| 1. |
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| 2. |
- Celik, Selvi, et al.
(author)
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Extracellular Vesicle-Associated TWEAK Contributes to Vascular Inflammation and Remodeling During Acute Cellular Rejection
- 2023
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In: JACC: Basic to Translational Science. - : Elsevier BV. - 2452-302X. ; 8:5, s. 439-456
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Journal article (peer-reviewed)abstract
- Acute cellular rejection (ACR) is a leading cause of graft loss and death after heart transplantation despite effective immunosuppressive therapies. The identification of factors that impair graft vascular barrier function or promote immune cell recruitment during ACR could provide new therapeutic opportunities for the treatment of patients who receive transplants. In 2 ACR cohorts, we found the extracellular vesicle-associated cytokine TWEAK to be elevated during ACR. Vesicular TWEAK promoted expression of proinflammatory genes and the release of chemoattractant cytokines from human cardiac endothelial cells. We conclude that vesicular TWEAK is a novel target with potential therapeutic implications in ACR.
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| 3. |
- Egerstedt, Anna, et al.
(author)
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Bioactive adrenomedullin for assessment of venous congestion in heart failure
- 2022
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In: ESC Heart Failure. - : Wiley. - 2055-5822. ; 9:5, s. 3543-3555
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Journal article (peer-reviewed)abstract
- Aims: Bioactive adrenomedullin (bio-ADM) is a vascular-derived peptide hormone that has emerged as a promising biomarker for assessment of congestion in decompensated heart failure (HF). We aimed to evaluate diagnostic and prognostic performance of bio-ADM for HF in comparison to amino-terminal pro-B-type natriuretic peptide (NT-proBNP), with decision thresholds derived from invasive haemodynamic and population-based studies. Methods and results: Normal reference ranges for bio-ADM were derived from a community-based cohort (n = 5060). Correlations with haemodynamic data were explored in a cohort of HF patients undergoing right heart catheterization (n = 346). Mortality and decision cutoffs for bio-ADM was explored in a cohort of patients presenting in the ER with acute dyspnoea (n = 1534), including patients with decompensated HF (n = 570). The normal reference range was 8–39 pg/mL. The area under the receiver operating characteristic curve (AUROC) for discrimination of elevated mean right atrial pressure (mRAP) and pulmonary arterial wedge pressure (PAWP) was 0.74 (95% CI = 0.67–0.79) and 0.70 (95% CI = 0.64–0.75), respectively, with optimal bio-ADM decision cutoff of 39 pg/mL, concordant with cubic spline analyses. NT-proBNP discriminated PAWP slightly better than mRAP (AUROC 0.73 [95% CI = 0.68–0.79] and 0.68 [95% CI = 0.61–0.75]). Bio-ADM correlated with (mRAP, r = 0.55) while NT-proBNP correlated with PAWP. Finally, a bio-ADM decision cutoff of 39 pg/mL associated with 30 and 90 day mortality and conferred a two-fold increased odds of HF diagnosis, independently from NT-proBNP. Conclusions: Bio-ADM tracks with mRAP and associates with measures of systemic congestion and with mortality in decompensated HF independently from NT-proBNP. Our findings support utility of bio-ADM as a biomarker of systemic venous congestion in HF and nominate a decision threshold.
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| 4. |
- Ghosh, Nilanjana, et al.
(author)
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Analysis of plasma metabolomes from 11 309 subjects in five population-based cohorts.
- 2024
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In: Scientific Reports. - 2045-2322. ; 14:1, s. 8933-
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Journal article (peer-reviewed)abstract
- Plasma metabolomics holds potential for precision medicine, but limited information is available to compare the performance of such methods across multiple cohorts. We compared plasma metabolite profiles after an overnight fast in 11,309 participants of five population-based Swedish cohorts (50-80 years, 52% women). Metabolite profiles were uniformly generated at a core laboratory (Metabolon Inc.) with untargeted liquid chromatography mass spectrometry and a comprehensive reference library. Analysis of a second sample obtained one year later was conducted in a subset. Of 1629 detected metabolites, 1074 (66%) were detected in all cohorts while only 10% were unique to one cohort, most of which were xenobiotics or uncharacterized. The major classes were lipids (28%), xenobiotics (22%), amino acids (14%), and uncharacterized (19%). The most abundant plasma metabolome components were the major dietary fatty acids and amino acids, glucose, lactate and creatinine. Most metabolites displayed a log-normal distribution. Temporal variability was generally similar to clinical chemistry analytes but more pronounced for xenobiotics. Extensive metabolite-metabolite correlations were observed but mainly restricted to within each class. Metabolites were broadly associated with clinical factors, particularly body mass index, sex and renal function. Collectively, our findings inform the conduct and interpretation of metabolite association and precision medicine studies.
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| 5. |
- Ghosh, Nilanjana, et al.
(author)
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Analysis of plasma metabolomes from 11 309 subjects in five population-based cohorts.
- 2024
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In: Scientific Reports. - 2045-2322. ; 14:1
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Journal article (peer-reviewed)abstract
- Plasma metabolomics holds potential for precision medicine, but limited information is available to compare the performance of such methods across multiple cohorts. We compared plasma metabolite profiles after an overnight fast in 11,309 participants of five population-based Swedish cohorts (50-80years, 52% women). Metabolite profiles were uniformly generated at a core laboratory (Metabolon Inc.) with untargeted liquid chromatography mass spectrometry and a comprehensive reference library. Analysis of a second sample obtained one year later was conducted in a subset. Of 1629 detected metabolites, 1074 (66%) were detected in all cohorts while only 10% were unique to one cohort, most of which were xenobiotics or uncharacterized. The major classes were lipids (28%), xenobiotics (22%), amino acids (14%), and uncharacterized (19%). The most abundant plasma metabolome components were the major dietary fatty acids and amino acids, glucose, lactate and creatinine. Most metabolites displayed a log-normal distribution. Temporal variability was generally similar to clinical chemistry analytes but more pronounced for xenobiotics. Extensive metabolite-metabolite correlations were observed but mainly restricted to within each class. Metabolites were broadly associated with clinical factors, particularly body mass index, sex and renal function. Collectively, our findings inform the conduct and interpretation of metabolite association and precision medicine studies.
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| 6. |
- Gjesdal, Grunde, et al.
(author)
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Validation of cause of death classification after heart transplantation and cause-specific life expectancy compared to the general population
- 2022
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In: Clinical Transplantation. - : Wiley. - 0902-0063 .- 1399-0012. ; 36:9
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Journal article (peer-reviewed)abstract
- Background: Post heart-transplant survival has increased, but information is lacking on specific causes of death and life expectancy. We aimed to assess cause-specific loss of life-years compared to the general population, evaluate classification for cause of death after heart transplantation, and assess validity of cause of death data from the International Society of Heart and Lung Transplant (ISHLT) registry. Methods: In this single center study, we included 239 heart recipients transplanted between 1988 and 2019 in Lund, Sweden (n = 239, 50% of the transplanted population where the cause of death was available). Two cardiologists retrospectively assigned causes of death according to a published classification (CLASS) in the 91 recipients who died during follow-up. Life expectancy was compared to data from the general population. Results: Compared to the average Swedish population, life expectancy for heart transplant recipients was 20 years shorter (IQR 12.9–27.2). The largest number of life-years lost were for deaths due to acute (49 years) and chronic rejection (27 years). Primary graft dysfunction (24 years) accounted for 24% of deaths, followed by malignancy (20 years) and infection (17 years), each accounting for ∼20% of deaths. Use of CLASS revealed moderate inter-rater agreement (56%) and moderate agreement with the ISHLT registry (62%). Conclusions: Survival after heart transplantation was 20 years lower than in the general population. In the young, more life-years were lost due to acute graft rejection, whereas chronic graft rejection and primary graft failure were more important causes of death in older patients. Agreement was moderate between CLASS and the ISHLT registry classifications.
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| 7. |
- Hägglund, Gunnar, et al.
(author)
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Back pain is more frequent in girls and in children with scoliosis in the context of cerebral palsy
- 2019
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In: Acta Paediatrica, International Journal of Paediatrics. - : Wiley. - 0803-5253. ; 108:12, s. 2229-2234
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Journal article (peer-reviewed)abstract
- 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.
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| 8. |
- Hägglund, Gunnar, et al.
(author)
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Incidence of scoliosis in cerebral palsy : A population-based study of 962 young individuals
- 2018
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In: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 89:4, s. 443-447
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Journal article (peer-reviewed)abstract
- Background and purpose - Surveillance of scoliosis in individuals with cerebral palsy (CP) is important for ensuring timely diagnosis and identification of curve progression. We analyzed the incidence of scoliosis in relation to age, sex, and gross motor function in a population-based cohort of individuals with CP.Patients and methods - This was a prospective register study of all 1,025 individuals born 1990-2012 in southern Sweden (1.4 million inhabitants) in the Swedish surveillance program for CP, which included >95% of the total population of people with CP in the area. Annual clinical examinations and radiographic measurement of the Cobb angle of those with a moderate or severe scoliosis were registered. We determined the incidence of scoliosis related to age, sex, and the Gross Motor Function Classification System (GMFCS) level.Results - The inclusion criteria were fulfilled by 962 individuals. The number of people (140/962) with scoliosis increased up to 20-25 years of age. The incidence of scoliosis was related to age and GMFCS level. In individuals at the lowest level of gross motor function (GMFCS V) scoliosis was seen in 10/131 before 5 years of age and at the age of 20 years 75% of these individuals had a Cobb angle >= 40 degrees. No one in the highest level of motor function (GMFCS I) developed a Cobb angle > 40 degreesInterpretation - Surveillance programs for scoliosis in CP should be based on age and GMFCS level and should be initiated at a young age and continued into adulthood.
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| 9. |
- Hägglund, Gunnar, et al.
(author)
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Self-versus Proxy-Reported Pain in Children with Cerebral Palsy : A Population-Based Registry Study of 3783 Children
- 2020
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In: Journal of Primary Care and Community Health. - : SAGE Publications. - 2150-1319 .- 2150-1327. ; 11
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Journal article (peer-reviewed)abstract
- 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.
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| 10. |
- Ibounig, Thomas, et al.
(author)
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Concordance of shoulder symptoms and imaging findings: a protocol for the Finnish Imaging of Shoulder (FIMAGE) study
- 2023
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In: BMJ open. - 2044-6055. ; 13:12
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Journal article (peer-reviewed)abstract
- INTRODUCTION: Shoulder pain is a substantial medical and socioeconomic problem in most societies, affecting the ability to work or carry out leisure time activities as well as subsequently influencing physical and psychological well-being. According to a nationwide survey in Finland, 27% of the population reported shoulder pain within the last 30 days. In clinical practice, imaging findings of structural abnormalities are typically thought to explain symptoms, even though such findings are also prevalent in asymptomatic individuals, particularly with increasing age. Overall, there is a paucity of high-quality evidence on the prevalence, clinical relevance and prognosis of 'abnormal' imaging findings of the shoulder.The aim of the Finnish Imaging of Shoulder (FIMAGE) study is fourfold: to assess (1) the prevalence of shoulder symptoms and the most common anatomical variants and imaging abnormalities of the shoulder; (2) the concordance between shoulder symptoms, function and imaging abnormalities; (3) the most important determinants of symptoms, function and imaging abnormalities; and (4) the course of shoulder complaints over 5 years. METHODS: The FIMAGE target population of 600 participants, aged 40-75 years, will be randomly selected from a nationally representative general population sample of 9922 individuals originally recruited for the Finnish Health 2000 Survey. On giving informed consent, the participants will be invited to a clinical visit that includes assessment of general health, shoulder symptoms, bilateral shoulder examination and imaging of both shoulders with plain radiography and MRI. ETHICS AND DISSEMINATION: The study has been approved by the Institutional Review Board of the Helsinki and Uusimaa Hospital District. The findings will be published according to the Strengthening the Reporting of Observational Studies in Epidemiology criteria.
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| 11. |
- Ivarsson, Kerstin M., et al.
(author)
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Cardiovascular and Cerebrovascular Events After Parathyroidectomy in Patients on Renal Replacement Therapy
- 2019
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In: World Journal of Surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 43:8, s. 1981-1988
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Journal article (peer-reviewed)abstract
- Background: A majority of patients with end-stage renal disease suffer from secondary hyperparathyroidism, which is associated with osteoporosis and cardiovascular disease. Parathyroidectomy (PTX) is often necessary despite medical treatment. However, the effect of PTX on cardio- and cerebrovascular events (CVE) remains unclear. Data on the effect of PTX from population-based studies are scarce. Some studies have shown decreased incidence of CVE after PTX. The aim of this study was to evaluate the effect of PTX on risk of CVE in patients on renal replacement therapy. Methods: We performed a nested case–control study within the Swedish Renal Registry (SRR) by matching PTX patients on dialysis or with functioning renal allograft with up to five non-PTX controls for age, sex and underlying renal disease. To calculate time to CVE, i.e., myocardial infarct, stroke and transient ischemic attack, control patients were assigned the calendar date (d) of the PTX of the case patient. Crude and adjusted proportional hazards regressions with random effect (frailty) were used to calculate hazard ratios for CVE. Results: The study cohort included 20,056 patients in the SRR between 1991 and 2009. Among these, 579 patients had undergone PTX, 423 during dialysis and 156 during time with functioning renal allograft. These patients were matched with 1234 dialysis and 736 transplanted non-PTX patients. The adjusted hazard ratio (HR) with 95% confidence interval (CI) of CVE after PTX was 1.24 (1.03–1.49) for dialysis patients compared with non-PTX patients. Corresponding results for patients with renal allograft at d were HR (95% CI) 0.53 (0.34–0.84). Conclusions: PTX patients on dialysis at d had a higher risk of CVE than patients without PTX. Patients with renal allograft at d on the other had a lower risk after PTX than patients without PTX.
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| 12. |
- Johansson, Madeleine, et al.
(author)
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Pharmacometabolomic Profiling Of The General Population: Relation Of Active Metabolite Levels To Cardiovascular Risk Factor Control And Manifest Atherosclerosis
- 2021
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In: Circulation. - 1524-4539. ; 144:suppl_1
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Conference paper (peer-reviewed)abstract
- Introduction: The use of medications in the general population has increased over time. Information on active metabolite concentrations for common drugs in the general population is limited. Recent advances in metabolomic technologies have made high-throughput profiling of many active metabolites in large epidemiological cohorts increasingly feasible.Aim: 1. Prospective assessment of the proportion of measurable active metabolite levels of major drugs in the general population using mass spectrometry. 2. Relation of cardiovascular (CV) drugs with inadequate risk factor control and CV disease.Methods: Assessment of CV risk factors by coronary CT angiography and carotid ultrasound imaging in a large prospective cohort of 6,251 individuals randomly selected from the general population in Malmö, Sweden (age 50-64 years). Untargeted metabolomic profiling of fasting plasma was performed by Metabolon, USA in a random subset of 3,986 subjects.Results: Intake of at least one prescribed drug was reported in 1840 subjects (46%). Combination drugs were reported in 249 subjects (6%). The most common drug classes reported were lipid-lowering (n=369, 9% of which most were statins), beta blockers (n=307, 8%), ARB (n=272, 7%), and ACE inhibitors (268, 7%), followed by levothyroxine, CCB, antidepressants, glucocorticoids, PPI, antidiabetic, bronchodilators and diuretics. For major CV drugs, detectable active metabolite levels ranged from 54% (atorvastatin and enalapril) to 96% (metoprolol and metformin). Non-detectable levels of lipid-lowering, antihypertensive, and antidiabetic drugs were associated with higher LDL, cholesterol, BP and glucose, although only antidiabetic drugs were significant (p<0.05). Non-detectable levels of lipid-lowering and antihypertensive drugs were also non-significantly associated with increased coronary calcium and carotid plaque.Conclusion: Our study provides an overview of the distribution of common drugs with detectable levels in a contemporary Swedish population. Pharmacometabolomic profiling revealed that non-measurable levels of common CV drugs were associated with lower risk factor control and non-significant trends towards more atherosclerotic disease by imaging in a substantial number of subjects.
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| 13. |
- Linton, Gustaf, et al.
(author)
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Epidemiology of fractures in children with cerebral palsy : a Swedish population-based registry study
- 2022
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In: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 23, s. 1-10
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Journal article (peer-reviewed)abstract
- 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.
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| 14. |
- Lumbers, R. T., et al.
(author)
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The genomics of heart failure: design and rationale of the HERMES consortium
- 2021
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In: Esc Heart Failure. - : Wiley. - 2055-5822. ; 8:6, s. 5531-5541
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Journal article (peer-reviewed)abstract
- Aims The HERMES (HEart failure Molecular Epidemiology for Therapeutic targets) consortium aims to identify the genomic and molecular basis of heart failure. Methods and results The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of >1.10 for common variants (allele frequency > 0.05) and >1.20 for low-frequency variants (allele frequency 0.01-0.05) at P < 5 x 10(-8) under an additive genetic model. Conclusions HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.
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| 15. |
- Lundkvist Josenby, Annika, et al.
(author)
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Gender differences in treatments and interventions received by children and adolescents with cerebral palsy
- 2020
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In: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 20:1
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Journal article (peer-reviewed)abstract
- 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.
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| 16. |
- Manousaki, Evgenia, et al.
(author)
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Evaluation of gait, relapse and compliance in clubfoot treatment with custom-made orthoses
- 2016
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In: Gait and Posture. - : Elsevier BV. - 0966-6362. ; 50, s. 8-13
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Journal article (peer-reviewed)abstract
- Relapse after successful initial correction of idiopathic clubfoot with the Ponseti method is often related to poor compliance with the foot abduction orthosis (FAO). The aim of this study was to evaluate treatment with custom-made dynamic orthoses. Twenty children with idiopathic clubfoot (30 feet) who had been treated with dynamic orthoses after the correction phase according to the Ponseti casting technique were evaluated. Relapse rates during orthotic treatment were registered. A Vicon gait analysis system was used to measure gait parameters at the age of seven years. The overall gait quality was estimated with the Gait Deviation Index (GDI). Data were analyzed with a nested mixed model and compared with a control group of 16 healthy children. No relapse occurred during the orthotic treatment. High compliance with the orthoses was observed based on parents’ self report and physiotherapist observations. Gait analysis showed decreased ankle power and moment, increased internal foot progression, decreased dorsiflexion during stance, and increased plantar flexion at initial contact compared with the control group. Hip and shank rotations were normal. No calcaneus or equinus gait was observed. The mean GDI was 89.7 (range 71.6–104). The gait analysis outcomes and frequency of relapse were comparable to those of previous studies. Internal foot progression originated primarily from the foot level and was not, as frequently found after FAO treatment, compensated by external rotation at knee or hip level. In children exhibiting poor compliance with an FAO, this dynamic model is considered an effective alternative.
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| 17. |
- Noten, S., et al.
(author)
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Probability of independent walking and wheeled mobility in individuals with cerebral palsy
- 2024
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In: Developmental Medicine and Child Neurology. - 0012-1622. ; 66:3, s. 326-332
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Journal article (peer-reviewed)abstract
- Aim: To estimate the probability of independent walking and wheeled mobility in individuals with cerebral palsy (CP) at home and in the community in relation to age and gross motor function.Method: This was a longitudinal cohort study using data reported into the combined Swedish CP follow-up programme and national quality registry from October 2000 to October 2022. Walking, walking with aids, wheeled mobility, and assisted mobility defined independent or assisted mobility at home and in the community, based on the Functional Mobility Scale with additional data on wheelchair performance, were assessed.Results; There were 52 858 examinations reported for 6647 individuals with CP (age range 0-32 years, follow-up period 0-22 years). Most children and adults in Gross Motor Function Classification System (GMFCS) levels I or II walked without assistive devices. The probability of dependence on others for mobility in the community was high for both children and adults in GMFCS levels III to V.Interpretation: Although independent mobility is vital for participation and social inclusion, many children and adults with CP are dependent on others for mobility. We recommend clinicians, together with families and individuals with CP, explore how to increase access to independent mobility from an early age and continuously throughout the life course.
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| 18. |
- O'Regan, Elisabeth, et al.
(author)
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Cognitive assessments among children with cerebral palsy in Sweden and the use of augmentative and alternative communication and interpreters : a cross-sectional registry study
- 2023
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In: Disability and Rehabilitation. - : Informa UK Limited. - 0963-8288 .- 1464-5165. ; 45:22, s. 3656-3667
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Journal article (peer-reviewed)abstract
- 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.
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| 19. |
- Persson-Bunke, Måns, et al.
(author)
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Psychometric evaluation of spinal assessment methods to screen for scoliosis in children and adolescents with cerebral palsy
- 2015
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In: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 16
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Journal article (peer-reviewed)abstract
- Background: In cerebral palsy (CP) there is an increased risk of scoliosis. It is important to identify a progressive scoliosis early-on because the results of surgery depend on the magnitude of the curve. The Swedish follow-up program for cerebral palsy (CPUP) includes clinical examinations of the spine. The reliability and validity of the assessment method have not been studied. In this study we evaluate the interrater reliability of the clinical spinal examination used in CPUP and scoliometer measurement in children with CP and we evaluate their validity compared to radiographic examination. Methods: Twenty-eight children (6-16 years) with CP in Gross Motor Function Classification System levels II-V were included. Clinical spinal examinations and scoliometer measurements in sitting position were performed by three independent examiners. The results were compared to the Cobb angle as determined by radiographic measurement. Interrater reliability was calculated using weighted kappa. Concurrent validity was analyzed using the Cobb angle as gold standard. Sensitivity, specificity, area under receiver operating characteristic curves (AUC) and likelihood ratios (LR) were calculated. Cut-off values for scoliosis were set to >= 20 degrees Cobb angle and >= 7 degrees scoliometer angle. Results: There was an excellent interrater reliability for both clinical examination (weighted kappa = 0.96) and scoliometer measurement (weighted kappa = 0.86). The clinical examination showed a sensitivity of 75 % (95 % CI: 19.4-99.4 %), specificity of 95.8 % (95 % CI: 78.9-99.9 %) and an AUC of 0.85 (95 % CI: 0.61-1.00). The positive LR was 18 and the negative LR was 0.3. The scoliometer measurement showed a sensitivity of 50 % (95 % CI: 6.8-93.2 %), specificity of 91.7 % (95 % CI: 73.0-99.0 %) and AUC of 0.71 (95 % CI: 0.42-0.99). The positive LR was 6 and the negative LR was 0.5. Conclusion: The psychometric evaluation of the clinical examination showed an excellent interrater reliability and a high concurrent validity compared to the Cobb angle. The findings should be interpreted cautiously until research with larger samples may further quantify the psychometric properties. Clinical spinal examinations seem appropriate as a screening tool to identify scoliosis in children with CP.
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| 20. |
- Pimpalwar, Neha, et al.
(author)
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Analysis of genetic variant associated with heart failure mortality implicates thymic stromal lymphopoietin as mediator of strain-induced myocardial fibroblast-mast cell crosstalk and fibrosis
- 2024
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In: FASEB JOURNAL. - 0892-6638 .- 1530-6860. ; 38:4
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Journal article (peer-reviewed)abstract
- Heart failure (HF) is a leading cause of death and disability globally. Heritable factors and the extent and pattern of myocardial fibrosis are important determinants of outcomes in patients with HF. In a genome-wide association study of mortality in HF, we recently identified a genetic polymorphism on chromosome 5q22 associated with HF mortality. Here, we sought to study the mechanisms by which this variant may influence myocardial disease processes. We find that the risk allele is located in an enhancer motif upstream of the TSLP gene (encoding thymic stromal lymphopoietin), conferring increased binding of the transcription factor nescient helix-loop helix 1 (NHLH1) and increased TSLP expression in human heart. Further, we find that increased strain of primary human myocardial fibroblasts results in increased TSLP expression and that the TSLP receptor is expressed in myocardial mast cells in human single nuclei RNA sequence data. Finally, we show that TSLP overexpression induces increased transforming growth factor beta expression in myocardial mast cells and tissue fibrosis. Collectively, our findings based on follow-up of a human genetic finding implicate a novel pathway in myocardial tissue homeostasis and remodeling. The extent and patterning of myocardial fibrosis are important determinants of outcome in heart disease. Here, we report that increased strain in myocardial cells results in increased expression of thymic stromal lymphopoietin (TSLP). Furthermore, increased TSLP expression, modulated by the transcription factor nescient helix-loop helix 1 (NHLH1), induces increased transforming growth factor beta (TGF-beta) expression in myocardial mast cells and tissue fibrosis. Our findings thus implicate a novel pathway in myocardial tissue homeostasis and putative therapeutic target to prevent fibrosis.image
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| 21. |
- Pimpalwar, Neha, et al.
(author)
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Methods for isolation and transcriptional profiling of individual cells from the human heart
- 2020
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In: Heliyon. - : Elsevier BV. - 2405-8440. ; 6:12
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Journal article (peer-reviewed)abstract
- Background: Global transcriptional profiling of individual cells represents a powerful approach to systematically survey contributions from cell-specific molecular phenotypes to human disease states but requires tissue-specific protocols. Here we sought to comprehensively evaluate protocols for single cell isolation and transcriptional profiling from heart tissue, focusing particularly on frozen tissue which is necessary for study of human hearts at scale. Methods and results: Using flow cytometry and high-content screening, we found that enzymatic dissociation of fresh murine heart tissue resulted in a sufficient yield of intact cells while for frozen murine or human heart resulted in low-quality cell suspensions across a range of protocols. These findings were consistent across enzymatic digestion protocols and whether samples were snap-frozen or treated with RNA-stabilizing agents before freezing. In contrast, we show that isolation of cardiac nuclei from frozen hearts results in a high yield of intact nuclei, and leverage expression arrays to show that nuclear transcriptomes reliably represent the cytoplasmic and whole-cell transcriptomes of the major cardiac cell types. Furthermore, coupling of nuclear isolation to PCM1-gated flow cytometry facilitated specific cardiomyocyte depletion, expanding resolution of the cardiac transcriptome beyond bulk tissue transcriptomes which were most strongly correlated with PCM1(+) transcriptomes (r = 0.8). We applied these methods to generate a transcriptional catalogue of human cardiac cells by droplet-based RNA-sequencing of 8,460 nuclei from which cellular identities were inferred. Reproducibility of identified clusters was confirmed in an independent biopsy (4,760 additional PCM1(-) nuclei) from the same human heart. Conclusion: Our results confirm the validity of single-nucleus but not single-cell isolation for transcriptional profiling of individual cells from frozen heart tissue, and establishes PCM1-gating as an efficient tool for cardiomyocyte depletion. In addition, our results provide a perspective of cell types inferred from single-nucleus transcriptomes that are present in an adult human heart.
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| 22. |
- Rodby Bousquet, Elisabet, et al.
(author)
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Interrater reliability and construct validity of the posture and postural ability scale in adults with cerebral pulsy in supine, prone, siting and standing position
- 2014
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In: Clinical Rehabilitation. - : SAGE Publications. - 0269-2155 .- 1477-0873. ; 28:1, s. 82-90
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Journal article (other academic/artistic)abstract
- Objective To evaluate reliability, internal consistency and construct validity of the Posture and Postural Ability Scale for adults with cerebral palsy. Design Psychometric evaluation of a clinical assessment tool. Setting Rehabilitation Centres in Sweden and Iceland. Subjects Thirty adults with cerebral palsy aged 19-22 years, six people at each level I-V of the Gross Motor Function Classification System. Main measures The Posture and Postural Ability Scale contains a 7-point ordinal scale for postural ability in supine, prone, sitting, and standing and items for assessment of posture. Posture and postural ability was rated from photos and videos by three independent assessors. Interrater reliability was calculated using weighted Kappa. Internal consistency was analysed with Cronbach’s alpha if item deleted and corrected item-total correlation. Construct validity was evaluated based on known groups, using Jonckheere Terpstra for averaged values of the three raters relative to the Gross Motor Function Classification System. Results There was an excellent interrater reliability (kappa=0.85-0.99) and a high internal consistency (alpha=0.96-0.97, item-total correlation=0.60-0.91). Median values differed (p<0.02) between known groups represented by the levels of gross motor function, showing construct validity for all items. Conclusion The Posture and Postural Ability scale showed an excellent interrater reliability for experienced raters, a high internal consistency and construct validity. It can detect postural asymmetries in adults with cerebral palsy at all levels of gross motor function.
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| 23. |
- Rodby-Bousquet, Elisabet, et al.
(author)
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Postural asymmetries in young adults with cerebral palsy
- 2013
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In: Developmental Medicine & Child Neurology. - : Wiley. - 0012-1622 .- 1469-8749. ; 55:11, s. 1009-1015
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Journal article (peer-reviewed)abstract
- AimThe purpose was to describe posture, ability to change position, and association between posture and contractures, hip dislocation, scoliosis, and pain in young adults with cerebral palsy (CP). MethodsCross-sectional data of 102 people (63 males, 39 females; age range 19-23y, median 21y) out of a total population with CP was analysed in relation to Gross Motor Function Classification System (GMFCS) levels I (n=38), II (n=21), III (n=13), IV (n=10), and V (n=20). The CP subtypes were unilateral spastic (n=26), bilateral spastic (n=45), ataxic (n=12), and dyskinetic CP (n=19). The Postural Ability Scale was used to assess posture. The relationship between posture and joint range of motion, hip dislocation, scoliosis, and pain was analysed using logistic regression and Spearman's correlation. ResultsAt GMFCS levels I to II, head and trunk asymmetries were most common; at GMFCS levels III to V postural asymmetries varied with position. The odds ratios (OR) for severe postural asymmetries were significantly higher for those with scoliosis (OR=33 sitting), limited hip extension (OR=39 supine), or limited knee extension (OR=37 standing). Postural asymmetries correlated to hip dislocations: supine (r(s)=0.48), sitting (r(s)=0.40), standing (r(s)=0.41), and inability to change position: supine (r(s)=0.60), sitting (r(s)=0.73), and standing (r(s)=0.64). ConclusionsPostural asymmetries were associated with scoliosis, hip dislocations, hip and knee contractures, and inability to change position.
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| 24. |
- Rodby-Bousquet, Elisabet, et al.
(author)
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Psychometric evaluation of the Posture and Postural Ability Scale for children with cerebral palsy
- 2016
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In: Clinical Rehabilitation. - : SAGE Publications. - 0269-2155 .- 1477-0873. ; 30:7, s. 697-704
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To evaluate construct validity, internal consistency and inter-rater reliability of the Posture and Postural Ability Scale for children with cerebral palsy.DESIGN: Evaluation of psychometric properties.SETTING: Five child rehabilitation centres in the south of Sweden, in November 2013 to March 2014.SUBJECTS: A total of 29 children with cerebral palsy (15 boys, 14 girls), 6-16 years old, classified at Gross Motor Function Classification System (GMFCS) levels II (n = 10), III (n = 7), IV (n = 6) and V (n = 6).MAIN MEASURES: Three independent raters (two physiotherapists and one orthopaedic surgeon) assessed posture and postural ability of all children in supine, prone, sitting and standing positions, according to the Posture and Postural Ability Scale. Construct validity was evaluated based on averaged values for the raters relative to known-groups in terms of GMFCS levels. Internal consistency was analysed with Cronbach's alpha and corrected Item-Total correlation. Inter-rater reliability was calculated using weighted kappa scores.RESULTS: The Posture and Postural Ability Scale showed construct validity and median values differed between GMFCS levels (p < 0.01). There was a good internal consistency (alpha = 0.95-0.96; item-total correlation = 0.55-0.91), and an excellent inter-rater reliability (kappa score = 0.77-0.99).CONCLUSION: The Posture and Postural Ability Scale shows high psychometric properties for children with cerebral palsy, as previously seen when evaluated for adults. It enables detection of postural deficits and asymmetries indicating potential need for support and where it needs to be applied.
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| 25. |
- Wordie, Sarah J., et al.
(author)
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The effect of femoral orientation on the measurement of the head shaft angle : an ex-vivo study
- 2019
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In: Journal of Pediatric Orthopedics. Part B. - 1473-5865. ; 28:5, s. 465-469
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Journal article (peer-reviewed)abstract
- This laboratory study evaluates head shaft angle (HSA) reliability using ranges of simulated femoral orientation often seen in children with cerebral palsy. A dry femur was mounted in a jig that enabled the bone to be positioned in a range of internal and external rotation (-40° to + 40°) and flexion (0°-60°), alone or in combination. A metal wire was placed as a surrogate physis to give two HSA angles of 140° and 160°. Radiographs were taken of the femur in differing combinations of rotation, flexion and the two HSA angles. The HSA was measured by four independent observers on two separate occasions. Intraclass correlation coefficients (ICCs) were used to assess interobserver and intraobserver reliability. The HSA was accurately measured within ± 5° when the femur was positioned between 20° internal rotation and 40° external rotation. Flexion up to 60° did not affect the accuracy of the measurement. The interobserver reliability for the HSA was excellent with an ICC of 0.9970 [95% confidence interval (CI): 0.9995-0.9983] for the first measurement and 0.9988 for the second (95% CI: 0.9979-0.9993, all P < 0.01). The intraobserver reliability was also excellent with an ICC of not less than 0.990 for all four observers (95% CI: 0.9806-0.9986, all P < 0.01). There was excellent interobserver and intraobserver reliability when measuring the HSA in an experimental model provided femoral rotation lay within 20° internal and 40° external rotation and less than 60° of flexion.
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