Current Epidemiology and Clinical Features of Cryptococcus Infection in Patients Without Human Immunodeficiency Virus: A Multicenter Study in 46 Hospitals in Australia and New Zealand.

BACKGROUND: Patients without human immunodeficiency virus (HIV) are increasingly recognized as being at risk for cryptococcosis. Knowledge of characteristics of cryptococcosis in these patients remains incomplete. METHODS: We conducted a retrospective study of cryptococcosis in 46 Australian and New Zealand hospitals to compare its frequency in patients with and without HIV and describe its characteristics in patients without HIV. Patients with cryptococcosis between January 2015 and December 2019 were included. RESULTS: Of 475 patients with cryptococcosis, 90% were without HIV (426 of 475) with marked predominance in both Cryptococcus neoformans (88.7%) and Cryptococcus gattii cases (94.3%). Most patients without HIV (60.8%) had a known immunocompromising condition: cancer (n = 91), organ transplantation (n = 81), or other immunocompromising condition (n = 97). Cryptococcosis presented as incidental imaging findings in 16.4% of patients (70 of 426). The serum cryptococcal antigen test was positive in 85.1% of tested patients (319 of 375); high titers independently predicted risk of central nervous system involvement. Lumbar puncture was performed in 167 patients to screen for asymptomatic meningitis, with a positivity rate of 13.2% where meningitis could have been predicted by a high serum cryptococcal antigen titer and/or fungemia in 95% of evaluable cases. One-year all-cause mortality was 20.9% in patients without HIV and 21.7% in patients with HIV (P = .89). CONCLUSIONS: Ninety percent of cryptococcosis cases occurred in patients without HIV (89% and 94% for C. neoformans and C. gattii, respectively). Emerging patient risk groups were evident. A high level of awareness is warranted to diagnose cryptococcosis in patients without HIV.

Is Chemotherapy Associated with Improved Overall Survival in Patients with Dedifferentiated Chondrosarcoma? A SEER Database Analysis.

BACKGROUND: Dedifferentiated chondrosarcoma is a chondrosarcoma subtype associated with high rates of recurrence and a poor prognosis. Others have proposed treatment of dedifferentiated chondrosarcoma using osteosarcoma protocols, including perioperative chemotherapy. However, the rarity of this condition poses difficulties in undertaking single- institution studies of sufficient sample size. QUESTION/PURPOSE: Is perioperative chemotherapy associated with improved overall survival in patients with dedifferentiated chondrosarcoma? METHODS: We queried the Surveillance, Epidemiology, and End Results (SEER) 1973 to 2016 database for patients with a diagnosis of dedifferentiated chondrosarcoma (n = 308). As dedifferentiated chondrosarcoma was only classified as a distinct entity in SEER starting in 2000, only patients treated in 2000 and later were included. We excluded from our analyses those patients with distant disease at diagnosis, a primary site of disease other than bone or joints, and those who did not receive cancer-directed surgery. These criteria yielded 185 dedifferentiated chondrosarcoma patients for inclusion. We used Kaplan-Meier analyses and Cox proportional hazards models to assess the association of clinical, demographic, and treatment characteristics on overall survival (OS). RESULTS: After controlling for confounding variables, including age, sex, tumor size, stage, grade, location, and radiation treatment status, and after adjusting for missing data, no overall survival benefit was associated with receipt of chemotherapy in patients with dedifferentiated chondrosarcoma (hazard ratio 0.75 [95% confidence interval 0.49 to 1.12]; p = 0.16). CONCLUSION: Chemotherapy treatment of dedifferentiated chondrosarcoma was not associated with improved OS. These results must be viewed cautiously, given the limited granularity of information on chemotherapy treatment, the concerns regarding chemotherapy misclassification in SEER data, and the small sample of patients with dedifferentiated chondrosarcoma, all of which limit the power to detect a difference. Our findings are nevertheless consistent with those of prior reports in which no benefit of chemotherapy could be detected. Lack of clear benefit from perioperative chemotherapy in dedifferentiated chondrosarcoma argues that it should be used only after careful consideration, and ideally in the context of a clinical trial. LEVEL OF EVIDENCE: Level III, therapeutic study.

Neoadjuvant Therapy Induces a Potent Immune Response to Sarcoma, Dominated by Myeloid and B Cells.

PURPOSE: To characterize changes in the soft-tissue sarcoma (STS) tumor immune microenvironment induced by standard neoadjuvant therapy with the goal of informing neoadjuvant immunotherapy trial design. EXPERIMENTAL DESIGN: Paired pre- and postneoadjuvant therapy specimens were retrospectively identified for 32 patients with STSs and analyzed by three modalities: multiplexed IHC, NanoString, and RNA sequencing with ImmunoPrism analysis. RESULTS: All 32 patients, representing a variety of STS histologic subtypes, received neoadjuvant radiotherapy and 21 (66%) received chemotherapy prior to radiotherapy. The most prevalent immune cells in the tumor before neoadjuvant therapy were myeloid cells (45% of all immune cells) and B cells (37%), with T (13%) and natural killer (NK) cells (5%) also present. Neoadjuvant therapy significantly increased the total immune cells infiltrating the tumors across all histologic subtypes for patients receiving neoadjuvant radiotherapy with or without chemotherapy. An increase in the percentage of monocytes and macrophages, particularly M2 macrophages, B cells, and CD4+ T cells was observed postneoadjuvant therapy. Upregulation of genes and cytokines associated with antigen presentation was also observed, and a favorable pathologic response (≥90% necrosis postneoadjuvant therapy) was associated with an increase in monocytic infiltrate. Upregulation of the T-cell checkpoint TIM3 and downregulation of OX40 were observed posttreatment. CONCLUSIONS: Standard neoadjuvant therapy induces both immunostimulatory and immunosuppressive effects within a complex sarcoma microenvironment dominated by myeloid and B cells. This work informs ongoing efforts to incorporate immune checkpoint inhibitors and novel immunotherapies into the neoadjuvant setting for STSs.

Durable Improvement in Patient Safety Culture Over 5 Years With Use of High-volume Incident Learning System.

PURPOSE: Incident learning systems (ILSs) require substantial time and effort to maintain, risking staff burnout and ILS disuse. Herein, we assess the durability of ILS-associated safety culture improvements and ILS engagement at 5 years. METHODS AND MATERIALS: A validated survey assessing safety culture was administered to all staff of an academic radiation oncology department before starting ILS and annually thereafter for 5 years. The survey consists of 70 questions assessing key cultural domains, overall patient safety grade, and barriers to incident reporting. A χ2 test was used to compare baseline scores before starting the ILS (pre-ILS) with the aggregate 5 years during which ILS was in use (with ILS). ILS engagement was measured by the self-reported number of ILS entries submitted in the previous 12 months. RESULTS: The survey response rate was ≥68% each year (range, 68%-80%). High-volume event reporting was sustained (4673 reports; average of 0.9 ILS entries per treatment course). ILS engagement increased, with 43% of respondents submitting reports during the 12 months pre-ILS compared with 64% with ILS in use (P < .001). Significant improvements (pre- vs. with-ILS) were observed in the cultural domains of patient safety perceptions (25% vs 39%; P < .03), and responsibility and self-efficacy (43% vs 60%; P < .01). The overall patient safety grade of very good or excellent significantly increased (69% vs 85%; P < .01). Significant reductions were seen in the following barriers to error reporting: embarrassment in front of colleagues, getting colleagues into trouble, and effect on department reputation. CONCLUSIONS: Comprehensive incident learning was sustained over 5 years and is associated with significant durable improvements in metrics of patient safety culture.

Radiation oncology resident training in patient safety and quality improvement: a national survey of residency program directors.

BACKGROUND: Physicians and physicists are expected to contribute to patient safety and quality improvement (QI) in Radiation Oncology (RO), but prior studies suggest that training for this may be inadequate. RO and medical physics (MP) program directors (PDs) were surveyed to better understand the current patient safety/QI training in their residency programs. METHODS: PDs were surveyed via email in January 2017. Survey questions inquired about current training, curriculum elements, and barriers to development and/or improvement of safety and QI training. RESULTS: Eighty-nine RO PDs and 84 MP PDs were surveyed, and 21 RO PDs (28%) and 31 MP PDs (37%) responded. Both RO and MP PDs had favorable opinions of current safety and QI training, and used a range of resources for program development, especially safety and QI publications. Various curriculum elements were reported. Curriculum elements used by RO and MP PDs were similar, except RO were more likely than MP PDs to implement morbidity and mortality (M&M) conference (72% vs. 45%, p < 0.05). RO and MP PDs similarly cited various barriers, but RO PDs were more likely to cite lack of experience than MP PDs (40% vs. 16%, p < 0.05). PDs responded similarly independent of whether they reported using a departmental incident learning system (ILS) or not. CONCLUSIONS: PDs view patient safety/QI as an important part of resident education. Most PDs agreed that residents are adequately exposed to patient safety/QI and prepared to meet the patient safety/QI expectations of clinical practice. This conflicts with other independent studies that indicate a majority of residents feel their patient safety/QI training is inadequate and lacks formal exposure to QI tools.

Step-by-step: a model for practice-based learning.

INTRODUCTION: Innovative technology has led to high-precision radiation therapy that has dramatically altered the practice of radiation oncology. This qualitative study explored the implementation of this innovation into practice from the perspective of the practitioners in a large academic radiation medicine program and aimed to improve understanding of and facilitate the educational process of this change. METHODS: Multiprofession staff participated in a series of seven focus groups and nine in-depth interviews, and the descriptive data from the transcripts were analyzed using grounded theory methodology. RESULTS: Practitioners believed that there had been a major effect on many aspects of their practice. The team structure supported the adoption of change. The technology changed the way the practices worked. Learning new skills increased workload and stress but led to a new conception of the discipline and the generation of new practice-based knowledge. When the concepts were examined longitudinally, a four-step process of learning was identified. In step 1, there was anxiety as staff acquired the skills to use the technology. Step 2 involved learning to interpret new findings and images, experiencing uncertainty until new perspectives developed. Step 3 involved questioning assumptions and critical reflection, which resulted in new understanding. The final step 4 identified a process of constructing new knowledge through research, development, and dialogue within the profession. DISCUSSION: These findings expand our understanding of how practice-based learning occurs in the context of change and can guide learning activities appropriate to each stage.

Targeting safety improvements through identification of incident origination and detection in a near-miss incident learning system.

PURPOSE: Radiation treatment planning involves a complex workflow that has multiple potential points of vulnerability. This study utilizes an incident reporting system to identify the origination and detection points of near-miss errors, in order to guide their departmental safety improvement efforts. Previous studies have examined where errors arise, but not where they are detected or applied a near-miss risk index (NMRI) to gauge severity. METHODS: From 3/2012 to 3/2014, 1897 incidents were analyzed from a departmental incident learning system. All incidents were prospectively reviewed weekly by a multidisciplinary team and assigned a NMRI score ranging from 0 to 4 reflecting potential harm to the patient (no potential harm to potential critical harm). Incidents were classified by point of incident origination and detection based on a 103-step workflow. The individual steps were divided among nine broad workflow categories (patient assessment, imaging for radiation therapy (RT) planning, treatment planning, pretreatment plan review, treatment delivery, on-treatment quality management, post-treatment completion, equipment/software quality management, and other). The average NMRI scores of incidents originating or detected within each broad workflow area were calculated. Additionally, out of 103 individual process steps, 35 were classified as safety barriers, the process steps whose primary function is to catch errors. The safety barriers which most frequently detected incidents were identified and analyzed. Finally, the distance between event origination and detection was explored by grouping events by the number of broad workflow area events passed through before detection, and average NMRI scores were compared. RESULTS: Near-miss incidents most commonly originated within treatment planning (33%). However, the incidents with the highest average NMRI scores originated during imaging for RT planning (NMRI = 2.0, average NMRI of all events = 1.5), specifically during the documentation of patient positioning and localization of the patient. Incidents were most frequently detected during treatment delivery (30%), and incidents identified at this point also had higher severity scores than other workflow areas (NMRI = 1.6). Incidents identified during on-treatment quality management were also more severe (NMRI = 1.7), and the specific process steps of reviewing portal and CBCT images tended to catch highest-severity incidents. On average, safety barriers caught 46% of all incidents, most frequently at physics chart review, therapist's chart check, and the review of portal images; however, most of the incidents that pass through a particular safety barrier are not designed to be capable of being captured at that barrier. CONCLUSIONS: Incident learning systems can be used to assess the most common points of error origination and detection in radiation oncology. This can help tailor safety improvement efforts and target the highest impact portions of the workflow. The most severe near-miss events tend to originate during simulation, with the most severe near-miss events detected at the time of patient treatment. Safety barriers can be improved to allow earlier detection of near-miss events.

Transbronchial lung biopsy (TBLB) in diagnosing pulmonary alveolar proteinosis (PAP): forgotten role in Australia?

Transbronchial lung biopsy (TBLB) is uncommonly performed in non-malignant conditions because of its low sensitivity and small tissue samples. It is not routinely performed in Australia to investigate idiopathic pulmonary fibrosis, although it can be a useful adjunct in obtaining tissue diagnosis in selected conditions in interstitial lung disease (ILD). A 52-year-old non-smoker received a living unrelated renal transplant in January 2014 but developed insidious onset of dyspnea on exertion 1 year later. Computed tomography of the thorax showed bilateral persistent ground glass opacifications with a characteristic crazy paving pattern, although P neumocystis jirovecii pneumonia was more concerning. He was treated as P neumocystis jirovecii pneumonia but his initial bronchoscopy failed to confirm either diagnoses. He then went on to TBLB that showed the presence of periodic acid-Schiff staining material. We conclude that TBLB is a useful adjunct to obtain histological diagnosis of ILD in carefully selected patients with appropriate radiological indications.

Problem solving for breast health care delivery in low and middle resource countries (LMCs): consensus statement from the Breast Health Global Initiative.

International collaborations like the Breast Health Global Initiative (BHGI) can help low and middle income countries (LMCs) to establish or improve breast cancer control programs by providing evidence-based, resource-stratified guidelines for the management and control of breast cancer. The Problem Solving Working Group of the BHGI 2010 Global Summit met to develop a consensus statement on problem-solving strategies addressing breast cancer in LMCs. To better assess breast cancer burden in poorly studied populations, countries require accurate statistics regarding breast cancer incidence and mortality. To better identify health care system strengths and weaknesses, countries require reasonable indicators of true health system quality and capacity. Using qualitative and quantitative research methods, countries should formulate cancer control strategies to identify both system inefficiencies and patient barriers. Patient navigation programs linked to public advocacy efforts feed and strengthen functional early detection and treatment programs. Cost-effectiveness research and implementation science are tools that can guide and expand successful pilot programs.