Improved adherence to hip fracture standards reduces mortality after hip fractures.

BACKGROUND: Hip fractures are increasing in incidence due to increasing life expectancy. Mortality continues to improve but it is important to explore which factors are responsible for driving improvements. METHODS: A cohort of hip fracture patients predating SARS-CoV-2 was examined to determine the predictors of adherence to the six Irish Hip Fracture Standards (IHFS) and the impact of adherence on short (30 day) and long term (1 year) mortality. Our primary aim was assess the impact of a single HFS and cumulative number of HFS on mortality after hip fracture. Our secondary aim was to determine the impact of the HFS which are intrinsically linked to specialist Geriatric care. RESULTS: Across 962 patients, over 5 years, the factors which were associated with adherence to HFS were female gender, increasing ASA grade and being nursed on an orthopaedic ward. Patients with increasing ASA were more likely to have met HFS 4-6 (Geriatrician review HFS4, bone health HFS5 & specialist falls assessment HFS6), less likely to have surgery within 48 h are more likely to develop a pressure ulcer. If the patient was not nursed on an orthopaedic ward all HFS were less likely to be met. At 30 days HFS 4-6 were associated with a statistically significant odds ratio (OR) of being alive, while at one year HFS 1 (admitted to an orthopaedic ward within 4 h), 5 and 6 were associated with a statistically significant OR of being alive. As increasing numbers of hip fracture standards were met patients were more likely to be alive at 30 days and one year. CONCLUSION: This study has identified that improved adherence to hip fracture standards are associated with improved mortality at 30 days and one year.

A growing challenge: The rise of femoral periprosthetic fractures - An 11-year observational study.

INTRODUCTION: The demand for joint arthroplasty has risen as our elderly population increases and ages. With this so to has the number of patients suffering periprosthetic fractures (PPF). The aim of our study was to quantify the burden of PPF and provide an up to date reference of the epidemiology of PPF in Ireland. We also sought to assess length of stay (LOS), resource utilisation and mortality associated with this cohort of patients. METHODS: An eleven-year retrospective observational study was conducted of a consecutive series of patients treated for a femoral PPF. Costs were obtained from activity based tariffs provided by the hospital inpatient enquiry system and mortality was confirmed using the national death events publication system. RESULTS: Over the 11-year study period 174 procedures for a femoral PPF were performed. Mean age of patients was 77.6 years (SD 11.1 years) with 44.7% male. Median ASA grade was 3 (range 1-4) and mean LOS was 19 days. There was a 700% increase in patients undergoing surgery for a PPF over the study period. The mean cost of care was €24,413 in 2017. Thirty-day mortality was 2.9% while one-year mortality was 12.4%. CONCLUSIONS: PPF occur in an elderly comorbid cohort of patients. Care of these patients now makes up a considerable part of the orthopaedic workload and consumes a significant portion of healthcare resources. Patients should be treated in tertiary referral centres with surgeons skilled in their management. Better access to rehabilitation is needed.

Where does Pelvic and Acetabular Fracture Treatment fit into the Newly Proposed Major Trauma Model in Ireland?

Aim To provide the most up to date reference of referral patterns for pelvis and acetabular (PA) fractures in Ireland and discuss where services should ideally be located. Methods A retrospective review was conducted of all referrals to the national referral centre for PA fractures in Ireland for 2016 and 2017. Results Over the two-year study period 456 referrals were made. Mean age of patients was 53 years, 62.9% were male. Management was conservative in 60.7%, operative in 38.2% while 1.1% died prior to transfer. Nearly half of fractures (47.8%) were due to falls with 38.6% due to road trauma. Referrals from the proposed central trauma network accounted for 76.1% of referrals. Median length of stay was 7 days. Average cost of operative treatment was €11,774. Conclusions PA trauma is associated with significant morbidity and costs to both patients and society. Consideration needs to be given to where best to place PA services to ensure the highest quality care in this cohort of patients

Osteochondral lesions of the ankle: The current evidence supporting scaffold-based techniques and biological adjuncts.

BACKGROUND: Talar osteochondral lesions are more common than has been previously recognized. Optimal treatment remains unclear and the subject of much debate in the literature. Although reparative techniques such as microfracture have produced initial good results and remain the gold standard in the management of these lesions, the literature is deficient in long-term data. Recently, techniques focused on enhancing the local biological environment have been developed which have demonstrated promising outcomes. METHODS: We reviewed the available evidence concerning scaffold-based techniques and biological adjuncts in the management of talar osteochondral lesions published in the English language on PubMed. RESULTS: An update is provided on the current evidence concerning the role of biological adjuncts in the management of osteochondral lesions of the talus. CONCLUSIONS: There has been an explosion of interest among the orthopaedic community in the role of biologics in the management of complex talar osteochondral lesions. A number of exciting new techniques have been developed which show promise. Robust randomized control trials are required to identify the optimal surgical strategy.

Key Service Improvements After the Introduction of an Integrated Orthogeriatric Service.

INTRODUCTION: Models of orthogeriatric care have been shown to improve functional outcomes for patients after hip fractures and can improve compliance with best practice guidelines for hip fracture care. METHODS: We evaluated improvements to key performance indicators in hip fracture care after implementation of a formal orthogeriatric service. Compliance with Irish Hip Fracture standards of care was reviewed, and additional outcomes such as length of stay, access to rehabilitation, and discharge destination were evaluated. RESULTS: Improvements were observed in all of the hip fracture standards of care. Mean length of stay decreased from 19 to 15.5 days (mean difference 3.5 days; P < .05). A higher proportion of patients were admitted to rehabilitation (16.7% vs 7.9%, P < .05), and this happened in a timelier fashion (17.8 vs 24.8 days, P < .05). We found that less patients required convalescence post-hip fracture. DISCUSSION: A standardized approach to integrated post-hip fracture care with orthogeriatrics has improved standards of care for patients. CONCLUSION: Introduction of orthogeriatric services has resulted in meaningful improvements in clinical outcomes for older people with hip fractures.

Tumour necrosis factor-alpha (TNF-alpha) increases nuclear factor kappaB (NFkappaB) activity in and interleukin-8 (IL-8) release from bovine mammary epithelial cells.

Epithelia play important immunological roles at a variety of mucosal sites. We examined NFkappaB activity in control and TNF-alpha treated bovine mammary epithelial monolayers (BME-UV cells). A region of the bovine IL-8 (bIL-8) promoter was sequenced and a putative kappaB consensus sequence was identified bioinformatically. We used this sequence to analyse nuclear extracts for IL-8 specific NFkappaB activity. As a surrogate marker of NFkappaB activation, we investigated IL-8 release in two models. Firstly in BME-UV monolayers, IL-8 release in the presence of pro- and anti-inflammatory agents was determined by enzyme-linked immunosorbent assay (ELISA). Secondly, we measured IL-8 secretion from a novel model of intact mucosal sheets of bovine teat sinus. IL-8 release into bathing solutions was assessed following treatment with pro- and anti-inflammatory agents. TNF-alpha enhanced NFkappaB activity in bovine mammary epithelial monolayers. p65 NFkappaB homodimer was identified in both control and TNF-alpha treated cells. Novel sequencing of the bovine IL-8 promoter identified a putative kappaB consensus sequence, which specifically bound TNF-alpha inducible p50/p65 heterodimer. TNF-alpha induced primarily serosal IL-8 release in the cell culture model. Pre-treatment with anti-TNF or dexamethasone inhibited TNF-alpha induced IL-8 release. High dose interleukin-1beta (IL-1beta) induced IL-8 release, however significantly less potently than TNF-alpha. Bovine mammary mucosal tissue released high basal levels of IL-8 which were unaffected by TNF-alpha or IL-1beta but inhibited by both dexamethasone and anti-TNF. These data support a role for TNF-alpha in activation of NFkappaB and release of IL-8 from bovine mammary epithelial cells.

Neuroendocrine regulation of the hypothalamic pituitary adrenal axis by the nurr1/nur77 subfamily of nuclear receptors.

The present study was designed to examine the role of the nurr1/nur77 subfamily of nuclear receptor transcription factors in the regulation of the hypothalamic/pituitary/adrenal axis at the neuroendocrine level. We demonstrate that this nuclear receptor subfamily can regulate the expression of the CRF and POMC genes by interacting with a specific cis-acting sequence in their proximal promoter regions. To examine the physiological significance of this response, we have focused on the POMC gene. We provide evidence that nurr1 and nur77 are rapidly induced by CRF in primary pituitary cells and that this induction is mimicked by forskolin in an anterior pituitary cell line. Further, we demonstrate that both nurr1- and forskolin-dependent induction of a POMC-chloramphenicol acetyltransferase reporter gene are inhibited by mutation of the nurr1-binding site within the POMC promoter and that this site alone can confer cAMP responsiveness to a heterologous promoter. Finally, we provide evidence that the nurr1/nur77 response sequence is pivotal to both nurr1/nur77-dependent positive regulation and glucocorticoid receptor-dependent negative regulation of the POMC gene. These data strongly support the conclusion that the nurr1/nur77 subfamily plays an important coordinate neuroendocrine-regulatory role at all levels of the hypothalamic/pituitary/adrenal axis.

Differential regulation of transcription by the NURR1/NUR77 subfamily of nuclear transcription factors.

NURR1 is an orphan member of the nuclear receptor superfamily of transcription factors that shares close sequence homology to the orphan nuclear receptor and immediate early gene product NUR77(NGF1 beta). The physiological role of NURR1 has not been established in mammalian cells. However, the observation that NURR1 and NUR77 interact with at least one common enhancer element (AAAAGGTCA), together with their partly overlapping but differential expression patterns in mammalian tissues, suggests that these proteins may have both shared and independent transcription regulatory functions. To identify potential target genes that may be regulated by NURR1, we analyzed its DNA binding properties to potential cis-acting enhancer elements. Using point mutagenesis of the AAAAGGTCA motif, we have identified three additional sequences that bind specifically to both NURR1 and NUR77, one of which serves as a functional enhancer element. Comparative analysis of the transcription regulatory properties of NURR1 and NUR77 indicates that the proteins can display opposing transregulatory activities that are influenced by the specific cis-acting sequences to which they bind. Our results indicate that the transcriptional responses of specific target genes to the NURR1/NUR77 subfamily may be differentially regulated by the relative cellular levels of NURR1 and NUR77 and influenced by the specific enhancer sequences that mediate their activity. Finally, we have identified several potential target genes of neuronal and neuroendocrine origin whose promoters contain this element.

The role of the hypothalamic-pituitary-adrenal axis in rheumatoid arthritis.

It has become clear that there is a bidirectional communication between the neuroendocrine and the immune system and that both systems influence each other and interact under physiological conditions and in response to inflammatory stimuli. The hypothalamic-pituitary axis plays an important role in regulating and controlling immune responses and dysfunction of the axis has been implicated in the pathogenesis of rheumatoid arthritis (RA). Corticotrophin-releasing hormone (CRH), one of the main hormones of the axis, is also released extra-hypothalamically, peripherally at the site of inflammation and may modulate inflammatory responses locally. In this chapter we will discuss the role of the hypothalamic-pituitary-adrenal (HPA) axis and peripheral CRH, its influences on immune function and what is known about the possible pathogenetic role of the HPA axis and peripheral CRH in RA.

Suppression of schedule-induced drinking and food-reinforced bar pressing by tail-pinch is not reversed by naloxone.

In Experiment 1 eleven food-deprived rats were tested in a schedule-induced drinking paradigm under both tail-pinch and non-tail-pinch conditions. Tail-pinch produced a strong suppression of schedule-induced drinking, licking, licks per milliliter, bar presses, and number of reinforcers received during 30-min test sessions. Experiment 2 showed that the narcotic antagonist naloxone (2 and 4 mg/kg) did not reverse the tail-pinch suppression of schedule-induced drinking and food-reinforced bar pressing. Experiment 3 demonstrated that the suppression of schedule-induced drinking by tail-pinch could not be attributed to a suppression of drinking behavior in general, as tail-pinch had no effect on deprivation-induced drinking. The failure of naloxone to reverse this blockade suggests that endogenous opiate systems do not play a very important role in the suppression of schedule-induced polydipsia by tail-pinch. It was suggested that the combination of both the schedule-induction paradigm and the tail-pinch procedure increased arousal levels to such a high level that all behaviors were suppressed.

Acute-phase serum amyloid A production by rheumatoid arthritis synovial tissue.

Acute-phase serum amyloid A (A-SAA) is a major component of the acute-phase response. A sustained acute-phase response in rheumatoid arthritis (RA) is associated with increased joint damage. A-SAA mRNA expression was confirmed in all samples obtained from patients with RA, but not in normal synovium. A-SAA mRNA expression was also demonstrated in cultured RA synoviocytes. A-SAA protein was identified in the supernatants of primary synoviocyte cultures, and its expression colocalized with sites of macrophage accumulation and with some vascular endothelial cells. It is concluded that A-SAA is produced by inflamed RA synovial tissue. The known association between the acute-phase response and progressive joint damage may be the direct result of synovial A-SAA-induced effects on cartilage degradation.

Involvement of the nuclear orphan receptor NURR1 in the regulation of corticotropin-releasing hormone expression and actions in human inflammatory arthritis.

OBJECTIVE: To examine the regulation and mode of action of peripheral corticotropin-releasing hormone (CRH) in human inflammatory arthritis. METHODS: CRH messenger RNA (mRNA) levels were measured in normal and inflamed synovial tissue and in primary synoviocytes prior to and following cytokine stimulation. Primary synoviocytes were transiently transfected with CRH promoter/reporter constructs, and promoter activity in response to cytokines was assessed. Immunohistochemical staining established CRH receptor expression, and Northern blot analysis confirmed that the nuclear transcription factors NUR77 and NURR1 contributed to synovial CRH receptor-mediated signaling. Primary synoviocytes were treated with pro- and antiinflammatory mediators, and the time course of NURR1 and NUR77 modulation was examined. Nuclear extracts were analyzed by electrophoretic mobility shift assay to determine NURR1 binding to the CRH promoter/enhancer. RESULTS: CRH mRNA was up-regulated in the synovial tissue in rheumatoid arthritis (RA), psoriatic arthritis (PsA), and sarcoid arthritis, but not in normal synovium. Inflammatory cytokines, such as interleukin-1beta and tumor necrosis factor alpha, enhanced the transcriptional activity of the human CRH promoter and increased levels of CRH mRNA in primary synoviocytes. Synovial CRH functioned in a paracrine manner to induce NURR1 and NUR77. NURR1 was abundantly expressed in the inflammatory cells of both RA and PsA synovium. NURR1 and NUR77 were differentially regulated, and NURR1 was the major cytokine-regulated member of the NURR subfamily as well as the mediator of cytokine- and CRH-dependent inflammatory responses in synovium. Furthermore, glucocorticoids dramatically suppressed cytokine- and CRH-induced synovial NURR1 mRNA. CONCLUSION: These data demonstrate the involvement of the transcription factor NURR1 in the regulation of CRH expression and activity in human inflammatory arthritis.

Corticotropin-releasing hormone signaling in synovial tissue from patients with early inflammatory arthritis is mediated by the type 1 alpha corticotropin-releasing hormone receptor.

OBJECTIVE: Elevated levels of corticotropin-releasing hormone (CRH) are produced locally in inflamed human synovial tissue, and previous observations indicate a role for CRH in the pathogenesis of inflammatory joint disease. To further elucidate the biologic role of CRH at peripheral sites, we examined the expression of known CRH receptor subtypes in inflamed human synovium and compared the expression patterns in normal synovium. METHODS: Immunohistochemical analysis was used to confirm enhanced expression of specific CRH receptor subtypes in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) synovium. Immunofluorescence double-labeling was used to further characterize CRH receptor-expressing cells. Reverse transcriptase-polymerase chain reaction analysis was performed to examine CRH receptor subtype messenger RNA (mRNA) expression in RA, PsA, and normal synovial tissue. In addition, CRH receptor expression was examined in isolated synovial endothelial cells and synoviocytes. RESULTS: Selective up-regulation of CRH receptors in inflamed synovial tissue indicated that CRH functions locally, in an autocrine/paracrine receptor-mediated manner. Immunoreactive CRH receptor type 1 (CRH-R1) was expressed abundantly on vascular endothelial cells and discrete perivascular cell populations, identified as mast cells. In all samples of inflamed synovium studied, CRH-R1alpha mRNA was detected; however, we were unable to identify CRH-R1beta or any CRH-R2 isoforms in samples from the same cohort of, patients. CRH receptor subtype expression in separated synovial cell populations revealed a pattern of staining similar to that seen in vivo. In contrast, neither CRH receptor subtype was expressed in normal synovial tissue. CONCLUSION: Our findings suggest that CRH signaling, via CRH-R1alpha, may play a role in both the vascular changes and the pathologic mechanisms associated with joint inflammation in human arthritis.

Society for Public Health Education: survey of membership.

The Society for Public Health Education, Inc. (SOPHE), through the Research and Evaluation Committee (REC) of the Tennessee chapter has surveyed its membership to determine characteristics of members, members' opinions of the organization and the benefits derived, usefulness of SOPHE publications, and the most important health education issues and goals. Survey results provide an employment profile of the membership, and indicate the membership benefits which are most valued; they also suggest that the organization's goals and its activities be expanded in scope to include, in addition to other areas, greater attention to health education practice, to planning legislation, to funding, and to cooperation with the American Public Health Association in the general promotion of health education. REC presents recommendations based on these findings.