Determinants of methicillin-susceptible Staphylococcus aureus native bone and joint infection treatment failure: a retrospective cohort study.

BACKGROUND: Although methicillin-susceptible Staphylococcus aureus (MSSA) native bone and joint infection (BJI) constitutes the more frequent clinical entity of BJI, prognostic studies mostly focused on methicillin-resistant S. aureus prosthetic joint infection. We aimed to assess the determinants of native MSSA BJI outcomes. METHODS: Retrospective cohort study (2001-2011) of patients admitted in a reference hospital centre for native MSSA BJI. Treatment failure determinants were assessed using Kaplan-Meier curves and binary logistic regression. RESULTS: Sixty-six patients (42 males [63.6%]; median age 61.2 years; interquartile range [IQR] 45.9-71.9) presented an acute (n = 38; 57.6%) or chronic (n = 28; 42.4%) native MSSA arthritis (n = 15; 22.7%), osteomyelitis (n = 19; 28.8%) or spondylodiscitis (n = 32; 48.5%), considered as "difficult-to-treat" in 61 cases (92.4%). All received a prolonged (27.1 weeks; IQR, 16.9-36.1) combined antimicrobial therapy, after surgical management in 37 cases (56.1%). Sixteen treatment failures (24.2%) were observed during a median follow-up period of 63.3 weeks (IQR, 44.7-103.1), including 13 persisting infections, 1 relapse after treatment disruption, and 2 super-infections. Independent determinants of treatment failure were the existence of a sinus tract (odds ratio [OR], 5.300; 95% confidence interval [CI], 1.166-24.103) and a prolonged delay to infectious disease specialist referral (OR, 1.134; 95% CI 1.013-1.271). CONCLUSIONS: The important treatment failure rate pinpointed the difficulty of cure encountered in complicated native MSSA BJI. An early infectious disease specialist referral is essential, especially in debilitated patients or in presence of sinus tract

Could Country-Level Factors Explain Sex Differences in Dementia Incidence and Prevalence? A Systematic Review and Meta-Analysis

Background: Despite rising interest in sex differences in dementia, it is unclear whether sex differences in dementia incidence and prevalence are apparent globally. Objective: We examine sex differences in incidence and prevalence of Any dementia, Alzheimer's disease (AD), and vascular dementia (VaD), and evaluate whether country-level indicators of gender inequality account for differences. Methods: Systematic review with meta-analysis was used to obtain estimates of incidence and prevalence of Any dementia, AD, and VaD using random effects meta-analysis, and population-based studies with clinical or validated dementia measures. Meta-regression was used to evaluate how country-specific factors of life expectancy, education, and gender differences in development, unemployment, and inequality indices influenced estimates. Results: We identified 205 eligible studies from 8,731 articles, representing 998,187 participants across 43 countries. There were no sex differences in the incidence of Any dementia, AD, or VaD, except in the 90+ age group (women higher). When examined by 5-year age bands, the only sex difference in prevalence of Any dementia was in the 85+ group and there was no sex difference in VaD. AD was more prevalent in women at most ages. Globally, the overall prevalence of dementia in adults 65 + was higher for women (80.22/1000, 95% CI 62.83-97.61) than men (54.86/1000, 95% CI 43.55-66.17). Meta-regression revealed that sex differences in Any dementia prevalence were associated with gender differences in life expectancy and in education. Conclusion: Globally, there are no sex differences in age-specific dementia incidence, but prevalence of AD is higher in women. Country-level factors like life expectancy and gender differences in education may explain variability in sex differences

Management of emerging multidrug-resistant tuberculosis in a low-prevalence setting

AbstractMultidrug-resistant (MDR) tuberculosis (TB) is an emerging concern in communities with a low TB prevalence and a high standard of public health. Twenty-three consecutive adult MDR TB patients who were treated at our institution between 2007 and 2013 were reviewed for demographic characteristics and anti-TB treatment management, which included surgical procedures and long-term patient follow-up. This report of our experience emphasizes the need for an individualized approach as MDR TB brings mycobacterial disease management to a higher level of expertise, and for a balance to be found between international current guidelines and patient-tailored treatment strategies

Phase II Clinical Trial With Pegylated Liposomal Doxorubicin (CAELYX®/Doxil®) and Quality of Life Evaluation (EORTC QLQ-C30) in Adult Patients With Advanced Soft Tissue Sarcomas: A study of the Spanish Group for Research in Sarcomas (GEIS)

Background: Pegylated liposomal doxorubicin (PLD), a formulation with pharmacokinetic differences with respect to doxorubicin (DXR), might benefit patients with advanced soft tissue sarcoma (STS) pretreated with DXR

Impact of herpes zoster and post-herpetic neuralgia on patients’ quality of life: a patient-reported outcomes survey

Background: The impact of herpes zoster (HZ) and post-herpetic neuralgia (PHN) on patients’ quality of life (QoL) is currently poorly documented. Subjects and methods: Telephone interviews in Germany identified patients ≥50 years old with painful HZ diagnosed during the previous 5 years. Bespoke questions evaluated previous HZ episodes. Results: Of 11,009 respondents, 280 met the screening criteria, and 32 (11%) developed PHN. PHN was associated with significantly worse outcomes than HZ (all P < 0.05). Mean pain scores associated with PHN and HZ, respectively, were 7.1 and 6.2 (average) and 8.2 and 7.0 (worst). Many patients with PHN (91%) and HZ (73%) experienced problems with daily activities, including work, studies, housework, family and leisure activities. Mean pain interference scores in patients with PHN versus HZ were highest for sleep (6.5 versus 4.9), normal work (6.1 versus 4.4) and mood (5.9 versus 4.4). Most employed interviewees with PHN (70%) and HZ (64%) stopped work during the disease. Pain and QoL outcomes were not significantly different between all patients versus those diagnosed during the previous 12 months or between patients aged 50–59 years versus ≥60 years. Conclusions: HZ causes substantial pain, which seriously interferes with many aspects of daily life, particularly in patients with PHN

DEAE-chitosan nanoparticles as a pneumococcus-biomimetic material for the development of antipneumococcal therapeutics

13 p.-7 fig.Advanced biomaterials provide an interesting and versatile platform to implement new and more effective strategies to fight bacterial infections. Chitosan is one of these biopolymers and possesses relevant features for biomedical applications. Here we synthesized nanoparticles of chitosan derivatized with diethylaminoethyl groups (ChiDENPs) to emulate the choline residues in the pneumococcal cell wall and act as ligands for choline-binding proteins (CBPs). Firstly, we assessed the ability of diethylaminoethyl (DEAE) to sequester the CBPs present in the bacterial surface, thus promoting chain formation. Secondly, the CBP-binding ability of ChiDENPs was purposed to encapsulate a bio-active molecule, the antimicrobial enzyme Cpl-711 (ChiDENPs-711), with improved stability over non-derivatized chitosan. The enzyme-loaded system released more than 90% of the active enzybiotic in ≈ 2 h, above the usual in vivo half-life of this kind of enzymes. Therefore, ChiDENPs provide a promising platform for the controlled release of CBP-enzybiotics in biological contexts.This study was funded by a grant from the Ministerio de Economía y Competitividad (MINECO-FEDER, SAF2017-88664-R) and the Ministerio de Ciencia e Innovación (MAT2017-84277-R, PID2019-105126RB-I00). F. J. Caro acknowledges financial support from CONACyT (Mexico) through the scholarship ‘Apoyo para estancias postdoctorales en el extranjero vinculadas a la consolidación de grupos de investigación y fortalecimiento del Posgrado nacional’. Additional funding was provided by the Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES) and Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), an initiative of the Instituto de Salud Carlos III.Peer reviewe

Agouti signalling protein is an inverse agonist to the wildtype and agonist to the melanic variant of the melanocortin-1 receptor in the grey squirrel (Sciurus carolinensis)

The melanocortin-1 receptor (MC1R) is a key regulator of mammalian pigmentation. Melanism in the grey squirrel is associated with an eight amino acid deletion in the mutant melanocortin-1 receptor with 24 base pair deletion (MC1RΔ24) variant. We demonstrate that the MC1RΔ24 exhibits a higher basal activity than the wildtype MC1R (MC1R-wt). We demonstrate that agouti signalling protein (ASIP) is an inverse agonist to the MC1R-wt but is an agonist to the MC1RΔ24. We conclude that the deletion in the MC1RΔ24 leads to a receptor with a high basal activity which is further activated by ASIP. This is the first report of ASIP acting as an agonist to MC1R

The impact of herpes zoster and post-herpetic neuralgia on quality-of-life

International audienceBACKGROUND: The potentially serious nature of herpes zoster (HZ) and the long-term complication post-herpetic neuralgia (PHN) are often underestimated. One in four people will contract herpes zoster in their lifetime, with this risk rising markedly after the age of 50 years, and affecting one in two in elderly individuals. Pain is the predominant symptom in all phases of HZ disease, being reported by up to 90% of patients. In the acute phase, pain is usually moderate or severe, with patients ranking HZ pain as more intense than post-surgical or labour pains. Up to 20% of patients with HZ develop PHN, which is moderate-to-severe chronic pain persisting for months or years after the acute phase. We review the available data on the effect of HZ and PHN on patients' quality-of-life. DISCUSSION: Findings show that HZ, and particularly PHN, have a major impact on patients' lives across all four health domains--physical, psychological, functional and social. There is a clear correlation between increasing severity of pain and greater interference with daily activities. Non-pain complications such as HZ ophthalmicus can increase the risk of permanent physical impairment. Some elderly individuals may experience a permanent loss of independence after an acute episode of HZ. Current challenges in the management of HZ and PHN are highlighted, including the difficulty in administering antiviral agents before pain becomes established and the limited efficacy of pain treatments in many patients. We discuss the clinical rationale for the HZ vaccine and evidence demonstrating that the vaccine reduces the burden of the disease. The Shingles Prevention Study, conducted among >38,000 people aged >or=60 years old, showed that the HZ vaccine significantly reduces the burden of illness and the incidence of both HZ and PHN. In the entire study population, zoster vaccination reduced the severity of interference of HZ and PHN with activities of daily living by two-thirds, as measured by two questionnaires specific to HZ. SUMMARY: A vaccination scheme may positively impact the incidence and course of HZ disease, thereby improving patients' quality-of-life