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Don’t give up giving up ▸
Alcohol dependence has often been perceived as a problem with a low rate of remission and a response to intervention that is ill sustained. The National Epidemiologic Survey on Alcohol and Related Conditions collected data from 43 093 subjects representing a non-institutionalised adult population of the United States. The survey oversampled adults aged 18–24 years to ensure adequate numbers within this high risk population. From these data, Dawson et al identified a subset of 4422 subjects who were classified as having alcohol dependence prior to the past year, based on the Diagnostic and Statistical Manual version IV. Thirty six per cent of these had full recovery from dependence, including 18.2% who were abstainers and 17.7% considered low risk drinkers (daily alcohol intake <4 drinks for males and <3 drinks for females). Only 25% remained dependant, with the risk higher in those with a history of illicit drug use and personality disorders. The likelihood of abstinence was higher among females (odds ratio 1.5) and married individuals (odds ratio 2.2). Thirty five per cent of those who received treatment for dependence were abstinent compared with 12% of those who were untreated.
These results reassure us that substantial proportions of patients can and do recover from alcohol dependence and treatment appears to be beneficial. Subjects who developed dependence between 18 and 24 years of age were more likely to be abstinent (odds ratio 3.3 (confidence interval 2.4–4.3)) and the likelihood of recovery increased with age (odds ratio 1.04). It could be argued that early onset alcohol dependence evolves into a spontaneous “maturing out”, paralleled with taking on adult responsibilities, such as marriage and parenthood. However, long term alcoholics may die early and selective survival of those who recover could have influenced the results. Longitudinal studies would be able to examine the natural history of alcohol dependence more reliably.
“Resetting” the immune system in Crohn’s disease? ▸
This study from the Northwestern UMC in Chicago reports an extended series of 12 refractory Crohn’s patients undergoing autologous haematopoietic stem cell transplantation, confirming that this procedure can result in rapid engraftment and low toxicity. The procedure involves peripheral blood stem cell mobilisation using cyclophosphamide and granulocyte colony stimulating factor with CD34 enrichment. Immune ablation is then achieved using cyclophosphamide and antithymocyte globulin. This is probably the main effector, with reinfusion of the saved stem cells giving quicker restoration and thus less toxicity. The procedure has been reported to be an effective treatment for a number of autoimmune diseases.
The results show that 11 of 12 patients achieved remission, but one patient relapsed at 15 months. Patients did however have histological evidence of subclinical Crohn’s, and half of the patients have been followed for less than 18 months. Only two patients to date have been in remission for more than three years, so it is to early to say whether this procedure cures Crohn’s.
If Crohn’s is caused by an aberrant response to an environmental factor, then resetting the immune system may eliminate a clone of T cells and would be curative. This can be done, at least partially, with autologous stem cell transplantation, but complete ablation of pathogenic T cell clones requires the graft versus autoimmune effect of an allogeneic transplant. Likewise, if Crohn’s is due to a genetically programmed abnormality of the immune system, then autologous stem cell transplantation is unlikely to be curative. Allogeneic transplantation is of course a far more toxic and high risk therapy. Although the autologous procedure reported here shows short term benefits in Crohn’s, controlled trials are now required to see whether autologous transplantation provides long term benefits.
Upper endoscopy is often uncomfortable and distressing without sedation. Intravenous sedation requires trained personnel, intravenous access, and availability of recovery facilities, and is expensive, labour intensive, and not without risk. In this prospective, blinded, and adequately powered trial, the authors randomised 130 patients to 7.5 mg of oral midazolam or placebo as premedication 20 minutes prior to endoscopy. Anxiety scores were measured before and after the procedure and nurses used questionnaires to assess anxiety during the procedure (the primary outcome measure). Total procedure time was monitored and patients were asked to rate overall tolerance and satisfaction and the extent of amnesia. Median anxiety score during the procedure was significantly lower in the midazolam group compared with the placebo group (2.0 v 3.8; p<0.001) and more patients rated procedure tolerance as excellent or good in the midazolam group (70.8% v 49.2%). Similarly, more patients in the treatment group said they would be willing to repeat endoscopy and more reported partial or complete amnesia. There was no difference in the incidence of hypotension, oxygen desaturation, or median recovery time.
This interesting study suggests that oral midazolam may be a suitable alternative to intravenous sedation but further questions need to be answered first. A fixed dosage rather than one tailored to body weight was used, the patients studied were relatively young and healthy (ASA 1 or 2), and the optimum timing prior to endoscopy also needs to be determined. Data directly comparing oral and intravenous midazolam are also needed before changing current practice.
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