Use of a Vaginal Ring Containing Dapivirine for HIV-1 Prevention in Women.

BACKGROUND: Antiretroviral medications that are used as prophylaxis can prevent acquisition of human immunodeficiency virus type 1 (HIV-1) infection. However, in clinical trials among African women, the incidence of HIV-1 infection was not reduced, probably because of low adherence. Longer-acting methods of drug delivery, such as vaginal rings, may simplify use of antiretroviral medications and provide HIV-1 protection. METHODS: We conducted a phase 3, randomized, double-blind, placebo-controlled trial of a monthly vaginal ring containing dapivirine, a non-nucleoside HIV-1 reverse-transcriptase inhibitor, involving women between the ages of 18 and 45 years in Malawi, South Africa, Uganda, and Zimbabwe. RESULTS: Among the 2629 women who were enrolled, 168 HIV-1 infections occurred: 71 in the dapivirine group and 97 in the placebo group (incidence, 3.3 and 4.5 per 100 person-years, respectively). The incidence of HIV-1 infection in the dapivirine group was lower by 27% (95% confidence interval [CI], 1 to 46; P=0.046) than that in the placebo group. In an analysis that excluded data from two sites that had reduced rates of retention and adherence, the incidence of HIV-1 infection in the dapivirine group was lower by 37% (95% CI, 12 to 56; P=0.007) than that in the placebo group. In a post hoc analysis, higher rates of HIV-1 protection were observed among women over the age of 21 years (56%; 95% CI, 31 to 71; P<0.001) but not among those 21 years of age or younger (-27%; 95% CI, -133 to 31; P=0.45), a difference that was correlated with reduced adherence. The rates of adverse medical events and antiretroviral resistance among women who acquired HIV-1 infection were similar in the two groups. CONCLUSIONS: A monthly vaginal ring containing dapivirine reduced the risk of HIV-1 infection among African women, with increased efficacy in subgroups with evidence of increased adherence. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01617096 .).

DELIVER: A Safety Study of a Dapivirine Vaginal Ring and Oral PrEP for the Prevention of HIV During Pregnancy.

BACKGROUND: Pregnancy represents a period of high HIV acquisition risk. Safety data for the monthly dapivirine vaginal ring (DVR) during pregnancy are limited. Here, we report data from the first 2 cohorts of pregnant participants in MTN-042/DELIVER, a phase 3b, randomized, open-label safety trial of DVR and oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC). MTN-042 is being conducted in 3 cohorts beginning with later gestational ages when risks of drug exposure are less. METHODS: Eligible pregnant individuals aged 18-40 years in Malawi, South Africa, Uganda, and Zimbabwe were randomized 2:1 to monthly DVR or daily TDF/FTC. Participants in cohort 1 initiated product use between 36 weeks 0 days (36 0/7 weeks) and 37 6/7 weeks gestation; participants in cohort 2 initiated product use between 30 0/7 and 35 6/7 weeks gestation. All participants continued product use until delivery or 41 6/7 weeks gestation. Pregnancy outcomes and complications were assessed and summarized using descriptive statistics and compared with local background rates obtained through a separate chart review. RESULTS: One-hundred and fifty participants were enrolled into cohort 1 with 101 randomized to DVR and 49 to TDF/FTC. One-hundred and fifty-seven participants were enrolled into cohort 2 with 106 randomized to DVR and 51 to TDF/FTC. In both cohorts, pregnancy complications were rare and similar to local background rates. CONCLUSION: In this first study of a long-acting HIV prevention agent in pregnancy, adverse pregnancy outcomes and complications were uncommon when DVR and TDF/FTC were used in the third trimester of pregnancy, suggesting a favorable safety profile for both prevention products.

How a menu of adherence support strategies facilitated high adherence to HIV prevention products among adolescent girls and young women in sub-Saharan Africa: a mixed methods analysis.

INTRODUCTION: Effective use of pre-exposure prophylaxis (PrEP) has been low among adolescent girls and young women (AGYW) in sub-Saharan Africa. The MTN-034/REACH trial offered AGYW a menu of adherence support strategies and achieved high adherence to both daily oral PrEP and the monthly dapivirine vaginal ring. Understanding how these strategies promoted product use could inform the design of adherence support systems in programmatic settings. METHODS: REACH was a randomized crossover trial evaluating the safety of and adherence to the ring and oral PrEP among 247 HIV-negative AGYW (ages 16-21) in South Africa, Uganda and Zimbabwe from January 2019 to September 2021 (NCT03593655). Adherence support included monthly counselling sessions with drug-level feedback (DLF) plus optional daily short message service (SMS) reminders, weekly phone or SMS check-ins, peer support clubs, "peer buddies" and additional counselling. Counsellors documented adherence support choices and counselling content on standardized forms. Through focus groups, serial in-depth interviews (IDIs) and single IDIs (n = 119 total), we explored participants' experiences with adherence support and how it encouraged product use. RESULTS: Participants received counselling at nearly all visits. DLF was provided at 54.3% of sessions and, across sites, 49%-68% received results showing high adherence for oral PrEP, and 73%-89% for the ring. The most popular support strategies were in-person clubs and weekly calls, followed by online clubs, additional counselling and SMS. Preferences differed across sites but were similar for both products. Qualitative results demonstrated that the REACH strategies supported adherence by providing information about HIV and PrEP, continually motivating participants, and supporting the development of behavioural skills and self-efficacy, aligning with the Information, Motivation, and Behavioural Skills (IMB) model. Effectiveness was supported by three foundational pillars: strong interpersonal relationships with counsellors; ongoing, easily accessible support and resources; and establishing trust in the counsellors and study products through counsellor relationships, peer-to-peer exchange and DLF. CONCLUSIONS: Implementation programmes could support effective PrEP use by offering a small menu of counsellor- and peer-based support options that are youth-friendly and developmentally appropriate. The same menu options can support both ring and oral PrEP users, though content should be tailored to the individual products.

Baseline preferences for oral pre-exposure prophylaxis (PrEP) or dapivirine intravaginal ring for HIV prevention among adolescent girls and young women in South Africa, Uganda and Zimbabwe (MTN-034/IPM-045 study).

INTRODUCTION: Adolescent girls and young women (AGYW) in sub-Saharan Africa are disproportionately affected by the HIV epidemic and face an array of challenges using proven behavioral and biomedical prevention methods. To address the urgent need for expanding prevention options, we evaluated the baseline preferences of HIV prevention methods among participants enrolled in the MTN-034/REACH crossover trial along with their stated product preference prior to product initiation. METHODS: AGYW aged 16-21 years were enrolled at 4 study sites: Cape Town and Johannesburg, South Africa; Kampala, Uganda; and Harare, Zimbabwe and randomly assigned to the sequence of using oral PrEP and the dapivirine ring for 6 months each, followed by a choice period in which they could choose either product (or neither) for an additional six months. Eligible AGYW were HIV-negative, not pregnant and using effective contraception for at least two months prior to enrollment. Descriptive statistics were used to summarize demographic and behavioral data while multinomial analysis was used to determine predictors of stated product preference (ring or oral PrEP). RESULTS: Of the 247 AGYW enrolled in REACH, 34% were aged 16-17 and 89% had a primary partner.The median age of sexual debut was 16 years and 40% had ever been pregnant. At screening, 35% of participants were diagnosed with a sexually transmitted infection (STI), 39% had an AUDIT-C score associated with harmful drinking and 11% reported intimate partner violence in the past 6 months. Overall, 28% of participants, had CESD-10 scores suggestive of depressive symptoms (≥12) in the past week. At baseline, similar proportions stated a preference for the ring and oral PrEP (38.1% and 40.5% respectively), with 19% of participants stating they preferred both products equally. Only study site was significantly associated with product preference (P<0.05) with AGYW from Johannesburg having higher odds of preferring the ring and those from Kampala having higher odds of preferring both options equally. CONCLUSIONS: We successfully enrolled African AGYW with a clear unmet need for HIV prevention. The balanced preference between the two products suggests that multiple biomedical prevention options may be appealing to this age group and could address their prevention needs.

Patterns of distress in US medical students.

BACKGROUND: How multiple forms of psychological distress coexist in individual medical students has not been formally studied. AIM: To explore the prevalence of various forms of distress in medical students and their relationship to recent suicidal ideation or serious thoughts of dropping out of school. METHODS: All medical students at seven US schools were surveyed with standardized instruments to evaluate burnout, depression, stress, mental quality of life (QOL), physical QOL, and fatigue. Additional items explored recent suicidal ideation and serious thoughts of dropping out of medical school. RESULTS: Nearly all (1846/2246, 82%) of medical students had at least one form of distress with 1066 (58%) having ≥3 forms of distress. A dose-response relationship was found between the number of manifestations of distress and recent suicidal ideation or serious thoughts of dropping out. For example, students with 2, 4, or 6 forms of distress were 5, 15, and 24 fold, respectively, more likely to have suicidal ideation than students with no forms of distress assessed. All forms of distress were independently associated with suicidal ideation or serious thoughts of dropping out on multivariable analysis. CONCLUSIONS: Most medical students experience ≥1 manifestation of distress with many experiencing multiple forms of distress simultaneously. The more forms of distress experienced the greater the risk for suicidal ideation and thoughts of dropping out of medical school.

HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial.

INTRODUCTION: A potential concern with the use of dapivirine (DPV) for HIV prevention is the selection of a drug-resistant virus that could spread and reduce the effectiveness of non-nucleoside reverse transcriptase (NNRTI)-based first-line antiretroviral therapy. We evaluated HIV-1 seroconversions in MTN-020/ASPIRE for selection of drug resistance and evaluated the genetic basis for observed reductions in susceptibility to DPV. METHODS: MTN-020/ASPIRE was a placebo-controlled, Phase III safety and effectiveness study of DPV ring for HIV-1 prevention conducted at 15 sites in South Africa, Zimbabwe, Malawi and Uganda between 2012 and 2015. Plasma from individuals who seroconverted in ASPIRE was analysed for HIV-1 drug resistance using both population Sanger sequencing and next-generation sequencing (NGS) with unique molecular identifiers to report mutations at ≥1% frequency. DPV susceptibility of plasma-derived recombinant HIV-1 containing bulk-cloned full-length reverse transcriptase sequences from MTN-020/ASPIRE seroconversions was determined in TZM-bl cells. Statistical significance was calculated using the Fisher's exact test. RESULTS: Plasma from all 168 HIV seroconversions were successfully tested by Sanger sequencing; 57 of 71 DPV arm and 82 of 97 placebo (PLB) arm participants had NGS results at 1% sensitivity. Overall, 18/168 (11%) had NNRTI mutations including K101E, K103N/S, V106M, V108I, E138A/G, V179D/I/T and H221Y. Five samples from both arms had low-frequency NNRTI mutations that were not detected by Sanger sequencing. The frequency of NNRTI mutations from the DPV arm (11%) was not different from the PLB arm (10%; p = 0.80). The E138A mutation was detected in both the DPV (3 of 71 [4.2%]) and PLB arm (5 of 97 [5.2%]) and conferred modest reductions in DPV susceptibility in some reverse transcriptase backgrounds but not others. CONCLUSIONS: HIV-1 drug resistance including NNRTI resistance did not differ between the DPV and placebo arms of the MTN-020/ASPIRE study, indicating that drug resistance was not preferentially acquired or selected by the DPV ring and that the preventive benefit of DPV ring outweighs resistance risk.

Safety, uptake, and use of a dapivirine vaginal ring for HIV-1 prevention in African women (HOPE): an open-label, extension study.

BACKGROUND: Two phase 3 clinical trials showed that use of a monthly vaginal ring containing 25 mg dapivirine was well tolerated and reduced HIV-1 incidence in women by approximately 30% compared with placebo. We aimed to evaluate use and safety of the dapivirine vaginal ring (DVR) in open-label settings with high background rates of HIV-1 infection, an important step for future implementation. METHODS: We did a phase 3B open-label extension trial of the DVR (MTN-025/HIV Open-label Prevention Extension [HOPE]). Women who were HIV-1-negative and had participated in the MTN-020/ASPIRE phase 3 trial were offered 12 months of access to the DVR at 14 clinical research centres in Malawi, South Africa, Uganda, and Zimbabwe. At each visit (monthly for 3 months, then once every 3 months), women chose whether or not to accept the offer of the ring. Used, returned rings were tested for residual amounts of dapivirine as a surrogate marker for adherence. HIV-1 serological testing was done at each visit. Dapivirine amounts in returned rings and HIV-1 incidence were compared with data from the ASPIRE trial, and safety was assessed. This study is registered with ClinicalTrials.gov, NCT02858037. FINDINGS: Between July 16, 2016, and Oct 10, 2018, of 1756 women assessed for eligibility, 1456 were enrolled and participated in the study. Median age was 31 years (IQR 27-37). At baseline, 1342 (92·2%) women chose to take the DVR; ring acceptance was more than 79% at each visit up until 12 months and 936 (73·2%) of 1279 chose to take the ring at all visits. 12 530 (89·3%) of 14 034 returned rings had residual dapivirine amounts consistent with some use during the previous month (>0·9 mg released) and the mean dapivirine amount released was greater than in the ASPIRE trial (by 0·21 mg; p<0·0001). HIV-1 incidence was 2·7 per 100 person-years (95% CI 1·9-3·8, 35 infections), compared with an expected incidence of 4·4 per 100 person-years (3·2-5·8) among a population matched on age, site, and presence of a sexually transmitted infection from the placebo group of ASPIRE. No serious adverse events or grade 3 or higher adverse events observed were assessed as related to the DVR. INTERPRETATION: High uptake and persistent use in this open-label extension study support the DVR as an HIV-1 prevention option for women. With an increasing number of HIV-1 prophylaxis choices on the horizon, these results suggest that the DVR will be an acceptable and practical option for women in Africa. FUNDING: The Microbicide Trials Network and the National Institute of Allergy and Infectious Diseases, The Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of Mental Health, all components of the US National Institutes of Health.

Gabapentin for the management of hot flashes in prostate cancer survivors: a longitudinal continuation Study-NCCTG Trial N00CB.

Hot flashes are a complication of androgen deprivation therapy for prostate cancer. A phase III study showed that use of low-dose gabapentin was well tolerated and moderately decreased the frequency of hot flashes due to androgen deprivation therapy when taken for 4 weeks. The current study, an open-label continuation of the randomized study, examined the efficacy and toxicity of gabapentin when taken for (an additional) 8 weeks. Patients were allowed to start, or continue, gabapentin and to titrate the dose to maximum efficacy, up to 900 mg/d. They were asked to complete a hot flash diary daily and keep weekly logs of toxicity, satisfaction with hot flash control, and quality of life. The moderate reduction in hot flash frequency and severity in the randomized phase of the study appeared to be maintained during this continuation phase. Men originally receiving the placebo or lowest dose of gabapentin (300 mg/d) had improved hot flash control relative to that at the end of the randomized phase. Minimal adverse effects were reported. These findings suggest that low-dose gabapentin is moderately efficacious for at least 12 weeks of hot flash treatment in men undergoing androgen deprivation therapy for prostate cancer and seems to be well tolerated. (NCT00028572)

Factors associated with resilience to and recovery from burnout: a prospective, multi-institutional study of US medical students.

CONTEXT: Burnout is prevalent among medical students and is a predictor of subsequent serious consideration of dropping out of medical school and suicide ideation. Understanding of the factors that protect against burnout is needed to guide student wellness programmes. METHODS: A total of 1321 medical students attending five institutions were studied longitudinally (2006-2007). The surveys included standardised instruments to evaluate burnout, quality of life, fatigue and stress. Additional items explored social support, learning climate, life events, employment status and demographics. Students who did not have burnout at either time-point (resilient students) were compared with those who indicated burnout at one or both time-points (vulnerable students) using a Wilcoxon-Mann-Whitney test or Fisher's exact test. Similarly, the differences between those who recovered and those who were chronically burned out were also compared in students with burnout at the first time-point. Logistic regression modelling was employed to evaluate associations between the independent variables and resiliency to and recovery from burnout. RESULTS: Overall, 792 (60.0%) students completed the burnout inventory at both time-points. No differences in demographic characteristics were observed between resilient (290/792 [36.6%]) and vulnerable (502/792 [63.4%]) students. Resilient students were less likely to experience depression, had a higher quality of life, were less likely to be employed, had experienced fewer stressful life events, reported higher levels of social support, perceived their learning climate more positively and experienced less stress and fatigue (all p < 0.05) than vulnerable students. On multivariable analysis, perceiving student education as a priority for faculty staff, experiencing less stress, not being employed and being a minority were factors independently associated with recovery from burnout. CONCLUSIONS: Modifiable individual factors and learning climate characteristics including employment status, stress level and perceptions of the prioritising of student education by faculty members relate to medical students' vulnerability to burnout.

Development and preliminary psychometric properties of a well-being index for medical students.

BACKGROUND: Psychological distress is common among medical students but manifests in a variety of forms. Currently, no brief, practical tool exists to simultaneously evaluate these domains of distress among medical students. The authors describe the development of a subject-reported assessment (Medical Student Well-Being Index, MSWBI) intended to screen for medical student distress across a variety of domains and examine its preliminary psychometric properties. METHODS: Relevant domains of distress were identified, items generated, and a screening instrument formed using a process of literature review, nominal group technique, input from deans and medical students, and correlation analysis from previously administered assessments. Eleven experts judged the clarity, relevance, and representativeness of the items. A Content Validity Index (CVI) was calculated. Interrater agreement was assessed using pair-wise percent agreement adjusted for chance agreement. Data from 2248 medical students who completed the MSWBI along with validated full-length instruments assessing domains of interest was used to calculate reliability and explore internal structure validity. RESULTS: Burnout (emotional exhaustion and depersonalization), depression, mental quality of life (QOL), physical QOL, stress, and fatigue were domains identified for inclusion in the MSWBI. Six of 7 items received item CVI-relevance and CVI-representativeness of >or=0.82. Overall scale CVI-relevance and CVI-representativeness was 0.94 and 0.91. Overall pair-wise percent agreement between raters was >or=85% for clarity, relevance, and representativeness. Cronbach's alpha was 0.68. Item by item percent pair-wise agreements and Phi were low, suggesting little overlap between items. The majority of MSWBI items had a >or=74% sensitivity and specificity for detecting distress within the intended domain. CONCLUSIONS: The results of this study provide evidence of reliability and content-related validity of the MSWBI. Further research is needed to assess remaining psychometric properties and establish scores for which intervention is warranted.

Brief Report: Phase IIa Safety Study of a Vaginal Ring Containing Dapivirine in Adolescent Young Women.

BACKGROUND: Young women aged 15-24 years are disproportionately affected by the HIV epidemic. Two phase III trials of a vaginal ring containing 25-mg dapivirine demonstrated HIV-1 risk reduction in adult women older than 21 years but not in those aged 18-21 years. Lack of protection was correlated with low adherence. METHODS: In this phase-IIa, randomized, double-blind, placebo-controlled, US, multicenter trial of the dapivirine ring in sexually active females, aged 15-17 years, participants were randomized 3:1 to a dapivirine or placebo ring to be inserted monthly for 6 months (NCT02028338). Primary safety end points included grade 2 product related adverse events and any grade 3 and higher adverse events. Adherence to ring use was assessed by plasma dapivirine concentrations, residual levels in used rings, and self-report. A plasma dapivirine concentration of >95 pg/mL was used to define short-term adherence; a residual ring level of <23.5 mg was used to define long-term adherence. Acceptability was assessed through computer-assisted self-interviews. RESULTS: Ninety-six participants were enrolled across 6 US sites. The median age was 16.0 years. There were no differences in safety outcomes between treatment arms. Adherence to the dapivirine ring was demonstrated by both plasma measurements (87%) and residual drug levels in rings (95%). Forty-two percent (95% confidence interval: 32 to 52) of participants reported that they never removed the ring. Participants noted no discomfort due to the ring at 87% of visits and "liking" the ring at 93% of visits. CONCLUSION: The dapivirine vaginal ring, a promising topical microbicide, was well tolerated and acceptable in young US adolescents.

The learning environment and medical student burnout: a multicentre study.

OBJECTIVES: Little is known about specific personal and professional factors influencing student distress. The authors conducted a comprehensive assessment of how learning environment, clinical rotation factors, workload, demographics and personal life events relate to student burnout. METHODS: All medical students (n = 3080) at five medical schools were surveyed in the spring of 2006 using a validated instrument to assess burnout. Students were also asked about the aforementioned factors. RESULTS: A total of 1701 medical students (response rate 55%) completed the survey. Learning climate factors were associated with student burnout on univariate analysis (odds ratio [OR] 1.36-2.07; all P < or = 0.02). Being on a hospital ward rotation or a rotation requiring overnight call was also associated with burnout (ORs 1.69 and 1.48, respectively; both P < or = 0.02). Other workload characteristics (e.g. number of admissions) had no relation to student burnout. Students who experienced a positive personal life event had a lower frequency of burnout (OR 0.70; P < or = 0.02), whereas those who experienced negative personal life events did not have a higher frequency of burnout than students who did not experience a negative personal life event. On multivariate analysis personal characteristics, learning environment and personal life events were all independently related to student burnout. CONCLUSIONS: Although a complex array of personal and professional factors influence student well-being, student satisfaction with specific characteristics of the learning environment appears to be a critical factor. Studies determining how to create a learning environment that cultivates student well-being are needed.

Burnout and suicidal ideation among U.S. medical students.

BACKGROUND: Little is known about the prevalence of suicidal ideation among U.S. medical students or how it relates to burnout. OBJECTIVE: To assess the frequency of suicidal ideation among medical students and explore its relationship with burnout. DESIGN: Cross-sectional 2007 and longitudinal 2006 to 2007 cohort study. SETTING: 7 medical schools in the United States. PARTICIPANTS: 4287 medical students at 7 medical schools, with students at 5 institutions studied longitudinally. MEASUREMENTS: Prevalence of suicidal ideation in the past year and its relationship to burnout, demographic characteristics, and quality of life. RESULTS: Burnout was reported by 49.6% (95% CI, 47.5% to 51.8%) of students, and 11.2% (CI, 9.9% to 12.6%) reported suicidal ideation within the past year. In a sensitivity analysis that assumed all nonresponders did not have suicidal ideation, the prevalence of suicidal ideation in the past 12 months would be 5.8%. In the longitudinal cohort, burnout (P < 0.001 for all domains), quality of life (P < 0.002 for each domain), and depressive symptoms (P < 0.001) at baseline predicted suicidal ideation over the following year. In multivariable analysis, burnout and low mental quality of life at baseline were independent predictors of suicidal ideation over the following year. Of the 370 students who met criteria for burnout in 2006, 99 (26.8%) recovered. Recovery from burnout was associated with markedly less suicidal ideation, which suggests that recovery from burnout decreased suicide risk. LIMITATION: Although response rates (52% for the cross-sectional study and 65% for the longitudinal cohort study) are typical of physician surveys, nonresponse by some students reduces the precision of the estimated frequency of suicidal ideation and burnout. CONCLUSION: Approximately 50% of students experience burnout and 10% experience suicidal ideation during medical school. Burnout seems to be associated with increased likelihood of subsequent suicidal ideation, whereas recovery from burnout is associated with less suicidal ideation.

Contraceptive method switching among women living in sub-Saharan Africa participating in an HIV-1 prevention trial: a prospective cohort study.

OBJECTIVE: Long-acting reversible contraceptive (LARC) method uptake has been low within the context of HIV prevention trials. Within a multinational study (MTN-020/ASPIRE), the Contraceptive Action Team improved LARC accessibility and uptake. In this secondary analysis, we determined the rate of contraceptive method continuation among the women enrolled. STUDY DESIGN: ASPIRE was a randomized, double-blinded, placebo-controlled phase III safety and effectiveness study of the Dapivirine Vaginal Ring for HIV-1 prevention. Between 2012 and 2014, sexually active women aged 18-45 from Malawi, South Africa, Uganda and Zimbabwe were enrolled. All participants were required to use contraception for enrollment to the study and could choose between all highly effective contraceptive methods available in their respective countries. Women were seen monthly and could change methods at any time. Continuation rates from study enrollment to 6 and 12 months were determined. RESULTS: The overall contraceptive method continuation rate was 77% (1972/2551) at 6 months and 66% (1694/2551) at 12 months. The 6- and 12-month continuation rates were highest for implantable contraceptives (89%, 82%) followed by copper intrauterine device (83%, 77%). Rates of continuation for injectable contraceptives depot medroxyprogesterone acetate (80%, 69%) and norethisterone enanthate (71%, 54%) were higher than for oral contraceptives, which were continued at 47% at 6 months and 35% at 12 months. The continuation rates of all methods did not differ by users with and without previous contraceptive experience. CONCLUSIONS: LARC methods have the highest rates of continuation at 12 months and should be routinely offered in the context of HIV prevention trials in sub-Saharan Africa. IMPLICATIONS: Intrauterine devices and contraceptive implant continuation was high at 12 months among women participating in an HIV prevention trial in sub-Saharan Africa and LARCs and should be routinely offered.

Efficacy of a brief screening tool to identify medical students in distress.

PURPOSE: To determine whether the Medical Student Well-Being Index (MSWBI) can serve as a brief assessment tool to identify medical students in severe psychological distress. METHOD: The authors used data from 2,248 medical students at seven U.S. medical schools who responded to a 2007 survey to explore the accuracy of the MSWBI in identifying medical students with three outcomes: low mental quality of life (QOL; defined by having a Medical Outcomes Study Short-Form Health Survey mental component summary score ≥1/2 standard deviation below that of the age- and gender-matched population norm), suicidal ideation, or serious thoughts of dropping out. The authors confirmed their analyses using data from a separate sample of 2,682 students evaluated in 2009. RESULTS: Students with low mental QOL, suicidal ideation, or serious thoughts of dropping out were more likely to endorse each individual MSWBI item and a greater number of total items than were students without such distress (all P < .001). The likelihood ratio for low mental QOL among students with MSWBI scores <4 was 0.47 as compared with 4.79 for those with scores ≥4. At an MSWBI threshold score of ≥4, the MSWBI's sensitivity and specificity for identifying students with low mental QOL or recent suicidal ideation/serious thoughts of dropping out were both ≥90%. On multivariable logistic regression, all MSWBI items were independently associated with at least one outcome. CONCLUSIONS: The MSWBI is a useful brief screening tool to help identify students with severe distress.

A pessimistic explanatory style is prognostic for poor lung cancer survival.

BACKGROUND: Several studies have demonstrated the importance of personality constructs on health behaviors and health status. Having a pessimistic outlook has been related to negative health behaviors and higher mortality. However, the construct has not been well explored in cancer populations. METHODS: Survival time of 534 adults who were diagnosed with lung cancer was examined. The patients had completed the Minnesota Multiphasic Personality Inventory approximately 18.2 years before receiving their lung cancer diagnosis. Minnesota Multiphasic Personality Inventory Optimism-Pessimism scores were divided into high (60 or more) and low scores (<60), and log-rank tests and Kaplan-Meier curves were used to determine survival differences. Multivariate Cox models were used for assessing prognostic values of pessimism along with other known predictors for lung cancer survival outcome. Bootstrapping of the survival models was used as a sensitivity analysis. RESULTS: At the time of lung cancer diagnosis, patients were at an average age of 67 years old; 48% of them were women, 85% had non-small cell lung cancer, 15% had small cell lung cancer, 30% were stage I, 4% were stage II, 31% were stage III/limited, and 35% were stage IV/extensive. Patients who exhibited a nonpessimistic explanatory style survived approximately 6 months longer than patients classified as having a pessimistic explanatory style. CONCLUSION: Among lung cancer patients, those having a pessimistic explanatory style experienced a less favorable survival outcome, which may be related to cancer treatment decisions. Further research in this area is warranted.

Burnout and serious thoughts of dropping out of medical school: a multi-institutional study.

PURPOSE: Little is known about students who seriously consider dropping out of medical school. The authors assessed the severity of thoughts of dropping out and explored the relationship of such thoughts with burnout and other indicators of distress. METHOD: The authors surveyed medical students attending five medical schools in 2006 and 2007 (prospective cohort) and included two additional medical schools in 2007 (cross-sectional cohort). The survey included questions about thoughts of dropping out, life events in the previous 12 months, and validated instruments evaluating burnout, depression symptoms, and quality of life (QOL). RESULTS: Data were provided by 858 (65%) students in the prospective cohort and 2,248 (52%) in the cross-sectional cohort. Of 2,222 respondents, 243 (11%) indicated having serious thoughts of dropping out within the last year. Burnout (P < .0001), QOL (P < .003 each domain), and depressive symptoms (P < .0001) at baseline predicted serious thoughts of dropping out during the following year. Each one-point increase in emotional exhaustion and depersonalization score and one-point decrease in personal accomplishment score at baseline was associated with a 7% increase in the odds of serious thoughts of dropping out during the following year. On subsequent confirmatory multivariable analysis, low scores for personal accomplishment, lower mental and physical QOL, and having children were independent predictors of students having serious thoughts of dropping out during the following year. CONCLUSIONS: Approximately 11% of students have serious thoughts of dropping out of medical school each year. Burnout seems to be associated with increased likelihood of serious thoughts of dropping out.