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PUBH6005 Epidemiology - Laureate International Universities

Assessment - Critical Appraisal

Learning outcome 1: Assess levels of evidence and make recommendations
Learning outcome 1: Interpret data arising from surveillance and research studies, including rates and ratios
Learning outcome 3: Understand the difference between association and causation, statistical and public health significance
Learning outcome 4: Critically evaluate epidemiological studies, including potential for bias, confounding and chance errors

Context:
This assessment requires you to apply the knowledge and skills gained in all the modules to undertake a critical appraisal. You will need to appraise 3 articles of a topic and research question given to you by your facilitator.

1. Search the library database to find three studies that answer your research question. All three studies must be of different study designs. For instance, you could include case control, cohort and RCTs. These studies do not have to prove their hypothesis or agree with each other. Please note that marks will be deducted if all identified papers are of similar study.

2. Critically appraise all three articles you found. Your answers are to be written in the tables provided to you which was based on CASP checklist and other types of checklist.

3. In the table, you are required to answer either "Yes", "No", "Unclear".

4. For each of the answer of "Yes", "No" or "Unclear", you will need to provide the "Evidence" that you found in the article to support your answers.

5. For each of the "Evidence", you will need to critically appraise stating your justification, compare and contrasting or/and providing solution. Please see table for an example of how "evidence" is written.

Table 3 Cohort study: The predictive and diagnostic accuracy of vascular endothelial growth factor and pentraxin-3 in severe dengue (Low et al., 2018)
Critical appraisal questions
Did the study address a clearly focused issue?

Evidence: justification, compare and contrasting or/and providing solution
The objective of this study was to evaluate VEGF and PTX-3 as predictive and diagnostic markers in differentiating severe dengue from non-severe dengue. The
objective is specific to evaluating the two biomarkers among so many markers mentioned in the pilot study that was conducted before this study. (Low, Gan, & Ho, 2015) The dengue classification (severe and non-severe) was validated, specific and measureable. It was derived from the World Health Organisation dengue guideline. (World Health Organization, 2009) The study also specifically evaluated the predictive and diagnostic
accuracy of the two markers.
Critical appraisal questions
Was the cohort recruited in an acceptable
way?

Evidence: justification, compare and contrasting or/and providing solution
The participants were recruited prospectively based on the eligibility criteria. All participants who are 15 years or older, presented only in the first 3 days of illness and a positive NS1 Ag test. However, it was unclear of the definition of the "illness" as it can represent a specific onset of a symptoms or whether it is due to fever. Majority of the existing studies defined the illness begin when patient developed fever. (Ahmed, 2010; Kumar, Gittens-St Hilaire, & Nielsen, 2013; Mahboob et al., 2010) Based on Table 1, we can assume that all patients were recruited based on the fever presented within the first 3 days of illness. Suggestion to the author is to clearly define what is "illness".

NS1 Ag is a standard diagnostic test but again, most other studies used Dengue IgM as confirmatory method. (Mahboob et al., 2010; Tang et al., 2015; Thein et al., 2014) However, the author justified that Dengue IgM and a more highly accurate RT-PCR was
used to double confirm the NS1 Ag positive cases.
Critical appraisal questions
Was the exposure accurately measured to minimise bias?

Evidence: justification, compare and contrasting or/and providing solution
This study did not measure any exposure (environmental, social determinants, etc). Perhaps, the exposure in this study was not the objective in assessing the biomarkers. The "exposure" here for this cohort study should be defined as the biomarkers itself. Thus, the "exposure" is considered accurately measured by the laboratory technique called as ELISA. (Dussart et al., 2008)
Critical appraisal questions
Was the outcome accurately measured to minimise bias?

Evidence: justification, compare and contrasting or/and providing solution
The outcome was the use of clinical dengue classification (World Health Organization, 2012). It was used by the clinician/treating physician to diagnose the patients recruited. The accuracy of the WHO clinical classification is well documented in other study citing that the "severe dengue" category has good sensitivity and specificity. (Alexander et al.,
2011)
Critical appraisal questions
Have the authors identified all important confounding factors?

Evidence: justification, compare and contrasting or/and providing solution
Confounding factors such as age, sex and ethnicity have been identified. There were other confounding factors such pregnancy; patient with autoimmune disorder, haematological disorder, cancer, cardiovascular disease or on long term warfarin and aspirin. These were identified and it was excluded from the analysis. The different days of illness could also affect the biomarker results and thus, this confounding factor has been included into the
statistical analysis.
Critical appraisal questions
Have they taken account of the confounding factors in the design and/or analysis?

Evidence: justification, compare and contrasting or/and providing solution
Confounding factors have been controlled for by exclusion (restricted analysis) and included into the multivariate regression analysis.
However, possible confounding factor that the author has not taken into account was the treatment effect. No analysis on the treatment in regards to the biomarker prediction.

Perhaps, future study to evaluate these biomarkers must include the types of treatment. Treatment for dengue are mainly fluid resuscitation and it should be noted down on the different commonly used fluids for resuscitation in dengue. (World Health Organization,
2012)
Critical appraisal questions
Was the follow up of subjects complete enough?

Evidence: justification, compare and contrasting or/and providing solution
The follow up of the subjects were up to the day of discharge from the hospital or health care facility. This should suffice as the patient recovered and free of the symptoms or complication of the disease. Other studies did not have long follow-up, instead they used cross-sectional study as their study design. This could possibly due to the availability of resources to support the long term follow-up. (Colbert et al., 2007; Mairuhu et al., 2005;
Thein et al., 2014)

Critical appraisal questions
Was the follow up of subjects long enough?

Evidence: justification, compare and contrasting or/and providing solution
The follow up of the subjects were up to the day of discharge from the hospital or health care facility. It was the maximum duration of the patients can be follow-up. Though some patients might develop another episode of dengue known as secondary dengue, this study has addressed their objective. It will be interesting to have future study that also follow-up even longer period of time to identify sequelae and secondary which is more common in dengue endemic countries/ tropical countries. (Guzmán et al., 2002; Ludolfs, Schilling, Altenschmidt, & Schmitz, 2002) However, this depends on the resources available to conduct such long-term study.

Attachment:- Critical Appraisal.rar