Improving the utility of evidence synthesis for decision makers in the face of insufficient evidence.

OBJECTIVE: To identify and suggest strategies to make insufficient evidence ratings in systematic reviews more actionable. STUDY DESIGN AND SETTING: A workgroup comprising members from the Evidence-Based Practice (EPC) Program of the Agency for Healthcare Research and Quality convened throughout 2020. We conducted iterative discussions considering information from three data sources: a literature review for relevant publications and frameworks, a review of a convenience sample of past systematic reviews conducted by the EPCs, and an audit of methods used in past EPC technical briefs. RESULTS: We identified five strategies for supplementing systematic review findings when evidence on benefits or harms is expected to be, or found to be, insufficient: 1) reconsider eligible study designs, 2) summarize indirect evidence, 3) summarize contextual and implementation evidence, 4) consider modelling, and 5) incorporate unpublished health system data in the evidence synthesis. While these strategies may not increase the strength of evidence, they may improve the utility of reports for decision makers. Adopting these strategies depends on feasibility, timeline, funding, and expertise of the systematic reviewers. CONCLUSION: Throughout the process of evidence synthesis of early scoping, protocol development, review conduct, and review presentation, authors can consider these five strategies to supplement evidence with insufficient rating to make it more actionable for end-users

Green Synthesis and Biomedical Applications of ZnO Nanoparticles: Role of PEGylated-ZnO Nanoparticles as Doxorubicin Drug Carrier against MDA-MB-231(TNBC) Cells Line

The present study aimed to develop the synthesis of zinc oxide nanoparticles (ZnO-NPs) using the green method, with Aloe barbadensis leaf extract as a stabilizing and capping agent. In vitro antitumor cytotoxic activity, as well as the surface-functionalization of ZnO-NPs and their drug loading capacity against doxorubicin (DOX) and gemcitabine (GEM) drugs, were also studied. Morphological and structural properties of the produced ZnO-NPs were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersion X-ray diffraction (EDX), UV-Vis spectrophotometry, Fourier-transform infrared analysis (FTIR), and X-ray diffraction (XRD). The prepared ZnO-NPs had a hexagonal shape and average particle size of 20–40 nm, with an absorption peak at 325 nm. The weight and atomic percentages of zinc (50.58% and 28.13%) and oxygen (26.71% and 60.71%) were also determined by EDAX (energy dispersive x-ray analysis) compositional analysis. The appearance of the FTIR peak at 3420 m–1 confirmed the synthesis of ZnO-NPs. The drug loading efficiency (LE) and loading capacity (LC) of unstabilized and PEGylated ZnO-NPs were determined by doxorubicin (DOX) and gemcitabine (GEM) drugs. DOX had superior LE 65% (650 mg/g) and higher LC 32% (320 mg/g) than GEM LE 30.5% (30 mg/g) and LC 16.25% (162 mg/g) on ZnO-NPs. Similar observation was observed in the case of PEG-ZnO-NPs, where DOX had enhanced LE 68% (680 mg/g) and LC 35% (350) mg/g in contrast to GEM, which had LE and LC values of 35% (350 mg/g) and 19% (190 mg/g), respectively. Therefore, DOX was chosen to encapsulate nanoparticles, along with the untreated nanoparticles, to check their in vitro antiproliferative potential against the triple-negative breast cancer (TNBC) cell line (MDA-MB-231) through the MTT (3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide) assay. This drug delivery strategy implies that the PEGylated biogenically synthesized ZnO-NPs occupy an important position in chemotherapeutic drug loading efficiency and can improve the therapeutic techniques of triple breast cancer

Associations of sociodemographic and clinical factors with gastrointestinal cancer risk assessment appointment completion

Cancer risk assessment services are important for patient care; effective use requires appropriate provider referral, accurate scheduling processes, and completed attendance at booked appointments. Sociodemographic and clinical factors associated with gastrointestinal cancer (GIC) specific risk assessment appointments remain unstudied; therefore, we aimed to identify factors associated with appointment completion in a GIC risk assessment program at a tertiary academic center. Retrospective chart review was conducted on all patients scheduled for an appointment in the Gastrointestinal Cancer Risk Evaluation Program (GI-CREP) between January 2016 and December 2017. Data collected included demographic and clinical factors. Chi-square and Wilcoxon rank-sum tests compared variables among patients based on the study outcome of whether a GI-CREP appointment was completed; marginal standardization was used to predict the standardized percentage of patients that had appointment completion. A total of 676 patients had a scheduled GI-CREP appointment; 32 individuals were excluded due to incomplete information or scheduling error, resulting in 644 patients available for final analysis. Our study population was predominantly female (61%), White (77%), married (64%), had private healthcare insurance (76%) and lacked a personal history of cancer (60%). Referrals internal to the healthcare system were most common (77%), with gastroenterologists as the most frequent referring provider (42%). Seventy-five percent of scheduled individuals had appointment completion, while 25% of individuals did not. Independent predictors for GI-CREP appointment incompletion included Medicaid insurance (OR 2.45, 95% CI 1.21-4.28, p=0.01), self-identified Black race (OR 1.97, 95% CI: 1.20-3.25, p=0.008), and personal history of cancer (OR 1.60, 95% CI 1.11-2.31, p=0.01). These data highlight existing disparities in GIC risk assessment appointment completion associated with race, health insurance coverage, and medical status. Further studies of these areas are necessary to ensure equitable access to important GIC risk assessment services

Low Referral Rate for Genetic Testing in Racially and Ethnically Diverse Patients Despite Universal Colorectal Cancer Screening

Guidelines recommend that all colorectal tumors be assessed for mismatch repair deficiency, which could increase identification of patients with Lynch syndrome. This is of particular importance for minority populations, in whom hereditary syndromes are under diagnosed. We compared rates and outcomes of testing all tumor samples (universal testing) collected from a racially and ethnically diverse population for features of Lynch syndrome. We performed a retrospective analysis of colorectal tumors tested from 2012 through 2016 at 4 academic centers. Tumor samples were collected from 767 patients with colorectal cancer (52% non-Hispanic white [NHW], 26% African American, and 17% Hispanic patients). We assessed rates of tumor testing, recommendations for genetic evaluation, rates of attending a genetic evaluation, and performance of germline testing overall and by race/ethnicity. We performed univariate and multivariate regression analyses. Overall, 92% of colorectal tumors were analyzed for mismatch repair deficiency without significant differences among races/ethnicities. However, minority patients were significantly less likely to be referred for genetic evaluation (21.2% for NHW patients vs 16.9% for African American patients and 10.9% for Hispanic patients; P = .02). Rates of genetic testing were also lower among minority patients (10.7% for NHW patients vs 6.0% for AA patients and 3.1% for Hispanic patients; P < .01). On multivariate analysis, African American race, older age, and medical center were independently associated with lack of referral for genetic evaluation and genetic testing. In a retrospective analysis, we found that despite similar rates of colorectal tumor analysis, minority patients are less likely to be recommended for genetic evaluation or to undergo germline testing for Lynch syndrome. Improvements in institutional practices in follow up after tumor testing could reduce barriers to diagnosis of Lynch diagnosis in minorities