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Preclinical studies have found radiotherapy enhances antitumour immune responses. We aimed to assess disease control and pulmonary toxicity in patients who previously received radiotherapy for non-small-cell lung cancer (NSCLC) before receiving pembrolizumab. We assessed patients with advanced NSCLC treated on the phase 1 KEYNOTE-001 trial at a single institution (University of California, Los Angeles, CA, USA). Patients were aged 18 years or older, had an Eastern Cooperative Oncology Group performance status of 1 or less, had adequate organ function, and no history of pneumonitis. Patients received pembrolizumab at a dose of either 2 mg/kg of bodyweight or 10 mg/kg every 3 weeks, or 10 mg/kg every 2 weeks, until disease progression, unacceptable toxicity, or other protocol-defined reasons for discontinuation. Disease response and pulmonary toxicity were prospectively assessed by Immune-related Response Criteria and Common Terminology Criteria for Adverse Events version 4.0. The primary objective of the KEYNOTE-001 trial was to assess the safety, side-effect profile, and antitumour activity of pembrolizumab. For our secondary analysis, patients were divided into subgroups to compare patients who previously received radiotherapy with patients who had not. Our primary objective was to determine whether previous radiotherapy affected progression-free survival, overall survival, and pulmonary toxicity in the intention-to-treat population. The KEYNOTE-001 trial was registered with ClinicalTrials.gov, number NCT01295827. Between May 22, 2012, and July 11, 2014, 98 patients were enrolled and received their first cycle of pembrolizumab. One patient was lost to follow-up. 42 (43%) of 97 patients had previously received any radiotherapy for the treatment of NSCLC before the first cycle of pembrolizumab. 38 (39%) of 97 patients received extracranial radiotherapy and 24 (25%) of 97 patients received thoracic radiotherapy. Median follow-up for surviving patients was 32·5 months (IQR 29·8–34·1). Progression-free survival with pembrolizumab was significantly longer in patients who previously received any radiotherapy than in patients without previous radiotherapy (hazard ratio [HR] 0·56 [95% CI 0·34–0·91], p=0·019; median progression-free survival 4·4 months [95% CI 2·1–8·6] vs 2·1 months [1·6–2·3]) and for patients who previously received extracranial radiotherapy compared with those without previous extracranial radiotherapy (HR 0·50 [0·30–0·84], p=0·0084; median progression-free survival 6·3 months [95% CI 2·1–10·4] vs 2·0 months [1·8–2·1]). Overall survival with pembrolizumab was significantly longer in patients who previously received any radiotherapy than in patients without previous radiotherapy (HR 0·58 [95% CI 0·36–0·94], p=0·026; median overall survival 10·7 months [95% CI 6·5–18·9] vs 5·3 months [2·7–7·7]) and for patients who previously received extracranial radiotherapy compared with those without previous extracranial radiotherapy (0·59 [95% CI 0·36–0·96], p=0·034; median overall survival 11·6 months [95% CI 6·5–20·5] vs 5·3 months [3·0–8·5]). 15 (63%) of 24 patients who had previously received thoracic radiotherapy had any recorded pulmonary toxicity versus 29 (40%) of 73 patients with no previous thoracic radiotherapy. Three (13%) patients with previous thoracic radiotherapy had treatment-related pulmonary toxicity compared with one (1%) of those without; frequency of grade 3 or worse treatment-related pulmonary toxicities was similar (one patient in each group). Our data suggest that previous treatment with radiotherapy in patients with advanced NSCLC results in longer progression-free survival and overall survival with pembrolizumab treatment than that seen in patients who did not have previous radiotherapy, with an acceptable safety profile. Further clinical trials investigating this combination are needed to determine the optimal treatment strategy for patients with advanced NSCLC. US National Institutes of Health.

Background COVID-19 studies are primarily from the inpatient setting, skewing towards severe disease. Race and comorbidities predict hospitalization, however, ambulatory presentation of milder COVID-19 disease and characteristics associated with progression to severe disease is not well-understood. Methods We conducted a retrospective chart review including all COVID-19 positive cases from Stanford Health Care (SHC) in March 2020 to assess demographics, comorbidities and symptoms in relationship to: 1) their access point of testing (outpatient, inpatient, and emergency room (ER)) and 2) development of severe disease. Results Two hundred fifty-seven patients tested positive: 127 (49%), 96 (37%), and 34 (13%) at outpatient, ER and inpatient, respectively. Overall, 61% were age < 55; age > 75 was rarer in outpatient setting (11%) than ER (14%) or inpatient (24%). Most patients presented with cough (86%), fever/chills (76%), or fatigue (63%). 65% of inpatients reported shortness of breath compared to 30–32% of outpatients and ER patients. Ethnic/minority patients had a significantly higher risk of developing severe disease (Asian OR = 4.8 [1.6–14.2], Hispanic OR = 3.6 [1.1–11.9]). Medicare-insured patients were marginally more likely (OR = 4.0 [0.9–17.8]). Other factors associated with developing severe disease included kidney disease (OR = 6.1 [1.0–38.1]), cardiovascular disease (OR = 4.7 [1.0–22.1], shortness of breath (OR = 5.4 [2.3–12.6]) and GI symptoms (OR = 3.3 [1.4–7.7]; hypertension without concomitant CVD or kidney disease was marginally significant (OR = 2.3 [0.8–6.5]). Conclusions Early widespread symptomatic testing for COVID-19 in Silicon Valley included many less severely ill patients. Thorough manual review of symptomatology reconfirms the heterogeneity of COVID-19 symptoms, and challenges in using clinical characteristics to predict decline. We re-demonstrate that socio-demographics are consistently associated with severity.

Introduction: Increasing demand for emergency department (ED) services and strained specialty- care access requires referral precision and was the impetus for a collaborative redesign of referrals between the Department of Emergency Medicine and Department of Orthopaedic Surgery. Methods: Guided by root cause analysis of delays in post-emergency department (ED) specialty follow-up in our academic health system, the intervention targeted the finding that all ED referrals were marked “urgent” without differentiation by acuity of orthopedic issues. After implementation, referrals were triaged into three tiers—immediate, urgent, and routine—with stipulated follow-up timeframes. We evaluated differences in completion of scheduling and realized visits, across five calendar months (July–November) pre- and post-implementation (2021 vs 2022). Logistic regression assessed the relationship between patient demographics and outcomes. We report medians and interquartile ranges. Results: Compared to the 393 urgent referrals to the Department of Orthopaedic Surgery pre-implementation, there were 463 total referrals post-implementation as follows: 11/463 (2.4%) marked as immediate; 123/463 (26.6%) urgent; and 329/463 (71.1%) routine. Similar proportions successfully scheduled pre- and post-implementation (41.5% vs 45.1%; P = .28). On average, immediate referrals completed scheduling within 1.0 (0.0 - 1.0) day and were seen in 4.0 (2.0 - 8.0) days, urgent referrals completed scheduling within 2.0 (1.0 – 4.0) and 7.0 (5.0 - 15.0) days, and routine within 3.0 (1.0 - 6.0) and 12.0 (6.0 - 19.5) days. Race/ethnicity and insurance were related to odds of successful scheduling; Black patients had lower odds than all other groups (odds ratio [OR] 0.3 - 0.4). All insurance categories had higher odds of successful scheduling relative to Medicaid out-of-network (OR 3.5 - 7.2). Conclusion: A three-tier ED-to-orthopedics referral triage system was quickly adopted and differentiated referrals by urgency but did not impact time to follow-up or loss to follow-up. Structural inequities in access to follow-up care remain

Assessing barriers to vaccination among healthcare workers may be particularly important given their roles in their respective communities. We conducted a mixed methods study to explore healthcare worker perspectives on receiving COVID-19 vaccines at a large multisite academic medical center. A total of 5,917 employees completed the COVID-19 vaccine confidence survey (20% response rate). Most participants were vaccinated (93%). Compared to vaccinated participants, unvaccinated participants were younger (60% < 44 years), more likely to be from a non-Asian minority group (48%), and more likely to be nonclinical employees (57% vs. 46%). Among the unvaccinated respondents, 53% indicated they would be influenced by their healthcare provider, while 19% reported that nothing would influence them to get vaccinated. Key perceived barriers to vaccination from the qualitative analysis included the need for more long-term safety and efficacy data, a belief in the right to make an individual choice, mistrust, a desire for greater public health information, personal health concerns, circumstances such as prior COVID-19 infection, and access issues. Strategies endorsed by some participants to address their concerns about safety and access included a communication campaign, personalized medicine approaches (e.g., individual appointments to discuss how the vaccine might interact with personal health conditions), and days off to recover. Mistrust and a belief in the right to make an individual choice may be harder barriers to overcome; further dialogue is needed. These findings reflect potential strategies for vaccine requirements that healthcare organizations can implement to enhance vaccine confidence. In addition, organizations can ask respected health professionals to serve as spokespeople, which may help shift the perspectives of unvaccinated healthcare workers.

BackgroundIncident reporting systems (IRS) can improve care quality and patient safety, yet their impact is limited by clinician engagement. Our objective was to assess barriers to reporting in a hospital-wide IRS and use data to inform ongoing improvement of a specialty-specific IRS embedded in the electronic health record targeting anaesthesiologists.MethodsThis quality improvement (QI) evaluation used mixed methods, including qualitative interviews, faculty surveys and user data from the specialty-specific IRS. We conducted 24 semi-structured interviews from January to May 2023 in a large academic health system in Northern California. Participants included adult and paediatric anaesthesiologists, operating room nurses, surgeons and QI operators, recruited through convenience and snowball sampling. We identified key themes and factors influencing engagement, which were classified using the Systems Engineering Initiative for Patient Safety framework. We surveyed hospital anaesthesiologists in January and May 2023, and characterised the quantity and type of reports submitted to the new system.ResultsParticipants shared organisation and technology-related barriers to engagement in traditional system-wide IRSs, many of which the specialty-specific IRS addressed-specifically those related to technological access to the system. Barriers related to building psychological safety for those who report remain. Survey results showed that most barriers to reporting improved following the specialty-specific IRS launch, but limited time remained an ongoing barrier (25 respondents out of 44, 56.8%). A total of 964 reports with quality/safety concerns were submitted over the first 8 months of implementation; 47–76 unique anaesthesiologists engaged per month. The top safety quality categories of concern were equipment and technology (25.9%), clinical complications (25.3%) and communication and scheduling (19.9%).ConclusionsThese findings suggest that a specialty-specific IRS can facilitate increased physician engagement in quality and safety reporting and complement existing system-wide IRSs.

Given the rising demand for emergency department (ED) services and coupled with the scarcity of specialty care availability, there is an urgency to design a system for appropriate, effective, and timely ED-to-specialty ambulatory referrals. Efficient care transitions are important to patient outcomes and experience and require cross-specialty cooperation, as care transitions affect practices and resources of individuals, departments, and institutions. Here, our objective was to (1) describe a collaboration between Stanford's Emergency Medicine and Neurology and Neurological Sciences departments aimed at designing and implementing an optimized discharge process and transition of care from ED to ambulatory neurology for follow-up care and (2) the resulting intervention from the collaboration. We describe the process for barrier identification, tools used to foster partnership and intervention ideation, and the resulting intervention. Our experience and findings are integrated into a 4-component framework for future interdepartmental collaborations: (1) cross-specialty team meetings, (2) preimplementation interviews, (3) a design thinking focus group session, and (4) small group meetings. Qualitative data included observational notes and document review from biweekly cross-specialty and small group meetings, preimplementation interviews, and design-thinking focus groups. Our process included 10 cross-specialty team meetings with 8 physicians and operational representatives, 18 individual preimplementation interviews, 10 focus group participants, and 9 small group meetings. The process components fostered collaboration and teamwork among the multidisciplinary team; supported early identification of barriers and facilitators, including divergent understanding of project goals; and developed creative ideas that contributed to intervention development. The collaboration resulted in a 4-pronged multimodal intervention. Two elements focused on modifying clinical practice to better triage clinically appropriate ED referrals to ambulatory neurology: (1) optimizing management of conditions in the ED to reduce preventable referrals, and (2) increasing deferral to Primary Care clinicians to direct appropriate specialty follow-up care. Two additional structural elements sought to directly improve appropriate referral timeliness by (3) streamlining insurance authorization processes and (4) increasing neurology appointment availability. This cross-specialty collaboration resulted in a multimodal intervention that called for both structural and practice changes, which were novel and supported by the results of comparable interventions. Future applications of this framework can validate its utility among different collaborative groups in new settings.

SUMMARY Goal: Assessing barriers to vaccination among healthcare workers may be particularly important given their roles in their respective communities. We conducted a mixed methods study to explore healthcare worker perspectives on receiving COVID-19 vaccines at a large multisite academic medical center. Methods: A total of 5,917 employees completed the COVID-19 vaccine confidence survey (20% response rate). Most participants were vaccinated (93%). Compared to vaccinated participants, unvaccinated participants were younger (60% < 44 years), more likely to be from a non-Asian minority group (48%), and more likely to be nonclinical employees (57% vs. 46%). Among the unvaccinated respondents, 53% indicated they would be influenced by their healthcare provider, while 19% reported that nothing would influence them to get vaccinated. Key perceived barriers to vaccination from the qualitative analysis included the need for more long-term safety and efficacy data, a belief in the right to make an individual choice, mistrust, a desire for greater public health information, personal health concerns, circumstances such as prior COVID-19 infection, and access issues. Principal Findings: Strategies endorsed by some participants to address their concerns about safety and access included a communication campaign, personalized medicine approaches (e.g., individual appointments to discuss how the vaccine might interact with personal health conditions), and days off to recover. Mistrust and a belief in the right to make an individual choice may be harder barriers to overcome; further dialogue is needed. Applications to Practice: These findings reflect potential strategies for vaccine requirements that healthcare organizations can implement to enhance vaccine confidence. In addition, organizations can ask respected health professionals to serve as spokespeople, which may help shift the perspectives of unvaccinated healthcare workers.

Purpose To report outcomes for breast-conserving therapy using adjuvant accelerated partial breast irradiation with interstitial multicatheter brachytherapy by a cooperative group of institutions. Methods From 1992 to 2013, a total of 1356 patients were treated with breast-conserving surgery and adjuvant accelerated partial breast irradiation using interstitial multicatheter brachytherapy. A total of 1131 patients had >1 year of data available to assess oncologic and cosmesis outcomes. Median age was 59 years old (range 22–90 years). Histologies treated included 1005 (73 %) invasive ductal carcinoma and 240 (18 %) ductal carcinoma-in situ. T stages were 18 % Tis, 75 % T1, and 8 % ≥T2. Nodal status was 73 % N0 and 6 % N1a. Estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 was positive in 83, 70, and 6 %, respectively. Cox multivariate analysis for local control was performed using histology, age, estrogen receptor status, tumor size, grade, margin, and nodal status. Results The mean (SD) follow-up was 6.9 years (4.3). The 10-year actuarial risk (95 % confidence interval) of an ipsilateral breast tumor recurrence was 7.6 % (5.6–10.1). Other 10-year actuarial risks (95 % confidence interval) were regional failure 2.3 % (1.4–3.7), distant metastasis 3.8 % (2.5–5.7), cause-specific survival 96.3 % (94.2–97.6), overall survival 86.5 (83.0–89.3), and new contralateral cancers 4.6 % (3.0–6.9). On multivariate analysis, high grade (hazard ratio 2.81) and positive margin status (hazard ratio 18.42) were the only two significant variables associated with an increased risk of local recurrence. Physician-reported cosmesis was excellent/good in 84 % (98 of 116) of patients with >5 years of follow-up. Conclusions This is the largest report of outcomes with interstitial breast brachytherapy. This treatment resulted in excellent long-term local control and cosmesis outcomes.

Purpose Managing juxtapapillary and circumpapillary choroidal melanoma with brachytherapy is challenging because of technical complications with accurate plaque placement and high radiation toxicity given tumor proximity to the optic nerve. We evaluated our center’s experience using ultrasound-guided, Iodine (I)-125 notched plaque brachytherapy for treating choroidal melanoma contiguous with (juxtapapillary) and at least partially surrounding the optic disc (circumpapillary). Methods All cases of choroidal melanoma treated with I-125 notched plaque brachytherapy at our center from September 2003–December 2013 were retrospectively reviewed. Only patients with ≥18 months of follow-up who had lesions contiguous with the optic disc (0 mm of separation) were included. The tumor apex prescription dose was 85 Gy. Outcomes evaluated included local control, distant metastasis-free survival (DMFS), cancer-specific survival (CSS), overall survival (OS), visual acuity, and radiation toxicity. Results Thirty-four patients were included with a median follow-up of 44.1 months (range 18.2–129.0). AJCC T-category was T1 in 58.8%, T2 in 26.5%, and T3 in 14.7%. Median circumferential optic disc involvement was 50% (range 10%–100%). Eye retention was achieved in 94.1%. Actuarial 2- and 4-year rates of local recurrence were 3.1% and 7.6%, DMFS were 97.0% and 88.5%, CSS were 97.0% and 92.8%, and OS were 97.0% and 88.9%, respectively. In addition, 23.5% had visual acuity ≥20/200 at last follow-up. Conclusions I-125 notched plaque brachytherapy provides high eye preservation rates with acceptable longer-term post-treatment visual outcomes. Based on our experience, choroidal melanoma directly contiguous with and partially encasing the optic disc may be effectively treated with this technique.

Disclosure: J.J. Chang: None. D. Veruttipong: None. O. Chu: None. W. Erin: None. V. Gates-Bazarbay: None. S. Kling: None. K. Vinluan: None. S. Chittum: None. M. Alhadha: None. J. Fernandez-Miranda: None. Background: Delayed hyponatremia due to syndrome of inappropriate antidiuretic hormone secretion is the most common cause of readmission after pituitary transsphenoidal surgery (TSS). Post-operative fluid restriction (FR) after discharge may effectively reduce hyponatremia and related readmissions. Methods: Our aim was to assess the effectiveness of FR after TTS. We compared post-operative day (POD) 8 hyponatremia and related readmission rates pre- and post- FR protocol implementation at our institution. Pre-FR (July 1, 2018-March 15, 2020) post-TSS patients were instructed to drink ad lib or to thirst on discharge. Post-FR (March 16, 2020-December 31, 2020), post-TSS patients were routinely provided education and documentation on the outpatient protocol that recommended 1 liter/day FR from POD 3-5 to POD 8-10. Serum sodium was assessed at POD-8 for all patients. Patients hospitalized for more than 5 days after surgery, had untreated adrenal insufficiency, or had pre-existing AVP deficiency were excluded. Results: The average POD-8 sodium level was lower in the 115 patients in the pre-FR cohort than the 216 patients in the post-FR cohort (135.8±6.7 vs. 138.1±4.4 mEq/L; Wilcoxon-Mann-Whitney test p=0.0081). POD-8 hyponatremia (Na ≤134 mEq/L) occurred in a lower proportion of patients post-FR (15.0%; 32/214) than pre-FR (28.9%; 30/104) (Chi-Square test p=0.0033). Similarly, severe hyponatremia (Na ≤124 mEq/L) occurred in a lower proportion of patients post-FR (1.4%; 3/214) than pre-FR (8.7%; 9/104) (Fisher test p= 0.01). Only 1.4% (3/216) of patients were readmitted post-FR compared to the 8.7% (10/115) pre-FR (Fisher test p=0.0020). Conclusions: Our retrospective evaluation showed that implementation of post-TSS FR protocol significantly decreased hyponatremia by nearly 50% and readmissions by over 80% compared to the prior standard of care of drink ad lib or to thirst. FR should be considered standard-of-care for eligible patients without ongoing AVP deficiency to reduce hyponatremia and readmission burden to both patient and healthcare system. Presentation: Saturday, June 17, 2023