Cost-Effective Use of Silver Dressings for the Treatment of Hard-to-Heal Chronic Venous Leg Ulcers

Aim To estimate the cost-effectiveness of silver dressings using a health economic model based on time-to-wound-healing in hard-to-heal chronic venous leg ulcers (VLUs). Background Chronic venous ulceration affects 1–3% of the adult population and typically has a protracted course of healing, resulting in considerable costs to the healthcare system. The pathogenesis of VLUs includes excessive and prolonged inflammation which is often related to critical colonisation and early infection. The use of silver dressings to control this bioburden and improve wound healing rates remains controversial. Methods A decision tree was constructed to evaluate the cost-effectiveness of treatment with silver compared with non-silver dressings for four weeks in a primary care setting. The outcomes: ‘Healed ulcer’, ‘Healing ulcer’ or ‘No improvement’ were developed, reflecting the relative reduction in ulcer area from baseline to four weeks of treatment. A data set from a recent meta-analysis, based on four RCTs, was applied to the model. Results Treatment with silver dressings for an initial four weeks was found to give a total cost saving (£141.57) compared with treatment with non-silver dressings. In addition, patients treated with silver dressings had a faster wound closure compared with those who had been treated with non-silver dressings. Conclusion The use of silver dressings improves healing time and can lead to overall cost savings. These results can be used to guide healthcare decision makers in evaluating the economic aspects of treatment with silver dressings in hard-to-heal chronic VLUs

Parametric methods outperformed non-parametric methods in comparisons of discrete numerical variables

<p>Abstract</p> <p>Background</p> <p>The number of events per individual is a widely reported variable in medical research papers. Such variables are the most common representation of the general variable type called discrete numerical. There is currently no consensus on how to compare and present such variables, and recommendations are lacking. The objective of this paper is to present recommendations for analysis and presentation of results for discrete numerical variables.</p> <p>Methods</p> <p>Two simulation studies were used to investigate the performance of hypothesis tests and confidence interval methods for variables with outcomes {0, 1, 2}, {0, 1, 2, 3}, {0, 1, 2, 3, 4}, and {0, 1, 2, 3, 4, 5}, using the difference between the means as an effect measure.</p> <p>Results</p> <p>The Welch U test (the T test with adjustment for unequal variances) and its associated confidence interval performed well for almost all situations considered. The Brunner-Munzel test also performed well, except for small sample sizes (10 in each group). The ordinary T test, the Wilcoxon-Mann-Whitney test, the percentile bootstrap interval, and the bootstrap-<it>t </it>interval did not perform satisfactorily.</p> <p>Conclusions</p> <p>The difference between the means is an appropriate effect measure for comparing two independent discrete numerical variables that has both lower and upper bounds. To analyze this problem, we encourage more frequent use of parametric hypothesis tests and confidence intervals.</p

Autoimmune and autoinflammatory mechanisms in uveitis

The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders

A Risk Assessment of Antibiotic Pan-Drug-Resistance in the UK: Bayesian Analysis of an Expert Elicitation Study.

To inform the UK antimicrobial resistance strategy, a risk assessment was undertaken of the likelihood, over a five-year time-frame, of the emergence and widespread dissemination of pan-drug-resistant (PDR) Gram-negative bacteria that would pose a major public health threat by compromising effective healthcare delivery. Subsequent impact over five- and 20-year time-frames was assessed in terms of morbidity and mortality attributable to PDR Gram-negative bacteraemia. A Bayesian approach, combining available data with expert prior opinion, was used to determine the probability of the emergence, persistence and spread of PDR bacteria. Overall probability was modelled using Monte Carlo simulation. Estimates of impact were also obtained using Bayesian methods. The estimated probability of widespread occurrence of PDR pathogens within five years was 0.2 (95% credibility interval (CrI): 0.07-0.37). Estimated annual numbers of PDR Gram-negative bacteraemias at five and 20 years were 6800 (95% CrI: 400-58,600) and 22,800 (95% CrI: 1500-160,000), respectively; corresponding estimates of excess deaths were 1900 (95% CrI: 0-23,000) and 6400 (95% CrI: 0-64,000). Over 20 years, cumulative estimates indicate 284,000 (95% CrI: 17,000-1,990,000) cases of PDR Gram-negative bacteraemia, leading to an estimated 79,000 (95% CrI: 0-821,000) deaths. This risk assessment reinforces the need for urgent national and international action to tackle antibiotic resistance

Combination of Two but Not Three Current Targeted Drugs Can Improve Therapy of Chronic Myeloid Leukemia

Chronic myeloid leukemia (CML) is a cancer of the hematopoietic system and has been treated with the drug Imatinib relatively successfully. Drug resistance, acquired by mutations, is an obstacle to success. Two additional drugs are now considered and could be combined with Imatinib to prevent resistance, Dasatinib and Nilotinib. While most mutations conferring resistance to one drug do not confer resistance to the other drugs, there is one mutation (T315I) that induces resistance against all three drugs. Using computational methods, the combination of two drugs is found to increase the probability of treatment success despite this cross-resistance. Combining more than two drugs, however, does not provide further advantages. We also explore possible combination therapies using drugs currently under development. We conclude that among the targeted drugs currently available for the treamtent of CML, only the two most effective ones should be used in combination for the prevention of drug resistance

Assessing personality in San Joaquin kit fox in situ: efficacy of field-based experimental methods and implications for conservation management

Utilisation of animal personality has potential benefit for conservation management. Due to logistics of robust behavioural evaluation in situ, the majority of studies on wild animals involve taking animals into captivity for testing, potentially compromising results. Three in situ tests for evaluation of boldness in San Joaquin kit fox (Vulpes macrotis mutica) were developed (ENOT: extended novel object test; RNOT: rapid novel object test; TH: trap/handling test). Each test successfully identified variation in boldness within its target age class(es). The TH test was suitable for use across all age classes. Tests were assessed for in situ suitability and for quantity/quality of data yielded. ENOT was rated as requiring high levels of time, cost and labour with greater likelihood of failure. However, it was rated highly for data quantity/quality. The TH test was rated as requiring little time, labour and cost, but yielding lower quality data. RNOT was rated in the middle. Each test had merit and could be adapted to suit project or species constraints. We recommend field-based evaluation of personality, reducing removal of animals from the wild and facilitating routine incorporation of personality assessment into conservation projects

Leukocyte capture and modulation of cell-mediated immunity during human sepsis: An ex vivo study

Introduction: Promising preclinical results have been obtained with blood purification therapies as adjuvant treatment for sepsis. However, the mechanisms by which these therapies exert beneficial effects remain unclear. Some investigators have suggested that removal of activated leukocytes from the circulation might help ameliorate remote organ injury. We designed an extracorporeal hemoadsorption device capable of capturing both cytokines and leukocytes in order to test the hypothesis that leukocyte capture would alter circulating cytokine profiles and influence immunological cell-cell interactions in whole blood taken from patients with sepsis.Methods: We performed a series of ex vivo studies in 21 patients with septic shock and 12 healthy volunteers. Blood circulated for four hours in closed loops with four specially designed miniaturized extracorporeal blood purification devices including two different hemoadsorption devices and a hemofilter in order to characterize leukocyte capture and to assess the effects of leukocyte removal on inflammation and immune function. Results: Hemoadsorption was selective for removal of activated neutrophils and monocytes. Capture of these cells led to local release of certain cytokines, especially IL-8, and resulted in complex cell-cell interactions involved in cellmediated immunity. Inhibition of cell adherence reversed the cytokine release and the effects on lymphocyte function. Conclusions: Monocyte and neutrophil capture using a sorbent polymer results in upregulation of IL-8 and modulation of cell-mediated immunity. Further studies are needed to understand better these cellular interactions in order to help design better blood purification therapies. © 2013 Rimmelé et al.; licensee BioMed Central Ltd

A New Digital Preoperative Planning Method for Total Hip Arthroplasties

Preoperative templating is an important part of a THA. The ability to accurately determine magnification of the hip on the radiograph and apply identical magnification to the radiograph and template will improve accuracy of preoperative templating of THA. We designed a templating method using a new way of determining the hip magnification with a linear relationship between magnification of the hip and the reference object on top of the pubis symphysis; the relationship was determined on 50 radiographs. We then compared our method with two other templating methods: an analog method assuming an average hip magnification of 15% and a digital method determining the hip magnification with a one-to-one relationship between the reference object and the hip. All methods were reproducible. Uniform undersizing occurred when templating with the digital method based on the one-to-one relationship; the analog method best predicted the implanted prosthesis size, closely followed by our new digital templating method; the new method will be particularly applicable for preoperative THA when analog methods are replaced by digital methods

Modulation of chemokine gradients by apheresis redirects leukocyte trafficking to different compartments during sepsis, studies in a rat model

Introduction: Prior work suggests that leukocyte trafficking is determined by local chemokine gradients between the nidus of infection and the plasma. We recently demonstrated that therapeutic apheresis can alter immune mediator concentrations in the plasma, protect against organ injury, and improve survival. Here we aimed to determine whether the removal of chemokines from the plasma by apheresis in experimental peritonitis changes chemokine gradients and subsequently enhances leukocyte localization into the infected compartment, and away from healthy tissues.Methods: In total, 76 male adult Sprague-Dawley rats weighing 400 g to 600 g were included in this study. Eighteen hours after inducing sepsis by cecal ligation and puncture, we randomized these rats to apheresis or sham treatment for 4 hours. Cytokines, chemokines, and leukocyte counts from blood, peritoneal cavity, and lung were measured. In a separate experiment, we labeled neutrophils from septic donor animals and injected them into either apheresis or sham-treated animals. All numeric data with normal distributions were compared with one-way analysis of variance, and numeric data not normally distributed were compared with the Mann-Whitney U test.Results: Apheresis significantly removed plasma cytokines and chemokines, increased peritoneal fluid-to-blood chemokine (C-X-C motif ligand 1, ligand 2, and C-C motif ligand 2) ratios, and decreased bronchoalveolar lavage fluid-to-blood chemokine ratios, resulting in enhanced leukocyte recruitment into the peritoneal cavity and improved bacterial clearance, but decreased recruitment into the lung. Apheresis also reduced myeloperoxidase activity and histologic injury in the lung, liver, and kidney. These Labeled donor neutrophils exhibited decreased localization in the lung when infused into apheresis-treated animals.Conclusions: Our results support the concept of chemokine gradient control of leukocyte trafficking and demonstrate the efficacy of apheresis to target this mechanism and reduce leukocyte infiltration into the lung. © 2014 Peng et al

Reliability and Validity of the Dutch Version of the Brief Infant-Toddler Social and Emotional Assessment (BITSEA)

Background: The Brief Infant-Toddler Social and Emotional Assessment (BITSEA) is a relatively new and short (42-item) questionnaire that measures psychosocial problems in toddlers and consists of a Problem and a Competence scale. In this study the reliability and validity of the Dutch version of the BITSEA were examined for the whole group and for gender and ethnicity subgroups. Methods: Parents of 7140 two-year-old children were invited in the study, of which 3170 (44.4%) parents completed the BITSEA. For evaluation of the score distribution, the presence of floor/ceiling effects was determined. The internal consistency (Cronbach's alpha) was evaluated and in subsamples the test-retest, parent-childcare provider interrater reliability and concurrent validity with regard to the Child Behavioral Checklist (CBCL). Discriminative validity was evaluated by comparing scores of parents that worry and parents that do not worry about their child's development. Results: The BITSEA showed no floor or ceiling effects. Psychometric properties of the BITSEA Problem and Competence scale were respectively: Cronbach's alphas were 0.76 and 0.63. Test-retest correlations were 0.75 and 0.61. Interrater reliability correlations were 0.30 and 0.17. Concurrent validity was as hypothesised. The BITSEA was able to discriminate between parents that worry about their child and parents that do not worry. The psychometric properties of the BITSEA were comparable across gender and ethnic background. Conclusion: The results in this large-scale study of a diverse sample support the reliability and validity of the BITSEA Problem scale. The BITSEA Competence scale needs further study. The performance of the BITSEA appears to be similar in subgroups by gender and ethnic background