Introduction: Mental health problems are common among students at university, representing a major public health concern. The internet and new technologies are widely used by students and represent a significant resource to them for mental health information and support. Aim: The aim of this systematic review is to summarize and critique studies of mental health-related digital use (including purposes, advantages, and barriers) by students worldwide, to support the implementation of future digital mental health interventions targeting university students. Methods: We searched for peer-reviewed articles published between January 2008 and May 2018 by using Pubmed, Google Scholar, PsycINFO, PsycARTICLES, Psychology and Behavioral Sciences Collection, and SocINDEX. Studies were coded by author, year of publication, country, research design, recruitment and sampling, data collection, analysis method, key findings, and mean quality score. Outcomes were synthetized through the textual narrative synthesis method. Results: Of the 1,487 titles and abstracts screened, 24 articles were critically reviewed. Sample sizes ranged from 19 to 6,034 participants. The two key findings were that students worldwide have a high need for mental health information and are prepared to use digital tools for their mental health and wellbeing. However, they are currently struggling to discern trustworthy information online and are expressing a desire for reliable devices handling their sensitive data. Conclusions: Through the description of patterns in university students' mental health-related digital use, this review outlines important features for potential web-and mobilebased interventions for promoting mental health and preventing mental illness at the university.
Precise management of kidney cancer requires the identification of prognostic factors. hPG80 (circulating progastrin) is a tumor promoting peptide present in the blood of patients with various cancers, including renal cell carcinoma (RCC). In this study, we evaluated the prognostic value of plasma hPG80 in 143 prospectively collected patients with metastatic RCC (mRCC). The prognostic impact of hPG80 levels on overall survival (OS) in mRCC patients after controlling for hPG80 levels in non-cancer age matched controls was determined and compared to the International Metastatic Database Consortium (IMDC) risk model (good, intermediate, poor). ROC curves were used to evaluate the diagnostic accuracy of hPG80 using the area under the curve (AUC). Our results showed that plasma hPG80 was detected in 94% of mRCC patients. hPG80 levels displayed high predictive accuracy with an AUC of 0.93 and 0.84 when compared to 18–25 year old controls and 50–80 year old controls, respectively. mRCC patients with high hPG80 levels (>4.5 pM) had significantly lower OS compared to patients with low hPG80 levels (<4.5 pM) (12 versus 31.2 months, respectively; p = 0.0031). Adding hPG80 levels (score of 1 for patients having hPG80 levels > 4.5 pM) to the six variables of the IMDC risk model showed a greater and significant difference in OS between the newly defined good-, intermediate- and poor-risk groups (p = 0.0003 compared to p = 0.0076). Finally, when patients with IMDC intermediate-risk group were further divided into two groups based on hPG80 levels within these subgroups, increased OS were observed in patients with low hPG80 levels (<4.5 pM). In conclusion, our data suggest that hPG80 could be used for prognosticating survival in mRCC alone or integrated to the IMDC score (by adding a variable to the IMDC score or by substratifying the IMDC risk groups), be a prognostic biomarker in mRCC patients.
Fever is frequently the only clinical sign of infection in patients with chemo-induced neutropenia. In this setting, empirical administration of broad spectrum antibiotics must be rapid. The aim of this work was to compare, for the first time, cefpirome (CPO) and piperacillin-tazobactam (PT) in a large randomized trial. Two hundred-eight febrile neutropenic episodes (FNE) (> or = 38.5 degrees C and ANC < or = 0.5 giga/l) were treated by randomization, as first line therapy, using either CPO 2 g x 2/day (105 cases) or PT 4 g x 3/day (103 cases), alone (CPO: 15/PT: 15), or plus aminoglycoside (165 cases, CPO: 82/PT: 83) or quinolone (CPO: 2/PT: 2). There were 131 men and 77 women aged between 17 and 83 years (median: 49) who received chemotherapy (n = 160) or allogeneic (n = 10) or autologous (n = 38) stem cell transplantations. Underlying diseases were: acute leukemia (n = 131), lymphoma (n = 33), myeloma (n = 16), solid tumor (n = 8), myeloproliferative disorder (n = 9), chronic lymphoid leukemia (n = 5), aplastic anemia (n = 3), myelodysplasia (n = 3). Distribution of age, neutropenia duration (median: 17 days), underlying disease, and protocol therapy duration (median: 11 days) was comparable in both arms. A microbiologically documented infection (MDI) was evidenced in 57 cases (27%). Bacteria were isolated from blood cultures in 54 cases (Gram positive: 32 cases). Their in vitro susceptibility rates to CPO and PT were not different. Two days after antibiotics initiation, clinical (fever disappearance) and microbiological (culture negativation) success rates (SR) were 62% for CPO versus 61% for PT and 50% versus 55% respectively in case of MDI (p = 0.89). Two deaths and 77 failures were registered. At the end of protocol, SR (no antibiotic change/absence of superinfection) was 59% with CPO versus 50% with PT (p = 0.27) and 53% versus 40% respectively in the 151 cases with neutropenia > or = 10 days (p = 0.17). The occurrence of side effects was similar in both arms. In our hands, the efficacy of CPO and PT was comparable for treating FNE.
The neonatal Fc Receptor (FcRn) is a key player in the maintenance of high serum levels of immunoglobulin G (IgG) antibodies. IgGs enter cells by pinocytic uptake and bind FcRn in acidic endosomal compartments. FcRn then recycles IgGs back to the cell surface where they are released into circulation at physiological pH. This half-life prolonging salvage pathway has obvious advantages in IgG-mediated pathogen clearance, but also leads to persistence of disease-causing autoantibodies present in various autoimmune indications like immune thrombocytopenia (ITP). Indeed, the principal characteristic of ITP is autoantibody-mediated peripheral platelet destruction and impaired platelet production in bone marrow which leads to an increased risk of bleeding. Functional inhibition of the FcRn receptor could therefore be a novel therapeutic modality in the treatment of ITP as standard treatment options, like immunomodulatory drugs, typically suffer from a high risk of comorbidities. ARGX-113 is a proprietary antibody Fc-fragment based on argenx' ABDEG™ technology. ABDEG™ mutations dramatically increase the Fc/FcRn binding both at neutral and acidic pH. This results in constitutive blockage of FcRn function by ARGX-113, and concomitantly leads to fast clearance of pathogenic antibodies in an autoimmune setting. The ABDEG™ concept was validated in various mouse models for IgG-induced autoimmune indications. In all models, a significant reduction of disease severity is observed upon ARGX-113 administration, which parallels with markedly reduced disease-causing antibody levels. Follow-up studies in cynomolgus monkeys demonstrated a highly effective and rapid elimination of immunoglobulins, which outperformed by far the pharmacodynamic effects of a 50-fold higher dose of intravenous immunoglobulin (IVIg), a standard-of-care therapy in many IgG-driven autoimmune indications. A first-in-human Phase I study was initiated to evaluate safety, tolerability, efficacy (reduction in IgG levels), pharmacokinetics and immunogenicity of ARGX-113 following single or multiple intravenous administration(s). Up to 68 healthy volunteers will be enrolled in this double-blind placebo-controlled study (48 active, 20 placebo). At present, the compound showed favorable safety and tolerability across multiple doses and dosing regimens with promising pharmacodynamics effects relating to speed, depth and duration of IgG reduction. Upon multiple dosing, IgG reduction of up to 85% is observed and IgG levels slowly return to baseline when dosing is terminated. Full study results, covering all planned doses and dosing regimens, will be presented focusing on safety, PK/PD relationship, IgG subset response, anti-drug antibody formation and dose/dosing regimen selection for future studies. In addition, the study design and outcome measures of a Phase II study evaluating safety, tolerability and efficacy of ARGX-113 in an ITP setting is being prepared and will be presented. Disclosures Ulrichts: argenx: Employment. Cousin:argenx: Employment. Dreier:argenx: Employment. de Haard:argenx: Employment. Leupin:argenx: Employment.
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