s regular cycle.
When colleagues at the Université Montpellier 1 and Université de Avignon in France trialled ranolazine on rats exposed to carbon monoxide, they found that the drug significantly reduced the chance of arrhythmia.
“Whilst the link between arrhythmias and carbon monoxide has been known for over 50 years, this is the first piece of research to explain the underlying process. At the molecular level, we have shown that the mechanism underlying this adverse effect of carbon monoxide is a rise in the level of nitric oxide within cells, which in turn alters the function of the sodium channel.” (Professor Derek Steele from University of Leeds, co-author of the research)
These findings may also be beneficial to those living in built up areas or whose employment involves the exposure to carbon monoxide. Human clinical trials are needed to confirm this, however.
“The next step will be to replicate these findings in human trials. As the drug has been clinically approved, roll out of this treatment could begin soon after we have these results.” (Peers)
“This study is a good example of research being used to better understand the underlying causes of an abnormal heart rhythm and in this case it has uncovered the ability of an old drug to perform a new trick. Carbon monoxide poisoning is tragically common but hopefully these promising results can be replicated in people so that it saves lives in the future.” (Dr Hélène Wilson, Research Advisor at the British Heart Foundation (BHF), which co-founded the study)
References
Hopewell, P.C. du Melle, F. and Murray, J.F. (2012) Evolution and Revolution: The formation of Today’s American Thoracic Society (part 2): American Journal of Respiratory and Critical Care Medicine
Images
10 (or more) Annoying Pre and Post Analytical Problems and how to Eliminate Them
The AACC Thought Leadership Series
10 (Or More) Annoying Pre and Post Analytical Problems and How to Eliminate Them – Webinar Notes
Speaker:
Michael Astion, MD, PhD
Division Chief of Laboratory Medicine, Seattle Children’s Hospital
Clinical Professor of Laboratory Medicine, University of Washington Dept. of Laboratory Medicine
Editor:
Patient Safety Focus Section of Clinical Laboratory News
Overview
- List of pre and post analytic errors
- Latent factors underlying many errors
- Strong vs. weak interventions
- A note about disciplined problem solving methods (e.g. Lean/CPI)
- Measurement: It’s important
- Error rates: What to aim for?
- Decreasing error rates for 10 (or more) pre and post analytic errors
- Conclusions
List of 10 Preanalytic Errors
- Physician orders wrong test
- Requisition incorrect
- Specimen unlabelled, mislabelled, illegible (includes swapped labels)
- Failure to collect a specimen
- Wrong container
- Specimen lost or delayed
- Other specimen transport error
- Data entry error during accessioning of requisition (e.g., wrong patient, wrong test)
- Specimen processing error (e.g. aliquot labelling error)
Postanalytic errors include one or more of the following six errors;
- Postanalytic data entry error
- Oral miscommunication of results
- Error in reporting to downstream printer, fox, or electronic medical record (EMR)
- Physician or other provider fails to retrieve test result
- Failure to communicate critical value
- Provider misinterprets lab result
Most of the errors discussed here are noncognitive and will not respond dramatically to simple interventions like more training and being more careful.
- Noncognitive errors: Due to interruption/lapse in a normally automatic task. Exacerbated by…
- Distractions
- Interruptions
- Fatigue
- Cognitive errors: A smaller per cent of errors are due to lack of knowledge
Latent Factors that Contribute to Many Different Types of Lab Errors
- Improper choice of work culture
- Incompetence
- Overuse of self-assessment
- Disconnection from patients
- Misaligned financial incentives
- Fatigue
- Shallow analysis
All interventions to errors require the measurement of quality and the monitoring of behaviour. Monitoring = better performance
Examples of quality measurements taken from a Quality Dashboard covering phlebotomy, lab transportation, processing and call centre
Phlebotomy
- % AM results available by rounds
- Productivity per FTE
- Error rates (mislabel, wrong tube…)
- Re-label rate
Couriers: arrival time (goal 98% on time delivery)
Call Centre
- Time to first answer (goal <6 secs)
- Abandon call rate (goal <3%)
- FTE: time logged into system
Specimen processing…
- Tally of each type of work by shift
- Goals: Increase number of interfaced requisitions apply special methods to highest risk work
- Workload as a function of time of day. (Goal: workload levelling)
- Number of specimens processed per hour per FTE (Goal: work at 70% to 80% of capacity)
- Log in error rate for each type of requisition
- Goal: error rate for manual login to 3 per 1000 reqs
Realistic Error Rates: Hard to be better than 1/1000 error rate without advanced design and technology
10-1 Clear process, reliance on education, vigilance to achieve goal
- Failure to wash hands
10-2 Clear process using basic human factors principles, reliance on education, vigilance
- Errors in filling out lab requisition
- Failure to give test results to patients
- Suboptimal specimen
10-3 Clear process using human factors and systems for error identification and mitigation
- Mislabelled specimens
10-4 Advanced designed and automation, error ID/mitigation
10-5 Specimen loss
- Computer interface errors
Choose strong interventions to reduce errors even though they are risky, time consuming and difficult to implement
A useful way – without jargon – to look at interventions:
The guide to intervention strengths
- Weaker interventions
- Training
- Call for enhanced vigilance
- Double checks
- Warning labels
- Memos
Intermediate Strength Interventions
| Intervention | Example |
| Reduce distractions |
|
| Enhanced inter-personal communication |
|
| Workflow adjustments |
|
| Intermediate software/hardware enhancements |
|
Stronger Interventions
| Intervention | Example |
| Eliminate steps and waste |
|
| Equipment and personnel Standardisation |
|
| Physical Plant Change |
|
| Major Software Enhancement |
|
Intervention strength as applied to data entry errors (pre or post analytic)
- Weaker (useless, feels good):
- Retrain the techs
- Tell them to slow down
- Weak but better:
- Retraining followed by frequent, random monitoring by supervisor
Intervention strength as applied to data entry errors
Automate maximally, then use special methods for remaining manual work
Intermediate:
- Redundant data entry
- Redesign of forms and data entry fields
Stronger: Eliminate data entry
- CPOE (Computerised Provider Order Entry)
- Instrument – LIS interfaces
- LIS-EMR interfaces
Strong interventions are difficult to implement, and sometimes expensive
Reducing errors in high risk work when work must remain manual
- Enhance supervision
- Isolate the high risk work (no multitasking)
- Specialise the work to a small group of highly trained people who are tightly monitored
- Standardise the work
- Remove time constraints from the group
- Reduce batch size, smooth (level) work flow
- Consider double checking with accountability
- For data entry, use redundant entry if feasible
Automating data entry is not easy:
For example: LIS-EMR interfaces are not easy to do well
- Intervention = more testing
- 3000 tests can be resulted in 30,000 different ways in 1 downstream system
- That is a lot of testing for only one interface
Interventions for Reducing Preanalytic Pipetting Errors
- Weak: Retrain techs, tell them to slow down
- Stronger: Automated pipetting (can produce error rates <10-5)
- Strongest: Eliminate pipetting
- Direct tube sampling
- By switching from assays requiring pipetting to automated platforms that don’t
Usability testing/site visits
- Best way to reduce risks associated with implementing technology
- Usability testing: not always possible, but great if you can do it
- Site visits better than talking on the phone
Total Laboratory Automation (TLA) decreases the opportunity to make Preanalytic errors including those related to aliquotting, sorting/routing, capping/decapping and centrifuging.
| Pre-TLA | Post-TLA | Change | |
| Sort out routing errors/week | 16,497 | 0 | -100% |
| Pour off errors/week | 5,120 | 0 | -100% |
| Biohazard exposures/week | 5,120 | 595 | -88% |
Human Error Opportunities at Ohio State University, before and after TLA (circa 1999)
(Lessons learned from total laboratory information at Ohio State: An Interview with Dr. Michael Bissell. 2006. Laboratory Errors and Patient Safety. 3(3): 1-8
Total Laboratory Automation (TLA) decreases the opportunity
Mislabelling: Definition of preanalytic, mislabelling error
- Identifies on requisition and container (e.g. blood tube) do not match
- Identifiers on requisition and collection container match but they are from the wrong patient (“swapped” also called “wrong blood in tube”)
- Collection container unlabelled or illegible
Weaker interventions for decreasing mislabelling errors
- Weak (useless, feels good):
- Retrain all the staff
- Tell them to slow down
- Weak but better:
- Retraining followed by:
- Frequent, random monitoring
- Individual report cards with peer review
- Retraining followed by:
Stronger interventions to decrease mislabelling errors
- Standardise around a smaller number of staff allowed to perform phlebotomy (e.g., 24-hour vascular access team)
- Remove or reduce time constraints on their work
- Allow single piece flow (1 patient at a time, no batching of specimens)
- Intensely monitor their competency
- Standardise around 1 or 2 policies and procedures
- Increase cooperation/accountability between nursing and lab
- Restrictive specimen acceptance policy
- Barcode-based semi-automated patient ID and specimen collection
- OK to use >1 intervention
Mislabelling errors:
Strongest intervention = semi-automation
- Good news: A number of hospital systems have now achieved 10-4 mislabelling rates using barcode-based patient Identification and specimen collection systems
- Bad news:
- Hard to implement
- ROI can be difficult to measure unless there has been harm and litigation
- Penetration into market has been slow, much slower than Total Lab Automation
- Still best to limit # of people performing phlebotomy
Stronger interventions to reduce mislabelling (e.g. dedicated vascular access teams) help with other preanalytic problems
- Incorrect container
- Failure to collect
- Specimen loss or delay
- Specimen quality problems
- Line contamination
- Quantity not sufficient
- Haemolysed specimens
- Clotted specimens
Further decrease mislabelling errors by involving patients
Advice to patients:
- Confirm your identity with the person collecting your specimen. Check your tubes
- If you have a common name or a name that it “2 first names”, change your name
- Leave your Google list of tests at home
A typical restrictive relabeling policy from a healthcare system in the United States
- “A repeat specimen collection may be deemed impossible ONLY by the Chief Nursing Officer or the Medical Director. This can occur in the rare cases in which:
- It is not possible to reproduce the circumstances necessitating the test (e.g. catheter tip cultures)
- Recollection causes undue risk to the patient (e.g., CSF from lumbar puncture, tissues from a biopsy, or other similarly obtained irreplaceable sample)
- In the exceptional case of allowed relabels, the following is required…”
Intervention strength as applied to relabeling. Stronger = …
- Apply restrictive policy that does not allow blood, urine or other replaceable specimens to be relabelled
- Minimise number of leaders authorised to relabel. Standardise around a few people from the medical and nursing directors offices and enforce the rule.
- Eliminate administrators from this medical decision
- The # of calls for relabeling decrease dramatically when relabeling policy is enforced
Failure to retrieve a test result
- Case: A doctor orders a test for C. Difficile, and forgets to retrieve it. By the time the result, which is positive, reaches a provider, the hospitalised patient has had serious complications from their diarrhoea
- Occurs for about 5% of tests, major source of lab-related, patient harm events and litigation
Intervention strength as applied to MD forgetting to retrieve a test result
Pull (weaker)
- MD retrieval from paper chart, LIS or EMR
- Give patients access to their EMR tell them no news is NOT good news
- Send results to MD’s electronic inbox with read receipt, link to patient note
- Phone 3rd party (e.g. nurse), who relays a result to MD
- LIS “pages” MD’s wide screen pager
- Phone M.D. directly and receive read back
Push (stronger)
Interventions to reduce oral miscommunication of results
- Case: A doctor calls the lab for a pregnancy test result. The tech communicated an old negative result, rather than the current positive result. Pregnant patient receives harmful medication.
Interventions to improve oral communication
- Weak: Retrain the technologists, tell them to slow down
- Intermediate: Read back with documentation/audit
- Strong: Call centre, redesign or results screen
Call centres, when properly outfitted and managed…
- Reduce abandon call rate
- Reduce time to answer phone
- Standardises answers to calls
- ~30% of hospital labs have call centres, and this is increasing
A comparison of methods for guiding or restricting provider choices regarding lab testing. Strong guidance involves restrictions on testing and peer pressure to influence behaviour
Gentle guidance
- Posting of guidelines on the requisition
- Computerised reminders regarding utilisation guidelines
- Utilisation report cards
- Changes to manual requisition or CPOE
- Utilisation report cards with peer or leadership review
- Requirement for high level approval (e.g. Pathologist) or consultation (e.g. Medical Geneticist)
- Utilisation report cards with leadership review and financial penalties or incentives to encourage desired behaviour
- Forbidding tests
Strong guidance
Astion, M.L. Interventions to Improve Laboratory Utilisation. Lab Err Pat Safety 2007; 4:1-5. At: www.pathology.med.umich.edu/intra/LabSafetyRept/July.September2007.pdf
Miller, C. Using genetic counsellors to decrease errors. Clinical Laboratory News. 2012 (1). www.aacc.org/publications/cln/2012/January/Pages/PSFGeneticTests.aspx#
Bonus Material: 10 ways to Reduce Errors in Send-outs
Preanalytic
- Establish computer interfaces to major reference labs
- Consolidate to as few reference labs as possible
- Establish a call centre to answer provider questions
- Get the specimens out the door as quickly as possible
- Implement active test utilisation management
- Define as many tests as possible in the LIS
- Adjust in-house test menu as needed to reduce sendouts
Conclusion
- The foundation of quality in clinical laboratories is a commitment to measure and the courage to perform carefully chosen, strong interventions
- Strong interventions, when combined with efforts to reduce latent factors underlying all errors, will lead to significant reductions in pre and post analytical errors
- You can do it!!
- Thanks
References
Update of Nurse’s Medical Bag will Reduce MRSA Risk
Dr David Swann, of the University of Huddersfield (subject area leader for product design and interior design), has designed a new medical bag for nurses which is easier to clean and can be transformed into a hygienic treatment area for clinical tools;
“The design of the traditional nursing bag used by mobile clinicians throughout the world is outdated and unsafe. It is an unfortunate case of 21st century professionals using 19th century kit. The aim of my design is to reinvent community healthcare and deliver a world-class patient experience in non-hospital settings.” (Swann)
This came after a study done by Swann which revealed that around one third of traditional medical bags used today carry the MRSA bug. He discovered that 55 per cent of nurse’s medical bags that have been used for community care for the past 150 years are never cleaned and only 6 per cent are cleaned once a week. Swann’s award winning “21st century” nursing bag will be commercialised next year. The new bag is made from non-permeable polypropylene white plastic and is simple to clean. Due to it being white in colour, it makes regular cleaning a necessity and is much easier to clean than the bags currently being used as these are made from absorbent material and have difficult to clean pockets and folds.
Swann’s design has recently been awarded highly commended status in the NHS Innovation Challenge;
“At a time when health services are turning increasingly to care in the community to save money, the 21st century nursing bag is an attempt to inspire a paradigm shift in home healthcare that guarantees patient safety, nurse productivity and service quality.” (Swann)
The project has earned Dr. Swann his PhD at the Royal College of Art and he has been nominated for four major awards including a James Dyson Fellowship and the globally prestigious Index Design Awards.
References
Images
http://eprints.hud.ac.uk/13323/1.haslightboxThumbnailVersion/DAVID_SWANN_NO2.jpg
FDA Approves Truvada Drug to Reduce Risk of HIV Infection
On Monday, the United States Food and Drug Administration (FDA) announced its approval of the existing drug, Truvada (emtricitabine/tenofovir disoproxil fumarate) for reducing the risk of sexually transmitted HIV-1 in adults. The drug is produced by Gilead Sciences Inc and should be used with safe sex practices;
“Truvada is the first drug approved to reduce the risk of HIV infection in uninfected individuals who are at high risk of HIV infection and who may engage in sexual activity with HIV-infected partners.” (FDA)
Human immunodeficiency virus (HIV) is a lentivirus that causes acquired immunodeficiency syndrome (AIDS). HIV-1 is the most common form of the virus. The aforementioned system of treating uninfected adults who may be at risk of contracting the HIV virus with Truvada is known as a Pre-Exposure Prophylaxis (PrEP). A trial which involved approximately 2,500 homosexual and bisexual men and transgender women resulted in the Truvada reducing the risk of HIV infection by 42%. This trial is called Pre-Exposure Prophylaxis Initiative (iPrEx), and was sponsored by the United States National Institute of Health (NIH) and the Bill and Melinda Gates Foundation.
“The data clearly demonstrate that Truvada as pre-exposure prophylaxis is effective at reducing the risk of HIV infection acquired through sexual exposure.” (Connie Celum, Professor of Global Health and Medicine at the University of Washington and lead investigator of the Partners PrEP trial)
Truvada, approved in 2004 and the most-prescribed antiretroviral in the United States, prevents HIV from becoming established in the body and stops it from multiplying.
A REMS (Risk Evaluation and Mitigation Strategy) has been developed by the FDA and Gilead that will help make sure that Truvada will be used safely for PrEP by patients and doctors.
References
Images
http://healthyblackmen.org/wp-content/uploads/2012/05/truvada-11.jpg
MicroRNA MiR-33 Manipulation can Improve Liver Toxicity caused by Statins
Angel Baldán, PhD., investigator at Saint Louis University, discovered that the microRNA miR-33 plays a key role in the regulation of bile metabolism. The research, which was funded by the National Institutes of Health and the American Heart Association and it is published in EMBO Molecular Medicine.
“As we learn more about the way cholesterol is moved and metabolised through the body, we have more tools at our disposal to try to limit potential side effects of cholesterol managing drugs like statins.” (Baldán – assistant professor of biochemistry and molecular biology at Saint Louis University)
Earlier research showed that miR-33 plays a key role in regulating cholesterol. Baldán’s team found that decreasing the levels of the microRNA aided the rise of HDL (“good cholesterol”) in an animal model. These results were mirrored in four other laboratories in 2010. Baldán examined the two bile transporters, ABCB11 and ATP8B1 to find that miR-33 directly regulates them. Baldán’s research team went on to discover that silencing miR-33 caused increases in bile secretion from the liver meaning more bile was recovered in the gallbladder. Researchers then treated two groups of mice with an anti-miR-33 drug and tracked radioactively labelled cholesterol as it moved.
“We hypothesised we should see changes in the amount of radioactivity in the cholesterol that was eliminated in the mice’s faeces, depending on whether they were given placebo or anti-miR-33. That is in fact what we found. When the microRNA is silenced, the pathway is enhanced and more cholesterol is passed through.” (Baldán)
Bile is partly made up of cholesterol and cholesterol-derived bile acids and it also helps regulate cholesterol in the body. If bile cannot flow from the liver to the small intestine due to a gall stone, medication side effects or genetic variation, cholestasis can occur (a type of liver damage).
Baldán’s researchers had a look at the genetic condition – progressive familial intrahepatic cholestasis (PFIC) which can lead to liver damage. It is caused by defects in the biliary transporters, such as the aforementioned ABCB11 and ATP8B1.
“Intriguingly, a very small number of patients who take statins develop a syndrome identical to BRIC, a milder version of the same illness experienced by people who have the genetic disease PFIC. In this case, though, statins caused the condition pharmacologically. We further hypothesised that conditions that involve miR-33 could, under certain circumstances, also induce a BRIC-like syndrome, by reducing the expression of ABCB11 and/or ATP8B1.” (Baldán)
To test this, the researchers gave the mice a special high fat, high cholesterol diet, in the presence or absence of statins. The results from this test are as follows;
- Mice that did not receive statins tolerated the diet with no problems
- Mice that did receive the statins developed liver damage
“To conclusively prove that this was due to the induction of miR-33, we treated the animals with anti-miR-33, and, when we did, their livers recovered. In effect, miR-33 encourages some of the undesired, hepatotoxic effects of statins and by silencing this signal we were able to avoid these toxic side effects. This discovery may ultimately lead to treatment options both for those with BRIC, and more broadly, those who suffer from statin side effects.” (Baldán)
Reference
Randox Toxicology – What can Randox offer Clinical Toxicologists?
Randox have 30 years’ experience in the development, manufacture and marketing of high quality clinical diagnostic equipment. Randox are a leading provider of customer-focused solutions to both the public and private clinical toxicology market. They have notably developed the largest toxicology test menu on the market, in-house.
Products offered by Randox range from conventional Drugs of Abuse Reagents and analysers to pioneering Biochip Array Technology, Quality Control material, Proficiency Testing and Assay development. These kinds of products, offered by Randox, have been applied for testing in hospitals, the workplace (drugs testing), sports (drugs testing), onsite drugs testing and for medico legal reasons.
Comprehensive Drug Profiling
Randox Biochip Array Technology advances on traditional methodologies, offering a comprehensive drug profile and allowing for more informed clinical decisions. The multiplex technology further improves laboratory practises with consolidated time, labour and consumable expenditure.
Highly Accurate Drug Detection
Multiplexing with Biochip arrays also eliminates any assay variation which can occur with single analyte assays on homogeneous EIA technologies, according to previous studies. Software on each of the four Biochip testing platforms permits selection of user defined cut off values, further allowing clinicians to tailor their testing to individual client needs. Above all, Biochip Array Technology ensures highly accurate and reliable drug detection. Clinicians have the ability to reduce the number of false results which are sent to confirmation and have complete confidence in their services.
Why Choose Randox Toxicology?
Randox Toxicology offer the most comprehensive range of solutions for drugs of abuse testing so that you can have one reliable supplier. With the largest test menu on the market and many more novel assays in development, Randox Toxicology enables you to remain at the cutting edge of clinical toxicology testing;
“Our global sales and customer support staff will assist your testing requirements; from small to high throughput testing we have the solution.” (Randox Toxicology)
Randox Toxicology ensures quality standards are met at every stage of the manufacturing, delivery and installation process.
Reference
Adapted from: www.randoxtoxicology.com/clinical-toxicology
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Prescription Drug Monitoring Program Needed According to Researchers
Misuse of prescription opioids and related deaths are on the rise in the United States. The use of these drugs more than quadrupled between 1997 and 2007, and a clear correlation has been found between the quantity prescribed and the risk of opioid overdose. Nearly 75 per cent of all fatal drug overdoses are due to prescription drugs and these significantly outnumber the mortality rate from heroin and cocaine.
Medical toxicologists Jeanmarie Perrone, M.D., an associate professor of Emergency Medicine in the Perelman School of Medicine at the University of Pennsylvania, and Lewis S. Nelson, M.D., a professor of Emergency Medicine at the New York University School of Medicine, outline a plan in the New England Journal of Medicine for a prescription-drug monitoring program that would allow researchers, law enforcement officials, dentists, medical professionals and pharmacists to access real-time data on the prescription drug histories of patients. These systems are called Prescription – Drug Monitoring Programs (PDMP’s);
“The White House Office of National Drug Control Policy, the Centres for Disease Control and Prevention, and the Food and Drug Administration suggest that state-based PDMP’s should be expanded. Yet many clinicians are unaware of these programs, and their use varies among states and specialities.” (Perrone and Nelson)
This could allow medical professionals to look after patients suffering from legitimate pain issues at a higher standard than at present. It would also enable the identification of potential drug abusers so that help can be administered to these individuals and therefore reducing the amount of painkiller-drugs in circulation for illegal sale.
“As the number of deaths associated with prescription-drug use surpasses the number of fatalities from motor-vehicle crashes in many states, we can learn from the success of auto-safety innovations that have mitigated mortality despite increased automobile use over the past three decades…We should initiate active safety measures to address the growing rates of illness and death associated with the pharmaceuticalisation of the 21st century.” (Perrone and Nelson)
Six of the 42 states, which have state-run prescription-drug monitoring programs, have enacted legislation to develop the programs. Some other recommendations included standardisation of the type of information submitted to the databases, bar-coded prescription paper to record entries faster and an e-prescribing system that would eliminate paper and prescription fraud. Programs are also recommended to track which drugs have the most potential for abuse or addiction.
“Although updating an existing prescription-drug monitoring database to incorporate these “ideal” goals would require additional support and money, the potential to protect the public health is substantial.” (Perrone and Nelson)
References
www.medicalnewstoday.com/articles/
Hiring at Ohio Businesses Hindered by Failed Drug Tests
Over half of Ohio manufacturing companies have rejected a candidate for an hourly position due to a failed drug tests in the past year.
According to a new survey done across all industries in the state, 25.5 per cent of businesses stated they had to dismiss otherwise qualified applicants for an hourly position, but for manufacturing it was 47.5 per cent. The survey was carried out by Employers Resource Council for the Alcohol, Drug Addiction and Mental Health Services Board of Cuyahoga County. The results from the survey appear to coincide with the assertion that Ohio employers are slow to fill vacancies due to rampant drug abuse. Drug abuse costs the American economy $193 billion per year, according to the United States Department of Justice.
Ohio Chamber of Commerce lobbyist Keith Lake said the state has the potential for expansion in a number of sectors, most notably energy. However, drug abuse jobseekers have the potential to derail those opportunities;
“At the end of the day, if the potential employees are still struggling to pass a drug test, it doesn’t matter how good our system is.” (Lake)
For non-manufacturing businesses, only 4 per cent had a single positive test of potential employees and 20 per cent of all employers said they did not have anyone fail a test. This did not worsen significantly in the past year;
“We really anticipated some higher percentages. They weren’t as high as we thought.” (ERC president Pat Perry)
The survey, conducted in May and involving 163 employers across Ohio, is believed to be the first of its kind, specific to Ohio.
Quest Diagnostics performs 9 million drug tests annually and releases an index that tracks positive results. In 2011, 3.5 per cent of pre-employment tests revealed drug use, Quest reported, which is different from ERC’s report.
The president of Columbus-based drug-free workplace promoter “Working Partners”, Dee Mason, stated that there are questions about whether the survey is reflecting the reality of the situation;
“Our statistics and experience do not match or mirror what is presented here.” (Mason)
Another possibility is whether the average pre-employment drug tests are looking for prescription drugs, especially opioids such as oxycodone or hydrocodone;
“The most popular drugs of abuse are alcohol and prescription drugs. It’s not illegal drugs anymore.” (Stacey Frohnapfel-Hasson, spokeswoman for the Ohio Department of Alcohol and Drug Addiction Services)
Karen Pierce, managing director of training and policy development at Working Partners stated that a traditional nine-panel test can detect some of these prescription painkillers and not others. She would not specify which drugs would go undetected.
If opioids are detected, a medical review officer will contact the test-taker and ask for proof of prescription, stated Lindsey Van Meter, spokeswoman for the Human Resources Association of Central Ohio.
Frohnapfel-Hasson stated that she would like to see businesses refer disqualified candidates to treatment providers and Lake commented that it was something the Chamber would look into;
“Frankly, from our perspective, that is a missed opportunity if those people are told ‘No thanks’ and that’s it.” (Frohnapfel-Hasson)
Reference
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