Health-Related Quality of Life and Costs Associated With Eosinophilic Esophagitis: A Systematic Review.

BACKGROUND & AIMS: Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease characterized by esophageal inflammation and dysfunction. Little is known about the humanistic and economic burden of the disease on patients, their caregivers, and the health care system. A systematic review was conducted to evaluate the existing literature on the disease burden of EoE for patients and their caregivers. METHODS: The MEDLINE, Embase, and Evidence-Based Medicine Reviews databases and recent congresses were searched on March 23, 2017, for English-language publications describing the impact of EoE on health-related quality of life (HRQoL) in children and adults, and the economic burden associated with the disease. RESULTS: Of 676 articles identified, 22 met the inclusion criteria and were included in this analysis (HRQoL, 13; economic burden, 7; cost effectiveness, 2). The included studies showed that EoE is associated with a significant impact on HRQoL, resulting in disruption to and restrictions on daily life for patients, their caregivers, and, in some instances, their families. Treatment with topical corticosteroids, the 6-food elimination diet, or the cow's milk elimination diet significantly improved the HRQoL of patients with EoE. Symptom severity was associated strongly with the impact of EoE on HRQoL. Medical resource utilization costs for patients with EoE were significantly higher than those for healthy controls. CONCLUSIONS: EoE negatively impacts the HRQoL of patients and their families, and is a burden to the health care system. Although data are sparse, currently available treatments appear to improve HRQoL.

Variation of community consultation and public disclosure for a pediatric multi-centered "Exception from Informed Consent" trial.

BACKGROUND: The US federal regulation "Exception from Informed Consent for Emergency Research," 21 Code of Federal Regulations 50.24, permits emergency research without informed consent under limited conditions. Additional safeguards to protect human subjects include requirements for community consultation and public disclosure prior to starting the research. Because the regulations are vague about these requirements, Institutional Review Boards determine the adequacy of these activities at a local level. Thus, there is potential for broad interpretation and practice variation. AIM: To describe the variation of community consultation and public disclosure activities approved by Institutional Review Boards, and the effectiveness of this process for a multi-center, Exception from Informed Consent, pediatric status epilepticus clinical research trial. METHODS: Community consultation and public disclosure activities were analyzed for each of the 15 participating sites. Surveys were conducted with participants enrolled in the status epilepticus trial to assess the effectiveness of public disclosure dissemination prior to study enrollment. RESULTS: Every Institutional Review Board, among the 15 participating sites, had a varied interpretation of Exception from Informed Consent regulations for community consultation and public disclosure activities. Institutional Review Boards required various combinations of focus groups, interviews, surveys, and meetings for community consultation, and news releases, mailings, and public service announcements for public disclosure. At least 4335 patients received information about the study from these efforts. In all, 158 chose to be included in the "Opt Out" list. Of the 304 participants who were enrolled under Exception from Informed Consent, 12 (5%) had heard about the study through community consultation or public disclosure activities. The activities reaching the highest number of participants were surveys and focus groups associated with existing meetings. Public disclosure activities were more efficient and cost-effective if they were part of an in-hospital resource for patients and families. CONCLUSION: There is substantial variation in Institutional Review Boards' interpretations of the federal regulations for community consultation and public disclosure. One of the goals of community consultation and public disclosure efforts for emergency research is to provide community members an opportunity to opt out of Exception from Informed Consent research; however, rarely do patients or their legally authorized representatives report having learned about a study prior to enrollment.

Gilteritinib as Post-Transplant Maintenance for AML With Internal Tandem Duplication Mutation of FLT3.

PURPOSE: Allogeneic hematopoietic cell transplantation (HCT) improves outcomes for patients with AML harboring an internal tandem duplication mutation of FLT3 (FLT3-ITD) AML. These patients are routinely treated with a FLT3 inhibitor after HCT, but there is limited evidence to support this. Accordingly, we conducted a randomized trial of post-HCT maintenance with the FLT3 inhibitor gilteritinib (ClinicalTrials.gov identifier: NCT02997202) to determine if all such patients benefit or if detection of measurable residual disease (MRD) could identify those who might benefit. METHODS: Adults with FLT3-ITD AML in first remission underwent HCT and were randomly assigned to placebo or 120 mg once daily gilteritinib for 24 months after HCT. The primary end point was relapse-free survival (RFS). Secondary end points included overall survival (OS) and the effect of MRD pre- and post-HCT on RFS and OS. RESULTS: Three hundred fifty-six participants were randomly assigned post-HCT to receive gilteritinib or placebo. Although RFS was higher in the gilteritinib arm, the difference was not statistically significant (hazard ratio [HR], 0.679 [95% CI, 0.459 to 1.005]; two-sided P = .0518). However, 50.5% of participants had MRD detectable pre- or post-HCT, and, in a prespecified subgroup analysis, gilteritinib was beneficial in this population (HR, 0.515 [95% CI, 0.316 to 0.838]; P = .0065). Those without detectable MRD showed no benefit (HR, 1.213 [95% CI, 0.616 to 2.387]; P = .575). CONCLUSION: Although the overall improvement in RFS was not statistically significant, RFS was higher for participants with detectable FLT3-ITD MRD pre- or post-HCT who received gilteritinib treatment. To our knowledge, these data are among the first to support the effectiveness of MRD-based post-HCT therapy.

SARS-CoV-2 seroprevalence among healthcare personnel at a large health system in Atlanta.

BACKGROUND: Estimates of the prevalence of SARS-CoV-2 antibodies and factors associated with infection among healthcare personnel (HCP) vary widely. We conducted a serosurvey of HCP at a large public healthcare system in the Atlanta area. MATERIALS AND METHODS: All employees of Grady Health System were invited to participate in mid-2020; a volunteer sample of those completing testing was included. Asymptomatic HCP were offered testing for IgG antibody and for SARS-CoV-2 RNA using polymerase chain reaction (PCR). Symptomatic HCP were offered PCR testing. Antibody index values for IgG and cycle threshold values for PCR were evaluated for those with a positive result. An online survey was distributed at the time of testing. RESULTS: 624 of 1677 distributed surveys (37.2%) were completed by 608 unique HCP. The majority were female (76.4%) and provided clinical care (70.9%). The most common occupations were clinician (24.8%) and nurse (23.5%). 37 of 608 (6.1%) HCP had detectable IgG. Exposure to a confirmed case of COVID-19 outside of the hospital was associated with detectable IgG (12.8% vs 4.4%, p = 0.02), but exposure to a patient with COVID-19 was not. CONCLUSIONS: Among HCP in a large healthcare system, 6.1% had detectable SARS-CoV-2 IgG. Seropositivity was associated with exposures outside of the healthcare setting.

Impact of Single Combination Inhaler versus Multiple Inhalers to Deliver the Same Medications for Patients with Asthma or COPD: A Systematic Literature Review.

With increasing choice of medications and devices for asthma and chronic obstructive pulmonary disease (COPD) treatment, comparative evidence may inform treatment decisions. This systematic literature review assessed clinical and economic evidence for using a single combination inhaler versus multiple inhalers to deliver the same medication for patients with asthma or COPD. In 2016, Embase, PubMed and the Cochrane library were searched for publications reporting studies in asthma or COPD comparing a single-inhaler combination medicine with multiple inhalers delivering the same medication. Publications included English-language articles published since 1996 and congress abstracts since 2013. Clinical, economic and adherence endpoints were assessed. Of 2031 abstracts screened, 18 randomized controlled trials (RCTs) in asthma and four in COPD, nine retrospective and three prospective observational studies in asthma, and four observational studies in COPD were identified. Of these, five retrospective and one prospective study in asthma, and two retrospective studies in COPD reported greater adherence with a single inhaler than multiple inhalers. Nine observational studies reported significantly (n=7) or numerically (n=2) higher rates of adherence with single- versus multiple-inhaler therapy. Economic analyses from retrospective and prospective studies showed that use of single-inhaler therapies was associated with reduced healthcare resource use (n=6) and was cost-effective (n=5) compared with multiple-inhaler therapies. Findings in 18 asthma RCTs and one prospective study reporting lung function, and six RCTs reporting exacerbation rates, showed no significant differences between a single inhaler and multiple inhalers. This was in contrast to several observational studies reporting reductions in healthcare resource use or exacerbation events with single-inhaler treatment, compared with multiple inhalers. Retrospective and prospective studies showed that single-inhaler use was associated with decreased healthcare resource utilization and improved cost-effectiveness compared with multiple inhalers. Lung function and exacerbation rates were mostly comparable in the RCTs, possibly due to study design.

Economic Burden of Chronic Obstructive Pulmonary Disease (COPD): A Systematic Literature Review.

Background and Objectives: Chronic obstructive pulmonary disease (COPD) affects over 250 million people globally, carrying a notable economic burden. This systematic literature review aimed to highlight the economic burden associated with moderate-to-very severe COPD and to investigate key drivers of healthcare resource utilization (HRU), direct costs and indirect costs for this patient population. Materials and Methods: Relevant publications published between January 1, 2006 and November 14, 2016 were captured from the Embase, MEDLINE and MEDLINE In-Process databases. Supplemental searches from relevant 2015-2016 conferences were also performed. Titles and abstracts were reviewed by two independent researchers against pre-defined inclusion and exclusion criteria. Studies were grouped by the type of economic outcome presented (HRU or costs). Where possible, data were also grouped according to COPD severity and/or patient exacerbation history. Results: In total, 73 primary publications were included in this review: 66 reported HRU, 22 reported direct costs and one reported indirect costs. Most of the studies (94%) reported on data from either Europe or North America. Trends were noted across multiple studies for higher direct costs (including mean costs per patient per year and mean costs per exacerbation) being associated with increasingly severe COPD and/or a history of more frequent or severe exacerbations. Similar trends were noted according to COPD severity and/or exacerbation history for rate of hospitalization and primary care visits. Multivariate analyses were reported by 29 studies and demonstrated the statistical significance of these associations. Several other drivers of increased costs and HRU were highlighted for patients with moderate-to-very severe COPD, including comorbidities, and treatment history. Conclusion: Moderate-to-very severe COPD represents a considerable economic burden for healthcare providers despite the availability of efficacious treatments and comprehensive guidelines on their use. Further research is warranted to ensure cost-efficient COPD management, to improve treatments and ease budgetary pressures.

Developing Interactive Exhibits with Scientists: Three Example Collaborations from the Life Sciences Collection at the Exploratorium.

Science museums have made a concerted effort to work with researchers to incorporate current scientific findings and practices into informal learning opportunities for museum visitors. Many of these efforts have focused on creating opportunities and support for researchers to interact face-to-face with the public through, for example, speaker series, community forums, and engineering competitions. However, there are other means by which practicing scientists can find a voice on the museum floor-through the design and development of exhibits. Here we describe how researchers and museum professionals have worked together to create innovative exhibit experiences for an interactive science museum. For each example: scientist as (1) data providers, (2) advisors, and (3) co-developers, we highlight essential components for a successful partnership and pitfalls to avoid when collaborating on museum exhibits. Not many museums prototype and build their own exhibits like the Exploratorium. In those cases, there may be similar opportunities in more mediated offerings such as public demonstrations or lectures or in other formats that allow for direct interactions between scientists and visitors. We believe there are many opportunities for researchers to share natural phenomena, to advise on exhibit development and interpretation, to provide much needed materials, and to otherwise incorporate authentic research into the learning experiences at museums, no matter what the format.

The Cost Effectiveness of High-Dose versus Conventional Haemodialysis: a Systematic Review.

BACKGROUND: End-stage renal disease (ESRD) is fatal if untreated. In the absence of transplant, approximately 50 % of dialysis patients die within 5 years. Although more frequent and/or longer haemodialysis (high-dose HD) improves survival, this regimen may add to the burden on dialysis services and healthcare costs. This systematic review summarised the cost effectiveness of high-dose HD compared with conventional HD. METHODS: English language publications reporting the cost-utility/effectiveness of high-dose HD in adults with ESRD were identified via a search of MEDLINE, Embase, and the Cochrane Library. Publications comparing any form of high-dose HD with conventional HD were reviewed. RESULTS: Seven publications (published between 2003 and 2014) reporting cost-utility analyses from the public healthcare payer perspective were identified. High-dose HD in-centre was compared with in-centre conventional HD in one US model; all other analyses (UK, Canada) compared high-dose HD at home with in-centre conventional HD (n = 5) or in-centre/home conventional HD (n = 1). The time horizon varied from one year to lifetime. Similar survival for high-dose HD and conventional HD was assumed, with the impact of higher survival only assessed in the sensitivity analyses of three models. High-dose HD at home was found to be cost effective compared with conventional HD in all six analyses. The analysis comparing high-dose HD in-centre with conventional in-centre HD produced an incremental cost-effectiveness ratio generally acceptable for the USA, but not for Europe, Canada or Australia. CONCLUSION: High-dose HD can be cost effective when performed at home. Future analyses assuming survival benefits for high-dose HD compared with conventional HD are needed.

Health state utility values associated with advanced gastric, oesophageal, or gastro-oesophageal junction adenocarcinoma: a systematic review.

OBJECTIVES: To systematically identify utility values associated with advanced gastric cancer (GC), oesophageal cancer (OC), or gastro-oesophageal junction (GEJ) cancer. Utility values relating to health states are an essential component for cost-utility analysis (CUA). METHODS: MEDLINE, Embase, Cochrane Library, and EconLit databases were reviewed for relevant studies using a pre-defined search strategy. Studies eligible for inclusion reported health state utility values (HSUVs) using direct (standard gamble [SG] and time-trade-off [TTO]) and indirect (such as EuroQol 5D [EQ-5D], short-form 6D [SF-6D], and the 15-dimensional instrument [15D]) methods for patients with advanced GC, OC, or GEJ cancer. RESULTS: A total of 539 unique publications were identified, of which eight met the inclusion criteria (GC, n = 2; mixed population [gastrointestinal cancers], n = 4; OC, n = ). The most commonly used instrument to estimate HSUVs was the EQ-5D (n = 7). Utilities were also estimated using the SF-6D and the 15D in the same study (n = 1). Direct elicitation methods included the TTO (n = 2) and SG (n = 1). Across the eight identified publications, health states and study populations were heterogeneous and sample sizes were limited. LIMITATIONS: This review, as with all summaries of this nature, is only as robust as the data derived from the identified studies. The systematic review process does not resolve any design issues or biases associated with the original studies. CONCLUSIONS: Limited data estimate HSUVs in patients with advanced GC, OC, or GEJ cancer. Utilities for advanced GC alone and advanced OC alone were reported in only two publications for each cancer type. No publications considered advanced GEJ utilities alone, and four publications considered utilities for a mixed population of gastrointestinal cancer types. Comparisons are confounded by heterogeneity across the identified publications. Further research into HSUVs associated with advanced GC and OC is required to improve the evidence available for use in CUAs.

Premature thelarche and granulosa cell tumors: a search for FSH receptor and G5alpha activating mutations.

Activating mutations of the Gsalpha gene are responsible for McCune-Albright syndrome and have also been identified in sporadic tumors of the pituitary and thyroid. When associated with malignancy, activating Gsalpha mutations are known as gsp-oncogenes. We hypothesized that similar activating mutations might also account for some cases of premature thelarche and/ or granulosa cell tumors. Polymerase chain reaction and DNA sequencing was used to screen for activating mutations of Gsalpha genes in children with premature thelarche and in pathologic specimens from juvenile and adult granulosa cell tumors. Because these disorders involve over-activity of the FSH-signaling pathway, we also screened for activating mutations of the FSH receptor. No mutations were detected in either the Gsalpha or the FSHR fragment studied. Previously reported polymorphisms (Ser680Asn and Ala307Thr) of the FSHR were detected in 25/27 tumor samples and 9/9 premature thelarche samples. We conclude that activating mutations in previously identified mutation 'hot-spots' in the Gsalpha and FSH receptor genes are probably not a major cause of premature thelarche or granulosa cell tumors. In contrast, polymorphisms of the FSH receptor are common.

Evaluation of the comprehensiveness and reliability of the chromium composition of foods in the literature ().

In the early 1960s, trivalent chromium Cr(3+) became recognized as an essential trace element due to its potential metabolic and cardiovascular benefits. No comprehensive chromium database currently exists; thus a thorough review of the literature was conducted to examine the availability and reliability of chromium data for foods. A number of key issues were identified that challenge the feasibility of adding chromium to a food and nutrient database. Foremost, dietary chromium data reported in the literature prior to 1980 cannot be relied on because of problematic analytical issues before that time. Next, paucity of data emerged as an issue that could impede database completeness. Finally, large variation in reported chromium content of foods may render disputable representative chromium values. This variation has been speculated to originate from differences in growing and particularly processing foods. Furthermore, contamination of chromium from laboratory equipment and/or materials is possible and also believed to contribute to the variation observed in reported values. As a result, database developers must carefully consider the availability and reliability of information on the chromium composition of foods when deciding whether to incorporate chromium into or exclude it from a nutrient database.

Religiosity as a mediator of caregiver well-being: does ethnicity make a difference?

This study used an adaptation of the stress and appraisal model to examine the mediating effects of religiosity on caregiving strain and gain with an ethnically diverse sample of 384 Alzheimer's disease caregivers. While the regression analysis indicated that religiosity did not mediate the stress of providing care for the entire sample, there were significant differences in the use of religiosity depending on the ethnicity (African American, Hispanic, and White non-Hispanic) of the caregiver, as well as significant differences between the three cohorts in the levels of caregiving strain (depression) and gain (self-acceptance). Implications for the use of religiosity as a protective factor for AD caregivers are discussed.

Differential expression of GRK isoforms in nonmalignant and malignant human granulosa cells.

Granulosa cell tumors are serious ovarian neoplasms that can occur in women of all ages. While there have been numerous attempts to understand the cause of these malignancies, the pathogenesis of granulosa cell tumors (GCTs) still remains largely unknown. G-protein coupled receptor kinases (GRKs) are important regulators of signal transduction through the process of receptor desensitization and internalization. Receptors that are regulated by GRKs are members of the large family of seven-transmembrane receptors and include the follicle stimulating hormone receptor (FSHR). In granulosa cells, the FSH signaling system is responsible for cell proliferation, differentiation, and steroidogenesis. In the studies presented, we examined GRK mRNA and protein expression in nonmalignant human granulosa cells, in KGN cells, a human GCT cell line, and in a panel of human GCT samples. The KGN tumor cells express significantly less GRK4 alpha/beta protein and higher levels of GRK2 and GRK4 gamma/delta protein as compared to nonmalignant human granulosa cells. In human GCT samples, GRK4 alpha/beta protein was detected in 3 of the 13 tumor samples, whereas gamma/delta proteins expression was detected in all samples. These findings suggest that GRK protein expression is altered in GCTs and may be involved in the pathogenesis of these tumors.