In adolescents with severe and persistent gender dysphoria (GD), gonadotropin releasing hormone analogues (GnRHa) are used from early/middle puberty with the aim of delaying irreversible and unwanted ...pubertal body changes. Evidence of outcomes of pubertal suppression in GD is limited.
We undertook an uncontrolled prospective observational study of GnRHa as monotherapy in 44 12-15 year olds with persistent and severe GD. Prespecified analyses were limited to key outcomes: bone mineral content (BMC) and bone mineral density (BMD); Child Behaviour CheckList (CBCL) total t-score; Youth Self-Report (YSR) total t-score; CBCL and YSR self-harm indices; at 12, 24 and 36 months. Semistructured interviews were conducted on GnRHa.
44 patients had data at 12 months follow-up, 24 at 24 months and 14 at 36 months. All had normal karyotype and endocrinology consistent with birth-registered sex. All achieved suppression of gonadotropins by 6 months. At the end of the study one ceased GnRHa and 43 (98%) elected to start cross-sex hormones. There was no change from baseline in spine BMD at 12 months nor in hip BMD at 24 and 36 months, but at 24 months lumbar spine BMC and BMD were higher than at baseline (BMC +6.0 (95% CI: 4.0, 7.9); BMD +0.05 (0.03, 0.07)). There were no changes from baseline to 12 or 24 months in CBCL or YSR total t-scores or for CBCL or YSR self-harm indices, nor for CBCL total t-score or self-harm index at 36 months. Most participants reported positive or a mixture of positive and negative life changes on GnRHa. Anticipated adverse events were common.
Overall patient experience of changes on GnRHa treatment was positive. We identified no changes in psychological function. Changes in BMD were consistent with suppression of growth. Larger and longer-term prospective studies using a range of designs are needed to more fully quantify the benefits and harms of pubertal suppression in GD.
Holocaust City Cole, Tim
2003, 20131018, 2013-10-18, 20030101
eBook
Drawing from the ideas of critical geography and based on extensive archival research, Cole brilliantly reconstructs the formation of the Jewish ghetto during the Holocaust, focusing primarily on the ...ghetto in Budapest, Hungary--one of the largest created during the war, but rarely examined. Cole maps the city illustrating how spaces--cafes, theaters, bars, bathhouses--became divided in two. Throughout the book, Cole discusses how the creation of this Jewish ghetto, just like the others being built across occupied Europe, tells us a great deal about the nature of Nazism, what life was like under Nazi-occupation, and the role the ghetto actually played in the Final Solution.
Individuals with obesity do not represent a homogeneous group in terms of cardiometabolic risk. Using 3 nationally representative British birth cohorts, we investigated whether the duration of ...obesity was related to heterogeneity in cardiometabolic risk.
We used harmonised body mass index (BMI) and cardiometabolic disease risk factor data from 20,746 participants (49.1% male and 97.2% white British) enrolled in 3 British birth cohort studies: the 1946 National Survey of Health and Development (NSHD), the 1958 National Child Development Study (NCDS), and the 1970 British Cohort Study (BCS70). Within each cohort, individual life course BMI trajectories were created between 10 and 40 years of age, and from these, age of obesity onset, duration spent obese (range 0 to 30 years), and cumulative obesity severity were derived. Obesity duration was examined in relation to a number of cardiometabolic disease risk factors collected in mid-adulthood: systolic (SBP) and diastolic blood pressure (DBP), high-density-lipoprotein cholesterol (HDL-C), and glycated haemoglobin (HbA1c). A greater obesity duration was associated with worse values for all cardiometabolic disease risk factors. The strongest association with obesity duration was for HbA1c: HbA1c levels in those with obesity for <5 years were relatively higher by 5% (95% CI: 4, 6), compared with never obese, increasing to 20% (95% CI: 17, 23) higher in those with obesity for 20 to 30 years. When adjustment was made for obesity severity, the association with obesity duration was largely attenuated for SBP, DBP, and HDL-C. For HbA1c, however, the association with obesity duration persisted, independent of obesity severity. Due to pooling of 3 cohorts and thus the availability of only a limited number harmonised variables across cohorts, our models included adjustment for only a small number of potential confounding variables, meaning there is a possibility of residual confounding.
Given that the obesity epidemic is characterised by a much earlier onset of obesity and consequently a greater lifetime exposure, our findings suggest that health policy recommendations aimed at preventing early obesity onset, and therefore reducing lifetime exposure, may help reduce the risk of diabetes, independently of obesity severity. However, to test the robustness of our observed associations, triangulation of evidence from different epidemiological approaches (e.g., mendelian randomization and negative control studies) should be obtained.
We explored the relationship between growth in tooth root length and the modern human extended period of childhood. Tooth roots provide support to counter chewing forces and so it is advantageous to ...grow roots quickly to allow teeth to erupt into function as early as possible. Growth in tooth root length occurs with a characteristic spurt or peak in rate sometime between tooth crown completion and root apex closure. Here we show that in Pan troglodytes the peak in root growth rate coincides with the period of time teeth are erupting into function. However, the timing of peak root velocity in modern humans occurs earlier than expected and coincides better with estimates for tooth eruption times in Homo erectus. With more time to grow longer roots prior to eruption and smaller teeth that now require less support at the time they come into function, the root growth spurt no longer confers any advantage in modern humans. We suggest that a prolonged life history schedule eventually neutralised this adaptation some time after the appearance of Homo erectus. The root spurt persists in modern humans as an intrinsic marker event that shows selection operated, not primarily on tooth tissue growth, but on the process of tooth eruption. This demonstrates the overarching influence of life history evolution on several aspects of dental development. These new insights into tooth root growth now provide an additional line of enquiry that may contribute to future studies of more recent life history and dietary adaptations within the genus Homo.
Summary
Background
The International Obesity Task Force (IOTF) and World Health Organization (WHO) body mass index (BMI) cut‐offs are widely used to assess child overweight, obesity and thinness ...prevalence, but the two references applied to the same children lead to different prevalence rates.
Objectives
To develop an algorithm to harmonize prevalence rates based on the IOTF and WHO cut‐offs, to make them comparable.
Methods
The cut‐offs are defined as age‐sex‐specific BMI z‐scores, for example, WHO +1 SD for overweight. To convert an age‐sex‐specific prevalence rate based on reference cut‐off A to the corresponding prevalence based on reference cut‐off B, first back‐transform the z‐score cut‐offs zA and zB to age‐sex‐specific BMI cut‐offs, then transform the BMIs to z‐scores zB,A and zA,B using the opposite reference. These z‐scores together define the distance between the two cut‐offs as the z‐score difference dzA,B=12zB−zA+zA,B−zB,A. Prevalence in the target group based on cut‐off A is then transformed to a z‐score, adjusted up or down according to dzA,B and back‐transformed, and this predicts prevalence based on cut‐off B. The algorithm's performance was tested on 74 groups of children from 14 European countries.
Results
The algorithm performed well. The standard deviation (SD) of the difference between pairs of prevalence rates was 6.6% (n = 604), while the residual SD, the difference between observed and predicted prevalence, was 2.3%, meaning that the algorithm explained 88% of the baseline variance.
Conclusions
The algorithm goes some way to addressing the problem of harmonizing overweight and obesity prevalence rates for children aged 2–18.
The aim of the Task Force was to derive continuous prediction equations and their lower limits of normal for spirometric indices, which are applicable globally. Over 160,000 data points from 72 ...centres in 33 countries were shared with the European Respiratory Society Global Lung Function Initiative. Eliminating data that could not be used (mostly missing ethnic group, some outliers) left 97,759 records of healthy nonsmokers (55.3% females) aged 2.5-95 yrs. Lung function data were collated and prediction equations derived using the LMS method, which allows simultaneous modelling of the mean (mu), the coefficient of variation (sigma) and skewness (lambda) of a distribution family. After discarding 23,572 records, mostly because they could not be combined with other ethnic or geographic groups, reference equations were derived for healthy individuals aged 3-95 yrs for Caucasians (n=57,395), African-Americans (n=3,545), and North (n=4,992) and South East Asians (n=8,255). Forced expiratory value in 1 s (FEV(1)) and forced vital capacity (FVC) between ethnic groups differed proportionally from that in Caucasians, such that FEV(1)/FVC remained virtually independent of ethnic group. For individuals not represented by these four groups, or of mixed ethnic origins, a composite equation taken as the average of the above equations is provided to facilitate interpretation until a more appropriate solution is developed. Spirometric prediction equations for the 3-95-age range are now available that include appropriate age-dependent lower limits of normal. They can be applied globally to different ethnic groups. Additional data from the Indian subcontinent and Arabic, Polynesian and Latin American countries, as well as Africa will further improve these equations in the future.
Limited information is available on what constitutes optimal growth in dogs. The primary aim of this study was to develop evidence-based growth standards for dogs, using retrospective analysis of ...bodyweight and age data from >6 million young dogs attending a large corporate network of primary care veterinary hospitals across the USA. Electronic medical records were used to generate bodyweight data from immature client-owned dogs, that were healthy and had remained in ideal body condition throughout the first 3 years of life. Growth centile curves were constructed using Generalised Additive Models for Location, Shape and Scale. Curves were displayed graphically as centile charts covering the age range 12 weeks to 2 years. Over 100 growth charts were modelled, specific to different combinations of breed, sex and neuter status. Neutering before 37 weeks was associated with a slight upward shift in growth trajectory, whilst neutering after 37 weeks was associated with a slight downward shift in growth trajectory. However, these shifts were small in comparison to inter-individual variability amongst dogs, suggesting that separate curves for neutered dogs were not needed. Five bodyweight categories were created to cover breeds up to 40kg, using both visual assessment and hierarchical cluster analysis of breed-specific growth curves. For 20/24 of the individual breed centile curves, agreement with curves for the corresponding bodyweight categories was good. For the remaining 4 breed curves, occasional deviation across centile lines was observed, but overall agreement was acceptable. This suggested that growth could be described using size categories rather than requiring curves for specific breeds. In the current study, a series of evidence-based growth standards have been developed to facilitate charting of bodyweight in healthy dogs. Additional studies are required to validate these standards and create a clinical tool for growth monitoring in pet dogs.
Objective To determine cut offs to define thinness in children and adolescents, based on body mass index at age 18 years.Design International survey of six large nationally representative cross ...sectional studies on growth.Setting Brazil, Great Britain, Hong Kong, the Netherlands, Singapore, and the United States.Subjects 97 876 males and 94 851 females from birth to 25 years.Main outcome measure Body mass index (BMI, weight/height2).Results The World Health Organization defines grade 2 thinness in adults as BMI <17. This same cut off, applied to the six datasets at age 18 years, gave mean BMI close to a z score of −2 and 80% of the median. Thus it matches existing criteria for wasting in children based on weight for height. For each dataset, centile curves were drawn to pass through the cut off of BMI 17 at 18 years. The resulting curves were averaged to provide age and sex specific cut-off points from 2-18 years. Similar cut offs were derived based on BMI 16 and 18.5 at 18 years, together providing definitions of thinness grades 1, 2, and 3 in children and adolescents consistent with the WHO adult definitions.Conclusions The proposed cut-off points should help to provide internationally comparable prevalence rates of thinness in children and adolescents.
Summary
Background
Prevalence rates of child overweight and obesity for a group of children vary depending on the BMI reference and cut‐off used. Previously we developed an algorithm to convert ...prevalence rates based on one reference to those based on another.
Objective
To improve the algorithm by combining information on overweight and obesity prevalence.
Methods
The original algorithm assumed that prevalence according to two different cut‐offs A and B differed by a constant amount dz on the z‐score scale. However the results showed that the z‐score difference tended to be greater in the upper tail of the distribution and was better represented by b×dz, where b was a constant that varied by group. The improved algorithm uses paired prevalence rates of overweight and obesity to estimate b for each group. Prevalence based on cut‐off A is then transformed to a z‐score, adjusted up or down according to b×dz and back‐transformed, and this predicts prevalence based on cut‐off B. The algorithm's performance was tested on 228 groups of children aged 6–17 years from 20 countries.
Results
The revised algorithm performed much better than the original. The standard deviation (SD) of residuals, the difference between observed and predicted prevalence, was 0.8% (n = 2320 comparisons), while the SD of the difference between pairs of the original prevalence rates was 4.3%, meaning that the algorithm explained 96.7% of the baseline variance (88.2% with original algorithm).
Conclusions
The improved algorithm appears to be effective at harmonizing prevalence rates of child overweight and obesity based on different references.
Often one of the two numbers to be compared is obviously appropriate as the divisor, such as the first of two measurements taken some time apart; the percentage difference is then the percentage ...change over time. Percentage differences arise in other contexts, such as fractional standard deviations and fractional regression coefficients. A separate Statistics Note 3 shows how the concepts are linked and how to calculate a percentage difference that is both symmetric and additive. 1 Freeman JV, Cole TJ, Chinn S, Jones PRM, White EM, Preece MA.
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