Publications by authors named "Michelle Wilson"

97 Publications

Interobserver and intraobserver variability of RECIST assessment in ovarian cancer.

Int J Gynecol Cancer 2022 May 3;32(5):656-661. Epub 2022 May 3.

Cancer and Blood, Auckland City Hospital, Auckland, New Zealand

Objectives: Measurement of Response Evaluation Criteria In Solid Tumors (RECIST) relies on reproducible unidimensional tumor measurements. This study assessed intraobserver and interobserver variability of target lesion selection and measurement, according to RECIST version 1.1 in patients with ovarian cancer.

Methods: Eight international radiologists independently viewed 47 images demonstrating malignant lesions in patients with ovarian cancer and selected and measured lesions according to RECIST V.1.1 criteria. Thirteen images were viewed twice. Interobserver variability of selection and measurement were calculated for all images. Intraobserver variability of selection and measurement were calculated for images viewed twice. Lesions were classified according to their anatomical site as pulmonary, hepatic, pelvic mass, peritoneal, lymph nodal, or other. Lesion selection variability was assessed by calculating the reproducibility rate. Lesion measurement variability was assessed with the intra-class correlation coefficient.

Results: From 47 images, 82 distinct lesions were identified. For lesion selection, the interobserver and intraobserver reproducibility rates were high, at 0.91 and 0.93, respectively. Interobserver selection reproducibility was highest (reproducibility rate 1) for pelvic mass and other lesions. Intraobserver selection reproducibility was highest (reproducibility rate 1) for pelvic mass, hepatic, nodal, and other lesions. Selection reproducibility was lowest for peritoneal lesions (interobserver reproducibility rate 0.76 and intraobserver reproducibility rate 0.69). For lesion measurement, the overall interobserver and intraobserver intraclass correlation coefficients showed very good concordance of 0.84 and 0.94, respectively. Interobserver intraclass correlation coefficient showed very good concordance for hepatic, pulmonary, peritoneal, and other lesions, and ranged from 0.84 to 0.97, but only moderate concordance for lymph node lesions (0.58). Intraobserver intraclass correlation coefficient showed very good concordance for all lesions, ranging from 0.82 to 0.99. In total, 85% of total measurement variability resulted from interobserver measurement difference.

Conclusions: Our study showed that while selection and measurement concordance were high, there was significant interobserver and intraobserver variability. Most resulted from interobserver variability. Compared with other lesions, peritoneal lesions had the lowest selection reproducibility, and lymph node lesions had the lowest measurement concordance. These factors need consideration to improve response assessment, especially as progression free survival remains the most common endpoint in phase III trials.
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http://dx.doi.org/10.1136/ijgc-2021-003319DOI Listing
May 2022

Parent ADHD Is Associated With Greater Parenting Distress in the First Year Postpartum.

J Atten Disord 2022 Jul 23;26(9):1257-1268. Epub 2021 Dec 23.

University of Pittsburgh School of Medicine, PA, USA.

Objective: Little is known about the experience of parenting infants when a mother or father has ADHD. This study examined cross-sectional predictors of parenting distress experienced by parents with and without ADHD who also have infants.

Methods: Participants were 73 mother-father pairs ( = 146) of infants 6 to 10 months old. Half of the families included a parent with ADHD. Psychosocial predictors were tested using multilevel modeling.

Results: Parent or partner ADHD, lower parent sleep quality, fewer social supports, and less infant surgency and effortful control were associated with greater parental distress. Infant negative affect and sleep were not associated.

Conclusions: Parents with ADHD and their partners experience greater parenting distress in the first year of their child's life than parents without ADHD. Addressing parent ADHD symptoms and co-occurring difficulties, including sleep disturbances, are potential targets for early interventions to maximize both parent and infant mental health outcomes.
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http://dx.doi.org/10.1177/10870547211066488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9098664PMC
July 2022

An Exploratory Analysis of Changes in Circulating Plasma Protein Profiles Following Image-Guided Ablation of Renal Tumours Provides Evidence for Effects on Multiple Biological Processes.

Cancers (Basel) 2021 Nov 30;13(23). Epub 2021 Nov 30.

Clinical and Biomedical Proteomics Group, Leeds Institute of Medical Research at St James's, University of Leeds, St. James's University Hospital, Beckett Street, Leeds LS9 7TF, UK.

Further biological understanding of the immune and inflammatory responses following ablation is critical to the rational development of combination ablation-immunotherapies. Our pilot exploratory study evaluated the circulating plasma protein profiles after image-guided ablation (IGA) of small renal masses to determine the resultant systemic effects and provide insight into impact both on the tumour and immune system. Patients undergoing cryotherapy (CRYO), radiofrequency ablation (RFA) or microwave ablation (MWA) for small renal tumours were recruited. Blood samples were obtained at four timepoints; two baselines prior to IGA and at 24 h and 1-3 months post-IGA, and a panel of 164 proteins measured. Of 55 patients recruited, 35 underwent ablation (25 CRYO, 8 RFA, 2 MWA) and biomarker measurements. The most marked changes were 24 h post-CRYO, with 29 proteins increasing and 18 decreasing significantly, principally cytokines and proteins involved in regulating inflammation, danger-associated molecular patterns (DAMPs), cell proliferation, hypoxic response, apoptosis and migration. Intra-individual variation was low but inter-individual variation was apparent, for example all patients showed increases in IL-6 (1.7 to 29-fold) but only 50% in CD27. Functional annotation analysis highlighted immune/inflammation and cell proliferation/angiogenesis-related clusters, with interaction networks around IL-6, IL-10, VEGF-A and several chemokines. Increases in IL-8, IL-6, and CCL23 correlated with cryoprobe number ( = 0.01, r = 0.546; = 0.009, r = 0.5515; = 0.005, r = 0.5873, respectively). This initial data provide further insights into ablation-induced biological changes of relevance in informing trial design of immunotherapies combined with ablation.
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http://dx.doi.org/10.3390/cancers13236037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8656737PMC
November 2021

Biomarkers During Recovery From AKI and Prediction of Long-term Reductions in Estimated GFR.

Am J Kidney Dis 2022 May 12;79(5):646-656.e1. Epub 2021 Oct 12.

Department of Renal Medicine, Royal Derby Hospital, Derby; Centre for Kidney Research and Innovation, University of Nottingham, Nottingham, United Kingdom. Electronic address:

Rationale & Objective: The effects of acute kidney injury (AKI) on long-term kidney function, cardiovascular disease, and mortality are well documented. We aimed to identify biomarkers for the estimation of risk of new or worsening chronic kidney disease (CKD) following AKI.

Study Design: Prospective cohort study.

Setting & Participants: Adults from a single clinical center who experienced AKI between May 2013 and May 2016 and survived until 3 years after the hospitalization during which AKI occurred. Participants included those with and without preexisting CKD.

Predictors: Panel of 11 plasma biomarkers measured 3 months after hospitalization.

Outcome: Kidney disease progression, defined as a≥25% decrease in estimated glomerular filtration rate (eGFR) combined with worsening CKD stage, assessed 3 years after the occurrence of AKI.

Analytical Approach: Associations between biomarkers and kidney disease progression were evaluated in multivariable logistic regression models. Importance of predictor variables was assessed by constructing multiple decision trees, with penalized least absolute shrinkage and selection operator logistic regression for variable selection used to produce multivariable models.

Results: A total of 500 patients were studied. Soluble tumor necrosis factor receptor (sTNFR) 1, sTNFR2, cystatin C, neutrophil gelatinase-associated lipocalin, 3-month eGFR, and urinary albumin-creatinine ratio were independently associated with kidney disease progression and were more important than AKI severity or duration. A multivariable model containing sTNFR1, sTNFR2, cystatin C, and eGFR discriminated between those with and without kidney disease progression (area under the curve, 0.79 [95% CI, 0.70-0.83]). Optimizing the cutoff point to maximize utility as a "rule-out" test to identify those at low risk increased the sensitivity of the model to 95% and its negative predictive value to 92%.

Limitations: Lack of external validation cohort. Analyses limited to patients who survived for 3 years after AKI. Mixed population of patients with and without baseline CKD.

Conclusions: A panel of plasma biomarkers measured 3 months after discharge from a hospitalization complicated by AKI provides a potential opportunity to identify patients who are at very low risk of incident or worsening CKD. Further study is required to determine its clinical utility through independent prospective validation.
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http://dx.doi.org/10.1053/j.ajkd.2021.08.017DOI Listing
May 2022

ATHENA (GOG-3020/ENGOT-ov45): a randomized, phase III trial to evaluate rucaparib as monotherapy (ATHENA-MONO) and rucaparib in combination with nivolumab (ATHENA-COMBO) as maintenance treatment following frontline platinum-based chemotherapy in ovarian cancer.

Int J Gynecol Cancer 2021 12 30;31(12):1589-1594. Epub 2021 Sep 30.

Department of Oncology, Guy's and St Thomas' NHS Foundation Trust, London, UK.

Background: The optimal treatment strategy for women with newly diagnosed ovarian cancer has yet to be determined. Poly(ADP-ribose) polymerase (PARP) inhibitors have demonstrated substantial improvement in progression-free survival as monotherapy maintenance treatment in the frontline setting versus active surveillance. Furthermore, preclinical and early clinical studies have shown that PARP inhibitors and immune checkpoint inhibitors have synergistic antitumor activity and may provide an additional therapeutic option for patients in this population.

Primary Objectives: In women with newly diagnosed ovarian, fallopian tube, or peritoneal cancer, we wish to assess the efficacy of frontline maintenance treatment with the PARP inhibitor rucaparib versus placebo following response to platinum-based chemotherapy (ATHENA-MONO), and to assess the combination of rucaparib plus nivolumab (a programmed death receptor 1 (PD-1)-blocking monoclonal antibody) versus rucaparib alone (ATHENA-COMBO).

Study Hypothesis: (1) Maintenance therapy with rucaparib monotherapy may extend progression-free survival following standard treatment for ovarian cancer in the frontline setting. (2) The combination of nivolumab plus rucaparib may extend progression-free survival following standard treatment for ovarian cancer in the frontline setting compared with rucaparib alone.

Trial Design: ATHENA is an international, randomized, double-blind, phase III trial consisting of two independent comparisons (ATHENA-MONO and ATHENA-COMBO) in patients with newly diagnosed platinum-sensitive ovarian cancer. Patients are randomized 4:4:1:1 to the following: oral rucaparib+ intravenous nivolumab (arm A); oral rucaparib + intravenous placebo (arm B); oral placebo+ intravenous nivolumab (arm C); and oral placebo + intravenous placebo (arm D). The starting dose of rucaparib is 600 mg orally twice a day and nivolumab 480 mg intravenously every 4 weeks. ATHENA-MONO compares arm B with arm D to evaluate rucaparib monotherapy versus placebo, and ATHENA-COMBO evaluates arm A versus arm B to investigate the effects of rucaparib and nivolumab in combination versus rucaparib monotherapy. ATHENA-MONO and ATHENA-COMBO share a common treatment arm (arm B) but each comparison is independently powered.

Major Inclusion/exclusion Criteria: Patients ≥18 years of age with newly diagnosed advanced, high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancer who have achieved a response after completion of cytoreductive surgery and initial platinum-based chemotherapy are enrolled. No other prior treatment for ovarian cancer, other than the frontline platinum regimen, is permitted.

Primary Endpoint: The primary endpoint is investigator-assessed progression-free survival by Response Evaluation Criteria in Solid Tumors v1.1.

Sample Size: Approximately 1000 patients have been enrolled and randomized.

Estimated Dates For Completing Accrual And Presenting Results: The trial completed accrual in 2020. While dependent on event rates, primary results of ATHENA-MONO are anticipated in early 2022 and results of ATHENA-COMBO are anticipated to mature at a later date.

Trial Registration: This trial is registered at clinicaltrials.gov (NCT03522246).
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http://dx.doi.org/10.1136/ijgc-2021-002933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8666815PMC
December 2021

Temperature memory and non-structural carbohydrates mediate legacies of a hot drought in trees across the southwestern USA.

Tree Physiol 2022 01;42(1):71-85

School of Informatics, Computing, and Cyber Systems, Northern Arizona University, Flagstaff, AZ 86011, USA.

Trees are long-lived organisms that integrate climate conditions across years or decades to produce secondary growth. This integration process is sometimes referred to as 'climatic memory.' While widely perceived, the physiological processes underlying this temporal integration, such as the storage and remobilization of non-structural carbohydrates (NSC), are rarely explicitly studied. This is perhaps most apparent when considering drought legacies (perturbed post-drought growth responses to climate), and the physiological mechanisms underlying these lagged responses to climatic extremes. Yet, drought legacies are likely to become more common if warming climate brings more frequent drought. To quantify the linkages between drought legacies, climate memory and NSC, we measured tree growth (via tree ring widths) and NSC concentrations in three dominant species across the southwestern USA. We analyzed these data with a hierarchical mixed effects model to evaluate the time-scales of influence of past climate (memory) on tree growth. We then evaluated the role of climate memory and the degree to which variation in NSC concentrations were related to forward-predicted growth during the hot 2011-2012 drought and subsequent 4-year recovery period. Populus tremuloides exhibited longer climatic memory compared to either Pinus edulis or Juniperus osteosperma, but following the 2011-2012 drought, P. tremuloides trees with relatively longer memory of temperature conditions showed larger (more negative) drought legacies. Conversely, Pinus edulis trees with longer temperature memory had smaller (less negative) drought legacies. For both species, higher NSC concentrations followed more negative (larger) drought legacies, though the relevant NSC fraction differed between P. tremuloides and P. edulis. Our results suggest that differences in tree NSC are also imprinted upon tree growth responses to climate across long time scales, which also underlie tree resilience to increasingly frequent drought events under climate change.
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http://dx.doi.org/10.1093/treephys/tpab091DOI Listing
January 2022

DALES, Drug Allergy Labels in Elective Surgical patients: a prospective, multicentre cross-sectional study of prevalence, nature and anaesthetists' approach to management.

Br J Anaesth 2021 12 7;127(6):897-904. Epub 2021 Jul 7.

Department of Anaesthesia, Leeds Teaching Hospitals NHS Trust, Leeds, UK.

Background: We sought to define the prevalence and nature of patient-reported drug allergies, determine their impact on prescribing, and explore drug allergy knowledge and attitudes amongst anaesthetists.

Methods: We performed a prospective cross-sectional study in 213 UK hospitals in 2018. Elective surgical patients were interviewed, with a detailed allergy history taken in those self-reporting drug allergy. Anaesthetists completed a questionnaire concerning perioperative drug allergy.

Results: Of 21 219 patients included, 6214 (29.3 %) (95% confidence interval [CI]: 28.7-29.9) reported drug allergy. Antibiotics, NSAIDs, and opioids were the most frequently implicated agents. Of a total of 8755 reactions, 2462 (28.1%) (95% CI: 29.2-31.1) were categorised as high risk for representing genuine allergy after risk stratification. A history suggestive of chronic spontaneous urticaria significantly increased the risk of reporting drug allergy (odds ratio 2.68; 95% CI: 2.4-3; P<0.01). Of 4756 anaesthetists completing the questionnaire, 1473 (31%) (95% CI: 29.7-32.3) routinely discuss perioperative allergy risk with patients. Prescribing habits in the presence of drug allergy labels differ depending on the implicated agent. Most anaesthetists (4678/4697; 99.6%) (95% CI: 99.4-99.8) prescribe opioids when reactions are consistent with side-effects, although 2269/4697 (48%) (95% CI: 46.9-49.7) would avoid the specific opioid reported.

Conclusions: Almost 30% of UK elective surgical patients report a history of drug allergies, but the majority of reported reactions are likely to be non-allergic reactions. Allergy labels can impact on perioperative prescribing through avoidance of important drugs and use of less effective alternatives. We highlight important knowledge gaps about drug allergy amongst anaesthetists, and the need for improved education around allergy.
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http://dx.doi.org/10.1016/j.bja.2021.05.026DOI Listing
December 2021

Research biopsies in patients with gynecologic cancers: patient-reported outcomes, perceptions, and preferences.

Am J Obstet Gynecol 2021 12 23;225(6):658.e1-658.e9. Epub 2021 Jun 23.

Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; University of Toronto, Toronto, Ontario, Canada. Electronic address:

Background: Despite the growing integration of mandatory biopsies for correlative endpoints within oncology clinical trials, there are sparse data on patient-reported outcomes, perceptions, and preferences.

Objective: This study aimed to prospectively assess the impact of research biopsies on the quality of life in patients with gynecologic cancer, evaluate patient-reported outcomes, and determine factors associated with patients' willingness to undergo sequential biopsies.

Study Design: We conducted a prospective study in patients with gynecologic malignancies undergoing research biopsies between 2015 and 2019 at Princess Margaret Cancer Centre (ClinicalTrials.gov Identifier: NCT02334761). Here, we report the results of the paper-based surveys performed before and 1 week after biopsy. Although the questionnaires each assessed the impact of anxiety using a modified version of the Hospital Anxiety and Depression Scale, the postbiopsy questionnaire specifically assessed the likelihood of future biopsies, postbiopsy symptoms, complications, and perceptions.

Results: A total of 129 patients were enrolled, of which 91 (70.5%) completed at least 1 questionnaire. These patients had either ovarian (89%; 81 of 91) or endometrial cancer (11%; 10 of 91). Of all biopsies taken, 75% were from the abdomen or pelvis (67 of 89). There was 1 clinician-reported complication, a perihepatic hematoma (1%). Pain during the biopsy and physical discomfort were experienced by 60.3% (41 of 68) and 61.8% (42 of 68), respectively. Embarrassment and loss of dignity were experienced by 13.2% (9 of 68) and 11.8% (8 of 68), respectively. Although the mean Hospital Anxiety and Depression Scale score was in the normal range before and after biopsy, there was a significant decline in the total score after the biopsy (prebiopsy, 5.3 [standard deviation, 4.7] vs postbiopsy, 3.7 [standard deviation, 4.5]; P=.005); 84% of subjects (58 of 69) stated that they would definitely or likely consent to another biopsy. There was no impact on patients' willingness for future biopsies based on Eastern Cooperative Oncology Group status, biopsy site, age, number of cores, and pain during the biopsy; however, subjects who reported feeling physically uncomfortable (odds ratio, 0.14; P=.005), embarrassed (odds ratio, 0.03; P=.004) or experienced loss of dignity (odds ratio, 0.05; P=.01) during the biopsy and those who experienced flu-like symptoms (odds ratio, 0.2; P=.018) or felt feverish (odds ratio, 0.2; P=.035) 1 week after biopsy, were less likely to undergo a sequential biopsy. Similarly, those with higher Hospital Anxiety and Depression Scale scores before biopsy (odds ratio, 0.83; P=.008) and after biopsy (odds ratio, 0.8; P=.003) were less likely to consent for another biopsy.

Conclusion: Research biopsies were generally well accepted. Most patients (83%) were willing to undergo serial biopsies if necessary. Addressing the potentially modifiable psychosocial aspects of the procedure may improve the experience with research biopsies for patients with gynecologic cancers.
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http://dx.doi.org/10.1016/j.ajog.2021.06.071DOI Listing
December 2021

The PREdictor of MAlnutrition in Systemic Sclerosis (PREMASS) Score: A Combined Index to Predict 12 Months Onset of Malnutrition in Systemic Sclerosis.

Front Med (Lausanne) 2021 17;8:651748. Epub 2021 Mar 17.

National Institute for Health Research (NIHR) Leeds Biomedical Research Centre (BRC), Leeds Teaching Hospitals National Health Service (NHS) Trust and Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, United Kingdom.

Malnutrition is a severe complication in Systemic Sclerosis (SSc) and it is associated with significant mortality. Notwithstanding, there is no defined screening or clinical pathway for patients, which is hampering effective management and limiting the opportunity for early intervention. Here we aim to identify a combined index predictive of malnutrition at 12 months using clinical data and specific serum adipokines. This was an international, multicentre observational study involving 159 SSc patients in two independent discovery ( = 98) and validation ( = 61) cohorts. Besides routine clinical and serum data at baseline and 12 months, Malnutrition Universal Screening Tool (MUST) score and serum concentration of leptin and adiponectin were measured for each participant at baseline. The endpoint of malnutrition was defined according to European Society of Clinical Nutrition and Metabolism (ESPEN) recommendation. Significant parameters from univariate analysis were tested in logistic regression analysis to identify the predictive index of malnutrition in the derivation cohort. The onset of malnutrition at 12 months correlated with adiponectin, leptin and their ratio (A/L), MUST, clinical subset, disease duration, Scl70 and Forced Vital Capaciy (FVC). Logistic regression analysis defined the formula: -2.13 + (A/L0.45) + (Scl700.28) as the best PREdictor of MAlnutrition in SSc (PREMASS) (AUC = 0.96; 95% CI 0.93, 0.99). PREMASS < -1.46 had a positive predictive value (PPV) > 62% and negative predictive value (NPV) > 97% for malnutrition at 12 months. PREMASS is a feasible index which has shown very good performance in two independent cohorts for predicting malnutrition at 12 months in SSc. The implementation of PREMASS could aid both in clinical management and clinical trial stratification/enrichment to target malnutrition in SSc.
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http://dx.doi.org/10.3389/fmed.2021.651748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010181PMC
March 2021

Temporal controls on crown nonstructural carbohydrates in southwestern US tree species.

Tree Physiol 2021 03;41(3):388-402

School of Informatics, Computing, and Cyber Systems, Northern Arizona University, Flagstaff, AZ 86011, USA.

In trees, large uncertainties remain in how nonstructural carbohydrates (NSCs) respond to variation in water availability in natural, intact ecosystems. Variation in NSC pools reflects temporal fluctuations in supply and demand, as well as physiological coordination across tree organs in ways that differ across species and NSC fractions (e.g., soluble sugars vs starch). Using landscape-scale crown (leaves and twigs) NSC concentration measurements in three foundation tree species (Populus tremuloides, Pinus edulis, Juniperus osteosperma), we evaluated in situ, seasonal variation in NSC responses to moisture stress on three timescales: short-term (via predawn water potential), seasonal (via leaf δ13C) and annual (via current year's ring width index). Crown NSC responses to moisture stress appeared to depend on hydraulic strategy, where J. osteosperma appears to regulate osmotic potentials (via higher sugar concentrations), P. edulis NSC responses suggest respiratory depletion and P. tremuloides responses were consistent with direct sink limitations. We also show that overly simplistic models can mask seasonal and tissue variation in NSC responses, as well as strong interactions among moisture stress at different timescales. In general, our results suggest large seasonal variation in crown NSC concentrations reflecting the multiple cofunctions of NSCs in plant tissues, including storage, growth and osmotic regulation of hydraulically vulnerable leaves. We emphasize that crown NSC pool size cannot be viewed as a simple physiological metric of stress; in situ NSC dynamics are complex, varying temporally, across species, among NSC fractions and among tissue types.
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http://dx.doi.org/10.1093/treephys/tpaa149DOI Listing
March 2021

Occupational silica exposure in an Australian systemic sclerosis cohort.

Rheumatology (Oxford) 2020 12;59(12):3900-3905

Department of Rheumatology, St Vincent's Hospital Melbourne, Melbourne, Victoria.

Objective: To determine the frequency of self-reported occupational exposure to silica in SSc patients enrolled in the Australian Scleroderma Cohort Study, and to compare the disease characteristics of the silica-exposed patients with those of the non-exposed patients.

Method: Data collected over a 12-year period from 1670 SSc patients were analysed. We compared the demographic and clinical characteristics of those who reported occupational silica exposure with those who did not. A subgroup analysis of male patients was performed, as well as a multivariable analysis of correlates of silica exposure.

Results: Overall, 126 (7.5%) of the cohort reported occupational silica exposure. These individuals were more likely to be male (73 of 231, i.e. 31.6% males exposed) and to have worked in mining and construction industries. Those who reported silica exposure were younger at the onset of SSc skin involvement [odds ratio (OR) 0.9, P = 0.02], of male gender (OR 14.9, P < 0.001), have joint contractures (OR 1.8, P = 0.05) and have higher physical disability as defined by scleroderma HAQ (OR 1.4, P = 0.01).

Conclusion: The highest percentage of silica exposure was found in males. These patients were more likely to have the presence of certain clinical manifestations and Scl-70 antibody, which is known to confer a poor prognosis. These findings support the association between occupational silica exposure and the subsequent development of SSc. Further investigation is required to describe the range of clinical manifestations and disease course, including prognosis and treatment response, in those diagnosed with occupationally induced SSc compared with idiopathic SSc.
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http://dx.doi.org/10.1093/rheumatology/keaa446DOI Listing
December 2020

Repurposing Clinical Decision Support System Data to Measure Dosing Errors and Clinician-Level Quality of Care.

J Med Syst 2020 Sep 8;44(10):185. Epub 2020 Sep 8.

Center for Healthcare Policy and Research, University of California, Davis, Sacramento, CA, USA.

We aimed to develop and validate an instrument to detect hospital medication prescribing errors using repurposed clinical decision support system data. Despite significant efforts to eliminate medication prescribing errors, these events remain common in hospitals. Data from clinical decision support systems have not been used to identify prescribing errors as an instrument for physician-level performance. We evaluated medication order alerts generated by a knowledge-based electronic prescribing system occurring in one large academic medical center's acute care facilities for patient encounters between 2009 and 2012. We developed and validated an instrument to detect medication prescribing errors through a clinical expert panel consensus process to assess physician quality of care. Six medication prescribing alert categories were evaluated for inclusion, one of which - dose - was included in the algorithm to detect prescribing errors. The instrument was 93% sensitive (recall), 51% specific, 40% precise, 62% accurate, with an F1 score of 55%, positive predictive value of 96%, and a negative predictive value of 32%. Using repurposed electronic prescribing system data, dose alert overrides can be used to systematically detect medication prescribing errors occurring in an inpatient setting with high sensitivity.
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http://dx.doi.org/10.1007/s10916-020-01603-9DOI Listing
September 2020

DALES, Drug Allergy Labels in Elective Surgical patients: a prospective multicentre cross-sectional study of incidence, risks, and attitudes in penicillin de-labelling strategies.

Br J Anaesth 2020 12 25;125(6):962-969. Epub 2020 Aug 25.

Departments of Anaesthesia and Critical Care Medicine, University College London Hospital, London, UK.

Background: Penicillin allergy is associated with a range of poor health outcomes. Allergy testing can be made simpler by using a direct drug provocation test in patients at low risk of genuine allergy. This approach could allow population-level 'de-labelling'. We sought to determine the incidence and nature of penicillin allergy labels in UK surgical patients and define patient and anaesthetist attitudes towards penicillin allergy testing.

Methods: A prospective cross-sectional questionnaire study was performed in 213 UK hospitals. 'Penicillin allergic' patients were interviewed and risk-stratified. Knowledge and attitudes around penicillin allergy were defined in patients and anaesthetists.

Results: Of 21 219 patients, 12% (n=2626) self-reported penicillin allergy; 27% reported low-risk histories potentially suitable for a direct drug provocation test; an additional 40% reported symptoms potentially suitable for a direct drug provocation test after more detailed assessment. Of 4798 anaesthetists, 40% claimed to administer penicillin routinely when they judged the label low risk. Only 47% of anaesthetists would be happy to administer penicillin to a patient previously de-labelled by an allergy specialist using a direct drug provocation test; perceived lack of support was the most common reason for not doing so.

Conclusions: At least 27% of patients with a penicillin allergy label may be suitable for a direct drug provocation test. Anaesthetists demonstrated potentially unsafe prescribing in patients with penicillin allergy labels. More than half of anaesthetists lack confidence in the results of a direct drug provocation tests undertaken by a specialist. Our findings highlight significant barriers to the effective implementation of widespread de-labelling in surgical patients.
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http://dx.doi.org/10.1016/j.bja.2020.07.048DOI Listing
December 2020

Performance of the 2017 EUSTAR activity index in an scleroderma cohort.

Clin Rheumatol 2020 Dec 21;39(12):3701-3705. Epub 2020 Jul 21.

Department of Medicine, The University of Melbourne at St Vincent's Hospital, Melbourne, Australia.

Assessment of disease activity in systemic sclerosis (SSc) is limited by the absence of a fully validated, multisystem measure of disease activity. The European Scleroderma Trials and Research Group (EUSTAR) SSc activity index (EScSG-AI) was recently revised, and a validation study within the EUSTAR cohort was performed. In this study, we evaluated the performance of the revised EScSG-AI in an external Australian cohort. The association between the EScSG-AI and the physician global assessment of disease activity (PhGA), both collected prospectively at each annual visit over up to 12 years follow-up, was evaluated using Pearson's correlation coefficient and Cohen's kappa coefficient. Generalized linear modelling and time-dependent Cox regression analysis were performed to determine the association of disease activity measured by the EScSG-AI and the summed Medsger Severity Scale (MSS) and death, respectively. There was a moderate correlation between EScSG-AI and PhGA scores (r 0.42, p < 0.001) and moderate association between rising EScSG-AI and summed MSS (r 0.60, p < 0.001). High disease activity, measured by the EScSG-AI at any time during follow-up, was associated with a hazard ratio of 2.07 (95% CI 1.51-2.79) for mortality. The EScSG-AI has a moderate correlation with physician-assessed SSc disease activity. This suggests that the criterion and construct validity of the EScSG-AI are yet to be demonstrated in an external cohort of SSc patients. Key Points •There remains no gold standard measure of SSc disease activity. •The revised 2017 EUSTAR SSc disease activity index shows moderate correlation with physician-rated global disease activity. •Significant work remains to develop a validated multisystem measure of disease activity in SSc.
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http://dx.doi.org/10.1007/s10067-020-05126-zDOI Listing
December 2020

A Case Report of Acute Heart Failure Due to Infective Aortic Endocarditis Diagnosed by Point-of-care Ultrasound.

Clin Pract Cases Emerg Med 2020 May 27;4(2):193-196. Epub 2020 Apr 27.

University of Kansas Health System, Department of Emergency Medicine, Kansas City, Kansas.

Introduction: Infective endocarditis (IE) is a life-threatening condition with significant morbidity and mortality, and can require surgical repair.

Case Report: A 36-year-old man presented to the emergency department for worsening dyspnea and chest pain. Point-of-care echocardiography demonstrated a mobile oscillating mass on the aortic valve with poor approximation of the valve leaflets, suggesting aortic valve insufficiency secondary to IE as the cause of acute heart failure. The patient underwent emergent aortic valve replacement within 24 hours.

Discussion: While point-of-care echocardiography has been well documented in identifying tricuspid vegetations, aortic valve involvement and subsequent heart failure is less well described. Earlier recognition of aortic valve vegetations and insufficiency can expedite surgical intervention, with decreased complication rates linked to earlier antimicrobial therapy.

Conclusion: This case report highlights the ability of point-of-care ultrasound to identify aortic vegetations, allowing for the earlier diagnosis and therapy.
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http://dx.doi.org/10.5811/cpcem.2020.3.45002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220014PMC
May 2020

Challenges of early renal cancer detection: symptom patterns and incidental diagnosis rate in a multicentre prospective UK cohort of patients presenting with suspected renal cancer.

BMJ Open 2020 05 11;10(5):e035938. Epub 2020 May 11.

Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK.

Objectives: To describe the frequency and nature of symptoms in patients presenting with suspected renal cell carcinoma (RCC) and examine their reliability in achieving early diagnosis.

Design: Multicentre prospective observational cohort study.

Setting And Participants: Eleven UK centres recruiting patients presenting with suspected newly diagnosed RCC. Symptoms reported by patients were recorded and reviewed. Comprehensive clinico-pathological and outcome data were also collected.

Outcomes: Type and frequency of reported symptoms, incidental diagnosis rate, metastasis-free survival and cancer-specific survival.

Results: Of 706 patients recruited between 2011 and 2014, 608 patients with a confirmed RCC formed the primary study population. The majority (60%) of patients were diagnosed incidentally. 87% of patients with stage Ia and 36% with stage III or IV disease presented incidentally. Visible haematuria was reported in 23% of patients and was commonly associated with advanced disease (49% had stage III or IV disease). Symptomatic presentation was associated with poorer outcomes, likely reflecting the presence of higher stage disease. Symptom patterns among the 54 patients subsequently found to have a benign renal mass were similar to those with a confirmed RCC.

Conclusions: Raising public awareness of RCC-related symptoms as a strategy to improve early detection rates is limited by the fact that related symptoms are relatively uncommon and often associated with advanced disease. Greater attention must be paid to the feasibility of screening strategies and the identification of circulating diagnostic biomarkers.
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http://dx.doi.org/10.1136/bmjopen-2019-035938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223292PMC
May 2020

Clinical Features of Systemic Sclerosis-Mixed Connective Tissue Disease and Systemic Sclerosis Overlap Syndromes.

Arthritis Care Res (Hoboken) 2021 05 3;73(5):732-741. Epub 2021 Apr 3.

St. Vincent's Hospital Melbourne, Melbourne, and The University of Melbourne at St Vincent's Hospital (Melbourne), Fitzroy, Victoria, Australia.

Objective: To describe the clinical characteristics and outcomes of systemic sclerosis-mixed connective tissue disease (SSc-MCTD) and SSc overlap syndrome.

Methods: We included patients from the Australian Scleroderma Cohort Study who met American College of Rheumatology/European Alliance of Associations for Rheumatology criteria for SSc. Three mutually exclusive groups were created: SSc-MCTD, SSc overlap, and SSc only. Univariate comparison of clinical features was performed by analysis of variance or chi-square test. Survival analysis was performed using Kaplan-Meier (KM) curves and Cox proportional hazards regression models.

Results: Of 1,728 patients, 97 (5.6%) had SSc-MCTD, and 126 (7.3%) had SSc overlap. Those with MCTD-SSc were more commonly Asian (18.3% versus 10.1% in SSc overlap, and 3.6% in SSc only; P < 0.0001) and younger at disease onset (38.4 years versus 46.5 or 46.8 years, P < 0.0001). Those with SSc-MCTD or SSc overlap were more likely to have limited cutaneous SSc. All 3 groups had similar frequency of interstitial lung disease (ILD), although pulmonary arterial hypertension (PAH) was less common in SSc overlap. Synovitis and myositis were more common in SSc overlap and SSc-MCTD than in SSc only. KM curves showed better survival in SSc-MCTD than SSc overlap or SSc only (P = 0.011), but this was not significant after adjustment for sex and age at disease onset. SSc-specific antibodies were survival prognostic markers, with antinuclear antibody centromere or anti-RNP conferring better survival than anti-Scl-70 or anti-RNA polymerase III (P = 0.005). Patients with SSc-MCTD and SSc overlap had lower mortality following diagnosis of ILD and PAH than patients with SSc only.

Conclusion: This study provides insights into the clinical characteristics of patients with SSc-MCTD, SSc overlap, and SSc only and shows that anti-RNP antibodies are associated with better survival than anti-Scl-70 and anti-RNA polymerase III antibodies.
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http://dx.doi.org/10.1002/acr.24167DOI Listing
May 2021

Prioritizing a sequence of short-duration groups as the standardized pathway for chronic noncancer pain at an Australian tertiary multidisciplinary pain service: preliminary outcomes.

Pain Rep 2019 Sep-Oct;4(5):e780. Epub 2019 Sep 18.

Hunter Integrated Pain Service, Hunter New England Health, Newcastle, New South Wales, Australia.

Objective: To describe implementation and report preliminary outcomes of a resource-efficient, standardized group pathway for chronic noncancer pain.

Design: Descriptive cross-sectional study of a group-based pain management pathway in comparison with an Australasian benchmarking data set.

Setting: An Australian tertiary multidisciplinary pain service.

Subjects: Patients with chronic noncancer pain actively participating in the group pathway in 2016.

Methods: Referred patients were prioritized to a short-duration group-based standardized pain management pathway linking education, assessment, and treatment groups. Measures of pain, mood, self-efficacy, and catastrophizing and reduction in daily opioid use were collated from the Australasian data set.

Results: In 2016, 928 patients were actively engaged with the pain service. More patients were prioritized to receive treatment in a group format in comparison with other Australasian services (68.4% vs 22%). A greater percentage of patients attended their first clinical contact within 3 months of referral (81.4%) compared with the Australasian average (68.6%). Comparable improvements in average pain intensity, pain interference, depression, anxiety, stress, pain catastrophizing, and self-efficacy were observed. There was significantly greater reduction in opioid use, including for those taking more than 40 mg of oral morphine equivalent daily dose.

Conclusion: Implementation of a sequence of short-duration groups as the default clinical pathway resulted in shorter waiting times and noninferior outcomes in key areas for patients completing the program, compared with Australasian averages. Given the resource efficiencies of the group process, this finding has implications for service design.
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http://dx.doi.org/10.1097/PR9.0000000000000780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882570PMC
September 2019

Can Patient-Reported Symptoms Be Used to Measure Disease Activity in Systemic Sclerosis?

Arthritis Care Res (Hoboken) 2020 10;72(10):1459-1465

St. Vincent's Hospital Melbourne and the University of Melbourne, Fitzroy, Victoria, Australia.

Objective: To evaluate the association between patient-reported symptoms and changes in disease activity over time in systemic sclerosis (SSc).

Methods: Using data from 1,636 patients enrolled in the Australian Scleroderma Cohort Study, we used generalized estimating equations to determine the relationship between patient-reported worsening of Raynaud's phenomenon (RP), skin involvement, and breathlessness in the month preceding each study visit and features of disease activity in the corresponding organ systems. The associations between the following parameters were analyzed: patient-reported worsening RP and the presence of new-onset digital pitting and digital ulcers; patient-reported worsening skin involvement and increasing modified Rodnan skin thickness score (MRSS); new areas of skin involvement and new-onset joint contractures; patient-reported worsening breathlessness and deteriorating respiratory functions test (RFT) results, indicated by a 10% decrease in forced vital capacity (FVC) and a 15% decrease in diffusing capacity for carbon monoxide (DLco), new-onset interstitial lung disease (ILD), and new-onset pulmonary arterial hypertension (PAH).

Results: We found a significant association between patient-reported worsening RP and the presence of digital ulcers (odds ratio [OR] 1.53 [95% confidence interval (95% CI) 0.60-0.93]), patient-reported worsening skin involvement and increasing MRSS (OR 2.10 [95% CI 1.54-2.86]), and worsening patient breathlessness and deteriorating RFTs (FVC OR 2.12 [95% CI 1.70-2.65]; DLco OR 1.97 [95% CI 1.34-2.02]), new-onset ILD (OR 1.91 [95% CI 1.40-2.61]), and new-onset PAH (OR 5.08 [95% CI 3.59-7.19]).

Conclusion: These results demonstrate that patient-reported symptoms are associated with clinically meaningful changes in disease activity in patients with SSc. This suggests that when objective measures of change in disease status are unavailable, patient-reported symptoms could be used to indicate a change in SSc disease activity.
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http://dx.doi.org/10.1002/acr.24053DOI Listing
October 2020

Investigating strategies to improve clinical trial opportunities for patients with cancer in New Zealand-INSIGHT.

N Z Med J 2019 07 12;132(1498):10-31. Epub 2019 Jul 12.

Medical Oncology, Auckland District Health Board (DHB), Auckland; Cancer Trials New Zealand, University of Auckland, Auckland.

Aims: Fewer than 5% of adult cancer patients participate in clinical trials, with multiple patient, clinician and institutional barriers identified. This study aimed to explore patient factors that impact access to cancer trials in New Zealand.

Methods: A questionnaire that included demographics and factors that might impact trial participation was circulated via nine district health boards (DHBs) and four cancer foundations to patients with a cancer diagnosis.

Results: Between July 2016 and August 2017, 691 patients responded, 62% female and 77% aged >50 years. Most patients (86%) would consider trial participation, which differed by income (p=0.0001) but not by age, tumour type or gender. Patients would consider attending another hospital (44%) or relocating (11%); 10% considered trials a last resort. Advantageous factors to participation included: benefiting others (92%), better treatment (82%), more scans and longer follow-up (47% and 51%). Disincentives included fear of randomisation (78%), treatment toxicities (71%), time and cost of more visits (40%) and unspecified future research (32%).

Conclusion: Identified barriers to trial participation were similar in New Zealand to other developed countries. In this motivated cohort, patients are very interested in trial participation at any stage of their treatment and did not mind extra travel or tests.
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July 2019

Significance of anti-neutrophil cytoplasmic antibodies in systemic sclerosis.

Arthritis Res Ther 2019 02 14;21(1):57. Epub 2019 Feb 14.

The University of Melbourne, 41 Victoria Parade Fitzroy, Melbourne, Victoria, 3065, Australia.

Background: Up to 12% of patients with systemic sclerosis (SSc) have anti-neutrophil cytoplasmic antibodies (ANCA). However, the majority of these patients do not manifest ANCA-associated vasculitis (AAV) and the significance of ANCA in these patients is unclear. The aim of this study is to determine the prevalence of ANCA in a well-characterised SSc cohort and to examine the association between ANCA and SSc clinical characteristics, other autoantibodies, treatments and mortality.

Methods: Clinical data were obtained from 5 centres in the Australian Scleroderma Cohort Study (ASCS). ANCA positive was defined as the presence of any one or combination of cytoplasmic ANCA (c-ANCA), perinuclear ANCA (p-ANCA), atypical ANCA, anti-myeloperoxidase (anti-MPO) or anti-proteinase-3 (anti-PR3). Associations of demographic and clinical features with ANCA were investigated by logistic or linear regression. Survival analysis was performed using Kaplan-Meyer curves and Cox regression models.

Results: Of 1303 patients, 116 (8.9%) were ANCA positive. Anti-PR3 was more common than anti-MPO (13.8% and 11.2% of ANCA-positive patients, respectively). Only 3 ANCA-positive patients had AAV. Anti-Scl-70 was more common in ANCA positive vs ANCA negative (25% vs 12.8%, p < 0.001), anti-MPO positive vs anti-MPO negative (38.5% vs 13.6%, p = 0.006) and anti-PR3 positive vs anti-PR3 negative patients (44.4% vs 13.4%, p < 0.001). A higher prevalence of interstitial lung disease (ILD) was found in the ANCA positive (44.8% vs 21.8%, p < 0.001) and the anti-PR3 positive groups (50.0% vs 23.4%, p = 0.009). In multivariable analysis, ANCA-positive status remained associated with ILD after adjusting for anti-Scl-70 antibodies. Pulmonary embolism (PE) was more common in ANCA-positive patients (8.6% vs 3.0%, p = 0.002) and anti-PR3-positive patients (16.7% vs 3.3%, p = 0.022). ANCA-positive status remained associated with PE in a multivariable analysis adjusting for anti-phospholipid antibodies. Kaplan-Meier analysis revealed increased mortality in ANCA-positive patients (p = 0.006). In Cox regression analysis, ANCA was associated with increased mortality, after adjusting for age and sex.

Conclusions: ANCA is associated with increased prevalence of ILD and PE in SSc. ANCA should be tested in SSc, as it identifies individuals with worse prognosis who require close monitoring for adverse outcomes.
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http://dx.doi.org/10.1186/s13075-019-1839-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6376778PMC
February 2019

Trials with proxy-reported outcomes registered on the Australian New Zealand Clinical Trials Registry (ANZCTR).

Qual Life Res 2019 Apr 15;28(4):955-962. Epub 2018 Dec 15.

Department of Health Services, Policy & Practice, Brown University School of Public Health, Providence, USA.

Aims: A proxy is someone other than a patient who reports a patient's outcomes as if they are the patient. Due to known discordance with patient reports, proxies are often not recommended in clinical trials; however, proxies may be needed in certain research contexts. We aimed to identify and describe trials registered on the Australian New Zealand Clinical Trials Registry (ANZCTR) with proxy-reported endpoints.

Methods: ANZCTR was systematically searched from inception (2005) to 31 March 2017 for trials with proxy-reported endpoints. Primary and secondary endpoints for each trial retrieved by the search were individually coded (proxy-reported: yes/no), and trials with confirmed proxy-reported endpoints were included in the analysis.

Results: Of 13,666 registered trials, 469 (3.4%) included a proxy-reported endpoint (867 individual proxy-reported endpoints in total: 62% family member proxy, 22% health professional). Proxy endpoint inclusion did not significantly increase over time (r = 0.18, p = 0.59). Mental health (11.5%), stroke (10.3%) and neurological (8.3%) trials had the highest proportion of trials using proxies. Of the 469 trials, 123 (26.2%) studies involved paediatric patients.

Discussion: Proxy-reported endpoints are included in a small but notable number of studies, which may indicate other types of outcomes are used for patients unable to self-report, or that these patients are under-researched.
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http://dx.doi.org/10.1007/s11136-018-2080-4DOI Listing
April 2019

International Gynecologic Cancer Society (IGCS) 2018: Meeting report.

Gynecol Oncol 2019 01 28;152(1):7-10. Epub 2018 Oct 28.

Department of Obstetrics and Gynecology, University of Chicago, Chicago IL USA.

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http://dx.doi.org/10.1016/j.ygyno.2018.10.020DOI Listing
January 2019

The role of inflammatory markers in assessment of disease activity in systemic sclerosis.

Clin Exp Rheumatol 2018 Jul-Aug;36 Suppl 113(4):126-134. Epub 2018 Sep 29.

Department of Medicine, The University of Melbourne at St Vincent's Hospital, and Department of Rheumatology, St Vincent's Hospital, Melbourne, Australia.

Objectives: The role of the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in the assessment of disease activity in systemic sclerosis (SSc) remains controversial. We sought to evaluate the relationship between clinical features of SSc and raised inflammatory markers and to determine if changes in ESR and CRP reflect changes in other disease features over time.

Methods: One thousand, five hundred and forty-five patients enrolled in the Australian Scleroderma Cohort Study were observed over a mean 3.52±2.91 years and assessed at 6,119 study visits. Generalised estimating equations were used to determine the relationship between ESR≥20mm/hr and CRP≥5mg/L and features of disease. The associations between change in inflammatory markers and change in skin scores and respiratory function tests were analysed.

Results: Overall, there was a significant association between raised ESR and forced vital capacity (FVC)<80% predicted, diffusing capacity of the lung (DLCO)<80% predicted, pulmonary arterial hypertension (PAH), body mass index (BMI), proximal muscle strength, anaemia, and hypocomplementaemia (p<0.05). Raised CRP was significantly associated with modified Rodnan Skin Score>20, FVC<80%, DLCO<80%, PAH, digital ulcers, BMI, synovitis, tendon friction rub, anaemia, and hypocomplementaemia (p<0.05). A significant deterioration in respiratory function tests (RFTs) was associated with a 2-fold increase in both ESR and CRP (p<0.05).

Conclusions: Raised inflammatory markers are associated with pulmonary, cutaneous and musculoskeletal manifestations of SSc. Rising inflammatory markers are correlated with declining respiratory function tests. This suggests inflammatory markers have a role in the assessment of SSc disease activity.
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January 2019

A practical guide to understanding, using and including patient reported outcomes in clinical trials in ovarian cancer.

J Gynecol Oncol 2018 Sep 9;29(5):e81. Epub 2018 Jun 9.

Prince of Wales Cancer Centre, Sydney, NSW, Australia.

Health related quality of life (HRQOL) is a key priority for patients with ovarian cancer as there is significant morbidity associated with the disease and the treatment. It is therefore essential to include measures of HRQOL and patient reported outcomes (PROs) in all clinical trials and ideally report them in the initial manuscript. The results of these analyses help interpret the primary trial endpoints which are typically progression free survival and overall survival from the perspective of the patients, but can also assist with regulatory approval of new drugs and inform future patients regarding the potential benefits and downsides of the treatment as well as help support clinical recommendations. Including PROs in clinical trials allows patient-defined clinical benefits to be assessed in parallel to traditional survival outcomes to provide a more holistic overview and aid in the interpretation of the trial results. Given the importance of these instruments in clinical trials, greater effort is required to improve the appropriate inclusion, quality of analyses and reporting of PROs. It is also essential that all clinicians understand the intricacies of the selection, implementation and interpretation of these measures of HRQOL and PRO's and how important their contribution is to clinical trials as well as clinical practice. This review is a practical guide for clinicians to gain a better understanding of PROs and how they can be incorporated into ovarian cancer trials.
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http://dx.doi.org/10.3802/jgo.2018.29.e81DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6078895PMC
September 2018

Correction to: Trials with patient-reported outcomes registered on the Australian New Zealand Clinical Trials Registry (ANZCTR).

Qual Life Res 2018 10;27(10):2593

Comparative Health Outcomes, Policy, and Economics (CHOICEc) Institute, University of Washington, Seattle, WA, USA.

In the original publication of the article, the sentence "The ANZCTR is the fifth largest trial registry internationally, with 21,330 registered trials as at January 2018 [5]" in the Introduction section was published incorrectly.
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http://dx.doi.org/10.1007/s11136-018-1934-0DOI Listing
October 2018

Switching From Originator to Biosimilar Infliximab in Paediatric Inflammatory Bowel Disease Is Feasible and Uneventful.

J Pediatr Gastroenterol Nutr 2018 12;67(6):745-748

Department of Paediatric Gastroenterology, Royal Hospital for Children, Glasgow.

The safety, clinical efficacy, and cost-effectiveness of biosimilar infliximab in adult inflammatory bowel disease (IBD) have now been extensively shown. Limited data have been collected in the paediatric setting. We report nationwide, prospective, clinical safety and effectiveness data for patients from all 3 Scottish paediatric inflammatory bowel disease networks switching from originator to biosimilar infliximab. Prospective clinical data were collected for 33 patients. Information was collected from electronic patient records, laboratory reports, and patient case notes. There were no clinically significant changes to disease activity, biomarkers, antidrug antibodies, or trough drug levels (P > 0.1) within a 12-month follow-up period; in addition, there were no significant adverse events reported. No infusion reactions were seen in the 264 infusions delivered. Switching from originator infliximab to the biosimilar (CT-P13) appears to be associated with neither an increase in infusion reactions nor significant loss of effectiveness in the short term.
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http://dx.doi.org/10.1097/MPG.0000000000002091DOI Listing
December 2018

Trials with patient-reported outcomes registered on the Australian New Zealand Clinical Trials Registry (ANZCTR).

Qual Life Res 2018 Oct 18;27(10):2581-2591. Epub 2018 Jun 18.

Comparative Health Outcomes, Policy, and Economics (CHOICEc) Institute, University of Washington, Seattle, WA, USA.

Aims: It is important to understand the number, types and regions of trials that include patient-reported outcomes (PROs) to appreciate how patient experiences have been considered in studies of health and interventions. Twenty-seven percent of trials registered with ClinicalTrials.gov (2007-2013) included PROs; however, a regional breakdown was not provided and no reviews have been conducted of the Australia New Zealand Clinical Trials Registry (ANZCTR). We aimed to identify trials registered with ANZCTR with PRO endpoints and describe their characteristics.

Methods: ANZCTR was systematically searched from inception (2005) to 31 March 2017 for trials with PRO endpoints. Search terms included PRO measures listed in Patient-Reported Outcomes Quality of Life Instrument Database and Grid-Enabled Measures, as well as generic PRO terms (e.g. "quality of life" (QOL)). Trial endpoints were individually coded using an established framework to identify trials with PROs for the analysis.

Results: Of 13,666 registered trials, 6168 (45.1%) included a PRO. The proportion of studies including PROs increased between 2006 and 2016 (r = 0.74, p = 0.009). Among the 6168 trials, there were 17,961 individual PRO endpoints, including symptoms/functional outcomes/condition-specific QOL (65.6%), generic QOL (13.2%), patient-reported experiences (9.9%), patient-reported behaviours (7.9%). Mental health was the most common category (99.8% included PROs), followed by physical medicine/rehabilitation (65.6%), musculoskeletal (63.5%), public health (63.1%), and cancer (54.2%).

Discussion: Our findings suggest growing use of PROs in the assessment of health and interventions in ANZ. Our review identifies trial categories with limited patient-reported information and provides a basis for future work on the impact of PRO findings in clinical care.
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http://dx.doi.org/10.1007/s11136-018-1921-5DOI Listing
October 2018

Increased serum levels of adhesion molecules ICAM-1 and VCAM-1 in systemic sclerosis are not specific for pulmonary manifestations.

Clin Rheumatol 2018 Jun 23;37(6):1563-1571. Epub 2018 Apr 23.

Department of Rheumatology, St Vincent's Hospital (Melbourne), 41 Parade, Fitzroy, VIC, 3065, Australia.

Studies suggest elevated serum intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) levels may be markers of pulmonary arterial hypertension in systemic sclerosis (SSc-PAH). We sought to evaluate whether ICAM-1 and VCAM-1 levels are useful screening biomarkers for incident SSc-PAH. In this cross-sectional study, four groups were selected from the Australian Scleroderma Cohort Study: group 1 (n = 15) had definite PAH; group 2 (n = 19) had interstitial lung disease (ILD); group 3 (n = 30) were SSc-controls; and group 4 (n = 34) were healthy controls. Serum ICAM-1 and VCAM-1 levels were measured using the Millipore Milliplex MAP Human 2-Plex Panel. There were no differences in ICAM-1 levels in the PAH versus ILD group (263.0 ± 85.4 vs 380.4 ± 168.3 ng/mL, p = 0.136), SSc-controls (263.0 ± 85.4 vs 253.1 ± 98.0 ng/mL, p = 1.00), or healthy controls (263.0 ± 85.4 vs 201.8 ± 57.2 ng/mL, p = 0.093). Similarly, there were no differences in VCAM-1 level in PAH versus ILD groups (1476.2 ± 434.9 vs 1424.8 ± 527.6 ng/mL, p = 1.00) and SSc-controls (1476.2 ± 434.9 vs 1409.5 ± 341.1 ng/mL, p = 1.00). SSc subjects had significantly higher levels of ICAM-1 (297.4 ± 134.0 vs 201.8 ± 57.2 ng/mL, p < 0.0001) and VCAM-1 compared to healthy controls (1432.7 ± 427.4 vs 1125.6 ± 273.4 ng/mL, p < 0.0001). Neither ICAM-1 nor VCAM-1 is a specific screening biomarker of SSc-PAH. Instead, increased levels of these adhesion molecules in SSc, irrespective of pulmonary complications, suggest that they may play a role in SSc pathogenesis.
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http://dx.doi.org/10.1007/s10067-018-4081-7DOI Listing
June 2018

Explicit and implicit attitudes towards people with intellectual disabilities: The role of contact and participant demographics.

J Appl Res Intellect Disabil 2018 Sep 23;31(5):778-784. Epub 2017 Nov 23.

Clinical Psychology, University College London, London, UK.

Background: Intellectual disability research has concentrated on self-reported explicit attitudes with little focus on implicit attitudes. Such attitudes are evaluations which occur with or without conscious awareness, respectively. This investigation examined participants' (N = 234) attitudes towards individuals with intellectual disabilities with reference to participants' gender, age, level of education, frequency of contact and closeness.

Method: UK adults completed explicit (ATTID) and implicit attitude (ST-IAT) measures, and provided demographics via an online survey.

Results: Participant demographics predicted explicit attitudes-with differing cognitive, affective and behavioural associations. Contact frequency was most significant. Implicit attitudes were not predicted, evidencing implicit-explicit attitude differences.

Conclusions: The results encourage more implicit-explicit attitude relationship research regarding disability. The associations between demographics, contact and implicit attitudes should be explored further. Research should question whether implicit attitudes reflect participants' true beliefs-denoting less importance to demographics-or whether they reflect wider societal values rather than individuals' attitudes.
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http://dx.doi.org/10.1111/jar.12429DOI Listing
September 2018
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