Negative results treating cocaine addiction

Cocaine is a potent psycho-stimulant; the consumption of this drug has been increasing since the 1960s, and therefore cocaine presents an important problem of public health. From the beginning, it was considered that cocaine abuse didn’t produce evident physical symptoms in comparison to heroin and alcohol, and that cocaine was not addictive. Therefore, there was not any specific treatment for cocaine addiction. However, the truth is that there is evidence of neurological effects produced by cocaine.

Cocaine stops the communication system in the brain. Cocaine also has effects on the gratification system of the brain, increasing the levels of dopamine, a neurotransmitter involved in pleasure feelings. As a consequence, for the normal function of a cocaine addict’s brain a constant activation of the gratification system is necessary, and for this cocaine is needed regularly. Therefore, the addict cannot control this craving because of the brain damage.

Erroneously, for a long time it was thought that if an addict didn’t stop their cocaine addiction, the reason was a lack of determination. Because of the ignorance of this, no treatments had been available for a long time and the success in treating cocaine addiction had been limited. The pharmacology used in cocaine abuse was orientated to treat the withdrawal symptoms, the anxiety, depression, etc.

Fortunately, nowadays, there is a new trend to develop new therapies orientated to recover the cognitive functions and affected zones of the brain. These therapies try to produce effects in the core of this disease and not just in the symptoms. As well as other addictions, cocaine abuse involves complicated social and familiar problems, and the addiction treatment must be integral, that is, the problem must be faced from the pharmacological, behavioral, and psychological points of view.

As a consequence of the erroneous consideration that cocaine addiction was not a disease, nowadays there is not any drug approved for cocaine treatment. But other drugs useful for other addictions such as baclofene, disulfiram, topiramate, etc. are being testing. Some of them had shown a diminution in cocaine consumption in some studies, with disulfiram (used in alcohol addiction) being the drug with the most promising results.

On the other hand, the increasing knowledge of the metabolism and the changes produced in the brain after cocaine ingestion is leading the research in this topic toward the restoration of the balance between excitant (glutamate) and inhibitory (gamma-aminobutyric acid, GABA) neurotransmission. Other interesting targets for cocaine-treatment drugs are the D3 dopamine receptors. Finally, some researchers are trying to get a vaccine to avoid the incorporation of cocaine into the brain in order to reduce the risk of relapses. Hopefully, the economic interest of the pharmaceutical companies will not be taken in account and valuable reports of both the positive and negative results will be published to find an efficient treatment for this problem as soon as possible.

Written by Dr. Daniel Jimenez and edited by Dr. Alcantara for The All Results Journals.

How to respect your listeners

Scientific research always speaks to many and ranging specific challenges -- one of which being consideration of the actual knowledge of your audience while not overestimating its expertise on the given topic. At the same time being too straightforward can often come across as disrespectful. The presentations given by scientists are often too complex -- a result of ego more than anything. The audience may perhaps want something pitched at a lower level.

On the other hand, some in the audience may complain that the presentation as a whole was "too simple" for them. Having said that, audiences can react negatively to simple-minded undertones. But the one point an audience never forgives is a lack of respect.

Respect is reflected much more in tone than the content of what is said. A matter-of-fact language is better -- claiming issues precisely how they are and with no doublespeak. For example, if you need something from your boss, just ask for it. A certain amount of straight forwardness should be used, with the end goal of making an effort to assist and not offend your listeners. Provide beneficial wisdom from the result of your failures.

The difference between respect and tone are not always clear and challenging to define. Indeed, they have more to do with the intention that a standard set of protocols that need to be done or accomplished. If you are a PhD student, for example, it would probably be more appropriate to address your supervisor by their first name. Of course, this will depend on him or her and what they are comfortable with, as well as the institutional culture. In email etiquette, opening an email "Dear John" or "Dear Dr Smith" creates distance and not just respect. Of course, the body of the email can also show a lack of respect no matter your opening.

Taking into consideration your intention when talking about science you can come up with a simple guideline. Since the aim is to make the audience an understanding of the topic in question perhaps it is better to get into the habit of writing and talking in a relatively simple way. Instead of perpetuating the complex style seen in papers and other journals, create a description of things as simply as you would when explaining them to a colleague or friend. Bypassing the unnecessary informality shows a respect for the audience. Notions of what should or should not sound "scientific" shouldn't really be catered for if you centre on your objective. And that is: Scientists understand your message.

Written by Dr. Charles Ebikeme and Dr. David Alcantara for The All Results Journals.

Why do we have negative results in antidepressant addiction treatments?

At present, there are about 30 different antidepressants available in the drugs stores classified in five different groups: tricyclics, monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), serotonin and noradrenaline reuptake inhibitors (SNRIs) and noradrenaline and specific serotoninergic antidepressants (NASSAs). Antidepressants are not addictive or chemically addictive in the same way that other drugs such as heroin, cocaine, crack, etc., however, it is true that many people find it very difficult to get off these drugs, and in addition, many people that consume them experience suicidal cravings and withdrawal symptoms when they stop them. The higher the dose, more difficult it is to get off these substances.

When many people try to get off antidepressants, they stop the drug abruptly instead of reducing the dose slowly. In this way, withdrawal symptoms are very hard and suicidal behavior can arise. This is normally the main reason why antidepressant addiction treatment fails. The dose must be reduced slowly over weeks or months to avoid relapse. The dose must be reduced sequentially and, previously to reduce the dose again, the addict must be stabilized in the new dosage, although many doctors prescribe to stop patients from using antidepressants since these drugs don’t present addictive substances. But the truth is that even though you cannot feel physically addicted, psychological addiction is possible. For this reason antidepressant addiction treatments are mainly based on psychological counseling, support and treatment. In this sense, it is very important that the addict feels that they are in a safe environment. Counseling sessions and group therapy provide this environment to treat the main problem of the addiction, the main problem of the depression. If the main problem of the depression is suppressed, the addiction will be eradicated easier.

The therapy for antidepressant addiction must be effective, non-harmful and fun. A fun treatment will be more effective than any other. Therefore, the treatment should be complemented with other activities such as massage therapy, exercise, yoga, relaxation, etc. Theoretically, antidepressants are not physically addictive, considering this fact: the treatment of the addiction doesn’t follow a conventional line. In other addictions, the first step is the detoxification process. In other addictions, detoxification is achieved using agonist, treating the symptoms of the withdrawal and with psychological help. In antidepressant addiction, the detoxification must be addressed with a reduction of the dose of the drug and with behavioral and/or psychological support. If these treatments are not combined, the detoxification will not be successful.

After the detoxification process the prevention of relapses is very important. Many treatments fail because the tracking of addiction evolution is not correct. The addiction must be tracked periodically and psychological and behavioral therapies must be applied in combination with support to achieve the social re-adaptation of the addict.

Finally, the post-treatment support is also very important to ensure the treatment’s success and avoid relapses. In this step, the tracking of the addict is very similar to the tracking after the detoxification process, but in this case the addict must attend group meetings, and psychological meetings in longer periods than in the previous case.

In many cases, we consider that the treatment ends after the addict’s detoxification, and this is not true. The treatment must continue beyond after the detoxification; in many cases, lack of post-attention is the main reason of the bad results on the treatments for antidepressant addiction

Written by Dr. Daniel Jimenez and edited by Dr. Alcantara for The All Results Journals. 

Interview with Prof. Sebastian Cerdan

We had the pleasure to interview last week Prof. Sebastián Cerdan in a meeting at the Andalusian Center for Nanomedicine and Biotechnology (Bionand, Spain).

ARJ: Could you please do a brief introduction of your research?

My group develops novel biomedical applications of Magnetic Resonance Imaging and Spectroscopy. We are currently engaged in projects concerning the development of intelligent contrast agents, the implementation of advanced methods of functional imaging (Diffusion Weighted), the detection and characterization of cerebral inflammation, the diagnosis and prognosis of cancers and the implementation of new, automatic, artificial intelligence algorithms to extract relevant image features.

ARJ: What do you think of publishing negative results? How can they improve our actual scientific methods?

The scientific method does not distinguish between positive and negative results. For me they are simply results. They both serve to confirm or decline the proposed hypothesis and this is the way science advances. The distinction between positive result and negative result is often contributed by the experimentalist, based in his feelings of success or failure, but these are not scientific attitudes. I have no problem is showing negative or positive results if they contribute to the advance in knowledge.

ARJ: How does the publication of negative results benefit the scientific community?

 Just as the publication of positive results does. No difference.

ARJ: Are researchers used to publish negative results? What are the reasons, from your point of view, that negative results are usually not reported (or published)?

I do not know. I am used to see papers reporting both types of results.

ARJ: What is the impact of not publishing negative results in your field and clinical research? Can it be influenced by the editors of the journal?

No, I do not think editors play any role in this. An article is good or bad based on the results, either positive or negative. Another question is the sales of the journal, but this is an economic, not scientific consideration.

ARJ: Is there a way that we can overcome the tendency for negative results to be viewed as being less useful than positive results?

I do not have the tendency to consider negative results worse than positive. Should this become an issu I would recommend better scientific education.

ARJ: How do you normally manage negative results on your lab?

 Just as positive. I report both.

ARJ: We're proud to be the first TOTAL Open Access publishers (no fee to authors or readers to publish or download), what do you think are the biggest advantages of Open Access?

Probably Freedom of Mind and lack of economic burdens.

ARJ: The All Results Journals is totally open, we try to uncover the soft spots of other journals. Normally, how other journals work is by financial and economic issues all the time… but we are a non-profit organization. We want to show results that are new, helpful to scientists so they don’t waste their time repeating experiments that were already performed by another researcher. What is the main objection, from your point of view, preventing the researcher from submitting negative results?

I do not know. A hipothesis may proven or disproven by the results. Both are equally valid.

ARJ: Government Agencies (GAs) normally promotes positive results, Should they also promote the publication of negative results?

I am not sure what they promote. They should promote good science and this requires accurate results, either positive or negative.

ARJ: Thank you for your time and your valuable insights.


Contact Info:

Prof. Sebastián Cerdan
Instituto de Investigaciones Biomédicas "Alberto Sols"
C/Arturo Duperier 4.
28029 Madrid. (Spain)
website

Interview made by Dr. David Alcantara for The All Results Journals

The value of negative results in science

“Well, we failed to reject the null hypothesis for our experiments. I guess we should just put that submission idea on hold for now since we have no good results to report.” – the Professor says to his advisee in a frustrated tone while flipping through some graphs. Another one bites the dust! Hours of intense work and significant monetary expenditures become a victim of the “file drawer effect”; or to modernize the expression: “the hidden computer folder”.

Unfortunately, this is not an isolated incident. Fanelli (2012) demonstrates that negative results have been gradually disappearing from academic literature over the past two decades. Meanwhile, articles primarily and clearly stating positive results have grown 22% between 1990 and 2007. As positive results are more likely to lead to prestigious publications, discarding odd and unexpected findings is common in the scientific publishing system that privileges these “successful” results. Traditionally, it is expected that successful studies will obtain research findings in alignment with well-established literature or expected outcomes.

However, are negative results indeed meaningless? Or is there potential value in sharing negative results with a broader academic community?

When examining reasons for the low profile of negative results publications, one common assumption is that publishing negative results might harm scientists’ reputations. Along these lines, negative results are believed to indirectly communicate to the scientific community that a study was poorly designed and researchers were either unknowledgeable about the phenomenon or incapable of tailoring more robust research hypotheses. Moreover, the discouragement to submit publications reporting negative results is due to a higher likelihood that these papers will be filtered by the peer-review firewall, given their perceived lack of soundness in comparison to studies with “successful” results.

Nevertheless, as Popper (left) states research is a “voyage of discovery”, which is subject to unpredictability and fallibility (Popper, 1963, p.33). Science evolves according to testability, which might result in refutations or confirmations. Thus, the absence of anticipated correlations should also be counted as important and publishable results because they advance science.

One recurring misunderstanding among scientists is that negative results are equivalent to bad results and are products of flawed or ill-designed science. This quality argument can be easily challenged, because even positive results are not exempted from having their quality questioned. Furthermore,, some of the most well-known examples of fraud and data fabrication in science (eg. Jon Sudbø, Hwang Woo-suk and Marc Hauser) were associated with studies claiming positive correlations or supporting researchers’ anticipated hypotheses. Instead of suggesting poorly conducted science, negative results can indicate novel findings or unexpected outcomes of rigorous scientific investigations, directly or indirectly contributing to scientific discovery.

A classic example of negative results being recognized by researchers as scientific and ushering in a paradigm shift in science took place in the 17th century. Albert Michelson (right) and Edward Morley conducted sequential experiments in the late 1880’s seeking to enhance the accuracy of the prevalent aether theory. All of their efforts to advance the theory led to a continual rejection of their research hypotheses. A few years later, these null results were published in the American Journal of Science and played an important role in inspiring new experiments, including a well known one that confirmed a major physical theory proposed by Albert Einstein in 1905: the special theory of relativity.

Examples like this one suggest that reporting negative results creates an information sharing opportunity with peer scientists that can potentially inspire new directions for further studies. This example also suggests that as far as reputation, negative results should not be mindlessly connected to unskilled researchers.

The potentially positive contributions of negative results to the scientific community and society at large lie in the possibility of reducing duplication of effort, and inspiring further investigations with new methods and/or variables. There is no doubt that journals devoted exclusively to publishing negative results still have to improve their visibility among scholars if they are to be widely accepted. These journals face two major challenges: overcoming the traditional, outdated, and vicious scientific publishing enterprises that have been prevailing for generations and convincing others of the need to improve the dynamics and transparency of the scientific information flow.

After all, it would be interesting to speculate what the current state of Physics and other sciences would be if more negative results such as Michelson and Morley’s had been published.

Written by  Gabriella Anderson (original source)

Towards open data: When Glaxo plead guilty...

The largest health care fraud settlement occurred this past July, with GlaxoSmithKline pleading guilty to the criminal charges brought by the US Justice Department. GSK will pay $1 billion in criminal fines and forfeitures as well as $2 billion in civil damages related to other drugs. The drug company also agreed to be monitored by government regulators for five years.

The crimes in question are severe -- marketing and targeting the drug Paxil to under 18s when only approved for adults; and pushing the drug Wellbutrin for uses it was not approved for, such as weight loss. Other cases of misconducted were highlighted during the well publicized case. Including neglecting to provide safety data to the FDA on the drug Avandia. A drug whose side effects prove lethal.

According to Reuters, guilty pleas in cases of alleged corporate misconduct are exceedingly rare. Perhaps this mea culpa on their part signals a change in mentality over at Big Pharma.

That was July, however. In what seems like a recent turn around, GSK have pushed for more inhouse openness when it comes to the sharing their data. The strive to become “open and transparent” is one adopted by many strands of researchers, politicians and guardians of data; but is definitely one that hasn’t found traction within the laboratories of Big Pharma.

Forbes magazine called it “an unprecedented move that could signal dramatic changes in the drug industry” when it was announced by Andrew Witty, GSK Chief Executive, in London. He promised to make clinical trial data freely available to independent researchers. Allowing the scientific community to build on that detailed data. Perhaps this should come as no big surprise, as the British drugmaker had also previously made its chemical libraries available to researchers working on drugs against specific diseases such as tuberculosis and malaria.

“Because of our unique role, we recognize that society holds us to higher standards than for other industries. This is how it should be. Over the last four or so years we at GSK have been working hard to be more open and transparent. As I have shown these new approaches are helping to provide new solutions for serious global health issues. They will also help build society’s trust.”

Whether or not the pledge for openness is a knee-jerk reaction to recent scandals and the massive US fine probably just depends on your point of view on Big Pharma.

Patrick Vallance, the senior vice president in charge of drug research at Glaxo remarked, “We think that it’s the right thing to do for patients, we think it’s the right thing to do for understanding our medicines. I think if you volunteered to be in a clinical trial, your legitimate expectation is that your data will be used to insure that future generations of patients get the maximal advantage.”

In the end, the hope is this gesture will be adopted by other drug companies across the industry. An industry that could do with both the good will and press this gesture evokes, as well as the wealth of information to be gathered from it.

Written by Dr. Charles Ebikeme for The All Results Journals.

Negative results of bapineuzumab clinical trials may question the basis of Alzheimer’s disease

After several years of clinical testing, Pzifer and Johnson&Johnson recently announced that one of their most promising drugs to treat Alzheimer’s, bapineuzumab, has failed to meet primary endpoints in a phase III trial. As a consequence, not only 130 positions have been eliminated, but also the molecular basis of this neurodegenerative disease itself has been questioned.

The drug consists of a monoclonal-humanised antibody against beta-amyloid, a toxic protein for the brain whose accumulation is believed by many scientists to be responsible for the degenerative changes associated with this illness. The immunotherapy seemed the perfect solution in order to clear the build-up of amyloid plaques or prevent its formation, as the binding of the antibodies to the plaques should be able to remove them from the brain, thus improving the cognition or daily functioning of the patients.

The intravenous formulation of bapineuzumab was tested on 1,100 people with mild-to-moderate disease. Moreover, all of them carried the ApoE4 genotype (about half of the Alzheimer’s population shares this genotype), which raises the risk of suffering from Alzheimer’s and may also worsen its symptoms. Although in early phase II trials performed on 2008 the drug did not show significant effects, they decided to keep on testing due to the promising theoretical benefits of this kind of treatment. However, in phase III trials patients who took the drug did not significantly outperform the placebo.

The negative results of the trial could suggest that beta-amyloid might not be the culprit in Alzheimer’s disease. Alternatively, some experts think there could be another reason behind this failure: the drug may have been administrated to people at a late stage of the disease. Yet, this statement doesn’t make any sense; if amyloid is in fact the toxic component, an effective anti-amyloid immunotherapy should succeed in slowing disease progression. Besides, there is a phase I case report published in The Lancet (Amyloid-β vaccination for Alzheimer's dementia, 2008) of an anti-amyloid vaccine in which the authors did not observe prevention of progressive degeneration despite of the clearance of amyloid plaques.

All in all, the publication of this negative result is expected to be a turning point with regard to the molecular basis of the disease; the amyloid hypothesis is probably dead for the moment.

References:
1.- Ed Silverman (October 2012) J&J Cuts 130 Jobs After Alzheimer Drug Fails. Pharmalot.
2.- Michelle Castillo (July 2012) Anticipated Alzheimer's drug bapineuzumab shows no patient benefits in trial. CBSNews.
3.- Nathan Sadeghi-Nejad (July 2012) The Lessons Of Failure: What We Can Learn From Bapineuzumab's Blowup. Forbes.
4.- doi:10.1016/S0140-6736(08)61580-9
5.- doi: 10.1212/WNL.0b013e3181c67808

Written by Julio Rios for The All Results Journals.

Negative results in a new heart implant device

St. Jude Medical shares are down 4% today after clinical trial results show no significant benefit from its Amplatzer heart implant.

The device is designed to treat a condition called patent foramen ovale, in which a naturally-occurring hole in the heart fails to close after birth, potentially allowing blood clots to travel from 1 side of the heart to the other and then to the brain, causing a stroke.

St. Jude Medical (NYSE:STJ) shares lost 4% today after studies of its Amplatzer heart implant failed to significantly reduce cryptogenic stroke compared with standard treatment with drugs.
The St. Paul-based medical device company sponsored the larger study, of 980 patients, which tracked them at intervals of 1 month, 6 months, 12 months, 18 months, 24 months and then annually until 25 strokes or deaths occurred. It showed that 9 patients in the Amplatzer arm suffered non-fatal strokes, compared with 16 for the drug treatment cohort. There were no deaths or fatal strokes in either arm.

St. Jude was quick to point out that a quirk in the study's design meant that 3 of the 9 patients in the study who never received the implant were included in the Amplatzer arm. Excluding those patients, and patients in the drug treatment cohort who dropped drug therapy, and the risk of stroke was 63% lower for patients treated with the Amplatzer device.

"Stroke is a devastating disease and we now have compelling evidence that shows a 46 to 72 percent risk reduction in recurrent strokes, which is meaningful for this otherwise healthy patient population with a long life expectancy," co-principal investigator Dr. John D. Carroll of the University of Colorado said in prepared remarks.

"We are pleased with the results of the RESPECT trial and remain confident in the safety and performance of the Amplatzer PFO Occluder and the strength of our clinical trial design," added St. Jude's cardiovascular & ablation president Frank Callaghan.

Original Source

Adapted by David Alcantara for The All Results Journals.