Concomitant Gastroparesis has a negative affect on children with Biliary Dyskinesia

Reference: Chumpitazi, B.P., et al., Concomitant gastroparesis negatively affects children with functional gallbladder disease. J Pediatr Gastroenterol Nutr, 2012. 54(6): p. 776-9.

A study out from Baylor on how concomitant gastroparesis (CG) can negatively affect biliary dyskinesia (BD). 

Brief Summary: Gastroparesis is a medical condition of the stomach where the food remains in the stomach for too long. It is thought that this condition can negatively effect patients with biliary dyskinesia (a disturbance of the biliary ducts).  The main objective of this retrospective study was to determine the prognostic effect that concomitant gastroparesis (CG) has on biliary dyskinesia (BD).  A total of 35 children were accrued into the investigation who had biliary dyskinesia (BD).  Of these 35 patients, 20 had CG, and the other 15 did not have CG.  The time of the last follow-up was then checked, and assigned to 4 clinical outcome groups based on the symptoms: poor, fair, good, excellent.  The children with CG were then compared to the children without CG. 

Results: The children who had CG were more likely to have un-favorable clinical outcome (defined as poor or fair) than children who did not have CG.   Furthermore, in children undergoing a cholecystectomy, the clinical outcomes were worse for children with CG.   

Implications for Practice:  Children who have both CG and BD need to be monitored closely as their clinical outcome may be worse than children who only have BD.  Particularly, the Gastroenterologist needs to be wary of mis-diagnosing CG patients as BD.   

Discussion:  Interesting study here on the interaction between CG and BD on clinical outcome.  I liked how the authors gave an explanation for the reason why children with both CG and BD have a less favorable outcome.  The authors noted that this may be due to miss-directed therapies.  Therapies that are directed solely against BD may not address the symptoms against CG.    

It is interesting to see that the author’s used schools absences as an indicator for limitations in activity.   I have never seen this variable used before to determine the level of severity, but I suppose that it would be a good indicator of severity.  As good as anything else I suppose for a more objective indicator.  

Commentary on Statistics and Study Design:  I guess I have two major suggestions for the authors: one related to the statistical technique used and one with the presentation of the results. 

First, let’s start with the statistical technique. The author’s took what was originally a 4 category response variable for the clinical outcome (poor, fair, good, excellent) and converted it into a 2 category (binary) response (favorable and un-favorable) and then performed your typical 2 category logistic regression analysis.  However, the author’s just have used a multi-variate outcome logistic regression technique for an ordinal response.   This is called polytomous logistic regression.  Polytomous logistic regression is incredibly easy to implement in SPSS.   In fact, the interpretation is just about exactly the same as your standard binary response logistic regression.    But back to the point: running this polytomous logistic regression would have prevented the loss of information from going down to 2 categories from 4 with the response variable.   The authors then could have reported the individual p-values for each level of the response variable.  Simple and easy to do really. 

As for the presentation, the author’s performed a multi-variate regression technique, but it would have been helpful to see the results in more of a table-like format.  I wish I would have my primer up already on how to visually report statistical results up correctly in a publication, but alas, in my busyness I don’t. The typical procedure here is to report both the uni-variate and final multi-variate (adjusted) results.   The reason you want to also report the multi-variate results is that it gives the reader a good idea of what final predictors are most indicative of outcome.   Come back when I have this final primer up – it could have helped this paper tremendously. 

Also, it may have been helpful to obtain more samples.  Given the small sample size - 35 children - it may have been difficult to make confident conclusions. This is one limitation that the author's should have probably noted at the end.  

A big  thanks to our Baylor pals for  doing this. Love RG3 – go Skins!            

Probe-Based confocal laser endomicroscopy shown not to be as effective as other advanced imaging techniques for the differentiation of colorectal lesions

Reference: Kuiper, T., et al., Feasibility and Accuracy of Confocal Endomicroscopy in Comparison With Narrow-Band Imaging and Chromoendoscopy for the Differentiation of Colorectal Lesions. Am J Gastroenterol, 2012. 


A study out of the Netherlands on the effectability of various advanced imaging techniques for the differentiation of colo-rectal lesions.

Brief Summary: The main objective of this study was to compare the accuracy of several advanced imaging techniques for the differentiation of colon cancer. Particularly, the advanced imagine techniques compared were Chromoendoscopy (CE), Narrow Band Imaging (NBI), and probe-based confoscal laser endomicscropy (pCLE).  Specifically, two different variations of the Narrow Band Imaging were analyzed - one that uses the Kudo pit pattern (NBI-Kudo) and another that used the vasculor pattern intensity for differential diagnosis (NBI-VPI).  

Results: The authors found that the pCLE imaging technique was significantly less effective than any of the other advanced imaging techniques (CE, NBI-Kudo, NBI-VPI). Specifically, the authors later showed that the CE and NBI-Kudo methods were the two best advanced imagine techniques.  

Implications for Practice: For the purpose of advanced imaging, Gastroenterologists can not yet place a high degree of confidence on the probe-based confoscal laser endomicscropy technique  for the differential diagnosis of colon lesions. Rather, they should place a greater priority on the Chromoendoscopy and the Narrow Band Imaging with the Kudo accessment advanced imaging techniques for the purpose of differentiating colon lesions.  

Brief Discussion: One of the advantages of the pCLE method is that it can provide a direct diagnosis of individual cells without the need for any biopsy - thus reducing the total time and cost of a colonoscopy considerably. However, in order to use the pCLE method, it needs to show a greater degree of effectiveness than other advanced imagine techniques, and this study shows that it does not.  

It was interesting to note that the authors found that the accuracy of the pCLE method increased for the high quality videos vs. the lower quality videos.  If more attention could possibly be put towards getting higher quality videos, then this could significantly enhance differential diagnostic accuracy.       

Brief Commentary on Statistics and Study Design: Overall, the statistical design of the experiment looked good.  The statistician decided to use the McNamara's test in order to compare the contingency tables derived from the various imagine techniques, which is the correct test to use for this.  One can obviously not assume that the evaluative results from the various imaging techniques are independent, so the McNamara's test is the correct one to use.   

It would have been interesting to see if the ratings from the different imaging techniques were different depending on various patient characteristics. For instance, would a certain test be more effective than another test based on the age of the patient? Common sense would probably say no, but it would still be interesting to see.

Twice-Daily Dosage of Rabeprazole (RPZ) found to be more effective than a Single-Daily Dosage for Severe Reflux-Esophagus Disease

Reference: Kinoshita, Y. and M. Hongo, Efficacy of Twice-Daily Rabeprazole for Reflux Esophagitis Patients Refractory to Standard Once-Daily Administration of PPI: The Japan-Based TWICE Study. Am J Gastroenterol, 2012.

A study out of Japan on the effect of a twice-daily dosage vs. a once-daily dosage for patients with severe Reflux Esophagitis disease who do not initially respond to a proton pump.  

Brief Summary:  About 10 percent of Reflux Esphagitis (RE) patients do not initially respond to proton pump inhibitors (PPIs) - especially common in those with severe RE.  The main objective of this study was to determine whether increasing the effective dosage of a type of PPI called rabeprazole (RPZ) would lead to significant healing.  Specifically, it was desired to see if a 10 or 20 m.g. b.i.d. (twice-daily) regime dosage is more effective than a 20 m.g. q.d. (once-daily) regime dosage of RZ.  About 330 patients were randomly assigned to three different groups consisting of a 10 m.g. b.i.d., 20 m.g. b.i.d., or 20 m.g. q.d. regime dosage.   The primary comparison end-point between the three groups was the rate of endoscopically confirmed healing after 8 weeks, and a second end-point comparison was the weekly heartburn resolution after 4 weeks.    

Results: In general, a regime of 10 or 20 m.g. twice-daily dosage of RPZ was found to be more effective than a 20 m.g. single-daily dosage among patients who did not respond to initial treatments of PPI. Specifically, patients with Los Angeles grade A or B RE were found to respond optimally to a regime dosage of 10 m.g. twice-daily RPZ whereas patients with Los Angeles grade C or D RE were found to respond optimally to a regimen dosage of 20 m.g. twice-daily RPZ.  The heartburn resolution also decreased for the two twice-daily regimens.  The Los Angeles classification system is typically used to classify Esophagitis patients into four different groups based on severity.  Group A is the least severe and Group D is the most severe.   

Implications for Practice: If a patient does not respond initially to the standard proton pump inhibitor (PPI) regimen, then the patient should be prescribed either a 10 or 20 m.g. b.i.d. regimen of Rabeprazole (RPZ). If it is known that the patient has type A or B, prescribe 10 m.g. twice-daily of RPZ; if it’s known that the patient has type C or D, prescribe 20 m.g. twice-daily of RPZ.

Discussion: More studies like this need to be done in order to elucidate the optimal dosage for a given condition.  It was interesting that Los Angeles group A and B patients were found to have a different optimal dosage than group C or D patients.

Brief Commentary on Statistics and Study Design: The authors used the Cochran-Armitrage test which can be used for this purpose. However, since the outcome variable was continuous, it would have been more simple and easy just to use simple general linear regression (GLR) or an ANOVA model, and this is what really should have been used. The advantage of using a GLR is that it is fairly simple to control for any other potential confounding variables.  Indeed, there are several other demographic variables that could have been included.  The ANOVA model could have then been used to compare the means from the three different groups and are setup specifically for experiments like this.  In statistics (as in most anything in life), the simplest solution is usually the best.  

Pancreatic stents (PS) should not be left in situ for more than 7 to 10 days during endoscopic retrograde cholangiopancreatography

Reference: Hill, S.K., C. Bhalla, and A. Thomson, Risk of bacterial colonization of pancreatic stents used in endoscopic retrograde cholangiopancreatography. J Clin Gastroenterol, 2012. 46(4): p. 324-7.

Brief Summary: Pancreatic stents (PS) are often used during endoscopic retrograde choloangiopancreatography to reduce the risk of pancreatitis.  However, if left in situ for more than 2 weeks, there is evidence that they may lead to pancreatic duct injury via micro-organism colonization.  The main objective of this study was to investigate the incidence of pancreatic stent colonization and study the relationship between the pancreatic stent colonization with type, length, duration and time the PS remained situ.   The authors were able to obtain 47 pancreatic stents in situ, and these stents were then sent away for microbial culture where the pancreatic stents were then classified as being either significant or insignificant based on their microscopic colonization.  The cultures were classified as being insignificant if there was no growth of pathological organisms with clinical significance. 

Results: Pancreatic stents left in situ for more than 10 days were found to have a 3.3 times greater risk of harmful microscopic colonization compared to just 2 days.  There was no significant relationship found based on type or length of pancreatic stent. 

Implications for Practice: Current recommendations suggest that pancreatic stents remain in place for no more than 14 days. However, this study shows that the Pancreatic Stents should not remain in place for more than 10 days.  More generally, the Pancreatic Stents should be removed as soon as their preventive value for post-ERCP pancreatitis is exhausted. 

Discussion: Studies like this which detail and optimize best practices are important and more should be done.  It would be interesting to find out why 10 days seemed to be the cutoff point.  This probably has to do with the rate of colonization of the bacteria, and there are probably some interesting follow up studies to elucidate this.

Brief Commentary on Statistics and Study Design:  The overall study design and statistical approach seemed to be good.  A multi-variate logistic regression model was fitted which is the correct statistical model to use for this.  It would appear as if the predictor variables in the model were duration and length of the Pancreatic Stent, and all other variables were thrown out of the logistic regression model due to their non-significance with the outcome variable.  The authors did say that the other variables (age, gender, indication, or diagnosis) had no significant correlation with bacterial colonization, and this was harmful.

I am curious as to why there were no power calculations done.  I assume that 47 samples would be ample though. 

A report on the incidence and mortality of liver cirrhosis - underscores why early diagnosis is important -

Reference: Fialla, A.D., O.B. de Muckadell, and A. Touborg Lassen, Incidence, etiology and mortality of cirrhosis: a population-based cohort study. Scand J Gastroenterol, 2012. 47(6): p. 702-9.

It’s not often I get to comment on an epidemiological based study, so this is exciting!  A study from Finland on the case incidence of cirrhosis. 

Brief Summary:  The main objective of this study was to detail the incidence and mortality of cirrhosis patients.   A total of 1369 patients were identified as having cirrhosis from the discharge diagnoses from the Funen Patient Administrative System (FPAS) from Funen, Denmark.  The patients were identified and differentiated based on their age, etiology (autoimmune hepatitis, alcohol cirrhosis, viral hepatitis, cryptogenic hepatitis, etc.), gender, and complications at diagnosis (present, absent).  The incidence and mortality rates were then calculated for each of the previously mentioned clinical variables. 

Results: The incidence was twice as high for women as it was for men with all age groups.  As for mortality, the mortality rate was significantly higher for men, age above 70 years compared with other age groups, complications present at diagnosis, and etiology due to alcoholic disease or cryptogenic cirrhosis. 

Implications for Practice:  If a patient is diagnosed with symptoms and is male, age > 70, has complications and an etiology due to alcoholic or cryptogenic cirrhosis, then there is a higher mortality rate.  Most importantly, the authors noted that it is important to diagnosis patients as early as possible for cirrhosis, because the likelihood of diagnosis will decrease significantly.  This was notable since patients which had complications at time of diagnosis (and thus a more further-along disease progression) had a 28% higher odds of mortality than those who did not initially present with complications.     

Discussion: Good study here. Like I said before, I don’t get to review epidemiology based papers too much, so it was good to do one finally.  I can’t tell you how fun it was to read this paper!  It was interesting to find that males have a higher rate of mortality than females.  I am curious as to why this is. 

                As the authors mentioned in the discussion section, the time of diagnosis is obviously critical here; patients with alcoholic and cryptogenic cirrhosis generally have a worse mortality rate than those with other etiological based causes, because their disease-progression is generally worse at initial diagnosis.  It was stunning to see that of the 1369 cirrhosis patients admitted into the sample cohort, 1076 (~79%) were alcohol induced! 

Commentary on Statistics and Study Design:  Overall, good statistics and study design here. I would have analyzed the paper in a very similar fashion to how the authors actually did it.  I especially like how the authors included both a uni- and multi-variate analysis, and reported the final results (Table 4).  I would have removed any variables which were significant in the multi-variate model to produce more precise odds ratios for the most significant variables, but since there were so few variables in the analysis here, the approach the authors took is OK.  It would not have resulted in a big difference.

                In the methods section, the authors said that they tested for interactions, but they did not report on them in the rest of the paper. I assume this means those interactions were not significant?  This would be useful information to know.  Other than that, great paper overall.

                A big thanks to our buddies in Denmark for doing this!  Hope to get there one day.       

The distribution of fat in the visceral and gastroesophageal junction is associated with BE

Reference: Nelsen, E.M., et al., Distribution of Body Fat and Its Influence on Esophageal Inflammation and Dysplasia in Patients With Barrett's Esophagus. Clin Gastroenterol Hepatol, 2012.

A study out of the Mayo Clinic in Minnesota on the distribution of body fat and its influence on  Barret’s Esophagus. 

Brief Summary: It is known that body fat can increase the risk of Barret’s Esophagus (BE). However, it is not known how the distribution of the body fat (visceral, abdominal, etc.) in particular influences Barret’s Esophagus.   The main objective of this retrospective study was to study the distriubution of the fat in patients with Barret’s Esophagus – particuarly with respect to the distriubtion of the fat.  A total of 100 pateints were sampled for this study from the Mayo clinic: 50 of those with BE (case) and 50 without BE (controls).  Fat measurements were then taken from all of the patients according to the following speicific fat regions: subcutaneous fat (SF), visceral fat (VF), and gastroesophageal junction (GEJ) fat.  

Results: The distribution of fat in the visceral and gastroesophageal junction region is signficantly associated with Barret’s Esophagus (BE).     

Implications  for Practice: Patients with a high fat content in the gastroesophageal and visceral regions are at a higher liklihood of acquiring Barret’s Esophagus (BE) if shown in unison with other symptoms. 

Discussion:  A good observational study which shows how the distribution of fat influences BE.   I liked how the authors talked about the potential mechanisms between the body fat distributions and their influece on BE – many authors do not do this.   

In order to further elucidate the relationship between fat and BE, it would be nice to see a comprehensive multi-variate study which includes the full array of interaction variables.  For instance, the authors mentioned that BMI (body-mass index) alone does not explain the male and Caucasian pre-dominance of BE in males, and the authors further go on to explain that this may be due to males and Caucasians having a greater proportion of fat in the abdominal area (visceral and/or subcutaneous fact).  All this being well known, it would be nice to see if there was an interaction between gender and nationality in conjunction with fat distibution area. For instance, does the effect on abdominal fat tendencies with Barreth's E ?  These types of questions can be answered by throwing interaction terms in the model  and by utilizing a multi-variate regresssion technique which I will get into with the next section.

Commentary on Statistics and Study Design:  I really liked some of the statistical consideratiosn in this papers.  Most notably, it was good to see that the authors used the concept of matching.  Matching is done to balance out the effects of any confouding variable in an observational study and should always be done if the investigator is highly suspicious of any confounding variable in the study.   This is especially pertinent to this study since it’s thought that gender may be highly associated with BE.  You don’t see many investigators do this even though it should be done for many investigations.   Also, I liked how the author’s gave explicit detail on the fat measurements in the Methods section.     

                However, I would have taken a different statistical approach to analyzing the relationship between the fat distribution variables and the BE response variable.  The authors investigated the uni-variate and bi-variate relationship (while controlling for BMI) between the fat distribution variables and the BE response variable.  In doing this, the author’s have obviously flagged BMI as an essential variable due to past literature knowledge for BE, and this would  seem to be correct.  However, for the fat distribution variables, I would have investigated the nature of the relationship between the fat distribution variables and the BE response while controlling for all variables – not just BMI.  This can be done with a typical multi-variate regression technique which includes all variables, and then the investigators could have simpy eliminated the un-necessary variables from the model in a backwards-stepwise approach.  At the end, one would then report both the uni- and multi- variate results.  Taking this approach would allow the investigator to come to a small set of variables which are most associated with BE. For instance, if may be that GEJ fat is not associated with BE while also controlling for Visceral fat, and GEJ fat can thus be eliminated as a significant predictor variable.  Furthermore, using this approach, one could also look at the presence of different interaction variables - which as I alluded to in the discussion section - may be present here.  For whatever reason, many investigators do not include the presence of interaction variables even though they should.  

                From a presentation standpoint, for the second aim in Figure 3, the author’s decided to present a box and whisker plot instead of a table.  Since one is only looking an uni-variate associates here, this seems to be OK.  Personally, for uni-variate assocations, I like the use of a box-and whisker plot more than a table since the actual numbers are visually more explicit, but either one works well.  As long as the knowledge comes across, it’s all good.

                A big thanks to our Mayo Clinic buddies for doing this!

      

The Probiotic Saccharomyces boulardii does not provide any significant benefit in the alleviation of Antiobotic-associated diarrhea (AAD)

Reference: Pozzoni, P., et al., Saccharomyces boulardii for the Prevention of Antibiotic-Associated Diarrhea in Adult Hospitalized Patients: A Single-Center, Randomized, Double-Blind, Placebo-Controlled Trial. Am J Gastroenterol, 2012.

A study out of Italy describing the effects of the probiotic Saccharomyces boulardii in the prevention of Antiobotic-associated diarrhea (AAD) and Clostridium difficuile-associated diarrhea (CDAD). 

Brief Summary: Antibiotics can effectively be used to mitigate several Gastroentestinal diseases, but one of their negative side effects is Antibiotic-associated diarrhea (AAD) and Clostridium difficile-associated diarrhea (CDAD).  In the past, probiotics have been effective used to prevent AAD and CCD. The main objective of this study was to test the effectiveness of the probiotic Saccharomyces boulardii on the occurrence of AAD and CDAD.  A total of 562 patients were accrued in a double-blind, placebo controlled study. The accrued patients were assigned either the S. boulardii capsule or the placebo.

Results: The patients who received the S. boulardii capsule (the probiotic) did not incur a significant reduction in the incidence of AAD or CDAD compared to the plecebo.

Implications for Practice: Gastroenterologists should not prescribe priobiotics for the purpose of alleviating AAD or CDAC symptoms.

Discussion: Previous studies have shown that probiotics can be used to decrease the incidence of AAD and CDAC, and it is interesting that this study came out with a negative result.  It is important that all results - both positive and negative – such as this one be published to increase the overall understanding. 

It is interesting that the only patient characteristic found to be associated with AAD was a low level of serum creatinine.  Another retrospective analysis did find an increased level of serum creatinine for patients with extreme AAD.  More studies will need to be done to elucidate the cause and effect relationship between AAD and serum creatinine.  It would be interesting to look at the cause and effect relationship at play here, especially on a more of a molecular biology level.

Commentary on Statistics and Study Design: The statistics and study design from this paper was well planned out. The author’s used a multi-variate logistic regression model to study the main effect between the treatment and the outcome, which is the correct model to use.  The advantage of using this model – over the typical univariate statistics – is that other variables can more easily be controlled for.  Also, I liked how the authors included clear and precise power calculations.  And of course, the double-blind nature of the study alleviates any measurement bias concerns – always the gold standard in medicine.

As for the previous studies detailing the relationship between AAD and probiotics, the authors said that these studies have had several methodological drawbacks including “non-calculated sample size, inadequate study power, lack of generalizibility of the results due to manner of the selection of the enrolled patients, and unspecified information about the application of non-pharmacological infection control measures”.  I have not had the chance to go back and read these papers in depth to verify all of this (I will in the future soon), but the author’s points are well noted – especially the concern over the manner in which the patients were selected. One of the biggest study design errors I see in medical studies such as this is a mistake in the population which is samples. In any sort-of statistical inference study, you want the population you draw from to be as similar to the general population as possible. The reason being is that the nature of the statistical relationship can differ from the general population based on the sub-set population that you draw from.  This is known as a “selection bias.”  It is a very difficult bias to overcome, and statisticians can only alleviate the issue as best as possible.       

Citrulline levels can not be used to delineate the severity of Chron's Disease for out-patients

Reference: Elkhatib, I. and A.L. Buchman, Plasma citrulline concentration as a marker for disease activity in patients with Crohn's disease. J Clin Gastroenterol, 2012.46(4): p. 308-10.

A study done on the use of citrulline levels to delineate the severity of Chron's disease.  

Brief Summary: Citrulline is an organic compound produced from the urea cycle, and it is thought to be an indicator for the severity of Chron’s Disease.  The main objective of this study was to determine if Citrulline could be used as an indicator for Chron’s.  The authors accrued 81 patients and obtained their Harvey-Bradshaw Index scores (HBI) to see if there was a significant correlation with their Citrulline levels.  The HBI scores are used to quantify the symptoms for a patient with Chron’s Disease.

Results: The author’s did not find a significant correlation between the HBI index and the Citrulline levels thus indicating that Citrulline cannot be used to delineate the severity of Chron’s Disease.  As the authors noted,  only outpatients were used and it’s possible that more severe Chron's cases with proximal bowel involvement (eg. jejunal or duodenal) might show a decrease in citrulline concentration.

Implications for Practice: Citrulline levels cannot be used to delineate the severity of Chron’s disease for out-patients.   

Discussion: It would be interesting to see what the citrulline levels would be for patients that have a more severe case of Chron’s.  It’s obviously hard to say, but my guess is that the nature of the statistical relationship between citruline and the HBI index would be significantly different for these patients.  Particularly, it would be interesting to look at the nature of the statistical relationship between citrulline levels and a whole slew of other clinical variables such as various bowel disruption variables.    

Commentary on Statistics and Study Design: The author’s used the simple Pearson's correlation measure to measure the correlation between the citrulline levels and the HBI index. However, the problem with using this simple correlation model is that other variables cannot be controlled for, and there were definitely other variables in this observational setting which could have been controlled and investigated on.
 

What should have been used is a multi-variate regression model.  By using this model, the outcome variable would have just simply been citrulline levels and the predictor variables would have been HBI index along with a bunch of other predictor variables such as post-operative recurrence, previous resection, etc. Remember, the advantage of using a multi-variate regression model is that it allows you to investigate the nature of the relationship between multiple predictor variables and a given outcome variable while controlling (keeping constant) all other predictor variables.  Hence, there was really no reason to get rid of the patients who had post-operative recurrence or previous resection.  These could have just been qualitative variables which were thrown into the multi-variate regression model and this would have taken care of any potential confounding effects.  One could then have also included a bunch of interaction variables to see if the nature of the relationship between HBI and the predictor variables depend on another variable.  As long as the patients are sampled independently, everything would have been OK. In fact, by throwing out the patients with post-operative recurrence abd previous resection , you are actually ‘losing’ valuable information.  You never want to throw out patients for the fear of a confounding variable amongst your patients.  Keep them in - you can't even assume a-priori that they would be confounding - and it would have been an interesting relationship to look at. 

What nutritional supplements are best?

Hey guys, so as you can tell, I mostly post stuff on here related to actual statistical based trials, but I would like to make the posts a little varied, and this will be one of those.  When it comes to IBD, there are a whole ton of different theories on what nutritional supplements work best from coconut, macaroons, Aloe Vera gel. So, as a UC patient myself, I would like to give you all my two cents on what works and what does not. I have tried them all at one time or another.  In the future, I will post more statistical related articles for this topic, but not right now.  Common word of mouth also means something!  :)  

Here are the candidates:

1. Coconut
2.  Macaroons
3. Aloe Vera Juice
4. organic based yogurt
5. calcium tablets
6. Iron pills.

Of these 6 commonly used nutritional supplements, the one I personally have had the most success with is Aloe Vera Juice.  Many people don't like the taste of it, but I just love it every morning!  It just goes through your body so naturally, and the herby feeling you get is just great!

The fact of that matter is that for every IBD patient, the optimal nutritional supplement can be different.  I've seen many people swear by macaroons. Tried it, but never really worked.  I love my Aloe Vera and will take it every day - even if my UC goes away completely!  Hope other IBD patients have as much luck with it as I do!    

The drug Infliximab can be used to improve quality of life for patients with IBD

Reference: Deboer, M.D., et al., Changes in Inflammation and QoL After a Single Dose of Infliximab During Ongoing IBD Treatment. J Pediatr Gastroenterol Nutr, 2012. 54(4): p. 486-90.

A study out of Virginia on the effect Inflixib on the effect of hormone growth and quality of life for patients with inflammatory bowel disease (IBD). 

Brief Summary: Infliximab is used in maintenance therapy for IBD. The main objective of this study was to investigate the drug’s effects on a number of outcome measures.  These outcome measures included the Pediatric Crohn's Disease Activity Index (PCDAI), High-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6 (a hormone indicator), and quality of life (QoL) measured by a survey called the IMPACT 3.  The author’s recruited 24 subjects (ages 6 to 22) - 14 of those classified as symptotic (symptoms 4 days before the clinical visit) and 10 as asymptotic (no symptoms 4 days before clinical visit).  Measurements were taken on all the outcome variables at day 0 and day 14 of Infliximab treatment.

Results: Among those patients which were symptotic, a rapid decrease in levels of hsCRP after 2 days and an increase in quality of life scores resulted.  Particularly, for quality of life, emotional symptoms and social functioning were found to have a drastic benefit for the symptotic patients.   These results did not occur for patients which were asymptotic. 

Implications for Practice: For pediatric Chron’s patients who show a strong sign of symptoms (defined as presence of diarrhea, abdominal pain, or blood in stool), Infiximab can help with the maintenance of pediatric Chron’s patients.   This is particularly true for patients with high levels of hsCRP or showing impaired emotional symptoms or social functioning.   

Discussion: This is a good study showing the effects of Infliximab for pediatric patients.  It was interesting that the only quality of life indicators showing an improvement (for the symptotic patients) from day 0 to day 14 were emotional symptoms and social functioning, but the other quality of life indicators such as bowel symptoms, systematic symptoms, and body image did not show a significant improvement.   Particularly, I would be interested to see the direct effect of Infliximab on various clinical measurements from the bowel. 

Commentary on Statistics and Study Design: This is a prospective observational study.  As the author’s noted, an experimental study is really needed in order to elucidate precisely the cause and effect relationship between Infliximab and the various outcome measures.  However, this study can be a good lead-way into those experimental studies. 

Only 24 patients were recruited. However, this should be enough patients since only one variable is being measured on.  And for this purpose, the simple t-test statics utilized are ample to answer this question, since there does not seem to be any concern for any other extraneous or confounding variables which may also be correlated with the outcome measures. 

However, it would still be interesting to look at those extraneous or confounding variables. Particularly, I would be interested to see if there are any interaction effects at play here with Infliximab – especially with some of the symptomatic variables. For instance, it may be that the improvement for Infliximab is greater among patients with severe diarrhea vs. non-severe diarrhea.  To answer this question, you would need to setup an multi-variate regression model, and these are the types of interesting questions which could be exhausted in a study like this. 

A big thanks to our friends at UV for running this study.  

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.