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Objective: Intra‐articular (IA) mineralization may contribute to osteoarthritis (OA) structural progression. We studied the association of IA mineralization on knee computed tomography (CT) with cartilage damage worsening on knee magnetic resonance imaging (MRI), with a focus on location‐ and tissue‐specific effects. Methods: Participants from the Multicenter Osteoarthritis Study with knee CT and MRI scans were included. Presence of IA mineralization on CT was defined as a Boston University Calcium Knee Score >0 anywhere in the knee. Cartilage worsening on MRI was defined as any increase in the MRI OA Knee Score, including incident damage. We evaluated the association of whole‐knee, compartment‐specific (ie, medial or lateral), and subregion‐specific (ie, location‐matched) IA mineralization at baseline with cartilage worsening at two years' follow‐up in the corresponding locations using binomial regression with generalized estimating equations, adjusting for age, sex, and body mass index (BMI). Results: We included 1,673 participants (mean age 60 years, 56% female, mean BMI 29). Nine percent had any IA mineralization in the knee, and 47.4% had any cartilage worsening on follow‐up. Mineralization of any tissue in the knee, regardless of location, was not associated with MRI cartilage worsening. However, cartilage mineralization was associated with 1.39 (95% confidence interval 1.04–1.88) times higher risk of cartilage worsening in the same compartment, with similar results in subregion‐specific analysis. Conclusion: CT‐detected IA mineralization in the cartilage was associated with higher risk of MRI cartilage worsening in the same compartment and subregion over two years. These findings suggest potential localized, tissue‐specific effects of IA mineralization on cartilage pathology in knee OA. [ABSTRACT FROM AUTHOR]

Issues: Although maternal substance use is a known risk factor for child maltreatment, evidence on the scale of substance use is needed to inform prevention responses. This systematic review synthesised prevalence estimates of maternal substance use during pregnancy and early life among children at risk of maltreatment. Ovid, Pubmed, CINAHL, PsychInfo and ProQuest databases were searched. We included observational studies that sampled children at risk of maltreatment in high‐income countries and reported information on maternal substance use during pregnancy and/or the child's first year of life. We extracted study characteristics and data to calculate prevalence, assessed risk of bias and conducted a narrative synthesis; there were insufficient comparable populations or outcomes to quantitatively synthesise results. Key Findings: Thirty five of 14,084 titles were included. Fifteen studies had adequately sized and representative samples to estimate prevalence. Maternal substance use prevalence ranged from 2.4% to 40.6%. Maternal substance use was highest among infants referred to child protection at birth (40.6%) and children in out‐of‐home care (10.4% to 37.2%). Prevalence was higher when studies defined substance use more broadly and when maternal substance use was ascertained from both child and mother records. Implications: Supportive, coordinated responses to maternal substance use are needed from health and child protection services, spanning alcohol and other drug treatment, antenatal and postnatal care. Conclusions: Prenatal and early life maternal substance use is common among child maltreatment populations, particularly among younger children and those with more serious maltreatment. [ABSTRACT FROM AUTHOR]

Objective: Intra‐articular (IA) calcium crystal deposition is common in knee osteoarthritis (OA), but of unclear significance. It is possible that low‐grade, crystal‐related inflammation may contribute to knee pain. We examined the longitudinal relation of computed tomography (CT)–detected IA mineralization to the development of knee pain. Methods: We used data from the National Institutes of Health–funded longitudinal Multicenter Osteoarthritis Study. Participants had knee radiographs and bilateral knee CTs at baseline, and pain assessments every 8 months for 2 years. CT images were scored using the Boston University Calcium Knee Score. We longitudinally examined the relation of CT‐detected IA mineralization to the risk of frequent knee pain (FKP), intermittent or constant knee pain worsening, and pain severity worsening using generalized linear mixed‐effects models. Results: We included 2,093 participants (mean age 61 years, 57% women, mean body mass index 28.8 kg/m2). Overall, 10.2% of knees had IA mineralization. The presence of any IA mineralization in the cartilage was associated with 2.0 times higher odds of having FKP (95% confidence interval [CI] 1.38–2.78) and 1.86 times more frequent intermittent or constant pain (95% CI 1.20–2.78), with similar results seen for the presence of any IA mineralization in the meniscus or joint capsule. A higher burden of IA mineralization anywhere within the knee was associated with a higher odds of all pain outcomes (odds ratio ranged from 2.14 to 2.21). Conclusion: CT‐detected IA mineralization was associated with risk of having more frequent, persistent, and worsening knee pain over 2 years. Targeting IA mineralization may have therapeutic potential for pain improvement in knee OA. [ABSTRACT FROM AUTHOR]

Objectives: This study developed predictive models for one‐week acute and six‐month persistent pain following root canal treatment (RCT). An additional aim was to study the gain in predictive efficacy of models containing clinical factors only, over models containing sociodemographic characteristics. Methods: A secondary data analysis of 708 patients who received RCTs was conducted. Three sets of predictors were used: (1) combined set, containing all predictors in the data set; (2) clinical set and (3) sociodemographic set. Missing data were handled by multiple imputation using the missing indicator method. The multilevel least absolute selection and shrinkage operator (LASSO) regression was used to select predictors into the final multilevel logistic models. Three measures, the area under the receiver operating characteristic curve (AUROC) and precision‐recall curve (AUPRC) and calibration curves, were used to assess the predictive performance of the models. Results: The selected‐in factors in the final models, using LASSO regression, are related to pre‐ and intra‐treatment clinical symptoms and pain experience. Predictive performance of the models remained the same with the inclusion (exclusion) of the socio‐demographic factors. For predicting one‐week outcome, the model built with combined set of predictors yielded the highest AUROC and AUPRC of 0.85 and 0.72, followed by the models built with clinical factors (AUROC = 0.82, AUPRC = 0.66). The lowest predictive ability was found in models with only sociodemographic characteristics (AUROC = 0.68, AUPRC = 0.40). Similar patterns were observed in predicting six‐month outcome, where the AUROC for models with combined, clinical and sociodemographic sets of predictors were 0.85, 0.89 and 0.66, respectively, and the AUPRC were 0.48, 0.53 and 0.22, respectively. Conclusions: Clinical factors such as the severity and experience of pre‐operative and intra‐operative pain were discovered important to the subsequent development of pain following RCTs. Adding sociodemographic characteristics to the models with clinical factors did not change the models' predictive performance or the proportion of explained variance. [ABSTRACT FROM AUTHOR]

Aim: To describe the cumulative incidence of child protection (CP) system contact, maltreatment type, source of reports to age 7 years, and socio‐demographic characteristics for culturally and linguistically diverse (CALD) Australian children. Methods: We used CP, education, health, and birth registrations data for children followed from birth up to age 7 from the South Australian Better Evidence, Better Outcomes, Linked Data (SA BEBOLD) platform. Participants: SA born children enrolled in their first year of school from 2009 to 2015 (n = 76 563). CALD defined as non‐Aboriginal or Torres Strait Islander, spoken language other than English, Indigenous or Sign, or had at least one parent born in a non‐English speaking country. Outcomes measures: For CALD and non‐CALD children, we estimated the cumulative incidence (risk) of CP contacts up to age 7, relative risk and risk differences for all levels of CP contact from notification to out‐of‐home care (OOHC), primary maltreatment type, reporter type, and socio‐economic characteristics. Sensitivity analyses explored different population selection criteria and CALD definitions. Results: By age 7, 11.2% of CALD children had 'screened‐in' notifications compared to 18.8% of non‐CALD (risk difference [RD] 7.6 percentage points (95% confidence interval: 6.9–8.3)), and 0.6% of CALD children experienced OOHC compared to 2.2% of non‐CALD (RD 1.6 percentage points (95% confidence interval: 1.3–1.8)). Emotional abuse was the most common substantiated maltreatment type for CALD and neglect for non‐CALD. Among both groups, the most common reporter sources were police and education sector. Socio‐economic characteristics were broadly similar. Sensitivity analyses results were consistent with primary analyses. Conclusion: By age 7, CALD children had lower risk of contact with all levels of CP. Estimates based on primary and sensitivity analyses suggested CALD children were 5–9 percentage points less likely to have a report screened‐in, and from 1.0 to 1.7 percentage points less likely to have experienced OOHC. [ABSTRACT FROM AUTHOR]

Objective: To assess the effects of weight loss and weight gain on hip and knee radiographic changes, pain, and joint replacement over 4 years. Methods: Participants (n = 2,752) from the Osteoarthritis Initiative were classified as those with weight gain (more than 5% gain), weight loss (more than –5% loss), or as controls (–3% to 3% change) over 4 years. Generalized estimating equations (adjusted for age, sex, and body mass index) were used to assess the relationship between the weight‐change group and 4‐year changes in knee radiographic osteoarthritis (OA) (Kellgren/Lawrence [K/L] grade), hip OA (Croft summary grade), joint space narrowing (JSN), and joint pain. Results: For radiographic knee OA, weight loss was associated with significantly lower odds of K/L grade worsening over 4 years (odds ratio [OR] 0.69 [95% confidence interval (95% CI) 0.53–0.91], P = 0.009), and weight gain was significantly associated with higher odds of medial knee JSN (OR 1.29 [95% CI 1.01–1.64], P = 0.038) compared to controls. For knee pain, weight loss was significantly associated with knee pain resolution over 4 years (OR 1.40 [95% CI 1.06–1.86], P = 0.019) while weight gain was associated with knee pain development (OR 1.34 [95% CI 1.08–1.67], P = 0.009) compared to controls. For all hip outcomes, no significant associations (P > 0.05) were found with weight‐change groups. The associations between the weight‐change group and total hip or total knee replacement were not significant (P > 0.05). Conclusion: This large, longitudinal study (n = 2,752 with 4‐year follow‐up) suggests that weight loss may protect against, and weight gain may exacerbate, radiographic and symptomatic knee OA, while weight change (at a 5% threshold) does not have significant effects on hip OA. [ABSTRACT FROM AUTHOR]

Background: Synovial inflammation is a risk factor for osteoarthritis (OA). But to date, there is limited information on how inflammation impacts progression of knee OA. Purpose: To investigate how sustained synovitis, assessed with semi‐quantitative magnetic resonance imaging (MRI) scores, impacts progression of knee degenerative changes over 4 years. Study Type: Retrospective cohort study. Subjects: In 249 participants (N = 132 women [53%]), from the Osteoarthritis Initiative (OAI) two definitions for synovitis were used resulting in two groups of participants with sustained synovitis at baseline, 2‐year, and 4‐year follow‐up (N = 80 and N = 132), and two groups without synovitis at all three time points (N = 81 and N = 47). Field Strength/Sequence: 3 T intermediate‐weighted (IW) turbo spin‐echo (TSE) sequence and three‐dimensional (3D) dual‐echo steady‐state (DESS) sequence. Assessment: Synovitis was scored semi‐quantitatively using the Anterior Cruciate Ligament Osteoarthritis Score (ACLOAS), MRI Osteoarthritis Knee Score (MOAKS), and synovial proliferation score (SPS). Two MRI‐based definitions of synovitis were used: (i) score ≥2 based on cumulative score of MOAKS and ACLOAS, and (ii) score ≥3 based on the cumulative score of ACLOAS, MOAKS, and SPS. Changes in structural abnormalities from baseline to year 4 measured using the whole‐organ MRI score (WORMS) were defined as outcomes. Statistical Tests: Linear regression models were used to compare the differences in longitudinal changes in WORMS scores between participants with and without sustained synovitis for each definition of sustained synovitis. A P‐value of <0.05 was considered statistically significant. Results: Significantly higher rates of progression were found in participants with synovitis for patellar (Beta coeff. = 0.29) and medial tibial cartilage abnormalities (Beta coeff. = 0.29) for definition (i). For definition (ii), patellar (Beta coeff. = 0.36) and medial femoral cartilage (Beta coeff. = 0.30) abnormalities demonstrated significant differences. Data Conclusion: Greater progression of structural degenerative disease was observed in individuals with sustained synovitis compared to those without sustained synovitis, suggesting that sustained synovitis is associated with progressive OA. Level of Evidence: 3 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

Objective: The lack of strong association between knee osteoarthritis (OA) structural features and pain continues to perplex researchers and clinicians. Evaluating the patellofemoral joint in addition to the tibiofemoral joint alone has contributed to explaining this structure–pain discordance, hence justifying a more comprehensive evaluation of whole‐knee OA and pain. The present study, therefore, was undertaken to evaluate the association between patellofemoral and tibiofemoral OA features with localized anterior knee pain (AKP) using 2 study designs. Methods: Using cross‐sectional data from the Multicenter Osteoarthritis Study, our first approach was a within‐person, knee‐matched design in which we identified participants with unilateral AKP. We then assessed magnetic resonance imaging (MRI)–derived OA features (cartilage damage, bone marrow lesions [BMLs], osteophytes, and inflammation) in both knees and evaluated the association of patellofemoral and tibiofemoral OA features to unilateral AKP. In our second approach, MRIs from 1 knee per person were scored, and we evaluated the association of OA features to AKP in participants with AKP and participants with no frequent knee pain. Results: Using the first approach (n = 71, 66% women, mean ± SD age 69 ± 8 years), lateral patellofemoral osteophytes (odds ratio [OR] 5.0 [95% confidence interval (95% CI) 1.7–14.6]), whole‐knee joint effusion‐synovitis (OR 4.7 [95% CI 1.3–16.2]), and infrapatellar synovitis (OR 2.8 [95% CI 1.0–7.8]) were associated with AKP. Using the second approach (n = 882, 59% women, mean ± SD age 69 ± 7 years), lateral and medial patellofemoral cartilage damage (prevalence ratio [PR] 2.3 [95% CI 1.3–4.0] and PR 1.9 [95% CI 1.1–3.3], respectively) and lateral patellofemoral BMLs (PR 2.6 [95% CI 1.5–4.7]) were associated with AKP. Conclusion: Patellofemoral but not tibiofemoral joint OA features and inflammation were associated with AKP. [ABSTRACT FROM AUTHOR]

Objective: To determine the optimal combination of imaging and biochemical biomarkers for use in the prediction of knee osteoarthritis (OA) progression. Methods: The present study was a nested case–control trial from the Foundation of the National Institutes of Health OA Biomarkers Consortium that assessed study participants with a Kellgren/Lawrence grade of 1–3 who had complete biomarker data available (n = 539 to 550). Cases were participants' knees that had radiographic and pain progression between 24 and 48 months compared to baseline. Radiographic progression only was assessed in secondary analyses. Biomarkers (baseline and 24‐month changes) that had a P value of <0.10 in univariate analysis were selected, including quantitative cartilage thickness and volume on magnetic resonance imaging (MRI), semiquantitative MRI markers, bone shape and area, quantitative meniscal volume, radiographic progression (trabecular bone texture [TBT]), and serum and/or urine biochemical markers. Multivariable logistic regression models were built using 3 different stepwise selection methods (complex models versus parsimonious models). Results: Among baseline biomarkers, the number of locations affected by osteophytes (semiquantitative), quantitative central medial femoral and central lateral femoral cartilage thickness, patellar bone shape, and semiquantitative Hoffa‐synovitis predicted OA progression in most models (C statistic 0.641–0.671). In most models, 24‐month changes in semiquantitative MRI markers (effusion‐synovitis, meniscal morphologic changes, and cartilage damage), quantitative central medial femoral cartilage thickness, quantitative medial tibial cartilage volume, quantitative lateral patellofemoral bone area, horizontal TBT (intercept term), and urine N‐telopeptide of type I collagen predicted OA progression (C statistic 0.680–0.724). A different combination of imaging and biochemical biomarkers (baseline and 24‐month change) predicted radiographic progression only, which had a higher C statistic of 0.716–0.832. Conclusion: The present study highlights the combination of biomarkers with potential prognostic utility in OA disease‐modifying trials. Properly qualified, these biomarkers could be used to enrich future trials with participants likely to experience progression of knee OA. [ABSTRACT FROM AUTHOR]

Objective: To examine whether knee subchondral cysts, measured on magnetic resonance imaging (MRI), are associated with incident knee osteoarthritis (OA) outcomes. Methods: We used longitudinal data from the Multicenter Osteoarthritis Study, a community‐based cohort of subjects with risk factors for knee OA. Participants without a history of knee surgery and/or inflammatory arthritis (i.e., rheumatoid arthritis and gout) were followed up for 84 months for the following incident outcomes: 1) radiographic knee OA (Kellgren/Lawrence grade ≥2), 2) symptomatic radiographic knee OA (radiographic knee OA and frequent knee pain), and 3) frequent knee pain (with or without radiographic knee OA). In a subset of participants, subchondral cysts were scored on baseline MRIs of 1 knee. Multiple logistic regression, with adjustment for participant characteristics and other baseline knee MRI findings, was used to assess whether subchondral cysts were predictive of incident outcomes. Results: Among the participants with knees eligible for analyses of outcomes over 84 months, incident radiographic knee OA occurred in 22.8% of knees with no baseline radiographic knee OA, symptomatic radiographic knee OA occurred in 17.0% of knees with no baseline symptomatic radiographic knee OA, and frequent knee pain (with or without radiographic knee OA) occurred in 28.8% of knees with no baseline radiographic knee OA and 43.7% of knees with baseline radiographic knee OA. With adjustment for age, sex, and body mass index, the presence of subchondral cysts was not associated with incident radiographic knee OA but was associated with increased odds of incident symptomatic radiographic knee OA (odds ratio 1.92 [95% confidence interval 1.16–3.19]) and increased odds of incident frequent knee pain in those who had radiographic knee OA at baseline (odds ratio 2.11 [95% confidence interval 0.87–5.12]). Stronger and significant associations were observed for outcomes based on consistent reports of frequent knee pain within ~1 month of the study visit. Conclusion: Subchondral cysts are likely to be a secondary phenomenon, rather than a primary trigger, of radiographic knee OA, and may predict symptoms in knees with existing disease. [ABSTRACT FROM AUTHOR]

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Objective Methods Results Conclusion Our objective was to investigate the overall and sex‐specific relationships between the presence and severity of knee osteoarthritis (KOA) and muscle composition, power, and energetics in older adults.Male and female patients (n = 655, mean ± SD age 76.1 ± 4.9 years; 57% female) enrolled in the Study of Muscle, Mobility, and Aging completed standing knee radiographs and knee pain assessments. Participants were divided into three groups using Kellgren‐Lawrence grade (KLG) of KOA severity (0–1, 2, or 3–4). Outcome measures included whole‐body muscle mass, thigh fat‐free muscle (FFM) volume and muscle fat infiltration (MFI), leg power, specific power (power normalized to muscle volume), and muscle mitochondrial energetics.Overall, the presence and severity of KOA is associated with greater MFI, lower leg power and specific power, and reduced oxidative phosphorylation (P trend < 0.036). Sex‐specific analysis revealed reduced energetics only in female patients with KOA (P trend < 0.007) compared to female patients without KOA. In models adjusted for age, sex, race, nonsteroidal anti‐inflammatory drug administration, site or technician, physical activity, height, and participants with abdominal adiposity with KLG 3 to 4 had greater MFI (mean 0.008%, 95% confidence interval [CI] 0.004%–0.011%) and lower leg power (mean −51.56 W, 95% CI −74.03 to −29.10 W) and specific power (mean −5.38 W/L, 95% CI −7.31 to −3.45 W/L) than those with KLG 0 to 1. No interactions were found between pain and KLG status. Among those with KOA, MFI and oxidative phosphorylation were associated with thigh FFM volume, leg power, and specific power.Muscle health is associated with the presence and severity of KOA and differs by sex. Although muscle composition and power are lower in both male and female patients with KOA, regardless of pain status, mitochondrial energetics is reduced only in female patients. [ABSTRACT FROM AUTHOR]

The association between proximal tibiofibular joint (PTFJ) and knee osteoarthritis (OA) has been understudied. The objective of this study was to determine whether the morphology of PTFJ has predictive value for the risk of total knee replacement (TKR). Case knees from Osteoarthritis Initiative participants with TKR at 24–60 months follow up (cases) were 1:1 matched with control knees (no TKR throughout 60 months) by baseline age, sex, and Kellgren–Lawrence grade. PTFJ morphological parameters, including coronal inclination angle (angle α), sagittal inclination angle (angle β), fibular contacting area (S), load‐bearing area (Sτ), lateral stress‐bolstering area (Sφ), and posterior stress‐bolstering area (Sυ) were assessed using coronal and sagittal magnetic resonance imaging (MRI), respectively. Associations of the morphological measures at baseline and the time point before TKR (T0) and their changes with TKR risks were examined using conditional logistic regression analyses. Two hundred and twenty‐three knees of 193 participants received TKR between 12 and 60 months and therefore were matched with 223 control knees. Of these, 173 paired knees had MRI readings available both at baseline and T0 time point. While baseline angle α was positively associated with TKR risk, other measures at baseline and all measures at T0 were not significantly associated with TKR risk. Changes in S, Sτ, and Sυ were significantly and negatively associated with the risk of TKR (ΔS, odds ratio [OR] = 0.38, 95% confidence interval [CI]: 0.19–0.76; ΔSτ, OR = 0.37, 95% CI: 0.16–0.87; ΔSυ, OR = 0.22, 95% CI: 0.08–0.62, respectively). This data shows that morphological changes of PTFJ predict the risk of TKR, suggesting PTFJ may play a role in knee OA. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the associations between weight cycling and knee joint degeneration in individuals with overweight or obesity with different patterns of weight change over 4 years.Methods: A total of 2,271 individuals from the Osteoarthritis Initiative database were assessed (case-control study). Linear regression models using annual BMI measurements over 4 years were used to classify participants as weight cyclers or noncyclers. 3-T magnetic resonance imaging was used to quantify knee cartilage transverse relaxation time (T2) and cartilage thickness annually over 4 years in all subjects. Whole-Organ Magnetic Resonance Imaging Scores (WORMS) were obtained for cartilage, meniscus, and bone-marrow abnormalities in 958 subjects at baseline and at the 4-year follow-up. The longitudinal differences in cartilage T2 and thickness between weight cyclers and noncyclers were assessed using general estimating equations, whereas the differences in WORMS outcomes were compared using general linear models.Results: No significant differences in the rate of change of cartilage thickness or T2 were found between weight cyclers and noncyclers. However, increases in maximum cartilage WORMS (P = 0.0025) and bone-marrow abnormalities (P = 0.04) were significantly greater in weight cyclers than in noncyclers.Conclusions: Although participants' intent for weight cycling in this study was unknown, weight cyclers had significantly greater increases in cartilage and bone-marrow abnormalities over 4 years than noncyclers, independent of weight gain and loss. [ABSTRACT FROM AUTHOR]

Background: Low Apgar scores are associated with neonatal morbidity and mortality, but effects of Apgar scores of 0–5, 6, 7, 8 and 9 (compared with 10) on longer‐term neurodevelopmental outcomes are less clear. Aim: To examine the associations between Apgar scores of 0–5, 6, 7, 8 and 9 (compared with 10) and children's educational outcomes as measured by the Australian National Assessment Program—Literacy and Numeracy (NAPLAN) tests at age eight. Materials and Methods: We merged perinatal data including all children born in South Australia from 1999 to 2008 with school assessment data (NAPLAN). School assessments included five learning areas (domains)—reading, writing, spelling, grammar and numeracy. Each domain was categorised according to performing at or below National Minimum Standards (≤NMS). Effects were estimated using Augmented Inverse Probability Weighting (AIPW) accounting for a range of maternal, perinatal and sociodemographic characteristics. Results: Risk differences comparing five‐minute Apgar scores of 0–5 with Apgar scores of 10 for children performing ≤NMS for each domain were: reading (0.07 (95% CI −0.16 to 0.29)), writing (0.27 (95% CI −0.14 to 0.68)), spelling (0.15 (95% CI −0.10 to 0.40)), grammar (0.04 (95% CI −0.21 to 0.29)) and numeracy (0.21 (95% CI −0.04 to 0.45)). Risk differences for children performing ≤NMS were also evident when Apgar score of 6 was compared with Apgar score of 10. Conclusions: Children with five‐minute Apgar scores of 0–5 and 6, compared with Apgar score of 10, are at higher risk of scoring at/below the NMS on the NAPLAN assessments at eight years. [ABSTRACT FROM AUTHOR]

Population‐based genomic screening has the potential to improve health outcomes by identifying genetic causes of disease before they occur. While much attention has been paid to supporting the needs of the small percentage of patients who will receive a life‐altering positive genomic screening result that requires medical attention, little attention has been given to the communication of negative screening results. As there are currently no best practices for returning negative genomic screening results, we drew on experiences across the electronic medical records and genomics (eMERGE) III Network to highlight the diversity of reporting methods employed, challenges encountered in reporting negative test results, and "lessons learned" across institutions. A 60‐item survey that consisted of both multiple choice and open‐ended questions was created to gather data across institutions. Even though institutions independently developed procedures for reporting negative results, and had very different study populations, we identified several similarities of approach, including but not limited to: returning results by mail, placing results in the electronic health record via an automated process, reporting results to participants' primary care provider, and providing genetic counseling to interested patients at no cost. Differences in procedures for reporting negative results included: differences in terminology used to describe negative results, definitions of negative results, guidance regarding the meaning of negative results for participants and their family members, and recommendations for clinical follow up. Our findings highlight emerging practices for reporting negative genomic screening results and highlight the need to create patient education and clinical support tools for reporting negative screening results. [ABSTRACT FROM AUTHOR]

Aim: To quantify the frequency of emergency department (ED) presentations and profile the socio‐demographic, health and presentation characteristics of paediatric ED frequent presenters. Methods: A population‐based data linkage study of 55 921 children in the South Australian Early Childhood Data Project aged 0–12 years with 100 976 presentations to public hospital EDs in South Australia. For each child, the total number of recurrent ED presentations during a 364‐day period post‐index presentation was calculated. Frequent presenters were children who experienced ≥4 recurrent ED presentations. We determined the socio‐demographic, health and presentation characteristics by number of recurrent presentations. Results: Children with ≥4 recurrent presentations (4.4%) accounted for 15.4% of all paediatric ED presentations and 22.5% of subsequent admissions to hospital during the 12‐month study period. Compared to children with no recurrent ED presentation, frequent presenters had higher proportions of socio‐economic and health disadvantage at birth. One in two (49.3%) frequent presenters had at least one injury presentation and one (21.3%) in five had at least one presentation related to a chronic condition. Conclusions: Children with ≥4 presentations do not represent the majority of ED users. Nevertheless, they represent a disproportionate burden accounting for 15% of all paediatric ED presentations in a 12‐month period. Frequent presenters were characterised by early socio‐economic and health disadvantage, and childhood injury. Strategies targeting social disadvantage and childhood injury may reduce the burden of ED presentations. [ABSTRACT FROM AUTHOR]

Aim: To describe and compare the incidence of type 1 diabetes (T1D) in South Australia by individual and area‐level socio‐economic characteristics among children aged ≤11 years. Methods: This is a whole‐of‐population, data linkage study (n = 231 685) conducted in South Australia, and included children born from 2002 to 2013, hospitalisation followed from 2002 to 2014. The study used de‐identified, linked administrative hospitalisation, birth and perinatal data from the South Australian Early Childhood Data Project. Incidence was calculated by identifying T1D cases from T1D‐related hospitalisations using International Classification of Disease, 10th Revision, Australian Modification diagnosis codes (E10, E101–E109). Results: Overall, 333 children aged ≤11 years (173 boys) were identified as having T1D. The T1D incidence rate was 23.0 per 100 000 person‐years (95% confidence interval (CI): 20.7–25.7), with no sex difference. T1D incidence was higher among children whose mothers were Caucasian, private patients and whose parents were employed. For example, T1D incidence was 26.0 per 100 000 (95% CI: 22.8–29.5) among children with both parents employed, compared to 20.0 per 100 000 (95% CI: 12.3–30.6) among children with both parents unemployed. There was no clear gradient in the association between area‐level socio‐economic position and T1D, with highest incidence for the fourth quintile (26.5 per 100 000 (95% CI: 20.9–33.1)). The most advantaged area (19.4 per 100 000 (95% CI: 13.8–26.5)) had lower incidence than the most disadvantaged area (23.5 per 100 000 (95% CI: 18.9–28.9)). Conclusion: T1D incidence rates differed depending on the measures of socio‐economic characteristics. Individual‐level indicators showed higher incidence among more advantaged children; however, there was no clear area‐level socio‐economic patterning of T1D. [ABSTRACT FROM AUTHOR]

Objective: To determine the cross-sectional and longitudinal associations of vitamin C and D intake with magnetic resonance imaging (MRI) measures of cartilage composition (T2) and joint structure (cartilage, meniscus, and bone marrow) using data from the Osteoarthritis Initiative (OAI) cohort.Methods: A total of 1,785 subjects with radiographic Kellgren/Lawrence knee grades 0-3 in the right knee were selected from the OAI database. Vitamins C and vitamin D intake (diet, supplements, and total) were assessed using the Block Brief 2000 Food Frequency Questionnaire at baseline. The MRI analysis protocol included 3T cartilage T2 quantification and semiquantitative joint morphology gradings (Whole-Organ Magnetic Resonance Imaging Score [WORMS]) at baseline and 4 years. Linear regression was used to assess the association between standardized baseline vitamin intake and both baseline WORMS scores and standardized cartilage T2 values.Results: Higher vitamin C intake was associated with lower average cartilage T2 values, medial tibia T2 values, and medial tibia WORMS scores (standardized coefficient range -0.07 to -0.05, P < 0.05). Higher vitamin D intake was associated with a lower cartilage WORMS sum score and medial femur WORMS score (standardized coefficient range -0.24 to -0.09, P < 0.05). Consistent use of vitamin D supplements of 400 IU at least once a week over 4 years was associated with significantly less worsening of cartilage, meniscus, and bone marrow abnormalities (odds ratio range 0.40-0.56, P < 0.05).Conclusion: Supplementation with vitamin D over 4 years was associated with significantly less progression of knee joint abnormalities. Given the observational nature of this study, future longitudinal randomized controlled trials of vitamin D supplementation are warranted. [ABSTRACT FROM AUTHOR]

This study describes the performance of handheld Raman devices for determining whether suspect pharmaceutical tablets declared to contain controlled substances were consistent with authentic (CWA) or not consistent with authentic (NCWA) tablets using a simple, rapid, field‐friendly method capable of being used by nonexperts. Twenty‐five authentic products and 84 known NCWA tablets were examined using three "parent" devices for a total of 327 analyses. On average, the parent devices yielded a true pass rate of 100%, a true fail rate of 98.4%, a false pass rate of 1.6%, and a false fail rate of 0%. The methods/libraries were then transferred to 13 identical "daughter" devices, which were used to examine 10 suspect finished dosage forms in duplicate (six known NCWA tablets and four authentic tablets) for a total of 260 measurements. On average, the daughter devices had a true pass rate of 100%, a true fail rate of 95.5%, a false pass rate of 4.5%, and a false fail rate of 0.0%. These data demonstrate that the parent–daughter electronic transfer method was successful, which permits the ability to develop methods in the laboratory that can be seamlessly pushed out to field devices. The methods can then be used to (i) prioritize samples for additional testing using other more time‐consuming laboratory‐based techniques needed to detect and quantify active ingredients and (ii) help support the interdiction of dangerous tablets at ports of entry, thereby preventing them from reaching the supply chain. [ABSTRACT FROM AUTHOR]

Limitations of plain radiographs may contribute to poor sensitivity in the detection of knee osteoarthritis and poor correlation with pain and physical function. Three‐dimensional (3D) joint space width (JSW), measured from weight‐bearing computed tomography (CT) images, may yield a more accurate correlation with patients' symptoms. We assessed the cross‐sectional association between 3D JSW and self‐reported pain and physical function. Five hundred twenty eight knees (57% women) were analyzed from Multicenter Osteoarthritis Study participants. An upright weight‐bearing CT scanner was used to acquire bilateral, weight‐bearing, fixed‐flexion images of the knees. A 3D dataset was reconstructed from cone beam projections and JSW was calculated across the joint surface. The percentages of the apposed medial tibiofemoral joint surface with JSW less than 2.0 and 2.5 mm, respectively, were calculated. Pain and physical function were measured using Western Ontario and McMaster Universities Osteoarthritis Index. Participants who reported greater pain severity tended to have a greater joint area with JSW less than 2.0 mm (P =.07 for the highest vs the lowest tertile). Participants who reported greater functional limitations had a greater joint area with JSW less than 2.0 mm (P =.02 for the highest vs the lowest tertile). There appears to be an association between the medial tibiofemoral area with JSW less than 2.0 mm and pain and physical function. [ABSTRACT FROM AUTHOR]

Avin et al (2005) showed that, in the presence of exposure-induced mediator-outcome confounding, decomposing the total causal effect (TCE) using standard conditional exchangeability assumptions is not possible even under a nonparametric structural equation model with all confounders observed. Subsequent research has investigated the assumptions required for such a decomposition to be identifiable and estimable from observed data. One approach was proposed by VanderWeele et al (2014). They decomposed the TCE under three different scenarios: (1) treating the mediator and the exposure-induced confounder as joint mediators; (2) generating path-specific effects albeit without distinguishing between multiple distinct paths through the exposure-induced confounder; and (3) using so-called randomised interventional analogues where sampling values from the distribution of the mediator within the levels of the exposure effectively marginalises over the exposure-induced confounder. In this paper, we extend their approach to the case where there are multiple mediators that do not influence each other directly but which are all influenced by an exposure-induced mediator-outcome confounder. We provide a motivating example and results from a simulation study based on from our work in dental epidemiology featuring the 1982 Pelotas Birth Cohort in Brazil. [ABSTRACT FROM AUTHOR]

Background: Vaginal instrumental delivery is a common obstetrical intervention, but its effect on children's later development is not well known. Aims: To determine if vaginal instrumental delivery is associated with adverse neurodevelopment as measured by school achievement. Material and methods: We performed a whole‐of‐population study involving linkage of routinely collected perinatal data with school assessments among children born in South Australia from 1999 to 2008. Participants were singleton children born by forceps (n = 5494), ventouse (n = 6988), or normal delivery (n = 80 803). School achievement was measured through performance on the National Assessment Program in Literacy and Numeracy (NAPLAN), at around eight years of age. This assessment involved five domains and scores were categorised according to performing at or above National Minimum Standards (NMS). Effects of instrumental versus normal vaginal delivery were analysed via augmented inverse probability weighting (AIPW), taking into account a variety of maternal, perinatal and sociodemographic characteristics. Results: In unadjusted analyses, instrumental delivery was not associated with poor NAPLAN scores. AIPW analyses also suggested that instrumental delivery had minimal adverse effect on NAPLAN scores, with the largest difference being lower spelling scores among forceps‐delivered children (−0.022 (95% CI −0.0053–0.009)) compared with spontaneous vaginal births. The findings were consistent among exploratory subgroup analyses involving births in the absence of prolonged labour, with APGAR ≥ 9, and among normotensive and non‐diabetic mothers. Conclusion: In singleton children born at term, instrumental delivery does not have an adverse effect on neurodevelopment as measured by NAPLAN performance at age eight. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the effect of a 2-year post-natal nurse home visiting (NHV) programme delivered in routine clinical practice to socially disadvantaged mothers on children's development at 5 years.Methods: The study was a natural experiment resulting from progressive rollout of NHV (2008-2012). Children of three groups of mothers, all eligible for NHV, were compared: (i) mothers receiving NHV in a metropolitan region (n = 197); (ii) mothers in a rural region prior to NHV being available (n = 94); and (iii) mothers receiving NHV in the rural region after it became available (n = 84). Outcomes were evaluated using the Child Behaviour Checklist, Child-Parent Relationships Scale, Behaviour Inventory of Executive Functioning and Australian Early Development Index.Results: Analyses were conducted using augmented inverse probability weighting accounting for differences in the groups' baseline characteristics. While some differences were observed in the range of 8-12% between the intervention and comparison groups (albeit with wide confidence intervals, e.g. 31% less likely to 4% more likely to be experiencing poor outcomes). For the majority of outcomes, however, there were no differences observed between the intervention and comparison groups.Conclusions: Post-natal NHV provided as a part of routine service delivery did not improve children's outcomes at 5 years. It may be that in the Australian context a NHV intervention, as offered in this study, does not provide additional benefits over standard care. [ABSTRACT FROM AUTHOR]

Background: Chronic pain is common after spinal cord injury (SCI) and dedicated SCI cognitive behavioural therapy pain management programmes (CBT-PMPs) have a growing evidence base to support their uptake clinically. The development of internet-delivered treatment options may overcome barriers to the access and uptake of centre-based programmes. This study examines such an approach on quality of lie (QoL), pain, mood and sleep.Methods: Adults with SCI pain (>3 months) were recruited and randomly assigned to the intervention or control group. The intervention comprised a six module CBT-PMP delivered once weekly. A blinded assessor determined changes in self-reported outcome measures post-intervention and at 3 months. Linear mixed models and effect sizes based on changes between groups were reported. Significance was set p < 0.05.Results: The recruitment rate was 32% (intervention n = 35, control n = 34), and the drop-out rate at 3 months was 26%. On average, participants accessed three (SD 2.1) of six modules. While no difference in QoL was reported, a significant group*time interaction was found for NRS of current pain (χ2  = 8.22, p = 0.016), worst pain (χ2  = 11.20, p = 0.004), and Brief Pain Inventory (interference) (χ2  = 6.924, p = 0.031). Moderate to large effect sizes favouring the intervention were demonstrated at each time point for the pain metrics (Cohen's d: 0.38-0.84). At 3-month follow-up, 48% of the intervention group rated themselves improved or very much improved (p < 0.05).Conclusions: This study demonstrates the potential of an internet-delivered SCI specific CBT-PMP in reporting significant statistical and clinical benefit in pain intensity and interference. Strategies to improve engagement are needed. [ABSTRACT FROM AUTHOR]

Objective: To describe the prevalence and predictors of burnout in USA and European urology residents, as although the rate of burnout in urologists is high and associated with severe negative sequelae, the extent and predictors of burnout in urology trainees remains poorly understood. Subjects and methods: An anonymous 32‐question survey of urology trainees across the USA and four European countries, analysing personal, programme, and institutional factors, was conducted. Burnout was assessed using the validated abridged Maslach Burnout Inventory. Univariate analysis and multivariable logistic regression models assessed drivers of burnout in the two cohorts. Results: Overall, 40% of participants met the criteria for burnout as follows: Portugal (68%), Italy (49%), USA (38%), Belgium (36%), and France (26%). Response rates were: USA, 20.9%; Italy, 45.2%; Portugal, 30.5%; France, 12.5%; and Belgium, 9.4%. Burnout was not associated with gender or level of training. In both cohorts, work–life balance (WLB) dissatisfaction was associated with increased burnout (odds ratio [OR] 4.5, P < 0.001), whilst non‐medical reading (OR 0.6, P = 0.001) and structured mentorship (OR 0.4, P = 0.002) were associated with decreased burnout risk. Lack of access to mental health services was associated with burnout in the USA only (OR 3.5, P = 0.006), whilst more weekends on‐call was associated with burnout in Europe only (OR 8.3, P = 0.033). In both cohorts, burned out residents were more likely to not choose a career in urology again (USA 54% vs 19%, P < 0.001; Europe 43% vs 25%, P = 0.047). Conclusion: In this study of USA and European urology residents, we found high rates of burnout on both continents. Despite regional differences in the predictors of burnout, awareness of the unique institutional drivers may help inform directions of future interventions. [ABSTRACT FROM AUTHOR]

We aimed to characterize peripheral blood gene expression profile of penumbra defined as MRI perfusion–diffusion mismatch (PD MM) in peripheral blood of patients with acute ischemic stroke. We studied 23 patients. Perfusion–diffusion mismatch volume was observed to be associated and significantly correlated with the expression of 34 genes including those related to inflammation, SUMOylation, and coagulation; while lipopolysaccharide inhibition was identified to be a candidate upstream regulator of these processes (z‐score −2.38, P = 0.04). Penumbral volume is correlated with a specific gene expression profile in the peripheral blood characterized by overlap of inflammatory and neuroprotective pathways that are regulated by lipopolysaccharide inhibition. [ABSTRACT FROM AUTHOR]

Life cycle assessment (LCA) provides an invaluable framework to systematically assess the impacts of products or activities. For example, an LCA study of a cattle production system will likely collect detailed on-farm management data but may have considerable uncertainty pertaining to the impacts of any feedstuffs imported from elsewhere. [Extracted from the article]

Aim: To estimate the frequency, duration and monthly pattern of discretionary food advertising on Australian free-to-air television.Methods: We logged 30 000 h of television collected in Adelaide during 2016 from one network that has four channels. The Australian Guide to Healthy Eating was used to identify discretionary foods. Data were examined according to all times, to children's peak viewing times (PVTs) and to when C-(children's) rated programmes may be broadcast.Results: Of the >800 000 advertisements logged during 2016, 11% were for foods (n = 97 837). The most frequently advertised products were: snack foods (e.g. crisps), crumbed/battered meats, fast foods/take away meals and sweetened beverages. The frequency and duration of discretionary food advertising was 1.7 times/h and 0.5 min/h respectively at all times. During children's PVTs, the frequency and duration of discretionary food advertising was 2.3 times/h and 0.7 min/h, respectively. When C-rated programmes can be broadcast, the frequency and duration of discretionary food advertising was 1.8 times/h and 0.6 min/h, respectively. Across the year, discretionary foods ranged between 41% (August) and 71% (January) of all food advertising.Conclusions: Discretionary foods dominate food advertising. On average, discretionary food advertising was higher during PVTs for children and during the summer school holidays (January). [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA), a multifactorial disease causing joint degeneration, often leads to severe disability. The rising rates of disability highlight the need for implementing preventative measures at early stages of the disease, which would especially benefit subjects at high risk for OA development.Purpose: To develop a risk prediction tool for moderate-severe OA (TOARP) over 8 years based on subject characteristics, knee radiographs, and MRI data at baseline using data from the Osteoarthritis Initiative (OAI).Study Type: Retrospective.Subjects: 641 subjects with no/mild radiographic OA (Kellgren-Lawrence [KL] 0-2) and no clinically significant symptoms (Western Ontario and McMaster Universities Arthritis Index [WOMAC] 0-1) were selected from the OAI.Field Strength/sequence: MR images were obtained using 3.0T.Assessment: Compartment-specific cartilage and meniscus morphology and cartilage T2 were assessed. Baseline subject demographics, risk factors, KL score, cartilage WORMS score, presence of meniscus tear, and cartilage T2 were used to predict the development of moderate/severe OA (KL = 3-4 or WOMAC pain ≥5 or total knee replacement [TKR]) over 8 years.Statistical Tests: Best subsets variable selection followed by cross-validation were used to assess which combinations of variables best predict moderate/severe OA.Results: Model 1 included KL score, previous knee injury in the last 12 months, age, gender, and BMI. Model 2 included all variables in Model 1 plus presence of cartilage defects in the lateral femur and patella, and presence of a meniscal tear. Model 3 included all variables in Models 1 and 2, plus cartilage T2 in the medial tibia and medial femur. Compared to Model 1 (cross-validated AUC = 0.67), Model 3 performed significantly better (AUC = 0.72, P = 0.04), while Model 2 showed a statistical trend (AUC = 0.71, P = 0.08).Data Conclusion: We established a risk calculator for the development of moderate/severe knee OA over 8 years that includes radiographic and MRI data. The inclusion of MRI-based morphological abnormalities and cartilage T2 significantly improved model performance.Level Of Evidence: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1517-1526. [ABSTRACT FROM AUTHOR]

Background and Purpose: Blood-brain barrier (BBB) disruption detected on magnetic resonance imaging (MRI) in acute ischemic stroke as a hyperintense acute reperfusion marker (HARM) is associated with upregulation of matrix metalloproteinase-9 (MMP-9). Although activated leukocytes, including monocytes, are the main source of MMPs, limited data exist to support relationship between leukocyte activation and BBB disruption in patients with acute ischemic stroke. The goal of this study is to investigate the relationship between neutrophils, lymphocytes, and monocytes with BBB disruption detected as HARM (+) in patients with acute ischemic stroke.Methods: We conducted a retrospective analysis of prospectively collected data in patients who did not receive any reperfusion therapy with acute (<12 hours) ischemic stroke. MRI scans were obtained at baseline, 24 hours, and 5 days. HARM was evaluated on the 24-hour follow-up scan.Results: Thirty-three patients were studied. HARM was detected in 27% of patients. Median volumes of baseline perfusion (mean transit time [MTT]) deficit (219.4 mL vs. 158.4 mL, P = .029) and DWI infarct growth at 24 hours (18.50 mL vs. .14 mL, P = .017), as well as the median absolute numbers (1 × 103 /mm3 ) of monocytes, were significantly higher in HARM (+) versus HARM (-) patients (0.9 vs. 0.6, p = 0.011).Conclusion: Increased monocyte count associated with HARM supports importance of systemic inflammation in BBB disruption in acute ischemic stroke. [ABSTRACT FROM AUTHOR]

Background: Preterm birth and developmental vulnerability are more common in Australian Aboriginal compared with non-Aboriginal children. We quantified how gestational age relates to developmental vulnerability in both populations.Methods: Perinatal datasets were linked to the Australian Early Development Census (AEDC), which collects data on five domains, including physical, social, emotional, language/cognitive, and general knowledge/communication development. We quantified the risk of developmental vulnerability on ≥1 domains at age 5, according to gestational age and Aboriginality, for 97 989 children born in New South Wales, Australia, who started school in 2009 or 2012.Results: Seven thousand and seventy-nine children (7%) were Aboriginal. Compared with non-Aboriginal children, Aboriginal children were more likely to be preterm (5% vs. 9%), and developmentally vulnerable on ≥1 domains (20% vs. 36%). Overall, the proportion of developmentally vulnerable children decreased with increasing gestational age, from 44% at ≤27 weeks to 20% at 40 weeks. Aboriginal children had higher risks than non-Aboriginal children across the gestational age range, peaking among early term children (risk difference [RD] 19.0, 95% confidence interval [CI] 16.3, 21.7; relative risk [RR] 1.91, 95% CI 1.77, 2.06). The relation of gestational age to developmental outcomes was the same in Aboriginal and non-Aboriginal children, and adjustment for socio-economic disadvantage attenuated the risk differences and risk ratios across the gestational age range.Conclusions: Although the relation of gestational age to developmental vulnerability was similar in Aboriginal and non-Aboriginal children, Aboriginal children had a higher risk of developmental vulnerability at all gestational ages, which was largely accounted for by socio-economic disadvantage. [ABSTRACT FROM AUTHOR]

It is quite common for boutique pharma companies, biotech firms, and university labs to license their intellectual property (a new compound) to large pharmaceutical companies. In such cases, the big pharma companies finance and manage the R&D process and, if successful, market the drugs. In exchange for use of their intellectual property, the outlicensing organizations receive licensing contracts that promise some combination of fixed payments, event-specific milestone payments, and revenue- or profit-based royalties. The authors show how to estimate the expected present value of the future cash flows promised by such licensing deals. The complicating factor in such valuations is that the licensing contracts are essentially derivative contracts written on drugs in development, which as the authors showed in a paper published in this journal a year ago, are themselves compound options on marketed drugs. The authors use the valuation example from the earlier paper, along with a proposed licensing deal, and walk the reader through the process of valuing the licensing deal's cash flows. [ABSTRACT FROM AUTHOR]

Objective To determine the association between changes in semiquantitative magnetic resonance imaging (MRI) biomarkers over 24 months and radiographic and pain progression over 48 months in knees with mild-to-moderate osteoarthritis (OA). Methods We undertook a nested case-control study as part of the Foundation for the National Institutes of Health Biomarkers Consortium Project. We used multivariable logistic regression models to examine the association between change over 24 months in semiquantitative MRI markers and radiographic and pain progression in knee OA. MRIs were read according to the MRI OA Knee Score system. We focused on changes in cartilage, osteophytes, meniscus, bone marrow lesions, Hoffa-synovitis, and effusion-synovitis. Results The most parsimonious model included changes in cartilage thickness and surface area, effusion-synovitis, Hoffa-synovitis, and meniscal morphology (C statistic 0.740). Compared with no worsening, worsening in cartilage thickness in ≥3 subregions was associated with 2.8-fold (95% confidence interval [95% CI] 1.3-5.9) greater odds of being a case, and worsening in cartilage surface area in ≥3 subregions was associated with 2.4-fold (95% CI 1.3-4.4) greater odds of being a case. Worsening of meniscal morphology in any region was associated with 2.2-fold (95% CI 1.3-3.8) greater odds of being a case. Worsening effusion-synovitis and Hoffa-synovitis were also associated with a greater odds of being a case (odds ratios 2.7 and 2.0, respectively). Conclusion Twenty-four-month changes in cartilage thickness, cartilage surface area, effusion-synovitis, Hoffa-synovitis, and meniscal morphology were independently associated with OA progression, suggesting that these factors may serve as efficacy biomarkers in clinical trials of disease-modifying interventions for knee OA. [ABSTRACT FROM AUTHOR]

Compartment syndromes, conditions of elevated intramuscular pressure (IMP) resulting from trauma or chronic overuse, frequently require invasive IMP monitoring for accurate diagnosis. Our objective was to test a noninvasive ultrasound technique for estimating IMP based on fascial displacement waveforms from arterial blood pressure pulses. IMP was increased in the legs of 23 healthy adult subjects up to 80 mmHg using two blood pressure cuffs covering the region from the knee to the ankle. Receiver operator characteristic curves and recursive partitioning were used to determine the sensitivity and specificity of diagnosing elevated IMP using fascial displacement. For one curve, in which several ultrasonic measurement parameters were used along with subject body mass index and blood pressure, the sensitivity and specificity for diagnosing normal IMP (below 30 mmHg) from elevated IMP (30 mmHg and up) was 0.61 and 0.94, respectively. Recursive partitioning, in which IMP was divided into three ranges (normal <30 mmHg, midrange of 30-40 mmHg, and elevated ≥50 mmHg), resulted in improved diagnostic sensitivity (0.77) with almost no change in specificity (0.93). © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 489-494, 2009 [ABSTRACT FROM AUTHOR]

Background Caesarean birth is one of the most frequently performed major obstetrical interventions. Although there is speculation that caesarean at term may have consequences for children's later health and development, longer-term studies are needed. Aim We aimed to evaluate risks to poor school achievement among children born by caesarean section compared with spontaneous vaginal birth. Materials and Methods This population-based observational study involved linkage of routinely collected perinatal data with children's school assessments. Perinatal data included all children born in South Australia from 1999 to 2005. Participants were children born by elective caesarean (exposed, n = 650) or vaginal birth (unexposed, n = 2959), to women who previously had a caesarean delivery. School assessments were reported via a standardised national assessment program for children attending grade three (at ~eight years of age). Assessments included reading, writing, spelling, grammar and numeracy and were categorised according to performing at above or ≤National Minimum Standards ( NMS). Statistical analyses involved augmented inverse probability weighting (apiw) and accounted for a range of maternal, perinatal and sociodemographic characteristics. Results Children performing ≤ NMS for vaginal birth versus caesarean section were as follows: reading 144/640 (23%) and 688/2921 (24%), writing 69/636(11%) and 351/2917 (12%), spelling 128/646 (20%) and 684/2937 (23%), grammar 132/646 (20%) and 655/2937 (22%), and numeracy 151/634 (24%) and 729/2922 (25%). Both the raw data and the aipw analyses suggested little differences in school achievement between children born by caesarean versus vaginal birth. Conclusion Analyses that carefully controlled for a wide range of confounders suggest that caesarean section does not increase the risk of poor school outcomes at age eight. [ABSTRACT FROM AUTHOR]

Valuing a capital investment as a real option (or series of options) has advantages over standard DCF valuation when the investment creates the future flexibility to delay, abandon, or expand an element of the project based on the resolution of a major source of uncertainty. The uncertainty is generally dealt with using a 'volatility' term that aims to reflect the variability in the future value of the underlying asset. But there are certain situations in which the uncertainty has a second dimension. For example, drugs in development can be abandoned either because of bad technical outcomes (the drug doesn't work) or unfavorable resolutions of market risk (though the drug works, its market potential turns out to be too limited). In an article published earlier in this journal, the authors illustrated the valuation of an early-stage pharma R&D investment using a real options approach in which the market and technical risks were folded together into the volatility parameter. In this article, the authors explain why they have concluded that this is an incorrect approach and then show how to handle market and technical risk as two separate dimensions of risk in valuing an R&D program. The potential use of this technique extends beyond pharma and biotech R&D to any situation in which the outcome of an important uncertainty is independent of the resolution of market risk associated with the underlying asset. [ABSTRACT FROM AUTHOR]

We recently developed a completely new type of Rh-catalyzed [5+2] cycloaddition by using 3-acyloxy-1,4-enyne (ACE) as the 5-carbon building block. In this update, we show that ACE can undergo intramolecular [5+2] cycloaddition with either an alkene or an allene in the presence of an appropriate rhodium catalyst and ligands to afford bicyclic compounds with multiple stereogenic centers. In most cases, cis-fused bicyclo[5.3.0]decadienes are prepared highly diastereoselectively. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship of step length to the sex-specific prevalence and worsening of magnetic resonance imaging (MRI)-detected structural damage in the patellofemoral (PF) joint among a cohort of older women and men with or at risk of knee osteoarthritis (OA).Methods: The Multicenter Osteoarthritis Study is a cohort study of persons ages 50-79 years with or at risk of knee OA. Step length was assessed using the GAITRite walkway (CIR Systems) at the 60-month visit, and cartilage damage and bone marrow lesions (BMLs) were graded on MRI at the 60- and 84-month visits. Step length was divided into sex-specific quintiles, and the relationship of step length to the prevalence and worsening of cartilage damage and BMLs in the PF joint was examined using logistic regression, adjusting for age, body mass index (BMI), leg length, and tibiofemoral joint structural damage.Results: In 1,053 knees, 4,094 and 4,083 PF joint subregions were studied for the cartilage and BML analyses, respectively. Mean ± SD age was 65.6 ± 8.1 years and mean ± SD BMI was 29.1 ± 4.7 kg/m(2) ; 62% of participants were female. In women, compared to those with the shortest step length, those with the longest step length had 0.62 (95% confidence interval [95% CI] 0.43-0.88) and 0.59 (95% CI 0.40-0.87) times the odds of cartilage damage and BMLs, respectively. There was no cross-sectional association in men, and no longitudinal association in either sex.Conclusion: Women with PF joint structural damage may adapt their gait by shortening their step length, but this may not be sufficient to reduce the risk of worsening damage over time. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to examine the identification of Aboriginal children in multiple administrative datasets and how this may affect estimates of health and development.Methods: Data collections containing a question about Aboriginal ethnicity: birth registrations, perinatal statistics, Australian Early Development Census and school enrolments were linked to datasets recording developmental outcomes: national literacy and numeracy tests (National Assessment Program - Literacy and Numeracy), Australian Early Development Census and perinatal statistics (birthweight) for South Australian children born 1999-2005 (n = 13 414-44 989). Six algorithms to derive Aboriginal ethnicity were specified. The proportions of children thus quantified were compared for developmental outcomes, including those scoring above the national minimum standard in year 3 National Assessment Program - Literacy and Numeracy reading.Results: The proportion of Aboriginal children identified varied from 1.9% to 4.7% when the algorithm incremented from once to ever identified as Aboriginal, the latter using linked datasets. The estimates of developmental outcomes were altered: for example, the proportion of Aboriginal children who performed above the national minimum standard in year 3 reading increased by 12 percentage points when the algorithm incremented from once to ever identified as Aboriginal. Similar differences by identification algorithm were seen for all outcomes.Conclusions: The proportion of South Australian children identified as Aboriginal in administrative datasets, and hence inequalities in developmental outcomes, varied depending on which and how many data sources were used. Linking multiple administrative datasets to determine the Aboriginal ethnicity of the child may be useful to inform policy, interventions, service delivery and how well we are closing developmental gaps. [ABSTRACT FROM AUTHOR]

Rapid PCR-based influenza tests are increasingly used as point-of-care diagnostics in hospitals and clinics. To our knowledge, no prior studies have described clinical outcomes with implementation of rapid PCR-based influenza tests in hospitalized adult inpatients. Electronic medical records were used to assess differences in laboratory testing time and antiviral use among a subset of 175 consecutive adult inpatients tested for influenza in two respiratory seasons before and after implementation of rapid PCR-based influenza testing at an academic medical center. Of the 350 hospitalized inpatients included in this analysis, 96 (27%) were over 65 years of age and 308 (88%) had a comorbid condition. The overall time to result decreased significantly from 25.2 to 1.7 hr ( P < 0.001) after implementation of rapid PCR-based influenza testing. Among influenza-negative patients, the frequency of oseltamivir initiation remained unchanged (before: 43% vs. after: 45%; P = 0.60), though the median duration of oseltamivir was significantly decreased from 1.1 to 0.0 days ( P < 0.001). By providing an earlier result to clinicians, rapid PCR-based influenza tests may decrease unnecessary antiviral use among adult inpatients who test negative for influenza. J. Med. Virol. 87:2021-2026, 2015. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Considerable prior statistical work has criticized replacing a continuously measured variable in a general linear model with a dichotomy based on a median split of that variable. Iacobucci, Posovac, Kardes, Schneider, and Popovich (2015-in this issue) defend the practice of “median splits” using both conceptual arguments and simulations. We dispute their conceptual arguments, and we have identified technical errors in their simulations that dramatically change the conclusions that follow from those simulations. We show that there are no real benefits to median splits, and there are real costs in increases in Type II errors through loss of power and increases in Type I errors through false–positive consumer psychology. We conclude that median splits remain a bad idea. [ABSTRACT FROM AUTHOR]

Aim This study investigated the association between early-life risk factors and school education outcomes. Methods This is an historical cohort study of 7601 children (61% were Indigenous) born in the Northern Territory between 1999 and 2004. Information was linked, for each child on: perinatal health, student enrolment and National Assessment Program - Literacy and Numeracy ( NAPLAN) Year 3 results. Logistic regression was used to estimate the association between selected risk factors and a NAPLAN result 'below' the national minimum standard ( NMS) in reading and numeracy. Results Indigenous children had much higher odds, than non- Indigenous children, of a result below the NMS for both reading (odds ratio ( OR): 8.58, 95% confidence interval ( CI): 7.55-9.74) ) and numeracy ( OR: 11.52, 95% CI: 9.94-13.35). When adjusted for all other variables, the increased odds were attenuated for both reading ( OR: 2.89, 95% CI: 2.46-3.40) and numeracy ( OR: 3.19, 95% CI: 2.65-3.84). Common risk factors for Indigenous and non- Indigenous children included higher birth order, maternal smoking in pregnancy and being a boy. There were gradients of decreasing risk with increasing education level of primary care giver and increasing maternal age. Among Indigenous children only, risks increased when living in remote areas, with younger age (<8 years) and low birthweight. Conclusions The study highlights that many of the risk factors associated with poor education outcomes among Indigenous children are shared with the general population. The results inform a targeted, cross-agency response to address modifiable early-life risk factors for educational disadvantage. Data linkage, using existing administrative datasets, provides a useful addition to methods that identify priority areas for prevention and early intervention. [ABSTRACT FROM AUTHOR]

Background To develop a semi-quantitative MR-based hip osteoarthritis (OA) evaluation system (Scoring hip osteoarthritis with MRI, SHOMRI), and to test its reproducibility and face validity. Methods The study involved 98 subjects with informed consent. Three-Tesla MR imaging of hip was performed in three planes with intermediate-weighted fat saturated FSE sequences. Two radiologists assessed cartilage loss, bone marrow edema pattern, subchondral cyst in 10 subregions, and assessed labrum in 4 subregions. In addition, presence or absence of ligamentum teres integrity, paralabral cysts, intra-articular body, and effusion in the hip joint were analyzed using the SHOMRI system. The reproducibility was assessed with intra-class correlation coefficient (ICC), Cohen's Kappa values and percent agreement. SHOMRI scores were correlated with radiographic Kellgren-Lawrence (KL) and OARSI atlas gradings, and clinical parameters, the hip osteoarthritis outcome score (HOOS) and hip range of motion (ROM), using Spearman's rank correlation and ordinal logistic regression. Results ICC values were in the excellent range, 0.91 to 0.97. Cohen's Kappa values and percent agreement ranged from 0.55 to 0.79 and 66 to 99%, respectively. SHOMRI demonstrated significant correlations with KL and OARSI gradings as well as with clinical parameters, HOOS and ROM ( P < 0.05). Among the SHOMRI features, subchondral cyst and bone marrow edema pattern showed the highest correlation with HOOS and ROM. Conclusion SHOMRI demonstrated moderate to excellent reproducibility and significant correlation with radiographic gradings and clinical parameters. J. Magn. Reson. Imaging 2015;41:1549-1557. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Purpose To assess whether changes in knee cartilage MR-based T2 relaxation times are associated with weight loss in individuals with risk factors for knee osteoarthritis (OA) compared with controls with stable weight. Materials and Methods One hundred twenty-seven individuals with risk factors for knee OA were studied: 62 subjects had a body mass index (BMI) decrease≥10% over 48 months and 65 controls had a BMI change <3%. Cartilage segmentation from five knee compartments at baseline and 48-month follow-up was performed, and T2 maps were generated. The association of change in T2 values over 48 months in the weight-loss group versus the control group was assessed using multiple linear regression models. Results Weight loss was associated with significantly smaller increases in cartilage T2 in the medial femoral condyle ( P = 0.035) and overall medial compartment ( P = 0.006) compared with the controls. In a subgroup analysis comparing weight-loss subjects who were obese (BMI≥30 kg/m2) and overweight (BMI 25-30 kg/m2) at baseline, obesity was associated with smaller increases in cartilage T2 values in the medial femoral condyle ( P = 0.022), lateral femoral condyle ( P = 0.015), patella ( P = 0.002), and globally across all compartments ( P = 0.002). Conclusion A decrease in BMI of ≥ 10% was associated with a slower progression of T2 values in individuals with risk factors for OA, suggesting a beneficial impact of weight loss on cartilage matrix degeneration. J. Magn. Reson. Imaging 2015;41:1272-1280. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Debate about the extent of breast cancer over-diagnosis due to mammography screening has continued for over a decade, without consensus. Estimates range from 0 to 54%, but many studies have been criticized for having flawed methodology. In this study we used a novel study design to estimate over-diagnosis due to organised mammography screening in South Australia (SA). To estimate breast cancer incidence at and following screening we used a population-based, age-matched case-control design involving 4,931 breast cancer cases and 22,914 controls to obtain OR for yearly time intervals since women's last screening mammogram. The level of over-diagnosis was estimated by comparing the cumulative breast cancer incidence with and without screening. The former was derived by applying ORs for each time window to incidence rates in the absence of screening, and the latter, by projecting pre-screening incidence rates. Sensitivity analyses were undertaken to assess potential biases. Over-diagnosis was estimated to be 8% (95%CI 2-14%) and 14% (95%CI 8-19%) among SA women aged 45 to 85 years from 2006-2010, for invasive breast cancer and all breast cancer respectively. These estimates were robust when applying various sensitivity analyses, except for adjustment for potential confounding assuming higher risk among screened than non-screened women, which reduced levels of over-diagnosis to 1% (95%CI 5-7%) and 8% (95%CI 2-14%) respectively when incidence rates for screening participants were adjusted by 10%. Our results indicate that the level of over-diagnosis due to mammography screening is modest and considerably lower than many previous estimates, including others for Australia. [ABSTRACT FROM AUTHOR]

ABSTRACT BACKGROUND Previous studies have demonstrated that cerebral dural sinus stenosis (DSS) may be a potential patho-physiological cause of idiopathic intracranial hypertension (IIH). Endovascular therapy for DSS is emerging as a potential alternative to treat IIH. Here, we present the results of our case series. METHOD We prospectively collected angiographic and manometric data on patients that underwent angioplasty/stenting for IIH. All patients had failed maximal medical therapy (MMT) and had confirmed sinus stenosis. Demographic, clinical and radiological presentation, and outcomes were collected retrospectively. RESULTS A total of 18 patients underwent 25 procedures. Demographics revealed a mean age of 30 (range 15-59), 83% (15/18) were female, 72% (13/18) were white, and mean body mass index of 36 (range 23-59.2). All patients presented with classic IIH. Symptom improvement or resolution was reported in 94% (17/18) of patients. All patients had resolution and/or stabilization/improvement of their papilledema. Headaches related to increased pressure improved in 56% (10/18). Re-stenosis and retreatment occurred in 33% (6/18). No procedural related complications were reported. CONCLUSION Dural sinus angioplasty and stenting is relatively safe, feasible, and clinically efficacious for patients with symptomatic sinus stenosis who have failed standard therapy. The long-term durability of patency and clinical improvement remains unknown. [ABSTRACT FROM AUTHOR]

Aim To evaluate the effectiveness of a 2-year post-natal home-visiting programme delivered by nurses to socially disadvantaged mothers in rural regions of South Australia. Methods The intervention group consisted of 225 mothers who lived in rural regions and enrolled in the programme between 2010 and 2012. The comparison group consisted of 239 mothers who lived in rural areas between 2008 and 2009 when the programme was not yet available. All participants were eligible for enrolment in the home-visiting programme. Participants in both groups were assessed at baseline (mean child age = 15.2 weeks, SD = 2.4), prior to programme enrolment, and again when children were aged 9, 18 and 24 months. Outcomes were evaluated using the Parent Stress Index, Kessler Psychological Distress Scale, Ages and Stages Questionnaire, Child Behaviour Checklist, and MacArthur Communicative Developmental Inventory. Results During the follow-up period, there was little difference in the pattern of scores across the two groups. Mixed models adjusting for baseline differences between the groups did not identify any significant Group × Time interactions. This suggests that the linear trajectories of scores on outcomes did not differ significantly between the two groups. Conclusions Findings suggest that the home-visiting programme did not have a measurable effect on maternal or child outcomes. However, the programme was relatively early in its rollout, and the greater challenges of recruitment, training and support, along with rural nurses' broader responsibilities for delivering other maternal and child health services, may explain why effects seen in the metropolitan area were not evident in rural regions. [ABSTRACT FROM AUTHOR]