Editor Emeritus on December 6th, 2009

In the November 2009 issue of the Journal of Urology, Stanford Medical School researcher Dr. Rodney Anderson and researchers at the National Center for Pelvic Pain Research, in a new study, demonstrated a high correlation between the location of painful trigger points inside the pelvic floor muscles of men with chronic prostatitis and the location in the body where they routinely complain of pain.

A new treatment called the Wise-Anderson Protocol, originally developed at Stanford University in the department of Urology, treats men with chronic prostatitis in a monthly 6 day immersion clinic. It has been successful in helping to reduce the symptoms of a large majority of men diagnosed with chronic prostatitis who have not responded to any other treatment. The clinic aims to rehabilitate chronically contracted pelvic muscles and modify the tendency to tighten the pelvic muscles under stress.

It is estimated that 8 to 10% of American men suffer from prostatitis in which they have symptoms of urinary frequency, urgency, sitting pain, genital, sexual and rectal discomfort. Prostatitis is typically treated with antibiotics according to the conventional model that the source of prostatitis symptoms is an infection or inflammation in the prostate gland. Antibiotics and anti-inflammatory medications routinely fail to resolve chronic symptoms of prostatitis in well over 90% of men diagnosed with chronic prostatitis.

The Stanford article adds to mounting evidence that prostatitis (chronic pelvic pain syndrome) is a psychoneuromuscular condition in which the muscles of the pelvic floor, in response to psychological or physical stress, become chronically contracted. Once this stress causes the muscles of the pelvic floor to chronically tighten, a condition of chronic spasm and muscle contraction occurs and is fed by a cycle of tension, anxiety, pain and protective guarding. Dr. Anderson et al have published other articles in the Journal of Urology showing the efficacy of their treatment. They have written about this new treatment in the popular book A Headache in the Pelvis, now in its 5th edition. More information about the Wise-Anderson Protocol is found on chronic prostatitis, pelvic pain and their treatment, in a number of videos at www.pelvicpainhelp.com and in written information.

Source: NATIONAL CENTER FOR PELVIC PAIN RESEARCH

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Editor Emeritus on December 5th, 2009

There is no scientific proof that people suffering from depression can benefit from taking reboxetine. However, clinical trials do provide proof of benefit of bupropion XL and mirtazapine: both agents can alleviate symptoms. This is the conclusion of the final report of the Institute for Quality and Efficiency in Health Care (IQWiG) published on 24 November 2009.

The final evaluation of reboxetine and mirtazapine was only possible after manufacturers disclosed data that had previously been concealed. This case re-emphasizes the need for a mandatory regulation, which would require all clinical trials to be registered at the start and to have their results published after study completion.

Manufacturers only release data when public pressure mounts

In its preliminary report published at the beginning of June 2009, the only results IQWiG could present without reservation were those for bupropion XL. It was forced to add a caveat to the results for mirtazapine, because the fact could not be ignored that study data not provided by Essex Pharma might seriously bias the result. In the case of reboxetine, IQWiG abandoned its analysis of the study data that was publicly available at that time, because it was evident that the manufacturer, Pfizer, was concealing almost two thirds of all data collected in trials to date. An analysis of the available data would have produced a biased picture. Despite several requests, Pfizer had steadfastly refused to provide IQWiG with a list of all published and unpublished data.

However, after the preliminary report was published, Pfizer and Essex Pharma decided to make the unpublished data and information on trials accessible. Only then was it possible to assess all three drugs based on complete data.

The analysis of the complete data reveals that IQWiG made the right decision in abandoning its assessment of reboxetine based only on published data. The summary of results from published and non-published trials does not provide proof of benefit of reboxetine, whereas the data from the published trials appear to suggest a benefit.

Many outcomes were considered

In line with the Federal Joint Committee’s (G-BA) commission, IQWiG and its external experts searched for trials that either compared each of the drugs with a sham treatment (placebo), with each other or with another antidepressant. The trials included both acute therapy and relapse prevention.

In addition to the change in depressive symptoms (remission, response) and secondary symptoms such as anxiety, pain or sleep disorders, outcomes in the benefit assessment also included mortality, suicidal tendencies, quality of life, social functioning level, and adverse effects.

Reboxetine: proof of harm, but not of benefit

IQWiG had access to a total of 17 trials on reboxetine when preparing the final report. Its analysis shows that there is no proof of benefit either for acute therapy or for relapse prevention. The patients did not respond any better to the therapy than to a placebo, nor was there an improvement in their social functioning level.

There were only two specific situations where indications of a benefit could be found. A very small trial with a total of 52 patients treated in hospital provided an indication that those receiving reboxetine responded better to the treatment than those receiving placebo. Nevertheless, it could not be shown in this trial that symptoms typical of depression completely disappeared. Another trial with outpatients also gives indications, although only for relapse prevention. In short-term acute therapy reboxetine does not alleviate symptoms of depression as well as drugs in the SSRI drug class.

Alongside the lack of evidence of benefit of reboxetine, there is also proof of harm: patients discontinued treatment more frequently due to adverse side effects, both when compared to placebo and in the comparison with fluoxetine, another antidepressant from the selective serotonin reuptake inhibitor class (SSRI).

Mirtazapine: patients respond better to therapy than to placebo

IQWiG was able to include 27 trials on mirtazapine in the assessment. As full information on these trials was now available, the Institute no longer needed to add a caveat to the results, as was the case with the preliminary report.

When compared to placebo there was proof that in acute treatment more patients experienced an improvement of depression when they were treated with mirtazapine. The prospect of a total cure was no better in the mirtazapine group than in the placebo group. However, this aspect was only investigated in 1 trial for mirtazapine. In numerous comparisons with other antidepressants, mirtazapine did not show proof of superiority. In addition, it was shown that patients treated with mirtazapine discontinued treatment more often due to side effects (adverse events) than patients treated with placebo or with some of the other antidepressants.

Bupropion: symptoms completely disappear in some patients

The search identified 7 trials on bupropion XL and the Institute was given access to the complete clinical study reports by manufacturers. There was proof of benefit for this agent compared to placebo in acute therapy and in the prevention of relapse into seasonal affective disorder. In some patients, the symptoms were reduced so much that they no longer met the criteria for a diagnosis of depression (remission). Moreover, the data provided no indications of harm.

The only antidepressant that was compared with bupropion XL in trials was venlafaxine XR. Bupropion XL showed inferiority to venlafaxine XR in acute therapy. Further information can be found in the executive summary of the final report (see below).

Obligation to publish trial results must be legally enforceable

As has been revealed in the process of preparing this report, a lack of willingness to cooperate on the part of the manufacturers leads to benefit evaluations of limited validity and causes considerable delays in producing assessments. “Deception through concealment of trial data is no trivial offence”, says IQWiG’s director, Peter Sawicki. “The study sponsors are depriving patients and doctors of the opportunity to make an informed decision on different therapy options. As the example of reboxetine shows, concealing trial data can lead to patients receiving a drug, for which there is not only no proof of benefit, but which can also cause harm.” Moreover, it is not only the work of the Institute that is hindered, but also that of the G-BA. According to the Institute’s director, “The G-BA then lacks the reliable scientific basis that it needs for its decisions on reimbursement of drugs.” IQWiG’s position on this issue is described in a second press release.

Reboxetine was approved in Germany in December 1997. For its part, however, the German drug regulatory authority could not consider all the trials that IQWiG had analysed, because IQWiG’s report also includes trials that were completed after 1997. Pfizer also applied for approval in the USA but this was evidently not granted in 2001.

Source: Dr. Anna-Sabine Ernst, Institute for Quality and Efficiency in Health Care

The National Prescribing Service (NPS) welcomes calls for improved complementary and alternate medicine training in universities and says all health professionals have a responsibility to ensure these products are used safely.

Speaking at the annual scientific meeting of the Australasian College for Emergency Medicine in Melbourne, Dr Lesley Braun said health professionals need better training at university about complementary medicines and their interactions with conventional drugs, and to make an effort to stay informed.

Research conducted by NPS last year into the complementary medicine information needs and uses found a number of issues relating to the transfer of information between health professionals and consumers.

“Most complementary medicine users are self-prescribing without understanding the implications of what they are taking, and in a number of cases, they aren’t using the products in the way they are intended,” NPS CEO, Dr Lynn Weekes said.

“At best, this may mean consumers aren’t getting the maximum benefit from the complementary medicine. At worst, they may be putting their health at risk.”

While half the consumers surveyed admitted to not telling their doctor or pharmacist they were taking complementary medicines, many health professionals said they often didn’t ask because they weren’t confident discussing these medicines with patients.

“A number of practising health professionals may not have received formal training about these medicines at university but the information is continuously changing so it’s up to each individual to keep informed,” Dr Weekes said.

A second piece of research conducted by NPS, Mater Health Services Brisbane, Bond University and the University of Queensland between June and November 2008 identified and ranked the most useful complementary medicine information sources available to health professionals.

Both studies noted the need for a centralised data point that includes accurate, independent information about adverse effects, interactions with other medicines, contraindications and clinical evidence.

“Between the growing rate of complementary medicine use, the prevalence of chronic diseases and the rising number of people being hospitalised for adverse events, it’s vital today’s medical and pharmacy students gain a comprehensive understanding of safe medicines use and have ongoing access to accurate information,” Dr Weekes said.

Source: The National Prescribing Service

Editor Emeritus on December 3rd, 2009

While we normally avoid the use of corporate press releases which contain little more than marketing intent, the following is an exception. I confess to being a long-time prescriber and user of ginger to treat nausea so while I do not advocate the use of cytotoxic chemotherapy used in oncology I do recommend the use of ginger and I consider the following worth publishing.

Reed’s, Inc. (NASDAQ: REED), maker of the top-selling sodas in natural food stores nationwide, attended the American Society of Clinical Oncology (ASCO) 2009 Annual Meeting in Orlando, Florida earlier this year. At that time, Reed’s reported on a recently released study, funded by the National Cancer Institute, which found that ginger can successfully treat post-chemo nausea in cancer patients. Some of the findings were:

— Up to 70% of patients become nauseated after chemo, according to the study of 644 people

— According to the study’s author, “Although drugs… can prevent vomiting, they don’t always relieve nausea”

— Ginger reduced patients’ nausea levels by half, according to the study

— The most effective doses were 1 gram and 0.5 gram a day, which are equal to half a teaspoon or one-quarter of a teaspoon of ground ginger, according to the study

— Reed’s Ginger Brews contain between 8 and 26 grams of ginger per serving

— Reed’s is the ONLY commercial soft drink manufacturer using fresh, whole ginger in its products

— Significantly, ginger caused no side effects, according to the study

Chris Reed, Founder and CEO of Reed’s commented then that, “We’ve known for years that people have been using our Ginger Brews for post-chemo nausea, we’ve even been contacted by doctors who have had cancer and have told us they drank our Reed’s Ginger Brew to relieve their own post-chemo nausea. With 8 to 26 grams of fresh ginger per bottle these drinks work quite well for any kind of nausea; from motion sickness to morning sickness to post chemo nausea. In fact, in medical tests ginger beats Dramamine, which is one of the top over the counter nausea medications.”

The study’s co-author, Julie Ryan, assistant professor of dermatology and radiation oncology at the University of Rochester Medical Center, commented in the study, “That’s why we’re so excited. This is something that people have access to, that won’t harm them.”

Reed added, “Other cultures have been using ginger as a folk remedy for thousands of years. It was only a matter of time until ginger would be tested for its effectiveness in treating post-chemo nausea.” Richard Schilsky, Oncology Society President, who wasn’t involved in the study, describes the trial’s results as “conclusive.”

SOURCE: Reed’s, Inc.

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Editor Emeritus on December 3rd, 2009

A study conducted by Children’s Hospital & Research Center Oakland scientists has identified a new class of therapeutic agents found naturally in soy that can prevent and possibly treat colon cancer, the third most deadly form of cancer. Sphingadienes (SDs) are natural lipid molecules found in soy that research shows may be the key to fighting colon cancer. The study, led by Julie Saba, MD, PhD, senior scientist and director of the Cancer Center at Children’s Hospital Oakland Research Institute (CHORI), will be featured in the December 15, 2009 issue of Cancer Research.

Soy has long been touted as protective against colon cancer, but Dr. Saba’s team made the groundbreaking discovery that SDs naturally found in soy may underlie the benefits of soy products. Dr. Saba and her team first identified SDs in the fruit fly, an organism that is sometimes used to study the genetics of human diseases. Further investigation indicated that elevated SDs actually induced the death of mutant cells in the fly, revealing SDs to be cytotoxic (cell killing) compounds.

Future research is needed to identify the best way to deliver SDs and to confirm the overall toxicity when the compounds are used for extended time periods and in combination with other agents. Dr. Saba, who has already received two grants to continue her research, also hopes to determine if SDs are effective in protection against other cancers.

Dr. Saba also acknowledges that future research is needed to determine if there are other components of soy that are beneficial in fighting colon cancer. In the meantime, Dr. Saba says, “I would be comfortable recommending soy products as a change in the diet that could protect against cancer. The more that soy is studied, the more of these protective agents are found, so it’s a very healthy diet choice.”

Source: Children’s Hospital & Research Center at Oakland

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