Many pharmaceutical companies provide Continuing Medical Education (CME) for prescribing physicians. Although these programmes run by drug companies do not overtly market their drugs, physicians may get the impression that a disease or condition is underdiagnosed and best treated with a prescription. Following on from the previous column about the influence of pharmaceutical companies on medical research there is now a resource listing ways for physicians to complete their CME credits without being influenced by the bias of drug companies.
The online resource, PharmedOut is an independent project run by Georgetown University School of Medicine staff members for physicians and other prescribers:
PharmedOut is one of more than 20 programmes funded by a $21 million grant from the Attorney General Consumer and Prescriber Grant Program that are intended to teach physicians and nurses to more critically evaluate information from pharmaceutical companies about prescription drugs. Ironically the funding for the grant comes from a drug company, a settlement from a court case about unlawful marketing of a drug:
The grant will fund programs designed to provide health care professionals and consumers information relating to prescription drugs, including the way in which drugs are marketed.
Mini syllabi available on PharmedOut include:
* Your Friendly Drug Rep
* Why You Get Samples
* Industry Sponsored Research
* Disease Mongering
* Direct to Consumer (DTC) Promotion
Resources also include many links to other websites of similar organisations. The CME suggestions include the National Center for Complementary and Alternative Medicine (NCCAM) video lecture series, along with many other options.
Pharmaceutical companies may be biasing the design of many large clinical trials to simply satisfy their own marketing needs rather than answering important clinical questions that may have a major influence on public health. According to an article in the New England Journal of Medicine (NEJM), both outcomes would be desirable in an ideal world, and are not mutually exclusive.
The NEJM article comments on a study published in The Lancet, the MEDAL programme, which compares the side-effects of two Cyclo-oxygenase-2 (COX-2) inhibitor non-steroidal anti-inflammatory drugs (NSAIDs): etoricoxib (Merck), and diclofenac (a 'well-tolerated' generic drug in use for over 30 years). This column has previously reported on the widely known association between COX-2 selective inhibitors and an increased risk of thrombotic cardiovascular events in placebo-controlled trials. The Lancet study also compared the risk of gastro-intestinal complications (Inhibition of COX reduces prostaglandins in the lining of the stomach, making it more sensitive to corrosion by gastric secretions).
The Lancet study states:
The conclusion of the study is:
At first glance it may appear that the study usefully demonstrates the comparative cardiovascular risks of the traditional NSAID diclofenac, previously held to be well tolerated (but also a drug that is poisoning vultures in India ), while etoricoxib had a lower risk of gastrointestinal side-effects. The NEJM article however points out that the relative COX-2 selectivity of diclofenac is similar to that of celecoxib, and that the potential for increased cardiovascular risk with celecoxib may actually be higher than that of naproxen by 70% (naproxen is also a COX-2 inhibitor). In addition, the Arthritis and Drug Safety and Risk Management Advisory Committees of the Food and Drug Administration recommended naproxen, not diclofenac, as the "preferred comparator" for large trials of COX-2 inhibitors. So why was diclofenac the drug chosen for comparison? In an interview with the NEJM, Dr. Robert Califf, vice chancellor for clinical research at Duke University said:
Dr. Califf suggests that if the study had been designed in a public forum it would "almost certainly" have used naproxen, and possibly a placebo, in which case it is unlikely that the company would spend hundreds of millions of dollars funding a study that would be likely to have adverse outcomes for their drug, but this is "probably about as good as it gets in the current system".
The NEJM article concludes:
The incentive to attract pharmaceutical companies to invest in clinical trials designed by an independent unbiased process could be the perceived impartiality of such a process, which would encourage sponsors to evaluate their drugs in a manner that highlights their potential clinical value and not their anticipated marketing potential. If a non-commercially funded body were designing clinical trials such as the MEDAL programme, there are many natural medicines without severe adverse side-effects which could also have the chance of being compared with pharmaceutical medicines in addition to using a placebo, and the results would probably be universally accepted rather than seen as simply adding to the plethora of biased pharmaceutical-funded drug trials.
The enzyme transglutaminase, which is added to some breads and croissants to make the dough more pliable, may act upon gliadin (a glycoprotein present in glutenous cereals) to generate the epitope associated with the coeliac response and with anaphylaxis to wheat.
A letter by two researchers in New Zealand published in the journal Trends in Food Science & Technology suggests that transglutaminase (TG) should not be added to cereal products containing wheat, barley, rye or oats until safety checks have been carried out.
A researcher from the biochemistry laboratory in the Centre Hospitalier Chubert , Vannes in France later published an article in the journal Allergie et immunologie about the rôle of TG in both coeliac disease and wheat-dependent exercise-induced anaphylaxis (multi-system allergic reaction on exposure to wheat and during subsequent exercise). The latter condition is not necessarily linked to gluten intolerance, but involves an IgE response.
Transglutaminases transform proteins by deamidation and/or transamidation, the latter cross-links proteins together. New epitopes have been suspected in cases of anaphylaxis to wheat isolates (a food ingredient consisting mainly of deamidated gluten proteins). As a microbial TG is included in many food technological processes, the author concludes: "its safe use should be checked. This assessment must cover not only the safety of the TG itself but also that of the deamidated/cross-linked proteins generated by this enzyme."
Diagnosis of wheat intolerance using skin prick testing and sensitization against wheat proteins is not very accurate. As a result of this, the number of individuals diagnosed with irritable bowel syndrome (IBS) patients who have "food allergy" may be larger than believed. If the interaction with the lectins in wheat germ agglutinin and blood group antigens is taken into account, a lot of the dietary intolerances to eating grain-based foods can be explained. Additives in factory-made baked goods is another reason to eat organically produced bread, with ingredients according to blood group.
Recent news in the world of genetics: the chromosomal makeup of Santa Claus (also known as Saint Nicholas, or Father Christmas) has a very individual genetic structure. Far from the theory that Santa Claus does not exist, scientists have now discovered the generous saint is endowed with three extra chromosomes, explaining his very individual abilities and personality.
The most common genetic makeup of humans is 23 pairs, but Santa Claus has 3 additional chromosomes (known as Trisomy 25), which is believed to account for his high levels of activity around December 25th. In Europe this is more correctly known as Trisomy 24, the presence of three additional homologous chromosomes (having the same structural features and pattern of genes) in addition to the 23 typical pairs. Inhabitants of many European countries open their presents on Christmas Eve (24th December), hence the difference in nomenclature.
A study of children with acute leukaemia found a statistically significant difference in the blood groups of the patients depending on the type of leukaemia diagnosed. The multicenter study, published in the journal Pediatric hematology and oncology,(1) analysed blood group data in patients under 12 years with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML)
In the ALL group there were more patients with blood group O and fewer patients with blood group A and B [confirming the results of an earlier study(2)]. In the AML group there were more patients with blood group A. The authors of the study conclude that "alteration in ABO antigens might be associated with an increased risk of ALL."(1)
This complements the information available in the Complete Blood Type Encyclopedia, which cites a study showing significantly lower incidence of acute (rapidly growing) leukaemia in females of blood group O, suggesting a sex-responsive gene near the ABO locus protecting females against acute leukaemia.(3)(4) In relation to diet there are also significant associations with acute leukaemia in women and consumption of milk, tea, beer, wine and beef.(5)
Individuals with the A2 phenotype have also been found to be significantly higher in a study of patients with chronic lymphocytic leukaemia.(6) Of other polymorphisms associated with leukaemia, slow metabolisers of the cytochrome P450 (CYP) polymorphisms 2C19 and 2D6 were found to be significantly higher in patients with acute leukaemia,(7) and folic acid metabolism.(8) Cytochrome P450 plays a central role in drug and xenobiotic metabolism as well as synthesis of stress hormones, metabolism of fat-soluble vitamins and polyunsaturated fatty acids. The CYP 2C19 slow metaboliser polymorphism was also found to affect personality traits in a study of Japanese females.(9) Of the 487 Japanese volunteers in the study, those found to have slow or fast metabolism of this cytochrome were compared. Female slow metabolisers had significantly lower scores for reward dependence, cooperativeness and self-transcendence than in fast metabolisers. In males, none of the seven personality traits was significantly different between slow and fast metabolisers. CYP 2C19 metabolizes sex hormones and 5-hydroxytryptamine, which are involved in multiple brain functions.