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Abstract About 5-10% of breast and ovarian carcinomas are hereditary and most of these result from germline mutations in the BRCA1 and BRCA2 genes. In women of Ashkenazi Jewish ascendance, up to 30% of breast and ovarian carcinomas may be attributable to mutations in these genes, where 3 founder mutations, c.68_69del (185delAG) and c.5266dup (5382insC) in BRCA1 and c.5946del (6174delT) in BRCA2, are commonly encountered. It has been suggested by some authors that screening for founder mutations should be undertaken in all Brazilian women with breast cancer. Thus, the goal of this study was to determine the prevalence of three founder mutations, commonly identified in Ashkenazi individuals in a sample of non-Ashkenazi cancer-affected Brazilian women with clearly defined risk factors for hereditary breast and ovarian cancer (HBOC) syndrome. Among 137 unrelated Brazilian women from HBOC families, the BRCA1c.5266dup mutation was identified in seven individuals (5%). This prevalence is similar to that encountered in non-Ashkenazi HBOC families in other populations. However, among patients with bilateral breast cancer, the frequency of c.5266dup was significantly higher when compared to patients with unilateral breast tumors (12.1% vs 1.2%, p = 0.023). The BRCA1 c.68_69del and BRCA2 c.5946del mutations did not occur in this sample. We conclude that screening non-Ashkenazi breast cancer-affected women from the ethnically heterogeneous Brazilian populations for the BRCA1 c.68_69del and BRCA2 c.5946del is not justified, and that screening for BRCA1c.5266dup should be considered in high risk patients, given its prevalence as a single mutation. In high-risk patients, a negative screening result should always be followed by comprehensive BRCA gene testing. The finding of a significantly higher frequency of BRCA1 c.5266dup in women with bilateral breast cancer, as well as existence of other as yet unidentified founder mutations in this population, should be further assessed in a larger well characterized high-risk cohort.

Abstract Background Breast cancer is a significant public health problem worldwide and the development of tools to identify individuals at-risk for hereditary breast cancer syndromes, where specific interventions can be proposed to reduce risk, has become increasingly relevant. A previous study in Southern Brazil has shown that a family history suggestive of these syndromes may be prevalent at the primary care level. Development of a simple and sensitive instrument, easily applicable in primary care units, would be particularly helpful in underserved communities in which identification and referral of high-risk individuals is difficult. Methods A simple 7-question instrument about family history of breast, ovarian and colorectal cancer, FHS-7, was developed to screen for individuals with an increased risk for hereditary breast cancer syndromes. FHS-7 was applied to 9218 women during routine visits to primary care units in Southern Brazil. Two consecutive samples of 885 women and 910 women who answered positively to at least one question and negatively to all questions were included, respectively. The sensitivity, specificity and positive and negative predictive values were determined. Results Of the 885 women reporting a positive family history, 211 (23.8%; CI95%: 21.5–26.2) had a pedigree suggestive of a hereditary breast and/or breast and colorectal cancer syndrome. Using as cut point one positive answer, the sensitivity and specificity of the instrument were 87.6% and 56.4%, respectively. Concordance between answers in two different applications was given by a intra-class correlation (ICC) of 0.84 for at least one positive answer. Temporal stability of the instrument was adequate (ICC = 0.65). Conclusion A simple instrument for the identification of the most common hereditary breast cancer syndrome phenotypes, showing good specificity and temporal stability was developed and could be used as a screening tool in primary care to refer at-risk individuals for genetic evaluations.

Background: Accurate pharmacokinetic modelling in PET necessitates measurements of an input function, which ideally is acquired non-invasively from image data. For hepatic pharmacokinetic modelling two input functions need to be considered, to account for the blood supply from the hepatic artery and portal vein. Image-derived measurements at the portal vein are challenging due to its small size and image artifacts caused by respiratory motion. In this work we seek to demonstrate, using phantom experiments, how a dedicated PET/MR protocol can tackle these challenges and potentially provide input function measurements of the portal vein in a clinical setup., Methods: A custom 3D printed PET/MR phantom was constructed to mimic the liver and portal vein. PET/MR acquisitions were made with emulated respiratory motion. The PET/MR imaging protocol consisted of high-resolution anatomical MR imaging of the portal vein, followed by a PET acquisition in parallel to a dedicated motion-tracking MR sequence. Motion tracking and deformation information were extracted from PET data and subsequently used in PET reconstruction to produce dynamic series of motion-free PET images. Anatomical MR images were used post PET reconstruction for partial volume correction of the input function measurements., Results: Reconstruction of dynamic PET data with motion-compensation provided nearly motion-free series of PET frame data, suitable for image derived input function measurements of the portal vein. After partial volume correction, the individual input function measurements were within a 16.1% error range from the true activity in the portal vein compartment at the time of PET acquisition., Conclusion: The proposed protocol demonstrates clinically feasible PET/MR imaging of the liver for pharmacokinetic studies with accurate quantification of the portal vein input function, including correction for respiratory motion and partial volume effects., (© 2024. The Author(s).)

Background: Thanks to improved medical care, individuals with spina bifida (SB) live well into adulthood and go through the process of reproductive maturation and the development of sexual desires. However, access to reproductive counselling and contraceptive use has been reported to be lower for women with physical and intellectual disabilities compared to the general population., Objective: We investigated oral contraceptive use in women with SB, residing in Sweden and how use varies based on the level of lesion and demographic factors., Methods: This was a population-based case-control study using annual data from national registers from 2006 to 2015. The sample consisted of 7045 women aged 15-49 years, of which 1173 had a diagnosis of SB. χ 2 tests and logistic regression were used to investigate the study objective., Results: The rate of oral contraceptive use in women with SB was 24.6 % compared to 34.5 % among the general population. After adjusting for potential confounders women with SB were found to have a lower probability of using oral contraceptives (OR 0.63 95 % CI 0.56-0.71) compared to women without SB. Among women with SB, those with diagnoses Q05.8 (Sacral SB without hydrocephalus) and Q05.9 (SB unspecified) had a higher likelihood of using oral contraceptives compared to other Q05 diagnoses., Conclusion: Women with SB had a lower likelihood of being on oral contraceptives compared to the control group. Further research should investigate if the lower use indicates that oral contraceptives are not an inappropriate method of contraception for women with SB., Competing Interests: Declaration of Competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Pain is common in individuals with cerebral palsy (CP) and the most reported pain site is the foot/lower leg. We analyzed the prevalence of pain in the foot/lower leg and the associations with age, sex, gross motor function, and clinical findings in individuals with CP., Method: This was a cross-sectional register-study, based on data reported to the Swedish Cerebral Palsy Follow-up Program (CPUP). All participants in CPUP, four years-of-age or older, were included. Pearson chi-square tests and logistic regression were used to analyze the prevalence and degree of pain in the foot/lower leg., Results: In total, 5,122 individuals were included from the CPUP database: 58% were males and 66% were under 18 years-of-age. Overall, 1,077 (21%) reported pain in the foot/lower leg. The odds ratios (ORs) of pain were higher in females (OR 1.31, 95% confidence interval (CI) 1.13-1.53), individuals who could ambulate (Gross Motor Function Classification System Level I (OR 1.84, CI 1.32-2.57) and II (OR 2.01, CI 1.46-2.79) compared to level V), and in individuals with decreased range of motion of the ankle (dorsiflexion 1-10 degrees (OR 1.43, CI 1.13-1.83) and ≤ 0 degrees (OR 1.46, CI 1.10-1.93) compared to ≥ 20 degrees). With increasing age the OR of pain increased (OR 1.02, CI 1.01-1.03) as well as the reported pain intensity (p < 0.001)., Conclusions: Pain in the foot and lower leg appears to be a significant problem in individuals with CP, particularly in those who walk. As with pain in general in this population, both pain intensity and frequency increase with age. The odds of pain in the foot and lower leg were increased in individuals with limited dorsiflexion of the ankle. Given the cross-sectional design causality cannot be inferred and it is unknown if pain causes decreased range of motion of the ankle or if decreased range of motion causes pain. Further research is needed on causal pathways and importantly on prevention., (© 2024. The Author(s).)

Objective: To analyse survival rates and causes of death in adults with spina bifida in Sweden compared with a matched control group., Design and Methods: This population-based study included 11,900 adults born between 1950 and 1997. Three national Swedish registers were used to identify individuals with a diagnosis of spina bifida and a matched control group without spina bifida in the period 1990-2015. International Classification of Diseases codes were used to identify causes of death. Survival analysis was conducted and causes of death in the 2 groups were compared., Results: There was a lower probability of survival for people with spina bifida in all age groups (p < 0.001) compared with the control group. The most prevalent causes of death in people with spina bifida were congenital, respiratory, nervous, cardiovascular, genitourinary, and injuries. People with spina bifida had a higher probability of dying from congenital (p < 0.001), respiratory (p = 0.002), genitourinary (p < 0.002), and nervous-related (p < 0.001) and lower probability of injury-related deaths (p < 0.001)., Conclusion: Adults with spina bifida in Sweden have a lower survival rate compared with the general population, with the frequency of certain causes of death differing between the two groups. In order to reduce excess premature mortality, prevention and careful management of potentially fatal conditions are essential throughout a patient's lifespan.

Purpose: Children with cerebral palsy (CP) have an increased risk of cognitive difficulties and should be offered cognitive assessments. In Sweden, the CP Cog protocol recommends children with CP undergo cognitive assessments at the start of primary and secondary school. To assess children with CP can be challenging, in particular when children are non-vocal or do not speak the local language. In such instances, augmentative and alternative communication (AAC) and qualified medical interpreters should be considered. The purpose of this study was to monitor the implementation and equitable delivery of the CP Cog protocol in Sweden between the years 2017-2020., Materials and Methods: In this cross-sectional study, registry data were extracted from the combined follow-up program and national registry for individuals with CP (CPUP), and a convenience sample of psychologists responded to an online survey., Results and Conclusions: Each year, less than 5% of eligible children had registered cognitive assessments in CPUP. There was underuse of AAC during assessments and a discrepancy between the registered versus reported use of interpreters. Psychologists perceived AAC as more reliable for cognitive assessments than interpreters. Greater availability of and capacity to offer cognitive assessments in other formats and languages could help increase test accessibility for all children with CP.Implications for RehabilitationThe cognitive assessment of children with cerebral palsy (CP) is a complex but important issue within disability and re/habilitation.Individualized cognitive assessments should be offered and carried out by psychologists.Rehabilitation centers should strive to be inclusive through reliable test adaptations for functional abilities, means of communication, and language.Greater availability of- and capacity to offer cognitive assessments in more formats and languages could help increase test accessibility for children with disabilities.

Purpose: Children with cerebral palsy (CP) are at risk of cognitive impairments and need to be cognitively assessed to allow for individualized interventions, if applicable. Therefore, a systematic protocol for the follow-up of cognition in children with CP, CP Cog , with assessments offered at five/six and 12/13 years of age, was developed. This report presents and discusses assessment practices in Sweden and Norway following the introduction of CP Cog and a quality improvement project in Norway aimed at increasing the number of children offered cognitive assessments., Materials and Methods: A questionnaire investigating assessment practices was sent to pediatric habilitation centers in Sweden and Norway. In Norway, the habilitation centers also participated in a quality improvement project aimed at increasing adherence to the CP Cog protocol., Results: Of the respondents, 64-70% report that they assess cognition in children with all degrees of motor impairment, and 70-80% assess at the ages recommended in CP Cog . Following the quality improvement project in Norway, the percentage of children assessed increased from 34 to 62%., Conclusions: The findings illustrate that the provision of information is not sufficient to change practice. Implementation of new re/habilitation procedures is aided by targeting health care practices individually.Implications for rehabilitationChildren with cerebral palsy (CP) have increased risk of cognitive impairments that require intervention.Assessments of cognition should be offered to all children with CP because the nature of cognitive impairments may vary.Introducing a follow-up protocol of how and when to perform cognitive assessments is a step towards ensuring equal access to the services for all children with CP.A quality improvement project might be a viable method for implementing a protocol into everyday clinical practice.

Background: Pain is a global health concern with substantial societal costs and limits the activity participation of individuals. The prevalence of pain is estimated to be high among individuals with cerebral palsy (CP)., Objectives: To estimate the association between pain and labor outcomes for adults with CP in Sweden., Methods: A longitudinal cohort study based on data from Swedish population-based administrative registers of 6899 individuals (53,657 person-years) with CP aged 20-64 years. Individual fixed effects regression models were used to analyze the association between pain and labor outcomes (employment and earnings from employment), as well as potential pathways through which pain might affect employment and earnings., Results: Pain was associated with adverse outcomes varying across severity, corresponding to a reduction of 7-12% in employment and 2-8% in earnings if employed. Pain might affect employment and earnings through increased likelihood of both sickness leave and early retirement., Conclusion: Pain management could potentially be important to improve labor outcomes for adults with CP, in addition to improving the quality of life., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Cerebral palsy (CP) is an umbrella term where an injury to the immature brain affects muscle tone and motor control, posture, and at times, the ability to walk and stand. Orthoses can be used to improve or maintain function. Ankle-foot orthoses (AFOs) are the most frequently used orthoses in children with CP. However, how commonly AFOs are used by children and adolescents with CP is still unknown. The aims of this study were to investigate and describe the use of AFOs in children with CP in Sweden, Norway, Finland, Iceland, Scotland, and Denmark, and compare AFO use between countries and by gross motor function classification system (GMFCS) level, CP subtype, sex, and age., Method: Aggregated data on 8,928 participants in the national follow-up programs for CP for the respective countries were used. Finland does not have a national follow-up program for individuals with CP and therefore a study cohort was used instead. Use of AFOs were presented as percentages. Logistic regression models were used to compare the use of AFOs among countries adjusted for age, CP subtype, GMFCS level, and sex., Results: The proportion of AFO use was highest in Scotland (57%; CI 54-59%) and lowest in Denmark (35%; CI 33-38%). After adjusting for GMFCS level, children in Denmark, Finland, and Iceland had statistically significantly lower odds of using AFOs whereas children in Norway and Scotland reported statistically significantly higher usage than Sweden., Conclusion: In this study, the use of AFOs in children with CP in countries with relatively similar healthcare systems, differed between countries, age, GMFCS level, and CP subtype. This indicates a lack of consensus as to which individuals benefit from using AFOs. Our findings present an important baseline for the future research and development of practical guidelines in terms of who stands to benefit from using AFOs., (© 2023. The Author(s).)

Background: Children with cerebral palsy (CP) form a heterogeneous group and may have risk or protective factors for fractures compared with typically developing children. The fracture sites may also differ from those of children who do not have CP. We analyzed the fracture epidemiology in a total population of children with CP., Methods: This was a retrospective registry study based on data from the Swedish Cerebral Palsy Follow-Up Program (CPUP) and the Swedish National Patient Register. All children in the CPUP born in 2000-2015 were included. The Gross Motor Function Classification System (GMFCS) level, reported fractures, fracture site, and epilepsy diagnosis were recorded up to 2018. Hazards and hazard ratios were calculated for first-time fractures., Results: Of the 3,902 participants, 368 (9.4%) had at least one reported fracture. The cumulative risk of sustaining a fracture before age 16 years was 38.3% (95% confidence interval 33.9-42.4). The hazard for fracture was 7 times higher in children with epilepsy. The overall fracture incidence was not statistically significantly related to sex or GMFCS level. Fractures in the upper extremities were most prevalent in children with a lower GMFCS level, and femoral fractures were most prevalent in children at GMFCS level V. Most fractures occurred in early childhood and after 8 years of age., Conclusions: Children with CP were at similar risk of sustaining fractures as typically developing children, but the risk was higher in children with comorbid epilepsy. Fractures occurred in children at GMFCS levels I-III at sites similar to those for typically developing children; fractures in the upper extremities were the most frequent. Children at GMFCS levels IV or V and those with epilepsy were more likely to have a fracture in the lower extremities, and the femur was the most frequent site., (© 2022. The Author(s).)

Aim: To investigate the occurrence of pressure injuries (PIs) in children with myelomeningocele (MMC) and to investigate the association between PIs and orthoses use by disability-specific variables., Methods: Population-based registry study including participants in the Swedish multidisciplinary follow-up programme for MMC. Risks of PIs were investigated by birth cohort, country of birth, sex, type of MMC, muscle function level (MFL), and continence status., Results: Of 180 participants, 29% had PIs recorded. Of the 132 participants with >1 assessment records, 17.4% reported multiple PI occasions. More assessments increased the likelihood of PIs (Odds Ratio [OR] = 1.33, 95% CI 1.15-1.54) and participants born 2015-2018 had a lower OR of PIs than those born 2007-2010 (OR = 0.08, 95% CI = 0.01-0.74). Those at MFL I had lower OR of PIs than those at MFL V (OR = 0.06, 95% CI 0.01-0.64). Of the 73 participants with orthoses on the lower extremities, 47% reported skin irritations/injuries in the last 4 weeks; 30% reported that it made them stop using orthoses., Conclusion: Pressure injuries are common even in young children with MMC. Many have recurring skin irritations. Inspecting for PIs should be part of a daily routine and tools to increase compliance are needed., (© 2022 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Purpose: The aim was to study the prevalence of hip displacements, dislocations, and the hip surgeries performed in a Finnish cohort of children with cerebral palsy not followed up in a hip surveillance program and to compare these with previous studies performed in Northern European countries before and after the implementation of hip surveillance programs., Methods: A cross-sectional study. A cohort including 480 children with cerebral palsy, born during the period 2000-2018, not enrolled in a hip surveillance program. Migration percentages were recorded from hip radiographs, age at first hip surgery and type of surgery was extracted from medical records. In a separate analysis, the inclusion criteria were adapted to fit two studies analyzing hip dislocation and hip surgery in Sweden, Norway, and Scotland before and after the implementation of a hip surveillance program. Chi-square tests were used to assess differences in proportions between the groups., Results: In total, 286 children (60%) have had at least one hip radiograph. Of these, 10 (3.5%) developed hip dislocation, which is more than in children of countries with hip surveillance programs (Sweden 0.7%, Scotland 1.3%, p  < 0.001). Initial surgery to prevent hip dislocation was performed at an older age ( p  < 0.001)., Conclusion: Children with cerebral palsy in Finland not participating in a surveillance hip program were more likely to undergo hip surgery at an older age and to develop hip displacements and dislocations. The results support the effectiveness of surveillance programs to prevent hip dislocation in children with cerebral palsy., Level of Evidence: III., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Purpose: This study aimed to describe health care use by type of health providers and care settings visited by children with spina bifida (SB) and to compare this use between children with and without a shunt., Methods: Health care use data were extracted from a larger study on the health and functioning of children with SB aged 3-6 years. The present study focused on the medical information subsection of a parent-reported survey related to SB care, general care, specialty care (e.g., neurosurgery), emergency care, and complications related to SB and shunts., Results: Parents of 101 children with SB participated. Most of the children were male with myelomeningocele and had a shunt. They visited a health care provider for SB care an average of 7.4 times and a specialist an average of 11.9 times in the previous 12 months. Most visited a multidisciplinary clinic for SB-related care and a private physician's office for general care. Children with a shunt had more SB-related medical visits, more visits to a specialist, and a greater number of different types of specialists than those without it. Frequency of emergency room visits did not differ between the two groups. Health providers informed parents about headaches, vomiting, and fever as signs of complications, and some parents did report shunt-related complications., Conclusion: SB is a complex medical condition requiring that children receive medical care from various medical specialists, especially for children with a shunt. Findings on health care use suggest high levels of monitoring and care coordination that parents navigate to care for their child.

Cerebral palsy (CP) comprises a heterogeneous group of conditions recognized by disturbances of movement and posture and is caused by a non-progressive injury to the developing brain. Birth prevalence of CP is about 2-2.5 per 1,000 live births. Although the motor impairment is the hallmark of the diagnosis, individuals with CP often have other impairments, including cognitive ones. Cognitive impairments may affect communication, education, vocational opportunities, participation, and mental health. For many years, CP has been considered a "childhood disability," but the challenges continue through the life course, and health issues may worsen and new challenges may arise with age. This is particularly true for cognitive impairments, which may become more pronounced as the demands of life increase. For individuals with CP, there is no one-to-one correlation between cognition and functioning in other areas, and therefore, cognition must be individually assessed to determine what targeted interventions might be beneficial. To facilitate this for children with CP, a systematic follow-up protocol of cognition, the CP Cog , has been implemented in Norway and Sweden. However, no such protocol currently exists for adults with CP. Such discontinuity in healthcare services that results from lack of follow-up of cognitive functioning and subsequent needs for adjustments and interventions makes transition from pediatric to adult healthcare services challenging. As a result, a protocol for the surveillance of cognition in adults with CP, the CP Cog -Adult, has been developed. It includes assessment of verbal skills, non-verbal reasoning, visual-spatial perception, and executive functioning. It is recommended to perform these assessments at least once in young adulthood and once in the mid-fifties. This report describes the process of developing the CP Cog- Adult, which has a three-fold purpose: (1) to provide equal access to healthcare services to enable the detection of cognitive impairments; (2) to provide interventions that increase educational and vocational participation, enhance quality of life, and prevent secondary impairments; and (3) to collect systematic data for research purposes. The consent-based registration of data in the well-established Swedish and Norwegian national CP registries will secure longitudinal data from childhood into adulthood., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Stadskleiv, van Walsem, Andersen, Bergqvist, Bøttcher, Christensen, Heyerdahl, Hollung, Høye, Jahnsen, Klevberg, Lindquist, Passmark, Rike, Rodby-Bousquet and Alriksson-Schmidt.)

Aims: This report reviews major laws, acts and regulations of social benefits and services for individuals with disabilities, focusing on cerebral palsy in the five Nordic countries. It summarizes the available benefits and services and the re-application process and provides comparative analyses among the countries., Methods: Published reports, articles and relevant government and municipal websites were reviewed for each respective country and used to compile an overview and comparison between the countries., Results: In the Nordic countries, there are a number of laws and regulations in place to support individuals with cerebral palsy and their families. In addition, there are numerous social benefits available for which individuals with disabilities can apply. Although there are national differences, the similarities across the five countries regarding laws, social benefits offered for individuals with cerebral palsy and the application processes are clear. However, the application processes seem cumbersome and, at times, redundant. Physicians and other healthcare specialists repeatedly need to write 'medical certificates' describing the diagnosis and its consequences for a disability that is chronic and lifelong., Conclusions: Participation in society for individuals with cerebral palsy disabilities can be enabled by social benefits. By extension, social benefits may indirectly have implications for public health in individuals with disabilities. Although the lives of individuals with cerebral palsy - as with others - can improve in certain areas, the need for social benefits will generally increase, not decrease, over time. Although it is clearly important to have checks and balances that prevent system misuse, it might be worthwhile from a cost-benefit perspective to investigate whether the current systems could be improved to better manage time and resources and avoid emotional distress by streamlining the application process.

Background: Spasticity is present in more than 80% of the population with cerebral palsy (CP). The aim of this study was to describe and compare the use of three spasticity reducing methods; Botulinum toxin-A therapy (BTX-A), Selective dorsal rhizotomy (SDR) and Intrathecal baclofen therapy (ITB) among children and adolescents with CP in six northern European countries., Methods: This registry-based study included population-based data in children and adolescents with CP born 2002 to 2017 and recorded in the follow-up programs for CP in Sweden, Norway, Denmark, Iceland and Scotland, and a defined cohort in Finland., Results: A total of 8,817 individuals were included. The proportion of individuals treated with SDR and ITB was significantly different between the countries. SDR treatment ranged from 0% ( Finland and Iceland) to 3.4% (Scotland) and ITB treatment from 2.2% (Sweden) to 3.7% (Denmark and Scotland). BTX-A treatment in the lower extremities reported 2017-2018 ranged from 8.6% in Denmark to 20% in Norway (p < 0.01). Mean age for undergoing SDR ranged from 4.5 years in Norway to 7.3 years in Denmark (p < 0.01). Mean age at ITB surgery ranged from 6.3 years in Norway to 10.1 years in Finland (p < 0.01). Mean age for BTX-A treatment ranged from 7.1 years in Denmark to 10.3 years in Iceland (p < 0.01). Treatment with SDR was most common in Gross Motor Function Classification System (GMFCS) level III, ITB in level V, and BTX-A in level I. The most common muscle treated with BTX-A was the calf muscle, with the highest proportion in GMFCS level I. BTX-A treatment of hamstring and hip muscles was most common in GMFCS levels IV-V in all countries., Conclusion: There were statistically significant differences between countries regarding the proportion of children and adolescents with CP treated with the three spasticity reducing methods, mean age for treatment and treatment related to GMFCS level. This is likely due to differences in the availability of these treatment methods and/or differences in preferences of treatment methods among professionals and possibly patients across countries., (© 2021. The Author(s).)

Aim: To describe the point prevalence of cerebral palsy (CP) and distribution of gross and fine motor function in individuals registered in a CP-North surveillance programme., Method: Aggregate data of individuals with CP aged 6 to 19 years, sex, CP subtype, and gross and fine motor function levels were collected from each programme. Overall and age-specific point prevalence of CP was calculated for each programme using 95% confidence intervals. Logistic regression was used to estimate prevalence and CP subtypes with age as the covariate variable. Pearson χ 2 tests were used to compare the distributions of CP subtypes, Gross Motor Function Classification System (GMFCS) levels, and Manual Ability Classification System (MACS) levels by age and between programmes., Results: Among 3 759 138 individuals residing in Scandinavia and Scotland, 8278 had a diagnosis of CP (57-59% were males). The overall point prevalence of CP ranged from 2.13 to 2.32 per 1000 residents. Age-specific prevalence in each programme varied with the exception of Denmark. While the proportions of bilateral spastic CP were similar between programmes, there were variations in all other CP subtypes and in GMFCS and MACS levels., Interpretation: While the results of this study may reflect real differences in CP populations between countries, they may not be clinically relevant. The variations may be attributable to differences in the year when each programme was first established, different data collection methods, and country-specific governmental policies., (© 2021 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.)

Pain is a significant health concern for children living with cerebral palsy (CP). There are no population-level or large-scale multi-national datasets using common measures characterizing pain experience and interference (ie, pain burden) and management practices for children with CP. The aim of the CPPain survey is to generate a comprehensive understanding of pain burden and current management of pain to change clinical practice in CP. The CPPain survey is a comprehensive cross-sectional study. Researchers plan to recruit approximately 1400 children with CP (primary participants) across several countries over 6-12 months using multimodal recruitment strategies. Data will be collected from parents or guardians of children with CP (0-17 years) and from children with CP (8-17 years) who are able to self-report. Siblings (12-17 years) will be invited to participate as controls. The CPPain survey consists of previously validated and study-specific questionnaires addressing demographic and diagnostic information, pain experience, pain management, pain interference, pain coping, activity and participation in everyday life, nutritional status, mental health, health-related quality of life, and the effect of the COVID-19 pandemic on pain and access to pain care. The survey will be distributed primarily online. Data will be analyzed using appropriate statistical methods for comparing groups. Stratification will be used to investigate subgroups, and analyses will be adjusted for appropriate sociodemographic variables. The Norwegian Regional Committee for Medical and Health Research Ethics and the Research Ethics Board at the University of Minnesota in USA have approved the study. Ethics approval in Canada, Sweden, and Finland is pending. In addition to dissemination through peer-reviewed journals and conferences, findings will be communicated through the CPPain Web site (www.sthf.no/cppain), Web sites directed toward users or clinicians, social media, special interest groups, stakeholder engagement activities, articles in user organization journals, and presentations in public media., (© 2021 The Authors. Paediatric and Neonatal Pain published by John Wiley & Sons Ltd.)

Purpose: To investigate the: (1) percent of children with spina bifida (SB) complaining of pain, (2) frequency, duration, and cause of pain by sex, level of lesion type of SB, and ambulation status, (3) body sites reported to hurt, by variables in objective 2, and (4) associations between physical and mental/emotional health between caregiver and child., Methods: Cross-sectional study of 101 caregivers of children (3 to 6 years old) with SB. Survey data and information from medical records were included. Pearson chi-square, one-way ANOVA, Fisher's exact test, logistic regressions, and bivariate correlations were used., Results: Seventy percent reported that their child complained of pain, which did not significantly differ by sex, level of lesion, type of SB, or ambulation status. Most (86%) were reported to have experienced pain for less than 24 hours. The most frequently reported pain site was the head, followed by the abdomen and the lower body. Number of pain sites was moderately correlated with frequency of pain complaints. Correlations between how caregivers reported their own physical/mental/emotional health and how they rated that of their children ranged from weak (r = 0.22) to moderate (r = 0.55)., Conclusion: Almost seven of ten children reportedly complained of pain ranging from at least once a month to everyday. Pain needs to be routinely assessed and treated in this population.

Aim: To investigate the relationships between pain in the lower extremities and back, and spasticity, bone/joint complications and mobility., Methods: Retrospective population-based registry study. Participants (N = 3256) with cerebral palsy (CP), 2.5-16 years of age, participating in the Swedish Cerebral Palsy Follow-up Program were included. Spasticity was measured using scissoring and the Modified Ashworth Scale. Bone/joint complications consisted of hip displacement, range of motion, windswept posture and scoliosis. Mobility was measured using the Functional Mobility Scale (5-, 50- and 500-metres), wheelchair use (outdoors) and the ability to stand/get up from sitting/use stairs, respectively. Pain was measured as presence of pain in hips, knees, feet and back. Data were analysed using structural equation modelling., Results: Bone/joint complications had the strongest direct pathway with pain in the lower extremities (standardised regression coefficient = 0.48), followed by reduced mobility (standardised regression coefficient = -0.24). The pathways between spasticity and pain, and age and pain were not significant. The R 2 of the model was 0.15., Conclusion: Bone/joint complications and reduced mobility were associated with pain in the lower extremities when controlling for sex. Considering the R 2 of the model, other factors not included in the model are also associated with pain in the lower extremities in children with CP., (© 2019 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Aims: To describe the early experiences of a Nordic multidisciplinary cerebral palsy (CP) registry research program combining data from national medical quality registries, follow-up programs and cohort data, in addition to data from other national registries; to explore the scientific and practical uses of such research, and provide recommendations for facilitating similar work in the future. Methods : The work was divided into three themes: medical outcomes, social and public health outcomes, and health economics; and three cross-cutting teams: a reference team, a challenge team, and a communication and dissemination team. Initially each country will perform domestic research, and in the second stage data will be merged across all Nordic countries. Data from national registries with vital statistics, education and work, social benefits, and healthcare will be used. Comparisons will be matched for both the individuals with CP and their parents. Results : Initial work has been done on agreeing which variables to request from the respective agencies and planning the correct procedures and steps required to acquire the data. As of 2018, Sweden, Norway, and Finland have received approved ethics board applications. Iceland and Denmark are waiting for their approvals. A webpage and a platform for internal communication have been created. Conclusions : Nordic register research has great potential. Linking national CP quality registries and follow-up programs with other large national registries holds particular promise because problems identified through research can be applied at a population level. It is imperative that ethical clearance and data delivery processes are streamlined and transparent, and that data variables are measured the same way in the different countries.

Background: In the Swedish population-based follow-up program and national quality registry for individuals with cerebral palsy (CPUP), physiotherapy (PT) and occupational therapy (OT) treatments are regularly recorded along with functional status. By Swedish law, all citizens irrespective of personal characteristics or socioeconomic status, have the right to receive healthcare and medical treatments as applicable. Previous research has shown gender differences in treatments and interventions received by children with cerebral palsy (CP). The purpose of this study was to examine differences in treatments and interventions by gender and place of birth in children and adolescents participating in CPUP., Methods: This was a cross-sectional registry study. Data from the latest PT (n = 2635) and OT assessment forms (n = 3480) in CPUP were extracted for individuals aged 0-17 years. Logistic regressions were used to assess the relationships between the outcome variables and gender and place of birth (including an interaction term gender X place of birth), adjusted for age, Gross Motor Function Classification System (GMFCS) levels and spasticity scores for PT interventions and Manual Ability Classification System (MACS) for OT interventions., Results: Results are presented as odds ratios [95% confidence intervals] and p-values. Girls were significantly more likely to have spinal braces than boys; 1.54 [1.07, 2.22] p < 0.05, a significant interaction with place of birth indicated fewer spinal braces prescribed to children born outside of the Nordic countries; 0.20 [0.079, 0.53] p < 0.001. Girls were less likely to have undergone selective dorsal rhizotomy (SDR); 0.49 [0.25, 0.94] p < 0.05. Individuals born outside of the Nordic countries, were significantly less likely to have received intrathecal baclofen (ITB) 0.27 [0.074, 0.98] p < 0.05., Conclusions: Of the treatments prescribed, gender differences were observed for spinal braces and having undergone SDR. A statistically significant difference based on place of birth was noted for spinal bracing and having received ITB treatment. Other PT and OT treatments were associated with age, level of spasticity, and functional severity as classified using the GMFCS and the MACS. Increased awareness of differences based on gender, and where a child is born, could be obtained by inter- and intraprofessional discussions.

Background: Pain is a common problem for individuals with cerebral palsy (CP). In Sweden, 95% of children and adolescents with CP are followed in a national follow-up programme (CPUP), which includes data on pain. The purpose of this study was to investigate the prevalence of pain based on age, sex, gross motor function and source of report (self or proxy). Pain intensity, pain site, and how much pain disturbed sleep and daily activities were also studied., Methods: This was a cross-sectional register study based on all participants in CPUP, 4-18-years of age, with data reported in 2017-2018. Gross motor function was classified using the Gross Motor Function Classification System (GMFCS). Logistic regression was used to analyse prevalence of pain and how much pain had disturbed sleep and daily activities in the last four weeks., Results: In total, 3545 participants (2065 boys) were included. The overall prevalence of pain was 44%. Older age and female sex were associated with higher risk of pain with odds ratios of 1.07 (95% confidence interval (CI) 1.06-1.09) and 1.28 (CI 1.12-1.47), respectively. Pain was most common in the lower extremities. There was no statistically significant difference in prevalence of pain related to source of report. Pain intensity was higher at older ages and higher GMFCS-levels. Hip/thigh pain and abdominal pain were associated with the most intense pain. Of those who reported pain, pain disturbed sleep for 36% and daily activities for 61%., Conclusions: Both pain frequency and pain intensity were higher at higher age. Pain intensity increased with increasing GMFCS-level. Two-thirds of all children and adolescents with CP reported that their pain disturbed their daily activities, and one-third reported that pain disturbed their sleep.

Objective: To assess how the prevalence of pain in a population-based sample of children and adolescents with cerebral palsy (CP) differ based on self- or proxy reporting. Methods: This cross-sectional registry study included 3783 children (58% boys), 1 to 18 years old, enrolled in the Swedish follow-up program for CP. Logistic regression was used to regress source of reporting (self or proxy) on the presence of general pain adjusted for age, sex, Gross Motor Function Classification System (GMFCS), and Communication Function Classification System (CFCS) levels, including marginal effects between source of reporting and adjusted covariates. Results: The pain item was self-reported in 45%, proxy-reported in 51%, and information was missing in 3%. Pain was reported in 44% of those who self-reported and in 41% of those who proxy-reported ( P = .04). The logistic regression showed that the average marginal effects of proxy versus self-reported pain were lower among children at GMFCS level IV (-0.14, 95% CI -0.17 to -0.03) and CFCS level I (-0.09, CI -0.16 to -0.01) and higher at CFCS level III (0.11, CI 0.00-0.22). There were no statistically significant differences in average marginal effects related to age, sex, or the other GMFCS and CFCS levels between proxy and self-reporting. Conclusions: Pain was more often reported by those who self-reported. However, after adjusting for age, sex, CFCS level, and GMFCS level, the proportion of reported pain was almost equal between self and proxy-reporting. Assuming that the self- and proxy-reported groups were not significantly different on relevant factors not controlled for the results indicate that presence of pain is equally reported by children and parents.

Aim: To investigate the prevalence of general and back pain in children with cerebral palsy and the relationships between scoliosis and back pain., Methods: Cross-sectional register study based on data from the Swedish Cerebral Palsy Follow-Up Programme. Descriptive analyses and logistic regression to regress age, sex, gross motor function, windswept, hip extension and source of report on the presence of pain., Results: The study included 3783 children (58% boys) 1-18 (mean 10.0) years of age. General pain was reported in 1538 (44% girls, 38% boys) and back pain in 226 (7% girls, 5% boys) children. The proportion of back pain increased from <4% prior to age 12 years to >12% from 16 years of age. Back pain increased from 4% in children without scoliosis to 16% in children with severe scoliosis. Moderate/severe back pain increased from 2% in children without scoliosis to 10% in children with severe scoliosis. Increased odds of reporting back pain were found for age, girls, low gross motor function and children with scoliosis., Conclusion: The proportion of children with general pain increased with age and was more frequent in girls. Age, female sex, low gross motor function and scoliosis were significant predictors of back pain., (© 2019 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Introduction: Cerebral palsy (CP) is one of the most common neurodevelopmental disabilities. Yet, most individuals with CP are adults. How individuals with CP fare in terms of health, quality of life (QoL), education, employment and income is largely unknown. Further, little is known about the effects of having a child with CP on the parents. The Nordic countries are known for their strong welfare systems, yet it is unknown to what extent the added burden related to disability is actually compensated for. We will explore how living with CP affects health , QoL, healthcare utilisation, education, labour market outcomes, socioeconomic status and mortality throughout the lifespan of individuals with CP and their parents. We will also investigate if these effects differ between subgroups, within and across the Nordic countries. METHODS AND ANALYSES: CP-North is a multidisciplinary 4-year (1 August 2017 to 31 July 2021) register research project. The research consortium comprises researchers and users from Sweden, Norway, Denmark, Iceland and Finland. Data from CP registries and follow-up programmes, or cohorts of individuals with CP, will be merged with general national registries. All individual studies are structured under three themes: medical outcomes, social and public health outcomes, and health economics. Both case-control and cohort designs will be included depending on the particular research question. Data will be analysed in the individual countries and later merged across nations., Ethics and Dissemination: The ethics approval processes in each individual country are followed. Findings will be published (open access) in international peer-reviewed journals in related fields. Updates on CP-North will be published online at http://rdi.arcada.fi/cpnorth/en/., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Hip pain is prevalent in children with cerebral palsy (CP). Hip displacement is a known risk factor for hip pain. However, many children do not have displaced hips but still have hip pain and the aetiologies are poorly understood. The aims of this study were to investigate: 1. the prevalence of hip pain related to age, gender, gross motor function, degree of hip displacement and 2. the associations between hip pain and age, gender, gross motor function, degree of hip displacement, ranges of hip and knee motion (ROM) and degree of spasticity in the muscles around the hip., Methods: This was a cross-sectional retrospective register study based on data from the Swedish follow-up programme and national healthcare registry CPUP, which includes > 95% of children with CP in Sweden. The participants were born in 2000 or later and 4-16 years of age. Data from the latest examination were used. In Aim 1, the prevalence of hip pain was calculated using frequencies and crosstabs. Differences between groups were calculated using chi-square tests and independent samples t-tests. In Aim 2, associations between hip pain and the variables were analysed using logistic regression., Results: The overall prevalence of hip pain was 7%. No significant gender difference was found. Hip pain prevalence increased with age, lower gross motor function and higher degree of hip displacement. The median migration percentage (MP) in painful hips was 26%, compared to 21% in hips where pain was not reported. In the multivariable analysis, significant associations with hip pain were found for MP > 30% and decreased ROM in abduction, flexion and inwards rotation of the hip (p < 0.05)., Conclusion: Hip displacement was associated with hip pain. However, hip displacement was not present in the majority of painful hips. In addition to hip displacement, decreased ROM was also associated with hip pain.

Pancreatic ductal adenocarcinoma (PDAC) is a particularly deadly disease. Chronic conditions, including obesity and type-2 diabetes are risk factors, thus making PDAC amenable to preventive strategies. We aimed to characterize the chemo-preventive effects of metformin, a widely used anti-diabetic drug, on PDAC development using the Kras G12D mouse model subjected to a diet high in fats and calories (HFCD). LSL-Kras G12D/+ ;p48-Cre (KC) mice were given control diet (CD), HFCD, or HFCD with 5 mg/ml metformin in drinking water for 3 or 9 months. After 3 months, metformin prevented HFCD-induced weight gain, hepatic steatosis, depletion of intact acini, formation of advanced PanIN lesions, and stimulation of ERK and mTORC1 in pancreas. In addition to reversing hepatic and pancreatic histopathology, metformin normalized HFCD-induced hyperinsulinemia and hyperleptinemia among the 9-month cohort. Importantly, the HFCD-increased PDAC incidence was completely abrogated by metformin (p < 0.01). The obesogenic diet also induced a marked increase in the expression of TAZ in pancreas, an effect abrogated by metformin. In conclusion, administration of metformin improved the metabolic profile and eliminated the promoting effects of diet-induced obesity on PDAC formation in KC mice. Given the established safety profile of metformin, our findings have a strong translational potential for novel chemo-preventive strategies for PDAC.

Purpose: To describe a concept for prevention of secondary conditions in individuals with chronic neuromuscular disabilities by using two Swedish developed follow-up-programmes for cerebral palsy (CP; CPUP) and myelomeningocele (MMC; MMCUP) respectively as examples., Method: This paper describes and outlines the rationale, development and implementation of CPUP and MMCUP., Results: Both programmes are multidisciplinary longitudinal follow-up programmes that simultaneously serve as national registries. The programmes are population-based and set in Swedish habilitation clinics. Most children (95%) born 2000 or later with CP are enrolled in CPUP and the recruitment of adults is underway. CPUP has also been implemented in Norway, Denmark, Iceland, Scotland and parts of Australia. In MMCUP, almost all children with MMC born 2007 or later participate and individuals of all ages are now invited. The registries provide epidemiological profiles associated with CP and MMC and platforms for population-based research and quality of care improvement., Conclusions: Through multidisciplinary follow-up and early detection of emerging complications individuals with CP or MMC can receive less complex and more effective interventions than if treatment is implemented at a later stage. Possibilities and challenges to design, implement and continuously run multidisciplinary secondary prevention follow-up programmes and quality registries for individuals with CP or MMC are described and discussed. Implications for rehabilitation Individuals with disabilities such as cerebral palsy or myelomeningocele are at risk of developing secondary conditions. Multidisciplinary population-based longitudinal follow-up programmes seem effective in preventing certain types of secondary conditions.

Introduction: In necrotizing acute pancreatitis (NAP), systemic inflammatory response syndrome (SIRS) and the compensatory anti-inflammatory response syndrome (CARS) decide overall outcome and mortality. In patients, low lymphocyte counts were found, but T-helper cells seemed to conversely increase. Our aim was to further categorize T-helper cells within the context of NAP induced SIRS and CARS., Methods: NAP was induced by injection of sodium-taurocholate into the common bile duct of male BALB/c mice; sham treated animals received saline infusion. The animals were sacrificed at 6, 12, 24 and 48 h later. Lymphocytes from blood, liver and spleen were isolated and examined by flow cytometry. Staining was performed for CD4, CD8, CD19, CD45RB, CD25, CD69, and CD152. CD4 + cells were sorted for their CD45RB expression and sought for gene regulation associated to T H1 /T H2 cells by quantitative RT-PCR., Results: In NAP, CD4 + was solely increased in all compartments. CD8 + remained without substantial alterations. CD45RB showed significant expression in RB high in T-helper cells, confirmed by the CD45RB high/low ratio (Liver, 24 h: NAP 2.2, SHAM 0.6; p < 0.001). CD45RB high and -low cells were not associated to patterns of T H1 /T H2 expression. In NAP, CCR4 expression was significantly decreased within RB high cells (fold change: 0.04, p < 0.05), while TLR6 showed significant overexpression (fold change: 2.36, p < 0.05)., Conclusion: T-helper cells increase in NAP, leaning towards CD45RB high expression. They resemble naive T-cells, in which NAP leads to expression profiles associated with an innate immune response. This suggests new findings in immunological pathomechanisms of NAP., (Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: Acute necrotizing pancreatitis (NAP) induces a systemic inflammatory response syndrome. We investigated the underlying changes of monocytes using different activation markers., Materials and Methods: A retrograde injection of 2 mL/kg bodyweight of sodium taurocholate into the common bile duct of BALB/c mice induced NAP, whereas sham-operated animals (SOP) were treated with saline. After 6, 12, 24, and 48 h, histologic alterations, pancreatic enzymes, and interleukin 6 in serum, albumin, and myeloperoxidase (MPO) in bronchoalveolar lavage fluid were examined. Isolation of mononuclear cells from the blood, spleen, and liver and the subsequent determination of macrophages (F4/80) and their activation marker CD121b and MHCII (1Ad) were performed by fluorescence-activated cell sorting (FACS analyses)., Results: After pancreatitis induction, pancreatic enzymes (amylase: SOP 7008 U/L, NAP 37,044 U/L, P < 0.001) and histologic pancreatic damage (SOP 0.80 ± 1.92, NAP 19.6 ± 0.64, P < 0.001) developed instantly. Pulmonary vascular damage and MPO were detected between 6 and 12 h after onset (6 h albumin SOP 132.0 ± 12.0 μg/mL, NAP 267.2 ± 49.6 μg/mL; P < 0.05; MPO SOP 0.23 ± 0.20 ng/mL, NAP 11.29 ± 3.12 ng/mL, P < 0.01). Blood levels of interleukin 6 increased after 12-24 h (12 h SOP 584 ± 300 pg/mL; NAP 2169 ± 942 pg/mL, P < 0.05), whereas monocytes increased fourfold within 48 h (P < 0.05). Furthermore, pancreatitis increased the percentage of activated monocytes in the blood (6 h and/or 48 h: MHCII (1Ad) 2196%/5.65%; CD121b 51,654%/82,146%). Similar observations were made for monocytes from the liver and spleen., Conclusions: Although inflammatory mediators increased during 24 h after pancreatitis induction, monocyte activation lasted for at least 48 h. The latter is not limited to blood but also detected in isolated liver and spleen monocytes., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objectives: Current guidelines tell us that intervention in severe necrotizing pancreatitis ought to be performed as late as possible. However, when pancreatic necrosis becomes infected, the necrotic tissue needs to be removed. Unfortunately, bacterial infection can only be proven by invasive methods., Methods: Necrotizing pancreatitis with sterile or infected necrosis was induced in mice. Mice serum samples were examined by antibody-based protein array. After identifying candidate proteins that showed strong regulation, the serum concentration of these proteins was examined by sandwich ELISA. Then, human serum samples were collected from patients with mild pancreatitis, severe pancreatitis with and without pancreatic necrosis and patients with microbiologically proven infection of pancreatic necrosis. These serum samples were then analyzed by sandwich ELISA., Results: In mice 6 proteins were strongly up-regulated and were further investigated by ELISAs. Of these proteins, CXCL16 and TRANCE (RANKL) concentrations were analyzed in human serum samples. CXCL16 and TRANCE were increased in patients with pancreatic necrosis and abdominal infection. Receiver operated characteristics showed that CXCL16 was superior in predicting infected pancreatic necrosis when compared to C-reactive protein and TRANCE., Conclusions: Serum CXCL16 is increased in severe pancreatitis with infected pancreatic necrosis and identifies patients who benefit from surgical necrosectomy., (Copyright © 2015 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: Population-based empirical information to inform health care professionals working with children with spina bifida currently is lacking. Spina bifida is a highly complex condition that not only affects mobility but many additional aspects of life. We have developed a pilot project that focuses on a broad range of domains: surgeries, development and learning, nutrition and physical growth, mobility and functioning, general health, and family demographics. Specifically, we will: (1) explore the feasibility of identifying and recruiting participants using different recruitment sources, (2) test a multidisciplinary module to collect the data, (3) determine the utility of different methods of retrieving the data, and (4) summarize descriptive information on living with spina bifida., Objective: The overall objective of the project was to provide information for a future multistate prospective study on the natural history of spina bifida., Methods: Families with a child 3 to 6 years of age with a diagnosis of spina bifida were eligible for enrollment. Eligible families were identified through a US population-based tracking system for birth defects and from a local spina bifida clinic., Results: This is an ongoing project with first results expected in 2013., Conclusions: This project, and the planned multistate follow-up project, will provide information both to health care professionals experienced in providing care to patients with spina bifida, and to those who have yet to work with this population. The long-term purpose of this project is to increase the knowledge about growing up with spina bifida and to guide health care practices by prospectively studying a cohort of children born with this condition.

This article focuses on how the Life Course Model Web site can help family members build on the strengths of individuals with spina bifida and address areas of difficulty. A developmental perspective is adopted, which maintains that the Life Course Model Web site is useful at all stages of development, with the information provided for families at one stage of development building on the information provided for those at earlier stages of development. A brief overview is provided of relevant theories that supported the development of the Life Course Model. There is a review of the literature on the adjustment of families of individuals with spina bifida and the psychosocial adjustment of affected youth. How families may benefit from engagement with the 3 content areas covered by the Web site is discussed, namely child health and the transfer of medical management from parent to child (health/self-management), the development of social relationships (social relationships), and the achievement of milestones during emerging adulthood, including achievements in the areas of education and employment (education, employment, and income support)., (Copyright © 2010 Elsevier Inc. All rights reserved.)

This article outlines and summarizes the rationale and the working process that was undertaken by the National Spina Bifida Program to address the issues of transitioning throughout the life course for persons growing up with spina bifida. Their challenges include achieving independent living, vocational independence, community mobility, and participation in social activities, and health management. The creation, the underlying concepts, and the dissemination of the Life Course Model are described., (Published by Elsevier Inc.)

Background: The purpose of this study was to investigate whether US female adolescents who self-reported having a physical disability or long-term health problem were more likely to report having been physically forced to have sexual intercourse than US female adolescents without a physical disability or long-term health problem., Methods: Using data from the 2005 U.S. National Youth Risk Behavior Survey (YRBS), we employed logistic regression analyses to estimate the association between physical disability (and other variables) and the risk for sexual violence among US high school girls., Results: Female high school students who reported a physical disability or long-term health problem were more likely to report having been physically forced to have sexual intercourse than those who did not (19.6% vs 9.4%; chi(2) = 14.51, p = .003). Results from our multivariate analysis reveal that this association remained significant (adjusted odds ratio [AOR], 1.57; 95% confidence interval [CI], 1.10-2.23) after adjusting for certain demographic characteristics, physical health problems, behavioral health risks, and violent conduct., Conclusions: Our findings suggest that adolescent girls in the United States with a physical disability or long-term health problem may be at increased risk for sexual violence. It is important that national efforts to reduce sexual violence consider how to address the unmet needs of children and adolescents with disabilities. As most adolescent girls spend the majority of their time in a school setting, it is of particular importance that school health professionals are aware of the current findings.

Objective: The purpose of this study was to determine the association between in utero exposure to acute inflammation and long-term major neurodevelopmental disability at age 6 years among children born prior to 32 weeks' gestation., Study Design: This was a follow-up investigation of a cohort of maternal-infant dyads delivered between 23 and < 32 weeks' gestation. Surviving infants (and their mothers or caregivers) underwent a battery of psychological and neurodevelopmental tests between 5 and 8 years of age. Pregnancy and neonatal data were analyzed among children with versus those without major neurodevelopmental disability (including IQ < 70 [n = 41], cerebral palsy [CP, n = 11], and a composite major disability [n = 52])., Results: A total of 261 (70%) of the 375 maternal-infant dyads with surviving children were successfully recruited and evaluated at 6.8 +/- 0.7 years. Mean delivery gestational age (GA) and birthweight were 28.8 +/- 2.2 weeks and 1163 +/- 382 g, respectively. Neither surrogate indicators for nor direct markers of in utero exposure to acute inflammation were significantly associated with severe adverse outcomes. Delivery GA was significantly associated with outcome. Logistic regression indicated that each increasing gestational week was associated with a significantly decreased risk of an IQ < 70 (OR 0.75, 95% CI 0.6-0.9). An average 1.9 point increase in IQ at 6 years of age was observed per gestational week gained (23 to 32 weeks). Periventricular leukomalacia was associated with a 9.6 point mean deficit in IQ. The perceptive vocabulary scores (IQ proxy) of primary caregivers were significantly lower among children with an IQ < 70 vs > or = 70 (87.5 +/- 11.5 vs 92.1 +/- 11.2, P = .016)., Conclusion: Among children born between 23 and 32 weeks' gestation, neonatal complications, GA at delivery, and caregiver IQ, but not in utero exposure to acute inflammation, were associated with increased risk of severe adverse neurodevelopmental outcomes at age 6 years.

Background: A survey on the practice of laparoscopic and thoracoscopic surgery in pediatric surgical departments in Germany is presented., Materials and Methods: A questionnaire was sent to all 71 pediatric surgical departments in Germany (population 82 million). Fifty institutions (70%) took part in the survey that mainly included data for the year 2004: spectrum of minimally invasive operations, quantity of procedures, conversions, major complications, number of performing surgeons and residents., Results: Laparoscopic techniques were used in 48 departments (96%) and thoracoscopic techniques in 37 (74%). The annual frequency of laparoscopies was less than 100 in 30 departments (62%) and more than 100 in 15 (31%). The number of thoracoscopies was less than 50 in 35 departments (73%) and more than 50 in 2 (4%). Appendectomy was offered in 45 (90%), varicocelectomy in 32 (64%), and Fowler-Stephens operation in 33 (66%). Twenty-one departments (42%) covered more advanced procedures such as laparoscopically assisted pull-through for Hirschsprung disease. Most demanding procedures such as laparoscopic choledochal cyst resection, duodeno-duodenostomy, heminephrectomy, or pyeloplasty were offered by 10 departments (20%). Minimally invasive surgery was performed by 1 surgeon (12%) in 6 institutions and by more than 5 surgeons (14%) in 7 institutions., Conclusion: Minimally invasive techniques are increasingly accepted in most German pediatric surgical institutions for a wide range of indications. However, the number of departments offering major minimally invasive procedures remains limited.

Objectives: To examine the influences from life stress and the hypothesized protective variables of social competence, family functioning, and peer social engagement on quality of life (QL) in adolescents with mobility disabilities within a stress-resilience model., Methods: Variables were assessed with questionnaires completed by 159 adolescents with a mobility disability (aged 11-18 years) and their parents. Both more subjective and objective QL measures were completed using both adolescent and parent reports., Results: Increased life stress was associated with worse QL. Hypothesized protective variables were used to explain significant variance in more subjective, but not objective, measures of QL beyond covariates and life stress. The hypothesized protective variables, however, did not moderate the effects of life stress on QL. There was a cumulative effect from the hypothesized protective variables such that adolescents with more of these factors had more subjective QL than those with just one factor, regardless of the specific factor., Conclusions: Consistent with the tested model, interventions to improve QL in adolescents with a mobility disability may focus on reducing life stress and developing resilience by enhancing a variety of personal and social resources.

Background/purpose: Fast-track surgery is not well established for infants and children. The aim of our prospective study was to investigate the feasibility of fast-track concepts for pediatric surgical procedures including laparoscopic techniques., Methods: Fast-track concepts, including immediate postoperative feeding, immediate mobilization, and morphine sparing pain treatment, were established for pyeloplasty, appendectomy, bowel anastomosis, fundoplication, hypospadia repair, and full/partial nephrectomy. All consecutive patients undergoing these procedures were prospectively investigated from June 2004 to June 2005. Patients with additional relevant diseases, reoperation, and perforated appendicitis were excluded from fast-track treatment. The length of hospital stay was compared with data derived from the German reimbursement system with German diagnosis-related groups for patients with a similar case mix index and hospitals with a similar structure., Results: Of a total of 159 patients (mean age, 5.8 +/- 5.3 years), 113 (71%) were finally treated according to the fast-track protocols. There were no complications associated with fast-track surgery. The intensity of pain during the immediate postoperative period was higher than 5 on a 10-point scale in children older than 4 years. Analgesia was excellent at all other time points. The mean hospital stay of fast-track patients was 2.3 +/- 1 days and was significantly shorter (P < .01) compared with German diagnosis-related group data for all procedures (pyeloplasty, 1.9 +/- 0.9 vs 12.2 +/- 0.2; nephrectomy, 1.9 +/- 1.0 vs 14.4 +/- 2.8; bowel anastomosis, 3.2 +/- 0.6 vs 12.9 +/- 2.4; fundoplication, 3.2 +/- 0.8 vs 15.2 +/- 4.2; appendectomy, 3.7 +/- 2.4 vs 6.3 +/- 1.8; hypospadia repair, 2.1 +/- 1 vs 8.4 +/- 1.4). Two readmissions were recorded. Ninety-six percent of patients and parents scored the fast-track concepts as excellent., Conclusion: The feasibility of fast-track concepts in children is excellent, with short duration of hospitalization and high comfort.

Background: Gastric perforation is a rare, life-threatening condition in neonates. To avoid deterioration, prompt surgical treatment is mandatory., Patients: We report on 2 neonates (1 and 8 days old) with feeding tube associated gastric perforation managed laparoscopically by single layer suture repair. Both children suffered from severe peritonitis. Operative time was 60 minutes in both cases. Oral feeding was started on postoperative day 3 and 7, respectively. No complications regarding the gastric perforation were encountered on follow-up (11 and 8 months, respectively) in both cases., Conclusions: We recommend laparoscopic suture repair as a safe and feasible method for surgical treatment of gastric perforation in neonates. These appear to be the first reported cases using this procedure for treatment of neonatal gastric perforation.

Background: Minimally invasive techniques are increasingly applied to children with malignant tumors. We showed previously that CO(2) used for pneumoperitoneum modulates the function of macrophages and polymorphonuclear cells via direct effects and via acidification. Numerous in vitro and small animal model studies also confirmed an alteration of the behavior of several types of adult tumor cells by CO(2). The impact of CO(2) and other gases used for pneumoperitoneum on the behavior of various pediatric tumors has not yet been determined., Methods: Cell lines of neuroblastoma (IMR 32, SK-N-SH, Sy5y), lymphoma (Daudi), hepatoblastoma (Huh 6), hepatocellular carcinoma (Hep G2), and rhabdomyosarcoma (Te 671) were incubated for 2 h. Incubation was performed with 100% CO(2), 100% helium, and 5% CO(2) as control. Cell proliferation was determined by the MTT-assay [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] by actively growing cells to produce a blue formazan product. The MTT-assay was performed before, directly after incubation, and daily for 4 days. Vitality of the cells was determined by trypan blue. The extracellular pH during incubation was measured during gas exposition every 10 min using Bayer Rapid Lab 855., Results: CO(2) for 2 h significantly decreased the proliferation of neuroblastoma, lymphoma, hepatoblastoma, and hepatocellular carcinoma cells. This decrease persisted over 4 days in neuroblastoma, lymphoma, and hepatocellular carcinoma cells. The CO(2) had no impact on hepatoblastoma and rhabdomyosarcoma cells. Helium had a similar effect on neuroblastoma cells. After 4 days, a significant decrease of cell activity was found in two neuroblastoma cell lines and in hepatoblastoma cells. Helium had no effect on lymphoma and hepatocellular carcinoma cells. The extracellular pH was 6.2 during incubation with CO(2), and 7.6 during incubation with helium., Conclusion: CO(2) and helium may affect the proliferation of some pediatric tumor cell lines in vitro. However, some of these effects and the impact on the extracellular pH are differential. The role of pH modulation, hypoxia and direct effects of gases remain to be investigated before a general recommendation on the use of minimally invasive techniques in pediatric oncology can be given.

Background: There is no generally accepted standard surgical approach to gastrooesophageal reflux disease (GERD) at present. However, laparoscopic fundoplication has been advocated to be the procedure of choice for gastrooesophageal reflux disease in children. We aimed to assess the standards of the diagnostic workup and operative techniques in paediatric surgical institutions in Germany., Material and Methods: A questionnaire including 14 items was sent to all 71 departments of paediatric surgery in Germany. Forty (56 %) took part in the survey. Concepts of routine diagnostic workup, operative techniques, number of procedures, and conversions were assessed., Results: The average annual frequency of fundoplications was less than 20 in 36 units (90 %). Experience with laparoscopic fundoplication was present in 24 institutions (60 %). In 19 out of these (79 %) fewer than 50 laparoscopic fundoplications had been performed altogether up to the time of the survey. Out of 584 fundoplications performed in the year 2002, 184 (32 %) had been done laparoscopically. The ratio of conventional versus laparoscopic fundoplication was 170/130 (57/43 %) in academic, and 226/54 (81/19 %) in non-academic departments. The preferred technique of fundoplication, irrespective of the approach, was the Nissen wrap in 28 (70 %) of the departments. The number of paediatric surgeons performing laparoscopic fundoplication was 1 - 2 in 16 institutions (67 %), 3 or 4 in 6 (25 %), and 5 in 2 (8 %) departments. The conversion rate was reported to be less than 5 % in 15 departments (63 %), and 5 - 10 % in 3 (13 %)., Conclusion: The laparoscopic approach for surgical repair of GERD in children is not yet generally accepted in Germany. In most departments, training remains problematic due to low numbers of procedures. However, the feasibility of laparoscopic fundoplication in Germany is excellent, with a low rate of conversions.

Numerous investigators have shown that video-assisted thoracoscopic surgery (VATS) can be safely used for specific conditions of newborns, infants, and children. The technique has been postulated to be associated with a lower morbidity, shorter hospital stay, lower costs, and clinical results similar to those achieved by open surgery. The present article reviews the state of the art of VATS for thoracic conditions in children. Most authors focus on the feasibility of single procedures, and only a small number of reports deals with the feasibility in series with multiple types of procedures and larger numbers of patients. Therefore, systematic research on the advantages and limits of VATS in children remains mandatory.

Background: The feasibility of laparoscopic resection of choledochal cyst and hepaticojejunostomy in children is still unclear. This report presents the author's experience with a first series of patients., Methods: Data from 11 consecutive children (median age 17.5 months, SD 22, range 2 to 70) with choledochal cyst scheduled for laparoscopy were collected prospectively. There were nine type I and 2 type V cysts according to Todani's classification. All except one patient had intermittent jaundice or recurrent pancreatitis. The laparoscopic technique included excision of the cyst. A Roux-en-Y anastomosis was constructed after exteriorization of the small bowel via the infraumbilical trocar incision. After repositioning of the bowel an end-to-side hepaticojejunostomy was carried out laparoscopically., Results: The procedures were carried out in nine children without intraoperative events and a median duration of 289 min (SD 62). In two patients, the operation was converted after 60 and 90 min due to a lack of overview at the dorsal margin with problems in separation of the portal vein. Oral food intake was started within 2 days and tolerated well in all except one patient, in whom biliar fluid from the drain led to laparoscopic reevaluation on day 1. A small leak was resutured and the patient was discharged on day 5. In one patient, recurrent cholangitis and a dilated Roux-en-Y loop led to correction of some kinking of the loop via laparotomy after 3 months. All other patients are well with bile-stained stools after a mean follow-up of 13 months., Conclusions: Laparoscopic resection of congenital choledochal cyst and choledochojejunostomy in children is feasible. We feel that there is a considerable learning curve with the technique. Future studies will have to prove the feasibility of laparoscopic Roux-en-Y bowel anastomosis without the need for bowel exteriorization.

We present a case of prenatally diagnosed gastroschisis combined with a sternal cleft, as well as the successful surgical management of this unusual condition. Successful management of gastroschisis combined with sternal cleft has not been reported before in the literature.

The etiology of gastroschisis is still unclear. To the authors' knowledge, there are only 14 cases of familial gastroschisis in the literature. The authors add the second case of mother-and-son occurrence and a case of siblings occurrence, thereby updating the current literature for family gastroschisis.