Assessing micro- vs macro-costing approaches for treating appendicitis in children with appendicectomy or non-operatively

OBJECTIVES: We conducted a health economic sub-study within a feasibility RCT comparing a non-operative treatment pathway as an alternative to appendicectomy for the treatment of uncomplicated acute appendicitis in children. The objectives were to understand and assess data collection tools and methods and to determine indicative costs and benefits assessing the feasibility of conducting a full economic evaluation within the definitive trial. METHODS: We compared different methods of estimating treatment costs including micro-costing, hospital administrative data (PLICS) and health system (NHS) reference costs. We compared two different HRQoL instruments (CHU-9D and EQ-5D-5L) in terms of data completeness and sensitivity to change over time, including potential ceiling effects. We also explored how the timing of data collection and duration of the analysis could affect QALYs (Quality Adjusted Life Years) and the results of the cost-utility analysis (CUA) within the future RCT. RESULTS: Using a micro-costing approach, the total per treatment costs were in alignment with hospital administrative data (PLICS). Average health system reference cost data (macro-costing using NHS costs) could potentially underestimate these treatment costs, particularly for non-operative treatment. Costs incurred following hospital discharge in the primary care setting were minimal, and limited family borne costs were reported by parents/carers. While both HRQoL instruments performed relatively well, our results highlight the problem of ceiling effect and the importance of the timing of data collection and the duration of the analysis in any future assessment using QALYs and CUA. CONCLUSIONS: We highlighted the importance of obtaining accurate individual-patient cost data when conducting economic evaluations. Our results suggest that timing of data collection and duration of the assessment are important considerations when evaluating cost-effectiveness and reporting cost per QALY. CLINICAL TRIAL REGISTRATION: Current Controlled Trials ISRCTN15830435

Patients\u27 Willingness to Accept Social Needs Navigation After In-Person Versus Remote Screening

Social needs screening and referral interventions are increasingly common in health care settings. Although remote screening offers a potentially more practical alternative to traditional in-person screening, there is concern that screening patients remotely could adversely affect patient engagement, including interest in accepting social needs navigation

The Lantern Vol. 58, No. 2, Summer 1991

• We All Fall Up • Clerical Nightmares • The Brass Bed • Mon Amour • The Lady of J. Alfred Prufrock • Forbidden Places • Edge of the Dance • Crystal World • Saturday, July 12, 1978, 4:59 pm • Of You I Think • Just Another Statistic • A $16 Word in a$4.99 Trashcan • Souvenir • The Jester • Against a Rock • I Wish I Were a Fish • Too Small, Too Weak • Somewheres in N.Y.C. • Stuck Up • Patterns • I Should Tell You Now • Me, Tommy, and Miss May • Two Hands • All-Natural, Organically Grown Macadamia Butter • Irony of a Suburban Deathhttps://digitalcommons.ursinus.edu/lantern/1138/thumbnail.jp

Field Demonstration of DNAPL Dehalogenation Using Emulsified Zero-Valent Iron

This paper describes the results of the first field-scale demonstration conducted to evaluate the performance of nano-scale emulsified zero-valent iron (EZVI) injected into the saturated zone to enhance in situ dehalogenation of dense, non-aqueous phase liquids (DNAPLs) containing trichloroethene (TCE). EZVI is an innovative and emerging remediation technology. EZVI is a surfactant-stabilized, biodegradable emulsion that forms emulsion droplets consisting of an oil-liquid membrane surrounding zero-valent iron (ZVI) particles in water. EZVI was injected over a five day period into eight wells in a demonstration test area within a larger DNAPL source area at NASA's Launch Complex 34 (LC34) using a pressure pulse injection method. Soil and groundwater samples were collected before and after treatment and analyzed for volatile organic compounds (V005) to evaluate the changes in VOC mass, concentration and mass flux. Significant reductions in TCE soil concentrations (>80%) were observed at four of the six soil sampling locations within 90 days of EZVI injection. Somewhat lower reductions were observed at the other two soil sampling locations where visual observations suggest that most of the EZVI migrated up above the target treatment depth. Significant reductions in TCE groundwater concentrations (57 to 100%) were observed at all depths targeted with EZVI. Groundwater samples from the treatment area also showed significant increases in the concentrations of cis-1,2-dichloroethene (cDCE), vinyl chloride (VC) and ethene. The decrease in concentrations of TCE in soil and groundwater samples following treatment with EZVI is believed to be due to abiotic degradation associated with the ZVI as well as biodegradation enhanced by the presence of the oil and surfactant in the EZVI emulsion

Convergent evolution of monocyte differentiation in adult skin instructs Langerhans cell identity

Langerhans cells (LCs) are distinct among phagocytes, functioning both as embryo-derived, tissue-resident macrophages in skin innervation and repair and as migrating professional antigen-presenting cells, a function classically assigned to dendritic cells (DCs). Here, we demonstrate that both intrinsic and extrinsic factors imprint this dual identity. Using ablation of embryo-derived LCs in the murine adult skin and tracking differentiation of incoming monocyte-derived replacements, we found intrinsic intraepidermal heterogeneity. We observed that ontogenically distinct monocytes give rise to LCs. Within the epidermis, Jagged-dependent activation of Notch signaling, likely within the hair follicle niche, provided an initial site of LC commitment before metabolic adaptation and survival of monocyte-derived LCs. In the human skin, embryo-derived LCs in newborns retained transcriptional evidence of their macrophage origin, but this was superseded by DC-like immune modules after postnatal expansion. Thus, adaptation to adult skin niches replicates conditioning of LC at birth, permitting repair of the embryo-derived LC network

Progressive multifocal leukoencephalopathy genetic risk variants for pharmacovigilance of immunosuppressant therapies

BackgroundProgressive multifocal leukoencephalopathy (PML) is a rare and often lethal brain disorder caused by the common, typically benign polyomavirus 2, also known as JC virus (JCV). In a small percentage of immunosuppressed individuals, JCV is reactivated and infects the brain, causing devastating neurological defects. A wide range of immunosuppressed groups can develop PML, such as patients with: HIV/AIDS, hematological malignancies (e.g., leukemias, lymphomas, and multiple myeloma), autoimmune disorders (e.g., psoriasis, rheumatoid arthritis, and systemic lupus erythematosus), and organ transplants. In some patients, iatrogenic (i.e., drug-induced) PML occurs as a serious adverse event from exposure to immunosuppressant therapies used to treat their disease (e.g., hematological malignancies and multiple sclerosis). While JCV infection and immunosuppression are necessary, they are not sufficient to cause PML.MethodsWe hypothesized that patients may also have a genetic susceptibility from the presence of rare deleterious genetic variants in immune-relevant genes (e.g., those that cause inborn errors of immunity). In our prior genetic study of 184 PML cases, we discovered 19 candidate PML risk variants. In the current study of another 152 cases, we validated 4 of 19 variants in both population controls (gnomAD 3.1) and matched controls (JCV+ multiple sclerosis patients on a PML-linked drug ≥ 2 years).ResultsThe four variants, found in immune system genes with strong biological links, are: C8B, 1-57409459-C-A, rs139498867; LY9 (alias SLAMF3), 1-160769595-AG-A, rs763811636; FCN2, 9-137779251-G-A, rs76267164; STXBP2, 19-7712287-G-C, rs35490401. Carriers of any one of these variants are shown to be at high risk of PML when drug-exposed PML cases are compared to drug-exposed matched controls: P value = 3.50E-06, OR = 8.7 [3.7–20.6]. Measures of clinical validity and utility compare favorably to other genetic risk tests, such as BRCA1 and BRCA2 screening for breast cancer risk and HLA-B*15:02 pharmacogenetic screening for pharmacovigilance of carbamazepine to prevent Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis.ConclusionFor the first time, a PML genetic risk test can be implemented for screening patients taking or considering treatment with a PML-linked drug in order to decrease the incidence of PML and enable safer use of highly effective therapies used to treat their underlying disease

Traumatic brain injury: integrated approaches to improve prevention, clinical care, and research

No abstract available

Variation in Structure and Process of Care in Traumatic Brain Injury: Provider Profiles of European Neurotrauma Centers Participating in the CENTER-TBI Study.

INTRODUCTION: The strength of evidence underpinning care and treatment recommendations in traumatic brain injury (TBI) is low. Comparative effectiveness research (CER) has been proposed as a framework to provide evidence for optimal care for TBI patients. The first step in CER is to map the existing variation. The aim of current study is to quantify variation in general structural and process characteristics among centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. METHODS: We designed a set of 11 provider profiling questionnaires with 321 questions about various aspects of TBI care, chosen based on literature and expert opinion. After pilot testing, questionnaires were disseminated to 71 centers from 20 countries participating in the CENTER-TBI study. Reliability of questionnaires was estimated by calculating a concordance rate among 5% duplicate questions. RESULTS: All 71 centers completed the questionnaires. Median concordance rate among duplicate questions was 0.85. The majority of centers were academic hospitals (n = 65, 92%), designated as a level I trauma center (n = 48, 68%) and situated in an urban location (n = 70, 99%). The availability of facilities for neuro-trauma care varied across centers; e.g. 40 (57%) had a dedicated neuro-intensive care unit (ICU), 36 (51%) had an in-hospital rehabilitation unit and the organization of the ICU was closed in 64% (n = 45) of the centers. In addition, we found wide variation in processes of care, such as the ICU admission policy and intracranial pressure monitoring policy among centers. CONCLUSION: Even among high-volume, specialized neurotrauma centers there is substantial variation in structures and processes of TBI care. This variation provides an opportunity to study effectiveness of specific aspects of TBI care and to identify best practices with CER approaches

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication