Barriers and co-designed strategies for the implementation of negative pressure wound therapy in acute pediatric burn care in Australia: A mixed method study.

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.

Bladder-draining lymph nodes support germinal center B cell responses during urinary tract infection in mice.

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.

Consumer Preference and Willingness to Pay for Direct-to-Consumer Mobile Teledermoscopy Services in Australia.

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.

Child protection training for professionals to improve reporting of child abuse and neglect.

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.

Physical activity levels among ovarian cancer survivors: a prospective longitudinal cohort study.

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.

Incidence and risk factors for lower limb lymphedema associated with endometrial cancer: Results from a prospective, longitudinal cohort study.

BACKGROUND: Evidence on the incidence and risk factors for lower limb lymphedema (LLL) associated with endometrial cancer is limited. Our objective was to use data from a prospective, longitudinal gynecological cancer cohort study to determine LLL incidence up to 24 months post-diagnosis of endometrial cancer and to explore the relationship between personal and treatment-related factors and risk of developing LLL. METHODS: Women recently diagnosed with endometrial cancer (n = 235) were evaluated at regular intervals post-diagnosis (up to 3-monthly) using bioimpedance spectroscopy (BIS) and self-reported leg swelling (SRLS). RESULTS: Incidence of LLL at 24 months post-diagnosis was 33% and 45% according to BIS and SRLS, respectively. When analyses were restricted to obese women, incidence at 24 months post-diagnosis increased to 67% (BIS) and 54% (SRLS). Following adjusted analyses, higher body mass index was associated with higher odds of baseline lymphedema (BIS: OR 1.91, 95% CI 1.47-2.49, p < .01; SRLS: OR 1.06, 95% CI 1.00-1.12, p < .01) and LLL incidence by 24 months post-diagnosis (BIS: OR 1.29, 95% CI: 0.99-1.68, p = .055; SRLS: OR 1.06, 95% CI 1.02-1.11, p = .008). According to SRLS, presence of comorbidities was also associated with baseline lymphedema (OR: 1.43, 95% CI: 1.15-1.78, p = .001), and more extensive lymph node dissection (OR 1.06, 95% CI: 1.01-1.12, p = .026) and receipt of chemotherapy (OR: 2.65, 95% CI: 1.12-6.29, p = .027) were identified as risk factors for lymphedema incidence. CONCLUSIONS: These findings suggest that LLL following endometrial cancer is common, particularly in women with high body mass index, or comorbidities, and those requiring more extensive lymph node dissection or chemotherapy. Future studies should examine the potential of weight loss intervention as a strategy to reduce LLL incidence.

Physical activity trajectories following gynecological cancer: results from a prospective, longitudinal cohort study.

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.

Is Teledermoscopy Ready to Replace Face-to-Face Examinations for the Early Detection of Skin Cancer? Consumer Views, Technology Acceptance, and Satisfaction with Care.

BACKGROUND: Previous cross-sectional research indicates high acceptance of mobile teledermoscopy-enhanced skin self-examination (SSE) by consumers based on the technology acceptance model (TAM) domains: perceived usefulness, ease of use, compatibility, attitude and intention, subjective norms, facilitator, and trust. However, no study has assessed this outcome longitudinally among people who actually used the technology in their own homes. METHODS: Participants were living in Brisbane, Australia, aged 18 years or older, and at high risk of skin cancer. Participants randomly assigned to the intervention group (n = 98) completed a self-administered questionnaire on mobile teledermoscopy acceptance for skin cancer detection both before use and after performing mobile teledermoscopy-enhanced SSE in their homes. The survey included a 25-item scale assessing seven TAM domains. Item scores ranged from 5 (strongly agree) to 1 (strongly disagree). Participants also answered survey questions on satisfaction with use of teledermoscopy, and a 9-item "thoughts about melanoma" scale that measures cancer worry. RESULTS: Participants were 19-73 years old, had high skin cancer risk, blue or grey eyes (53.1%), fair or very fair skin (88.8%), and previous skin cancer treatments (61.2%). Participants were more accepting of mobile teledermoscopy at baseline: mean TAM score of 4.15 (SE 0.05); their level of acceptance decreased significantly after teledermoscopy use: mean score 3.94 (SE 0.05; p = 0.001). In linear regression analysis, the decrease in TAM scores was similar across demographic and skin cancer risk categories. Ninety-two percent (n = 90) of participants agreed that mobile teledermoscopy was easy to use. The mean score of the "thoughts about melanoma" scale did not change significantly from baseline to follow-up. CONCLUSION: Consumers had high TAM scores before they used mobile teledermoscopy within a randomised control trial. At the end of the intervention period, TAM scores decreased, although participants' average score still indicated "agreement" that mobile teledermoscopy was acceptable.

Exercise therapies for preventing or treating aromatase inhibitor-induced musculoskeletal symptoms in early breast cancer.

BACKGROUND: Survival for stage I to III, hormone receptor-positive, breast cancer has substantially improved over time due to advances in screening, surgery and adjuvant therapy. However many adjuvant therapies have significant treatment-related toxicities, which worsen quality of life for breast cancer survivors. Postmenopausal women with hormone receptor-positive breast cancer are now prescribed aromatase inhibitors (AI) as standard, with longer durations of therapy, up to 10 years, being considered for certain women. AI treatment is associated with a high incidence of AI-induced musculoskeletal symptoms (AIMSS), often described as symmetrical pain and soreness in the joints, musculoskeletal pain and joint stiffness. AIMSS reduces compliance with AI therapy in up to one half of women undergoing adjuvant AI therapy, potentially compromising breast cancer outcomes. Exercise has been investigated for the prevention and treatment of AIMSS but the effect of this intervention remains unclear. OBJECTIVES: To assess the effects of exercise therapies on the prevention or management of aromatase inhibitor-induced musculoskeletal symptoms (AIMSS) in women with stage I to III hormone receptor-positive breast cancer. SEARCH METHODS: We searched Cochrane Breast Cancer's Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases up to 13 December 2018. We also searched two conference proceedings portals and two clinical trials registries for ongoing studies or unpublished trials, or both, in August 2019. We also reviewed reference lists of the included studies. SELECTION CRITERIA: We included randomised controlled trials that compared exercise versus a comparator arm. We did not impose any restriction on the comparator arm, which could include an alternative type of exercise, no exercise or a waiting list control. Both published and non-peer-reviewed studies were eligible. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data, assessed risk of bias and certainty of the evidence using the GRADE approach. The outcomes investigated were pain, joint stiffness, grip strength, health-related quality of life, cancer-specific quality of life, adherence to AI therapy, adverse events, incidence of AIMSS, breast cancer-specific survival and overall survival. For continuous outcomes that were assessed with the same instrument, we used the mean difference (MD); for those outcomes that used different instruments, we used the standardised mean difference (SMD) for the analysis. For dichotomous outcomes, we reported outcomes as an odds ratio (OR). MAIN RESULTS: We included seven studies with 400 randomised participants; one study assessed exercise for preventing AIMSS and six studies assessed treating AIMSS. For preventing AIMSS, the single study reported no difference in pain scores, grip strength or compliance to taking AI medication between groups. Data values were not provided in the study and no other outcomes were reported. For managing AIMSS, we found that the evidence for the effect of exercise therapies on overall change in worst pain scores was very uncertain (SMD -0.23, 95% confidence interval (CI) -0.78 to 0.32; 4 studies, 284 women; very low-certainty evidence). The evidence suggested that exercise therapies result in little to no difference in overall change in stiffness scores (Western Ontario McMasters Universities Osteoarthritis Index (WOMAC) stiffness score MD -0.76, 95% CI -1.67 to 0.15 and Visual Analogues Scale (VAS) stiffness score MD -0.42, 95% CI -2.10 to 1.26; 1 study, 53 women; low-certainty evidence). The evidence was very uncertain for the outcomes of overall change in grip strength (MD 0.30, 95% CI -0.55 to 1.15; 1 study, 83 women; very low-certainty evidence); overall change in health-related quality of life (subscales of SF-36 tool ranged from least benefit of MD 1.88, 95% CI -2.69 to 6.45 to most benefit of MD 9.70, 95% CI 1.67 to 17.73; 2 studies, 123 women, very low-certainty evidence); overall change in cancer-specific quality of life (MD 4.58, 95% CI -0.61 to 9.78; 2 studies, 136 women; very low-certainty evidence); and adherence to aromatase inhibitors (OR 2.43, 95% CI 0.41 to 14.63; 2 studies, 224 women; very low-certainty evidence). There were no adverse events identified across four studies in either arm (0 events reported; 4 studies; 331 participants; low-certainty evidence). There were no data reported on incidence of AIMSS, breast cancer-specific survival or overall survival. AUTHORS' CONCLUSIONS: Given the wide-ranging benefits of exercise for people affected by cancer, it was surprising that this review provided no clear evidence of benefit for exercise therapies in women with early breast cancer with AIMSS. This review only yielded seven eligible studies with 400 participants, which is likely to have underpowered the findings. The meta-analysis was challenging due to the considerable heterogeneity amongst the trials, with a wide range of exercise regimens and follow-up periods. Despite these inconclusive findings, exercise needs to be part of routine care for women with breast cancer due to its wide-ranging benefits. Future research in this area would be enhanced with further understanding of the mechanism of AIMSS, a single clear definition of the condition, and phase III randomised controlled trials that are adequately powered to test targeted exercise interventions on the key clinical outcomes in this condition.

Skin Doctor Consultations Using Mobile Teledermoscopy: Exploring Virtual Care Business Models.

Background: Technological advances have given rise to virtual health care services, resulting in a shift in how traditional health care services are being delivered. Consumers are increasingly demanding efficient access to health care information and services irrespective of time and distance, which is further driving the digitization of health care. This digital economy has created new opportunities for innovative new business models to meet the needs of these new markets. This study explores several in-use business models of virtual health care service platforms that incorporate mobile teledermoscopy (MTD) technologies. By comparing the different building blocks of these commercial ventures, we provide insights on business model choices and discuss the elements that contribute to economically sustainable and viable service offerings incorporating MTD applications. Materials and Methods: We searched the literature on teledermatology, complemented by searches using Google and other mobile app store platforms, and identified seven commercial ventures using teledermoscopy. We analyzed the building blocks of each business model by using an adapted version of Ash Maurya's Lean Canvas and Alexander Osterwalder's Business Model Canvas. Results: We identified three business elements that support the viability, sustainability, and growth of online dermatology services: developing key partnerships, clinician involvement in the design and implementation process, and managing the medico-legal risks and liabilities that are relevant for each country. Conclusions: Leveraging mobile technologies to deliver virtual health care present new business opportunities for health care providers. A better understanding of the business features associated with existing commercial ventures may increase uptake and improve financial viability of MTD applications as a complementary tool to traditional patient care models.

Consumer Acceptance and Expectations of a Mobile Health Application to Photograph Skin Lesions for Early Detection of Melanoma.

BACKGROUND: Mobile teledermoscopy may facilitate skin self-examinations (SSEs) and further improve monitoring and detection of melanoma. OBJECTIVE: To assess consumer acceptability and expectations of a mobile health app used to: (i) instruct SSE and (ii) conduct consumer-performed mobile teledermoscopy. METHODS: People aged 18 years and above were invited to participate in either (i) an online survey or (ii) focus group in Brisbane, Australia. Participants were asked about their SSE practices, mobile teledermoscopy acceptance, and app design and functionality. The online survey responses and focus group discussions were coded by two researchers who conducted thematic analysis. RESULTS: Four focus groups were held with a total of 28 participants; 88 participants completed the online survey. The mean ages of participants in the focus group and online survey were 46 and 38 years, respectively. There were more males in the focus groups (61%, 17/28) compared to the online survey (19%, 17/88). Regular SSEs were conducted by 56 (64%) of the online survey participants. Barriers to SSE were forgetfulness (44%), low self-perceived risk of melanoma (25%) and low confidence in conducting SSEs (25%). The large majority of online survey participants (95%) would consider sending photos of their skin lesions to a medical practitioner via an app. Focus group participants reported that they would accept using mobile teledermoscopy; however, they would prefer to use it to monitor lesions between face-to-face consultations. CONCLUSIONS: Overall, participants had positive views on using mobile teledermoscopy to send images of skin lesions to a dermatologist or other medical practitioner.

Redesigning Skin Cancer Early Detection and Care Using a New Mobile Health Application: Protocol of the SKIN Research Project, a Randomised Controlled Trial.

Patients often detect melanoma themselves; therefore, regular skin self-examinations (SSEs) play an important role in the early detection and prompt treatment of melanoma. Mobile teledermoscopy is a technology that may facilitate consumer SSEs and rapid communication with a dermatologist. This paper describes the planned randomised controlled trial of an intervention to determine whether mobile technologies can help improve the precision of SSE in consumers. A randomised controlled trial will be conducted to evaluate mobile teledermoscopy-enhanced SSE versus naked-eye SSE. Participants in each group will conduct three home whole-body SSEs at baseline, 1 and 2 months, then present for a clinical skin examination (CSE) by a doctor after the 2-month SSE. Specifically, participants will identify skin lesions that meet the AC (asymmetry and colour) rule for detecting a suspicious skin spot. The primary outcomes are sensitivity and specificity of the skin lesions selected by the participants as needing attention by a doctor, compared to the clinical diagnosis by the dermatologist that will serve as the reference standard for this analysis. For the mobile teledermoscopy-enhanced SSE group, researchers will assess the number, location and type of lesions (1) sent by the participant via mobile teledermoscopy, (2) found at CSE or (3) missed by the participant. For the naked-eye SSE group, researchers will assess the number, location and type of lesions (1) recorded on their body chart by the participant, (2) found at CSE or (3) missed by the participant. Secondary outcomes are based on participants' self-reported data via online questionnaires.

Intestinal Colonization Traits of Pandemic Multidrug-Resistant Escherichia coli ST131.

Background: Epidemiological studies point to the gut as a key reservoir of multidrug resistant Escherichia coli multilocus sequence type 131 (ST131), a globally dominant pathogenic clone causing urinary tract and bloodstream infections. Here we report a detailed investigation of its intestinal lifestyle. Methods: Clinical ST131 isolates and type 1 fimbriae null mutants were assessed for colonization of human intestinal epithelia and in mouse intestinal colonization models. Mouse gut tissue underwent histologic analysis for pathology and ST131 localization. Key findings were corroborated in mucus-producing human cell lines and intestinal biopsy specimens. Results: ST131 strains adhered to and invaded human intestinal epithelial cells more than probiotic and commensal strains. The reference ST131 strain EC958 established persistent intestinal colonization in mice, and expression of type 1 fimbriae mediated higher colonization levels. Bacterial loads were highest in the distal parts of the mouse intestine and did not cause any obvious pathology. Further analysis revealed that EC958 could bind to both mucus and underlying human intestinal epithelia. Conclusions: ST131 strains can efficiently colonize the mammalian gut and persist long term. Type 1 fimbriae enhance ST131 intestinal colonization, suggesting that mannosides, currently developed as therapeutics for bladder infections and Crohn's disease, could also be used to limit intestinal ST131 reservoirs.

Longitudinal study of quality of life among children with acute respiratory infection and cough.

PURPOSE: Acute respiratory infections (ARIs), and associated symptoms such as cough, are frequently experienced among children and impose a burden on families (e.g., use of medical resources and time off work/school). However, there are little data on changes in, and predictors of, quality of life (QoL) over the duration of an ARI with cough (ARIwC) episode. We therefore aimed to determine cough-specific QoL and identify its influencing factors among children with ARIwC, at the time of presentation to a pediatric emergency department (ED), and over the following 4 weeks. METHODS: Data from 283 children aged < 15 years were included in our analyses. We used the validated parent-proxy children's acute cough-specific QoL questionnaire (PAC-QoL) at each time-point. Linear regression and mixed effect modeling were used to identify factors influencing QoL at baseline and over the follow-up period. RESULTS: Median PAC-QoL at baseline was 2.7 (IQR 2.1-3.6) and significantly improved by Day-7 (4.9, IQR 3.8-6.1) and Day-14 (6.59, IQR 5.1-7.0), both p < 0.001. The improvements in median PAC-QoL between Days-14, -21, and -28 were not significant. Regression modeling identified that day-cough severity, night-cough severity, and financial concerns had the highest impact on both baseline, and follow-up, PAC-QoL scores. There were five additional independent significant factors at baseline and six at follow-up. CONCLUSIONS: Quality of life is considerably impaired at presentation to ED, but improves significantly by Days-7 and -14. As cough severity and financial concerns had the highest impact on QoL, effectively managing cough to reduce the clinical and financial burden on children and families is important.

Salivary DNA methylation panel to diagnose HPV-positive and HPV-negative head and neck cancers.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of tumours with a typical 5 year survival rate of <40 %. DNA methylation in tumour-suppressor genes often occurs at an early stage of tumorigenesis, hence DNA methylation can be used as an early tumour biomarker. Saliva is an ideal diagnostic medium to detect early HNSCC tumour activities due to its proximity to tumour site, non-invasiveness and ease of sampling. We test the hypothesis that the surveillance of DNA methylation in five tumour-suppressor genes (RASSF1α, p16 INK4a , TIMP3, PCQAP/MED15) will allow us to diagnose HNSCC patients from a normal healthy control group as well as to discriminate between Human Papillomavirus (HPV)-positive and HPV-negative patients. METHODS: Methylation-specific PCR (MSP) was used to determine the methylation levels of RASSF1α, p16 INK4a , TIMP3 and PCQAP/MED15 in DNA isolated from saliva. Statistical analysis was carried out using non-parametric Mann-Whitney's U-test for individually methylated genes. A logistic regression analysis was carried out to determine the assay sensitivity when combing the five genes. Further, a five-fold cross-validation with a bootstrap procedure was carried out to determine how well the panel will perform in a real clinical scenario. RESULTS: Salivary DNA methylation levels were not affected by age. Salivary DNA methylation levels for RASSF1α, p16 INK4a , TIMP3 and PCQAP/MED15 were higher in HPV-negative HNSCC patients (n = 88) compared with a normal healthy control group (n = 122) (sensitivity of 71 % and specificity of 80 %). Conversely, DNA methylation levels for these genes were lower in HPV-positive HNSCC patients (n = 45) compared with a normal healthy control group (sensitivity of 80 % and specificity of 74 %), consistent with the proposed aetiology of HPV-positive HNSCCs. CONCLUSIONS: Salivary DNA tumour-suppressor methylation gene panel has the potential to detect early-stage tumours in HPV-negative HNSCC patients. HPV infection was found to deregulate the methylation levels in HPV-positive HNSCC patients. Large-scale double-blinded clinical trials are crucial before this panel can potentially be integrated into a clinical setting.

Retinal thickness profile of individuals with diabetes.

PURPOSE: To examine the retinal thickness profiles of individuals with and without diabetic retinopathy (DR). METHODS: Full retinal thickness in the central zone, overall and hemisphere thicknesses of the parafovea and perifovea, ganglion cell complex (GCC) thickness and retinal nerve fibre layer (RNFL) thickness were assessed in 185 individuals using spectral domain optical coherence tomography (88 individuals with diabetes but no DR, 55 with DR, and 42 non-diabetic controls). The DR group comprised of 60% of participants with very mild non-proliferative diabetic retinopathy (NPDR) (representing microaneurysms only) and 40% with mild NPDR (hard exudates, cotton-wool spots, and/or mild retinal haemorrhages). Regression analysis was performed to determine the factors associated with retinal tissue thickness, taking into account, age, sex, presence of DR, duration of diabetes, HbA1c levels and type of diabetes. RESULTS: The mean (S.D.) of the overall parafoveal thickness was 306 (16) in the DR group and 314 (14) in the control group (p = 0.02). The mean (S.D.) of the superior hemisphere parafoveal thickness was 309 (16) in the DR group and 318 (14) in the control group (p = 0.02). The mean (S.D.) of the inferior hemisphere parafoveal thickness was 303 (17) in the DR group and 311 (15) in the control group (p = 0.02). There were no significant differences in retinal thickness between groups in the central zone (p = 0.27) or perifovea (p > 0.41). Neither the overall nor the hemisphere RNFL (p > 0.75) and GCC thickness (p > 0.37) were significantly different between the groups. Regression analysis revealed that parafoveal thickness in diabetic individuals was reduced in association with presence of DR (B = -5.9 µm, p = 0.02) and with advancing age (B = -4.5 µm, p = 0.004, for every 10 year increase in age) when adjusted for sex, duration of diabetes, HbA1c levels and type of diabetes. CONCLUSION: The inner macula is thinner in the presence of clinical signs of diabetic retinopathy and is compounded by advancing age. The influence of any macular oedema or that by cotton-wool spots could not be ruled out and may still confound these results.

Weight and weight change following breast cancer: evidence from a prospective, population-based, breast cancer cohort study.

BACKGROUND: While weight gain following breast cancer is considered common, results supporting these findings are dated. This work describes changes in body weight following breast cancer over 72 months, compares weight with normative data and explores whether weight changes over time are associated with personal, diagnostic, treatment or behavioral characteristics. METHODS: A population-based sample of 287 Australian women diagnosed with early-stage invasive breast cancer was assessed prospectively at six, 12, 18 and 72 months post-surgery. Weight was clinically measured and linear mixed models were used to explore associations between weight and participant characteristics (collected via self-administered questionnaire). Those with BMI changes of one or more units were considered to have experienced clinically significant changes in weight. RESULTS: More than half (57%) of participants were overweight or obese at 6 months post-surgery, and by 72 months post-surgery 68% of women were overweight or obese. Among those who gained more weight than age-matched norms, clinically significant weight gain between 6 and 18 months and 6 and 72 months post-surgery was observed in 24% and 39% of participants, respectively (median [range] weight gain: 3.9 kg [2.0-11.3 kg] and 5.2 kg [0.6-28.7], respectively). Clinically-significant weight losses were observed in up to 24% of the sample (median [range] weight loss between 6 and 72 months post-surgery: -6.4 kg [-1.9--24.6 kg]). More extensive lymph node removal, being treated on the non-dominant side, receiving radiation therapy and lower physical activity levels at 6 months was associated with higher body weights post-breast cancer (group differences >3 kg; all p < 0.05). CONCLUSIONS: While average weight gain among breast cancer survivors in the long-term is small, subgroups of women experience greater gains linked with adverse health and above that experienced by age-matched counterparts. Weight change post-breast cancer is a contemporary public health issue and the integration of healthy weight education and support into standard breast cancer care has potential to significantly improve the length and quality of cancer survivorship.

Four-Component Statistical Copolymers by RAFT Polymerization.

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.