Allergy Safety Events in Health Care: Development and Application of a Classification Schema Based on Retrospective Review.

BACKGROUND: Allergy safety requires understanding the operational processes that expose patients to their known allergens, including how and when such processes fail. OBJECTIVE: To improve health care safety for patients with allergies, we developed and assessed an allergy safety event classification schema to describe failures resulting in allergy-related safety events. METHODS: Using keyword searches followed by expert manual review of 299,031 voluntarily-filed safety event reports at 2 large academic medical centers, we identified and classified allergy-related safety events from 5 years of safety reports. We used driver diagrams to elucidate root causes for commonly observed allergy safety events in health care settings. RESULTS: From 299,031 safety reports, 1922 (0.6%) were extracted with keywords and 744 (0.2%) were manually confirmed as allergy-related safety events. Safety failures were due to incomplete/inaccurate electronic health record documentation (n = 375, 50.4%), human factors (n = 175, 23.5%), allergy alert limitation and/or malfunction (n = 127, 17.1%), data exchange and interoperability failures (n = 92, 12.4%), and electronic health record system default options (n = 30, 4.0%). Safety failures resulted in known allergen exposures to drugs (n = 537), including heparin (n = 27) and topical anesthetics such as lidocaine (n = 8); latex (n = 114); food allergens (n = 73); and adhesive (n = 23). CONCLUSIONS: We identified 744 allergy-related safety events to inform a novel safety failure classification schema as an important step toward a safer health care environment for patients with allergies. Improved systems are required to address safety issues with certain food and drug allergens.

Improving Allergy Documentation: A Retrospective Electronic Health Record System-Wide Patient Safety Initiative.

OBJECTIVES: Documentation of allergies in a coded, non-free-text format in the electronic health record (EHR) triggers clinical decision support to prevent adverse events. Health system-wide patient safety initiatives to improve EHR allergy documentation by specifically decreasing free-text allergy entries have not been reported. The goal of this initiative was to systematically reduce free-text allergen entries in the EHR allergy module. METHODS: We assessed free-text allergy entries in a commercial EHR used at a multihospital integrated health care system in the greater Boston area. Using both manual and automated methods, a multidisciplinary consensus group prioritized high-risk and frequently used free-text allergens for conversion to coded entries, added new allergen entries, and deleted duplicate allergen entries. Environmental allergies were moved to the patient problem list. RESULTS: We identified 242,330 free-text entries, which included a variety of environmental allergies (42%), food allergies (18%), contrast media allergies (13%), "no known allergy" (12%), drug allergies (2%), and "no contrast allergy" (2%). Most free-text entries were entered by medical assistants in ambulatory settings (34%) and registered nurses in perioperative settings (20%). We remediated a total of 52,206 free-text entries with automated methods and 79,578 free-text entries with manual methods. CONCLUSIONS: Through this multidisciplinary intervention, we identified and remediated 131,784 free-text entries in our EHR to improve clinical decision support and patient safety. Additional strategies are required to completely eliminate free-text allergy entry, and establish systematic, consistent, and safe guidelines for documenting allergies.

Interdisciplinary Patient Tracers: Routine, Systematic Safety Surveillance.

Patient tracers and leadership WalkRounds proactively identify quality and safety issues. However, these programs have been inconsistent in application, results, and sustainability. The goal was to identify a more consistent and efficient approach to survey health care facilities. The authors developed a Peer-to-Peer Interdisciplinary Patient Tracer program to assess compliance with National Patient Safety Goals and to proactively identify areas of inpatient, ambulatory, and procedural risk. The program has been operational for more than 5 years, with continued expansion annually. In all, 96% of frontline leadership reported satisfaction; 100% reported that they would recommend the program to others (Kirkpatrick level 1 results). Mean absolute change in performance scores from 2014 to 2018 was 15%. All survey findings triggered the development of an improvement project. This novel integrated program advanced institutional improvement by strengthening internal peer-to-peer surveillance, engaging leadership, and creating an accountability structure for internal improvement efforts.

Allergic Reactions Captured by Voluntary Reporting.

BACKGROUND: The epidemiology of hospital adverse reactions (ARs), particularly allergic reactions, or hypersensitivity reactions (HSRs), is poorly defined. To determine priorities for allergy safety in healthcare, we identified and described safety reports of allergic reactions. METHODS: We searched the safety report database of a large academic medical center from April 2006 to March 2016 using 101 complete, truncated, and/or misspelled key words related to allergic symptoms, treatments, and culprits (e.g., medications, foods). Patient and event data were summarized for ARs and two types of ARs, HSRs and side effects/toxicities. RESULTS: Among 9111 key word search-identified events, 876 (10%) were ARs, of which 436 (5%) were HSRs and the remaining 440 (5%) were side effect reactions or toxicities. Whereas the most common HSRs were simple cutaneous reactions (83%), the following severe immediate HSRs were also identified: shortness of breath (16%), anaphylaxis (14%), and angioedema (12%). Most HSRs were caused by drugs (81%), with antibiotics (26%), particularly ß-lactams (11%), and vancomycin (8%), commonly implicated. Other causes of drug HSRs included contrast agents (24%), chemotherapeutics (7%), and opioids (6%). Nondrug HSRs were from blood products (8%), latex (3%), and devices (3%). Food reactions were rarely identified (1%). CONCLUSIONS: We identified ARs, HSRs, and side effects/toxicities, contained in a decade of safety reports at an academic medical center. Allergy safety in the healthcare setting should target approaches to common and severe reactions, with a focus on the safe administration of ß-lactams, vancomycin, contrast agents, chemotherapeutics, and opioids. Priority nondrug HSR culprits include blood products, latex, and devices.

Conducting Safety Research Safely: A Policy-Based Approach for Conducting Research with Peer Review Protected Material.

A multidisciplinary team developed a policy-based approach that provides guidance for using peer review protected information for safety research while maintaining peer review privilege. The approach includes project approval by an ad hoc review committee, signed confidentiality agreements by investigators and study staff, early removal of case identification numbers, standards for maintaining data security, and publication of aggregate data without data set sharing. By describing this procedure and embedding into an institutional policy on Data for Performance Improvement, the team encourages other institutions to develop similar policies consistent with their state regulations.

A Survey of Nurse Leaders to Explore the Relationship Between Grit and Measures of Success and Well-being.

OBJECTIVE: The aim of this study was to explore how a personality quality termed grit impacts the well-being and success of nurses who serve in positions of healthcare leadership. BACKGROUND: As the responsibilities of nurse leaders become increasingly complex, there is concern that job satisfaction is becoming more difficult, and burnout and attrition more common. Grit, perseverance, and passion for long-term goals are associated with reduced burnout and predictable success in other industries, but less is known about its impact on nurse leaders. METHODS: Surveys measuring grit and well-being were completed by nurses who identified as leaders. RESULTS: Grit was significantly related to an increased sense of personal accomplishment, increased longevity in leadership roles, and reduced burnout. CONCLUSIONS: Grit contributes to longevity and associates with both higher educational attainment and lower scores for burnout among a large group of nurse leaders surveyed across the United States.

Transfusion Medicine in Sub-Saharan Africa: Conference Summary.

In November 2014, a 3-day conference devoted to transfusion medicine in sub-Saharan Africa was held in Kampala, Uganda. Faculty from academic institutions in Uganda provided a broad overview of issues pertinent to transfusion medicine in Africa. The conference consisted of lectures, demonstrations, and discussions followed by 5 small group workshops held at the Uganda Blood Transfusion Service Laboratories, the Ugandan Cancer Institute, and the Mulago National Referral Hospital. Highlighted topics included the challenges posed by increasing clinical demands for blood, the need for better patient identification at the time of transfusion, inadequate application of the antiglobulin reagent during pretransfusion testing, concern regarding proper recognition and evaluation of transfusion reactions, the expanded role for nurse leadership as a means to improve patient outcomes, and the need for an epidemiologic map of blood usage in Africa. Specialty areas of focus included the potential for broader application of transcranial Doppler and hydroxyurea therapy in sickle cell disease, African-specific guidelines for transfusion support of cancer patients, the challenges of transfusion support in trauma, and the importance of African-centered clinical research in pediatric and obstetric transfusion medicine. The course concluded by summarizing the benefits derived from an organized quality program that extended from the donor to the recipient. As an educational tool, the slide-audio presentation of the lectures will be made freely available at the International Society of Blood Transfusion Academy Web site: http://www.isbtweb.org/academy/.

A phase Ib study of the effects of black raspberries on rectal polyps in patients with familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) is characterized by the early onset of colonic polyposis and a high risk for colorectal cancer. FAP is treated by colectomy followed by lifelong removal of rectal polyps. This study determined whether black raspberries (BRBs) might regress rectal polyps in patients with FAP. Fourteen patients with FAP were treated with BRBs daily for 9 months. Seven patients received BRB powder orally plus two BRB suppositories inserted into the rectum at bedtime. The other 7 received an oral placebo plus the suppositories. Rectal polyp counts and polyp sizes were obtained at time zero and after 9 months of BRB treatment. Polyps and adjacent normal tissue were collected at both time points. The burden (P = 0.036) but not number (P = 0.069) of rectal polyps was significantly decreased. No benefit was noted with the addition of oral BRBs. Three patients were nonresponders. BRBs significantly decreased cellular proliferation, DNA methylation methyl transferase 1 protein expression, and p16 promoter methylation, but not promoter methylation of the Wnt pathway antagonists, SFRP2 and WIF1, in rectal polyps (adenomas) from responders but not from nonresponders. The MBD-seq assay revealed more demethylated transcription start sites (TSS), including those for miRNAs, in BRB-treated adenomas from the responders. In conclusion, BRB suppositories seem sufficient for regressing rectal polyps in patients with FAP.

Black raspberry-derived anthocyanins demethylate tumor suppressor genes through the inhibition of DNMT1 and DNMT3B in colon cancer cells.

We previously reported that oral administration of black raspberry powder decreased promoter methylation of tumor suppressor genes in tumors from patients with colorectal cancer. The anthocyanins (ACs) in black raspberries are responsible, at least in part, for their cancer-inhibitory effects. In the present study, we asked if ACs are responsible for the demethylation effects observed in colorectal cancers. Three days of treatment of ACs at 0.5, 5, and 25 µg/ml suppressed activity and protein expression of DNMT1 and DNMT3B in HCT116, Caco2 and SW480 cells. Promoters of CDKN2A, and SFRP2, SFRP5, and WIF1, upstream of Wnt pathway, were demethylated by ACs. mRNA expression of some of these genes was increased. mRNA expression of ß-catenin and c-Myc, downstream of Wnt pathway, and cell proliferation were decreased; apoptosis was increased. ACs were taken up into HCT116 cells and were differentially localized with DNMT1 and DNMT3B in the same cells visualized using confocal laser scanning microscopy. Although it was reported that DNMT3B is regulated by c-Myc in mouse lymphoma, DNMT3B did not bind with c-Myc in HCT116 cells. In conclusion, our results suggest that ACs are responsible, at least in part, for the demethylation effects of whole black raspberries in colorectal cancers.

Mechanistic basis for the chemopreventive effects of black raspberries at a late stage of rat esophageal carcinogenesis.

The present study used a postinitiation protocol to investigate molecular mechanisms by which black raspberries (BRBs) influence the late stages of N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumorigenesis in rats. F344 rats were injected with NMBA and then fed either control diet or a diet containing 5% BRB powder. Control rats were injected with DMSO/water (20:80), the vehicle for NMBA. Esophagi from control, NMBA- and NMBA + BRB-treated rats were collected at 35 wk for histopathological, molecular, and immunohistochemical analyses. Treatment with 5% BRBs reduced the number of dysplastic lesions and the number and size of esophageal papillomas in NMBA-treated rats. When compared to esophagi from control rats, NMBA treatment led to the differential expression of 4807 genes in preneoplastic esophagus (PE) and 17 846 genes in esophageal papillomas. Dietary BRBs modulated 626 of the 4807 differentially expressed genes in PE and 625 of the 17 846 differentially expressed genes in esophageal papillomas towards normal levels of expression. In both PE and in papillomas, BRBs modulated the mRNA expression of genes associated with carbohydrate and lipid metabolism, cell proliferation and death, and inflammation. In these same tissues, BRBs modulated the expression of proteins associated with proliferation, apoptosis, inflammation, angiogenesis, and both cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism. Interestingly, matrix metalloproteinases involved in tissue invasion and metastasis, and proteins associated with cell-cell adhesion, were also modulated by BRBs. This is the first report of the effects of berries on the expression of genes associated with the late stages of rat esophageal carcinogenesis.

Modulation of genetic and epigenetic biomarkers of colorectal cancer in humans by black raspberries: a phase I pilot study.

PURPOSE: This study evaluated the effects of black raspberries (BRBs) on biomarkers of tumor development in the human colon and rectum including methylation of relevant tumor suppressor genes, cell proliferation, apoptosis, angiogenesis, and expression of Wnt pathway genes. EXPERIMENTAL DESIGN: Biopsies of adjacent normal tissues and colorectal adenocarcinomas were taken from 20 patients before and after oral consumption of BRB powder (60 g/d) for 1-9 weeks. Methylation status of promoter regions of five tumor suppressor genes was quantified. Protein expression of DNA methyltransferase 1 (DNMT1) and genes associated with cell proliferation, apoptosis, angiogenesis, and Wnt signaling were measured. RESULTS: The methylation of three Wnt inhibitors, SFRP2, SFRP5, and WIF1, upstream genes in Wnt pathway, and PAX6a, a developmental regulator, was modulated in a protective direction by BRBs in normal tissues and in colorectal tumors only in patients who received BRB treatment for an average of 4 weeks, but not in all 20 patients with 1-9 weeks of BRB treatment. This was associated with decreased expression of DNMT1. BRBs modulated expression of genes associated with Wnt pathway, proliferation, apoptosis, and angiogenesis in a protective direction. CONCLUSIONS: These data provide evidence of the ability of BRBs to demethylate tumor suppressor genes and to modulate other biomarkers of tumor development in the human colon and rectum. While demethylation of genes did not occur in colorectal tissues from all treated patients, the positive results with the secondary endpoints suggest that additional studies of BRBs for the prevention of colorectal cancer in humans now appear warranted.

Multiple berry types prevent N-nitrosomethylbenzylamine-induced esophageal cancer in rats.

PURPOSE: The present study compared the ability of different berry types to prevent chemically-induced tumorigenesis in the rat esophagus. We also determined if berries influence the levels of inflammatory cytokines in the serum of carcinogen-treated rats. METHODS: Rats were treated with the carcinogen N-nitrosomethylbenzylamine (NMBA) for 5 weeks, then placed on diets containing 5% of either black or red raspberries, strawberries, blueberries, noni, açaí or wolfberry until the end of the study. The effects of the berries on tumor incidence, multiplicity and size were determined, as well as their effects on the levels of selected inflammatory cytokines in serum. RESULTS: All berry types were about equally effective in inhibiting NMBA-induced tumorigenesis in the rat esophagus. They also reduced the levels of the serum cytokines, interleukin 5 (IL-5) and GRO/KC, the rat homologue for human interleukin-8 (IL-8), and this was associated with increased serum antioxidant capacity. CONCLUSIONS: Seven berry types were about equally capable of inhibiting tumor progression in the rat esophagus in spite of known differences in levels of anthocyanins and ellagitannins. Serum levels of IL-5 and GRO/KC (IL-8) may be predictive of the inhibitory effect of chemopreventive agents on rat esophageal carcinogenesis.

Berry ellagitannins may not be sufficient for prevention of tumors in the rodent esophagus.

Biodirected fractionation is used to identify the active inhibitory constituents in berries for esophageal cancer in rats. The present study was undertaken to determine if ellagitannins contribute to the chemopreventive activity of an alcohol/water-insoluble (residue) fraction of berries. Rats consumed diets containing residue fractions of three berry types, that is, black raspberries (BRBs), strawberries (STRWs), and blueberries (BBs), that differ in their content of ellagitannins in the order BRB > STRW > BB. Animals were fed residue diets beginning 2 weeks before treatment with the esophageal carcinogen N-nitrosomethylbenzylamine (NMBA) and throughout the 30-week bioassay. Residue fractions from all three berry types were about equally effective in reducing NMBA tumorigenesis in the rat esophagus irrespective of their ellagitannin content (0.01-0.62 g/kg of diet). These results suggest that the ellagitannins may not be responsible for the chemopreventive effects of the alcohol/water-insoluble fraction of berries.