Lower limb biomechanical characetristics of patients with neuropathic diabetic foot ulcers: The diabetes foot ulcer study protocol

Background  Foot ulceration is the main precursor to lower limb amputation in patients with type 2 diabetes worldwide. Biomechanical factors have been implicated in the development of foot ulceration; however the association of these factors to ulcer healing remains less clear. It may be hypothesised that abnormalities in temporal spatial parameters (stride to stride measurements), kinematics (joint movements), kinetics (forces on the lower limb) and plantar pressures (pressure placed on the foot during walking) contribute to foot ulcer healing. The primary aim of this study is to establish the biomechanical characteristics (temporal spatial parameters, kinematics, kinetics and plantar pressures) of patients with plantar neuropathic foot ulcers compared to controls without a history of foot ulcers. The secondary aim is to assess the same biomechanical characteristics in patients with foot ulcers and controls over-time to assess whether these characteristics remain the same or change throughout ulcer healing.  Methods/Design  The design is a case–control study nested in a six-month longitudinal study. Cases will be participants with active plantar neuropathic foot ulcers (DFU group). Controls will consist of patients with type 2 diabetes (DMC group) and healthy participants (HC group) with no history of foot ulceration. Standardised gait and plantar pressure protocols will be used to collect biomechanical data at baseline, three and six months. Descriptive variables and primary and secondary outcome variables will be compared between the three groups at baseline and follow-up.  Discussion  It is anticipated that the findings from this longitudinal study will provide important information regarding the biomechanical characteristic of type 2 diabetes patients with neuropathic foot ulcers. We hypothesise that people with foot ulcers will demonstrate a significantly compromised gait pattern (reduced temporal spatial parameters, kinematics and kinetics) at base line and then throughout the follow-up period compared to controls. The study may provide evidence for the design of gait-retraining, neuro-muscular conditioning and other approaches to off-load the limbs of those with foot ulcers in order to reduce the mechanical loading on the foot during gait and promote ulcer healing

The reproducibility of acquiring three dimensional gait and plantar pressure data using established protocols in participants with and without type 2 diabetes and foot ulcers

Background  Several prospective studies have suggested that gait and plantar pressure abnormalities secondary to diabetic peripheral neuropathy contributes to foot ulceration. There are many different methods by which gait and plantar pressures are assessed and currently there is no agreed standardised approach. This study aimed to describe the methods and reproducibility of three-dimensional gait and plantar pressure assessments in a small subset of participants using pre-existing protocols.  Methods  Fourteen participants were conveniently sampled prior to a planned longitudinal study; four patients with diabetes and plantar foot ulcers, five patients with diabetes but no foot ulcers and five healthy controls. The repeatability of measuring key biomechanical data was assessed including the identification of 16 key anatomical landmarks, the measurement of seven leg dimensions, the processing of 22 three-dimensional gait parameters and the analysis of four different plantar pressures measures at 20 foot regions.  Results  The mean inter-observer differences were within the pre-defined acceptable level (<7mm) for 100% (16 of 16) of key anatomical landmarks measured for gait analysis. The intra-observer assessment concordance correlation coefficients were > 0.9 for 100% (7 of 7) of leg dimensions. The coefficients of variations (CVs) were within the pre-defined acceptable level (<10%) for 100% (22 of 22) of gait parameters. The CVs were within the pre-defined acceptable level (<30%) for 95% (19 of 20) of the contact area measures, 85% (17 of 20) of mean plantar pressures, 70% (14 of 20) of pressure time integrals and 55% (11 of 20) of maximum sensor plantar pressure measures.  Conclusion  Overall, the findings of this study suggest that important gait and plantar pressure measurements can be reliably acquired. Nearly all measures contributing to three-dimensional gait parameter assessments were within predefined acceptable limits. Most plantar pressure measurements were also within predefined acceptable limits; however, reproducibility was not as good for assessment of the maximum sensor pressure. To our knowledge, this is the first study to investigate the reproducibility of several biomechanical methods in a heterogeneous cohort

Plantar Pressure in Diabetic Peripheral Neuropathy Patients with Active Foot Ulceration, Previous Ulceration and No History of Ulceration: A Meta-Analysis of Observational Studies

Aims: Elevated dynamic plantar pressures are a consistent finding in diabetes patients with peripheral neuropathy with implications for plantar foot ulceration. This meta-analysis aimed to compare the plantar pressures of diabetes patients that had peripheral neuropathy and those with neuropathy with active or previous foot ulcers. Methods: Published articles were identified from Medline via OVID, CINAHL, SCOPUS, INFORMIT, Cochrane Central EMBASE via OVID and Web of Science via ISI Web of Knowledge bibliographic databases. Observational studies reporting barefoot dynamic plantar pressure in adults with diabetic peripheral neuropathy, where at least one group had a history of plantar foot ulcers were included. Interventional studies, shod plantar pressure studies and studies not published in English were excluded. Overall mean peak plantar pressure (MPP) and pressure time integral (PTI) were primary outcomes. The six secondary outcomes were MPP and PTI at the rear foot, mid foot and fore foot. The protocol of the meta-analysis was published with PROPSERO, (registration number CRD42013004310). Results: Eight observational studies were included. Overall MPP and PTI were greater in diabetic peripheral neuropathy patients with foot ulceration compared to those without ulceration (standardised mean difference 0.551, 95% CI 0.290-0.811, p<0.001; and 0.762, 95% CI 0.303-1.221, p = 0.001, respectively). Sub-group analyses demonstrated no significant difference in MPP for those with neuropathy with active ulceration compared to those without ulcers. A significant difference in MPP was found for those with neuropathy with a past history of ulceration compared to those without ulcers; (0.467, 95% CI 0.181- 0.753, p = 0.001). Statistical heterogeneity between studies was moderate. Conclusions: Plantar pressures appear to be significantly higher in patients with diabetic peripheral neuropathy with a history of foot ulceration compared to those with diabetic neuropathy without a history of ulceration. More homogenous data is needed to confirm these findings

Intensive versus conventional glycaemic control for treating diabetic foot ulcers

Background  The estimated likelihood of lower limb amputation is 10 to 30 times higher amongst people with diabetes compared to those without diabetes. Of all non-traumatic amputations in people with diabetes, 85% are preceded by a foot ulcer. Foot ulceration associated with diabetes (diabetic foot ulcers) is caused by the interplay of several factors, most notably diabetic peripheral neuropathy (DPN), peripheral arterial disease (PAD) and changes in foot structure. These factors have been linked to chronic hyperglycaemia (high levels of glucose in the blood) and the altered metabolic state of diabetes. Control of hyperglycaemia may be important in the healing of ulcers.  Objectives  To assess the effects of intensive glycaemic control compared to conventional control on the outcome of foot ulcers in people with type 1 and type 2 diabetes.  Search methods  In December 2015 we searched: The Cochrane Wounds Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; EBSCO CINAHL; Elsevier SCOPUS; ISI Web of Knowledge Web of Science; BioMed Central and LILACS. We also searched clinical trial databases, pharmaceutical trial databases and current international and national clinical guidelines on diabetes foot management for relevant published, non-published, ongoing and terminated clinical trials. There were no restrictions based on language or date of publication or study setting.  Selection criteria  Published, unpublished and ongoing randomised controlled trials (RCTs) were considered for inclusion where they investigated the effects of intensive glycaemic control on the outcome of active foot ulcers in people with diabetes. Non randomised and quasi-randomised trials were excluded. In order to be included the trial had to have: 1) attempted to maintain or control blood glucose levels and measured changes in markers of glycaemic control (HbA1c or fasting, random, mean, home capillary or urine glucose), and 2) documented the effect of these interventions on active foot ulcer outcomes. Glycaemic interventions included subcutaneous insulin administration, continuous insulin infusion, oral anti-diabetes agents, lifestyle interventions or a combination of these interventions. The definition of the interventional (intensive) group was that it should have a lower glycaemic target than the comparison (conventional) group.  Data collection and analysis  All review authors independently evaluated the papers identified by the search strategy against the inclusion criteria. Two review authors then independently reviewed all potential full-text articles and trials registry results for inclusion.  Main results  We only identified one trial that met the inclusion criteria but this trial did not have any results so we could not perform the planned subgroup and sensitivity analyses in the absence of data. Two ongoing trials were identified which may provide data for analyses in a later version of this review. The completion date of these trials is currently unknown.  Authors’ conclusions  The current review failed to find any completed randomised clinical trials with results. Therefore we are unable to conclude whether intensive glycaemic control when compared to conventional glycaemic control has a positive or detrimental effect on the treatment of foot ulcers in people with diabetes. Previous evidence has however highlighted a reduction in risk of limb amputation (from various causes) in people with type 2 diabetes with intensive glycaemic control. Whether this applies to people with foot ulcers in particular is unknown. The exact role that intensive glycaemic control has in treating foot ulcers in multidisciplinary care (alongside other interventions targeted at treating foot ulcers) requires further investigation

Spatially-Resolved Recent Star Formation History in NGC 6946

The nearby face-on star forming spiral galaxy NGC 6946 is known as the Fireworks Galaxy due to its hosting an unusually large number of supernova. We analyze its resolved near-ultraviolet (NUV) stellar photometry measured from images taken with the Hubble Space Telescope's (HST) Wide Field Camera 3 (WFC3) with F275W and F336W filters. We model the color-magnitude diagrams (CMD) of the UV photometry to derive the spatially-resolved star formation history (SFH) of NGC 6946 over the last 25 Myr. From this analysis, we produce maps of the spatial distribution of young stellar populations and measure the total recent star formation rate (SFR) of nearly the entire young stellar disk. We find the global SFR(age$\leq$25 Myr)=$13.17 \substack{+0.91 \\-0.79} M_\odot/\rm yr$. Over this period, the SFR is initially very high ($23.39\substack{+2.43\\-2.11} M_\odot/\rm yr$ between 16-25 Myr ago), then monotonically decreases to a recent SFR of $5.31\substack{+0.19\\-0.17} M_\odot/\rm yr$ in the last 10 Myr. This decrease in global star formation rate over the last 25 Myr is consistent with measurements made with other SFR indicators. We discuss in detail two of the most active regions of the galaxy, which we find are responsible for 3% and 5% of the total star formation over the past 6.3 Myr.Comment: 19 pages, 11 figures, accepted for publication in Ap

Early Career Perspectives For the NASA SMD Bridge Program

In line with the Astro2020 Decadal Report State of the Profession findings and the NASA core value of Inclusion, the NASA Science Mission Directorate (SMD) Bridge Program was created to provide financial and programmatic support to efforts that work to increase the representation and inclusion of students from under-represented minorities in the STEM fields. To ensure an effective program, particularly for those who are often left out of these conversations, the NASA SMD Bridge Program Workshop was developed as a way to gather feedback from a diverse group of people about their unique needs and interests. The Early Career Perspectives Working Group was tasked with examining the current state of bridge programs, academia in general, and its effect on students and early career professionals. The working group, comprised of 10 early career and student members, analyzed the discussions and responses from workshop breakout sessions and two surveys, as well as their own experiences, to develop specific recommendations and metrics for implementing a successful and supportive bridge program. In this white paper, we will discuss the key themes that arose through our work, and highlight select recommendations for the NASA SMD Bridge Program to best support students and early career professionals.Comment: White paper developed by the Early Career Perspectives Working Group for the NASA SMD Bridge Program Workshop. 11 page

The Masses of Supernova Remnant Progenitors in M33

Using resolved optical stellar photometry from the Panchromatic Hubble Andromeda Treasury Triangulum Extended Region (PHATTER) survey, we measured the star formation history (SFH) near the position of 85 supernova remnants (SNRs) in M33. We constrained the progenitor masses for 60 of these SNRs, finding the remaining 25 remnants had no local SF in the last 56 Myr consistent with core-collapse SNe (CCSNe), making them potential Type Ia candidates. We then infer a progenitor mass distribution from the age distribution, assuming single star evolution. We find that the progenitor mass distribution is consistent with being drawn from a power-law with an index of $-2.9^{+1.2}_{-1.0}$. Additionally, we infer a minimum progenitor mass of $7.1^{+0.1}_{-0.2}\ M_{\odot}$from this sample, consistent with several previous studies, providing further evidence that stars with ages older than the lifetimes of single 8$M_{\odot}$ stars are producing supernovae.Comment: 20 pages, 7 figures, 2 tables, Accepted at Ap

The influence of bias in randomized controlled trials on rehabilitation intervention effect estimates: what we have learned from meta-epidemiological studies

This study aimed to synthesize evidence from studies that addressed the influence of bias domains in randomized controlled trials on rehabilitation intervention effect estimates and discuss how these findings can maximize the trustworthiness of an RCT in rehabilitation. We screened studies about the influence of bias on rehabilitation intervention effect estimates published until June 2023. The characteristics and results of the included studies were categorized based on methodological characteristics and summarized narratively. We included seven studies with data on 227,806 RCT participants. Our findings showed that rehabilitation intervention effect estimates are likely exaggerated in trials with inadequate/unclear sequence generation and allocation concealment when using continuous outcomes. The influence of blinding was inconsistent and different from the rest of medical science, as meta-epidemiological studies showed overestimation, underestimation, or neutral associations for different types of blinding on rehabilitation treatment effect estimates. Still, it showed a more consistent pattern when looking at patient-reported outcomes. The impact of attrition bias and intention to treat has been analyzed only in two studies with inconsistent results. The risk of reporting bias seems to be associated with overestimation of treatment effects. Bias domains can influence rehabilitation treatment effects in different directions. The evidence is mixed and inconclusive due to the poor methodological quality of RCTs and the limited number and quality of studies looking at the influence of bias and treatment effects in rehabilitation. Further studies about the influence of bias in RCTs on rehabilitation intervention effect estimates are needed