Tailoring and evaluating treatment with the Patient-Specific Needs Evaluation:A Patient-Centered Approach

BACKGROUND: No patient-reported instrument assesses patient-specific information needs, treatment goals, and Personal Meaningful Gain (PMG, a novel construct evaluating individualized, clinically relevant improvement). This study reports the development of the Patient-Specific Needs Evaluation (PSN) and examines its discriminative validity (i.e., its ability to distinguish satisfied from dissatisfied patients) and test-retest reliability in patients with hand or wrist conditions.METHODS: A mixed-methods approach was used to develop and validate the PSN, following COSMIN guidelines, including pilot testing, a survey (pilot: n=223, final PSN: n=275), cognitive debriefing (n=16), expert input, and validation. Discriminative validity was assessed by comparing the satisfaction level of patients who did or did not achieve their PMG (n=1,985) and test-retest reliability using absolute agreement, Cohen's kappa, and ICCs (n=102). We used a sample of 2,860 patients to describe responses to the final PSN.RESULTS: The PSN has only five questions (completion time ±3 minutes) and is freely accessible online. The items and response options were considered understandable by 90-92% and complete by 84-89% of the end-users. The PSN had excellent discriminative validity (Cramer's V: 0.48, p&lt;0.001) and moderate to high test-retest reliability (Kappa: 0.46-0.68, ICCs: 0.53-0.73).CONCLUSIONS: The PSN is a freely available patient-centered decision-support tool that helps clinicians tailor their consultations to the patient's individual needs and goals. It contains the PMG, a novel construct evaluating individualized, clinically relevant treatment outcomes. The PSN may function as a conversation starter, facilitate expectation management, and aid shared decision-making. The PSN is implementation-ready and can be readily adapted to other patient populations.LEVEL OF EVIDENCE: I.</p

Canadian Burden of Skin Disease From 1990 to 2017: Results From the Global Burden of Disease 2017 Study

Background: Skin diseases can have high morbidity that can be costly to society and individuals. To date, there has been no comprehensive assessment of the burden of skin disease in Canada. Objectives: To evaluate the burden of 18 skin and subcutaneous diseases from 1990 to 2017 in Canada using the Global Burden of Disease (GBD) data. Methods: The 2017 GBD study measures health loss from 359 diseases and injuries in 195 countries; we evaluated trends in population health in Canada from 1990 to 2017 using incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life years (DALYs). Data are presented as rates (per 100 000), counts, or percent change with the uncertainty interval in brackets. Results: From 1990 to 2017 for all skin diseases, DALY rates increased by 8 to 971 per 100 000 (674-1319), YLD rates increased by 8 to 897 per 100 000 (616-1235), YLL rates increased by 4 to 74 per 100 000 (53-89), and death rates increased by 18 to 5 per 100 000 (3-6). DALY rates for melanoma increased by 2 to 54 per 100 000 (39-68), for keratinocyte carcinoma by 14 to 17 per 100 000 (16-19), and for skin and subcutaneous disease by 8 to 900 per 100 000 (619-1233). The observed over expected ratios were higher for skin and subcutaneous disease (1.37) and keratinocyte carcinoma (1.17) and were lower for melanoma (0.73). Conclusions: The burden of skin disease has increased in Canada since 1990. These results can be used to guide health policy regarding skin disease in Canada. © The Author(s) 2020

The Burden of Skin and Subcutaneous Diseases in the United States From 1990 to 2017

IMPORTANCE Skin and subcutaneous diseases affect the health of millions of individuals in the US. Data are needed that highlight the geographic trends and variations of skin disease burden across the country to guide health care decision-making. OBJECTIVE To characterize trends and variations in the burden of skin and subcutaneous tissue diseases across the US from 1990 to 2017. DESIGN, SETTING, AND PARTICIPANTS For this cohort study, data were obtained from the Global Burden of Disease (GBD), a study with an online database that incorporates current and previous epidemiological studies of disease burden, and from GBD 2017, which includes more than 90 000 data sources such as systematic reviews, surveys, population-based disease registries, hospital inpatient and outpatient data, cohort studies, and autopsy data. The GBD separated skin conditions into 15 subcategories according to incidence, prevalence, adequacy of data, and standardized disease definitions. GBD 2017 also estimated the burden from melanoma of the skin and keratinocyte carcinoma. Data analysis for the present study was conducted from September 9, 2019, to March 31, 2020. MAIN OUTCOMES AND MEASURES Primary study outcomes included age-standardized disability-adjusted life-years (DALYs), incidence, and prevalence. The data were stratified by US states with the highest and lowest age-standardized DALY rate per 100 000 people, incidence, and prevalence of each skin condition. The percentage change in DALY rates in each state was calculated from 1990 to 2017. RESULTS Overall, age-standardized DALY rates for skin and subcutaneous diseases increased from 1990 (821.6; 95% uncertainty interval [UI], 570.3-1124.9) to 2017 (884.2; 95% UI, 614.0-1207.9) in all 50 states and the District of Columbia. The degree of increase varied according to geographic location, with the largest percentage change of 0.12% (95% UI, 0.09%-0.15%) in New York and the smallest percentage change of 0.04% (95% UI, 0.02%-0.07%) in Colorado, 0.04% (95% UI, 0.01%-0.06%) in Nevada, 0.04% (95% UI, 0.02%-0.07%) in New Mexico, and 0.04% (95% UI, 0.02%-0.07%) in Utah. The age-standardized DALY rate, incidence, and prevalence of specific skin conditions differed among the states. New York had the highest age-standardized DALY rate for skin and subcutaneous disease in 2017 (1097.0 [95% UI, 764.9-1496.1]), whereas Wyoming had the lowest age-standardized DALY rate (672.9 [95% UI, 465.6-922.3]). In all 50 states and the District of Columbia, women had higher age-standardized DALY rates for overall skin and subcutaneous diseases than men (women: 971.20 [95% UI, 676.76-1334.59] vs men: 799.23 [95% UI, 559.62-1091.50]). However, men had higher DALY rates than women for malignant melanoma (men: 80.82 [95% UI, 51.68-123.18] vs women: 42.74 [95% UI, 34.05-70.66]) and keratinocyte carcinomas (men: 37.56 [95% UI, 29.35-49.52] vs women: 14.42 [95% UI, 10.01-20.66]). CONCLUSIONS AND RELEVANCE Data from the GBD suggest that the burden of skin and subcutaneous disease was large and that DALY rate trends varied across the US; the age-standardized DALY rate for keratinocyte carcinoma appeared greater in men. These findings can be used by states to target interventions and meet the needs of their population

CAR-T cell. the long and winding road to solid tumors

Adoptive cell therapy of solid tumors with reprogrammed T cells can be considered the "next generation" of cancer hallmarks. CAR-T cells fail to be as effective as in liquid tumors for the inability to reach and survive in the microenvironment surrounding the neoplastic foci. The intricate net of cross-interactions occurring between tumor components, stromal and immune cells leads to an ineffective anergic status favoring the evasion from the host's defenses. Our goal is hereby to trace the road imposed by solid tumors to CAR-T cells, highlighting pitfalls and strategies to be developed and refined to possibly overcome these hurdles

The boomerang effect of radicalism in Discursive Psychology: A critical overview of the controversy with the Social Representations Theory.

This article provides a critical overview of the controversy between the Radical approach to Discursive Psychology (RDP) and the Social Representations Theory (SRT) and aims: a)?to show what is potentially complementary and contradictory in Discursive Psychology (DP) and the Social Representations Theory, when and why they are incompatible, and whether and how it is possible and/or desirable to integrate these two approaches. b)?to describe how the radicalism of the socio-constructionist thesis upheld by Discourse Analysis can give rise to several hard-to-solve problems, which may then be translated into a boomerang effect. In the final section, it highlights interest in dialog and “cross-fertilization” between researchers inspired by the less radical approach to discursive psychology and those inspired by the Social Representations Theory, pointing out the effect of methodological implications that would ensue

The Association between Intrauterine Inflammation and Spontaneous Vaginal Delivery at Term: A Cross-Sectional Study

BACKGROUND:Different factors contribute to the onset of labor at term. In animal models onset of labor is characterized by an inflammatory response. The role of intrauterine inflammation, although implicated in preterm birth, is not yet established in human term labor. We hypothesized that intrauterine inflammation at term is associated with spontaneous onset of labor. METHODS/RESULTS:In two large urban hospitals in the Netherlands, a cross-sectional study of spontaneous onset term vaginal deliveries and elective caesarean sections (CS), without signs of labor, was carried out. Placentas and amniotic fluid samples were collected during labor and/or at delivery. Histological signs of placenta inflammation were determined. Amniotic fluid proinflammatory cytokine concentrations were measured using ELISA. A total of 375 women were included. In term vaginal deliveries, more signs of intrauterine inflammation were found than in elective CS: the prevalence of chorioamnionitis was higher (18 vs 4%, p = 0.02) and amniotic fluid concentration of IL-6 was higher (3.1 vs 0.37 ng/mL, p<0.001). Similar results were obtained for IL-8 (10.93 vs 0.96 ng/mL, p<0.001) and percentage of detectable TNF-alpha (50 vs 4%, p<0.001). CONCLUSIONS:This large cross-sectional study shows that spontaneous term delivery is characterized by histopathological signs of placenta inflammation and increased amniotic fluid proinflammatory cytokines

Facilitated sequence assembly using densely labeled optical DNA barcodes:A combinatorial auction approach

<div><p>The output from whole genome sequencing is a set of contigs, i.e. short non-overlapping DNA sequences (sizes 1-100 kilobasepairs). Piecing the contigs together is an especially difficult task for previously unsequenced DNA, and may not be feasible due to factors such as the lack of sufficient coverage or larger repetitive regions which generate gaps in the final sequence. Here we propose a new method for scaffolding such contigs. The proposed method uses densely labeled optical DNA barcodes from competitive binding experiments as scaffolds. On these scaffolds we position theoretical barcodes which are calculated from the contig sequences. This allows us to construct longer DNA sequences from the contig sequences. This proof-of-principle study extends previous studies which use sparsely labeled DNA barcodes for scaffolding purposes. Our method applies a probabilistic approach that allows us to discard “foreign” contigs from mixed samples with contigs from different types of DNA. We satisfy the contig non-overlap constraint by formulating the contig placement challenge as a combinatorial auction problem. Our exact algorithm for solving this problem reduces computational costs compared to previous methods in the combinatorial auction field. We demonstrate the usefulness of the proposed scaffolding method both for synthetic contigs and for contigs obtained using Illumina sequencing for a mixed sample with plasmid and chromosomal DNA.</p></div

Longitudinal Tracking of Human Fetal Cells Labeled with Super Paramagnetic Iron Oxide Nanoparticles in the Brain of Mice with Motor Neuron Disease

Stem Cell (SC) therapy is one of the most promising approaches for the treatment of Amyotrophic Lateral Sclerosis (ALS). Here we employed Super Paramagnetic Iron Oxide nanoparticles (SPIOn) and Hoechst 33258 to track human Amniotic Fluid Cells (hAFCs) after transplantation in the lateral ventricles of wobbler (a murine model of ALS) and healthy mice. By in vitro, in vivo and ex vivo approaches we found that: 1) the main physical parameters of SPIOn were maintained over time; 2) hAFCs efficiently internalized SPIOn into the cytoplasm while Hoechst 33258 labeled nuclei; 3) SPIOn internalization did not alter survival, cell cycle, proliferation, metabolism and phenotype of hAFCs; 4) after transplantation hAFCs rapidly spread to the whole ventricular system, but did not migrate into the brain parenchyma; 5) hAFCs survived for a long time in the ventricles of both wobbler and healthy mice; 6) the transplantation of double-labeled hAFCs did not influence mice survival

New challenges for BRCA testing:a view from the diagnostic laboratory

Increased demand for BRCA testing is placing pressures on diagnostic laboratories to raise their mutation screening capacity and handle the challenges associated with classifying BRCA sequence variants for clinical significance, for example interpretation of pathogenic mutations or variants of unknown significance, accurate determination of large genomic rearrangements and detection of somatic mutations in DNA extracted from formalin-fixed, paraffin-embedded tumour samples. Many diagnostic laboratories are adopting next-generation sequencing (NGS) technology to increase their screening capacity and reduce processing time and unit costs. However, migration to NGS introduces complexities arising from choice of components of the BRCA testing workflow, such as NGS platform, enrichment method and bioinformatics analysis process. An efficient, cost-effective accurate mutation detection strategy and a standardised, systematic approach to the reporting of BRCA test results is imperative for diagnostic laboratories. This review covers the challenges of BRCA testing from the perspective of a diagnostics laboratory