Kawasaki isease - Intervention and Causality - Assignment Example

Epidemiology May 3, Introduction A 2007 multicenter, randomized, double blind, placebo controlled trial sought to determine if the addition of intravenous methylprednisolone to conventional primary therapy of Kawasaki disease reduces the risk of coronary-artery abnormalities (Newburger, Sleeper, Mcrindle, 2007). This study focuses on an intervention and other similar studies have suggested that corticosteroids may be beneficial in preventing coronary artery aneurisms. Kawasaki disease is an acute inflammatory syndrome, primarily affecting children (Senzaki, 2006). Complications related to Kawasaki disease include aneurysm formation and coronary artery dilation. Kawasaki disease occurs most frequently in Japan though it is the second leading cause of heart disease in children within the United States. The disease is more prevalent in boys rather than girls and the majority of patients are under age five. The cause of Kawasaki disease has not been determined and it is a disease that is poorly understood. Symptoms usually begin with a high fever which does not go away with repeated doses of acetaminophen or ibuprofen. Other symptoms can include red and bloodshot eyes, swollen lymph nodes, and other classic symptoms that are similar to the flu or having a cold. Serious complications of Kawasaki disease can include vessel inflammation and aneurysms and can even lead to heart attack later on in life. This particular study is focused on a proposed intervention though extensive research has failed to identify a microbiological cause for this disease (Senzaki, MD, nd).Treatment is the only area in which evidence derived from clinical trials is established due to the inability to obtain affected tissues from living beings and the limited availability of autopsy specimens. What is the Research Question? The research question is poorly defined in the article; is primary corticosteroid beneficial in reducing the development of coronary-artery abnormalities in the treatment of acute Kawasaki disease and are the adverse events infrequent? Though the study explains the reasoning behind the trial it does not really specify a well written research question, the research question should be narrowed and more defined with regards to adverse events. Is it concerned with the impact of an intervention, causality, or determining the magnitude of a health problem? This research is concerned with the impact of an intervention, namely primary intravenous methylprednisolone when added to the standard treatment regime of Kawasaki disease. Intervention research includes studies in which specific systemic changes in conditions determine the effects of treatment or other intervention type. Intervention research addresses issues that can be controlled and measured experimentally. The role of corticosteroids in the treatment of Kawasaki disease has been subject to case studies and open trials though there has been insufficient evidence to make recommendations on their use (Newburger and McCrindle, 2007). What is the study type? This particular study type was a multi-center, randomized, double-blind, placebo controlled trial conducted within the pediatric heart network. Is the study type appropriate to the research question? Yes. A randomized controlled study uses a treatment group and a control group with the treatment group receiving the treatment that is being investigated. The patients are assigned randomly to groups. The control group in this trial received a placebo infusion while the treatment group received intravenous methylprednisolone equal to 30mg per kilogram, of body weight over two-three hours. This study type is appropriate for the original research question; is primary corticosteroid treatment beneficial and are adverse effects infrequent with short term use? Both the study group and control group have the same characteristics. Using blinding in the study prevents participants from knowing which intervention was received thus avoiding factors such as a placebo effect, observer or statistical bias, and statistical illusions. This type of study is appropriate for the research question. What are the reference population and source population? The reference population is patients recruited December 2002 through December 2004 from a total of eight centers and patients were between days four and ten of illness. The patient must also have met one of the following requirements; the patient had four or more principal clinical criteria, the patient had a coronary artery z score of 2.5 or more for the proximal right coronary artery or the left anterior descending coronary, as measured by two dimensional echocardiogram and met two or three principal clinical criteria dependent upon age, or the patient had a coronary aneurysm and met at least on principal clinical criteria. (Newburger, 2007) source population? The source of the population was eight different centers in North America which recruited patients; these centers were New England Research Institute University of Toronto, Hospital for Sick Children Primary Children Medical Center Columbia University Medical Center Children’s Hospital of Philadelphia Medical University of South Carolina Duke University Medical Center Children’s Hospital of Las Angeles and University of Southern California Is there any selection bias? If yes, does this threaten the external validity of the study? The population of interest is well defined though there is some exclusion bias. Exclusion bias occurs when an epidemiologists excludes portions of the population to prevent confounding. Exclusions in this trial include; previous treatment with intravenous immune globulin treatment with corticosteroids within the previous two weeks presence of a disease thought to mimic Kawasaki previous diagnosis of Kawasaki contradictions to corticosteroid use or inability to take aspirin (Newburger, 2007) There is some bias which threatens the validity of the study such as previous diagnosis with Kawasaki or of a similar disease; this factor would be difficult to ascertain among the general public for treatment purposes. It would be difficult to determine if the results would be as valid among the general population with so many factors beings excluded. The selection bias means that the study is not representative of the general population with very specific criteria being used to select the population. It becomes difficult to predict how effective this treatment would be in the average patient. The study results remain valid in the population that it covers. With the various factors used to exclude out of 589 children seen for Kawasaki disease during the time period only 199 were actually eligible for the study. Much more research is needed before results can be considered valid or conclusive though these results determined that methylprednisolone did not change the outcome of the disease. Was the assignment of patients to treatments randomized? Do you think the randomization process was adequate? The study participants were assigned to either a control or treatment group randomly with dynamic balancing at each center, dynamic balancing ensures that each group remains similarly sized to the other group so that results can be considered accurate. The randomization process was accurate. Was blinding done in this study? If yes, who were blinded? Blinding was done; echocardiograms were completed in such as a way as to ensure that blinding remained during interpretation and patient identity and illness remained unidentified. The interpreters of the echocardiogram were blinded so that data could not be subject to bias. What are the outcome measures and how are they measured? The primary outcome variable was the larger of the z scores for the right coronary artery and the left anterior descending coronary artery at week five after randomization. For the results to be significant the study would need to enroll 194 patients and 199 were enrolled. These outcomes were measured using echocardiogram studies blinded. Laboratory studies were also done including sedimentation rates and other lab measures. The groups did not differ significantly in weeks one or five in coronary artery outcomes; the groups also had very similar z scores for the left and right coronary measurements at week one and five. Those in the treatment group did have lower laboratory values. Adverse effects did not vary significantly in either group. Are statistical tests considered? Were the tests appropriate for the data? Were patients analyzed in the groups to which they were randomized? Do the conclusions drawn follow logically from the results of the analyses? Statistical tests which were used included hospital discharge times, though the rest of the tests used were laboratory tests and comparison of reported adverse effects among patients. The tests with the echocardiogram were appropriate in order to determine the purpose of the research question and lab tests that were used secondarily were appropriate to note underlying adverse reactions. The patients were analyzed in each group in which they were randomized and the conclusions are logical that were obtained from the result. Are the results clinically or socially significant? Was the sample size adequate to detect a clinically or socially significant result? The results were not clinically or socially significant showing very little difference between the two groups. Larger sampling sizes would need to be used to verify this information though enough people were used to make the results valid. The sample size was considered large enough to detect a result though nothing significant was detected. What conclusions did the authors reach about the study questions? Do you accept the results of this study? The authors found that no coronary artery outcomes were improved and the data did not provide support for the addition of methylprednisolone to the conventional treatment of Kawasaki disease, I accept the results of this study though were I in this field I would complete as much research as possible before dismissing the treatment as beneficial because of the small amount of data involved in this particular study. References Newburger, MD, MPH, J., Sleeper, ScD, L., McCrindle, M.D., M.P.H, B., Minich, M.D., L., Gersony, M.D, W., Vetter, M.D, V., ... Sundel, M.D., R. (2007, February 15). Randomized Trial of Pulsed Corticosteroid Therapy for Primary Treatment of Kawasaki Disease. The New England Journal of Medicine. Retrieved May 4, 2012, from http://www.nejm.org/doi/full/10.1056/NEJMoa061235#t=article Senzaki, H. (2006, June 12). The Pathophysiology of Coronary Artery Aneurysms in Kawasaki Disease: Role of Matrix Metalloproteinases. -- Senzaki 91 (10): 847. doi: 10.1136/adc.2005.087437 Senzaki, MD, H. (n.d.). Long-Term Outcome of Kawasaki Disease. Long-Term Outcome of Kawasaki Disease. doi: 10.1161/​CIRCULATIONAHA.107.749515 Read More