Comparison of lung cancer occurring in fibrotic versus non-fibrotic lung on chest CT.

PURPOSE: Evaluate the behavior of lung nodules occurring in areas of pulmonary fibrosis and compare them to pulmonary nodules occurring in the non-fibrotic lung parenchyma. METHODS: This retrospective review of chest CT scans and electronic medical records received expedited IRB approval and a waiver of informed consent. 4500 consecutive patients with a chest CT scan report containing the word fibrosis or a specific type of fibrosis were identified using the system M*Model Catalyst (Maplewood, Minnesota, U.S.). The largest nodule was measured in the longest dimension and re-evaluated, in the same way, on the follow-up exam if multiple time points were available. The nodule doubling time was calculated. If the patient developed cancer, the histologic diagnosis was documented. RESULTS: Six hundred and nine patients were found to have at least one pulmonary nodule on either the first or the second CT scan. 274 of the largest pulmonary nodules were in the fibrotic tissue and 335 were in the non-fibrotic lung parenchyma. Pathology proven cancer was more common in nodules occurring in areas of pulmonary fibrosis compared to nodules occurring in areas of non-fibrotic lung (34% vs 15%, p < 0.01). Adenocarcinoma was the most common cell type in both groups but more frequent in cancers occurring in non-fibrotic tissue. In the non-fibrotic lung, 1 of 126 (0.8%) of nodules measuring 1 to 6 mm were cancer. In contrast, 5 of 49 (10.2%) of nodules in fibrosis measuring 1 to 6 mm represented biopsy-proven cancer (p < 0.01). The doubling time for squamous cell cancer was shorter in the fibrotic lung compared to non-fibrotic lung, however, the difference was not statistically significant (p = 0.24). 15 incident lung nodules on second CT obtained ≤ 18 months after first CT scan was found in fibrotic lung and eight (53%) were diagnosed as cancer. CONCLUSIONS: Nodules occurring in fibrotic lung tissue are more likely to be cancer than nodules in the nonfibrotic lung. Incident pulmonary nodules in pulmonary fibrosis have a high likelihood of being cancer.

Patient and Provider Web-Based Decision Support for Breast Cancer Chemoprevention: A Randomized Controlled Trial.

Significant underutilization of breast cancer chemoprevention remains, despite guidelines stating that physicians should recommend chemoprevention with antiestrogen therapy to high-risk women. We randomized women, ages 35 to 75 years, who met high-risk criteria for breast cancer, without a personal history of breast cancer or prior chemoprevention use, to standard educational materials alone or combined with a web-based decision aid. All healthcare providers, including primary care providers and breast specialists, were given access to a web-based decision support tool. The primary endpoint was chemoprevention uptake at 6 months. Secondary outcomes included decision antecedents (perceived breast cancer risk/worry, chemoprevention knowledge, self-efficacy) and decision quality (decision conflict, chemoprevention informed choice) based upon patient surveys administered at baseline, 1 and 6 months after randomization. Among 282 evaluable high-risk women enrolled from November 2016 to March 2020, mean age was 57 years (SD, 9.9) and mean 5-year invasive breast cancer risk was 2.98% (SD, 1.42). There was no significant difference in chemoprevention uptake at 6 months between the intervention and control groups (2.1% vs. 3.5%). Comparing the intervention and control arms at 1 month, there were significant differences among high-risk women in accurate breast cancer risk perceptions (56% vs. 39%, P = 0.017), adequate chemoprevention knowledge (49% vs. 27%, P < 0.001), mean decision conflict (34.0 vs. 47.0, P < 0.001), and informed choice (41% vs. 23%, P = 0.003). These differences were no longer significant at 6 months. Although our decision support tools did not result in a significant increase in chemoprevention uptake, we did observe improvements in decision antecedents and decision quality measures. PREVENTION RELEVANCE: In this randomized controlled trial of decision support for 300 high-risk women and 50 healthcare providers, we did not observe a significant increase in chemoprevention uptake, which remained low at under 5%. However, these decision support tools may increase knowledge and informed choice about breast cancer chemoprevention.

Associations Between Acculturation and Weight, Diet Quality, and Physical Activity Among Latina Breast Cancer Survivors: The ¡Mi Vida Saludable! Study.

BACKGROUND: Among Latinos, greater acculturation to the United States (US) is associated with risk of obesity and obesity-related comorbidities. Less is known about the associations between acculturation and obesity-related modifiable risk factors, such as diet quality and physical activity (PA) among Latina breast cancer survivors. OBJECTIVE: The aim of this study was to explore associations between acculturation and weight status, diet quality, and PA among Latina breast cancer survivors. DESIGN: This is a cross-sectional secondary analysis of baseline data on demographic and clinical characteristics, acculturation, anthropometric measures, diet quality, and PA collected from Latina breast cancer survivors enrolled in the ¡Mi Vida Saludable! (My Healthy Life) behavioral diet and PA intervention trial. PARTICIPANTS/SETTING: Participants were Latina women (n = 167) residing in New York City, with a medical history of stage 0 to III breast cancer, no evidence of recurrent or metastatic disease, and at least 90 days post cancer treatment who participated in the ¡Mi Vida Saludable! randomized controlled trial between July 2016 and October 2018. MAIN OUTCOME MEASURES: Acculturation status was measured by the Short Acculturation Scale for Hispanics score, language preference, place of birth, and duration of US residence. Weight, height, and waist and hip circumferences were measured at an in-person clinic visit. Diet information was collected via 3 telephone-based 24-hour dietary recalls and PA information was collected via staff administered 7-day recalls. STATISTICAL ANALYSES PERFORMED: Linear regression models examined associations between acculturation and weight status, diet quality, and PA. RESULTS: Based on the Short Acculturation Scale for Hispanics acculturation score, more acculturated compared with less acculturated Latinas were younger in age, more educated, and had higher annual household incomes (all, P < .05). Compared with Spanish-speaking Latinas, English-speaking Latinas had larger waist circumference (103 vs 96.1 cm; P = .01) and poorer-quality diets (Healthy Eating Index 2015 scores, 57.3 vs 71.5; P < .001). Greater levels of acculturation were also associated with higher levels of leisure walking at a moderate-to-vigorous intensity (265.8 vs 179.0 min/wk; P =.04). CONCLUSIONS: Greater levels of acculturation were associated with higher central obesity and poorer-quality diets. Future lifestyle modification trials tailored to the unique role of acculturation on adopting behavior change recommendations is a promising next step in this line of research.

Clinical Utility of Reflex Testing with Cancer Biomarkers to Improve Diagnostic Accuracy of Primary Human Papillomavirus Screening.

BACKGROUND: Human papillomavirus (HPV) testing is the cornerstone of cervical cancer screening, with outstanding sensitivity but only moderate specificity. We evaluated whether reflex testing for cancer biomarkers improves the sensitivity/specificity balance of screening. METHODS: Cervical samples from women in Cape Town, South Africa, ages 30-65 years, were collected and tested with Xpert HPV and with real-time PCR to detect mRNA for cyclin-dependent kinase inhibitor 2A (CDKN2A), topoisomerase 2 alpha (TOP2A), and Ki67 (MKi67). Women with histologically confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+; 85 women without and 166 with HIV) and women with no cervical disease (331 without and 257 with HIV) were included. RESULTS: When used as reflex tests after a positive HPV result, biomarkers discriminated well between women with and without CIN2+. The inclusion of both CDKN2A and MKi67 had the best performance, with area under the curve (AUC) of 0.9171 and 0.8734 in women without and with HIV, respectively. Although excellent, these performance parameters did not improve on an approach utilizing only HPV testing with more stringent cycle threshold cutoffs and HPV genotype selection, which achieved AUC of 0.9059 and 0.8705 in women without and with HIV, respectively. CONCLUSIONS: Biomarkers can be used as triage after positive HPV results but do not outperform an approach utilizing higher viral load cutoffs on selected high-risk genotypes. IMPACT: A screening approach using HPV testing alone can be more easily implemented at the point of care.

¡Mi Vida Saludable! A randomized, controlled, 2 × 2 factorial trial of a diet and physical activity intervention among Latina breast cancer survivors: Study design and methods.

BACKGROUND: Most Latina breast cancer survivors do not meet diet and physical activity (PA) guidelines for cancer survivors and effective lifestyle interventions to adopt and maintain these recommendations are limited, especially among underserved populations. Here we describe the design, methods and enrollment of a 2 × 2 factorial-designed trial testing the separate effects of the ¡Mi Vida Saludable! (My Healthy Life!) intervention program on changes in diet and PA behaviors among Latina breast cancer survivors. METHODS: Latinas with a history of stage 0-III breast cancer, no evidence of recurrent/metastatic disease, and > 90 days post-treatment were primarily identified via cancer registries and physician referral. Participants were randomized to four arms: 1) 4 weeks of in-person group sessions plus 11 months of eHealth communication, 2) in-person group sessions alone, 3) eHealth alone, or 4) control. All participants received a Fitbit to self-monitor PA. Assessments at baseline, 6 and 12 months include diet, PA, anthropometrics, predictors and mediators of behavior change, psychosocial and quality of life outcomes, and blood draw. RESULTS: Of 884 women screened between January 2016 and September 2018, 27% were eligible. Primary reasons for ineligibility included not being willing/able to participate due to work/life responsibilities, health reasons, or transportation. Of 241 eligible women, 167 completed baseline assessment and enrolled. CONCLUSIONS: We successfully enrolled a diverse group of breast cancer survivors representing more than 15 Latin American nationalities to a diet and physical activity trial. If effective, the ¡Mi Vida Saludable! program can be implemented by community groups and medical centers. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02780271, registered May 2016.

Performance of Xpert HPV on Self-collected Vaginal Samples for Cervical Cancer Screening Among Women in South Africa.

OBJECTIVES: Self-sampling may increase access to cervical cancer screening in low-resource settings. Using Xpert HPV, we compared test performance of self- and clinician-collected samples in HIV-positive and HIV-negative women in South Africa. MATERIALS AND METHODS: Three hundred thirty HIV-positive and 375 HIV-negative women in the screening group and 202 HIV-negative and 200 HIV-positive women in the referral group, aged 30-65 years, participated in the study. All women self-collected a vaginal sample, and then, a cervical sample was collected by a clinician (both tested using Xpert HPV), followed by colposcopic examination and collection of histologic specimens. RESULTS: There was good agreement between self- and clinician-collected samples for detection of any high-risk human papillomavirus (HPV, κ = 0.72 [95% CI = 0.669-0.771]). Prevalence of HPV and sensitivity of the test to detect cervical intraepithelial neoplasia 2+ was similar in self- and clinician-collected samples. Specificity was lower in self-collected than in clinician-collected samples in both HIV-negative (self: 77.5% [95% CI = 72.8-81.8] vs clinician: 86.9% [95% CI = 82.9-90.2]) and HIV-positive (self: 44.0% [95% CI = 38.0-50.1] vs clinician: 59.7% [95% CI = 53.6-65.6]) women. Restricting the definition of screen-positive to 3 of 5 channels on HPV Xpert improved specificity in both HIV-negative (self: 83.2% [95% CI = 78.8-87.0] vs clinician: 89.7% [95% CI = 86.1-92.7]) and HIV-positive (self: 54.2% [95% CI = 48.1-60.2] vs clinician: 67.4% [95% CI = 61.5-72.9]) women. CONCLUSIONS: The self-collected sample had good agreement with the clinician-collected sample for the detection of HPV, and restricting the HPV types may improve the specificity in HIV-positive women.

Selecting human papillomavirus genotypes to optimize the performance of screening tests among South African women.

Human papillomavirus (HPV) testing is highly sensitive compared to cytology, with the trade-off of being less specific. We investigated whether select combinations of HPV genotypes, ascertained by Linear Array (LA) and Xpert HPV (GX), can optimize sensitivity/specificity trade-offs to detect high-grade cervical intraepithelial neoplasia (CIN2+). In a study in Cape Town, South Africa, 586 women living without and 535 living with HIV, aged 30-65 years, were recruited. Each woman underwent a pelvic exam to collect cervical samples (tested by LA and GX for 14 high-risk HPV genotypes) and underwent colposcopy with histological sampling to determine CIN2+. In multivariable logistic regression of LA results, only HPV genotypes 16, 18, 31, 33, 35, 52, 58 were significantly associated with CIN2+ (P < .05). Xpert includes these seven types along with HPV 45 within three of the test's five channels and we defined these eight types as restricted genotyping (ie 16, 18, 31, 33, 35, 45, 52, 58). Full genotyping was defined as all 14 high-risk types. Sensitivity estimates for full genotyping using LA were similar to that of restricted genotyping: 83.9% (full) vs 79.0% (restricted) in women without HIV and 93.0% (full) vs 88.9% (restricted) in women living with HIV. Specificity estimates improved for restricted vs full genotyping: 87.4% (full) vs 90.8% (restricted) in women without HIV and 63.7% (full) vs 71.4% (restricted) in women living with HIV. To optimize the performance of HPV testing for cervical cancer screening in high-burden, under-resourced settings like South Africa, only HPV 16, 18, 31, 33, 35, 45, 52, 58 could be included to define screen-positive. We recommend the inclusion of HPV45 for its known link to adenocarcinoma.

Early antiretroviral treatment of infants to attain HIV remission.

BACKGROUND: Studies in adults and children suggested that starting antiretroviral therapy (ART) soon after infection positively influences early events in HIV infection raising the possibility that remission may be achieved in some. METHODS: We designed an analytic treatment interruption (ATI) trial to test the hypothesis that a sizable minority of HIV-infected neonates who initiated ART <14 days of birth and maintained on ART would be able to maintain viral suppression when ART was withdrawn. To yield the target cohort for this trial, 73 HIV-infected neonates identified at one hospital in Johannesburg, South Africa, were initiated on ART <14 days of birth and maintained on ART tracking viral load (VL) decline and immune recovery (clinicaltrials.gov # NCT02431975). FINDINGS: Three HIV-infected infants (4.1%) died and nine (12.3%) were lost to follow-up before 48 weeks of age. Of those surviving on study, 52.5% attained and sustained VL <50 copies/ml and half of these sustained CD4+ T-cell percentage >30% which were the primary entry criteria for the ATI trial. Proportions achieving ATI eligibility criteria were similar in the 46 infants starting ART <48 h (19.6%) to 27 infants starting 2-14 days (25.9%) (p = 0.567). INTERPRETATION: Very early ART on its own, using regimens available when the trial was designed, is insufficient to attain minimum entry criteria needed to justify our trial of ART interruption. Decisions about how quickly to start ART should be based on optimizing standard clinical outcomes rather than with the expectation that remission can be attained. FUNDING: NICHD/NIAID (U01HD080441), South African Research Chairs Initiative of DST and NRF (South Africa).

Clinical evaluation of modifications to a human papillomavirus assay to optimise its utility for cervical cancer screening in low-resource settings: a diagnostic accuracy study.

BACKGROUND: HPV-based screen and treat is the recommended approach for cervical cancer screening in low-resource settings, but quite low specificity of human papillomavirus (HPV) testing, particularly in women living with HIV, leads to overtreatment. We evaluated whether HPV type restriction and more stringent cutoffs on Xpert HPV optimise performance characteristics of this assay for screen and treat. METHODS: We recruited HIV-negative and HIV-positive women aged 30-65 years from a primary care facility and a referral colposcopy clinic in Cape Town, South Africa. Women included had no history of any anogenital cancer or treatment for cervical dysplasia, had no hysterectomy, and were not pregnancy at the time of recruitment. All women had cervical samples collected for Xpert HPV (an assay that detects high-risk HPV types in five channels: HPV type 16; HPV types 18 or 45, or both; HPV types 31, 33, 35, 52, or 58, or more than one of these types; HPV types 51 or 59, or both; and HPV types 39, 56, 66, or 68, or more than one of these types) and underwent colposcopy and histological sampling with consensus pathology review. Logistic regression and receiver operating characteristic curves were used to evaluate improvements in specificity attained by modifying cycle threshold cutoffs to define screen-positive results. RESULTS: We recruited 1121 women aged 30-65 years, 586 of whom were HIV-negative and 535 HIV-positive. Sensitivity of detecting cervical intraepithelial neoplasia grade 2 or greater in HIV-negative women using manufacturer-defined cycle threshold cutoffs for all channels was 88·7% (95% CI 83·1-94·3), and specificity was 86·9% (83·4-90·4). Sensitivity was 93·6% (90·0-97·3) and specificity 59·9% (54·1-65·7) in HIV-positive women. Cycle threshold values from channels detecting HPV type 16, HPV types 18 or 45 (or both), and HPV types 31, 33, 35, 52, or 58 (or more than one of these types) were informative to predict cervical intraepithelial neoplasia grade 2 or greater. Shifting cycle threshold cutoffs on these three channels allowing sensitivity to decline to 75-85%, led to specificities of 91·3-95·3% in HIV-negative women and 77·0-85·8% in HIV-positive women. INTERPRETATION: More stringent cycle threshold cutoffs on selected channels in Xpert HPV improve specificity with only modest losses in sensitivity, making this assay an optimal choice for HPV-based screen and treat in settings with a high prevalence of HIV. These modifications can be made from standard output with no need for new engineering. Decision making about performance characteristics of HPV testing can be shifted to programme implementers and cutoffs selected according to resource availability and community preferences. FUNDING: Supported by the National Cancer Institute UH2/3 CA189908.

Study protocol: Randomized controlled trial of web-based decision support tools for high-risk women and healthcare providers to increase breast cancer chemoprevention.

BACKGROUND: Chemoprevention using selective estrogen receptor modulators and aromatase inhibitors has been shown to reduce invasive breast cancer incidence in high-risk women. Despite this evidence, few high-risk women who are eligible for chemoprevention utilize it as a risk-reducing strategy. Reasons for low uptake include inadequate knowledge about chemoprevention among patients and healthcare providers, concerns about side effects, time constraints during the clinical encounter, and competing comorbidities. METHODS/DESIGN: We describe the study design of a randomized controlled trial examining the effect of two web-based decision support tools on chemoprevention decision antecedents and quality, referral for specialized counseling, and chemoprevention uptake among women at an increased risk for breast cancer. The trial is being conducted at a large, urban medical center. A total of 300 patients and 50 healthcare providers will be recruited and randomized to standard educational materials alone or in combination with the decision support tools. Patient reported outcomes will be assessed at baseline, one and six months after randomization, and after their clinic visit with their healthcare provider. DISCUSSION: We are conducting this trial to provide evidence on how best to support personalized breast cancer risk assessment and informed and shared decision-making for chemoprevention. We propose to integrate the decision support tools into clinical workflow, which can potentially expand quality decision-making and chemoprevention uptake. TRIAL REGISTRATION: NCT03069742.

Sequential tests of promise with discrete time-to-event data.

We introduce a family of sequential test procedures in the context of a futility study design, or as we prefer to call it, a formal test of promise, suitable for use with time-to-event data. The procedures are motivated by an actual trial that was undertaken to test the promise of very early antiretroviral therapy to achieve viral remission in infants with perinatally-acquired HIV. Important gains in efficiency are illustrated in terms of early stopping and statistical power compared with other methods such as Simon's two-stage design with binary outcomes. We show how to calculate the operating characteristics of the proposed sequential tests of promise and provide optimal or near-optimal boundaries for small or medium size samples which provide the typical context for the tests under consideration. The design features discussed in this article are also of immediate pertinence to trials designed to test disease cures which may require treatment interruption and small numbers of participants.

A Trial of Sertraline or Cognitive Behavior Therapy for Depression in Epilepsy.

OBJECTIVE: Limited evidence is available to guide treatment of depression for persons with epilepsy. We evaluated the comparative effectiveness of sertraline and cognitive behavior therapy (CBT) for depression, quality of life, seizures, and adverse treatment effects. METHODS: We randomly assigned 140 adult outpatients with epilepsy and current major depressive disorder to sertraline or weekly CBT for 16 weeks. The primary outcome was remission from depression based on the Mini International Neuropsychiatric Interview (MINI). Secondary outcomes included the Quality of Life in Epilepsy Inventory-89 (QOLIE-89) seizure rates, the Adverse Events Profile (AEP), the Beck Depression Inventory, and MINI Suicide Risk Module. RESULTS: In the intention-to-treat analysis, 38 (52.8%; 95% confidence interval [CI] = ±12) of the 72 subjects assigned to sertraline and 41 (60.3%; 95% CI = ±11.6) of the 68 subjects in the CBT group achieved remission; the lower bound of efficacy for both groups was greater than our historical placebo control group upper bound of 33.7%. Difference in time to remission between groups was 2.8 days (95% CI = ±0.43; p = 0.79). The percent improvement of mean QOLIE-89 scores was significant for both the CBT (25.7%; p < 0.001) and sertraline (28.3%; p < 0.001) groups. The difference in occurrence of generalized tonic-clonic seizures between groups was 0.3% (95% CI = ±8.6; p = 0.95). Suicide risk at final assessment was associated with persistent depression (p < 0.0001) but not seizures or sertraline. INTERPRETATION: Depression remitted in just over one-half of subjects following sertraline or CBT. Despite the complex psychosocial disability associated with epilepsy, improving depression benefits quality of life. Serotonin reuptake inhibition does not appear to increase seizures or suicidality in persons with epilepsy. ANN NEUROL 2019;86:552-560.

Use of Bisphosphonates in Elderly Patients With Newly Diagnosed Multiple Myeloma.

Background: Bisphosphonates reduce skeletal-related events (SREs) in patients with multiple myeloma (MM) and, in some studies, improved survival. Since 2011, bisphosphonate use has been recommended by NCCN for all patients with newly diagnosed MM receiving antineoplastic therapy independent of the presence of bone disease. This study investigated their use after these guidelines were established. Methods: We identified patients aged ≥65 years in the SEER-Medicare database with newly diagnosed MM between January 1, 2012, and December 31, 2013, who received antineoplastic therapy, had ≥6 months of follow-up, and did not receive prior bisphosphonates. Presence of SREs at diagnosis was identified, including pathologic fracture, spinal cord compression, radiation to bone, or surgery to bone. Use of bisphosphonates was defined as having ≥1 claim for an intravenous or oral bisphosphonate within 6 months after the start of antineoplastic therapy. We used multivariable modeling to compare users with nonusers, controlling for demographic and clinical covariates. We compared overall survival between users and nonusers using proportional hazards analysis. Results: Of 1,309 patients identified, 720 (55%) used a bisphosphonate. Factors associated with use included SRE at diagnosis (adjusted odds ratio [AOR], 2.60; 95% CI, 1.98-3.40), hypercalcemia (AOR, 1.74; 95% CI, 1.26-2.41), and use of proteasome inhibitor + immunomodulatory imide therapy (AOR, 1.70; 95% CI, 1.21-2.39). Chronic kidney disease (AOR, 0.48; 95% CI, 0.35-0.66) was associated with decreased use. Bisphosphonate use was associated with reduced mortality (hazard ratio, 0.70; 95% CI, 0.56-0.88). Conclusions: Although bisphosphonate use is recommended for all patients with newly diagnosed MM receiving antineoplastic therapy, 45% of patients in the United States did not receive this guideline-recommended care.

HHLA2 is a novel immune checkpoint protein in pancreatic ductal adenocarcinoma and predicts post-surgical survival.

HHLA2 is a newly identified member of the B7 immune checkpoint family, but its function and crosstalk with immune cells is not fully understood. To gain insights into the HHLA2 expression profile and to determine the clinical significance and function of HHLA2 in pancreatic cancer, we performed immunohistochemistry (IHC) analyses on tissue microarrays (TMAs) of pancreatic ductal adenocarcinoma (PDAC, n = 92) with matched peritumoral tissues as well as in cohorts of precancerous lesions: pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm (IPMN). We found that HHLA2 was rarely detected in normal acinar, islet, and ductal cells but widely expressed from early pancreatic precancerous lesions to invasive PDAC. The overall HHLA2 positivity was 95% (19/20) in low grade PanIN and 70.73% (29/41) in IPMN. HHLA2 expression was detected in 77.17% (71/92) of the PDAC cases and was significantly associated with better prognosis in this cohort. Our findings suggest that HHLA2 may behave as a costimulatory ligand in pancreatic cancer, which differs from other B7 family members that are largely characterized as checkpoint inhibitors. Further investigation of the HHLA2 signaling pathway and its receptors is warranted by our data and may lead to novel therapeutic interventions.

Study protocol: a cluster randomized controlled trial of web-based decision support tools for increasing BRCA1/2 genetic counseling referral in primary care.

BACKGROUND: BRCA1 and BRCA2 mutations confer a substantial breast risk of developing breast cancer to those who carry them. For this reason, the United States Preventative Services Task Force (USPSTF) has recommended that all women be screened in the primary care setting for a family history indicative of a mutation, and women with strong family histories of breast or ovarian cancer be referred to genetic counseling. However, few high-risk women are being routinely screened and fewer are referred to genetic counseling. To address this need we have developed two decision support tools that are integrated into clinical care. METHOD: This study is a cluster randomized controlled trial of high-risk patients and their health care providers. Patient-provider dyads will be randomized to receive either standard education that is supplemented with the patient-facing decision aid, RealRisks, and the provider-facing Breast Cancer Risk Navigation Toolbox (BNAV) or standard education alone. We will assess these tools' effectiveness in promoting genetic counseling uptake and informed and shared decision making about genetic testing. DISCUSSION: If found to be effective, these tools can help integrate genomic risk assessment into primary care and, ultimately, help expand access to risk-appropriate breast cancer prevention options to a broader population of high-risk women. TRIAL REGISTRATION: This trial is retrospectively registered with ClinicalTrials.gov Identifier: NCT03470402 : 20 March 2018.

Substituting Abacavir for Stavudine in Children Who Are Virally Suppressed Without Lipodystrophy: Randomized Clinical Trial in Johannesburg, South Africa.

OBJECTIVES: Abacavir has replaced stavudine in antiretroviral therapy (ART) regimens because it has largely been phased out as a result of toxicity concerns; this loss has reduced further the already-limited drug options for children. Few data regarding virologic and metabolic outcomes among children who undergo substitution of stavudine exist. We evaluated the effects of preemptive substitution of abacavir for stavudine in children initially without lipodystrophy and virally suppressed on a stavudine-containing regimen. METHODS: At Rahima Moosa Mother and Child Hospital in Johannesburg, South Africa, virally suppressed human immunodeficiency virus (HIV)-infected children ≥36 months of age without lipodystrophy were randomly assigned to continue taking stavudine as part of their ART regimen (n = 106) or to have abacavir substituted for stavudine (n = 107). The children were followed for 56 weeks after randomization in the context of a larger trial of treatment options for ART-experienced children. RESULTS: The mean age of the children was 4.3 years, and the mean duration of ART before random assignment was 3.5 years. No differences in virological outcomes, CD4 response, growth, or dyslipidemia were noted between the stavudine and abacavir groups. By 56 weeks, children in the abacavir group had less clinically detected lipodystrophy (4.7% vs 16%, respectively), a higher proportion of leg fat relative to total fat (0.243 vs 0.230, respectively; P = .006), and a lower trunk/leg-skinfold ratio (0.547 vs 0.569, respectively; P = .003) than the children in the stavudine group. CONCLUSION: Substituting abacavir for stavudine did not compromise virological response to treatment and was associated with significantly less lipodystrophy. These results support recommendations that favor abacavir in this population.