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Introduction: This study examined the distribution of histopathological disease severity amongst a cohort of patients treated for clinically suspected ocular surface squamous neoplasia and evaluated the relationship between various patient and clinical factors and the severity of pathological grade as well as treatment outcomes. Methods: A retrospective cohort study of demographic and clinicopathological factors of 150 patients clinically diagnosed with suspected ocular surface squamous neoplasia who underwent excision of lesion with histopathological diagnosis. Results: The study included 125 cases; the mean age at diagnosis was 64 years (SD = 11.26). 74% of cases were histologically confirmed as ocular surface squamous neoplasia. Pathological distribution was conjunctival intraepithelial neoplasia I (13.6%), conjunctival intraepithelial neoplasia II (16.8%), conjunctival intraepithelial neoplasia III (21.6%), carcinoma in situ (21.6%), and squamous cell carcinoma (2.4%). Lesion appearance was leukoplakic (18%), gelatinous (15%), dysplastic (11%), vascular (6%), papilliform (2%), nodular (2%). Lesion location was nasal (43%), temporal (42%), and superior or inferior (14%). Recurrence occurred in 7 cases (5.6%). A significant association was found between presence of leukoplakia and pathological grade (p = 0.05). Conclusions: Ocular surface squamous neoplasia is most frequently diagnosed in conjunctival intraepithelial neoplasia III and carcinoma in situ stages, and treatment outcomes are usually favourable.
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PURPOSE: Pediatric burn injuries are a global clinical issue causing significant morbidity. Early adjunctive negative pressure wound therapy improves re-epithelialization rates in children with burns, yet adoption in acute burn care is inconsistent. This investigation aimed to determine barriers to the implementation of adjunctive negative pressure wound therapy for the acute management of pediatric burns and co-design targeted implementation strategies. METHODS: A sequential mixed methods design was used explore barriers to adjunctive negative pressure wound therapy implementation in acute pediatric burn care. An online questionnaire was disseminated to healthcare professionals within four major Australian pediatric hospitals, each with a dedicated burns service. Barriers were coded according to the Consolidated Framework for Implementation Research (CFIR). Semi-structured interviews with senior clinicians tailored implementation strategies to local contexts. A stakeholder consensus meeting consolidated implementation strategies and local processes. RESULTS: Sixty-three healthcare professionals participated in the questionnaire, and semi-structured interviews involved nine senior burn clinicians. We identified eight implementation barriers across all five CFIR domains then co-designed targeted strategies to address identified barriers. Barriers included lack of available resources, limited access to knowledge and information, individual stage of change, patient needs and resources, limited knowledge and beliefs about the intervention, lack of external policies, intervention complexity, and poor implementation planning. CONCLUSION: Multiple contextual factors affect negative pressure wound therapy uptake in acute pediatric burn settings. Results will inform a multi-state stepped-wedge cluster randomized controlled trial. Additional resources, education, training, updated policies, and guidelines are required for successful implementation. It is anticipated that adjunctive negative pressure wound therapy, in conjunction with tailored implementation strategies, will enhance adoption and sustainability. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry: ACTRN12622000166774. Registered 1 February 2022.
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Quemaduras , Terapia de Presión Negativa para Heridas , Humanos , Quemaduras/terapia , Australia , Masculino , Niño , Femenino , Encuestas y Cuestionarios , Unidades de Quemados/organización & administraciónRESUMEN
This manuscript serves as the starting point for in-depth research of multicomponent, statistical, methacrylate-based copolymers that potentially mimic the behavior of proteins in aqueous solutions. These synthetic macromolecules are composed of specially chosen comonomers: methacrylic acid (MAA), oligoethylene glycol methyl ether methacrylate (OEGMA475), 2-(dimethylamino)ethyl methacrylate (DMAEMA) and benzyl methacrylate (BzMA). Monomer choice was based on factors such as the chemical nature of pendant functional groups, the polyelectrolyte/polyampholyte and amphiphilic character and the overall hydrophobic-hydrophilic balance (HLB) of the obtained quaterpolymers. Their synthesis was achieved via a one-pot reversible addition fragmentation chain transfer (RAFT) polymerization in two distinct compositions and molecular architectures, linear and hyperbranched, respectively, in order to explore the effects of macromolecular topology. The resulting statistical quaterpolymers were characterized via 1H-NMR and ATR-FTIR spectroscopies. Their behavior in aqueous solutions was studied by dynamic (DLS) and electrophoretic light scattering (ELS) and fluorescence spectroscopy (FS), producing vital information concerning their self-assembly and the structure of the formed aggregates. The physicochemical studies were extended by tuning parameters such as the solution pH and ionic strength. Finally, the quaterpolymer behavior in FBS/PBS solutions was investigated to test their colloid stability and biocompatibility in an in vivo-mimicking, biological fluid environment.
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BACKGROUND: Paediatric donor site wounds are often complicated by dyspigmentation following a split-thickness skin graft. These easily identifiable scars can potentially never return to normal pigmentation. A Regenerative Epidermal Suspension (RES) has been shown to improve pigmentation in patients with vitiligo, and in adult patients following a burn injury. Very little is known regarding the efficacy of RES for the management of donor site scars in children. METHODS AND ANALYSIS: A pilot randomised controlled trial of 40 children allocated to two groups (RES or no RES) standard dressing applied to donor site wounds will be conducted. All children aged 16 years or younger requiring a split thickness skin graft will be screened for eligibility. The primary outcome is donor site scar pigmentation 12 months after skin grafting. Secondary outcomes include re-epithelialisation time, pain, itch, dressing application ease, treatment satisfaction, scar thickness and health-related quality of life. Commencing 7 days after the skin graft, the dressing will be changed every 3-5 days until the donor site is ≥ 95% re-epithelialised. Data will be collected at each dressing change and 3, 6 and 12 months post skin graft. ETHICS AND DISSEMINATION: Ethics approval was confirmed on 11 February 2019 by the study site Human Research Ethics Committee (HREC) (HREC/18/QCHQ/45807). Study findings will be published in peer-reviewed journals and presented at national and international conferences. This study was prospectively registered on the Australian New Zealand Clinical Trials Registry (available at https://anzctr.org.au/ACTRN12620000227998.aspx). TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry [Available at https://anzctr.org.au/ACTRN12620000227998.aspx].
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Quemaduras , Cicatriz , Adulto , Niño , Humanos , Cicatriz/etiología , Cicatrización de Heridas , Trasplante de Piel/efectos adversos , Trasplante de Piel/métodos , Calidad de Vida , Proyectos Piloto , Australia , Vendajes , Quemaduras/cirugía , Quemaduras/complicaciones , Pigmentación , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Background: New non-pharmacological treatments for improving non-motor symptoms in Parkinson's disease (PD) are urgently needed. Previous light therapies for modifying sleep behaviour lacked standardised protocols and were not personalised for an individual patient chronotype. We aimed to assess the efficacy of a biologically-directed light therapy in PD that targets retinal inputs to the circadian system on sleep, as well as other non-motor and motor functions. Methods: In this randomised, double-blind, parallel-group, active-controlled trial at the Queensland University of Technology, Australia, participants with mild to moderate PD were computer randomised (1:1) to receive one of two light therapies that had the same photometric luminance and visual appearance to allow blinding of investigators and participants to the intervention. One of these biologically-directed lights matched natural daylight (Day Mel), which is known to stimulate melanopsin cells. The light therapy of the other treatment arm of the study, specifically supplemented the stimulation of retinal melanopsin cells (Enhanced Mel), targeting deficits to the circadian system. Both lights were administered 30 min per day over 4-weeks and personalised to an individual patient's chronotype, while monitoring environmental light exposure with actigraphy. Co-primary endpoints were a change from baseline in mean sleep macrostructure (polysomnography, PSG) and an endocrine biomarker of circadian phase (dim light melatonin secretion onset, DLMO) at weeks 4 and 6. Participants data were analysed using an intention to treat principle. All endpoints were evaluated by applying a mixed model analysis. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12621000077864. Findings: Between February 4, 2021 and August 8, 2022, 144 participants with PD were consecutively screened, 60 enrolled and randomly assigned to a light intervention. There was no significant difference in co-primary outcomes between randomised groups overall or at any individual timepoint during follow-up. The mean (95% CI) for PSG, N3% was 24.15 (19.82-28.48) for Day Mel (n = 23) and 19.34 (15.20-23.47) for the Enhanced Mel group (n = 25) in week 4 (p = 0.12); and 21.13 (16.99-25.28) for Day Mel (n = 26) and 18.48 (14.34-22.62) for the Enhanced Mel group (n = 25) in week 6, (p = 0.37). The mean (95% CI) DLMO (decimal time) was 19.82 (19.20-20.44) for Day Mel (n = 22) and 19.44 (18.85-20.04) for the Enhanced Mel group (n = 24) in week 4 (p = 0.38); and 19.90 (19.27-20.53) for Day Mel (n = 23) and 19.04 (18.44-19.64) for the Enhanced Mel group (n = 25) in week 6 (p = 0.05). However, both the controlled daylight (Day Mel) and the enhanced melanopsin (Enhanced Mel) interventions demonstrated significant improvement in primary PSG sleep macrostructure. The restorative deep sleep phase (PSG, N3) significantly improved at week 6 in both groups [model-based mean difference to baseline (95% CI): -3.87 (-6.91 to -0.83), p = 0.04]. There was a phase-advance in DLMO in both groups which did not reach statistical significance between groups at any time-point. There were no safety concerns or severe adverse events related to the intervention. Interpretation: Both the controlled daylight and melanopsin booster light showed efficacy in improving measures of restorative deep sleep in people with mild to moderate PD. That there was no significant difference between the two intervention groups may be due to the early disease stage. The findings suggest that controlled indoor daylight that is personalised to the individuals' chronotype could be effective for improving sleep in early to moderate PD, and further studies evaluating controlled daylight interventions are now required utilising this standardised approach, including in advanced PD. Funding: The Michael J Fox Foundation for Parkinson's Research, Shake IT Up Australia, National Health and Medical Research Council, and Australian Research Council.
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INTRODUCTION: The benefits of exercise in reducing treatment-related morbidity and improving quality of life following a primary diagnosis of cancer have been well documented and have led to exercise being recommended by oncology societies for all people with a cancer diagnosis. However, these recommendations are derived from research typically involving cohorts with more common cancers and relatively good prognosis, such as breast and prostate. Evidence from these cancers may not apply to women with recurrent ovarian cancer. Therefore, the primary objective of this trial is to evaluate the feasibility and safety of a home-based, telephone-delivered exercise intervention for women undergoing chemotherapy for recurrent ovarian cancer. METHODS AND ANALYSIS: The Exercise During Chemotherapy for Recurrent Ovarian Cancer (ECHO-R) trial is a single-arm, phase II, pre/postintervention trial of a 6-month, telephone-delivered exercise intervention (consistent with recommended exercise oncology prescription). The target sample size is 80 women who are currently undergoing (or are scheduled to receive) chemotherapy for recurrent ovarian cancer. Recruitment is through participating hospital sites in Queensland, Australia, or via self-referral. The exercise intervention comprises 12 telephone sessions over a 6-month period delivered by trial-trained exercise professionals and supplemented (where feasible) by five sessions face to face. Exercise prescription is individualised and works towards an overall goal of achieving a weekly target of 150 min of moderate-intensity, mixed-mode exercise. Assessments via self-administered survey and physical fitness and function tests occur at baseline and then at 6 and 9 months postbaseline. Data to inform feasibility and safety are recorded as case notes by the exercise professional during each session. ETHICS AND DISSEMINATION: Ethics approval for the ECHO-R trial was granted by the Metro North Human Research Ethics Committee (HREC/2020/QRBW/67223) on 6 November 2020. Findings from the trial are planned to be disseminated via peer-reviewed publications and both national and international exercise and oncology conferences. TRIAL REGISTRATION NUMBER: ACTRN12621000042842.
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Neoplasias Ováricas , Calidad de Vida , Femenino , Humanos , Masculino , Carcinoma Epitelial de Ovario , Terapia por Ejercicio/efectos adversos , Estudios de Factibilidad , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/etiología , TeléfonoRESUMEN
Bacterial urinary tract infections (UTIs) are both common and exhibit high recurrence rates in women. UTI healthcare costs are increasing due to the rise of multidrug-resistant (MDR) bacteria, necessitating alternative approaches for infection control. Here, we directly observed host adaptive immune responses in acute UTI. We employed a mouse model in which wild-type C57BL/6J mice were transurethrally inoculated with a clinically relevant MDR UTI strain of uropathogenic Escherichia coli (UPEC). Firstly, we noted that rag1-/- C57BL/6J mice harbored larger bacterial burdens than wild-type counterparts, consistent with a role for adaptive immunity in UTI control. Consistent with this, UTI triggered in the bladders of wild-type mice early increases of myeloid cells, including CD11chi conventional dendritic cells, suggesting possible involvement of these professional antigen-presenting cells. Importantly, germinal center B cell responses developed by 4 weeks post-infection in bladder-draining lymph nodes of wild-type mice and, although modest in magnitude and transient in nature, could not be boosted with a second UTI. Thus, our data reveal for the first time in a mouse model that UPEC UTI induces local B cell immune responses in bladder-draining lymph nodes, which could potentially serve to control infection.
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Infecciones por Escherichia coli , Infecciones Urinarias , Sistema Urinario , Escherichia coli Uropatógena , Humanos , Femenino , Ratones , Animales , Vejiga Urinaria/microbiología , Infecciones por Escherichia coli/microbiología , Ratones Endogámicos C57BL , Infecciones Urinarias/microbiología , Centro Germinal , Sistema Urinario/microbiologíaRESUMEN
In this work, we report the synthesis of novel triple hydrophilic statistical terpolymers consisting of three different methacrylate monomers with varying degrees of responsivity to solution conditions. Terpolymers of the type poly(di(ethylene glycol) methyl ether methacrylate-co-2-(dimethylamino)ethylmethacrylate-co-oligoethylene glycol methyl ether methacrylate), P(DEGMA-co-DMAEMA-co-OEGMA), and of different compositions, were prepared by using the RAFT methodology. Their molecular characterization was carried out using size exclusion chromatography (SEC) and spectroscopic techniques, including 1H-NMR and ATR-FTIR. Studies in dilute aqueous media by dynamic and electrophoretic light scattering (DLS and ELS) show their potential responsiveness regarding changes in temperature, pH, and kosmotropic salt concentration. Finally, the change in hydrophilic/hydrophobic balance of the formed terpolymer nanoparticles during heating and cooling was studied using fluorescence spectroscopy (FS) in conjunction with pyrene giving additional information on the responsiveness and internal structure of the self-assembled nanoaggregates.
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INTRODUCTION: Epidemiological evidence supports an association between higher levels of physical activity and improved cancer survival. Trial evidence is now needed to demonstrate the effect of exercise in a clinical setting. The Exercise during CHemotherapy for Ovarian cancer (ECHO) trial is a phase III, randomised controlled trial, designed to determine the effect of exercise on progression-free survival and physical well-being for patients receiving first-line chemotherapy for ovarian cancer. METHODS AND ANALYSIS: Participants (target sample size: n=500) include women with newly diagnosed primary ovarian cancer, scheduled to receive first-line chemotherapy. Consenting participants are randomly allocated (1:1) to either the exercise intervention (plus usual care) or usual care alone, with stratification for recruitment site, age, stage of disease and chemotherapy delivery (neoadjuvant vs adjuvant). The exercise intervention involves individualised exercise prescription with a weekly target of 150 minutes of moderate-intensity, mixed-mode exercise (equivalent to 450 metabolic equivalent minutes per week), delivered for the duration of first-line chemotherapy through weekly telephone sessions with a trial-trained exercise professional. The primary outcomes are progression-free survival and physical well-being. Secondary outcomes include overall survival, physical function, body composition, quality of life, fatigue, sleep, lymphoedema, anxiety, depression, chemotherapy completion rate, chemotherapy-related adverse events, physical activity levels and healthcare usage. ETHICS AND DISSEMINATION: Ethics approval for the ECHO trial (2019/ETH08923) was granted by the Sydney Local Health District Ethics Review Committee (Royal Prince Alfred Zone) on 21 November 2014. Subsequent approvals were granted for an additional 11 sites across Queensland, New South Wales, Victoria and the Australian Capital Territory. Findings from the ECHO trial are planned to be disseminated via peer-reviewed publications and international exercise and oncology conferences. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trial Registry (ANZCTRN12614001311640; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=367123&isReview=true).
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Neoplasias Ováricas , Calidad de Vida , Humanos , Femenino , Australia , Ejercicio Físico , Neoplasias Ováricas/tratamiento farmacológico , Terapia por EjercicioRESUMEN
PURPOSE: The aim of this analysis was to compare the cost-consequences of a 12 week exercise intervention when delivered under high- versus low-level supervision conditions by an Exercise Professional (ExP) to women with breast cancer. METHODS: 60 women (50 ± 9 years) with stage II + breast cancer, who were insufficiently active, and reported ≥ 1 comorbidities or persistent treatment-related side-effects, were randomized to the high- or low-supervision group. The high-supervision group received 20 supervised sessions with an ExP over a 12 week period (reflecting a typical research model), whereas the low-supervision group received five sessions over the same period (replicating what is publicly funded within Australia). Health outcomes including health-related quality of life, and physical and psychosocial outcomes were assessed at baseline and post-intervention. To assess intervention consequences, composite effectiveness scores were created by calculating mean z-scores from raw data for all outcomes per participant. Total program costs were calculated including program development, staff training, program implementation, and equipment. RESULTS: 79.3% of the high- and 63.0% of the low-supervision group showed clinically relevant health improvements. Cost per improver was $1,814 for 23 improvers and $1,571 for 17 improvers in the high- and low-supervision groups, respectively. CONCLUSION: The SAFE exercise intervention, when delivered via high- or low-supervised conditions, represents good value with over 60% of women in both groups reporting health improvements. High-supervision levels resulted in a greater proportion of women experiencing health benefits, but future research will need to determine the longer term health impacts of these group differences.
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Neoplasias de la Mama , Humanos , Femenino , Calidad de Vida , Ejercicio Físico , Terapia por Ejercicio/métodos , Análisis Costo-BeneficioRESUMEN
BACKGROUND: Many nations require child-serving professionals to report known or suspected cases of significant child abuse and neglect to statutory child protection or safeguarding authorities. Considered globally, there are millions of professionals who fulfil these roles, and many more who will do so in future. Ensuring they are trained in reporting child abuse and neglect is a key priority for nations and organisations if efforts to address violence against children are to succeed. OBJECTIVES: To assess the effectiveness of training aimed at improving reporting of child abuse and neglect by professionals and to investigate possible components of effective training interventions. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, 18 other databases, and one trials register up to 4 June 2021. We also handsearched reference lists, selected journals, and websites, and circulated a request for studies to researchers via an email discussion list. SELECTION CRITERIA: All randomised controlled trials (RCTs), quasi-RCTs, and controlled before-and-after studies examining the effects of training interventions for qualified professionals (e.g. teachers, childcare professionals, doctors, nurses, and mental health professionals) to improve reporting of child abuse and neglect, compared with no training, waitlist control, or alternative training (not related to child abuse and neglect). DATA COLLECTION AND ANALYSIS: We used methodological procedures described in the Cochrane Handbook for Systematic Reviews of Interventions. We synthesised training effects in meta-analysis where possible and summarised findings for primary outcomes (number of reported cases of child abuse and neglect, quality of reported cases, adverse events) and secondary outcomes (knowledge, skills, and attitudes towards the reporting duty). We used the GRADE approach to rate the certainty of the evidence. MAIN RESULTS: We included 11 trials (1484 participants), using data from 9 of the 11 trials in quantitative synthesis. Trials took place in high-income countries, including the USA, Canada, and the Netherlands, with qualified professionals. In 8 of the 11 trials, interventions were delivered in face-to-face workshops or seminars, and in 3 trials interventions were delivered as self-paced e-learning modules. Interventions were developed by experts and delivered by specialist facilitators, content area experts, or interdisciplinary teams. Only 3 of the 11 included studies were conducted in the past 10 years. Primary outcomes Three studies measured the number of cases of child abuse and neglect via participants' self-report of actual cases reported, three months after training. The results of one study (42 participants) favoured the intervention over waitlist, but the evidence is very uncertain (standardised mean difference (SMD) 0.81, 95% confidence interval (CI) 0.18 to 1.43; very low-certainty evidence). Three studies measured the number of cases of child abuse and neglect via participants' responses to hypothetical case vignettes immediately after training. A meta-analysis of two studies (87 participants) favoured training over no training or waitlist for training, but the evidence is very uncertain (SMD 1.81, 95% CI 1.30 to 2.32; very low-certainty evidence). We identified no studies that measured the number of cases of child abuse and neglect via official records of reports made to child protection authorities, or adverse effects of training. Secondary outcomes Four studies measured professionals' knowledge of reporting duty, processes, and procedures postintervention. The results of one study (744 participants) may favour the intervention over waitlist for training (SMD 1.06, 95% CI 0.90 to 1.21; low-certainty evidence). Four studies measured professionals' knowledge of core concepts in all forms of child abuse and neglect postintervention. A meta-analysis of two studies (154 participants) favoured training over no training, but the evidence is very uncertain (SMD 0.68, 95% CI 0.35 to 1.01; very low-certainty evidence). Three studies measured professionals' knowledge of core concepts in child sexual abuse postintervention. A meta-analysis of these three studies (238 participants) favoured training over no training or waitlist for training, but the evidence is very uncertain (SMD 1.44, 95% CI 0.43 to 2.45; very low-certainty evidence). One study (25 participants) measured professionals' skill in distinguishing reportable and non-reportable cases postintervention. The results favoured the intervention over no training, but the evidence is very uncertain (SMD 0.94, 95% CI 0.11 to 1.77; very low-certainty evidence). Two studies measured professionals' attitudes towards the duty to report child abuse and neglect postintervention. The results of one study (741 participants) favoured the intervention over waitlist, but the evidence is very uncertain (SMD 0.61, 95% CI 0.47 to 0.76; very low-certainty evidence). AUTHORS' CONCLUSIONS: The studies included in this review suggest there may be evidence of improvements in training outcomes for professionals exposed to training compared with those who are not exposed. However, the evidence is very uncertain. We rated the certainty of evidence as low to very low, downgrading due to study design and reporting limitations. Our findings rest on a small number of largely older studies, confined to single professional groups. Whether similar effects would be seen for a wider range of professionals remains unknown. Considering the many professional groups with reporting duties, we strongly recommend further research to assess the effectiveness of training interventions, with a wider range of child-serving professionals. There is a need for larger trials that use appropriate methods for group allocation, and statistical methods to account for the delivery of training to professionals in workplace groups.
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Maltrato a los Niños , Notificación Obligatoria , Niño , Maltrato a los Niños/diagnóstico , Maltrato a los Niños/prevención & control , Familia , Personal de Salud , Humanos , Revisiones Sistemáticas como AsuntoRESUMEN
The aim of this comparative, effectiveness trial was to evaluate the safety, feasibility and effect of an exercise intervention delivered via low-level versus high-level supervision. The target population were women who were diagnosed with ≥stage II breast cancer, had ≥ one comorbidity and/or persistent treatment-related side-effects, and were insufficiently physically active. Sixty women (50 ± 9 years) were randomized to the low-supervision group (n = 30) or high-supervision group (n = 30). The low-supervision group participated in a 12-week, individually-tailored exercise intervention supported by five supervised sessions with an exercise professional. The high-supervision group participated in the same exercise intervention but received 20 supervised sessions across the 12-week period. The target weekly dosage of 600 metabolic equivalent minutes of exercise per week (MET-mins/wk) and the session content, such as safety and behaviour change topics, were standardized between the groups. The primary outcomes were intervention safety, defined as the number, type, and severity of exercise-related adverse events (e.g., musculoskeletal injury or exacerbated treatment-related side effects), and feasibility, which was defined as compliance to target exercise dosage. The effect of the intervention on quality of life, physical activity, self-efficacy, fitness, and strength was also assessed (pre- and post-intervention, and at 12-week follow-up). The intervention was safe, with no exercise-related adverse events of grade 3 or above in either group. Both groups reported high compliance to the target exercise dosage (median MET-mins/wk: High = 817; Low = 663), suggesting the exercise intervention was feasible, irrespective of supervision level. Improvements in quality of life, physical activity and fitness were observed post-intervention and maintained at follow-up for both groups (p < 0.05). Only the high-supervision group showed clinically-relevant improvements in strength and self-efficacy at post-intervention (p < 0.05). Individually-targeted exercise delivered under high- or low-levels of supervision is safe, feasible and beneficial for women with stage II+ breast cancer. Future research needs to assess whether the greater gains observed in the group who received higher supervision may contribute to longer term maintenance of physical activity levels and overall health benefits. Australian and New Zealand Clinical Trials Registry: ACTRN12616000547448.
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OBJECTIVE: To investigate consumer preference and willingness to pay for mobile teledermoscopy services in Australia. METHODS: Consumers who were taking part in a randomised controlled trial comparing mobile teledermoscopy and skin self-examination were asked to complete a survey which incorporated a discrete choice experiment (DCE) and a contingent valuation question. Responses were used to determine their willingness to pay for mobile teledermoscopy services in Australia and their overall service preferences. RESULTS: The 199 consumers who responded were 71% female and had a mean age of 42 years (range, 18-73). The DCE results showed that consumers prefer a trained medical professional to be involved in their skin cancer screening. Consumers were willing to pay AUD 41 to change from a general practitioner reviewing their lesions in-person to having a dermatologist reviewing the teledermoscopy images. Additionally, they were willing to pay for services that had shorter waiting times, that reduced the time away from their usual activities, and that have higher accuracy and lower likelihood of unnecessary excision of a skin lesion. When asked directly about their willingness to pay for a teledermoscopy service using a contingent valuation question, the majority (73%) of consumers selected the lowest two value brackets of AUD 1-20 or AUD 21-40. CONCLUSION: Consumers are willing to pay out of pocket to access services with attributes such as a dermatologist review, improved accuracy, and fewer excisions.
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Comportamiento del Consumidor , Telemedicina , Adulto , Australia , Dermoscopía/métodos , Femenino , Humanos , Masculino , Autoexamen/métodos , Telemedicina/métodosRESUMEN
PURPOSE: Perioperative hypothermia prevention requires regular, accurate, and consistent temperature monitoring. Zero-heat-flux (ZHF) thermometry offers a non-invasive, measurement method that can be applied across all surgical phases. The purpose of this study was to measure agreement between the zero-heat-flux device and esophageal monitoring, sensitivity, and specificity to detect hypothermia and patient acceptability amongst patients undergoing upper and lower limb orthopedic surgery. PATIENTS AND METHODS: This prospective, observational study utilized Bland-Altman analysis and Lin's concordance coefficient to measure agreement between devices, sensitivity and specificity to detect hypothermia and assessed patient acceptability amongst 30 patients between December 2018 and June 2019. RESULTS: Bias was observed between devices via Bland Altman, with bias dependent on actual temperature. The mean difference ranged from -0.16°C at 34.9°C (where the mean of ZHF was lower than the esophageal device) to 0.46°C at 37.25°C (where the mean of ZHF was higher than esophageal device), with 95% limits of agreement (max) upper LOA = 0.80 to 1.41, lower LOA = -1.12 to -0.50. Seventy-five percentage of zero-heat-flux measurements were within 0.5°C of esophageal readings. Patient acceptability was high; 96% (n=27) stated that the device was comfortable. CONCLUSION: ZHF device achieved lesser measurement accuracy with core (esophageal) temperature compared to earlier findings. Nonetheless, due to continuous capability, non-invasiveness and patient reported acceptability, the device warrants further evaluation. TITLE REGISTRATION: The study was registered at www.ANZCTR.org.au (reference: ACTRN12619000842167).
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Inhibition of the DiSulfide Bond (DSB) oxidative protein folding machinery, a major facilitator of virulence in Gram-negative bacteria, represents a promising antivirulence strategy. We previously developed small molecule inhibitors of DsbA from Escherichia coli K-12 (EcDsbA) and showed that they attenuate virulence of Gram-negative pathogens by directly inhibiting multiple diverse DsbA homologues. Here we tested the evolutionary robustness of DsbA inhibitors as antivirulence antimicrobials against Salmonella enterica serovar Typhimurium under pathophysiological conditions in vitro. We show that phenylthiophene DsbA inhibitors slow S. Typhimurium growth in minimal media, phenocopying S. Typhimurium isogenic dsbA null mutants. Through passaging experiments, we found that DsbA inhibitor resistance was not induced under conditions that rapidly induced resistance to ciprofloxacin, an antibiotic commonly used to treat Salmonella infections. Furthermore, no mutations were identified in the dsbA gene of inhibitor-treated S. Typhimurium, and S. Typhimurium virulence remained susceptible to DsbA inhibitors. Our work demonstrates that under in vitro pathophysiological conditions, DsbA inhibitors can have both antivirulence and antibiotic action. Importantly, our finding that DsbA inhibitors appear to be evolutionarily robust offers promise for their further development as next-generation antimicrobials against Gram-negative pathogens.
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OBJECTIVE: Physical activity following cancer diagnosis is associated with improved outcomes, including potential survival benefits, yet physical activity levels among common cancer types tend to decrease following diagnosis and remain low. Physical activity levels following diagnosis of less common cancers, such as ovarian cancer, are less known. The objectives of this study were to describe physical activity levels and to explore characteristics associated with physical activity levels in women with ovarian cancer from pre-diagnosis to 2 years post-diagnosis. METHODS: As part of a prospective longitudinal study, physical activity levels of women with ovarian cancer were assessed at multiple time points between pre-diagnosis and 2 years post-diagnosis. Physical activity levels and change in physical activity were described using metabolic equivalent task hours and minutes per week, and categorically (sedentary, insufficiently, or sufficiently active). Generalized Estimating Equations were used to explore whether participant characteristics were related to physical activity levels. RESULTS: A total of 110 women with ovarian cancer with a median age of 62 years (range 33-88) at diagnosis were included. 53-57% of the women were sufficiently active post-diagnosis, although average physical activity levels for the cohort were below recommended levels throughout the 2-year follow-up period (120-142.5min/week). A decrease or no change in post-diagnosis physical activity was reported by 44-60% of women compared with pre-diagnosis physical activity levels. Women diagnosed with stage IV disease, those earning a lower income, those receiving chemotherapy, and those currently smoking or working were more likely to report lower physical activity levels and had increased odds of being insufficiently active or sedentary. CONCLUSIONS: Interventions providing patients with appropriate physical activity advice and support for behavior change could potentially improve physical activity levels and health outcomes.
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Supervivientes de Cáncer/estadística & datos numéricos , Ejercicio Físico/fisiología , Neoplasias Ováricas/terapia , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Estudios Longitudinales , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
BACKGROUND: Skin self-examinations supplemented with mobile teledermoscopy might improve early detection of skin cancers compared with naked-eye skin self-examinations. We aimed to assess whether mobile teledermoscopy-enhanced skin self-examination can improve sensitivity and specificity of self-detection of skin cancers when compared with naked-eye skin self-examination. METHODS: This randomised, controlled trial was done in Brisbane (QLD, Australia). Eligible participants (aged ≥18 years) had at least two skin cancer risk factors as self-reported in the eligibility survey and had to own or have access to an iPhone compatible with a dermatoscope attachment (iPhone versions 5-8). Participants were randomly assigned (1:1), via a computer-generated randomisation procedure, to the intervention group (mobile dermoscopy-enhanced self-skin examination) or the control group (naked-eye skin self-examination). Control group and intervention group participants received web-based instructions on how to complete a whole body skin self-examination. All participants completed skin examinations at baseline, 1 month, and 2 months; intervention group participants submitted photographs of suspicious lesions to a dermatologist for telediagnosis after each skin examination and control group participants noted lesions on a body chart that was sent to the research team after each skin examination. All participants had an in-person whole-body clinical skin examination within 3 months of their last skin self-examination. Primary outcomes were sensitivity and specificity of skin self-examination, patient selection of clinically atypical lesions suspicious for melanoma or keratinocyte skin cancers (body sites examined, number of lesions photographed, types of lesions, and lesions missed), and diagnostic concordance of telediagnosis versus in-person whole-body clinical skin examination diagnosis. All primary outcomes were analysed in the modified intention-to-treat population, which included all patients who had a clinical skin examination within 3 months of their last skin self-examination. This trial was registered with the Australian and New Zealand Clinical Trials Registry, ACTRN12616000989448. FINDINGS: Between March 6, 2017, and June 7, 2018, 234 participants consented to enrol in the study, of whom 116 (50%) were assigned to the intervention group and 118 (50%) were assigned to the control group. 199 participants (98 participants in the intervention group and 101 participants in the control group) attended the clinical skin examination and thus were eligible for analyses. Participants in the intervention group submitted 615 lesions (median 6·0 per person; range 1-24) for telediagnosis and participants in the control group identified and recorded 673 lesions (median 6·0 per person; range 1-16). At the lesion level, sensitivity for lesions clinically suspicious for skin cancer was 75% (95% CI 63-84) in the intervention group and 88% (95% CI 80-91) in the control group (p=0·04). Specificity was 87% (95% CI 85-90) in the intervention group and 89% (95% CI 87-91) in the control group (p=0·42). At the individual level, the intervention group had a sensitivity of 87% (95% CI 76-99) compared with 97% (95% CI 91-100) in the control group (p=0·26), and a specificity of 95% (95% CI 90-100) compared with 96% (95% CI 91-100) in the control group. The overall diagnostic concordance between the telediagnosis and in-person clinical skin examination was 88%. INTERPRETATION: The use of mobile teledermoscopy did not increase sensitivity for the detection of skin cancers compared with naked-eye skin self-examination; thus, further evidence is necessary for inclusion of skin self-examination technology for public health benefit. FUNDING: National Health and Medical Research Council (Australia).
Asunto(s)
Dermoscopía/métodos , Aplicaciones Móviles , Autoexamen , Neoplasias Cutáneas/patología , Telemedicina , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Medición de Riesgo , Neoplasias Cutáneas/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Participating in physical activity after a diagnosis of cancer is associated with reduced morbidity and improved outcomes. However, declines in, and low levels of, physical activity are well documented in the broader cancer population, but with limited evidence following gynecological cancer. OBJECTIVE: To describe physical activity levels from before and up to 2 years after gynecological cancer surgery; to explore the relationship between physical activity patterns and quality of life; and to describe characteristics associated with physical activity trajectories post-gynecological cancer. METHODS: Women with gynecological cancer (n=408) participated in a prospective study that assessed physical activity and quality of life pre-surgery (baseline), at 6 weeks, and 3, 6, 9, 12, 15, 18 and 24 months post-surgery. Validated questionnaires were used to assess physical activity (Active Australia Survey) and quality of life outcomes (Functional Assessment of Cancer Therapy-General). Generalized estimating equation modeling, group-based trajectory analysis, and analysis of variance were used to identify physical activity levels over time, to categorize women into physical activity trajectory groups, and to assess the relationship between physical activity levels and quality of life, respectively. RESULTS: Women had a mean±SD age of 60±11.4 years at diagnosis, with the majority diagnosed with endometrial cancer (n=235, 58%) or stage I disease (n=241, 59%). Most women (80%) started with and maintained low levels of physical activity (1-10 metabolic equivalent task hours per week), reported no physical activity throughout the follow-up period, or reduced physical activity levels over time. Only 19% of women maintained or doubled physical activity levels, so that by 24 months post-diagnosis they were engaging in sufficient levels of physical activity. Women with endometrial cancer (58% of the sample) were more likely to be overweight or obese and to report low levels of physical activity or none at all. Higher physical activity levels were associated with higher quality of life (p<0.05). CONCLUSION: The low baseline and surveillance levels of physical activity show that the vast majority of gynecological cancer survivors have the ability to improve their physical activity levels. Integration of physical activity advice and support into standard care could lead to gains in quality of life during gynecological cancer survivorship.