Systematic Reviews in Hematopoietic Cell Transplantation and Cellular Therapy: Considerations and Guidance from the American Society for Transplantation and Cellular Therapy, European Society for Blood and Marrow Transplantation, and Center for International Blood and Marrow Transplant Research Late Effects and Quality of Life Working Committee.

Systematic reviews apply rigorous methodologies to address a prespecified, clearly formulated clinical research question. The conclusion that results is often cited to more robustly inform decision making by clinicians, third-party payers, and managed care organizations about the clinical question of interest. Although systematic reviews provide a rigorous standard, they may be infeasible when the task is to create general disease-focused guidelines comprising multiple clinical practice questions versus a single major clinical practice question. Collaborating transplantation and cellular therapy society committees also recognize that the quantity and or quality of reference sources may be insufficient for a meaningful systematic review. As the conduct of systematic reviews has evolved over time in terms of grading systems, reporting requirements, and use of technology, here we provide current guidance on methodologies, resources for reviewers, and approaches to overcome challenges in conducting systematic reviews in transplantation and cellular therapy.

Compiling Evidence for EVALI: A Scoping Review of In Vivo Pulmonary Effects After Inhaling Vitamin E or Vitamin E Acetate.

BACKGROUND: Vitamin E acetate (VEA) has come under significant scrutiny due to its association with E-cigarette or vaping product use-associated lung injury (EVALI). Various theoretical mechanisms have been proposed for toxicity, including tocopherol (vitamin E)-mediated surfactant damage, recruitment of inflammation, and pyrolysis of acetate to the pulmonary irritant ketene. OBJECTIVE: Characterize studies in mammals evaluating inhaled VEA, vitamin E analogues, or pyrolyzed acetate that describe subsequent effects on the lung. ELIGIBILITY: Research in all languages from time of inception to October 1, 2020, regarding mammals (human or animal) exposed to inhaled vitamin E analogues, or any compound containing acetate administered via inhalation after pyrolysis, and subsequent description of pulmonary effect. SOURCES OF EVIDENCE: Ovid MEDLINE, Scopus, and Web of Science Core Collection. RESULTS: In total, 786 unique articles were identified. After duplicate reviewer screening, 16 articles were eligible for inclusion. Tocopherol was evaluated in 68.8% (11/16) of the studies, VEA in 18.8% (3/16), and both VEA and tocopherol were evaluated in 12.5% (2/16). Of the five studies evaluating VEA, it was given by pyrolysis in 60.0% (3/5). No human studies were identified. All included trials were conducted on non-human mammals: 75.0% (12/16) rodent models and 25.0% (4/16) sheep models. Outcomes assessed were heterogeneous and included 57 unique outcomes. CONCLUSIONS: Several questions still exist regarding the pulmonary toxicity of inhaled tocopherol and VEA. More studies are needed to determine whether tocopherol alone (i.e., without acetate) can cause pulmonary injury. Additionally, further studies of VEA should evaluate the impact that pyrolysis and co-administration with other compounds, such as tetrahydrocannabinol, have on the toxic potential of VEA.

Systematic reviews in hematopoietic cell transplantation and cellular therapy: considerations and guidance from the American Society for Transplantation and Cellular Therapy, European Society for Blood and Marrow Transplantation, and the Center for International Blood and Marrow Transplant Research late effects and quality of life working committee.

Systematic reviews apply rigorous methodologies to address a pre-specified, clearly formulated clinical research question. The conclusion that results is often cited to more robustly inform decision-making by clinicians, third-party payers and managed care organizations about the clinical question of interest. While systematic reviews provide a rigorous standard, they may be unfeasible when the task is to create general disease-focused guidelines comprised of multiple clinical practice questions versus a single major clinical practice question. Collaborating transplantation and cellular therapy societal committees also recognize that the quantity and or quality of reference sources may be insufficient for a meaningful systematic review. As the conduct of systematic reviews has evolved over time in terms of grading systems, reporting requirements and use of technology, here we provide current guidance in methodologies, resources for reviewers, and approaches to overcome challenges in conducting systematic reviews in transplantation and cellular therapy.

Assessment of Citations of the Retracted Article by Wakefield et al With Fraudulent Claims of an Association Between Vaccination and Autism.

Importance: The number of citations can be used to show the influence of an article or to measure the validity of a research study. The article by Wakefield et al that fraudulently reported an association between vaccination and autism continues to accumulate citations even after it was retracted. Objectives: To examine the characteristics of citations from scholarly literature that reference the 1998 article by Wakefield et al and to investigate whether authors are accurately citing retracted references. Design, Setting, and Participants: In this cross-sectional bibliographic analysis of the scholarly publications that cited a 1998 article by Wakefield et al, cited references were collected from a Web of Science Core Collection search performed on March 11, 2019. A total of 1211 articles were identified, with 58 citing works excluded because they were non-English-language publications or the citation to the study by Wakefield et al could not be located by reviewers. Citing works consisted of books, research articles, letters, editorials, news items, and other scholarly literature. Citations to the article by Wakefield et al were identified and analyzed by 2 reviewers in a blinded screening. Reviewers assigned a characteristic to each citation and indicated whether the retraction was documented. Main Outcomes and Measures: The characteristics of citations to the article by Wakefield et al, were categorized as negative, affirmative, or contrastive; if not, persuasive; and if not, assumptive, perfunctory, methodologic, or conceptual. Whether the partial retraction or notice of retraction was included in the citing work was also documented. Results: Among the 1153 citing works included in this analysis, the most common citation characteristics were negative (838 [72.7%]) followed by perfunctory (106 [9.2%]) and affirmative (94 [8.2%]). A total of 123 of 322 citing works (38.2%) published between 2005 and 2010 documented the partial retraction. After the notice of retraction was published in 2010, the percentage of citing works that documented the partial retraction and/or notice of retraction between 2011 and 2018 increased to 360 of 502 (71.7%). Conclusions and Relevance: Since the article by Wakefield et al was initially published, authors have mostly negated the findings of the study. A significant number of authors did not document retractions of the article by Wakefield et al. The findings suggest that improvements are needed from publishers, bibliographic databases, and citation management software to ensure that retracted articles are accurately documented.

Advanced biomarkers of pediatric mild traumatic brain injury: Progress and perils.

There is growing public concern about neurodegenerative changes (e.g., Chronic Traumatic Encephalopathy) that may occur chronically following clinically apparent and clinically silent (i.e., sub-concussive blows) pediatric mild traumatic brain injury (pmTBI). However, there are currently no biomarkers that clinicians can use to objectively diagnose patients or predict those who may struggle to recover. Non-invasive neuroimaging, electrophysiological and neuromodulation biomarkers have promise for providing evidence of the so-called "invisible wounds" of pmTBI. Our systematic review, however, belies that notion, identifying a relative paucity of high-quality, clinically impactful, diagnostic or prognostic biomarker studies in the sub-acute injury phase (36 studies on unique samples in 28 years), with the majority focusing on adolescent pmTBI. Ultimately, well-powered longitudinal studies with appropriate control groups, as well as standardized and clearly-defined inclusion criteria (time post-injury, injury severity and past history) are needed to truly understand the complex pathophysiology that is hypothesized (i.e., still needs to be determined) to exist during the acute and sub-acute stages of pmTBI and may underlie post-concussive symptoms.