Urinary Ferritin as a Noninvasive Means of Assessing Iron Status in Young Children.

BACKGROUND: Iron deficiency (ID) is the most common nutritional deficiency affecting young children. Serum ferritin concentration is the preferred biomarker for measuring iron status because it reflects iron stores; however, blood collection can be distressing for young children and can be logistically difficult. A noninvasive means to measure iron status would be attractive to either diagnose or screen for ID in young children. OBJECTIVES: This study aimed to determine the correlation between urinary and serum ferritin concentrations in young children; to determine whether correcting urinary ferritin for creatinine and specific gravity improves the correlation; and to determine a urine ferritin cut point to predict ID. METHODS: Validation study was conducted using paired serum and urine collected from 3-y-old children (n = 142) participating in a longitudinal birth cohort study: the ORIGINS project in Perth, Western Australia. We calculated the sensitivity, specificity, positive, and negative predictive values of urinary ferritin amount in identifying those with ID at the clinical cut point used by the World Health Organization (serum ferritin concentration of <12 ng/mL). RESULTS: Urine ferritin, corrected for creatinine, correlated moderately with serum ferritin [r = 0.53 (0.40-0.64)] and performed well in predicting those with ID (area under the curve: 0.85; 95% confidence interval: 0.75, 0.94). Urine ferritin <2.28 ng/mg creatinine was sensitive (86%) and specific (77%) in predicting ID and had a high negative predictive value of 97%; however, the positive predictive value was low (40%) owing to the low prevalence of ID in the sample (16%). CONCLUSIONS: Urine ferritin shows good diagnostic performance for ID. This noninvasive biomarker maybe a useful screening tool to exclude ID in healthy young children; however, further research is needed in other populations.

Miniature wireless LED-device for photodynamic-induced cell pyroptosis.

The inability of visible light to penetrate far through biological tissue limits its use for phototherapy and photodiagnosis of deep-tissue sites of disease. This is unfortunate because many visible dyes are excellent photosensitizers and photocatalysts that can induce a wide range of photochemical processes, including photogeneration of reactive oxygen species. One potential solution is to bring the light source closer to the site of disease by using a miniature implantable LED. With this goal in mind, we fabricated a wireless LED-based device (volume of 23 mm3) that is powered by RF energy and emits light with a wavelength of 573 nm. It has the capacity to excite the green absorbing dye Rose Bengal, which is an efficient type II photosensitizer. The wireless transfer of RF power is effective even when the device is buried in chicken breast and located 6 cm from the transmitting antenna. The combination of a wireless device as light source and Rose Bengal as photosensitizer was found to induce cell death of cultured HT-29 human colorectal adenocarcinoma cells. Time-dependent generation of protruding bubbles was observed in the photoactivated cells suggesting cell death by light-induced pyroptosis and supporting evidence was gained by cell staining with the fluorescence probes Annexin-V FITC and Propidium Iodide. The results reveal a future path towards a wireless implanted LED-based device that can trigger photodynamic immunogenic cell death in deep-seated cancerous tissue.

Laboratory characterization of hydrothermally processed oligopeptides in ice grains emitted by Enceladus and Europa.

The Cassini mission provided evidence for a global subsurface ocean and ongoing hydrothermal activity on Enceladus, based on results from Cassini's mass spectrometers. Laboratory simulations of hydrothermal conditions on icy moons are needed to further constrain the composition of ejected ice grains containing hydrothermally altered organic material. Here, we present results from our newly established facility to simulate the processing of ocean material within the temperature range 80-150°C and the pressure range 80-130 bar, representing conditions suggested for the water-rock interface on Enceladus. With this new facility, we investigate the hydrothermal processing of triglycine (GGG) peptide and, for the first time, analyse the extracted samples using laser-induced liquid beam ion desorption (LILBID) mass spectrometry, a laboratory analogue for impact ionization mass spectrometry of ice grains in space. We outline an approach to elucidate hydrothermally processed GGG in ice grains ejected from icy moons based on characteristic differences between GGG anion and cation mass spectra. These differences are linked to hydrothermal processing and thus provide a fingerprint of hydrothermal activity on extraterrestrial bodies. These results will serve as important guidelines for biosignatures potentially obtained by a future Enceladus mission and the SUrface Dust Analyzer (SUDA) instrument onboard Europa Clipper. This article is part of the theme issue 'Dust in the Solar System and beyond'.

Maternal serum unmetabolized folic acid concentration following multivitamin and mineral supplementation with or without folic acid after 12 weeks gestation: A randomized controlled trial.

Pregnant women are advised to take folic acid (FA) supplements before conception and during the first trimester of pregnancy. Many women continue FA supplementation throughout pregnancy, and concerns have been raised about associations between excessive FA intake and adverse maternal and child health outcomes. Unmetabolized folic acid (UMFA) is found in serum after high FA intakes and is proposed as a biomarker for excessive FA intake. We aimed to determine if removing FA from prenatal micronutrient supplements after 12 weeks of pregnancy reduces serum UMFA concentrations at 36 weeks gestation. In this double-blind, randomized controlled trial conducted in South Australia, 103 women with a singleton pregnancy were randomly assigned at 12-16 weeks gestation to take a micronutrient supplement containing no FA or 800 µg/day FA from enrollment until 36 weeks gestation. Ninety women (0 µg/day FA n = 46; 800 µg/day FA n = 44) completed the study. Mean, UMFA concentration was lower in the women randomized to the 0 µg/day group compared to the 800 µg/day FA group, 0.6 ± 0.7 and 1.4 ± 2.7 nmol/L, respectively. The adjusted mean difference (95% CI) in UMFA between the groups was [-0.85 (-1.62, -0.08) nmol/L, p = 0.03]. Maternal serum and red blood cell folate concentrations were lower in the 0 µg/day FA group than in the 800 µg/day group (median 23.2 vs. 49.3 and 1335 vs. 1914 nmol/L, respectively; p < 0.001). Removing FA at 12-16 weeks gestation from prenatal micronutrient supplements reduced the concentration of UMFA at 36 weeks gestation.

Lifestyle and sociodemographic risk factors for stillbirth by region of residence in South Australia: a retrospective cohort study.

BACKGROUND: Stillbirth rates remain a global priority and in Australia, progress has been slow. Risk factors of stillbirth are unique in Australia due to large areas of remoteness, and limited resource availability affecting the ability to identify areas of need and prevalence of factors associated with stillbirth. This retrospective cohort study describes lifestyle and sociodemographic factors associated with stillbirth in South Australia (SA), between 1998 and 2016. METHODS: All restigered births in SA between 1998 ad 2016 are included. The primary outcome was stillbirth (birth with no signs of life ≥ 20 weeks gestation or ≥ 400 g if gestational age was not reported). Associations between stillbirth and lifestyle and sociodemographic factors were evaluated using multivariable logistic regression and described using adjusted odds ratios (aORs). RESULTS: A total of 363,959 births (including 1767 stillbirths) were included. Inadequate antenatal care access (assessed against the Australian Pregnancy Care Guidelines) was associated with the highest odds of stillbirth (aOR 3.93, 95% confidence interval (CI) 3.41-4.52). Other factors with important associations with stillbirth were plant/machine operation (aOR, 1.99; 95% CI, 1.16-2.45), birthing person age ≥ 40 years (aOR, 1.92; 95% CI, 1.50-2.45), partner reported as a pensioner (aOR, 1.83; 95% CI, 1.12-2.99), Asian country of birth (aOR, 1.58; 95% CI, 1.19-2.10) and Aboriginal/Torres Strait Islander status (aOR, 1.50; 95% CI, 1.20-1.88). The odds of stillbirth were increased in regional/remote areas in association with inadequate antenatal care (aOR, 4.64; 95% CI, 2.98-7.23), birthing age 35-40 years (aOR, 1.92; 95% CI, 1.02-3.64), Aboriginal and/or Torres Strait Islander status (aOR, 1.90; 95% CI, 1.12-3.21), paternal occupations: tradesperson (aOR, 1.69; 95% CI, 1.17-6.16) and unemployment (aOR, 4.06; 95% CI, 1.41-11.73). CONCLUSION: Factors identified as independently associated with stillbirth odds include factors that could be addressed through timely access to adequate antenatal care and are likely relevant throughout Australia. The identified factors should be the target of stillbirth prevention strategies/efforts. SThe stillbirth rate in Australia is a national concern. Reducing preventable stillbirths remains a global priority.

THE ROLE OF SCHOOLS IN MENINGOCOCCAL CARRIAGE AMONG ADOLESCENTS AND YOUNG ADULTS IN SOUTH AUSTRALIA.

Neisseria meningitidis carriage peaks in adolescents. This secondary analysis of a randomized controlled trial (NCT03089086) assessing 4CMenB herd protection in South Australia ("B-Part-of-It" study) explored school attributes linked to baseline carriage in 34,489 adolescents prevaccination. Carriage was higher in students attending single-sex [adjusted odds ratio (aOR): 1.49; 95% confidence interval (CI): 1.14-1.93], boarding (aOR: 1.92; 1.13-3.27) and government schools (aOR: 1.32, 1.09-1.61).

Alignment in Total Knee Arthroplasty: Avoid Crossing Over From Varus to Valgus.

BACKGROUND: Ideal target limb alignment remains a debated topic in total knee arthroplasty (TKA). We aimed to determine the effect of limb alignment correction on patient-reported outcomes and knee range of motion (ROM) following TKA. METHODS: In this retrospective analysis, patients (N = 409) undergoing primary TKA at a single institution were studied. Using full leg-length radiographs, limb alignment was measured preoperatively and postoperatively. Patients were categorized by preoperative (Preop) alignment (varus > 0°; valgus < 0°). Preop varus patients were then divided as follows based on postoperative alignment: neutral (VAR-NEUT, 0°± 2), remaining in varus (VAR-rVAR, ≥3°), and cross-over to valgus (VAR-CO, ≤-3°). Similarly, Preop valgus patients were divided as follows for postoperative alignment: neutral (VAL-NEUT, 0°± 2), remaining in valgus (VAL-rVAL, ≤-3°), and cross-over to varus (VAL-CO, ≥3°). The Knee Injury and Osteoarthritis Outcome Score for Joint Replacement survey scores were collected at preoperatively as well as at 6 weeks, 3, 6, and 12 months postoperatively. Knee ROM was collected at 2 weeks, 6 to 12 weeks, and >6 months postoperatively. An analysis of variance repeated on time followed by a Bonferroni post hoc test was used to compare outcomes for the postoperative alignment subgroups. RESULTS: Preop Varus patients: Those in the VAR-CO group (overcorrected to -4.03° ± 1.95valgus) were observed to have lower Knee Injury and Osteoarthritis Outcome Score for Joint Replacement scores at 3, 6, and 12 months postoperatively compared to those in the NEUT group (P < .05). This finding was paired with reduced ROM at 6 to 12 weeks postoperatively in the VAR-CO group compared to VAR-NEUT and VAR-rVAR (P < .05). Preop Valgus patients: Those in the VAL-rVal group (left in -4.39° ± 1.39valgus) were observed to have reduced knee flexion at 6 to 12 weeks postoperatively compared to VAL-NEUT and VAL-CO. CONCLUSIONS: These findings indicate that postoperative valgus alignment via either crossing over to valgus (VAR-CO) or remaining in valgus (VAL-rVAL) alignment may result in less preferable outcomes than correction to neutral or slightly varus alignment.

Intraosseous Versus Intravenous Vancomycin in Tourniquetless Primary Total Knee Arthroplasty: A Randomized Trial.

BACKGROUND: Intraosseous (IO) administration of vancomycin at the time of total knee arthroplasty (TKA) has been shown to be safer and more effective than intravenous (IV) administration at preventing early periprosthetic joint infection. Previous studies have relied on tourniquet inflation to enhance local tissue concentrations and mitigate systemic release. METHODS: A single-blinded, randomized clinical trial was performed on 20 patients (10 IV, 10 IO) undergoing primary TKA. The control (IV) group received weight-dosed vancomycin approximately 1 hour prior to the incision and weight-dosed cefazolin immediately prior to the incision. The interventional (IO) group received weight-dosed cefazolin immediately prior to the incision and 500 mg of vancomycin delivered via the IO technique at the time of the incision. Systemic samples for vancomycin levels were taken prior to the incision and at closure. During the procedure, tissue samples were taken from the distal femur, proximal tibia, and suprapatellar synovium. There were no differences in patient demographics or changes in serum creatinine from preoperative to postoperatively between groups. RESULTS: Significant differences in systemic vancomycin levels (ug/mL) were found at the start of the case (IV = 27.9 ± 4.9 versus IO = 0 ± 0, P = .0004) and at the end of the case (IV = 19.6 ± 2.6 versus IO = 7.8 ± 1.0, P = .001). No significant differences were seen in the average vancomycin concentration in the distal femur (IV = 61.0 ± 16.0 versus IO = 66.2 ± 12.3, P = .80), proximal tibia (IV = 52.8 ± 13.5 versus IO = 57.1 ± 17.0, P = .84), or suprapatellar synovial tissue (IV = 10.7 ± 5.3 versus IO = 9.0 ± 3.3, P = .80). There were no complications associated with vancomycin administration in either group. CONCLUSIONS: This study demonstrates the utility of IO vancomycin in tourniquetless TKA with similar local tissue and significantly lower systemic concentrations than IV administration. LEVEL OF EVIDENCE: Level 1 therapeutic randomized trial.

Categorisation of continuous covariates for stratified randomisation: How should we adjust?

To obtain valid inference following stratified randomisation, treatment effects should be estimated with adjustment for stratification variables. Stratification sometimes requires categorisation of a continuous prognostic variable (eg, age), which raises the question: should adjustment be based on randomisation categories or underlying continuous values? In practice, adjustment for randomisation categories is more common. We reviewed trials published in general medical journals and found none of the 32 trials that stratified randomisation based on a continuous variable adjusted for continuous values in the primary analysis. Using data simulation, this article evaluates the performance of different adjustment strategies for continuous and binary outcomes where the covariate-outcome relationship (via the link function) was either linear or non-linear. Given the utility of covariate adjustment for addressing missing data, we also considered settings with complete or missing outcome data. Analysis methods included linear or logistic regression with no adjustment for the stratification variable, adjustment for randomisation categories, or adjustment for continuous values assuming a linear covariate-outcome relationship or allowing for non-linearity using fractional polynomials or restricted cubic splines. Unadjusted analysis performed poorly throughout. Adjustment approaches that misspecified the underlying covariate-outcome relationship were less powerful and, alarmingly, biased in settings where the stratification variable predicted missing outcome data. Adjustment for randomisation categories tends to involve the highest degree of misspecification, and so should be avoided in practice. To guard against misspecification, we recommend use of flexible approaches such as fractional polynomials and restricted cubic splines when adjusting for continuous stratification variables in randomised trials.

Health Status of Total Hip Versus Total Knee Arthroplasty Patients and Possible Effects on Decisions Regarding Surgical Location, Cost, and Access to Care.

Background: Total hip arthroplasty (THA) and total knee arthroplasty (TKA) are no longer considered inpatient-only procedures. Qualifying for inpatient status reimbursement requires additional, unreimbursed administrative effort, and may limit care to these patients. Purpose: We sought to evaluate and compare the overall health status of patients receiving THA and TKA. Methods: We conducted a retrospective review evaluating 2207 patients undergoing primary THA and TKA from 2015 to 2018 at a single institution. Clinical parameters, surgical procedure, medical history, laboratory values, length of stay (LOS), and discharge location were recorded and compared between the 2 groups. Results: In 2202 patients, we observed differences for body mass index (THA = 29.4 ± 0.4, TKA = 32.1 ± 0.3), low-density lipoprotein cholesterol levels (THA = 105.8 ± 13.5 mg/dL; TKA = 128.6 ± 13.7 mg/dL), and blood glucose levels (THA = 98.2 ± 1.7 mg/dL; TKA = 101.4 ± 1.3 mg/dL), indicating that TKA patients were more likely than THA patients to be classified as obese, hypercholesterolemic, and hyperglycemic. We observed longer LOS in THA patients (51.25 hours, 95% CI ± 3.87 hours) than in TKA patients (36.93 hours, 95% CI ± 1.17 hours). A greater proportion of TKA patients were discharged home (81.97%, N = 1155) rather than to additional care facilities compared with THA patients (71.84%, N = 539). Conclusion: In this retrospective study, we observed that TKA patients had higher rates of comorbidities than did THA patients, but TKA patients spent less time in the hospital and were more likely to be discharged home. Future studies should evaluate reasons for poor clinical outcomes for patients undergoing total joint arthroplasty with an outpatient designation.

Patient Perceptions of Same-Day Discharge Versus Overnight Stay After Total Joint Arthroplasty: Results of a Survey.

Background: In the COVID-19 era, there has been increasing interest in same-day discharge (SDD) after total joint arthroplasty (TJA). However, patient perception of SDD is not well reported. Purpose: We sought to understand patients' perceptions and preferences of postoperative care by surveying patients who have completed both an overnight stay (ONS) and an SDD after TJA. Methods: We emailed survey links to 67 patients who previously underwent either 2 total hip arthroplasties (THAs) or 2 total knee arthroplasties (TKAs). Results: Fifty-two patients (78%) responded to the survey. Thirty-four (65%) patients underwent staged, bilateral TKAs, and 18 (35%) patients underwent staged, bilateral THAs. Overall, 63% of patients preferred their SDD, 12% had no preference, and 25% preferred their ONS, with no difference in preference between TKA and THA groups. Those who preferred their SDD reported being more comfortable at home. Those who preferred their ONS felt their pain and concerns were better addressed. No differences were found in comfort, sleep quality, appetite, burden on family, return to function, feelings of being discharged too soon, overall experience, 30-day emergency department (ED) visits, or readmissions within 30 days between patients' SDD and ONS. There was a small statistically significant difference between patients' perception of safety between SDD and ONS. Conclusion: Our survey found that most patients reported a preference for SDD after TJA over ONS. Although there was a small difference in patient perception of safety, there were no differences in return to the ED or readmissions after SDD and ONS.

Nudging towards COVID-19 and influenza vaccination uptake in medically at-risk children: EPIC study protocol of randomised controlled trials in Australian paediatric outpatient clinics.

INTRODUCTION: Children with chronic medical diseases are at an unacceptable risk of hospitalisation and death from influenza and SARS-CoV-2 infections. Over the past two decades, behavioural scientists have learnt how to design non-coercive 'nudge' interventions to encourage positive health behaviours. Our study aims to evaluate the impact of multicomponent nudge interventions on the uptake of COVID-19 and influenza vaccines in medically at-risk children. METHODS AND ANALYSES: Two separate randomised controlled trials (RCTs), each with 1038 children, will enrol a total of approximately 2076 children with chronic medical conditions who are attending tertiary hospitals in South Australia, Western Australia and Victoria. Participants will be randomly assigned (1:1) to the standard care or intervention group. The nudge intervention in each RCT will consist of three text message reminders with four behavioural nudges including (1) social norm messages, (2) different messengers through links to short educational videos from a paediatrician, medically at-risk child and parent and nurse, (3) a pledge to have their child or themselves vaccinated and (4) information salience through links to the current guidelines and vaccine safety information. The primary outcome is the proportion of medically at-risk children who receive at least one dose of vaccine within 3 months of randomisation. Logistic regression analysis will be performed to determine the effect of the intervention on the probability of vaccination uptake. ETHICS AND DISSEMINATION: The protocol and study documents have been reviewed and approved by the Women's and Children's Health Network Human Research Ethics Committee (HREC/22/WCHN/2022/00082). The results will be published via peer-reviewed journals and presented at scientific meetings and public forums. TRIAL REGISTRATION NUMBER: NCT05613751.

Longitudinal study of meningococcal carriage in adolescents and young adults in South Australia 2017-2020.

BACKGROUND: This analysis investigated longitudinal changes in meningococcal carriage in adolescents in South Australia over 4 years. METHODS: Data from the "B Part of It" study, which included a state-wide cluster randomized controlled trial in secondary-school students (n = 34,489 in 2017 and 2018) and serial cross-sectional studies in school leavers aged 17-25 years (n = 4028 in 2019-2020). Individuals had oropharyngeal swabs collected annually. This study included two unique cohorts: (1) individuals enrolled in 2019, with three consecutive annual swabs taken in 2017, 2018 and 2019; and (2) individuals enrolled in 2020, with swabs taken in 2017, 2018, and 2020. Disease-associated N. meningitidis genogroups were identified using PCR and whole genome sequencing. Univariate analysis identified risk factors for recurrent carriage (≥2). RESULTS: Among school leavers, 50 (1.7%, total n = 2980) had carriage detected at successive visits. In participants with meningococcal carriage at successive visits, 38/50 (76.0%) had the same genogroup detected by porA PCR. Of those, 19 had the same MLST type and demonstrated minimal variation, indicating they most likely had sustained carriage of the same isolate (range 226 to 490 days, mean duration 352 [SD 51] days). In the 2019 school leaver cohort, 6.7% acquired carriage in their first year out of school compared to 3.3% in their final school year. Compared to single carriage detection, recurrent carriage was potentially more likely in older adolescents (16 compared to ≤15 years; OR = 1.97 (95%CI 1.0, 3.86); p = 0.048). CONCLUSION: Whilst carriage is typically transient, some adolescents/young adults may have persistent carriage and are likely to be an important group in the transmission of meningococci.

Too Much Too Little: Clarifying the Relationship Between Maternal Iodine Intake and Neurodevelopmental Outcomes.

BACKGROUND: In 2009, the Australian government mandated the fortification of bread salt with iodine. In 2010, pregnant and lactating women were also advised to take an iodine-containing supplement. Our assessment of this policy in an iodine-sufficient population showed that children whose mothers were in the highest and lowest quartiles of iodine intake performed more poorly on early childhood tests of cognition and language than those in the second quartile. However, we did not quantify the iodine intake associated with optimal neurodevelopment. OBJECTIVES: The aim was to establish the iodine intake range in pregnancy associated with optimal child neurodevelopment. METHODS: A prospective cohort study of pregnant women and their young children (n = 699). Iodine intake was assessed by a validated food frequency questionnaire at 16 and 28 wk of gestation. Child neurodevelopment at 18 mo of age was measured using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). The relationship between average iodine intake during pregnancy and child neurodevelopment was assessed using linear regression with fractional polynomials and adjustment for confounders. RESULTS: Mean (SD) iodine intake was similar at study entry and 28 wk, 308 (120) µg/d, with 82% of women taking iodine supplements at study entry. The relationship between iodine intake during pregnancy and Bayley-III cognitive and language scores was curvilinear (P = 0.001 and P = 0.004, respectively), with the lowest Bayley-III scores observed at lower and higher iodine intakes. The inflection point that drove the association between lower iodine intake in pregnancy and poorer child neurodevelopment scores was around 185 µg/d; for the higher pregnancy iodine intakes, language and cognitive scores were negatively affected from ∼350 µg/d to 370 µg/d, respectively. Higher iodine intakes were being driven by supplement use. CONCLUSIONS: Targeted, not blanket, iodine supplementation may be needed for pregnant women with low-iodine intake from food.

Treatment of Postoperative Neck Dissection Cervical Lymphocele With Percutaneous Bleomycin Sclerotherapy.

Lymphatic leak after lymph node dissection is a rare but well-known surgical complication that is often treated with conservative management and ultimately reoperation. The purpose of this report is to offer an alternative treatment for chyle leak that avoids hospitalization and subsequent surgery. Sclerotherapy has been used to treat lymphatic leaks in the past and has been shown to be safe and effective. This report presents a patient with a known cervical lymphocele who was followed through multiple sclerotherapy appointments until resolution of the lymphocele.

High-Dose Docosahexaenoic Acid in Newborns Born at Less Than 29 Weeks' Gestation and Behavior at Age 5 Years: Follow-Up of a Randomized Clinical Trial.

Importance: Children born at less than 29 weeks' gestation are at risk of behavioral difficulties. This may be due in part to the lack of transplacental supply of docosahexaenoic acid (DHA), a key fatty acid with structural and functional roles in the brain. Objective: To determine whether meeting the neonatal DHA requirement through supplementation is associated with improved behavioral functioning of children born at less than 29 weeks' gestation. Design, Setting and Participants: This was a follow-up of children from 10 Australian participating centers in a multi-center, blinded, parallel group randomized clinical trial of infants born at less than 29 weeks' gestation conducted from June 2012 and September 2015, excluding those with additional fatty acid supplementation or major congenital or chromosomal abnormalities. Follow-up took place from August 2018 to May 2021. Parents of surviving children who had not withdrawn from the original trial were invited to complete questionnaires when the child turned 5 years' corrected age. Interventions: Infants were randomized to receive daily enteral emulsions providing 60 mg/kg/d of DHA or a soy-oil emulsion (with no DHA) from within the first 3 days of enteral feeding until 36 weeks' postmenstrual age or discharge home, whichever occurred first. Main Outcomes and Measures: The primary outcome of this follow-up was parent-rated behavior and emotional functioning as indicated by the Total Difficulties score of the Strengths and Difficulties Questionnaire. Parents also completed questionnaires about their child's behavioral manifestations of executive functioning, as well as a range of health outcomes to assess potential longer-term side effects of DHA intervention. Results: Primary outcome data were available for 731 children (76% of 958 surviving eligible children; 361 in the intervention group and 370 in the control group). Of these 731, 452 (47%) were female, and the mean (SD) corrected age at follow-up was 5.4 (0.5) years. Following imputation for missing data, the mean Total Difficulties score was the same in both groups (intervention group, n = 465; mean [SD], 11.8 [6.3]; control group, n = 493; mean [SD], 11.8 [6.0]; mean difference adjusted for sex, gestational age stratum, and hospital, 0.01; 95% CI, -0.87 to 0.89; P = .98). There was no evidence for differences between the groups in any secondary outcomes of behavior, executive functioning, or health. Conclusions and Relevance: In this follow-up of a randomized clinical trial, enteral DHA supplementation at the equivalent of the estimated in utero dose for infants born at less than 29 weeks' gestation did not improve behavioral functioning at age 5 years. There were no indications of adverse effects with DHA supplementation. Trial Registration: Australian New Zealand Clinical Trial Registry: ACTRN12612000503820.

Predictors of compliance with higher dose omega-3 fatty acid supplementation during pregnancy and implications for the risk of prematurity: exploratory analysis of the ORIP randomised trial.

BACKGROUND: Intention-to-treat analyses of the Omega-3 to Reduce the Incidence of Prematurity (ORIP) trial found that omega-3 (n-3) fatty acid supplementation reduces the risk of prematurity in the subgroup of women with a singleton pregnancy and low n-3 status early in pregnancy, but not overall. However, results may have been influenced by less-than-optimal compliance. OBJECTIVES: To identify predictors of compliance with n-3 supplementation and determine treatment effects among compliers. DESIGN: Exploratory analyses of a multicentre-blinded randomised trial. SETTING: 6 tertiary care centres in Australia. PARTICIPANTS: 5328 singleton pregnancies. INTERVENTIONS: Daily capsules containing 900 mg n-3 long-chain polyunsaturated fatty acids or vegetable oil, consumed from before 20 weeks gestation until 34 weeks gestation. OUTCOME MEASURES: Early preterm (<34 weeks gestation) and preterm birth (<37 weeks gestation). Women were considered compliant if they reported missing less than a third of their allocated capsules in the previous week during a mid-pregnancy appointment. RESULTS: Among 2654 singleton pregnancies in the n-3 intervention group, 1727 (65%) were deemed compliant with supplementation. Maternal characteristics associated with compliance included age, years of full-time education, consuming alcohol but not smoking in the 3 months leading up to pregnancy, fewer previous births and taking dietary supplements at enrolment. Based on complier average causal effects, n-3 supplementation reduced the risk of preterm birth in compliers (relative risk=0.76; 95% CI 0.60 to 0.97), but not early preterm birth (relative risk=0.80; 95% CI 0.44 to 1.46). Consistent with intention-to-treat analyses, the lack of an overall effect on early preterm birth in compliers appeared to be due to beneficial effects in women with low n-3 status at enrolment but not women with replete status. CONCLUSIONS: Results in compliers were similar to those from intention-to-treat analyses, suggesting that non-compliance was not a major factor in explaining outcomes from the ORIP trial. TRIAL REGISTRATION NUMBER: ACTRN12613001142729.

Robotic-Assisted Total Knee Arthroplasty Can Increase Frequency of Achieving Target Limb Alignment in Primary Total Knee Arthroplasty for Preoperative Valgus Deformity.

Background: Robotic-assisted total knee arthroplasty (rTKA) has been shown to reduce the number of alignment outliers and to improve component positioning compared to manual TKA (mTKA). The primary purpose of this investigation was to compare the frequency of achieving target postoperative limb alignment and component positioning for rTKA vs mTKA. Methods: A retrospective comparative study was performed on 250 patients undergoing primary TKA by 2 fellowship-trained arthroplasty surgeons. Surgeon A performed predominantly rTKA (103 cases) with the ROSA system (Zimmer Biomet, Warsaw, IN) and less frequently mTKA (44 cases) with conventional instrumentation. Surgeon B performed only mTKA (103 cases). Target limb alignment for surgeon A was 0° for all cases and for surgeon B was 2° varus for varus knees and 0° for valgus knees. Radiographic measurements were determined by 2 reviewers. Target zone was set at ± 2 degrees from the predefined target. Results: When comparing rTKA to mTKA performed by different surgeons, there were no differences in the percentage within the target zone (57.28% vs 53.40%, P = .575), but rTKA did result in a greater percentage for cases with preoperative valgus (71.42% vs 44.12%, P = .031). Patient-reported Outcomes Measurement Information System Global-10 physical scores were statistically higher at both 3 (P = .016) and 6 months (P = .001) postoperatively for rTKA compared to mTKA performed by different surgeons. Conclusions: Although experienced surgeons can achieve target limb alignment correction with similar frequency when comparing rTKA to mTKA for all cases, rTKA may achieve target limb alignment with more accuracy for preoperative valgus deformity. Level of Evidence: Retrospective Cohort Study, Level III.

Routine Histopathologic Examination of Bone Obtained During Elective Primary Total Knee Arthroplasty May Not Be Necessary.

Background: Many institutions require the routine collection of pathology samples from every primary total knee arthroplasty (TKA) performed. These policies are controversial, and their cost-effectiveness is difficult to define. We sought to judge the cost-effectiveness of one such policy according to World Health Organization recommendations. Methods: We analyzed 3200 consecutive primary TKAs, comparing our presumed preoperative diagnoses against the diagnoses made by the pathologist. Diagnoses were categorized as concordant (matching), discrepant (not matching but without impact to patient management), or discordant (not matching and resulting in a direct change to patient management). An incremental cost-utility ratio analysis was performed to determine the cost-effectiveness of our institution's policy to routinely collect pathology samples from every primary TKA performed. Cost-effectiveness was defined by World Health Organization guidelines as a cost of less than $228,090 per quality-adjusted life year gained. Results: Twelve pathology samples were lost before reaching a pathologist. From the remaining 3188 samples, we identified 3158 concordant cases, 29 discrepant diagnoses, and 1 discordant diagnosis. It cost an estimated $10,522.60 to identify each discrepant diagnosis and an estimated $305,155.36 to diagnose one discordant case in our cohort. Our incremental cost-utility ratio analysis revealed that we spent $305,155.36 to gain 0 quality-adjusted life years for our patients. Conclusions: Routine histopathologic analysis of TKA samples was cost-ineffective in our patient cohort and may not be necessary during routine TKA.