Automating Quantitative Measures of an Established Conventional MRI Scoring System for Preterm-Born Infants Scanned between 29 and 47 Weeks' Postmenstrual Age.

BACKGROUND AND PURPOSE: Conventional MR imaging scoring is a valuable tool for risk stratification and prognostication of outcomes, but manual scoring is time-consuming, operator-dependent, and requires high-level expertise. This study aimed to automate the regional measurements of an established brain MR imaging scoring system for preterm neonates scanned between 29 and 47 weeks' postmenstrual age. MATERIALS AND METHODS: This study used T2WI from the longitudinal Prediction of PREterm Motor Outcomes cohort study and the developing Human Connectome Project. Measures of biparietal width, interhemispheric distance, callosal thickness, transcerebellar diameter, lateral ventricular diameter, and deep gray matter area were extracted manually (Prediction of PREterm Motor Outcomes study only) and automatically. Scans with poor quality, failure of automated analysis, or severe pathology were excluded. Agreement, reliability, and associations between manual and automated measures were assessed and compared against statistics for manual measures. Associations between measures with postmenstrual age, gestational age at birth, and birth weight were examined (Pearson correlation) in both cohorts. RESULTS: A total of 652 MRIs (86%) were suitable for analysis. Automated measures showed good-to-excellent agreement and good reliability with manual measures, except for interhemispheric distance at early MR imaging (scanned between 29 and 35 weeks, postmenstrual age; in line with poor manual reliability) and callosal thickness measures. All measures were positively associated with postmenstrual age (r = 0.11-0.94; R2 = 0.01-0.89). Negative and positive associations were found with gestational age at birth (r = -0.26-0.71; R2 = 0.05-0.52) and birth weight (r = -0.25-0.75; R2 = 0.06-0.56). Automated measures were successfully extracted for 80%-99% of suitable scans. CONCLUSIONS: Measures of brain injury and impaired brain growth can be automatically extracted from neonatal MR imaging, which could assist with clinical reporting.

Using the health beliefs model to explore children's attitudes and beliefs on air pollution.

OBJECTIVES: Traffic-related air pollution (TRAP) negatively impacts children's health. Self-protective measures are available, but population uptake is variable. It is essential to understand human beliefs and behaviours related to air pollution in order to understand the lack of self-protection in communities. As a prelude to undertaking a comprehensive assessment of children's attitudes and beliefs on the health effects of TRAP exposure, we sought to develop and validate an appropriate instrument. STUDY DESIGN: This study used exploratory sequential mixed methods. METHODS: This instrument, based on the constructs of the health belief model (HBM), aimed to determine factors predicting wearing a mask to protect against TRAP exposure. An initial literature-based questionnaire was modified using in-depth interviews, focus group discussions, and a quantitative survey pilot. This study included 121 school students and nine professional experts in Vietnam. The questionnaire was tested for content validity, agreement, test-retest reliability, and internal consistency. RESULTS: The concordance of questionnaire items between two repeated assessments ranged from 47.2% to 78.3%, intraclass correlation coefficients ranged from 0.16 to 0.87 and Cronbach's internal reliability coefficient for the instrument was 0.60. CONCLUSION: The self-administered instrument, based on the HBM, is suitable to understand health attitudes and beliefs related to self-protective behaviours to reduce TRAP exposure.

Psychotropic medication use in adults with intellectual disability in Queensland, Australia, from 1999 to 2015: a cohort study.

BACKGROUND: Longitudinal data on medication use in adults with intellectual disability (ID) are scarce. We describe the longitudinal use of and factors associated with psychotropic medication prescribing in adults with ID living in the Australian community. METHODS: Longitudinal data were obtained from adults with ID in the community in Queensland, Australia, between 1999 and 2015. Participant characteristics and medication use information were extracted from baseline questionnaires and health check booklets. Logistic regression was used to investigate the associations between participant characteristics and psychotropic medication use, commencement or cessation. RESULTS: Longitudinal data were available for 138 participants on 697 reviews. The proportion of participants prescribed psychotropic medications increased from 43% to 54% between 1999 and 2015. The rates of commencement and cessation of psychotropic medications between consecutive time periods ranged from 9% to 18% and 7% to 15%, respectively. Challenging behaviour was associated with psychotropic medication use (adjusted odds ratio = 4.1; 95% confidence interval: 2.1-7.9). Presence of challenging behaviour, either consistent or newly identified, was positively associated with ongoing use or commencement of psychotropic medications. CONCLUSIONS: Psychotropic medications are commonly prescribed to adults with ID. Challenging behaviour is positively associated with ongoing use and commencement.

Combined nestorone-testosterone gel suppresses serum gonadotropins to concentrations associated with effective hormonal contraception in men.

BACKGROUND: Novel male-based contraceptives are needed to broaden family planning choices. A progestin, Nestorone® (Nes) gel, plus a testosterone (T) gel suppresses sperm concentrations to levels associated with effective contraception in normal men. However, administration of two gels on different parts of the body daily is impractical. OBJECTIVE: Compare the effectiveness of daily application of a single, combined 8.3 mg Nes-62.5 mg T gel (Nes-T) vs. 62.7 mg T gel to suppress serum FSH and LH concentrations to ≤1.0 IU/L (a threshold associated with suppression of sperm concentrations to ≤1 million and effective contraception) and to compare the pharmacokinetics of serum Nes and T concentrations between the gel groups. DESIGN: We conducted a 28-day, double-blind, controlled trial of 44 healthy men randomized to daily Nes-T or T gel with measurement of hormones at baseline, treatment, and recovery and during 24-h pharmacokinetic studies on days 1 and 28 of treatment. RESULTS: Of the subjects who met pre-defined inclusion criteria, 84% of the Nes-T group suppressed serum gonadotropin concentrations to ≤1.0 IU/L at days 21-28 vs. 16.7% in the T group (p < 0.001). On day 1, Nes concentrations rose significantly above baseline by 2 h and continued to rise up to 24 h after Nes-T gel application. Nes concentrations were not detectable in the T group. Serum total T concentrations rose and were significantly higher in the T gel group compared to the Nes-T group at 24 h on day 1 and days 11, 14, and 21 (p < 0.01). There were no serious adverse events in either group. About 80% of the subjects reported satisfaction with both gels. CONCLUSION: Daily Nes-T gel effectively and safely suppresses serum gonadotropins and is acceptable to most men. It should be studied further in efficacy trials of hormonal male contraception.

Does attrition affect estimates of association: A longitudinal study.

Survey research frequently involves missing cases attributable to refusals to participate, lack of success in accessing all potential respondents or loss to follow-up in longitudinal studies. There is concern that those not recruited or those lost are a select group whose absence from a study may bias the findings of the study. This study provides a test of the extent to which selective loss to follow-up in a longitudinal study may lead to biased findings. The Mater-University Study of Pregnancy collected baseline information for 7718 pregnant women. Follow-ups occurred five years, 14 years, 21 years and 27 years after the birth, for 6753 eligible women. Participants at baseline were partitioned according to follow-up status for each follow-up. We compare baseline (at recruitment) measures of association, with these same measures of association for those retained in the study (Group A) and those lost to follow-up (Group B) at each phase of data. Using univariate logistic regression we compared the strength of association between maternal mental health and various baseline socio-demographic factors for different rates of loss to follow-up. Estimates of association at baseline, and at each follow-up are similar irrespective of the rate of loss to follow-up and whether the comparison is with those retained in the study or those lost to follow-up. There were no statistically significant differences in 90.8% of baseline comparisons with Group A, and 96.9% of comparisons with Group B measures of association. We conclude that differential loss to follow-up rarely affects estimates of association. We suggest that loss to follow-up may produce misleading findings only in circumstances where loss to follow-up is combined with a number of other sources of bias.

Preventing secondary exposure to women from men applying a novel nestorone/testosterone contraceptive gel.

BACKGROUND: Testosterone (T)/Nestorone (NES) combination gel is a potential transdermal male contraceptive that suppresses gonadotropins and spermatogenesis. Transfer of transdermal T from men to women can be prevented by washing or covering application sites with clothing. OBJECTIVES: We hypothesized that showering or wearing a shirt over gel application sites would prevent secondary exposure of T and NES to a woman after close skin contact. MATERIALS AND METHODS: Twelve healthy male and 12 healthy female participants were recruited. Men applied T/NES 62 mg/8 mg gel to their shoulders and upper arms. Two hours after application, female partners rubbed the application site for 15 min. Exposure in the female partner was assessed under three conditions: a shirt covered the application site; the man showered prior to skin contact; or without intervention to reduce transfer. Serum T and NES concentrations were measured by LC-MS/MS in serial blood samples for 24 h after gel exposure. MAIN OUTCOMES: Change in female serum T and NES levels as measured by average concentration over 24 h (Cavg ). RESULTS: Median female serum T Cavg was 23.9 ng/dL (interquartile range, 19.3, 33.9) with the shirt barrier and 26.7 ng/dL (20.7, 33.9) after showering, which was higher than baseline 20.9 ng/dL (16.7, 25.0), both p < 0.03) but lower than without intervention (58.2 ng/dL [30.9, 89.1], both p < 0.01). Female serum NES Cavg and maximum concentration were below the lower limit of quantification with the shirt barrier and after showering, but increased without intervention in six of 12 women (maximum concentration <60 pg/mL). Men had lower average serum NES levels after showering (47 pg/ml [20, 94] compared to no intervention (153.3 pg/mL [51, 241], p < 0.02). CONCLUSION: Secondary transfer of T and NES occurs after intensive skin contact with the gel application site. Secondary transfer is decreased by a shirt barrier or showering before contact.

Non-clinical studies of progesterone.

Progesterone is a steroid hormone that is essential for the regulation of reproductive function. Progesterone has been approved for several indications including the treatment of anovulatory menstrual cycles, assisted reproductive technology, contraception during lactation and, when combined with estrogen, for the prevention of endometrial hyperplasia in postmenopausal hormonal therapy. In addition to its role in reproduction, progesterone regulates a number of biologically distinct processes in other tissues, particularly in the nervous system. This physiological hormone is poorly absorbed when administered in a crystalline form and is not active when given orally, unless in micronized form, or from different non-oral delivery systems that allow a more constant delivery rate. A limited number of preclinical studies have been conducted to document the toxicity, carcinogenicity and overall animal safety of progesterone delivered from different formulations, and these rather old studies showed no safety concern. More recently, it has been shown in animal experiments that progesterone, its metabolite allopregnanolone and structurally related progestins have positive effects on neuroregeneration and repair of brain damage, as well as myelin repair. These recent preclinical findings have the potential to accelerate therapeutic translation for multiple unmet neurological needs.

Meteorological factors and respiratory syncytial virus seasonality in subtropical Australia.

Evidence is emerging regarding the influence of meteorological factors on seasonal respiratory syncytial virus outbreaks. Data however, are limited for subtropical regions, especially in the southern hemisphere. We examined whether meteorological data (daily minimum and maximum temperatures, rainfall, relative humidity, dew point, daily global solar exposure) and tourist numbers were associated with the incidence of RSV in children aged <5 years for the Gold Coast region of South-East Queensland, Australia (latitude 28.0°S). RSV cases between 1 July 2007 and 30 June 2016 were identified from the Pathology Queensland Gold Coast Laboratory database. Time-series methods were used to identify seasonal patterns. RSV activity peaked in mid-to-late autumn (April-May), tapering in winter (June-August). While most meteorological variables measured were associated with RSV incidence, rainfall (ρ = 0.40, 95% confidence interval (CI) 0.32-0.48) and humidity (ρ = 0.38, 95% CI 0.29-0.46) 8 weeks earlier had the nearest temporal relationship. Tourist numbers were not correlated with RSV activity. Identifying meteorological conditions associated with seasonal RSV epidemics can improve understanding of virus transmission and assist planning for their impact upon the health sector, including timing of passive RSV immunoprophylaxis for high-risk infants and future public health interventions, such as maternal immunisation with RSV vaccines.

The relationship between socio-economic status and diagnosed Type 2 diabetes is changing with economic growth in Nanjing, China.

AIM: In developed countries, the relationship between socio-economic status (SES) and Type 2 diabetes was positive several decades ago but is now negative. However, in developing societies such as China the relationship remains positive. It is likely that at some stage of economic development the SES-Type 2 diabetes association will become negative in developing communities. This study aimed to examine whether this inflexion is approaching in China. METHODS: Two cross-sectional surveys were undertaken in Nanjing, China, in 2000 and 2011. The same sampling approach was used to randomly select participants. Diagnosed Type 2 diabetes was the outcome variable. SES was measured using monthly family average income and divided into thirds. Mixed-effects models were used to calculate the association between SES and Type 2 diabetes. RESULTS: There were 19 861 (response rate, 90.1%) and 7824 (response rate, 82.8%) participants in 2000 and 2011, respectively. A 2.6-fold increase in Type 2 diabetes prevalence was observed from 3.0% (95% confidence interval 2.8%, 3.3%) in 2000 to 8.2% (7.7%, 8.8%) in 2011 (P < 0.01). After controlling for potential confounders, the odds ratios of having Type 2 diabetes decreased from 2.06 (95% CI 1.55, 2.73) and 1.83 (1.40, 2.37) in 2000 to 1.58 (1.23, 2.02) and 1.35 (1.06, 1.74) in 2011 for the higher and middle SES groups respectively, compared with those in the lower SES category. CONCLUSIONS: The SES-Type 2 diabetes association remained positive in Nanjing, China, in 2011 but the disparity diminished significantly compared with 2000. These results can inform the delivery of appropriate interventions to people at risk of developing Type 2 diabetes.

Continuous dosing of a novel contraceptive vaginal ring releasing Nestorone® and estradiol: pharmacokinetics from a dose-finding study.

BACKGROUND: As part of a program to develop a novel estradiol-releasing contraceptive vaginal ring (CVR), we evaluated the pharmacokinetic (PK) profile of CVRs releasing segesterone acetate (Nestorone® (NES)) combined with one of three different estradiol (E2) doses. STUDY DESIGN: A prospective, double-blind, randomized, multi-centered study to evaluate a 90-day CVR releasing NES [200mcg/day] plus E2, either 10mcg/day, 20mcg/day, or 40mcg/day in healthy reproductive-age women with regular cycles. Participants provided blood samples twice weekly for NES and E2 levels during the first 60 days (ring 1) and the last 30 days (ring 2) of use. A subset underwent formal PK assessments at ring initiation, ring exchange (limited PK), and study completion. RESULTS: The main study enrolled 197 women; 22 participated in the PK substudy. Baseline characteristics between the main and PK participants were comparable, with an average BMI of 25.8 kg/m2 (SD 4.3). In the PK substudy, all three rings showed similar NES PK: mean area under the curve (AUC(0-72)) 34,181 pg*day/mL; concentration maximum (Cmax) 918 pg/mL; time to maximum concentration (Tmax) 3.5 h. For E2, the Cmax occurred at 2 h, and was significantly higher with the 20 mcg/day ring (mean 390 pg/mL); 10 mcg/day, 189 pg/mL, p=.003; 40 mcg/day, 189 pg/mL, p<.001), and declined rapidly to≤50 pg/mL for all doses by 24 h. For all subjects, the median E2 levels remained under 35 pg/mL during treatment. CONCLUSION: PK parameters of NES were not affected when paired with different doses of E2, but E2 levels from all three doses were lower than anticipated and no dose response was observed. IMPLICATIONS: While these novel estradiol-releasing combination contraceptive vaginal rings provided sustained release of contraceptive levels of Nestorone over 90 days, the E2 levels achieved were not consistent with bone protection, and a dose-response was not observed.

Pregabalin versus placebo in targeting pro-nociceptive mechanisms to prevent chronic pain after whiplash injury in at-risk individuals - a feasibility study for a randomised controlled trial.

BACKGROUND: Whiplash-associated disorders (WAD) are an enormous and costly burden to Australian society. Up to 50% of people who experience a whiplash injury will never fully recover. Whiplash is resistant to treatment and no early management approach has yet been shown to prevent chronic pain. The early presence of central sensitization is associated with poor recovery. Pregabalin's effects on central sensitization indicate the potential to prevent or modulate these processes after whiplash injury and to improve health outcomes, but this has not been investigated. This paper describes the protocol for a feasibility study for a randomised controlled trial of pregabalin plus evidence-based advice compared to placebo plus evidence-based advice for individuals with acute whiplash injury who are at risk of poor recovery. METHODS: This double blind, placebo-controlled randomised feasibility study will examine the feasibility and potential effectiveness of pregabalin and evidence-based advice (intervention) compared to placebo and evidence-based advice (control) for individuals with acute whiplash injury at risk of poor recovery. Thirty participants (15 per group) aged 18-65 years with Grade II WAD, within 48 hours of injury and currently experiencing at least moderate pain (NRS: ≥ 5/10) will be recruited from Emergency Departments of public hospitals in Queensland, Australia. Pregabalin will be commenced at 75 mg bd and titrated up to 300 mg bd as tolerated for 4 weeks followed by 1 week of weaning. RESULTS: The feasibility of trial procedures will be tested, as well as the potential effect of the intervention on the outcomes. The primary outcome of neck pain intensity at 3 months from randomisation will be compared between the treatment groups using standard analysis of variance techniques. DISCUSSION: Feasibility and potential effectiveness data will inform an appropriately powered full trial, which if successful, will provide an effective and cost-effective intervention for a costly and treatment resistant condition. It will also have implications for the early management of other traumatic conditions beyond whiplash. TRIAL REGISTRATION: Clinical Trials Primary Registry: Australian and New Zealand Clinical Trials Registry. CLINICAL TRIAL REGISTRATION NUMBER: ACTRN12617000059369 . Date of Registration: 11/01/2017. Primary Trial Sponsor: The University of Queensland, Brisbane QLD 4072 Australia.

Processes of care in surgical patients who died with hospital-acquired infections in Australian hospitals.

BACKGROUND: Infection may complicate surgical patients' hospital admission. The effect of hospital-acquired infections (HAIs) on processes of care among surgical patients who died is unknown. AIM: To investigate the effect of HAIs on processes of care in surgical patients who died in hospital. METHODS: Surgeon-recorded infection data extracted from a national Australian surgical mortality audit (2012-2016) were grouped into HAIs and no infection. The audit included all-age surgical patients, who died in hospital. Not all patients had surgery. Excluded from analysis were patients with community-acquired infection and those with missing timing of infection. Multivariate logistic regression was used to determine the adjusted effects of HAIs on the processes of care in these patients. Costs associated with HAIs were estimated. FINDINGS: One-fifth of surgical patients who died did so with an HAI (2242 out of 11,681; 19.2%). HAI patients had increased processes of care compared to those who died without infection: postoperative complications [51.0% vs 30.3%; adjusted odds ratio (aOR): 2.20; 95% confidence interval (CI): 1.98-2.45; P < 0.001]; unplanned reoperations (22.6% vs 10.9%; aOR: 2.38; 95% CI: 2.09-2.71; P < 0.001) and unplanned intensive care unit admission (29.3% vs 14.8%; aOR: 2.18; 95% CI: 1.94-2.45; P < 0.001). HAI patients had longer hospital admissions and greater hospital costs than those without infection. CONCLUSION: HAIs were associated with increased processes of care and costs in surgical patients who died; these outcomes need to be investigated in surgical patients who survive.

Neurosteroidogenesis and progesterone anti-inflammatory/neuroprotective effects.

Progesterone shows anti-inflammatory and promyelinating effects in mice with experimental autoimmune encephalomyelitis (EAE), a commonly used model for multiple sclerosis (MS). Because neurosteroids have been implicated as protective factors for MS and EAE, we analysed the expression of neurosteroidogenic enzymes in the compromised spinal cord of EAE mice. EAE was induced in female C57Bl6 mice, which were then killed on day 16 after induction. Progesterone was given by pellet implantation 1 week before EAE induction. Untreated EAE mice showed decreased mRNAs for the steroidogenic acute regulatory protein (Star), voltage-dependent anion channel (VDAC), cholesterol side-chain cleavage (P450scc), 5α-reductase, 3α-hydroxysteroid dehydrogenase (3α-HSOR) and aromatase, whereas changes of 3ß-hydroxysteroid dehydrogenase (3ß-HSD) were not significant. mRNA translocator protein (18 kDa) (TSPO) was elevated, concomitantly with a reactive microgliosis. EAE mice also showed abnormal mitochondrial ultrastructure in axons and neuronal bodies, as well as reduced expression of fission and fusion protein mRNAs. Progesterone pretreatment before EAE induction increased Star, VDAC, P450scc, 5α-reductase type I, 3α-HSOR and aromatase mRNAs and did not modify 3ß-HSD. TSPO mRNA was decreased, possibly as a result of reversal of microgliosis. Progesterone pretreatment also improved mitochondrial ultrastructure and increased fission/fusion protein mRNAs. These mitochondrial effects may be part of the progesterone recovery of neurosteroidogenesis. The enzymes 3ß-HSD, 3α-HSOR and 5α-reductase are also responsible for the formation of androgens. Because MS patients and EAE rodents show changes of central androgen levels, it is likely that, together with progestins and oestrogens, neuroandrogens afford neuroprotection for EAE and MS. The data reviewed suggest that enhanced synthesis of neurosteroids contributes in an auto/paracrine manner to reinforce the neuroprotective and anti-inflammatory effects of exogenous progesterone given to EAE mice.

Methodological quality and reporting of systematic reviews in hand and wrist pathology.

The objective of this study was to assess methodological and reporting quality of systematic reviews in hand and wrist pathology. MEDLINE, EMBASE and Cochrane Library were searched from inception to November 2016 for relevant studies. Reporting quality was evaluated using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and methodological quality using a measurement tool to assess systematic reviews, the Assessment of Multiple Systematic Reviews (AMSTAR). Descriptive statistics and linear regression were used to identify features associated with improved methodological quality. A total of 91 studies were included in the analysis. Most reviews inadequately reported PRISMA items regarding study protocol, search strategy and bias and AMSTAR items regarding protocol, publication bias and funding. Systematic reviews published in a plastics journal, or which included more authors, were associated with higher AMSTAR scores. A large proportion of systematic reviews within hand and wrist pathology literature score poorly with validated methodological assessment tools, which may affect the reliability of their conclusions. LEVEL OF EVIDENCE: I.

Validation of an MRI Brain Injury and Growth Scoring System in Very Preterm Infants Scanned at 29- to 35-Week Postmenstrual Age.

BACKGROUND AND PURPOSE: The diagnostic and prognostic potential of brain MR imaging before term-equivalent age is limited until valid MR imaging scoring systems are available. This study aimed to validate an MR imaging scoring system of brain injury and impaired growth for use at 29 to 35 weeks postmenstrual age in infants born at <31 weeks gestational age. MATERIALS AND METHODS: Eighty-three infants in a prospective cohort study underwent early 3T MR imaging between 29 and 35 weeks' postmenstrual age (mean, 32+2 ± 1+3 weeks; 49 males, born at median gestation of 28+4 weeks; range, 23+6-30+6 weeks; mean birthweight, 1068 ± 312 g). Seventy-seven infants had a second MR scan at term-equivalent age (mean, 40+6 ± 1+3 weeks). Structural images were scored using a modified scoring system which generated WM, cortical gray matter, deep gray matter, cerebellar, and global scores. Outcome at 12-months corrected age (mean, 12 months 4 days ± 1+2 weeks) consisted of the Bayley Scales of Infant and Toddler Development, 3rd ed. (Bayley III), and the Neuro-Sensory Motor Developmental Assessment. RESULTS: Early MR imaging global, WM, and deep gray matter scores were negatively associated with Bayley III motor (regression coefficient for global score ß = -1.31; 95% CI, -2.39 to -0.23; P = .02), cognitive (ß = -1.52; 95% CI, -2.39 to -0.65; P < .01) and the Neuro-Sensory Motor Developmental Assessment outcomes (ß = -1.73; 95% CI, -3.19 to -0.28; P = .02). Early MR imaging cerebellar scores were negatively associated with the Neuro-Sensory Motor Developmental Assessment (ß = -5.99; 95% CI, -11.82 to -0.16; P = .04). Results were reconfirmed at term-equivalent-age MR imaging. CONCLUSIONS: This clinically accessible MR imaging scoring system is valid for use at 29 to 35 weeks postmenstrual age in infants born very preterm. It enables identification of infants at risk of adverse outcomes before the current standard of term-equivalent age.

Reproducibility of the Balance Evaluation Systems Test (BESTest) and the Mini-BESTest in school-aged children.

This study evaluated the intra-rater, inter-rater and test-retest reproducibility of the Full-BESTest and Mini-BESTest when assessing postural control in children. Thirty-four children aged 7-17 years participated in intra-rater and inter-rater evaluation, and 22 children repeated assessment six weeks later for evaluation of test-retest reliability. Postural control was assessed using the Full Balance Evaluation Systems Test (Full-BESTest) and the short-form Mini-BESTest. Intra-rater, inter-rater and test-retest reproducibility were examined using video assessment. Test-retest reproducibility was also assessed in real-time. Reproducibility was examined by agreement and reliability statistics. Agreement was calculated using percentage of agreement, Limits of Agreement and Smallest Detectable Change. Reliability was calculated using Intra-class Correlation Coefficients. Results showed that the reliability of Total Scores was excellent for the Full-BESTest for all conditions (all ICCs>0.82), whereas the Mini-BESTest ranged from fair to excellent (ICC=0.56-0.86). Percentage of Domain Scores with good-excellent reliability (ICCs>0.60) was slightly higher for the Full-BESTest (66%) compared to the Mini-BESTest (59%). Smallest Detectable Change scores were good to excellent for the Full-BESTest (2%-6%) and for the Mini-BESTest (5%-10%) relative to total test scores. Both the Full-BESTest and Mini-BESTest can discriminate postural control abilities within and between days in school-aged children. The Full-BESTest has slightly better reproducibility and a broader range of items, which could be the most useful version for treatment planning. We propose minor modifications to improve reproducibility for children, and indicate the modified version by the title Kids-BESTest. Future psychometric research is recommended for specific paediatric clinical populations.

Impact of various progestins with or without transdermal testosterone on gonadotropin levels for non-invasive hormonal male contraception: a randomized clinical trial.

Although several progestins have been tested for hormonal male contraception, the effects of dosage and nature of various progestins on gonadotropin suppression combined with and without additional testosterone has not been performed in a comparative trial. The aim of this study was to evaluate the differential impact of four oral or transdermal progestins on the suppression of gonadotropins in healthy men: oral: cyproterone acetate (CPA), levonorgestrel (LNG), norethisterone acetate (NETA), and transdermal: Nestorone® (NES), all in combination with transdermal testosterone (T). Randomized clinical trial testing was performed with four progestins at two doses each. After a 2-week progestin-only treatment, transdermal T was added for further 4 weeks and was followed by a 3-week recovery period. Progestin-dose per day: CPA 10 mg/20 mg, NES 2 mg/3 mg/dose e.g. 200/300 µg/day absorbed, NETA 5 mg/10 mg, LNG 120 µg/240 µg. From an andrology outpatient clinic, 56 healthy men aged 18-50 years, with body mass index ≤33 kg × m-2 were included in the study. Serum concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were studied. Secondary outcome measure included were serum testosterone concentrations, sperm concentrations, and safety parameters. Intergroup comparisons demonstrated that CPA and LNG had the strongest effect on LH/FSH suppression. Nevertheless, every substance showed significant inhibitory effects on gonadotropin secretion, especially in combination with transdermal T. A decrease in hematocrit and insulin sensitivity as well as cholesterol subfractions and triglycerides was uniformly seen for every group. The combination of oral or transdermal progestins with a transdermal testosterone preparation is able to suppress gonadotropins. Further dose titration studies with sperm suppression as an end-point should be conducted to determine the lowest effective dose for hormonal male contraception.

The Iodine Status of Queensland Preschool Children After the Introduction of Mandatory Iodine Fortification in Bread: An Exploratory Study Using a Convenience Sample.

Introduction Appropriate dietary iodine is essential for thyroid hormone synthesis, especially in young children. Following an iodine fortification in bread initiative, approximately 6 % of Australian preschool children were expected to have an excessive iodine status. The aim of this study was to document the current iodine status of preschool children using urinary iodine concentration (UIC) as a biomarker of iodine intake. Methods A convenience sample of fifty-one preschool children, aged 2-3 years, were recruited from south east Queensland. UIC was ascertained from spot morning and afternoon urine samples collected on two consecutive days and food frequency questionnaires were completed for each participant. Dietary iodine intake was extrapolated from UIC assuming 90 % of dietary iodine is excreted in urine and a urine volume of 0.5 L/day. Results A median UIC of 223.3 µg/L was found. The calculated median dietary iodine intake was 124.8 µg/day (SD 47.0) with 9.8 % of samples above the upper level of 200 µg for dietary iodine for children within this age group. No foods were associated with UIC. Discussion Limited by sample size and recruitment strategies, no association was found between usual food intake and UIC. Extrapolated dietary iodine intake indicated that children within this cohort consumed adequate amounts of dietary iodine, although the number of children consuming above the upper limit of 300 µg/day was almost double of expected. The development of a UIC criteria to assess appropriate parameters for varying degrees of iodine status is required for the monitoring of iodine nutrition in this vulnerable age group.