Culture of per-wound bone specimens: a simplified approach for the medical management of diabetic foot osteomyelitis

AbstractSurgical percutaneous bone biopsy specimen after a 14-day antibiotic-free period represents the gold standard of care for diabetic foot osteomyelitis but may be difficult to implement in many institutions. We evaluate a simplified strategy based on the results of per-wound bone specimen culture. For that purpose, we retrospectively reviewed the charts of 80 consecutive patients with diabetic osteomyelitis and bone sample obtained via the wound after a careful debridement. The outcome was defined as favourable if there was a complete healing of the wound with no sign of infection and stable or improved bone X-ray 6 months after antibiotic therapy completion. Culture of bone specimens was positive in 96% of patients, although half of the patients did receive a course of antimicrobials within 14 days of the bone specimen being obtained. A total of 129 bacterial isolates were obtained from bone cultures with a mean of 1.6 ± 1 isolates per patient (Staphylococcus aureus: 33%; coagulase-negative staphylococci: 14%; streptococci: 9%; enterococci: 12%; corynebacteria: 4%; Gram-negative bacilli: 20%; anaerobes: 4%). Forty-six percent of cultures were monomicrobial. The mean duration of follow-up from diagnosis was 17 ± 1 months. Six months after discontinuation of antibiotics, six patients (7.5%) had died, nine were considered as therapeutic failures and 65 were considered as cured. Fifty-four of these 65 patients had follow-up data available at 1 year and remained in remission. In conclusion, a simplified procedure based on the culture of bone sample obtained via the ulcer after a careful debridement of the wound is effective in the medical management of diabetic foot osteomyelitis

On biases in precise point positioning with multi-constellation and multi-frequency GNSS data

© 2016 IOP Publishing Ltd. Various types of biases in Global Navigation Satellite System (GNSS) data preclude integer ambiguity fixing and degrade solution accuracy when not being corrected during precise point positioning (PPP). In this contribution, these biases are first reviewed, including satellite and receiver hardware biases, differential code biases, differential phase biases, initial fractional phase biases, inter-system receiver time biases, and system time scale offset. PPP models that take account of these biases are presented for two cases using ionosphere-free observations. The first case is when using primary signals that are used to generate precise orbits and clock corrections. The second case applies when using additional signals to the primary ones. In both cases, measurements from single and multiple constellations are addressed. It is suggested that the satellite-related code biases be handled as calibrated quantities that are obtained from multi-GNSS experiment products and the fractional phase cycle biases obtained from a network to allow for integer ambiguity fixing. Some receiver-related biases are removed using between-satellite single differencing, whereas other receiver biases such as inter-system biases are lumped with differential code and phase biases and need to be estimated. The testing results show that the treatment of biases significantly improves solution convergence in the float ambiguity PPP mode, and leads to ambiguity-fixed PPP within a few minutes with a small improvement in solution precision

Review of code and phase biases in multi-GNSS positioning

A review of the research conducted until present on the subject of Global Navigation Satellite System (GNSS) hardware-induced phase and code biases is here provided. Biases in GNSS positioning occur because of imperfections and/or physical limitations in the GNSS hardware. The biases are a result of small delays between events that ideally should be simultaneous in the transmission of the signal from a satellite or in the reception of the signal in a GNSS receiver. Consequently, these biases will also be present in the GNSS code and phase measurements and may there affect the accuracy of positions and other quantities derived from the observations. For instance, biases affect the ability to resolve the integer ambiguities in Precise Point Positioning (PPP), and in relative carrier phase positioning when measurements from multiple GNSSs are used. In addition, code biases affect ionospheric modeling when the Total Electron Content is estimated from GNSS measurements. The paper illustrates how satellite phase biases inhibit the resolution of the phase ambiguity to an integer in PPP, while receiver phase biases affect multi-GNSS positioning. It is also discussed how biases in the receiver channels affect relative GLONASS positioning with baselines of mixed receiver types. In addition, the importance of code biases between signals modulated onto different carriers as is required for modeling the ionosphere from GNSS measurements is discussed. The origin of biases is discussed along with their effect on GNSS positioning, and descriptions of how biases can be estimated or in other ways handled in the positioning process are provided.QC 20170922</p

Review and principles of PPP-RTK methods

PPP-RTK is integer ambiguity resolution-enabled precise point positioning. In this contribution, we present the principles of PPP-RTK, together with a review of different mechanizations that have been proposed in the literature. By application of S-system theory, the estimable parameters of the different methods are identified and compared. Their interpretation is essential for gaining a proper insight into PPP-RTK in general, and into the role of the PPP-RTK corrections in particular. We show that PPP-RTK is a relative technique for which the ‘single-receiver user’ integer ambiguities are in fact double-differenced ambiguities. We determine the transformational links between the different methods and their PPP-RTK corrections, thereby showing how different PPP-RTK methods can be mixed between network and users. We also present and discuss four different estimators of the PPP-RTK corrections. It is shown how they apply to the different PPP-RTK models, as well as why some of the proposed estimation methods cannot be accepted as PPP-RTK proper. We determine analytical expressions for the variance matrices of the ambiguity-fixed and ambiguity-float PPP-RTK corrections. This gives important insight into their precision, as well as allows us to discuss which parts of the PPP-RTK correction variance matrix are essential for the user and which are not

CD4saurus Rex &HIVelociraptor vs. development of clinically useful immunological markers: a Jurassic tale of frozen evolution

One of the most neglected areas of everyday clinical practice for HIV physicians is unexpectedly represented by CD4 T cell counts when used as an aid to clinical decisions. All who care for HIV patients believe that CD4+ T cell counts are a reliable method to evaluate a patient immune status. There is however a fatalistic acceptance that besides its general usefulness, CD4+ T cell counts have relevant clincal and immunological limits. Shortcomings of CD4 counts appear in certain clinical scenarios including identification of immunological nonresponders, subsequent development of cancer on antiretroviral teatment, failure on tretment simplification. Historical and recently described parameters might be better suited to advise management of patients at certain times during their disease history. Immunogenotypic parameters and innate immune parameters that define progression as well as immune parameters associated with immune recovery are available and have not been introduced into validation processes in larger trials. The scientific and clinical community needs an effort in stimulating clinical evolution of immunological tests beyond "CD4saurus Rex" introducing new parameters in the clinical arena after appropriate validatio

Are the pneumococcal polysaccharide vaccines effective? Meta-analysis of the prospective trials

The objective was to review the evidence of effectiveness of the polyvalent polysaccharide pneumococcal vaccine from prospective properly randomised controlled trials comparing pneumococcal vaccines with placebo in subjects who are immunocompetent and those likely to have an impaired immune system. Databases searched included the Cochrane Library, (issue 2, 2000), MEDLINE (1966-August 2000), PubMed (to August 2000) and EMBASE ( to August 2000). Reference lists of reports and reviews were also searched. To be included in the analysis, a study had to have been a prospective randomised comparison of a polysaccharide pneumococcal vaccine (any valency) and to have a placebo or no treatment comparison group. Papers had to report important clinical outcomes, such as rates of pneumonia, pneumococcal pneumonia, lower respiratory tract infections, pneumonia deaths or bacteraemia. Serological outcomes were not sought. Thirteen randomised comparisons with over 45,000 subjects were identified in an extensive literature review. Eight studies had a quality score of 3 or more on a scale of 1 to 5. In three comparisons with 21,152 immunocompetent subjects (South African gold miners, New Guinea highlanders) pneumococcal vaccination was effective in reducing the incidence of all-cause pneumonia (relative risk 0.56, 95% confidence interval 0.47 to 0.66), pneumococcal pneumonia (0.16; 0.11 to 0.23), pneumonia deaths (0.70; 0.50 to 0.96) and bacteraemia (0.18; 0.09 to 0.34). In ten comparisons in over 24,000 people who were elderly or likely to have impaired immune systems, pneumococcal vaccination was without effect for any outcome. Present guidelines recommend pneumococcal vaccination for "high-risk" groups. There is no evidence from randomised trials that this is of any benefit

Ten Years of Surveillance for Invasive Streptococcus pneumoniae during the Era of Antiretroviral Scale-Up and Cotrimoxazole Prophylaxis in Malawi

OBJECTIVE: To document trends in invasive pneumococcal disease (IPD) in a central hospital in Malawi during the period of national scale-up of antiretroviral therapy (ART) and cotrimoxazole prophylaxis. METHODS: Between 1 January 2000 and 31 December 2009 almost 100,000 blood cultures and 40,000 cerebrospinal fluid (CSF) cultures were obtained from adults and children admitted to the Queen Elizabeth Central Hospital, Blantyre, Malawi with suspected severe bacterial infection. RESULTS: 4,445 pneumococcal isolates were obtained over the 10 year period. 1,837 were from children: 885 (19.9%) from blood and 952 (21.4%) from CSF. 2,608 were from adults: 1,813 (40.8%) from blood and 795 (17.9%) from CSF. At the start of the surveillance period cotrimoxazole resistance was 73.8% and at the end was 92.6%. Multidrug resistance (MDR) was present in almost one third of isolates and was constant over time. Free ART was introduced in Malawi in 2004. From 2005 onwards there was a decline in invasive pneumococcal infections with a negative correlation between ART scale-up and the decline in IPD (Pearson's correlation r = -0.91; p<0.001). CONCLUSION: During 2004-2009, national ART scale-up in Malawi was associated with a downward trend in IPD at QECH. The introduction of cotrimoxazole prophylaxis in HIV-infected groups has not coincided with a further increase in pneumococcal cotrimoxazole or multidrug resistance. These data highlight the importance of surveillance for high disease burden infections such as IPD in the region, which will be vital for monitoring pneumococcal conjugate vaccine introduction into national immunisation programmes

Review on catalytic cleavage of C-C inter-unit linkages in lignin model compounds: Towards lignin depolymerisation

Lignin depolymerisation has received considerable attention recently due to the pressing need to find sustainable alternatives to fossil fuel feedstock to produce chemicals and fuels. Two types of interunit linkages (C–C and C–O linkages) link several aromatic units in the structure of lignin. Between these two inter-unit linkages, the bond energies of C–C linkages are higher than that of C–O linkages, making them harder to break. However, for an efficient lignin depolymerisation, both types of inter-unit linkages have to be broken. This is more relevant because of the fact that many delignification processes tend to result in the formation of additional C–C inter-unit bonds. Here we review the strategies reported for the cleavage of C–C inter-unit linkages in lignin model compounds and lignin. Although a number of articles are available on the cleavage of C–O inter-unit linkages, reports on the selective cleavage of C–C inter-unit linkages are relatively less. Oxidative cleavage, hydrogenolysis, two-step redox-neutral process, microwave assisted cleavage, biocatalytic and photocatalytic methods have been reported for the breaking of C–C inter-unit linkages in lignin. Here we review all these methods in detail, focused only on the breaking of C–C linkages. The objective of this review is to motivate researchers to design new strategies to break this strong C–C inter-unit bonds to valorise lignins, technical lignins in particular