Medical marijuana to be available in Canada on open market.

Ailing Canadians were only hours away from being able to legally buy marijuana for medical purposes on the free market, officials said Monday.

As of Tuesday, Health Canada will phase out a system of homegrown marijuana for a factory-style operation that will grow, package and distribute a variety of marijuana, the Toronto Star reported Sunday.

 About 37,400 patients use medical marijuana, Health Canada says. That number is expected to rise to as many as 450,000 by 2024.

The sanctioned growers are required to raise the plants indoors and have vaults and security systems to prevent thefts of their products, which could be sold on the black market. One firm plans to initially produce 20 strains.

Recreational use of marijuana will still be banned.

Since June, 156 companies have applied for licenses. The first two were awarded last week.

Under the system being phased out, about 4,200 people were licensed to grow marijuana on their property for no more than two patients each. That type of cottage industry will now be banned. The Royal Canadian Mounted Police has charged such operations were fronts for illegal activity.

The price of legal weed is expected to soon undercut the stuff sold on the streets, where it goes for about $10 a gram, or about $280 an ounce. Health Canada projects the factory-grown marijuana will retail next year for about $7.60 a gram, or $215 an ounce. Within 10 years, industry revenues are projected to reach $1.3 billion a year.

Sophie Galarneau, a senior Health Canada official, said she expects competition to eventually get the price down to $3 a gram, or about $85 an ounce.



Characteristics and Outcomes of Patients With Vasoplegic Versus Tissue Dysoxic Septic Shock.


Background: The current consensus definition of septic shock requires hypotension after adequate fluid challenge or vasopressor requirement. Some patients with septic shock present with hypotension and hyperlactatemia greater than 2 mmol/L (tissue dysoxic shock), whereas others have hypotension alone with normal lactate (vasoplegic shock).

Objective: The objective of this study was to determine differences in outcomes of patients with tissue dysoxic versus vasoplegic septic shock.

Methods: This was a secondary analysis of a large, multicenter randomized controlled trial. Inclusion criteria were suspected infection, two or more systemic inflammatory response criteria, and systolic blood pressure less than 90 mmHg after a fluid bolus. Patients were categorized by presence of vasoplegic or tissue dysoxic shock. Demographics and Sequential Organ Failure Assessment scores were evaluated between the groups. The primary outcome was in-hospital mortality.

Results: A total of 247 patients were included, 90 patients with vasoplegic shock and 157 with tissue dysoxic shock. There were no significant differences in age, race, or sex between the vasoplegic and tissue dysoxic shock groups. The group with vasoplegic shock had a lower initial Sequential Organ Failure Assessment score than did the group with tissue dysoxic shock (5.5 vs. 7.0 points; P = 0.0002). The primary outcome of in-hospital mortality occurred in 8 (9%) of 90 patients with vasoplegic shock compared with 41 (26%) of 157 in the group with tissue dysoxic shock (proportion difference, 17%; 95% confidence interval, 7%–26%; P < 0.0001; log-rank test P = 0.02). After adjusting for confounders, tissue dysoxic shock remained an independent predictor of in-hospital mortality.

Conclusions: In this analysis of patients with septic shock, we found a significant difference in in-hospital mortality between patients with vasoplegic versus tissue dysoxic septic shock. These findings suggest a need to consider these differences when designing future studies of septic shock therapies.


New Evidence about an Old Drug — Risk with Codeine after Adenotonsillectomy.

During the past 10 years, efforts in pharmacogenomics have generated insights into the efficacy and safety of drugs, enhancing our understanding of the safety profile of even some of the oldest drugs, such as codeine sulfate, an opioid analgesic first approved in 1950 for relief of mild or moderate pain. Simultaneously, an increased awareness of the value of both personalized medicine and the reporting of rare adverse outcomes has resulted in the publication of information on adverse events that previously might not have been reported. These developments, in turn, led the Food and Drug Administration (FDA) to reanalyze the safety of — and ultimately restrict — codeine use in patients after adenotonsillectomy.

The activity of codeine depends on its conversion to morphine by the cytochrome P-450 isoenzyme 2D6 (CYP2D6); morphine is subsequently metabolized to the active morphine-6-glucuronide by means of UDP-glucuronosyltransferase 2B7. The gene encoding CYP2D6 has many genetic variations that affect the amount of codeine that is converted to an active form and that result in the drug’s variable effect. Patients with a normal range of CYP2D6 activity represent 75 to 92% of the population and are called extensive metabolizers. At the low end of the activity spectrum are poor metabolizers (approximately 5 to 10% of the population), who have no functional alleles and therefore receive little to no morphine or analgesia from codeine. At the high end of the CYP2D6 activity spectrum, ultrarapid metabolizers have two or more functional alleles, and their bodies can convert codeine into large amounts of morphine. The prevalence of ultrarapid metabolism varies by ethnic group: it is lower than 1% among Chinese and Japanese patients but potentially higher than 15% among Middle Eastern and North African patients. Clinically significant toxic effects related to opioid excess have been reported in ultrarapid metabolizers, which suggests that the risk of toxic effects from codeine depends, in part, on genotype.1

In April 2012, a case series was published reporting two deaths and one case of respiratory depression in children 3 to 5 years of age who had received typical doses of codeine after tonsillectomy, adenoidectomy, or both performed because of obstructive sleep apnea.2 The two deaths occurred in children who had evidence of being ultrarapid metabolizers, and the postmortem morphine levels in these children were substantially higher than the therapeutic range. The third child was an extensive metabolizer. Signs of morphine toxicity developed within 1 to 2 days after codeine treatment began.

In response to that publication, the FDA initiated an evaluation of the safety of codeine in children. This assessment included a comprehensive review of the literature and case reports that were submitted to the FDA’s Adverse Event Reporting System (AERS, now known as FAERS) between 1969 and May 1, 2012. This search identified 13 cases, including 10 deaths and 3 cases of life-threatening respiratory depression associated with therapeutic codeine use. Seven of these 13 cases (including the 3 from the case series mentioned above) had been reported in the medical literature. Patients ranged in age from 21 months to 9 years. Most of the patients had undergone adenotonsillectomy (eight patients) or had a respiratory tract infection (three patients), and they appeared to receive appropriate doses of codeine. Of the seven children described in the published cases, three were characterized as ultrarapid metabolizers, three as extensive metabolizers, and one as a probable ultrarapid metabolizer. A search of the medical literature and AERS for cases of pediatric death or life-threatening respiratory depression with therapeutic use of hydrocodone, oxycodone, or morphine was also conducted and did not identify robust cases of unexplainable or unconfounded death or life-threatening respiratory depression after the use of these drugs.

In late 2011, the Patient Safety and Quality Improvement Committee of the American Academy of Otolaryngology–Head and Neck Surgery (AAO-HNS) was also becoming concerned about adverse events, particularly respiratory depression, after adenotonsillectomy. Such events have been described informally for decades but rarely reported. In 2012, the committee conducted a nationwide, anonymous survey of otolaryngologists to learn more about these events. When the FDA announced its investigation (, the committee reached out to share prepublication results with the agency. Limited information was available; however, two children (a 3-year-old and a 12-year-old) with obstructive sleep apnea who died after adenotonsillectomy were confirmed (by genotype) to be ultrarapid metabolizers or suspected (because of high postmortem blood morphine levels) of being ultrarapid metabolizers.3

The only well-documented cases of death or respiratory arrest after codeine treatment in ultrarapid-metabolizing children have involved patients who have just undergone adenotonsillectomy. That does not mean that the risk is not present in other situations, but currently available evidence suggests that the risk is most substantial in children after they have undergone tonsillectomy, adenoidectomy, or both. Many such children have sleep-disordered breathing, and children with sleep-disordered breathing are known to be more sensitive to opioids.4

Therefore, the FDA recently required that the manufacturers of all codeine-containing products add a boxed warning to the labeling of their product that describes the risk posed by codeine after a child has undergone tonsillectomy or adenoidectomy. A contraindication will be added to restrict codeine use in such patients. The “Warnings/Precautions,” “Pediatric Use,” and “Patient Counseling Information” sections of the labeling will also be updated.

Performing routine genotyping before prescribing codeine was not recommended for several reasons. Some of the patients who died or in whom respiratory depression developed were genetically extensive metabolizers, so patients with “normal” genotyping results may still be at risk. Also, since the number that would need to be screened to prevent such a rare toxic effect would be very high, and since preoperative laboratory assessments are not routine before adenotonsillectomy, the practicality of genotyping is questionable.

Although it did not participate in the FDA’s decision process, the AAO-HNS supported the labeling changes because of the increasing evidence that these extremely rare but catastrophic events can be related to codeine use, because codeine is ineffective in some patients (poor metabolizers), and because of emerging clarity that a variety of other drugs (e.g., some nonsteroidal antiinflammatory drugs) are safe to use and do not increase the risk of bleeding.5 The AAO-HNS informally surveyed opinion leaders in academic medicine, private practice, and pediatric otolaryngology and reached a consensus that the availability of other analgesic agents and the risk of catastrophic events outweighed the value of codeine.

Even old and commonly used drugs may cause rare but catastrophic events that will not be recognized without a vigorous effort by the profession to share information in the literature. In the case of codeine, a combination of case reporting and our evolving understanding of genetic influences on drug response has clarified the need to avoid this drug after adenotonsillectomy.

Source: NEJM


Researchers assess multiple vitamin D doses in healthy breast-fed infants.

Researchers in Canada suggest that vitamin D supplementation of 1,600 IU per day increased plasma 25-hydroxyvitamin D concentrations to at least 75 nmol/L among 97.5% of infants aged 3 months. However, this dosage also increased concentrations associated with hypocalcemia, according to data.

The literature has established that vitamin D supplementation for infants is required to support healthy bone mineral accretion. However, conflicting recommendations for this patient population have led to further research.

“We have generated strong support using evidence-based dose response studies that the 400 IU dosage is quite satisfactory and that this is recommended now by the Institute of Medicine, Health Canada, Canadian Pediatric Society and the American Academy of Pediatrics,” researcher Hope Weiler, RD, PhD, of the School of Dietetics and Human Nutrition at McGill University in Quebec, said during a media telebriefing. “We also know that the higher dose recommended by the Canadian Pediatrics Society was well received by our infants and did generate a nice response in 25-hydroxyvitamin D, and the upper limits of 1,000 IU and 1,200 IU would be suitable as safety markers across the first year of life.”

According to data from a double blind, randomized study published in JAMA, Weiler and colleagues investigated the efficacy of various dosages of vitamin D supplements in supporting plasma 25-(OH)D concentrations in healthy, breast-fed infants (n=132) aged 1 month. The patients were randomly assigned to oral cholecalciferol (vitamin D3) supplements of 400 IU per day (n=39), 800 IU per day (n=39), 1,200 IU per day (n=38) or 1,600 IU per day (n=16), and they were followed for 11 months.

According to 3-month data, 55% (95% CI, 38-72) of infants in the 400-IU group demonstrated a 25-(OH)D concentration of at least 75 nmol/L vs. 81% (95% CI, 65-91) in the 800-IU group, 92% (95% CI, 77-98) in the 1,200-IU group and 100% in the 1,600-IU group. Due to elevations in 25-(OH)D concentrations, the 1,600 IU dosage was discontinued, researchers wrote. Moreover, the concentration did not continue in 97.5% of the infants at age 12 months in any of the groups.

Further data indicate that all dosages established 25-(OH)D concentrations of at least 50 nmol/L among 97% (95% CI, 94-100) of the infants at 3 months. This continued in 98% (95% CI, 94-100) at 12 months, the researchers wrote.

“Future studies should be larger and, hopefully, be able to detect early, as well as [determine], long-term benefits to bone. We may also consider other health benefits such as the immune system. Our future studies should consider other populations,” Weiler said. “We should also consider those at higher risk for deficiency, whether it’s due to geographic location where a mother’s exposure to sunshine is limited or the infant is born with vitamin D deficiency.”

In an accompanying editorial, Steven A. Abrams, MD, of the department of pediatrics at the US Department of Agriculture/Agricultural Research Service Children’s Nutrition Research Center at Baylor College of Medicine and Texas Children’s Hospital in Houston, said the study did not answer the question of what the target should be for plasma 25-(OH)D concentrations.

“Of importance, higher vitamin D dosages in this study did not lead to improved bone outcomes as reflected by DXA results for bone mineral content,” Abrams wrote.

He suggested that higher vitamin D intake and target plasma 25-(OH)D concentrations should be tested in clinical trials with markedly defined outcomes and precise safety monitoring.


Weiler H. JAMA. Theme Issue on Child Health: New research on the optimal dosing and possible adverse effects of different levels of vitamin D supplementation, important for bone health, for infants. Presented at: the JAMA Network 2013 Media Briefing; April 30, 2013; New York.

Disclosure: Abrams reports payment for lectures’/speakers’ bureaus from Mead-Johnson Nutrition and Abbott Nutrition and grants to his institution from Mead-Johnson Nutrition. Gallo reports travel support from CIHR Human Development Child and Youth Health and the American Society for Bone and Mineral Research. Sharma reports consulting fees for analyses prepared for Rodd and Weiler. Jones reports being cofounder and scientific advisory board member for Cytochroma Inc., and for receiving payment for speakers’ bureaus from Genzyme/Sanofi.





  • I  think it’s a helpful study in terms of the fact that they had different groups of newborn children treated with vitamin D with 400 IU being the recommended dose up to 12 months according to the Institute of Medicine and Endocrine Society guidelines. It was a well-designed study and relevant because vitamin D is a very hot topic right now due to the deficiencies in children and adults.

I agree with the editorial. This group of patients was a mostly white group with relatively high socioeconomic status. In the group that was administered 400 IU per day, researchers found that those infants reached 25(OH)D level of at least 20 ng/mL. That is a big debate. The IOM thinks 25(OH)D levels of 20 ng/mL are adequate for most, and I think a lot of endocrinologists and the Endocrine Society says most people need a level of 30 ng/mL.

This study shows that infants who were administered up to 400 IU per day reached a level of at least 20 ng/mL by 3 months. The whole group did not attain the level of 30 ng/mL, which again is what some endocrinologists think is an optimal level. To achieve a level of 30 ng/mL, perhaps 400 IU is not enough per day for some infants (especially those with darker skin pigmentation or at higher risk for deficiencies).

In addition to looking at the levels or how much vitamin D is needed to achieve a level of 20 ng/mL or 30 ng/mL, they also looked at the bone mineral content but found no significant difference in the groups. I think the editorial comment summed up this point. In treating infants with higher doses of vitamin D corresponding to higher serum levels above 30 ng/mL; does that confer other benefits? There are many early studies now looking at the relationship between vitamin D and asthma, food allergies, incidence of type 1 diabetes and autoimmune disease.

The important point Abrams raises is that we need more long-term studies to see if there is a skeletal benefit in terms of having a higher vitamin D level which would correspond to having a higher dose of vitamin D administered.

  • Dominique Noё Long, MD
  • Instructor of pediatric endocrinology
    The Johns Hopkins Children’s Center
    Baltimore, Md.



  • The strengths and usefulness of the study are the quantification of serum 25-OH vitamin D levels with various doses of vitamin D supplementation. The currently recommended dose of vitamin D, 400 IU daily, was chosen because historically this dose has proven to prevent rickets, which as pediatric endocrinologists, is our main objective. Therefore this study helps provide information in the ongoing debate regarding the optimal serum level of 25(OH) D. Interestingly, all doses of cholecalciferol increased serum levels of 25(OH) D to >50 nmol/L. Higher doses of cholecalciferol correlated with higher levels of 25(OH) D, however no group sustained >97.5% of infants to vitamin D levels >75 nmol/L. No one truly knows the ideal serum level of vitamin D, but this study suggests that >50 nmol/L was sufficient in this patient population. This study also provides information on the safety of higher doses of vitamin D supplementation. It may be harder to extrapolate in the darker-skin pigmented population who may need more vs. the white population. It’s just another piece to the puzzle of the debate on vitamin D.
  • Janet Crane, MD
  • Clinical research fellow in pediatric endocrinology
    The Johns Hopkins Children’s Center
    Baltimore, Md.



Major Problems With Food Safety That Could Make You Sick.

The latest recall of E. coli infected beef should not only be a concern for beef and beef products but also other meats, cheeses, vegetables and water.

E. coli is a generic name for billions of such bacteria thriving in the alimentary canal of humans and animals. Their presence in food or water indicates fecal contamination.

The consumption of any such food or water can cause deadly disease. It cannot become safe by cooking or irradiation. Irradiation of the end products, such as steaks, hamburger, etc., may kill microbes but it does not exclude their original source which is feces and urine. Irradiation of meat may also generate carcinogenic substances. All such food and water must be rejected.

What Promotes E.Coli Infection?

Virtually every E. coli infection traces to unsanitary conditions in which food-producing crops and animals are being cultivated, processed, transported, stored, and ultimately sold for human consumption.

Most food-producing animals these days are raised at mega farms, commonly called factory farms. From there, they get transported for thousands of miles to similarly large slaughterhouses without being fed or watered for as long as 48 hours.

Covered in feces and urine, dehydrated, frozen and badly bruised, approximately 50 percent of them are reported to arrive there already dead. Moreover, the mechanized tools and procedures used to slaughter these animals convey their infection-loaded excreta into the eventual meat and meat products for human consumption.

Finally, the waste water from these mega farms, slaughterhouses, packing plants and other establishments gets drained into fields, rivers, lakes and wells. Reports indicate that every year approximately 36 million Americans and 11 million Canadians contract food-borne infections, out of which many thousand get hospitalized and several thousand die.

Drugs Used in Livestock are Central to the Problem of Food Borne Illness

Central to this problem are the drug manufacturers selling tons of different antibiotics to prevent frivolous infections in farm animals. However, what ends up happening in these animals is that thus used antibiotics destroy harmless microbes in their alimentary canal and yield room to antibiotic resistant “super-bugs”, such as E. coli, Salmonella, Listeria, etc.

Due to these problems, large scale use of antibiotics is no longer allowed in the EU. In contrast, it continues to prevail in the US and Canada with government approval.

Another cause for concern is illegal approval of sex hormones by USFDA and Health Canada in beef production. Beef stimulating hormones are recognized to be “complete carcinogens”. In other words, they can initiate cancers and also promote existing cancers. In addition, sex hormones are recognized to cause endocrine disruption.

As such, sex hormones cause reproductive disorders, such as infertility, precocious puberty, drop in sperm count, etc. Like antibiotics, no such hormones to increase beef production are allowed to be utilized in the EU.

Other Food Safety Concerns: Slaughterhouse Waste Used in Animal Feed, and GMO’s…

Yet another concern for food safety should be the Canadian approval of slaughterhouse waste being fed to food-producing animals, which is known to transmit BSE in cattle (mad cow disease) and CJD (a fatal neurogenerative disorder) in people. Once again, any such use of slaughterhouse waste is strictly forbidden in the EU. The only other industrialized country allowing agricultural applications of antibiotics hormones and slaughterhouse waste is the US, whose food safety record is no better than that of Canada.

At issue also are genetically modified organisms (GMOs) attached to various herbicides and pesticides to increase agricultural yields of milk, meat, vegetables, fruits and ethanol whose public safety is being questioned throughout the world but not in Canada or the US.

These should be sobering thoughts for both Health Canada and CFIA. They cannot go on pretending the Canadian food supply to be the safest in the world when it is so frequently found to be unsafe. People have the right to know how their food is produced. The only sure way to know that is to conduct a public inquiry.

Source: Dr. Mercola