Is E-WORTH, a culturally tailored HIV and sexually transmitted infection (STI) prevention intervention, effective in reducing STIs and condomless sex among Black women in community supervision programs (CSPs)?In this randomized clinical trial of 352 women, participants assigned to the E-WORTH condition, compared with those in an HIV testing–only control condition, had 54% lower odds of testing positive for any STI at the 12-month follow-up and reported 38% fewer acts of condomless vaginal or anal intercourse during the 12-month period.The findings suggest that implementing a culturally tailored HIV/STI intervention designed for Black women in CSPs is feasible and effective and holds promise for reducing the disproportionate burden of HIV/STIs in this population. This randomized clinical trial evaluates the effectiveness of a 5-session culturally tailored group-based intervention with individualized computerized modules and streamlined HIV testing in reducing STIs and condomless sex among Black women in community supervision programs. Concentrated epidemics of HIV and sexually transmitted infections (STIs) have persisted among Black women in community supervision programs (CSPs) in the United States. Accumulating research has highlighted the effectiveness of culturally tailored HIV/STI interventions for Black women; however, there is a dearth of such interventions for the large number of Black women in CSPs.To determine the effectiveness of a 5-session culturally tailored group-based intervention  with individualized computerized modules and streamlined HIV testing in reducing STIs and condomless sex vs a 1-session streamlined HIV testing control condition.This randomized clinical trial was conducted from November 18, 2015, (first recruitment) to August 20, 2019 (last 12-month follow-up). Black women mandated to probation, parole, or alternative-to-incarceration programs in New York City who had a history of drug use were recruited and randomized to receive either E-WORTH or a streamlined HIV testing control condition. Both conditions were delivered by Black female staff at a large CSP. The analysis took an intention-to-treat approach.E-WORTH included a 1-hour individual HIV testing and orientation session and 4 weekly 90-minute group sessions. The control condition included one 30-minute session of HIV testing and information.Trichomonas vaginalis) at the 12-month assessment and the number of condomless acts of vaginal or anal intercourse in the past 90 days during the 12-month period.Primary outcomes were incidence of any STI  and reported 38% fewer acts of condomless vaginal or anal intercourse during the 12-month period .A total of 352 participants who identified as Black or African American were enrolled, including 79 (22.5%) who also identified as Latinx. The mean (SD) age was 32.4 (11.0) years. A total of 172 participants (48.9%) were assigned to the E-WORTH condition, and 180 (51.1%) were assigned to the control condition. Compared with control participants, participants assigned to the E-WORTH condition had 54% lower odds of testing positive for any STI at the 12-month follow-up (odds ratio, 0.46; 95% CI, 0.25-0.88; The magnitudes of effects found across biological and behavioral outcomes in this randomized clinical trial indicate the feasibility and effectiveness of implementing E-WORTH in real-world CSPs. The findings lend further evidence to the promise of culturally tailored HIV/STI interventions for Black women.NCT02391233ClinicalTrials.gov Identifier:  These factors include discrimination from health care and social service workers, racial inequities in access to HIV treatment, residential segregation, segregated social and sexual networks, racialized drug laws, and mass incarceration. Racialized drug laws  and racialized policing practices4 have led to a vast overrepresentation of Black individuals in community supervision programs (CSPs), the largest segment of the criminal justice system5 that includes probation, parole, and alternative-to-incarceration (ATI) programs. In 2016, 1 of every 23 Black adults in the United States was mandated to CSPs,6 which is 3.5 times higher than the rate among non-Hispanic White adults.6 Studies have found extremely high rates of HIV (as high as 17%) and STIs (as high as 25%) among samples of all or mostly Black women in CSPs.10 Moreover, an estimated 45% of women in CSPs have a substance use disorder (SUD),5 a well-established risk factor for HIV/STIs.11 These statistics indicate an urgent public health need for effective interventions to reverse the concentrated HIV/STI and SUD epidemics among Black women in CSPs.Black justice-involved women in the United States continue to be heavily impacted by concentrated epidemics of HIV and sexually transmitted infections (STIs). Compared with non-Hispanic White women in the United States, Black women had 23.1 times the rate of new HIV infections in 2018.14 and Black women in particular.18 However, there remains a dearth of HIV interventions designed for Black women in CSPs. A systematic review of 42 HIV interventions in criminal justice settings found that only 7 were delivered in CSPs and only 1 of the 7 was for women,19 but it was not culturally tailored for Black women.Accumulating research indicates the efficacy of culturally tailored interventions in reducing HIV/STIs among individuals from underrepresented minority groups22 that we developed for this study using a community-based participatory research methods.23 E-WORTH is woven with Afrocentric themes of historical trauma and resiliency stemming from slavery to Jim Crow to the mass incarceration of Black individuals.4 E-WORTH is designed to be delivered in low-resource CSPs. The streamlined HIV testing intervention, which served as the control condition, is recommended by the CDC as an evidence-based best practice HIV testing intervention26 and meets the criteria as a feasible cost-effective standard of care for a control condition. We hypothesized that E-WORTH would be more effective than the streamlined HIV testing condition in reducing any biologically confirmed STI  at the 12-month assessment and in reducing the number of condomless sex acts during the 12-month follow-up period.To address this gap in culturally tailored interventions, we conducted a randomized clinical trial to test the effectiveness of implementing Empowering African-American Women on the Road to Health (E-WORTH), a group-based HIV/STI intervention with computerized self-paced modules designed for Black women with a drug history who are currently in CSPs. E-WORTH is a new cultural adaptation of WORTH, a US Centers for Disease Control and Prevention (CDC) best practice HIV/STI intervention for women who use drugsCONSORT) reporting guideline, and the trial protocol appears in We conducted the study from November 18, 2015, through August 20, 2019, among 352 Black women who were recruited from CSPs in New York City. The intervention sessions for both study groups were delivered at 2 sites by Black female staff in a large community-based organization, which serves more than 8000 individuals in CSPs annually at 2 New York City sites. The study was approved by the Columbia University institutional review board. All participants provided their written informed consent. This study followed the Consolidated Standards of Reporting Trials  was necessary to achieve 80% power to detect a clinically meaningful 50% reduction in STI incidence, taking into account 20% attrition at 12-month follow-up. The study flowchart is presented in the 27 Women were screened and eligible to participate if they (1) were 18 years or older; (2) identified as African American and/or Black; (3) had been charged with a misdemeanor and/or felony and served a CSP sentence in the past 90 days; (4) reported any binge drinking (≥4 drinks at a time), illicit drug use, and/or having been in substance use treatment in the past 90 days; (5) reported any condomless vaginal or anal sex in the past 90 days; and (6) reported other HIV/STI risks in the past year  and/or being HIV positive. Exclusion criteria included (1) not being fluent in English and/or (2) being unable to provide informed consent.We recruited participants on-site at CSPs and through word-of-mouth referrals. We enrolled most participants (250 [71.0%]) from New York City probation sites, representing nearly 1 in 8 Black women (n = 1808) who were on probation in New York City in 2015.Consistent with an intention-to-treat approach, participants were considered enrolled only after randomization. Allocation sequences for assembling cohorts were generated using an Excel 2013 version 15.0 (Microsoft Corp) spreadsheet managed by the study’s project director who was masked to assignment until the time of randomization. The randomization scheme was concealed from participants, study staff, and investigators until each cohort was assembled. Periods of randomization were followed by periods of time block assignments to recruit a sufficient number of participants for E-WORTH groups . To eliminate bias during periods of time block assignments, we adhered to fixed randomization and assignment windows governed by the number of days it took to enroll enough participants for an E-WORTH group. We balanced intervention assignments first by condition and second by site. There were no differences between conditions on background characteristics or outcomes at baseline, except for baseline STI rates which were higher in the E-WORTH condition. Given that STI results were not available at the time of randomization and there were no differences in any other baseline outcomes, we believe this difference was spurious. We included baseline STI status as a covariate in all outcome models to adjust for this difference.28 and social cognitive theory,29 E-WORTH provides participants with opportunities to develop risk reduction self-efficacy and skills. E-WORTH raises awareness of structural racism rooted in slavery and historical responses of resilience among Black women. E-WORTH optimizes group and individual modalities in a hybrid intervention design. The first session includes an individual orientation to E-WORTH with streamlined HIV testing (described in the control condition section). The 4 weekly 90-minute group sessions feature an in-room Black female staff who facilitates group opening and closing activities and include individualized computerized interactive activities with Black women characters. Core components include raising awareness about HIV/STI risks, condom use technical skills, sexual negotiation skills, risk reduction goal setting, increasing social support and linkage to services, intimate partner violence (IPV) screening, safety planning, and referral to IPV services.23Consistent with empowerment theory31 in drug treatment programs. The single 30-minute individual HIV testing session included: (1) watching a 5-minute HIV testing information video; (2) reviewing the OraSure testing pamphlet on transmission risks and strategies for reducing risks; (3) taking the rapid OraQuick HIV test; and (4) receiving the test results and a service manual. Free condoms were regularly distributed for both conditions at both CSP sites.The streamlined HIV testing intervention was tested in the National Institute on Drug Abuse Clinical Trial Network 0032 HIV Testing study and found to be effective and cost-effective in increasing HIV testingBlack women who were employed as counselors or case managers at the 2 sites were trained to deliver both E-WORTH and streamlined HIV testing control condition to avoid inextricable facilitator effects. Facilitators completed a 4-day training on both conditions and received biweekly supervision from the project director.Biological assays for HIV and STIs were performed at baseline and at the 12-month follow-up. We also collected behavioral data at baseline and at 3-, 6-, and 12-month follow-ups through audio computer-assisted self-interviews (ACASI). Participants received a maximum of $240 for all interviews. Transportation was covered for intervention sessions. We also collected sociodemographic characteristics on age, race/ethnicity, marital status, education, employment status, homelessness, food insecurity, and history of incarceration.T. vaginalis using a real-time polymerase chain reaction assay. Participants with reactive HIV/STI test results were linked or referred to treatment. Participants who were treated for STIs by their own medical practitioners were asked to provide proof of treatment by a prescription bottle or note. Of the 109 participants who tested positive for an STI at baseline, 87 (79.8%) had proof of treatment (38 of 47 control participants [80.9%] and 49 of 62 E-WORTH participants [79.0%]). We included STI outcomes for the total sample, consistent with intention-to-treat approach, but also conducted a sensitivity analysis on new STI cases by excluding 22 participants who lacked proof of treatment. We collected saliva specimens using rapid OraQuick ADVANCE Rapid HIV-1/2 Antibody Test.Participants provided vaginal swab specimens that were tested for chlamydia and gonorrhea using a DNA assay  and The primary behavioral outcome was the total number of acts of condomless vaginal and/or anal intercourse across all partners in the prior 90 days. Secondary behavioral outcomes included the number of condomless vaginal or anal sex acts in the prior 90 days with primary partners, the proportion of protected total vaginal or anal sex acts, and having had vaginal or anal sex with more than 1 partner in the past 90 days.t tests or χ2 tests. To examine the effects of E-WORTH, we used an intention-to-treat approach. To test the difference in the new incidence of STIs at the 12-month follow-up between the 2 study groups, we used logistic regression models that included age, high school graduate (yes or no), employed (yes or no), marital status (married or common law vs single), and confirmed STI at the baseline as covariate adjustments. For behavioral risk outcomes, we used mixed-effects generalized linear models and included a random effect for repeated measures. To estimate the effects over the entire follow-up period, we used the mixed-effects model, including intervention condition, measures of the outcome variable reported at baseline, and the same covariates listed previously. We then obtained the effects from the coefficients associated with the intervention condition. To estimate the effects at each follow-up time point, we included intervention condition, follow-up time, and interaction between intervention condition and follow-up time, baseline measures of the outcome, and covariate adjustment in the mixed-effects models. We then obtained the effects at each follow-up by linear combinations of the coefficient associated with the intervention condition plus the coefficient for the interaction between intervention condition and respective follow-up point. Hypothesis testing for intervention effects on the number of condomless sex acts was based on incident rate ratios (IRRs) from mixed-effects negative binomial regression models. The differences indicated by regression coefficients (b) from mixed-effects linear regression were used for proportion of protected acts of intercourse. Odds ratios (ORs) from mixed-effects logistic regression models were obtained to test intervention effects for the other behavioral outcomes. Statistical significance was assessed using 95% confidence intervals (CI) and P value for each estimate. Statistical analyses were performed using Stata 15 (StataCorp).Descriptive statistics were used to describe baseline background characteristics for the total sample and by study condition and baseline outcomes among the total sample and by study condition. We assessed differences between the 2 study groups for these variables with 2-tailed 32 MI imputes values for missing data by using the information that we observed or that were available from a participant’s prior assessments  to calculate predicted values for the unobserved. Our MI procedures involved 60 imputed data sets using the same mixed-effects generalized linear models described previously.There were missing data due to loss at follow-up: 70 participants (19.9%) at 3 months, 53 participants (15.1%) at 6 months, and 51 participants (14.5%) at 12 months. Sensitivity analyses for the potential impact of missing data relied on using multiple imputation procedures (MI).The mean (SD) age was 32.4 (11.0) years . All parP = .01) (P = .02). During the 12-month follow-up, E-WORTH participants reported 38% fewer total acts of condomless sex in the prior 90 days , and 42% fewer condomless sex acts with their main partners . Compared with control participants. E-WORTH participants reported 11 percentage points higher acts of protected intercourse across all partners  and with their main partners  and were more likely to always use condoms with all partners  and with their main partners  over the 12-month follow-up. The sensitivity analysis using MI yielded similar parameter estimates and significant patterns with the complete case results reported previously (data not shown).Compared with control participants, E-WORTH participants had 54% lower odds for detecting any STI at the 12-month follow-up  . These r12 Another meta-analysis of 45 HIV/STI interventions for women from ethnic minority groups found only 5 significantly reduced STIs by an average effect of 41%.12T. vaginalis constituted most STIs. The significant decrease in T. vaginalis incidence at the 12-month follow-up largely contributed to the significance of the STI outcome. The magnitudes of both biological and behavioral outcomes found in this study are clinically and statistically meaningful, indicating the effectiveness of the culturally tailored E-WORTH intervention.To our knowledge, this randomized clinical trial is the first to show positive effects of a culturally tailored intervention on reducing STI incidence and condomless sex among Black women in CSPs. Compared with control participants, E-WORTH participants had 54% lower odds of testing positive for an STI at the 12-month follow-up and reported 38% fewer acts of condomless sex during the 12-month period. To consider these findings in context, the intervention effect on reducing STI incidence found in this study was stronger than the average effect from a meta-analysis of 17 HIV/STI interventions conducted among Black women, which observed a 19% reduced odds of STI incidence among intervention participants relative to comparison participants.34 combined with the high rate of sex with multiple partners (48.5%) suggest that this sample of Black women was at high risk of acquiring HIV. The high rates of food insecurity, homelessness, incarceration, and unemployment found in this study are also established risk factors for HIV/STIs rooted in structural racism. E-WORTH’s explicit focus on structural racism along with its novel hybrid group format led by Black female CSP staff and a computerized individualized tool with Black women characters promoted effective cultural tailoring of content. This tool further ensured standard delivery of HIV/STI prevention activities and lowered the bar for staff training, increasing the promise of future uptake in CSPs.Despite the relatively low rate of HIV infection, the high baseline rate of STIs (30.9%), a risk factor for HIV transmission,20 The diverse sample recruited from probation, parole, and ATI programs and the delivery of E-WORTH in a real-world CSP further suggests the feasibility of implementing E-WORTH in a range of CSPs.This study had several limitations. Generalizability of findings is limited to Black women in CSPs in New York City, specifically to 1 large CSP at 2 sites. The significant STI difference between groups arms at baseline was an unexpected finding that we believe was spurious given the robust randomization procedure and receipt of STI results after randomization. The large effect sizes observed across our outcomes further lend confidence in the STI outcome results. Although the eligibility criteria included having condomless sex with a male partner, 31% identified as bisexual. However, this study did not measure risk behaviors with same-sex partners. Despite these limitations, this study has several strengths, including high rates of participation, attendance, and retention that were similar to the rates in the original WORTH trial.18 There remains an urgent public health need to scale up culturally tailored interventions to redress the concentrated HIV/STI epidemics among Black justice-involved women that continue to be driven by structural racism.This randomized clinical trial demonstrated the promise of implementing a culturally tailored HIV/STI intervention to Black women in CSPs, consistent with numerous studies documenting the effectiveness of culturally tailored HIV/STI interventions.


Health self-tracking is an evidence-based approach to optimize health and well-being for personal self-improvement through lifestyle changes. At the same time, user-generated health-related data can be of particular value for  research. As longitudinal data, these data can provide evidence for developing better and new medications, diagnosing rare diseases faster, or treating chronic diseases.This quantitative study aims to investigate the impact of digital forced-choice nudges on the willingness of German health self-trackers to donate self-tracked health-related data for research. This study contributes to the body of knowledge on the effectiveness of nonmonetary incentives. Our study enables a gender-specific statement on influencing factors on the voluntary donation of personal health data and, at the same time, on the effectiveness of digital forced-choice nudges within tracking apps.We implemented a digital experiment using a web-based questionnaire by graphical manipulation of the Runtastic tracking app interface. We asked 5 groups independently to indicate their willingness to donate tracked data for research. We used a digital forced-choice nudge via a pop-up window, which framed the data donation request with 4 different counter values. We generated the counter values according to the specific target group needs identified from the research literature.r=0.21), men are significantly more likely (P=.04) to donate their self-tracked data for research if the need to take on social responsibility is addressed  compared with the control group without counter value. Selfish or pseudoprosocial counter values had no significant effect on willingness to donate health data among male or female health self-trackers in Germany when presented as a forced-choice nudge within a tracking app.A sample of 919 was generated, of which, 625 (68%) were women and 294 (32%) were men. By dividing the sample into male and female participants, we take into account research on gender differences in privacy tendencies on the web and offline, showing that female participants display higher privacy concerns than male participants. A statistical group comparison shows that with a small effect size  of the health self-trackers would donate their self-collected health data to research. Although selfish motives do not significantly influence willingness to donate, linking data donation to added societal value could significantly increase the likelihood of donating among male self-trackers by 15.5%. Thus, addressing the need to contribute to society promotes the willingness to donate data among male health self-trackers. The implementation of forced-choice framing nudges within tracking apps presented in a pop-up window can add to the accessibility of user-generated health-related data for research. As of April 2020, more than half a million enthusiastic health self-trackers donated collected data to the federal government research institute responsible for disease control and prevention in Germany, via fitness wristbands or smartwatches . As of FThe approach described is only one instance of how user-generated health-related data could add value to research and support public health measures . MoreoveWe argue that digital forced-choice nudging in general is an appropriate tool to introduce behavioral change toward donating personal health-related data among health self-trackers because health self-trackers are very likely to share their self-tracked data with third parties and primarily have other intentions for tracking. Thus, data donation for research might be perceived as rather unimportant and therefore present an appropriate field for effective nudging.This quantitative study aims to investigate whether a digital forced-choice nudge can influence the willingness of German health self-trackers to donate self-tracked health-related data for research. We want to contribute to the body of knowledge on the effectiveness of nonmonetary incentives derived from the known needs of the target population. For this, we also consider research on gender differences in privacy tendencies on the web and offline. This shows that women display higher privacy concerns than men. This is in line with both evolutionary and social role theories. Therefore, we analyzed male and female health self-trackers separately ,18. Our When discussing the active decision to donate self-collected health data and possible contributing factors, we already know that various psychological effects influence individuals, consciously or unconsciously, during their decision-making process ,20. PeopIn this context, nudges are tools for influencing behavior in decision-making processes without resorting to prohibition, commandments, or economic incentives ,23,24. TNudges are widely applied in health systems, with the ultimate goal of a healthy population. According to Holland et al , most nuWith the extensive use of digital devices, decision-making in digital choice environments  has emerged, especially in the field of e-commerce ,32. DigiTo test the effectiveness of digital forced-choice nudges for data donation among health self-trackers in Germany, we need to identify the needs of our test group to use the right triggers for behavior change—in our experiment, donate tracked data. The prospect of need satisfaction could be a potentially attractive reward, which might encourage self-trackers to donate their data in return. To this end, we will derive potentially attractive counter values (benefits) for framing in a digital forced-choice nudge based on the known prevailing motives and needs of our target group and for data donation in general.People with a diagnosed disease predominantly track vital signs or biological parameters -42. IntrPeople with self-perceived disease risk factors mainly track their dietary and physical activities. Motives include potential and subjectively perceived risk prevention (such as obesity) or the desire to learn and promote a healthier lifestyle ,44. PeopHealth self-trackers thus collectively possess a desire to use digital technologies to optimize health and well-being via self-monitoring ,51. SelfH1A: The prospect of receiving individualized tips to improve one’s health has a positive influence on female health self-trackers’ willingness to donate personal self-collected health-related data for research.H1B: The prospect of receiving individualized tips to improve one’s health has a positive influence on male health self-trackers’ willingness to donate personal self-collected health-related data for research.Research on the motives to donate personal data, for example, to charity, is consistent with findings on motives supporting prosocial behavior, such as blood donation -63. DonaSecond, an individual’s perception of the significance of their own contributions to the community is crucial. Nudging intervention can realize this by emphasizing benefits, such as potentially accelerating the cure of disease by valid research findings and improved therapeutic interventions ,70.Derived from identified positive influences on data donation in general and underlying needs, our second hypothesis is as follows:H2A: The prospect of contributing to the community has a positive influence on female health self-trackers’ willingness to donate personal self-collected health-related data for research.H2B: The prospect of contributing to the community has a positive influence on male health self-trackers’ willingness to donate personal self-collected health-related data for research.According to Gimpel et al , motivesH3A: The prospect of recognition by the peer group  has a positive influence on female health self-trackers’ willingness to donate personal self-collected health-related data for research.H3B: The prospect of recognition by the peer group  has a positive influence on male health self-trackers’ willingness to donate personal self-collected health-related data for research.H4A: The prospect of belonging to a peer group  has a positive influence on female health self-trackers’ willingness to donate personal self-collected health-related data for research.H4B: The prospect of belonging to a peer group  has a positive influence on male health self-trackers’ willingness to donate personal self-collected health-related data for research.To test hypotheses 1 to 4 using digital forced-choice nudges, we set up a web-based experiment with the questionnaire tool LimeSurvey for health self-trackers in Germany. We generated 5 different mock-ups of the tracking app, Runtastic. We chose the app for its continued popularity, familiarity across all age groups, and duration in the market  -75. Thesthe user has just tracked a run of 5.2 km with Runtastic. This screen in particular is a characteristic of a frequently shared status update on Facebook or Twitter . It reprOn completion, a pop-up window with call to action appeared. The pop-up is a new built-in hurdle before reaching the desired results. The person is in a state of physical exertion, having just completed an intense sports session. Attention and interest in pop-up content could be considered lower at this point .Each pop-up window had a recommendation to the user—donating the tracked data to research, followed by information that motivates and helps him choose the suggested behavior—1 of 4 different nudges (N1 to N4) . PresentDonate Now?). Only one of the pop-up windows was randomly included in each questionnaire. In addition to three sociodemographic parameters, gender, age, and education, we added 2 items as inclusion criteria to the questionnaire. We started by querying devices used for tracking health-related data , allowing multiple answers as well as the frequency of accessing the tracked data .Willingness to donate was queried by assessing the likelihood of donating on an 11-point scale, ranging from 0% to 100%  if participants never used a tracking device and (2) if participants never actively or consciously tracked any health-related data.After collection, the data preparation included cleaning and organizing the raw data set in Excel (Microsoft Inc). We diligently checked for errors to eliminate incomplete questionnaires. Data processing involved encoding text format data into numeric indicator variables. Ultimately, our sample included exclusively ordinal-scaled variables suitable for statistical analysis in SPSS. We divided the sample into female and male participants to examine gender-specific differences.U tests as nonparametric tests to compare independent samples with homogeneous variances. The Kruskal-Wallis test can evaluate whether there is an actual effect of group affiliation in the first step. With a subsequent post hoc test, we checked which of the groups differed significantly. We used the Dunn-Bonferroni test.To perform appropriate statistical analysis for the experimental evaluation, we checked the data distribution. In addition, we checked for variance homogeneity within the 5 different test groups for each gender. To validate experimental hypotheses H1 to H4, we compared our 5 groups with each other for men and women separately. Regarding the data set characteristics, we applied the Kruskal-Wallis and Mann-Whitney We collected 1091 questionnaires in January and February 2021. Following our defined exclusion criteria, we excluded 5.04% (55/1091) of observations because of participants not using a tracking device and 0.73% (8/1091) of observations because they did not track any health-related data actively or consciously. Furthermore, we removed 9.99% (109/1091) of incomplete questionnaires. The final sample consisted of 919 participants.Our data set was not normally distributed but left-sided (skewness=0.087) and compressed  women and 32% (294/919) men. Overall, 45.1% (414/919) of the participants were aged between 18 and 34 years, 46% (423/919) of the participants were aged between 35 and 54 years, and 8.9% (82/919) of the participants were aged >55 years. Overall, only 0.2% (2/919) of participants did not finish high school. Overall, 4.5% (41/919) of the participants were still in school or high school graduates with no additional formal education. In addition, 43.5% (400/919) of the participants were attending or had graduated from college, and 51.8% (476/919) of the participants were going to or had graduated from a university. In terms of tracking frequency, 85.4% (785/919) of the participants reported daily tracking, 10.8% (99/919) of the participants tracked weekly, 1.4% (13/919) of the participants tracked monthly, and 2.4% (22/919) of the participants tracked less than once per month.We found that 60.3% (554/919) of our sample used a smartwatch for health self-tracking. Overall, 43.2% (397/919) of the participants used a smartphone, and 33% (303/919) of the participants used a fitness tracker (multiple answers were possible).The sample (N=919) was divided into 5 test groups with N0 as 186  and 4 different nudge groups .Taking gender differences in privacy concerns into account, we split the sample into female  and maleThe female sample contained 625 questionnaires. Regardless of the nudge applied, 77% (481/625) of women surveyed were willing to donate their tracked data for research (with a probability between 10% and 100%).The Levene test indicates homogeneous variances for female health self-trackers .P=.03) exist across at least 2 groups.Using the Kruskal-Wallis test, we examined whether the probability of data donation is the same across the 5 sample groups. As a result, we had to reject the nil hypothesis because significant differences  and between groups 3 and 4 .The post hoc test results and plot visualization suggest a potential significant difference between groups 1 and 4 and between groups 3 and 2. We further applied a median-based pairwise group comparison using the Mann–Whitney In summary, for female health self-trackers, no offered counter value, based on egoistic, social, or prosocial motives or needs, has a significant positive or negative influence on the willingness to donate tracked data for research. However, the prospect of showing one’s donation behavior to other users has a negative effect on willingness to donate data in direct comparison with groups that receive a prosocial or a self-serving return for their data donation.Overall, 79.9% (235/294) of the male respondents would donate their data (with a probability between 10% and 100%), regardless of the nudge queried .The Levene test indicates homogeneous variances for male health self-trackers .P=.02) using the Kruskal-Wallis test.Testing for differences among groups in terms of donation probability also revealed a significant difference among male participants  and 4 , between groups 0 and 2 (P=.04), and between groups 3 and 4 (P=.02).The Mann-Whitney As with female health self-trackers, we had to reject hypotheses H1B, H3B, and H4B for men as well. Thus, the prospect of a self-serving benefit or displaying data donation activity, named pseudoprosocial in our experiment, has no significant positive or negative influence on willingness to donate.r=0.21; Z=−2.087; N=104). Accordingly, we could not reject hypothesis H2B. Comparing means, nudging male health self-trackers in their donating decision-making process with a prosocial nudge would increase the willingness to donate data by 15.5%. At the same time, for male health self-trackers, we found evidence that open data donation significantly reduces the probability of donation compared with a secret donation (nudge 2), as well as compared with test groups 1 and 3, receiving a personal benefit. In addition, a group comparison of participants receiving personal tips and participants merely making a prosocial contribution reveals again that prosocial reasons are superior to selfish ones and increase the likelihood of donating data in direct comparisons.On the other hand, the prospect of making a prosocial contribution significantly influences the likelihood of donating self-tracked  data with a small effect size (P=.001).By dividing the sample into male and female participants, we considered gender differences because of the known privacy concern differences between men and women. We also split the sample into different groups regarding age, education, devices used for tracking health-related data, and tracking frequency during analysis. The results show that there are no significant increases or decreases in the willingness to donate self-tracked health-related data when the sample is divided into the stated groups. A correlation analysis did not show any significant positive or negative correlations with the willingness to donate any other variable but gender  as well as on the effectiveness of offline nudges in health care (16%) ,35. We ncharity, therefore, negatively influences willingness to donate data. This finding should be taken into account when framing a data donation plea, for example, by explicitly referring to donor anonymity.The experimental results confirm the findings of previous research on the motives to donate personal data for the health area. Specifically, for health self-trackers, our study confirms the results of Skatova and Goulding  and MujcCompared with polls regarding willingness to donate data, our results show a significantly lower willingness among active health self-trackers. In contrast to population surveys, which put a willingness to donate data at 80% or social media users’ willingness at 95% ,16, onlyOur results also show that women, who are evolutionarily more concerned about protecting their privacy, do not respond to any of the nudges presented adding to the findings by Tifferet  and FariThe findings have a number of limitations. Owing to recruiting primarily via social media and fitness influencers, the sample includes a disproportionately large number of younger and higher educated people as well as mostly female compared with male health self-trackers (2/3 to 1/3), which can bias our results.Thus, the sample may not represent all German health self-trackers. Furthermore, people engaging in social media and following a call to action from influencers on Instagram and from peers in fitness Facebook groups (participating in the experiment in this case) have fewer privacy concerns and are more likely to share their health-related information with others. We did not perform ex ante power calculations to determine the sample size. Future research may therefore repeat the survey with a larger sample via additional recruitment channels to assess the reliability of our findings. In addition, the chosen geographic focus (Germany) might have biased the results because of cultural differences in terms of relevance and general attitudes toward privacy . FurtherParticipants’ nonreproducible or untruthful answers can also limit the results. The reasons could be the chosen and not clearly comprehensible scale levels or phrasing of the individual benefit. Future experiments could also imbed nudges in a different environment (a different app) and use an even more realistic situation with clickable mock-ups. Our hypothetical request for web-based health data donation may not represent reality. Future experiments could implement a real data donation tool within a popular health self-tracking app to verify our results.The growing trend toward digital health and increasing acceptance as well as the use of health apps such as fitness trackers, digital check-ups, and nutrition apps will contribute to a significant increase in nudging measures. This study could aid access to health data for research and long-term care improvement.Although selfish motives do not significantly influence willingness to donate, linking data donation to added societal value could significantly increase the likelihood of donating among male self-trackers by 15.5%. Thus, addressing the need to contribute to society promotes willingness to donate data among male health self-trackers and should be emphasized when designing campaigns to donate health data. The implementation of forced-choice framing nudges within tracking apps presented in a pop-up window can add to the accessibility of user-generated health-related data for research.


Emerging epidemic-prone diseases have introduced numerous health and economic challenges in recent years. Given current knowledge of COVID-19, herd immunity through vaccines alone is unlikely. In addition, vaccination of the global population is an ongoing challenge. Besides, the questions regarding the prevalence and the timing of immunization are still under investigation. Therefore, medical treatment remains essential in the management of COVID-19. Herein, recent advances from beginning observations of COVID-19 outbreak to an understanding of the essential factors contributing to the spread and transmission of COVID-19 and its treatment are reviewed. Furthermore, an in-depth discussion on the epidemiological aspects, clinical symptoms and most efficient medical treatment strategies to mitigate the mortality and spread rates of COVID-19 is presented. The current epidemic of SARS-CoV-2, the virus that induces illness known as COVID-19, is an important wake-up call for all countries around the world. Given the dire global consequence that outbreaks of emerging diseases like COVID-19 can trigger, there is an urgent need to improve preparedness for such epidemic-prone diseases. COVID-19 is not the first global pandemic, and emergence of new epidemic-prone diseases is inevitable due to poor humanitarian habits.Since the start of this century, large outbreaks such as COVID-19, Ebola virus, MERS-CoV, SARS-CoV-2 and influenza A virus subtype H1N1 (A/H1N1) have shattered several myths about the global vulnerability to threats arising from such epidemic-prone diseases [SARS-CoV-2  is a virus that contains a single-stranded ribonucleic acid genome and a nucleocapsid phosphoprotein . BindingSARS-CoV-2 can target human cells by the binding of spike glycoprotein (S-protein) to ACE2 receptor, a membrane-bound carboxypeptidase . ACE2 haSince ACE2 acts as an entry pathway for viral infection, blocking this receptor through ACE inhibitors and receptor blockers is promising to prevent viral infection into the lungs and whole body. Also, it has been suggested that the implementation of human recombinant ACE2 (hr-ACE2) protein would be helpful to saturate viral S- proteins and prevent SARS-CoV-2 cell entrance .According to Padhi and Tripathi have explored putative drug binding sites in the main protease of SARS-CoV-2. They report mutation hot spots that may explain probable drug resistance . This teCoronaviruses are categorized into four subgroups: alpha, beta, delta and gamma. Only alpha and beta may be transmitted to humans and therefore are characterized as human coronaviruses (HCoVs) .In late 2019, new cases of beta coronavirus infections were identified in Wuhan, China. Due to the acute respiratory symptoms of this recently recognized coronavirus, it was subsequently named SARS-CoV-2, and the WHO named this new coronavirus disease COVID-19.Patients infected with this virus show different signs and symptoms in the following organ systems: respiratory, neurological, gastrointestinal and cardiovascular. The more prevalent symptoms include cough, sore throat, fever, fatigue, headache, arthralgia, anosmia and ageusia .In less than 14 months from the first reported cases, the virus spread globally. The pandemic became one of the world's leading challenges in 2020, with a major impact on the economy and more than 5 million mortalities worldwide.Many efforts have been made to develop an efficient vaccine for this viral infection. The main types of COVID-19 vaccines could be categorized as mRNA ,11, viraIn addition to the vaccines mentioned above, more than 200 additional vaccine candidates are currently in the development phase, of which more than 60 are under clinical investigation . HoweverAs previously mentioned, emerging epidemic-prone diseases in the 21st century have introduced numerous health and economic challenges, resulting in considerable mortality of the human population. To control and mitigate COVID-19 and address the immediate and long-term health outcomes, it is imperative to have comprehensive understanding of the nature of COVID-19 evolution, its mode of action and transmission, the potential ecological factors influencing its emergence  and its potential connection to previous events.As the delta variant of the coronavirus spreads throughout the world, it is essential to develop efficient therapeutic strategies to protect infected patients against severe illness, hospitalization and death. A guide to understanding the limiting factors for large-scale trials of therapeutic strategies for COVID-19 treatment albeit the spread of the delta variant and vaccine hesitancy and refusal is highly encouraged. Given the rapid spread of the delta variant, and the worldwide economic loss, it is imperative to develop effective therapeutic drugs to treat COVID-19 patients. Significant research efforts have been invested in the development of therapeutic drugs to treat COVID-19 patients. It has been a challenging process communicating pandemic-related information, especially amid misinformation, disinformation, conspiracy theories and politicization. As a result, health communicators are facing difficulties in coming across as credible, transparent and trustworthy. The delta variant has also dramatically upended recent progress against the pandemic and is forcing a reset everywhere. In this review article, the authors summarize the current understanding of COVID-19, such as its epidemiological aspects, clinical symptoms, pathophysiology and pharmacologic categories, as well as the most efficient medical treatment strategies supported by the NIH and WHO to help reduce severity and mortality rates. The potential mechanisms of action, dosing, adverse drug reactions and contraindications are also discussed in detail. Further, the most recent information about COVID-19 transmission and prevention is presented. Finally, research insights, existing knowledge gaps, challenges and future research direction are described, and a state-of-the-art snapshot of drug-based therapeutic strategies for COVID-19 and the attempts to repurpose various classes of drugs is presented.Compared with SARS-CoV, COVID-19 has a robust transmission capacity . PatientIt is noteworthy that epidemiological trends in the outbreak and fatality rate of COVID-19 vary on a daily basis and new mutants of the virus were reported in Africa, Brazil and the UK. At the beginning of the pandemic, China was leading in several diagnosed cases. Still, the incidence progressively increased in other countries, mainly Europe, the USA and the Middle East ,21.Among the diseases caused by coronaviruses, SARS, MERS and COVID-19 are most prevalent, resulting in severe outcomes in humans. Herein, the root of such diseases and their symptoms are discussed.In 2003, SARS was transmitted to humans and other animals (civet cats) by bats. The first infected human was diagnosed in Guangdong Province, China. Since then, the virus has spread to 26 countries and resulted in more than 8098 cases, with a fatality rate of 9.6% .Like those of influenza, the symptoms included fever, malaise, myalgia, headache, diarrhea and chills (rigors). In the first and second weeks of illness, patients experienced dry cough, shortness of breath, gasp and diarrhea. In severe cases, the disease often progressed rapidly, leading to respiratory failure and requiring intensive care, such as supplementary oxygen .MERS was first diagnosed in Saudi Arabia in September 2012. It infected 124 people and caused 52 deaths. The clinical manifestations of this disease were respiratory problems such as sore throat, dry cough and dyspnea. The mortality rate was approximately 60% .Although clinical symptoms are important in diagnosis, no individual symptom has been found to diagnose SARS-CoV-2. In less than a week, the symptoms include fever, nasal congestion, cough and fatigue, and other signs related to upper respiratory infections appear . Some reIn addition to the respiratory manifestations of COVID-19, other complications such as neurologic , psychiaThe most common dermatological manifestations presented in COVID-19 patients are urticaria, erythematous rash, livedo reticularis and petechiae ,34. SeveIn a study on patients with mild infection, abnormal laboratory results were obtained, such as increased levels of the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), D-dimer and lactate dehydrogenase (LDH) ,36. StudA concerning point in this illness is the possibility of reinfection. Vaccines can stop most people, but not everyone, from getting sick with COVID-19. Despite having been fully vaccinated, there is still a chance that people can get infected.et al. [Tillett et al.  reportedet al. . HoweverTo date, the association between immunodeficiency and SARS-CoV-2 reinfections has not been confirmed. The exact incidence of SARS-CoV-2 reinfection is not clear and, given the vast number of asymptomatic cases, this rate is likely underreported . The moset al. in writing review articles on various pharmaceutical topics [Despite all efforts, the mortality rate related to COVID-19 is still high. Researchers worldwide are investigating alternative approaches to fighting the COVID-19 global pandemic. Herein, putative therapeutic agents under investigation for the management of COVID-19 are discussed. Therapeutic agents of various categories—including antiviral, antimalarial, antiparasitic, anti-inflammatory, mucolytic, immunomodulator, corticosteroid, immunosuppressant, anticoagulant and cardioprotective drugs—have been prescribed to treat COVID-19 patients and were shown to be efficacious in their recovery. This review will be a new collection in COVID-19 treatment in continuation of the previous efforts of Farjadian l topics .in vivo [in vitro study reported that favipiravir demonstrated an inhibitory effect on COVID-19 [Favipiravir is a purine nucleic acid analog  that is in vivo . It is win vivo . It is ain vivo . A recenCOVID-19 .A clinical trial on 35 patients receiving favipiravir compared with LPV/ritonavir was performed on COVID-19 patients. The first group demonstrated a faster recovery period and shorter clearance time of the virus than the control group . However® showed a viral inhibitory effect in in vitro studies. The outcomes of LPV-ritonavir treatment for COVID-19 patients were investigated [These are protease inhibitors that were first approved in 2000 to prevent HIV infection. Ritonavir also raises the plasma levels of lopinavir (LPV) by inhibiting cytochrome p 450 (CYP450) ,56. Withstigated . The admstigated .in vitro study in Vero E6 cells demonstrated the antiviral effects of remdesivir (GS-5734) against COVID-19. Remdesivir was shown to be capable of inhibiting the virus with higher sensitivity and at a lower concentration [Remdesivir was first discovered by Gilead Sciences Company . Also, rntration .In a study conducted on patients from the US, Europe, Canada and Japan, remdesivir improved clinical manifestations . A recenRibavirin is another RNA antiviral drug. It received US FDA approval in 1998 to treat chronic hepatitis C (CHC). According to the primary case study in the USA, the flagship study on ribavirin did not show more benefits in treating patients than LPV/ritonavir. However, new clinical studies have shown therapeutic effects on patients ,67. In gin vitro study have also confirmed its role in COVID-19 [Sofosbuvir is an antiviral that directly targets the RNA of the virus. It is used as a combinatorial therapy with ribavirin and interferon alpha (IFN-α)  to treatCOVID-19 ,71.Umifenovir is an antiviral drug utilized as a prophylaxis for influenza A and B viruses in Russia and China for several decades . Umifeno®) in comparison with LPV/ritonavir could be effective, as seen by faster viral clearance compared with patients who received LPV/ritonavir. Based on the reports in a 14-day period, all patients receiving Arbidol® had a negative viral load, whereas the patients in the LPV group had a positive viral load [A clinical study reported that the administration of umifenovir  infection. However, CQ is limited by an increased risk of high-grade side effects such as cardiac arrhythmias . Hydroxychloroquine (HCQ) has been formulated and found to be less toxic (∼40%). HCQ is now prescribed as an immune modulator for autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) [in vitro (Vero E6 cells) study revealed that CQ with half-maximum effective concentration (EC50) of 1.13 μm, half cytotoxic concentration (CC50) >100 μm was required to reduce the viral load of COVID-19 [in vitro study reported that HCQ had more potent inhibitory effects compared with CQ in SARS-CoV-2. Both CQ and HCQ prevented the entrance of the virus into the cell through an increase in the pH value of the endosome and alteration of the glycoside transferase of the SARS ACE2 receptor [Chloroquine (CQ) is the standard of care to prevent malaria (tis (RA) . An in vCOVID-19 . Moreovereceptor . Importareceptor .It was reported that patients receiving high doses of CQ diphosphate lowered mortality rate compared with patients who received low doses of CQ diphosphate. However, the high-dosage group demonstrated more toxic effects and lethality compared with the low-dosage group 2M3 ,77. In cin vitro studies have recognized that AZN is effective against Ebola and SARS-Cov-2 with EC50 values of 2.792 and 2.12 μm, respectively [in vitro study, concomitant administration of AZN and HCQ resulted in a synergistic effect in COVID-19 treatment [Plasmodium falciparum and SARS-CoV-2 invasion [Plasmodium falciparum invasion and has shown efficacy in SARS-CoV-2 infection treatment, likely through ligand/receptor interactions [AZN is a macrolide that is efficacious against Gram-negative and Gram-positive bacteria. It has been used to treat respiratory (bronchitis and pneumonia), enteric and genitourinary tract infections . Severalectively . Furtherreatment . Howeverreatment . Howeverreatment . Clusterinvasion . AZN couractions . A possiractions . By decrractions . Influenractions .In Nitazoxanide (NTZ), an antiprotozoal, is the active and oral form of nitrothiazolysalicylamide . It can in vitro, such as dengue virus [Ivermectin is FDA approved for parasitic infections and tropical diseases. It has been shown that this drug can inhibit the replication of some ssRNA viruses ue virus ,94,95, yue virus  and Zikaue virus . It has ue virus ,99. Despue virus . Recentlue virus .Colchicine is a pleiotropic anti-inflammatory cytotoxic agent. One of the proposed pathways is to inhibit the polymerization of microtubules by binding to the tubulin protein. In addition to preventing mitosis, colchicine prevents neutrophil activation and migration to the site of inflammation. This important anti-inflammatory drug is commonly utilized to treat several inflammatory diseases such as gout and inflammatory bowel disease (IBD). Furthermore, several studies have reported efficacy in the treatment of Epstein-Barr virus (EBV) , hepatitFurthermore, viral infections targeting endothelial cells often induce a significant amount of oxidative stress . ColchicIbuprofen is an NSAID used to suppress inflammation, fever and pain. Research on the effectiveness of this drug on COVID-19 infection is still in the infancy stage of development. Recent studies have shown that the virus must bind with the ACE2 receptors to enter eukaryotic cells . The virNaproxen, a member of the NSAID family, reduces fever, pain and inflammation by reducing the mediators involved in inflammation, such as prostaglandins. Given the current crisis caused by the SARS-CoV-2 virus, scientists are finding many ways to fight it. One way is to target the viral N-nucleoprotein to prevent it from binding to the RNA of the virus. This pathway can be an essential strategy to decrease the outbreak of the virus and any possible role associated with the N-nucleoprotein. Previous studies have shown the beneficial effects of naproxen on infections caused by the influenza A virus ,126. TodThis drug is used in the treatment and improvement of some diseases such as cystic fibrosis. Some anti-inflammatory and anti-cytokine activities via the nuclear-factor-kappa-B (NF-κB) pathway have been suggested for this drug .The reason for focusing on this drug to improve the condition of patients with COVID-19 is the effect of acetylcysteine on increasing the production of glutathione (GSH). GSH is an intracellular antioxidant substance that is not able to transport across the membrane. On the other hand, acetylcysteine can easily cross the membrane and enter the cell from the extracellular environment. When acetylcysteine enters the cell, GSH production eventually increases, and the cell's antioxidant power increases during inflammatory diseases . The thiOn the other hand, the positive effects observed from the consumption of acetylcysteine in patients may also be due to the anti-cytokine activity. These cases need to be further studied. Due to the inherent increase in the level of oxidants in the older body, the risk of death increases in the elderly infected with this virus. Especially in people over the age of 80 and for males, the risk of death is very high. As mentioned, acetylcysteine can delay this process by increasing GSH levels in the cells and can greatly help the recovery of older patients from the disease . These tJusticia adhatoda [Bromhexine is extracted from vasicine, an alkaloid and a major component of the plant adhatoda . Bromhexadhatoda . Deformiadhatoda , it ultiadhatoda  and bronadhatoda . In prevadhatoda . ConsideIn addition to the ACE2 membrane surface protein, serine proteinase 2 also plays a significant role in viral attachment to cells. Bromhexine has been shown to be potent in binding to this protein, eventually inhibiting this receptor and preventing the virus from entering human cells. Because the positive effect of this drug in treating MERS and SARS has already been observed , many efARDS could happen during COVID-19 infection. This syndrome can cause hyperinflammation and CSS, leading to organ failure . The admAnakinra is an IL-1 receptor antagonist. Anakinra is authorized for use in patients with RA. Moreover, it has also shown therapeutic benefit for severe sepsis in patients with multi-organ dysfunction . An effeIFN-α and interferon-beta (IFN-β) have shown both antiviral and immunomodulatory effects . These cThere is much controversy in the literature regarding the advantageous effects of corticosteroids in dealing with COVID-19. From the pathophysiological perspective, after SARS-CoV-2 virus enters the host cells, the innate immune system is the initial responder. Unless the inflammatory response is regulated, CSS can occur . CSS ind2 protein, which plays a major role in synthesizing inflammatory mediators such as prostaglandins and leukotrienes [Methylprednisolone is an anti-inflammatory drug that interacts with specific cytoplasmic receptors and regulates protein synthesis. Methylprednisolone inhibits the phospholipase Aotrienes . In an ootrienes . Resultsotrienes .Dexamethasone is another corticosteroid with antiemetic properties. Dexamethasone is an agonist for the glucocorticoid receptor (GR) . Its antBecause this corticosteroid has a prolonged clearance rate, broad-spectrum effects can take place on the innate and adaptive immune systems and can suppress the cytokines' destructive function . In a caHydrocortisone is a corticosteroid that interacts with both glucocorticoid and mineralocorticoid receptors. Some reports indicate that hydrocortisone can inhibit oxidative metabolism, although it has lower anti-inflammatory properties than prednisolone and dexamethasone . HydrocoFor hospitalized patients suffering from critical conditions such as ARDS and exacerbating conditions, higher doses of corticosteroids are administered. For example, a study suggested that hydrocortisone 50–100 mg as bolus administration and then infusion of 200 mg/day was a suitable regimen for adrenal-insufficient patients with sepsis . Adrenal®) is a corticosteroid and beta-2 (β2) adrenergic agonist. Budesonide/formoterol is another anti-inflammatory agent and bronchodilator [2 agonist as a bronchodilator such as budesonide + formoterol was previously used for the management of asthma and chronic obstructive pulmonary disease (COPD) [Budesonide/formoterol combined preparation  ,176.Often, the early signs of COVID-19 are cough and fever. After 8 days, the onset of dyspnea occurs in 20% of patients and is followed by ARDS in hospitalized patients . There iFingolimod is an immunomodulatory drug. It is an analog of sphingosine, which is phosphorylated by sphingosine kinase; it regulates sphingosine 1 phosphate receptor. Fingolimod can influence the aggregation and distribution of lymphocytes. It isolates and captures lymphocytes in the lymph nodes to prevent their contribution to autoimmune diseases . FingoliLeflunomide is considered for autoimmune disorders, mainly influencing joints. Leflunomide inhibits dihydroorotate dehydrogenase (DHODH) and has a critical role in the synthesis of uridine monophosphate (rUMP), which is vital for DNA and RNA synthesis. This inhibition activates a series of steps that eventually lead to G1-phase cell cycle arrest . It has In one study, leflunomide was evaluated in COVID-19 patients . It was Thalidomide is an immunomodulatory drug that inhibits angiogenesis. Nowadays, this drug is prescribed for its anti-inflammatory properties in cancer comorbidities, including multiple myeloma leprosy and graft-versus-host disease. Moreover, thalidomide significantly reduces oxidative stress and TNF-α, IL-1 and IL-6 production . One stuAs mentioned before, COVID-19 affects several organs, particularly the lungs undergo damage by inflammation and a cytokine storm . MonocloThis drug is a recombinant humanized mAB IL-6 inhibitor. It binds to the IL-6 receptor and dampens its inflammatory properties . In 2010Also, a study on severely ill COVID-19 patients demonstrated that the administration of tocilizumab remarkably reduced fever within a few days and limited the need for oxygen supplementation . HoweverSarilumab is a human monoclonal antibody that is an IL-6 receptor antagonist; it is approved to treat RA in patients with severe or critical COVID-19 . SarilumConsidering the major role of IL-6 in the pathophysiology of COVID-19, sarilumab as another mAB against IL-6 was suggested to alleviate respiratory symptoms . The levAdalimumab is a TNF-α inhibitor that has more advantages than other TNF-α inhibitors due to its large antigen size, which increases the binding affinity to tumor necrosis factor receptor (TNFRS) . TNF-α pCOVID-19 patients have higher circulating levels of TNF-α in the plasma and tissues . TherefoBevacizumab is a humanized mAB that targets VEGF. VEGF is known to be elevated during the hyperinflammation stage and is upregulated in infected respiratory tract epithelial cells . VEGF prRavulizumab is a recombinant mAB that attaches to the complement protein C5 with high affinity and inhibits the production of terminal complement complexes while playing a critical role in the immune system. When C5 is blocked, immune system responsiveness is reduced. Ravulizumab is used to treat adults with paroxysmal nocturnal hemoglobin (PNH) . RecentlSome reports indicate that in severe COVID-19 cases, some vital molecules of the complement system, such as C3a and C5a, are activated. This complement activation leads to systemic thrombotic microangiopathy (TMA) and multi-organ damage ,212. In Lenzilumab is a recombinant mAB against granulocyte macrophage colony-stimulating factor (GM-CSF). GM-CSF has a critical role as an initiator in inflammatory reactions . LenziluSystemic inflammatory responses, including the activation of innate immunity by viral infections, lead to activation of coagulation and thrombin pathways called ‘immuno-thrombosis’ . The comLow molecular weight heparin (LMWH), or enoxaparin sodium, is an anticoagulant therapy. LMWH activates antithrombin (AT), which in turn inactivates enzymes involved in coagulation. It is used to treat deep vein thrombosis (DVT) and ST-segment elevation myocardial infarction (STEMI) .in vivo [There are some reports of DVT in hospitalized COVID-19 patients. Although the administration of LMWH would be beneficial for COVID-19 patients with coagulopathy , identifin vivo . Thus, tin vivo . Moreovein vivo .a. It is a derivative of oxazoline and exerts its pharmacological effect by binding to factor Xa [Rivaroxaban is another anticoagulant. It was the first oral medication that exerts its effects through the direct inhibition of thrombin or factor Xactor Xa . It is uactor Xa .A 79-year-old patient, hospitalized for COVID-19 pneumonia, experienced an episode of acute PE 4 weeks after discharge . HoweverAspirin  is authorized for use in various illnesses such as angina pectoris, colorectal cancer, osteoarthritis and SLE . Aspirinet al. also showed that 25% of the 3855 patients who received aspirin scored higher on an acute physiologic and chronic health evaluation and had a lower incidence of ALI/ARDS [et al. suggested that patients who took aspirin and statins before hospitalization had the lowest mortality rates from ALI/ARDS [Aspirin is not ordinarily recommended in the guidelines of COVID-19 treatment. However, it has been confirmed to exhibit antiviral effects by inhibiting prostaglandin E2 (PGE2) in macrophages and upregulate type I IFN, and inhibit virus replication . Under cALI/ARDS . A studyALI/ARDS .atorvastatin is contraindicated in active liver disease” [MYD88 gene and eventually activates NF-κB to activate the inflammatory cascade. Statins have been shown to stabilize MYD88 expression levels after a pro-inflammatory trigger and significantly attenuate NF-κB activation [Atorvastatin is an FDA-approved lipid-lowering agent. When combined with dietary modifications, it lowers the risk of cardiovascular events in individuals with cardiac risk factors and abnormal lipid profiles . Atorvasdisease” , unexplativation . The schtivation .Clopidogrel is an anticoagulant drug that is used to lessen ‘the rate of stroke in patients with non-ST-segment elevation, acute coronary syndrome’ (ACS), acute ‘ST-elevation MI, and unstable angina/non-ST-elevation MI’ . Clopido2/fractional inspired oxygen (FiO2) ratio in patients by preventing the formation of clots in the capillaries of the lung and improving the function of megakaryocytes and platelet adhesion. Inhibition and modulation of COX by clopidogrel in platelets as well as megakaryocytes can prevent the formation of thrombosis and increase the level of PaO2 [Patients with COVID-19 may experience hypoxia, endothelial dysfunction and alveolar involvement, which in turn cause micro-pulmonary thrombosis. The effect of antiplatelet therapy on arterial oxygenation in patients was assessed in a clinical setting . Antipla of PaO2 .Imatinib is a bcr-abl tyrosine kinase inhibitor. Imatinib also inhibits tyrosine kinase receptors involved in the function of stem cell factor (SCF), platelet-derived growth factor (PDGF) and c-kit and in turn inhibits PDGF- and SCF-mediated cellular action .in vitro against two viruses phylogenetically related to SARS-CoV-2, SARS and MERS. In this sense, Abelson kinases type 2 (ABL2) seem to be involved in the virus–cell fusion process. Inhibition of ABL2 could control viral entry into the host cells. Imatinib also inhibits c-KIT and PDGF receptors. Imatinib has been shown to prevent lung injury in animal models of COVID-19 by reducing pulmonary edema, it prevents histological damage and it improves endothelial barrier dysfunction. This phenomenon is likely mediated by reducing pro-inflammatory cytokine release such as IL-6 and TNF-α. These effects could be implemented by inhibiting transcription factor NF-κB based on recent in vivo and in vitro evidence [Imatinib is a curative therapy prescribed to adolescent patients with chronic myeloid leukemia ‘Philadelphia chromosome-positive’ in blast crisis, in accelerated phase, and in chronic phase following failure of IFN-α treatment . It is aevidence ,255.Acalabrutinib is the inhibitor of Bruton tyrosine kinase (BTK). Acalabrutinib – and its active metabolite, ACP-5862 –bind to the active site of BTK, leading to the inhibition of BTK. BTK signaling triggers B-cell proliferation . This drAcalabrutinib is used to treat patients who are diagnosed with mantle cell lymphoma. Serious and opportunistic infections, hemorrhage and cytopenia are among the significant side effects of this drug . A studyBlood samples collected from COVID-19 patients showed that BTK was active in all . In a clFedratinib is a tyrosine kinase inhibitor acting on Janus-associated kinase 2 (JAK2) and FMS-like tyrosine kinase 3 (FLT3) . Fedrati2/FiO2 ratio, were improved in the convalescent plasma group, the clinical status was the same in both treatment groups [Since the 20th century, convalescent plasma transfusion has been recognized as an alternative therapeutic plan of action in preventing and managing several infectious diseases and is thought to induce passive immunization. Convalescent plasma is drawn from a patient who has recently survived an infectious disease and whose plasma is rich in antibodies that can help another person who is suffering from the same infectious disease. It has been reported that early administration of convalescent plasma therapy remarkably lowered the mortality rate in respiratory viral infectious diseases during previous pandemics, including HINI influenza, SARS and MERS . Convalet groups . Howevert groups . The inct groups . Finallyt groups .Since the most effective therapeutic agents in COVID-19 management have emerged from the immunomodulation basis, the administration of intravenous immunoglobulin (IVIG) would be a promising strategy. IVIG is a liquid human immunoglobulin that contains polyclonal IgG antibodies . IVIG haAscorbic acid, also known as vitamin C, is an antioxidant agent that is a potential scavenger of the harmful reactive oxygen species (ROS) and prevents oxidative stress damage to cells and tissues. Vitamin C also plays a role as an essential supporter of a healthy immune system . VitaminIt is suggested that SARS-CoV-2 can damage hemoglobin molecules. New SARS-CoV-2 can damage the beta chain of hemoglobin, resulting in the separation of iron from the heme molecule. Hence, iron overload would be a common consequence of SARS-CoV-2 infection. Recent reports show many COVID-19 patients had high serum ferritin values . The relin vitro and in vivo immunomodulatory and antiviral effects. Also, deferoxamine can reduce viral replication through the induction of the iron deprivation that is a crucial element in the SARS-CoV-2 replication process [Another possible mechanism of deferoxamine in decreasing the COVID-19 severity course would be through reducing IL-6 values and diminished endothelial inflammation, which could prevent COVID-19-induced MOF . Hyperfe process ,283. So,+/H+ exchangers and interference with viral endocytosis [Metformin, a biguanide antidiabetic agent, has been recently introduced as a promising therapeutic agent in COVID-19 pneumonia patients with underlying Type 2 diabetes mellitus (DM) due to its pleiotropic effects. The possible mechanisms of metformin in COVID-19 management were subjected to control blood sugar levels, body weight reduction, diminished insulin resistance and prevent hyperactivation immune responses. ARDS is likely prevented through inhibition of the mammalian target of rapamycin pathway and neutrophil reduction. Additionally, the blockade of mitochondrial ROS signaling pathway can occur through cellular pH enhancement via endosomal Naocytosis . Viral pocytosis ,286. ACEocytosis . Also, iocytosis . Resultsocytosis . Althougocytosis . So, it ocytosis .6 cells/kg through MSC transplantation could ameliorate all clinical symptoms related to COVID-19 pneumonia [6 cells/kg allogeneic human umbilical cord MSC) could significantly induce symptom reversal with no severe adverse reactions [Mesenchymal stem cells (MSCs) are multipotent cells that would be considered in many inflammatory and immunologic diseases. The most common sources of MSC transplantation are the umbilical cord, bone marrow and adipose tissue. The possible mechanism of MSC therapy in COVID-19 management is by initiating MSC differentiation . Also, Mneumonia . Recent eactions ,296. Sineactions . A studyeactions . A receneactions . Accordieactions . A summaAlthough numerous drugs and clinical trials have been reviewed in this paper, due to this pandemic's economic, social and health concerns, an appropriate selection of therapeutic regimens according to a patient-specific status is essential. So, early diagnosis, close patient monitoring and the selection of appropriate therapeutic options based on disease severity should be scheduled. In this regard, a list of recommended therapeutic regimens for COVID-19 management based on the severity of the infection and stage of the disease is given in An overview of existing drugs in the treatment of COVID-19 is illustrated in The new COVID-19 rapidly spread around the world, and because of a high transmission rate, it became a pandemic within a few months. Many people suffer from this disease, and over 5 million deaths have been recorded. COVID-19 created one of the greatest global economic crises in history. The economic crises and control measures negatively impacted businesses and working conditions and highlighted inequalities in several communities. Although the first COVID-19 vaccine was administered in December 2020, immunization of 7.8 billion people worldwide is challenging due to the limited supply of vaccines and the new strains of the virus. In order to control and mitigate COVID-19, as well as address the immediate and long-term health outcomes, it is essential to have comprehensive information about the nature of COVID-19: its evolution, characteristics, mode of action and transmission. Due to the circulation of highly transmissible variants, more infections are likely, and unvaccinated people are most at risk. No vaccine is 100% effective; a small percentage of vaccinated people can also become infected, and some breakthrough infections are to be expected. As the delta variant of the coronavirus spreads globally, it is important to develop efficient therapeutic strategies to protect infected patients against severe illness, hospitalization and death. To better understand the risk factors related to epidemic-prone diseases such as COVID-19, an in-depth understanding of the ecological and genetic risk factors is required. One of the best ways to mitigate and prevent transmission of emerging epidemic-prone diseases such as COVID-19 is to understand the virus and how it spreads early on to enable quick intervention strategies. Concerted efforts among communities are vital for this effort. To sum up, regarding the vast spread of COVID-19 worldwide, efficacious medical treatment against COVID-19 should remain a priority to control the growing epidemic and treat COVID-19 patients.The COVID-19 pandemic has proven to be an unprecedented catastrophe affecting all ages, races and countries. The outbreak has taken millions of lives and has dramatically affected all aspects of our lives from health to economic. Although different platforms of vaccines have been developed and administered globally, not all residents have been fortunate to receive them. The more transmittable the virus becomes, the harder it is to achieve community-level protection. Two distinct kinds of advantages can be obtained from immunizing individuals. For any one person, the vaccine does protect against getting the illness, and it protects against severe illness, reduces hospitalization and decreases death rate. Additionally, community protection, sometimes referred to as herd immunity, is also achieved. More specifically, herd immunity refers to many people with an increased level of individual protection that the virus cannot find enough susceptible new individuals to infect and gradually diminishes, eventually disappearing in circulation in the community. To date, only about 51% of people worldwide have received their first dose, and nearly 40% have received the second dose, which indicates slow vaccination rates. It will take vaccination rates of about 70–85% to reach the herd immunity threshold and bring this pandemic to an end. If we do not reach the herd immunity threshold by next winter, COVID-19 may resurface as a seasonal virus. Due to the limited capacity of production of the vaccine in some countries and fast transmission rates, an important concern is the incidence of new viral mutant strains and their resistance to current vaccines. To meet global demands, vaccine production technology can be transported from developed countries to developing countries. Oxford AstraZeneca has worked with countries such as India and more recently with South Korea in this effort. Also, health education leaders are facing a serious challenge regarding vaccine hesitancy. It will be difficult for people who do not have sufficient knowledge of health systems to accept that an attenuated virus is to be injected into their body in the form of a vaccine; therefore, it presents resistance to vaccination. To overcome this challenge, educating the public about vaccines is essential. Another important issue to consider is that a percentage of breakthrough cases have been reported, highlighting the importance of having efficient therapeutic strategies for dealing with infected patients. It is likely that we will encounter a virus with greater lethality and wider spread in the future. It goes without saying that the capacity to produce modern vaccines, to help advance the production of nanoparticle-based vaccines and provide general knowledge to international communities must be prioritized by world governments. Hence, in the current scenario, we still need to rely on preventive measures as well as smart therapeutic plans. Along with the application of repurposed drugs used to manage COVID-19, the development of specific anti-COVID-19 drugs is necessary. In case the virus is not eradicated, therapeutic strategies will remain a pivotal tool for the future.The coronavirus is a kind of virus that contains RNA genome and nucleocapsid phosphoprotein, which causes many respiratory diseases in humans and various ranges of diseases in animals.The epidemiological trends in the outbreak and fatality rate of COVID-19 vary from day to day, and new mutants of the virus were reported.Among the antiviral agents used in managing the COVID-19 crisis, favipiravir as a purine nucleic acid analog is used to shorten the clearance time of the virus from the body. Also, remdesivir was shown to be capable of inhibiting the virus with higher sensitivity and lower concentration.Azithromycin is a macrolide that is effective in both Gram-negative and Gram-positive bacteria and is used to treat respiratory tract infections. However, to date, there is no reliable clinical proof for the success of azithromycin in COVID-19.Among the antiparasitic agents used in COVID-19, ivermectin can reduce the infectivity of coronavirus through binding to imp-α and imp-β1 proteins.Ibuprofen and naproxen as NSAIDs are used to suppress inflammation, fever and pain in the COVID-19 crisis. The virus must bind to angiotensin-converting enzyme 2 receptors to enter eukaryotic cells. These drugs inhibit the virus from attaching to the receptor. However, there is a great deal of disagreement about NSAIDs to improve patients' condition.Among the mucolytic agents used in COVID-19, N-acetylcysteine and bromhexine help reduce mucus secretion. N-acetylcysteine leads to a reduction in disulfide bonds. These drugs also prevent the attachment of viruses to the angiotensin-converting enzyme 2 receptors.The administration of immune modulators could be a promising approach to circumvent harmful immunological responses. For instance, anakinra as an IL-1 antagonist is an effective immune modulator that can eliminate the requirement for mechanical ventilation in COVID-19 patients.It is supposed that keeping a balance between immune response and viral replication and infection should be considered. So, the administration of corticosteroids may be beneficial in avoiding cytokin storm. However, there are some controversy regarding the use of corticosteroids in COVID-19 patients.Among the immunosuppressant drugs, fingolimod can influence the aggregation and distribution of lymphocytes. Moreover, leflunomide can shorten the duration of virus shedding and hospitalization.To suppress the release of cytokine storm and activation of immune responses, monoclonal antibodies are used to bind to the pivotal inflammatory cytokines and inhibit organ damage. For example, tocilizumab and sarilumab as inhibitors of IL-6 can be promising options in alleviating symptoms in COVID-19 patients.The activation of innate immunity during viral replication leads to the activation of immune-thrombosis. Therefore, it is thought that anticoagulants such as low molecular weight heparin and rivaroxaban can reduce the risk of thrombosis while enhancing microcirculation and preventing organ damage.The administration of some cardioprotective agents, such as aspirin and statins, before hospitalization can reduce mortality rates from acute lung injury and acute respiratory distress syndrome.It is suggested that SARS-CoV-2 can damage hemoglobin molecules. Hence, iron overload would be a common consequence of SARS-CoV-2 infection. Therefore, deferoxamine, which acts as a chelating agent may benefit these patients. Also, deferoxamine can reduce viral replication in the SARS-CoV-2 replication process. However, randomized, controlled trials are required in the management of COVID-19 patients.The possible mechanism of mesenchymal stem cell therapy in COVID-19 management would be through stimulation of the differentiation process and its immunomodulatory effects. Also, it could induce tissue repair through various mechanisms, including the secretion of anti-inflammatory cytokines, angiogenesis induction, immunomodulatory potential and extracellular vesicle release.


Although retinal disease is known to be a relative contraindication for MF-IOL implantation, there are no detailed guidelines for MF-IOL implantation with respect to the type and severity of retinal diseases/statuses. In this study, because retinal diseases can affect the performance of MF-IOLs, we analyzed the opinions of 111 retinal specialists, who were members of the Korean Retina Society, on the implantation of diffractive MF-IOLs in eyes with 15 retinal diseases/statuses using a web-based survey. For each underlying condition, retinal specialists were asked to rate their approval regarding implantation of MF-IOLs on a scale from 1 (completely disapprove) to 7 (completely approve), under the assumption that there were no known contraindications except for a given retinal disease/status. As a result, retinal specialists disapproved MF-IOL implantation  in the eyes with wet age-related macular degeneration, dry age-related macular degeneration with geographic atrophy, proliferative diabetic retinopathy, nonproliferative diabetic retinopathy with macular edema, previous macula-off retinal detachment, previous retinal vein occlusion, and epiretinal membrane, but the scores varied by disease/status. The factors that affected the specialists’ opinions were the type of practice and the frequency of MF-IOL implantation ( As the use of digital devices has increased, good near- and intermediate-distance vision has become an increasingly important issue even for elderly individuals . HoweverMF-IOL makes two or more focal points, thereby improving near and/or intermediate vision. Of the diverse designs of MF-IOLs, diffractive IOLs generate multifocality based on light interference and the spreading of waves around obstacles ,7. A serComorbid retinal disease has been reported in approximately 22% to 31% of patients who have undergone cataract surgery ,10. PatiBecause of the challenges of prospective clinical trials for this population, this study aims to provide information to help cataract surgeons make decisions about implanting diffractive MF-IOLs in eyes with underlying retinal diseases by summarizing the opinions of retinal specialists.The study was conducted with the cooperation of the Korean Retina Society (KRS) between March 2019 and April 2019 using email-distributed surveys linked to SurveyMonkey.com . Members of the KRS were invited by e-mail to participate in the survey. The KRS consists of qualified experts who have completed a retinal fellowship that lasted more than a year and published two or more papers on the retina as a first or corresponding author during the training period. Of the 364 KRS members in 2019, 111 specialists completed the survey (30.5%). Participation in the study was voluntary, responses were confidential, data were submitted anonymously, and no incentives were provided for participation. The participants were informed of the purpose of the study in the cover letters of the questionnaires. The study adhered to the tenets of the Declaration of Helsinki and was considered exempt from the institutional review board and ethical committee at the HanGil Eye Hospital since only expert opinions regarding the implantation of MF-IOLs in eyes with retinal diseases were collected, and no patient data were used.The survey aimed to obtain the opinions of Korean retinal specialists on implanting MF-IOLs in eyes with diverse underlying retinal diseases/statuses considering the potential effect of implanting MF-IOLs on the diagnosis and treatment of underlying diseases. Based on previous literature and the results of a preliminary survey, fifteen retinal diseases/statuses were chosen by the authors (M.K. and J.-H.S.). The preliminary survey included open-ended essay questions about the challenges of diagnosing and treating retinal diseases in eyes with MF-IOLs. The preliminary survey was distributed to retinal specialists by e-mail between August and October 2018 and received 32 responses. Based on these responses, 15 retinal diseases/statuses were chosen for the survey, namely (1) nonproliferative diabetic retinopathy (NPDR) without macular edema (ME); (2) NPDR with ME; (3) proliferative diabetic retinopathy (PDR) without ME; (4) PDR with ME; (5) resolved CSC; (6) previous retinal vein occlusion (RVO); (7) dry AMD with geographic atrophy (GA); (8) dry AMD without GA; (9) wet AMD; (10) epiretinal membrane; (11) high myopia; (12) previous macula-on retinal detachment (RD); (13) previous macula-off RD; (14) lattice degeneration; and (15) a history of barrier laser photocoagulation due to retinal breaks.The survey was created, completed, and submitted on SurveyMonkey.com. It was designed to be completed within 5 min to encourage participation. The survey was performed under the basic assumption that there was no known contraindication to diffractive MF-IOLs except for a given retinal disease/status and that the patient preferred MF-IOL after being fully informed about the general advantages and disadvantages. In the survey, the experts were asked to use a 7-point Likert scale to rate their degree of approval of diffractive MF-IOLs in eyes with each of the 15 retinal diseases/statuses that might affect the performance of MF-IOLs; a rating of 1 meant “completely disapprove”; 2, “strongly disapprove”; 3, “slightly disapprove”; 4, “neither approve nor disapprove” ; 5, “slightly approve”; 6, “strongly approve”; and 7, “completely approve” .At the end of the survey, the specialists’ age group, career duration, type of practice, and frequency with which they implanted MF-IOLs were collected to analyze the factors that might affect specialists’ opinions.The median values of the specialists’ opinions on each retinal disease/status were analyzed. Then, the percentage of permissive opinions was analyzed, with ratings from 5 (slightly approve) to 7 (completely approve) defined as permissive. In contrast, ratings from 1 (completely disapprove) to 3 (slightly disapprove) were defined as indicating disapproval of the procedure.Analysis of the factors affecting the opinions was performed by adding all the scores for the 15 retinal diseases/statuses per respondent and categorizing the scores based on specialist age , career duration (<10 years or ≥10 years), type of practice , and frequency of MF-IOL implantation .p < 0.05 was considered to indicate statistical significance.The Mann–Whitney U test and one-way ANOVA were used to analyze the tendency of opinions according to the characteristics of the respondents, namely their age, career duration, type of practice, and frequency of MF-IOL implantation. All statistical analyses were performed using IBM SPSS Statistics , and Of the KRS members, 30.5% participated in this survey. The characteristics of the survey respondents are shown in The Korean retinal specialists’ recommendations regarding MF-IOLs based on a given retinal disease/status are summarized in Regarding the distribution of opinions, less than 30% were within the permissive range for the implantation of MF-IOLs in eyes with wet AMD, PDR with/without ME, NPDR with ME, dry AMD with GA, and previous history of macula-off RD/RVO. On the other hand, most of the specialists were not reluctant to implant MF-IOLs in eyes with a history of barrier laser due to retinal breaks (82.0%) or in eyes with lattice degeneration (82.9%).p = 0.014 and p = 0.021, respectively; one-way ANOVA). However, age group and career duration did not significantly affect the opinions.The average sums of the questionnaire scores in subgroups defined by age, career duration, type of practice, and frequency of MF-IOL implantation are analyzed in In this study, retinal specialists expressed disapproval of MF-IOL implantation in eyes with wet AMD, PDR regardless of ME, NPDR with ME, dry AMD with GA, previous macula-off RD, previous RVO, and epiretinal membrane. Relatively permissive opinions were expressed regarding MF-IOL implantation in eyes with retinal diseases/statuses that did not prominently involve the macula, including previous macula-on RD, previous history of barrier laser, and lattice degeneration. Neutral opinions were expressed for implantation in eyes with dry AMD without GA, resolved CSC with relatively intact outer-retinal structures, NPDR without ME, and high myopia.Because patients with macular disease often complain of unsatisfactory vision related to decreased contrast sensitivity despite objectively good visual acuity , the impThe problems with MF-IOL implantation in eyes with retinal disease include not only the reduction in contrast sensitivity but also the effect on the diagnosis and treatment of preexisting retinal diseases ,19,20,21Confusion in interpreting examination results has also been reported in eyes with MF-IOLs. Wavy, horizontal artifacts have been reported on OCT line-scanning ophthalmoscopy images (monitor images) in eyes with diffractive MF-IOLs; however, there were no artifacts in OCT images or scanning laser ophthalmoscopy images . Retinalp = 0.021) (p = 0.013), with more disapproving opinions associated with working in a tertiary hospital. Age and career duration were added to the survey items because they were expected to be related in terms of whether cataract surgery was performed by themselves, as discussed above, and possible conservative view on the newly developed IOL in older age group, but they did not have a significant effect on opinions on implanting MF-IOL in eyes with retinal diseases.Among the diverse factors that might affect specialists’ opinions, the type of practice and the frequency of MF-IOL implantation were associated with significant differences. In order to interpret these analysis results, it is necessary to understand the role of the retinal specialist (surgeon) in Korea. In Korea, previously, retinal specialists did not perform cataract surgery (about age over 60), but recently, as vitrectomy has become dominant, most retinal specialists perform cataract surgery combined with vitrectomy by themselves. Although some retinal surgeons often perform cataract surgery without vitrectomy, implantation of MF-IOL is not generally considered when considering the underlying disease of the eyes that retinal specialists mainly deal with. That is why the MF-IOL implantation frequency option was set relatively low  in the questionnaire compared with usual proportion of MF-IOL implantation in Korea. In a previous survey of ophthalmologists regarding which IOLs they would choose for themselves, ophthalmologists who had performed more than 50 MF-IOL implantations were twice as likely to choose the MF-IOL option . Althoug= 0.021) . Furtherp = 0.447, chi-square test, data not shown). Third, our study design was based on expert option rather than prospective clinical trials, which could have produced more concrete results. Summarizing the opinions of retinal specialists in this study cannot provide an opinion that completely ignores any possible existing misconceptions. However, considering the ethical issues and difficulties of conducting clinical trials in patients with retinal diseases in the real world, the results of this study can help cataract surgeons make decisions about diffractive MF-IOL implantation in eyes with underlying retinal diseases until more concrete evidence is established.There are several limitations to our study. First, our survey focused only on diffractive MF-IOLs and excluded newly developed MF-IOLs with sectoral refractive design and extended depth of focus design because it takes time for retinal specialists to acquire sufficient experience with new types of IOLs. Opinions on diffractive MF-IOLs have already been based on more than 10 years of experience, while other newly designed types, which are expected to be more tolerable for retinal diseases, have relatively short experience. Second, the survey response rate was only 30.5%. However, due to the limitations of the web-based, e-mail-distributed survey method, it was difficult to increase the response rate beyond this level even after sending multiple e-mails. To indirectly overcome this limitation, we evaluated whether survey respondents had different demographic characteristics from all the KRS members. In particular, the age distribution, which has the potential to affect the ability to access the email distributed surveys and cause selection bias, was compared between the survey respondents and all KRS members, and there was no statistically significant difference between them (Despite these limitations, one merit of this study is that it is the first attempt to collect the opinions of qualified retinal specialists on the conditions for MF-IOL implantation. Retinal specialists are expected to have a realistic view of MF-IOL implantation in eyes with retinal diseases because they can receive continuous feedback through clinical experiences. A second merit is that our suggestions do not merely show dichotomous results between approval and disapproval of MF-IOL implantation; instead, they show varying degrees of approval depending on disease/status and severity. In real-world clinical situations, it is expected that the degree of patient demand for presbyopia correction and the degree of approval of the retinal specialist should be in harmony when an appropriate IOL is being selected for each patient. The results of this study are expected to help cataract surgeons make decisions on appropriate IOL selection in patients with underlying retinal diseases who prefer to correct presbyopia with cataracts.In conclusion, most of the respondents disapproved of MF-IOL implantation in eyes with retinal diseases involving the macula although varying degrees of disapproval were reported. The results of this study, consisting of the degree of approval for each of several retinal disease categories, are expected facilitate the decision-making process for MF-IOL implantation. The factors that affected the specialists’ opinions were the type of practice and the frequency with which they implanted MF-IOLs.