Inflammatory Alterations to Renal Lymphatic Endothelial Cell Gene Expression in Mouse Models of Hypertension.

INTRODUCTION: Hypertension (HTN) is a major cardiovascular disease that can cause and be worsened by renal damage and inflammation. We previously reported that renal lymphatic endothelial cells (LECs) increase in response to HTN and that augmenting lymphangiogenesis in the kidneys reduces blood pressure and renal pro-inflammatory immune cells in mice with various forms of HTN. Our aim was to evaluate the specific changes that renal LECs undergo in HTN. METHODS: We performed single-cell RNA sequencing. Using the angiotensin II-induced and salt-sensitive mouse models of HTN, we isolated renal CD31+ and podoplanin+ cells. RESULTS: Sequencing of these cells revealed three distinct cell types with unique expression profiles, including LECs. The number and transcriptional diversity of LECs increased in samples from mice with HTN, as demonstrated by 597 differentially expressed genes (p<0.01), 274 significantly enriched pathways (p<0.01), and 331 regulons with specific enrichment in HTN LECs. These changes demonstrate a profound inflammatory response in renal LECs in HTN, leading to an increase in genes and pathways associated with inflammation-driven growth and immune checkpoint activity in LECs. CONCLUSION: These results reinforce and help to further explain the benefits of renal LECs and lymphangiogenesis in HTN.

Differential changes in end organ immune cells and inflammation in salt-sensitive hypertension: effects of increasing M2 macrophages.

Salt-sensitive hypertension (SSHTN) is associated with M1 macrophage polarization and inflammatory responses, leading to inflammation-associated lymphangiogenesis and functional impairment across multiple organs, including kidneys and gonads. However, it remains unclear whether promoting M2 macrophage polarization can alleviate the hypertension, inflammation, and end organ damage in mice with salt sensitive hypertension (SSHTN). Male and female mice were made hypertensive by administering nitro-L-arginine methyl ester hydrochloride (L-NAME; 0.5 mg/ml) for 2 weeks in the drinking water, followed by a 2-week interval without any treatments, and a subsequent high salt diet for 3 weeks (SSHTN). AVE0991 (AVE) was intraperitoneally administered concurrently with the high salt diet. Control mice were provided standard diet and tap water. AVE treatment significantly attenuated BP and inflammation in mice with SSHTN. Notably, AVE promoted M2 macrophage polarization, decreased pro-inflammatory immune cell populations, and improved function in renal and gonadal tissues of mice with SSHTN. Additionally, AVE decreased lymphangiogenesis in the kidneys and testes of male SSHTN mice and the ovaries of female SSHTN mice. These findings highlight the effectiveness of AVE in mitigating SSHTN-induced elevated BP, inflammation, and end organ damage by promoting M2 macrophage polarization and suppressing pro-inflammatory immune responses. Targeting macrophage polarization emerges as a promising therapeutic approach for alleviating inflammation and organ damage in SSHTN. Further studies are warranted to elucidate the precise mechanisms underlying AVE-mediated effects and to assess its clinical potential in managing SSHTN.

Differential changes in end organ immune cells and inflammation in salt-sensitive hypertension: effects of lowering blood pressure.

We reported that salt-sensitive hypertension (SSHTN) is associated with increased pro-inflammatory immune cells, inflammation, and inflammation-associated lymphangiogenesis in the kidneys and gonads of male and female mice. However, it is unknown whether these adverse end organ effects result from increased blood pressure (BP), elevated levels of salt, or both. We hypothesized that pharmaceutically lowering BP would not fully alleviate the renal and gonadal immune cell accumulation, inflammation, and lymphangiogenesis associated with SSHTN. SSHTN was induced in male and female C57BL6/J mice by administering nitro-L-arginine methyl ester hydrochloride (L-NAME; 0.5 mg/ml) in their drinking water for 2 weeks, followed by a 2-week washout period. Subsequently, the mice received a 3-week 4% high salt diet (SSHTN). The treatment group underwent the same SSHTN induction protocol but received hydralazine (HYD; 250 mg/L) in their drinking water during the diet phase (SSHTN+HYD). Control mice received tap water and a standard diet for 7 weeks. In addition to decreasing systolic BP, HYD treatment generally decreased pro-inflammatory immune cells and inflammation in the kidneys and gonads of SSHTN mice. Furthermore, the decrease in BP partially alleviated elevated renal and gonadal lymphatics and improved renal and gonadal function in mice with SSHTN. These data demonstrate that high systemic pressure and salt differentially act on end organ immune cells, contributing to the broader understanding of how BP and salt intake collectively shape immune responses and highlight implications for targeted therapeutic interventions.

Movement patterns of two reintegrated African elephant (Loxodonta africana) herds: transitioning from captivity to free-living.

With the escalating challenges in captive elephant management, the study of elephant reintegration emerges as a pivotal area of research, primarily addressing the enhancement of animal welfare. The term 'reintegration' refers to the process of rehabilitating captive elephants to a natural system, allowing them to roam freely without intensive human intervention. There is a relative paucity of research addressing the behavioural adaptations post-reintegration, despite reintegration of over 20 elephants across various fenced reserves in South Africa. Our study centres on two distinct herds of reintegrated African elephants, monitoring their movement patterns in two South African reserves over a 57-month period post-release. The primary goal of the study was to establish whether the flexibility and adaptability of movement behaviour of reintegrated elephants can be considered as one of the indicators of determining the success of such an operation. The second aim of our study was to investigate if the reintegrated elephants demonstrated an adaptability to their environment through their hourly, daily, and seasonal ranging patterns after a period of free roaming that exceeded 4 years. Our findings indicated that reintegrated elephants, much like their wild counterparts (movement based on literature), displayed notable seasonal and diurnal variations in key movement parameters, such as utilisation distribution areas and reserve utilization. These patterns changed over time, reflecting an adaptive shift in movement patterns after several years of free roaming. Notably, the trajectory of changes in movement parameters varied between herds, indicating unique adaptation responses, likely resulting from differences in the reintegration process (familiarity of reserve, season of release, presence of wild elephants). Although our study is constrained by the limited number of reintegrated herds available for analysis, it underscores the potential of captive elephants to successfully adapt to a free-living environment, emphasising the promising implications of reintegration initiatives.

Fighting behavior, conflict perceptions, and firearm access among U.S. adolescents in a pediatric emergency department.

OBJECTIVE: Prior evidence demonstrates that both firearm access and fighting can predict future violence and injury in adolescents. We aimed to examine associations between firearm access with fighting behavior and conflict perception in a sample of adolescents in an urban emergency department (ED) setting. METHODS: In 2023, we conducted a secondary analysis of 13,610 adolescent encounters in the ED of a U.S. children's hospital from 2013 to 2020, using a universally applied, self-administered computerized behavioral health survey. We compared patient characteristics by reported firearm access and fighting behavior using chi-squared tests. Generalized estimating equations (GEE) were used to investigate associations between 1) fighting behavior and firearm access, and 2) between fighting behavior and respondent preference to and reporting of fighting incident to law enforcement after adjusting for race and ethnicity, age, and gender. RESULTS: Approximately one-quarter of the sample reported past year fighting. Youth who reported fighting were more likely to report firearm access (AOR = 1.66, 95%CI = [1.49-1.86]). This association strengthened among youth who perceived continued conflict after a fight (AOR = 2.05, 95%CI = [1.73-2.43]). Youth who perceived continued conflict following a fight were more likely to report (AOR = 1.97, 95%CI = [1.65-2.36]) or want to report (AOR = 2.63, 95%CI = [1.81-3.81]) the fight to law enforcement. CONCLUSIONS: Those perceiving continued conflict after a fight were more likely to report access to firearms and endorse retaliation; however, they were more likely to want to report the fight to law enforcement. These findings highlight the potential for more comprehensive ED risk assessment to reduce retaliation and reinjury for adolescents reporting fighting behavior.

Oral care practices and hospital-acquired pneumonia prevention: A national survey of Australian nurses.

BACKGROUND: Hospital-acquired pneumonia (HAP) also known as non-ventilator associated pneumonia, is one of the most common infections acquired in hospitalised patients. Improving oral hygiene appears to reduce the incidence of HAP. This study aimed to describe current practices, barriers and facilitators, knowledge and educational preferences of registered nurses performing oral health care in the Australian hospital setting, with a focus on the prevention of HAP. We present this as a short research report. METHODS: We undertook a cross sectional online anonymous survey of Australian registered nurses. Participants were recruited via electronic distribution through existing professional networks and social media. The survey used was modified from an existing survey on oral care practice. RESULTS: The survey was completed by 179 participants. Hand hygiene was considered a very important strategy to prevent pneumonia (n = 90, 58%), while 45% (n = 71) felt that oral care was very important. The most highly reported barriers for providing oral care included: an uncooperative patient; inadequate staffing; and a lack of oral hygiene requisite. Patients' reminders, prompts and the provision of toothbrushes were common ways believed to help facilitate improvements in oral care. CONCLUSION: Findings from this survey will be used in conjunction with consumer feedback, to help inform a planned multi-centre randomised trial, the Hospital Acquired Pneumonia PrEveNtion (HAPPEN) study, aimed at reducing the incidence of HAP. Findings may also be useful for informing studies and quality improvement initiatives aimed at improving oral care to reduce the incidence of HAP.

Single-Cell RNA Sequencing Identifies Response of Renal Lymphatic Endothelial Cells to Acute Kidney Injury.

SIGNIFICANCE STATEMENT: The renal lymphatic vasculature and the lymphatic endothelial cells that make up this network play important immunomodulatory roles during inflammation. How lymphatics respond to AKI may affect AKI outcomes. The authors used single-cell RNA sequencing to characterize mouse renal lymphatic endothelial cells in quiescent and cisplatin-injured kidneys. Lymphatic endothelial cell gene expression changes were confirmed in ischemia-reperfusion injury and in cultured lymphatic endothelial cells, validating renal lymphatic endothelial cells single-cell RNA sequencing data. This study is the first to describe renal lymphatic endothelial cell heterogeneity and uncovers molecular pathways demonstrating lymphatic endothelial cells regulate the local immune response to AKI. These findings provide insights into previously unidentified molecular pathways for lymphatic endothelial cells and roles that may serve as potential therapeutic targets in limiting the progression of AKI. BACKGROUND: The inflammatory response to AKI likely dictates future kidney health. Lymphatic vessels are responsible for maintaining tissue homeostasis through transport and immunomodulatory roles. Owing to the relative sparsity of lymphatic endothelial cells in the kidney, past sequencing efforts have not characterized these cells and their response to AKI. METHODS: Here, we characterized murine renal lymphatic endothelial cell subpopulations by single-cell RNA sequencing and investigated their changes in cisplatin AKI 72 hours postinjury. Data were processed using the Seurat package. We validated our findings by quantitative PCR in lymphatic endothelial cells isolated from both cisplatin-injured and ischemia-reperfusion injury, by immunofluorescence, and confirmation in in vitro human lymphatic endothelial cells. RESULTS: We have identified renal lymphatic endothelial cells and their lymphatic vascular roles that have yet to be characterized in previous studies. We report unique gene changes mapped across control and cisplatin-injured conditions. After AKI, renal lymphatic endothelial cells alter genes involved in endothelial cell apoptosis and vasculogenic processes as well as immunoregulatory signaling and metabolism. Differences between injury models were also identified with renal lymphatic endothelial cells further demonstrating changed gene expression between cisplatin and ischemia-reperfusion injury models, indicating the renal lymphatic endothelial cell response is both specific to where they lie in the lymphatic vasculature and the kidney injury type. CONCLUSIONS: In this study, we uncover lymphatic vessel structural features of captured populations and injury-induced genetic changes. We further determine that lymphatic endothelial cell gene expression is altered between injury models. How lymphatic endothelial cells respond to AKI may therefore be key in regulating future kidney disease progression.

Sodium, Interstitium, Lymphatics and Hypertension-A Tale of Hydraulics.

Blood pressure is regulated by vascular resistance and intravascular volume. However, exchanges of electrolytes and water between intra and extracellular spaces and filtration of fluid and solutes in the capillary beds blur the separation between intravascular, interstitial and intracellular compartments. Contemporary paradigms of microvascular exchange posit filtration of fluids and solutes along the whole capillary bed and a prominent role of lymphatic vessels, rather than its venous end, for their reabsorption. In the last decade, these concepts have stimulated greater interest in and better understanding of the lymphatic system as one of the master regulators of interstitial volume homeostasis. Here, we describe the anatomy and function of the lymphatic system and focus on its plasticity in relation to the accumulation of interstitial sodium in hypertension. The pathophysiological relevance of the lymphatic system is exemplified in the kidneys, which are crucially involved in the control of blood pressure, but also hypertension-mediated cardiac damage. Preclinical modulation of the lymphatic reserve for tissue drainage has demonstrated promise, but has also generated conflicting results. A better understanding of the hydraulic element of hypertension and the role of lymphatics in maintaining fluid balance can open new approaches to prevent and treat hypertension and its consequences, such as heart failure.

Multimodal environmental cleaning strategies to prevent healthcare-associated infections.

Infection transmission in healthcare is multifaceted and by in large involves the complex interplay between a pathogen, a host and their environment. To prevent transmission, infection prevention strategies must also consider these complexities and incorporate targeted interventions aimed at all possible transmission pathways. One strategy to prevent and control infection is environmental cleaning. There are many aspects to an environmental cleaning strategy. We believe the key to successfully reducing the risk of healthcare-associated infections through the environment, is to design and implement a multimodal intervention. This paper aims to provide an overview of important considerations for designing a meaningful and sustainable environmental program for healthcare facilities.

The incidence of nosocomial bloodstream infection and urinary tract infection in Australian hospitals before and during the COVID-19 pandemic: an interrupted time series study.

BACKGROUND: The COVID-19 pandemic has had a significant impact on healthcare including increased awareness of infection prevention and control (IPC). The aim of this study was to explore if the heightened awareness of IPC measures implemented in response to the pandemic influenced the rates of healthcare associated infections (HAI) using positive bloodstream and urine cultures as a proxy measure. METHODS: A 3 year retrospective review of laboratory data from 5 hospitals (4 acute public, 1 private) from two states in Australia was undertaken. Monthly positive bloodstream culture data and urinary culture data were collected from January 2017 to March 2021. Occupied bed days (OBDs) were used to generate monthly HAI incidence per 10,000 OBDs. An interrupted time series analysis was undertaken to compare incidence pre and post February 2020 (the pre COVID-19 cohort and the COVID-19 cohort respectively). A HAI was assumed if positive cultures were obtained 48 h after admission and met other criteria. RESULTS: A total of 1,988 bloodstream and 7,697 urine positive cultures were identified. The unadjusted incident rate was 25.5 /10,000 OBDs in the pre-COVID-19 cohort, and 25.1/10,000 OBDs in the COVID-19 cohort. The overall rate of HAI aggregated for all sites did not differ significantly between the two periods. The two hospitals in one state which experienced an earlier and larger outbreak demonstrated a significant downward trend in the COVID-19 cohort (p = 0.011). CONCLUSION: These mixed findings reflect the uncertainty of the effect the pandemic has had on HAI's. Factors to consider in this analysis include local epidemiology, differences between public and private sector facilities, changes in patient populations and profiles between hospitals, and timing of enhanced IPC interventions. Future studies which factor in these differences may provide further insight on the effect of COVID-19 on HAIs.

Risk of organism acquisition from prior room occupants: An updated systematic review.

BACKGROUND: Evidence from a previous systematic review indicates that patients admitted to a room where the previous occupant had a multidrug-resistant bacterial infection resulted in an increased risk of subsequent colonisation and infection with the same organism for the next room occupant. In this paper, we have sought to expand and update this review. METHODS: A systematic review and meta-analysis was undertaken. A search using Medline/PubMed, Cochrane and CINHAL databases was conducted. Risk of bias was assessed by the ROB-2 tool for randomised control studies and ROBIN-I for non-randomised studies. RESULTS: From 5175 identified, 12 papers from 11 studies were included in the review for analysis. From 28,299 patients who were admitted into a room where the prior room occupant had any of the organisms of interest, 651 (2.3%) were shown to acquire the same species of organism. In contrast, 981,865 patients were admitted to a room where the prior occupant did not have an organism of interest, 3818 (0.39%) acquired an organism(s). The pooled acquisition odds ratio (OR) for all the organisms across all studies was 2.45 (95% CI: 1.53-3.93]. There was heterogeneity between the studies (I2 89%, P < 0.001). CONCLUSION: The pooled OR for all the pathogens in this latest review has increased since the original review. Findings from our review provide some evidence to help inform a risk management approach when determining patient room allocation. The risk of pathogen acquisition appears to remain high, supporting the need for continued investment in this area.

Single-cell RNA sequencing identifies response of renal lymphatic endothelial cells to acute kidney injury.

The inflammatory response to acute kidney injury (AKI) likely dictates future renal health. Lymphatic vessels are responsible for maintaining tissue homeostasis through transport and immunomodulatory roles. Due to the relative sparsity of lymphatic endothelial cells (LECs) in the kidney, past sequencing efforts have not characterized these cells and their response to AKI. Here we characterized murine renal LEC subpopulations by single-cell RNA sequencing and investigated their changes in cisplatin AKI. We validated our findings by qPCR in LECs isolated from both cisplatin-injured and ischemia reperfusion injury, by immunofluorescence, and confirmation in in vitro human LECs. We have identified renal LECs and their lymphatic vascular roles that have yet to be characterized in previous studies. We report unique gene changes mapped across control and cisplatin injured conditions. Following AKI, renal LECs alter genes involved endothelial cell apoptosis and vasculogenic processes as well as immunoregulatory signaling and metabolism. Differences between injury models are also identified with renal LECs further demonstrating changed gene expression between cisplatin and ischemia reperfusion injury models, indicating the renal LEC response is both specific to where they lie in the lymphatic vasculature and the renal injury type. How LECs respond to AKI may therefore be key in regulating future kidney disease progression.

Indole Propionic Acid Increases T Regulatory Cells and Decreases T Helper 17 Cells and Blood Pressure in Mice with Salt-Sensitive Hypertension.

Hypertension affects over a billion adults worldwide and is a major risk factor for cardiovascular disease. Studies have reported that the microbiota and its metabolites regulate hypertension pathophysiology. Recently, tryptophan metabolites have been identified to contribute to and inhibit the progression of metabolic disorders and cardiovascular diseases, including hypertension. Indole propionic acid (IPA) is a tryptophan metabolite with reported protective effects in neurodegenerative and cardiovascular diseases; however, its involvement in renal immunomodulation and sodium handling in hypertension is unknown. In the current study, targeted metabolomic analysis revealed decreased serum and fecal IPA levels in mice with L-arginine methyl ester hydrochloride (L-NAME)/high salt diet-induced hypertension (LSHTN) compared to normotensive control mice. Additionally, kidneys from LSHTN mice had increased T helper 17 (Th17) cells and decreased T regulatory (Treg) cells. Dietary IPA supplementation in LSHTN mice for 3 weeks resulted in decreased systolic blood pressure, along with increased total 24 h and fractional sodium excretion. Kidney immunophenotyping demonstrated decreased Th17 cells and a trend toward increased Treg cells in IPA-supplemented LSHTN mice. In vitro, naïve T cells from control mice were skewed into Th17 or Treg cells. The presence of IPA decreased Th17 cells and increased Treg cells after 3 days. These results identify a direct role for IPA in attenuating renal Th17 cells and increasing Treg cells, leading to improved sodium handling and decreased blood pressure. IPA may be a potential metabolite-based therapeutic option for hypertension.

Air purifiers for reducing the incidence of acute respiratory infections in australian residential aged care facilities: A study protocol for a randomised control trial.

INTRODUCTION: Adults living in Residential Aged Care Facilities (RACFs) are highly susceptible to seasonal respiratory infections. Evidence indicates that the aerosols contaminated with virus particles in closed indoor spaces may play a significant role in the transmission of respiratory infections. In this protocol paper, we outline details of a planned RCT which aims to evaluate the effectiveness of portable in room air purifiers in reducing the risk of ARIs among residents in Australian RACFs. This study uses a multi-centre double-blind randomised crossover design. Three RACFs in a regional area of New South Wales will be invited to participate in the study. Air purifiers with or without high-efficiency particulate absorbing (HEPA) filters will be placed in the rooms of residents who are enrolled in the trial. The primary outcome will be a reduction in the incidence of ARI and the secondary outcomes will be the time to first infection, number of emergency department admissions, hospital admissions, and medical consultations due to an ARI. CONCLUSION: To our knowledge, this will be the first RCT using air purifiers in resident rooms to identify their effect in reducing ARIs in RACFs. If our findings indicate some potential benefit for in-room air purification, it will help provide support and justification for larger trials, which may include a facility wide approach to air purification.

Moisturizers, Emollients, or Barrier Preparations for the Prevention of Pressure Injury: A Systematic Review and Meta-Analysis.

Significance: Pressure injuries are prevalent, yet preventable global health care problem estimated to affect 14% of hospital patients and up to 46% of aged care residents. One common prevention strategy is improving skin integrity through emollient therapy to optimize hydration and avoid skin breakdown. Therefore, this study aimed to review the literature and determine effectiveness of inert emollients, moisturizers, and barrier preparations compared with standard care, to prevent pressure injury in aged care or hospital settings. Recent Advances: Search terms were derived with database searches, including ProQuest, Cumulative Index of Nursing and Allied Health Literature (CINAHL), Medline, Science Direct, Scopus, and the Cochrane library. The Robins1 and Risk of Bias 2 (Rob2) quality appraisal tools were used. A meta-analysis of the effects of interventions was conducted (random effects). Four studies met the inclusion criteria, with heterogeneous quality. Pooling of nonrandomized studies found that the application of emollients, moisturizers or barrier preparations did not significantly reduce incidence of pressure injury compared with standard care (relative risk 0.50, 95% confidence interval: 0.15-1.63, Z = 1.15, p = 0.25). Critical Issues: This review suggests that the use of inert moisturizers, emollients, or barrier preparations for preventing pressure injuries was not effective to prevent pressure injury in aged care or hospital settings. However, there was a distinct lack of randomized controlled trials (RCTs), with only one meeting the inclusion criteria. Furthermore, most of the included studies did not report on the frequency of application of the product, making it difficult to determine if application was in line with current international guidelines. One included study, which utilized a combination of neutral body wash and emollient demonstrated a significant reduction in the development of stage one and two pressure injuries. This combination of care may further support skin integrity and should be further examined in future trials. Future Directions: Future studies should ideally be RCTs, which control for skin cleansing, and implement an inert moisturizer emollient or barrier preparation as part of a pressure injury reduction bundle of care. Standardization of the application of the product, the volume of product applied at each application, and the quality of the product should also be considered.

Have gloves and gowns had their day? An Australian and New Zealand practice and attitudes survey about contact precautions for MRSA and VRE colonisation.

BACKGROUND: 'Contact precautions,' are recommended for hospitalised patients with known methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) colonisation. Despite increasing observational evidence suggesting that gowns and gloves are of no added benefit over hand hygiene and environmental cleaning, guidelines continue to recommend them. METHODS: A cross-sectional online survey of infection prevention professionals, infectious diseases physicians and microbiologists in Australian and New Zealand hospitals was conducted. The purpose was to explore variations in current approaches to known MRSA and VRE colonisation, and determine clinical equipoise for a proposed randomised control trial (RCT) to withdraw the use of gowns and gloves in this setting. RESULTS: 226 responses from 122 hospitals across all Australian jurisdiction and multiple regions of New Zealand were received. While most hospitals implement contact precautions for MRSA (86%) and VRE (92%), variations based on MRSA and VRE subtypes are common. There was strong interest in removing glove and gown use for MRSA (72% and 73%, respectively) and VRE (70% and 68%, respectively). 62% of surveyed hospitals expressed interest in participating in a proposed cluster RCT comparing discontinuation of gown and glove use as part of contact precautions for MRSA and VRE, with their ongoing use. CONCLUSION: The mandated use of PPE in the context of MRSA and VRE colonisation warrants further examination. An RCT is needed to definitively address this issue and to promote a widespread change in practice, if warranted.

A randomised controlled trial investigating the effect of improving the cleaning and disinfection of shared medical equipment on healthcare-associated infections: the CLEaning and Enhanced disiNfection (CLEEN) study.

BACKGROUND: Healthcare-associated infections (HAIs) are a common, costly, yet largely preventable complication impacting patients in healthcare settings globally. Improving routine cleaning and disinfection of the hospital environment has been shown to reduce the risk of HAI. Contaminated shared medical equipment presents a primary transmission route for infectious pathogens, yet is rarely studied. The CLEEN study will assess how enhanced cleaning and disinfection of shared medical equipment affects the rate of HAIs in a tertiary hospital setting. The initiative is an evidence-based approach combining staff training, auditing and feedback to environmental services staff to enhance cleaning and disinfection practices. METHODS: The CLEEN study will use a stepped wedge randomised controlled design in 10 wards of one large Australian hospital over 36 weeks. The intervention will consist of 3 additional hours per weekday for the dedicated cleaning and disinfection of shared medical equipment on each ward. The primary outcome is to demonstrate the effectiveness of improving the quality and frequency of cleaning shared medical equipment in reducing HAIs, as measured by a HAI point prevalence study (PPS). The secondary outcomes include the thoroughness of equipment cleaning assessed using fluorescent marker technology and the cost-effectiveness of the intervention. DISCUSSION: Evidence from the CLEEN study will contribute to future policy and practice guidelines about the cleaning and disinfection of shared medical equipment. It will be used by healthcare leaders and clinicians to inform decision-making and implementation of best-practice infection prevention strategies to reduce HAIs in healthcare facilities. TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry ACTRN12622001143718.