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Heavy marijuana use in youth could lead to irreversible changes in brain structures affecting memory 

MD-FM Thursday December 19, 2012 


MDFM: Medical News from around the world with Peter Goodwin.


SEGMENT 1: CANNABIS: Brain structural changes correlated with working memory deficits in young adults with past history of chronic marijuana use.


Hello, and with me is Sarah Maxwell. To begin with, chronic cannabis use, at a young age, could be associated with irreversible changes in brain structures that affect memory. That’s according to a study published in Schizophrenia Bulletin



Yes, it’s a point-in-time study looking at young adults who’d used marijuana daily for about three years and then stopped, compared with non-users. MRI scans were performed two years after they’d quit, and shape abnormalities were found inside brain regions associated with working memory. This is the first time this has been shown in a study, and these changes in structure were directly correlated with poorer performance during memory tasks. Also, the younger the subjects had started using cannabis, the more severe the brain abnormality.



Even though we cannot say that our data shows causation, that relationship between the younger the use the more abnormal the brain supports causation. But we need longitudinal data to see if marijuana really does change the brain.



That was lead study author Dr. Matthew Smith, from Northwestern University in Chicago.



And one point I noticed in the study was a frighteningly high incidence of nicotine use among subjects using cannabis…



Right. Lisa Blecha, who did not participate in the study, said these findings strongly suggest that using cannabis is not harmless:



It just counters the perception that cannabis is a drug that doesn’t have a really big impact. Really, you need to be very cautious about cannabis use in your patients, especially in young adolescents. We’re talking about 12, 13, 14 year olds who are starting cannabis use and these are particularly vulnerable ages --the earlier you use cannabis, the greater the working memory deficits and that’s going to have some very long term consequences.



Dr. Lisa Blecha, from Hopital Paul Brousse in Villejuif France.



SEGMENT 2: Adding carboplatin or bevacizumab to standard adjuvant chemotherapy improved complete response rates in women with triple negative breast cancer.


News now from last week’s San Antonio Breast Cancer Symposium: For women with triple-negative breast cancer, adding the chemotherapy drug carboplatin or the antibody agent bevacizumab pre-operatively to standard neo-adjuvant chemotherapy, significantly increased the percentage of those with no residual cancer detected at surgery. Very encouraging results for this difficult to treat patient population...



Yes, this is from a study that looked at 450 women with stage-2 and 3 triple negative breast cancers. Complete responses went from 34 per cent in those on standard chemotherapy, to 48 per cent when carboplatin was added and 51 percent with bevacizumab. However, it was carboplatin that showed the best overall profile:



While bevacizumab clearly improves responses to the chemotherapy, the cost for doing that, the side effects for doing that, is greater. With the carboplatin, there were more problems with low blood counts but not many serious or life threatening side effects. But also, we don’t know that adding the carboplatin will improve the long-term results. Obviously we hope that it will translate into fewer patients in whom the cancer recurs



That was William Sikov, from Brown University in Rhode Island and senior author Eric Winer added that despite these encouraging data, it’s still too early to use carboplatin in practice:



We still don’t know how best to use it --whether it should be added to the standard therapy or whether it should be substituted for one of the drugs and finally, we don’t know which patients seem to benefit the most and that’s something we are going to be investigating in this study and something that other studies will be investigating. So I think it’s an exciting finding but it should not lead to doctors giving patients adriamycin, cytoxan, paclitaxel and carboplatin for treatment of triple negative breast-cancer.



Dr Eric Winer, from the Dana Farber Institute in Boston.


SEGMENT 3: Adding carboplatin and veliparib to standard chemotherapy improved outcomes in triple-negative breast cancer in adaptive randomization trial.



And another study looking at improving neo-adjuvant therapy for patients with triple negative breast cancer was also highlighted in San Antonio. When both carboplatin and the targeted agent veliparib were added to standard pre-operative chemotherapy the estimated complete response rate went up from 26 per cent to 52 per cent. This was in an independent randomized trial sponsored by the NIH, with an ‘adaptive’ statistical design — that’s to say a technique used to identify optimal therapy by evaluating different regimens in relatively small groups of patients with specific tumour biomarker signatures.

SEGMENT 4: Wrist fracture significantly raises risk of hip fracture.




People who have had recent wrist fractures are at significantly higher risk of hip fractures the following year. That’s according to data presented at the International Osteoporosis Foundation’s 4th Asia-Pacific Meeting, which took place in Hong Kong last week…



Yes, the incidence of hip-fractures at one year was six times higher in patients who had had a Colles' fracture — that’s a fracture of the distal radius in the forearm — than in those who hadn’t. The highest incidence of subsequent hip fractures was in the first month after the wrist fracture, and the numbers also increased with patient age.



And, did the researchers only look at the relationship between Colles’ fractures and hip fractures then?



No, besides Colles' fracture, they showed that osteoporosis was also an independent predictive factor for hip fracture. However, the risk was much greater in patients with wrist fractures — a hazard ratio of 6.6 compared to 4.3 in those with osteoporosis. And patients who had both osteoporosis and Colles’ fracture were at even greater risk — suggesting that patients have reductions of both bone quality and quantity.

SEGMENT 5: New data suggests no significant association between antidepressant use during pregnancy and autism in offspring. 



No statistically significant association has been found between the use of selective-serotonin-reuptake-inhibitors during pregnancy, and an increased risk of autism spectrum disorder when the child is born. Contradicting smaller recent studies suggesting a possible link...



Yes, this latest finding comes from a large population-based cohort study — published in the New England Journal of Medicine — looking at over 620,000 births in Denmark. In their unadjusted analysis, the researchers actually did find an increased risk of autism when mothers used SSRIs during pregnancy. But that risk was no longer significant when they adjusted for factors such as psychiatric diagnoses that could, themselves, be associated with autism.



OK, but three previous studies — admittedly smaller — have shown an increased risk of autism… One of them found SSRIs during the first trimester of pregnancy tripled the risk of autism in children!



Yes, and to be fair, the lead author of the Danish study — Professor Anders Hviid from Statens Serum Institut in Copenhagen — did tell MDFM that further studies are needed. So, understandably some experts aren’t quite convinced by these Danish findings:



When you actually look at their data, it’s actually on the border of statistical significance. and we know that database studies tend to underestimate risk --You really can’t know if a woman is taking a medication when you’re looking at 600,000 women… So I am not reassured by this. We seem to keep trying to explain these away, often by blaming the underlying depression, but I think that really we need to have caution here. We don’t have good examples of treating developing embryos and fetuses with such chemicals and having good results from that.



That was Adam Urato, from Tufts Medical Center in Boston.

IN BRIEF 1: Medical communication companies receive substantial financial support from drug and device companies.



Finally, in brief: Medical communication companies received about 100 million dollars from 13 drug companies and a device company according to combined data from the 2010 grant registries. Research, published in JAMA, found that most of the 18 communication companies were ‘for profit’ and were conducting continuing medical education programs. The authors cautioned that physicians who interact with such communication companies should be aware that all of them require personal data, which might be shared with unnamed third parties.

IN BRIEF 2: ACE inhibitors and ARBs associated with lower mortality for pre-dialysis patients with advanced chronic kidney disease.

Patients with stable hypertension who were at the most advanced stage of chronic kidney disease, just before dialysis, appeared to have a lower risk of dying and long-term dialysis if they were treated with angiotensin-converting enzyme inhibitors or angiotensin-II receptor blockers. This was the finding of a study — published in JAMA Internal Medicine — looking at over 28,000 patients with the most advanced pre-dialysis stage of chronic kidney disease, hypertension and anaemia.


That's all from MDFM for now. Sarah Maxwell and I will be back in January! So until then, from me Peter Goodwin, have a merry Christmas and a happy new year!


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