Variability Among Breast Cancer Risk Classification Models When Applied at the Level of the Individual Woman.

BACKGROUND: Breast cancer risk models guide screening and chemoprevention decisions, but the extent and effect of variability among models, particularly at the individual level, is uncertain. OBJECTIVE: To quantify the accuracy and disagreement between commonly used risk models in categorizing individual women as average vs. high risk for developing invasive breast cancer. DESIGN: Comparison of three risk prediction models: Breast Cancer Risk Assessment Tool (BCRAT), Breast Cancer Surveillance Consortium (BCSC) model, and International Breast Intervention Study (IBIS) model. SUBJECTS: Women 40 to 74 years of age presenting for screening mammography at a multisite health system between 2011 and 2015, with 5-year follow-up for cancer outcome. MAIN MEASURES: Comparison of model discrimination and calibration at the population level and inter-model agreement for 5-year breast cancer risk at the individual level using two cutoffs (≥ 1.67% and ≥ 3.0%). KEY RESULTS: A total of 31,115 women were included. When using the ≥ 1.67% threshold, more than 21% of women were classified as high risk for developing breast cancer in the next 5 years by one model, but average risk by another model. When using the ≥ 3.0% threshold, more than 5% of women had disagreements in risk severity between models. Almost half of the women (46.6%) were classified as high risk by at least one of the three models (e.g., if all three models were applied) for the threshold of ≥ 1.67%, and 11.1% were classified as high risk for ≥ 3.0%. All three models had similar accuracy at the population level. CONCLUSIONS: Breast cancer risk estimates for individual women vary substantially, depending on which risk assessment model is used. The choice of cutoff used to define high risk can lead to adverse effects for screening, preventive care, and quality of life for misidentified individuals. Clinicians need to be aware of the high false-positive and false-negative rates and variation between models when talking with patients.

Retrospective Detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Symptomatic Patients Prior to Widespread Diagnostic Testing in Southern California.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused one of the worst pandemics in recent history. Few reports have revealed that SARS-CoV-2 was spreading in the United States as early as the end of January. In this study, we aimed to determine if SARS-CoV-2 had been circulating in the Los Angeles (LA) area at a time when access to diagnostic testing for coronavirus disease 2019 (COVID-19) was severely limited. METHODS: We used a pooling strategy to look for SARS-CoV-2 in remnant respiratory samples submitted for regular respiratory pathogen testing from symptomatic patients from November 2019 to early March 2020. We then performed sequencing on the positive samples. RESULTS: We detected SARS-CoV-2 in 7 specimens from 6 patients, dating back to mid-January. The earliest positive patient, with a sample collected on January 13, 2020 had no relevant travel history but did have a sibling with similar symptoms. Sequencing of these SARS-CoV-2 genomes revealed that the virus was introduced into the LA area from both domestic and international sources as early as January. CONCLUSIONS: We present strong evidence of community spread of SARS-CoV-2 in the LA area well before widespread diagnostic testing was being performed in early 2020. These genomic data demonstrate that SARS-CoV-2 was being introduced into Los Angeles County from both international and domestic sources in January 2020.

Excess Patient Visits for Cough and Pulmonary Disease at a Large US Health System in the Months Prior to the COVID-19 Pandemic: Time-Series Analysis.

BACKGROUND: Accurately assessing the regional activity of diseases such as COVID-19 is important in guiding public health interventions. Leveraging electronic health records (EHRs) to monitor outpatient clinical encounters may lead to the identification of emerging outbreaks. OBJECTIVE: The aim of this study is to investigate whether excess visits where the word "cough" was present in the EHR reason for visit, and hospitalizations with acute respiratory failure were more frequent from December 2019 to February 2020 compared with the preceding 5 years. METHODS: A retrospective observational cohort was identified from a large US health system with 3 hospitals, over 180 clinics, and 2.5 million patient encounters annually. Data from patient encounters from July 1, 2014, to February 29, 2020, were included. Seasonal autoregressive integrated moving average (SARIMA) time-series models were used to evaluate if the observed winter 2019/2020 rates were higher than the forecast 95% prediction intervals. The estimated excess number of visits and hospitalizations in winter 2019/2020 were calculated compared to previous seasons. RESULTS: The percentage of patients presenting with an EHR reason for visit containing the word "cough" to clinics exceeded the 95% prediction interval the week of December 22, 2019, and was consistently above the 95% prediction interval all 10 weeks through the end of February 2020. Similar trends were noted for emergency department visits and hospitalizations starting December 22, 2019, where observed data exceeded the 95% prediction interval in 6 and 7 of the 10 weeks, respectively. The estimated excess over the 3-month 2019/2020 winter season, obtained by either subtracting the maximum or subtracting the average of the five previous seasons from the current season, was 1.6 or 2.0 excess visits for cough per 1000 outpatient visits, 11.0 or 19.2 excess visits for cough per 1000 emergency department visits, and 21.4 or 39.1 excess visits per 1000 hospitalizations with acute respiratory failure, respectively. The total numbers of excess cases above the 95% predicted forecast interval were 168 cases in the outpatient clinics, 56 cases for the emergency department, and 18 hospitalized with acute respiratory failure. CONCLUSIONS: A significantly higher number of patients with respiratory complaints and diseases starting in late December 2019 and continuing through February 2020 suggests community spread of SARS-CoV-2 prior to established clinical awareness and testing capabilities. This provides a case example of how health system analytics combined with EHR data can provide powerful and agile tools for identifying when future trends in patient populations are outside of the expected ranges.

Patient-reported quality-of-life outcomes after de-escalated chemoradiation for human papillomavirus-positive oropharyngeal carcinoma: Findings from a phase 2 trial.

BACKGROUND: The current study represents a subset analysis of quality-of-life (QOL) outcomes among patients treated on a phase 2 trial of de-escalated chemoradiation for human papillomavirus (HPV)-associated oropharyngeal cancer. METHODS: Eligibility included newly diagnosed, (American Joint Committee on Cancer, 7th edition) stage III or IV oropharyngeal squamous cell carcinoma, p16 positivity, age ≥ 18 years, and a Zubrod performance status of 0 to 1. Treatment was induction paclitaxel at a dose of 175 mg/m2 and carboplatin at an area under the curve of 6 for 2 cycles followed by response-adapted, dose-reduced radiation of 54 Gy or 60 Gy with weekly concurrent paclitaxel at a dose of 30 mg/m2 . The University of Washington Quality of Life (UW-QOL) and the Functional Assessment of Cancer Therapy-Head and Neck questionnaires were used to assess patient-reported QOL as a secondary endpoint. RESULTS: A total of 45 patients were registered, 40 of whom completed QOL surveys and were evaluable. Nadirs for overall UW-QOL and Functional Assessment of Cancer Therapy-Head and Neck scores were reached at 4 weeks after treatment but returned to baseline at 3 months. Nearly all functional indices returned to baseline levels by 6 to 9 months. The mean overall UW-QOL score was 71.6 at baseline compared with 70.8, 73.0, 83.3, and 81.1, respectively, at 3 months, 6 months, 1 year, and 2 years after therapy. The percentage of patients rating their overall QOL as "very good" or "outstanding" at 6 months, 1 year, and 2 years using the UW-QOL was 50%, 77%, and 84%, respectively. CONCLUSIONS: This de-escalation regimen achieved QOL outcomes that were favorable compared with historical controls. These results serve as powerful evidence that ongoing de-escalation efforts lead to tangible gains in function and QOL. Cancer 2018;124:521-9. © 2017 American Cancer Society.

Prognostic significance of HPV status in the re-irradiation of recurrent and second primary cancers of the head and neck.

PURPOSE: To evaluate the prognostic significance of human papillomavirus (HPV) status among patients treated by salvage radiation therapy for local-regional recurrences and second primary cancers of the head and neck arising in a previously irradiated field. METHODS AND MATERIALS: The medical records of 54 consecutive patients who underwent re-irradiation for squamous cell carcinoma of the head and neck occurring in a previously irradiated field were reviewed. Only patients with biopsy-proven evidence of recurrent disease that had previously been treated with doses of radiation therapy of at least 60 Gy were included. Determination of HPV status at the time of recurrence was performed by p16 immunohistochemistry. The median age at re-irradiation was 58.5 years (range, 27.9 to 81.5 years). Thirty patients (55.5%) were lifelong never-smokers. The Kaplan Meier method was used to calculate overall survival, progression-free survival, and local-regional control, and distant metastasis-free survival with comparisons between groups performed using the log-rank test. RESULTS: HPV status among tumors that were re-irradiated was as follows: 16 positive (29.7%); 7 negative (12.9%); 31 unknown (57.4%). The median overall survival in the entire cohort was 11.7 months (range, 8 to 27 months), with the 1-year and 2-year estimates of overall survival being 47.2% and 38.4%, respectively. A statistical trend was identified favoring patients with HPV-positive cancers with respect to the endpoints of overall survival (p = 0.06) and progression-free survival (p = 0.08) after re-irradiation when compared to the HPV-negative/unknown population. There was no significant difference in distant control between the two cohorts (p = 0.40). CONCLUSIONS: The favorable prognostic significance of HPV seemingly extends to patients treated by re-irradiation suggesting that this biomarker may be useful in risk stratification in this setting.

Reduced-dose radiotherapy for human papillomavirus-associated squamous-cell carcinoma of the oropharynx: a single-arm, phase 2 study.

BACKGROUND: Head and neck cancers positive for human papillomavirus (HPV) are exquisitely radiosensitive. We investigated whether chemoradiotherapy with reduced-dose radiation would maintain survival outcomes while improving tolerability for patients with HPV-positive oropharyngeal carcinoma. METHODS: We did a single-arm, phase 2 trial at two academic hospitals in the USA, enrolling patients with newly diagnosed, biopsy-proven stage III or IV squamous-cell carcinoma of the oropharynx, positive for HPV by p16 testing, and with Zubrod performance status scores of 0 or 1. Patients received two cycles of induction chemotherapy with 175 mg/m2 paclitaxel and carboplatin (target area under the curve of 6) given 21 days apart, followed by intensity-modulated radiotherapy with daily image guidance plus 30 mg/m2 paclitaxel per week concomitantly. Complete or partial responders to induction chemotherapy received 54 Gy in 27 fractions, and those with less than partial or no responses received 60 Gy in 30 fractions. The primary endpoint was progression-free survival at 2 years, assessed in all eligible patients who completed protocol treatment. This study is registered with ClinicalTrials.gov, numbers NCT02048020 and NCT01716195. FINDINGS: Between Oct 4, 2012, and March 3, 2015, 45 patients were enrolled with a median age of 60 years (IQR 54-67). One patient did not receive treatment and 44 were included in the analysis. 24 (55%) patients with complete or partial responses to induction chemotherapy received 54 Gy radiation, and 20 (45%) with less than partial responses received 60 Gy. Median follow-up was 30 months (IQR 26-37). Three (7%) patients had locoregional recurrence and one (2%) had distant metastasis; 2-year progression-free survival was 92% (95% CI 77-97). 26 (39%) of 44 patients had grade 3 adverse events, but no grade 4 events were reported. The most common grade 3 events during induction chemotherapy were leucopenia (17 [39%]) and neutropenia (five [11%]), and during chemoradiotherapy were dysphagia (four [9%]) and mucositis (four [9%]). One (2%) of 44 patients was dependent on a gastrostomy tube at 3 months and none was dependent 6 months after treatment. INTERPRETATION: Chemoradiotherapy with radiation doses reduced by 15-20% was associated with high progression-free survival and an improved toxicity profile compared with historical regimens using standard doses. Radiotherapy de-escalation has the potential to improve the therapeutic ratio and long-term function for these patients. FUNDING: University of California.

Juxtapapillary and circumpapillary choroidal melanoma: globe-sparing treatment outcomes with iodine-125 notched plaque brachytherapy.

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.

Prognostic significance of p16 in squamous cell carcinoma of the larynx and hypopharynx.

PURPOSE: To evaluate the prognostic significance of p16 expression among patients with squamous cell carcinoma of the larynx (LSCC) and hypopharynx (HSCC). METHODS: The medical records of all patients with locally advanced, non-metastatic LSCC/HSCC were reviewed. p16INK4A (p16) protein expression was evaluated on pathological specimens by immunohistochemistry (IHC), and the Kaplan-Meier method was used to estimate overall survival (OS) and locoregional control (LRC). In select cases, p16 expression was correlated to high-risk and low-risk HPV genotypes using in situ hybridization (ISH). RESULTS: Thirty-one patients (23 LSCC; 8 HSCC) were identified. Seventeen (54.8%) patients were p16 negative; 14 (45.2%) were p16-positive. The primary treatment modality was radiation therapy for 22 (71.0%) patients and surgery for 9 (29.0%). Nineteen (61.3%) patients were evaluated for high-risk HPV and low-risk HPV genotypes by IHC, of whom 2 (10.5%) patients were positive for high-risk HPV and 1 (5.3%) was positive for low-risk HPV. For high-risk HPV, the positive predictive value (PPV), sensitivity, and specificity of p16 was 20.0%, 100%, and 52.9%. There was no significant difference in the 2-year actuarial rates of OS (91% vs. 64%, p=0.34) or LRC (51% vs. 46%, p=0.69) between the p16-positive and p-16 negative patients. CONCLUSION: In this small cohort of 31 LSCC and HSCC patients, p16 was not a significant predictive of either LRC or OS. Furthermore, p16 was poorly correlated with HPV genotyping as identified by ISH.

Long term results from a prospective database on high dose rate (HDR) interstitial brachytherapy for primary cervical carcinoma.

OBJECTIVE: Present long-term outcomes in primary cervical cancer treated with external beam and high dose rate interstitial brachytherapy. METHODS: High dose rate (HDR) interstitial (IS) brachytherapy (BT) and external beam (EBRT) were administered from 1992 to 2009 to 315 patients who were unsuitable for intracavitary (IC) BT alone. Histology was 89% squamous cell, 8% adenocarcinoma, and 3% adenosquamous. FIGO stage was I-14%, II-47%, III-34%, and IVA-5%. Median tumor size was 6cm. Lymph node metastases were 26% pelvic and 9.5% para-aortic. Treatment planning was 49% 2D and 51% 3D-CT. The mean doses were central EBRT EQD210 37.3±4.3Gy (sidewall 49.2±3.6Gy) and HDR EQD210 42.3±5.3Gy (nominal 5.4Gy×6 fractions using a mean of 24 catheters and 1 tandem). Total EQD210 mean target dose was 79.5±5.4Gy. Standardized planned dose constraints were ICRU points or D0.1cc bladder 80%, rectum 75% and urethra 90% of the HDR dose per fraction. Morbidity assessment was CTCAEv3. Median and mean follow-up were 50 and 61months (3-234). RESULTS: The 10-year actuarial local control was 87%, regional control 84%, and loco-regional control 77%. Distant metastasis free survival was 66%, cause specific survival 56%, disease free survival 54%, and overall survival 40%. The rates of late grade GU and GI toxicities were 4.8% G3 and 5.4% G4. CONCLUSIONS: Template-guided interstitial can be safely performed to successfully deliver high radiation dose to locally advanced cervix cancer and avoid excessive dose and injury to adjacent vital pelvic organs. We achieved high tumor control with low morbidity in patients who were poor candidates for intracavitary brachytherapy.

Outcomes of Breast Cancer Patients Treated with Accelerated Partial Breast Irradiation Via Multicatheter Interstitial Brachytherapy: The Pooled Registry of Multicatheter Interstitial Sites (PROMIS) Experience.

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.

Quantitative multiparametric MRI in uveal melanoma: increased tumor permeability may predict monosomy 3.

INTRODUCTION: Uveal melanoma is a rare intraocular tumor with heterogeneous biological behavior, and additional noninvasive markers that may predict outcome are needed. Diffusion- and perfusion-weighted imaging may prove useful but have previously been limited in their ability to evaluate ocular tumors. Our purpose was to show the feasibility and potential value of a multiparametric (mp-) MRI protocol employing state of the art diffusion- and perfusion-weighted imaging techniques. METHODS: Sixteen patients with uveal melanoma were imaged with mp-MRI. Multishot readout-segmented echoplanar diffusion-weighted imaging, quantitative dynamic contrast-enhanced (DCE) MR perfusion imaging, and anatomic sequences were obtained. Regions of interest (ROIs) were drawn around tumors for calculation of apparent diffusion coefficient (ADC) and perfusion metrics (K (trans) , v e , k ep , and v p ). A generalized linear fit model was used to compare various MRI values with the American Joint Commission on Cancer (AJCC) tumor group and monosomy 3 status with significance set at P < 0.05. RESULTS: mp-MRI was performed successfully in all cases. MRI tumor height (mean [standard deviation]) was 6.5 mm (3.0). ROI volume was 278 mm(3) (222). ADC was 1.07 (0.27) × 10-3 mm(2)/s. DCE metrics were K (trans) 0.085/min (0.063), v e 0.060 (0.052), k ep 1.20/min (0.32), and v p 1.48 % (0.82). Patients with >33 % monosomy 3 had higher K (trans) and higher v e values than those with disomy 3 or ≤33 % monosomy (P < 0.01). There were no significant differences between ADC (P = 0.07), k ep (P = 0.37), and v p with respect to monosomy 3. CONCLUSION: mp-MRI for ocular tumor imaging using multishot EPI DWI and quantitative DCE perfusion is technically feasible. mp-MRI may help predict monosomy 3 in uveal melanoma.

Musculoskeletal disorders among clerical workers in Los Angeles: a labor management approach.

BACKGROUND: Musculoskeletal disorders (MSDs) persist among clerical workers despite ergonomic advances. METHODS: A cross-sectional survey among 2,310 clerical workers investigated MSD cases, defined as musculoskeletal discomfort and seeking treatment for that discomfort in the past 12 months. A modified Poisson regression model was adopted to assess the association between work and individual factors and the risk of MSDs. RESULTS: Over half of respondents reported musculoskeletal discomfort. The prevalence of MSD cases was: 37.2% neck/shoulders, 21.7% upper extremities, 18% lower extremities, and 34.3% back region. Elevated risk of MSDs was associated with less workstation adjustability; work schedule, gender, age, and BMI were also significant. Positive trends were observed between computer use and MSDs for the neck/shoulder region and the effect was amplified among those reporting insufficient workstation adjustability and lacking computer ergonomics training. CONCLUSIONS: Results demonstrate the need to limit continuous computer use and to improve the human-machine interface through adjustable workstations and worker training to enhance use of adjustable features.

Health literacy screening of geriatric monolingual Spanish-speaking patients using single-item literacy screening questions and education.

OBJECTIVE: We describe the performance of Single Item Literacy Screener (SILS) questions, and educational attainment, as screening for inadequate health literacy (IHL) in older monolingual Spanish speakers. DESIGN: We used a cross-sectional design, interviewing participants once at the time of their arrival for a clinic appointment. SETTING: We conducted this study in primary care and geriatrics clinics in an urban US safety-net hospital. METHOD: We conducted in-person interviews with older monolingual Spanish-speaking diabetes patients, comparing responses to three SILS questions, and education, to shortened Test of Functional Health Literacy in Adults (sTOFHLA) scores. We calculated sensitivities, specificities and areas under the receiving-operator characteristic (AUROC) curve. RESULTS: We interviewed 160 patients - 134 (84%) had IHL by sTOFHLA scores. The best performing SILS question, 'How confident are you filling out medical forms by yourself?' had an AUROC curve of 0.82 (95% CI 0.75-0.89). Using this question's most stringent cut-off, sensitivity was 0.93 (95% CI 0.89-0.97); specificity was 0.27 (95% CI 0.20-0.34). The other two SILS questions had AUROC curves less than 0.50. The educational achievement AUROC curve was 0.88 (95% CI 0.78-0.97); using an education cut-off of six years or less had a specificity to 0.81 (95% CI 0.75-0.87) and sensitivity of 0.83 (95% CI 0.77-0.89). CONCLUSION: Clinicians and investigators considering using single items as screeners for IHL in older US monolingual Spanish speakers should either use the 'confidence with forms' SILS, being aware of its specificity limitations, or a single question assessing educational achievement.

E-scooter related injuries: Using natural language processing to rapidly search 36 million medical notes.

BACKGROUND: Shareable e-scooters have become popular, but injuries to riders and bystanders have not been well characterized. The goal of this study was to describe e-scooter injuries and estimate the rate of injury per e-scooter trip. METHODS AND FINDINGS: Retrospective review of patients presenting to 180 clinics and 2 hospitals in greater Los Angeles between January 1, 2014 and May 14, 2020. Injuries were identified using a natural language processing (NLP) algorithm not previously used to identify injuries, tallied, and described along with required healthcare resources. We combine these tallies with municipal data on scooter use to report a monthly utilization-corrected rate of e-scooter injuries. We searched 36 million clinical notes. Our NLP algorithm correctly classified 92% of notes in the testing set compared with the gold standard of investigator review. In total, we identified 1,354 people injured by e-scooters; 30% were seen in more than one clinical setting (e.g., emergency department and a follow-up outpatient visit), 29% required advanced imaging, 6% required inpatient admission, and 2 died. We estimate 115 injuries per million e-scooter trips were treated in our health system. CONCLUSIONS: Our observed e-scooter injury rate is likely an underestimate, but is similar to that previously reported for motorcycles. However, the comparative severity of injuries is unknown. Our methodology may prove useful to study other clinical conditions not identifiable by existing diagnostic systems.

An analysis of pathologists' viewing processes as they diagnose whole slide digital images.

Although pathologists have their own viewing habits while diagnosing, viewing behaviors leading to the most accurate diagnoses are under-investigated. Digital whole slide imaging has enabled investigators to analyze pathologists' visual interpretation of histopathological features using mouse and viewport tracking techniques. In this study, we provide definitions for basic viewing behavior variables and investigate the association of pathologists' characteristics and viewing behaviors, and how they relate to diagnostic accuracy when interpreting whole slide images. We use recordings of 32 pathologists' actions while interpreting a set of 36 digital whole slide skin biopsy images (5 sets of 36 cases; 180 cases total). These viewport tracking data include the coordinates of a viewport scene on pathologists' screens, the magnification level at which that viewport was viewed, as well as a timestamp. We define a set of variables to quantify pathologists' viewing behaviors such as zooming, panning, and interacting with a consensus reference panel's selected region of interest (ROI). We examine the association of these viewing behaviors with pathologists' demographics, clinical characteristics, and diagnostic accuracy using cross-classified multilevel models. Viewing behaviors differ based on clinical experience of the pathologists. Pathologists with a higher caseload of melanocytic skin biopsy cases and pathologists with board certification and/or fellowship training in dermatopathology have lower average zoom and lower variance of zoom levels. Viewing behaviors associated with higher diagnostic accuracy include higher average and variance of zoom levels, a lower magnification percentage (a measure of consecutive zooming behavior), higher total interpretation time, and higher amount of time spent viewing ROIs. Scanning behavior, which refers to panning with a fixed zoom level, has marginally significant positive association with accuracy. Pathologists' training, clinical experience, and their exposure to a range of cases are associated with their viewing behaviors, which may contribute to their diagnostic accuracy. Research in computational pathology integrating digital imaging and clinical informatics opens up new avenues for leveraging viewing behaviors in medical education and training, potentially improving patient care and the effectiveness of clinical workflow.

External Validation of an Ensemble Model for Automated Mammography Interpretation by Artificial Intelligence.

Importance: With a shortfall in fellowship-trained breast radiologists, mammography screening programs are looking toward artificial intelligence (AI) to increase efficiency and diagnostic accuracy. External validation studies provide an initial assessment of how promising AI algorithms perform in different practice settings. Objective: To externally validate an ensemble deep-learning model using data from a high-volume, distributed screening program of an academic health system with a diverse patient population. Design, Setting, and Participants: In this diagnostic study, an ensemble learning method, which reweights outputs of the 11 highest-performing individual AI models from the Digital Mammography Dialogue on Reverse Engineering Assessment and Methods (DREAM) Mammography Challenge, was used to predict the cancer status of an individual using a standard set of screening mammography images. This study was conducted using retrospective patient data collected between 2010 and 2020 from women aged 40 years and older who underwent a routine breast screening examination and participated in the Athena Breast Health Network at the University of California, Los Angeles (UCLA). Main Outcomes and Measures: Performance of the challenge ensemble method (CEM) and the CEM combined with radiologist assessment (CEM+R) were compared with diagnosed ductal carcinoma in situ and invasive cancers within a year of the screening examination using performance metrics, such as sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC). Results: Evaluated on 37 317 examinations from 26 817 women (mean [SD] age, 58.4 [11.5] years), individual model AUROC estimates ranged from 0.77 (95% CI, 0.75-0.79) to 0.83 (95% CI, 0.81-0.85). The CEM model achieved an AUROC of 0.85 (95% CI, 0.84-0.87) in the UCLA cohort, lower than the performance achieved in the Kaiser Permanente Washington (AUROC, 0.90) and Karolinska Institute (AUROC, 0.92) cohorts. The CEM+R model achieved a sensitivity (0.813 [95% CI, 0.781-0.843] vs 0.826 [95% CI, 0.795-0.856]; P = .20) and specificity (0.925 [95% CI, 0.916-0.934] vs 0.930 [95% CI, 0.929-0.932]; P = .18) similar to the radiologist performance. The CEM+R model had significantly lower sensitivity (0.596 [95% CI, 0.466-0.717] vs 0.850 [95% CI, 0.766-0.923]; P < .001) and specificity (0.803 [95% CI, 0.734-0.861] vs 0.945 [95% CI, 0.936-0.954]; P < .001) than the radiologist in women with a prior history of breast cancer and Hispanic women (0.894 [95% CI, 0.873-0.910] vs 0.926 [95% CI, 0.919-0.933]; P = .004). Conclusions and Relevance: This study found that the high performance of an ensemble deep-learning model for automated screening mammography interpretation did not generalize to a more diverse screening cohort, suggesting that the model experienced underspecification. This study suggests the need for model transparency and fine-tuning of AI models for specific target populations prior to their clinical adoption.

Follow-up of neck and shoulder pain among sewing machine operators: The Los Angeles garment study.

BACKGROUND: The aim of the present study is to explore factors affecting or modifying self-reported neck/shoulder pain in sewing machine operators. METHODS: We investigated self-report neck/shoulder pain in 247 workers who participated in a 4-month prospective intervention study for musculoskeletal disorders. All participants were immigrants. We examine the influence of individual and work-related factors on changes in neck/shoulder pain during follow-up employing linear mixed models with time-spline functions. RESULTS: We observed a dramatic decline (72%) in self-reported pain intensity in the first month of follow-up, followed by a small increase from the first to fourth month (4% per month). Workers who perceived and reported their physical workload as high or worked overtime experienced less overall pain reduction. Higher baseline pain intensity, being of Hispanic ethnicity (vs. Asian), and taking cumulative daily rest time during work of 35 min or more allowing for muscles to rest were associated with a larger pain reduction in the first month, but not thereafter. CONCLUSION: Our findings indicate that some work-related factors may be of clinical relevance for reducing neck/shoulder pain. Having lower physical workloads and less overtime work should be considered when treating patients or planning workplace interventions for managing work-related musculoskeletal disorders in this underserved immigrant population.

Pathology Trainees' Experience and Attitudes on Use of Digital Whole Slide Images.

Digital whole slide images are Food and Drug Administration approved for clinical diagnostic use in pathology; however, integration is nascent. Trainees from 9 pathology training programs completed an online survey to ascertain attitudes toward and experiences with whole slide images for pathological interpretations. Respondents (n = 76) reported attending 63 unique medical schools (45 United States, 18 international). While 63% reported medical school exposure to whole slide images, most reported ≤ 5 hours. Those who began training more recently were more likely to report at least some exposure to digital whole slide image training in medical school compared to those who began training earlier: 75% of respondents beginning training in 2017 or 2018 reported exposure to whole slide images compared to 54% for trainees beginning earlier. Trainees exposed to whole slide images in medical school were more likely to agree they were comfortable using whole slide images for interpretation compared to those not exposed (29% vs 12%; P = .06). Most trainees agreed that accurate diagnoses can be made using whole slide images for primary diagnosis (92%; 95% CI: 86-98) and that whole slide images are useful for obtaining second opinions (93%; 95% CI: 88-99). Trainees reporting whole slide image experience during training, compared to those with no experience, were more likely to agree they would use whole slide images in 5 years for primary diagnosis (64% vs 50%; P = .3) and second opinions (86% vs 76%; P = .4). In conclusion, although exposure to whole slide images in medical school has increased, overall exposure is limited. Positive attitudes toward future whole slide image diagnostic use were associated with exposure to this technology during medical training. Curricular integration may promote adoption.

Dermatopathologists' Experience With and Perceptions of Patient Online Access to Pathologic Test Result Reports.

Importance: Many patients presently have access to their pathologic test result reports via online patient portals, yet little is known about pathologists' perspective on this topic. Objective: To examine dermatopathologists' experience and perceptions of patient online access to pathology reports. Design, Setting, and Participants: A survey of 160 dermatopathologists currently practicing in the United States who are board certified and/or fellowship trained in dermatopathology was conducted between July 15, 2018, and September 23, 2019. Those who reported interpreting skin biopsies of melanocytic lesions within the previous year and expected to continue interpreting them for the next 2 years were included. Main Outcomes and Measures: Dermatopathologists' demographic and clinical characteristics, experiences with patient online access to pathologic test result reports, potential behaviors and reactions to patient online access to those reports, and effects on patients who read their pathologic test result reports online. Results: Of the 160 participating dermatopathologists from the 226 eligible for participation (71% response rate), 107 were men (67%); mean (SD) age was 49 (9.7) years (range, 34-77 years). Ninety-one participants (57%) reported that patients have contacted them directly about pathologic test reports they had written. Some participants noted that they would decrease their use of abbreviations and/or specialized terminology (57 [36%]), change the way they describe lesions suspicious for cancer (29 [18%]), and need specialized training in communicating with patients (39 [24%]) if patients were reading their reports. Most respondents perceived that patient understanding would increase (97 [61%]) and the quality of patient-physician communication would increase (98 [61%]) owing to the availability of online reports. Slightly higher proportions perceived increased patient worry (114 [71%]) and confusion (116 [73%]). However, on balance, most participants (114 [71%]) agreed that making pathologic test result reports available to patients online is a good idea. Conclusions and Relevance: Dermatopathologists in this survey study perceived both positive and negative consequences of patient online access to pathologic test result reports written by the respondents. Most participants believe that making pathologic test result reports available to patients online is a good idea; however, they also report concerns about patient worry and confusion increasing as a result. Further research regarding best practices and the effect on both patients and clinicians is warranted.

Factors associated with HIV viral load in a respondent driven sample in Los Angeles.

This study used a modified version of the Behavioral Model for Vulnerable Populations to examine the predisposing, enabling, and need factors associated with detectable viral load (VL). HIV status was measured using saliva and confirmed by blood. Of 797 persons enrolled, 193 were HIV positive and provided VL counts. A hierarchical multivariate logistic regression approach demonstrated that the predisposing factors of homelessness and recent substance abuse, particularly methamphetamine abuse, had a negative association with VL. The negative association of homelessness on VL was weakened with the introduction of enabling and need utilization factors. Mediation analysis indicated homelessness and HIV medication taking significantly associated with methamphetamine use as a predictor of detectable viral load. Guided policy to address substance abuse among those who are HIV positive is needed to improve biological outcomes.