1. CRITICAL APPRAISALS IN HIV RESEARCHBY
LOIS I. COLLIE-ACASIO

2. SUMMARY Critical Appraisal is an important decision-
making skill that Clinical Researchers use to
compare published findings of head-to-head studies
and to compare the results of systematic reviews in
order to do meta-analyses of RCTs. Clinical trials
have only three possible outcomes:
The trial may be biased,
The trial may have a small sample size that
makes the results unreliable.
3. The trial may be correct.

3. SUMMARY (CONTINUED)
The lung is the organ that HIV most frequently infects, and
respiratory complications are a common cause of death.
Whenever researchers need to know which is the better
of two possible interventions for patients, they may implement
critical appraisal skills to make evidence-based informed
decisions.
Here, two examples of critical appraisals are presented:
One to find which antibiotic is best for HIV patients
with pneumonia, and
The other, to find the most cost-effective NRT
smoking cessation program to recommend to the HIV
patients that need to stop smoking.

4. INTRODUCTION OF THE PROBLEM
According to the World Health Organization,
daily deaths from respiratory infections and
HIV/AIDS are higher than that of other
infectious diseases, and are mainly poverty-
related. (WHO, 2004) Because of this, critical
analysis of applicable head-to-head studies may
need to be done to find cost effective therapies
and lifestyle changes that may help poverty-
stricken HIV patients to have a better
quality of life.

5. DEATHS FROM HIV AND RESPIRATORY INFECTIONS Source: http://www. who
The graph shows the number of daily deaths from respiratory infections and HIV/AIDs.
Infectious diseases are poverty-related. (WHO, 2004):

6. INTRODUCTION (CONTINUED)
This presentation is a critical appraisal of two clinical trial reports upon which the evidence statements are based: 1. A research paper by (Cordero, E., Bouza, E., Ruiz, I., Pachon, J., 2001). Cefepime versus cefotaxime for empirical treatment of bacterial pneumonia in HIV- Infected patients: an open, randomized trial, and,

7. INTRODUCTION (CONTINUED)
2. A research paper by (Silagy, C., 1994)
Meta-analysis on the efficacy of nicotine replacement
therapies in smoking cessation. Due to:
their vulnerability to respiratory infections, and also
because of enzyme induction concerns,
it is recommended that HIV patients cease
smoking. A cost-effective smoking cessation
program may be found through
critical analysis.

8. METHODS
SUMMARY OF REVIEW OF LITERATURE 1. Metanalysis of antibiotics for HIV patients 2. Metanalysis of NRT smoking cessation programs 3. Information on Critical Appraisal Skills 4. Review of Related Studies and Information

9. EVIDENCE STATEMENTS 1-3 TO FIND THE BEST ANTIBIOTIC FOR HIV PTS.
TO FIND A SMOKING CESSATION PROGRAM
1. Yes, the clearly focused issue was the effectiveness of every known NRT smoking cessation interventions. (Silagy, 1994) 2. Yes, the authors used the most relevant papers with the right study design. (Si 3. Relevant and important studies from 7 searchable databases were included.
1.The question was clearly focused and addressed patients, intervention, comparing interventions and the outcomes. (PICO) 2. The study was a RCT. Randomization was computerized and concealed. 3. Subjects were allocated in appropriately and balanced to both arms of the study.

10. EVIDENCE STATEMENTS 4-6
4. The study was open and not blinded. It was conducted in full compliance with GCP Guidelines and the Declaration of Helsinki. 5. All of the participants, (both PP and ITT) were accounted for at the end of the study. 6. The method of follow up and data collection were the same for all the groups.
4. The reviewers did enough to assess the quality or rigor of the included 14 metanalysis and several published systematic NRT reviews. 5. It was reasonable to combine the data extracted from similar studies. 6. Yes, it was clear that the all of the NRT interventions were successful and free of AE when compared to placebo. The results were expressed in odds ratio.

11. EVIDENCE STATEMENTS 7-8
7. Based on statistical calculation enough subjects were enrolled in the study to minimize the possibility of chance and to give the right statistical power to the study. (Guyatt G.H, Sackett D.L, Cook D.J.,1993) 8. Data was tabulated, analyzed and compared and the results were positive. The size of the treatment effect was significantly high.
7. The results were precise and presented with 95% CI. The number of smokers who quit using NRT were statistically compared with the control. (Silagy, 1994) 8. Yes, the results will help locally as the patients represented in the group is representative of all smokers.

12. EVIDENCE STATEMENTS 9-10
9. The authors considered all important outcomes. They extracted data about NRT intervention, target population, and objectives. 10. Yes, the benefits are worth the expense. Subjects who are motivated to stop smoking due to a health crisis will succeed with the NRT approach.
9. The results from confidence intervals CI data and p- values were precise enough to show that both drugs were equally tolerated by the subjects. 10. Important outcomes and results were applicable to society. HIV patients may suffer from end-stage liver disease, drug intervention must be adjusted to lessen liver damage. (Crowe, David, 2011)

13. TABLES FOR THE CRITICAL APPRAISAL OF THE ANTIBIOTICS
In order to determine factors that contributed to any failure of the treatment, the researchers used logistic regression analysis. From the calculations for Relative Risks and Relative Risks Reduction that follow in Tables 1, a, b, c, and d, it may be shown that no significant difference was observed in the way subjects tolerated both study drugs neither in the efficacy and clinical endpoints of both antibiotics.

14. RESULTS: TABLE 1 A. CALCULATIONS
As Per Protocol (PP)
Outcome event
Primary Endpoint: Tolerance after 3-5 days
Group n=150
Yes No
Total
Experimental group
Cefepime a
72 (93.5%) b
5(6.5%)
a + b 77
Control group
Cefotaxime c
59 (80.8%) d
14(19.1%)
c + d 73

15. TABLE 1 A. CALCULATIONS (CONTINUED)
Experimental event rate = risk of outcome event in
experimental group = EER = a/ (a+b)
= 72/77
= 0.93
Control event rate = risk of outcome event in control group = CER = c/(c+d)
=59/73
=0.80
Relative risk (RR) = EER/ CER
=0.93/0.80 = 1.16

16. TABLE 1 B. CALCULATIONS Intention-to-treat (ITT) Outcome event
Primary Endpoint: Tolerance after 3-5 days
Group n=160
Yes No
Total
Experimental group
Cefepime 84 a
72 (85.7%) b
12 (14.3%)
a + b 84
Control group
Cefotaxime 76 c
59 (77.6%) d
17 (22.4%)
c + d 76

17. TABLE 1 B. CALCULATIONS (CONTINUED)
Experimental event rate = risk of outcome event in
experimental group = EER = a/ (a+b)
=72/84
=0.857
Control event rate = risk of outcome event in control group = CER = c/(c+d)
=59/76
=0.77
Relative risk (RR) = EER/ CER
=0.857/0.77 =1.11

18. TABLE 1 C. CALCULATIONS As Per Protocol (PP)
Outcome event Clinical Response to antibiotics EOT
Group n=150
Yes No
Total
Experimental group
Cefepime a
50 (65.8%) b
13 (17.1%)
a + b 63
Control group
Cefotaxime c
50 (68.5%) d
10 (13.7%)
c + d 60

19. TABLE 1 C. CALCULATIONS (CONTINUED)
Experimental event rate = risk of outcome event in the
experimental group = EER = a/ (a+b)
= 50/63
= 0.79
Control event rate = risk of outcome event in the control group
= CER = c/(c+d)
=50/60 = 0.83
Relative risk (RR) = EER/ CER =0.79/0.83 =1.25
Relative risk reduction (RRR) = (CER - EER)/ CER
( )/0.83 = 0.04/0.83
= 0.04 or 4%
*The bacterial infection may be reduced by 4% more
in the treatment group than in the control group.

20. TABLE 1 D. CALCULATIONS Intention-to-treat (ITT)
Outcome event Clinical Response to antibiotics EOT
Group n=160
Yes No
Total
Experimental group
Cefepime 84 a
59 (70.2%) b
14 (16.7%)
a + b 63
Control group
Cefotaxime 76 c
59 (77.6%) d
6 (7.9%)
c + d 65

21. TABLE 1 D. CALCULATIONS (CONTINUED)
Experimental event rate = risk of outcome event in the experimental group = EER = a/ (a+b)
= 59/63
= 0.79
Control event rate = risk of outcome event in the control group = CER = c/(c+d)
=59/65
= 0.91
Relative risk (RR) = EER/ CER
=0.93/0.91=1.02

22. CRITICAL APPRAISAL:
VALIDITY OF BOTH STUDIES Critical appraisal revealed that the clinical trials were properly conducted and that all the critical points were properly addressed. All of the questions were answered positively. The PEDro scales also did not find any fault with the design of the studies. (PEDro, 1999) INTERPRETATION OF RESULTS The outcomes were favorable. The alpha level of probability was estimated to be 5% (p – value <0.05), so it is statistically significant and not likely due to chance. CI scores were provided.

23. REFERENCES
Cordero, E., Bouza, E., Ruiz, I., Pachon, J. (2001).Cefepime versus cefotaxime for empirical treatment of bacterial pneumonia in HIV-infected patients: an open, randomized trial. J Antimicrob Chemother 48: [Online] Available at (Accessed 15 September, 2016) 
Edelstein H, Chirurgi V, Oster S, Karp R, Cassano K, Aiken S, McCabe R(1991) A randomized trial of cefepime (BMY-28142) and ceftazidime for the treatment of pneumonia.J Antimicrob Chemotherapy,28(4): [Online] Available at h_j-antimicrob-chemother_ html (Accessed 15 September, 2016)
FDA, (2009) Maxipime (cefepime hydrochloride), Statistical Review and Evaluation, [Online] Available athttp:// andProviders/DrugSafetyInformationforHeathcareProfessionals/UCM pdf (Accessed 26 September, 2016)
Silagy, C., Mant D, Fowler G, Lodge M., (1994) Meta-analysis on efficacy of nicotine replacement therapies in smoking cessation, The Lancet, 343, 8890 p. 139 [Online] Available at (Accessed 15 September, 2016)
WHO (2004) Disease of poverty and the 10/90 Gap, World Health Organization [Online] Available at (Accessed 16 September, 2016)
Wu, P., (2006) Effectiveness of smoking cessation therapies: a systematic review and meta- analysis, Biomed Central Journal, 6:300 [Online] Available at /6/300, (Accessed 15 September, 2016)

24. CONCLUSION
Critical Appraisal identifies evidence-based interventions, and also cost-effective smoking cessation programs for patients. Respiratory infections and HIV/AIDS are poverty-related communicable diseases with high mortality. (WHO, 2004) The risks of morbidity and mortality need to be reduced. Patients need to maintain an optimal QOL in spite of opportunistic diseases. More critical appraisals are needed to identify safe, effective, and affordable interventions for poverty-stricken and unemployed patients. The economically disadvantaged deserve better than watered-down HIV/AIDS drugs.

25. THANK YOU VERY MUCH!