Evaluating remote facilitation intensity for multi-national translation of nurse-initiated stroke protocols (QASC Australasia): a protocol for a cluster randomised controlled trial.

BACKGROUND: Facilitated implementation of nurse-initiated protocols to manage fever, hyperglycaemia (sugar) and swallowing difficulties (FeSS Protocols) in 19 Australian stroke units resulted in reduced death and dependency for stroke patients. However, a significant gap remains in translating this evidence-based care bundle protocol into standard practice in Australia and New Zealand. Facilitation is a key component for increasing implementation. However, its contribution to evidence translation initiatives requires further investigation. We aim to evaluate two levels of intensity of external remote facilitation as part of a multifaceted intervention to improve FeSS Protocol uptake and quality of care for patients with stroke in Australian and New Zealand acute care hospitals. METHODS: A three-arm cluster randomised controlled trial with a process evaluation and economic evaluation. Australian and New Zealand hospitals with a stroke unit or service will be recruited and randomised in blocks of five to one of the three study arms-high- or low-intensity external remote facilitation or a no facilitation control group-in a 2:2:1 ratio. The multicomponent implementation strategy will incorporate implementation science frameworks (Theoretical Domains Framework, Capability, Opportunity, Motivation - Behaviour Model and the Consolidated Framework for Implementation Research) and include an online education package, audit and feedback reports, local clinical champions, barrier and enabler assessments, action plans, reminders and external remote facilitation. The primary outcome is implementation effectiveness using a composite measure comprising six monitoring and treatment elements of the FeSS Protocols. Secondary outcome measures are as follows: composite outcome of adherence to each of the combined monitoring and treatment elements for (i) fever (n=5); (ii) hyperglycaemia (n=6); and (iii) swallowing protocols (n=7); adherence to the individual elements that make up each of these protocols; comparison for composite outcomes between (i) metropolitan and rural/remote hospitals; and (ii) stroke units and stroke services. A process evaluation will examine contextual factors influencing intervention uptake. An economic evaluation will describe cost differences relative to each intervention and study outcomes. DISCUSSION: We will generate new evidence on the most effective facilitation intensity to support implementation of nurse-initiated stroke protocols nationwide, reducing geographical barriers for those in rural and remote areas. TRIAL REGISTRATION: ACTRN12622000028707. Registered 14 January, 2022.

Deletion of endothelial cell-specific liver kinase B1 increases angiogenesis and tumor growth via vascular endothelial growth factor.

Liver kinase B1 (LKB1) is a serine/threonine protein kinase ubiquitously expressed in mammalian cells. It was first identified in Peutz-Jeghers syndrome as a tumor suppressor gene. Whether endothelial LKB1 regulates angiogenesis and tumor growth is unknown. In this study, we generated endothelial cell-specific LKB1-knockout (LKB1endo-/-) mice by crossbreeding vascular endothelial-cadherin-Cre mice with LKB1flox/flox mice. Vascular endothelial growth factor (VEGF) level was highly co-stained in endothelial cells but not in macrophages in LKB1endo-/- mice. Consistently, LKB1endo-/- mouse tissues including the lung, skin, kidney and liver showed increased vascular permeability. Tumors implanted in LKB1endo-/- mice but not macrophage-specific LKB1-knockout mice grew faster and showed enhanced vascular permeability and increased angiogenesis as compared with those implanted in wild-type mice. Injection of VEGF-neutralizing antibody but not the isotype-matched control antibody decreased endothelial-cell angiogenesis and tumor growth in vivo. Furthermore, LKB1 deletion enhanced mouse retinal and cell angiogenesis, and knockdown of VEGF by small-interfering RNA decreased endothelial cell proliferation and migration. Re-expression of LKB1 or knockdown of VEGF receptor 2 decreased the overproliferation and -migration observed in LKB1endo-/- cells. Mechanistically, LKB1 could bind to the VEGF transcription factor, specificity protein 1 (Sp1), which then inhibited the binding of Sp1 to the VEGF promoter to reduce VEGF expression. Endothelial LKB1 may regulate endothelial angiogenesis and tumor growth by modulating Sp1-mediated VEGF expression.

Are suspected stroke patients identified by paramedics transported to appropriate stroke centres in Victoria, Australia?

Emergency medical services (EMS) are vital to ensuring acute stroke patients are transported to thrombolysis and/or stroke unit centres. This 6-month audit of Victorian EMS cases found the majority of suspected acute strokes are transported to appropriate stroke centres. However, there is still room for improvement, in particular, strategies to improve access to stroke services in some rural regions and to ensure patients/relatives are fully informed when requesting transport to a non-stroke service hospital.

Acidotoxicity and acid-sensing ion channels contribute to motoneuron degeneration.

Amyotrophic lateral sclerosis (ALS) is a fatal neurological condition with no cure. Mitochondrial dysfunction, Ca(2+) overloading and local hypoxic/ischemic environments have been implicated in the pathophysiology of ALS and are conditions that may initiate metabolic acidosis in the affected tissue. We tested the hypothesis that acidotoxicity and acid-sensing ion channels (ASICs) are involved in the pathophysiology of ALS. We found that motoneurons were selectively vulnerable to acidotoxicity in vitro, and that acidotoxicity was partially reduced in asic1a-deficient motoneuron cultures. Cross-breeding of SOD1(G93A) ALS mice with asic1a-deficient mice delayed the onset and progression of motor dysfunction in SOD1 mice. Interestingly, we also noted a strong increase in ASIC2 expression in motoneurons of SOD1 mice and sporadic ALS patients during disease progression. Pharmacological pan-inhibition of ASIC channels with the lipophilic amiloride derivative, 5-(N,N-dimethyl)-amiloride hydrochloride, potently protected cultured motoneurons against acidotoxicity, and, given post-symptom onset, significantly improved lifespan, motor performance and motoneuron survival in SOD1 mice. Together, our data provide strong evidence for the involvement of acidotoxicity and ASIC channels in motoneuron degeneration, and highlight the potential of ASIC inhibitors as a new treatment approach for ALS.

Methicillin-resistant Staphylococcus aureus in resident animals of a long-term care facility.

UNLABELLED: Animals provide benefits to elderly and chronically ill people by decreasing loneliness, increasing social interactions, and improving mental health. As a result, many hospitals and long-term care facilities allow family pets to visit ill or convalescing patients or support animal-assisted therapy programs. These include programs that have resident animals in long-term care facilities. Despite the benefits, there are concerns about disease transmission between pets and patients. Antibiotic-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), are a recognized problem in healthcare settings leading to refractory infections and potentially life-threatening illnesses. MRSA has been isolated from numerous animal species, yet few studies are available on the carriage of this pathogen in animals residing in long-term care facilities. Our objective was to characterize MRSA carriage among resident animals in a long-term care facility. METHODS: To document MRSA colonization, nasal swabs from 12 resident animals (one dogs and 11 cats) of a long-term care facility were collected weekly for 8 weeks. Staphylococcus isolates were characterized by antimicrobial susceptibility and MRSA isolates were further characterized by pulsed-field gel electrophoresis (PFGE). PFGE isolate patterns were compared with an existing database of MRSA isolate patterns at the Minnesota Department of Health. RESULTS: Two of 11 cats were colonized with MRSA. MRSA was recovered from five of eight weekly samples in one cat and two of eight weekly samples in the other cat. All isolates were classified as USA100 (healthcare-associated strains). DISCUSSION: Long-term care resident animals may acquire MRSA. Clonally related strains were identified over the 8-week sampling period. It is unclear if pets serve as an on-going source of infection to their human companions in long-term care facilities.

Thrombolytic therapy for acute ischaemic stroke: successful implementation in an Australian tertiary hospital.

The use of tissue-type plasminogen activator (t-PA) in ischaemic stroke outside of experienced stroke centres remains controversial. The aim of this study was to present the initial experience with t-PA in patients with ischaemic stroke at an institution with no prior experience in i.v. stroke thrombolysis and to compare results to published reports. Prospective audit of 888 patients with consecutive stroke and transient ischaemic attack admitted to a 426-bed tertiary referral hospital from March 2003 to October 2005. Main outcome measures were treatment rate, exclusion criteria, protocol violations, intracerebral haemorrhage, disability (modified Rankin scale) and mortality at 3 months. Over the study period, 72 patients received t-PA (11% of ischaemic strokes). The main reason for exclusion was presentation beyond 3 h of onset (44%); if all eligible patients had arrived within 3 h, treatment rate was estimated at 32.5%. Protocol violations occurred in 15 (21%) patients. There were seven (10%) asymptomatic intracerebral haemorrhage and one (1%) non-fatal symptomatic intracerebral haemorrhage. At 3 months, 37% had achieved excellent recovery (modified Rankin scale 0-1) and seven (10%) had died. The delivery and outcomes associated with the use of t-PA were comparable to the results of the National Institute of Neurological Disorders and Stroke trial and meta-analysis of open-labelled studies. With appropriate infrastructure and protocols, previously inexperienced tertiary referral centres can replicate the experience and outcome measures reported by clinical trials of t-PA in patients with stroke.

Exogenous TGF-beta1 promotes stromal development in the heifer mammary gland.

The objectives of this study were to determine the local effects of transforming growth factor-beta1 (TGF-beta1) on mammary epithelial and stromal cell proliferation and expression of the TGF-beta1 responsive genes c-myc and fibronectin. A single slow-release plastic pellet containing 5 microg of TGF-beta1 and 20 mg of BSA was implanted in the parenchyma of the right rear quarter of the mammary gland of 9-mo-old prepubertal heifers. A control pellet containing 20 mg of BSA was implanted in the left rear quarter of each heifer. All heifers were treated with bromodeoxyuridine (BrdU) at 4, 12.5, and 22 h after the pellets were implanted to label proliferating cells. Two hours after the last BrdU injection, the animals were euthanatized, and their mammary glands were recovered. Proliferation of mammary stromal cells was significantly higher in TGF-beta1-treated quarters than in BSA-treated, control quarters (3.5 vs. 1.8% BrdU-positive cells). This result coincided with a lack of significant effect of TGF-beta1 on proliferation of mammary epithelial cells and apoptosis. By quantitative reverse transcriptase-polymerase chain reaction, we found that c-myc gene expression was unchanged after TGF-beta1 treatment, but fibronectin gene expression was increased 3-fold in TGF-beta1-treated quarters compared with BSA-treated, control quarters. Thus, we concluded that TGF-beta1 selectively acts on the stromal compartment of the bovine mammary gland by increasing cell proliferation and gene expression of the extracellular matrix protein fibronectin.

Patellofemoral contact forces and pressures during intramedullary tibial nailing.

Patellofemoral joint forces and pressures were measured in a cadaver model during intramedullary nailing of the tibia. A significant increase in contact pressures was found at the lateral facet of the patellofemoral articulation using the medial paratendinous approach (P = 0.01) and at the medial facet when using the trans-patellar tendon approach (P = 0.001) to the proximal tibia. Increased contact pressures at the patello-femoral joint may result in chondral injury, which in turn may cause anterior knee pain, a common complication of tibial nailing.

A new trichrome-blue stain for detection of microsporidial species in urine, stool, and nasopharyngeal specimens.

Detection of microsporidia in clinical specimens has relied on electron microscopy, histology, or staining. This article describes further alterations to the modified trichrome staining method which make it easier to identify microsporidial spores. The changes are a decrease in the phosphotungstic acid level and the substitution of a colorfast counterstain, aniline blue, for the fast green of the original stain. The modified stain provides good contrast between microsporidial spores and background material including human and fungal cells. Stool specimens from 139 human immunodeficiency virus-seropositive patients revealed that 5 patients were infected with Enterocytozoon bieneusi and 6 patients had larger spores. Thin-section electron microscopy of the larger spores showed a structure consistent with that of either Encephalitozoon or Septata species. Three of the patients with Encephalitozoon- or Septata-like species had disseminated infection, with spores detected in nasopharyngeal aspirates and urine samples.