An Economic Evaluation of a Web-Based Management Support System for Children With Urinary Incontinence: The eADVICE Trial.

PURPOSE: Children who require specialist outpatient care typically wait substantial periods during which their condition may progress, making treatment more difficult and costly. Timely and effective therapy during this period may reduce the need for lengthy specialist care. This study evaluated the cost-effectiveness of an individualized, evidence-informed, web-based program for children with urinary incontinence awaiting a specialist appointment (Electronic Advice and Diagnosis Via the Internet following Computerized Evaluation [eADVICE]) compared to usual care. eADVICE was supervised by a primary physician and delivered by an embodied conversational agent. MATERIALS AND METHODS: A trial-based cost-effectiveness analysis was performed from the perspective of the health care funder as a substudy of eADVICE, a multicenter, waitlist-controlled, randomized trial. Outcomes measures were incremental cost per incremental change in continence status and quality of life on an intention-to-treat basis. Uncertainty was examined using cost-effectiveness planes, scenarios, and 1-way sensitivity analyses. Costs were valued in 2021 Australian dollars. RESULTS: The use of eADVICE was found to be cost saving and beneficial (dominant) over usual care, with a higher proportion of children dry over 14 days at 6 months (risk difference 0.13; 95%CI 0.02-0.23, P = .03) and mean health care costs reduced by $188 (95%CI $61-$315) per participant. CONCLUSIONS: An individualized, evidence-informed, web-based program delivered by an embodied conversational agent is likely cost saving for children with urinary incontinence awaiting a specialist appointment. The potential economic impact of such a program is favorable and substantial, and may be transferable to outpatient clinic settings for other chronic health conditions.

Longitudinal assessment of the health-related quality of life of children and adolescents with chronic kidney disease.

In this multi-center longitudinal cohort study conducted in Australia and New Zealand, we assessed the trajectories of health-related quality of life (HRQoL) in children with chronic kidney disease (CKD) over time. A total of 377 children (aged 6-18 years) with CKD stages 1-5 (pre-dialysis), dialysis, or transplant, were followed biennially for four years. Multi Attribute Utility (MAU) scores of HRQoL were measured at baseline and at two and four years using the McMaster Health Utilities Index Mark 3 tool, a generic multi-attribute, preference-based system. A multivariable linear mixed model was used to assess the trajectories of HRQoL over time in 199 children with CKD stage 1-5, 43 children receiving dialysis and 135 kidney transplant recipients. An interaction between CKD stage at baseline and follow-up time indicated that the slopes of the HRQoL scores differed between children by CKD stage at inception. Over half of the cohort on dialysis at baseline had received a kidney transplant by the end of year four and the MAU scores of these children increased by a meaningful amount averaging 0.05 (95% confidence interval 0.01 to 0.09) per year in comparison to those who were transplant recipients at baseline. The mean difference between baseline and year two MAU scores was 0.09 (95% confidence interval -0.05, 0.23), (Cohen's d effect size 0.31). Thus, improvement in HRQoL over time of children on dialysis at baseline was likely to have been driven by their transition from dialysis to transplantation. Additionally, children with CKD stage 1-5 and transplant recipients at baseline had no changes in their disease stage or treatment modality and experienced stable HRQoL over time.

Acute Rejection, Overall Graft Loss, and Infection-related Deaths After Kidney Transplantation in Indigenous Australians.

Introduction: Aboriginal and Torres Strait Islander peoples (hereafter respectfully termed Indigenous Australians) experience a 3-fold increased risk of acute rejection after transplantation compared to non-Indigenous Australians. We investigated whether acute rejection explains the association between Indigenous status, infection-related deaths, and all-cause deaths after kidney transplantation, and whether acute rejection mediates the relationship between Indigenous status and overall graft loss. Methods: This cohort study included all recipients who received their first kidney transplant between 2005 and 2018 in Australia, using data from the Australia and New Zealand Dialysis and Transplant registry. Multivariable Cox regression models determined the associations between Indigenous status, graft loss, infection-related deaths, and all-cause deaths. Mediation analyses examined if acute rejection mediated these relationships. Primary outcome was infection-related death. Secondary outcomes included all-cause death and overall graft loss. Results: There were 9993 patients (n = 390 (3.9%) Indigenous Australians) who received a kidney transplant between 2005 and 2018, and they were followed-up with for 56,876 patient-years. A total of 1165 died (12%) (211 infection-related deaths) and 1957 (20%) lost their allografts. Compared with non-Indigenous recipients, the adjusted hazard ratio (HR) (95% confidence interval [CI]) for graft loss, infection-related deaths and all-cause deaths among Indigenous Australians were 2.27 (1.90-2.71), 3.01 (1.90-4.77) and 2.36 (1.89-2.94), respectively. The mediation analysis showed the association between Indigenous status and graft loss (but not infection-related death or all-cause death) was partially mediated by acute rejection (1.06 [1.03-1.09]), and the proportion of effects mediated by acute rejection was 0.10. Conclusion: Indigenous Australians experienced a higher risk of graft loss, a relationship mediated partially through acute rejection. The higher risk of infection-related death was independent of acute rejection.

Avoiding overadjustment bias in social epidemiology through appropriate covariate selection: a primer.

Obtaining accurate estimates of the causal effects of socioeconomic position (SEP) on health is important for public health interventions. To do this, researchers must identify and adjust for all potential confounding variables, while avoiding inappropriate adjustment for mediator variables on a causal pathway between the exposure and outcome. Unfortunately, 'overadjustment bias' remains a common and under-recognized problem in social epidemiology. This paper offers an introduction on selecting appropriate variables for adjustment when examining effects of SEP on health, with a focus on overadjustment bias. We discuss the challenges of estimating different causal effects including overadjustment bias, provide guidance on overcoming them, and consider specific issues including the timing of variables across the life-course, mutual adjustment for socioeconomic indicators, and conducting systematic reviews. We recommend three key steps to select the most appropriate variables for adjustment. First, researchers should be clear about their research question and causal effect of interest. Second, using expert knowledge and theory, researchers should draw causal diagrams representing their assumptions about the interrelationships between their variables of interest. Third, based on their causal diagram(s) and causal effect(s) of interest, researchers should select the most appropriate set of variables, which maximizes adjustment for confounding while minimizing adjustment for mediators.

Special health care needs during childhood and academic achievement in secondary school.

BACKGROUND: Secondary education has lifelong implications for wellbeing. We evaluated associations between the duration and timing of special health care needs (SHCN) across childhood and academic achievement in secondary school. METHODS: Cohort design. The structured modelling approach was used to evaluate life-course models for associations between the duration and timing of SHCN (measured using a two-item SHCN screener across ages 4-5, 6-7, 8-9 and 10-11 years) and Grade 7 (median age 12.5 years) reading and numeracy achievement. Linear regressions were fitted for each life-course model: four critical period models (each including SHCN exposure in one period), one sensitive period model (including SHCN exposure in all periods) and two strict accumulation models (including the duration of SHCN exposure in linear form then categorical form). Interactions of SHCN with child sex and family socio-economic status (SES) were examined. RESULTS: Of 3734 children, 1845 were female. The number of children with SHCN was 434 (11.7%), 458 (12.9%), 534 (14.7%), 551 (15.4%) at 4-5, 6-7, 8-9 and 10-11 years respectively. For both outcomes, the linear strict accumulation model fitted best, and interactions of SHCN with sex and SES were non-significant. The average decrease in school achievement z score (95% confidence interval) per period of having SHCN was 0.04 (-0.07 to -0.02) for reading and 0.08 (-0.11 to -0.05) for numeracy. CONCLUSIONS: A longer duration of SHCN from age 4-11 years has small-sized cumulative associations with poorer Grade 7 reading and numeracy achievement. Each period of SHCN between 4 and 5 and 10-11 years was associated with nearly 0.05 and 0.1 of a standard deviation reduction in Grade 7 reading and numeracy scores respectively, and these associations did not appear to differ across sex or SES. These findings suggest that children with persistent SHCN are at risk of academic deficits and should receive focused interventions.

Improve in-depth immunological risk assessment to optimize genetic-compatibility and clinical outcomes in child and adolescent recipients of parental donor kidney transplants: protocol for the INCEPTION study.

BACKGROUND: Parental donor kidney transplantation is the most common treatment option for children and adolescents with kidney failure. Emerging data from observational studies have reported improved short- and medium-term allograft outcomes in recipients of paternal compared to maternal donors. The INCEPTION study aims to identify potential differences in immunological compatibility between maternal and paternal donor kidneys and ascertain how this affects kidney allograft outcomes in children and adolescents with kidney failure. METHODS: This longitudinal observational study will recruit kidney transplant recipients aged ≤18 years who have received a parental donor kidney transplant across 4 countries (Australia, New Zealand, United Kingdom and the Netherlands) between 1990 and 2020. High resolution human leukocyte antigen (HLA) typing of both recipients and corresponding parental donors will be undertaken, to provide an in-depth assessment of immunological compatibility. The primary outcome is a composite of de novo donor-specific anti-HLA antibody (DSA), biopsy-proven acute rejection or allograft loss up to 60-months post-transplantation. Secondary outcomes are de novo DSA, biopsy-proven acute rejection, acute or chronic antibody mediated rejection or Chronic Allograft Damage Index (CADI) score of > 1 on allograft biopsy post-transplant, allograft function, proteinuria and allograft loss. Using principal component analysis and Cox proportional hazards regression modelling, we will determine the associations between defined sets of immunological and clinical parameters that may identify risk stratification for the primary and secondary outcome measures among young people accepting a parental donor kidney for transplantation. This study design will allow us to specifically investigate the relative importance of accepting a maternal compared to paternal donor, for families deciding on the best option for donation. DISCUSSION: The INCEPTION study findings will explore potentially differential immunological risks of maternal and paternal donor kidneys for transplantation among children and adolescents. Our study will provide the evidence base underpinning the selection of parental donor in order to achieve the best projected long-term kidney transplant and overall health outcomes for children and adolescents, a recognized vulnerable population. TRIAL REGISTRATION: The INCEPTION study has been registered with the Australian New Zealand Clinical Trials Registry, with the trial registration number of ACTRN12620000911998 (14th September 2020).

Estimating Age- and Sex-Specific Utility Values from the CHU9D Associated with Child and Adolescent BMI z-Score.

OBJECTIVE: Our objective was to identify age- and sex-specific utilities for children and adolescents by body mass index (BMI) z-score. METHODS: We used data from 6822 participants and 12,094 observations from two cohorts and two waves of interviews from the Longitudinal Study of Australian Children. We fit linear models using generalised estimating equations to investigate associations between Child Health Utility 9D and BMI z-score in girls and boys aged 10-17 years. We initially fit models for each sex, fully adjusted for known predictors of health-related quality of life, including socioeconomic position, long-term medical condition and maternal smoking status and also included an interaction between age and BMI z-score to examine age-specific effects. Finally, we derived a minimal model for each sex by eliminating interaction terms with P > 0.01 and predictors with P > 0.05. RESULTS: Our adjusted results show different utility patterns in girls and boys. In girls, utility decrements for each unit increase in BMI z-score changed with age (P < 0.01 for interaction between age and BMI z-score). At age 10 years, the mean utility decrement for each unit increase in BMI z-score was 0.002 (95% confidence interval [CI] 0.011 decrement to 0.006 increment), but, by age 17 years, this utility decrement was 0.023 (95% CI 0.013 to 0.032). In boys, small non-significant decrements were found in utility for each unit increase in BMI z-score, with no observable change with age. CONCLUSION: Our analyses demonstrated that age and sex should be considered when attributing utility values and decrements to BMI z-scores.

Dementia and caregiver burden: A three-year longitudinal study.

OBJECTIVES: Dementia, with its progressive cognitive and functional decline and associated neuropsychiatric symptoms, places a large burden on caregivers. While frequently studied, longitudinal findings about the overall trajectory of burden are mixed. The study sought to characterize caregiver burden over a 3-year period and identify predictors of this burden. METHODS: Seven-hundred-and-eighty-one patients with dementia were recruited from nine memory clinics around Australia. Measures of caregiver burden, cognition, function, and neuropsychiatric symptoms were completed with patients and their caregivers at regular intervals over a 3-year period. Patients' level of services and medication use were also recorded. RESULTS: Of the 720 patients with measures of caregiver burden at baseline, 47.4% of caregivers had clinically significant levels of burden. This proportion increased over time, with 56.8% affected at 3 years. Overall levels of burden increased for caregivers of patients without services, though did not change for caregivers of patients receiving services or residential care after controlling for other variables. Patient characteristics-including greater neuropsychiatric symptoms, lower functional ability, fewer medications, lack of driving ability-and female sex of caregivers were associated with greater burden. CONCLUSIONS: High levels of caregiver burden are present in a large proportion of caregivers of people with dementia and this increases over time for those without services. Clinical characteristics of patients (including neuropsychiatric symptoms, function, overall health, driving status), level of services, and caregiver sex appear to be the best predictors of this burden. These characteristics may help identify caregivers at greater risk of burden to target for intervention.

Mild Cognitive Impairment and Caregiver Burden: A 3-Year-Longitudinal Study.

OBJECTIVES: Mild cognitive impairment (MCI) is common, affecting 10%-35% of people over 65, and poses unique challenges for patients and their caregivers. Comparatively little research has examined caregiver burden in this population, with longitudinal research, in particular, lacking. We examined caregiver burden in a sample of people with MCI over 3 years. DESIGN: Three-year observational study. SETTING: Nine memory clinics in Australia. PARTICIPANTS: One-hundred-and-eighty-five people with MCI and their caregivers. MEASUREMENTS: Measures of caregiver burden, cognition, function, neuropsychiatric symptoms, driving status, and medication use were completed with patients and their caregivers at regular intervals over a 3-year period. RESULTS: Between 21.1% and 29.5% of caregivers reported a clinically significant level of burden over the study. Patients' higher levels of neuropsychiatric symptoms, lower functional ability, and lack of driving ability, and caregivers' employment were associated with greater caregiver burden over time. Caregiver burden did not increase over time when controlling for patient and caregiver characteristics. CONCLUSIONS: High levels of caregiver burden are present in a significant proportion of caregivers of people with MCI. Clinical characteristics of patients - including severity of neuropsychiatric symptoms and functional impairment - and the employment status of caregivers predict burden. Such characteristics may help identify caregivers at greater risk of burden to target for intervention.

Identifying Important Outcomes for Young People With CKD and Their Caregivers: A Nominal Group Technique Study.

RATIONALE & OBJECTIVE: Chronic kidney disease (CKD) has wide-ranging and long-term consequences for young people and their families. The omission of outcomes that are important to young people with CKD and their caregivers limits knowledge to guide shared decision making. We aimed to identify the outcomes that are important to young people with CKD and their caregivers. STUDY DESIGN: We used the nominal group technique whereby participants identified and ranked outcomes and explained their priorities. SETTINGS & PARTICIPANTS: Young people with CKD (stages 1-5, dialysis, or transplantation) and their caregivers were purposively sampled from 6 centers across Australia, the United States, and Canada. ANALYTICAL APPROACH: Importance scores were calculated (scale of 0-1), and qualitative data were analyzed thematically. RESULTS: 34 patients (aged 8-21 years) and 62 caregivers participated in 16 groups and identified 48 outcomes. The 5 highest ranked outcomes for patients were survival (importance score, 0.25), physical activity (0.24), fatigue (0.20), lifestyle restrictions (0.20), and growth (0.20); and for caregivers, kidney function (0.53), survival (0.28), infection (0.22), anemia (0.20), and growth (0.17). 12 themes were identified reflecting their immediate and current priorities (wanting to feel normal, strengthening resilience, minimizing intrusion into daily life, imminent threats to life, devastating family burdens, and seeking control over health) and considerations regarding future impacts (protecting health/development, remaining hopeful, concern for limited opportunities, prognostic uncertainty, dreading painful and invasive procedures, and managing expectations). LIMITATIONS: Only English-speaking participants were recruited. CONCLUSIONS: Kidney function, infection, survival, and growth were the highest priorities for patients with CKD and their caregivers. Young people with CKD also prioritized highly the outcomes that directly affected their lifestyle and sense of normality, while caregiver's highest priorities concerned the long-term health of their child, current health problems, and the financial and family burdens of caring for a child with CKD.

Identifying patient-important outcomes in polycystic kidney disease: An international nominal group technique study.

AIM: Patients with autosomal dominant polycystic kidney disease (ADPKD) are at increased risk of premature mortality, morbidities and complications, which severely impair quality of life. However, patient-centered outcomes are not consistently reported in trials in ADPKD, which can limit shared decision-making. We aimed to identify outcomes important to patients and caregivers and the reasons for their priorities. METHODS: Nominal group technique was adopted involving patients with ADPKD and caregivers who were purposively selected from eight centres across Australia, France and the Republic of Korea. Participants identified, ranked and discussed outcomes for trials in ADPKD. We calculated an importance score (0-1) for each outcome and conducted thematic analyses. RESULTS: Across 17 groups, 154 participants (121 patients, 33 caregivers) aged 19 to 78 (mean 54.5 years) identified 55 outcomes. The 10 highest ranked outcomes were: kidney function (importance score 0.36), end-stage kidney disease (0.32), survival (0.21), cyst size/growth (0.20), cyst pain/bleeding (0.18), blood pressure (0.17), ability to work (0.16), cerebral aneurysm/stroke (0.14), mobility/physical function (0.12), and fatigue (0.12). Three themes were identified: threatening semblance of normality, inability to control and making sense of diverse risks. CONCLUSION: For patients with ADPKD and their caregivers, kidney function, delayed progression to end-stage kidney disease and survival were the highest priorities, and were focused on achieving normality, and maintaining control over health and lifestyle. Implementing these patient-important outcomes may improve the meaning and relevance of trials to inform clinical care in ADPKD.

The Impact of Age on Income-Related Health Status Inequalities from Birth to Adolescence: A Systematic Review with Cross-Country Comparisons.

OBJECTIVES: To examine the effect of age on associations between household income and overall health from birth to adolescence, and whether age patterns vary by country. It is uncertain whether income-related health inequalities remain stable, widen, or narrow as children age, which impacts optimal timing of equity-focused interventions. STUDY DESIGN: Systematic review (CRD42016038583) of MEDLINE, Embase, PsycINFO, CINAHL, SocINDEX (full-text), and EconLit (full-text) to April 2017. We included observational studies and trials in children and adolescents (0-18 years of age), examining age differences in associations between income and overall health (self-rated, clinician-rated, proxy-rated). One reviewer extracted data; 2 evaluated risk of bias. RESULTS: Thirty-eight articles containing 43 studies (30 cross-sectional, 13 cohort) were identified, from high-income (n = 39) and middle-income (n = 4) countries. In the US (n = 21), positive income-health associations emerged in early childhood, and these inequalities typically widened progressively into adolescence. Relative to 0- to 3-year-olds, ratios of income-health coefficients ranged from 1.10-3.71 for 4-8 years of age, 1.26-3.86 for 9-12 years of age, 1.36-6.71 for 13-17 years. In the United Kingdom and Ireland (n = 8), inequalities emerged in early-to-mid childhood, but age patterns were less consistent. In other high-income countries (Australia, Canada, France, Germany, Japan, Republic of Korea), inequalities mostly persisted or widened with age. In middle-income countries, inequalities appeared to narrow (Indonesia n = 2) or persist (Brazil n = 2) with age. Limitations are unclear/high risk of bias and dataset overlap for some studies. CONCLUSIONS: In many countries, income-related health status inequalities persist or widen as children age. Interventions that improve health equity early in the life-course are needed.

Identifying Outcomes that Are Important to Living Kidney Donors: A Nominal Group Technique Study.

BACKGROUND AND OBJECTIVES: Living kidney donor candidates accept a range of risks and benefits when they decide to proceed with nephrectomy. Informed consent around this decision assumes they receive reliable data about outcomes they regard as critical to their decision making. We identified the outcomes most important to living kidney donors and described the reasons for their choices. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Previous donors were purposively sampled from three transplant units in Australia (Sydney and Melbourne) and Canada (Vancouver). In focus groups using the nominal group technique, participants identified outcomes of donation, ranked them in order of importance, and discussed the reasons for their preferences. An importance score was calculated for each outcome. Qualitative data were analyzed thematically. RESULTS: Across 14 groups, 123 donors aged 27-78 years identified 35 outcomes. Across all participants, the ten highest ranked outcomes were kidney function (importance=0.40, scale 0-1), time to recovery (0.27), surgical complications (0.24), effect on family (0.22), donor-recipient relationship (0.21), life satisfaction (0.18), lifestyle restrictions (0.18), kidney failure (0.14), mortality (0.13), and acute pain/discomfort (0.12). Kidney function and kidney failure were more important to Canadian participants, compared with Australian donors. The themes identified included worthwhile sacrifice, insignificance of risks and harms, confidence and empowerment, unfulfilled expectations, and heightened susceptibility. CONCLUSIONS: Living kidney donors prioritized a range of outcomes, with the most important being kidney health and the surgical, lifestyle, functional, and psychosocial effects of donation. Donors also valued improvements to their family life and donor-recipient relationship. There were clear regional differences in the rankings.

Autoregressive and cross-lagged model for bivariate non-commensurate outcomes.

Autoregressive and cross-lagged models have been widely used to understand the relationship between bivariate commensurate outcomes in social and behavioral sciences, but not much work has been carried out in modeling bivariate non-commensurate (e.g., mixed binary and continuous) outcomes simultaneously. We develop a likelihood-based methodology combining ordinary autoregressive and cross-lagged models with a shared subject-specific random effect in the mixed-model framework to model two correlated longitudinal non-commensurate outcomes. The estimates of the cross-lagged and the autoregressive effects from our model are shown to be consistent with smaller mean-squared error than the estimates from the univariate generalized linear models. Inclusion of the subject-specific random effects in the proposed model accounts for between-subject variability arising from the omitted and/or unobservable, but possibly explanatory, subject-level predictors. Our model is not restricted to the case with equal number of events per subject, and it can be extended to different types of bivariate outcomes. We apply our model to an ecological momentary assessment study with complex dependence and sampling data structures. Specifically, we study the dependence between the condom use and sexual satisfaction based on the data reported in a longitudinal study of sexually transmitted infections. We find negative cross-lagged effect between these two outcomes and positive autoregressive effect within each outcome. Copyright © 2017 John Wiley & Sons, Ltd.

Getting it Right: study protocol to determine the diagnostic accuracy of a culturally-specific measure to screen for depression in Aboriginal and/or Torres Strait Islander people.

INTRODUCTION: A freely available, culturally valid depression screening tool is required for use by primary care services across Australia to screen for depression in Aboriginal and/or Torres Strait Islander populations. This is the protocol for a study aiming to determine the validity, sensitivity and specificity of the culturally adapted 9-item Patient Health Questionnaire (aPHQ-9). METHODS AND ANALYSIS: Cross-sectional validation study. A total of 500 people who self-identify as Aboriginal and/or Torres Strait Islander, are ≥18 years of age, attending 1 of 10 primary healthcare services or service events across Australia and able to communicate sufficiently to answer study questions will be recruited. All participants will complete the aPHQ-9 and the criterion standard MINI International Neuropsychiatric Interview (MINI) 6.0.0. The primary outcome is the criterion validity of the aPHQ-9. Process outcomes related to acceptability and feasibility of the aPHQ-9 will be analysed only if the measure is found to be valid. ETHICS AND DISSEMINATION: Lead ethical approval was obtained jointly from the University of Sydney Human Research Ethics Committee (project 2014/361) and the Aboriginal Health and Medical Research Council of New South Wales (project 1044/14). Results will be disseminated via the usual scientific forums, including peer-reviewed publications and presentations at international conferences following presentation to, discussion with and approval by participating primary healthcare service staff and community. TRIAL REGISTRATION NUMBER: ACTRN12614000705684.

Prospective diagnostic test accuracy comparison of computed tomography during arterial portography and Primovist magnetic resonance imaging in the pre-operative assessment of colorectal cancer liver metastases.

OBJECTIVES: To assess and compare the accuracy and inter-observer agreement for the detection of liver lesions using Primovist magnetic resonance imaging (pMRI) and computed tomography during arterial portography (CTAP). METHODS: Patients evaluated at St George Hospital Liver Unit for colorectal liver metastases (CRCLM) underwent CTAP as part of standard staging. pMRI was added to the pre-operative assessment. Two radiologists reported CTAP and two reported pMRI. The sensitivity and specificity of CTAP and pMRI were calculated using histopathology as the gold standard. RESULTS: Complete data were available for 62 patients corresponding to 219 lesions confirmed on histopathology. Agreement on the detection of lesions between the two radiologists that reported pMRI was higher than for CTAP (Kappa = 0.80 versus 0.74). Specificity of lesion detection for pMRI was 0.88 and 0.83 for CTAP (P = 0.112). Sensitivity for pMRI was 0.83 and 0.81 for CTAP. For patients who had chemotherapy before evaluation, pMRI had a significantly higher specificity than CTAP (0.79 versus 0.63, P = 0.011). CONCLUSIONS: pMRI is less invasive, has a good inter-observer agreement, has comparable sensitivity and specificity to CTAP in the pre-chemotherapy population and demonstrates better specificity in patients assessed post-chemotherapy. pMRI is a valid alternative to CTAP in the assessment of CRCLM.

General practitioners' use of absolute risk versus individual risk factors in cardiovascular disease prevention: an experimental study.

OBJECTIVE: To understand general practitioners' (GPs) use of individual risk factors (blood pressure and cholesterol levels) versus absolute risk in cardiovascular disease (CVD) risk management decision-making. DESIGN: Randomised experiment. Absolute risk, systolic blood pressure (SBP), cholesterol ratio (total cholesterol/high-density lipoprotein (TC/HDL)) and age were systematically varied in hypothetical cases. High absolute risk was defined as 5-year risk of a cardiovascular event >15%, high blood pressure levels varied between SBP 147 and 179 mm Hg and high cholesterol (TC/HDL ratio) between 6.5 and 7.2 mmol/L. SETTING: 4 GP conferences in Australia. PARTICIPANTS: 144 Australian GPs. OUTCOMES: GPs indicated whether they would prescribe cholesterol and/or blood pressure lowering medication. Analyses involved logistic regression. RESULTS: For patients with high blood pressure: 93% (95% CI 86% to 96%) of high absolute risk patients and 83% (95% CI 76% to 88%) of lower absolute risk patients were prescribed blood pressure medication. Conversely, 30% (95% CI 25% to 36%) of lower blood pressure patients were prescribed blood pressure medication if absolute risk was high and 4% (95% CI 3% to 5%) if lower. 69% of high cholesterol/high absolute risk patients were prescribed cholesterol medication (95% CI 61% to 77%) versus 34% of high cholesterol/lower absolute risk patients (95% CI 28% to 41%). 36% of patients with lower cholesterol (95% CI 30% to 43%) were prescribed cholesterol medication if absolute risk was high versus 10% if lower (95% CI 8% to 13%). CONCLUSIONS: GPs' decision-making was more consistent with the management of individual risk factors than an absolute risk approach, especially when prescribing blood pressure medication. The results suggest medical treatment of lower risk patients (5-year risk of CVD event <15%) with mildly elevated blood pressure or cholesterol levels is likely to occur even when an absolute risk assessment is specifically provided. The results indicate a need for improving uptake of absolute risk guidelines and GP understanding of the rationale for using absolute risk.

Flow cytometry assessment of graft-infiltrating lymphocytes can accurately identify acute rejection in kidney transplants.

BACKGROUND: Previously, we have reported that flow cytometry analysis of fine-needle aspirates can accurately predict rejection in kidney transplants treated with cyclosporine-azathioprine-prednisolone. In this study, we examined this technique's accuracy using current immunosuppression. METHODS: Kidney transplant recipients were treated with calcineurin inhibitors, mycophenolate mofetil, and prednisolone: 92 remained rejection-free - Group I - and 37 developed acute rejection - Group II. An allograft aspiration specimen and peripheral blood were collected from Group I on post-transplant day 7 and from Group II on the day of clinical rejection. RESULTS: Significant changes were seen in both aspiration and peripheral blood samples in several T cell subsets when comparing Groups I and II. A sensitivity of 94.6%, specificity of 85%, and AUC = 0.966 were observed through combining CD8DR with CD3CD69 values from aspiration specimen; the corresponding AUC in peripheral blood was 0.847. Irreversible rejections displayed a significantly higher activation score (p = 0.024). CONCLUSIONS: Flow cytometry analysis of aspiration specimen achieved high diagnostic performance in renal transplants through studying CD8DR and CD3CD69 under current immunosuppressive therapy. Peripheral blood analysis, although not significant, showed the same trend. The activation score anticipated the irreversibility of rejection. The data suggest this test, through an easily tolerated technique, merits further diagnostic use.

Clinical assessment of pediatric obstructive sleep apnea: a systematic review and meta-analysis.

OBJECTIVES/HYPOTHESIS: Clinical symptoms and signs are routinely used to investigate pediatric obstructive sleep apnea (OSA). This study aimed to systematically assess the evidence for the diagnostic accuracy of individual or combined clinical symptoms and signs in predicting pediatric OSA. STUDY DESIGN: A systematic review of the literature and diagnostic meta-analysis. METHODS: Four medical databases were searched (from inception to August 2011). Studies were included that compared the clinical assessment with the current gold standard (full polysomnography). The study quality was assessed using the quality assessment tool for diagnostic accuracy studies. Summary estimates of diagnostic accuracy were determined using the sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio, and hierarchical summary receiver operating characteristic (HSROC) model for meta-analyses. RESULTS: Ten diagnostic studies with 1,525 patients were included in the review. There was substantial variation in the sensitivity and specificity among different symptoms and signs, as well as across studies. Tonsillar size and snoring reported by parents or caregivers had high sensitivity but low specificity. In contrast, excessive daytime somnolence, observed apnea, and difficulty in breathing during sleep had high specificity but low sensitivity. Seven models of a combination of symptoms and signs presented moderate sensitivity (range, 0.04-0.94) and specificity (range, 0.28-0.99). The HSROC indicates poor diagnostic performance of the symptoms and signs in predicting pediatric OSA. CONCLUSIONS: Neither single nor combined symptoms and signs have satisfactory performance in predicting pediatric OSA. Alternative diagnostic models are necessary to improve the accuracy.