Healthy eating interventions delivered in early childhood education and care settings for improving the diet of children aged six months to six years.

BACKGROUND: Dietary intake during early childhood can have implications on child health and developmental trajectories. Early childhood education and care (ECEC) services are recommended settings to deliver healthy eating interventions as they provide access to many children during this important period. Healthy eating interventions delivered in ECEC settings can include strategies targeting the curriculum (e.g. nutrition education), ethos and environment (e.g. menu modification) and partnerships (e.g. workshops for families). Despite guidelines supporting the delivery of healthy eating interventions in this setting, little is known about their impact on child health. OBJECTIVES: To assess the effectiveness of healthy eating interventions delivered in ECEC settings for improving dietary intake in children aged six months to six years, relative to usual care, no intervention or an alternative, non-dietary intervention. Secondary objectives were to assess the impact of ECEC-based healthy eating interventions on physical outcomes (e.g. child body mass index (BMI), weight, waist circumference), language and cognitive outcomes, social/emotional and quality-of-life outcomes. We also report on cost and adverse consequences of ECEC-based healthy eating interventions. SEARCH METHODS: We searched eight electronic databases including CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, ERIC, Scopus and SportDiscus on 24 February 2022. We searched reference lists of included studies, reference lists of relevant systematic reviews, the World Health Organization International Clinical Trials Registry Platform, ClinicalTrials.gov and Google Scholar, and contacted authors of relevant papers. SELECTION CRITERIA: We included randomised controlled trials (RCTs), including cluster-RCTs, stepped-wedge RCTs, factorial RCTs, multiple baseline RCTs and randomised cross-over trials, of healthy eating interventions targeting children aged six months to six years that were conducted within the ECEC setting. ECEC settings included preschools, nurseries, kindergartens, long day care and family day care. To be included, studies had to include at least one intervention component targeting child diet within the ECEC setting and measure child dietary or physical outcomes, or both. DATA COLLECTION AND ANALYSIS: Pairs of review authors independently screened titles and abstracts and extracted study data. We assessed risk of bias for all studies against 12 criteria within RoB 1, which allows for consideration of how selection, performance, attrition, publication and reporting biases impact outcomes. We resolved discrepancies via consensus or by consulting a third review author. Where we identified studies with suitable data and homogeneity, we performed meta-analyses using a random-effects model; otherwise, we described findings using vote-counting approaches and via harvest plots. For measures with similar metrics, we calculated mean differences (MDs) for continuous outcomes and risk ratios (RRs) for dichotomous outcomes. We calculated standardised mean differences (SMDs) for primary and secondary outcomes where studies used different measures. We applied GRADE to assess certainty of evidence for dietary, cost and adverse outcomes. MAIN RESULTS: We included 52 studies that investigated 58 interventions (described across 96 articles). All studies were cluster-RCTs. Twenty-nine studies were large (≥ 400 participants) and 23 were small (< 400 participants). Of the 58 interventions, 43 targeted curriculum, 56 targeted ethos and environment, and 50 targeted partnerships. Thirty-eight interventions incorporated all three components. For the primary outcomes (dietary outcomes), we assessed 19 studies as overall high risk of bias, with performance and detection bias being most commonly judged as high risk of bias. ECEC-based healthy eating interventions versus usual practice or no intervention may have a positive effect on child diet quality (SMD 0.34, 95% confidence interval (CI) 0.04 to 0.65; P = 0.03, I2 = 91%; 6 studies, 1973 children) but the evidence is very uncertain. There is moderate-certainty evidence that ECEC-based healthy eating interventions likely increase children's consumption of fruit (SMD 0.11, 95% CI 0.04 to 0.18; P < 0.01, I2 = 0%; 11 studies, 2901 children). The evidence is very uncertain about the effect of ECEC-based healthy eating interventions on children's consumption of vegetables (SMD 0.12, 95% CI -0.01 to 0.25; P =0.08, I2 = 70%; 13 studies, 3335 children). There is moderate-certainty evidence that ECEC-based healthy eating interventions likely result in little to no difference in children's consumption of non-core (i.e. less healthy/discretionary) foods (SMD -0.05, 95% CI -0.17 to 0.08; P = 0.48, I2 = 16%; 7 studies, 1369 children) or consumption of sugar-sweetened beverages (SMD -0.10, 95% CI -0.34 to 0.14; P = 0.41, I2 = 45%; 3 studies, 522 children). Thirty-six studies measured BMI, BMI z-score, weight, overweight and obesity, or waist circumference, or a combination of some or all of these. ECEC-based healthy eating interventions may result in little to no difference in child BMI (MD -0.08, 95% CI -0.23 to 0.07; P = 0.30, I2 = 65%; 15 studies, 3932 children) or in child BMI z-score (MD -0.03, 95% CI -0.09 to 0.03; P = 0.36, I2 = 0%; 17 studies; 4766 children). ECEC-based healthy eating interventions may decrease child weight (MD -0.23, 95% CI -0.49 to 0.03; P = 0.09, I2 = 0%; 9 studies, 2071 children) and risk of overweight and obesity (RR 0.81, 95% CI 0.65 to 1.01; P = 0.07, I2 = 0%; 5 studies, 1070 children). ECEC-based healthy eating interventions may be cost-effective but the evidence is very uncertain (6 studies). ECEC-based healthy eating interventions may have little to no effect on adverse consequences but the evidence is very uncertain (3 studies). Few studies measured language and cognitive skills (n = 2), social/emotional outcomes (n = 2) and quality of life (n = 3). AUTHORS' CONCLUSIONS: ECEC-based healthy eating interventions may improve child diet quality slightly, but the evidence is very uncertain, and likely increase child fruit consumption slightly. There is uncertainty about the effect of ECEC-based healthy eating interventions on vegetable consumption. ECEC-based healthy eating interventions may result in little to no difference in child consumption of non-core foods and sugar-sweetened beverages. Healthy eating interventions could have favourable effects on child weight and risk of overweight and obesity, although there was little to no difference in BMI and BMI z-scores. Future studies exploring the impact of specific intervention components, and describing cost-effectiveness and adverse outcomes are needed to better understand how to maximise the impact of ECEC-based healthy eating interventions.

Feasibility and preliminary results of a call centre delivered continuing care intervention following residential alcohol and other drug treatment.

INTRODUCTION: To help reduce relapse rates following alcohol and other drug (AOD) treatment, continuing care interventions have been recommended. Previous continuing care interventions have incorporated telephone and face-to-face sessions to help promote participant engagement. The study was conducted as a randomised controlled feasibility study and examined a call centre delivered continuing care intervention for people leaving residential rehabilitation services. METHODS: Participants were attending AOD residential treatment services in NSW, Australia (N = 154). Participants were randomised to either 12- or 4-sessions of continuing care. Follow up assessments were completed at 6-months. The primary outcomes were demand and implementation. Secondary outcomes were AOD use, mental health and physical health at 6-months. RESULTS: Interest in continuing care was high, with 93% of participants approached reporting an interest in being involved. Of the participants who completed the consent and baseline procedures, 29% of people were contacted post residential treatment and randomised. For those people randomised, the average number of sessions completed was 2.78 (SD = 1.65) for the 4-session arm and 4.81 (SD = 4.46) for the 12-session arm. Fidelity to the treatment manual was high. Both treatment arms showed higher complete abstinence at 6-months compared to baseline (12-session OR 28.57 [2.3, 353.8]; 4-session OR 28.11 [3.6, 221.2]). DISCUSSION AND CONCLUSIONS: A major challenge associated with the call centre approach was re-engaging participants once they left the residential facility and delivering the planned dose of treatment. Further work is required to promote greater uptake of these protocols once people leave residential treatment.

Development and psychometric evaluation of the Khaini Smokeless Tobacco Dependence Scale.

INTRODUCTION: Khaini is a smokeless tobacco (SLT) product commonly used in the South-Asian region. It is the most common smokeless tobacco product used in India, having a prevalence of 11.2% and is used by 104.1 million adults. No scales exist to assess khaini dependence. Existing scales available to assess dependence on smokeless tobacco products are not ideal as these are adapted from cigarette dependence scales and developed for western populations. This study aimed to develop a khaini dependence scale and assess its reliability and validity. METHODS: Recommended methods for scale development were followed for item development, scale development and scale evaluation. Scale development was guided by a theoretical framework, a review of existing scales and in-depth interviews with 21 khaini users recruited from a tertiary care hospital in Mumbai, India. The process involved the identification of domains for dependence and the development of an item pool. Cognitive interviews and pre-testing were conducted with 20 khaini users to assess content validity. A cross-sectional survey with 323 khaini users was conducted, and Exploratory Factor Analysis (EFA) was used to determine the factor structure of the draft scale. The content validity, criterion validity (by cross-referencing with the cotinine level of users), convergent validity and internal consistency of the new scale were assessed. RESULTS: The final version of the Khaini SLT Dependence Scale (KSLTDS) had 20 items. EFA indicated an acceptable goodness of fit for a three-factor structure with physical, psychological and sociocultural-behavioral sub-scales. It showed evidence of acceptable criterion validity with cotinine (ρ=0.43, p=0.0002), convergent validity with FTND-ST (ρ=0.51, p<0.0001) and frequency of khaini use (ρ=0.38, p<0.0001). The sub-scales (α=0.87-0.90) showed acceptable internal consistency. CONCLUSIONS: The psychometric evaluation of the KSLTDS showed preliminary validity and reliability for assessing dependence on khaini, and therefore, it is appropriate for clinical and research purposes. Re-validation studies are required with various khaini user populations.

Mixed messages: most spinal pain and osteoarthritis observational research is unclear or misaligned.

OBJECTIVES: We assessed authors' language and methods to determine alignment between reported aims, methods, intent, and interpretations in observational studies in spinal pain or osteoarthritis. STUDY DESIGN AND SETTING: We searched five databases for observational studies that included people with spinal pain or osteoarthritis published in the last 5 years. We randomized 100 eligible studies, and classified study intent (aims and methods) and interpretations as causal, non-causal, unclear, or misaligned. RESULTS: Overall, 38% of studies were aligned regarding their intent and interpretation (either causally (22%) or non-causally (16%)). 29% of studies' aims and 29% of study methods were unclear. Intent was misaligned in 16% of studies (where aim differed to method) and 23% of studies had misaligned interpretations (where there were multiple conflicting claims). The most common kind of aim was non-causal (38%), and the most common type of method (39%), intent (38%), and interpretations (35%) was causal. CONCLUSIONS: Misalignment and mixed messages are common in observational research of spinal pain and osteoarthritis. More than 6 in 10 observational studies may be uninterpretable, because study intent and interpretations do not align. While causal methods and intent are most common in observational research, authors commonly shroud causal intent in non-causal terminology.

Efficacy of intermittent compression devices for thromboembolic prophylaxis in major abdominal surgery: a systematic review and meta-analysis.

BACKGROUND: The benefits of mechanical prophylaxis for the prevention of venous thromboembolism (VTE) in abdominal and pelvic surgery are uncertain, with different guidelines stating that graduated compression stockings (GCS) and intermittent pneumatic compression devices (IPCDs) can be used either alone or in combination. To review the efficacy of IPCDs in preventing VTE following abdominal and pelvic surgery. METHODS: A systematic review was conducted, identifying relevant literature reporting clinical trials conducted in abdominopelvic surgery, comparing the effect of IPCDs alone or in combination with no prophylaxis, GCS and chemical prophylaxis. The review identified studies reported from 1966 to 2022 in Medline, Embase, PubMed and Cochrane databases for randomized controlled trials. RESULTS: Thirteen RCTs involving 1914 participants were identified. IPCDs were superior to placebo (OR VTE 0.39; 95% CI 0.20-0.76) but not superior to other forms of prophylaxis (OR 0.83; 95% CI 0.30-2.27) or to GCS alone (OR 0.9; 95% CI 0.24-3.36). The addition of IPCDs to GCS compared with GCS alone was beneficial (OR 0.45; 95% CI 0.23-0.91) as was the addition of IPCDs to standard perioperative chemoprophylaxis (OR 0.25; 95% CI 0.09-0.74). The overall quality and reliability of trials were low, with high risk of bias. CONCLUSIONS: IPCDs are more effective than placebo in reducing VTE rates but are not more effective than other forms of thrombo-prophylaxis (chemical or mechanical) following abdominal and pelvic surgery. There is poor quality evidence to suggest that they might have a role as additional prophylaxis when combined with GCS and chemical prophylaxis.

Strategies for enhancing the implementation of school-based policies or practices targeting diet, physical activity, obesity, tobacco or alcohol use.

BACKGROUND: Several school-based interventions are effective in improving child diet and physical activity, and preventing excessive weight gain, and tobacco or harmful alcohol use. However, schools are frequently unsuccessful in implementing such evidence-based interventions. OBJECTIVES: 1. To evaluate the benefits and harms of strategies aiming to improve school implementation of interventions to address student diet, physical activity, tobacco or alcohol use, and obesity. 2. To evaluate the benefits and harms of strategies to improve intervention implementation on measures of student diet, physical activity, obesity, tobacco use or alcohol use; describe their cost or cost-effectiveness; and any harms of strategies on schools, school staff or students. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search was between 1 September 2016 and 30 April 2021 to identify any relevant trials published since the last published review. SELECTION CRITERIA: We defined 'Implementation' as the use of strategies to adopt and integrate evidence-based health interventions and to change practice patterns within specific settings. We included any trial (randomised controlled trial (RCT) or non-randomised controlled trial (non-RCT)) conducted at any scale, with a parallel control group that compared a strategy to implement policies or practices to address diet, physical activity, overweight or obesity, tobacco or alcohol use by students to 'no intervention', 'usual' practice or a different implementation strategy. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Given the large number of outcomes reported, we selected and included the effects of a single outcome measure for each trial for the primary (implementation) and secondary (student health behaviour and obesity) outcomes using a decision hierarchy. Where possible, we calculated standardised mean differences (SMDs) to account for variable outcome measures with 95% confidence intervals (CI). For RCTs, we conducted meta-analyses of primary and secondary outcomes using a random-effects model, or in instances where there were between two and five studies, a fixed-effect model. The synthesis of the effects for non-randomised studies followed the 'Synthesis without meta-analysis' (SWiM) guidelines. MAIN RESULTS: We included an additional 11 trials in this update bringing the total number of included studies in the review to 38. Of these, 22 were conducted in the USA. Twenty-six studies used RCT designs. Seventeen trials tested strategies to implement healthy eating, 12 physical activity and six a combination of risk factors. Just one trial sought to increase the implementation of interventions to delay initiation or reduce the consumption of alcohol. All trials used multiple implementation strategies, the most common being educational materials, educational outreach and educational meetings. The overall certainty of evidence was low and ranged from very low to moderate for secondary review outcomes. Pooled analyses of RCTs found, relative to a control, the use of implementation strategies may result in a large increase in the implementation of interventions in schools (SMD 1.04, 95% CI 0.74 to 1.34; 22 RCTs, 1917 participants; low-certainty evidence). For secondary outcomes we found, relative to control, the use of implementation strategies to support intervention implementation may result in a slight improvement on measures of student diet (SMD 0.08, 95% CI 0.02 to 0.15; 11 RCTs, 16,649 participants; low-certainty evidence) and physical activity (SMD 0.09, 95% CI -0.02 to 0.19; 9 RCTs, 16,389 participants; low-certainty evidence). The effects on obesity probably suggest little to no difference (SMD -0.02, 95% CI -0.05 to 0.02; 8 RCTs, 18,618 participants; moderate-certainty evidence). The effects on tobacco use are very uncertain (SMD -0.03, 95% CIs -0.23 to 0.18; 3 RCTs, 3635 participants; very low-certainty evidence). One RCT assessed measures of student alcohol use and found strategies to support implementation may result in a slight increase in use (odds ratio 1.10, 95% CI 0.77 to 1.56; P = 0.60; 2105 participants). Few trials reported the economic evaluations of implementation strategies, the methods of which were heterogeneous and evidence graded as very uncertain. A lack of consistent terminology describing implementation strategies was an important limitation of the review. AUTHORS' CONCLUSIONS: The use of implementation strategies may result in large increases in implementation of interventions, and slight improvements in measures of student diet, and physical activity. Further research is required to assess the impact of implementation strategies on such behavioural- and obesity-related outcomes, including on measures of alcohol use, where the findings of one trial suggest it may slightly increase student risk. Given the low certainty of the available evidence for most measures further research is required to guide efforts to facilitate the translation of evidence into practice in this setting.

"Myths and Facts" Education Is Comparable to "Facts Only" for Recall of Back Pain Information but May Improve Fear-Avoidance Beliefs: An Embedded Randomized Trial.

OBJECTIVE: To assess the effectiveness of patient education with "myths and facts" versus "facts only" on recall of back pain information and fear-avoidance beliefs in patients with chronic low back pain (LBP). DESIGN: Randomized Study Within A Trial. METHODS: One hundred fifty-two participants with chronic LBP were included. Participants allocated to the "facts only" group received an information sheet with 6 LBP facts, whereas those allocated to the "myths and facts" group received the same information sheet, with each myth refuted by its respective fact. The primary outcome was a correct recall of back pain facts, and the secondary outcome was the physical activity component of the Fear-Avoidance Beliefs Questionnaire (FABQ-PA), 2 weeks after the provision of the information sheet. RESULTS: There was no evidence of a difference in the proportion of participants with a correct recall between the "myths and facts" and "facts only" groups (odds ratio = 0.98; 95% confidence interval [CI]: 0.48, 1.99) and no significant difference in FABQ-PA mean scores between groups (-1.58; 95% CI: -3.77, 0.61). Sensitivity analyses adjusted for prognostic factors showed no difference in information recall but a larger difference in FABQ-PA scores (-2.3; 95% CI: -4.56, -0.04). CONCLUSION: We found no overall difference in the recall of back pain information for patients provided with "myths and facts" compared with that for patients provided with "facts only" and a slight reduction in fear-avoidance beliefs for physical activity using "myths and facts" compared with that using "facts only," but the meaningfulness of this result is uncertain. J Orthop Sports Phys Ther 2022;52(9):586-594. Epub: 9 July 2022. doi:10.2519/jospt.2022.10989.

Glycoprotein nonmetastatic melanoma protein B (GNMPB) as a novel biomarker for cerebral adrenoleukodystrophy.

Adrenoleukodystrophy (ALD) is an X-linked peroxisomal disease caused by a mutation in the ABCD1 gene, producing mutations in the very long chain fatty acid transporter, ALD protein. Cerebral ALD (cALD) is a severe phenotype of ALD with neuroinflammation and neurodegeneration. Elevated levels of Glycoprotein Nonmetastatic Melanoma Protein B (GNMPB) have been recently documented in neurodegenerative diseases such as Alzheimer's disease, Multiple Sclerosis and Amyotrophic Lateral Sclerosis. Our objective was to measure the levels cerebral spinal fluid (CSF) GNMPB in cALD patients to determine if GNMPB could be a potential biomarker in tracking cALD disease progression. CSF GNMPB levels were significantly higher in cALD patients versus controls (2407 ± 1672 pg/mL vs. 639.5 ± 404 pg/mL, p = 0.0009). We found a positive correlation between CSF GNMPB and MRI disease severity score levels (R2 = 0.3225, p < 0.0001) as well as the gadolinium intensity score (p = 0.0204). Boys with more severe neurologic deficits also had higher levels of CSF GNMPB (p < 0.0001). A positive correlation was shown between CSF GNMPB and another biomarker, chitotriosidase (R2 = 0.2512, p = 0.0244). These data show that GNMPB could be a potential biomarker of cALD disease state and further studies should evaluate it as a predictor of the disease progression.

Evaluation of Neurofilament Light Chain as a Biomarker of Neurodegeneration in X-Linked Childhood Cerebral Adrenoleukodystrophy.

Cerebral adrenoleukodystrophy (CALD) is a devastating, demyelinating neuroinflammatory manifestation found in up to 40% of young males with an inherited mutation in ABCD1, the causative gene in adrenoleukodystrophy. The search for biomarkers which correlate to CALD disease burden and respond to intervention has long been sought after. We used the Olink Proximity Extension Assay (Uppsala, Sweden) to explore the cerebral spinal fluid (CSF) of young males with CALD followed by correlative analysis with plasma. Using the Target 96 Neuro Exploratory panel, we found that, of the five proteins significantly increased in CSF, only neurofilament light chain (NfL) showed a significant correlation between CSF and plasma levels. Young males with CALD had a 11.3-fold increase in plasma NfL compared with controls. Importantly, 9 of 11 young males with CALD who underwent HCT showed a mean decrease in plasma NfL of 50% at 1 year after HCT compared with pre-HCT levels. In conclusion, plasma NfL could be a great value in determining outcomes in CALD and should be scrutinized in future studies in patients prior to CALD development and after therapeutic intervention.

An irradiated marrow niche reveals a small noncollagenous protein mediator of homing, dermatopontin.

Hematopoietic cell homing after hematopoietic cell transplant (HCT) is governed by several pathways involving marrow niche cells that are evoked after pre-HCT conditioning. To understand the factors that play a role in homing, we performed expression analysis on zebrafish marrow niche cells following conditioning. We determined that the noncollagenous protein extracellular matrix related protein dermatopontin (Dpt) was upregulated sevenfold in response to irradiation. Studies in mice revealed DPT induction with radiation and lipopolysaccharide exposure. Interestingly, we found that coincubation of zebrafish or murine hematopoietic cells with recombinant DPT impedes hematopoietic stem and progenitor cell homing by 50% and 86%, respectively. Similarly, this translated into a 24% reduction in long-term engraftment (vs control; P = .01). We found DPT to interact with VLA-4 and block hematopoietic cell-endothelial cell adhesion and transendothelial migration. Finally, a DPT-knockout mouse displayed a 60% increase in the homing of hematopoietic cells vs wild-type mice (P = .03) with a slight improvement in long-term lin-SCA1+cKIT+-SLAM cell engraftment (twofold; P = .04). These data show that the extracellular matrix-related protein DPT increases with radiation and transiently impedes the transendothelial migration of hematopoietic cells to the marrow.

Clustering of multiple health-risk factors among vocational education students: a latent class analysis.

Physical and mental health risks often commence during young adulthood. Vocational education institutions are an ideal setting for understanding how health-risks cluster together in students to develop holistic multiple health-risk interventions. This is the first study to examine clustering of tobacco smoking, fruit intake, vegetable intake, alcohol consumption, physical inactivity, overweight/obesity, depression, and anxiety in vocational education students and the socio-demographic characteristics associated with cluster membership. A cross-sectional survey with vocational education students (n = 1134, mean age = 24.3 years) in New South Wales, Australia. Latent class analysis identified clusters and latent class regression examined characteristics associated with clusters. Four clusters were identified. All clusters had moderate inadequate fruit intake and moderate overweight/obesity. Cluster 1 (13% of sample) had "high anxiety, high inadequate vegetable intake, low tobacco, and low alcohol use." Cluster 2 (16% of sample) had "high tobacco smoking, high alcohol use, high anxiety, high depression, and high inadequate vegetable intake." Cluster 3 (52% of sample) had "high risky alcohol use, high inadequate vegetable intake, low depression, low anxiety, low tobacco smoking, and low physical inactivity." Cluster 4 (19% of sample) was a "lower risk cluster with high inadequate vegetable intake." Compared to cluster 4, 16-25-year-olds and those experiencing financial stress were more likely to belong to clusters 1, 2, and 3. Interventions for vocational education students should address fruit and vegetable intake and overweight/obesity and recognize that tobacco use and risky alcohol use sometimes occurs in the context of mental health issues.

A comparison of the Cox model to the Fine-Gray model for survival analyses of re-fracture rates.

We compared the Cox model with the Fine-Gray model when assessing the risk of low-trauma re-fractures. The risk of re-fracture was consistently higher when using the Cox model compared with the Fine-Gray model. The Fine-Gray model more accurately assesses the risk of re-fracture when a competing risk is present. PURPOSE: Compared with the Kaplan-Meier and Cox model, the Fine-Gray competing risk model was developed to take competing risks into account, which provides a better estimation for the risk of the main outcome of interest when one or more competing risks are presented. To date, it remains underused. This study aims to use a case study to illustrate why and how the Fine-Gray model should be used and interpreted, especially when a competing risk is present. METHODS: Using a cohort of patients who presented to a NSW hospital with a non-trauma-related fracture between 2013/2014 and 2017/2018, the cumulative incidence and rate of re-fracture were estimated by the Kaplan-Meier and the Cox model, and by the Fine-Gray model when deaths present as competing events. RESULTS: The cumulative incidence of re-fracture at day 1825 (5 years) was 20.7% when using the Kaplan-Meier model and was 17.7% when using the Fine-Gray model. The estimations of cumulative incidence or rate of re-fracture were consistently higher by traditional survival analyses (Kaplan-Meier or Cox) compared with the Fine-Gray model. For patients aged 90 years and older, the re-fracture incidence at year 5 was estimated to be 66% vs. 28% whereas patients with a history of osteoporosis were 44% vs. 31%. Similarly, compared with patients without osteoporosis history, the estimated re-fracture rate for those with osteoporosis was 9.2 times higher by the Cox model but only 2.6 times higher by the Fine-Gray model. CONCLUSION: The Fine-Gray model more accurately estimates the cumulative incidence of re-fracture and the effect of covariates on the hazard rate than the Kaplan-Meier and Cox models in the presence of a competing risk. This accuracy improves the larger the rate of a competing event.

Inflammatory biomarkers are associated with ketosis in periparturient Holstein cows.

Ketosis is a prevalent periparturient metabolic disorder and we hypothesize that lipopolysaccharide (LPS) infiltration may play a key role in its etiology. Study objectives were to characterize biomarkers of inflammation during the transition period in healthy and clinically diagnosed ketotic cows. Cows were retrospectively categorized into one of two groups: healthy and clinically diagnosed ketotic. Two data sets were utilized; the first dataset (Study A) was obtained as a subset of cows (n=16) enrolled in a larger experiment conducted at the Iowa State University Dairy utilizing Holstein cows (8 healthy; 8 ketotic), and the second dataset (Study B; 22 healthy; 22 ketotic) was obtained from a commercial farm. For both experiments, blood samples were collected prior to and following calving. Ketotic cows in both studies had reduced milk production compared to healthy cows (P<0.01). Post-calving, ketotic cows had increased serum amyloid A (4.2 and 1.8 fold in studies A and B, respectively; P=0.03 and P=0.04), haptoglobin (>6 fold and ~4 fold; P=0.04 and P=0.03), and lipopolysaccharide binding protein (66 and 45%; P<0.01 and P=0.02) compared with their healthy counterparts. Antepartum circulating LPS in ketotic cows was increased (2.3 fold; P=0.01) compared to healthy cows in Study B. In summary, increased biomarkers of inflammation appear to be closely associated with ketosis in transition dairy cows.