A summary of the 2023 Society of Obstetric Medicine of Australia and New Zealand (SOMANZ) hypertension in pregnancy guideline.

INTRODUCTION: Hypertensive disorders of pregnancy (HDP) affect up to 10% of all pregnancies annually and are associated with an increased risk of maternal and fetal morbidity and mortality. This guideline represents an update of the Society of Obstetric Medicine of Australia and New Zealand (SOMANZ) guidelines for the management of hypertensive disorders of pregnancy 2014 and has been approved by the National Health and Medical Research Council (NHMRC) under section 14A of the National Health and Medical Research Council Act 1992. In approving the guideline recommendations, NHMRC considers that the guideline meets NHMRC's standard for clinical practice guidelines. MAIN RECOMMENDATIONS: A total of 39 recommendations on screening, preventing, diagnosing and managing HDP, especially preeclampsia, are presented in this guideline. Recommendations are presented as either evidence-based recommendations or practice points. Evidence-based recommendations are presented with the strength of recommendation and quality of evidence. Practice points were generated where there was inadequate evidence to develop specific recommendations and are based on the expertise of the working group. CHANGES IN MANAGEMENT RESULTING FROM THE GUIDELINE: This version of the SOMANZ guideline was developed in an academically robust and rigorous manner and includes recommendations on the use of combined first trimester screening to identify women at risk of developing preeclampsia, 14 pharmacological and two non-pharmacological preventive interventions, clinical use of angiogenic biomarkers and the long term care of women who experience HDP. The guideline also includes six multilingual patient infographics which can be accessed through the main website of the guideline. All measures were taken to ensure that this guideline is applicable and relevant to clinicians and multicultural women in regional and metropolitan settings in Australia and New Zealand.

Saline dry fixation for improved cell composition analysis using Raman spectroscopy.

Raman spectroscopy enables the label-free assessment of cellular composition. While live cell analysis is the most accurate approach for cellular Raman spectroscopy, the analysis of fixed cells has proved to be very useful, particularly in collaborative projects where samples need to be serially examined by different laboratories or stored and reanalyzed at a later date. However, many chemicals that are widely used for cell fixation directly affect cellular biomolecules, yielding Raman spectra with missing or altered information. In this article, we compared the suitability of dry-fixation with saline versus chemical fixatives. We compared the Raman spectroscopy of saline dry-fixed cells with the more commonly used formaldehyde and methanol fixation and found that dry-fixed cell spectra preserved more cellular information than either chemical fixative. We also assessed the stability of dry-fixed cells over time and found that they were stable for at least 5 months. Finally, a comparison of dry-fixed and live cell spectra revealed effects due to the hydration state of the cells since they were recovered upon rehydrating dry-fixed samples. Thus, for fixed cell Raman spectroscopy, we recommend dry-fixation with unbuffered saline as a superior method to formaldehyde or methanol fixation.

Describing the health-related quality of life of Maori adults in Aotearoa me Te Waipounamu (New Zealand).

PURPOSE: In Aotearoa me Te Waipounamu (New Zealand; NZ) there are considerable inequities in health status and outcomes for Maori, the Indigenous peoples of NZ. It is therefore important that the health status and preferences of Maori are specifically considered in healthcare policy and decision making. This paper describes the health-related quality of life of 390 Maori adults who took part in the NZ EQ-5D-5L valuation study. METHODS: Responses on the five dimensions of the EQ-5D-5L were dichotomised into "no problems" and "any problems", summarised and disaggregated by age group. Mean preference weights were reported by age group and overall. Mean utility values (calculated by applying each participant's preference weights to their EQ-5D-5L profile) were summed and respective means and standard deviations reported by age, chronic disease status and disability. RESULTS: The EQ-5D-5L dimensions with the highest proportion of participants reporting any problems were pain/discomfort (61.5%) and anxiety/depression (50%). The most commonly-reported chronic disease was mental illness/distress (24.6%). Anxiety/depression ranked as the most important dimension, with usual activities, the least important. The mean utility value was 0.83 with the lowest value (0.79) found in the 18-24 and 45-54 age groups. For participants with at least one chronic disease the mean utility value was 0.76 compared to 0.91 for those with none. CONCLUSION: To reduce inequities experienced by Maori it is crucial that the health status of Maori and the values Maori place on health-related quality of life are properly understood. This can only be achieved using Maori-specific data.

Trends in BMI of Indonesian adults between 1993 and 2014: a longitudinal population-based study.

OBJECTIVE: To examine the trajectories of BMI in Indonesian adults from 1993 to 2014, investigating different patterns by sex and birth cohort. DESIGN: Longitudinal study: secondary data analysis of the Indonesian Family Life Survey, a large-scale population-based longitudinal study, had their height and weight measured up to five times throughout the 21-year study period (1993-2014). The change in BMI across time was estimated using group-based trajectory models, then differences by sex and birth cohort were investigated using random effect (mixed) models. SETTING: Thirteen out of twenty-seven provinces in Indonesia. PARTICIPANTS: Indonesian adults aged 19 years and older (n 42 537) were included in the analysis. RESULTS: Mean BMI in adults increased between 1993 (21·4 kg/m2) and 2014 (23·5 kg/m2). The group-based trajectory model found three distinct groups with mean BMI increasing more rapidly in the most recent time periods. The first group (56·7 % of participants) had a mean BMI entirely within the normal weight range; the second group (34·7 %) started in the normal weight category and were obese, on average by the end of the study period; and the third group (8·6 %) were always in the obese category, on average. The shape of these three trajectories differed by gender (P < 0·001) and birth cohort (P < 0·001). CONCLUSIONS: The mean BMI among Indonesian adults has increased between 1993 and 2014, driven by those in the most recent birth cohorts. Our findings support the urgent need for targeted overweight and obesity prevention and intervention programmes in Indonesia.

Factors Associated With Advanced Colorectal Neoplasia in Patients With CKD.

RATIONALE & OBJECTIVE: The risk of developing colorectal cancer in patients with chronic kidney disease (CKD) is twice that of the general population, but the factors associated with colorectal cancer are poorly understood. The aim of this study was to identify factors associated with advanced colorectal neoplasia in patients with CKD. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Patients with CKD stages 3-5, including those treated with maintenance dialysis or transplantation across 11 sites in Australia, New Zealand, Canada, and Spain, were screened for colorectal neoplasia using a fecal immunochemical test (FIT) as part of the Detecting Bowel Cancer in CKD (DETECT) Study. EXPOSURE: Baseline characteristics for patients at the time of study enrollment were ascertained, including duration of CKD, comorbidities, and medications. OUTCOME: Advanced colorectal neoplasia was identified through a 2-step verification process with colonoscopy following positive FIT and 2-year clinical follow-up for all patients. ANALYTICAL APPROACH: Potential factors associated with advanced colorectal neoplasia were explored using multivariable logistic regression. Sensitivity analyses were performed using grouped LASSO (least absolute shrinkage and selection operator) logistic regression. RESULTS: Among 1,706 patients who received FIT-based screening-791 with CKD stages 3-5 not receiving kidney replacement therapy (KRT), 418 receiving dialysis, and 497 patients with a functioning kidney transplant-117 patients (6.9%) were detected to have advanced colorectal neoplasia (54 with CKD stages 3-5 without KRT, 34 receiving dialysis, and 29 transplant recipients), including 9 colorectal cancers. The factors found to be associated with advanced colorectal neoplasia included older age (OR per year older, 1.05 [95% CI, 1.03-1.07], P<0.001), male sex (OR, 2.27 [95% CI, 1.45-3.54], P<0.001), azathioprine use (OR, 2.99 [95% CI, 1.40-6.37], P=0.005), and erythropoiesis-stimulating agent use (OR, 1.92 [95% CI, 1.22-3.03], P=0.005). Grouped LASSO logistic regression revealed similar associations between these factors and advanced colorectal neoplasia. LIMITATIONS: Unmeasured confounding factors. CONCLUSIONS: Older age, male sex, erythropoiesis-stimulating agents, and azathioprine were found to be significantly associated with advanced colorectal neoplasia in patients with CKD.

The Impact of Surveillance Imaging Frequency on the Detection of Distant Disease for Patients with Resected Stage III Melanoma.

BACKGROUND: It is not known whether there is a survival benefit associated with more frequent surveillance imaging in patients with resected American Joint Committee on Cancer stage III melanoma. OBJECTIVE: The aim of this study was to investigate distant disease-free survival (DDFS), melanoma-specific survival (MSS), post distant recurrence MSS (dMSS), and overall survival for patients with resected stage III melanoma undergoing regular computed tomography (CT) or positron emission tomography (PET)/CT surveillance imaging at different intervals. PATIENTS AND METHODS: A closely followed longitudinal cohort of patients with resected stage IIIA-D disease treated at a tertiary referral center underwent 3- to 4-monthly, 6-monthly, or 12-monthly surveillance imaging between 2000 and 2017. Survival outcomes were estimated using the Kaplan-Meier method, and log-rank tests assessed the significance of survival differences between imaging frequency groups. RESULTS: Of 473 patients (IIIA, 19%; IIIB, 31%; IIIC, 49%; IIID, 1%) 30% underwent 3- to 4-monthly imaging, 10% underwent 6-monthly imaging, and 60% underwent 12-monthly imaging. After a median follow-up of 6.2 years, distant recurrence was recorded in 252 patients (53%), with 40% detected by surveillance CT or PET/CT, 43% detected clinically, and 17% with another imaging modality. Median DDFS was 5.1 years (95% confidence interval 3.9-6.6). Among 139 IIIC patients who developed distant disease, the median dMSS was 4.4 months shorter in those who underwent 3- to 4-monthly imaging than those who underwent 12-monthly imaging. CONCLUSION: Selecting patients at higher risk of distant recurrence for more frequent surveillance imaging yields a higher proportion of imaging-detected distant recurrences but is not associated with improved survival. A randomized comparison of low versus high frequency imaging is needed.

The prevalence of chronic kidney disease in Samoans living in Auckland, New Zealand.

AIMS: Pacific peoples have higher rates of chronic kidney disease (CKD) and are five times more likely to commence kidney replacement therapy compared with New Zealand (NZ) Europeans. As the majority live Auckland, this study looked at the prevalence of CKD in two Auckland Pacific Island health providers caring for a large proportion of Pacific peoples, of which almost 50% are Samoan, as well as NZ Europeans. METHODS: De-identified information was requested on individuals who had two or more CKD tests (serum creatinine and urinary albumin creatinine ratios) more than 3 months apart. CKD prevalence across different demographic groups was determined. Logistic regression was used to look at associations of known risk factors and CKD. RESULTS: Data from 25 127 patients was evaluated. Of the total sample, 7451 individuals identified as Samoans. The prevalence of CKD amongst all Samoans in this sample was 17.8% increasing to 36.3% in those Samoans that had been tested for CKD. The prevalence of CKD in this total sample was 13% increasing to 27.5% considering only those who had CKD testing. The odds of Samoans having CKD (adjOR: 1.9 [95%CI 1.7, 2.2]), all other Pacific Island ethnicities identified and NZ Maori (adjOR:1.5 [95%CI 1.3, 1.8]), were increased compared with non-Maori-non-Pacific (likelihood p value <.001). CONCLUSION: We report the high prevalence of CKD (15.9%-33.4%) in Samoans living in New Zealand. This reveals an urgent need for further studies to develop strategies to prevent or reduce the development of kidney failure and premature death.

Creating opportunities to improve detection of older adult abuse: a national interRAI study.

Despite being recognized as a major global health issue, older adult abuse (OAA) remains largely undetected and under-reported. Most OAA assessment tools fail to capture true prevalence. Follow up of patients where abuse exposure is not easily determined is a necessity. The interRAI-HC (International Resident Assessment Instrument-Home Care) currently underestimates the extent of abuse. We investigated how to improve detection of OAA using the interRAI-HC. Analysis of 7 years of interRAI-HC data from an Aotearoa New Zealand cohort was completed. We identified that through altering the criteria for suspicion of OAA, capture rates of at-risk individuals could be nearly doubled from 2.6% to 4.8%. We propose that via adapting the interRAI-HC criteria to include the "unable to determine" whether abuse occurred (UDA) category, identification of OAA sufferers could be substantially improved. Improved identification will facilitate enhanced protection of this vulnerable population.

Performance of Long-Term CT and PET/CT Surveillance for Detection of Distant Recurrence in Patients with Resected Stage IIIA-D Melanoma.

BACKGROUND: Follow-up for patients with resected stage IIIA-D melanoma may include computed tomography (CT) or positron emission tomography (PET)/CT imaging to identify distant metastases. The aim of this study was to evaluate the test performance over follow-up time, of structured 6- and 12-monthly follow-up imaging schedules in these patients. METHODS: We conducted a retrospective analysis of consecutive resected stage IIIA-D melanoma patients from Melanoma Institute Australia (2000-2017). Patients were followed until a confirmed diagnosis of distant metastasis, end of follow-up schedule, or death. Test accuracy was evaluated by cross-classifying the results of the test against a composite reference standard of histopathology, cytology, radiologic imaging, and/or clinical follow-up, and then quantified longitudinally using logistic regression models with random effects. RESULTS: In total, 1373 imaging tests were performed among 332 patients. Distant metastases were detected in 110 (33%) patients during a median follow-up of 61 months (interquartile range 38-86), and first detected by imaging in 86 (78%) patients. 152 (68%) patients had at least one false-positive result. Sensitivity of the schedule over 5 years was 79% [95% confidence interval (CI) 70-86%] and specificity was 88% (95% CI 86-90%). There was no evidence of a significant difference in test performance over follow-up time or by American Joint Committee on Cancer (AJCC) substage. The positive predictive value ranged between 33 and 48% over follow-up time, reflecting a ratio of 1:2 false-positives per true-positive finding. CONCLUSIONS: Regular 6- or 12-monthly surveillance imaging using CT or PET/CT has reasonable and consistent sensitivity and specificity over 5-year follow-up for resected stage IIIA-D melanoma patients. These data are useful when discussing the risks and benefits of long-term follow-up.

Non-invasive monitoring of red blood cells during cold storage using handheld Raman spectroscopy.

BACKGROUND: The current best practices allow for the red blood cells (RBCs) to be stored for prolonged periods in blood banks worldwide. However, due to the individual-related variability in donated blood and RBCs continual degradation within transfusion bags, the quality of stored blood varies considerably. There is currently no method for assessing the blood product quality without compromising the sterility of the unit. This study demonstrates the feasibility of monitoring storage lesion of RBCs in situ while maintaining sterility using an optical approach. STUDY DESIGN AND METHODS: A handheld spatially offset Raman spectroscopy (RS) device was employed to non-invasively monitor hemolysis and metabolic changes in 12 red cell concentrate (RCC) units within standard sealed transfusion bags over 7 weeks of cold storage. The donated blood was analyzed in parallel by biochemical (chemical analysis, spectrophotometry, hematology analysis) and RS measurements, which were then correlated through multisource correlation analysis. RESULTS: Raman bands of lactate (857 cm-1 ), glucose (787 cm-1 ), and hemolysis (1003 cm-1 ) were found to correlate strongly with bioanalytical data over the length of storage, with correlation values 0.98 (95% confidence interval [CI]: 0.86-1.00; p = .0001), 0.95 (95% CI: 0.71-0.99; p = .0008) and 0.97 (95% CI: 0.79-1.00; p = .0004) respectively. DISCUSSION: This study demonstrates the potential of collecting information on the clinical quality of blood units without breaching the sterility using Raman technology. This could significantly benefit quality control of RCC units, patient safety and inventory management in blood banks and hospitals.

New Zealand Population Norms for the EQ-5D-5L Constructed From the Personal Value Sets of Participants in a National Survey.

OBJECTIVES: To derive New Zealand (NZ) population norms for the EQ-5D-5L and to examine the association between participants' sociodemographic characteristics and their health-related quality of life. METHODS: Data from the 2018 NZ EQ-5D-5L valuation study (n = 2468) were used. Each participant's 5-digit profile was converted to a single utility value using their personal value set. The profiles, mean utility values, and mean EuroQol visual analog scale (EQ-VAS) scores were summarized by dimension and disaggregated by age group and gender. Multivariable logistic and Tobit regressions were used to investigate the association between participants' sociodemographic characteristics and the EQ-5D-5L dimensions, utility values, and EQ-VAS scores. RESULTS: The mean utility value was 0.847 and the mean EQ-VAS score was 74.8. Of the 3125 possible EQ-5D-5L profiles, 25 profiles represented the current health status of the majority of participants (78%). The odds of having problems with anxiety or depression was greatest for people aged 18 to 24 years and decreased with age. People with a long-term disability or chronic illness had greater odds of problems on all dimensions and lower (poorer) utility values and EQ-VAS scores. Age, ethnicity, employment status, long-term disability, and chronic illness were associated with utility. CONCLUSION: EQ-5D-5L population norms were derived for the NZ population using the personal value sets of 2468 participants. Consistent with other countries' population norms, EQ-5D-5L utility values and EQ-VAS scores were associated with age, employment status, long-term disability, and chronic illness. These norms will support resource allocation decision making and help in understanding the health-related quality of life of the NZ population.

Effectiveness of oral health education methods on oral hygiene in children and adolescents with visual impairment: A systematic review.

BACKGROUND: Conventional methods of oral health education (OHE) are not suitable for children with visual impairment, as these methods usually involve visual demonstration with models or plaque-disclosing dyes. AIM: To systematically review the literature to support the best approach for providing OHE to children and adolescents with visual impairment. DESIGN: A systematic search of five electronic databases and grey literature was conducted. Randomized controlled trials that compared different OHE methods in children and adolescents with visual impairment were included. The Cochrane risk-of-bias tool (RoB 2) was used for the risk-of-bias assessment. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework was used to determine the certainty of evidence. RESULTS: Nine randomized controlled trials with a total of 804 participants were included in this review. Seven OHE methods were compared. Seven studies were assessed to be at high risk of bias, one study was assessed to have some concerns, and one study was assessed to be at low risk of bias. The overall certainty of evidence was very low according to GRADE. CONCLUSION: There was insufficient evidence to recommend a particular method of OHE as more effective in improving the oral hygiene of children with visual impairment, but combination methods may show similar or better results.

Effects of health literacy, screening, and participant choice on action plans for reducing unhealthy snacking in Australia: A randomised controlled trial.

BACKGROUND: Low health literacy is associated with poorer health outcomes. A key strategy to address health literacy is a universal precautions approach, which recommends using health-literate design for all health interventions, not just those targeting people with low health literacy. This approach has advantages: Health literacy assessment and tailoring are not required. However, action plans may be more effective when tailored by health literacy. This study evaluated the impact of health literacy and action plan type on unhealthy snacking for people who have high BMI or type 2 diabetes (Aim 1) and the most effective method of action plan allocation (Aim 2). METHODS AND FINDINGS: We performed a 2-stage randomised controlled trial in Australia between 14 February and 6 June 2019. In total, 1,769 participants (mean age: 49.8 years [SD = 11.7]; 56.1% female [n = 992]; mean BMI: 32.9 kg/m2 [SD = 8.7]; 29.6% self-reported type 2 diabetes [n = 523]) were randomised to 1 of 3 allocation methods (random, health literacy screening, or participant selection) and 1 of 2 action plans to reduce unhealthy snacking (standard versus literacy-sensitive). Regression analysis evaluated the impact of health literacy (Newest Vital Sign [NVS]), allocation method, and action plan on reduction in self-reported serves of unhealthy snacks (primary outcome) at 4-week follow-up. Secondary outcomes were perceived extent of unhealthy snacking, difficulty using the plans, habit strength, and action control. Analyses controlled for age, level of education, language spoken at home, diabetes status, baseline habit strength, and baseline self-reported serves of unhealthy snacks. Average NVS score was 3.6 out of 6 (SD = 2.0). Participants reported consuming 25.0 serves of snacks on average per week at baseline (SD = 28.0). Regarding Aim 1, 398 participants in the random allocation arm completed follow-up (67.7%). On average, people scoring 1 SD below the mean for health literacy consumed 10.0 fewer serves per week using the literacy-sensitive action plan compared to the standard action plan (95% CI: 0.05 to 19.5; p = 0.039), whereas those scoring 1 SD above the mean consumed 3.0 fewer serves using the standard action plan compared to the literacy-sensitive action plan (95% CI: -6.3 to 12.2; p = 0.529), although this difference did not reach statistical significance. In addition, we observed a non-significant action plan × health literacy (NVS) interaction (b = -3.25; 95% CI: -6.55 to 0.05; p = 0.054). Regarding Aim 2, 1,177 participants across the 3 allocation method arms completed follow-up (66.5%). There was no effect of allocation method on reduction of unhealthy snacking, including no effect of health literacy screening compared to participant selection (b = 1.79; 95% CI: -0.16 to 3.73; p = 0.067). Key limitations include low-moderate retention, use of a single-occasion self-reported primary outcome, and reporting of a number of extreme, yet plausible, snacking scores, which rendered interpretation more challenging. Adverse events were not assessed. CONCLUSIONS: In our study we observed nominal improvements in effectiveness of action plans tailored to health literacy; however, these improvements did not reach statistical significance, and the costs associated with such strategies compared with universal precautions need further investigation. This study highlights the importance of considering differential effects of health literacy on intervention effectiveness. TRIAL REGISTRATION: Australia and New Zealand Clinical Trial Registry ACTRN12618001409268.

Correction to: Estimation of treatment preference effects in clinical trials when some participants are indifferent to treatment choice.

In the original publication of this article [1], the number "- 0.49" in the below sentence in the Results section should be changed to "-3.23", and this typo does not affect the wider conclusions.

Correction: Applications of Raman spectroscopy in the development of cell therapies: state of the art and future perspectives.

Correction for 'Applications of Raman spectroscopy in the development of cell therapies: state of the art and future perspectives' by Shreyas Rangan et al., Analyst, 2020, DOI: 10.1039/c9an01811e.

Applications of Raman spectroscopy in the development of cell therapies: state of the art and future perspectives.

Therapies based on injecting living cells into patients offer a huge potential to cure many degenerative and deadly diseases, with hundreds of clinical trials ongoing. Due to their complex nature, a basic understanding of their biochemical and functional characteristics, how to manufacture them for safe and efficacious therapy, and how to effectively implement them in clinical settings are very challenging. Raman spectroscopy could provide an information-rich, non-invasive, non-destructive analytical method to complement the use of conventional sample-based, infrequent and destructive biochemical assays typically employed to analyze and validate the quality of therapeutic cells. This article provides an overview of the current state of emerging cell therapies, and then reviews the related Raman spectroscopic state of the art analysis of human cells. This includes spectroscopic data processing considerations, the scope offered by technical variants of Raman spectroscopy, and analytical difficulties encountered by spectroscopists working with therapeutic cells. Finally, we outline a number of salient challenges as cell therapy products are translated from the laboratory to the clinic, and propose how Raman spectroscopy-based solutions could address these challenges.

Patient attitude and acceptance towards episiotomy during pregnancy before and after information provision: a questionnaire.

INTRODUCTION AND HYPOTHESIS: Evidence regarding how women feel about episiotomies is not recorded in the literature. As the most common surgical procedure, there is a need to understand how women feel about episiotomy. METHODS: The primary outcome was to identify the percentage of women who would accept an episiotomy if required. A literature review was compiled to provide nulliparous women in their third trimester with evidence-based information about episiotomies and perineal tears. Questions eliciting demographics, pre-information level of anxiety and acceptance of episiotomy were asked. After reading the information sheets, anxiety and knowledge were assessed again. Changes in anxiety levels from pre- to post-information were investigated using paired samples t tests. Because anxiety was measured on a scale, we assessed potential departures from normality by using the Wilcoxon signed-rank test. Questions also assessed the value women placed on this form of education. RESULTS: There were 105 responses, with 88% accepting episiotomy, 2% declining and 10% seeking more information to decide. Eighty-one percent of women agreed that the information provided helped them to understand more about childbirth and 62% agreed that they felt more comfortable with the birthing process after reading the material. There was a reduction in anxiety levels regarding episiotomies after reading information (p = 0.002) and perineal tears (p = 0.02). CONCLUSIONS: Most women will accept an episiotomy if required. Antenatal education about episiotomies is important to women and helps them feel more comfortable with the birthing process. Written information increases acceptance and reduces anxiety levels regarding episiotomies.

One-Time Fecal Immunochemical Screening for Advanced Colorectal Neoplasia in Patients with CKD (DETECT Study).

BACKGROUND: In patients with CKD, the risk of developing colorectal cancer is high and outcomes are poor. Screening using fecal immunochemical testing (FIT) is effective in reducing mortality from colorectal cancer, but performance characteristics of FIT in CKD are unknown. METHODS: To determine the detection rates and performance characteristics of FIT for advanced colorectal neoplasia (ACN) in patients with CKD, we used FIT to prospectively screen patients aged 35-74 years with CKD (stages 3-5 CKD, dialysis, and renal transplant) from 11 sites in Australia, New Zealand, Canada, and Spain. All participants received clinical follow-up at 2 years. We used a two-step reference standard approach to estimate disease status. RESULTS: Overall, 369 out of 1706 patients who completed FIT (21.6%) tested positive; 323 (87.5%) underwent colonoscopies. A total of 1553 (91.0%) completed follow-up; 82 (4.8%) had died and 71 (4.2%) were lost. The detection rate of ACN using FIT was 6.0% (5.6%, 7.4%, and 5.6% for stages 3-5 CKD, dialysis, and transplant). Sensitivity, specificity, and positive and negative predictive values of FIT for ACN were 0.90, 0.83, 0.30, and 0.99, respectively. Of participants who underwent colonoscopy, five (1.5%) experienced major colonoscopy-related complications, including bowel perforation and major bleeding. CONCLUSIONS: FIT appears to be an accurate screening test for patients with CKD, such that a negative test may rule out the diagnosis of colorectal cancer within 2 years. However, the risk of major complications from work-up colonoscopy are at least ten-fold higher than in the general population.

Altered Regulation of adipomiR Editing with Aging.

Adipose dysfunction with aging increases risk to insulin resistance and other chronic metabolic diseases. We previously showed functional changes in microRNAs involved in pre-adipocyte differentiation with aging resulting in adipose dysfunction. However, the mechanisms leading to this dysfunction in microRNAs in adipose tissue (adipomiRs) during aging are not well understood. We determined the longitudinal changes in expression of adipomiRs and studied their regulatory mechanisms, such as miRNA biogenesis and editing, in an aging rodent model, with Fischer344 × Brown-Norway hybrid rats at ages ranging from 3 to 30 months (male/females, n > 8). Expression of adipomiRs and their edited forms were determined by small-RNA sequencing. RT-qPCR was used to measure the mRNA expression of biogenesis and editing enzymes. Sanger sequencing was used to validate editing with aging. Differential expression of adipomiRs involved in adipocyte differentiation and insulin signaling was altered with aging. Sex- and age-specific changes in edited adipomiRs were observed. An increase in miRNA biogenesis and editing enzymes (ADARs and their splice variants) were observed with increasing age, more so in female than male rats. The adipose dysfunction observed with age is attributed to differences in editing of adipomiRs, suggesting a novel regulatory pathway in aging.

False-Positive Results and Incidental Findings with Annual CT or PET/CT Surveillance in Asymptomatic Patients with Resected Stage III Melanoma.

OBJECTIVE: The aim of this study was to quantify false-positive and incidental findings from annual surveillance imaging in asymptomatic, American Joint Committee on Cancer stage III melanoma patients. METHODS: This was a cohort study of patients treated at Melanoma Institute Australia (2000-2015) with baseline computed tomography (CT) or positron emission tomography (PET)/CT imaging and at least two annual surveillance scans. False-positives were defined as findings suspicious for melanoma recurrence that were not melanoma, confirmed by histopathology, subsequent imaging, or clinical follow-up, while incidental findings were defined as non-melanoma-related findings requiring further action. Outcomes of incidental findings were classified as 'benign' if they resolved spontaneously or were not seriously harmful; 'malignant' if a second malignancy was identified; or 'other' if potentially harmful. RESULTS: Among 154 patients, 1022 scans were performed (154 baseline staging, 868 surveillance) during a median follow-up of 85 months (interquartile range 56-112); 57 patients (37%) developed a recurrence. For baseline and surveillance imaging, 124 false-positive results and incidental findings were identified in 81 patients (53%). The frequency of these findings was 5-14% per year, and an additional 181 tests, procedures, and referrals were initiated to investigate these findings. The diagnosis was benign in 109 findings of 124 findings (88%). Fifteen patients with a benign finding underwent an unnecessary invasive procedure. Surveillance imaging identified distant metastases in 20 patients (13%). CONCLUSION: False-positive results and incidental findings occur in at least half of all patients undergoing annual surveillance imaging, and the additional healthcare use is substantial. These findings persist over time. Clinicians need to be aware of these risks and discuss them with patients, alongside the expected benefits of surveillance imaging.