Tau misprocessing to form aggregates and other toxic species has emerged as a major feature in our developing understanding of the etiology and pathogenesis of Alzheimer's Disease (AD). The significance of tau misprocessing in AD has been further emphasized by recent studies showing that tau can be secreted from neurons via exosomes and may itself be an important agent in the spreading of neurofibrillary lesions within the brain. Tau secretion occurs most readily under disease-associated conditions in cellular models, suggesting that cellular changes responsible for secretion, possibly including tau oligomerization, could play a key role in the propagation of neurofibrillary lesions in neurodegenerative disease. Here we show that overexpression of 4R0N human tau in neuroblastoma cells recruits mitochondrial and axonogenesis-associated proteins relevant to neurodegeneration into the exosomal secretion pathway via distinct mechanisms. The recruitment of mitochondrial proteins appears to be linked to autophagy disruption (exophagy) in multiple neurodegenerative conditions but but has few known direct links to AD and tau. By contrast, the involvement of synaptic plasticity and axonogenesis markers is highly specific to both tau and AD and may be relevant to the reactivation of developmental programs involving tau in AD and the recently demonstrated ability of secreted tau to establish tissue distribution gradients in CNS neuropil. We also found a highly significant correlation between genes that are significantly downregulated in multiple forms of AD and proteins that have been recruited to exosomes by tau, which we interpret as strong evidence for the central involvement of tau secretion in AD cytopathogenesis. Our results suggest that multiple cellular mechanisms may link tau secretion to both toxicity and and neurofibrillary lesion spreading in Alzheimer's disease and other tauopathies.

Background. The early integration of supportive care in oncology improves patient-centered outcomes. However, data is lacking regarding how to achieve this in resourcelimited settings. We studied whether patient navigation increased access to multidisciplinary supportive care among Mexican patients with advanced cancer. Materials and Methods. This randomized controlled trial was conducted between 08/17 and 04/2018 at a public hospital in Mexico City. Patients aged ≥18 with metastatic tumors ≤six weeks from diagnosis were randomized (1:1) to a patient navigation intervention or usual care. Patients randomized to patient navigation received personalized supportive care from a navigator and a multidisciplinary team. Patients randomized to usual care obtained supportive care referrals from treating oncologists. The primary outcome was the implementation of supportive care interventions at 12 weeks. Secondary outcomes included advance directive completion, supportive care needs, and quality of life. Results. 134 patients were randomized: 67 to patient navigation and 67 to usual care. Supportive care interventions were provided to 74% of patients in the patient navigation arm vs. 24% in usual care (difference 0.50, 95% CI 0.34-0.62; p<0.0001). In the patient navigation arm, 48% of eligible patients completed advance directives, compared to 0% in usual care (p<0.0001). At 12 weeks, patients randomized to patient navigation had less moderate/severe pain (10 vs. 33%; difference 0.23, 95% CI 0.07-0.38; p = 0.006), without differences in quality of life between arms. Conclusions and Relevance. Patient navigation improves access to early supportive care, advance care planning, and pain for patients with advanced cancer in resource-limited settings. The Oncologist 2020;9999:• •

OBJECTIVE: To describe a pilot implementation of couple’s human immunodeficiency virus (HIV) testing and counseling in an antenatal care clinic in the United States. METHODS: We used a cross-sectional study design. Couples were recruited from an antenatal care clinic of a large, urban, tertiary medical center, and were eligible if both partners agreed to receive HIV test results together and reported no coercion to participate in testing and counseling and no intimate partner violence. We assessed relationship characteristics, HIV risk-related behaviors and concordance of couples' sexual agreement (ie, mutual agreement about sexual risk behaviors that are permissible within or outside of their relationship). Acceptability of couple’s HIV testing and counseling (ie, format, quality of the sessions, ability to meet their needs) was assessed after completing the session. Barriers and facilitators to couple’s HIV testing and counseling were assessed at the individual-level among decliners and participants and at the clinic-level among members of the care team. RESULTS: Dyadic data were collected from 82 individuals (41 couples). Most partners (n=56, 68%) did not have a sexual agreement or had differing expectations about their sexual agreement. Partners with a concordant sexual agreement (n=26) felt more confident working with their partners on condom use when having sex outside of their relationship (P=.008) and were more likely to agree with their partner to get tested regularly for HIV or sexually transmitted infections (P=.015). Acceptability was high, with a rating of 93 or more (out of 100) among all items. Individual-level barriers to couple’s HIV testing and counseling included difficulty bringing the male partner for counseling and a perception by either member of the couple that they were at low-risk for HIV. At the clinic level, need for training, staff turnover, and integration of couple’s HIV testing and counseling in the clinic flow presented as barriers, whereas commitment by the clinic leadership facilitated the couple’s HIV testing and counseling program. CONCLUSION: Despite barriers, couple’s HIV testing and counseling can be implemented in antenatal clinics and is a highly acceptable method of HIV testing.

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PURPOSE As access to cancer care expands in low-income countries, developing tools to educate patients is paramount. We took a picture booklet, which was initially developed by the nonprofit Global Oncology for Malawi and Rwanda, and adapted it for use in Nigeria. The primary goal was to assess acceptability and provide education. The secondary goals were (1) to describe the collaboration, (2) to assess knowledge gained from the intervention, (3) to assess patient understanding of their therapy intent, and (4) to explore patient's experiences via qualitative analysis. METHODS We piloted the original English booklet at a single site and requested feedback from patients and providers. The booklet was updated; translated into Hausa, Yoruba, Igbo, and Pidgin English; and used at three additional sites. For the three-site cohort, we collected basic demographics, pretest and post-test assessing content in the booklet, and performed a qualitative analysis. RESULTS The original booklet was widely acceptable and recommended by patients at site one (n = 31) and by providers (N = 26) representing all four sites. In the three-site cohort (n = 103), 94% of patients recommended the booklet. An immediate post-test focusing on when patients should present to care showed a statistically significant improvement in one of the seven questions. Fifty-one percent of the patients (n = 103) knew their treatment intent (curative v palliative). Qualitative analysis highlighted that the patient's thoughts on cancer are dominated by negative associations, although curability and modern therapy are also frequently cited. CONCLUSION We adapted an educational booklet to a novel context and had it delivered by local partners. The booklet was widely recommended to future patients. The booklet had an impact on patient's knowledge of cancer treatment, potentially allowing for decreased abandonment.

e18577 Background: In Nigeria, cervical cancer is the second most common cancer in part due to disparities in education, access to screening, and access to treatment. In Nigeria, the HPV vaccine is planned for introduction into the public sector but will not be mandated. Given the preventable nature of the disease and need for public awareness, we developed an easy-to-understand teaching tool, the Global Oncology (GO) Comic Book focused on both general cancer education and about cervical cancer and HPV vaccination. Methods: The GO Comic Book is set in modern-day Lagos, Nigeria and aims to dispel myths and misconceptions associated with cancer in general and cervical cancer in particular. After developing the comic book, we developed a teaching guide and a plan for a pilot distribution of the comic book to students in Nigeria. In late 2019, GO and programmatic partners including the Clinton Health Access Initiative (CHAI), Cancer Education and Advocacy Foundation of Nigeria (CEAFON) and Panaramic Comics (based in Lagos, Nigeria) successfully conducted a pilot distribution of the GO Comic Book to nearly 5,000 students representing 18 junior secondary schools in Lagos and Rivers states. The comic books were distributed as part of 12 school assemblies which featured interactive, live-readings of the comic book by students and Nigerian physician volunteers. Pre-/post-tests with 9 questions were administered to a subset of the students (N = 202) to assess change in knowledge before and after the educational assemblies and data was analyzed using descriptive statistics. Results: The response rate of the 202 administered surveys was 98% (N = 198) with 193 female (97.5%) and 5 male (2.5%) respondents. Participants were an average of 11.2 years of age. All multiple-choice-type assessment items showed shifts to better-informed responses following the educational intervention. The item with the highest positive-percent change as assessed in the post survey queried: “what types of virus can cause cervical cancer?” (pre-test = 25.2%, post-test = 68.2%). The table below shows the cervical cancer related questions that were asked and the proportion of correct answers. Conclusions: The GO comic book in conjunction with school assemblies, improved the knowledge regarding cervical cancer causes and risk factors in Nigerian school children. Findings highlight the lack of knowledge regarding cervical cancer among the young population eligible for HPV vaccination, and describe an effective educational strategy in this setting.[Table: see text]

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11505 Background: Early integration of SC to the treatment of advanced cancer can improve outcomes, but this may be challenging in developing countries due to a lack of resources and knowledge. In this RCT, we examined whether PN could improve early access to SC among Mexican patients with metastatic solid tumors as recommended by ASCO guidelines. Methods: Adult patients with newly-diagnosed metastatic cancer were randomly assigned to PN or standard oncologic care. At baseline, a navigator assessed the patients’ SC needs (depression, anxiety, fatigue, pain, caregiver burden) using validated questionnaires administered with an electronic tablet. For those in the PN arm, a personalized SC plan was created and implemented by a multidisciplinary team (palliative care, physical therapy, geriatrics, psychology, psychiatry). The primary outcome was access to SC, defined as receipt of SC interventions in the first 3 months (mo) after diagnosis. Secondary outcomes included advanced directive (AD) completion (for patients with expected survival ≤6 mo in accordance to Mexican law), changes in SC needs, and changes in quality of life (assessed using FACT-G). Results: 133 patients (median age 60, range 23-93; 52% male) were randomized (66 PN, 67 control). 61% of patients had gastrointestinal tumors. 94% of patients in the PN arm completed baseline assessments and received recommendations from the navigator. At 3 mo, 37 patients died or were lost to follow-up (16 PN, 21 control; p = 0.45), and 96 completed assessments. SC interventions were provided to 73% of patients in the PN arm and 24% of controls (p < 0.01). In the PN arm, 48% of 29 eligible patients completed AD, compared to 0% of eligible controls (p < 0.01). At 3 mo, patients in the PN arm were significantly less likely to report moderate/severe pain than controls (10 vs 33%, p = 0.006). There were no significant differences in other symptoms or in FACT-G scores (76 vs 76.3, p = 0.46) between PN and control arms at 3 mo. Conclusions: PN can lead to significant improvements in early access to SC, AD completion, and pain control among patients with metastatic cancer treated in a resource-limited setting. Clinical trial information: NCT03293849.