Comparative Effectiveness of a Web-Based Patient Decision Aid for Therapeutic Options for Sickle Cell Disease: Randomized Controlled Trial.

BACKGROUND: Hydroxyurea, chronic blood transfusions, and bone marrow transplantation are efficacious, disease-modifying therapies for sickle cell disease but involve complex risk-benefit trade-offs and decisional dilemma compounded by the lack of comparative studies. A patient decision aid can inform patients about their treatment options, the associated risks and benefits, help them clarify their values, and allow them to participate in medical decision making. OBJECTIVE: The objective of this study was to develop a literacy-sensitive Web-based patient decision aid based on the Ottawa decision support framework, and through a randomized clinical trial estimate the effectiveness of the patient decision aid in improving patient knowledge and their involvement in decision making. METHODS: We conducted population decisional needs assessments in a nationwide sample of patients, caregivers, community advocates, policy makers, and health care providers using qualitative interviews to identify decisional conflict, knowledge and expectations, values, support and resources, decision types, timing, stages and learning, and personal clinical characteristics. Interview transcripts were coded using QSR NVivo 10. Alpha testing of the patient decision aid prototype was done to establish usability and the accuracy of the information it conveyed, and then was followed by iterative cycles of beta testing. We conducted a randomized clinical trial of adults and of caregivers of pediatric patients to evaluate the efficacy of the patient decision aid. RESULTS: In a decisional needs assessment, 223 stakeholders described their preferences, helping to guide the development of the patient decision aid, which then underwent alpha testing by 30 patients and 38 health care providers and iterative cycles of beta testing by 87 stakeholders. In a randomized clinical trial, 120 participants were assigned to either the patient decision aid or standard care (SC) arm. Qualitative interviews revealed high levels of usability, acceptability, and utility of the patient decision aid in education, values clarification, and preparation for decision making. On the acceptability survey, 72% (86/120) of participants rated the patient decision aid as good or excellent. Participants on the patient decision aid arm compared to the SC arm demonstrated a statistically significant improvement in decisional self-efficacy (P=.05) and a reduction in the informed sub-score of decisional conflict (P=.003) at 3 months, with an improvement in preparation for decision making (P<.001) at 6 months. However, there was no improvement in terms of the change in knowledge, the total or other domain scores of decisional conflicts, or decisional self-efficacies at 6 months. The large amount of missing data from survey completion limited our ability to draw conclusions about the effectiveness of the patient decision aid. The patient decision aid met 61 of 62 benchmarks of the international patient decision aid collaboration standards for content, development process, and efficacy. CONCLUSIONS: We have developed a patient decision aid for sickle cell disease with extensive input from stakeholders and in a randomized clinical trial demonstrated its acceptability and utility in education and decision making. We were unable to demonstrate its effectiveness in improving patient knowledge and involvement in decision making. TRIAL REGISTRATION: ClinicalTrials.gov NCT03224429; https://clinicaltrials.gov/ct2/show/NCT03224429 and ClinicalTrials.gov NCT02326597; https://clinicaltrials.gov/ct2/show/NCT02326597.

Clinical impact of perineural invasion encircled completely vs. incompletely by prostate cancer on needle core biopsy.

The clinical significance of the pattern or degree of perineural invasion (PNI) by prostate cancer remains largely unknown. We herein assessed radical prostatectomy findings and postoperative oncologic outcomes in 125 patients who had undergone systematic sextant prostate biopsy exhibiting only a single focus of PNI encircled completely (n = 57; 46 %) vs. incompletely (n = 68; 54 %) by cancer. Between these two cohorts, there were no significant differences in clinicopathological features on biopsy or prostatectomy, including tumor grade, stage, and length or volume, and surgical margin status, as well as the need for adjuvant therapy immediately after prostatectomy. Similarly, survival analysis demonstrated no significant difference in the risk of disease progression following prostatectomy in patients with encircled vs. non-encircled PNI on biopsy (P = 0.679). When the non-encircled cases were further divided into four groups [i.e. 1-25 % enclosed (n = 12; 18 %), 26-50 % enclosed (n = 18; 26 %), 51-75 % enclosed (n = 10; 15 %), 76-99 % enclosed (n = 28; 41 %)], the rates of progression-free survival were comparable among the five groups (P = 0.954). In prostate biopsy specimens exhibiting PNI at only one focus, the degree of nerve involvement thus appears to have little clinical impact. Accordingly, PNI detected on prostate biopsy may need to be similarly taken into consideration irrespective of the degree of nerve involvement.

Radiologic-Pathologic Correlation of COVID-19-Associated Acute Disseminated Encephalomyelitis.

A 42-year-old woman presented with drooling, slurred speech, inability to walk and talk, and a recent positive COVID-19 test. She had two prior hospital admissions within the past week for similar symptoms with inconclusive evaluation. MRI of the brain demonstrated multifocal white matter hyperintense lesions on fluid-attenuated inversion recovery (FLAIR)/diffusion with variable enhancement. These imaging findings have been described in recent literature and are associated with inflammatory demyelinating disease, such as acute disseminated encephalomyelitis. The patient subsequently underwent a brain biopsy with a final diagnosis of inflammatory demyelinating lesion. To our knowledge, this is the first radiologic-pathologic correlation of COVID-19-associated acute disseminated encephalomyelitis.

MYC Immunohistochemistry Predicts MYC Rearrangements by FISH.

MYC is the proto-oncogene classically associated with Burkitt lymphoma (BL) located at chromosomal locus 8q24. Rearrangements of MYC are seen in nearly 100% of BL but have been reported in 3-16% of diffuse large B-cell lymphomas (DLBCLs). Rearrangements of MYC are tested for by flourescence in situ hybridization (FISH). In this study, we compared immunohistochemistry (IHC) using a monoclonal antibody directed against the human Myc protein to the current method, FISH. 31 cases were identified that had been tested for MYC rearrangements by FISH over 27 months with heterogeneity in the diagnoses: 5 BL; 10 DLBCL; 3 B-cell lymphoma unclassifiable between DLBCL and BL; 5 B-cell lymphoma not otherwise specified; 1 EBV-related B-cell lymphoma; 1 composite CLL/SLL-large cell lymphoma; and 6 designated as high-grade or aggressive B-cell lymphoma. Analysis by FISH was performed as part of the clinical workup, where a MYC rearrangement is defined as a split fusion signal in at least 5.7% of cells. Myc-IHC was interpreted as a qualitative positive (overexpressed) or negative (not overexpressed) result. 12 cases (39%) were positive for MYC rearrangements by FISH. Overall, 13 cases (42%) showed Myc overexpression by IHC, 11 of which harbored a MYC rearrangement by FISH. There were two false positives and one false negative. Thus, Myc-IHC predicted a MYC rearrangement by FISH with 92% sensitivity and 89% specificity. We can thus conclude that Myc-IHC should be a potentially useful screening tool for identifying lymphomas that may harbor a MYC rearrangement.

ß-Catenin Expression in Oropharyngeal Squamous Cell Carcinomas: Comparison and Correlation with p16 and Human Papillomavirus in situ Hybridization.

BACKGROUND: The Wnt/ß-catenin signaling pathway has been noted to be upregulated in head and neck cancers, including oropharyngeal squamous cell carcinoma (OSCC). This study compared the efficacy of ß-catenin immunohistochemistry (IHC), p16 IHC and automated human papillomavirus (HPV) in situ hybridization (ISH) in OSCC. METHODS: Sixty-eight OSCCs (48 surgical specimens and 20 fine-needle aspirations) were evaluated. Nuclear staining only of ß-catenin was assessed as 0-3+ intensity (relative to controls of benign squamous mucosa). p16 was interpreted as positive if 70% of tumor cells showed brown nuclear and cytoplasmic staining. HPV ISH was interpreted as positive if a minimum of one tumor cell showed brown punctate dot-like nuclear positivity. p16 IHC and HPV ISH were then correlated with ß-catenin staining. HPV ISH was used as the gold standard. RESULTS: Twenty-five of 48 surgical specimens (52.1%) and 11 of 20 cell blocks (55%) stained positively for ß-catenin, making a total of 36 of 68 (52.9%) staining positively for ß-catenin, as compared to 61.7% positive for p16 IHC and 70.6% positive by automated HPV ISH, the gold standard method for OSCC diagnosis. x03C7;2 analysis revealed no significant correlation between ß-catenin and HPV ISH (p > 0.05) and demonstrated a strong correlation between p16 and HPV ISH (p < 0.05). CONCLUSION: ß-Catenin IHC is not a sensitive or specific marker of HPV and is unlikely to be a useful adjunct to p16 IHC or HPV ISH in the setting of advanced OSCC. However, as this study focused on samples of advanced OSCC, ß-catenin IHC may still find some use in the diagnosis of early-stage OSCC.