Freda Halim
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Previous Organizations / Institutes
The organizations / institutes from the scholar's other articles in the past ten years
Research Subjects
Freda Halim has a total of 34 co-authors. Here are the top co-authors by number of shared publications:
- Yohana Azhar
Department of Surgery, Hasan Sadikin General Hospital Faculty of Medicine, Universitas Padjadjaran Bandung West Java Indonesia
6 shared publications - Andry Irawan
Universitas Pelita Harapan, Faculty of Medicine, Jl. Boulvard Jendral Sudirman No. 15N, Lippo Village, Tangerang 15811, Indonesia; Siloam Hospitals Lippo Village, Jl. No. 6, Bencongan, Kelapa Dua, Tangerang 15810, Indonesia
3 shared publications Bethy Hernowo
Department of Anatomical Pathology, Universitas Padjajaran, Bandung, West Java, Indonesia
3 shared publicationsEka Julianta Wahjoepramono
Department of Neurosurgery, Faculty of Medicine, Pelita Harapan University, Tangerang, Banten, 15810, Indonesia
3 shared publicationsRicarhdo Valentino Hanafi
Faculty of Medicine, Pelita Harapan University, Tangerang, Banten, 15810, Indonesia
3 shared publications- Valeska Siulinda Candrawinata
Faculty of Medicine, Pelita Harapan University, Tangerang, Indonesia
3 shared publications
Latest Publications
- 30 October 2024
- Published by Springer Nature
- p. 273-312
Recent Development of Biopsy Techniques on Solid Tumor and Its Relevance in Solid Tumor Management
- 30 October 2024
- Published by Springer Nature
- p. 273-312
Recent Development of Biopsy Techniques on Solid Tumor and Its Relevance in Solid Tumor Management
- Open Access
- 30 August 2024
- Published by JMIR Publications Inc. in JMIR Medical Education
- Vol. 10 (1) , e52631
Objective Comparison of the First-Person–View Live Streaming Method Versus Face-to-Face Teaching Method in Improving Wound Suturing Skills for Skin Closure in Surgical Clerkship Students: Randomized Controlled Trial
Background: The use of digital online teaching media in improving the surgical skills of medical students is indispensable, yet it is still not widely explored objectively. The first-person–view online teaching method may be more effective as it provides more realism to surgical clerkship students in achieving basic surgical skills. Objective: This study aims to objectively assess the effectiveness of the first-person–view live streaming (LS) method using a GoPro camera compared to the standard face-to-face (FTF) teaching method in improving simple wound suturing skills in surgical clerkship students. Methods: A prospective, parallel, nonblinded, single-center, randomized controlled trial was performed. Between January and April 2023, clerkship students of the Department of Surgery, Pelita Harapan University, were randomly selected and recruited into either the LS or FTF teaching method for simple interrupted suturing skills. All the participants were assessed objectively before and 1 week after training, using the direct observational procedural skills (DOPS) method. DOPS results and poststudy questionnaires were analyzed. Results: A total of 74 students were included in this study, with 37 (50%) participants in each group. Paired analysis of each participant’s pre-experiment and postexperiment DOPS scores revealed that the LS method’s outcome is comparable to the FTF method’s outcome (LS: mean 27.5, SD 20.6 vs FTF: mean 24.4, SD 16.7; P=.48) in improving the students’ surgical skills. Conclusions: First-person–view LS training sessions could enhance students’ ability to master simple procedural skills such as simple wound suturing and has comparable results to the current FTF teaching method. Teaching a practical skill using the LS method also gives more confidence for the participants to perform the procedure independently. Other advantages of the LS method, such as the ability to study from outside the sterile environment, are also promising. We recommend improvements in the audiovisual quality of the camera and a stable internet connection before performing the LS teaching method.
- 30 August 2024
- Published by JMIR Publications Inc. in JMIR Medical Education
- Vol. 10 (1) , e52631
Open AccessObjective Comparison of the First-Person–View Live Streaming Method Versus Face-to-Face Teaching Method in Improving Wound Suturing Skills for Skin Closure in Surgical Clerkship Students: Randomized Controlled Trial
Background: The use of digital online teaching media in improving the surgical skills of medical students is indispensable, yet it is still not widely explored objectively. The first-person–view online teaching method may be more effective as it provides more realism to surgical clerkship students in achieving basic surgical skills. Objective: This study aims to objectively assess the effectiveness of the first-person–view live streaming (LS) method using a GoPro camera compared to the standard face-to-face (FTF) teaching method in improving simple wound suturing skills in surgical clerkship students. Methods: A prospective, parallel, nonblinded, single-center, randomized controlled trial was performed. Between January and April 2023, clerkship students of the Department of Surgery, Pelita Harapan University, were randomly selected and recruited into either the LS or FTF teaching method for simple interrupted suturing skills. All the participants were assessed objectively before and 1 week after training, using the direct observational procedural skills (DOPS) method. DOPS results and poststudy questionnaires were analyzed. Results: A total of 74 students were included in this study, with 37 (50%) participants in each group. Paired analysis of each participant’s pre-experiment and postexperiment DOPS scores revealed that the LS method’s outcome is comparable to the FTF method’s outcome (LS: mean 27.5, SD 20.6 vs FTF: mean 24.4, SD 16.7; P=.48) in improving the students’ surgical skills. Conclusions: First-person–view LS training sessions could enhance students’ ability to master simple procedural skills such as simple wound suturing and has comparable results to the current FTF teaching method. Teaching a practical skill using the LS method also gives more confidence for the participants to perform the procedure independently. Other advantages of the LS method, such as the ability to study from outside the sterile environment, are also promising. We recommend improvements in the audiovisual quality of the camera and a stable internet connection before performing the LS teaching method.
- Open Access
- 6 September 2023
- Published by F1000 Research Ltd in F1000Research
- Vol. 12, 188
Antibiotic versus surgery in the treatment of acute appendicitis in the pregnant population: A systematic review and meta-analysis
Introduction: Acute appendicitis is the most common surgical emergency in pregnant women. There has been a wide variance in clinical practice worldwide, with some favoring an antibiotic-only approach while others prefer surgery as the first-line management. Therefore, we designed the current analysis to synthesize the available evidence on the efficacy and safety of antibiotics versus surgery management. Methods: We searched PubMed, Scopus, EuropePMC, and Cochrane Central from March 4, 1904 until November 25, 2022, to look for studies comparing antibiotics and surgery in pregnant patients with acute appendicitis. We only included studies that provided a comparison between the two treatments. Measured outcomes included preterm delivery, fetal loss, maternal death, and complications, defined as those arising from the pathological processes or treatment, including, but not limited to, sepsis or septic shock, pneumonia, venous thromboembolism (VTE), and surgical site infection. The results were compared using an odds ratio and 95% confidence interval. We also performed a sensitivity analysis by excluding studies with a serious risk of bias. Results: We included five non-randomized studies for the analysis. We found that patients in the antibiotic group had a lower risk of preterm labor (OR 0.63 [95% CI 0.43–0.92]; p 0.02) but a higher risk of complications (OR 1.79 [95% CI 1.19–2.69]; p 0.005). We did not find any difference in the other outcomes. Conclusion: The increased risk of complications should caution clinicians about using antibiotics as the first-line management. More studies are required to identify patients who would benefit the most before antibiotics could be adopted as a treatment for acute appendicitis in pregnant patients.
- 6 September 2023
- Published by F1000 Research Ltd in F1000Research
- Vol. 12, 188
Open AccessAntibiotic versus surgery in the treatment of acute appendicitis in the pregnant population: A systematic review and meta-analysis
Introduction: Acute appendicitis is the most common surgical emergency in pregnant women. There has been a wide variance in clinical practice worldwide, with some favoring an antibiotic-only approach while others prefer surgery as the first-line management. Therefore, we designed the current analysis to synthesize the available evidence on the efficacy and safety of antibiotics versus surgery management. Methods: We searched PubMed, Scopus, EuropePMC, and Cochrane Central from March 4, 1904 until November 25, 2022, to look for studies comparing antibiotics and surgery in pregnant patients with acute appendicitis. We only included studies that provided a comparison between the two treatments. Measured outcomes included preterm delivery, fetal loss, maternal death, and complications, defined as those arising from the pathological processes or treatment, including, but not limited to, sepsis or septic shock, pneumonia, venous thromboembolism (VTE), and surgical site infection. The results were compared using an odds ratio and 95% confidence interval. We also performed a sensitivity analysis by excluding studies with a serious risk of bias. Results: We included five non-randomized studies for the analysis. We found that patients in the antibiotic group had a lower risk of preterm labor (OR 0.63 [95% CI 0.43–0.92]; p 0.02) but a higher risk of complications (OR 1.79 [95% CI 1.19–2.69]; p 0.005). We did not find any difference in the other outcomes. Conclusion: The increased risk of complications should caution clinicians about using antibiotics as the first-line management. More studies are required to identify patients who would benefit the most before antibiotics could be adopted as a treatment for acute appendicitis in pregnant patients.
- Open Access
- 2 August 2023
- Published by MDPI AG in Diagnostics
- Vol. 13 (15) , 2577
Breast Self-Examination Practice and Its Determinants among Women in Indonesia: A Systematic Review, Meta-Analysis, and Meta-Regression
Breast cancer (BC) is a heavy burden for Indonesian healthcare, but there is still no thorough evaluation for Breast self-examination (BSE) practice as routine BC screening. In this study, we aimed to synthesize the pooled prevalence data of BSE practice, compare BSE practice prevalence between Java Island and non-Java Islands in Indonesia, and identify the determinants that we thought could affect the BSE practice in the Indonesian population. Intensive searches were conducted in Cochrane Library, PubMed, Google Scholar, and SINTA (Indonesian Web of Science and Technology Index) from September 2017–2022. We utilized Review Manager 5.4 for conducting the meta-analysis. We found the overall national prevalence of BSE practice was 43.14% (95% CI: 36.08, 50.20, p < 0.00001). BSE practice in Java Island was higher compared to non-Java Island (44.58% vs. 41.62%). The highest prevalence of BSE practice was found among university students, with a 49.90% prevalence. Good knowledge, good attitude toward BSE, family history of BC, family support, and BC information exposure were all statistically associated with a higher determinant of BSE practice. We concluded that BSE practice in Indonesia is still low, especially in non-Java Islands. Integrative and collaborative programs should be established to promote BSE as routine screening for BC.
- 2 August 2023
- Published by MDPI AG in Diagnostics
- Vol. 13 (15) , 2577
Open AccessBreast Self-Examination Practice and Its Determinants among Women in Indonesia: A Systematic Review, Meta-Analysis, and Meta-Regression
Breast cancer (BC) is a heavy burden for Indonesian healthcare, but there is still no thorough evaluation for Breast self-examination (BSE) practice as routine BC screening. In this study, we aimed to synthesize the pooled prevalence data of BSE practice, compare BSE practice prevalence between Java Island and non-Java Islands in Indonesia, and identify the determinants that we thought could affect the BSE practice in the Indonesian population. Intensive searches were conducted in Cochrane Library, PubMed, Google Scholar, and SINTA (Indonesian Web of Science and Technology Index) from September 2017–2022. We utilized Review Manager 5.4 for conducting the meta-analysis. We found the overall national prevalence of BSE practice was 43.14% (95% CI: 36.08, 50.20, p < 0.00001). BSE practice in Java Island was higher compared to non-Java Island (44.58% vs. 41.62%). The highest prevalence of BSE practice was found among university students, with a 49.90% prevalence. Good knowledge, good attitude toward BSE, family history of BC, family support, and BC information exposure were all statistically associated with a higher determinant of BSE practice. We concluded that BSE practice in Indonesia is still low, especially in non-Java Islands. Integrative and collaborative programs should be established to promote BSE as routine screening for BC.
- Open Access
- 24 May 2023
- Published by MDPI AG in Diagnostics
- Vol. 13 (11) , 1838
Positive p53 Expression Is Associated with Primary Endocrine Therapy Resistance in Locally Advanced Stage Luminal B HER2-Negative Breast Cancer Patients: A Cross-Sectional Study in Indonesia
Luminal B HER2-negative breast cancer (BC) is the most common type in Indonesian BC patients, and frequently manifests with locally advanced staging. Recurrence often occurs within two years of the endocrine therapy course (primary endocrine therapy (ET) resistance). p53 mutation often exists in luminal B HER2-negative BC, but its application as an ET resistance predictor in those populations is still limited. The primary purpose of this research is to evaluate p53 expression and its association with primary ET resistance in luminal B HER2-negative BC. This cross-sectional study compiled 67 luminal B HER2-negative patients’ clinical data during their pre-treatment period until they completed a two-year course of endocrine therapy. They were divided into two groups: 29 patients with primary ET resistance and 38 without primary ET resistance. Pre-treatment paraffin blocks from each patient were retrieved, and the p53 expression difference between the two groups was analyzed. Positive p53 expression was significantly higher in patients with primary ET resistance [odds ratio (OR) of 11.78 (95% CI: 3.72–37.37, p-value < 0.0001)]. We conclude that p53 expression could be a beneficial marker for primary ET resistance in locally advanced luminal B HER2-negative BC.
- 24 May 2023
- Published by MDPI AG in Diagnostics
- Vol. 13 (11) , 1838
Open AccessPositive p53 Expression Is Associated with Primary Endocrine Therapy Resistance in Locally Advanced Stage Luminal B HER2-Negative Breast Cancer Patients: A Cross-Sectional Study in Indonesia
Luminal B HER2-negative breast cancer (BC) is the most common type in Indonesian BC patients, and frequently manifests with locally advanced staging. Recurrence often occurs within two years of the endocrine therapy course (primary endocrine therapy (ET) resistance). p53 mutation often exists in luminal B HER2-negative BC, but its application as an ET resistance predictor in those populations is still limited. The primary purpose of this research is to evaluate p53 expression and its association with primary ET resistance in luminal B HER2-negative BC. This cross-sectional study compiled 67 luminal B HER2-negative patients’ clinical data during their pre-treatment period until they completed a two-year course of endocrine therapy. They were divided into two groups: 29 patients with primary ET resistance and 38 without primary ET resistance. Pre-treatment paraffin blocks from each patient were retrieved, and the p53 expression difference between the two groups was analyzed. Positive p53 expression was significantly higher in patients with primary ET resistance [odds ratio (OR) of 11.78 (95% CI: 3.72–37.37, p-value < 0.0001)]. We conclude that p53 expression could be a beneficial marker for primary ET resistance in locally advanced luminal B HER2-negative BC.
- Open Access
- 18 March 2023
- Published by Springer Nature
Hematoxyllin-Eosin ( HE ) Staining v1
This is a protocol to stain tissue with Hematoxyllin-Eosin ( HE ) Staining. We use human breast cancer tissue for running this protocol.
- 18 March 2023
- Published by Springer Nature
Open AccessHematoxyllin-Eosin ( HE ) Staining v1
This is a protocol to stain tissue with Hematoxyllin-Eosin ( HE ) Staining. We use human breast cancer tissue for running this protocol.
- Open Access
- 13 March 2023
- Published by Springer Nature
Immunohistochemistry for p53 staining in Breast Cancer Tissue v1
These are protocols used for study of p53 expression differences in Luminal B Her-2 negative patients. The aim of the study is to show p53 expression differences in Luminal B Her-2 negative patients with and without primary endocrine therapy resistance.We used using paraffin sections of 67 samples and stained the slides for p53 expression, using primary antibody Clone DO-7 ( DAKO).
- 13 March 2023
- Published by Springer Nature
Open AccessImmunohistochemistry for p53 staining in Breast Cancer Tissue v1
These are protocols used for study of p53 expression differences in Luminal B Her-2 negative patients. The aim of the study is to show p53 expression differences in Luminal B Her-2 negative patients with and without primary endocrine therapy resistance.We used using paraffin sections of 67 samples and stained the slides for p53 expression, using primary antibody Clone DO-7 ( DAKO).
- Open Access
- 16 February 2023
- Published by F1000 Research Ltd in F1000Research
- Vol. 12, 188
Antibiotic versus surgery in the treatment of acute appendicitis in the pregnant population: A systematic review and meta-analysis
Introduction: Acute appendicitis is the most common surgical emergency in pregnant women. There has been a wide variance in clinical practice worldwide, with some favoring an antibiotic-only approach while others prefer surgery as the first-line management. Therefore, we designed the current analysis to synthesize the available evidence on the efficacy and safety of antibiotics versus surgery management. Methods: We searched PubMed, Scopus, EuropePMC, and Cochrane Central from March 4, 1904 until November 25, 2022, to look for studies comparing antibiotics and surgery in pregnant patients with acute appendicitis. We only included studies that provided a comparison between the two treatments. We included preterm delivery, fetal loss, maternal death, and complications as outcomes. The results were compared using an odds ratio and 95% confidence interval. We also performed a sensitivity analysis by excluding studies with a serious risk of bias. Results: We included five non-randomized studies for the analysis. We found that patients in the antibiotic group had a lower risk of preterm labor (OR 0.63 [95% CI 0.43–0.92]; p 0.02) but a higher risk of complications (OR 1.79 [95% CI 1.19–2.69]; p 0.005). We did not find any difference in the other outcomes. Conclusion: The increased risk of complications should caution clinicians about using antibiotics as the first-line management. More studies are required to identify patients who would benefit the most before antibiotics could be adopted as a treatment for acute appendicitis in pregnant patients.
- 16 February 2023
- Published by F1000 Research Ltd in F1000Research
- Vol. 12, 188
Open AccessAntibiotic versus surgery in the treatment of acute appendicitis in the pregnant population: A systematic review and meta-analysis
Introduction: Acute appendicitis is the most common surgical emergency in pregnant women. There has been a wide variance in clinical practice worldwide, with some favoring an antibiotic-only approach while others prefer surgery as the first-line management. Therefore, we designed the current analysis to synthesize the available evidence on the efficacy and safety of antibiotics versus surgery management. Methods: We searched PubMed, Scopus, EuropePMC, and Cochrane Central from March 4, 1904 until November 25, 2022, to look for studies comparing antibiotics and surgery in pregnant patients with acute appendicitis. We only included studies that provided a comparison between the two treatments. We included preterm delivery, fetal loss, maternal death, and complications as outcomes. The results were compared using an odds ratio and 95% confidence interval. We also performed a sensitivity analysis by excluding studies with a serious risk of bias. Results: We included five non-randomized studies for the analysis. We found that patients in the antibiotic group had a lower risk of preterm labor (OR 0.63 [95% CI 0.43–0.92]; p 0.02) but a higher risk of complications (OR 1.79 [95% CI 1.19–2.69]; p 0.005). We did not find any difference in the other outcomes. Conclusion: The increased risk of complications should caution clinicians about using antibiotics as the first-line management. More studies are required to identify patients who would benefit the most before antibiotics could be adopted as a treatment for acute appendicitis in pregnant patients.
- Open Access
- 30 November 2022
- Published by F1000 Research Ltd in F1000Research
- Vol. 11, 330
p53 Mutation as Plausible Predictor for Endocrine Resistance Therapy in Luminal Breast Cancer
Endocrine therapy resistance in Luminal Breast Cancer is a significant issue to be tackled, but currently, no specific biomarker could be used to anticipate this event. p53 mutation is widely known as one of Breast Cancer’s most prominent genetic alterations. Its mutation could generate various effects in Estrogen Receptor and Progesterone Receptor molecular works, tangled in events leading to the aggravation of endocrine therapy resistance. Hence the possibility of p53 mutation utilization as an endocrine therapy resistance predictive biomarker is plausible. The purpose of this review is to explore the latest knowledge of p53 role in Estrogen Receptor and Progesterone Receptor molecular actions, thus aggravating the Endocrine Therapy resistance in Luminal Breast Cancer, from which we could define possibilities and limitations to utilize p53 as the predictive biomarker of endocrine therapy resistance in Luminal Breast Cancer.
- 30 November 2022
- Published by F1000 Research Ltd in F1000Research
- Vol. 11, 330
Open Accessp53 Mutation as Plausible Predictor for Endocrine Resistance Therapy in Luminal Breast Cancer
Endocrine therapy resistance in Luminal Breast Cancer is a significant issue to be tackled, but currently, no specific biomarker could be used to anticipate this event. p53 mutation is widely known as one of Breast Cancer’s most prominent genetic alterations. Its mutation could generate various effects in Estrogen Receptor and Progesterone Receptor molecular works, tangled in events leading to the aggravation of endocrine therapy resistance. Hence the possibility of p53 mutation utilization as an endocrine therapy resistance predictive biomarker is plausible. The purpose of this review is to explore the latest knowledge of p53 role in Estrogen Receptor and Progesterone Receptor molecular actions, thus aggravating the Endocrine Therapy resistance in Luminal Breast Cancer, from which we could define possibilities and limitations to utilize p53 as the predictive biomarker of endocrine therapy resistance in Luminal Breast Cancer.
- Open Access
- 21 July 2022
- Published by Wiley in International Wound Journal
- Vol. 20 (2) , 543-553
The efficacy of topical sucralfate in improving pain and wound healing after haemorrhoidectomy procedure: A systematic review, meta‐analysis, and meta‐regression of randomised clinical trials
Pain and wound after haemorrhoidectomy constantly bothered the patient's convenience. Recurrently, topical sucralfate is used to treat excoriations and burns. It is considered to enhance epidermal growth and tissue granulation, thus, alleviating patients' problems. This study evaluated topical sucralfate's feasibility, safety, and superiority after haemorrhoidectomy. We searched randomised controlled trial (RCT) studies in PubMed, Google Scholar, Europe PMC, and ClinicalTrials.gov until March 29th, 2022. We investigated the influence of topical sucralfate on pain score postoperatively (24 hours, 7 days, and 14 days), pethidine usage, diclofenac usage, and wound healing rate compared to placebo. This study was conducted following the PRISMA guidelines. This study sorted the final six studies with 439 patients underwent haemorrhoidectomy. Topical sucralfate demonstrated significant outcomes on VAS 24 hours post‐operative [Std. Mean Difference −1.00 (95% CI −1.70, −0.31), P = .005], VAS 7 days post‐operative [Std. Mean Difference −2.29 (95% CI −3.34, −1.25), P < .0001], VAS 14 days post‐operative [Std. Mean Difference −1.88 (95% CI −2.74, −1.01), P < .0001], pethidine usage within 24 hours post‐operative [Std. Mean Difference −0.62 (95% CI −0.96, −0.27), P = .0004], diclofenac usage 7 days post‐operative [Std. Mean Difference −1.76 (95% CI −2.61, −0.92), P < .0001], diclofenac usage 14 days post‐operative [Std. Mean Difference −1.64 (95% CI −2.38, −0.91), P < .0001], and wound healing rate at 28‐day post‐operative [RR 1.45 (95% CI 1.25–1.68), P < .00001]. Topical sucralfate alleviated pain, improved wound healing, and minimised the usage of pethidine and diclofenac compared to placebo.
- 21 July 2022
- Published by Wiley in International Wound Journal
- Vol. 20 (2) , 543-553
Open AccessThe efficacy of topical sucralfate in improving pain and wound healing after haemorrhoidectomy procedure: A systematic review, meta‐analysis, and meta‐regression of randomised clinical trials
Pain and wound after haemorrhoidectomy constantly bothered the patient's convenience. Recurrently, topical sucralfate is used to treat excoriations and burns. It is considered to enhance epidermal growth and tissue granulation, thus, alleviating patients' problems. This study evaluated topical sucralfate's feasibility, safety, and superiority after haemorrhoidectomy. We searched randomised controlled trial (RCT) studies in PubMed, Google Scholar, Europe PMC, and ClinicalTrials.gov until March 29th, 2022. We investigated the influence of topical sucralfate on pain score postoperatively (24 hours, 7 days, and 14 days), pethidine usage, diclofenac usage, and wound healing rate compared to placebo. This study was conducted following the PRISMA guidelines. This study sorted the final six studies with 439 patients underwent haemorrhoidectomy. Topical sucralfate demonstrated significant outcomes on VAS 24 hours post‐operative [Std. Mean Difference −1.00 (95% CI −1.70, −0.31), P = .005], VAS 7 days post‐operative [Std. Mean Difference −2.29 (95% CI −3.34, −1.25), P < .0001], VAS 14 days post‐operative [Std. Mean Difference −1.88 (95% CI −2.74, −1.01), P < .0001], pethidine usage within 24 hours post‐operative [Std. Mean Difference −0.62 (95% CI −0.96, −0.27), P = .0004], diclofenac usage 7 days post‐operative [Std. Mean Difference −1.76 (95% CI −2.61, −0.92), P < .0001], diclofenac usage 14 days post‐operative [Std. Mean Difference −1.64 (95% CI −2.38, −0.91), P < .0001], and wound healing rate at 28‐day post‐operative [RR 1.45 (95% CI 1.25–1.68), P < .00001]. Topical sucralfate alleviated pain, improved wound healing, and minimised the usage of pethidine and diclofenac compared to placebo.