Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Therapeutics for enhanced chronic wound healing

Chronic wounds are a major drain on healthcare resources and can lead to substantial reductions in quality of life for those affected. Moreover, they often precede serious events such as limb amputations and premature death. In the long run, this burden is likely to escalate with an ageing population and lifestyle diseases such as obesity. At present, current chronic wound management approaches can only manage wounds and are limited in their ability to actively promote the repair of chronic wounds. Although significant progress has been made in the development of different therapeutic agents, the lack of an optimal preclinical animal model is a major impediment in the translation of drugs and/or biological products to the clinic. Thus, this highlights an urgent need for the development of more relevant, robust, and reproducible animal models of delayed healing. Chronic wounds are uncommon in animals and challenging to simulate. Thus far, only the thoroughbred horses are known to suffer from chronic wounds with similar features to the human condition. However, the high economic costs of utilizing horses as an alternative model of study alongside ethical concerns, limit its feasibility. Hence, other studies have focused on identifying and isolating the main causative factors of chronic wounds, such as diabetes, ischemia-reperfusion (IR) injury and biofilm colonization. Consequently, delayed models of healing, including the streptozotocin diabetic model, skin flap model and magnet-induced IR models have emerged. However, chronic wounds are multifactorial in nature and arise through a combination of factors, which collectively overwhelm the normal healing response. While these models have been widely adopted for preclinical therapeutic testing, their relevance towards human chronic wounds remains debatable. In particular, current delayed healing models often fail to fully incorporate the key characteristics of chronic ulcers. These include features such as delayed re-epithelialization, hyper thickened non-migratory wound edges with overexpression of the gap junction protein connexin 43 (Cx43), persistent inflammation, elevated reactive oxygen species (ROS) levels, alkaline wound environment, excessive extracellular matrix (ECM) degradation at wound edges, disrupted/impaired vasculature, and sustained presence of senescent cells. Concurrently, without the protection of delivery systems, bioactive molecules are highly susceptible to degradation. Accordingly, the aim of this thesis was to explore how the effective delivery of therapeutics on a more clinically relevant animal model, can benefit chronic wound healing. Here, the methodology of exploiting the host’s response towards an oversized three-dimensional (3D) polycaprolactone (PCL)/collagen (Coll) scaffold for the development of a novel rat perturbed wound model was explored. Notably, more pronounced perturbed wound features such as a hyper-thickened non-migratory wound edge epidermis, persistent inflammation, presence of wound edge senescent cells and excessive ECM degradation in the wound edges were induced with longer scaffold contact duration, of 10 days. Upon removal of the scaffold at Day 10, the induced features remained intact, and a clean wound bed was left behind. As an extension of this work, the perturbed wound model was transferred into pigs, to enhance its clinical relevance and contribute to the establishment of a two-species preclinical testing platform. Here, the perturbed model was successfully established in pigs. Notably, many aspects of human chronic wound were recapitulated in pig perturbed wounds, such as delayed wound closure, chronic inflammation, overexpressed Cx43, high senescence levels and excessive wound edge ECM degradation and hindered ECM deposition in wound beds. Leveraging on the pig perturbed wound model, different Cx43-based therapeutics, were then explored. In this thesis, the efficacy of Cx43 antisense oligodeoxynucleotide (asODN), delivered in pluronic gel, was tested in the pig perturbed wound model. Here, transient downregulation of Cx43 expression in the leading-edge keratinocytes as well as in perturbed wound edges, resulted in accelerated re-epithelialization and a significant decrease in inflammatory cell infiltration, especially at early timepoints. The current results support the therapeutic potential of Cx43asODN in promoting chronic wound healing. However, both pluronic gel and Cx43asODN were speculated to undergo rapid degradation in the harsh perturbed wound environment, accounting for the transient downregulation seen in this study. Therefore, an alternative delivery system, capable of facilitating sustained delivery of Cx43asODN might be necessary to achieve improved wound healing outcomes. Other than Cx43asODN, the effect of Tonabersat which is a connexin hemichannel blocker was also evaluated in the pig perturbed wound model. In this study, localized delivery of Tonabersat, in pluronic gel, resulted in significantly improved functional outcomes. In particular, Tonabersat treatment led to significantly faster wound closure rates as well as reduction in both inflammatory cell infiltration and senescent cell levels in pig perturbed wounds. As mentioned above, an alternative delivery strategy to improve the bioavailability of Cx43asODN in perturbed wounds was necessary. Here, the use of chitosan as a coating material was explored as a strategy to increase the adsorption of asODN onto electrospun PCL scaffolds and thereby achieve sustained release of Cx43 asODN. Here, the surface modification of PCL scaffolds with chitosan significantly enhanced the adsorption of Cx43asODN and resulted in a sustained and significant release of asODNs over a 5-day period. In the rat perturbed wound model, this corresponded with a sustained downregulation of Cx43 protein levels at the epidermal tongue, wound edge, and perturbed wound beds. Consequently, the rate of re-epithelialization was significantly improved, and inflammation is reduced. With respect to Molecule T, delivering higher concentrations of this drug could further promote perturbed wound healing. However, a corresponding increase in organic solvents could be toxic to cells. This highlights the need for an alternative delivery system, capable of delivering high concentrations of Molecule T while allowing the removal of potentially toxic organic solvents. In this work, a particle-based delivery system was employed using an emulsion-based method to encapsulate Molecule T within PLGA particles. Here, the organic solvent used to dissolve both PLGA and Molecule T was removed, as a part of the process involved in the formation of the PLGA particles. Consequently, delivery of the PLGA-Molecule T particles in the rat perturbed wound model promoted wound healing, without any adverse effects. In particular, Molecule T-treated wounds were observed to have faster re-epithelialization rates. Concurrently, Molecule T application also led to reductions in NLRP3 and caspase-1 levels. Taken together, this thesis demonstrated the potential of the newly developed perturbed wound model in both rats and pigs, as a clinically relevant therapeutic testing platform. Importantly, this model was successful in recapitulating many features of human chronic wounds. Accordingly, different therapeutics, and their respective delivery systems, targeted at different aspects of the pathophysiology of chronic wounds can be tested in this model. This would allow the evaluation of how each therapeutic could potentially promote perturbed wound healing and thus provide critical information on its performance upon translation to human chronic wounds.Doctor of Philosoph

Challenges faced in developing an ideal chronic wound model

Introduction: Chronic wounds are a major drain on healthcare resources and can lead to substantial reductions in quality of life for those affected. Moreover, they often precede serious events such as limb amputations and premature death. In the long run, this burden is likely to escalate with an ageing population and lifestyle diseases such as obesity. Thus far, the identification of beneficial therapeutics against chronic wounds have been hindered by the lack of an ideal chronic wound animal model. Although animal models of delayed healing have been developed, none of these models fully recapitulate the complexity of the human chronic wound condition. Furthermore, most animals do not develop chronic wounds. Only the thoroughbred racehorse develops chronic ulcers. Areas covered: In this review, the different characteristics of chronic wounds that highlight its complexity are described. In addition, currently available models reflecting different aspects of chronic wound pathology and their relevance to human chronic wounds are discussed. This article concludes by listing relevant features representative of an ideal chronic wound model. Additionally, alternative approaches for the development of chronic wound models are discussed. Expert opinion: Delayed models of healing, including the streptozotocin diabetic model, skin flap model and magnet-induced IR models have emerged. While these models have been widely adopted for preclinical therapeutic testing, their relevance towards human chronic wounds remains debatable. In particular, current delayed healing models often fail to fully incorporate the key characteristics of chronic ulcers. Ultimately, more representative models are required to expedite the advancement of novel therapeutics to the clinic.Agency for Science, Technology and Research (A*STAR)Ministry of Education (MOE)Nanyang Technological UniversityPublished versionThis research is supported by the Agency for Science, Technology and Research (A*STAR) under its Industry Alignment Fund–Pre-Positioning Programme (IAF-PP) grant number H17/01/a0/0C9 as part of the Wound Care Innovation for the Tropics (WCIT) Programme. This research is also supported by the Agency for Science, Technology and Research (A*STAR) under its Industry Alignment Fund–Pre-Positioning Programme (IAF-PP) grant number H1701a0004 and the Skin Research Institute of Singapore, Phase 2: SRIS@Novena. Nanyang Technological University (Start-up grant) and the Ministry of Education (Tier 1 T1-002-098 and T1-002-013) also supported this research

A flexible multiplexed immunosensor for point-of-care in situ wound monitoring

10.1126/sciadv.abg9614Science Advances721eabg961

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study (Intensive Care Medicine, (2021), 47, 2, (160-169), 10.1007/s00134-020-06234-9)

The original version of this article unfortunately contained a mistake. The members of the ESICM Trials Group Collaborators were not shown in the article but only in the ESM. The full list of collaborators is shown below. The original article has been corrected

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat