Efficacy of SARS-CoV-2 Vaccine Doses in Allogeneic Hemopoietic Stem Cell Recipients: A Systematic Review and Meta-Analysis.

OBJECTIVE: Recipients of allogeneic hematopoietic cell transplantation (alloHCT) are at increased risk of morbidity and mortality due to COVID-19. Immune responses to SARS-CoV-2 vaccines are blunted in these profoundly immunocompromised patients. As a result, novel strategies for protection, such as additional vaccine doses (boosters), are being explored. However, data regarding the efficacy of a third dose of SARS-CoV-2 vaccine in alloHCT recipients are limited and conflicting. METHODS: In this systematic review and meta-analysis, we investigated the efficacy of a third dose of SARS-CoV-2 vaccine in alloHCT recipients. The review was conducted following PRISMA guidelines, and 7 studies with 385 alloHCT recipients who received 3 vaccine doses were included. The primary outcomes assessed were the rate of seroconversion following the third dose of vaccine and the rate of seroconversion in patients who did not respond to the initial 2-dose vaccination series. RESULTS: The pooled humoral response rate after 3 doses of SARS-CoV-2 vaccine in alloHCT recipients was 74%. In a subgroup analysis of patients who did not respond to the initial 2-dose series, the seroconversion rate following the third vaccine dose was 49%. Notably, male patients and those with a shorter interval between alloHCT and the first vaccine dose were more likely to not respond to the third dose. CONCLUSION: In conclusion, the pooled humoral response rate of 74% following three doses of SARS-CoV-2 vaccine in alloHCT recipients highlights the potential for protection in this immunosuppressed population. Additionally, encouraging responses in nearly half of the patients who did not seroconvert with the initial 2-dose series suggest the continued utilization of additional vaccine doses until results from large prospective studies become available. These findings are critical for informing vaccination strategies in alloHCT recipients to mitigate the high mortality risk associated with COVID-19.

An emerging field: An evaluation of biomedical graduate student and postdoctoral education and training research across seven decades.

Biomedical graduate student and postdoctoral education and training research has expanded greatly over the last seven decades, leading to increased publications and the emergence of a field. The goal of this study was to analyze this growth by performing a cross-sectional bibliometric analysis using a systematic approach to better understand the publishing trends (including historical vs. emerging themes and research priorities); depth, structure, and evidence-basis of content; and venues for publication. The analysis documented a dramatic increase in biomedical trainee-related publications over time and showed that this area of research is maturing into its own independent field. Results demonstrated that the most frequently published article types in this field are shorter editorial and opinion pieces, and that evidence-based articles are less numerous. However, if current trends continue, projections indicate that by the year 2035, evidence-based articles will be the dominating article type published in this field. Most frequently published topics included career outcomes and workforce characterization and professional development. In recent years, the most cited articles were publications focused on diversity, equity, and inclusion, career outcomes and workforce characterization, and wellness. This study also shows that although a small subset of journals publishes most of this literature, publications are distributed diffusely across a wide range of journals and that surprisingly 68% of these journals have published only a single article on the topic. Further, we noted that the assignment of author- and index-supplied keywords was variable and inconsistent and speculate that this could create challenges to conducting comprehensive literature searches. Recommendations to address this include establishing standard keyword assignment criteria and proposing new index-supplied keywords to improve accessibility of research findings. These changes will be important for bringing visibility of this literature to our community, institutional leaders, national trainee organizations, and funding agencies.

Electronic Medical Record-Based Electronic Messaging Among Patients with Breast Cancer: A Systematic Review.

BACKGROUND: Electronic medical record (EMR) systems and electronic messages are an increasingly common conduit between physicians and patients. Clear benefits of this type of communication have been established, especially among cancer patients. Studies suggest that patient portals and electronic messaging platforms can help with care coordination between oncology providers and facilitate asynchronous patient-provider communication. Despite the many benefits, there is little research regarding EMR and secure messaging use, particularly among patients with breast cancer. OBJECTIVES: The objective of this systematic review was to examine the evidence supporting the use of EMR-based messaging systems in patients with breast cancer. METHODS: A systematic literature search of Ovid MEDLINE, PubMed, Scopus, Web of Science CINAHL, and Cochrane Library was conducted. Studies were required to be published between 2005 and 2022 and report data on demographic information and electronic messaging between patients and providers. Studies were excluded if they reported insufficient data, did not include breast cancer patients, or were not published in English. RESULTS: This study identified 10 articles that met inclusion criteria. The resulting studies investigated topics such as: patterns of messaging and medication adherence, cancer screening, messaging as a predictor of behavior or outcomes, and symptom management. The literature indicates that electronic messaging with providers was associated with clinical benefits for breast cancer patients and improved screening behaviors. CONCLUSION: This review uncovered multiple areas to focus future research on, including ideal volume of electronic messages sent and their relation to prescription adherence, studies focusing solely on the breast cancer population, racial disparities in electronic messaging, and provider perceptions of electronic messaging. It is vital that more work be done to understand barriers and gaps in EMR usage to ensure that all individuals can access this increasingly essential medical service while minimizing physician workload and burnout.

Patient-reported cognitive function among hematopoietic stem cell transplant and cellular therapy patients: a scoping review.

PURPOSE: Cognitive dysfunction is a known complication following cellular therapies (CT), which can be assessed through performance based and patient-reported measures. We performed a systematic scoping review to assess self-reported cognitive function measures used among adult CT patients and describe long-term results, including associations with clinical outcomes. METHODS: Library databases were searched from inception to February 2020 according to PRISMA guidelines. Additional studies were identified through reference lists and trial protocols. Two members of the research team screened titles and abstracts and resolved discrepancies. Articles that met eligibility criteria continued to full-text review, with 25% double screening. Articles were removed if they (1) were not original research, peer-reviewed articles; (2) were the wrong disease, age, or treatment-specific patient population; (3) did not use patient-reported outcomes; (4) did not separately report cognitive function outcomes. RESULTS: Of the1952 articles, 56 were included. Twenty-one patient-reported measures of cognitive function were used; most frequently the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30), which includes a two-item cognitive function subscale (57%; n = 32). Thirteen studies collected performance-based and self-reported measures and of those (n = 6) who assessed associations found moderate correlations (range r = .13-.58). Longitudinal patterns showed declines in cognitive function soon after treatment (< 1 month) returning to baseline at 1 year. Cognitive function was often associated with other quality of life measures, chiefly depression (n = 5). CONCLUSIONS: EORTC-QLQ-C30 is the most commonly used to measure, though there remain numerous measures used, including several measures with little previous validation and investigator developed items.

Long peripheral catheters in children: A scoping review.

BACKGROUND AND OBJECTIVES: Long peripheral catheters (LPCs) are emerging vascular access devices used for short-medium term vascular access needs. Literature in adults suggests LPCs have longer dwell-times than peripheral intravenous catheters (PIVs) and lower rates of serious complications than peripherally inserted central catheters (PICCs). The role of LPCs in children is less established. The objective of this scoping review is to describe and synthesize the existing literature on the effectiveness and safety of LPCs in children. METHODS: This review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. Searches were done in MEDLINE (Ovid), Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science Core Collection, Scopus, CINAHL (Ebsco), and Google Scholar most recently on February 22, 2022. Studies were included if published in English on or after 2000 and included patients <18 years of age. RESULTS: Twenty-one studies were included. The body of literature is variable in quality, measurements, and reported outcomes. Median dwell-time ranged from 5 to 14 days. The rate of completion of therapy ranged from 20% to 86%. Dislodgement, occlusion, and infiltration were the most common complications reported (0%-31%). Venous thromboembolism rates ranged from 0% to 13%. The rate of catheter-related bloodstream infection was 0% in 9 of 10 studies. Less than 50% of studies reported comparative outcomes. CONCLUSION: LPCs show promising outcomes in select populations, with longer dwell-time than PIVs and possibly lower rates of serious complications than PICCs. However, more research is needed to clarify the optimal use of LPCs in pediatrics.

Male-specific late effects in adult hematopoietic cell transplantation recipients: a systematic review from the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation.

Male-specific late effects after hematopoietic cell transplantation (HCT) include genital chronic graft-versus-host disease (GvHD), hypogonadism, sexual dysfunction, infertility, and subsequent malignancies. They may be closely intertwined and cause prolonged morbidity and decreased quality of life after HCT. We provide a systematic review of male-specific late effects in a collaboration between transplant physicians, endocrinologists, urologists, dermatologists, and sexual health professionals through the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research, and the Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation. The systematic review summarizes incidence, risk factors, screening, prevention and treatment of these complications and provides consensus evidence-based recommendations for clinical practice and future research.

Male-Specific Late Effects in Adult Hematopoietic Cell Transplantation Recipients: A Systematic Review from the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation.

Male-specific late effects after hematopoietic cell transplantation (HCT) include genital chronic graft-versus-host disease (GVHD), hypogonadism, sexual dysfunction, infertility, and subsequent malignancies, such as prostate, penile, and testicular cancer. These effects may be closely intertwined and cause prolonged morbidity and decreased quality of life after HCT. Here we provide a systematic review of male-specific late effects in a collaboration among transplantation physicians, endocrinologists, urologists, dermatologists, and sexual health professionals through the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and the Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation. We used a systematic review methodology to summarize incidence, risk factors, screening, prevention, and treatment of these complications and provide consensus evidence-based recommendations for clinical practice and future research. Most of the evidence regarding male GVHD is still based on limited data, precluding strong therapeutic recommendations. Therefore, we recommend systematic screening for male genital GVHD regularly and reporting of cases to large registries to allow for a better understanding. Future research also should address treatment, given the little published evidence currently available. Male-specific endocrine consequences of HCT include hypogonadism, which also may affect bone health. Given the scanty evidence, current recommendations for hormone substitution and/or bone health treatment are based on similar principles as for the general population. Following HCT, sexual health decreases, and this topic should be addressed at regular intervals. Future studies should focus on interventional strategies to address sexual dysfunction. Infertility remains prevalent in patients having undergone myeloablative conditioning, warranting the offer of sperm preservation for all HCT candidates. Most studies on fertility rely on descriptive registry analysis and surveys, underscoring the importance of reporting post-HCT conception data to large registries. Although the quality of evidence is low, the development of cancer in male genital organs does not seem more prevalent in HCT recipients compared with the general population; however, subsequent malignancies in general seem to be more prevalent in males than in females, and special attention should be given to skin and oral mucosa. Male-specific late effects, which likely are more underreported than female-specific complications, should be systematically considered during the regular follow-up visits of male survivors who have undergone HCT. Care of patients with male-specific late effects warrants close collaboration between transplantation physicians and specialists from other involved disciplines. Future research should be directed toward better data collection on male-specific late effects and on studies about the interrelationships among these late effects, to allow the development of evidence-based effective management practices.

Evaluation and Medical Management of the Pediatric Patient With Orbital Cellulitis/Abscess: A Systematic Review.

BACKGROUND AND OBJECTIVES: Pediatric orbital cellulitis/abscess (OCA) can lead to vision loss, intracranial extension of infection, or cavernous thrombosis if not treated promptly. No widely recognized guidelines exist for the medical management of OCA. The objective of this review was to summarize existing evidence regarding the role of inflammatory markers in distinguishing disease severity and need for surgery; the role of imaging in OCA evaluation; and the microbiology of OCA over the past 2 decades. METHODS: This review was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Searches were performed in MEDLINE (Ovid), Web of Science Core Collection, Scopus, CINAHL (EBSCO), and Cochrane Central Register of Controlled Trials (CENTRAL), most recently on February 9, 2021. RESULTS: A total of 63 studies were included. Most were descriptive and assessed to have poor quality with high risk of bias. The existing publications evaluating inflammatory markers in the diagnosis of OCA have inconsistent results. Computed tomography imaging remains the modality of choice for evaluating orbital infection. The most common organisms recovered from intraoperative cultures are Streptococcus species (Streptococcus anginosus group, group A Streptococcus, and pneumococcus) and Staphylococcus aureus. Methicillin-resistant S aureus in culture-positive cases had a median prevalence of 3% (interquartile range, 0%-13%). CONCLUSION: This systematic review summarizes existing literature concerning inflammatory markers, imaging, and microbiology for OCA evaluation and management. High-quality evidence is still needed to define the optimal medical management of OCA.

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.

Effectiveness of Mobile Apps to Promote Health and Manage Disease: Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Interventions aimed at modifying behavior for promoting health and disease management are traditionally resource intensive and difficult to scale. Mobile health apps are being used for these purposes; however, their effects on health outcomes have been mixed. OBJECTIVE: This study aims to summarize the evidence of rigorously evaluated health-related apps on health outcomes and explore the effects of features present in studies that reported a statistically significant difference in health outcomes. METHODS: A literature search was conducted in 7 databases (MEDLINE, Scopus, PsycINFO, CINAHL, Global Index Medicus, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews). A total of 5 reviewers independently screened and extracted the study characteristics. We used a random-effects model to calculate the pooled effect size estimates for meta-analysis. Sensitivity analysis was conducted based on follow-up time, stand-alone app interventions, level of personalization, and pilot studies. Logistic regression was used to examine the structure of app features. RESULTS: From the database searches, 8230 records were initially identified. Of these, 172 met the inclusion criteria. Studies were predominantly conducted in high-income countries (164/172, 94.3%). The majority had follow-up periods of 6 months or less (143/172, 83.1%). Over half of the interventions were delivered by a stand-alone app (106/172, 61.6%). Static/one-size-fits-all (97/172, 56.4%) was the most common level of personalization. Intervention frequency was daily or more frequent for the majority of the studies (123/172, 71.5%). A total of 156 studies involving 21,422 participants reported continuous health outcome data. The use of an app to modify behavior (either as a stand-alone or as part of a larger intervention) confers a slight/weak advantage over standard care in health interventions (standardized mean difference=0.38 [95% CI 0.31-0.45]; I2=80%), although heterogeneity was high. CONCLUSIONS: The evidence in the literature demonstrates a steady increase in the rigorous evaluation of apps aimed at modifying behavior to promote health and manage disease. Although the literature is growing, the evidence that apps can improve health outcomes is weak. This finding may reflect the need for improved methodological and evaluative approaches to the development and assessment of health care improvement apps. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42018106868; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=106868.

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.