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1.
BMJ Open ; 12(6): e058179, 2022 06 03.
Artículo en Inglés | MEDLINE | ID: mdl-36691235

RESUMEN

Waste in research has been well documented, but initiatives to reduce it are scarce. Here, we share our initial experiences of implementing Lean thinking and visual management into hospital research units in the Region of Southern Denmark. A Transformation Guiding Team (TGT) anchored in the top management was established with participation from leaders, researchers and patient representatives. The role of the TGT was to implement Lean methods, considering patients as primary end-users of the research results. This is in line with an explicit decision on setting patient values first in clinical settings at participating hospitals. The leaders of the research units were instructed in Lean thinking and Lean methods during a five-module course focusing on increasing value and reducing waste in research production. Initial experiences were that Lean tools could create a patient-centred vision that through visual management could identify waste in work processes. Concerns were lack of evidence for using Lean methods in research leadership and that the model itself could be a time consumer. Some lessons learnt were that adding Lean tools in research leadership should not just provide increased research productivity, but also improve other important key performance indicators such as quality of research and patient-relevant results. We intend to evaluate the value of the initiative by follow-up research and publish the outcome of key behavioural and key performance indicators.


Asunto(s)
Eficiencia , Liderazgo , Humanos , Eficiencia Organizacional
2.
Clin Epidemiol ; 11: 93-99, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30666164

RESUMEN

BACKGROUND: The completeness of REarranged during Transfection (RET) testing in patients with medullary thyroid carcinoma (MTC) was recently reported as 60%. However, the completeness on a population level is unknown. Similarly, it is unknown if the first Danish guidelines from 2002, recommending RET testing in all MTC patients, improved completeness in Denmark. We conducted a nationwide retrospective cohort study aiming to evaluate the completeness of RET testing in the Danish MTC cohort. Additionally, we aimed to assess the completeness before and after publication of the first Danish guidelines and characterize MTC patients who had not been tested. METHODS: The study included 200 patients identified from the nationwide Danish MTC cohort 1997-2013. To identify RET tested MTC patients before December 31, 2014, the MTC cohort was cross-checked with the nationwide Danish RET cohort 1994-2014. To characterize MTC patients who had not been RET tested, we reviewed their medical records and compared them with MTC patients who had been tested. RESULTS: Completeness of RET testing in the overall MTC cohort was 87% (95% CI: 0.81-0.91; 173/200). In the adjusted MTC cohort, after excluding patients diagnosed with hereditary MTC by screening, completeness was 83% (95% CI: 0.76-0.88; 131/158). Completeness was 88% (95% CI: 0.75-0.95; 42/48) and 81% (95% CI: 0.72-0.88) (89/110) before and after publication of the first Danish guidelines, respectively. Patients not RET tested had a higher median age at diagnosis compared to those RET tested. Median time to death was shorter in those not tested relative to those tested. CONCLUSION: The completeness of RET testing in MTC patients in Denmark seems to be higher than reported in other cohorts. No improvement in completeness was detected after publication of the first Danish guidelines. In addition, data indicate that advanced age and low life expectancy at MTC diagnosis may serve as prognostic indicators to identify patients having a higher likelihood of missing the compulsory RET test.

3.
Thyroid ; 29(3): 368-377, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30618340

RESUMEN

BACKGROUND: Survival of medullary thyroid carcinoma (MTC) subgroups in relation to the general population is poorly described. Data on the factors predicting long-term biochemical cure in MTC patients are nonexistent at a population level. A nationwide retrospective cohort study of MTC in Denmark from 1997 to 2014 was conducted, aiming to detect subgroups with survival similar to that of the general population and to identify prognostic factors for disease-specific survival and long-term biochemical cure. METHODS: The study included 220 patients identified from the nationwide Danish MTC cohort between 1997 and 2014. As a representative sample of the general population, a reference population matched 50:1 to the MTC cohort was used. RESULTS: Patients diagnosed with hereditary MTC by screening (hazard ratio [HR] = 1.5 [confidence interval (CI) 0.5-4.3]), patients without regional metastases (HR = 1.4 [CI 0.9-2.3]), and patients with stage I (HR = 1.3 [CI 0.6-3.1]), stage II (HR = 1.1 [CI 0.6-2.3]), and III (HR = 1.3 [CI 0.4-4.2]) disease had an overall survival similar to the reference population. On multivariate analysis, the presence of distant metastases (HR = 12.3 [CI 6.0-25.0]) predicted worse disease-specific survival, while the absence of regional lymph node metastases (odds ratio = 40.1 [CI 12.0-133.7]) was the only independent prognostic factor for long-term biochemical cure. CONCLUSIONS: Patients with hereditary MTC diagnosed by screening, patients without regional metastases, and patients with stages I, II, and III disease may have similar survival as the general population. The presence of distant metastases predicted worse disease-specific survival, while the absence of regional metastases predicted long-term biochemical cure.


Asunto(s)
Carcinoma Medular/congénito , Neoplasia Endocrina Múltiple Tipo 2a/epidemiología , Neoplasia Endocrina Múltiple Tipo 2a/mortalidad , Neoplasias de la Tiroides/epidemiología , Neoplasias de la Tiroides/mortalidad , Adulto , Anciano , Carcinoma Medular/epidemiología , Carcinoma Medular/mortalidad , Carcinoma Medular/terapia , Bases de Datos Factuales , Dinamarca/epidemiología , Supervivencia sin Enfermedad , Femenino , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Neoplasia Endocrina Múltiple Tipo 2a/terapia , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Neoplasias de la Tiroides/terapia , Resultado del Tratamiento , Adulto Joven
4.
Endocr Connect ; 8(1): 1-7, 2019 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-30550378

RESUMEN

A recent study proposed new TNM groupings for better survival discrimination among stage groups for medullary thyroid carcinoma (MTC) and validated these groupings in a population-based cohort in the United States. However, it is unknown how well the groupings perform in populations outside the United States. Consequently, we conducted the first population-based study aiming to evaluate if the recently proposed TNM groupings provide better survival discrimination than the current American Joint Committee on Cancer (AJCC) TNM staging system (seventh and eighth edition) in a nationwide MTC cohort outside the United States. This retrospective cohort study included 191 patients identified from the nationwide Danish MTC cohort between 1997 and 2014. In multivariate analysis, hazard ratios for overall survival under the current AJCC TNM staging system vs the proposed TNM groupings with stage I as reference were 1.32 (95% CI: 0.38-4.57) vs 3.04 (95% CI: 1.38-6.67) for stage II, 2.06 (95% CI: 0.45-9.39) vs 3.59 (95% CI: 1.61-8.03) for stage III and 5.87 (95% CI: 2.02-17.01) vs 59.26 (20.53-171.02) for stage IV. The newly proposed TNM groupings appear to provide better survival discrimination in the nationwide Danish MTC cohort than the current AJCC TNM staging. Adaption of the proposed TNM groupings by the current AJCC TNM staging system may potentially improve accurateness in survival discrimination. However, before such an adaption further population-based studies securing external validity are needed.

5.
Clin Epidemiol ; 10: 1479-1487, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30349395

RESUMEN

BACKGROUND: The incidence and prevalence of multiple endocrine neoplasia 2A (MEN2A) have only been reported once in a nationwide setting. However, it is unclear whether the figures are representative of other populations, as the major component of the syndrome, hereditary medullary thyroid carcinoma (MTC), has been reported as rare in the same country. We conducted a nationwide retrospective cohort study of MEN2A in Denmark from 1901 to 2014, aiming to describe the incidence and prevalence. METHODS: This study included 250 unique MEN2A patients born or resident in Denmark before December 31, 2014. Patients were identified through the Danish REarranged during Transfection (RET) cohort, linkage of MEN2A pedigrees, the Danish MTC cohort, a nationwide collaboration of MEN2 centers, cross-checking of other relevant cohorts, and a systematic literature search. RESULTS: The incidence from 1971 to 2000 was 28 (95% CI: 21-37) per million live births per year. Incidence for the specific mutations or for the overall MEN2A group did not change significantly from 1901 to 2014 (P>0.05). Point prevalence at January 1, 2015, was 24 per million (95% CI: 20-28). CONCLUSION: The incidence and prevalence of MEN2A in Denmark seem higher than those reported in other countries. This is likely explained by the Danish C611Y founder effect. Also, our data indicate no significant change in MEN2A incidence during the last century.

6.
Endocr Connect ; 7(6): 829-839, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29760189

RESUMEN

Recent studies have shown a significant increase in the temporal trend of medullary thyroid carcinoma (MTC) incidence. However, it remains unknown to which extent sporadic medullary thyroid carcinoma (SMTC) and hereditary MTC (HMTC) affect the MTC incidence over time. We conducted a nationwide retrospective study using previously described RET and MTC cohorts combined with review of medical records, pedigree comparison and relevant nationwide registries. The study included 474 MTC patients diagnosed in Denmark between 1960 and 2014. In the nationwide period from 1997 to 2014, we recorded a mean age-standardized incidence of all MTC, SMTC and HMTC of 0.19, 0.13 and 0.06 per 100,000 per year, respectively. The average annual percentage change in incidence for all MTC, SMTC and HMTC were 1.0 (P = 0.542), 2.8 (P = 0.125) and -3.1 (P = 0.324), respectively. The corresponding figures for point prevalence at January 1, 2015 were 3.8, 2.5 and 1.3 per 100,000, respectively. The average annual percentage change in prevalence from 1998 to 2015 for all MTC, SMTC and HMTC was 2.8 (P < 0.001), 3.8 (P < 0.001) and 1.5 (P = 0.010), respectively. We found no significant change in the incidence of all MTC, SMTC and HMTC possibly due to our small sample size. However, due to an increasing trend in the incidence of all MTC and opposing trends of SMTC (increasing) and HMTC (decreasing) incidence, it seems plausible that an increase for all MTC seen by others may be driven by the SMTC group rather than the HMTC group.

7.
Thyroid ; 27(12): 1505-1510, 2017 12.
Artículo en Inglés | MEDLINE | ID: mdl-29020875

RESUMEN

BACKGROUND: Multiple endocrine neoplasia (MEN) 2A and 2B are caused by REarranged during Transfection (RET) germline mutations. In a recent nationwide study, an unusually high prevalence (33%) of families with the C611Y mutation was reported, and it was hypothesized that this might be due to a founder effect. The first nationwide study of haplotypes in MEN2A families was conducted, with the aim of investigating the relatedness and occurrence of de novo mutations among Danish families carrying similar mutations. METHODS: The study included 21 apparently unrelated MEN2A families identified from a nationwide Danish RET cohort from 1994 to 2014. Twelve, two, two, three, and two families carried the C611Y, C618F, C618Y, C620R, and C634R mutations, respectively. Single nucleotide polymorphism chip data and identity by descent analysis were used to assess relatedness. RESULTS: A common founder mutation was found among all 12 C611Y families and between both C618Y families. No relatedness was identified in the remaining families. CONCLUSION: The data suggest that all families with the C611Y germline mutation in Denmark originate from a recent common ancestor, probably explaining the unusually high prevalence of this mutation. Additionally, the results indicate that the C611Y mutation rarely arises de novo, thus underlining the need for thorough multigenerational genetic work up in carriers of this mutation.


Asunto(s)
Efecto Fundador , Mutación de Línea Germinal , Neoplasia Endocrina Múltiple Tipo 2a/genética , Proteínas Proto-Oncogénicas c-ret/genética , Neoplasias de la Tiroides/genética , Dinamarca , Exones , Frecuencia de los Genes , Genotipo , Humanos , Linaje , Polimorfismo de Nucleótido Simple
9.
Calcif Tissue Int ; 101(5): 473-478, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28676897

RESUMEN

Osteogenesis imperfecta (OI) is a systemic connective tissue disorder most often caused by mutations in collagen type 1 related genes. Patients with OI suffer from multiple fractures and various degrees of growth deficiency and bone deformity. It is unknown whether the systemic effect of defect collagen type 1 influences the quality of life in patients with OI. We therefore aimed to investigate health-related quality of life (HRQoL) in a well-characterized cohort of adult patients with OI. We included 85 adult patients with mild to severe OI (types I, III, and IV) and obtained information about skeletal- and non-skeletal phenotypes and patient demographics. We investigated physical and mental HRQoL using a validated questionnaire, SF-36, and compared the data to values obtained in a population without OI. Patients with mild, moderate, and severe OI all had lower mean scores on domains describing physical HRQoL and a lower mean physical component score compared to the general population, p < 0.001. Patients with severe OI had lower mean scores on physical HRQoL, p < 0.05. The scores on domains reflecting mental HRQoL were more inhomogenously affected, but did not differ significantly from the general population. OI has an impact on physical and some aspects of mental HRQoL. The scores on physical health were correlated to severity of the OI disease. The mental component score in the OI patients was unaffected and comparable with the general population.


Asunto(s)
Osteogénesis Imperfecta/diagnóstico , Calidad de Vida , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
10.
Lancet Diabetes Endocrinol ; 5(10): 827-838, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28546096

RESUMEN

Type 1 and type 2 diabetes are generally accepted to be associated with increased bone fracture risk. However, the pathophysiological mechanisms of diabetic bone disease are poorly understood, and whether the associated increased skeletal fragility is a comorbidity or a complication of diabetes remains under debate. Although there is some indication of a direct deleterious effect of microangiopathy on bone, the evidence is open to question, and whether diabetic osteopathy can be classified as a chronic, microvascular complication of diabetes remains uncertain. Here, we review the current knowledge of potential contributory factors to diabetic bone disease, particularly the association between diabetic microangiopathy and bone mineral density, bone structure, and bone turnover. Additionally, we discuss and propose a pathophysiological model of the effects of diabetic microvascular disease on bone, and examine the progression of bone disease alongside the evolution of diabetes.


Asunto(s)
Enfermedades Óseas/complicaciones , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Angiopatías Diabéticas/complicaciones , Animales , Densidad Ósea , Enfermedades Óseas/fisiopatología , Comorbilidad , Diabetes Mellitus Tipo 1/fisiopatología , Diabetes Mellitus Tipo 2/fisiopatología , Angiopatías Diabéticas/fisiopatología , Fracturas Óseas/complicaciones , Fracturas Óseas/fisiopatología , Humanos , Microvasos/fisiopatología , Factores de Riesgo
12.
Eur J Endocrinol ; 176(6): 685-693, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28289103

RESUMEN

OBJECTIVE, DESIGN AND METHODS: Roux-en-Y gastric bypass (RYGB) has proved successful in attaining sustained weight loss but may lead to metabolic bone disease. To assess impact on bone mass and structure, we measured a real bone mineral density at the hip and spine by dual-energy X-ray absorptiometry, and volumetric BMD (vBMD) and bone microarchitecture at the distal radius and tibia by high-resolution peripheral quantitative CT in 25 morbidly obese subjects (15 females, 10 males) at 0, 12 and 24 months after RYGB. Bone turnover markers (BTMs), calciotropic and gut hormones and adipokines were measured at the same time points. RESULTS: After a 24.1% mean weight loss from baseline to month 12 (P < 0.001), body weight plateaued from month 12 to 24 (-0.9%, P = 0.50). However, cortical and trabecular vBMD and microarchitecture deteriorated through the 24 months, such that there was a 5 and 7% reduction in estimated bone strength at the radius and tibia respectively (both P < 0.001). The declines observed in the first 12 months were matched or exceeded by declines in the 12- to 24-month period. While a significant increase in BTMs and decrease in leptin and insulin were seen at 24 months, these changes were maximal at month 12 and stabilized from month 12 to 24. CONCLUSIONS: Despite weight stabilization and maintenance of metabolic parameters, bone loss and deterioration in bone strength continued and were substantial in the second year. The clinical importance of these changes in terms of increased risk of developing osteoporosis and fragility fractures remain an important concern.


Asunto(s)
Derivación Gástrica/efectos adversos , Obesidad Mórbida/cirugía , Osteoporosis/etiología , Complicaciones Posoperatorias/etiología , Absorciometría de Fotón , Adiponectina/metabolismo , Adulto , Densidad Ósea , Enfermedades Óseas Metabólicas/diagnóstico por imagen , Enfermedades Óseas Metabólicas/etiología , Enfermedades Óseas Metabólicas/metabolismo , Remodelación Ósea , Colágeno Tipo I/metabolismo , Femenino , Hormona Folículo Estimulante/metabolismo , Articulación de la Cadera/diagnóstico por imagen , Humanos , Insulina/metabolismo , Leptina/metabolismo , Estudios Longitudinales , Vértebras Lumbares/diagnóstico por imagen , Hormona Luteinizante/metabolismo , Masculino , Persona de Mediana Edad , Osteoporosis/diagnóstico por imagen , Osteoporosis/metabolismo , Hormona Paratiroidea/metabolismo , Fragmentos de Péptidos/metabolismo , Péptidos/metabolismo , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/metabolismo , Procolágeno/metabolismo , Radio (Anatomía)/diagnóstico por imagen , Tibia/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Vitamina D/análogos & derivados , Vitamina D/metabolismo , Pérdida de Peso
13.
Calcif Tissue Int ; 100(3): 244-249, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-28078366

RESUMEN

A role for WNT4 and WNT5B in bone metabolism was indicated by genome-wide association studies (GWAS) and a Wnt4 knockout mouse model. The aim of this study was therefore to replicate and further investigate the causality between genetic variation in WNT4 and WNT5B and deviating bone mineral density (BMD) values. A WNT4 and WNT5B mutation screening was performed in patients with craniotubular hyperostosis using Sanger sequencing. Here, no putative causal mutations were detected. Moreover, a high and low BMD cohort was selected from the Odense Androgen Study population for re-sequencing. In WNT4 we detected four variants (three rare, one common), while in WNT5B we detected five variants (two rare, three common). For the common variants, no significant difference in genotype frequencies between the high and low BMD cohorts was observed. The SNPs associated with the GWAS were genotyped in these cohorts, but again no significant difference in genotype frequencies was observed. Despite the findings of the GWAS, we were not able to replicate or further verify the genetic association of polymorphisms in WNT4 and WNT5B with BMD. In order to do so, the intronic regions of both genes could be investigated more thoroughly in more extended populations (or extremes) with greater power. Future genetic and functional studies toward adjacent genes of WNT4 and WNT5B can also be interesting to figure out whether the signal from GWAS could possibly be attributed to genetic variation in these genes.


Asunto(s)
Densidad Ósea/genética , Predisposición Genética a la Enfermedad , Osteoporosis/genética , Proteínas Wnt/genética , Proteína Wnt4/genética , Estudios de Cohortes , Pruebas Genéticas/métodos , Variación Genética/genética , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Persona de Mediana Edad , Osteoporosis/fisiopatología , Polimorfismo de Nucleótido Simple/genética
14.
J Bone Miner Res ; 32(1): 125-134, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27448250

RESUMEN

Osteogenesis imperfecta (OI) is a hereditary, clinically heterogeneous, connective tissue disorder. The population prevalence of OI in Denmark is 10.6 in 100,000. A hallmark of the disease is frequent fractures that are often precipitated by minimal trauma. The aim of the current study was to compare the fracture rates across the lifespan of patients with OI with that of a reference population from the general population. The present study was a Danish nationwide, population-based, cohort study using register data. We identified 644 (55.6% females) patients in the OI cohort through the Danish National Patient Register and 3361 (55.2% females) persons, randomly selected from the Civil Registry System. A total of 416 patients with OI experienced a total of 1566 fractures during the observation period of median 17.9 years (interquartile range [IQR], 12.4 to 18.0 years), summing to 10137 person years. In comparison, 709 persons in the reference population experienced a total of 1018 fractures during follow-up. Both male and female patients with OI had an increased fracture rate throughout their life. The fracture rate ratio for participants aged 0 to 19 years was 10.7, for participants aged 20 to 54 years 17.2, and for participants aged 55 years and over 4.1 when compared to the reference population. The highest fracture rate was seen in males with OI aged 0 to 19 years (257 fractures per 1000 person-years). The fractures appear to follow the same pattern as in the general population, with a peak during the toddler and adolescent years (incidence rate [IR] 233.9 per 1000 person years), fewer fractures during adulthood (IR 84.5 per 1000 person years), and increased fracture rates in older women (IR 111.9 per 1000 person years). This is the largest register-based nationwide study on the fracture epidemiology of patients with OI. The risk of fractures seems largest in the childhood and adolescent years, and the relative risk of fracture declines with age in patients with OI compared to the general population. © 2016 American Society for Bone and Mineral Research.


Asunto(s)
Fracturas Óseas/complicaciones , Fracturas Óseas/epidemiología , Osteogénesis Imperfecta/complicaciones , Osteogénesis Imperfecta/epidemiología , Sistema de Registros , Adolescente , Adulto , Niño , Preescolar , Estudios de Cohortes , Dinamarca/epidemiología , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Valores de Referencia , Adulto Joven
15.
Thyroid ; 27(2): 215-223, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-27809725

RESUMEN

BACKGROUND: Germline mutations of the REarranged during Transfection (RET) proto-oncogene cause multiple endocrine neoplasia 2 (MEN2). It is unclear whether the distribution of RET mutations varies among populations. The first nationwide study of the distribution of RET mutations was conducted, and the results were compared to those of other populations. METHODS: This retrospective cohort study included 1583 patients who underwent RET gene testing in one of three centers covering all of Denmark between September 1994 and December 2014. Primary testing method was Sanger sequencing, which included exons 8-11 and 13-16. Mutations were defined according to the ARUP database July 1, 2016. RESULTS: RET mutations were identified in 163 patients from 36 apparently unrelated families. Among the 36 families 13 (36.1%) carried mutations in codon 611, four (11.1%) in codon 618, three (8.3%) in codon 620, one (2.8%) in codon 631, six (16.7%) in codon 634, one (2.8%) in codon 790, one (2.8%) in codon 804, one (2.8%) in codon 852, one (2.8%) in codon 883, and five (13.9%) in codon 918. Among the 13 families with codon 611 mutations, 12 had the p.C611Y mutation. CONCLUSIONS: The distribution of RET mutations in Denmark appears to differ from that of other populations. Mutations in codon 611 were the most prevalent, followed by more frequently reported mutations. This might be due to a possible founder effect for the p.C611Y mutation. However, further studies are needed to find possible explanations for the skewed mutational spectrum in Denmark.


Asunto(s)
Neoplasia Endocrina Múltiple Tipo 2a/genética , Neoplasia Endocrina Múltiple Tipo 2b/genética , Proteínas Proto-Oncogénicas c-ret/genética , Dinamarca , Efecto Fundador , Mutación de Línea Germinal , Humanos , Proto-Oncogenes Mas , Estudios Retrospectivos , Población Blanca/genética
16.
Int J Cardiol ; 225: 250-257, 2016 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-27741483

RESUMEN

BACKGROUND: Osteogenesis imperfecta (OI) is a hereditary connective tissue disease often due to mutations in genes coding for type 1 collagen. Collagen type 1 is important in the development of the heart and vasculature. Little is known about the risk of cardiovascular disease (CVD) in OI. OBJECTIVE: To investigate the risk of symptomatic CVD in OI. DESIGN: A Danish nationwide, population-based and register-based longitudinal open cohort study. PARTICIPANTS: All patients registered with the diagnosis of OI from 1977 to 2013 and a reference population matched 5:1 to the OI cohort. MEASUREMENTS: Sub-hazard ratios for mitral and aortic valve regurgitation, atrial fibrillation and flutter, heart failure and vascular aneurisms and dissections comparing the OI cohort to the reference population. RESULTS: We identified 687 cases with OI (379 women) and included 3435 reference persons (1895 women). The SHR was 6.3 [95% CI: 2.5-15.5] for mitral valve regurgitation, 4.5 [95% CI: 1.4-13.9] for aortic valve regurgitation, 1.7 [95% CI: 1.1-2.8] for atrial fibrillation/flutter, and 2.3 [95% CI: 1.4-3.7] for heart failure. The SHRs were not increased arterial aneurisms or dissections. LIMITATION: Our results were limited by lacking clinical information about phenotype and genotype of the included patients. CONCLUSION: We confirm that patients with OI have an increased risk of CVD compared to the general population. This held true even when adjusting for factors that are known to contribute to development of these diseases. Our results suggest that the collagenopathy seen in OI may be part of the pathogenesis of CVD in OI.


Asunto(s)
Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Osteogénesis Imperfecta/diagnóstico , Osteogénesis Imperfecta/epidemiología , Sistema de Registros , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Estudios de Cohortes , Dinamarca/epidemiología , Femenino , Humanos , Lactante , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Distribución Aleatoria , Factores de Riesgo , Adulto Joven
17.
J Bone Miner Res ; 31(12): 2159-2166, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27345018

RESUMEN

Osteogenesis imperfecta (OI) is a hereditary connective tissue disease that causes frequent fractures. Little is known about causes of death and length of survival in OI. The objective of this work was to calculate the risk and cause of death, and the median survival time in patients with OI. This study was a Danish nationwide, population-based and register-based cohort study. We used National Patient Register data from 1977 until 2013 with complete long-term follow-up. Participants comprised all patients registered with the diagnosis of OI from 1977 until 2013, and a reference population matched five to one to the OI cohort. We calculated hazard ratios for all-cause mortality and subhazard ratios for cause-specific mortality in a comparison of the OI cohort and the reference population. We also calculated all-cause mortality hazard ratios for males, females, and age groups (0 to 17.99 years, 18.00 to 34.99 years, 35.00 to 54.99 years, 55.00 to 74.99 years, and >75 years). We identified 687 cases of OI (379 women) and included 3435 reference persons (1895 women). A total of 112 patients with OI and 257 persons in the reference population died during the observation period. The all-cause mortality hazard ratio between the OI cohort and the reference population was 2.90. The median survival time for males with OI was 72.4 years, compared to 81.9 in the reference population. The median survival time for females with OI was 77.4 years, compared to 84.5 years in the reference population. Patients with OI had a higher risk of death from respiratory diseases, gastrointestinal diseases, and trauma. We were limited by the lack of clinical information about phenotype and genotype of the included patients. Patients with OI had a higher mortality rate throughout their life compared to the general population. © 2016 American Society for Bone and Mineral Research.


Asunto(s)
Causas de Muerte , Osteogénesis Imperfecta/mortalidad , Sistema de Registros , Adolescente , Adulto , Anciano , Niño , Preescolar , Estudios de Cohortes , Comorbilidad , Femenino , Humanos , Lactante , Recién Nacido , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Adulto Joven
18.
J Bone Miner Res ; 31(8): 1541-9, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-26896351

RESUMEN

Although projections from cross-sectional studies have shown that bone loss leading to osteoporosis begins around menopause in women and later in life in men, this has not been examined longitudinally in population-based studies using high-resolution technology capable of distinguishing cortical (Ct) and trabecular (Tb) bone microarchitecture. The aim of this 3-year prospective study was to investigate age- and sex-related changes in bone compartment-specific geometry, volumetric bone mineral density (vBMD), microarchitecture, and estimated strength. The distal radius and tibia were imaged at baseline and after 3 years (median 3.0; range, 2.7 to 3.9 years) using high-resolution peripheral computed tomography (HRpCT) in an age- and sex-stratified, population-based, random sample of white men and women (n = 260) aged 21 to 82 years. In general, at the radius and tibia there was a moderate annual increase in cortical thickness (Ct.Th) that seemed to offset the increase in cortical porosity (Ct.Po), resulting in net annual increase in cortical vBMD (Ct.vBMD) in premenopausal women and young men. With advancing age, postmenopausal women displayed significant bone loss with decreased trabecular vBMD (Tb.vBMD) (due to loss of entire trabeculae) and Ct.vBMD (manifested as increase in Ct.Po and decrease in Ct.Th) at the radius, and a decline in Ct.vBMD (with increasing Ct.Po) at the tibia, resulting in loss of estimated bone strength. In contrast, men had a lower rate of bone loss with advancing age with smaller increases in Ct.Po at both the skeletal sites. In summary, the pattern of bone loss in men and women was discrepant, with women losing more bone than men with aging, although with a dominance of cortical over trabecular bone loss at the peripheral sites in both sexes. This conforms to epidemiological evidence that most fractures occurring in old age are predominantly at cortical peripheral sites, with women having a higher incidence of fractures than men at any given age. © 2016 American Society for Bone and Mineral Research.


Asunto(s)
Envejecimiento/fisiología , Huesos/anatomía & histología , Huesos/fisiología , Caracteres Sexuales , Tomografía Computarizada por Rayos X/métodos , Absorciometría de Fotón , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Densidad Ósea , Huesos/diagnóstico por imagen , Hueso Esponjoso/anatomía & histología , Hueso Esponjoso/diagnóstico por imagen , Hueso Esponjoso/fisiología , Hueso Cortical/anatomía & histología , Hueso Cortical/diagnóstico por imagen , Hueso Cortical/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Porosidad , Estudios Prospectivos , Radio (Anatomía)/anatomía & histología , Radio (Anatomía)/diagnóstico por imagen , Radio (Anatomía)/fisiología , Tibia/anatomía & histología , Tibia/diagnóstico por imagen , Tibia/fisiología , Adulto Joven
19.
Acta Derm Venereol ; 96(5): 602-12, 2016 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-26694951

RESUMEN

Mastocytosis is a heterogeneous group of diseases defined by an increased number and accumulation of mast cells, and often also by signs and symptoms of mast cell activation. Disease subtypes range from indolent to rare aggressive forms. Mastocytosis affects people of all ages and has been considered rare; however, it is probably underdiagnosed with potential severe implications. Diagnosis can be challenging and symptoms may be complex and involve multiple organ-systems. In general it is advised that patients should be referred to centres with experience in the disease offering an individualized, multidisciplinary approach. We present here consensus recommendations from a Nordic expert group for the diagnosis and general management of patients with mastocytosis.


Asunto(s)
Mastocitosis/diagnóstico , Mastocitosis/terapia , Congresos como Asunto , Consenso , Diagnóstico Diferencial , Humanos , Mastocitosis/clasificación , Mastocitosis/epidemiología , Guías de Práctica Clínica como Asunto , Prevalencia , Países Escandinavos y Nórdicos/epidemiología , Organización Mundial de la Salud
20.
Calcif Tissue Int ; 98(3): 244-52, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26590810

RESUMEN

Identifying persons with a high risk of osteoporotic fractures remains a challenge. DXA uptake in women with elevated risk of osteoporosis seems to be depending on distance to scanning facilities. This study aimed to investigate the ability of a small portable scanner in identifying women with reduced bone mineral density (BMD), and to define triage thresholds for pre-selection. Total hip and lumbar spine BMD was measured by dual-energy X-ray absorptiometry and phalangeal BMD by radiographic absorptiometry in 121 Danish women with intermediate or high 10-year fracture probability (aged 61-81 years). Correlation between the two methods was estimated using correlation coefficient (r) and Bland-Altman plots. A moderate correlation between phalangeal BMD versus total hip (r = 0.47) and lumbar spine (r = 0.51), and an AUC on 0.80 was found. The mean difference between phalangeal T score and total hip T score/lumbar spine T score was low, and ranged from -0.26 SD to -0.31 SD depending on site and reference database used for calculation of T scores, but, large variation was seen at an individual level. When applying a triage approach approx. one-third of all DXA scan could be avoided and only 6 % of women in the low-risk group would be false negatives.


Asunto(s)
Absorciometría de Fotón , Densidad Ósea , Falanges de los Dedos de la Mano/diagnóstico por imagen , Fracturas Osteoporóticas/diagnóstico por imagen , Fracturas Osteoporóticas/epidemiología , Pruebas en el Punto de Atención , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Dinamarca , Reacciones Falso Negativas , Femenino , Cadera/diagnóstico por imagen , Humanos , Vértebras Lumbares/diagnóstico por imagen , Persona de Mediana Edad , Probabilidad , Sistema de Registros , Medición de Riesgo , Sensibilidad y Especificidad
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