COVID-19 lockdowns affected birthing outcomes in a regional New South Wales Health District.

INTRODUCTION: The 400 000 residents of the Illawarra Shoalhaven Local Health District (ISLHD) experienced two distinct lockdowns aimed at mitigating the transmission of severe acute respiratory syndrome coronavirus 2 infection. Analysing effects of these lockdowns on maternal and neonatal outcomes presents a valuable opportunity to assess the impact of pandemic-level restrictions on maternal and neonatal outcomes. AIM: Evaluate the impacts of restrictions from two lockdown periods on maternal, birthing, and neonatal outcomes within a regional local health district. MATERIALS AND METHODS: The study included 22 166 women who gave birth within ISLHD between 2017 and 2022. Groups included for analysis: Control Group - mothers pregnant before the pandemic (conception before 3 April 2019); Exposure Group 1 - mothers pregnant during the first lockdown (conception date 22 January 2020 to 5 May 2020); and Exposure Group 2 - mothers pregnant during the second lockdown (conception date 30 April 2021 to 13 Sep 2021). RESULTS: Odds of adverse birthing outcomes including non-reassuring fetal status (odds ratio (OR) 1.34; 95% CI 1.14-1.56 and OR 1.20; 95% CI 1.03-1.40), and postpartum haemorrhage (OR 2.04; 95% CI 1.73-2.41 and OR 1.74; 95% CI 1.48-2.05) were substantially increased in Exposure Groups 1 and 2, respectively. Gestational diabetes, gestational hypertension, low birth weight and admission to neonatal intensive care rates improved. CONCLUSIONS: Pregnant women exposed to pandemic restrictions within ISLHD had decreased odds of adverse antenatal and neonatal outcomes, but increased odds of poor peripartum outcomes.

Implementation Evaluation of an Early Notification Care Bundle for Patients with Hip Fracture (eHIP).

INTRODUCTION: Hip fracture in older adults results in significant mortality and is one of the costliest fall-related injuries. The Australian Commission for Quality and Safety in Health Care hip fracture clinical care standards consolidate the best available evidence for managing this patient group; however, uptake is variable. The aim of this study was to evaluate the implementation and effectiveness of a multidisciplinary early activation mechanism and bundle of care (eHIP) on patient and health service outcomes. METHODS: This controlled pre- and post-test study was conducted from June 2019-June 2021 at a large regional hospital in Australia. We hypothesised that eHIP would result in at least 50% of hip fracture patients receiving six or more components of the ACSQHC Hip Fracture Clinical Care Standard. Secondary outcomes include hospital-acquired complication rates and acute treatment costs. RESULTS: There were 565 cases included for analysis. After implementation of eHIP (the post-period), 88% of patients received a correct activation of the eHIP pathway, sustained over 12 months. The proportion of patients receiving the primary outcome of six or more components increased from 36% to 49%. Care at presentation (pain and cognitive assessment) increased by 23%, and unrestricted mobilisation within 24 h improved by 10%. Prescription of appropriate analgesia improved 10-fold (5.2-57%), and patients receiving the gold standard fascia iliaca block increased from 68% to 88%. Acute treatment costs did not significantly change. DISCUSSION/CONCLUSION: eHIP, a hip fracture care program incorporating evidence-based behaviour change theory, resulted in sustained improvements to patient care as recommended by the ACSQHC Hip Fracture Clinical Care Standard.

MCP-1 expression in breast cancer and its association with distant relapse.

BACKGROUND: Distant relapse of breast cancer complicates management of the disease and accounts for 90% of breast cancer-related deaths. Monocyte chemoattractant protein-1 (MCP-1) has critical roles in breast cancer progression and is widely accepted as a pro-metastatic chemokine. METHODS: This study explored MCP-1 expression in the primary tumour of 251 breast cancer patients. A simplified 'histoscore' was used to determine if each tumour had high or low expression of MCP-1. Patient breast cancers were retrospectively staged based on available patient data. p < 0.05 was used to determine significance and changes in hazard ratios between models were considered. RESULTS: Low MCP-1 expression in the primary tumour was associated with breast cancer-related death with distant relapse in ER- breast cancers (p < 0.01); however, this was likely a result of most low MCP-1-expressing ER- breast cancers being Stage III or Stage IV, with high MCP-1 expression in the primary tumour significantly correlated with Stage I breast cancers (p < 0.05). Expression of MCP-1 in the primary ER- tumours varied across Stage I, II, III and IV and we highlighted a switch in MCP-1 expression from high in Stage I ER- cancers to low in Stage IV ER- cancers. CONCLUSION: This study has emphasised a critical need for further investigation into MCP-1's role in breast cancer progression and improved characterisation of MCP-1 in breast cancers, particularly in light of the development of anti-MCP-1, anti-metastatic therapies.

New Insights Into Osteoclast Biology.

Osteoclasts are multinucleated cells that are characterized by their unique ability to resorb large quantities of bone. Therefore, they are frequently the target of therapeutic interventions to ameliorate bone loss. In an adult organism, osteoclasts derive from hematopoietic stem cells and differentiate into osteoclasts within a multistep process under the influence of macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL). Historically, the osteoclast life cycle has been defined as linear, whereby lineage-committed mononuclear precursors fuse to generate multinucleated highly specialized and localized bone phagocytic cells, which then undergo apoptosis within weeks. Recent advances through lineage tracing, single cell RNA sequencing, parabiosis, and intravital imaging approaches have challenged this dogma, revealing they have greater longevity and the capacity to circulate and undergo cell recycling. Indeed, these new insights highlight that under homeostatic conditions very few incidences of osteoclast apoptosis occur. More importantly, as we revisit the formation and fate of the osteoclast, novel methods to target osteoclast biology in bone pathology and regeneration are emerging. This review briefly summarizes the historical life cycle of osteoclasts and highlights recent discoveries made through advanced methodologies, which have led to a paradigm shift in osteoclast biology. These findings are discussed in light of both existing and emerging bone targeted therapeutics, bone pathologies, and communication between osteoclasts and cells resident in bone or at distant sites. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Monocyte Chemoattractant Protein-1 (MCP-1/CCL2) Drives Activation of Bone Remodelling and Skeletal Metastasis.

PURPOSE OF REVIEW: The purpose of this review is to explore the role of monocyte chemoattractant protein-1 (MCP-1 or CCL2) in the processes that underpin bone remodelling, particularly the action of osteoblasts and osteoclasts, and its role in the development and metastasis of cancers that target the bone. RECENT FINDINGS: MCP-1 is a key mediator of osteoclastogenesis, being the highest induced gene during intermittent treatment with parathyroid hormone (iPTH), but also regulates catabolic effects of continuous PTH on bone including monocyte and macrophage recruitment, osteoclast formation and bone resorption. In concert with PTH-related protein (PTHrP), MCP-1 mediates the interaction between tumour-derived factors and host-derived chemokines to promote skeletal metastasis. In breast and prostate cancers, an osteolytic cascade is driven by tumour cell-derived PTHrP that upregulates MCP-1 in osteoblastic cells. This relationship between PTHrP and osteoblastic expression of MCP-1 may drive the colonisation of disseminated breast cancer cells in the bone. There is mounting evidence to suggest a pivotal role of MCP-1 in many diseases and an important role in the establishment of comorbidities. Coupled with its role in bone remodelling and the regulation of bone turnover, there is the potential for pathological relationships between bone disorders and bone-related cancers driven by MCP-1. MCP-1's role in bone remodelling and bone-related cancers highlights its potential as a novel anti-resorptive and anti-metastatic target.