Frailty in Chile: Development of a Frailty Index Score Using the Chilean National Health Survey 2016-2017.

BACKGROUND: The Frailty Index (FI) is used to quantify and summarize vulnerability status in people. In Chile, no development and assessment of a FI have been explored. OBJECTIVE: To develop and evaluate a FI using representative data from Chilean adults aged 40 years and older stratified by sex. DESIGN: Cross-sectional study. SETTING: National representative data from the Chilean National Health Survey 2016-2017 (CNHS 2016-2017). PARTICIPANTS: 3,036 participants older than 40 years with complete data for all variables. MEASUREMENTS: A 49-item FI was developed and evaluated. This FI included deficits from comorbidities, functional limitations, mental health status, physical activity, anthropometry, medications, and falls. A score between 0 and 1 was calculated for each person. Descriptive statistics and linear regression models were employed to evaluate the FI's performance in the population. Comparative analyses were carried out to evaluate the FI score by age (1<60 and ≥ 60 years). RESULTS: The mean FI score was 0.15 (SD:0.09), with a 99% upper limit of 0.46. Scores were greater in women than men (0.17 [SD:0.09]) vs. 0.12 [0.08]); in people older than 80 years (0.22 [0.11]), and in people with ≤8 years of education (0.18 [0.10]) compared with those with >12 years (0.12 [0.08]). The average age-related increase in the FI was 2.3%. When a cut-off point ≥ 0.25 was applied, the prevalence of frail individuals was 11.8% (95% CI: 10.0 to 13.8) in the general population. The prevalence was higher in women 15.9% [95% CI: 13.3 to 18.9] than men 7.4% [95% CI: 5.3 to 10.1]. In a comparative analysis by age, higher FI mean scores and prevalence of frail were observed in people ≥ 60 than younger than 60. CONCLUSIONS: The mean FI score and frailty prevalence were higher in women than men, in people with fewer years of formal education, and incremented markedly with age. This FI can be used for early detection of frailty status focusing on women and middle-aged people as a strategy to delay or prevent frailty-related consequences.

Streptococcal superantigen-induced expansion of human tonsil T cells leads to altered T follicular helper cell phenotype, B cell death and reduced immunoglobulin release.

Streptococcal pyrogenic exotoxin (Spe) A expression is epidemiologically linked to streptococcal tonsillo-pharyngitis and outbreaks of scarlet fever, although the mechanisms by which superantigens confer advantage to Streptococcus pyogenes are unclear. S. pyogenes is an exclusively human pathogen. As the leucocyte profile of tonsil is unique, the impact of SpeA production on human tonsil cell function was investigated. Human tonsil cells from routine tonsillectomy were co-incubated with purified streptococcal superantigens or culture supernatants from isogenic streptococcal isolates, differing only in superantigen production. Tonsil cell proliferation was quantified by tritiated thymidine incorporation, and cell surface characteristics assessed by flow cytometry. Soluble mediators including immunoglobulin were measured using enzyme-linked immunosorbent assay. Tonsil T cells proliferated in response to SpeA and demonstrated typical release of proinflammatory cytokines. When cultured in the absence of superantigen, tonsil preparations released large quantities of immunoglobulin over 7 days. In contrast, marked B cell apoptosis and abrogation of total immunoglobulin (Ig)A, IgM, and IgG production occurred in the presence of SpeA and other superantigens. In SpeA-stimulated cultures, T follicular helper (Tfh) cells showed a reduction in C-X-C chemokine receptor (CXCR)5 (CD185) expression, but up-regulation of OX40 (CD134) and inducible T cell co-stimulator (ICOS) (CD278) expression. The phenotypical change in the Tfh population was associated with impaired chemotactic response to CXCL13. SpeA and other superantigens cause dysregulated tonsil immune function, driving T cells from Tfh to a proliferating phenotype, with resultant loss of B cells and immunoglobulin production, providing superantigen-producing bacteria with a probable survival advantage.

Impact of contusion injury on intramuscular emm1 group a streptococcus infection and lymphatic spread.

Invasive group A Streptococcus (iGAS) is frequently associated with emm1 isolates, with an attendant mortality of around 20%. Cases occasionally arise in previously healthy individuals with a history of upper respiratory tract infection, soft tissue contusion, and no obvious portal of entry. Using a new murine model of contusion, we determined the impact of contusion on iGAS bacterial burden and phenotype. Calibrated mild blunt contusion did not provide a focus for initiation or seeding of GAS that was detectable following systemic GAS bacteremia, but instead enhanced GAS migration to the local draining lymph node following GAS inoculation at the same time and site of contusion. Increased migration to lymph node was associated with emergence of mucoid bacteria, although was not specific to mucoid bacteria. In one study, mucoid colonies demonstrated a significant increase in capsular hyaluronan that was not linked to a covRS or rocA mutation, but to a deletion in the promoter of the capsule synthesis locus, hasABC, resulting in a strain with increased fitness for lymph node migration. In summary, in the mild contusion model used, we could not detect seeding of muscle by GAS. Contusion promoted bacterial transit to the local lymph node. The consequences of contusion-associated bacterial lymphatic migration may vary depending on the pathogen and virulence traits selected.

Leflunomide use in New Zealand. A national prospective post-marketing study.

BACKGROUND: This post-marketing study aimed to record rates of retention, adverse effects and efficacy of leflunomide in the treatment of rheumatoid arthritis (RA). The secondary objectives were to make a semi-quantitative assessment of response to treatment and to examine the effect of a loading dose on adverse events and treatment duration. METHODS: Rheumatologists in New Zealand contributed to a prospective leflunomide treatment registry. Baseline data were collected on leflunomide initiation and information about treatment experience was sought every 6 months. Each patient was followed for 2 years. Kaplan-Meier analysis was used to evaluate differences in stopping rates between lack of efficacy and adverse effects. Hazard analysis was used to evaluate the effect of using a loading dose on retention rate. RESULTS: Three hundred and eight patients were enrolled in the study; complete follow-up data were available for 244 patients. Retention of patients on leflunomide was 64% at 12 months and 49.4% at 2 years. Reasons for stopping were adverse events (54 patients), loss of effect (25 patients) and miscellaneous reasons (14 patients). Use of a loading dose had no effect on retention; there was no difference in treatment duration between those who stopped from adverse effects or loss of efficacy. CONCLUSION: Leflunomide was effective in treating RA in a group that had longer duration of disease and greater prior use of disease-modifying agents than the groups studied in clinical trials. Rates of withdrawal were lower than those reported in other post-marketing studies, but were higher than those from phase III clinical trials.

Idiopathic osteoarthritis and contracture: causal implications.

OBJECTIVE: To use the known association of idiopathic osteoarthritis with contracture as a means of searching for its cause. There are currently two theories concerning this association, one assuming that the contracture is a consequence of the osteoarthritis and the other that it precedes and causes the osteoarthritis. This study tested both theories. METHODS: Flexion ranges in the 12 finger joints were obtained by goniometric measurement in two samples of normal female subjects, one group with a mean age of 22 years (25 subjects) and one with a mean age of 45 years (50 subjects). The results were compared with the known regional prevalence of osteoarthritis in the finger joints of women. RESULTS: The older group showed evidence of reduced flexion range consistent with development of contracture in the extensor mechanism of the fingers. The distribution of the contracture showed a strong negative correlation with the regional prevalence of osteoarthritis. CONCLUSIONS: An early dorsal contracture develops in the fingers of normal subjects, but it is neither a consequence of nor the cause of digital osteoarthritis. The most parsimonious explanation for the association is that both contracture and idiopathic osteoarthritis are independent consequences of failure to use the full movement range. If this hypothesis is correct, the disease could be preventable.