A Delphi panel to build consensus on assessing disease severity and disease progression in adult patients with hypophosphatasia in the United States.

BACKGROUND: Hypophosphatasia (HPP) is an inborn error of metabolism with a variable presentation. We conducted a modified Delphi panel to obtain expert consensus on knowledge gaps regarding disease severity and progression in adult patients with HPP. METHODS: Healthcare professionals (HCPs) with experience managing adult patients with HPP were recruited to participate in a 3-round Delphi panel (round 1: paper survey and 1:1 interview; rounds 2-3: email survey). Panelists rated the extent of their agreement with statements about disease severity and progression in adult patients with HPP. Consensus was defined as ≥ 80% agreement. RESULTS: Ten HCPs completed round 1; nine completed rounds 2 and 3. Consensus was reached on 46/120 statements derived from steering committee input. Disease severity markers in adult patients with HPP can be bone-related (recurrent/poorly healing fractures, pseudo-fractures, metatarsal fractures, osteomalacia) or involve dentition or physiologic/functional manifestations (use of mobility devices/home modifications, abnormal gait, pain). Disease progression markers can include recurrent/poorly healing low-trauma fractures, development of ectopic calcifications, and/or impairment of functional activity. Panelists supported the development of a tool to help assess disease severity in the clinic and track changes in severity over time. Panelists also highlighted the role of a multidisciplinary team, centers with expertise, and the need to refer patients when disease severity is not clear. CONCLUSIONS: These statements regarding disease severity, progression, and assessment methods address some knowledge gaps in adult patients with HPP and may be helpful for treating HCPs, although the small sample size affects the ability to generalize the healthcare provider experience.

Dietary diversity scores, nutrient intakes and biomarkers vitamin B12, folate and Hb in rural youth from the Pune Maternal Nutrition Study.

Hidden hunger is widespread in India. Individual dietary diversity score (IDDS) is a measure of the nutrient adequacy of the diet. The FAO has set guidelines for the measurement of dietary diversity: the IDDS and the minimum dietary diversity score for women (MDD-W) to assess nutritional deficiency, but validation against nutritional biomarkers is required. Using available data among rural youth (17 years) from the Pune Maternal Nutrition Study, the validity of DDS was assessed to measure deficiencies of vitamin B12, folate and Hb. Of the 355 boys and 305 girls, 19 % were classified as underweight, 57 % as vitamin B12 deficient (<150 pmol/l) and 22 % as anaemic (<120/130 g/l). Cereals, legumes and 'other-vegetables' were the most frequently consumed foods. More boys than girls consumed milk, flesh, eggs and micronutrient-dense foods. Median IDDS of 4 (interquartile range (IQR) 3-4) and MDD-W of 6 (IQR 5-7) were low. Youth with vitamin B12 deficiency had a higher likelihood of an IDDS ≤ 4 (1·89; 95 % CI 1·24, 2·87) or an MDD-W ≤ 5 (1·40; 95 % CI 1·02, 1·94). Youth with anaemia were more likely to have an IDDS ≤ 4 (1·76; 95 % CI 1·01, 3·14) adjusted for socio-economic scores, BMI, energy intake and sex. Folate deficiency was low (3 %) and was not associated with either score. Youth with lowest plasma vitamin B12 and Hb infrequently or never consumed dairy products/non-vegetarian foods. These rural Indian youth were underweight, had low DDS and consumed foods low in good-quality proteins and micronutrients. Associations of DDS with circulating micronutrients indicate that DDS is a valid measure to predict vitamin B12 deficiency and anaemia.

Timing of Atlantic salmon Salmo salar smolt migration predicts successful passage through a reservoir.

Around 30% of Atlantic salmon Salmo salar smolts successfully survived passage through Loch Meig, a reservoir in the north of Scotland, en route to the sea. However, this survival rate was in turn dependent on the timing of migration, with the earliest migrants in the spring having the best chance of survival. This could have implication for fisheries management, since the estimation of smolt downstream survival may be influenced by which time period of the smolt run is analysed.

Cohort profile: Pacific Islands Families (PIF) growth study, Auckland, New Zealand.

PURPOSE: This article profiles a birth cohort of Pacific children participating in an observational prospective study and describes the study protocol used at ages 14-15 years to investigate how food and activity patterns, metabolic risk and family and built environment are related to rates of physical growth of Pacific children. PARTICIPANTS: From 2000 to 2015, the Pacific Islands Families Study has followed, from birth, the growth and development of over 1000 Pacific children born in Auckland, New Zealand. In 2014, 931 (66%) of the original cohort had field measures of body composition, blood pressure and glycated haemoglobin. A nested subsample (n=204) was drawn by randomly selecting 10 males and 10 females from each decile of body weight. These participants had measurement of body composition by dual-energy X-ray absorptiometry, food frequency, 6 min walk test and accelerometer-determined physical activity and sedentary behaviours, and blood biomarkers for metabolic disease such as diabetes. Built environment variables were generated from individual addresses. FINDINGS TO DATE: Compared to the Centres for Disease Control and Prevention (CDC) reference population with mean SD scores (SDS) of 0, this cohort of 931 14-year-olds was taller, weighed more and had a higher body mass index (BMI) (mean SDS height >0.6, weight >1.6 and BMI >1.4). 7 of 10 youth were overweight or obese. The nested-sampling frame achieved an even distribution by body weight. FUTURE PLANS: Cross-sectional relationships between body size, fatness and growth rate, food patterns, activity patterns, pubertal development, risks for diabetes and hypertension and the family and wider environment will be examined. In addition, analyses will investigate relationships with data collected earlier in the life course and measures of the cohort in the future. Understanding past and present influences on child growth and health will inform timely interventions to optimise future health and reduce inequalities for Pacific people.

Growing skull fracture in a red-tailed hawk (Buteo jamaicensis).

Growing skull fractures have been reported in humans for many years, usually resulting from injury to the soft skull during the rapid growth period of an infant's life. Nestling raptors have thin, fragile skulls, a rapid growth rate, and compete aggressively for food items. Skull trauma may occur, which may lead to the development of a growing skull fracture. Growing skull fractures may be under-diagnosed in raptor rehabilitation facilities that do not have access to advanced technologic equipment. Three-dimensional (3-D) computed tomography was used to diagnose a growing skull fracture in a red-tailed hawk (Buteo jamaicensis). The lesion was surgically repaired and the animal was eventually returned to the wild. This is the first report of a growing skull fracture in an animal. In this case, 3-D computed topographic imaging was utilized to diagnose a growing skull fracture in a red-tailed hawk, surgical repair was performed, and the bird recovered completely and was ultimately released.

Preventing vitamin B12 deficiency in South Asian women of childbearing age: a randomised controlled trial comparing an oral vitamin B12 supplement with B12 dietary advice.

BACKGROUND/OBJECTIVES: To examine the effectiveness, acceptability and sustainability of interventions to reduce vitamin B12 (B12) deficiency in South Asian women before conception. SUBJECTS/METHODS: A 6-month randomised controlled trial conducted in Auckland, New Zealand. Participants (62 South Asian women, 18-50 years old) were stratified by dietary practices, then randomised to three treatment groups: B12 Supplement (oral cyanocobalamin 6 µg/day) (n=21), Placebo (n=21), or B12 Dietary Advice (n=20). Primary outcome measures were changes in B12 biomarkers (serum B12 and holotranscobalamin (holoTC)) at 6 months. Dietary B12 intake was estimated from a B12 food-specific frequency questionnaire (B12FFQ). Intention-to-treat analysis was applied using 'last observation carried forward' method. Changes in B12 biomarkers by treatment were compared using analysis of variance. Pearson's correlations tested relationships between dietary B12 intake and B12 biomarkers. RESULTS: At baseline, 48% of women tested as insufficient or deficient in serum B12 (<222 pmol/l) and 51% as insufficient or deficient in holoTC (<45 pmol/l). B12 status was moderately correlated with dietary B12 intake (r=0.5, 95% confidence interval (CI) (0.3-0.7)) and 44% of women reported insufficient dietary intake (<2.4 µg/day). B12 Supplement was the only treatment group to record a significant increase in B12 biomarkers over 6 months: serum B12 by 30% (95% CI (11-48%)) and holoTC by 42% (12-72%). CONCLUSIONS: The prevalence of B12 insufficiency among Auckland South Asian women is high and moderately correlated with inadequate intake of foods that contain B12. Cyanocobalamin supplementation (6 µg/day) was associated with improved B12 biomarkers, with a potential to improve preconception B12 status in South Asian women.

Vitamin B12: one carbon metabolism, fetal growth and programming for chronic disease.

This review brings together human and animal studies and reviews that examine the possible role of maternal vitamin B12 (B12) on fetal growth and its programming for susceptibility to chronic disease. A selective literature review was undertaken to identify studies and reviews that investigate these issues, particularly in the context of a vegetarian diet that may be low in B12 and protein and high in carbohydrate. Evidence is accumulating that maternal B12 status influences fetal growth and development. Low maternal vitamin B12 status and protein intake are associated with increased risk of neural tube defect, low lean mass and excess adiposity, increased insulin resistance, impaired neurodevelopment and altered risk of cancer in the offspring. Vitamin B12 is a key nutrient associated with one carbon metabolic pathways related to substrate metabolism, synthesis and stability of nucleic acids and methylation of DNA which regulates gene expression. Understanding of factors regulating maternal-fetal one carbon metabolism and its role in fetal programming of non communicable diseases could help design effective interventions, starting with maternal nutrition before conception.

Overall care cost comparison between robotic and laparoscopic surgery for endometrial and cervical cancer.

OBJECTIVE: The aim of our medico-economic study was to compare robotic surgery cost with conventional laparoscopic cost in endometrial and cervical cancer. STUDY DESIGN: Our study included laparoscopic and robot-assisted procedures (radical hysterectomies and lymphadenectomies) for endometrial or cervical cancer ever since first using the Da Vinci® in 2008 within a hospital setting. In the hospital perspective, direct costs were determined by examining the overall medical pathway for each type of intervention. Actual costs were calculated for 27 conventional laparoscopic procedures and for 30 robot-assisted procedures including initial cost of the robot and its maintenance. We estimated the complete medical "overall care" costs by adding the costs of consultations, surgery and post-operative hospital stay to the costs of any eventual emergency consultation and/or hospitalisation within the two months that followed surgery. A sensitivity analysis was performed to evaluate the effects of variable modulations. RESULTS: For endometrial cancer, surgical procedure cost for robotic-assisted surgery was €7402 compared to €2733 for conventional laparoscopic surgery. When considering overall medical care, the patient treatment average cost was €6666 for the laparoscopic group (with an average length of stay of 5.27 days) as compared to €10,816 for robotic group (with an average hospital stay of 4.60 days), p=0.39. For cervical cancer, average surgical cost with robotic-assisted surgery was €8501 compared to conventional laparoscopic surgery at €3239. For cervical cancer, overall care average cost was €7803 for the laparoscopic group (with an average length of stay of 5.83 days) as compared to €12,211 for the robotic group (with an average hospital stay of 4.70 days) p=0.07. Sensitivity analysis results confirmed the cost overrun with the use of robotic assisted surgery. CONCLUSIONS: Conventional laparoscopy was less expensive in our institution than robotic-assisted surgery for the surgery of endometrial (1:2.7) and cervical (1:2.6) cancers. When considering overall medical care, the use of robotic-assisted surgery was found to be 1.6 times more expensive than conventional surgery.

Enzogenol for cognitive functioning in traumatic brain injury: a pilot placebo-controlled RCT.

BACKGROUND AND PURPOSE: Enzogenol, a flavonoid-rich extract from Pinus radiata bark with antioxidant and anti-inflammatory properties has been shown to improve working memory in healthy adults. In traumatic brain injury (TBI), oxidation and inflammation have been linked to poorer cognitive outcomes. Hence, this phase II, randomized controlled trial investigated safety, compliance and efficacy of Enzogenol for improving cognitive functioning in people following mild TBI. METHODS: Sixty adults, who sustained a mild TBI, 3-12 months prior to recruitment, and who were experiencing persistent cognitive difficulties [Cognitive Failures Questionnaire (CFQ) score > 38], were randomized to receive Enzogenol (1000 mg/day) or matching placebo for 6 weeks. Subsequently, all participants received Enzogenol for a further 6 weeks, followed by placebo for 4 weeks. Compliance, side-effects, cognitive failures, working and episodic memory, post-concussive symptoms and mood were assessed at baseline, 6, 12 and 16 weeks. Simultaneous estimation of treatment effect and breakpoint was effected, with confidence intervals (CIs) obtained through a treatment-placebo balance-preserving bootstrap procedure. RESULTS: Enzogenol was found to be safe and well tolerated. Trend and breakpoint analyses showed a significant reduction in cognitive failures after 6 weeks [mean CFQ score, 95% CI, Enzogenol versus placebo -6.9 (-10.8 to -4.1)]. Improvements in the frequency of self-reported cognitive failures were estimated to continue until week 11 before stabilizing. Other outcome measures showed some positive trends but no significant treatment effects. CONCLUSIONS: Enzogenol supplementation is safe and well tolerated in people after mild TBI, and may improve cognitive functioning in this patient population. This study provides Class IIB evidence that Enzogenol is well tolerated and may reduce self-perceived cognitive failures in patients 3-12 months post-mild TBI.

Water: neglected, unappreciated and under researched.

Water, an essential nutrient, is often ignored in reports of dietary surveys and nutrition. Although it is ubiquitous in foods and beverages, the attention is often focused on the minerals or calorific values of the fluids imbibed rather than the water per se. Water is often taken for granted by many in Western countries due to its abundant availability through water systems. In developing countries, however, water and sanitation raise significant problems. This review overviews (i) the global perspective of the potable water supply, (ii) human rights and water, (iii) dietary guidelines and sources of water and (iv) the physiology of water balance. Gaps in knowledge and understanding around hydration and water requirements are also discussed. Nutritionists are urged to look at the bigger picture of the global water supply and to use good judgement and common sense when advising on water requirements.

Bioimpedance prediction of fat-free mass from dual-energy X-ray absorptiometry in a multi-ethnic group of 2-year-old children.

BACKGROUND/OBJECTIVES: Bioimpedance analysis (BIA) is a simple, convenient and widely used tool for the measurement of body composition in population surveys and surveillance. Prediction equations based on BIA applicable to preschool children are available but are based on total body water estimation and have not been developed across multiple ethnic groups. Our aim was to develop a BIA-based equation in a multi-ethnic sample of 2-year old using fat-free mass (FFM) from dual-energy X-ray absorptiometry (DXA) as criterion measure. SUBJECTS/METHODS: Single-frequency hand-to-foot BIA (model BIM4, Impedimed) and whole-body DXA measurements were carried out in 77 (35 boys, 42 girls; 27 European, 20 Polynesian, 30 Asian and other) healthy preschool children (age range 22-38 months). Body mass index s.d. scores were 0.41 ± 1.23 for boys and 0.61 ± 1.09 for girls. The performance of published equations applicable to this age group was assessed. The predicted residual sum of squares method was used to develop and cross-validate a multiple regression equation relating FFM to BIA measures. RESULTS: Published equations performed poorly for estimating FFM in this group of children. The prediction equation developed in all 77 children was: FFM (kg)=0.367 height(cm)(2)/resistance+0.188 weight (kg)+0.077 height (cm)+0.273 sex (male=1, female=0)-2.490, R(2)=0.89, standard error of estimate=0.50 kg. Ethnicity and age did not add significantly to the model. CONCLUSIONS: We have developed an equation that may have application for prediction of FFM in 2-3-year-old children, which does not require determination of hydration factors. Further work should be carried out using DXA scanning to extend the applicable age range.

Implantation of a titanium partial limb prosthesis in a white-naped crane (Grus vipio).

A female white-naped crane (Grus vipio) was presented with an open, oblique fracture of the distal right tarsometatarsus and concomitant vascular and nerve damage. Conventional fracture fixation repairs failed, which led to implantation of a custom titanium limb prosthesis. After subsequent revisions with 2 different prosthetic devices, limb function was ultimately restored but a later yolk embolism caused a circulatory compromise in the opposite leg, which necessitated euthanasia. Histopathologic results revealed limited ingrowth of bone into the porous coated implant, which indicated that a limb prosthesis may provide salvage for long-legged, heavy-bodied birds with fractures of the tarsometatarsus.

Tracking of body mass indices over 2 years in Maori and European children.

BACKGROUND/OBJECTIVES: In 2002, the prevalence of overweight and obesity, defined by body mass index (BMI), was higher in New Zealand Maori (40%) and Pacific (60%) than in European (24%) children; however, this does not take into account interethnic differences in body composition. This study compared trajectories of anthropometric indices from 2004 to 2006 among 5- and 10-year-old Maori and European children. SUBJECTS/METHODS: In 2004 and then in 2006, 1244 children (639 boys and 605 girls) aged 5 and 10 years had height, weight and fat-free mass (FFM) by bioimpedance measured to derive measures of fat mass (FM), percentage body fat (%BF), FM index (FMI, FM/height(2)), FFM index (FFMI, FFM/height(2)), and s.d. scores for BMI and %BF and BMI categories by International Obesity Task Force criteria. RESULTS: Body composition and growth in Maori children is different from European children. Over 2 years, the BMI and %BF s.d. scores in both 5- and 10-year-old cohorts increased more in Maori children than in European children. The prevalence of overweight and obesity also increased within ethnicity and age group. The relative change of FMI and FFMI differed by age group, gender and ethnicity. In Maori girls, the magnitude of the changes between 10 and 12 years of age was most marked-the major contribution was from an increase in FMI. At 12 years, the mean %BF of Maori girls was 31.7% (95% confidence interval (CI): 30.1 and 33.3) compared with that of European girls (28.0%; 95% CI: 27.0 and 29.0). CONCLUSIONS: FM and FFM measures provide a more appropriate understanding of growth and body composition change in children than BMI, and vary with gender and ethnicity. Thus, FMI and FFMI should be tracked and compared among populations.

Child's homocysteine concentration at 2 years is influenced by pregnancy vitamin B12 and folate status.

Longitudinal studies investigating vitamin B12 and folate status of mothers and their offspring will provide a better understanding of intergenerational nutrition. During pregnancy and 2 years (2y) after delivery, we measured plasma vitamin B12 and folate concentrations in 118 women [aged (mean ± s.d.) 22.9 ± 3.9y] who attended a rural (n = 68) or an urban (n = 50) antenatal clinic in Pune, India. Cord blood vitamin B12 and folate were measured, and when the child was 2y total homocysteine (tHcy) was also measured. Demographic and diet measurements were recorded using standard methods. Pregnancy plasma vitamin B12 concentration at 34 weeks was low [median (25th, 75th), 115 (95, 147) pm]; 75% had low status (<150 pm). Plasma folate was high (mean ± s.d., 33 ± 21 nm); one had a folate concentration <7 pm. Cord plasma vitamin B12 and folate concentrations were higher than and positively associated with maternal concentrations. In stepwise regression, higher child vitamin B12 at 2y was predicted (total R 2 15.7%) by pregnancy vitamin B12 (std ß 0.201, R 2 7.7%), current consumption of cow's milk (std ß 0.194, R 2 3.3%) and whether breast feeding was stopped before 2y (std ß -0.234 R 2 7.2%). Child's 2y tHcy concentration was high (11.4 ± 3.6 µm) and predicted by lower pregnancy vitamin B12 (std ß -0.206, R 2 4.1%), lack of vitamin supplementation (std ß -0.256, R 2 5.6%) in pregnancy and whether currently breastfed (std ß 0.268, R 2 8.4%). Low maternal vitamin B12 status in pregnancy and prolonged breast-feeding results in disturbed one-carbon metabolism in offspring at 2y. Supplementation of women of child-bearing age, particularly during pregnancy and lactation, may improve the homocysteine status of these children.

Vitamin B12 and folate during pregnancy and offspring motor, mental and social development at 2 years of age.

Insufficiency of vitamin B12 (B12) and folate during pregnancy can result in low concentrations in the fetus and have adverse effects on brain development. We investigated the relationship between maternal B12 and folate nutrition during pregnancy and offspring motor, mental and social development at two years of age (2 y). Mothers (n = 123) and their offspring (62 girls, 61 boys) from rural and middle-class urban communities in and around Pune city were followed through pregnancy up to 2 y. Maternal B12 and folate concentrations were measured at 28 and 34 weeks of gestation. At 2 y, the Developmental Assessment Scale for Indian Infants was used to determine motor and mental developmental quotients and the Vineland Social Maturity Scale for the social developmental quotient. Overall, 62% of the mothers had low B12 levels (<150 pmol/l) and one mother was folate deficient during pregnancy. Maternal B12 at 28 and 34 weeks of gestation was associated with offspring B12 at 2 y (r = 0.29, r = 0.32, P < 0.001), but folate was not associated with offspring folate. At 2 y, motor development was associated with maternal folate at 28 and 34 weeks of gestation. Mental and social development quotients were associated positively with head circumference and negatively with birth weight. In addition, pregnancy B12 and folate were positively associated with mental and social development quotients. Maternal B12 and folate during intrauterine life may favorably influence brain development and function. Pregnancy provides a window of opportunity to enhance fetal psychomotor (motor and mental) development.

Prediction of fat-free mass by bioelectrical impedance analysis in older adults from developing countries: a cross-validation study using the deuterium dilution method.

OBJECTIVE: Several limitations of published bioelectrical impedance analysis (BIA) equations have been reported. The aims were to develop in a multiethnic, elderly population a new prediction equation and cross-validate it along with some published BIA equations for estimating fat-free mass using deuterium oxide dilution as the reference method. DESIGN AND SETTING: Cross-sectional study of elderly from five developing countries. METHODS: Total body water (TBW) measured by deuterium dilution was used to determine fat-free mass (FFM) in 383 subjects. Anthropometric and BIA variables were also measured. Only 377 subjects were included for the analysis, randomly divided into development and cross-validation groups after stratified by gender. Stepwise model selection was used to generate the model and Bland Altman analysis was used to test agreement. RESULTS: FFM = 2.95 - 3.89 (Gender) + 0.514 (Ht2/Z) + 0.090 (Waist) + 0.156 (Body weight). The model fit parameters were an R2, total F-Ratio, and the SEE of 0.88, 314.3, and 3.3, respectively. None of the published BIA equations met the criteria for agreement. The new BIA equation underestimated FFM by just 0.3 kg in the cross-validation sample. The mean of the difference between FFM by TBW and the new BIA equation were not significantly different; 95% of the differences were between the limits of agreement of -6.3 to 6.9 kg of FFM. There was no significant association between the mean of the differences and their averages (r= 0.008 and p= 0.2). CONCLUSIONS: This new BIA equation offers a valid option compared with some of the current published BIA equations to estimate FFM in elderly subjects from five developing countries.

Energy intake and expenditure during a 6-day cycling stage race.

Energy intake (EI) and energy expenditure (EE) are relatively easy to measure accurately over short periods in a laboratory setting, but less so during a multi-day competition. Our goal was to measure EI and EE as accurately as possible during a 6-day, 10-stage cycling race. We prepared all meals and supplements, assessed EI (weighed diet-records) and macrontrient intake, total EE (doubly labelled water), resting metabolic rate (respiratory gas exchange), exercise EE (power meters), and body mass. Body composition was measured several days before and after racing (dual x-ray absorptiometry). Body mass remained stable over the course of the race. The mean EI (27.3+/-3.8 MJ/day) nearly matched EE (27.4+/-2.0 MJ/day). The majority (62%) of EE was exercise EE. Macronutrient intake was within or exceeded the recommendations. Lean body mass increased and fat mass decreased in most of our participants. Our study indicates that EI can match high EE with adequate macronutrient intake during multi-day cycle racing and may be facilitated by appropriate foods being available at appropriate times. This optimization of nutritional provision supports positive changes in body composition.