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Practice Editing Here (Nov 15th in-class Wiki session work)

 * This is a place to practice clicking the "edit" button and practice adding references (via the citation button).

Task:


 * 1) Find a peer-reviewed journal article on PubMed. Practice inserting your citation in the above space using the "cite" tool
 * 2) Choose one "B-level" medical article on Wikipedia from the following list: https://wp1.openzim.org/#/project/Medicine/articles?quality=B-Class&importance=High-Class
 * 3) Practice editing live on Wikipedia by finding a typo in the text or improving the clarity/readability of a sentence by adjusting a few words in a sentence.

Assignment # 3- please post an anonymous copy here!
Proposed Changes


 * 1) Expanding on the Refractory CLL section from a “disease that no longer responds favorably to treatment” to a “disease that no longer responds favorably to treatment within 6 months following the last cancer therapy”.
 * 2) Clarifying the recommended treatment for Refractory CLL from “In this case, more aggressive therapies, including lenalidomide, flavopiridol, and bone marrow (stem cell) transplantation, are considered. The monoclonal antibody alemtuzumab (directed against CD52) may be used in patients with refractory, bone marrow-based disease.” to “In this case, more aggressive targeted therapies, such as BCR or BCL2 pathway inhibitors, have been associated with increased survival”
 * 3) I have adjusted and added language to clarify the recommendations and information with regards to treatment while also adding an updated reference.

"" Indicates change or addition:

Because of it's slow onset, "asymptomatic" early-stage CLL "(Rai 0, Binet A)" is, in general, not treated since it is believed that "early-stage" CLL intervention does not improve survival time or quality of life. Instead, the condition is monitored over time to detect a change in the disease pattern. "new reference"

The decision to start CLL treatment is taken when "there is evidence for progressive symptomatic disease (summarized as "active disease")."

Determining when to start treatment and by what means is often difficult; no survival advantage is seen in treating "people with asymptomatic early-stage CLL." The "National Working Group on CLL" has issued guidelines with specific markers that should be met "to initiate treatment." "new reference"

2.      Rationale for proposed change.


 * 1) It’s important to clarify the definition of refractory CLL by specifying the length of disease progression or lack of response to treatment. This influences the management of the disease and the selection of appropriate treatment. According to the International Workshop Group on CLL (IWCLL) criteria, “Treatment-refractory CLL is defined as a disease without partial or complete response or disease progression within 6 months following the last antileukemic therapy”.

·       Source: Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Döhner H, et al. iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL. Blood. 2018 Jun 21;131(25):2745–60.

2.              More recent evidence indicates that BCR or BCL2 pathway inhibitors offer the best prognosis for refractory CLL.

·       Source: Stefano Molica, Diana Giannarelli, Rosanna Mirabelli, Luciano Levato & Tait D. Shanafelt (2019) The magnitude of improvement in progression-free survival with targeted therapy in relapsed/refractory chronic lymphocytic leukemia based on prognostic risk category: a systematic review and meta-analysis, Leukemia & Lymphoma, 60:7, 1644-1649, DOI: 10.1080/10428194.2018.1543882

3.              The recommendations and guidelines proposed within the current Wikipedia article are based off of the guidelines developed by the National Cancer Institute Working Group on CLL in 1988 (referenced in wikipedia article). The guidelines were revisited in 2008 with slight changes. In 2018, the guidelines were again improved upon by the National Working Group on CLL and have taken additional information and evidence into account that allows for greater clarity and understanding when it comes to CLL. I believe the updated guidelines and information (2018) allow for more appropriate language to address "the decision to treat" section. Overall, the information provided is acceptable but there is room for greater detail and clarity. Firstly, as CLL can be classified by stages (Rai and Binet), those stages provide a reference point when addressing disease progression and treatment. The current Wikipedia article suggests that early CLL intervention is not used but rather a watchful waiting period is used for those with early-stage CLL. This is not entirely clear and more specifically applies to those with "asymptomatic" early-stage CLL. I believe the slight change in language to "asymptomatic early-stage CLL" with reference to the Rai and Binet classification system (Rai 0, Binet A) is precise and clear. In addition, the sentence that follows within the wikipedia article is more debatable and needs the most adjustment. It suggests that the decision to initiate treatment is contingent upon a person's symptoms or blood counts. However, current guidelines are very straightforward about what constitutes initiating treatment. Treatment should be initiated when there is evidence for progressive symptomatic disease (summarized as active disease). Guidelines go as far to say that blood counts do not automatically require initiation of treatment and that the absolute lymphocyte count should not be used as the sole indicator for treatment. In addition, using appropriate wording such as "treating people with asymptomatic early-stage disease" as opposed to "treating the disease very early" is more concurrent with the classification system. It allows for greater clarity when trying to navigate the recommendations as well as when and how to apply them. Lastly, although the information does not vary significantly between the 1988 guidelines and the guidelines revisited in 2018, there is greater understanding of CLL and the decision to treat. Thus, the reference should be updated with our modern understanding.

·       Source: Michael Hallek, Bruce D. Cheson, Daniel Catovsky, Federico Caligaris-Cappio, Guillermo Dighiero, Hartmut Döhner, Peter Hillmen, Michael Keating, Emili Montserrat, Nicholas Chiorazzi, Stephan Stilgenbauer, Kanti R. Rai, John C. Byrd, Barbara Eichhorst, Susan O’Brien, Tadeusz Robak, John F. Seymour, Thomas J. Kipps; iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL. Blood 2018; 131 (25): 2745–2760. doi: https://doi.org/10.1182/blood-2017-09-806398

3.      Area of controversy


 * 1) No area of controversy has been identified. The change is supported in other sources such as: https://www.lls.org/leukemia/chronic-lymphocytic-leukemia/treatment/relapsed-and-refractory
 * 2) No controversy as this change seems to be supported by other professional socieities such as: https://ashpublications.org/hematology/article/2020/1/33/474290/Standard-treatment-approaches-for-relapsed
 * 3) The information provided in the article is accurate but could be better communicated with slight language adjustments to clarify the recommendations. In addition, while blood counts are used and inform the decision to treat, they should not be used alone or as a sole indicator. That is why, to say, "the decision to treat is taken when the person's symptoms "OR" blood counts indicate..." is not entirely accurate and may leave room for misunderstanding. To simply state "the decision to start CLL treatment is taken when there is evidence for progressive or symptomatic disease" as it is stated by the National Working Group on CLL, followed by directing viewers to the guidelines is ideal.

4.      Critique of source


 * 1) There are no areas of bias identified. I chose a clinical practice guideline by the International workshop on chronic lymphocytic leukemia published consensus guidelines for the design and conduct of clinical trials for patients with CLL.
 * 2) As the cited source is a meta-analysis, there is a chance of publication bias. Further, this meta-analysis only used MEDLINE in order to identify eligible studies. However, a funnel plot was included in the supplemental data (Supplemental table 4) and this demonstrated no statistically significant asymmetry, suggesting a lack of significant publication bias. All other aspects of their search and selection criteria seemed appropriate. A test for homogeneity was performed and was statistically insignificant suggesting homogeneity between the studies included in the meta-analysis.
 * 3) The National Cancer Institutes Working Group convened to develop a set of standardized eligibility, response, and toxicity criteria for clinical trials and issued the guidelines on CLL through their summation of data as a result. The original guidelines have served as the foundation of CLL understanding and the improved guidelines by the National Working Group on CLL have further improved our understanding. The working group has rigorously reviewed the literature including meta analyses within the field of CLL. Clinical practice concerning CLL operates based off of the updated guidelines and as such there is a consensus within the medical community on these guidelines. They serve as the standard of care. The authors declare no competing financial interests. All authors debated on all recommendations until an evidence based consensus was reached.



What to post on the Wikipedia article talk page (part of assignment 3)

 * This will also be covered on Nov 15th in class. Your group should use the below template to share an outline of your proposed improvements (including your new wording and citations). Article talk pages are not places to share your assignment answers. The Wikipedia community will be more interested in viewing your exact article improvement suggestions including where you plan to improve the article (which section), what wording you suggest, and the exact citation (Note: all citations must meet WP:MEDRS)
 * You will not be able to paste citations directly from your sandbox to talk pages (unless you are interested in editing/learning Wiki-code in the "source editing" mode). We suggest re-adding your citations on the talk page manually (using the cite button and populating the citation by pasting in the DOI, website, or PMID). You will have to repeat this process yet again when you edit the actual article live.
 * Talk Page Template: CARL Medical Editing Initiative/Fall 2021/Talk Page Template