Citations

Identification of a CD4 + helper T cell population providing in situ help to B and CD8 + T cells in the respiratory mucosa.

Background. Participant withdrawal from clinical trials occurs for various reasons, predominantly adverse effects or intervention inefficacy. Because these missing participant data can have implications for the validity, reproducibility, and generalizability of study results, when conducting a systematic review, it is important to collect and appropriately analyze missing data information to assess its effects on the robustness of the study results. Methods. In this methodologic survey of missing participant data reporting and handling in systematic reviews, we included meta-analyses that provided pooled estimates of at least 1 dichotomous intervention outcome of a randomized controlled trial performed in adult kidney transplant subjects. Results. Eighty-three systematic reviews (17 Cochrane and 66 non-Cochrane reviews) met the inclusion criteria. The most common intervention was drugs (80%), with the majority involving immunosuppressant drugs 55% (n = 46), followed by surgery in 14% (n = 12). The median follow-up duration was 12 months (maximum, 240 mo). Intention-to-treat or modified intention-to-treat analysis was reported in 24% (n = 20) of the reviews (76% of Cochrane and 10% of non-Cochrane). Overall, the majority of systematic reviews did not quantify (90% [n = 60] non-Cochrane and 29% [n = 5] Cochrane) or include the reasons for missing participant data (88% [n = 58] non-Cochrane and 24% [n = 4] Cochrane). Eleven percent (n = 9) handled missing participant data, 5% (n = 4) justified the analytical method(s) used to handle it, and 2% (n = 2) performed a sensitivity analysis for it. Conclusions. Systematic reviews of kidney transplantation provide inadequate information on missing participant data and usually do not handle or discuss the associated risk of bias with it.

The burden of cirrhosis hospitalizations is increasing. The admission Model for End‐Stage Liver Disease–lactate (MELD‐lactate) was recently demonstrated to be a superior predictor of in‐hospital mortality compared with MELD in limited cohorts. We identified specific classes of hospitalizations where MELD‐lactate may be especially useful and evaluated the predictive role of lactate clearance. This was a retrospective cohort study of 1036 cirrhosis hospitalizations for gastrointestinal bleeding, infection, or other portal hypertension–related indications in the Veterans Health Administration where MELD‐lactate was measured on admission. Performance characteristics for in‐hospital mortality were compared between MELD‐lactate and MELD/MELD‐sodium (MELD‐Na), with stratified analyses of MELD categories (≤15, >15 to <25, ≥25) and reason for admission. We also incorporated day 3 lactate levels into modeling and tested for an interaction between day 1 MELD‐lactate and day 3 lactate clearance. MELD‐lactate had superior discrimination for in‐hospital mortality compared with MELD or MELD‐Na (area under the curve [AUC] 0.789 versus 0.776 versus 0.760, respectively; P < 0.001) and superior calibration. MELD‐lactate had higher discrimination among hospitalizations with MELD ≤15 (AUC 0.763 versus 0.608 for MELD, global P = 0.01) and hospitalizations for infection (AUC 0.791 versus 0.674 for MELD, global P < 0.001). We found a significant interaction between day 1 MELD‐lactate and day 3 lactate clearance; heat maps were created as clinical tools to risk‐stratify patients based on these clinical data. MELD‐lactate had significantly superior performance in predicting in‐hospital mortality among patients hospitalized for infection and/or with MELD ≤15 when compared with MELD or MELD‐Na. Incorporating day 3 lactate clearance may further improve prognostication.

8560 Background: Lenalidomide has shown activity in a wide range of hematological malignancies. We conducted a phase II trial of single-agent lenalidomide in indolent non-Hodgkin's lymphoma (NHL). Methods: Patients with relapsed or refractory indolent NHL were eligible, with no limit on the number of previous therapies. Oral lenalidomide 25 mg was self-administered once-daily on days 1–21 of every 28-day cycle for up to 52 weeks as tolerated, or until disease progression. The primary endpoint was overall response rate (ORR), with secondary endpoints of response duration, progression-free survival (PFS), and safety. Results: Forty-three patients were enrolled and were evaluable for response and safety. Patients had received a median of 3 prior systemic therapies (1–17) and half of all patients were refractory to their last therapy. The ORR was 23% (10/43), including a complete response (CR) or unconfirmed CR (CRu) rate of 7%. The median time to first response was 3.6 months (1.7–4.2) and the median time to CR or CRu was 4.2 months (1.9–11.1). Twenty-seven percent (6/22) of patients with follicular lymphoma grade 1 or 2, and 22% (4/18) of patients with small lymphocytic lymphoma responded to therapy. The median duration of response has not reached, but is longer than 16.5 months with 7 of 10 responses ongoing at 15–28 months. Median PFS was 4.4 months (2.5–10.4). Adverse events were consistent with the known safety profile of lenalidomide and manageable; the most common grade 3 or 4 adverse events were neutropenia (30% and 16%, respectively) and thrombocytopenia (14% and 5%, respectively). Conclusions: Oral lenalidomide monotherapy produces durable responses with manageable side effects in relapsed or refractory indolent NHL and warrants further investigation in the treatment of indolent NHL. [Table: see text]

AbstractThe COVID-19 pandemic response in the United States has exposed significant gaps in information systems and processes that prevent timely clinical and public health decision-making. Specifically, the use of informatics to mitigate the spread of SARS-CoV-2, support COVID-19 care delivery, and accelerate knowledge discovery bring to the forefront issues of privacy, surveillance, limits of state powers, and interoperability between public health and clinical information systems. Using a consensus-building process, we critically analyze informatics-related ethical issues in light of the pandemic across 3 themes: (1) public health reporting and data sharing, (2) contact tracing and tracking, and (3) clinical scoring tools for critical care. We provide context and rationale for ethical considerations and recommendations that are actionable during the pandemic and conclude with recommendations calling for longer-term, broader change (beyond the pandemic) for public health organization and policy reform.