Enhancing paediatric palliative care: A rapid review to inform continued development of care for children with life-limiting conditions.

AIM: Following the establishment of paediatric palliative care services over recent decades, this study sought to identify information to inform future policy and practice. METHODS: A rapid review using thematic synthesis was conducted to synthesise existing information about improving paediatric palliative care. Information was extracted in relation to key areas for investment and change: quality, access, advance care planning, skills, research, collaboration and community awareness. RESULTS: A total of 2228 literature sources were screened, with 369 included. Synthesised information identified clear ways to improve quality of care, access to care, advance care planning, and research and data collection. The synthesis identified knowledge gaps in understanding how to improve skills in paediatric palliative care, collaboration across Australian jurisdictions and community awareness. CONCLUSIONS: The findings of this review bring together information from a vast range of sources to provide action-oriented information to target investment and change in paediatric palliative care over the coming decades.

Predictive factors for carboplatin hypersensitivity reactions in gynecologic cancers: Effect of BRCA status.

INTRODUCTION: Carboplatin hypersensitivity reactions have been reported to occur in up to 16% of patients with gynecologic cancers. Several predisposing factors have been suggested including presence of BRCA1/2 mutation, however, contribution of these mutations to reaction development has not been extensively studied. The purpose of this study was to determine if there is an association between BRCA1/2 mutation status and the development of carboplatin hypersensitivity reactions.Methodology: Eligible patients were women aged 18 years or older with a diagnosis of ovarian, fallopian tube, uterine, endometrial, or primary peritoneal cancer who attempted to receive at least one dose of carboplatin. The primary outcome was the effect of BRCA1/2 status on the development of carboplatin hypersensitivity reactions with regard to: reaction frequency, timing, and severity. Secondary outcomes included identification of additional risk factors that may help identify predisposition to carboplatin hypersensitivity reaction. RESULTS: A total of 44 patients were included in this study. Five patients (38%) in the reaction group and 4 patients (31%) in the no reaction group had a documented mutation in one or both BRCA genes (p = 1.00). No significant differences were found in terms of reaction severity or symptoms, and timing of reaction after dose administration. Incidence of thyroid disorder was significantly higher among patients who experienced a hypersensitivity reaction (1 (4%) vs 10 (45%); p = 0.004). CONCLUSION: BRCA mutation status was not associated with an increased risk of carboplatin hypersensitivity in our patient population. Further investigation into thyroid dysfunction as a risk factor for reaction development is warranted.

Pharmacological management of cardiac cachexia: a review of potential therapy options.

Cardiac cachexia is a syndrome of progressive skeletal muscle and fat loss affecting a significant number of congestive heart failure patients. With the potential detrimental effects of cardiac muscle wasting, greater attention is needed to understanding the prevention and treatment of the condition. Potential therapeutic approaches are aimed at the various mechanisms for the pathogenesis of cardiac cachexia including neurohormonal abnormalities, immune activation and inflammation, metabolic hormonal imbalance, and gastrointestinal abnormalities. While there are no current guideline-recommended treatments for the prevention of cardiac cachexia, targeting an imbalance of the renin-angiotensin-aldosterone system with beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers appears to be the most well-studied therapeutic approaches. Treatment of inflammation with monoclonal antibodies, hormonal imbalance with testosterone, and nutritional deficiencies with appetite stimulants has also been suggested. Proposed therapies may prove beneficial in heart failure patients; however, further studies specifically focusing on the cardiac component of cachexia are needed before definitive therapy options can be established.

Quantitative Differences in the Urinary Proteome of Siblings Discordant for Type 1 Diabetes Include Lysosomal Enzymes.

Individuals with type 1 diabetes (T1D) often have higher than normal blood glucose levels, causing advanced glycation end product formation and inflammation and increasing the risk of vascular complications years or decades later. To examine the urinary proteome in juveniles with T1D for signatures indicative of inflammatory consequences of hyperglycemia, we profiled the proteome of 40 T1D patients with an average of 6.3 years after disease onset and normal or elevated HbA1C levels, in comparison with a cohort of 41 healthy siblings. Using shotgun proteomics, 1036 proteins were identified, on average, per experiment, and 50 proteins showed significant abundance differences using a Wilcoxon signed-rank test (FDR q-value ≤ 0.05). Thirteen lysosomal proteins were increased in abundance in the T1D versus control cohort. Fifteen proteins with functional roles in vascular permeability and adhesion were quantitatively changed, including CD166 antigen and angiotensin-converting enzyme 2. α-N-Acetyl-galactosaminidase and α-fucosidase 2, two differentially abundant lysosomal enzymes, were detected in western blots with often elevated quantities in the T1D versus control cohort. Increased release of proteins derived from lysosomes and vascular epithelium into urine may result from hyperglycemia-associated inflammation in the kidney vasculature.

Similar Neutrophil-Driven Inflammatory and Antibacterial Responses in Elderly Patients with Symptomatic and Asymptomatic Bacteriuria.

Differential diagnosis of asymptomatic bacteriuria (ASB) and urinary tract infection (UTI) is based on the presence of diverse symptoms, including fever (≥38.5°C), rigors, malaise, lethargy, flank pain, hematuria, suprapubic discomfort, dysuria, and urgent or frequent urination. There is consensus in the medical community that ASB warrants antibiotic treatment only for patients undergoing urological procedures that lead to mucosal bleeding, catheterized individuals whose ASB persists for more than 48 h after catheter removal, and pregnant women. Pyuria is associated with UTI and implicates host immune responses via release of antibacterial effectors and phagocytosis of pathogens by neutrophils. Such responses are not sufficiently described for ASB. Metaproteomic methods were used here to identify the pathogens and evaluate molecular evidence of distinct immune responses in cases of ASB compared to UTI in elderly patients who were hospitalized upon injury. Neutrophil-driven inflammatory responses to invading bacteria were not discernible in most patients diagnosed with ASB compared to those with UTI. In contrast, proteomic urine analysis for trauma patients with no evidence of bacteriuria, including those who suffered mucosal injuries via urethral catheterization, rarely showed evidence of neutrophil infiltration. The same enzymes contributing to the synthesis of leukotrienes LTB4 and LTC4, mediators of inflammation and pain, were found in the UTI and ASB cohorts. These data support the notion that the pathways mediating inflammation and pain in most elderly patients with ASB are not quantitatively different from those seen in most elderly patients with UTI and warrant larger clinical studies to assess whether a common antibiotic treatment strategy for elderly ASB and UTI patients is justified.

Practice pathways, education, and regulation influencing nurse practitioners' decision to provide primary care: a rapid scoping review.

BACKGROUND/OBJECTIVE: Initially established to improve access to healthcare, particularly for primary care, the full potential of the nurse practitioner role is yet to be realised in most countries. Despite this, most countries are working to meet an ageing population's increasing healthcare needs and reduce healthcare costs and access disparities. Achieving these outcomes requires reform at multiple levels, including nurse practitioner practice pathways, education and regulation, and identifying the barriers and facilitators to optimising their primary care role. METHODS: A rapid scoping review of nurse practitioner practice pathways, education and regulation inclusive of: (1) a systematic search of Medline and CINAHL for peer-reviewed English language articles, including opinion pieces published between January 2015 and February 2022; and (2) a web-based search of nurse practitioner program entry requirements of International Nurse Regulator Collaborative country members with a protected nurse practitioner title and prescribing rights, plus the Netherlands. The individually summarised search data was integrated and synthesised using Popay's narrative approach. RESULTS: Emerging evidence from the included nurse practitioner courses (n = 86) and articles (n = 79) suggests nurse practitioners working in primary care provide safe, effective care and improve healthcare efficiencies. However, different regulatory and educational models are required if the primary care nurse practitioner is to meet growing demand. CONCLUSIONS: International variations in entry criteria, curriculum, and regulation shape the global profile of the nurse practitioner primary care workforce and their practice setting. For countries to grow their primary care nurse practitioner workforce to meet unmet needs, different entry requirements, program content and accredited post-registration transitional programs must be urgently considered.

Family meetings in paediatric palliative care: an integrative review.

OBJECTIVE: Our aim was to synthesise the available evidence surrounding the structure, processes and outcomes of family meetings in the paediatric palliative care literature. METHODS: We undertook an integrative literature review informed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The protocol was registered with PROSPERO (CRD42019138938). Electronic databases were systematically search using keywords and hand searching of reference articles and grey literature was also completed. RESULTS: Ten empirical studies and five theoretical articles were included in the synthesis. Empirical studies provided more information about meeting structure, whereas theoretical articles more frequently described a desired process for planning and undertaking meetings. No articles identified how the success of a meeting was defined or made recommendations for doing so. Despite reports that family meetings are commonly occurring, few articles described outcomes from either the family or clinician perspectives. CONCLUSIONS: Family meetings are essential communication strategies commonly used in paediatric palliative care, yet there is little guidance about how meetings should be organised and conducted, who should participate and when they should occur. The limited data available on the outcomes of family meetings suggest improvements are required to meet the needs of families. We present a framework that synthesises the available evidence. The framework offers an overview of the elements to consider when planning for and undertaking family meetings in paediatric palliative care and may be useful for both clinicians and researchers.

Nitroxoline: a broad-spectrum biofilm-eradicating agent against pathogenic bacteria.

Bacterial biofilms are surface-attached communities of slow-growing or non-replicating bacteria tolerant to conventional antibiotic therapies. Although biofilms are known to occur in ca. 80% of all bacterial infections, no therapeutic agent has been developed to eradicate bacteria housed within biofilms. We have discovered that nitroxoline, an antibacterial agent used to treat urinary tract infections, displays broad-spectrum biofilm-eradicating activities against major human pathogens, including drug-resistant Staphylococcus aureus and Acinetobacter baumannii strains. In this study, the effectiveness of nitroxoline to eradicate biofilms was determined using an in vitro [minimum biofilm eradication concentration (MBEC) = 46.9 µM against A. baumannii] and ex vivo porcine skin model (2-3 log reduction in viable biofilm cells). Nitroxoline was also found to eradicate methicillin-resistant S. aureus (MRSA) persister cells in non-biofilm (stationary) cultures, whereas vancomycin and daptomycin were found to be inactive. These findings could lead to effective, nitroxoline-based therapies for biofilm-associated infections.

Structure-Activity Relationships of a Diverse Class of Halogenated Phenazines That Targets Persistent, Antibiotic-Tolerant Bacterial Biofilms and Mycobacterium tuberculosis.

Persistent bacteria, including persister cells within surface-attached biofilms and slow-growing pathogens lead to chronic infections that are tolerant to antibiotics. Here, we describe the structure-activity relationships of a series of halogenated phenazines (HP) inspired by 2-bromo-1-hydroxyphenazine 1. Using multiple synthetic pathways, we probed diverse substitutions of the HP scaffold in the 2-, 4-, 7-, and 8-positions, providing critical information regarding their antibacterial and bacterial eradication profiles. Halogenated phenazine 14 proved to be the most potent biofilm-eradicating agent (≥99.9% persister cell killing) against MRSA (MBEC < 10 µM), MRSE (MBEC = 2.35 µM), and VRE (MBEC = 0.20 µM) biofilms while 11 and 12 demonstrated excellent antibacterial activity against M. tuberculosis (MIC = 3.13 µM). Unlike antimicrobial peptide mimics that eradicate biofilms through the general lysing of membranes, HPs do not lyse red blood cells. HPs are promising agents that effectively target persistent bacteria while demonstrating negligible toxicity against mammalian cells.