Proactive Decision Support for Glaucoma Treatment: Predicting Surgical Interventions with Clinically Available Data.

A longitudinal ophthalmic dataset was used to investigate multi-modal machine learning (ML) models incorporating patient demographics and history, clinical measurements, optical coherence tomography (OCT), and visual field (VF) testing in predicting glaucoma surgical interventions. The cohort included 369 patients who underwent glaucoma surgery and 592 patients who did not undergo surgery. The data types used for prediction included patient demographics, history of systemic conditions, medication history, ophthalmic measurements, 24-2 VF results, and thickness measurements from OCT imaging. The ML models were trained to predict surgical interventions and evaluated on independent data collected at a separate study site. The models were evaluated based on their ability to predict surgeries at varying lengths of time prior to surgical intervention. The highest performing predictions achieved an AUC of 0.93, 0.92, and 0.93 in predicting surgical intervention at 1 year, 2 years, and 3 years, respectively. The models were also able to achieve high sensitivity (0.89, 0.77, 0.86 at 1, 2, and 3 years, respectively) and specificity (0.85, 0.90, and 0.91 at 1, 2, and 3 years, respectively) at an 0.80 level of precision. The multi-modal models trained on a combination of data types predicted surgical interventions with high accuracy up to three years prior to surgery and could provide an important tool to predict the need for glaucoma intervention.

Deep Learning Identifies High-Quality Fundus Photographs and Increases Accuracy in Automated Primary Open Angle Glaucoma Detection.

Purpose: To develop and evaluate a deep learning (DL) model to assess fundus photograph quality, and quantitatively measure its impact on automated POAG detection in independent study populations. Methods: Image quality ground truth was determined by manual review of 2815 fundus photographs of healthy and POAG eyes from the Diagnostic Innovations in Glaucoma Study and African Descent and Glaucoma Evaluation Study (DIGS/ADAGES), as well as 11,350 from the Ocular Hypertension Treatment Study (OHTS). Human experts assessed a photograph as high quality if of sufficient quality to determine POAG status and poor quality if not. A DL quality model was trained on photographs from DIGS/ADAGES and tested on OHTS. The effect of DL quality assessment on DL POAG detection was measured using area under the receiver operating characteristic (AUROC). Results: The DL quality model yielded an AUROC of 0.97 for differentiating between high- and low-quality photographs; qualitative human review affirmed high model performance. Diagnostic accuracy of the DL POAG model was significantly greater (P < 0.001) in good (AUROC, 0.87; 95% CI, 0.80-0.92) compared with poor quality photographs (AUROC, 0.77; 95% CI, 0.67-0.88). Conclusions: The DL quality model was able to accurately assess fundus photograph quality. Using automated quality assessment to filter out low-quality photographs increased the accuracy of a DL POAG detection model. Translational Relevance: Incorporating DL quality assessment into automated review of fundus photographs can help to decrease the burden of manual review and improve accuracy for automated DL POAG detection.

Comparative cost savings of biosimilar and dose rounding utilization in oncology care.

INTRODUCTION: The exponential rise in cancer costs has led many centers to utilize dose rounding to the nearest vial size when the difference in dose is ≤10% to decrease costs. The recent approval of several biosimilar products has presented another opportunity to mitigate the rising costs of oncology care. Scarce information exists about the expected cost savings of combining dose rounding strategies (DRS) with biosimilar use (BU). We therefore assessed the cost savings of combining DRS and BU. METHODS: Electronic health record data for two health systems in Rhode Island were used to identify patients who received ≥1 of trastuzumab, trastuzumab-anns, bevacizumab, or bevacizumab-awwb from October 1, 2015 to September 1, 2020. Costs were estimated using Medicare drug pricing. Multivariable generalized estimating equations adjusting for age, gender, presence of metastases, dosing weight, and dose administered were used to compare costs per dose between the four exposure groups: DRS + BU, DRS only, BU only, and neither DRS or BU. RESULTS: A total of 1156 patients were administered 15,145 doses of drug. After covariate adjustment, average savings per dose was greatest in the DRS + BU group (vs. the neither DRS nor BU group); $331 for trastuzumab and $497 for bevacizumab. CONCLUSIONS: Combining dose rounding with biosimilar substitution for trastuzumab and bevacizumab resulted in significant cost savings per dose and should be implemented by healthcare systems.

Survival outcomes associated with corticosteroid use before chemoimmunotherapy in patients with advanced lung cancer.

BACKGROUND: How corticosteroid use affects treatment response to chemotherapy and immune-checkpoint inhibitors (CICPIs) remains unknown. We assessed how systemic corticosteroid exposure before CICPI modifies the effect of CICPI on outcomes among patients with metastatic non-small cell lung cancer (mNSCLC) or extensive-stage small-cell lung cancer (ES-SCLC). METHODS: We conducted a retrospective cohort study using electronic health records to examine patients with mNSCLC or ES-SCLC who received chemotherapy (CT) between 1st April 2015 and 31st January 2018 or CICPI between 1st February 2018 and 31st August 2019. We excluded those with an actionable driver mutation. Baseline corticosteroid use was defined as systemic corticosteroids within 28 days before the initiation of CT or CICPI, not including premedications. Coprimary outcomes included overall survival (OS), real-world progression (rwP), and real-world progression-free survival (rwPFS) in CICPI-treated corticosteroid users versus non-users. We used inverse probability of treatment weighting (IPW) to adjust for potential confounding. RESULTS: The cohort of 316 patients (median [interquartile range] age, 67 [61-73] years; 156 [49%] male) included 228 CT-treated and 88 CICPI-treated patients. After applying IPW, characteristics were well-balanced between the CT and CICPI groups, and steroid users and non-users. Using CT-treated steroid non-users as a common comparator, CICPI-treated steroid users were as likely as CICPI-treated steroid non-users to die (users IPW hazard ratio [HR] = 0.67, 95% CI = 0.35-1.28 versus non-users IPW-HR = 0.88, 95% C = I0.55-1.42; p = 0.49), have rwP (IPW-HR = 0.35, 95% C = I0.12-0.99 versus IPW-HR = 0.41, 95% C = I0.24-0.70; p = 0.77), or experience rwPFS (IPW-HR = 0.56, 95% C = I0.29-1.09 versus IPW-HR = 0.69, 95% CI0.46-1.03; p = 0.59). CONCLUSION: Corticosteroid use before CICPIs was not associated with worse outcomes, suggesting that corticosteroids should be used with CICPIs when indicated.

Pertuzumab-associated diarrhea in HER2/neu-positive breast cancer patients: A comparison of trials to actual practice.

BACKGROUND: Although landmark trials in the metastatic (CLEOPATRA) and neo-adjuvant (NeoSphere; TRYPHAENA) settings identified all-grade diarrhea as a pertuzumab-associated adverse event, it was not classified as dose-limiting. In actual practice, diarrhea is often a reason for treatment modifications. OBJECTIVES: To compare the risk of pertuzumab-associated diarrhea in actual practice to the risks in randomized controlled trials. METHODS: We conducted a retrospective cohort study of HER2/neu-positive breast cancer patients who received a pertuzumab-containing regimen between January 2012 and August 2015. We calculated the risk of diarrhea with 95% confidence limits (CLs), and then used two-sample t-tests to compare the risk between trials and actual practice. RESULTS: A total of 27 patients in the study cohort received a pertuzumab-containing treatment regimen for HER2/neu-positive breast cancer. The overall risk of all-grade and severe diarrhea in actual practice was 70% (95% CLs 55-90%) and 37% (95% CLs 20-66%), respectively. No severe diarrhea was observed in the metastatic setting, and the risk of all-grade diarrhea (44%, 95% CLs 21-92%) was similar to the CLEOPATRA study (67%). The risk of all-grade diarrhea in the neo-adjuvant setting was 83% (95% CLs 68-100%), compared to 46% in the NeoSphere trial (p = 0.03). The risk of severe diarrhea (Grade 3-4) in the neo-adjuvant setting was 47% (95% CLs 27-80%) versus 6% in the NeoSphere (p < 0.0001) and 12% in the TRYPHAENA (p < 0.01) trials. CONCLUSIONS: The risk of all-grade and severe diarrhea associated with neoadjuvant pertuzumab use for HER2/neu-positive breast cancer was greater in actual practice than in trials.

Overuse and underuse of pegfilgrastim for primary prophylaxis of febrile neutropenia.

INTRODUCTION: Guidelines recommend pegfilgrastim for primary prophylaxis of febrile neutropenia after highly myelosuppressive chemotherapy. While deviations from guidelines could result in overuse and increased costs, underuse is also a concern and could compromise quality of care. Our objectives were to evaluate guideline adherence and quantify the extent to which physician heterogeneity may influence pegfilgrastim use. METHODS: We randomly sampled 550 patients from a retrospective cohort of those who received infusions at an academic cancer center between 1 September 2013 and 1 September 2014. Electronic medical and drug dispensing records provided information on patient characteristics, chemotherapy characteristics, prescribing physician, and pegfilgrastim administration. RESULTS: We included 154 patients treated by 25 physicians. About half of patients were male and mean age was 61.3 years. Forty (26.1%) patients had no febrile neutropenia risk factors, 62 (40.5%) had one, and 51 (33.3%) had two or more. Thirty patients (19.5%) received pegfilgrastim, of which 12 (40%) received palliative chemotherapy. Nine (60%) of 15 patients on a regimen with a febrile neutropenia risk ≥ 20% received pegfilgrastim. Pegfilgrastim use significantly varied by cancer type (p < 0.01), chemotherapy regimen (p < 0.001), and regimen febrile neutropenia risk (p < 0.001). Multivariable analysis reaffirmed the association between chemotherapy regimen febrile neutropenia risk ≥ 20% and pegfilgrastim use (odds ratio (OR) = 10.1, 95% confidence interval (CI): 1.6-62.7) and suggested that 31% (95% CI: 8%-71%) of the variation in use was attributable to physician characteristics. CONCLUSION: Pegfilgrastim was potentially overused for palliative chemotherapy and underused for chemotherapy regimens with febrile neutropenia risk ≥ 20%. Successful interventions to modify prescribing practices likely require an understanding of the relationship between specific physician characteristics and pegfilgrastim use.

Use of Charity Financial Assistance for Novel Oral Anticancer Agents.

Novel oral targeted drugs are increasingly used for cancer therapy, but their extreme cost, often exceeding $10,000 per month, poses a significant barrier for patients and insurers alike, leading to the potential breakdown of traditional cost-sharing strategies. Insured patients' routine use of charity assistance to supplement their coverage would indicate a major deficiency in the current health care policies. By using data from a specialty pharmacy affiliated with an academic center (1,557 prescriptions dispensed between January 2014 and March 2017), we examined sources of payment for novel oral anticancer agents, distinguishing contributions from health insurance, patients, and from charitable assistance organizations. Thirty-six percent of 211 patients received charity assistance, including 47% of patients who were 65 years old or older. Charity sources covered 4% of total drug costs and 64% of out-of-pocket expenditures. The proportion of patients receiving financial assistance ranged from 7% when the upfront out-of-pocket requirement was less than $100 to 67% when it exceeded $1,000. When patients' out-of-pocket requirement exceeded $1,000, the median direct cash contribution paradoxically fell to $0 because of extensive use of charity support. Receipt of upfront charity assistance was associated with a longer time to filling the first prescription (median 9 v 7 days; P = .011) and with longer overall duration of therapy (median, 261 v 134 days; P = .014). These findings indicate that high out-of-pocket burden for expensive novel oral anticancer drugs leads to widespread use of charity support in the United States and that a significant financial barrier disparately affects older Medicare beneficiaries.

Improving Glycemic Control With a Standardized Text-Message and Phone-Based Intervention: A Community Implementation.

BACKGROUND: Type II diabetes mellitus (T2DM) presents a major disease burden in the United States. Outpatient glycemic control among patients with T2DM remains difficult. Telemedicine shows great potential as an adjunct therapy to aid in glycemic control in real-world settings. OBJECTIVE: We aimed to explore the effectiveness of EpxDiabetes, a novel digital health intervention, in improving hemoglobin A1c (HbA1c) and fasting blood glucose (FBG) among patients with uncontrolled diabetes. METHODS: We recruited 396 patients from a community clinic in St. Louis, Missouri, from a database of patients diagnosed with T2DM and with a most recent HbA1c >7% as part of a quality improvement project. An automated call or text-messaging system was used to monitor patient-reported FBG. If determined to be elevated, care managers were notified by email, text, or electronic medical record alert. Participants self-reported their FBG data by replying to EpxDiabetes automated phone calls or text messages. Data were subsequently analyzed, triaged, and shared with providers to enable appropriate follow-up and care plan adjustments. Absolute HbA1c reduction, patient engagement, and absolute patient-reported FBG reduction were examined at approximately 6 months post implementation. RESULTS: EpxDiabetes had an average 95.6% patient response rate to messages at least once per month and an average 71.1% response rate to messages at least once per week. Subsequent HbA1c drop with EpxDiabetes use over 4 months was -1.15% (95% CI -1.58 to -0.71) for patients with HbA1c >8% at baseline compared to the change in HbA1c over 4 months prior to the implementation of EpxDiabetes of only -0.005 points (95% CI -0.28 to 0.27), P=.0018. CONCLUSIONS: EpxDiabetes may help reduce HbA1c in patients with high HbA1c baselines (>8%). The intervention demonstrates high patient engagement sustainable for at least 6 months.

Assessing the Utility of a Novel SMS- and Phone-Based System for Blood Pressure Control in Hypertensive Patients: Feasibility Study.

BACKGROUND: Although hypertension (HTN) is a major modifiable risk factor for arterial damage, blood pressure (BP) remains poorly controlled in the hypertensive population. Telemedicine is a promising adjunct intervention that may complement traditional therapies and improve adherence rates; however, current approaches have multiple barriers to entry, including the use of relatively expensive Bluetooth devices or the dependence on smart phone utilization, which tend to exclude low-income and more elderly populations. OBJECTIVE: The aim of this study was to design and implement a new phone call- and short message service text messaging-based intervention, Epharmix's EpxHypertension, in a quality improvement project that demonstrates the feasibility of this system for BP control in a family medicine setting. METHODS: We recruited 174 patients from a community clinic in St Louis from a database of patients diagnosed with HTN. An automated call or text messaging system was used to monitor patient-reported BPs. If determined to be elevated, physicians were notified by an email, text, or electronic medical record alert. Mean systolic BPs (SBPs) and diastolic BPs (DBPs) were compared at the beginning and end of 12 weeks. RESULTS: After 12 weeks on the system, patients with a baseline SBP of 140 mm Hg or higher reduced SBP by 10.8 mm Hg (95% CI -14.5 to -7.2, P<.001) and DBP by 6.6 mm Hg (95% CI -9.9 to -3.4, P=.002), but no significant changes were observed in overall BPs and BPs in the group with baseline SBP less than 140 mm Hg. CONCLUSIONS: EpxHypertension provides a viable means to control HTN in patients with high baseline BPs despite previous therapy. This community implementation study demonstrates the feasibility of implementing EpxHypertension across a primary care setting without the need for smartphones or Bluetooth-linked BP cuffs. Future studies should evaluate its effectiveness in a randomized control trial compared with standard of care.

Is radiology presented to medical students as a fulfilling career?

The Pathway Evaluation Program is a resource that provides profiles of 42 different medical specialities, including diagnostic radiology. It is widely used by medical students. The portrait of radiologic practice it presents is a sobering one and has the potential to deflect top students from careers in radiology. Radiologic educators and practicing radiologists need to understand its findings to improve educational experience and enhance professional fulfillment in the field.