IBD patients with PSC are more likely to have total colonic involvement than those without PSC

Reference: O'Toole, A., et al., Primary sclerosing cholangitis and disease distribution in inflammatory bowel disease. Clin Gastroenterol Hepatol, 2012. 10(4): p. 439-41.

Brief Summary: Primary sclerosing chogangitis (PSC) is a liver disease cuased by a scarring and inflamation of the the liver, and many of these patients also have IBD.  The exact relationship between intestinal site inflammation and and primary sclerosing cholangitis is not entirely clear. The main objective of this study was to determine the disease extent relationship for IBD patients with and without PSC.  The study was performed in two parts. The first part incluced 2754 IBD patients attenting a University Hospital between 1983 and 2011, and the second part included 82 PSC patients from the Irish National Liver Transplant Unity.  For the first part, IBD and PSC were diagnosed using standard protocals. 

Results: PSC was significantly associated with disease extent in both Ulcerative Colitis (UC) and Chron’s Disease (CD) patients.  Particuarly, two-thirds of UC patients with PSC had total colonic involvement wheras only 43 percent of UC patients without PSC had total colonic involvement.  Furthermore, males were more likely to have PSC than females. There was not found to be any signficant association with age.  

Implications for Practice: If a patient has PSC and IBD, there is a high liklihood of total colonic involvement vs. just left or rectal involvement. 

Discussion:  Good study here and I like the statistical design which I will get to in a bit.  It will be interesting to see follow-up studies on the the causal relationship between IBD and PSC, but little is known right now. As the authors noted, there is likely to be more than one causal pathway to PSC, since PSC can develop in the absense of IBD. 

It was interesting that males have a greater probability of contracting PSC than females, and I wonder why.  This would be another good follow up study.  This paper leaves more questions than answers, which is always a good thing!  

Commentary on Statistics and Study Design: The statistical and study design layout of the paper was good.   I like how the author looked at the relationship between several extraneous clinical and demographic variables in their association with PSC or no-PSC.  This is always an important thing to do, because it often leaves open new questions to look at, and helps fulfill the overall knowledge. 

I am a little confused, because the paper says the authors used a binary logistic regression model to generate the p-values in Table 3 but then in the table it-self, it says that various statistical measures were used such as the Mann-Whitney t-test.  Either way, the p-values would be roughly equivlant regardless of the method used, so it’s good either way.

A beer in the pub for our guys in Ireland on this.    

Hispanics are more likely to have biliary pancreatitis than Caucasians or African-Americans

Reference: Ma, M.H., et al., Risk factors associated with biliary pancreatitis in children. J Pediatr Gastroenterol Nutr, 2012. 54(5): p. 651-6.

A study out from Yale on the risk factors associated with biliary pancreatitis in children.

Brief Summary: Acute pancreatitis is an inflammatorty disease of the pancreas and has several leading causes in children including biliary pancreatitis.  There are several causes of biliary induced pancreatitis including obstrucction of the bile duct via gallstones and biliary sludge build-up.  The main objective of this investigation was to idetify the clinical features which differentiate biliary pancreatitis vs. non-biliary pancreatitis.  Another objective was to identify the clinical features which differentiate gallstone from sludge induced biliary pancreatitis.  A total of 271 patients were sampled from the Yale New Haven’s Children Hospital with pancreatitis.  Of these 271 patients, 71 had biliary pancreatitis.  A number of clinical features were collected from the patients (ethnicity, weight, calcium range, etc.). 

Results: The following clinical features were signifiantly associated with the presense of biliary pancreatitis vs. non-biliary pancreatitis: Hispanic ethnicity (vs. white or black), higher levels of medium sereum analyse and lipase, and levels of the biomarker aspartate aminotransferase.  Obesity was found to be the major clinical feature associated with the presense of gallstone induced biliary pancreatitis vs. sludge induced biliary pancreatitis. 

Implications for Practice: If a Hispanic child presents symptoms of pancreatitis, the doctor should be highly wary of biliary pancreatitis as the cause vs. other causes.  Furtermore, if the child is obese and has biliary pancreatitis, the doctor should be wary that the cause is gallstone induced biliary pancreatits vs. sludge induced pancreatitis. 

Discussion: The find that ethnicity (particulary being Hispanic) is found to be significantly associated with the presense of biliary pancreatitis was rather surprising and somewhat suspect in my mind.  From a biological perspective, how can this be?  How can Hispanics be all that different biologically from caucasians or african-americans which would lead to a greater probability of them having biliary pancreatitis?   This is really interesting.   I am curious as if other potential confounding variables were left out of the model - particuarly a diet variable which I will get to in just  a bit in the next section.

            The find that obesity also leads to a greater probability of gallstone vs. sludge induced biliary pancreatits is also another interesting find yet not as suprising.  This would make for a good follow-up study as to why this occurred for obese children vs. non-obsese children.  I am always curious to the under-causing biological mechanisms at play here.    

Commentary on Statistics and Study Design:  Overall, a good study design.  These are just some nit-picky things really which I tend to prefer.  The odds ratios were presented in the first table (Table 1) that differentiated the biliary vs. non-biliary cases, but it would also be helpful to see the odds ratios for the second table (Table 2) which differentiated the gallstone vs. sludge induced biliary pancreatitis as well.  In general, you want to be consistent in your presentation of results throughout the whole paper.  Also, for the first table, it would have been helpful to see the mean scores and/or percentages of the various quantitative and qualitative variables. In general, you want your information from the table to be as descriptive (and succinct) as possible. 

           I liked how the authors presented an interpretation for the reader of the odds ratios in the discussion and results section.  Many authors don't dot this, and this is important for those who are not as statistically inclined. Also, the general layout of the tables is really nice.  

           My biggest concern though is with the first part of the analysis which compared the biliary vs. non-bililary results where Hispanic ethnicity came out to be a significant predictor. I am concerned that there may have been a potential confounding or interacting variable left out of the investigation which may have changed the relationship between ethnicity and the main outcome - even from a signifcant to a non-significant one.  I don’t know enough about the given domain to think of any other variables which would cause the ethnicity variable to change in a full multi-variate regression model, so I will just leave this up to the authors.

            A thanks to our buddies at Yale for doing this!    

Patients with Ulcerative Colitis and Primary sclerosing cholangitis who ultimately underwent a liver transplantation were found to have a significantly reduced need for a colectomy

Reference: Navaneethan, U., et al., Progressive primary sclerosing cholangitis requiring liver transplantation is associated with reduced need for colectomy in patients with ulcerative colitis. Clin Gastroenterol Hepatol, 2012. 10(5): p. 540-6.

A study out from Cleveland on the identification and comparison of clinical features for PSC-UC patients who 1) required liver transplantation vs. no-transplantation and 2) those who underwent a colectomy vs. no-colectomy.   

Brief Summary: Primary sclerosing cholangitis (PSC) is a chronic liver disease which causes inflammation of the bile ducts in the liver and often times, orthotopic liver transplantation (OLT) is required.  PSC is very common in patients with IBD – especially Ulcerative Colitis (UC) in particular.  The main objective of this investigation was to identify and compare the clinical and endoscopic features of those patients – with both PSC and UC - who ultimately required orthotpic liver transplantation (OLT) from those who did not undergo liver transplantation.  The authors analyzed data from 167 patients who had both PSC and UC and followed them from a period from 1985 until 2011.  The patients were followed until they either had OLT or their last clinical visit (in the case of no OLT).  A secondary objective was to investigate the risk factors for patients with PSC-UC who ultimately may require colectomy. 

Results: In general, UC-PSC patients who ultimately underwent an OLT had a much milder form of UC during the follow-up.  Particularly, the number of flares and needed medication use in the OLT group was significantly less than the non-OLT during follow-up.  Furthermore, the PSC-UC patient who ultimately underwent a OLT significantly reduced the need for a colectomy. 

Implications for Practice: If a patient has a severe form of UC along with PSC, a liver transplantation may lead to a milder form of UC post-liver transplantation.   

Discussion: Investigations like this are important, and I’m glad they are done.  The find that OLT transplantations lead to a milder form of UC (in many different respects) can definitely help the decision process of both patients and doctors when it comes down to doing a liver transplantation or not for UC patients.  For patients who have a more severe form of UC and PSC, it could definitely help. 

Some of the discussion points are really interesting.  Particularly, the authors noted in the discussion section that liver cirrhosis can actually be a preventive mechanism against more severe forms of UC.  This is due to the assumption that patients with liver cirrhosis have an impaired immune system.  As someone currently investigating the bio-pathogenesis of Ulcerative Colitis heavily, this really intrigues me. 

            Also, the authors noted in the discussion that UC may cause PSC through bacterial translocation and absorption of endotoxins into the liver.  This is also really interesting. I don’t know a whole lot on the background of PSC, and this makes me want to read up on it more.    

     

Commentary on Statistics  and Study Design: Overall, a good study design.  As the authors rightly noted, there are a number of limitations in this (really any) retrospective based study.  Most notably, there is a selection limitation (not bias).  This occurs since the observational units (the patients) recruited for the observational study may be un-like the general population of PSC-UC patients throughout the world according to several variables (both known and un-known).  However, there is little the investigator can do about this limitation other than just note it at the end of the discussion section.  It would obviously be better to perform a prospective rather than retrospective study (and follow the cohort into the future) in order to identify the risk factors of a given medical outcome, but sometimes this is also difficult to do.  Even with these limitations, useful information can still be gained – especially since a previous study in London concluded similar results.  This is important. 

            The only question I would have is why a multi-variate analysis was done for the secondary aim (colectomy vs. no-colectomy) but not the main aim (OLT vs. no-OLT).  This multi-variate analysis would be interesting to look it, because it would allow the doctor to narrow down the factors which are most associated with the outcome relative to all other factors.  It is usually best to report both uni-variate and multi-variate results.  The authors may have a reason that I don’t know for doing this.

            A big thanks for my buddies up in Cleveland for doing this.   Great job!  

The risk factors for an inadequate bowel preparation

Reference: Hassan, C., et al., A predictive model identifies patients most likely to have inadequate bowel preparation for colonoscopy. Clin Gastroenterol Hepatol, 2012. 10(5): p. 501-6.

A study from Italy on the the factors which are most likely to lead to inadaquate bowel preperation for Colonoscopy. 

Brief Summary:   An inadaquate bowel preperation can severly affect the safety and efficacy of Colonoscopy – particularly for the detection of polyps and cancer lesions.  The main objective of this investigation was to identify the risk factors for an inadaquate level of bowel preperation.  Both patient (gender, age, etc.) and non-patient (type of regimine, time of preperation, etc) risk factors were considered.  A  total of 2811 patients were recruited for the study from a number of clinics throughout Italy.  The patients were accessed to have either an adaquate or inadaquate bowel preperation by an endoscopist at time of colonoscopy. 

Results: The patient factors deemed to be predictive of an inadaquate bowel preperation were being over weight, male sex, a high body mass index, older age, previous coloretal surgery, cirrhosis, having Parkison’s disease, having diabaetes and a negative result in a fecal occult test.   Among the non-patient risk factors, some of the factors which were deemed to be predictive were the type of bowel preperation regimine , the difference in time between the preperation and the actual colonoscopy (less time is better), and information on the preperation (oral+written info is better than just oral).   The authors found a moderate predictive accuracy on a validaiton test set (AUC=0.63).   The clinical detection rate of polyps and cancer lesions along with the cecal intubation rate was significantly higher in patients with an adaquate bowel prep vs. an inadaquate bowel prep.      

Implications for Practice: It is important that patients undergo an adaquate bowel preperation, and the probability of an adaquate bowel prep can be enhanced if the patient is given both a written and oral information for the bowel prep. 

Discussion: Really interesting finds here and very comprehensive to say the least.  It is alarming the difference in clinical detection rate for polpys and cancer lesions between adaquate vs. inadaquate bowel preperations.  For adaquate bowel preperations, the rate was 41% and for inadaquate bowel preps, the rate was 35% which is a rather significant difference. 

Some of the risk factors that came up positive were rather surprising.  It is interesting to see that males and those with Parkinson’s and diabates had a higher chance of an inadaquate test.  It would be neat to do a follow up explanation on many of the risk factors that came up.  It seems like the best bowel prep regimine was the Sennosides.  This seemed to be better than the use of any regimines which used the polyethylene glycol (PEG) solution or sodium phosphate. 

Commentary on Statistics and Study Design:  The study design and presentation was very good. This is an exploratory based perspective study.  In any type of exploratory based study, there are often many variables at play in the model building step, and the investigators handled them well here.  I particularly like how the authors included the results of both the uni-variate and multi-variate analysis for the logistic regression. It is always helpful to see the results of both, because it gives the reader a sense of what variables are independently and also dependently associated with the outcome variable.  The multi-variate results also tell you which variables (or risk factors) would be most likely to be associated with the outcome variable.  The only suggestion I have for the authors here would be to also include the odds ratios for the uni-variate analysis.  This could help the reader and statisticians like me.

            Going on, I also liked how the authors left out data for a validation sample.  In many exploratory based investigations, this is not done. Fortunately, the authors were able to collect a large among of data points from a quite a few clinics in order to do this, and this is why collecting a sufficient data sample size can always be a big plus.  In short, the investigator should always collect as much data points as possible for the investigation - regardless of what the power sample sizes might tell you.  More is always better if possible.      

            Overall, great layout and study design for this investigation.  I really don’t have too much to suggest.  I always try to assemble in my mind the best study designs and layouts of various papers in order to bring everything together, and this is definitely a paper I hope to reference in the future. 

The antibiotic trimethoprim-sulfamethoxazole does not benefit children with Recurrent Abdominal Pain who are positive for Blastocystis hominis

Reference: Klaas Heyland, M.F., Patrick Buehr, and Christian P. Braegger, No Advantage for Antibiotic Treatment Over Placebo in Blastocystis hominis–positive Children With Recurrent Abdominal Pain.

Journal of Pediatric Gastroenterology and Nutrition, 2012. 54(5): p. 677–679.

Brief Summary: Blastocystis hominis (B. hominis) is a parasite sometimes found in the stools of healthy people and those with diarrhea which can cause abdominal pain or other gastrointestinal problems.  The main objective of this study was to determine if the antiobiotic trimethoprim-sulfamethoxazole (TMP/SMX) can be used to effectively treat children with recurrent abdominal pain (RAP) who are also positive for Blastocystis hominis.  Forty patients were recruited for the investigation and randomly assigned to either the TMP/SMX group or the placebo group.  The main outcome measure was the difference in Pain Index (PI) from initial treatment with TMP/SMX compared to 7 days later.    

Results: There was no significant reduction in PI between the treatment and placebo group.  A treatment with Metronidazole did reduce the PI index.    

Implications for Practice: Do not prescribe the the antiobiotic TMP/SMX for children with recurrent abdominal pain who are positive for Blastocystis hominis.

Discussion: Negative results are just as important as positive results, so I am glad to see that the author’s decided to move on with a publication on this.  I am further curious as to why the TMP/SMX anti-biotic did not work from a biological perspective.   There are some signaling pathway databases that could be used to look this up; this could be an interesting follow up study perhaps.  

At the end, the author’s suggested that since the antibiotic did not work, this is evidence that B. hominis has no causative role in recurrent abdominal pain (RAP).   It seems as if an observational study could easily verify this and would be interesting to follow up with.   

Since this study showed that the antibiotic TMP/SMX does not work, it would be interesting to see if the alternative drug – metronidazole – does significantly work vs. a placebo. 

Commentary on Statistics and Study Design:  Overall, the study design looked good. It was good to see that the investigators under-took a double blind study.  Also, I liked how the author’s included a table on the demographic properties of the placebo vs. the treatment group.  This is a really good idea, because it shows – from an actual visual standpoint - that potential confounding factors were balanced between the treatment and placebo groups.   I’m assuming the authors did an exhaustive search of any potential confounding factors here.    

The author’s had to exclude any patients from the investigation with a past history of a gastrointestinal or systematic disease.  When you have a potential confounding factor which could severely hinder the investigation such as these ones, excluding subjects with these criteria is probably the best possible option, because it is obviously not possible to really block on these types of confounding factors – especially if the sample size is small.

The statistical technique used was the Mann-Whittney U Test (also known as the Wilcoxan Rank Sum Test), and this is an appropriate technique to use since – with a small sample size – it may not be feasible to assume a normal distribution.    

A big thanks to our friends in Switzerland for doing this investigation!     

A prospective study to determine if Helicobacter pylori infection is strongly associated with gastric and duodenal ulcers

Reference:  Schottker, B., et al., Helicobacter pylori Infection Is Strongly Associated With Gastric and Duodenal Ulcers in a Large Prospective Study. Clin Gastroenterol Hepatol, 2012. 10(5): p. 487-493 e1.

A study out of Germany on the effect of Heliocobacter pylori Infection in patients with either gastric or duodenal ulcers. 

Brief Summary:   It is known that Heliocobacter pylori infection (a type of bacteria which infects the stomach) is a risk factor and strongly associated with peptic ulcer disease (PUD), but it is un-known if it is associated specifically with gastric and duodenal ulcers – two specific sub-types of peptic ulcer disease (PUD).  The main objective of this prospective study was to determine the degree of association between Heliocobacter pylori infection with both gastric and duodenal ulcer disease separately.  Furthermore, patients with Heliocobacter pylori infections were further delineated between those which had expression of the cytotoxin-associated gene A (cagA+) and those that did not express the gene (cagA-).  A series of demographic factors along with whether the patient had an infection of Helicobacter pylori was collected over a period of 2 to 5 years from a German population of about 10000 individuals.   The authors also conducted a cross-sectional study to identify the risk factors of lifetime history of peptic ulcer disease.  

Results: For those patients who had a cagA positive strain (cagA+) and a Helicobacter pylori infection, there was a significant association between the presence of both the gastric and duodena ulcers separately and the Heliocobacter infection.  For those patients who did not have the cagA positive strain (cagA-) and a Heliocobacter pylori infection, the association with a Heliocobacter infection was not significant.

 

Implications For Practice: Heliocobacter infection is a strong risk factor for both gastric and duodena ulcers – especially if the patient has a positive expression for the cytotoxin-associated gene (cagA+).

Discussion: Really great investigative work here – especially the study design which I will get to in a bit.  From a biological perspective, I wonder why the patients which had an expression for the cytotoxin-associated gene A also had a much higher likelihood of association than those which did not.  Obviously, since I’m not the main author and it’s hard for me to find time to divulge myself into an investigation like this, questions like this are probably straight forward for the authors (but not to me).

Also, curious   

Commentary and Statistics and Design:  aww man, where do I start?  I really like the statistical analysis and study design of this investigation.  First, the authors were correct in the statement that prospective studies are better able to detect a true causal relationship for a given observational factor than a cross-sectional study.  The reason being is that prospective studies are better able to delineate out any potential confounding factors by the means of excluding certain patients who could confound the investigation in the first place.  This is especially true with medical based studies and is the reason why prospective studies should be chosen over cross-sectional studies for the purpose of identifying risk factors of a given disease.

           Also, I liked how the authors performed both a cross-sectional and longitudanal study with essentially the same data.  Often times in the search for risk factors, the authors will only conduct a prospective study for the risk factors, but there is a-lot of other useful information that the authors could extract initially with a cross-sectional study.    

Also, I liked how the authors included both the results from the logistic regression in both the univariate and multi-variate perspective.  Often times, I see authors include results only from the univariate perspective, but it is often best to report the results of both, because it gives a reader a sense of how the associations change from non-control to a control based setting based on the other variables.   Also, the tables were made very nicely for visualization by the reader.    The authors definitely did their job in searching for any and all potential variables to include in the model – good job here. 

My only question is the following.  In the cross-sectional study, why did the authors decide to separate the categorical and continuous variables for the use of the full multi-variate model?  I couldn’t find an answer from this in the paper, but I’m sure the authors have good reason.  I see no reason why the full model could not have included both. 

A big beer at the Hofberhaus for our German friends!  This paper will definitely be one of the references I go back to when it comes to statistics and study design.

  

Gone for a long time

Sorry for being gone for some time folks.  Been really busy on my end finishing up some school-work and what-not. However, I look forward to updating this blog on a regular basis from now on for some time!