{"id":1079,"date":"2015-04-17T21:00:51","date_gmt":"2015-04-17T20:00:51","guid":{"rendered":"http:\/\/stg-blogs.bmj.com\/adc\/?p=1079"},"modified":"2015-04-14T00:12:35","modified_gmt":"2015-04-13T23:12:35","slug":"bunging-up-the-flow","status":"publish","type":"post","link":"https:\/\/stg-blogs.bmj.com\/adc\/2015\/04\/17\/bunging-up-the-flow\/","title":{"rendered":"Bunging up the flow"},"content":{"rendered":"<p><img loading=\"lazy\" decoding=\"async\" class=\"alignleft\" src=\"https:\/\/pbs.twimg.com\/media\/CBAkP2eUMAAK0ns.png:large\" alt=\"\" width=\"200\" height=\"167\" \/>I was intrigued to see the <a href=\"http:\/\/adc.bmj.com\/content\/early\/2015\/03\/17\/archdischild-2014-307632.short?g=w_adc_ahead_tab&amp;utm_content=buffer47cb6&amp;utm_medium=social&amp;utm_source=twitter.com&amp;utm_campaign=buffer\">meta-analysis of diosmectite in acute diarrhoea <\/a>appear in the Arch Dis Child recently &#8211; partly &#8217;cause I&#8217;d no idea what diosmectite was, and partly because I spend a lot of my time with folk who poo too little or too much.<\/p>\n<p>When taking a look at a <a title=\"Basics. Why bother with systematic reviews?\" href=\"https:\/\/stg-blogs.bmj.com\/adc\/2014\/09\/07\/basics-why-bother-with-systematic-reviews\/\">systematic review<\/a>, it&#8217;s worth using a <a title=\"FAST appraisals\" href=\"https:\/\/stg-blogs.bmj.com\/adc\/2010\/03\/07\/fast-appraisals\/\">FAST appraisal schema<\/a>, but starting by identifying the <a title=\"Ask, and it might be given unto you.\" href=\"https:\/\/stg-blogs.bmj.com\/adc\/2008\/11\/07\/ask-and-it-might-be-given-unto-you\/\">PICO question that the review seeks to answer<\/a>.<\/p>\n<p><!--more--><\/p>\n<p>You may recall that an <a title=\"Trial registration. Free, easy and important.\" href=\"https:\/\/stg-blogs.bmj.com\/adc\/2013\/12\/04\/trial-registration-free-easy-and-important\/\">emerging standard for systematic reviews is their protocol having been pre-registered<\/a>. This group <a href=\"http:\/\/www.crd.york.ac.uk\/PROSPERO\/display_record.asp?ID=CRD42014013783\">did do<\/a>:<\/p>\n<p>The PICO <a href=\"http:\/\/adc.bmj.com\/content\/early\/2015\/03\/17\/archdischild-2014-307632.full#sec-8\">is pretty much what I&#8217;d be expecting<\/a>;<\/p>\n<p>[Patients]: Children (&lt;5y) with acute diarrhoea<\/p>\n<p>[Intervention]: Diosmectite, added to standard treatment<\/p>\n<p>[Comparison]: Standard treatment alone<\/p>\n<p>[Outcome]: Decreased duration &amp;\/or intensity of diarrhoea, no increased risk of ileus, constipation or vomiting.<\/p>\n<p>Given this is relatively sensible, the next thing to do is move onwards to the FAST appraisal.<\/p>\n<p><strong>F<\/strong> &#8211; did they <a href=\"http:\/\/adc.bmj.com\/content\/early\/2015\/03\/17\/archdischild-2014-307632.full#sec-16\">find all the studies<\/a>? (Look for the search technique; should be multiple databases, using wide spread of key words, and\u00a0independently examined with two different researchers.) \u00a0Looks\u00a0pretty reasonable.<\/p>\n<p><strong>A<\/strong> &#8211; was an assessment of study quality undertaken? (Look for them using a <a title=\"Reading between the lines part 2: Some \u2018equal groups\u2019 are more equal than others\" href=\"https:\/\/stg-blogs.bmj.com\/adc\/2013\/10\/18\/reading-between-the-lines-part-2-some-equal-groups-are-more-equal-than-others\/\">&#8216;risk of bias&#8217; assessment<\/a>. This should include elements of randomisation, follow-up, measurements and blinding.) Well, the group used a <a href=\"http:\/\/adc.bmj.com\/content\/early\/2015\/03\/17\/archdischild-2014-307632.full#sec-18\">classical assessment <\/a>tool &#8211; the<a href=\"http:\/\/handbook.cochrane.org\/chapter_8\/8_assessing_risk_of_bias_in_included_studies.htm\"> Cochrane risk of bias tool<\/a> &#8211; and show us that there are a range of biases in the\u00a0studies that are included.<\/p>\n<p>Beyond the assessment of individual studies, an assessment of how that risk of bias may affect results is warranted. This group looked at the\u00a0major single factor &#8211;<a title=\"Remember Rambo?\" href=\"https:\/\/stg-blogs.bmj.com\/adc\/2007\/07\/11\/remember-rambo-2\/\"> allocation concealment<\/a> &#8211; for a <a title=\"StatsMiniBlog: Subgroup or sensitivity analyses?\" href=\"https:\/\/stg-blogs.bmj.com\/adc\/2014\/02\/12\/statsminiblog-subgroup-or-sensitivity-analyses\/\">subgroup analysis<\/a>, along with <a title=\"Reading between the lines part 3: Hiding who got what\" href=\"https:\/\/stg-blogs.bmj.com\/adc\/2013\/10\/25\/reading-between-the-lines-part-3-hiding-who-got-what\/\">blinding<\/a>, a further sensible approach.<\/p>\n<p><strong>S<\/strong> &#8211; what synthesis was undertaken &#8211; how were the studies combined? (Think about the nature of the heterogeneity in the studies &#8211; <a title=\"What about mixedupness?\" href=\"https:\/\/stg-blogs.bmj.com\/adc\/2015\/03\/27\/what-about-mixedupness\/\">clinical, <\/a>and <a title=\"StatsMiniBlog: I-squared\" href=\"https:\/\/stg-blogs.bmj.com\/adc\/2015\/04\/07\/statsminiblog-i-squared\/\">statistical<\/a>, and <a title=\"It\u2019s how mixed up? Meta analysis models step one.\" href=\"https:\/\/stg-blogs.bmj.com\/adc\/2011\/03\/27\/its-how-mixed-up-meta-analysis-models-step-one\/\">what would be reasonable and unreasonable to combine?<\/a>) The group used a <a title=\"Confident in predicting? Meta analysis models step two.\" href=\"https:\/\/stg-blogs.bmj.com\/adc\/2011\/03\/27\/confident-in-predicting-meta-analysis-models-step-two\/\">random effects<\/a> model, and then took a series of predefined subgroups to see if the initial heterogeneity (I\u00b2 of 91% &#8211; really very high) was reduced by looking for difference between the studies. It was: splitting by age of child seemed to reduce the heterogeneity, with older children showing, apparently,\u00a0less of a benefit than younger ones in <a title=\"StatsMiniBlog: Continuous vs. Categorical\" href=\"https:\/\/stg-blogs.bmj.com\/adc\/2013\/05\/13\/statsminiblog-continuous-vs-categorical\/\">mean difference<\/a> of\u00a0time to resolution of diarrhoea: &lt;12m -31 hours, cf -20 hours for &lt;24m, and -18 hours in 24-60m old.<\/p>\n<p>The assessment in other outcome descriptions (e.g. proportional cure rate, stool output volumes) were reported less thoroughly and an analysis could not be undertaken. This is a good reason why <a href=\"http:\/\/adc.bmj.com\/content\/early\/2014\/11\/20\/archdischild-2014-307403.abstract\">standard core outcome sets <\/a>are important in trials.<\/p>\n<p>There should also be an <a title=\"Missing. Presumed suppressed.\" href=\"https:\/\/stg-blogs.bmj.com\/adc\/2013\/03\/10\/missing-presumed-suppressed\/\">assessment of\u00a0publication bias<\/a>; the chance of publication of a study being more or less likely depending upon the results it showed. This group undertook this, with a <a href=\"http:\/\/adc.bmj.com\/content\/early\/2015\/03\/17\/archdischild-2014-307632.full#F3\">funnel plot too<\/a>, and showed<\/p>\n<p><a href=\"http:\/\/adc.bmj.com\/content\/early\/2015\/03\/17\/archdischild-2014-307632.full#sec-34\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter\" src=\"http:\/\/adc.bmj.com\/content\/early\/2015\/03\/17\/archdischild-2014-307632\/F3.medium.gif\" alt=\"\" width=\"440\" height=\"288\" \/><\/a><\/p>\n<p>&nbsp;<\/p>\n<p>The funnel plot shows studies on the right of the dotted triangle appear to be &#8216;missing&#8217;,\u00a0looking like there may have been an increased likelihood of publication if the studies showed an effect from diosmectite.<\/p>\n<p><strong>T<\/strong> &#8211; transferability \/ take home message. (What can you\u00a0take out of the review?) The authors here have undertaken a <a href=\"http:\/\/adc.bmj.com\/content\/early\/2015\/03\/17\/archdischild-2014-307632\/T2.expansion.html\">GRADE table review <\/a>of the results, to come up with a clinically interpretable conclusion.\u00a0There&#8217;s also a practical issue &#8211; could\u00a0diosmectite be prescribed in your hospital?<\/p>\n<p>For me, the take home message is that this adjuvant (diosmectite) might have a benefit, but the uncertainties in potential publication bias, the relatively small average duration improved &#8211; if any &#8211; and the lack of clarity in a coherent answer to the &#8216;side effects&#8217; side of the question make this an intervention I will not be seeking to source. there&#8217;s another element too &#8211;\u00a0I start from a relatively nihilistic view with medications to improve diarrhoea &#8211; and so anything that&#8217;s going to change my view will have to have a large effect size\u00a0and be convincing in the rigour of the studies.<\/p>\n<p>&nbsp;<!--TrendMD v2.4.8--><\/p>\n","protected":false},"excerpt":{"rendered":"<p>I was intrigued to see the meta-analysis of diosmectite in acute diarrhoea appear in the Arch Dis Child recently &#8211; partly &#8217;cause I&#8217;d no idea what diosmectite was, and partly because I spend a lot of my time with folk who poo too little or too much. When taking a look at a systematic review, [&#8230;]<\/p>\n<p><a class=\"btn btn-secondary understrap-read-more-link\" href=\"https:\/\/stg-blogs.bmj.com\/adc\/2015\/04\/17\/bunging-up-the-flow\/\">Read More&#8230;<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[79],"tags":[],"class_list":["post-1079","post","type-post","status-publish","format-standard","hentry","category-archimedes"],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"_links":{"self":[{"href":"https:\/\/stg-blogs.bmj.com\/adc\/wp-json\/wp\/v2\/posts\/1079","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/stg-blogs.bmj.com\/adc\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/stg-blogs.bmj.com\/adc\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/adc\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/adc\/wp-json\/wp\/v2\/comments?post=1079"}],"version-history":[{"count":0,"href":"https:\/\/stg-blogs.bmj.com\/adc\/wp-json\/wp\/v2\/posts\/1079\/revisions"}],"wp:attachment":[{"href":"https:\/\/stg-blogs.bmj.com\/adc\/wp-json\/wp\/v2\/media?parent=1079"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/adc\/wp-json\/wp\/v2\/categories?post=1079"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/adc\/wp-json\/wp\/v2\/tags?post=1079"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}