"If the mother does not know, there is no way she can tell the adolescent to go for drugs": Challenges in promoting health and preventing transmission among pregnant and parenting Kenyan adolescents living with HIV.

Adolescents living with HIV (ALHIV) who are pregnant, or parenting, are an important but understudied group. This study explores the challenges in promoting the health of these adolescents and preventing onward transmission. We used existing semi-structured interview data from a 2014 study conducted among Kenyan ALHIV (ages 15-19), their family members, and local health staff to examine adolescent HIV-testing, disclosure, and treatment engagement, focusing on participants who were pregnant, had given birth, or had fathered a child. A total of 28 participant interviews were analyzed, including those conducted with nine ALHIV, four family members, and 15 HIV providers. Four adolescent participants were not in care at the time of their interview. Our analysis also included a transcript from a stakeholder meeting involving HIV providers and associated administrators, held to disseminate and garner feedback on, preliminary findings from the original study. Based on our analysis, adolescents frequently reported being alone during testing, experiencing fear and denial on receiving their results, and delaying disclosure to family and linkage to treatment. They also mentioned a lack of contraceptive counseling, with some reporting multiple pregnancies. Providers voiced misgivings and uncertainty about disclosing HIV diagnoses to minor adolescents without a family member present and reported severe shortages of personnel and resources to adequately serve ALHIV in rural clinics. These findings highlight gaps in services that limit adolescent engagement in HIV treatment prior to sexual debut and conceiving a child, and in PMTCT during and after pregnancy. Greater research attention is needed to address ALHIV reproductive health needs, improve linkage to HIV treatment, and prevent onward sexual transmission. Empirical ethics studies of current adolescent disclosure policies are also warranted to examine cultural and developmental appropriateness, and effectiveness in fostering support and engagement in HIV services.

An adapted instrument to assess informed consent comprehension among youth and parents in rural western Kenya: a validation study.

OBJECTIVE: To adapt and validate a questionnaire originally developed in a research setting for assessment of comprehension of consent information in a different cultural and linguistic research setting. DESIGN: The adaptation process involved development and customisation of a questionnaire for each of the three study groups, modelled closely on the previously validated questionnaire. The three adapted draft questionnaires were further reviewed by two bioethicists and the developer of the original questionnaire for face and content validity. The revised questionnaire was subsequently programmed into an audio computerised format, with translations and back translations in three widely spoken languages by the study participants: Luo, Swahili and English. SETTING: The questionnaire was validated among adolescents, their parents and young adults living in Siaya County, a rural region of western Kenya. PARTICIPANTS: Twenty-five-item adapted questionnaires consisting of close-ended, multiple-choice and open-ended questions were administered to 235 participants consisting of 107 adolescents, 92 parents and 36 young adults. Test-retest was conducted 2-4 weeks after first questionnaire administration among 74 adolescents, young adults and parents. OUTCOME MEASURE: Primary outcome measures included ceiling/floor analysis to identify questions with extremes in responses and item-level correlation to determine the test-retest relationships. Given the data format, tetrachoric correlations were conducted for dichotomous items and polychoric correlations for ordinal items. The qualitative validation assessment included face and content validity evaluation of the adapted instrument by technical experts. RESULTS: Ceiling/floor analysis showed eight question items for which >80% of one or more groups responded correctly, while for nine questions, including all seven open-ended questions,<20% responded correctly. Majority of the question items had moderate to strong test-retest correlation estimates indicating temporal stability. CONCLUSIONS: Our study demonstrates that cross-cultural adaptation and validation of an informed consent comprehension questionnaire is feasible. However, further research is needed to develop a tool which can estimate a quantifiable threshold of comprehension thereby serving as an objective indicator of the need for interventions to improve comprehension.

School Support as Structural HIV Prevention for Adolescent Orphans in Western Kenya.

PURPOSE: Using a clustered randomized controlled trial design, we evaluated whether support to keep Kenyan orphaned adolescents in school reduces the risk of HIV infection. METHODS: Participants included 835 orphaned boys and girls in grades 7 and 8 (mean age at the baseline = 15 years) in western Kenya. Primary schools (N = 26) were randomized to the study condition. Intervention participants received school uniforms, payment of tuition when they transitioned into high school, and nurse visits to monitor school absenteeism and provide assistance to stay in school. Annual surveys were conducted from 2011 through 2014, and HIV and herpes simplex virus 2 (HSV-2) biomarker data were collected at the baseline and the end line. Data were analyzed using survey logistic regression or generalized estimating equations controlling for age, gender, and socioeconomic status. RESULTS: Intervention and control groups were equivalent at the baseline and did not differ on new HIV or HSV-2 incidence at the end line. The school support intervention increased school retention but had few HIV-related effects, except increased circumcision among male participants and reduced likelihood of transactional sex. CONCLUSIONS: Despite a strong study design, we found no relative reduction in HIV or HSV-2 infection after 3 years of intervention implementation. New incidence of HIV was lower than expected in this region among youth whose average age at end line was 18 years (range = 14-23). Although support for secondary school promises many benefits for vulnerable youth, our study adds to the growing body of research showing weak evidence for its effectiveness as an HIV prevention.

Experiences along the HIV care continuum: perspectives of Kenyan adolescents and caregivers.

To be effective, HIV programmes should be responsive to the unique needs of diverse groups of infected adolescents. We highlight a range of adolescent perspectives on HIV services, including those who acquired HIV perinatally or sexually and those who were either in care, had dropped out of care, or had never enrolled in care. We conducted semi-structured interviews with 29 adolescents (aged 15-19) and 14 caregivers in western Kenya. Data were analysed using a descriptive analytical approach. Adolescents who were successfully linked had a supportive adult present during diagnosis; tested during hospitalisation or treatment for a recurrent or severe illness; and initiated treatment soon after diagnosis. Barriers to retention included side effects from HIV drugs, pill burden, and limited access to clean water and nutritious food. Support in family, school, and health facility environments was key for diagnosis, linkage, and retention. We make recommendations that may improve adolescent engagement in HIV services.

Process Evaluation of a Clinical Trial to Test School Support as HIV Prevention Among Orphaned Adolescents in Western Kenya.

Orphaned adolescents are a large and vulnerable population in sub-Saharan Africa, at higher risk for HIV than non-orphans. Yet prevention of new infection is critical for adolescents since they are less likely than adults to enter and remain in treatment and are the only age group with rising AIDS death rates. We report process evaluation for a randomized controlled trial (RCT) testing support to stay in school (tuition, uniform, nurse visits) as an HIV prevention strategy for orphaned Kenyan adolescents. The RCT found no intervention effect on HIV/HSV-2 biomarker outcomes. With process evaluation, we examined the extent to which intervention elements were implemented as intended among the intervention group (N = 412) over the 3-year study period (2012-2014), the implementation effects on school enrollment (0-9 terms), and whether more time in school impacted HIV/HSV-2. All analyses examined differences as a whole, and by gender. Findings indicate that school fees and uniforms were fully implemented in 94 and 96% of cases, respectively. On average, participants received 79% of the required nurse visits. Although better implementation of nurse visits predicted more terms in school, a number of terms did not predict the likelihood of HIV/HSV-2 infection. Attending boarding school also increased number of school terms, but reduced the odds of infection for boys only. Four previous RCTs have been conducted in sub-Saharan Africa, and only one found limited evidence of school impact on adolescent HIV/HSV-2 infection. Our findings add further indication that the association between school support and HIV/HSV-2 prevention appears to be weak or under-specified.

The Significance of Benefit Perceptions for the Ethics of HIV Research Involving Adolescents in Kenya.

Assessment of benefits is traditionally regarded as crucial to the ethical evaluation of research involving human participants. We conducted focus group discussions (FGDs) with health and other professionals engaged with adolescents, caregivers/parents, and adolescents in Siaya County, Kenya, to solicit opinions about appropriate ways of conducting HIV research with adolescents. Our data revealed that many focus group participants have a profoundly positive conception of participation in health research, including studies conferring seemingly few benefits. In this article, we identify and analyze five different but interrelated types of benefits as perceived by Kenyan adolescent and adult stakeholders in HIV research, and discuss their ethical significance. Our findings suggest that future empirical and conceptual research should concentrate on factors that may trigger researcher obligations to improve benefit perceptions among research participants.

Influence of school support on early marriage experiences and health services utilization among young orphaned women in Zimbabwe.

School support programs reduce school dropout, early marriage, and early pregnancy for a majority of young orphaned women. We used a mixed-methods approach to examine why these programs are less effective for a significant minority by exploring their influence on marriage and health services utilization. Participants were from a randomized controlled trial testing school support as HIV prevention. Half as many intervention as control participants had been married; married intervention participants had 1 more year of education compared with married control participants. Receiving school support did not appear to improve health-related factors. Pregnancy was among the most common reasons for marriage across both groups. The greatest benefit of school support appears to be in delaying marriage and pregnancy while increasing educational attainment.

'I thought if I marry the prophet I would not die': The significance of religious affiliation on marriage, HIV testing, and reproductive health practices among young married women in Zimbabwe.

This study examines the association between religious affiliation and reasons for marriage, perceived church attitudes, and reproductive health-seeking behaviors, including HIV testing, among young women in eastern rural Zimbabwe. The sample comprised women (N = 35) who had married by 2012 while participating in a larger randomized controlled trial (RCT) to test the effects of school support on HIV-related risk. The RCT sample was identified in 2007 as all female sixth graders in 25 rural eastern Zimbabwe primary schools whose parents, one or both, had died (N = 328). In our previous RCT analyses, we found that participants who affiliated with an Apostolic church were more than four times more likely to marry than those from non-Apostolic churches and that control group participants were twice as likely to marry as those in the intervention group. Other studies had found that marriage greatly increased the odds of HIV infection among adolescent women. Given the link between Apostolic affiliation and marriage, we conducted semi-structured interviews to explore type of marriage, reasons for marrying, church affiliation and attitudes, family planning, HIV testing, schooling, and family life. We were interested in differences, as perceived by our sample of young married women congregants, among Apostolic sects and other denominations in their attitudes about marriage and health-seeking behaviors. We were also interested in the influence of church affiliation on intervention participants' decision to marry, since they had comprehensive school support and education is highly valued in Zimbabwe, but costly and often out of financial reach. Interviews were conducted from October 2012 through November 2013; data were analyzed using a general inductive approach. We found that pressure or perceived deception for coitus or marriage was reported only by intervention participants affiliated with Apostolic denominations. Other reasons for marriage were similar between Apostolic and non-Apostolic adherents, as well as intervention and control conditions. All participants believed HIV testing was important, but while all non-Apostolic denominations encouraged HIV testing and clinic/hospital care, there was considerable heterogeneity in attitudes among Apostolics, with ultraconservative denominations most likely to proscribe non-religious health care. We conclude that some, but not all, Apostolic-affiliated women are afforded discretion in their health-seeking behaviors. Since HIV screening and treatment depend on access to clinic/hospital care, continued public health efforts to engage Apostolic leaders is needed, along with monitoring of progress in access and outcomes.

Marital Age Disparity Among Orphaned Young Women and Their Husbands: A Mixed Methods Study in Rural Zimbabwe.

Our study reports the results from a mixed method study comparing age-similar (AS) marriages of orphaned young women to age disparate (AD) marriages, defined as spousal age difference of 5 or more years. Research in Zimbabwe and sub-Saharan Africa suggests that AD sexual relationships between older men and young women increase the risk for HIV but few studies have examined this association among married couples or explored why young women marry much older men. In this study, a total of 35 orphaned young women aged 17-26 years in rural Zimbabwe participated in semi-structured interviews during 2012-2013. Twenty-four were in AD marriages and 11 AS. All had participated in a 5-year HIV prevention trial, during which they had married and dropped out of school. We examined two research questions: were AD wives more likely than AS to cite economic considerations as a reason to marry, and were AD marriages associated with different health and economic outcomes compared to AS? Our results showed that the reasons the women married were essentially the same among the two groups; economic considerations for marriage were uncommon. Nevertheless, AD wives generally fared somewhat better than AS wives on economic and well-being measures. HIV prevalence was similar; however, the AD group accounted for all five cases of herpes simplex virus-2. Findings suggest the complexity of sexual and reproductive health in rural Africa, where AD marriages are common and accepted. The challenge for primary prevention is to develop strategies to mitigate the risk of sexually transmitted infections, as well as the potential abuse of young women, within the appropriate cultural context.

Educational Outcomes for Orphan Girls in Rural Zimbabwe: Effects of a School Support Intervention.

Educational achievement has important implications for the health and well-being of young women in sub-Saharan Africa. The authors assessed the effects of providing school support on educational outcomes of orphan girls in rural Zimbabwe. Data were from a randomized controlled trial offering the intervention group comprehensive schooling support and controls no treatment initially and then fees only. Results indicated comprehensive support reduced school dropout and absence but did not improve test scores. Providing support to orphan girls is promising for addressing World Health Organization Millennium Development Goals, but further research is needed about contextual factors affecting girls' school participation and learning.

Disclosure of HSV-2 serological test results in the context of an adolescent HIV prevention trial in Kenya.

OBJECTIVES: Herpes simplex virus type 2 (HSV-2) biomarkers are often used in adolescent sub-Saharan HIV prevention studies, but evaluations of test performance and disclosure outcomes are rare in the published literature. Therefore, we investigated the proportion of ELISA-positive and indeterminate samples confirmed by western blot (WB), the psychosocial response to disclosure and whether reports of sexual behaviour and HSV-2 symptoms are consistent with WB confirmatory results among adolescent orphans in Kenya. METHODS: In 2011, 837 Kenyan orphan youth in grades 7 and 8 enrolled in an HIV prevention clinical trial with HSV-2 biomarker outcomes. We used a modified algorithm for the Kalon HSV-2 ELISA to improve specificity; positive and indeterminate results were WB tested. We developed culturally sensitive protocols for disclosing positive results, and documented psychosocial responses, reports of sexual contact and HSV-2 symptoms. RESULTS: 28 adolescents (3.3%) were identified as HSV-2 seropositive, six as indeterminate. Of these, 22 positive and all indeterminates were WB tested; 20 and 5, respectively, were confirmed positive. Most youth reported moderate brief stress after disclosure; 22% reported longer and more severe distress. Boys were more likely to be in the latter category. Self-reported virginity was highly inconsistent with WB-confirmed positives. CONCLUSIONS: The higher than manufacturer's cut-off for Kalon ELISA modestly reduced the rate of false-positive test results, but also increased false negatives. Investigators should consider the risk:benefit ratio in deciding whether or not to disclose HSV-2 results to adolescent participants under specific field conditions. TRIAL REGISTRATION NUMBER: NCT01501864.

Discordance of HIV and HSV-2 biomarkers and self-reported sexual behaviour among orphan adolescents in Western Kenya.

BACKGROUND: This paper examines the discordance between biological data of HIV and herpes simplex virus type 2 (HSV-2) infections and self-reported questionnaire responses among orphan adolescents in Western Kenya. METHODS: In 2011, 837 orphan adolescents from 26 primary schools were enrolled in an HIV prevention trial. At baseline, blood samples were drawn for HIV and HSV-2 infection biomarker testing, and participants completed an audio computer-assisted self-interviewing survey. RESULTS: Comparing biological data with self-reported responses indicated that 70% of HIV-positive (7 out of 10) and 64% of HSV-2-positive (18 out of 28 positive) participants reported never having had sex. Among ever-married adolescents, 65% (57 out of 88) reported never having had sex. Overall, 10% of study participants appeared to have inconsistently reported their sexual behaviour. Logistic regression analyses indicated that lower educational level and exam scores were significant predictors of inconsistent reporting. CONCLUSIONS: Our study demonstrates the discordance between infections measured by biomarkers and self-reports of having had sex among orphan adolescents in Kenya. In order to detect programme effects accurately in prevention research, it is necessary to collect both baseline and endline biological data. Furthermore, it is recommended to triangulate multiple data sources about adolescent participants' self-reported information about marriage and pregnancies from school records and parent/guardians to verify the information. Researchers should recognise potential threats to validity in data and design surveys to consider cognitive factors and/or cultural context to obtain more accurate and reliable information from adolescents regarding HIV/sexually transmitted infection risk behaviours. CLINICAL TRAIL REGISTRATION NUMBER: NCT01501864.

The impact of school subsidies on HIV-related outcomes among adolescent female orphans.

PURPOSE: We examine effects of school support as a structural HIV prevention intervention for adolescent female orphans in Zimbabwe after 5 years. METHODS: Three hundred twenty-eight orphan adolescent girls were followed in a clustered randomized controlled trial from 2007 to 2010. The experimental group received school fees, uniforms, and school supplies and were assigned a school-based "helper." In 2011-2012, the control group received delayed partial treatment of school fees only. At the final data point in 2012, survey, HIV, and Herpes Simplex Virus Type 2 (HSV-2) biomarker data were collected from approximately 88% of the sample. Bivariate and multivariate analyses were conducted on end point outcomes, controlling for age, religious affiliation, and baseline socioeconomic status. RESULTS: The two groups did not differ on HIV or HSV-2 biomarkers. The comprehensive 5-year intervention continued to reduce the likelihood of marriage, improve school retention, improve socioeconomic status (food security), and marginally maintain gains in quality of life, even after providing school fees to the control group. CONCLUSIONS: Paying school fees and expenses resulted in significant improvements in life outcomes for orphan adolescent girls. Biological evidence of HIV infection prevention, however, was not observed. Our study adds to the growing body of research on school support as HIV prevention for girls in sub-Saharan Africa, but as yet, no clear picture of effectiveness has emerged.

A Mixed Methods Mapping of Church versus Secular School Messages to Influence Sexual Decision-Making as Perceived by Zimbabwean Orphan Girl Students.

This study examined the messages perceived by adolescent girls with orphanhood to influence their sexual decision-making. Participants were 125 students (mean age =14.7 years), 54% of whom attended church schools in a rural district of eastern Zimbabwe. We collected and analyzed data using concept mapping, a mixed method approach that enabled the construction of message clusters, with weighting for their relative importance. Messages that clustered under Biblical Teachings and Life Planning ranked highest in salience among students in both church and secular schools. Protecting Family Honor, HIV Prevention, and Social Stigma messages ranked next, respectively. Contrary to study hypotheses, the messages that orphan adolescent girls perceived to influence their sexual decisions did not vary by type of school attended.

Use of HIV and HSV-2 biomarkers in sub-saharan adolescent prevention research: a comparison of two approaches.

Self-report of sexual behavior among adolescents is notoriously inconsistent, yet such measures are commonly used as outcomes for human immunodeficiency virus (HIV) prevention intervention trials. There has been a growing interest in the use of HIV and other sexually transmitted disease biomarkers as more valid measures of intervention impact in high HIV prevalence areas, particularly in sub-Saharan Africa. We examine the challenges, benefits, and feasibility of including HIV and herpes simplex virus type 2 (HSV-2) biomarker data, with details about different data collection and disclosure methods from two adolescent prevention trials in Kenya and Zimbabwe. In Kenya, whole blood samples were collected using venipuncture; adult guardians were present during biomarker procedures and test results were disclosed to participants and their guardians. In contrast, in Zimbabwe, samples were collected using finger pricks for dried blood spots (DBS); guardians were not present during biomarker procedures, and results were not disclosed to participants and/or their guardians. In both countries, prevalence in the study samples was low. Although the standard of care for testing for HIV and other sexually transmitted infections includes disclosure in the presence of a guardian for adolescents under age 18, we conclude that more research about the risks and benefits of disclosure to adolescents in the context of a clinical trial is needed. Notably, current serological diagnosis for HSV-2 has a low positive predictive value when prevalence is low, resulting in an unacceptable proportion of false positives and serious concerns about disclosing test results to adolescents within a trial. We also conclude that the DBS approach is more convenient and efficient than venipuncture for field research, although both approaches are feasible. Manufacturer validation studies using DBS for HSV-2, however, are needed for widespread use.

Mapping structural influences on sex and HIV education in church and secular schools in Zimbabwe.

The authors used state-of-the-art concept mapping approaches to examine structural institutional effects of church and secular high schools on the types of sexual and HIV-prevention education messages transmitted to learners in Zimbabwe. Participants were school teachers (n = 26), school counselors (n = 28), and pastors involved in student pastoral care (n = 14; males = 27, females = 41). They reported on messages perceived to influence sexual decisions of learners in their school setting. The self-report data were clustered into message types using concept mapping and contrasted for consistency of content and structure both between and within type of school. The authors also engaged in curriculum document study with member checks in the participant schools to determine convergence of the evidence on school-type effects of the messages transmitted to students. Church schools prioritized faith-informed sexual and HIV-prevention messages, whereas both types of schools prioritized Life skills education and a future focus. Secular schools prioritized sex and HIV messages in the context of community norms. Facts about HIV and AIDS were relatively underemphasized by church schools. The implicit knowledge values that differentiate types of schools influence learner access to information important for their sexual decisions.

Apostolic faith church organization contexts for health and wellbeing in women and children.

OBJECTIVE: The study explored contexts for health and wellbeing for women and children influenced by the structural behavior of an Apostolic faith church organization in Zimbabwe. METHODS: Twenty-three purposively selected members of an African indigenous Apostolic church (males = 12; females = 11; age range 22-95 years) were informants to a focus group discussion session. They provided data on the institutional behaviors that were culturally-historically embedded in the organization's activities. Data were analyzed thematically and using cultural-historical activity theory (CHAT) to foreground essential themes. RESULTS: The church organization provided social capital to support health and wellbeing in members. However, the culturally embedded practices to minimize decision making by women and child members potentially compromised their health and wellbeing. CONCLUSION: The findings suggest that the structural activities of the church for health and wellbeing could also have the paradoxical effect of exposing women and children to health risks from obligatory roles.

Evaluating Group-Based Interventions When Control Participants Are Ungrouped.

Individually randomized treatments are often administered within a group setting. As a consequence, outcomes for treated individuals may be correlated due to provider effects, common experiences within the group, and/or informal processes of socialization. In contrast, it is often reasonable to regard outcomes for control participants as independent, given that these individuals are not placed into groups. Although this kind of design is common in intervention research, the statistical models applied to evaluate the treatment effects are usually inconsistent with the resulting data structure, potentially leading to biased inferences. This article presents an alternative model that explicitly accounts for the fact that only treated participants are grouped. In addition to providing a useful test of the overall treatment effect, this approach also permits one to formally determine the extent to which treatment effects vary over treatment groups and whether there is evidence that individuals within treatment groups become similar to one another. This strategy is demonstrated with data from the Reconnecting Youth program for high school students at risk of school failure and behavioral disorders.

Program characteristics and organizational factors affecting the implementation of a school-based indicated prevention program.

Reconnecting Youth (RY) is a school-based drug prevention program designed to address academic, substance use and mood management goals among youth at risk of dropping out of high school. This paper presents the organizational factors and RY program characteristics that either promoted or hindered the implementation of the program during a randomized controlled effectiveness trial in 10 schools in two school districts in the United States. Data were collected using surveys and interviews from teachers and school and district staff who participated in the implementation of the RY program in these schools. Results suggest that certain RY program characteristics made it difficult to implement. Small class size, resource-intensive procedures for student selection and recruitment and special training, qualities and skills needed to be an effective RY teacher meant that schools had to significantly change their usual practices to implement the program. Organizational barriers included a lack of financial resources and leadership support for program implementation, and low priority for non-academic courses for high-risk students. Transient student populations, staff turnover and district-wide scheduling and curriculum changes all resulted in high levels of organizational turbulence at most schools, further hindering program implementation.

Crystal methamphetamine use among young adults in the USA.

AIMS: To examine the prevalence and correlates of crystal methamphetamine use among young adults in the USA. DESIGN: Cross-sectional analyses of nationally representative data of young adults from the National Longitudinal Study of Adolescent Health (Add Health). SETTING: In-home interviews conducted in 2001-02. PARTICIPANTS: A total of 14,322 respondents aged 18-26 years. MEASUREMENTS: Past year and 30-day crystal methamphetamine use; crime/violence (ever arrested, past year drug selling, past year violent behavior) and sexual risk behaviors (multiple partners, poor condom use, regretted sex, sex for money). FINDINGS: Prevalence of past year crystal methamphetamine use was 2.8%; past month was 1.3%. White or Native American race, residence in the west or south, having an ever-incarcerated father, marijuana, cocaine, intravenous drug use and high novelty seeking were associated with greater likelihood of past year use in multivariate analyses. Compared to marijuana and cocaine users, crystal methamphetamine users were more likely to be male, unemployed, reside in the west or south, have an ever-incarcerated father and less likely to be black or Hispanic. Frequent users were no different from occasional users, except being more likely to have dropped out of school. Although crystal methamphetamine use was associated with crime and risky sex, controlling for covariates greatly diminished this relationship. CONCLUSIONS: Most users are occasional users, but any past year use is associated with risky and antisocial behaviors, including other illicit drug use. Further research is needed to examine how other drug addiction is associated with methamphetamine use, and to identify longitudinal antecedents for prevention.