Search

Aim Predicting progression in diabetic kidney disease (DKD) is critical to improving outcomes. We sought to develop/validate a machine-learned, prognostic risk score (KidneyIntelX™) combining electronic health records (EHR) and biomarkers. Methods This is an observational cohort study of patients with prevalent DKD/banked plasma from two EHR-linked biobanks. A random forest model was trained, and performance (AUC, positive and negative predictive values [PPV/NPV], and net reclassification index [NRI]) was compared with that of a clinical model and Kidney Disease: Improving Global Outcomes (KDIGO) categories for predicting a composite outcome of eGFR decline of ≥5 ml/min per year, ≥40% sustained decline, or kidney failure within 5 years. Results In 1146 patients, the median age was 63 years, 51% were female, the baseline eGFR was 54 ml min−1 [1.73 m]−2, the urine albumin to creatinine ratio (uACR) was 6.9 mg/mmol, follow-up was 4.3 years and 21% had the composite endpoint. On cross-validation in derivation (n = 686), KidneyIntelX had an AUC of 0.77 (95% CI 0.74, 0.79). In validation (n = 460), the AUC was 0.77 (95% CI 0.76, 0.79). By comparison, the AUC for the clinical model was 0.62 (95% CI 0.61, 0.63) in derivation and 0.61 (95% CI 0.60, 0.63) in validation. Using derivation cut-offs, KidneyIntelX stratified 46%, 37% and 17% of the validation cohort into low-, intermediate- and high-risk groups for the composite kidney endpoint, respectively. The PPV for progressive decline in kidney function in the high-risk group was 61% for KidneyIntelX vs 40% for the highest risk strata by KDIGO categorisation (p event for the high-risk group was 41% (p Conclusions KidneyIntelX improved prediction of kidney outcomes over KDIGO and clinical models in individuals with early stages of DKD. Graphical abstract

The detection of infection in clinical practice is time consuming and laborious. The ability to monitor infection status in real time, for example in wounds, would enable earlier intervention and improved prognosis. This study describes the real time electrochemical detection of clinically important wound pathogens. Using impedance spectroscopy in conjunction with a normalisation approach, the growth of Proteus mirabilis in LB medium was detected 1 hour after sample inoculation at a cell concentration of 7.4 x106 CFU/mL. Furthermore, a significant decrease in charge transfer resistance arose over the 24 hour growth period (p = 0.009), modelled using a simple equivalent circuit. Additional experiments performed in 0.9% w/v NaCl (where growth was inhibited) indicated that processes facilitated by this organism’s metabolism and growth dominated the impedance response in LB medium. Further, immediate detection of a high concentration of P. mirabilis cells was possible (5.0 x108 CFU/mL). Finally, a simulated wound fluid was used to explore the growths of P. mirabilis, Pseudomonas aeruginosa and Staphylococcus aureus in a more complex environment representative of a wound bed. Similar changes to normalised impedance were observed, and decreases in normalised phase emerged as a characteristic indicator of bacterial growth. The ability of these low cost sensors to rapidly detect bacteria highlights their potential for adoption into point-of-care infection monitoring devices.

The detection of infection in clinical practice is a time consuming and laborious process. The ability to monitor infection status in real time, for example in wounds, would enable earlier intervention and improved prognosis. This study describes the real time electrochemical detection of the clinically important pathogen Proteus mirabilis. Using impedance spectroscopy in conjunction with a normalisation approach, the growth of P. mirabilis in LB medium was detected 1 hour after sample inoculation at a cell concentration of 7.4 x106 CFU/mL. Furthermore, a significant decrease in charge transfer resistance arose over the 24 hour growth period (p = 0.009), modelled using a simple equivalent circuit. Additional experiments performed in 0.9% w/v NaCl (where growth was inhibited) indicated that processes facilitated by the organism’s metabolism and growth dominated the impedance response in LB medium. A simulated wound fluid was used to explore a more complex environment, and similar changes to normalised impedance were observed. The ability of these low cost sensors to rapidly detect P. mirabilis highlights their potential for adoption into point-of-care infection monitoring devices.

Silk can be processed into a broad spectrum of material formats and is explored for a wide range of medical applications, including hydrogels for wound care. The current paradigm is that solution-stable silk fibroin in the hydrogels is responsible for their therapeutic response in wound healing. Here, we generated physically cross-linked silk fibroin hydrogels with tuned secondary structure and examined their ability to influence their biological response by leaching silk fibroin. Significantly more silk fibroin leached from hydrogels with an amorphous silk fibroin structure than with a beta sheet-rich silk fibroin structure, although all hydrogels leached silk fibroin. The leached silk was biologically active, as it induced vitro chemokinesis and faster scratch assay wound healing by activating receptor tyrosine kinases. Overall, these effects are desirable for wound management and show the promise of silk fibroin and hydrogel leaching in the wider healthcare setting.

Background The KidneyIntelX™ test applies a machine learning algorithm that incorporates plasma biomarkers and clinical variables to produce a composite risk score to predict a progressive decline in kidney function in patients with type 2 diabetes (T2D) and early-stage chronic kidney disease (CKD). The following studies describe the analytical validation of the KidneyIntelX assay including impact of observed methodologic variability on the composite risk score. Methods Analytical performance studies of sensitivity, precision, and linearity were performed on three biomarkers assayed in multiplexed format: kidney injury molecule-1 (KIM-1), soluble tumor necrosis factor receptor-1 (sTNFR-1) and soluble tumor necrosis factor receptor-2 (sTNFR-2) based on Clinical Laboratory Standards Institute (CLSI) guidelines. Analytical variability across twenty (20) experiments across multiple days, operators, and reagent lots was assessed to examine the impact on the reproducibility of the composite risk score. Analysis of cross-reactivity and interfering substances was also performed. Results Assays for KIM-1, sTNFR-1 and sTNFR-2 demonstrated acceptable sensitivity. Mean within-laboratory imprecision coefficient of variation (CV) was established as less than 9% across all assays in a multi-lot study. The linear range of the assays was determined as 12–5807 pg/mL, 969–23,806 pg/mL and 4256–68,087 pg/mL for KIM-1, sTNFR-1 and sTNFR-2, respectively. The average risk score CV% was less than 5%, with 98% concordance observed for assignment of risk categories. Cross-reactivity between critical assay components in a multiplexed format did not exceed 1.1%. Conclusions The set of analytical validation studies demonstrated robust analytical performance across all three biomarkers contributing to the KidneyIntelX risk score, meeting or exceeding specifications established during characterization studies. Notably, reproducibility of the composite risk score demonstrated that expected analytical laboratory variation did not impact the assigned risk category, and therefore, the clinical validity of the reported results.

Host cell proteins (HCPs) are process-related impurities that may co-purify with biopharmaceutical drug products. Within this class of impurities there are some that are more problematic. These problematic HCPs can be considered high-risk and can include those that are immunogenic, biologically active, or enzymatically active with the potential to degrade either product molecules or excipients used in formulation, and often are difficult-to-purify. Why should the biopharmaceutical industry worry about these high-risk host cell proteins? What approach could be taken to understand the origin of this co-purification and to deal with these high-risk HCPs? To answer these questions, the BioPhorum Development Group (BPDG) HCP Workstream initiated a collaboration among its 26-company team with the goal of industry alignment around high-risk HCPs. A sub team was formed, in which the members performed literature searches and discussed the information available around this topic. A survey to the BPDG HCP Workstream team members led to team discussions and insights into a list of frequently seen problematic HCPs. These HCPs were further classified based on their potential impact into different risk categories that could be beneficial to the biopharmaceutical industry for targeted monitoring of those HCP impurities in CHO-produced biologics to minimize risk to product quality, safety, and efficacy.

Chronic wound infections represent a significant burden to healthcare providers globally. Often, chronic wound healing is impeded by the presence of infection within the wound or wound bed. This can result in an increased healing time, healthcare cost and poor patient outcomes. Thus, there is a need for dressings that help the wound heal, in combination with early detection of wound infections to support prompt treatment. In this study, we demonstrate a novel, biocompatible wound dressing material, based on Polyhydroxyalkanoates, doped with graphene platelets, which can be used as an electrochemical sensing substrate for the detection of a common wound pathogen, Pseudomonas aeruginosa. Through the detection of the redox active secondary metabolite, pyocyanin, we demonstrate that a dressing can be produced that will detect the presence of pyocyanin across clinically relevant concentrations. Furthermore, we show that this sensor can be used to identify the presence of pyocyanin in a culture of P. aeruginosa. Overall, the sensor substrate presented in this paper represents the first step toward a new dressing with the capacity to promote wound healing, detect the presence of infection and release antimicrobial drugs, on demand, to optimized healing.

No clinical trials for histoplasmosis have been performed with the newer azoles, leaving itraconazole as the azole of choice. In vitro studies suggest that Histoplasma capsulatum from patients that relapse on fluconazole has higher minimum inhibitory concentrations (MICs) to fluconazole and voriconazole but not itraconazole and posaconazole. The newest azole, isavuconazole, shares structural similarity to voriconazole, but to date nobody has explored emergence of resistance. In vitro susceptibilities to isavucoanzole and fluconazole were performed on previously obtained isolates from the patients who relapsed on fluconazole therapy. Susceptibilities were determined by NCCLS method M27A developed for yeasts, as modified for H. capsulatum. The change in the MIC from the primary to the relapse isolate was tested using Wilcoxon Rank-Sum for paired data. Among the primary isolates, the median MICs were 1.0 (range 0.25 to 4.0) μg/ml for fluconazole and ≤0.007 (range ≤0.007 to 0.015) μg/ml for isavuconazole. In the group of relapsed isolates, the median MICs rose to 8.0 (range 0.25 to 64.0) μg/ml for fluconazole and remained unchanged at ≤0.007 (range ≤0.007 to 0.015) μg/ml for isavuconazole (P < .001). Only one isolate exhibited a nonsignificant increase in MIC to isavuconazole. Histoplasma isolates from patients who relapsed on fluconazole did not have an elevation in MICs to isavuconazole. This differs from the results previously seen with voriconazole and suggests that despite a closer structural similarity to voriconazole than itraconazole and posaconazole, isavuconazole has a higher barrier to resistance and may be effective as therapy for histoplasmosis.

A conformable device for wearable phototherapy applications is presented. The device consists of a 1 mm thick elastomeric membrane edge-lit by specially fabricated micro-sized LEDs. Nanoparticle based scattering films are utilized to extract light and a uniform emission of 15 µW/cm2 is reported over an area of 2 cm2.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that causes loss of joint function and significantly reduces quality of life. Plasma metabolite concentrations of disease-modifying anti-rheumatic drugs (DMARDs) can influence treatment efficacy and toxicity. This study explored the relationship between DMARD-metabolising gene variants and plasma metabolite levels in RA patients. DMARD metabolite concentrations were determined by tandem mass-spectrometry in plasma samples from 100 RA patients with actively flaring disease collected at two intervals. Taqman probes were used to discriminate single-nucleotide polymorphism (SNP) genotypes in cohort genomic DNA: rs246240 (ABCC1), rs1476413 (MTHFR), rs2231142 (ABCG2), rs3740065 (ABCC2), rs4149081 (SLCO1B1), rs4846051 (MTHFR), rs10280623 (ABCB1), rs16853826 (ATIC), rs17421511 (MTHFR) and rs717620 (ABCC2). Mean plasma concentrations of methotrexate (MTX) and MTX-7-OH metabolites were higher (p &lt, 0.05) at baseline in rs4149081 GA genotype patients. Patients with rs1476413 SNP TT or CT alleles have significantly higher (p &lt, 0.001) plasma poly-glutamate metabolites at both study time points and correspondingly elevated disease activity scores. Patients with the rs17421511 SNP AA allele reported significantly lower pain scores (p &lt, 0.05) at both study intervals. Genotyping strategies could help prioritise treatments to RA patients most likely to gain clinical benefit whilst minimizing toxicity.

A mechanically-flexible device for uniform area illumination is presented. The device consists of a 1 mm-thick elastomeric membrane edge-lit by a GaN LED. Homogenous irradiance above 0.13 mW/cm2 at 450 nm over a 2.2 cm2 area is reported. Performance improvements, scalability and operation at other wavelengths are discussed.

Anastomotic leak (AL) in colorectal surgery leads to significant morbidity, mortality and poorer oncological outcomes. Diagnosis of AL is frequently delayed as current methods of detection are not 100% sensitive or specific. ‘Biomarkers’, such as cytokines and markers of ischaemia, from the milieu of the anastomosis may aid early detection. This paper aims to review the evidence for their role in AL detection, allowing identification of targets for future research. A systematic review was performed using PubMed, MEDLINE and Cochrane Library databases. Papers concerning detection or prediction of AL with biomarkers were identified. References within the papers were used to identify further relevant articles. Research has taken place in small cohorts with varying definitions of AL. Lactate has consistently been shown to be elevated in patients with intra-abdominal complications and ALs. pH on post-operative day 3 showed excellent specificity. Despite mixed results, a meta-analysis found that the cytokines tumour necrosis factor-α and interleukin-6 were elevated early in AL. Detection of bacteria in drain fluid by RT-PCR has good specificity but a high rate of false positives. Peritoneal cytokines, lactate and pH have the potential to identify AL early. The consistency of the results for lactate and pH, alongside the fact that they are easy, quick and inexpensive to test, makes them the most attractive targets. Studies in larger cohorts with standardized definitions of AL are required to clarify their usefulness. Emerging biosensor technology may facilitate the development of small, low-cost and degradable intra-abdominal devices to measure peritoneal fluid biomarkers.

Serologic tests for antibodies toBlastomyces dermatitidisare not thought to be useful for the diagnosis of blastomycosis, in part due to the low sensitivity of immunodiffusion and complement fixation. Earlier studies have shown that the enzyme immunoassay improves the sensitivity of antibody detection for the diagnosis of blastomycosis. Microplates coated with theB. dermatitidissurface protein BAD-1 were used for testing sera from patients with proven blastomycosis or histoplasmosis and controls. Semiquantification was accomplished by using standards containing human anti-B. dermatitidisantibodies. The antibodies were detected in 87.8% of the patients with blastomycosis by the enzyme immunoassay compared to 15.0% by immunodiffusion. The specificities were 99.2% for patients with nonfungal infections and healthy subjects and 94.0% for patients with histoplasmosis. The results were highly reproducible on repeat testing. When combined with antigen testing, antibody testing improved the sensitivity from 87.8% to 97.6%. Enzyme immunoassay detection of antibodies against BAD-1 is highly specific, has greatly improved sensitivity over immunodiffusion, and may identify cases with negative results by antigen testing. This assay has the potential to aid in the diagnosis of blastomycosis.

Wound moisture is known to be a key parameter to ensure optimum healing conditions in wound care. This study tests the moisture content of wounds in normal practice in order to observe the moisture condition of the wound at the point of dressing change. This study is also the first large‐scale observational study that investigates wound moisture status at dressing change. The WoundSense sensor is a commercially available moisture sensor which sits directly on the wound in order to find the moisture status of the wound without disturbing or removing the dressing. The results show that of the 588 dressing changes recorded, 44·9% were made when the moisture reading was in the optimum moisture zone. Of the 30 patients recruited for this study, 11 patients had an optimum moisture reading for at least 50% of the measurements before dressing change. These results suggest that a large number of unnecessary dressing changes are being made. This is a significant finding of the study as it suggests that the protocols currently followed can be modified to allow fewer dressing changes and less disturbance of the healing wound bed.

Non-invasive patient monitoring by reverse iontophoresis has the potential to drive improved treatment of a variety of conditions within many healthcare settings. We have focussed on the application of this sensor technology to the monitoring of diabetes and cardiovascular disease. Effective monitoring of glucose and potassium levels is crucial to the effective management of these conditions, and the ultimate aim of our study was to investigate the transdermal extraction of these molecules using reverse iontophoresis. Using a novel ethanol enhanced skin gel patch we have recently developed, we applied a low level current (100 mu A/cm(2)) across the skin of nine healthy volunteers for two separate 60 min periods, and quantified the glucose and potassium extracted into the gel, using photometric and electrochemical means respectively. Subjects were in a fasted state during the first 60 min measurement period, while the second measurement period followed the ingestion of a high glucose drink. Finger stick blood samples were obtained at regular intervals during the procedure and these were analysed for glucose and potassium using standard clinical assays. We found that both potassium and glucose were extracted across the skin in readily quantifiable amounts, and the extraction methodology displayed sensitivity to relatively small changes in analyte levels within the blood. We also investigated potassium as an internal standard, and although it improved the correlation between blood and transdermal glucose measurements, alternative calibration approaches will be necessary if the level of accuracy required for clinical application of this sensor technology is to be realised. (C) 2012 Elsevier B.V. All rights reserved.

The aim of this study was to evaluate the mode of death and hospitalizations in advanced heart failure (HF) patients with renal dysfunction and to examine the rate of concordance between events reported by the clinical events committee and site investigators (using case report forms) in the Second Follow-Up Serial Infusions of Nesiritide (FUSION II) trial. Little is known about the cause of death and hospitalization in patients with advanced HF. FUSION II was a randomized, double-blind, placebo-controlled trial evaluating outpatient nesiritide infusions versus placebo, with 911 patients with advanced HF (New York Heart Association class III or IV) and renal dysfunction enrolled. There were 151 deaths and 1,041 hospitalizations at 24 weeks. The clinical events committee classified events as cardiac, renal, cardiorenal, other or noncardiovascular, or unknown. Kappa statistics and McNemar tests were used to assess agreement (overall and by individual modes of death and hospitalization indications). In conclusion, the most common cause of death or hospitalization was cardiac related, with 70% of deaths and 60% of hospitalizations due to cardiac causes. There was 74% agreement (26% disagreement) on cardiac cause of death (κ = 0.40, McNemar p = 0.001) and 75% agreement (25% disagreement) between the investigators and the clinical events committee on cardiac classification for hospitalization (κ = 0.49, McNemar p

Micafungin alone and combined with liposomal amphotericin B was evaluated against two strains of Histoplasma capsulatum . Micafungin was active in vitro against the mold but not the yeast form but was ineffective in vivo . Micafungin appears to be ineffective in treatment of histoplasmosis.

During a Histoplasma outbreak in a colony of fruit bats at a southern United States zoo, it was observed that although Histoplasma was recovered in culture from multiple sites at necropsy, none of the samples collected from those bats tested positive for Histoplasma antigen (HAg). Five of the Histoplasma isolates from the bats were subsequently identified as Latin American (LA) clade A, restriction fragment length polymorphism (RFLP) class 6. These observations raised concern as to whether the commercially available HAg test could detect Histoplasma antigen not of the North American clade upon which the HAg test had been developed. To evaluate this concern, a murine model of disseminated histoplasmosis was established, and mice were infected with multiple LA Histoplasma isolates, including clinical isolates recovered from Brazilian AIDS patients (RFLP class 5 and class 6) and isolates recovered from the bats during the outbreak (RFLP class 6). Histoplasma antigen was detected in all infected mice in our experiments, even when Histoplasma was not recovered in culture. Because the currently available HAg test is able to detect Histoplasma antigen in mice infected with Latin American isolates, this suggests that bat host factors rather than differences among Histoplasma RFLP classes were responsible for the inability to detect HAg in infected bats.

This in vitro study focused on the investigation of the effect of current waveform on simultaneous glucose and lactate extraction by reverse iontophoresis. Experiments were performed using diffusion cells. An iontophoretic current (0.3 mA cm−2) at four different current waveforms (a combination of 0-, 5-, 10- and 15-s pulse intervals and 15-min polarity reversal intervals) were applied for 90 min via Ag/AgCl electrodes. Glucose and lactate extraction were quantified by spectrometric analysis. The result suggests that extraction of glucose and lactate by pulsed bipolar current are pulse-frequent dependent and pulsed bipolar current at a particular pulse-frequent is found to be more effective on glucose and lactate extraction than bipolar current.

Blood lactate monitoring is beneficial to many patients, e.g. critical care patients. However, there are very few non-invasive or continuous monitoring systems for this parameter and significant clinical benefit could be achieved if such systems were readily available. Therefore, the aim of the current study was to investigate the possibility of non-invasively extracting lactate from blood through skin using reverse iontophoresis to monitor blood lactate levels in humans. In vitro reverse iontophoresis studies have indicated that the optimum switching mode for reverse iontophoresis of lactate is continuous direct current but application of current combined with electrode polarity reversal every 15 min was suggested to be used in humans. The reverse iontophoresis technique was applied to 10 healthy volunteers and lactate was successfully extracted through their skin into the methylcellulose gel of the electrodes. A moderate correlation (r2 = 0.6) between lactate concentrations in collection gels and lactate levels in the blood was observed after an outlier was removed from the regression equation. The result suggests that it may be possible to non-invasively monitor the blood lactate levels using reverse iontophoresis technique.

A novel diffusion cell has been constructed which allows study of membrane extraction/permeation processes in a more realistic approach. To examine the performance of this new design, the extraction of glucose in this diffusion cell by reverse iontophoresis has been studied. Reverse iontophoresis refers to the passage of a low level of current through a synthetic or biological membrane to promote the transport of both charged and neutral molecules. The performance of this diffusion cell is compared with results from the extraction studies using a diffusion cell developed by Connolly et al. [P. Connolly, C. Cotton, F. Morin, Opportunities at the skin interface for continuous patient monitoring: a reverse iontophoresis model tested on lactate and glucose, IEEE Trans. Nanobiosci. 1 (1) (2002) 37-41] and results from the human glucose extraction studies in vivo. This newly developed diffusion cell can be easily fabricated for membrane extraction/permeation studies and for device and sensor development.

The second-generation Histoplasma antigen immunoassay is semiquantitative, expressing results as a comparison to a negative control, which requires repeat testing of the prior specimen with the current specimen to accurately determine a change in antigen. Reporting results in this manner often is confusing to the ordering physician and laboratory. Development of a quantitative assay could improve accuracy, reduce interassay variability, and eliminate the need to test the prior sample with the current sample in the same assay. Calibrators with known concentrations of Histoplasma antigen were used to quantitate antigen in specimens from patients with histoplasmosis and from controls. Samples from cases of disseminated histoplasmosis or other mycoses and controls were tested to evaluate the performance characteristics of the quantitative assay. Paired specimens were evaluated to determine if quantitation eliminated the need to test the current and prior specimens in the same assay to assess a change in antigen. The sensitivity in samples from patients with AIDS and disseminated histoplasmosis was 100% in urine and 92.3% in serum. Cross-reactions occurred in 70% of other endemic mycoses, but not in aspergillosis. Specificity was 99% in controls with community-acquired pneumonia, medical conditions in which histoplasmosis was excluded, or healthy subjects. A change in antigen level categorized as an increase, no change, or decrease based on antigen units determined in the same assay agreed closely with the category of change in nanograms/milliliter determined from testing current and prior specimens in different assays. Sensitivity, specificity, and interassay precision are excellent in the new third-generation quantitative Histoplasma antigen immunoassay.

Galactomannans (GalMs) are complex polysaccharides composed of D-galactose and D-mannose. Alkaline-extracted GalMs from Aspergillus fumigatus contain a core of (136)--D-mannopyranosyl residues, with (135)-linked -galactofuranosyl units. The pathogenic fungus Cryptococcus neoformans also contains complex capsular polysaccharides composed of glucuronoxylomannan (GXM) and galactoxylomannans (GalXM). GXM makes up about 90% of the capsular mass and is a polymer of up to six different repeating units that consist mostly of a linear (133)-mannan trisaccharide with side groups consisting of (132)-glucopyranosyluronic acid and (132)- and (134)xylopyranosyl (2, 6). Additionally, the mannan backbone of GXM is modified by acetyl groups. GalXM constitutes about 7% of the capsular mass (2) and has an (136) galactan backbone containing four potential short oligosaccharide branch structures. The branches are 3-O

Invasive fungal infections are often difficult to diagnose using radiology, culture methods, histopathology, or serology, and turnaround time is often lengthy. Antigen testing has been developed for several important invasive mycoses, offering rapid turnaround time and sensitivity comparable or superior to those of other methods. This review provides an update on rapid antigen testing for several invasive fungal infections, including histoplasmosis, blastomycosis, coccidioidomycosis, and aspergillosis and is intended as an addendum to previous reviews on the subject.

Audrey Cund,1–4 Jayne L Birch-Jones,1,3,4 Martin Kay,1 Patricia Connolly4 1School of Health, Nursing and Midwifery, University of The West of Scotland, Paisley, Scotland, UK; 2Nottinghamshire Health and Social Care Assistive Technology Programme, Mansfield and Ashfield Clinical Commissioning Group, National Health Service, Rainworth, Mansfield, Nottinghamshire, UK; 3Kay Consultancy Ltd, Newark, UK; 4Department of Biomedical Engineering, University of Strathclyde, Glasgow, Scotland, UK Background: Living with and managing a long-term condition are complex processes that are further compounded by a range of medical and psychosocial factors. The size and scale of long-term conditions in the UK is vast, with strategic drivers seeking to find innovative ways to managing this problem. Methods: This project introduced Simple Telehealth “Florence,” a software-based short message service texting system to monitor a variety of conditions, such as diabetes, hypertension, and wounds, initially in one region of the East Midlands, England, UK. This article discusses the findings from our patient and staff evaluations of using the system. In total, 37 patients across four conditions, diabetes, chronic obstructive pulmonary disease, hypertension, and Asperger's syndrome, evaluated the study and this exercise involved 33 nurses in teams across three locations over a 6-month period. Evaluation was made using a simple, self-completed questionnaire and analysis of qualitative comments. Results: The majority of patients find the service easy to use, reassuring, and reducing the number of contacts they had with their doctor. The results also show that staff did notice a reduction in consultation time, highlighting the potential of the system to save time; the majority viewed it as a support to existing approaches aimed at the management of long-term conditions. Discussion: This study adds to the growing body of evidence that supports community nurses through the use of innovative ways to assess, support, and monitor long-term conditions. It also offers insight into the experience of patients and staff working together in one region of England, UK. Recommendations: Embedding Simple Telehealth “Florence” as an option within primary care services in the UK is hereby proposed. This would add to the range of options and therapeutic approaches available through modern Telehealth. Keywords: self-management, simple telehealth, Flo, patient experience, community nurse

Objectives: To determine the activity of newer triazoles against strains of Histoplasma capsulatum resistant to fluconazole. Methods: Susceptibility testing was performed on 17 paired pre- and post-treatment H. capsulatum isolates from patients with AIDS who failed fluconazole. Results: The median MICs of fluconazole, voriconazole, and posaconazole and ravuconazole for the pre-treatment isolates were 1 mg/L, 0.015 mg/L and

We developed a colorimetric microtiter plate polymerase chain reaction enzyme immunoassay (PCR-EIA) for the detection of Histoplasma capsulatum in urine. The specificity of the PCR assay was confirmed using H. capsulatum (positive control) and Blastomyces dermatitidis (negative control) isolates. The analytical sensitivity of the PCR assay was determined by testing urine samples spiked with freshly grown H. capsulatum organisms and was 2 yeasts per reaction in urine and 0.2 yeasts per reaction in urine sediment after centrifugation. Fifty-one urine specimens positive for H. capsulatum antigen and 25 urine specimens from healthy volunteers were tested blindly. Patient specimens also were cultured for H. capsulatum. The PCR assay was positive in 4 (7.8%) of 51 urine specimens containing antigen and negative in urine specimens from healthy volunteers. The positive PCR results occurred in 4 of 5 urine specimens that were positive by culture, and each exhibited high level of antigenuria (>20 U). Urine cultures were not positive in 24 urine specimens with an antigenuria of 1-19.9 U, but were positive in 5 of 27 urine specimens with antigenuria >20 U. Thus, positive PCR results in urine specimens correlate with positive culture results, but not with antigenuria. The low sensitivity of this PCR assay in urine limits its use in the diagnosis of disseminated histoplasmosis.

Iontophoresis for the localised delivery of drugs through skin or for non-invasive, remote monitoring of patients by extraction of blood-borne components through skin could allow a new generation of medical devices to be developed for low-cost healthcare. Iontophoresis systems in existence today are generally not very portable and too expensive for all world markets. Accordingly, a low-cost, low-power, miniature and programmable device was developed and evaluated which can be programmed to deliver various current profiles during iontophoresis. It can provide a range of current (1–300 μA) of various signal waveforms (dc, pulsed dc, bipolar dc and pulsed bipolar dc) of the type required for iontophoresis. Evaluation showed that this device provides for precise regulation of the magnitude and waveform of a current. The current can be maintained over a wide range of impedance, important for use in medical application, and is independent of the battery voltage.

Clinical differences in histoplasmosis between North America and Brazil prompted investigation of experimental infection with representative strains. Mortality was higher with Latin American strains, and lung pathology showed large necrotizing granuloma with prominent neutrophilic infiltration. Chronic disease was unique to the North American strain.

False-positive Histoplasma antigen results were identified in two patients who received rabbit antithymocyte globulin (ATG, Thymoglobulin®) to prevent allograft rejection. To determine the prevalence of false-positive results following the administration of Thymoglobulin®, sequential specimens were tested from a cohort of transplant recipients. Of 107 such patients, 17 (15.9%) demonstrated false-positive tests for Histoplasma antigenemia. False antigenemia peaked at 2–4 weeks after ATG administration and cleared over the next few months. Physicians should be aware of the potential for false-positive results in specimens from patients who have received ATG.

Cardiopulmonary (CPB) bypass is 50 years old this year, and has undergone considerable change in that time, particularly with regard to developing technology. However, in recent years the routine application of CPB, as the treatment of choice for patients undergoing reparative heart surgery, has been challenged by new, evolving techniques, particularly Off-Pump Coronary Artery Bypass (OPCAB) and stenting. This paper considers whether CPB still represents a sound investment prospect, with particular emphasis on the biomaterial developments currently taking place. Whilst we accept that routine application of CPB is shrinking under pressure from less invasive techniques, we suggest that this may represent an opportunity to deliever a more highly evolved perfusion to the core of very sick and complex patients who may not be suitable candidates for OPCAB or stenting. These patients will benefit from the application of new technologies currently under development, such as smaller perfusion circuits, improved biomaterial surfaces, smart membranes, and biosensor technology, all aimed at making clinical perfusion a safer and more predictable procedure for the patient. All things conssidered, we feel that CPB, although shrinking in absolute size, still represents a good investment.

In recent years a specialist interest has developed worldwide in advanced wound management for difficult to heal chronic wounds. Further progress in advanced wound management will require an improvement in personalized medicine for the patient and in particular an improvement in the availability of diagnostic tests and parameters that fulfil clinical need in wound management decisions. However, without easy to use sensors for nurses and carers these potentially important near-patient diagnostic parameters will not enter clinical diagnostics. This study focuses on a number of metrics for wound condition and wound healing: wound fluid pH, wound moisture, and wound matrix metalloproteinases (MMP) enzyme activity. To observe these important markers state of the art sensors have been developed that are based on inexpensive sensing technologies that can be integrated within wound dressings. These sensors will enable the wound healing markers to be studied and profiled in clinics which will further enhance the understanding of these markers and their relationship in the complex healing process involved in chronic wound healing.

Demographic and clinical parameters among patients with acquired immunodeficiency syndrome and histoplasmosis in Brazil and United States were compared. The Brazilian isolates were typed by restriction-fragment length polymorphism analysis and were DNA fingerprinted by random amplification of polymorphic DNA (RAPD)-polymerase chain reaction (PCR). Skin lesions occurred in 66% of Brazilian case patients, compared with 1%-7% of US case patients. Of 21 treated case patients, 4 (19%) died, a rate similar to that of the US case patients (5%-13%). By nuclear gene typing, the Brazilian isolates were equally divided between South American classes 5 and 6, and RAPD-PCR showed 18 distinct genetic fingerprints in 20 isolates. Skin lesions are more common in infection with class 5 or 6 organisms than with class 2 Histoplasma capsulatum. The role of genetic differences in the organism as a cause for the clinical differences requires investigation.

Pseudomonas aeruginosa, widely present in the environment, is well known for its ability to cause infection in immune compromised individuals. For example, P. aeruginosa is the leading cause of morbidity and mortality in patients with cystic fibrosis (CF). Here, we describe how Electrochemical Impedance Spectroscopy (EIS) can be used to detect the presence of four different strains of P. aeruginosa. Using a low cost, screen printed carbon electrode significant changes can be seen in impedance data in the presence of P. aeruginosa after 24 hours. Furthermore, through the use of a normalization technique whereby the phase angle of the impedance (a commonly used parameter) is divided by a starting measurement, it is possible to identify differences between a non-mucoid and mucoid strain of P. aeruginosa. Sensors based upon the techniques described here could be used in a number of healthcare scenarios, where there is a need for low cost, real time detection of P. aeruginosa, such as CF.

Objective: This study examines the effect of various wound dressings on the pH levels of a wound, using a simulated wound environment. Method: The pH levels of a 4 different wound dressings (manuka honey dressing, sodium carboxymethylcellulose hydrofiber dressing, polyhydrated ionogen-coated polymer mesh dressing, and a protease modulating collagen cellulose dressing) were tested in a simulated horse serum wound environment. The effect of local buffering was observed and pH changes in real time were measured. Results: All dressings were found to have low pH (below pH 4), with the lowest being the protease modulating collage cellulose dressing, with a pH of 2.3. The dressing with the strongest acid concentration was the polyhydrated, ionogen-coated, polymer mesh dressing. Conclusion: The low pH and strong acidic nature of the dressing investigated indicate that they may play a role in influencing the healing process in a wound. Declaration of interest: The authors have no conflicts of interest to declare. This study was funded by the EPSRC.