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Background Perinatal cannabis use is increasing, and clinician counselling is an important aspect of reducing the potential harm of cannabis use during pregnancy and lactation. To understand current counselling practices, we conducted a systematic review and integrative mixed-methods synthesis to determine “how do perinatal clinicians respond to pregnant and lactating patients who use cannabis?” Methods We searched 6 databases up until 2021-05-31. Eligible studies described the attitudes, perceptions, or beliefs of perinatal clinician about cannabis use during pregnancy or lactation. Eligible clinicians were those whose practice particularly focusses on pregnant and postpartum patients. The search was not limited by study design, geography, or year. We used a convergent integrative analysis method to extract relevant findings for inductive analysis. Results Thirteen studies were included; describing perspectives of 1,366 clinicians in 4 countries. We found no unified approach to screening and counselling. Clinicians often cited insufficient evidence around the effects of perinatal cannabis use and lacked confidence in counselling about use. At times, this meant clinicians did not address cannabis use with patients. Most counselled for cessation and there was little recognition of the varied reasons that patients might use cannabis, and an over-reliance on counselling focussed on the legal implications of use. Conclusion Current approaches to responding to cannabis use might result in inadequate counselling. Counselling may be improved through increased education and training, which would facilitate conversations to mitigate the potential harm of perinatal cannabis use while recognizing the benefits patients perceive.

Background: Lymphedema has been a prevalent and often severe side effect for patients receiving treatment for breast cancer typically resulting in physical and psychosocial distress as well as decreased quality of life. With no widely effective or safe drug treatment(s) for lymphedema, this study aimed to assess the efficacy of combined Lymphdiaral™ drops and ointment for treatment-related lymphedema. Methods: This open label, randomized, parallel-group trial ran over 12 weeks with a final follow-up visit at 24 weeks. One hundred and thirty-four (n = 134) patients were consented to the study. Of these, 119 patients were randomized to either standard care group (compression garment) or treatment group (compression garment plus Lymphdiaral™ drops and ointment) and follow-up data was obtained. The primary objective was the reduction in lymphedema as measured by change in arm volume. Results: The values for the arm volumes did not show a statistically significant decrease in both the standard care or treatment groups. Additionally, there was no statistical difference in arm volume reduction between the groups. Conclusions: This first randomized trial shows, that the homeopathic drug combination of Lymphdiaral™ drops and ointment does not improve lymphedema in breast cancer patients. Citation Format: Jawaid Younus, Morgan Black, Lyn Kligman, Brenda Leung. Efficacy of Lymphdiaral™ in breast cancer patients with lymphedema [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-12-15.

Objective. Detection of circulating tumor DNA (ctDNA) in cancer patients can potentially serve as a noninvasive, sensitive test of disease status. The purpose of this study was to determine the ability to detect BRAF (V600E) mutations in the plasma of patients with thyroid nodules, with the goal of distinguishing between benign and malignant nodules. Methods. Consecutive patients with thyroid nodules who consented for surgery were recruited. Plasma samples were obtained preoperatively and one month postoperatively. Quantitative PCR was used to determine the levels of the BRAF (V600E) mutation preoperatively and postoperatively. Results. A total of 109 patients were recruited. On final pathology, 38 (32.8%) patients had benign thyroid nodules, 45 (38.8%) had classical papillary thyroid cancer (PTC), 23 (19.8%) had nonclassical PTC, and 3 (2.6%) had follicular thyroid cancer. 15/109 patients had detectable BRAF (V600E) ctDNA in their preoperative samples—all of them having classical PTC. Higher T-stage and extrathyroidal extension in PTC were associated with positive BRAF (V600E) ctDNA ( p < 0.05 ). Eighty-eight pairs of preoperative and postoperative plasma samples were collected and analyzed. Of these eighty-eight paired samples, a total of 13/88 (14.8%) patients had detectable BRAF (V600E) ctDNA in their preoperative samples—all of them having classical PTC. 12 of these 13 patients had no detectable BRAF (V600E) postoperatively, while one remaining patient had a significant decline in his levels ( p < 0.05 ). Conclusion. BRAF (V600E) circulating thyroid tumor DNA can be detected in plasma and is correlated with a final diagnosis of the classical variant of PTC. Given that a postoperative drop in BRAF (V600E) ctDNA levels was observed in all cases suggests its utility as a tumor marker.

To examine the utility of a patient-level information video as part of the contraception consultation visit. Specifically, to assess the impact of the video on women's contraception choice, and, further, to assess patient and provider acceptability of incorporating the video into the patient visit.A pre-post study design was used to assess the impact on patients' contraceptive choices and knowledge. Participants (n = 49) answered questions regarding contraceptive preferences and knowledge of long-acting reversible contraception (LARC), then watched a 12-minute patient-level counselling video that presented evidence-based information about contraception in descending order of effectiveness. Clinicians (n = 39) also viewed the video and completed a survey. A retrospective chart review of 100 contraception visits was completed.Patient preference for IUDs increased significantly, whereas condoms decreased pre-to-post video (hormonal: 8.2% to 20.4%; copper: 0% to 16%; condoms: 32.7% to 18%, P 0.05). Although 74.4% of clinicians believed that the hormonal IUD was the "ideal" form of contraception when no contraindications were present, 95% stated that the oral contraceptive pill was most often prescribed, and a chart review revealed that the oral contraceptive pill was discussed at 88% of contraceptive counselling visits. Both patients and clinicians found the video useful and acceptable.A patient-level contraceptive information video improved interest in LARC. Both patients and clinicians viewed the video as an acceptable addition to the contraceptive counselling visit.

One barrier to the use of intrauterine devices (IUDs) as a contraceptive method is the experience of anxiety and pain during the insertion procedure. Previous reviews have focused on pharmacological methods used to relieve pain during IUD insertion; however, few similar reviews have examined non-pharmacological methods to relieve pain or strategies to reduce anxiety. The objectives of this study were to identify and categorize strategies for reducing anxiety and pain with respect to IUD insertion and the ways in which anxiety and pain were assessed. In particular, the study aimed to identify non-pharmacological interventions and studies that included anxiety as a research outcome. A literature search was conducted of all English-language studies between inception and the week of July 29, 2018 from the following online databases: Medline, Embase, Cochrane Library, and PubMed. The search revealed 426 studies after removal of duplicates, 35 of which fulfilled the inclusion criteria. A total of 29 studies were identified as assessing pharmacological interventions for the management of pain, and six studies assessed non-pharmacological interventions. Only one study included a measurement of patient anxiety during the procedure as an outcome measure. Research on non-pharmacological interventions for the management of anxiety and pain during IUD insertion is lacking. This review found that evidence for the studied pharmacological interventions is conflicting, and there is very little evidence on understanding the effectiveness of strategies to manage anxiety during the IUD insertion procedure. Further high-quality research on non-pharmacological pain and anxiety management strategies is warranted.

e12532 Background: Early Breast Cancer Trialist Collaborative Group meta-analysis suggested significant reduction in bone metastasis and breast cancer mortality among post-menopausal women diagnosed with early breast cancer when treated with an adjuvant bisphosphonate. Cancer Care Ontario and American Society of Clinical Oncology clinical practice guideline published in 2017, recommends the use of an adjuvant bisphosphonate in postmenopausal women who are candidates for adjuvant systemic therapy. Our goal was to evaluate trends and factors associated with adjuvant bisphosphonate usage since the guideline’s publication. Methods: This study is a retrospective review of postmenopausal women treated for early breast at the London Regional Cancer Program from 2017-2018. Univariate and a multivariable logistic regression models were used to investigate factors potentially associated with adjuvant bisphosphonate use including age, stage, grade, estrogen receptor, progesterone receptor, HER2 receptor status and previous use of adjuvant chemotherapy. The percentage of patients offered, receiving and declining therapy was also recorded and the time interval from surgery to start of bisphosphonate therapy (< 6 months, 6-12 months or >12 months). Results: We identified 286 postmenopausal breast cancer patients, of whom 75 (28%) received adjuvant bisphosphonate therapy. In our multivariable model, cancer stage [odds ratio (OR) stage II vs. I=2.26, 95% confidence interval (CI) 1.08-4.74) and OR Stage III vs. I=4.94, 95% CI 1.84-13.17] and previous use of adjuvant chemotherapy (OR=2.76, 95%CI 1.37-5.55) were significantly associated with adjuvant bisphosphonate use. Among 133 patients who received adjuvant systemic chemotherapy, 51% were offered adjuvant bisphosphonate and of these 81% patients accepted therapy. Among a total of 75 patients receiving adjuvant bisphosphonate therapy 19% initiated therapy within 6 months of surgery, 48% within 6-12 months of surgery, and 33% after 12 months following surgery. Conclusions: Stage and previous use of chemotherapy were significantly associated with adjuvant bisphosphonate therapy. Our study observes the potential underutilization of adjuvant bisphosphonate therapy and possible need to start treatment earlier in some patients. Further education and awareness of the clinical practice guidelines regarding adjuvant bisphosphonate therapy may be warranted and additional population-based study investigating treatment patterns and real-world effectiveness.

PIK3CA is the only frequently-mutated, directly druggable oncogene in head and neck squamous cell carcinoma (HNSCC). However, it is unclear if a molecularly-driven intervention trial can be launched successfully, particularly within a single-institution setting secondary to the infrastructure necessary for mutation detection, mutation prevalence, and patient willingness to participate. This study aimed to evaluate 1) local frequency of PIK3CA activating mutations in HNSCC, 2) timeliness of our mutation-profiling clinical pathway, and 3) patients' willingness to enroll in a novel neoadjuvant drug trial. Tissue biopsies of 25 consecutive cases of HNSCC were tested for activating PIK3CA mutations at three mutational hotspots by real-time polymerase chain reaction. Mutations prevalence and number of working days accrued in determining PIK3CA mutational status were calculated. In addition, 30 HNSCC patients were surveyed prospectively regarding their willingness to participate in a hypothetical drug trial. Survey data were summarized descriptively. 4 of 25 (16 %) tumors harbored a PIK3CA activating mutation, including one at codon E542K, two at codon E545K/D, and one at codon H1047R. On average, this result was obtained in approximately 15 working days (range, 9-24 working days). The majority of patients surveyed (70 %) indicated their willingness to participate in a targeted PIK3CA trial. This study provides evidence that within a single institution, PIK3CA activating mutations can be detected with expected frequency, with sufficient timeliness and sufficient patient interest to mount a targeted intervention trial that may lead to improved tumor response in selected HNSCC patients.

Background Evidence-based patient education and consistent, timely communication is key to ensuring good outcomes among joint replacement patients. Mount Sinai Hospital (MSH) participates in the mandatory CMS bundle for comprehensive joint replacement (CJR). MSH’s bundled payment strategy focuses on the development of a standardized model of care, built around evidence-based best practices to achieve the triple aims of strengthening population health while controlling cost and improving the quality of care. MSH launched a comprehensive digital navigation program (DNP) to guide joint replacement patients and their caregivers through pre-surgical preparation and recovery. Objective The objective was to improve the quality of care for joint replacement patients through creation of a digital navigation program specifically tailored to Medicare patients (age 65+) across the continuum of care. Methods Mount Sinai App Lab, in collaboration with the Department of Orthopedics, developed three digital therapeutic modules that were delivered through the RxUniverse Digital Medicine platform (Rx.Health, NY). These automated messages, programmed to send at specific times, included exercise instructions, medication reminders, and suggestions for how to prepare the home for optimal recovery. Messages specifically targeted key patient outcomes: length of stay, readmissions, ambulation on postoperative day 0, and discharge disposition. Staff “prescribed” each module to patients to ensure that engagement aligned with their process of care. Results Clinicians, patients, and their caregivers were receptive to the DNP. Patients showed a high rate of engagement, clicking links to educational content 873 times, and patients called their case manager or surgeon’s office to clarify their next steps when prompted. After 9 months, clinical outcomes for the digital navigation program were compared to other Medicare patients who had not received it. DNP patients had significantly shorter length of stay than their peers (2.81 vs 4.31 days). They also had a lower readmission rate (1.9% vs 2.9%) as well as a higher rate of discharge to home (87.8% vs 64.3%) and were more likely to ambulate on the day of surgery (47.9% vs 33.3%). Twenty patients responded to an end-of-program survey about their experience; 18 patients (90%) agreed that the program was helpful with the process of their total joint replacement surgery, 2 patients neither agreed nor disagreed (10%), and 0 patients disagreed. When asked about their satisfaction with the message volume, 19 patients answered “yes, this was the perfect number,” (95%) and 1 patient answered “no, I want fewer messages” (5%). Patient qualitative feedback was very positive. Patients reported, “Texts reassured me and helped me along with my progress and recovery,” and “Good support. Thank you.” A third said, “The texting program serves as a great reminder as what to do and when.” Conclusions The CJR DNP provided a direct, automated channel to educate and support patients at each stage of care. It demonstrated that digital navigation technology can be used even among non-digital native populations. It resulted in a significantly reduced length of stay and hospital readmissions among participating patients. Next steps include scaling the program across the health system and adding Spanish-language support. Similar programs are now being implemented for other surgical and disease use cases.

Urinary tract infections (UTIs) are common in young children and are seen in emergency departments (EDs) frequently. Left untreated, UTIs can lead to more severe conditions. Our goal was to undertake a quality improvement (QI) initiative to help minimize the number of children with missed UTIs in a newly established tertiary care pediatric emergency department (PED). A retrospective chart review was undertaken to identify missed UTIs in children < 3 years old who presented to a children’s hospital’s ED with positive urine cultures. It was found that there was no treatment or follow-up in 12% of positive urine cultures, indicating a missed or possible missed UTI in a significant number of children. Key stakeholders were then gathered and process mapping (PM) was completed, where gaps and barriers were identified and interventions were subsequently implemented. A follow-up chart review was completed to assess the impact of PM in reducing the number of missed UTIs. Following PM and its implementation within the ED, there was no treatment or follow-up in only 1% of cases. Based on our results, the number of potentially missed UTIs in the ED decreased dramatically, indicating that PM can be a successful QI tool in an acute care pediatric setting.

Introduction: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, with an incidence of ~600 000 new cases per year and a 50% mortality rate for advanced disease. The mutational landscape of HNSCC has been recently elucidated, introducing the possibility for targeted therapeutic approaches. PIK3CA—which encodes the α-catalytic subunit of PI3K (PI3Kα)—is the most frequently altered actionable target in HNSCC, however it is not presently clear which patients benefit most from PI3Kα-inhibition. BYL719 is a leading PI3Kα inhibitor in clinical development for HNSCC. We previously examined the responses of a large panel of genetically-characterized HNSCC cell lines to BYL719 and identified activating HRAS G12V mutations as strong predictors for BYL719 resistance. Here we examine if this mutation is able to individually modulate BYL719 response through overexpression and knockdown studies. Methods: To determine if HRAS G12V was able to modulate BYL719 sensitivity, we knocked down HRAS in HRAS G12V and HRAS wild-type (WT) cell lines using RNA interference, and then treated cells over 10-point dose ranges with BYL719. Sensitivity was determined by calculating IC50 (half-maximal inhibitory concentration) values at 72 hours using PrestoBlue®. Constructs expressing wildtype (WT) HRAS or HRAS G12V were transfected into BYL719-sensitive cells for overexpression studies and cells were selected using G418 Sulfate for 1 month. Proliferation and BYL719 sensitivity (IC50 values) were measured as described. Immunoblotting was used to examine activity of the PI3K-AKT axis with and without BYL719 (1μM) for 24 hours. Results & Conclusions: HRAS knockdown sensitized HRAS G12V lines to BYL719 (lower IC50), but did not affect the response of WT HRAS cells. WT HRAS and HRAS G12V overexpression significantly increased cellular proliferation and promoted BYL719 resistance. In HRAS G12V cell lines, we observed high levels of active phosphorylated AKT (S473/T308), even in the presence of BYL719. Collectively these findings highlight the predictive role of HRAS G12V for innate BYL719 resistance and contribute to our understanding of which patients may respond best on BYL719 therapy. Citation Format: Kara M. Ruicci, Ren Sun, Morgan Black, Nicole Pinto, John Yoo, Kevin Fung, Danielle Macneil, Lauire Aillies, Joseph S. Mymryk, Paul C. Boutros, John W. Barrett, Anthony C. Nichols. HRAS G12V predicts for innate resistance to PI3Kα inhibition in head and neck squamous cell cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3162. doi:10.1158/1538-7445.AM2017-3162

Introduction While most types of thyroid cancer are treatable, anaplastic thyroid cancer (ATC) is the most lethal human malignancy. Current treatment strategies are largely ineffective with only 10% of patients surviving longer than one year. As such, new treatments are desperately needed to improve patient survival in this aggressive cancer. Objective Identify highly effective drugs using high-throughput screening methods with a large panel of kinase inhibitors that can be used in the treatment of ATC. Methods High-throughput screening (HTS) of 13 genetically characterized ATC cell lines was carried out over a 6-dose range using 320 kinase inhibitors. Dose-response curves were generated and drugs with high potency were identified. Drugs with the highest activity were selected for further evaluation including investigating mechanism of action and cell death, and assays for migration and invasion. Results Based on HTS studies, Lestaurtinib was identified as a highly effective agent with submicromolar mean inhibitory concentrations in all 13 ATC cell lines. Lestaurtinib was found to inhibit STAT5 phosphorylation, as well as cell line migration and invasion. The anti-proliferative effect of Lestaurtinib did not cause apoptosis, autophagy or cell senescence. Conclusions With the use of HTS, we have identified many (>20) kinase inhibitors as highly effective agents in the control of ATC. The kinase inhibitor Lestaurtinib was effective at controlling ATC cell proliferation, invasion and migration. Future in vivo analysis of Lestaurtinib with patient-derived xenografts are planned to continue preclinical development of this drug with the ultimate goal of improving outcomes for patients suffering with ATC. Citation Format: Nicole C. Pinto, Morgan Black, Kara Ruicci, John Yoo, Danielle MacNeil, Kevin Fung, Alessandro Datti, Stephenie Prokopec, Paul Boutros, John Barrett, Anthony Nichols. Highly effective inhibitory agent identified by high-throughput screening of genetically characterized anaplastic thyroid cancer cell lines. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3767.