(1→3)-β-D-Glucan Does Not Induce Acute Inflammation After Nasal Deposition

To assess if (1→3)-β-D-glucan, a microbial cell wall agent normally present in pollen, has the ability to produce pollenlike response, sensitive persons received a nasal deposition of two doses of (1→3)-β-D-glucan. The percentage of eosinophils and amount of eotaxin were measured in nasal lavage 30 minutes and 24 hours after challenge. No effect could be demonstrated. The absence of an inflammatory response after (1→3)-β-D-glucan application confirms earlier findings in inhalation studies

Supramolecular polymer

A polymer comprising monomeric units linked via 4 H-bridges and bound within said polymer via a different bond. The bond via the H-bridges is much stronger than with known supramolecular polymers

Is CT-based body composition associated with long-term chemotherapy-induced peripheral neuropathy in colorectal cancer survivors?

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect among colorectal cancer (CRC) survivors, and the severity is mainly dependent on the chemotherapy dose. Nowadays, chemotherapy dose is based on body surface area, while determination based on more accurate measures of body composition may be better. This study aimed to investigate the association between body composition and long-term CIPN among CRC survivors 2–11 years after diagnosis. METHODS: Data from CRC survivors from the population-based PROFILES registry were used. Survivors were included when they received chemotherapy, filled in the EORTC QLQ-CIPN20, and had a computed tomography (CT) scan at diagnosis (n = 202). Total, sensory, motor, and autonomic CIPN were based upon the EORTC QLQ-CIPN20. The abdominal CT scans were used to determine skeletal muscle index (SMI), skeletal muscle density (SMD), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and total adipose tissue (TAT). Logistic regression was used to analyze the association between CIPN outcomes and body composition variables. RESULTS: CIPN was experienced by 64% of the CRC survivors several years after chemotherapy. More SAT was associated with a higher odds of reporting total CIPN (OR = 1.01 95% CI 1.00–1.01, p = 0.01), motor CIPN (OR = 1.01 95% CI 1.00–1.01, p = 0.01), and sensory CIPN (OR = 1.01 95% CI 1.00–1.01, p = 0.04). No associations of other body composition parameters with CIPN were observed. CONCLUSION: Only SAT was associated with total, motor, and sensory CIPN. Based on these results, we cannot conclude that determining the chemotherapy dose based on body composition is preferred over determining the chemotherapy dose based on body surface to prevent CIPN. More research is needed to assess associations of body composition with CIPN, a common side effect of chemotherapy

Induction of broad multifunctional CD8+ and CD4+ T cells by hepatitis B virus antigen-based synthetic long peptides ex vivo

Introduction: Therapeutic vaccination based on synthetic long peptides (SLP®) containing both CD4+ and CD8+ T cell epitopes is a promising treatment strategy for chronic hepatitis B infection (cHBV). Methods: We designed SLPs for three HBV proteins, HBcAg and the non-secreted proteins polymerase and X, and investigated their ability to induce T cell responses ex vivo. A set of 17 SLPs was constructed based on viral protein conservation, functionality, predicted and validated binders for prevalent human leukocyte antigen (HLA) supertypes, validated HLA I epitopes, and chemical producibility. Results: All 17 SLPs were capable of inducing interferon gamma (IFNɣ) production in samples from four or more donors that had resolved an HBV infection in the past (resolver). Further analysis of the best performing SLPs demonstrated activation of both CD8+ and CD4+ multi-functional T cells in one or more resolver and patient sample(s). When investigating which SLP could activate HBV-specific T cells, the responses could be traced back to different peptides for each patient or resolver. Discussion: This indicates that a large population of subjects with different HLA types can be covered by selecting a suitable mix of SLPs for therapeutic vaccine design. In conclusion, we designed a set of SLPs capable of inducing multifunctional CD8+ and CD4+ T cells ex vivo that create important components for a novel therapeutic vaccine to cure cHBV.</p

Geriatric pharmacotherapy : optimisation through integrated approach in the hospital setting

Since older patients are more vulnerable to adverse drug-related events, there is a need to ensure appropriate prescribing in these patients in order to prevent misuse, overuse and underuse of drugs. Different tools and strategies have been developed to reduce inappropriate prescribing; the available measures can be divided into medication assessment tools, and specific interventions to reduce inappropriate prescribing. Implicit criteria of inappropriate prescribing focus on appropriate dosing, search for drug-drug interactions, and increase adherence. Explicit criteria are consensus-based standards focusing on drugs and diseases and include lists of drugs to avoid in general or lists combining drugs with clinical data. These criteria take into consideration differences between patients, and stand for a medication review, by using a systematic approach. Different types of interventions exist in order to reduce inappropriate prescribing in older patients, such as: educational interventions, computerized decision support systems, pharmacist-based interventions, and geriatric assessment. The effects of these interventions have been studied, sometimes in a multifaceted approach combining different techniques, and all types seem to have positive effects on appropriateness of prescribing. Interdisciplinary teamwork within the integrative pharmaceutical care is important for improving of outcomes and safety of drug therapy. The pharmaceutical care process consists offour steps, which are cyclic for an individual patient. These steps are pharmaceutical anamnesis, medication review, design and follow-up of a pharmaceutical care plan. A standardized approach is necessary for the adequate detection and evaluation of drug-related problems. Furthermore, it is clear that drug therapy should be reviewed in-depth, by having full access to medical records, laboratory values and nursing notes. Although clinical pharmacists perform the pharmaceutical care process to manage the patient’s drug therapy in every day clinical practice, the physician takes the ultimate responsibility for the care of the patient in close collaboration with nurses

Development and internal validation of a machine learning prediction model for low back pain non-recovery in patients with an acute episode consulting a physiotherapist in primary care

BACKGROUND: While low back pain occurs in nearly everybody and is the leading cause of disability worldwide, we lack instruments to accurately predict persistence of acute low back pain. We aimed to develop and internally validate a machine learning model predicting non-recovery in acute low back pain and to compare this with current practice and 'traditional' prediction modeling. METHODS: Prognostic cohort-study in primary care physiotherapy. Patients (n = 247) with acute low back pain (≤ one month) consulting physiotherapists were included. Candidate predictors were assessed by questionnaire at baseline and (to capture early recovery) after one and two weeks. Primary outcome was non-recovery after three months, defined as at least mild pain (Numeric Rating Scale > 2/10). Machine learning models to predict non-recovery were developed and internally validated, and compared with two current practices in physiotherapy (STarT Back tool and physiotherapists' expectation) and 'traditional' logistic regression analysis. RESULTS: Forty-seven percent of the participants did not recover at three months. The best performing machine learning model showed acceptable predictive performance (area under the curve: 0.66). Although this was no better than a'traditional' logistic regression model, it outperformed current practice. CONCLUSIONS: We developed two prognostic models containing partially different predictors, with acceptable performance for predicting (non-)recovery in patients with acute LBP, which was better than current practice. Our prognostic models have the potential of integration in a clinical decision support system to facilitate data-driven, personalized treatment of acute low back pain, but needs external validation first