A phase 1 study to investigate the absorption, distribution, metabolism and excretion of brepocitinib in healthy males using a 14 C-microdose approach.

AIMS: Brepocitinib is a tyrosine kinase 2/Janus kinase 1 inhibitor being investigated for the treatment of several autoimmune diseases. This study assessed the absorption, distribution, metabolism and excretion of oral brepocitinib, and the absolute oral bioavailability (F) and fraction absorbed (Fa ) using a 14 C microtracer approach. METHODS: This was a phase 1 open-label, nonrandomized, fixed sequence, two-period, single-dose study of brepocitinib in healthy male participants. Participants received a single oral 60 mg dose of 14 C brepocitinib (~300 nCi) in Period A, then an unlabelled oral 60 mg dose followed by an intravenous (IV) 30 µg dose of 14 C labelled brepocitinib (~300 nCi) in Period B. Mass balance, pharmacokinetic parameters and safety were assessed. RESULTS: Six participants were enrolled. Brepocitinib was absorbed rapidly following oral administration. In Period A, total recovery of the oral dose was 96.7% ± 6.3% (88.0% ± 8.0% in urine, 8.7% ± 2.1% in faeces). In Period B, a small fraction (6.0% of the oral dose) was recovered unchanged in urine. F and Fa were 74.6% (90% confidence interval 67.3%, 82.8%) and 106.9%, respectively. Brepocitinib demonstrated an acceptable safety profile and was well tolerated following oral or oral then IV administrations. No deaths, serious adverse events or discontinuations were reported. CONCLUSION: Intestinal absorption of brepocitinib was essentially complete after oral administration, with F ~75%. Drug-related material recovery was high, with the majority excreted in urine. The major route of elimination of brepocitinib was renal excretion as metabolites, whereas urinary elimination of unchanged brepocitinib was minor. NCT: NCT03770039.

Information technology and changing role models in German libraries: The example of OPEN-CAM.

Germany has a long tradition of health libraries. From their origin in monasteries, they became centres of knowledge and education. In modern times, this tradition has been continued by the Central Library of Medicine. In addition, as a specialty in Germany, special collection areas and special libraries that focus on one topic were established. Those services were transformed to specialized information services and portals as part of the digital transformation process. One of such projects is OPEN-CAM, which provides literature on integrative medicine in a specialist library and hosts the literature database CAMbase. Based on this example, we show how digital transformation has influenced the library landscape and its structures in Germany.

Cancer-related fatigue in patients treated with mistletoe extracts: a systematic review and meta-analysis.

PURPOSE: Cancer-related fatigue remains one of the most prevalent and distressing symptoms experienced by cancer patients. Effective treatments for cancer-related fatigue are needed. The objective of this meta-analysis is to determine the impact of mistletoe extracts as a pharmacological treatment for the management of cancer-related fatigue. METHODS: We included randomized clinical trials (RCTs) and non-randomized studies of interventions (NRSIs) in cancer patients. Inclusion criteria were cancer-related fatigue severity or prevalence as an outcome and testing of mistletoe extracts compared to control groups. We searched Medline (EuropePMC), Embase, the Cochrane Central Register of Controlled Trials, Clinicaltrials.gov, and opengrey.org through October 2020. We assessed the risk of bias using the Cochrane risk of bias tools for RCTs and NRSIs and conducted a meta-analysis. RESULTS: We performed one meta-analysis with 12 RCTs, including 1494 participants, and one meta-analysis with seven retrospective NRSIs, including 2668 participants. Heterogeneity between the studies was high in both meta-analyses. Most studies had a high risk of bias. A random-effects model showed for RCTs a standardized mean difference of -0.48 (95% confidence interval -0.82 to -0.14; p = 0.006) and for NRSIs an odds ratio of 0.36 (95% confidence interval 0.20 to 0.66; p = 0.0008). CONCLUSION: Treatment with mistletoe extracts shows a moderate effect on cancer-related fatigue of similar size to physical activity. These results need to be confirmed by more placebo-controlled trials. Future trials should investigate different treatment durations and their effect on cancer-related fatigue in post-treatment cancer survivors. TRIAL REGISTRATION: This meta-analysis has been registered under the PROSPERO registration number CRD42020191967 on October 7, 2020.

Healing Architecture for Sick Kids.

Scientific data are sparse on hospital design in child and adolescent psychiatry. The present article aims to give an overview of various concepts of hospital design and to develop concepts how architecture can consider the special needs of children and adolescents in their recovery from psychiatric diseases. Literature research is provided from PubMed and collected from architectural and anthroposophic bibliography. Access to daylight and nature, reduced level of noise and an atmosphere of privacy are general principles to support convalescence in patients. Especially in psychiatry, spatial structures and colour can strengthen appropriate social interrelations on both the patient and staff level. Authors suggest that children and adolescents benefit from architectural concepts which consider the issues: Welcome, Path, Territory, Area of Freedom, Outdoor Space, Access to Light, Motion in the Structure and Orientation of Space.

Automated determination of bone age from hand X-rays at the end of puberty and its applicability for age estimation.

The BoneXpert method for automated determination of bone age from hand X-rays was introduced in 2009, covering the Greulich-Pyle bone age ranges up to 17 years for boys and 15 years for girls. This paper presents an extension of the method up to bone age 19 years for boys and 18 years for girls. The extension was developed based on images from the First Zurich Longitudinal Study of 231 healthy children born in 1954-1956 and followed with annual X-rays of both hands until adulthood. The method was validated on two cross-sectional studies of healthy children from Rotterdam and Los Angeles. We found root mean square deviations from manual rating of 0.69 and 0.45 years in these two studies for boys in the bone age range 17-19 years. For girls, the deviations were 0.75 and 0.59 years, respectively, in the bone age range 15-18 years. It is shown how the automated bone age method can be applied to infer the age probability distribution for healthy Caucasian European males. Considering a population with age 15.0-21.0 years, the method can be used to decide whether the subject is above 18 years with a false positive rate (children classified as adults) of 10 % (95% confidence interval = 7-13%) and a false negative rate of 30 % (adults classified as children). To apply this method in other ethnicities will require a study of the average of "bone age - age" at the end of puberty, i.e. how much this population is shifted relative to the Greulich-Pyle standard.

Validation of adult height prediction based on automated bone age determination in the Paris Longitudinal Study of healthy children.

BACKGROUND: An adult height prediction model based on automated determination of bone age was developed and validated in two studies from Zurich, Switzerland. Varied living conditions and genetic backgrounds might make the model less accurate. OBJECTIVE: To validate the adult height prediction model on children from another geographical location. MATERIALS AND METHODS: We included 51 boys and 58 girls from the Paris Longitudinal Study of children born 1953 to 1958. Radiographs were obtained once or twice a year in these children from birth to age 18. Bone age was determined using the BoneXpert method. Radiographs in children with bone age greater than 6 years were considered, in total 1,124 images. RESULTS: The root mean square deviation between the predicted and the observed adult height was 2.8 cm for boys in the bone age range 6-15 years and 3.1 cm for girls in the bone age range 6-13 years. The bias (the average signed difference) was zero, except for girls below bone age 12, where the predictions were 0.8 cm too low. CONCLUSION: The accuracy of the BoneXpert method in terms of root mean square error was as predicted by the model, i.e. in line with what was observed in the Zurich studies.

FeverApp for Parents: A Multilingual and Socially Accountable Approach to Paediatric Fever Management in Germany.

Policymakers and practitioners are increasingly focused on achieving health equity and meeting the specific health needs of diverse populations, including vulnerable groups such as children. To address these challenges, the Fever App for Parents has emerged as a solution to guide parents through the complexities of managing fever in their children by improving fever management in children through real-time data collection and comprehensive educational support. This systematic approach aims to reduce unnecessary medical interventions and overuse of antibiotics, thereby improving the overall quality of pediatric care and reducing parental anxiety. In Germany, almost every second child aged 0-10 is a child with migration status and/or migration experience. This means that the parents of these children also need to be targeted in fever management and informed about the correct behavior in case of fever. This information will also be monitored anonymously to provide a feedback loop on the parent's experience with the menu navigation and information design. The FeverApp provides parents with a structured, step-by-step guide to accurately track their child's temperature and medication intake to encourage adherence to established fever management protocols. This study examines how the FeverApp embodies the principles of social responsibility through its multilingualism and digital development stages that incorporate user feedback. It shows why this app can be a resource to promote health equity through social responsibility in medical education and practice for parents, but also what barriers need to be considered at different stages of app development for parents from different cultural backgrounds to enable informal medical learning through apps.

Distribution of mHealth applications in Germany: analysis of the FeverApp registry.

OBJECTIVE: In this observational study, we determined the distribution of mHealth applications (apps) in Germany using data from the FeverApp registry. METHODS: The registry data were processed to assess general monthly trends in app distribution, and a seasonal autoregressive integrated moving average model was decomposed to investigate time series. A sample comparison was made matching data from cold-called against self-registered distributers of the FeverApp. RESULTS: Among 881 pediatric and adolescent medical practices, 27,300 app users were recruited between 2019 and August 2023. The number of monthly recruited users increased steadily. A seasonal trend was observed, showing a higher distribution in winter months. Self-registered pediatric practices did not recruit significantly more app users than cold-called practices, with approximately every 25th family recruited in both groups. CONCLUSIONS: The trend of more app sign-ups during winter is likely related to the flu season in Germany. Intrinsic and extrinsic motivational factors of the practices seem to have a large impact on the distribution. We observed a positive trend in the app distribution. Seasonal febrile infections and individual distribution methods among practices influence the distribution of the FeverApp in Germany. Family factors may have a greater influence than the motivation of distributing practices.

Deaths Related to Domestic Violence in Washington State.

Importance: Domestic violence (DV; including intimate partner and family violence) is associated with heightened lethality risks, yet limited research has comprehensively assessed the connection between DV and fatal violence considering both homicides and suicides. Understanding the fatal consequences of DV can point to missed opportunities to support individuals and their families. Objective: To assess the proportion of violent deaths that were connected to DV and describe contacts with the legal system or social services prior to each DV-related fatality. Design, Setting, and Participants: This cross-sectional study used quantitative and qualitative data from the National Violent Death Reporting System (NVDRS) for all individuals who died by homicide or suicide in Washington from January 1, 2015, to December 31, 2020. Analyses were conducted from August 1, 2022, to September 30, 2023. Main Outcomes and Measures: A multipronged approach was used to assess DV history using existing NVDRS variables, leveraging data from prior review of NVDRS death narratives, applying a validated natural language processing tool, and linking related deaths. Domestic violence was recorded as yes or no, but the decedent's role in the abusive relationship (ie, experiencing or enacting DV) could not be differentiated. To describe system involvement prior to each death, keyword searching and hand review of NVDRS death narratives were used. Results: A total of 7352 intentional violent deaths (1192 homicides [16.2%]; 6160 suicides [83.8%]) with known circumstances were recorded in Washington during the study period. Of these, 948 deaths (12.9%) were connected to DV (624 [65.8%] among males; mean [SD] age at death, 45.3 [19.2] years), including 588 suicides (62.0%) and 360 homicides (38.0%). For 420 DV-related deaths (44.3%), there was evidence to suggest that the person who died or their intimate partner(s), family, or cohabitants had prior contacts with the legal system or social services. Specifically, 318 records (33.5%) mentioned prior contacts with law enforcement or the criminal legal system (eg, prior 9-1-1 calls, criminal convictions), and 225 (23.7%) described engagement with social services or the civil legal system (eg, civil protection order, divorce, or child custody problems). Conclusions and Relevance: In this cross-sectional study, 12.9% of violent deaths in Washington were connected to DV. The findings suggest that more resources are needed to support law enforcement, court professionals, and social services specialists to proactively identify and refer families to wraparound supports before the situation can escalate to a fatality.

Fatigue and quality of life during neoadjuvant chemotherapy of early breast cancer: a prospective multicenter cohort study.

BACKGROUND: Few measurements of fatigue and quality of life have been performed during neoadjuvant chemotherapy of early breast cancer. This study evaluates fatigue and quality of life experienced by early breast cancer patients during neoadjuvant chemotherapy and their association with different clinical parameters. METHODS: Fifty-four stage I-III patients' responses to the Multidimensional Fatigue Inventory (MFI) and to the Functional Assessment of Cancer Therapy-Breast (FACT-B) were analyzed by a linear covariance pattern model. Chemotherapy regimen, age, baseline fatigue level, body-mass-index and cancer stage were added to the model to estimate their impact on both outcomes. RESULTS: All fatigue dimensions worsened in clinically relevant levels. Physical fatigue worsened the most, mental fatigue the least. For quality of life, physical and functional well-being worsened the most. Only emotional well-being improved during chemotherapy. Physical well-being worsened more during standard than during dose-dense chemotherapy, and more during anthracycline than during taxane cycles. Age, body-mass-index and cancer stage had no impact. The higher the fatigue levels at baseline, the less they worsened during chemotherapy. CONCLUSIONS: Further actions to reduce fatigue and improve quality of life during neoadjuvant chemotherapy of early breast cancer are needed. Focus should be laid on the physical dimension. Future research should also investigate the impact of different chemotherapy sequences and densities on fatigue and quality of life. STUDY REGISTRATION: The study was registered in the German Clinical Trials Register in May 2019 (DRKS00016761).

Validation of automatic bone age determination in children with congenital adrenal hyperplasia.

BACKGROUND: Determination of bone age is routinely used for following up substitution therapy in congenital adrenal hyperplasia (CAH) but today is a procedure with significant subjectivity. OBJECTIVE: The aim was to test the performance of automatic bone age rating by the BoneXpert software package in all radiographs of children with CAH seen at our clinic from 1975 to 2006. MATERIALS AND METHODS: Eight hundred and ninety-two left-hand radiographs from 100 children aged 0 to 17 years were presented to a human rater and BoneXpert for bone age rating. Images where ratings differed by more than 1.5 years were each rerated by four human raters. RESULTS: Rerating was necessary in 20 images and the rerating result was closer to the BoneXpert result than to the original manual rating in 18/20 (90 %). Bone age rating precision based on the smoothness of longitudinal curves comprising a total of 327 data triplets spanning less than 1.7 years showed BoneXpert to be more precise (P<0.001). CONCLUSION: BoneXpert performs reliable bone age ratings in children with CAH.

Efficacy and safety of oclacitinib for the control of pruritus and associated skin lesions in dogs with canine allergic dermatitis.

BACKGROUND: Oclacitinib (Apoquel(®) ) inhibits the function of a variety of pro-inflammatory, pro-allergic and pruritogenic cytokines that are dependent on Janus kinase enzyme activity. Oclacitinib selectively inhibits Janus kinase 1. HYPOTHESIS/OBJECTIVES: We aimed to evaluate the safety and efficacy of oclacitinib for the control of pruritus associated with allergic dermatitis in a randomized, double-blinded, placebo-controlled trial. METHODS: Client-owned dogs (n = 436) with moderate to severe owner-assessed pruritus and a presumptive diagnosis of allergic dermatitis were enrolled. Dogs were randomized to either oclacitinib at 0.4-0.6 mg/kg orally twice daily or an excipient-matched placebo. An enhanced 10 cm visual analog scale (VAS) was used by the owners to assess the severity of pruritus from day 0 to 7 and by veterinarians to assess the severity of dermatitis on days 0 and 7. Dogs could remain on the study for 28 days. RESULTS: Pretreatment owner and veterinary VAS scores were similar for the two treatment groups. Oclacitinib produced a rapid onset of efficacy within 24 h. Mean oclacitinib Owner Pruritus VAS scores were significantly better than placebo scores (P < 0.0001) on each assessment day. Pruritus scores decreased from 7.58 to 2.59 cm following oclacitinib treatment. The day 7 mean oclacitinib Veterinarian Dermatitis VAS scores were also significantly better (P < 0.0001) than placebo scores. Diarrhoea and vomiting were reported with similar frequency in both groups. CONCLUSIONS AND CLINICAL IMPORTANCE: In this study, oclacitinib provided rapid, effective and safe control of pruritus associated with allergic dermatitis, with owners and veterinarians noting substantial improvements in pruritus and dermatitis VAS scores.

Hydrotherapeutic Heat Application as Support in Febrile Patients: A Scoping Review.

Background: Most often, fever is still treated by lowering body temperature with medication. In complementary and integrative health care, patients are supported during illness to use the positive effects of fever. Accompanying applications from the field of hydrotherapy are often used for gentle cooling, but there are references that warming in fever can also be used as a support. The aim of this scoping review was to identify available evidence on how, when, and why patients with fever are treated with heat application. Methods: The MEDLINE, CINAHL, EMBASE, COCHRANE, Google, and Google Scholar databases as well as references of identified literature were searched. As sources of evidence, publications studying patients who received heat application or were kept warm in febrile condition, regardless of medical situation, type of health care setting, and geographical background, were taken into consideration. Results: The literature search identified 1698 publications, of which only 7 were included. Methods of applying heat were the use of electric warming blankets, hot packs, hot-water bottles, or hot water footbaths. Most of the studies on heat application used temperatures of about 40°C and reported significantly lower body temperature after heat application. Conclusions: The literature suggests that hydrotherapeutic heat application is a common and well-appreciated method in Middle Eastern and Asian regions to support febrile patients. Using heat to support the energy-intensive and uncomfortable phase of rising fever may improve comfort, prevent unnecessarily high fever, and save biological energy. Therefore, high-quality studies on the role of heat application in fever are expected to be of high relevance for future fever management guidelines and integrative health care in general.

Increase of jump performance during GH treatment in short children born SGA.

Background: Short children born small for gestational age (SGA) often have low muscle mass. Studies on maximal isometric grip-force (MIGF) observed lower muscle strength in these children. In contrast to MIGF, jumping is an everyday muscle activity for children. Our hypothesis was that GH treatment would cause an increase in jumping strength. So, we aimed to study jumping by mechanography in short SGA children before and during GH treatment. Methods: Monocentric prospective longitudinal study in a tertiary pediatric endocrinology center. We studied 50 prepubertal short children (23 females) born SGA (mean age 7.2 y, height -3.24 SDS) during GH treatment (mean dose 45 µg/kg/d). Main outcome measures were Peak jump force (PJF) and peak jump power (PJP) measured by Leonardo® ground reaction force plate at baseline and after 12 months of GH treatment. Mechanography data were compared to sex, age and height related references (SD-Score). Fitness was estimated as PJP/kg body weight by use of the Esslinger-Fitness-Index (EFI). Results: At start of GH treatment PJP/body weight was low at -1.52 SDS and increased significantly to -0.95 SDS during 12 months of treatment (p<0.001). PJF was low-normal compared to height dependent references and remained unchanged. PJP was normal compared to height dependent references and increased only slightly from -0.34 to -0.19 SDSHT. Conclusions: Jumping performance (EFI) measured by mechanography increased during one year of GH treatment in short children born SGA.

Infants' immunisations, their timing and the risk of allergic diseases (INITIAL): an observational prospective cohort study protocol.

INTRODUCTION: Vaccinations are considered to have a large impact on disease control, hence a multitude of vaccines in infancy is recommended. Retrospective studies suggest a possible relation between timing, kind or number of vaccines given in the first year of life and the subsequent incidence of allergic diseases. It must be clarified whether a causal relationship exists to ensure safety and reduce vaccine hesitancy. METHODS AND ANALYSIS: Due to the high recommendation rate of vaccines, a long-term randomised controlled trial is not considered as ethically acceptable. Therefore, this study aims to observe prospectively the allergic incidence at the age of 5 years after various vaccine interventions in the early months of life.Parents of infants up to the age of 4-6 weeks will be recruited before the first recommended vaccination. Relevant prognostic factors for allergies, status of immunisation and general health will be evaluated up to the age of 5.Allergic symptoms will be assessed by the International Study of Asthma and Allergies in Childhood-questionnaire and a medical confirmation of the allergy is mandatory.The main objective is to compare the incidence of asthma, atopic dermatitis, rhinoconjunctivitis, food allergy or any of these atopies at the age of 5 between infants who were not vaccinated or were vaccinated according to recommendations in the first year of life.The sample size calculation with about 4000 participants can prove a 5% difference to the basic prevalence with about 80% power and global 5% alpha error for the five primary endpoints adjusting according to Bonferroni-Holm and assuming a rate of 10% not early vaccinated infants. ETHICS AND DISSEMINATION: The study was registered (DRKS00029677) and has received approval by the ethics committee of Universität Witten/Herdecke (no. 113/2022). The results will be published.

Predictors of sustained use of mobile health applications: Content analysis of user perspectives from a fever management app.

Objectives: Mobile health applications could be means of educating and changing behaviours of their users. Their features and qualities determine the sustainability of use. The FeverApp with two main features of information and documentation is a research-based app. In this observational cohort study, to evaluate the influential predictors of use, users' feedback on the FeverApp, were analyzed. Methods: Feedback is given using a structured questionnaire, four Likert items and two open questions regarding positive and negative impressions, available via app menu. Conventional content analysis (inductive approach) on the two open questions was performed. Comments were grouped into 12 codes. These codes were grouped hierarchically in an iterative process into nine subcategories and lastly into two main categories 'format' and 'content'. Descriptive and quantitative analysis were performed. Results: Out of 8243 users, 1804 of them answered the feedback questionnaire. The features of the app (N = 344), followed by the information aspect (N = 330) were most frequently mentioned. Documentation process (N = 226), request for new features or improvement of the current ones (N = 193), and functioning (N = 132) were also highlighted in users' feedback. App's ease of use, design and being informative were important for the users. The first impression of the app seems important as the majority of feedback were given during the first month of using the app. Conclusion: In-app feedback function could highlight shortcomings and strengths of mobile health apps. Taking users' feedback into consideration could increase the chance of sustained use. Besides ease of use and clear, likeable designs, users want apps that serve their needs while saving time.

Reliability of Data Collected via Ecological Momentary Assessment on the Example of FeverApp Registry.

The FeverApp registry is an ambulant ecological momentary assessment (EMA) model registry focusing on research of fever in children. Verification of EMA reliability is a challenge, due to absence of other source data. To ensure the reliability of EMA data, 973 families were invited to reassess their documentation in a survey. The survey contained questions (a) regarding the number of children, (b) genuineness of entries, (c) completeness of submitted fever episodes, (d) medication, (e) usefulness and further usage of the app. Of those invited, 438 families (45% response rate) participated in the survey. Of these, 363 (83%) families have registered all their children, 208 families have one child. The majority (n = 325, 74.2%) of families stated that they only made genuine entries in the app. Agreement between survey and app for fever episodes is 90% (Cohen's κ = 0.75 [0.66, 0.82]). Medication shows 73.7% agreement, κ = 0.49 [0.42; 0.54]. The majority (n = 245, 55.9%) consider the app as an additional benefit and 87.3% would like to use it further. Email surveys are a possible approach to evaluate EMA based registry data. The possible observation units (children and fever episodes) show an adequate reliability. With this approach, surveys of further samples and variables could help to improve the quality of EMA based registries.

Children's Symptoms with a Febrile Illness and a Positive or Negative Test of SARS-CoV-2 during the Omicron Wave.

Febrile infections are common in childhood. Children can be infected with SARS-CoV-2, but their course is milder than in adults. So far, a comparison between febrile infections with a positive or negative Corona test with the Omicron variant is missing. The data used are from the FeverApp registry, which collects parent-reported data on febrile infections in children and informs about fever management. A comparison of symptomatic differences between episodes with a positive or negative Corona test was performed using Χ2-tests. During the Omicron wave, reported tests doubled and positive test results nearly 12-folded. In episodes with positive Corona saliva tests, more cough, fatigue, disturbed smell/taste, limb pain, sore throat, signs of serious sickness, and touch sensitivity were reported. Children with a negative Corona test show more tonsillitis, teething, any pain symptoms, earaches, and rashes. Thus, there are some significant differences between febrile infections with a positive or negative Corona test, but symptoms are present on both sides. The omicron variant seems to be more infectious than the alpha or delta variants in children, but the symptoms remain mild and do not differ much from other febrile infections.

Comparison of radiogrammetrical metacarpal indices in children and reference data from the First Zurich Longitudinal Study.

BACKGROUND: A number of radiogrammetrical metacarpal indices are in use, some of which have been adapted for children. OBJECTIVE: The purpose of this study was to compare four known indices-bone mineral density (BMD), relative cortical area, Exton-Smith index, bending breaking resistance index-and the more recently defined pediatric bone index (PBI) according to the two criteria of minimum height dependence and minimum variability in children of equal bone age. MATERIALS AND METHODS: A total of 3,121 left-hand radiographs from 231 healthy Caucasian children ranging in age from 3 to 19 years old were analysed using BoneXpert®, a programme for automatic analysis of hand radiographs and assessment of bone age. RESULTS: Dependence on height for chronological age or bone age and the mean relative standard deviation were lowest in the PBI for both genders pooled. The differences in height dependence were statistically significant and are shown to be clinically relevant. Reference data for PBI are presented. CONCLUSION: PBI may be a better indicator than BMD for bone health in children; however, verification in a clinical group is needed.

Standardization of the Tanner-Whitehouse bone age method in the context of automated image analysis.

BACKGROUND/AIMS: The Tanner-Whitehouse (TW) method for bone age determination has been the basis for many population studies and it is used in many clinics. However, TW bone age raters can differ systematically from each other. The aim of the study was to present a new standard version of TW bone age rating implemented by the automated BoneXpert method and calibrated on the manual TW stage ratings of the First Zurich Longitudinal Study. SUBJECTS: Hand radiographs of 231 children born in 1954-1956 were recorded annually from an average age of 5-20 years. For validation, 76 X-rays of Tanner's original Gold Series from eight boys were used. RESULTS: The root mean square deviation between manual and automated TW ratings in the Zurich data was 0.67 years for boys in the TW bone age range 5-15 years and 0.63 years for girls, 5-14 years. The new standard TW rating differs systematically from two previous TW versions of the automated method, based on different raters. CONCLUSION: The new automated TW ratings show good accuracy relative to the manual ratings of the Zurich data and the Gold Series. There are significant differences between manual TW raters, an effect which is eliminated with the automated method.