Assessing and measuring chronic multimorbidity in the older population: a proposal for its operationalization

Background Although the definition of multimorbidity as “the simultaneous presence of two or more chronic diseases” is well established, its operationalization is not yet agreed. This study aims to provide a clinically driven comprehensive list of chronic conditions to be included when measuring multimorbidity. Methods Based on a consensus definition of chronic disease, all four-digit level codes from the International Classification of Diseases, 10th revision (ICD-10) were classified as chronic or not by an international and multidisciplinary team. Chronic ICD-10 codes were subsequently grouped into broader categories according to clinical criteria. Last, we showed proof of concept by applying the classification to older adults from the Swedish National study of Aging and Care in Kungsholmen (SNAC-K) using also inpatient data from the Swedish National Patient Register. Results A disease or condition was considered to be chronic if it had a prolonged duration and either (a) left residual disability or worsening quality of life or (b) required a long period of care, treatment, or rehabilitation. After applying this definition in relation to populations of older adults, 918 chronic ICD-10 codes were identified and grouped into 60 chronic disease categories. In SNAC-K, 88.6% had =2 of these 60 disease categories, 73.2% had =3, and 55.8% had =4. Conclusions This operational measure of multimorbidity, which can be implemented using either or both clinical and administrative data, may facilitate its monitoring and international comparison. Once validated, it may enable the advancement and evolution of conceptual and theoretical aspects of multimorbidity that will eventually lead to better care

A site of varicella-zoster virus vulnerability identified by structural studies of neutralizing antibodies bound to the glycoprotein complex gHgL.

Varicella-zoster virus (VZV), of the family Alphaherpesvirinae, causes varicella in children and young adults, potentially leading to herpes zoster later in life on reactivation from latency. The conserved herpesvirus glycoprotein gB and the heterodimer gHgL mediate virion envelope fusion with cell membranes during virus entry. Naturally occurring neutralizing antibodies against herpesviruses target these entry proteins. To determine the molecular basis for VZV neutralization, crystal structures of gHgL were determined in complex with fragments of antigen binding (Fabs) from two human monoclonal antibodies, IgG-94 and IgG-RC, isolated from seropositive subjects. These structures reveal that the antibodies target the same site, composed of residues from both gH and gL, distinct from two other neutralizing epitopes identified by negative-stain electron microscopy and mutational analysis. Inhibition of gB/gHgL-mediated membrane fusion and structural comparisons with herpesvirus homologs suggest that the IgG-RC/94 epitope is in proximity to the site on VZV gHgL that activates gB. Immunization studies proved that the anti-gHgL IgG-RC/94 epitope is a critical target for antibodies that neutralize VZV. Thus, the gHgL/Fab structures delineate a site of herpesvirus vulnerability targeted by natural immunity

Assessing and Measuring Chronic Multimorbidity in the Older Population: A Proposal for Its Operationalization

Although the definition of multimorbidity as "the simultaneous presence of two or more chronic diseases" is well established, its operationalization is not yet agreed. This study aims to provide a clinically driven comprehensive list of chronic conditions to be included when measuring multimorbidity

Safety assessment of titanium dioxide (E171) as a food additive

The present opinion deals with an updated safety assessment of the food additive titanium dioxide (E&nbsp;171) based on new relevant scientific evidence considered by the Panel&nbsp;to be reliable, including data obtained with TiO2&nbsp;nanoparticles (NPs) and data from an extended one-generation reproductive toxicity (EOGRT) study. Less than 50% of constituent particles by number in E&nbsp;171 have a minimum external dimension &lt; 100 nm. In addition, the Panel&nbsp;noted that constituent particles &lt; 30 nm amounted to less than 1% of particles by number. The Panel&nbsp;therefore considered that studies with TiO2&nbsp;NPs &lt; 30 nm were of limited relevance to the safety assessment of E&nbsp;171. The Panel&nbsp;concluded that although gastrointestinal absorption of TiO2&nbsp;particles is low, they may accumulate in the body. Studies on general and organ toxicity did not indicate adverse effects with either E&nbsp;171 up to a dose of 1,000 mg/kg body weight (bw) per day or with TiO2&nbsp;NPs (&gt; 30 nm) up to the highest dose tested of 100 mg/kg bw per day. No effects on reproductive and developmental toxicity were observed up to a dose of 1,000 mg E 171/kg bw per day, the highest dose tested in the EOGRT study. However, observations of potential immunotoxicity and inflammation with E&nbsp;171 and potential neurotoxicity with TiO2&nbsp;NPs, together with the potential induction of aberrant crypt foci with E&nbsp;171, may indicate adverse effects. With respect to genotoxicity, the Panel&nbsp;concluded that TiO2&nbsp;particles have the potential to induce DNA strand breaks and chromosomal damage, but not gene mutations. No clear correlation was observed between the physico-chemical properties of TiO2&nbsp;particles and the outcome of either&nbsp;in&nbsp;vitro&nbsp;or&nbsp;in&nbsp;vivo&nbsp;genotoxicity assays. A concern for genotoxicity of TiO2&nbsp;particles that may be present in E&nbsp;171 could therefore not be ruled out. Several modes of action for the genotoxicity may operate in parallel and the relative contributions of different molecular mechanisms elicited by TiO2&nbsp;particles are not known. There was uncertainty as to whether a threshold mode of action could be assumed. In addition, a cut-off value for TiO2&nbsp;particle size with respect to genotoxicity could not be identified. No appropriately designed study was available to investigate the potential carcinogenic effects of TiO2&nbsp;NPs. Based on all the evidence available, a concern for genotoxicity could not be ruled out, and given the many uncertainties, the Panel&nbsp;concluded that E&nbsp;171 can no longer be considered as safe when used as a food&nbsp;additive.</p