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.

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.

Ferroportin expression and regulation in human placenta/fetal membranes: Implications for ferroptosis and adverse pregnancy outcomes.

Iron overload is associated with pregnancy complications. Ferroportin (FPN) is the only known iron exporter in mammalian cells. We hypothesize that FPN is functionally important in ferrotopsis, a process of iron-dependent non-apoptotic programmed cell death, and may have a critical role to play in pregnancy success. We investigated the expression of FPN in placenta/fetal membranes by immunohistochemistry in tissues collected from pregnancies with/without preeclampsia (PE) and spontaneous preterm birth (SPTB). FPN was highly expressed in both trophoblasts and decidual cells found in placenta/fetal membranes. Staining was significantly reduced in fetal membranes from SPTB versus healthy pregnancies (P = 0.046). FPN expression in immortalized human endometrial stromal cells (HESC) increased with in vitro decidualization induction using 1 µM of medroxyprogesterone acetate and 0.5 mM of dibutyryl-cAMP. In addition, both HESC cells and immortalized extravillous trophoblast SW71 cells with FPN knockdown showed significant sensitivity to ferroptosis inducer, erastin (P < 0.001 and P = 0.009, respectively). The survival of both HESC and SW71 cells was not negatively affected by iron supplementation with ferric ammonium citrate in the medium. However, SW71 cells were more sensitive than HESC cells to physiologic iron in the presence of a non-lethal dose of erastin (P < 0.001). Taken together, our data demonstrating increased sensitivity of FPN knockdown HESC and SW71 cells to erastin and increased sensitivity of trophoblasts to iron overload under ferroptotic stress support the hypothesis that FPN protects against ferroptosis during pregnancy.

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.

The determinants of growth failure in children under five in 25 low- and middle-income countries.

Background: Past studies have identified determinants of growth failure (GF) such as socio-economic, nutritional, parenting, and inequality factors. However, few studies investigate the numerous causes of GF across multiple countries. By analysing the data of children under five in 25 low and middle-income countries, this study aims to examine the correlations of determinants with GF to identify the strongest modifiable risk factors. Methods: Cross-sectional study design was used, and data were collected across 25 LMICs by the United Nations Children's Fund in 2019. Regions and households were randomly selected in participating LMICs. The four outcome measures were stunting, wasting, underweight and low body mass index (BMI). Results: Multilevel analysis was performed to identify the impact of country, suburb, and household levels on the variance of outcome variables. GF measures were significantly correlated with low gross domestic product (GDP) per capita (odds ratio (OR) = 2.482), rural areas (OR = 1.223), lack of health insurance (OR = 1.474), low maternal education (OR = 2.260), lack of plain water (OR = 1.402), poor maternal physical caregiving ability (OR = 1.112), low carbohydrate consumption (OR = 1.470), and continued breastfeeding in children >12 months old (OR = 0.802). Conclusions: By identifying key GF risk factors, this study may provide valuable insights for policymaking and interventions. This may allow the prioritisation of resources within countries for preventative measures to be developed.

Are clinical outcomes associated with baseline sensory profiles in people with musculoskeletal shoulder pain? Protocol for a prospective longitudinal observational study.

BACKGROUND: Musculoskeletal shoulder pain is a common problem and its symptoms often become persistent. The experience of pain is multidimensional, and therefore, a range of patient characteristics may influence treatment response. An altered sensory processing has been associated with persistent musculoskeletal pain states and may contribute to outcomes in patients with musculoskeletal shoulder pain. The presence and potential impact of altered sensory processing in this patient cohort is not currently known. The aim of this prospective longitudinal cohort study is to investigate if baseline sensory characteristics are associated with clinical outcomes in patients presenting to a tertiary hospital with persistent musculoskeletal shoulder pain. If found, a relationship between sensory characteristics and outcome may lead to the creation of more effective treatment strategies and improvements in risk adjustment and prognosis. METHODS: This is a single-centre prospective cohort study with 6-, 12- and 24-month follow-up. A total of 120 participants aged ≥18 years with persistent musculoskeletal shoulder pain (≥3 months) will be recruited from an Australian public tertiary hospital orthopaedic department. Baseline assessments, including quantitative sensory tests and a standardised physical examination, will be performed. In addition, information will be obtained from patient interviews, self-report questionnaires and medical records. Follow-up outcome measures will comprise information from the Shoulder Pain and Disability Index and a six-point Global Rating of Change scale. ANALYSIS: Descriptive statistics will be used to report baseline characteristics and outcome measures over time. Change in outcome measures at the primary endpoint of six months from baseline will be calculated using paired t-tests. Associations between baseline characteristics and outcomes at a 6-month follow-up will be reported using multivariable linear and logistic regression models. DISCUSSION: Understanding the relationship between sensory profile and the variable response to treatment in people with persistent musculoskeletal shoulder pain may enhance our understanding of the mechanisms contributing to the presentation. In addition, through better understanding of the contributing factors, the results of this study may contribute to the development of an individualised, patient-centred approach to treatment for people with this highly prevalent and debilitating condition.

Seemingly Unrelated Regression Analysis of the Cost and Health-Related Quality of Life Outcomes of the REVAMP Randomized Clinical Trial.

OBJECTIVE: This study aimed to evaluate the 9-month cost and health-related quality of life (HRQOL) outcomes of resistance versus viral load testing strategies to manage virological failure in low-middle income countries. METHODS: We analyzed secondary outcomes from the REVAMP clinical trial: a pragmatic, open label, parallel-arm randomized trial investigating resistance versus viral load testing for individuals failing first-line treatment in South Africa and Uganda. We collected resource data, valued according to local cost data and used the 3-level version of EQ-5D to measure HRQOL at baseline and 9 months. We applied seemingly unrelated regression equations to account for the correlation between cost and HRQOL. We conducted intention-to-treat analyses with multiple imputation using chained equations for missing data and performed sensitivity analyses using complete cases. RESULTS: For South Africa, resistance testing and opportunistic infections were associated with statistically significantly higher total costs, and virological suppression was associated with lower total cost. Higher baseline utility, higher cluster of differentiation 4 (CD4) count, and virological suppression were associated with better HRQOL. For Uganda, resistance testing and switching to second-line treatment were associated with higher total cost, and higher CD4 was associated with lower total cost. Higher baseline utility, higher CD4 count, and virological suppression were associated with better HRQOL. Sensitivity analyses of the complete-case analysis confirmed the overall results. CONCLUSION: Resistance testing showed no cost or HRQOL advantage in South Africa or Uganda over the 9-month REVAMP clinical trial.

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.

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.

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.

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.

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.

Can Administrative Health Data Improve the Gold Standard? Evidence from a Model of the Progression of Myocardial Infarction.

Background: Myocardial infarction (MI), remains one of the leading causes of death and disability globally but publications on the progression of MI using data from the real world are limited. Multistate models have been widely used to estimate transition rates between disease states to evaluate the cost-effectiveness of healthcare interventions. We apply a Bayesian multistate hidden Markov model to investigate the progression of MI using a longitudinal dataset from Queensland, Australia. Objective: To apply a new model to investigate the progression of myocardial infarction (MI) and to show the potential to use administrative data for economic evaluation and modeling disease progression. Methods: The cohort includes 135,399 patients admitted to public hospitals in Queensland, Australia, in 2010 treatment of cardiovascular diseases. Any subsequent hospitalizations of these patients were followed until 2015. This study focused on the sub-cohort of 8705 patients hospitalized for MI. We apply a Bayesian multistate hidden Markov model to estimate transition rates between health states of MI patients and adjust for delayed enrolment biases and misclassification errors. We also estimate the association between age, sex, and ethnicity with the progression of MI. Results: On average, the risk of developing Non-ST segment elevation myocardial infarction (NSTEMI) was 8.7%, and ST-segment elevation myocardial infarction (STEMI) was 4.3%. The risk varied with age, sex, and ethnicity. The progression rates to STEMI or NSTEMI were higher among males, Indigenous, or elderly patients. For example, the risk of STEMI among males was 4.35%, while the corresponding figure for females was 3.71%. After adjustment for misclassification, the probability of STEMI increased by 1.2%, while NSTEMI increased by 1.4%. Conclusions: This study shows that administrative health data were useful to estimate factors determining the risk of MI and the progression of this health condition. It also shows that misclassification may cause the incidence of MI to be under-estimated.

Trading Health for Wealth: The Effect of COVID-19 Response Stringency.

International governments' COVID-19 responses must balance human and economic health. Beyond slowing viral transmission, strict lockdowns have severe economic consequences. This work investigated response stringency, quantified by the Oxford COVID-19 Government Response Tracker's Stringency Index, and examined how restrictive interventions affected infection rates and gross domestic product (GDP) in China and OECD countries. Accounting for response timing, China imposed the most stringent restrictions, while Sweden and Japan were the least stringent. Expected GDP declines range from -8% (Japan) to -15.4% (UK). While greater restrictions generally slowed viral transmission, they failed to reach statistical significance and reduced GDP (p = 0.006). Timing was fundamental: governments who responded to the pandemic faster saw greater reductions in viral transmission (p = 0.013), but worse decreases in GDP (p = 0.044). Thus, response stringency has a greater effect on GDP than infection rates, which are instead affected by the timing of COVID-19 interventions. Attempts to mitigate economic impacts by delaying restrictions or decreasing stringency may buoy GDP in the short term but increase infection rates, the longer-term economic consequences of which are not yet fully understood. As highly restrictive interventions were successful in some but not all countries, decision-makers must consider whether their strategies are appropriate for the country on health and economic grounds.

Characterization of miR-200 family members as blood biomarkers for human and laying hen ovarian cancer.

MicroRNA-200 (miR-200) family is highly expressed in ovarian cancer. We evaluated the levels of family members relative to the internal control miR-103a in ovarian cancer and control blood specimens collected from American and Hong Kong Chinese institutions, as well as from a laying hen spontaneous ovarian cancer model. The levels of miR-200a, miR-200b and miR-200c were significantly elevated in all human cancer versus all control blood samples. Further analyses showed significantly higher miR-200 levels in Chinese control (except miR-429) and cancer (except miR-200a and miR141) samples than their respective American counterparts. Subtype-specific analysis showed that miR-200b had an overall elevated level in serous cancer compared with controls, whereas miR-429 was significantly elevated in clear cell and endometrioid cancer versus controls. MiR-429 was also significantly elevated in cancer versus control in laying hen plasma samples, consistent with the fact that endometrioid tumor is the prevalent type in this species. A neural network model consisting of miR-200a/200b/429/141 showed an area under the curve (AUC) value of 0.904 for American ovarian cancer prediction, whereas a model consisting of miR-200b/200c/429/141 showed an AUC value of 0.901 for Chinese women. Hence, miR-200 is informative as blood biomarkers for both human and laying hen ovarian cancer.

The Effect of Multimorbidity Patterns and the Impact of Comorbid Anxiety and Depression on Primary Health Service Use: The Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) Study.

This study sought to determine patterns of multimorbidity and quantify their impact on use of primary health services in the presence and absence of anxiety and depression among a cohort of urban community-dwelling men in Australia. The analytic sample consisted of men (n = 2039; age 38-85) from the follow-up wave of a prospective cohort study of all participants of the Florey Adelaide Male Ageing Study (FAMAS; Stage 2 [2007-2010]) and age-matched men from the North-West Adelaide Health Study (NWAHS; Stage 3 [2008-2010]). Self-reported data and linkage with a national universal health coverage scheme (Medicare) provided information on the prevalence of eight chronic conditions and health service utilization information (including annual GP visits). Obesity and cardiovascular disease (CVD) were associated with the highest number of comorbid conditions. Two nonrandom multimorbidity "clusters" emerged: "CVD, Obesity, Diabetes" and "CVD, Obesity, Osteoarthritis." Participants with conditions comorbid with CVD were more likely to have 10 or more annual GP visits, compared to multimorbidity involving other conditions. In comparison to participants without CVD, the presence of CVD increased the chance of having 10 or more annual GP visits (adjusted risk ratio: 3.7; 95% CI [2.8, 4.8]). When CVD was comorbid with anxiety and depression, having 10 or more annual GP visits was more common (adjusted risk ratio: 1.8; 95% CI [1.2, 2.5]). Multimorbidity patterns involving CVD, especially for multimorbidity that includes CVD with comorbid anxiety and depression, should be considered in developing clinical trials to better inform medical decision-making and care for patients with CVD and comorbid conditions.

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.

Transanal total mesorectal excision the Gold Coast experience: learning curve and comparison to traditional technique.

BACKGROUND: Laparoscopic and open techniques in rectal cancer are well-published, however, technical challenges remain for mid to low rectal cancer resections in the narrow pelvis. Transanal total mesorectal excision (taTME) has been pioneered to potentially circumvent these challenges. The aims of this study were to evaluate the learning curve associated with our first cases of taTME as well as compare outcomes to that of conventionally performed rectal resections. METHODS: This was a single-centre retrospective study with data collated from all elective resections by the colorectal unit from 2015 to 2017. Primary outcome was completeness of total mesorectal excision and secondary outcomes were intra- and post-operative morbidity and mortality. RESULTS: A total of 43 patients were identified. Of which, 20 underwent taTME. Mesorectal completeness was obtained in only 47.4% in the taTME group compared to 78.3% in the anterior resection group (p = 0.115). 5.9% of patients in our taTME group had positive circumferential resection margin compared to nil in the anterior resection. Conversion rates were greater in the taTME group (15% versus 0%; 0.028). Operative time, length of stay and clavien IV and V complications were greater in the taTME group. CONCLUSION: This study highlights the difficulty in introducing a novel technique given the learning curve. Our results would expect to improve with increased caseload.

Pharmacokinetic modeling to determine the minimum effective dose of disease-specific antibodies for preventing hepatitis A post-exposure.

BACKGROUND: The minimum effective dose of intramuscular polyvalent immune globulin for prevention of hepatitis A post-exposure is unknown. In Australia current dosing is according to weight category. METHODS: The peak concentration and decay of hepatitis A antibodies after intramuscular dosing of immune globulin in adults was modeled utilizing published parameters. Models simulated dosing according to current Australian guidelines, then adjusted the dose in clinically relevant increments to estimate the optimal dose of hepatitis A antibodies for post-exposure prophylaxis of nonimmune individuals. Optimal dosing assumed a target serum concentration of hepatitis A antibodies of the correlate of protection plus a 10% margin of error at an incubation period. The effect of weight on hepatitis A antibody concentration at an incubation period under current guidelines was examined by fixing weight in 5 kg increments. RESULTS: Current dosing guidelines in Australia may underdose people who weigh in excess of 85 kg. The optimal dose of hepatitis A-specific antibodies according to the model was 3.6, 2.5, and 1.9 IU/kg assuming 50%, 75% and 100% bioavailability respectively. CONCLUSIONS: For individuals in Australia recommended passive immunization as post-exposure prophylaxis and weighing in excess of 85 kg, conservative management would include dosing between 2.5 and 3.6 IU hepatitis A antibodies/kg.

MicroRNA-200 family governs ovarian inclusion cyst formation and mode of ovarian cancer spread.

Epidemiologic and histopathologic findings and the laying hen model support the long-standing incessant ovulation hypothesis and cortical inclusion cyst involvement in sporadic ovarian cancer development. MicroRNA-200 (miR-200) family is highly expressed in ovarian cancer. Herewith, we show that ovarian surface epithelial (OSE) cells with ectopic miR-200 expression formed stabilized cysts in three-dimensional (3D) organotypic culture with E-cadherin fragment expression and steroid hormone pathway activation, whereas ovarian cancer 3D cultures with miR-200 knockdown showed elevated TGF-ß expression, mitotic spindle disorientation, increased lumenization, disruption of ROCK-mediated myosin II phosphorylation, and SRC signaling, which led to histotype-dependent loss of collective movement in tumor spread. Gene expression profiling revealed that epithelial-mesenchymal transition and hypoxia were the top enriched gene sets regulated by miR-200 in both OSE and ovarian cancer cells. The molecular changes uncovered by the in vitro studies were verified in both human and laying hen ovarian cysts and tumor specimens. As miR-200 is also essential for ovulation, our results of estrogen pathway activation in miR-200-expressing OSE cells add another intriguing link between incessant ovulation and ovarian carcinogenesis.