CELPI: trial protocol for a randomised controlled trial of a Carer End of Life Planning Intervention in people dying with dementia.

BACKGROUND: Dementia is a leading cause of death in developed nations. Despite an often distressing and symptom laden end of life, there are systematic barriers to accessing palliative care in older people dying of dementia. Evidence exists that 70% of people living with severe dementia attend an emergency department (ED) in their last year of life. The aim of this trial is to test whether a Carer End of Life Planning Intervention (CELPI), co-designed by consumers, clinicians and content specialists, improves access to end of life care for older people with severe dementia, using an ED visit as a catalyst for recognising unmet needs and specialist palliative care referral where indicated. METHODS: A randomised controlled trial (RCT) enrolling at six EDs across three states in Australia will be conducted, enrolling four hundred and forty dyads comprising a person with severe dementia aged ≥ 65 years, and their primary carer. Participants will be randomly allocated to CELPI or the control group. CELPI incorporates a structured carer needs assessment and referral to specialist palliative care services where indicated by patient symptom burden and needs assessment. The primary outcome measure is death of the person with dementia in the carer-nominated preferred location. Secondary outcomes include carer reported quality of life of the person dying of dementia, hospital bed day occupancy in the last 12 months of life, and carer stress. An economic evaluation from the perspective of a health funder will be conducted. DISCUSSION: CELPI seeks to support carers and provide optimal end of life care for the person dying of dementia. This trial will provide high level evidence as to the clinical and cost effectiveness of this intervention. TRIAL REGISTRATION: ACTRN12622000611729 registered 22/04/2022.

Crosswalks between the Oxford hip and knee scores and the HOOS-12 and KOOS-12 instruments.

OBJECTIVE: To develop and validate bi-directional crosswalks between the Oxford Hip Score (OHS) and HOOS-12 summary impact score, and between the Oxford Knee Score (OKS) and KOOS-12 summary impact score. METHODS: Data were sourced from the Australian Orthopaedic Association National Joint Replacement Registry Patient-Reported Outcome Measures Program. Patients undergoing primary joint replacement for osteoarthritis who completed the OHS and HOOS-12 or OKS and KOOS-12 instruments were included in the analysis. An equipercentile method was used to create four crosswalks, with the distribution of scores smoothed using log-linear models prior to equating. Crosswalk validity was assessed through comparison of actual vs derived scores, Pearson correlation coefficients, root mean square errors (RMSE) and Bland-Altman plots. RESULTS: Paired OHS/HOOS-12 data and paired OKS/KOOS-12 data were available for 4,513 patients undergoing total hip replacement and 5,942 patients undergoing total knee replacement, respectively. Minimal differences were observed between actual and crosswalk-derived mean scores (actual OHS 27.55 vs derived OHS 27.56; actual HOOS-12 53.28 vs derived HOOS-12 53.31; actual OKS 27.34 vs derived OKS 27.34; actual KOOS-12 50.51 vs derived KOOS-12 50.58). High correlation was observed between actual and derived scores (Pearson's r for hip-specific instruments: 0.943-0.946; Pearson's r for knee-specific instruments: 0.925-0.931). Plotted actual vs mean derived scores also indicated robust concordance across the breadth of the instrument scales. CONCLUSION: These crosswalks provide close approximations of actual OHS, OKS, HOOS-12 and KOOS-12 scores, as indicated by multiple validation metrics. They offer a resource for clinicians, researchers and arthroplasty registries to support PROMs score conversion and data harmonisation efforts.

Selective use of Peptide Receptor Radionuclide Therapy following comparative imaging of Ga-68 DOTATATE PET/CT against I-131 MIBG scintigraphy in a small Asian cohort of Adult Neuroblastoma.

Adult neuroblastoma (AN) is rare with an extremely poor prognosis. No standard therapy exists for this entity and treatment options are limited in recurrent or refractory disease. 131I-MIBG has been used in combination with myeloablative therapy before autologous bone marrow transplantation or in a salvage therapy setting. However, myelotoxicity is a dose-limiting factor in heavily pre-treated patients and response is not always sustained. Somatostatin receptor scintigraphy and theranostics with radiolabelled somatostatin receptor analogues are becoming more commonplace with the recognition of these receptors in over 90% of neuroblastoma cells. We describe three AN patients assessed for somatostatin receptor status and the novel use of 177Lu-based peptide recep-tor radionuclide therapy (PRRT) in two of them and a literature review.

Implications for research and clinical use from a Rasch analysis of the HOOS-12 and KOOS-12 instruments.

OBJECTIVE: To evaluate the structural validity of the 12-item Hip disability and Osteoarthritis Outcome Score (HOOS-12) and 12-item Knee injury and Osteoarthritis Outcome Score (KOOS-12) using Rasch analysis and consider psychometric implications for research and clinical use. METHOD: Individual-level HOOS-12 and KOOS-12 data from the Australian Orthopaedic Association National Joint Replacement Registry, collected before and after primary total hip and knee replacement, were used for this analysis. Using the Rasch analytic approach, overall model fit and item fit were examined, together with potential reasons for misfit including response threshold ordering, differential item functioning, internal consistency, unidimensionality and item targeting. RESULTS: Overall misfit to the Rasch model was evident for both instruments. A degree of item misfit was also observed, although most items demonstrated logical sequencing of response options. Only two items (hip/knee pain frequency and awareness of hip/knee problems) displayed disordered response thresholds. The pain, function, and quality of life domains of the HOOS-12 and KOOS-12 demonstrated excellent internal consistency reliability (person separation index: 0.80-0.93) and unidimensionality. A mismatch between item difficulty and person ability scores at the highest end of the HOOS-12 and KOOS-12 scales contributed to post-operative ceiling effects (mean logit for HOOS-12: 3.57; KOOS-12: 2.58; ≈0 indicates well-targeted scale). CONCLUSION: We found evidence to support the structural validity of the three HOOS-12 and KOOS-12 domains for evaluating joint replacement outcomes. However, there may be missing content in both instruments particularly for high-functioning patients. Minor refinement of some response options may be warranted to improve item performance.

Performance of the HOOS-12 and KOOS-12 instruments for evaluating outcomes from joint replacement surgery.

OBJECTIVE: To evaluate the psychometric properties of the 12-item Hip disability and Osteoarthritis Outcome Score (HOOS-12) and Knee injury and Osteoarthritis Outcome Score (KOOS-12) for use in evaluating outcomes after joint replacement for osteoarthritis. DESIGN: Patient-reported outcomes data collected by the Australian Orthopaedic Association National Joint Replacement Registry were used for this analysis. HOOS-12 and KOOS-12 domain (pain, function, quality of life) and summary impact data were available. The Oxford Hip Score (OHS), Oxford Knee Score (OKS) and EQ-5D-5L were used as comparators. Instruments were administered pre-operatively and at 6 months post-operatively. Internal consistency reliability, floor and ceiling effects, convergent validity, known groups validity, and responsiveness were evaluated using standard psychometric techniques. RESULTS: Baseline HOOS-12 and KOOS-12 data were available for 3,023 patients undergoing primary total hip replacement and 4,010 patients undergoing primary total knee replacement. At baseline, high internal consistency was demonstrated for all domains and summary scores (Cronbach's alpha: HOOS-12 = 0.81-0.93; KOOS-12 = 0.82-0.92). Post-operative ceiling effects (>15% of patients scoring the best possible score) were identified for the HOOS-12 pain (46%), function (39%) and quality of life domains (26%) and summary score (17%), and for the KOOS-12 pain (21%) and function domains (18%). The HOOS-12 and KOOS-12 could differentiate between two known groups (lowest/highest OHS or OKS quartiles post-operatively; p < 0.001) and were highly responsive to change (effect sizes for HOOS-12: 2.20-2.83; KOOS-12: 1.82-2.35). CONCLUSION: The HOOS-12 and KOOS-12 have good psychometric properties for capturing joint replacement outcomes including excellent responsiveness, although ceiling effects may limit monitoring of post-operative improvement.

Female adiposity and time-to-pregnancy: a multiethnic prospective cohort.

STUDY QUESTION: Are higher overall and central adiposity associated with reduced fecundability, measured by time-to-pregnancy (TTP), in Asian women? SUMMARY ANSWER: Higher overall adiposity, but not central adiposity, was associated with longer TTP in Asian women. WHAT IS KNOWN ALREADY: High body mass index (BMI) has been associated with a longer TTP, although the associations of body composition and distribution with TTP are less clear. There are no previous studies of TTP in Asian women, who have a relatively higher percentage of body fat and abdominal fat at relatively lower BMI. STUDY DESIGN, SIZE, DURATION: Prospective preconception cohort using data from 477 Asian (Chinese, Malay and Indian) women who were planning to conceive and enrolled in the Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO) study, 2015-2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women's mean age was 30.7 years. Overall adiposity was assessed by BMI, sum of 4-site skinfold thicknesses (SFT) and total body fat percentage (TBF%, measured using air displacement plethysmography); central adiposity was assessed by waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and A body Shape Index (ABSI). Pregnancy occurring within one year from recruitment was ascertained by ultrasonography. Those who did not conceive within one year of recruitment, were lost to follow-up, or initiated fertility treatment were censored. TTP was measured in cycles. Discrete-time proportional hazards models were used to estimate the fecundability ratio (FR) and 95% confidence interval (CI) for each anthropometric measure in association with fecundability, adjusting for confounders. MAIN RESULTS AND THE ROLE OF CHANCE: Compared to women with a normal BMI of 18.5-22.9 kg/m2, women with higher BMI of 23-27.4 and ≥27.5 kg/m2 showed lower FR of 0.66 (95% CI 0.45, 0.97) and 0.53 (0.31, 0.89), respectively. Compared to women in the lowest quartile of SFT (25-52.9 mm), those in the highest quartile of ≥90.1 mm showed lower FR of 0.58 (95% CI 0.36, 0.95). Compared to women in the lowest quartile of TBF% (13.6-27.2%), those in the upper two quartiles of 33.0-39.7% and ≥39.8% showed lower FR of 0.56 (95% CI 0.32, 0.98) and 0.43 (0.24, 0.80), respectively. Association of high BMI with reduced fecundability was particularly evident among nulliparous women. Measures of central adiposity (WC, WHR, WHtR, ABSI) were not associated with fecundability. LIMITATIONS REASONS FOR CAUTION: Small sample size could restrict power of analysis.The analysis was confined to planned pregnancies, which could limit generalizability of findings to non-planned pregnancies, estimated at around 44% in Singapore. Information on the date of last menstrual period for each month was not available, hence the accuracy of self-reported menstrual cycle length could not be validated, potentially introducing error into TTP estimation. Measures of exposures and covariates such as cycle length were not performed repeatedly over time; cycle length might have changed during the period before getting pregnant. WIDER IMPLICATIONS OF THE FINDINGS: Other than using BMI as the surrogate measure of body fat, we provide additional evidence showing that higher amounts of subcutaneous fat that based on the measure of SFT at the sites of biceps, triceps, suprailiac and subscapular, and TBF% are associated with longer TTP. Achieving optimal weight and reducing total percentage body fat may be a potential intervention target to improve female fertility. The null results observed between central adiposity and TTP requires confirmation in further studies. STUDY FUNDING/COMPETING INTEREST(S): This research is supported by Singapore National Research Foundation under its Translational and Clinical Research Flagship Programme and administered by the Singapore Ministry of Health's National Medical Research Council, (NMRC/TCR/004-NUS/2008; NMRC/TCR/012-NUHS/2014). Additional funding is provided by the Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore. Y.S.C., K.M.G., F.Y. and Y.S.L. have received reimbursement to speak at conferences sponsored by companies selling nutritional products. Y.S.C., K.M.G. and S.Y.C. are part of an academic consortium that has received research funding from Abbott, Nutrition, Nestle and Danone. Other authors declared no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Modifiable risk factors in the first 1000 days for subsequent risk of childhood overweight in an Asian cohort: significance of parental overweight status.

BACKGROUND/OBJECTIVE: Many studies have identified early-life risk factors for subsequent childhood overweight/obesity, but few have evaluated how they combine to influence risk of childhood overweight/obesity. We examined associations, individually and in combination, of potentially modifiable risk factors in the first 1000 days after conception with childhood adiposity and risk of overweight/obesity in an Asian cohort. METHODS: Six risk factors were examined: maternal pre-pregnancy overweight/obesity (body mass index (BMI) ⩾25 kg m-2), paternal overweight/obesity at 24 months post delivery, maternal excessive gestational weight gain, raised maternal fasting glucose during pregnancy (⩾5.1 mmol l-1), breastfeeding duration <4 months and early introduction of solid foods (<4 months). Associations between number of risk factors and adiposity measures (BMI, waist-to-height ratio (WHtR), sum of skinfolds (SSFs), fat mass index (FMI) and overweight/obesity) at 48 months were assessed using multivariable regression models. RESULTS: Of 858 children followed up at 48 months, 172 (19%) had none, 274 (32%) had 1, 244 (29%) had 2, 126 (15%) had 3 and 42 (5%) had ⩾4 risk factors. Adjusting for confounders, significant graded positive associations were observed between number of risk factors and adiposity outcomes at 48 months. Compared with children with no risk factors, those with four or more risk factors had s.d. unit increases of 0.78 (95% confidence interval 0.41-1.15) for BMI, 0.79 (0.41-1.16) for WHtR, 0.46 (0.06-0.83) for SSF and 0.67 (0.07-1.27) for FMI. The adjusted relative risk of overweight/obesity in children with four or more risk factors was 11.1(2.5-49.1) compared with children with no risk factors. Children exposed to maternal pre-pregnancy (11.8(9.8-13.8)%) or paternal overweight status (10.6(9.6-11.6)%) had the largest individual predicted probability of child overweight/obesity. CONCLUSIONS: Early-life risk factors added cumulatively to increase childhood adiposity and risk of overweight/obesity. Early-life and preconception intervention programmes may be more effective in preventing overweight/obesity if they concurrently address these multiple modifiable risk factors.

Ratio of Klebsiella/Bifidobacterium in early life correlates with later development of paediatric allergy.

Several studies have reported that intestinal microbial colonisation patterns differ between non-allergic and allergic infants. However, the microbial signature underlying the pathogenesis of allergies remains unclear. We aim to gain insight into the development of the intestinal microbiota of healthy infants and infants who develop allergy in early life, and identify potential microbiota biomarkers of later allergic disease. Using a case-control design in a Chinese sub-cohort of a Singaporean birth cohort (GUSTO), we utilised 16S rRNA gene sequencing to assess intestinal microbial composition and diversity of 21 allergic and 18 healthy infants at 3 weeks, 3 months and 6 months of age, and correlated the microbiota with allergy at ages 18 and 36 months. Pronounced differences in intestinal microbiota composition between allergic and healthy infants were observed at 3 months of age. The intestine of healthy infants was colonised with higher abundance of commensal Bifidobacterium. Conversely, Klebsiella, an opportunistic pathogen, was significantly enriched in the allergic infants. Interestingly, infants with a high Klebsiella/Bifidobacterium (K/B) ratio (above the population median K/B ratio) at age 3 months had an odds ratio of developing allergy by 3 years of age of 9.00 (95% confidence interval 1.46-55.50) compared to those with low K/B ratio. This study demonstrated a relationship between the ratio of genera Klebsiella and Bifidobacterium during early infancy and development of paediatric allergy in childhood. Our study postulates that an elevated K/B ratio in early infancy could be a potential indicator of an increased risk of allergy development. This line of research might enable future intervention strategies in early life to prevent or treat allergy. Our study provides new insights into microbial signatures associated with childhood allergy, in particular, suggests that an elevated K/B ratio could be a potential early-life microbiota biomarker of allergic disease.

Does the maternal vaginal microbiota play a role in seeding the microbiota of neonatal gut and nose?

The acquisition and early maturation of infant microbiota is not well understood despite its likely influence on later health. We investigated the contribution of the maternal microbiota to the microbiota of infant gut and nose in the context of mode of delivery and feeding. Using 16S rRNA sequencing and specific qPCR, we profiled microbiota of 42 mother-infant pairs from the GUSTO birth cohort, at body sites including maternal vagina, rectum and skin; and infant stool and nose. In our study, overlap between maternal vaginal microbiota and infant faecal microbiota was minimal, while the similarity between maternal rectal microbiota and infant microbiota was more pronounced. However, an infant's nasal and gut microbiota were no more similar to that of its own mother, than to that of unrelated mothers. These findings were independent of delivery mode. We conclude that the transfer of maternal vaginal microbes play a minor role in seeding infant stool microbiota. Transfer of maternal rectal microbiota could play a larger role in seeding infant stool microbiota, but approaches other than the generally used analyses of community similarity measures are likely to be needed to quantify bacterial transmission. We confirmed the clear difference between microbiota of infants born by Caesarean section compared to vaginally delivered infants and the impact of feeding mode on infant gut microbiota. Only vaginally delivered, fully breastfed infants had gut microbiota dominated by Bifidobacteria. Our data suggest that reduced transfer of maternal vaginal microbial is not the main mechanism underlying the differential infant microbiota composition associated with Caesarean delivery. The sources of a large proportion of infant microbiota could not be identified in maternal microbiota, and the sources of seeding of infant gut and nasal microbiota remain to be elucidated.

Postnatal height and adiposity gain, childhood blood pressure and prehypertension risk in an Asian birth cohort.

OBJECTIVE: There have been hypotheses that early life adiposity gain may influence blood pressure (BP) later in life. We examined associations between timing of height, body mass index (BMI) and adiposity gains in early life with BP at 48 months in an Asian pregnancy-birth cohort. METHODS: In 719 children, velocities for height, BMI and abdominal circumference (AC) were calculated at five intervals [0-3, 3-12, 12-24, 24-36 and 36-48 months]. Triceps (TS) and subscapular skinfold (SS) velocities were calculated between 0-18, 18-36 and 36-48 months. Systolic (SBP) and diastolic blood pressure (DBP) was measured at 48 months. Growth velocities at later periods were adjusted for growth velocities in preceding intervals, as well as measurements at birth. RESULTS: After adjusting for confounders and child height at BP measurement, each unit z-score gain in BMI, AC, TS and SS velocities at 36-48 months were associated with 2.3 (95% CI:1.6, 3.1), 2.1 (1.3, 2.8), 1.4 (0.6, 2.2) and 1.8 (1, 2.6) mmHg higher SBP respectively, and 0.9 (0.4, 1.4), 0.9 (0.4, 1.3), 0.6 (0.1, 1.1) and 0.8 (0.3, 1.3) mmHg higher DBP respectively. BMI and adiposity velocities (AC, TS or SS) at various intervals in the first 36 months however, were not associated with BP. Faster BMI, AC, TS and SS velocities, but not height, at 36-48 months were associated with 0.22 (0.15, 0.29), 0.17 (0.10, 0.24), 0.11 (0.04, 0.19) and 0.15 (0.08, 0.23) units higher SBP z-score respectively, and OR=1.46 (95% CI: 1.13-1.90), 1.49 (1.17-1.92), 1.45 (1.09-1.92) and 1.43 (1.09, 1.88) times higher risk of prehypertension/hypertension respectively at 48 months. CONCLUSIONS: Our results indicated that faster BMI and adiposity (AC, TS or SS) velocities only at the preceding interval before 48 months (36-48 months), but not at earlier intervals in the first 36 months, are predictive of BP and prehypertension/hypertension at 48 months.

Sodium bicarbonate does not prevent postoperative acute kidney injury after off-pump coronary revascularization: a double-blinded randomized controlled trial.

BACKGROUND: Acute kidney injury (AKI) is a common morbidity after off-pump coronary revascularization. We investigated whether perioperative administration of sodium bicarbonate, which might reduce renal injury by alleviating oxidative stress in renal tubules, prevents postoperative AKI in off-pump coronary revascularization patients having renal risk factors. METHODS: Patients (n=162) having at least one of the following AKI risk factors were enrolled: (i) age >70 yr; (ii) diabetes mellitus; (iii) chronic renal disease; (iv) congestive heart failure or left ventricular ejection fraction <35%; and (v) reoperation or emergency. Patients were evenly randomized to receive either sodium bicarbonate (0.5 mmol kg-1 for 1 h upon induction of anaesthesia followed by 0.15 mmol kg-1 h-1 for 23 h) or 0.9% saline. Acute kidney injury within 48 h after surgery was assessed using the Acute Kidney Injury Network criteria. RESULTS: The incidences of AKI were 21 and 26% in the bicarbonate and control groups, respectively (P=0.458). Serially measured serum creatinine concentrations and perioperative fluid balance were also comparable between the groups. The length of postoperative hospitalization and incidence of morbidity end points were similar between the groups, whereas significantly more patients in the bicarbonate group required prolonged mechanical ventilation (>24 h) relative to the control group (20 vs 6, P=0.003). CONCLUSIONS: Perioperative sodium bicarbonate administration did not decrease the incidence of AKI after off-pump coronary revascularization in high-risk patients and might even be associated with a need for prolonged ventilatory care. CLINICAL TRIAL REGISTRATION: NCT01840241.

Tobacco smoke exposure and respiratory morbidity in young children.

OBJECTIVE: Secondhand smoke exposure is a potentially preventable cause of significant respiratory morbidity in young children. Our study aimed to quantify respiratory morbidity in young children exposed to secondhand smoke to identify potentially modifiable factors. MATERIALS AND METHODS: This study was embedded in a prospective birth cohort study of pregnant women and their children from fetal life onwards in Singapore (Growing Up in Singapore Towards healthy Outcomes, or GUSTO). Data on prenatal, antenatal and postnatal active and secondhand tobacco smoke exposure were obtained by an investigator-administered questionnaire for the periods before pregnancy, at 26-28 weeks' gestation and 24 months after delivery. Data on respiratory morbidity (wheezing episodes, croupy cough, nebuliser use, snoring) and other morbidity (fever, hospitalisation, ear infection) of the child was collected at week 3 and at months 3, 6, 9, 12, 15, 18 and 24 after delivery. Information on parental atopy and potential confounders such as socioeconomic status and maternal educational level were also obtained. Statistical analysis of the data was performed to quantify any significant differences in incidence of respiratory morbidity in children exposed to tobacco smoke in utero and postdelivery, compared with those in smoke-free environments. RESULTS: Women who smoked regularly prior to pregnancy comprised 12.5% (n=155) of the study population; this number fell to 2.3% (n=29) during pregnancy. Mothers exposed to secondhand smoke in the household before pregnancy comprised 35.7% of the study population (n=441) and 31.5% (n=389) were exposed during pregnancy. Postnatally, the prevalence of secondhand tobacco smoke exposure from birth to 2 years of age was 29% (n=359). Participants of Malay ethnicity (p<0.001), mothers with no or primary level education (p<0.001) and mothers with low socioeconomic status (p<0.001) had the highest exposure to tobacco smoke. Offspring secondhand smoke exposure at home by 12 months and by 24 months of age was associated with an increase in hospital admissions due to respiratory disease (RR 1.89, 95% CI 1.02 to 3.50, p=0.04 by 12 months and RR 1.64, 95% CI 1.05 to 2.55, p=0.03 by 24 months) as well as all-cause hospitalisation (RR 1.57, 95% CI 1.14 to 2.17, p=0.01 by 12 months and RR 1.49, 95% CI 1.17 to 1.90, p=0.001 by 24 months), adjusting for parental atopy and child atopic dermatitis. Participants exposed to secondhand smoke by 12 months postdelivery had a significantly increased risk of having at least one wheezing episode (RR 1.71, 95% CI 1.38 to 2.11, p<0.001). CONCLUSIONS: Secondhand smoke exposure during the prenatal and postnatal periods is associated with increased respiratory morbidity in children. Opportunistic screening and targeted smoking cessation counselling for parents at child hospital admissions and well-child outpatient visits, as well as preconception smoking cessation counselling for future pregnancies, may be beneficial to protect the child from negative health impacts.

MC3R gene polymorphisms are associated with early childhood adiposity gain and infant appetite in an Asian population.

BACKGROUND: Polymorphic variants within human melanocortin-3 receptor gene (MC3R) gene have been associated with obesity. However, its influence on infancy and early childhood adiposity has not been reported before. OBJECTIVES: We assessed associations between genotype at polymorphic sites within MC3R with early childhood adiposity and interaction with early childhood appetitive traits. METHODS: We studied 1090 singletons in an Asian mother-offspring cohort genotyped for MC3R and in a subgroup (n = 422) who had completed Child Eating Behaviour Questionnaires (CEBQ) at 12 months. Children were followed from birth to 48 months, and up to 10 measurements of body mass index and five measures of triceps and subscapular skin-folds were obtained. RESULTS: Independent of potential confounders, each additional MC3R minor allele copy was associated with greater body mass index standard deviation score [B{95% confidence interval}: 0.004 units/month {0.001,0.007}; p = 0.007], triceps [0.009 mm/month {0.001,0.02}; p = 0.021] and subscapular skin-fold [0.008 mm/month {0.002,0.01}; p = 0.011] gain velocity in the first 48 months. Each additional MC3R minor allele copy was also associated with increased odds of overweight [odds ratio {95% confidence interval}: 1.48{1.17-1.88}] and obesity [1.58{1.10-2.28}] in the first 48 months. Every additional copy of MC3R minor allele was positively associated with 'slowness-in-eating' appetitive trait [0.24{0.06,0.39}, p = 0.006]; however, the relationship between 'slowness-in-eating' with adiposity gain was not statistically significant. CONCLUSIONS: Our findings support the role of MC3R genetic variants in adiposity gain during early childhood.

Is reduced susceptibility to disinfectants and antiseptics a risk in healthcare settings? A point/counterpoint review.

BACKGROUND: Given the breadth and depth of antiseptic use, it is surprising how few large-scale studies have been undertaken into the consequences of their use, particularly in clinical practice. Depending on your point of view, this may either reflect an assurance that reduced susceptibility to antiseptics, and notably whether this confers cross-resistance to systemically administered antimicrobial agents, is not an issue of concern, or relative ignorance about the potential threat. AIM: This point/counterpoint review offers a differentiated perspective and possible answers to the question, 'Should we be worried about reduced susceptibility to disinfectants and antiseptics in healthcare settings?'. METHODS: This topic was the subject of a debate by MHW (point) and SH (counterpoint) during the SHEA Spring Conference 2013: Advancing healthcare epidemiology and the role of the environment, held in Atlanta, GA, USA on 4(th) May 2013. This review is a general representation of the main themes presented during the debate, rather than a systematic review of the literature. FINDINGS: There are examples of reduced susceptibility to antiseptics in clinical practice; however, to date, there is no strong evidence that reduced susceptibility to antiseptics is a major clinical problem. Given the growing number of potential indications for use of biocidal active ingredients, the potential for emergence of reduced susceptibility remains a concern. CONCLUSIONS: Changes in the clinical use of antiseptics should be matched with surveillance studies to understand whether there are unintended microbiological or clinical consequences, including the selection of bacterial strains that can survive exposure to antiseptics.

Body fat in Singaporean infants: development of body fat prediction equations in Asian newborns.

BACKGROUND/OBJECTIVES: Prediction equations are commonly used to estimate body fat from anthropometric measurements, but are population specific. We aimed to establish and validate a body composition prediction formula for Asian newborns, and compared the performance of this formula with that of a published equation. SUBJECTS/METHODS: Among 262 neonates (174 from day 0, 88 from days 1-3 post delivery) from a prospective cohort study, body composition was measured using air-displacement plethysmography (PEA POD), with standard anthropometric measurements, including triceps and subscapular skinfolds. Using fat mass measurement by PEA POD as a reference, stepwise linear regression was utilized to develop a prediction equation in a randomly selected subgroup of 62 infants measured on days 1-3, which was then validated in another subgroup of 200 infants measured on days 0-3. RESULTS: Regression analyses revealed subscapular skinfolds, weight, gender and gestational age were significant predictors of neonatal fat mass, explaining 81.1% of the variance, but not triceps skinfold or ethnicity. By Bland-Altman analyses, our prediction equation revealed a non-significant bias with limits of agreement (LOA) similar to those of a published equation for infants measured on days 1-3 (95% LOA: (-0.25, 0.26) kg vs (-0.23, 0.21) kg) and on day 0 (95% LOA: (-0.19, 0.17) kg vs (-0.17, 0.18) kg). The published equation, however, exhibited a systematic bias in our sample. CONCLUSIONS: Our equation requires only one skinfold site measurement, which can significantly reduce time and effort. It does not require the input of ethnicity and, thus, aid its application to other Asian neonatal populations.

Motor neuron degeneration in a mouse model of seipinopathy.

Heterozygosity for missense mutations (N88S/S90L) in BSCL2 (Berardinelli-Seip congenital lipodystrophy type 2)/Seipin is associated with a broad spectrum of motoneuron diseases. To understand the underlying mechanisms how the mutations lead to motor neuropathy, we generated transgenic mice with neuron-specific expression of wild-type (tgWT) or N88S/S90L mutant (tgMT) human Seipin. Transgenes led to the broad expression of WT or mutant Seipin in the brain and spinal cord. TgMT, but not tgWT, mice exhibited late-onset altered locomotor activities and gait abnormalities that recapitulate symptoms of seipinopathy patients. We found loss of alpha motor neurons in tgMT spinal cord. Mild endoreticular stress was present in both tgMT and tgWT neurons; however, only tgMT mice exhibited protein aggregates and disrupted Golgi apparatus. Furthermore, autophagosomes were significantly increased, along with elevated light chain 3 (LC3)-II level in tgMT spinal cord, consistent with the activation of autophagy pathway in response to mutant Seipin expression and protein aggregation. These results suggest that induction of autophagy pathway is involved in the cellular response to mutant Seipin in seipinopathy and that motoneuron loss is a key pathogenic process underlying the development of locomotor abnormalities.

Rural living and health-related quality of life in Australians with Parkinson's disease.

INTRODUCTION: The motor and non-motor symptoms associated with idiopathic Parkinson's disease (PD) may compromise the health-related quality of life (HRQOL) of some individuals living with this debilitating condition. Although growing evidence suggests that PD may be more prevalent in rural communities, there is little information about the life quality of these individuals. This study examines whether HRQOL ratings vary in relation to rural and metropolitan life settings. METHODS: An analytic cross-sectional study was conducted to compare the HRQOL of two separate samples of people with PD living in metropolitan Melbourne and rural Victoria. The metropolitan sample consisted of 210 individuals who had participated in the baseline assessment for an existing clinical trial. The rural sample comprised 24 participants who attended community-based rehabilitation programs and support groups in rural Victoria. Health-related quality of life was quantified using the Parkinson's Disease Questionnaire-39 (PDQ-39). RESULTS: The HRQOL of participants in rural Australia differed from individuals living in a large metropolitan city (p=0.025). Participants in rural Australia reported worse overall HRQOL, after controlling for differences in disease duration. Their overall HRQOL was lower than for city dwellers. Rural living was also found to be a significant negative predictor of HRQOL (ß=0.14; 95% CI -1.27 to -0.08; p=0.027). CONCLUSION: The findings of this study suggest that some people with PD living in rural Victoria perceive their HRQOL to be relatively poor. In order to minimise the debilitating consequences of this disease, further studies examining the factors that may contribute to the HRQOL of individuals living in rural and remote areas are required.

Smooth emergence in men undergoing nasal surgery: the effect site concentration of remifentanil for preventing cough after sevoflurane-balanced anaesthesia.

BACKGROUND: Suppression of cough during emergence after nasal surgery is practical to avoid bleeding from the surgical site. Previously recommended effect-site concentration of remifentanil for preventing cough during emergence is restricted to female patients undergoing thyroid surgery, so we evaluated effective effect-site concentration of remifentanil for preventing cough during emergence for men undergoing nasal surgery. METHODS: Twenty-four American Society of Anesthesiologists (ASA) physical status I or II, between the ages of 18 and 60 years old, non-smoker male patients undergoing nasal surgery were enrolled in this study. The effective effect-site concentration for 50% of patients (EC(50) ) and and that for 95% of patients (EC(95) ) of remifentanil for preventing cough were determined by Dixon's up-and-down method and by isotonic regression method with a bootstrapping approach. Haemodynamic variables were compared in patients with cough and without cough during emergence. RESULTS: The EC(50) of remifentanil for preventing cough during emergence by Dixon's method was 2.17 ng/ml [standard deviation (SD) 0.38]. The estimated EC(50) and EC(95) of remifentanil using isotonic regression model with a bootstrapping approach were 2.35 ng/ml [95% confidence interval (CI) 1.89-2.66] and 2.94 ng/ml (95% CI 2.83-2.97), respectively. Mean arterial pressure and heart rate were significantly higher in patients with cough during emergence. Three out of 13 patients that received more than 2.5 ng/ml of remifentanil experienced a brief episode of bradypnea. CONCLUSIONS: The EC(95) of remifentanil for preventing cough in men after nasal surgery is 2.94 ng/ml. Remifentanil target-controlled infusion with established effect-site concentration could suppress cough in men during emergence from sevoflurane anaesthesia after nasal surgery, though reversible respiratory depression might arise at high effect-site concentration of remifentanil.

The mosaic of surface charge in contact electrification.

When dielectric materials are brought into contact and then separated, they develop static electricity. For centuries, it has been assumed that such contact charging derives from the spatially homogeneous material properties (along the material's surface) and that within a given pair of materials, one charges uniformly positively and the other negatively. We demonstrate that this picture of contact charging is incorrect. Whereas each contact-electrified piece develops a net charge of either positive or negative polarity, each surface supports a random "mosaic" of oppositely charged regions of nanoscopic dimensions. These mosaics of surface charge have the same topological characteristics for different types of electrified dielectrics and accommodate significantly more charge per unit area than previously thought.

Compliance with topical nasal medication--an evaluation in children with rhinitis.

It is our impression that children with rhinitis often dislike or struggle with the administration of topical nasal sprays and drops. This study aims to investigate children's acceptance of topical nasal sprays/drops, and to identify patient factors that may affect their acceptance. An interview (by WYZI) questionnaire survey was carried out on parents/guardians of children aged 1-15 with rhinitis, where information on the diagnosis and treatment, patients' use and responses to these medications, and their preferred treatment routes were collected. Two hundred questionnaires were completed, of which 194 were valid for analysis. The mean age of patients was 7.54 yr; male to female ratio was 1:1.6, and Chinese made up the majority (62.4%). About one quarter (24.7%) of children disliked the use of topical nasal sprays/drops sufficiently to affect compliance with the medication. Furthermore, of those who could indicate their preferred route of drug administration (n = 75), 73% indicated a preference for oral medication, while only 11% preferred the nasal route. Topical nasal sprays/drops were more acceptable in older children (7-15 yr) compared to the younger ones (1-6 yr) (OR = 2.383, CI 1.223-4.644). The acceptance of nasal sprays/drops was not associated with gender, ethnic group, concurrent use by other family members, length and amount of usage, and the response to therapy. A substantial proportion of children prescribed topical nasal sprays/drops did not find it acceptable. Age played a significant factor to the acceptance of the use of topical nasal sprays/drops.