Nutrition environments in early childhood education: do they align with best practice?

OBJECTIVE: To assess the comprehensiveness (scope of nutrition guidance) and strength (clarity of written language) of centre-based nutrition policies (CBNP) within early childhood education (ECE) centres. To also consider the applicability of an existing CBNP assessment tool and policy alignment with best practice food provision and feeding practices. DESIGN: Cross-sectional online study to assess written ECE CNBP using the Wellness Child Care Assessment Tool. SETTING: Licenced ECE centres in the state of Victoria, Australia. PARTICIPANTS: ECE centres (operating at least 8 h per d, 48 weeks per annum), stratified by location (rural and metropolitan), centre management type (profit and not-for-profit) and socio-economic area (low, middle, high). RESULTS: Included individual CBNP (n 118), predominantly from metropolitan centres (56 %) and low-medium socio-economic areas (78 %). Policies had low overall Wellness Child Care Assessment Tool scores, particularly strength scores which were low across all four domains (i.e. nutrition education, nutrition standards, health promotion and communication/evaluation). The nutrition standards domain had the lowest strength score. The communication/evaluation domain had the lowest comprehensiveness score. Content analysis indicated low scores may relate to the Wellness Child Care Assessment Tool applicability for the Australian context due to differences in best practice guidance. CONCLUSION: Despite the presence of written nutrition policies in ECE centres, many showed weak language and lacked comprehensiveness and strength. This may relate to poor implementation of best practice food provision or feeding practices. Low scores, however, may partly stem from using an assessment tool that is not country-specific. The redevelopment of country-specific tools to assess ECE CNBP may be warranted.

Clinical, pathologic, and molecular features of amphicrine prostate cancer.

BACKGROUND: Amphicrine prostate carcinoma (AMPC) is a poorly defined subset of prostate cancer in which cells co-express luminal prostate epithelial and neuroendocrine markers. The optimal treatment strategy is unknown. We sought to further characterize the clinical, histomorphologic, and molecular characteristics of AMPC and to identify areas of potential future treatment investigations. METHODS: We retrospectively identified 17 cases of AMPC at a single institution, defined as synaptophysin expression in >70% of cells and co-expression of androgen receptor (AR) signaling markers (either AR, PSA, or NKX3.1) in >50% of cells. Clinical and histologic features of AMPC cases as well as response to treatment and clinical outcomes were described. RESULTS: Five AMPC cases arose de novo in the absence of prior systemic treatment and behaved distinctly from cases that were treatment-emergent. In these de novo cases, despite expression of neuroendocrine markers, prognosis appeared more favorable than high-grade neuroendocrine carcinoma, with two (40%) patients with de novo metastatic disease, universal response to androgen deprivation therapy, and no deaths at a median follow-up of 12.3 months. Treatment-emergent AMPC arose a median of 41.1 months after androgen deprivation therapy initiation and was associated with poor response to therapy. CONCLUSIONS: We show that amphicrine prostate cancer is a unique entity and differs in clinical and molecular features from high-grade neuroendocrine carcinomas of the prostate. Our study highlights the need to recognize AMPC as a unique molecularly defined subgroup of prostate cancer.

Mismatch repair deficiency and clinical implications in prostate cancer.

Despite recent therapeutic advances, castration-resistant prostate cancer (CRPC) remains a lethal disease and novel therapies are needed. Precision oncology provides an avenue for developing effective tailored approaches for treating malignancies based on a tumor's molecular profile. Indeed, the presence of mismatch repair deficiency (MMRd) has proven to be an important predictive biomarker for response to immune checkpoint blockade across multiple tumor types, including prostate cancer, and represents a major precision oncology success story. The mismatch repair (MMR) system is integral to maintaining genomic fidelity during cellular replication. Cancers with deficiencies in this system accumulate high numbers of mutations and express many neoantigens that may be recognized by the immune system. The checkpoint inhibitor pembrolizumab has recently been approved for all cancers that are MMR deficient, and several retrospective series have specifically shown that pembrolizumab is effective in MMRd prostate cancer. Although the prevalence of MMRd in CRPC is low (approximately 3%-5% of cases), this is an important subset of men that require a unique therapeutic approach. This review will focus on MMRd in prostate cancer, highlighting the clinical implications, role of immunotherapy, and areas of future research.

Gender bias in autoimmunity is influenced by microbiota.

Gender bias and the role of sex hormones in autoimmune diseases are well established. In specific pathogen-free nonobese diabetic (NOD) mice, females have 1.3-4.4 times higher incidence of type 1 diabetes (T1D). Germ-free (GF) mice lost the gender bias (female-to-male ratio 1.1-1.2). Gut microbiota differed in males and females, a trend reversed by male castration, confirming that androgens influence gut microbiota. Colonization of GF NOD mice with defined microbiota revealed that some, but not all, lineages overrepresented in male mice supported a gender bias in T1D. Although protection of males did not correlate with blood androgen concentration, hormone-supported expansion of selected microbial lineages may work as a positive-feedback mechanism contributing to the sexual dimorphism of autoimmune diseases. Gene-expression analysis suggested pathways involved in protection of males from T1D by microbiota. Our results favor a two-signal model of gender bias, in which hormones and microbes together trigger protective pathways.

Targeting backdoor androgen synthesis through AKR1C3 inhibition: A presurgical hormonal ablative neoadjuvant trial in high-risk localized prostate cancer.

BACKGROUND: Localized prostate cancers (PCs) may resist neoadjuvant androgen receptor (AR)-targeted therapies as a result of persistent intraprostatic androgens arising through upregulation of steroidogenic enzymes. Therefore, we sought to evaluate clinical effects of neoadjuvant indomethacin (Indo), which inhibits the steroidogenic enzyme AKR1C3, in addition to combinatorial anti-androgen blockade, in men with high-risk PC undergoing radical prostatectomy (RP). METHODS: This was an open label, single-site, Phase II neoadjuvant trial in men with high to very-high-risk PC, as defined by NCCN criteria. Patients received 12 weeks of apalutamide (Apa), abiraterone acetate plus prednisone (AAP), degarelix, and Indo followed by RP. Primary objective was to determine the pathologic complete response (pCR) rate. Secondary objectives included minimal residual disease (MRD) rate, defined as residual cancer burden (RCB) ≤ 0.25cm3 (tumor volume multiplied by tumor cellularity) and elucidation of molecular features of resistance. RESULTS: Twenty patients were evaluable for the primary endpoint. Baseline median prostate-specific antigen (PSA) was 10.1 ng/ml, 4 (20%) patients had Gleason grade group (GG) 4 disease and 16 had GG 5 disease. At RP, 1 (5%) patient had pCR and 6 (30%) had MRD. Therapy was well tolerated. Over a median follow-up of 23.8 months, 1 of 7 (14%) men with pathologic response and 6 of 13 (46%) men without pathologic response had a PSA relapse. There was no association between prostate hormone levels or HSD3B1 genotype with pathologic response. CONCLUSIONS: In men with high-risk PC, pCR rates remained low even with combinatorial AR-directed therapy, although rates of MRD were higher. Ongoing follow-up is needed to validate clinical outcomes of men who achieve MRD.

Psychosocial Determinants of Readmission After Surgery.

BACKGROUND: Quality of life and psychosocial determinants of health, such as health literacy and social support, are associated with increased health care utilization and adverse outcomes in medical populations. However, the effect on surgical health care utilization is less understood. OBJECTIVE: We sought to examine the effect of patient-reported quality of life and psychosocial determinants of health on unplanned hospital readmissions in a surgical population. RESEARCH DESIGN: This is a prospective cohort study using patient interviews at the time of hospital discharge from a Veterans Affairs hospital. SUBJECTS: We include Veterans undergoing elective inpatient general, vascular, or thoracic surgery (August 1, 2015-June 30, 2017). MEASURES: We assessed unplanned readmission to any medical facility within 30 days of hospital discharge. RESULTS: A total of 736 patients completed the 30-day postoperative follow-up, and 16.3% experienced readmission. Lower patient-reported physical and mental health, inadequate health literacy, and discharge home with help after surgery or to a skilled nursing or rehabilitation facility were associated with an increased incidence of readmission. Classification regression identified the patient-reported Veterans Short Form 12 (SF12) Mental Component Score <31 as the most important psychosocial determinant of readmission after surgery. CONCLUSIONS: Mental health concerns, inadequate health literacy, and lower social support after hospital discharge are significant predictors of increased unplanned readmissions after major general, vascular, or thoracic surgery. These elements should be incorporated into routinely collected electronic health record data. Also, discharge plans should accommodate varying levels of health literacy and consider how the patient's mental health and social support needs will affect recovery.

Gender Differences in Faculty Rank and Subspecialty Choice among Academic Medical Oncologists.

Gender parity within academic oncology is important. We hypothesized that gender differences exist in subspecialty choice and academic rank among medical oncologists. We performed a cross-sectional study of adult medical oncologists at the top 15 cancer centers. Gender, rank, subspecialty (breast, thoracic, gastrointestinal, and genitourinary) and board certification year were recorded. 570 medical oncologists were identified (60% men; 40% women). More women practice breast oncology (OR 3.1, p < 0.001), but less practice genitourinary oncology (OR 0.37, p < 0.001). 22% of women were full professors vs 34% of men (OR 0.55, p = 0.001). Gender differences persist in academic adult medical oncology.

Timing and Cost of Wound Complications After Colorectal Resection.

BACKGROUND: More than 50% of postoperative wound complications occur after discharge. They are the most common postoperative complication and the most common reason for readmission after a surgical procedure. Little is known about the long-term costs of postdischarge wound complications after surgery. OBJECTIVE: We sought to understand the differences in costs and characteristics of wound complications identified after hospital discharge for patients undergoing colorectal surgery in comparison with in-hospital complications. DESIGN: This is an observational cohort study using Veterans Health Administration Surgical Quality Improvement Program data. SETTING: This study was conducted at a Veterans Affairs medical center. SETTING: Patients undergoing colorectal resection between October 1, 2007 and September 30, 2014. MAIN OUTCOME MEASURES: The primary outcomes measured were adjusted costs of care at discharge, 30 days, and 90 days after surgery. RESULTS: Of 20,146 procedures, 11.9% had a wound complication within 30 days of surgery (49.2% index-hospital, 50.8% postdischarge). In comparison with patients with index-hospital complications, patients with postdischarge complications had fewer superficial infections (65.0% vs 72.2%, p < 0.01), more organ/space surgical site infections (14.3% vs 10.1%, p < 0.01), and higher rates of diabetes (29.1% vs 25.0%, p = 0.02), and they were to have had a laparoscopic approach for their surgery (24.7% vs 18.2%, p < 0.01). The average cost including surgery at 30 days was $37,315 (SD = $29,319). Compared with index-hospital wound complications, postdischarge wound complications were $9500 (22%, p < 0.001) less expensive at 30 days and $9736 (15%, p < 0.001) less expensive at 90 days. Patients with an index-hospital wound complication were 40% less likely to require readmission at 30 days, but their readmissions were $12,518 more expensive than readmissions among patients with a newly identified postdischarge wound complication (p < 0.001). LIMITATIONS: This study was limited to patient characteristics and costs accrued only within the Veterans Affairs system. CONCLUSIONS: Patients with postdischarge wound complications have lower 30- and 90-day postoperative costs than those with wound complications identified during their index hospitalization and almost half were managed as an outpatient. TIEMPO Y COSTO DE LAS COMPLICACIONES LA HERIDA DESPUS DE LA RESECCIN COLORRECTAL: ANTECEDENTES:Más del 50% de complicaciones postoperatorias de la herida ocurren después del alta. Es la complicación postoperatoria más común y el motivo más frecuente de reingreso después del procedimiento quirúrgico. Poco se sabe sobre los costos a largo plazo de las complicaciones de la herida después del alta quirúrgica.OBJETIVO:Intentar en comprender las diferencias en los costos y las características de las complicaciones de la herida, identificadas después del alta hospitalaria, en pacientes sometidos a cirugía colorrectal, en comparación con las complicaciones intrahospitalarias.DISEÑO:Estudio de cohorte observacional utilizando datos del Programa de Mejora de la Calidad Quirúrgica de la Administración de Salud de Veteranos.ENTORNO CLÍNICO:Administración de Veteranos.PACIENTES:Pacientes sometidos a resección colorrectal entre el 1/10/2007 y el 30/9/2014.PRINCIPALES MEDIDAS DE VALORACIÓN:Costos de atención ajustados al alta, 30 días y 90 días después de la cirugía.RESULTADOS:De 20146 procedimientos, el 11,9% tuvo una complicación de la herida dentro de los 30 días de la cirugía. (49,2% índice hospitalario, 50,8% después del alta). En comparación con los pacientes, del índice de complicaciones hospitalarias, los pacientes con complicaciones posteriores al alta, tuvieron menos infecciones superficiales (65,0% frente a 72,2%, p <0,01), más infecciones de órganos/espacios quirúrgicos (14,3% frente a 10,1%, p <0,01), tasas más altas de diabetes (29,1% versus 25,0%, p = 0,02), y deberían de haber tenido un abordaje laparoscópico para su cirugía (24,7% versus 18,2%, p <0,01). El costo promedio, incluida la cirugía a los 30 días, fue de $ 37,315 (desviación estándar = $ 29,319). En comparación con el índice de complicaciones de las herida hospitalaria, las complicaciones de la herida después del alta fueron $ 9,500 (22%, p <0,001) menor costo a los 30 días y $ 9,736 (15%, p<0,001) y menor costo a los 90 días. Los pacientes con índice de complicación de la herida hospitalaria, tenían un 40% menos de probabilidades de requerir reingreso a los 30 días, pero sus reingresos eran $ 12,518 más costosos que los reingresos entre los pacientes presentando complicación de la herida recién identificada después del alta (p <0,001).LIMITACIONES:Limitado a las características del paciente y los costos acumulados solo dentro del sistema VA.CONCLUSIONES:Pacientes con complicaciones de la herida post alta, tienen menores costos postoperatorios a los 30 y 90 días, que aquellos con complicaciones de la herida identificadas durante su índice de hospitalización y aproximadamente la mitad fueron tratados de forma ambulatoria.

Local and distant tumor dormancy during early stage breast cancer are associated with the predominance of infiltrating T effector subsets.

BACKGROUND: Although breast cancer mortality is a result of distant recurrences associated with the establishment of tumor dormancy, current clinical practice guidelines recommend a wait and watch approach for tumor recurrences. This is because of our limited understanding of tumor dormancy and insufficient evidence in support of immunological control of tumor dormancy. METHODS: We used FVBN202 transgenic mice expressing rat neu oncogene in the mammary glands, and their parental FVB strain lacking neu expression. These models allowed the detection of tumor dormancy at distant sites using the rat neu protein as a tumor marker. We also used Ki67 for the detection of the indolent and quiescent types of tumor dormancy. Multicolor flow cytometry was used to detect dormant tumor cells and T cell subsets. Co-culture studies were performed to determine the role of T cells in preventing regrowth of dormant cells. RESULTS: We demonstrated that dormant tumor cells were present at the site of primary breast cancer and at distant sites in the lungs and in the liver very early in the course of early stage breast cancer when no distant metastasis was evident. Dormant tumor cells were characterized as neu expressing Ki67- and Ki67low fractions associated with the induction of local immune responses predominated by CD4+ and CD8+ T effector cell subsets. The presence of neu-autoreactive T cells from FVBN202 mice only prevented regrowth of dormant cells. On the other hand, presence of neu-alloreactive anti-tumor T cells in FVB mice prior to tumor challenge resulted in the protection of mice from the dissemination of dormant tumor cells to distant organs. CONCLUSION: Our results suggest that immunotherapeutic targeting of semi-allogeneic mutant neoantigens during tumor dormancy might prevent distant recurrence of the disease.

The DNA methyltransferase inhibitor, guadecitabine, targets tumor-induced myelopoiesis and recovers T cell activity to slow tumor growth in combination with adoptive immunotherapy in a mouse model of breast cancer.

BACKGROUND: Myeloid derived suppressor cells (MDSCs) present a significant obstacle to cancer immunotherapy because they dampen anti-tumor cytotoxic T cell responses. Previous groups, including our own, have reported on the myelo-depletive effects of certain chemotherapy agents. We have shown previously that decitabine increased tumor cell Class I and tumor antigen expression, increased ability of tumor cells to stimulate T lymphocytes, depleted tumor-induced MDSC in vivo and augmented immunotherapy of a murine mammary carcinoma. RESULTS: In this study, we expand upon this observation by testing a next-generation DNA methyltransferase inhibitor (DNMTi), guadecitabine, which has increased stability in the circulation. Using the 4 T1 murine mammary carcinoma model, in BALB/cJ female mice, we found that guadecitabine significantly reduces tumor burden in a T cell-dependent manner by preventing excessive myeloid proliferation and systemic accumulation of MDSC. The remaining MDSC were shifted to an antigen-presenting phenotype. Building upon our previous publication, we show that guadecitabine enhances the therapeutic effect of adoptively transferred antigen-experienced lymphocytes to diminish tumor growth and improve overall survival. We also show guadecitabine's versatility with similar tumor reduction and augmentation of immunotherapy in the C57BL/6 J E0771 murine breast cancer model. CONCLUSIONS: Guadecitabine depleted and altered MDSC, inhibited growth of two different murine mammary carcinomas in vivo, and augmented immunotherapeutic efficacy. Based on these findings, we believe the immune-modulatory effects of guadecitabine can help rescue anti-tumor immune response and contribute to the overall effectiveness of current cancer immunotherapies.

Dynamics of a human-modified tropical peat swamp forest revealed by repeat lidar surveys.

Tropical peat swamp forests (PSFs) are globally important carbon stores under threat. In Southeast Asia, 35% of peatlands had been drained and converted to plantations by 2010, and much of the remaining forest had been logged, contributing significantly to global carbon emissions. Yet, tropical forests have the capacity to regain biomass quickly and forests on drained peatlands may grow faster in response to soil aeration, so the net effect of humans on forest biomass remains poorly understood. In this study, two lidar surveys (made in 2011 and 2014) are compared to map forest biomass dynamics across 96 km2 of PSF in Kalimantan, Indonesia. The peatland is now legally protected for conservation, but large expanses were logged under concessions until 1998 and illegal logging continues in accessible portions. It was hypothesized that historically logged areas would be recovering biomass while recently logged areas would be losing biomass. We found that historically logged forests were recovering biomass near old canals and railways used by the concessions. Lidar detected substantial illegal logging activity-579 km of logging canals were located beneath the canopy. Some patches close to these canals have been logged in the 2011-2104 period (i.e. substantial biomass loss) but, on aggregate, these illegally logged regions were also recovering. Unexpectedly, rapid growth was also observed in intact forest that had not been logged and was over a kilometre from the nearest known canal, perhaps in response to greater aeration of surface peat. Comparing these results with flux measurements taken at other nearby sites, we find that carbon sequestration in above-ground biomass may have offset roughly half the carbon efflux from peat oxidation. This study demonstrates the power of repeat lidar survey to map fine-scale forest dynamics in remote areas, revealing previously unrecognized impacts of anthropogenic global change.

The redemption and contamination research form: exploring relations with narrative identity, personality traits, response styles, and life satisfaction.

Narrative identity is typically assessed by collecting participants' autobiographical scenes and then coding these stories for themes including redemption (negative beginning, positive ending) and contamination (positive beginning, negative ending). Complimenting this approach, we introduce a self-report measure capturing the degree to which individuals explicitly view their lives and social worlds in redemptive and contaminated ways - the Redemption and Contamination Research Form (RCRF). In Studies 1 and 2, participants completed the RCRF and a measure of life satisfaction. In Study 2, participants also provided three autobiographical scenes, later coded for redemption and contamination. Across studies, our novel self-rated redemptive mindset variable corresponded positively with life satisfaction and, in Study 2, the redemption present in scenes. Relations remained significant after considering several covariates (e.g., traits, response styles). These results, which illustrate the utility of self-rated redemptive mindsets, carry implications for the multi-method assessment of constructs indigenous to narrative identity.

Pilot implementation of elder-friendly care practices in acute care setting: a mixed methods study.

BACKGROUND: Frail older patients are at risk of experiencing a decline in physical and cognitive function unrelated to the reason for admission. The Elder-Friendly Care (EFC) program was designed to improve the care, experiences, and outcomes of frail older adults. The project supported 8 Early Adoption Sites (EAS) in a large Canadian healthcare organization by providing multiple strategies, educational opportunities, and resources. The purpose of this study was to assess the usefulness of EFC educational materials and resources, staff practice changes and perceptions in pilot sites, and readiness for scale and spread. METHODS: The study was conducted from May 2017 to June 2018 using a mixed-methods approach incorporating the Kirkpatrick Model of Training/Evaluation. A total of 76 Direct Care Staff participated in the staff survey, which assessed their awareness of, satisfaction with, and utilization of EFC principles, resources, and practices. Additionally, 12 interviews were conducted with staff who were directly involved in site implementation of EFC. RESULTS: Most survey participants were aware (86%, n = 63) of the EFC program, and 85% (n = 41) indicated they or their site/unit had implemented EFC. Out of these 41 participants, the most common practice changes identified were: incorporating alternatives to restraint (81%, n = 33), decreased use of pharmacological restraint (78%, n = 32), and patient and family care planning (76%, n = 31). Participants that attended all 3 EFC Learning Workshops (LWs) were significantly more likely to recommend the EFC Toolkit to others (87% versus 40%; χ2 = 8.82, p < 0.01) compared to participants attending less than 3 EFC LWs. Interview participants indicated that the program was well structured and flexible as sites/units could adopt changes that suited their individual sites, needs, contexts, and challenges. CONCLUSIONS: The educational materials and resources used for the EFC project are useful and appreciated by the Direct Care Staff. Further, participants perceive the EFC intervention as effective in creating positive practice change and useful in reducing hospital-related complications for older patients. Future implementation will investigate the impact of EFC on system-level outcomes in acute care.

Bioenergetic status modulates motor neuron vulnerability and pathogenesis in a zebrafish model of spinal muscular atrophy.

Degeneration and loss of lower motor neurons is the major pathological hallmark of spinal muscular atrophy (SMA), resulting from low levels of ubiquitously-expressed survival motor neuron (SMN) protein. One remarkable, yet unresolved, feature of SMA is that not all motor neurons are equally affected, with some populations displaying a robust resistance to the disease. Here, we demonstrate that selective vulnerability of distinct motor neuron pools arises from fundamental modifications to their basal molecular profiles. Comparative gene expression profiling of motor neurons innervating the extensor digitorum longus (disease-resistant), gastrocnemius (intermediate vulnerability), and tibialis anterior (vulnerable) muscles in mice revealed that disease susceptibility correlates strongly with a modified bioenergetic profile. Targeting of identified bioenergetic pathways by enhancing mitochondrial biogenesis rescued motor axon defects in SMA zebrafish. Moreover, targeting of a single bioenergetic protein, phosphoglycerate kinase 1 (Pgk1), was found to modulate motor neuron vulnerability in vivo. Knockdown of pgk1 alone was sufficient to partially mimic the SMA phenotype in wild-type zebrafish. Conversely, Pgk1 overexpression, or treatment with terazosin (an FDA-approved small molecule that binds and activates Pgk1), rescued motor axon phenotypes in SMA zebrafish. We conclude that global bioenergetics pathways can be therapeutically manipulated to ameliorate SMA motor neuron phenotypes in vivo.

Implementation of a multifaceted nurse-led intervention to reduce indwelling urinary catheter use in four Australian hospitals: A pre- and postintervention study.

AIMS AND OBJECTIVES: This study aimed to reduce indwelling urinary catheter (IDC) use and duration through implementation of a multifaceted "bundled" care intervention. BACKGROUND: Indwelling urinary catheters present a risk for patients through the potential development of catheter-associated urinary tract infection (CAUTI), with duration of IDC a key risk factor. Catheter-associated urinary tract infection is considered preventable yet accounts for over a third of all hospital-acquired infections. The most effective CAUTI reduction strategy is to avoid IDC use where ever possible and to remove the IDC as early as appropriate. DESIGN: A cluster-controlled pre- and poststudy at a facility level with a phased intervention implementation approach. METHODS: A multifaceted intervention involving a "No CAUTI" catheter care bundle was implemented, in 4 acute-care hospitals, 2 in metropolitan and 2 in rural locations, in New South Wales, Australia. Indwelling urinary catheter point prevalence and duration data were collected at the bedside on 1,630 adult inpatients at preintervention and 1,677 and 1,551 at 4 and 9 months postintervention. This study is presented in line with the StaRI checklist (see Appendix S1). RESULTS: A nonsignificant trend towards reduction in IDC prevalence was identified, from 12% preintervention to 10% of all inpatients at 4 and 9 months. Variability in preintervention IDC prevalence existed across hospitals (8%-16%). Variability in reduction was evident across hospitals at 4 months (between -2% and 4%) and 9 months (between 0%-8%). Hospitals with higher preintervention prevalence showed larger decreases, up to 50% when preintervention prevalence was 16%. Indwelling urinary catheter duration increased as more of the short-term IDC placements were avoided. CONCLUSIONS: Implementation of a multifaceted intervention resulted in reduced IDC use in four acute-care hospitals in Australia. This result was not statistically significant but did reflect a positive trend of reduction. There was a significant reduction in short-term IDC use at 9 months postintervention. RELEVANCE TO CLINICAL PRACTICE: Clinical nurse leaders can effectively implement change strategies that influence patient outcomes. Implementation of the evidence-based "No CAUTI" bundle increased awareness of appropriate indications and provided nurses with the tools to inform decision-making related to insertion and removal of IDCs in acute inpatient settings. Working in partnership with inpatients and the multidisciplinary team is essential in minimising acute-care IDC use.

Recommendations for determining HPV status in patients with oropharyngeal cancers under TNM8 guidelines: a two-tier approach.

BACKGROUND: TNM8 staging for oropharyngeal squamous cell carcinomas (OPSCC) surrogates p16 immunohistochemistry for HPV testing. Patients with p16+ OPSCC may lack HPV aetiology. Here, we evaluate the suitability of TNM8 staging for guiding prognosis in such patients. METHODS: HPV status was ascertained using p16 immunohistochemistry and high-risk HPV RNA and DNA in situ hybridisation. Survival by stage in a cohort of OPSCC patients was evaluated using TNM7/TNM8 staging. Survival of p16+/HPV- patients was compared to p16 status. RESULTS: TNM8 staging was found to improve on TNM7 (log rank p = 0·0190 for TNM8 compared with p = 0·0530 for TNM7) in p16+ patients. Patients who tested p16+ but were HPV- (n = 20) had significantly reduced five-year survival (33%) compared to p16+ patients (77%) but not p16- patients (35%). Cancer stage was reduced in 95% of p16+/HPV- patients despite having a mortality rate twice (HR 2.66 [95% CI: 1.37-5.15]) that of p16+/HPV+ patients under new TNM8 staging criteria. CONCLUSION: Given the significantly poorer survival of p16+/HPV- OPSCCs, these data provide compelling evidence for use of an HPV-specific test for staging classification. This has particular relevance in light of potential treatment de-escalation that could expose these patients to inappropriately reduced treatment intensity as treatment algorithms evolve.

Sideroflexin 3 is an α-synuclein-dependent mitochondrial protein that regulates synaptic morphology.

α-Synuclein plays a central role in Parkinson's disease, where it contributes to the vulnerability of synapses to degeneration. However, the downstream mechanisms through which α-synuclein controls synaptic stability and degeneration are not fully understood. Here, comparative proteomics on synapses isolated from α-synuclein-/- mouse brain identified mitochondrial proteins as primary targets of α-synuclein, revealing 37 mitochondrial proteins not previously linked to α-synuclein or neurodegeneration pathways. Of these, sideroflexin 3 (SFXN3) was found to be a mitochondrial protein localized to the inner mitochondrial membrane. Loss of SFXN3 did not disturb mitochondrial electron transport chain function in mouse synapses, suggesting that its function in mitochondria is likely to be independent of canonical bioenergetic pathways. In contrast, experimental manipulation of SFXN3 levels disrupted synaptic morphology at the Drosophila neuromuscular junction. These results provide novel insights into α-synuclein-dependent pathways, highlighting an important influence on mitochondrial proteins at the synapse, including SFXN3. We also identify SFXN3 as a new mitochondrial protein capable of regulating synaptic morphology in vivo.

Development and first validation of a patient-reported experience measure in chronic obstructive pulmonary disease (PREM-C9).

We developed a chronic obstructive pulmonary disease (COPD) patient-reported experience measure (PREM-C9). 174 patients with COPD (86 [49%] with a confirmed diagnosis and 88 [51%] with a self-reported diagnosis of COPD) completed a 38-item list, COPD Assessment Test (CAT) and Hospital Anxiety and Depression Scale (HADS). Hierarchical and Rasch analysis produced a 9-item list (PREM-C9). It demonstrated fit to the Rasch model (χ² p=0.33) and correlated moderately with CAT (r=0.42), HAD-anxiety (r=0.30) and HAD-depression (r=0.41) (p<0.05). A substudy confirmed its ability to detect change prepulmonary and postpulmonary rehabilitation. The PREM-C9 is a simple, valid measure of experience of patients living with COPD, validated in this study population with mild to very severe disease; it may be a useful measure in research and clinical audits.

What growth sounds like: Redemption, self-improvement, and eudaimonic growth across different life narratives in relation to well-being.

OBJECTIVE: We disentangled three growth-relevant concepts (redemption, self-improvement, and eudaimonic growth) in personal narratives of high, low, and turning points and tested their relations to well-being. METHOD: In two studies, participants (Study 1 n = 111, Study 2 n = 206; overall ages 17-83, 56% women, 75% white) wrote narratives of high points, low points, and turning points. Researchers coded each narrative for redemption sequences (i.e., affectively valenced changes in life from bad to good), self-improvement sequences (i.e., affectively valenced changes in oneself for the better), and themes of eudaimonic growth (i.e., values or motives for cultivating meaningful activities or relationships, helping others, or wisdom). Participants also self-reported well-being. RESULTS: Redemption sequences in low points predicted higher well-being but in high points predicted lower well-being. Self-improvement sequences and growth themes each predicted higher well-being in each life event (and interacted in high points). Growth themes consistently mediated predicted relations between both redemption and self-improvement sequences and well-being. Findings held when controlling for global narrative affect, self-reported growth motivation, and big-five traits. CONCLUSIONS: Thematic motives for eudaimonic growth were more closely tied to well-being than were affective evaluations of either changes from bad to good (redemption) or one's becoming better (self-improvement).

Variations in indwelling urinary catheter use in four Australian acute care hospitals.

AIMS AND OBJECTIVES: To identify the point prevalence of indwelling urinary catheters (IDCs) in adult inpatients in acute care hospitals, and to describe the indications for IDC insertion based on patient age, gender, specialty and hospital. BACKGROUND: Catheter-associated urinary tract infections (CAUTIs) are preventable healthcare-associated infections. IDC duration is the strongest predictor of CAUTI, and little is known about characteristics of patients who receive an IDC. DESIGN: Two single-day point prevalence surveys collected baseline patient data as part of a larger pre-post control-intervention study. METHODS: Surveys were conducted at four acute care hospitals in NSW, Australia, for all adult patients. Data collection included IDC presence, insertion details and urine culture collection. Point prevalence data were linked with electronically extracted patient demographic data. This study is presented in line with STROBE checklist (See Supplementary File 1). RESULT: Data from 1,630 patients were analysed, with 196 patients (12%) identified as having an IDC on the survey dates. IDC prevalence rates were higher in males (13%) than in females (11%). Critical care had the highest rate of patients with IDCs (42%). Urine cultures were collected in 70 patients with an IDC (43%). CONCLUSIONS: Findings indicated similar rates of IDC use in males and females, and there was no significant difference in age between patients with or without an IDC. However, indication for IDC varied by patient age and gender. High rates of urine culture collection may represent routine collection. RELEVANCE TO CLINICAL PRACTICE: IDC use is found across genders, all age groups and specialties. Nurses should be aware that any of their patients may have an IDC and be particularly aware of certain indications based on patient age and gender. Routine urine culture collection is not advised, and instead, nurses should be guided by clinical decision-making tools.