Effectiveness of offloading interventions for people with diabetes-related foot ulcers: A systematic review and meta-analysis.

BACKGROUND: Offloading treatment is crucial to heal diabetes-related foot ulcers (DFU). This systematic review aimed to assess the effectiveness of offloading interventions for people with DFU. METHODS: We searched PubMed, EMBASE, Cochrane databases, and trials registries for all studies relating to offloading interventions in people with DFU to address 14 clinical question comparisons. Outcomes included ulcers healed, plantar pressure, weight-bearing activity, adherence, new lesions, falls, infections, amputations, quality of life, costs, cost-effectiveness, balance, and sustained healing. Included controlled studies were independently assessed for risk of bias and had key data extracted. Meta-analyses were performed when outcome data from studies could be pooled. Evidence statements were developed using the GRADE approach when outcome data existed. RESULTS: From 19,923 studies screened, 194 eligible studies were identified (47 controlled, 147 non-controlled), 35 meta-analyses performed, and 128 evidence statements developed. We found non-removable offloading devices likely increase ulcers healed compared to removable offloading devices (risk ratio [RR] 1.24, 95% CI 1.09-1.41; N = 14, n = 1083), and may increase adherence, cost-effectiveness and decrease infections, but may increase new lesions. Removable knee-high offloading devices may make little difference to ulcers healed compared to removable ankle-high offloading devices (RR 1.00, 0.86-1.16; N = 6, n = 439), but may decrease plantar pressure and adherence. Any offloading device may increase ulcers healed (RR 1.39, 0.89-2.18; N = 5, n = 235) and cost-effectiveness compared to therapeutic footwear and may decrease plantar pressure and infections. Digital flexor tenotomies with offloading devices likely increase ulcers healed (RR 2.43, 1.05-5.59; N = 1, n = 16) and sustained healing compared to devices alone, and may decrease plantar pressure and infections, but may increase new transfer lesions. Achilles tendon lengthening with offloading devices likely increase ulcers healed (RR 1.10, 0.97-1.27; N = 1, n = 64) and sustained healing compared to devices alone, but likely increase new heel ulcers. CONCLUSIONS: Non-removable offloading devices are likely superior to all other offloading interventions to heal most plantar DFU. Digital flexor tenotomies and Achilles tendon lengthening in combination with offloading devices are likely superior for some specific plantar DFU locations. Otherwise, any offloading device is probably superior to therapeutic footwear and other non-surgical offloading interventions to heal most plantar DFU. However, all these interventions have low-to-moderate certainty of evidence supporting their outcomes and more high-quality trials are needed to improve our certainty for the effectiveness of most offloading interventions.

Selective treatment of clinical mastitis: Assessment of the Net Cash Impact on Dairy Farms Under Diverse Scenarios. A European Perspective.

Selective treatment of clinical mastitis (STCM) potentially reduces antimicrobial use without negative implications on cow's milk production or health. However, this approach comes with additional costs. The aim of this study was to evaluate the net cash impact (NCI) of implementing STCM compared with blanket treatment of clinical mastitis (BTCM) under different diagnostic-test turnaround times (24 h, 14 h, and 8 h) using a stochastic partial budget analysis with Monte Carlo simulation. The target population was European commercial dairy herds; therefore, the model inputs were primarily from European sources. Additionally, variables associated with dairy management programs were obtained from USDA sources, worldwide multisite clinical trials, and expert opinion. The output was calculated by subtracting the cost of STCM from the cost of BTCM and it represented the expected NCI if a herd switched from BTCM to STCM. Depending on the time-to-treatment efficiency and diagnostic-test turnaround time, the expected mean NCI, assuming that STCM has no impact on the cow's future health or production, ranged from +€8.7 to +€12.4 per case with 72.4% to 84.8% of the iterations being ≥ €0. Moreover, using the numerically favorable health and production effects of STCM reported in the literature, the expected mean NCI ranged from +€44.5 to +€48.1 per case with 93.6% to 95.4% of the iterations being ≥ €0. The variables with the greatest contribution to NCI variance were proportion of gram-positive cases (39.2% of the variance) and days out of the tank for treated cows (22.0%). However, if future cow's health and production were accounted for, culling risk (24.6%), recurrence risk (19.4%), and milk yield (10.6%) would have the greatest contribution to NCI. The sensitivity analysis indicated that farms with high clinical mastitis incidence, low proportion of gram-positive cases, large number of days out of the tank for treated cows, higher milking frequency or using automatic milking systems, not using the highest priced diagnostic tests, and having high antimicrobial treatment costs are the best candidates for STCM. Improving time-to-treatment efficiency, for example, by using a rapid diagnostic test, leads to a favorable NCI, while high daily milk yield and milk price enhances the NCI in already positive scenarios. Finally, the cash flow entirely depends on future cow's health and milk yield. In conclusion, results indicate that overall, STCM is a practice that positively impacts the NCI of many herds.

Benralizumab: A novel treatment for the cutaneous features of paediatric eosinophilic granulomatosis with polyangiitis (pEGPA).

Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic vasculitis presenting primarily with pulmonary and cutaneous features. The disease is typically seen in the fifth or sixth decade of life (1, 2). We report a case of EGPA in an adolescent who was successfully treated with the interleukin-5 (IL-5) receptor inhibitor, benralizumab.

Mercury Contamination of an Introduced Generalist Fish of Intermediate Trophic Level.

Mercury contamination is a global issue because mercury concentrations in aquatic systems are influenced by both natural and anthropogenic pathways. Here, liver and muscle total mercury (THg) concentrations in black crappie Pomoxis nigromaculatus from three boreal lakes in southeastern Manitoba, Canada, were related to age, morphology and physiological traits to better understand the dynamics of mercury accumulation in an introduced generalist fish species. These THg concentrations were then compared to black crappie mercury concentrations in other Canadian water bodies and to mercury concentrations in other freshwater fishes in southeastern Manitoba. Age and size had strong positive correlations (P < 0.001, r ≥ 0.60) with muscle mercury concentrations. No evidence of acute point source contamination or physiological impairment in black crappie was found in the study area. Analysis of liver THg revealed the possible impacts of seasonal and ontogenetic differences in diet on exposure. Furthermore, THg analysis of liver and muscle tissue showed how generalist foraging may curb the progressively greater mercury exposure and resultant physiological consequences expected from ontogenetic diet shifts in black crappie. Although there appeared to be temporally varied levels of mercury exposure (i.e., liver THg) by sex, there was no sex effect observed in long-term mercury accumulation in the muscle. Black crappie bioaccumulated less mercury at age than primary piscivore species in the region. These results will help foster a better understanding of mercury biomagnification within a region impacted by legacy mercury.

Determination of the

We report the first measurement of the parity-violating elastic electron scattering asymmetry on ^{27}Al. The ^{27}Al elastic asymmetry is A_{PV}=2.16±0.11(stat)±0.16(syst) ppm, and was measured at ⟨Q^{2}⟩=0.02357±0.00010 GeV^{2}, ⟨θ_{lab}⟩=7.61°±0.02°, and ⟨E_{lab}⟩=1.157 GeV with the Q_{weak} apparatus at Jefferson Lab. Predictions using a simple Born approximation as well as more sophisticated distorted-wave calculations are in good agreement with this result. From this asymmetry the ^{27}Al neutron radius R_{n}=2.89±0.12 fm was determined using a many-models correlation technique. The corresponding neutron skin thickness R_{n}-R_{p}=-0.04±0.12 fm is small, as expected for a light nucleus with a neutron excess of only 1. This result thus serves as a successful benchmark for electroweak determinations of neutron radii on heavier nuclei. A tree-level approach was used to extract the ^{27}Al weak radius R_{w}=3.00±0.15 fm, and the weak skin thickness R_{wk}-R_{ch}=-0.04±0.15 fm. The weak form factor at this Q^{2} is F_{wk}=0.39±0.04.

Precision Determination of the Neutral Weak Form Factor of

We report a precise measurement of the parity-violating (PV) asymmetry A_{PV} in the elastic scattering of longitudinally polarized electrons from ^{48}Ca. We measure A_{PV}=2668±106(stat)±40(syst) parts per billion, leading to an extraction of the neutral weak form factor F_{W}(q=0.8733 fm^{-1})=0.1304±0.0052(stat)±0.0020(syst) and the charge minus the weak form factor F_{ch}-F_{W}=0.0277±0.0055. The resulting neutron skin thickness R_{n}-R_{p}=0.121±0.026(exp)±0.024(model) fm is relatively thin yet consistent with many model calculations. The combined CREX and PREX results will have implications for future energy density functional calculations and on the density dependence of the symmetry energy of nuclear matter.

New Measurements of the Beam-Normal Single Spin Asymmetry in Elastic Electron Scattering over a Range of Spin-0 Nuclei.

We report precision determinations of the beam-normal single spin asymmetries (A_{n}) in the elastic scattering of 0.95 and 2.18 GeV electrons off ^{12}C, ^{40}Ca, ^{48}Ca, and ^{208}Pb at very forward angles where the most detailed theoretical calculations have been performed. The first measurements of A_{n} for ^{40}Ca and ^{48}Ca are found to be similar to that of ^{12}C, consistent with expectations and thus demonstrating the validity of theoretical calculations for nuclei with Z≤20. We also report A_{n} for ^{208}Pb at two new momentum transfers (Q^{2}) extending the previous measurement. Our new data confirm the surprising result previously reported, with all three data points showing significant disagreement with the results from the Z≤20 nuclei. These data confirm our basic understanding of the underlying dynamics that govern A_{n} for nuclei containing ≲50 nucleons, but point to the need for further investigation to understand the unusual A_{n} behavior discovered for scattering off ^{208}Pb.

Accurate Determination of the Neutron Skin Thickness of

We report a precision measurement of the parity-violating asymmetry A_{PV} in the elastic scattering of longitudinally polarized electrons from ^{208}Pb. We measure A_{PV}=550±16(stat)±8(syst) parts per billion, leading to an extraction of the neutral weak form factor F_{W}(Q^{2}=0.00616 GeV^{2})=0.368±0.013. Combined with our previous measurement, the extracted neutron skin thickness is R_{n}-R_{p}=0.283±0.071 fm. The result also yields the first significant direct measurement of the interior weak density of ^{208}Pb: ρ_{W}^{0}=-0.0796±0.0036(exp)±0.0013(theo) fm^{-3} leading to the interior baryon density ρ_{b}^{0}=0.1480±0.0036(exp)±0.0013(theo) fm^{-3}. The measurement accurately constrains the density dependence of the symmetry energy of nuclear matter near saturation density, with implications for the size and composition of neutron stars.

An Interactive Web-Based Educational Tool Improves Detection and Delineation of Barrett's Esophagus-Related Neoplasia.

BACKGROUND & AIMS: Endoscopic detection of early Barrett's esophagus-related neoplasia (BORN) is a challenge. We aimed to develop a web-based teaching tool for improving detection and delineation of BORN. METHODS: We made high-definition digital videos during endoscopies of patients with BORN and non-dysplastic Barrett's esophagus. Three experts superimposed their delineations of BORN lesions on the videos using special tools. In phase one, 68 general endoscopists from 4 countries assessed 4 batches of 20 videos. After each batch, mandatory feedback compared the assessors' interpretations with those from experts. These data informed the selection of 25 videos for the phase 2 module, which was completed by 121 new assessors from 5 countries. A 5-video test batch was completed before and after scoring of the four 5-video training batches. Mandatory feedback was as in phase 1. Outcome measures were scores for detection, delineation, agreement delineation, and relative delineation of BORN. RESULTS: A linear mixed-effect model showed significant sequential improvement for all 4 outcomes over successive training batches in both phases. In phase 2, median detection rates of BORN in the test batch increased by 30% (P < .001) after training. From baseline to the end of the study, there were relative increases in scores of 46% for detection, 129% for delineation, 105% for agreement delineation, and 106% for relative delineation (all, P < .001). Scores improved independent of assessors' country of origin or level of endoscopic experience. CONCLUSIONS: We developed a web-based teaching tool for endoscopic recognition of BORN that is easily accessible, efficient, and increases detection and delineation of neoplastic lesions. Widespread use of this tool might improve management of Barrett's esophagus by general endoscopists.

Precision Measurement of the Beam-Normal Single-Spin Asymmetry in Forward-Angle Elastic Electron-Proton Scattering.

A beam-normal single-spin asymmetry generated in the scattering of transversely polarized electrons from unpolarized nucleons is an observable related to the imaginary part of the two-photon exchange process. We report a 2% precision measurement of the beam-normal single-spin asymmetry in elastic electron-proton scattering with a mean scattering angle of θ_{lab}=7.9° and a mean energy of 1.149 GeV. The asymmetry result is B_{n}=-5.194±0.067(stat)±0.082 (syst) ppm. This is the most precise measurement of this quantity available to date and therefore provides a stringent test of two-photon exchange models at far-forward scattering angles (θ_{lab}→0) where they should be most reliable.

Physical and economic comparison of pasture-based automatic and conventional milking systems.

Automatic milking systems (AMS) have the potential to increase dairy farm productivity and profitability; however, adoption rates, particularly in pasture-based systems, have been lower than expected. The objectives of this study were to compare the physical and economic performance of pasture-based AMS with conventional milking systems (CMS) and to identify gaps for improving AMS productivity and profitability. We used data from 14 AMS and 100 CMS located in the main Australian dairy regions and collected over 3 yr (2015-2016, 2016-2017, 2017-2018). Farms within similar regions and herd sizes were compared. Results showed that all the main physical performance indicators evaluated such as milk production per cow, milk production per hectare, pasture grazed per hectare, or milk solids per full-time equivalent were similar between systems. The AMS farms had higher overhead costs such as depreciation and repairs and maintenance; however, no differences in total labor costs were observed between systems. Profitability, measured as earnings before interest and tax, operating profit margin, and return on total assets, was not significantly different between AMS and CMS. Opportunities for improving pasture utilization, labor efficiency, and robot utilization in AMS farms were identified. Improving efficiency in these areas could improve productivity and profitability of these systems, and therefore increase the interest of this technology.

Final report on serial phase II trials of all-intraperitoneal chemotherapy with or without bevacizumab for women with newly diagnosed, optimally cytoreduced carcinoma of Müllerian origin.

BACKGROUND: Intraperitoneal (IP) chemotherapy can improve outcomes for women with optimally cytoreduced epithelial ovarian cancer but toxicities are a concern. We conducted 2 phase 2 trials of an IV/IP regimen using carboplatin and paclitaxel without (Trial A) and with bevacizumab (Trial B). METHODS: Both trials consisted of carboplatin AUC 6 day 1, and paclitaxel 60 mg/m2 on days 1,8, 15 of a 21-day cycle; in Trial B, patients received IV bevacizumab 15 mg/kg every cycle starting cycle 2. Chemotherapy was administered IV for cycle 1 and then IP for all subsequent cycles. Primary objectives included safety and tolerability, pathologic CR rate (Trial A), and the rate of completion of IP cycles of therapy (Trial B). Progression-free (PFS), overall survival (OS), and pharmacokinetic analysis were secondary endpoints. RESULTS: 81 patients were treated on both trials (n = 40 and 41 in trials A and B, respectively). Median age for trials A and B was 59 (range, 36-76) and 55 (range, 19-69) years, respectively. 68% and 85% of patients, respectively for A and B, completed at least 4 cycles of treatment in both trials. Treatment with bevacizumab resulted in higher rates of grade 3 fatigue (37 versus 33%) and grade 3-4 diarrhea (22 versus 8%). Median PFS was 23.5 (95%CI 16.2-35.3) and 25 (95%CI 16.4-42.7) months, respectively; median OS was 68 (95%CI 49.5-NR) and 79.7 (95%CI 59.0-79.7) months, respectively for Trial A and B. CONCLUSIONS: Weekly administered IP carboplatin and IP paclitaxel is tolerable and safe with similar activity with and without concommittant bevacizumab in these 2 trials.

OV21/PETROC: a randomized Gynecologic Cancer Intergroup phase II study of intraperitoneal versus intravenous chemotherapy following neoadjuvant chemotherapy and optimal debulking surgery in epithelial ovarian cancer.

Background: The purpose of this multistage, adaptively, designed randomized phase II study was to evaluate the role of intraperitoneal (i.p.) chemotherapy following neoadjuvant chemotherapy (NACT) and optimal debulking surgery in women with epithelial ovarian cancer (EOC). Patients and methods: We carried out a multicenter, two-stage, phase II trial. Eligible patients with stage IIB-IVA EOC treated with platinum-based intravenous (i.v.) NACT followed by optimal (<1 cm) debulking surgery were randomized to one of the three treatment arms: (i) i.v. carboplatin/paclitaxel, (ii) i.p. cisplatin plus i.v./i.p. paclitaxel, or (iii) i.p. carboplatin plus i.v./i.p. paclitaxel. The primary end point was 9-month progressive disease rate (PD9). Secondary end points included progression-free survival (PFS), overall survival (OS), toxicity, and quality of life (QOL). Results: Between 2009 and 2015, 275 patients were randomized; i.p. cisplatin containing arm did not progress beyond the first stage of the study after failing to meet the pre-set superiority rule. The final analysis compared i.v. carboplatin/paclitaxel (n = 101) with i.p. carboplatin, i.v./i.p. paclitaxel (n = 102). The intention to treat PD9 was lower in the i.p. carboplatin arm compared with the i.v. carboplatin arm: 24.5% (95% CI 16.2% to 32.9%) versus 38.6% (95% CI 29.1% to 48.1%) P = 0.065. The study was underpowered to detect differences in PFS: HR PFS 0.82 (95% CI 0.57-1.17); P = 0.27 and OS HR 0.80 (95% CI 0.47-1.35) P = 0.40. The i.p. carboplatin-based regimen was well tolerated with no reduction in QOL or increase in toxicity compared with i.v. administration alone. Conclusion: In women with stage IIIC or IVA EOC treated with NACT and optimal debulking surgery, i.p. carboplatin-based chemotherapy is well tolerated and associated with an improved PD9 compared with i.v. carboplatin-based chemotherapy. Clinical trial number: clinicaltrials.gov, NCT01622543.

Diabetes-related lower-extremity complications are a leading cause of the global burden of disability.

Globally ~435 million people have diabetes [1], and an estimated 19-34% (~83-148 million people) of those will be expected to develop foot ulcers in their lifetime [2]. Foot ulcers are typically precipitated by other diabetes-related lower-extremity complications, (DRLECs) including peripheral neuropathy and peripheral vascular disease [2,3]. Collectively, DRLECs are a leading cause of infection, hospitalization and amputation outcomes [2-5], yet, these outcomes are readily preventable with evidence-based care [6,7]. This suggests the burden caused by DRLECs is a large, yet reducible, cause of the global burden of disease. This article is protected by copyright. All rights reserved.

How to improve threatened species management: An Australian perspective.

Targeted threatened species management is a central component of efforts to prevent species extinction. Despite the development of a range of management frameworks to improve conservation outcomes over the past decade, threatened species management is still commonly characterised as ad hoc. Although there are notable successes, many management programs are ineffective, with relatively few species experiencing improvements in their conservation status. We identify underlying factors that commonly lead to ineffective and inefficient management. Drawing attention to some of the key challenges, and suggesting ways forward, may lead to improved management effectiveness and better conservation outcomes. We highlight six key areas where improvements are needed: 1) stakeholder engagement and communication; 2) fostering strong leadership and the development of achievable long-term goals; 3) knowledge of target species' biology and threats, particularly focusing on filling knowledge gaps that impede management, while noting that in many cases there will be a need for conservation management to proceed initially despite knowledge gaps; 4) setting objectives with measurable outcomes; 5) strategic monitoring to evaluate management effectiveness; and 6) greater accountability for species declines and failure to recover species to ensure timely action and guard against complacency. We demonstrate the importance of these six key areas by providing examples of innovative approaches leading to successful species management. We also discuss overarching factors outside the realm of management influence that can help or impede conservation success. Clear recognition of factors that make species' management more straightforward - or more challenging - is important for setting realistic management objectives, outlining strategic action, and prioritising resources. We also highlight the need to more clearly demonstrate the benefit of current investment, and communicate that the risk of under-investment is species extinctions. Together, improvements in conservation practice, along with increased resource allocation and re-evaluation of the prioritisation of competing interests that threaten species, will help enhance conservation outcomes for threatened species.

Identifying physiological measures of lifetime welfare status in pigs: exploring the usefulness of haptoglobin, C- reactive protein and hair cortisol sampled at the time of slaughter.

BACKGROUND: Physiological measures indicative of the welfare status of animals during rearing could form part of an abattoir-based animal health and welfare assessment tool. A total of 66 pigs were used in this study, the aim of which was to assess how serum concentrations of haptoglobin (Hp) and C-reactive protein (CRP) (assessed in 51 pigs), and hair concentrations of cortisol (assessed in 65 pigs), measured at or close to slaughter, reflected welfare-related indicators recorded from the animal during its lifetime. These indicators were recorded at intervals between 7 and 21 weeks of age and included assigning scores for levels of tail and skin lesions, recording the presence or absence of certain health issues, and conducting qualitative behavioural assessments (QBA). RESULTS: Pigs recorded as having tail lesions during their lifetime had higher hair cortisol levels than those with no tail lesions (tail lesions: 47.87 ± 3.34 pg/mg, no tail lesions: 42.20 ± 3.29 pg/mg, P = 0.023), and pigs recorded as having moderate or severe tail lesions had higher Hp levels than those with no or mild tail lesions (moderate/severe: 1.711 mg/ml ± 0.74, none/mild: 0.731 mg/ml ±0.10, P = 0.010). Pigs recorded as being lame during their lifetime tended to have higher hair cortisol levels than non-lame pigs (lame: 52.72 pg/mg ± 3.83, not lame: 43.07 pg/mg ± 2.69, P = 0.062). QBA scores were not associated with any of the physiological measures (P > 0.05). Receiver Operator Curve (ROC) analysis was also carried out to get a better understanding of the usefulness of the physiological measures in discriminating animals that had had welfare-related issues recorded during their lifetime from those that had not. Hair cortisol was determined as having 'moderate' accuracy in discriminating pigs that were tail bitten on-farm from unbitten pigs (AUC: 0.748) while Hp and CRP were determined to have no meaningful discriminatory ability (AUC < 0.600). CONCLUSION: This research should be repeated on a larger scale, but the results suggest that hair cortisol measured at slaughter could provide insight into the welfare status of pigs during their lifetime. Hp may be a useful indicator of tail lesions in pigs. However, further research utilising a greater proportion of severely bitten pigs is required before conclusions can be drawn.

Characterization and application studies of ProxyPhos, a chemosensor for the detection of proximally phosphorylated peptides and proteins in aqueous solutions.

Proximal phosphorylation on proteins appears to have functional significance and has been associated with several diseases, including Alzheimer's and cancer. While much remains to be learned about the role of proximal phosphorylation in biological systems, no simple and/or affordable technique is available for its detection. To this end, we have previously developed a ProxyPhos chemosensor, which detects proximally phosphorylated peptides and proteins over mono- and non-phosphorylated motifs in aqueous solutions. In this follow-up work, we performed extensive characterization of peptide and protein ProxyPhos assay conditions to achieve enhanced detection, and further explored the selectivity of ProxyPhos, and its potential off-targets. As a result of characterization studies, selective sensing of proximally phosphorylated over mono-phosphorylated peptides and proteins was achieved. Moreover, studies demonstrated that ProxyPhos was compatible with the detection of all commonly phosphorylated residues (i.e. tyrosine, serine and threonine residues). Under optimized conditions, ProxyPhos efficiently discriminated between peptides derived from the activated (proximally phosphorylated, disease-relevant) and inactive (mono-phosphorylated) forms of JAK2, SYK and MAPK1 kinases. In addition, ProxyPhos can be used to probe phosphatase activity on peptides and proteins via detecting changes in proximal phosphorylation, demonstrating immediate utility of this chemosensing system.

Characteristics and clinical assessment of antibiotic delivery by chitosan sponge in the high-risk diabetic foot: a case series.

OBJECTIVE: The local delivery of antimicrobials is attractive for a number of reasons. Chitosan, a biodegradable polysaccharide sponge material, has been proposed as medium to deliver antibiotics directly to wounds. In this report we evaluate the safety and practicality of antimicrobial delivery via chitosan sponge. METHOD: We present the clinical course and systemic absorption characteristics of three cases of people with diabetic foot wounds treated with antibiotic soaked chitosan sponge (Sentrex BioSponge, Bionova Medical, Germantown, TN). The antibiotic sponge was made by reconstituting 1.2g tobramycin or 100mg doxycycline in 10-15ml saline and saturating the sponge with the solution. The sponge was then applied to the wounds. Serum levels of each respective antibiotic were evaluated after application. Additional in vitro studies were conducted evaluating elution of antibiotics from the chitosan sponge at established minimum inhibitory concentrations (MIC) for Staphylococcus aureus over 28 days. RESULTS: No patient experienced adverse local or systemic effects due to the sponge treatment. The measured serum levels applied antibiotics remained far less than established minimums after intravenous therapy. Each patient required further treatment, however local infection or contamination resolved during the course of their hospital stay after the chitosan/antibiotic application. CONCLUSION: The use of antibiotic-impregnated chitosan sponges appears a safe and effective mechanism of local delivery of antimicrobials in wounds. Future studies and clinical trials are ongoing to confirm these results and to guide clinical applications.

Footwear and offloading interventions to prevent and heal foot ulcers and reduce plantar pressure in patients with diabetes: a systematic review.

BACKGROUND: Footwear and offloading techniques are commonly used in clinical practice for preventing and healing of foot ulcers in persons with diabetes. The goal of this systematic review is to assess the medical scientific literature on this topic to better inform clinical practice about effective treatment. METHODS: We searched the medical scientific literature indexed in PubMed, EMBASE, CINAHL, and the Cochrane database for original research studies published since 1 May 2006 related to four groups of interventions: (1) casting; (2) footwear; (3) surgical offloading; and (4) other offloading interventions. Primary outcomes were ulcer prevention, ulcer healing, and pressure reduction. We reviewed both controlled and non-controlled studies. Controlled studies were assessed for methodological quality, and extracted key data was presented in evidence and risk of bias tables. Uncontrolled studies were assessed and summarized on a narrative basis. Outcomes are presented and discussed in conjunction with data from our previous systematic review covering the literature from before 1 May 2006. RESULTS: We included two systematic reviews and meta-analyses, 32 randomized controlled trials, 15 other controlled studies, and another 127 non-controlled studies. Several randomized controlled trials with low risk of bias show the efficacy of therapeutic footwear that demonstrates to relief plantar pressure and is worn by the patient, in the prevention of plantar foot ulcer recurrence. Two meta-analyses show non-removable offloading to be more effective than removable offloading for healing plantar neuropathic forefoot ulcers. Due to the limited number of controlled studies, clear evidence on the efficacy of surgical offloading and felted foam is not yet available. Interestingly, surgical offloading seems more effective in preventing than in healing ulcers. A number of controlled and uncontrolled studies show that plantar pressure can be reduced by several conservative and surgical approaches. CONCLUSIONS: Sufficient evidence of good quality supports the use of non-removable offloading to heal plantar neuropathic forefoot ulcers and therapeutic footwear with demonstrated pressure relief that is worn by the patient to prevent plantar foot ulcer recurrence. The evidence base to support the use of other offloading interventions is still limited and of variable quality. The evidence for the use of interventions to prevent a first foot ulcer or heal ischemic, infected, non-plantar, or proximal foot ulcers is practically non-existent. High-quality controlled studies are needed in these areas.

Reduced peripheral activity leading to hepato-preferential action of basal insulin peglispro compared with insulin glargine in patients with type 1 diabetes.

AIMS: Basal insulin peglispro (BIL), a novel PEGylated basal insulin with a large hydrodynamic size, has a delayed absorption and reduced clearance that prolongs the duration of action. The current study compared the effects of BIL and insulin glargine (GL) on endogenous glucose production (EGP), glucose disposal rate (GDR) and lipolysis in patients with type 1 diabetes. MATERIALS AND METHODS: This was a randomized, open-label, four-period, crossover study. Patients received intravenous infusions of BIL and GL, each at two dose levels selected for partial and maximal suppression of EGP, during an 8 to 10 h euglycemic clamp procedure with d-[3-3 H] glucose. RESULTS: Following correction for equivalent human insulin concentrations (EHIC), low-dose GL infusion resulted in similar EGP at the end of the clamp compared to low-dose BIL infusion (GL/BIL ratio of 1.03) but a higher GDR (GL/BIL ratio of 2.42), indicating similar hepatic activity but attenuated peripheral activity of BIL. Consistent with this, the EHIC-corrected GDR/EGP at the end of the clamp was 1.72-fold greater for GL than BIL following low-dose administration. At the lower dose of BIL and GL (concentrations in the therapeutic range), BIL produced less suppression of lipolysis compared with GL as indicated by free fatty acid and glycerol levels at the end of the clamp. CONCLUSIONS: Compared with GL, BIL restored the hepato-peripheral insulin action gradient seen in normal physiology via its peripherally restricted action on target tissues related to carbohydrate and lipid metabolism.