Comparison of skin cancer risk between renal transplant recipients and patients with glomerular diseases in rural Queensland.

INTROUDCTION: There is increased risk of skin cancer in patients with gloermular disease or those with renal transplant. OBJECTIVES: To compare the risk of skin cancer between kidney recipients (KTRs) and patients with glomerular disease (GD). DESIGN: The cohort comprised patients with KTRs (n = 61) and GD (n = 51) in Central and Central West Queensland, Australia. A quantitative cohort study was undertaken to study the risk of skin cancer in rural communities between two subgroups of patients with kidney diseases in relationship to immunosuppression. Statistical analyses of the differences in incidence of skin cancers between the two groups were done by chi-square test, Fisher's exact test, independent t-test and McNemar's test. FINDINGS: KTRs with non-melanoma skin carcinoma (NMSC) increased significantly after treatment with immunosuppressants (pre-transplantation, n = 11 [18.0%], post-transplantation, n = 28 [45.9%]; p < 0.001). There were no differences in number of patients with NMSC observed in the GD group (pre-diagnosis, n = 6 [11.8%], post-diagnosis, n = 7 [13.7%]; p = 1.000). Compared to the risks at 1 year post-immunosuppressants, the incidence of NMSC of KTRs increased significantly at 3 years (20.3% vs. 35.4%, p < 0.001) and 5 years (20.3% vs. 62.2%, p < 0.001) post-immunosuppressants, whereas the increased incidence of NMSC was observed only at 5 years (2.1% vs. 11.8%, p = 0.012) in the GD cohort. The mean cumulative number of NMSC in KTRs increased significantly at 3 years (p = 0.011), and 5 years (p = 0.001) post-immunosuppressants, compared to the risks at 1 year post-immunosuppressants, however, no differences were noted in the GD cohort. DISCUSSION: Immunosuppressants increased the risk of NMSC in KTRs. The increased risk is likely dependent on the intensity and duration of immunosuppressants. CONCLUSION: In patients with a high risk of NMSC, reducing skin cancer risk should be considered in conjunction with the optimisation of treatment.

Joint frailty modeling of time-to-event data to elicit the evolution pathway of events: a generalized linear mixed model approach.

Multimorbidity constitutes a serious challenge on the healthcare systems in the world, due to its association with poorer health-related outcomes, more complex clinical management, increases in health service utilization and costs, but a decrease in productivity. However, to date, most evidence on multimorbidity is derived from cross-sectional studies that have limited capacity to understand the pathway of multimorbid conditions. In this article, we present an innovative perspective on analyzing longitudinal data within a statistical framework of survival analysis of time-to-event recurrent data. The proposed methodology is based on a joint frailty modeling approach with multivariate random effects to account for the heterogeneous risk of failure and the presence of informative censoring due to a terminal event. We develop a generalized linear mixed model method for the efficient estimation of parameters. We demonstrate the capacity of our approach using a real cancer registry data set on the multimorbidity of melanoma patients and document the relative performance of the proposed joint frailty model to the natural competitor of a standard frailty model via extensive simulation studies. Our new approach is timely to advance evidence-based knowledge to address increasingly complex needs related to multimorbidity and develop interventions that are most effective and viable to better help a large number of individuals with multiple conditions.

Determinants of health-related quality of life in people with Human Immunodeficiency Virus, failing first-line treatment in Africa.

BACKGROUND: Antiretroviral treatment improves health related quality of life (HRQoL) of people with human immunodeficiency virus (PWH). However, one third initiating first-line treatment experience virological failure and the determinants of HRQoL in this key population are unknown. Our study aims to identify determinants of among PWH failing antiretroviral treatment in sub-Saharan Africa. METHODS: We analysed data from a cohort of PWH having virological failure (> 1,000 copies/mL) on first-line ART in South Africa and Uganda. We measured HRQoL using the EuroQOL EQ-5D-3L and used a two-part regression model to obtain by-country analyses for South Africa and Uganda. The first part identifies risk factors that were associated with the likelihood of participants reporting perfect health (utility = 1) versus non-perfect health (utility < 1). The second part identifies risk factors that were associated with the EQ-5 L-3L utility scores for participants reporting non-perfect health. We performed sensitivity analyses to compare the results between the two-part model using tobit models and ordinary least squares regression. RESULTS: In both countries, males were more likely to report perfect health and participants with at least one comorbidity were less likely to report perfect health. In South Africa, participants with side effects and in Uganda those with opportunistic infections were also less likely to report perfect health. In Uganda, participants with 100% ART adherence were more likely to report perfect health. In South Africa, high HIV viral load, experiencing ART side effects, and the presence of opportunistic infections were each associated with lower HRQoL, whereas participants with 100% ART adherence reported higher HRQoL. In Uganda participants with lower CD4 count had lower HRQoL. CONCLUSION: Markers of advanced disease (opportunistic infection, high viral load, low CD4), side effects, comorbidities and lack of ART adherence negatively impacted HRQoL for PWH experiencing virological failure. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02787499.

A cross-sectional study of symptoms and health-related quality of life in menopausal-aged women in China.

OBJECTIVE: To measure symptoms and health-related quality of life in a cross-sectional cohort of menopausal-aged women in China. METHOD: A cross-sectional survey was conducted in a general population cohort of 2,000 Chinese females over the age of 45 years. Patients completed the Chinese version of the EuroQol-5D five level (EQ5D5L) health-related quality of life instrument via Personal Digital Assistant. Raw scores were converted to utility tariffs using value sets for China. Statistical analysis included Pearson's chi-square test, z test for multiple comparisons with adjustment by the Bonferroni method, independent-sample t-test, ANOVA, and adjustment by the Tukey method for multiple comparison. Results were considered statistically significant when p < 0.05 and the study was reported according to the STROBE recommendations. RESULTS: In a cohort of 2000 women, 732 (37%) were premenopausal, 798 (40%) were perimenopausal and 470 (23%) were postmenopausal. Perimenopausal women reported significantly more symptoms (91%) compared to premenopausal (77%) and postmenopausal (81%) women. Health-related quality of life was significantly lower in symptomatic perimenopausal women compared to premenopausal (0.919, p < 0.05) and postmenopausal (0.877, p < 0.05) women. Within each group there was a statistically significant difference between the health-related quality of life of women with symptoms compared to without symptoms. CONCLUSION: The perimenopausal phase of menopause is associated with significantly more symptoms and significantly lower HRQoL compared to premenopausal and postmenopausal phases.

Why is this study needed?• It is important to understand the impact of menopausal symptoms on women's quality of life so that decisions can be made about what healthcare services to provide and what treatments to fund.• Currently there are only a few older studies investigating menopausal symptoms in the perimenopausal phase, which is characterised by hormone fluctuations and symptoms likely to impact quality of life, and lasts up to four years. What is the key problem this manuscript addresses?• This research measures symptoms and the impact on quality of life of menopausal women in China. What are your main results and what do they mean?• Women in the perimenopausal phase are disproportionately affected by symptoms compared to premenopausal and postmenopausal women.• Perimenopausal women have significantly lower HRQoL compared to premenopausal and postmenopausal women.• This information is critical to informing pharmacoeconomic decisions about healthcare provision and publicly funded treatments in China.

Clinical and economic burden of benign and malignant skin lesions in renal transplant recipients.

BACKGROUND: Studies evaluating the economic burden of dermatological care in the transplant setting are currently not available in Australia. AIMS: To evaluate the clinical and economic burden of benign and malignant skin lesions in renal transplant recipients in Central Queensland. METHODS: A bottom-up approach was used to determine the clinical burden and direct costs from patient-level Medicare data obtained from Service Australia for skin lesions. RESULTS: Seventy-six percent of the renal transplant population in Central Queensland participated in this study. The median age was 57.0 years (standard deviation ± 13.6) and the majority (61.8%) of participants were men. The mean duration after transplant surgery was 99.9 months (interquartile range, 73.2-126.6 months). During a 2-year follow-up, 22 (40%) patients were diagnosed with benign skin lesions, 21 (38%) with nonmelanoma skin carcinoma (NMSC) and one (2%) with melanoma. There was a total of 231 visits to clinicians for diagnostic and therapeutic skin procedures and the direct costs to Medicare was $48 806 Australian Dollars (AUD) or $30 427 US Dollars (USD). Approximately 86% of the total direct costs was spent for nonNMSC and mean direct costs for NMSC was $763 AUD (or $476 USD). CONCLUSION: This Medicare data-based study provides further insight into the burgeoning clinical and economic burden of the care for benign and malignant skin lesions in the renal transplantation setting in Australia.

Risk of extracolonic second primary cancers following a primary colorectal cancer: a systematic review and meta-analysis.

PURPOSE: The purpose of the study is to assess the global risk of extracolonic secondary primary cancers (SPCs) in patients with colorectal cancer (CRC). METHODS: Studies of SPC in patients with CRC were included if they reported the standardised incidence ratio (SIR) for extracolonic SPCs in patients with CRC compared with the general population. Pooled summary estimates were calculated using a random-effects model. RESULTS: A total of 7,716,750 patients with CRC from 13 retrospective cohort studies that reported extracolonic SPC incidence were included. The overall risk of several SPCs was significantly higher in patients with CRC compared with the general population, including cancers of the urinary bladder (pooled SIR 1.19, 95% confidence interval (CI) 1.06-1.33; p = 0.003), female genital tract (1.88, 1.07-3.31; p = 0.03), kidney (1.50, 1.19-1.89; p = 0.0007), thorax (lung, bronchus and mediastinum) (1.16, 1.01-1.32; p = 0.03), small intestine (4.26, 2.58-7.01; p < 0.0001), stomach (1.22, 1.07-1.39; p = 0.003), and thyroid (1.40, 1.28-1.53; p < 0.0001), as well as melanoma (1.28, 1.01-1.62; p = 0.04). There was also a decreased risk of developing cancer of the gall bladder (0.75, 0.60-0.94; p = 0.01). CONCLUSION: Patients with CRC had a significantly increased risk of extracolonic SPCs compared with the general population. These findings highlight the need to develop research strategies for the management of second primary cancer in patients with CRC.

An integrated skin cancer education program in renal transplant recipients and patients with glomerular disease.

Sun-protective strategies focusing on skin cancer awareness are needed in immunosuppressed patients at risk of skin cancers. The study aims to determine the effect of an integrated skin cancer education program on skin cancer awareness and sun-protective behaviours in renal transplant recipients (RTRs) and patients with glomerular disease (GD) treated with long-term immunosuppressants. A pilot prospective cohort study in Central Queensland, Australia was undertaken among adult RTRs and patients with GD, who completed survey questionaries on skin cancer and sun-health knowledge (SCSK), sun-protection practices and skin examination pre- and post-education. Fifty patients (25 RTRs, 25 patients with GD) participated in the study. All of them completed questionnaires at pre-, 3-month post-education and 92%(n = 46) at 6-month post-education. There was a significant increase in SCSK scores from baseline at 3-months (p < 0.001) and 6-months post-intervention (p < 0.01). Improved knowledge was retained for 6 months after education. There were changes in 2 of 8 photoprotective behaviours at 6 months. Interventional education enhanced regular self-skin examination rate (p < 0.001) as well as the frequency of full skin checks by general practitioners (GPs) (p < 0.001). Overall, RTRs had better compliance with sun-protective methods and higher skin examination rates by themselves and/ or GPs before and after the intervention of education compared to patients with GD. To conclude, an integrated skin cancer education program improved knowledge of skin cancer and skin health as well as the frequency of self-skin examination and formal skin assessments. However, improvement in patient compliance did not extend to other sun-protective practices.

Comparison of skin cancer awareness and sun protection behaviours between renal transplant recipients and patients with glomerular disease treated with immunosuppressants.

BACKGROUND: There is no previous study that compare skin cancer awareness and photoprotective behaviours between renal transplant recipients (RTR) and patients with glomerular disease (GD). OBJECTIVES/METHODS: Sixty-one RTR and 51 patients with GD were given a self-reported questionnaire to evaluate skin cancer awareness and photoprotective behaviours in this cross-sectional study. The former group received a formal education on skin cancer and the latter an informal session prior to immunosuppressant use. RESULTS: Ninety-three percent (n = 57) of RTRs and 88% (n = 45) of patients with GD responded to the survey. Majority of participants from both groups were aware that ultraviolet radiation could play a role in the occurrence of skin cancers and the awareness increased in participants with higher education (odds ratio [OR] = 1.50, 95% confidence interval [CI] = 1.15-1.95, P = .003). Ninety-eight percent vs 71% were aware that immunosuppressants can increase the risk of developing cancer (P < .001) and higher awareness was noted in younger participants (OR = 0.92, 95% CI = 0.87-0.97, P = .003). Suboptimal photoprotective behaviours (sun avoidance, sunscreen usage and sun-protective clothing) were noted in both cohorts and slightly lower sun protection rates were reported in RTR when compared with patients having GD. The level of sun protective measures in RTR based on high, moderate and minimal use of photoprotective measures were 21%, 46% and 33%, respectively. In terms of patients with GD, the latter practices were 13%, 50% and 37%, respectively (P = .560). Higher educational status was significantly associated with better sunscreen usage in RTR (P = .017) whereas this finding was not observed in patients with GD. CONCLUSION: Patients with GD and RTR should have formal education on the risks of skin cancers before starting immunosuppressants. Follow-up education and surveillance is required to improve skin protective practices in these patients.

A bivariate joint frailty model with mixture framework for survival analysis of recurrent events with dependent censoring and cure fraction.

In the study of multiple failure time data with recurrent clinical endpoints, the classical independent censoring assumption in survival analysis can be violated when the evolution of the recurrent events is correlated with a censoring mechanism such as death. Moreover, in some situations, a cure fraction appears in the data because a tangible proportion of the study population benefits from treatment and becomes recurrence free and insusceptible to death related to the disease. A bivariate joint frailty mixture cure model is proposed to allow for dependent censoring and cure fraction in recurrent event data. The latency part of the model consists of two intensity functions for the hazard rates of recurrent events and death, wherein a bivariate frailty is introduced by means of the generalized linear mixed model methodology to adjust for dependent censoring. The model allows covariates and frailties in both the incidence and the latency parts, and it further accounts for the possibility of cure after each recurrence. It includes the joint frailty model and other related models as special cases. An expectation-maximization (EM)-type algorithm is developed to provide residual maximum likelihood estimation of model parameters. Through simulation studies, the performance of the model is investigated under different magnitudes of dependent censoring and cure rate. The model is applied to data sets from two colorectal cancer studies to illustrate its practical value.

Protocol and establishment of a Queensland renal biopsy registry in Australia.

BACKGROUND: Renal biopsy is often required to obtain information for diagnosis, management and prognosis of kidney disease that can be broadly classified into acute kidney injury (AKI) and chronic kidney disease (CKD). The most common conditions identified on renal biopsy are glomerulonephritis and tubulo-interstitial disorders. There is a paucity of information on management strategies and therapeutic outcomes in AKI and CKD patients. A renal biopsy registry will provide information on biopsy-proven kidney disorders to improve disease understanding and tracking, healthcare planning, patient care and outcomes. METHODS: A registry of patients, that includes biopsy-proven kidney disease, was established through the collaboration of nephrologists from Queensland Hospital and Health Services and pathologists from Pathology Queensland services. The registry is in keeping with directions of the Advancing Kidney Care 2026 Collaborative, established in September 2018 as a Queensland Health initiative. Phase 1 of the registry entailed retrospective acquisition of data from all adult native kidney biopsies performed in Queensland, Australia, from 2002 to 2018. Data were also linked with the existing CKD.QLD patient registry. From 2019 onwards, phase 2 of the registry involves prospective collection of all incident consenting patients referred to Queensland public hospitals and having a renal biopsy. Annual reports on patient outcomes will be generated and disseminated. DISCUSSION: Establishment of the Queensland Renal Biopsy Registry (QRBR) aims to provide a profile of patients with biopsy-proven kidney disease that will lead to better understanding of clinico-pathological association and facilitate future research. It is expected to improve patient care and outcomes.

The Impact of Population-Based Disease Management Services on Health Care Utilisation and Costs: Results of the CAPICHe Trial.

BACKGROUND: Disease management programmes may improve quality of care, improve health outcomes and potentially reduce total healthcare costs. To date, only one very large population-based study has been undertaken and indicated reductions in hospital admissions > 10%. OBJECTIVE: We sought to confirm the effectiveness of population-based disease management programmes. The objective of this study was to evaluate the relative impact on healthcare utilisation and cost of participants the Costs to Australian Private Insurance - Coaching Health (CAPICHe) trial. DESIGN: Parallel-group randomised controlled trial, intention-to-treat analysis SETTING: Australian population PARTICIPANTS: Forty-four thousand four hundred eighteen individuals (18-90 years of age) with private health insurance and diagnosis of heart failure, chronic obstructive pulmonary disease (COPD), coronary artery disease (CAD), diabetes, or low back pain, with predicted high cost claims for the following 12 months. INTERVENTION: Health coaching for disease management from Bupa Health Dialog, vs Usual Care. MAIN OUTCOME MEASURES: Total cost of claims per member to the private health insurer 1 year post-randomisation for hospital admissions, including same-day, medical and prostheses hospital claims, excluding any maternity costs. Analysis was based on the intent-to-treat population. RESULTS: Estimated total cost 1 year post-randomisation was not significantly different (means: intervention group A$4934; 95% CI A$4823-A$5045 vs control group A$4868; 95% CI A$4680-A$5058; p = 0.524). However, the intervention group had significantly lower same-day admission costs (A$468; 95% CI A$454-A$482 vs A$508; 95% CI A$484-A$533; p = 0.002) and fewer same-day admissions per 1000 person-years (intervention group, 530; 95% CI 508-552 vs control group, 614; 95% CI 571-657; p = 0.002). Subgroup analyses indicated that the intervention group had significantly fewer admissions for patients with COPD and fewer same-day admissions for patients with diabetes. CONCLUSIONS: Chronic disease health coaching was not effective to reduce the total cost after 12 months of follow-up for higher risk individuals with a chronic condition. Statistically significant changes were found with fewer same-day admissions; however, these did not translate into cost savings from a private health insurance perspective.

Adaptations to cognitive problems reported by breast cancer survivors seeking cognitive rehabilitation: A qualitative study.

OBJECTIVE: Qualitative studies have elucidated cancer survivors' experiences of cognitive changes associated with cancer and cancer treatment. This study specifically explored experiences of women treated for breast cancer who were seeking cognitive rehabilitation. The objective was to characterise the frequency and nature of cognitive changes and adaptations to cognitive change reported by these participants to better understand treatment needs of this group. METHOD: Australian women who had completed primary treatments for breast cancer (surgery, chemotherapy, and/or radiotherapy) and volunteered to participate in one of two cognitive rehabilitation intervention studies were interviewed via telephone. Interview responses regarding cognitive changes and adaptations to cognitive change were transcribed by the interviewers, then coded and analysed by two researchers using content analysis. RESULTS: Among the 95 participants (age M=54.3 years, SD=9.6), the most commonly reported cognitive change was memory (79% of participants) and 61% reported more than one type of cognitive change. Adaptations to change were reported by 87% of participants, with written or electronic cues the most common (51%). Most often, participants reported using a single type of adaptation (48%) with only 39% reporting multiple types of adaptations. CONCLUSIONS: Women treated for breast cancer, who were seeking cognitive rehabilitation, most commonly reported memory changes, which were mainly managed through a single type of adaptation. These results suggest that there is considerable scope for increasing the range of cognitive adaptations to improve the quality of life of cancer survivors who experience adverse cognitive changes.

Multilevel model with random effects for clustered survival data with multiple failure outcomes.

We present a multilevel frailty model for handling serial dependence and simultaneous heterogeneity in survival data with a multilevel structure attributed to clustering of subjects and the presence of multiple failure outcomes. One commonly observes such data, for example, in multi-institutional, randomized placebo-controlled trials in which patients suffer repeated episodes (eg, recurrent migraines) of the disease outcome being measured. The model extends the proportional hazards model by incorporating a random covariate and unobservable random institution effect to respectively account for treatment-by-institution interaction and institutional variation in the baseline risk. Moreover, a random effect term with correlation structure driven by a first-order autoregressive process is attached to the model to facilitate estimation of between patient heterogeneity and serial dependence. By means of the generalized linear mixed model methodology, the random effects distribution is assumed normal and the residual maximum likelihood and the maximum likelihood methods are extended for estimation of model parameters. Simulation studies are carried out to evaluate the performance of the residual maximum likelihood and the maximum likelihood estimators and to assess the impact of misspecifying random effects distribution on the proposed inference. We demonstrate the practical feasibility of the modeling methodology by analyzing real data from a double-blind randomized multi-institutional clinical trial, designed to examine the effect of rhDNase on the occurrence of respiratory exacerbations among patients with cystic fibrosis.

Prolotherapy injections and physiotherapy used singly and in combination for lateral epicondylalgia: a single-blinded randomised clinical trial.

BACKGROUND: Lateral epicondylalgia (tennis elbow) is a common, debilitating and often treatment-resistant condition. Two treatments thought to address the pathology of lateral epicondylalgia are hypertonic glucose plus lignocaine injections (prolotherapy) and a physiotherapist guided manual therapy/exercise program (physiotherapy). This trial aimed to compare the short- and long-term clinical effectiveness, cost effectiveness, and safety of prolotherapy used singly and in combination with physiotherapy. METHODS: Using a single-blinded randomised clinical trial design, 120 participants with lateral epicondylalgia of at least 6 weeks' duration were randomly assigned to prolotherapy (4 sessions, monthly intervals), physiotherapy (weekly for 4 sessions) or combined (prolotherapy+physiotherapy). The Patient-Rated Tennis Elbow Evaluation (PRTEE) and participant global impression of change scores were assessed by blinded evaluators at baseline, 6, 12, 26 and 52 weeks. Success rate was defined as the percentage of participants indicating elbow condition was either 'much improved' or 'completely recovered.' Analysis was by intention-to-treat. RESULTS: Eighty-eight percent completed the 12-month assessment. At 52 weeks, there were substantial, significant improvements compared with baseline status for all outcomes and groups, but no significant differences between groups. The physiotherapy group exhibited greater reductions in PRTEE at 12 weeks than the prolotherapy group (p = 0.014). CONCLUSION: There were no significant differences amongst the Physiotherapy, Prolotherapy and Combined groups in PRTEE and global impression of change measures over the course of the 12-month trial. TRIAL REGISTRATION: ACTRN12612000993897 .

Pelvic floor ultrasound findings in Ugandan women with obstetric fistula, unrepaired fourth degree obstetric tear, and pelvic organ prolapse.

BACKGROUND: While pelvic floor ultrasound is commonly utilised in high-resource locations, our understanding of pelvic floor characteristics in women suffering with obstetric fistula and unrepaired fourth degree obstetric tears in low-resource areas is limited. AIMS: This study aimed to assess the pelvic floor ultrasound characteristics of Ugandan women suffering with obstetric fistula, unrepaired fourth degree obstetric tears and pelvic organ prolapse, and determine whether obstructed labour resulting in obstetric fistula causes more levator muscle defects compared to parous women without a history of obstructed labour. MATERIALS AND METHODS: This was a prospective study in western Uganda assessing 82 women with obstetric fistula, unrepaired fourth degree obstetric tears and pelvic organ prolapse with a pelvic floor ultrasound scan. RESULTS: Demographic characteristics were significantly different, with women suffering pelvic organ prolapse being older and more parous. Hiatal area on Valsalva was significantly smaller in the obstetric fistula group (mean 21.45 cm2 ) compared to non-obstetric fistula group (unrepaired fourth degree obstetric tears and pelvic organ prolapse; mean 30.44 cm2 ); a mean difference of 9.0 cm2 (95% CI: 5.4-12.6 cm2 , P < 0.001). Overall, levator muscle defects were significantly more common in women with obstetric fistula (66.7%) compared to the non-obstetric fistula group (44.7%) with P = 0.048; however, there were no significant differences in complete levator muscle defects between obstetric fistula (28.6%) and non-obstetric fistula (23.7%). CONCLUSIONS: Increased hiatal area on Valsalva was noted in the non-obstetric fistula group compared to women with obstetric fistula; however, there were no differences in proportions of complete levator muscle defects.

Life stress and symptoms of anxiety and depression in women after cancer: The mediating effect of stress appraisal and coping.

OBJECTIVE: This paper examines the direct and intermediary relationships between life stress, stress appraisal, and resilience, and increased anxiety and depressive symptoms in Australian women after cancer treatment. METHODS: Data examined from 278 women aged 18 years and older previously treated for breast, gynaecological, or blood cancer, participating in the Australian Women's Wellness after Cancer Program. Serial mediation models interrogated the effect of stressful life events (List of Threatening Experiences-Modified) mediated by appraisal and coping (Perceived Stress Scale and Connor-Davidson Resilience Scale), on symptoms of anxiety and depression (Zung Self-rating Anxiety Scale and Center for Epidemiologic Studies Depression Scale). RESULTS: Over one-quarter (30.2%) of participants reported 1 or more stressful life events, other than their cancer, in the previous 6 months. Results indicate that perceived stress fully mediated the relationships between life stress, anxiety (indirect effect = 0.09, Bias-corrected bootstrap 95% CI 0.02-0.18, Percent mediation = 0.51), and depressive symptoms (indirect effect = 0.11, Bias-corrected bootstrap 95% CI 0.02-0.23, Percent mediation = 0.71) and accounted for more than half of the relationship between predictor and outcome. CONCLUSIONS: Findings indicate that stress appraisal mediated the relationship between past life stressors and anxiety and depressive symptoms. This analysis also highlights the need to consider wellness within a broader care context to identify potentially vulnerable patients to possibly avert future health concerns.

Harvest of lymph nodes in colorectal cancer depends on demographic and clinical characteristics of the patients.

PURPOSE: This study aims to study the impact of clinical factors on the lymph node sampling in a large cohort of patients with colorectal cancer. METHODS: A colorectal cancer database of 2298 patients in Queensland, Australia, was established. Zero-inflated regression method was used to model positive lymph node counts given the number of lymph nodes examined, with patient's demographic and clinical factors as covariates in the model. Sensitivity and survival analyses were performed to illustrate the applicability of the recommendation of the minimum number of lymph nodes need to be pathologically examined. RESULTS: Younger patients with a larger sized tumour located at the left colon or rectum require fewer lymph nodes to be pathologically examined. Overall, 45.9% of the patients require eight or nine lymph nodes and 31.5% needs ten or 11 lymph nodes to be harvested for pathological examination. A simple formula could be used to obtain the minimum number of lymph node sampling required in patients with colorectal cancer based on patients' age as well as site and dimension of the cancer. CONCLUSIONS: The findings provide practical information about that the minimum number of lymph nodes that could be harvested at the time of collection of lymph nodes for pathological examination for patients with colorectal cancer. The minimum number of lymph nodes harvested depends on demographic (age) and clinical (location and dimension of cancer) characteristics of the patients with colorectal cancer.

Dietary patterns of Australian children at three and five years of age and their changes over time: A latent class and latent transition analysis.

Consuming a healthy diet characterised by a variety of nutritious foods is essential for promoting and maintaining health and wellbeing, yet the diets of Australian children continue to fall well short of national healthy eating recommendations. This research endeavours to identify patterns of dietary intake in Australian children at three and five years of age and investigate associations between early childhood dietary patterns and socio-economic and demographic indicators and Body Mass Index (BMI), as well as identify changes in children's dietary patterns over time. Cross-sectional dietary patterns were derived for 1565 and 631 children aged three and five years, respectively using Latent Class Analysis (LCA), with changes over time analysed with Latent Transition Analysis (LTA). Demographic variables of interest included child sex, parental age, family status, and use of childcare services and socio-economic variables included education, income and employment status. Three patterns of dietary intake were identified at three years (Highly Unhealthy, Healthier and Moderately Unhealthy) and two patterns at five years (Unhealthy and Healthier). Children with younger mothers, working mothers, fathers with a higher BMI and living in a two-carer household were more likely to have unhealthy eating patterns at three years, and children with working mothers and living in a two-carer household were more likely to have unhealthy patterns of dietary intake at five years. Approximately one eighth of the sample transitioned from the healthier to unhealthy pattern of dietary intake from three to five years. The quality of Australian children's diets appears to be declining through the early childhood years, continuing to highlight the importance of nutrition policies and interventions targeted towards the early years of life.

Characterization of MicroRNA-200 pathway in ovarian cancer and serous intraepithelial carcinoma of fallopian tube.

BACKGROUND: Ovarian cancer is the leading cause of death among gynecologic diseases in Western countries. We have previously identified a miR-200-E-cadherin axis that plays an important role in ovarian inclusion cyst formation and tumor invasion. The purpose of this study was to determine if the miR-200 pathway is involved in the early stages of ovarian cancer pathogenesis by studying the expression levels of the pathway components in a panel of clinical ovarian tissues, and fallopian tube tissues harboring serous tubal intraepithelial carcinomas (STICs), a suggested precursor lesion for high-grade serous tumors. METHODS: RNA prepared from ovarian and fallopian tube epithelial and stromal fibroblasts was subjected to quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) to determine the expression of miR-200 families, target and effector genes and analyzed for clinical association. The effects of exogenous miR-200 on marker expression in normal cells were determined by qRT-PCR and fluorescence imaging after transfection of miR-200 precursors. RESULTS: Ovarian epithelial tumor cells showed concurrent up-regulation of miR-200, down-regulation of the four target genes (ZEB1, ZEB2, TGFß1 and TGFß2), and up-regulation of effector genes that were negatively regulated by the target genes. STIC tumor cells showed a similar trend of expression patterns, although the effects did not reach significance because of small sample sizes. Transfection of synthetic miR-200 precursors into normal ovarian surface epithelial (OSE) and fallopian tube epithelial (FTE) cells confirmed reduced expression of the target genes and elevated levels of the effector genes CDH1, CRB3 and EpCAM in both normal OSE and FTE cells. However, only FTE cells had a specific induction of CA125 after miR-200 precursor transfection. CONCLUSIONS: The activation of the miR-200 pathway may be an early event that renders the OSE and FTE cells more susceptible to oncogenic mutations and histologic differentiation. As high-grade serous ovarian carcinomas (HGSOC) usually express high levels of CA125, the induction of CA125 expression in FTE cells by miR-200 precursor transfection is consistent with the notion that HGSOC has an origin in the distal fallopian tube.

Trajectories of quality of life, life satisfaction, and psychological adjustment after prostate cancer.

BACKGROUND: To describe trajectories of health-related quality of life (QoL), life satisfaction, and psychological adjustment for men with prostate cancer over the medium to long term and identify predictors of poorer outcomes using growth mixture models. METHODS: One-thousand sixty-four (82.4% response) men diagnosed with prostate cancer were recruited close to diagnosis and assessed over a 72-month (6-year) period with self-report assessment of health-related QoL, life satisfaction, cancer-related distress, and prostate specific antigen anxiety. Urinary, bowel, and sexual function were also assessed using validated questionnaires. RESULTS: Poorer physical QOL was predicted by older age, lower education, lower income, comorbidities, and receiving hormone therapy. Lower life satisfaction was related to younger age, lower income, not being partnered, and comorbidities. Poorer psychological trajectories were predicted by younger age, lower income, comorbidities, and receiving radical prostatectomy or brachytherapy. Better urinary, bowel, and sexual function were related to better global outcomes over time. Anxiety about prostate specific antigen testing was rare. CONCLUSIONS: Distinct trajectories exist for medium- to long-term QoL, life satisfaction, and psychological adjustment after prostate cancer; with age and socioeconomic deprivation playing a differential role in men's survivorship profile and the impact of functional status on outcomes increasing over time. These results reinforce the need for an appraisal of men's life course in addition to treatment side effects when planning survivorship care after cancer.