Arthritis in adults with community-acquired bacterial meningitis: a prospective cohort study

BACKGROUND: Although the coexistence of bacterial meningitis and arthritis has been noted in several studies, it remains unclear how often both conditions occur simultaneously. METHODS: We evaluated the presence of arthritis in a prospective nationwide cohort of 696 episodes of community-acquired bacterial meningitis, confirmed by culture of cerebrospinal fluid, which occurred in patients aged >16 years. The diagnosis of arthritis was based upon the judgment of the treating physician. To identify differences between groups Fisher exact statistics and the Mann-Whitney U test were used. RESULTS: Arthritis was recorded in 48 of 696 (7%) episodes of community-acquired bacterial meningitis in adults. Joint-fluid aspirations were performed in 23 of 48 patients (48%) and joint-fluid cultures yielded bacteria in 6 of 23 patients (26%). Arthritis occurred most frequently in patients with meningococcal meningitis (12%). Of the 48 patients with bacterial meningitis and coexisting arthritis, four died (8%) and 10 (23%) had residual joint symptoms. CONCLUSION: Arthritis is a common manifestation in patients with community-acquired bacterial meningitis. Functional outcome of arthritis in bacterial meningitis is generally good because meningococcal arthritis is usually immune-mediated, and pneumococcal arthritis is generally less deforming than staphylococcal arthritis. Nevertheless, additional therapeutic measures should be considered if clinical course is complicated by arthritis. In patients with infectious arthritis prolonged antibiotic therapy is mandatory

Pneumococcal meningitis: Clinical-pathological correlations (meningene-path)

Pneumococcal meningitis is associated with substantial mortality and morbidity. We systematically assessed brain histopathology of 31 patients who died of pneumococcal meningitis from a nationwide study (median age 67 years; 21 (67 %) were male) using a pathology score including inflammation and vascular damage. Of the 27 patients with known time from the admission to death, 14 patients died within 7 days of admission and 13 after 7 days of admission. Eleven of 25 (44 %) patients had been treated with adjunctive dexamethasone therapy. Observed pathological processes were inflammation of medium-large arteries in 30 brains (97 %), cerebral haemorrhage in 24 (77 %), cerebritis in 24 (77 %), thrombosis in 21 (68 %), infarction in 19 (61 %) and ventriculitis in 19 (of 28 cases, 68 %). Inflammation of medium-large arteries led to obstruction of the vascular lumen in 14 (of 31 cases, 45 %). Vascular inflammation was associated with infarction and thrombosis of brain parenchymal vessels. Hippocampal dentate gyrus apoptosis between patients treated with and without dexamethasone was similar (p = 0.66); however, dexamethasone treated patients had higher total pathology score than non-dexamethasone treated patients (p = 0.003). Our study shows that vascular damage is key in the process of brain damage in pneumococcal meningitis. Data and material of this study will be made open-access for translational research in pneumococcal meningitis (MeninGene-Path)

Daptomycin in experimental murine pneumococcal meningitis

<p>Abstract</p> <p>Background</p> <p>Daptomycin, a lipopeptide antibiotic, could be an alternative to vancomycin for treatment of pneumococcal meningitis. We determined the activity of daptomycin versus vancomycin, with dexamethasone as an adjuvant, in a murine model of pneumococcal meningitis.</p> <p>Methods</p> <p>Ninety-six 25–30 gram mice were inoculated intracisternally with serotype 3 <it>Streptococcus pneumoniae </it>modified by the integration of a luminescent <it>lux </it>operon. All mice were treated with either dexamethasone 1 mg/kg intraperitoneally every 6 hours alone or in combination with either vancomycin or daptomycin, also administered intraperitoneally. Serum antimicrobial concentrations were selected to approximate those achieved in humans. Following treatment, bioluminescence and cerebrospinal fluid (CSF) bacterial concentrations were determined. Caspase-3 staining was used to assess apoptosis on brain histopathology.</p> <p>Results</p> <p>Sixteen hours post intracisternal inoculation, bacterial titers in CSF were 6.8 log₁₀cfu/ml. Amongst the animals given no antibiotic, vancomycin 50 mg/kg at 16 and 20 hours or daptomycin 25 mg/kg at 16 hours, CSF titers were 7.6, 3.4, and 3.9 log₁₀cfu/ml, respectively, at 24 hours post infection (p-value, < 0.001 for both vancomycin or daptomycin versus no antibiotic); there was no significant difference in bactericidal activity between the vancomycin and daptomycin groups (p-value, 0.18). CSF bioluminescence correlated with bacterial titer (Pearson regression coefficient, 0.75). The amount of apoptosis of brain parenchymal cells was equivalent among treatment groups.</p> <p>Conclusion</p> <p>Daptomycin or vancomycin, when given in combination with dexamethasone, is active in the treatment of experimental pneumococcal meningitis.</p

Current Pyuria Cutoffs Promote Inappropriate Urinary Tract Infection Diagnosis in Older Women

Background: Pre-existing lower urinary tract symptoms (LUTS), cognitive impairment, and the high prevalence of asymptomatic bacteriuria (ASB) complicate the diagnosis of urinary tract infection (UTI) in older women. The presence of pyuria remains the cornerstone of UTI diagnosis. However, >90% of ASB patients have pyuria, prompting unnecessary treatment. We quantified pyuria by automated microscopy and flowcytometry to determine the diagnostic accuracy for UTI and to derive pyuria thresholds for UTI in older women. Methods: Women ≥65 years with ≥2 new-onset LUTS and 1 uropathogen ≥104 colony-forming units (CFU)/mL were included in the UTI group. Controls were asymptomatic and classified as ASB (1 uropathogen ≥105 CFU/mL), negative culture, or mixed flora. Patients with an indwelling catheter or antimicrobial pretreatment were excluded. Leukocyte medians were compared and sensitivity–specificity pairs were derived from a receiver operating characteristic curve. Results: We included 164 participants. UTI patients had higher median urinary leukocytes compared with control patients (microscopy: 900 vs 26 leukocytes/µL; flowcytometry: 1575 vs 23 leukocytes/µL; P < .001). Area under the curve was 0.93 for both methods. At a cutoff of 264 leukocytes/µL, sensitivity and specificity of microscopy were 88% (positive and negative likelihood ratio: 7.2 and 0.1, respectively). The commonly used cutoff of 10 leukocytes/µL had a poor specificity (36%) and a sensitivity of 100%. Conclusions: The degree of pyuria can help to distinguish UTI in older women from ASB and asymptomatic controls with pyuria. Current pyuria cutoffs are too low and promote inappropriate UTI diagnosis in older women

The role of bisphosphonates in breast cancer: Development of bisphosphonates

Bisphosphonates are synthetic compounds characterized by a P–C–P group, and are thus analogs of inorganic pyrophosphate. They are used in medicine mainly to inhibit bone resorption in diseases like osteoporosis, Paget's disease and tumor bone disease. They have been used for over a century in industry, and only in 1968 was it shown that bisphosphonates have biological effects. These effects consist mainly of an inhibition of bone resorption and, when given in large amounts, an inhibition of ectopic and normal calcification. While the latter effect is the consequence of a physical-chemical inhibition of calcium phosphate crystal formation, the former is due to a cellular effect involving both apoptosis of the osteoclasts and a destruction of the osteoclastic cytoskeleton, inducing a decrease in osteoclast activity. The biochemical basis of these effects for the nitrogen-containing compounds is an inhibition of the mevalonate pathway caused by the inhibition of farnesylpyrophosphate synthase, which leads to a decrease of the formation of isoprenoid lipids such as farnesylpyrophosphate and geranylgeranylpyrophosphate. The other bisphosphonates are incorporated into the phosphate chain of ATP-containing compounds so that they become non-hydrolyzable. The new P–C–P-containing ATP analogs inhibit cell function and may lead to apoptosis and death of osteoclasts

Cumulative Low Back Load at Work as a Risk Factor of Low Back Pain: A Prospective Cohort Study

Purpose Much research has been performed on physical exposures during work (e.g. lifting, trunk flexion or body vibrations) as risk factors for low back pain (LBP), however results are inconsistent. Information on the effect of doses (e.g. spinal force or low back moments) on LBP may be more reliable but is lacking yet. The aim of the present study was to investigate the prospective relationship of cumulative low back loads (CLBL) with LBP and to compare the association of this mechanical load measure to exposure measures used previously. Methods The current study was part of the Study on Musculoskeletal disorders, Absenteeism and Health (SMASH) study in which 1,745 workers completed questionnaires. Physical load at the workplace was assessed by video-observations and force measurements. These measures were used to calculate CLBL. Furthermore, a 3-year follow-up was conducted to assess the occurrence of LBP. Logistic regressions were performed to assess associations of CLBL and physical risk factors established earlier (i.e. lifting and working in a flexed posture) with LBP. Furthermore, CLBL and the risk factors combined were assessed as predictors in logistic regression analyses to assess the association with LBP. Results Results showed that CLBL is a significant risk factor for LBP (OR: 2.06 (1.32-3.20)). Furthermore, CLBL had a more consistent association with LBP than two of the three risk factors reported earlier. Conclusions From these results it can be concluded that CLBL is a risk factor for the occurrence of LBP, having a more consistent association with LBP compared to most risk factors reported earlier. © 2012 The Author(s)

Persistent fluctuations in stride intervals under fractal auditory stimulation

Copyright @ 2014 Marmelat et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Stride sequences of healthy gait are characterized by persistent long-range correlations, which become anti-persistent in the presence of an isochronous metronome. The latter phenomenon is of particular interest because auditory cueing is generally considered to reduce stride variability and may hence be beneficial for stabilizing gait. Complex systems tend to match their correlation structure when synchronizing. In gait training, can one capitalize on this tendency by using a fractal metronome rather than an isochronous one? We examined whether auditory cues with fractal variations in inter-beat intervals yield similar fractal inter-stride interval variability as isochronous auditory cueing in two complementary experiments. In Experiment 1, participants walked on a treadmill while being paced by either an isochronous or a fractal metronome with different variation strengths between beats in order to test whether participants managed to synchronize with a fractal metronome and to determine the necessary amount of variability for participants to switch from anti-persistent to persistent inter-stride intervals. Participants did synchronize with the metronome despite its fractal randomness. The corresponding coefficient of variation of inter-beat intervals was fixed in Experiment 2, in which participants walked on a treadmill while being paced by non-isochronous metronomes with different scaling exponents. As expected, inter-stride intervals showed persistent correlations similar to self-paced walking only when cueing contained persistent correlations. Our results open up a new window to optimize rhythmic auditory cueing for gait stabilization by integrating fractal fluctuations in the inter-beat intervals.Commission of the European Community and the Netherlands Organisation for Scientific Research

SOWL QL: Querying Spatio - Temporal Ontologies in OWL

We introduce SOWL QL, a query language for spatio-temporal information in ontologies. Buildingupon SOWL (Spatio-Temporal OWL), an ontology for handling spatio-temporal information in OWL, SOWL QL supports querying over qualitative spatio-temporal information (expressed using natural language expressions such as “before”, “after”, “north of”, “south of”) rather than merely quantitative information (exact dates, times, locations). SOWL QL extends SPARQL with a powerful set of temporal and spatial operators, including temporal Allen topological, spatial directional and topological operations or combinations of the above. SOWL QL maintains simplicity of expression and also, upward and downward compatibility with SPARQL. Query translation in SOWL QL yields SPARQL queries implying that, querying spatio-temporal ontologies using SPARQL is still feasible but suffers from several drawbacks the most important of them being that, queries in SPARQL become particularly complicated and users must be familiar with the underlying spatio-temporal representation (the “N-ary relations” or the “4D-fluents” approach in this work). Finally, querying in SOWL QL is supported by the SOWL reasoner which is not part of the standard SPARQL translation. The run-time performance of SOWL QL has been assessed experimentally in a real data setting. A critical analysis of its performance is also presented