Improving Diabetic Wound Healing Outcomes with Topical Growth Factor Therapies: Systematic Review and Network Meta-analysis of Randomised-controlled Trials.

CONTEXT: Diabetes mellitus is associated with morbid complications such as diabetic foot ulcers (DFUs) that may lead to amputations or mortality if not managed adequately. OBJECTIVE: New adjunctive interventions to treat diabetic wounds include topical biologics and growth factors. This study aims to evaluate their efficacy in improving wound healing outcomes and safety. DATA SOURCES: Comprehensive database searches of MEDLINE via PubMed, EMBASE and Cochrane performed from inception to December 2022. STUDY SELECTION: Three independent researchers selected the studies. Randomised-controlled trials that compared the use of a topical biologic growth factor-containing regimen to other biologics or standard of care (SOC) were included. DATA EXTRACTION AND SYNTHESIS: This review followed PRISMA guidelines. Risk of bias analysis was performed using the Jadad scale. Network meta-analysis was performed. Treatments were grouped into common nodes based on the type of biologic agent. MAIN OUTCOMES AND MEASURES: Primary outcomes of interest were healing rate and time to wound closure. Secondary outcomes included wound infection, serious adverse events, and amputation rate. RESULTS: Human umbilical cord (HUC) was associated with the highest cure, followed by recombinant human epidermal growth factor (hEGF). A significantly greater reduction in the time to cure DFUs was seen in HUC, hEGF and fibroblast growth factor (FGF). There was a significantly lower risk of adverse events (AEs) when platelet-rich plasma (PRP) was administered. CONCLUSION: HUC, hEGF and FGF are promising topical biologics with statistically significant primary outcomes compared to SOC, while PRP is effective in reducing ulcer-related AEs. HUC has been found to be the most effective in terms of cure rate and a reduction in time to cure.

Topical Biological Agents as Adjuncts to Improve Wound Healing in Chronic Diabetic Wounds: A Systematic Review of Clinical Evidence and Future Directions.

Diabetes is a leading chronic illness in the modern world and 19-34% develop chronic diabetic foot ulcers (DFUs) in their lifetime, often necessitating amputation. The reduction in tissue growth factors and resulting imbalance between proteolytic enzymes and their inhibitors, along with systemic factors impairing healing appear particularly important in chronic wounds. Growth factors applied topically have thus been suggested to be a non-invasive, safe, and cost-effective adjunct to improve wound healing and prevent complications. Comprehensive database searches of MEDLINE via PubMed, EMBASE, Cochrane, and ClinicalTrials.gov were performed to identify clinical evidence and ongoing trials. The risk of bias analysis included randomized controlled trials (RCTs) was performed using the Cochrane Risk of Bias 2.0 tool. We included randomized controlled trials that compared the use of a topical biologic growth factor-containing regimen to any other regimen. Primary outcomes of interest were time to wound closure, healing rate, and time. Secondary outcomes included the incidence of adverse events such as infection. A total of 41 trials from 1992-2020 were included in this review, with a total recorded 3,112 patients. Platelet-derived growth factors (PDGF) in the form of becaplermin gel are likely to reduce the time of closure, increase the incidence of wound closure, and complete wound healing. Human umbilical cord-related treatments, dehydrated human amnion and chorion allograft (dHACA), and hypothermically stored amniotic membrane (HSAM), consistently increased the rates and incidence of complete ulcer healing while reducing ulcer size and time to complete ulcer healing. Fibroblast growth factor-1 (FGF1) showed only a slight benefit in multiple studies regarding increasing complete ulcer healing rates and incidence while reducing ulcer size and time to complete ulcer healing, with a few studies showing no statistical difference from placebo. Platelet-rich fibrin (PRF) is consistent in reducing the time to complete ulcer healing and increasing wound healing rate but may not reduce ulcer size or increase the incidence of complete ulcer healing. Targeting the wound healing pathway via the extrinsic administration of growth factors is a promising option to augment wound healing in diabetic patients. Growth factors have also shown promise in specific subgroups of patients who are at risk of significantly impaired wound healing such as those with a history of secondary infection and vasculopathy. As diabetes impairs multiple stages of wound healing, combining growth factors in diabetic wound care may prove to be an area of interest. Evidence from this systematic literature review suggests that topical adjuncts probably reduce time to wound closure, reduce healing time, and increase the healing rate in patients with chronic DFUs.

Fabricating scalable, personalized wound dressings with customizable drug loadings via 3D printing.

In recent times, 3D printing has been gaining traction as a fabrication platform for customizable drug dosages as a form of personalized medicine. While this has been recently demonstrated as oral dosages, there is potential to provide the same customizability and personalization as topical applications for wound healing. In this paper, the application of 3D printing to fabricate hydrogel wound dressings with customizable architectures and drug dosages was investigated. Chitosan methacrylate was synthesized and mixed with Lidocaine Hydrochloride and Levofloxacin respectively along with a photoinitiator before being used to print wound dressings of various designs. These designs were then investigated for their effect on drug release rates and profiles. Our results show the ability of 3D printing to customize drug dosages and drug release rates through co-loading different drugs at various positions and varying the thickness of drug-free layers over drug-loaded layers in the wound dressing respectively. Two scale-up approaches were also investigated for their effects on drug release rates from the wound dressing. The influence that each wound dressing design has on the release profile of drugs was also shown by fitting them with drug release kinetic models. This study thus shows the feasibility of utilizing 3D printing to fabricate wound dressings with customizable shapes, drug dosage and drug release rates that can be tuned according to the patient's requirements.

Mobile learning in clinical settings: unveiling the paradox.

PURPOSE: The use of mobile devices among medical students and residents to access online material in real-time has become more prevalent. Most literature focused on the technical/functional aspects of mobile use. This study, on the other hands, explored students, doctors and patients' preferences and reasons towards the use of mobile devices in clinical settings underpinned by the Technology Acceptance Model 2 (TAM 2). METHODS: This research employs an exploratory research design using survey and semi-structured interviews. An online survey was administered to clinical year medical students, followed by semi-structured interviews with the doctors and patients. Questions for the online survey and semi-structured interviews were derived from previous literature and was then reviewed by authors and an expert panel. A convenience sampling was used to invite voluntary participants. RESULTS: Survey findings showed that most medical students used their devices to find drug information and practice guidelines. The majority of the students accessed UpToDate followed by Google to access medical resources. Key barriers that students often encountered during the use of mobile devices were internet connectivity in the clinical settings, reliability of the information, and technical issues. Thematic analysis of the interviews revealed four themes: general usage by students, receptivity of the use of mobile devices by students, features in selecting resources for mobile learning, and limitation in the current use of mobile devices for learning. CONCLUSION: The findings from this study assist in recommending suitable material using mobile devices to enhance learning in the clinical environment and expand the TAM 2.

Incidence and analysis of sharps injuries and splash exposures in a tertiary hospital in Southeast Asia: a ten-year review.

INTRODUCTION: We aimed to report the ten-year incidence and trend of sharps injuries and splash exposures (SISE), and analyse the causative instruments and risk factors leading to these injuries to identify potential areas of improvement. METHODS: A retrospective review of self-reported SISE incidents from 2005 to 2014 was conducted in Singapore General Hospital. Data was extracted from the electronic database of the Department of Infection Prevention and Control. Incidence of SISE was calculated per 1,000 healthcare workers (HCWs) per year. RESULTS: Over the ten-year period, a total of 1,901 SISE were reported. The average SISE incidence per year was 110.5 per 1,000 doctors and 22.8 per 1,000 nursing staff, with an overall incidence of 28.9 per 1,000 HCWs. The incidence of SISE decreased from 30.3 to 22.0 per 1,000 HCWs per year from 2005 to 2014, while that for splash exposures increased from 1.9 to 3.7 per 1,000 HCWs per year. Doctors reported the highest number of SISE (43.7%), followed by nurses (37.7%). Top mechanisms of injury were intraoperative procedures (22.8%), drawing blood (14.4%) and splash exposures (13.7%). CONCLUSION: Overall incidence of SISE decreased over the decade. Improved training and increasing use of safety devices, education and awareness could have contributed to the fall in incidence of sharps injuries; these measures should be reinforced and continued. However, the incidence of splash exposures increased over the same period. Preventive measures such as the use of protective goggles and face shields, together with personal protective equipment, should be emphasised and encouraged.

Perceived Neighborhood Environment and Its Association with Health Screening and Exercise Participation amongst Low-Income Public Rental Flat Residents in Singapore.

Background: In Singapore, an Asian city-state, more than 80% live in public housing. While the majority (90%) own their homes, a needy minority lives in rental flats. Public rental flats are built in the same location as owner-occupied blocks. We evaluated factors associated with perceptions of the neighborhood environment and its association with exercise and health screening participation. Methods: Logistic regression was used to identify associations between perceptions of the neighborhood environment (overall perceived neighborhood disadvantage, safety, and convenience) and sociodemographic factors, as well as exercise and screening participation, amongst residents aged ≥60 years in two Singaporean public housing precincts in 2016. Results: Our response rate was 62.1% (528/800). Staying in a rental flat independently was associated with increased neighborhood disadvantage (adjusted odds ratio, aOR = 1.58, 95%CI = 1.06⁻2.35). Staying in a stand-alone block (as opposed to staying in a mixed block comprised of both rental and owner-occupied units) was associated with perceptions of a poorer physical environment (aOR = 1.81, 95%CI = 1.22⁻2.68) and lower perceived proximity to recreational areas (aOR = 1.14, 95%CI = 1.04⁻1.25). Perceptions of neighborhood disadvantage were independently associated with reduced exercise participation (aOR = 0.67, 95%CI = 0.45⁻0.98) and reduced participation in diabetes screening (aOR = 0.63, 95%CI = 0.41⁻0.95). Conclusion: Despite sharing the same built environment, differences in the perception of the neighborhood environment between low-socioeconomic status (SES) and high-SES communities persist. Perceived neighborhood disadvantage is associated with lower participation in regular exercise and diabetes screening.

Comparison of clinical outcomes in diabetic and non-diabetic burns patients in a national burns referral centre in southeast Asia: A 3-year retrospective review.

OBJECTIVE: Diabetic burns patients may be at risk of worse clinical outcomes. This study aims to further investigate the impact of diabetes mellitus on clinical outcomes in burns patients in Singapore. METHODS: A 3-year retrospective review was performed at the Singapore General Hospital Burns Centre (2011-2013). Pure inhalational burns were excluded. Diabetic (N=53) and non-diabetic (N=533) patients were compared, and the impact of diabetes on clinical outcomes, adjusting for confounders, was investigated using multivariate logistic regression. RESULTS: The diabetic group had a significantly higher incidence of wound infection and severe renal impairment, as well as a longer length of stay, higher number of operations and higher rate of unplanned readmission. ICU admission was significantly associated with hyperglycaemia (OR 5.44 [2.61-11.35], p<0.001) and a higher total body surface area of burn (OR per 1% TBSA 1.07 [1.05-1.09], p<0.001). Unplanned readmission was significantly associated with wound infection (OR 4.29 [1.70-10.83], p=0.002), and mortality associated with a higher TBSA (OR per 1% TBSA 1.1 [1.07-1.14], p<0.001). After adjusting for confounders, diabetes mellitus was not significantly associated with unplanned readmission or mortality. CONCLUSIONS: Diabetic burns patients have an increased risk of worse clinical outcomes, including wound infections, renal impairment and longer length of stay.