Body Image, Libido; Loss, Aversion, Sexual Dysfunction, Physiological
Conditions
Keywords
breast cancer, vulvovaginal atrophy, libido, body image
Brief summary
The overall objective of this program of research is to improve sexual health outcomes for women diagnosed with breast cancer. Our team is developing a multi-component intervention for the four key predictors of sexual health in female cancer survivors: self-image, vulvovaginal tissue quality and symptoms, desire/energy, and relationship-partner concerns. This proposal begins the proof-of-concept pilot study in women with a history of breast cancer to deliver a multi-component intervention to improve vulvo-vaginal atrophy with a vaginal moisturizer, and sexual energy and self-image with a mind-body intervention that involves relaxation and subconscious suggestions with a hypnotic induction delivered via audio file. The primary outcome will be to evaluate the feasibility and acceptability of a multi-component intervention for sexual function. It is hypothesized that at least eighty percent of randomized participants will complete the study without differential withdraws from the control group.
Detailed description
Women's Interventions for Sexual Health (WISH), is a two-arm randomized clinical trial to evaluate the feasibility and acceptability of a multi-component intervention addressing changes in body image, sexual desire, and vaginal dryness in thirty adult post-treatment breast cancer survivors. The study is eight weeks long and does not require any in-person visits. If a breast cancer survivor is determined eligible, they will be educated on the purpose, requirements, and procedures. If interested, they will be emailed the consent form and will schedule a virtual consent/baseline visit. After consent is obtained, the participant will be randomly assigned to a study arm, HRI (hypnotic relaxation intervention plus vaginal moisturizer) or VVA (vulvovaginal atrophy moisturizer only), given a study number, and educated on the use of Replens™ vaginal moisturizer. The participant will complete online surveys at the virtual baseline visit. Replens™ vaginal moisturizer will be sent to the participant's address and receipt of the moisturizer will be confirmed by study staff before the agreed upon week one start date. The participant will use the moisturizer every day during weeks one and two and every other day during weeks three through eight. Participants randomized to the HRI group will also receive an MP3 player with three hypnotic relaxation audio files and asked to complete a weekly practice log. Each hypnotic induction audio file will be used for two weeks, three times per week, for a total of six weeks of hypnosis. A second virtual visit will be held at two weeks to assess progress, adverse events and provide education to the HRI group. Check in phone calls will be scheduled for weeks four, six and eight. A link to online follow up surveys will be shared during weeks six and eight.
Interventions
OTHERHypnotic Relaxation Intervention (HRI)
HRI is a combination intervention (Replens™ vaginal moisturizer device and hypnotic relaxation behavioral intervention)
DEVICEVulvovaginal Atrophy (VVA)
VVA is a standard of care intervention (Replens™ vaginal moisturizer device)
Sponsors
Breast Cancer Research Foundation
The University of Tennessee, Knoxville
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Intervention model description
This is a two-arm, randomized clinical trial.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* History of breast cancer, stages I, II or III * Completed primary treatment (chemotherapy, radiation and/or surgery) ≥3 months and ≤ 5 years prior to registration * May use concurrent adjuvant endocrine therapy or HER2-targeted therapy while on study * May use topical products (e.g., lidocaine) vaginally prior to penetrative vaginal sex * Ability to read and write English * Able to engage in sexual activity * Currently has a sexual partner Responds yes to Do you currently experience vaginal or vulvar dryness and/or pain with sexual activity? * Responds yes to at least one of the following questions: 1. Have you experienced negative changes in your body image since being diagnosed or treated for cancer? or 2. Have you experienced negative changes in your sexual desire since being diagnosed or treated for cancer?
Exclusion criteria
* Antidepressants are allowed if a person has been on them for 30 days prior to registration, and dose or treatment is not expected to change * History of sexual abuse * Psychiatric disorder such as major depressive disorder, bipolar disorder, obsessive compulsive disorder or schizophrenia. (Defined per medical history and/or patient self-report) * Currently enrolled in another study that addresses sexual health (enrollment in other clinical trials will be allowed) * Use of oral, transdermal or vaginal estrogen is not allowed while on study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Screen Failure Rate (a Measure of Feasibility) | Up to 30 days Recruitment to screening | The number of women screened ineligible / number of individuals for whom full eligibility criteria were evaluated |
| Accrual Rate (a Measure of Feasibility) | Up to 30 days Screening to consent | The number of participants who consented divided by the number eligible |
| Retention Rate/Acceptability (a Measure of Feasibility) | Baseline through study completion, 8 weeks | The number of participants who completed the 8 weeks of the study divided by the number who consented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Female Sexual Function Index (FSFI) | consent to week 8 | The Female Sexual Function Index (FSFI) is a 19-item scale that measures the following domains of female sexual functioning: desire (subscale scale = 1.2-6), arousal (subscale = 0-6), satisfaction (subscale = 0.8-6), orgasm (subscale = 0-6), lubrication (subscale = 0-6) and pain (subscale = 0-6). When the scores of these domains are added together, the sum represents an FSFI total score. The following subscales were examined in this study: FSFI total (subscale range = 2-36 where higher scores indicate better sexual function); lubrication (subscale = 0-6 where higher scores indicate greater lubrication), pain (subscale = 0-6 where lower scores indicate greater pain); and desire (subscale scale = 1.2-6 where higher scores indicate greater desire). |
| Breast Impact of Treatment Scale (BITS) | consent to week 8 | The Breast Impact of Treatment Scale (BITS) is a 13-item scale that measures body change stress in women with breast cancer. Scores range from 0-65. Higher scores indicate greater body change stress. |
| Patient Reported Outcomes Measurement Information System (PROMIS) Sexual Function and Satisfaction V2.0 (PROMIS SexF V2 ) | consent to week 8 | The PROMIS SexF V2 is a 14-item scale that includes screener items and measures sexual activities, symptoms, functioning, and evaluation of sexual experiences. It includes the following domains: interest in sexual activity, lubrication, vaginal discomfort, clitoral discomfort, labial discomfort, orgasm and pleasure, and satisfaction. Raw scores were converted to t-scores where the mean(standard deviation) = 50(10) in the referent population. Higher scores indicate more of the thing being described. Researchers are encouraged to select the sexual function and satisfaction domains and items that are relevant to the specific sample being studied. In this study, the interest, satisfaction and lubrication subscales were used. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited through community recruitment efforts, social media, and ResearchMatch.org. The first participant was enrolled on February15, 2023 and the last on December 5, 2023.
Participants by arm
| Arm | Count |
|---|---|
| Hypnotic Relaxation Intervention (HRI), Moisturizer and Self Hypnosis The hypnotic relaxation intervention consists of three different audio files, each about 20 minutes in length. These three hypnotic inductions build upon each other. The first hypnotic induction audio focuses on relaxation, feelings of wellness, wholeness, strength, and confidence. The second hypnotic induction audio focuses more specifically on body image related to sexuality and being a sexual being. The third hypnotic induction audio focuses on sexual desire, passion, and energy. Each hypnotic induction will be used for two weeks, three times per week for a total of six weeks of hypnosis.
The vaginal moisturizer component of this arm is the same as that described for the VVA study arm.
Hypnotic Relaxation Intervention (HRI): HRI is a combination intervention (Replens™ vaginal moisturizer device and hypnotic relaxation behavioral intervention) | 14 |
| Vulvovaginal Atrophy (VVA), Moisturizer Only This study arm might best be described as standard of care. Vulvovaginal dryness will be treated with a daily moisturizer for two weeks, then every other day for the remaining six weeks. Vaginal moisturizer will be applied at night, before sleep and after all sexual activity. Several moisturizers are available, including vaginal DHEA (IntraRosa®). Due to the need for reproducibility, we have decided to use one non-hormonal vaginal moisturizer, Replens™ moisture, which is a vaginal moisturizer consisting primarily of a purified water, glycerin, and mineral oil. Other ingredients included in the formulation are polycarbophyl, carbomer, homopolymer type B, hydrogenated palm oil glyceride, sorbic acid, sodium hydroxide. The moisturizing gel was determined to be a medical device for marketing by the FDA in 2010. It is non-hormonal (unlike vaginal DHEA) and therefore will be more likely to be acceptable by a broader range of oncology providers.
Vulvovaginal Atrophy (VVA): VVA is a standard of care intervention (Replens™ vaginal moisturizer device) | 16 |
| Total | 30 |
Baseline characteristics
| Characteristic | Total | Vulvovaginal Atrophy (VVA), Moisturizer Only | Hypnotic Relaxation Intervention (HRI), Moisturizer and Self Hypnosis |
|---|---|---|---|
| Age, Continuous | 55 years STANDARD_DEVIATION 10.84 | 56.94 years STANDARD_DEVIATION 10.83 | 52.79 years STANDARD_DEVIATION 10.82 |
| Cancer stage at time of diagnosis Stage I | 15 Participants | 8 Participants | 7 Participants |
| Cancer stage at time of diagnosis Stage II | 13 Participants | 7 Participants | 6 Participants |
| Cancer stage at time of diagnosis Stage III | 2 Participants | 1 Participants | 1 Participants |
| Education Level Did not complete high school | 0 Participants | 0 Participants | 0 Participants |
| Education Level Doctorate | 1 Participants | 1 Participants | 0 Participants |
| Education Level High school graduate or GED | 1 Participants | 1 Participants | 0 Participants |
| Education Level Master's degree | 15 Participants | 9 Participants | 6 Participants |
| Education Level Prefer not to answer | 0 Participants | 0 Participants | 0 Participants |
| Education Level Some college | 4 Participants | 1 Participants | 3 Participants |
| Education Level Undergraduate degree | 9 Participants | 4 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants | 16 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Marital status Divorced | 0 Participants | 0 Participants | 0 Participants |
| Marital status Married | 29 Participants | 15 Participants | 14 Participants |
| Marital status Other | 0 Participants | 0 Participants | 0 Participants |
| Marital status Single, living with partner | 1 Participants | 1 Participants | 0 Participants |
| Marital status Single, never married | 0 Participants | 0 Participants | 0 Participants |
| Marital status Widowed | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 28 Participants | 14 Participants | 14 Participants |
| Region of Enrollment United States | 30 participants | 16 participants | 14 participants |
| Sex: Female, Male Female | 30 Participants | 16 Participants | 14 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Sexual Orientation Asexual | 0 Participants | 0 Participants | 0 Participants |
| Sexual Orientation Bisexual | 1 Participants | 1 Participants | 0 Participants |
| Sexual Orientation Fluid | 0 Participants | 0 Participants | 0 Participants |
| Sexual Orientation Gay | 0 Participants | 0 Participants | 0 Participants |
| Sexual Orientation Lesbian | 1 Participants | 1 Participants | 0 Participants |
| Sexual Orientation Other not listed | 0 Participants | 0 Participants | 0 Participants |
| Sexual Orientation Pansexual | 0 Participants | 0 Participants | 0 Participants |
| Sexual Orientation Prefer not to disclose | 0 Participants | 0 Participants | 0 Participants |
| Sexual Orientation Queer | 0 Participants | 0 Participants | 0 Participants |
| Sexual Orientation Straight (heterosexual) | 28 Participants | 14 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 16 |
| other Total, other adverse events | 8 / 14 | 7 / 16 |
| serious Total, serious adverse events | 0 / 14 | 0 / 16 |
Outcome results
Primary
Accrual Rate (a Measure of Feasibility)
The number of participants who consented divided by the number eligible
Time frame: Up to 30 days Screening to consent
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All Individuals Contacted | Accrual Rate (a Measure of Feasibility) | 30 Participants |
Primary
Retention Rate/Acceptability (a Measure of Feasibility)
The number of participants who completed the 8 weeks of the study divided by the number who consented.
Time frame: Baseline through study completion, 8 weeks
Population: The number of participants who completed all 8 weeks of the study divided by the number who were randomized.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All Individuals Contacted | Retention Rate/Acceptability (a Measure of Feasibility) | 14 Participants |
| Vulvovaginal Atrophy (VVA), Moisturizer Only | Retention Rate/Acceptability (a Measure of Feasibility) | 16 Participants |
Primary
Screen Failure Rate (a Measure of Feasibility)
The number of women screened ineligible / number of individuals for whom full eligibility criteria were evaluated
Time frame: Up to 30 days Recruitment to screening
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All Individuals Contacted | Screen Failure Rate (a Measure of Feasibility) | 36 Participants |
Secondary
Breast Impact of Treatment Scale (BITS)
The Breast Impact of Treatment Scale (BITS) is a 13-item scale that measures body change stress in women with breast cancer. Scores range from 0-65. Higher scores indicate greater body change stress.
Time frame: consent to week 8
Population: All participants who were assigned to the study arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Individuals Contacted | Breast Impact of Treatment Scale (BITS) | BITS, Baseline | 30.71 units on a scale | Standard Deviation 14.91 |
| All Individuals Contacted | Breast Impact of Treatment Scale (BITS) | BITS, Week 8 | 19.50 units on a scale | Standard Deviation 14.85 |
| Vulvovaginal Atrophy (VVA), Moisturizer Only | Breast Impact of Treatment Scale (BITS) | BITS, Baseline | 35.00 units on a scale | Standard Deviation 16.54 |
| Vulvovaginal Atrophy (VVA), Moisturizer Only | Breast Impact of Treatment Scale (BITS) | BITS, Week 8 | 28.81 units on a scale | Standard Deviation 16.67 |
Comparison: Effect sizes, Cohen's d, were calculated for both study arms using paired t-tests for the BITS. Means and 95% confidence intervals were also calculated.95% CI: [0.34, 1.63]
95% CI: [0.03, 1.01]
Secondary
Female Sexual Function Index (FSFI)
The Female Sexual Function Index (FSFI) is a 19-item scale that measures the following domains of female sexual functioning: desire (subscale scale = 1.2-6), arousal (subscale = 0-6), satisfaction (subscale = 0.8-6), orgasm (subscale = 0-6), lubrication (subscale = 0-6) and pain (subscale = 0-6). When the scores of these domains are added together, the sum represents an FSFI total score. The following subscales were examined in this study: FSFI total (subscale range = 2-36 where higher scores indicate better sexual function); lubrication (subscale = 0-6 where higher scores indicate greater lubrication), pain (subscale = 0-6 where lower scores indicate greater pain); and desire (subscale scale = 1.2-6 where higher scores indicate greater desire).
Time frame: consent to week 8
Population: All participants who were assigned to the study arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Individuals Contacted | Female Sexual Function Index (FSFI) | FSFI Total, Baseline | 14.56 score on a scale | Standard Deviation 5.21 |
| All Individuals Contacted | Female Sexual Function Index (FSFI) | FSFI Pain, Baseline | 2.26 score on a scale | Standard Deviation 1.58 |
| All Individuals Contacted | Female Sexual Function Index (FSFI) | FSFI Lubrication, Baseline | 2.06 score on a scale | Standard Deviation 1.26 |
| All Individuals Contacted | Female Sexual Function Index (FSFI) | FSFI Pain, Week 8 | 3.54 score on a scale | Standard Deviation 2.13 |
| All Individuals Contacted | Female Sexual Function Index (FSFI) | FSFI Total, Week 8 | 22.35 score on a scale | Standard Deviation 8.21 |
| All Individuals Contacted | Female Sexual Function Index (FSFI) | FSFI Lubrication, Week 8 | 3.90 score on a scale | Standard Deviation 1.71 |
| All Individuals Contacted | Female Sexual Function Index (FSFI) | FSFI Desire, Week 8 | 3.17 score on a scale | Standard Deviation 1.09 |
| All Individuals Contacted | Female Sexual Function Index (FSFI) | FSFI Desire, Baseline | 2.06 score on a scale | Standard Deviation 0.84 |
| Vulvovaginal Atrophy (VVA), Moisturizer Only | Female Sexual Function Index (FSFI) | FSFI Desire, Week 8 | 3.08 score on a scale | Standard Deviation 0.75 |
| Vulvovaginal Atrophy (VVA), Moisturizer Only | Female Sexual Function Index (FSFI) | FSFI Total, Baseline | 12.82 score on a scale | Standard Deviation 6.97 |
| Vulvovaginal Atrophy (VVA), Moisturizer Only | Female Sexual Function Index (FSFI) | FSFI Total, Week 8 | 21.44 score on a scale | Standard Deviation 7.34 |
| Vulvovaginal Atrophy (VVA), Moisturizer Only | Female Sexual Function Index (FSFI) | FSFI Lubrication, Baseline | 1.65 score on a scale | Standard Deviation 1.33 |
| Vulvovaginal Atrophy (VVA), Moisturizer Only | Female Sexual Function Index (FSFI) | FSFI Lubrication, Week 8 | 3.92 score on a scale | Standard Deviation 1.76 |
| Vulvovaginal Atrophy (VVA), Moisturizer Only | Female Sexual Function Index (FSFI) | FSFI Pain, Baseline | 1.80 score on a scale | Standard Deviation 1.54 |
| Vulvovaginal Atrophy (VVA), Moisturizer Only | Female Sexual Function Index (FSFI) | FSFI Pain, Week 8 | 3.20 score on a scale | Standard Deviation 2.23 |
| Vulvovaginal Atrophy (VVA), Moisturizer Only | Female Sexual Function Index (FSFI) | FSFI Desire, Baseline | 2.03 score on a scale | Standard Deviation 0.95 |
Comparison: Effect sizes, Cohen's d, were calculated for both study arms using paired t-tests for FSFI total, FSFI lubrication, FSFI pain, and FSFI desire subscales. Means and 95% confidence intervals were also calculated.95% CI: [0.62, 2.1]
95% CI: [0.86, 2.37]
95% CI: [0.49, 1.87]
95% CI: [1.02, 2.66]
95% CI: [0.16, 1.36]
95% CI: [0.24, 1.38]
95% CI: [0.46, 1.82]
95% CI: [0.55, 1.86]
Secondary
Patient Reported Outcomes Measurement Information System (PROMIS) Sexual Function and Satisfaction V2.0 (PROMIS SexF V2 )
The PROMIS SexF V2 is a 14-item scale that includes screener items and measures sexual activities, symptoms, functioning, and evaluation of sexual experiences. It includes the following domains: interest in sexual activity, lubrication, vaginal discomfort, clitoral discomfort, labial discomfort, orgasm and pleasure, and satisfaction. Raw scores were converted to t-scores where the mean(standard deviation) = 50(10) in the referent population. Higher scores indicate more of the thing being described. Researchers are encouraged to select the sexual function and satisfaction domains and items that are relevant to the specific sample being studied. In this study, the interest, satisfaction and lubrication subscales were used.
Time frame: consent to week 8
Population: All participants who were assigned to the study arm and completed PROMIS survey. The interest subscale was completed without missing data. Both the satisfaction and lubrication subscales begin with a screening question that asks In the past 30 days, did you have any type of sexual activity? A total of 5 participants responded no this item. For these subscales, total participants in HRI=13 and VVA=12.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Individuals Contacted | Patient Reported Outcomes Measurement Information System (PROMIS) Sexual Function and Satisfaction V2.0 (PROMIS SexF V2 ) | PROMIS Interest Baseline | 31.33 score on a scale | Standard Deviation 9.01 |
| All Individuals Contacted | Patient Reported Outcomes Measurement Information System (PROMIS) Sexual Function and Satisfaction V2.0 (PROMIS SexF V2 ) | PROMIS Interest Week 8 | 40.34 score on a scale | Standard Deviation 11.1 |
| All Individuals Contacted | Patient Reported Outcomes Measurement Information System (PROMIS) Sexual Function and Satisfaction V2.0 (PROMIS SexF V2 ) | PROMIS Lubrication Baseline | 32.68 score on a scale | Standard Deviation 7.11 |
| All Individuals Contacted | Patient Reported Outcomes Measurement Information System (PROMIS) Sexual Function and Satisfaction V2.0 (PROMIS SexF V2 ) | PROMIS Lubrication Week 8 | 45.65 score on a scale | Standard Deviation 9.74 |
| All Individuals Contacted | Patient Reported Outcomes Measurement Information System (PROMIS) Sexual Function and Satisfaction V2.0 (PROMIS SexF V2 ) | PROMIS Satisfaction Baseline | 38.23 score on a scale | Standard Deviation 5.49 |
| All Individuals Contacted | Patient Reported Outcomes Measurement Information System (PROMIS) Sexual Function and Satisfaction V2.0 (PROMIS SexF V2 ) | PROMIS Satisfaction Week 8 | 44.37 score on a scale | Standard Deviation 8.14 |
| Vulvovaginal Atrophy (VVA), Moisturizer Only | Patient Reported Outcomes Measurement Information System (PROMIS) Sexual Function and Satisfaction V2.0 (PROMIS SexF V2 ) | PROMIS Satisfaction Baseline | 39.80 score on a scale | Standard Deviation 4.19 |
| Vulvovaginal Atrophy (VVA), Moisturizer Only | Patient Reported Outcomes Measurement Information System (PROMIS) Sexual Function and Satisfaction V2.0 (PROMIS SexF V2 ) | PROMIS Interest Baseline | 35.65 score on a scale | Standard Deviation 7.51 |
| Vulvovaginal Atrophy (VVA), Moisturizer Only | Patient Reported Outcomes Measurement Information System (PROMIS) Sexual Function and Satisfaction V2.0 (PROMIS SexF V2 ) | PROMIS Lubrication Week 8 | 46.11 score on a scale | Standard Deviation 8.63 |
| Vulvovaginal Atrophy (VVA), Moisturizer Only | Patient Reported Outcomes Measurement Information System (PROMIS) Sexual Function and Satisfaction V2.0 (PROMIS SexF V2 ) | PROMIS Interest Week 8 | 41.48 score on a scale | Standard Deviation 7.78 |
| Vulvovaginal Atrophy (VVA), Moisturizer Only | Patient Reported Outcomes Measurement Information System (PROMIS) Sexual Function and Satisfaction V2.0 (PROMIS SexF V2 ) | PROMIS Satisfaction Week 8 | 47.16 score on a scale | Standard Deviation 8.26 |
| Vulvovaginal Atrophy (VVA), Moisturizer Only | Patient Reported Outcomes Measurement Information System (PROMIS) Sexual Function and Satisfaction V2.0 (PROMIS SexF V2 ) | PROMIS Lubrication Baseline | 34.28 score on a scale | Standard Deviation 6.23 |
Comparison: Effect sizes, Cohen's d, were calculated for both study arms using paired t-test for PROMIS interest, lubrication and satisfaction subscales. Means and 95% confidence intervals were also calculated.95% CI: [0.41, 1.75]
95% CI: [0.09, 1.18]
95% CI: [0.45, 1.89]
95% CI: [0.13, 1.44]
95% CI: [0.88, 2.67]
95% CI: [0.74, 2.5]