COVID-19 and Other Viral Infections in Patients With Hematologic Malignancies.

COVID-19 and our armamentarium of strategies to combat it have evolved dramatically since the virus first emerged in late 2019. Vaccination remains the primary strategy to prevent severe illness, although the protective effect can vary in patients with hematologic malignancy. Strategies such as additional vaccine doses and now bivalent boosters can contribute to increased immune response, especially in the face of evolving viral variants. Because of these new variants, no approved monoclonal antibodies are available for pre-exposure or postexposure prophylaxis. Patients with symptomatic, mild-to-moderate COVID-19 and risk features for developing severe COVID-19, who present within 5-7 days of symptom onset, should be offered outpatient therapy with nirmatrelvir/ritonavir (NR) or in some cases with intravenous (IV) remdesivir. NR interacts with many blood cancer treatments, and reviewing drug interactions is essential. Patients with severe COVID-19 should be managed with IV remdesivir, tocilizumab (or an alternate interleukin-6 receptor blocker), or baricitinib, as indicated based on the severity of illness. Dexamethasone can be considered on an individual basis, weighing oxygen requirements and patients' underlying disease and their perceived ability to clear infection. Finally, as CD19-targeted and B-cell maturation (BCMA)-targeted chimeric antigen receptor (CAR) T-cell therapies become more heavily used for relapsed/refractory hematologic malignancies, viral infections including COVID-19 are increasingly recognized as common complications, but data on risk factors and prophylaxis in this patient population are scarce. We summarize the available evidence regarding viral infections after CAR T-cell therapy.

Deep Learning Assistance Closes the Accuracy Gap in Fracture Detection Across Clinician Types.

BACKGROUND: Missed fractures are the most common diagnostic errors in musculoskeletal imaging and can result in treatment delays and preventable morbidity. Deep learning, a subfield of artificial intelligence, can be used to accurately detect fractures by training algorithms to emulate the judgments of expert clinicians. Deep learning systems that detect fractures are often limited to specific anatomic regions and require regulatory approval to be used in practice. Once these hurdles are overcome, deep learning systems have the potential to improve clinician diagnostic accuracy and patient care. QUESTIONS/PURPOSES: This study aimed to evaluate whether a Food and Drug Administration-cleared deep learning system that identifies fractures in adult musculoskeletal radiographs would improve diagnostic accuracy for fracture detection across different types of clinicians. Specifically, this study asked: (1) What are the trends in musculoskeletal radiograph interpretation by different clinician types in the publicly available Medicare claims data? (2) Does the deep learning system improve clinician accuracy in diagnosing fractures on radiographs and, if so, is there a greater benefit for clinicians with limited training in musculoskeletal imaging? METHODS: We used the publicly available Medicare Part B Physician/Supplier Procedure Summary data provided by the Centers for Medicare & Medicaid Services to determine the trends in musculoskeletal radiograph interpretation by clinician type. In addition, we conducted a multiple-reader, multiple-case study to assess whether clinician accuracy in diagnosing fractures on radiographs was superior when aided by the deep learning system compared with when unaided. Twenty-four clinicians (radiologists, orthopaedic surgeons, physician assistants, primary care physicians, and emergency medicine physicians) with a median (range) of 16 years (2 to 37) of experience postresidency each assessed 175 unique musculoskeletal radiographic cases under aided and unaided conditions (4200 total case-physician pairs per condition). These cases were comprised of radiographs from 12 different anatomic regions (ankle, clavicle, elbow, femur, forearm, hip, humerus, knee, pelvis, shoulder, tibia and fibula, and wrist) and were randomly selected from 12 hospitals and healthcare centers. The gold standard for fracture diagnosis was the majority opinion of three US board-certified orthopaedic surgeons or radiologists who independently interpreted the case. The clinicians' diagnostic accuracy was determined by the area under the curve (AUC) of the receiver operating characteristic (ROC) curve, sensitivity, and specificity. Secondary analyses evaluated the fracture miss rate (1-sensitivity) by clinicians with and without extensive training in musculoskeletal imaging. RESULTS: Medicare claims data revealed that physician assistants showed the greatest increase in interpretation of musculoskeletal radiographs within the analyzed time period (2012 to 2018), although clinicians with extensive training in imaging (radiologists and orthopaedic surgeons) still interpreted the majority of the musculoskeletal radiographs. Clinicians aided by the deep learning system had higher accuracy diagnosing fractures in radiographs compared with when unaided (unaided AUC: 0.90 [95% CI 0.89 to 0.92]; aided AUC: 0.94 [95% CI 0.93 to 0.95]; difference in least square mean per the Dorfman, Berbaum, Metz model AUC: 0.04 [95% CI 0.01 to 0.07]; p < 0.01). Clinician sensitivity increased when aided compared with when unaided (aided: 90% [95% CI 88% to 92%]; unaided: 82% [95% CI 79% to 84%]), and specificity increased when aided compared with when unaided (aided: 92% [95% CI 91% to 93%]; unaided: 89% [95% CI 88% to 90%]). Clinicians with limited training in musculoskeletal imaging missed a higher percentage of fractures when unaided compared with radiologists (miss rate for clinicians with limited imaging training: 20% [95% CI 17% to 24%]; miss rate for radiologists: 14% [95% CI 9% to 19%]). However, when assisted by the deep learning system, clinicians with limited training in musculoskeletal imaging reduced their fracture miss rate, resulting in a similar miss rate to radiologists (miss rate for clinicians with limited imaging training: 9% [95% CI 7% to 12%]; miss rate for radiologists: 10% [95% CI 6% to 15%]). CONCLUSION: Clinicians were more accurate at diagnosing fractures when aided by the deep learning system, particularly those clinicians with limited training in musculoskeletal image interpretation. Reducing the number of missed fractures may allow for improved patient care and increased patient mobility. LEVEL OF EVIDENCE: Level III, diagnostic study.

Reevaluation of missed lung cancer with artificial intelligence.

Lung cancer is often missed on chest radiographs, despite chest radiography typically being the first imaging modality in the diagnosis pathway. We present a 46 year-old male with chest pain referred for chest X-ray, and initial interpretation reported no abnormality within the patient's lungs. The patient was discharged but returned 4 months later with persistent and worsening symptoms. At this time, chest X-ray was again performed and revealed an enlarging left perihilar mass with post-obstructive atelectasis in the left lower lobe. Follow-up chest computerized tomography scan confirmed lung cancer with post-obstructive atelectasis, and subsequent bronchoscopy-assisted biopsy confirmed squamous cell carcinoma. Retrospective analysis of the initial chest radiograph, which had reported normal findings, was performed with Chest-CAD, a Food and Drug Administration (FDA) cleared computer-assisted detection (CAD) software device that analyzes chest radiograph studies using artificial intelligence. The device highlighted the perihilar region of the left lung as suspicious. Additional information provided by artificial intelligence software holds promise to prevent missed detection of lung cancer on chest radiographs.

Assessment of a deep-learning system for fracture detection in musculoskeletal radiographs.

Missed fractures are the most common diagnostic error in emergency departments and can lead to treatment delays and long-term disability. Here we show through a multi-site study that a deep-learning system can accurately identify fractures throughout the adult musculoskeletal system. This approach may have the potential to reduce future diagnostic errors in radiograph interpretation.

Deep neural network improves fracture detection by clinicians.

Suspected fractures are among the most common reasons for patients to visit emergency departments (EDs), and X-ray imaging is the primary diagnostic tool used by clinicians to assess patients for fractures. Missing a fracture in a radiograph often has severe consequences for patients, resulting in delayed treatment and poor recovery of function. Nevertheless, radiographs in emergency settings are often read out of necessity by emergency medicine clinicians who lack subspecialized expertise in orthopedics, and misdiagnosed fractures account for upward of four of every five reported diagnostic errors in certain EDs. In this work, we developed a deep neural network to detect and localize fractures in radiographs. We trained it to accurately emulate the expertise of 18 senior subspecialized orthopedic surgeons by having them annotate 135,409 radiographs. We then ran a controlled experiment with emergency medicine clinicians to evaluate their ability to detect fractures in wrist radiographs with and without the assistance of the deep learning model. The average clinician's sensitivity was 80.8% (95% CI, 76.7-84.1%) unaided and 91.5% (95% CI, 89.3-92.9%) aided, and specificity was 87.5% (95 CI, 85.3-89.5%) unaided and 93.9% (95% CI, 92.9-94.9%) aided. The average clinician experienced a relative reduction in misinterpretation rate of 47.0% (95% CI, 37.4-53.9%). The significant improvements in diagnostic accuracy that we observed in this study show that deep learning methods are a mechanism by which senior medical specialists can deliver their expertise to generalists on the front lines of medicine, thereby providing substantial improvements to patient care.

Prevention and Treatment of Cancer-Related Infections, Version 2.2016, NCCN Clinical Practice Guidelines in Oncology.

Infectious diseases are important causes of morbidity and mortality in patients with cancer. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prevention and Treatment of Cancer-Related Infections characterize the major pathogens to which patients with cancer are susceptible, with a focus on the prevention, diagnosis, and treatment of major common and opportunistic infections. This portion of the guidelines highlights the sections on antifungal and antiviral prophylaxis. Antifungal and antiviral prophylaxis recommendations have expanded over the past few years. New agents for the treatment of fungal infections and incorporation of therapeutic drug monitoring are presented. Antiviral prophylaxis for hepatitis B and management considerations for hepatitis C and HIV have been further developed.

Retrieval practice over the long term: should spacing be expanding or equal-interval?

If multiple opportunities are available to review to-be-learned material, should a review occur soon after initial study and recur at progressively expanding intervals, or should the reviews occur at equal intervals? Landauer and Bjork (1978) argued for the superiority of expanding intervals, whereas more recent research has often failed to find any advantage. However, these prior studies have generally compared expanding versus equal-interval training within a single session, and have assessed effects only upon a single final test. We argue that a more generally important goal would be to maintain high average performance over a considerable period of training. For the learning of foreign vocabulary spread over four weeks, we found that expanding retrieval practice (i.e., sessions separated by increasing numbers of days) produced recall equivalent to that from equal-interval practice on a final test given eight weeks after training. However, the expanding schedule yielded much higher average recallability over the whole training period.

Maximizing students' retention via spaced review: practical guidance from computational models of memory.

During each school semester, students face an onslaught of material to be learned. Students work hard to achieve initial mastery of the material, but when they move on, the newly learned facts, concepts, and skills degrade in memory. Although both students and educators appreciate that review can help stabilize learning, time constraints result in a trade-off between acquiring new knowledge and preserving old knowledge. To use time efficiently, when should review take place? Experimental studies have shown benefits to long-term retention with spaced study, but little practical advice is available to students and educators about the optimal spacing of study. The dearth of advice is due to the challenge of conducting experimental studies of learning in educational settings, especially where material is introduced in blocks over the time frame of a semester. In this study, we turn to two established models of memory-ACT-R and MCM-to conduct simulation studies exploring the impact of study schedule on long-term retention. Based on the premise of a fixed time each week to review, converging evidence from the two models suggests that an optimal review schedule obtains significant benefits over haphazard (suboptimal) review schedules. Furthermore, we identify two scheduling heuristics that obtain near optimal review performance: (a) review the material from µ-weeks back, and (b) review material whose predicted memory strength is closest to a particular threshold. The former has implications for classroom instruction and the latter for the design of digital tutors.

Improving students' long-term knowledge retention through personalized review.

Human memory is imperfect; thus, periodic review is required for the long-term preservation of knowledge and skills. However, students at every educational level are challenged by an ever-growing amount of material to review and an ongoing imperative to master new material. We developed a method for efficient, systematic, personalized review that combines statistical techniques for inferring individual differences with a psychological theory of memory. The method was integrated into a semester-long middle-school foreign-language course via retrieval-practice software. Using a cumulative exam administered after the semester's end, we compared time-matched review strategies and found that personalized review yielded a 16.5% boost in course retention over current educational practice (massed study) and a 10.0% improvement over a one-size-fits-all strategy for spaced study.

Prevention and treatment of cancer-related infections.

Patients with cancer are at increased risk for developing infectious complications during the course of their disease and treatment. The following sections of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prevention and Treatment of Cancer-Related Infections provide an overview of the risk factors for infectious complications, recommendations for infectious risk categorization, and strategies for prevention of infections in high-risk patient populations with cancer. Individualized risk evaluation for infections and incorporation of preventative measures are essential components of the overall spectrum of cancer care, and may contribute to optimizing treatment outcomes for patients.

Fever and neutropenia clinical practice guidelines.

Significant progress has been made in managing fever and neutropenia in patients with cancer. Although initial empiric antimicrobial treatment remains the foundation of therapy for such patients, improved diagnostic modalities, models of risk assessment, and an understanding of the various clinical situations in which infections occur have required that treatment approaches and options evolve. The development of broad-spectrum antibiotics with decreased toxicity has improved patient outcomes. Nevertheless, the increasing prevalence of antibiotic-resistant pathogens has challenged the clinician to use antimicrobial therapy wisely. Infection control should not rely exclusively on antimicrobial prophylaxis but, rather, should continue to incorporate standard infection control measures and demand careful handwashing by all health care professionals who come into contact with immunocompromised patients. Invasive fungal pathogens have increased and remain a major concern. Diagnostic and therapeutic modalities for fungal infections remain limited, but careful clinical investigation of new approaches will be needed to define the proper use of these probably expensive new therapeutic additions.