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Dementia with Lewy bodies is characterized by a high burden of autonomic dysfunction and Lewy pathology in peripheral organs and components of the sympathetic and parasympathetic nervous system. Parasympathetic terminals may be quantified with 18F-fluoroetoxybenzovesamicol, a PET tracer that binds to the vesicular acetylcholine transporter in cholinergic presynaptic terminals. Parasympathetic imaging may be useful for diagnostics, improving our understanding of autonomic dysfunction and for clarifying the spatiotemporal relationship of neuronal degeneration in prodromal disease. Therefore, we aimed to investigate the cholinergic parasympathetic integrity in peripheral organs and central autonomic regions of subjects with dementia with Lewy bodies and its association with subjective and objective measures of autonomic dysfunction. We hypothesized that organs with known parasympathetic innervation, especially the pancreas and colon, would have impaired cholinergic integrity. To achieve these aims, we conducted a cross-sectional comparison study including 23 newly diagnosed non-diabetic subjects with dementia with Lewy bodies (74 ± 6 years, 83% male) and 21 elderly control subjects (74 ± 6 years, 67% male). We obtained whole-body images to quantify PET uptake in peripheral organs and brain images to quantify PET uptake in regions of the brainstem and hypothalamus. Autonomic dysfunction was assessed with questionnaires and measurements of orthostatic blood pressure. Subjects with dementia with Lewy bodies displayed reduced cholinergic tracer uptake in the pancreas (32% reduction, P = 0.0003) and colon (19% reduction, P = 0.0048), but not in organs with little or no parasympathetic innervation. Tracer uptake in a region of the medulla oblongata overlapping the dorsal motor nucleus of the vagus correlated with autonomic symptoms (rs = -0.54, P = 0.0077) and changes in orthostatic blood pressure (rs = 0.76, P < 0.0001). Tracer uptake in the pedunculopontine region correlated with autonomic symptoms (rs = -0.52, P = 0.0104) and a measure of non-motor symptoms (rs = -0.47, P = 0.0230). In conclusion, our findings provide the first imaging-based evidence of impaired cholinergic integrity of the pancreas and colon in dementia with Lewy bodies. The observed changes may reflect parasympathetic denervation, implying that this process is initiated well before the point of diagnosis. The findings also support that cholinergic denervation in the brainstem contributes to dysautonomia.
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Enfermedades del Sistema Nervioso Autónomo , Enfermedad por Cuerpos de Lewy , Humanos , Masculino , Anciano , Femenino , Enfermedad por Cuerpos de Lewy/diagnóstico por imagen , Enfermedad por Cuerpos de Lewy/patología , Estudios Transversales , Enfermedades del Sistema Nervioso Autónomo/diagnóstico por imagen , Enfermedades del Sistema Nervioso Autónomo/etiología , Páncreas/patología , Colinérgicos , Colon/patologíaRESUMEN
BACKGROUND: Multiple system atrophy (MSA) is a rare, progressive, neurodegenerative disorder presenting glia pathology. Still, disease etiology and pathophysiology are unknown, but neuro-inflammation and vascular disruption may be contributing factors to the disease progression. Here, we performed an ex vivo deep proteome profiling of the prefrontal cortex of MSA patients to reveal disease-relevant molecular neuropathological processes. Observations were validated in plasma and cerebrospinal fluid (CSF) of novel cross-sectional patient cohorts. METHODS: Brains from 45 MSA patients and 30 normal controls (CTRLs) were included. Brain samples were homogenized and trypsinized for peptide formation and analyzed by high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS). Results were supplemented by western blotting, immuno-capture, tissue clearing and 3D imaging, immunohistochemistry and immunofluorescence. Subsequent measurements of glial fibrillary acid protein (GFAP) and neuro-filament light chain (NFL) levels were performed by immunoblotting in plasma of 20 MSA patients and 20 CTRLs. Finally, we performed a proteome profiling of 144 CSF samples from MSA and CTRLs, as well as other parkinsonian disorders. Data were analyzed using relevant parametric and non-parametric two-sample tests or linear regression tests followed by post hoc tests corrected for multiple testing. Additionally, high-throughput bioinformatic analyses were applied. RESULTS: We quantified more than 4,000 proteins across samples and identified 49 differentially expressed proteins with significantly different abundances in MSA patients compared with CTRLs. Pathway analyses showed enrichment of processes related to fibrinolysis and complement cascade activation. Increased fibrinogen subunit ß (FGB) protein levels were further verified, and we identified an enriched recognition of FGB by IgGs as well as intra-parenchymal accumulation around blood vessels. We corroborated blood-brain barrier leakage by a significant increase in GFAP and NFL plasma levels in MSA patients that correlated to disease severity and/or duration. Proteome profiling of CSF samples acquired during the disease course, confirmed increased total fibrinogen levels and immune-related components in the soluble fraction of MSA patients. This was also true for the other atypical parkinsonian disorders, dementia with Lewy bodies and progressive supra-nuclear palsy, but not for Parkinson's disease patients. CONCLUSION: Our results implicate activation of the fibrinolytic cascade and immune system in the brain as contributing factors in MSA associated with a more severe disease course.
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Atrofia de Múltiples Sistemas , Enfermedad de Parkinson , Trastornos Parkinsonianos , Encéfalo/metabolismo , Cromatografía Liquida , Estudios Transversales , Progresión de la Enfermedad , Fibrinógeno/metabolismo , Proteína Ácida Fibrilar de la Glía/metabolismo , Humanos , Atrofia de Múltiples Sistemas/metabolismo , Enfermedad de Parkinson/metabolismo , Trastornos Parkinsonianos/metabolismo , Trastornos Parkinsonianos/patología , Proteoma/metabolismo , Espectrometría de Masas en TándemRESUMEN
We aimed to estimate the effect of organized mammography screening on incidence-based breast cancer mortality by comparing changes in mortality among women eligible for screening to concurrent changes in younger and older ineligible women. In a county-wise balanced, open-cohort study, we used birth cohorts (1896-1982) to construct three age groups in both the historical and screening period: women eligible for screening, and younger or older women ineligible for screening. We included women diagnosed with breast cancer who died within the same age-period group during 1987-2010 (n = 4,903). We estimated relative incidence-based mortality rate ratios (relative MRR) comparing temporal changes in eligible women to concurrent changes in ineligible women. Additionally, we conducted analyses comparing the change in eligible women to younger, ineligible women with either continued accrual and follow-up period (eligible women only) or continued follow-up period. All three age groups experienced a reduction in mortality, but the decrease among eligible women was about the same among ineligible women (relative MRR = 1.05, 95% CI: (0.94-1.18)). Varying the definition of follow-up yielded similar results. Mammography screening was not associated with a larger breast cancer mortality reduction in women eligible relative to ineligible women.
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Neoplasias de la Mama/diagnóstico , Detección Precoz del Cáncer/métodos , Mamografía/métodos , Tamizaje Masivo/métodos , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/mortalidad , Estudios de Cohortes , Femenino , Humanos , Incidencia , Persona de Mediana Edad , Noruega/epidemiología , Tasa de SupervivenciaRESUMEN
Background: Mammography screening increases incidence because cancers are detected earlier in time and because of overdiagnosis. We developed an Excel-based model to visualize the expected increase from lead-time amplified by increasing background incidence. Subsequently, we added overdiagnosis to the model. Methods: We constructed two hypothetical populations of women aged 50-79 in 5-year age and calendar groups: one with screening for women aged 50-69 and one without. The user enters information on population at risk, number of breast cancers, trends in background incidence, average length of lead-time and, optionally, overdiagnosis. The model computes incidence rate ratios (IRRs) comparing incidence changes with screening to changes without in open and closed cohorts. Results: We entered information from Norway from 1990 to 1994, the period preceding the gradual introduction of a national mammography screening programme. As expected, the Screening Illustrator showed prevalence peaks and compensatory drops. Only the closed cohort approach remained unaffected by increasing background incidence. The model showed a 20% sustained increase in incidence (IRR: 1.20) from lead-time and increasing background incidence in the open cohort approach for women aged 50-69. However, real life Norwegian data show a corresponding 38% increase. For the model to achieve the observed incidence, 10-14% overdiagnosis had to be added. Conclusion: The observed breast cancer incidence increase in Norway after screening implementation could not be obtained from an average lead-time of 2.5 years and empirical background incidence trends, but had to incorporate overdiagnosis.
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Neoplasias de la Mama/diagnóstico , Detección Precoz del Cáncer/tendencias , Mamografía , Uso Excesivo de los Servicios de Salud/tendencias , Anciano , Femenino , Humanos , Incidencia , Persona de Mediana Edad , Modelos Estadísticos , NoruegaRESUMEN
Regular measurement of prothrombin time as an international normalized ratio PT (INR) is mandatory for optimal and safe use of warfarin. Scandinavian evaluation of laboratory equipment for primary health care (SKUP) evaluated the microINR portable coagulometer (microINR®) (iLine Microsystems S.L., Spain) for measurement of PT (INR). Analytical quality and user-friendliness were evaluated under optimal conditions at an accredited hospital laboratory and at two primary health care centres (PHCCs). Patients were recruited at the outpatient clinic of the Laboratory of Medical Biochemistry, St Olav's University Hospital, Trondheim, Norway (n = 98) and from two PHCCs (n = 88). Venous blood samples were analyzed under optimal conditions on the STA-R®Evolution with STA-SPA + reagent (Stago, France) (Owren method), and the results were compared to capillary measurements on the microINR®. The imprecision of the microINR® was 6% (90% CI: 5.3-7.0%) and 6.3% (90% CI: 5.1-8.3) in the outpatient clinic and PHCC2, respectively for INR ≥2.5. The microINR® did not meet the SKUP quality requirement for imprecision ≤5.0%. For INR <2.5 at PHCC2 and at both levels in PHCC1, CV% was ≤5.0. The accuracy fulfilled the SKUP quality goal in both outpatient clinic and PHCCs. User-friendliness of the operation manual was rated as intermediate, defined by SKUP as neutral ratings assessed as neither good nor bad. Operation facilities was rated unsatisfactory, and time factors satisfactory. In conclusion, quality requirements for imprecision were not met. The SKUP criteria for accuracy was fulfilled both at the hospital and at the PHCCs. The user-friendliness was rated intermediate.
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Automatización de Laboratorios/normas , Relación Normalizada Internacional/instrumentación , Sistemas de Atención de Punto/normas , Tiempo de Protrombina/instrumentación , Análisis de Varianza , Anticoagulantes/farmacología , Automatización de Laboratorios/instrumentación , Coagulación Sanguínea/efectos de los fármacos , Humanos , Laboratorios de Hospital , Noruega , Reproducibilidad de los Resultados , Warfarina/farmacologíaRESUMEN
OBJECTIVE: To estimate changes in the stage distribution of prostate cancer during the time period where opportunistic prostate-specific antigen (PSA) testing was introduced. PATIENTS AND METHODS: Cancer stage, age, and year of diagnosis were obtained for all men aged >50 years diagnosed with prostate cancer in Norway during the period 1980-2010. Three calendar-time periods (1980-1989, 1990-2000, and 2001-2010) and three age groups (50-65, 66-74, and ≥75 years) were defined. Birth cohorts were categorised into four intervals: ≤1915, 1916-1925, 1926-1940 and ≥1941. We used Poisson regressions to conduct both a time period and cohort-based analysis of trends in the incidence of localised, regional, and distant cancer for each combination of age groups and calendar-time periods or birth cohorts, respectively. Additionally, we explored the effect of cohorts on the stage-specific incidence graphically with a Poisson regression using 5-year age groups, and by estimating cumulative incidence rates for each birth cohort. RESULTS: The annual incidence of localised cancers among men aged 50-65 and 66-74 years rose from 41.4 and 255.2 per 100 000, respectively, before the introduction of PSA testing to 137.9 and 418.7 in 2001-2010 afterwards, corresponding to 3.3 [95% confidence interval (CI) 3.1-3.5] and 1.6 (95% CI 1.6-1.7) fold increases. The incidence of regional cancers increased by a factor seven among men aged <75 years. The incidence of distant cancers in men aged ≥75 years decreased by 29% (95% CI 25-33%). These findings were confirmed in the cohort-based approach. CONCLUSION: Opportunistic PSA testing substantially increased the incidence of localised and regional prostate cancers among men aged 50-74 years, which was not fully compensated by the 30% decrease in incidence of distant prostate cancers in older men.
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Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/patología , Anciano , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Noruega/epidemiología , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Factores de TiempoAsunto(s)
Neoplasias de la Mama , Aminoacridinas , Neoplasias de la Mama/radioterapia , Toma de Decisiones , Toma de Decisiones Conjunta , Dinamarca , Miedo , Femenino , Humanos , Recurrencia Local de Neoplasia/radioterapia , Participación del Paciente , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Suitable procedures for transport of blood samples from general practitioners to hospital laboratories are requested. Here we explore routine testing on samples stored and transported as whole blood in lithium-heparin or serum tubes. METHODS: Blood samples were collected from 106 hospitalized patients, and analyzed on Architect c8000 or Advia Centaur XP for 35 analytes at base line, and after storage and transport of whole blood in lithium-heparin or serum tubes at 21 ± 1°C for 10 h. Bias and imprecision (representing variation from analysis and storage) were calculated from values at baseline and after storage, and differences tested by paired t-tests. Results were compared to goals set by the laboratory. RESULTS: We observed no statistically significant bias and results within the goal for imprecision between baseline samples and 10-h samples for albumin, alkaline phosphatase, antitrypsin, bilirubin, creatinine, free triiodothyronine, γ-glutamyl transferase, haptoglobin, immunoglobulin G, lactate dehydrogenase, prostate specific antigen, total carbon dioxide, and urea. Alanine aminotransferase, amylase, C-reactive protein, calcium, cholesterol, creatine kinase, ferritin, free thyroxine, immunoglobulin A, immunoglobulin M, orosomucoid, sodium, transferrin, and triglycerides met goals for imprecision, though they showed a minor, but statistically significant bias in results after storage. Cobalamin, folate, HDL-cholesterol, iron, phosphate, potassium, thyroid stimulating hormone and urate warranted concern, but only folate and phosphate showed deviations of clinical importance. CONCLUSIONS: We conclude that whole blood in lithium-heparin or serum tubes stored for 10 h at 21 ± 1°C, may be used for routine analysis without restrictions for all investigated analytes but folate and phosphate.
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Análisis Químico de la Sangre/normas , Recolección de Muestras de Sangre/normas , Sangre/metabolismo , Análisis Químico de la Sangre/instrumentación , Recolección de Muestras de Sangre/instrumentación , Humanos , Pruebas Inmunológicas/normas , Control de Calidad , Temperatura , Factores de Tiempo , TransportesRESUMEN
BACKGROUND AND OBJECTIVES: In Parkinson's disease (PD) patients, verbal suggestions have been shown to modulate motor and clinical outcomes in treatment with subthalamic deep brain stimulation (DBS). Furthermore, DBS may alleviate pain in PD. However, it is unknown if verbal suggestions influence DBS' effects on pain. METHODS: Twenty-four people with PD and DBS had stimulation downregulated (80-60 to 20%) and upregulated (from 20-60 to 80%) in a blinded manner on randomized test days: (1) with negative and positive suggestions of pain for down- and upregulation, respectively, and (2) with no suggestions to effect (control). Effects of DBS and verbal suggestions were assessed on ongoing and evoked pain (hypertonic saline injections) via 0-10 numerical rating scales along with motor symptoms, expectations, and blinding. RESULTS: Stimulation did not influence ongoing and evoked pain but influenced motor symptoms in the expected direction. Baseline and experimental pain measures showed no patterns in degree of pain. There was a trend toward negative suggestions increasing pain and positive suggestions decreasing pain. Results show significant differences in identical stimulation with negative vs positive suggestions (60% conditions AUC 38.75 vs 23.32, t(13) = 3.10, p < 0.001). Expectations to pain had small to moderate effects on evoked pain. Patients estimated stimulation level correctly within 10 points. CONCLUSION: Stimulation does not seem to influence ongoing and evoked pain, but verbal suggestions may influence pain levels. Patients appear to be unblinded to stimulation level which is an important consideration for future studies testing DBS in an attempted blind fashion.
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Estimulación Encefálica Profunda , Enfermedad de Parkinson , Núcleo Subtalámico , Humanos , Estimulación Encefálica Profunda/métodos , Dolor , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/terapia , Núcleo Subtalámico/fisiologíaRESUMEN
INTRODUCTION: Shared decision making (SDM) has become a crucial element on the political agenda and represents a vital aspect of modern healthcare. However, successful implementation of SDM highly depends on the attitude of clinicians towards SDM. The overall aim of our study was to explore the experience of oncologists and nurses with SDM using the Decision Helper, an in-consultation decision aid, at four Danish radiotherapy departments. METHODS: Semi-structured interviews were conducted with 20 clinicians. The participants were selected using purposive sampling to include nurses and oncologists, male and female, with different levels of experience with SDM and clinical work. The analysis was a data-driven, iterative process with inductive coding of all interviews and meaning condensation. RESULTS: Two main themes emerged: "Using the Decision Helper changes the consultation" and "Change of attitude among Danish oncologists." Each of the two themes included four elaborative subthemes, which are reported with supporting citations in this paper. In brief, the use of SDM and the Decision Helper should ideally be adjusted to the individual patient and depends highly on the oncologist. The participants described ambitions towards "making the right decision for this patient at this time." The healthcare system, however, has pitfalls that may hinder SDM, e.g., rigid interpretation of guideline-based recommendations. CONCLUSION: Using an in-consultation Decision Helper has the potential for individualized, structured patient engagement in decision making. There is a need for patient decision aids in clinical guidelines to ensure patient engagement in decision making.
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Actitud del Personal de Salud , Neoplasias de la Mama , Toma de Decisiones Conjunta , Técnicas de Apoyo para la Decisión , Investigación Cualitativa , Humanos , Femenino , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/psicología , Masculino , Derivación y Consulta , Dinamarca , Participación del Paciente/psicología , Oncólogos/psicología , Relaciones Médico-Paciente , Adulto , Persona de Mediana EdadRESUMEN
BACKGROUND AND PURPOSE: Shared decision making (SDM) is a patient engaging process advocated especially for preference-sensitive decisions, such as adjuvant treatment after breast cancer. An increasing call for patient engagement in decision making highlights the need for a systematic SDM approach. The objective of this trial was to investigate whether the Decision Helper (DH), an in-consultation patient decision aid, increases patient engagement in decisions regarding adjuvant whole breast irradiation. MATERIAL AND METHODS: Oncologists at four radiotherapy units were randomized to practice SDM using the DH versus usual practice. Patient candidates for adjuvant whole breast irradiation after breast conserving surgery for node-negative breast cancer were eligible. The primary endpoint was patient-reported engagement in the decision process assessed with the Shared Decision Making Questionnaire (SDM-Q-9) (range 0-100, 4 points difference considered clinical relevant). Other endpoints included oncologist-reported patient engagement, decisional conflict, fear of cancer recurrence, and decision regret after 6 months. RESULTS: Of the 674 included patients, 635 (94.2%) completed the SDM-Q-9. Patients in the intervention group reported higher level of engagement (median 80; IQR 68.9 to 94.4) than the control group (71.1; IQR 55.6 to 82.2; p < 0.0001). Oncologist-reported patient engagement was higher in the invention group (93.3; IQR 82.2 to 100) compared to control group (73.3; IQR 60.0 to 84.4) (p < 0.0001). CONCLUSION: Patient engagement in medical decision making was significantly improved with the use of an in-consultation patient decision aid compared to standard. The DH on adjuvant whole breast irradiation is now recommended as standard of care in the Danish guideline.
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Aminoacridinas , Neoplasias de la Mama , Toma de Decisiones Conjunta , Humanos , Femenino , Toma de Decisiones , Neoplasias de la Mama/cirugía , Recurrencia Local de Neoplasia , Participación del PacienteRESUMEN
This Data in Brief (DiB) article presents the differences in cycling behaviors related to violations, errors, and positive behaviors by region. The study data were collected by means of a structured questionnaire applied to a full sample of 7,001 participants from 19 countries, distributed over 5 continents. This paper proposes descriptive statistics, as well as common statistical tests. The aim is to enable authors to make their own analyses, not to provide precise interpretations. For further information about the macro project supporting the collection of these data, it is advised to refer to the paper titled "Cross-culturally approaching the cycling behavior questionnaire (CBQ): Evidence from 19 countries", published in Transportation Research Part F: Traffic Psychology and Behavior.
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The aim of this article is to address critical challenges in the OECD 309 "Aerobic mineralization in surface water - simulation biodegradation test" for volatile chemicals, highly hydrophobic chemicals, mixtures or UVCBs (unknown or variable composition, complex reaction products or biological materials). Several modifications are presented to address technical challenges (minimize and account for losses), make testing more environmentally relevant (lower concentrations) and generate data for multiple substances (more and better aligned data):â¢Minimizing and accounting for test substance losses: Aqueous solutions are handled using gas tight syringes, tests are conducted in gas tight vials, and automated analysis is performed directly on unopened test vials. Abiotic losses are accounted for via concentration ratios between test systems and abiotic controls that are incubated and measured in parallel.â¢Testing at low environmentally relevant concentrations: Substances are tested at low concentrations to avoid toxicity and solubility artefacts and analyzed using a sensitive analytical method. Substances are added without co-solvent (using passive dosing) or with a minimum of co-solvent (using microvolume spiking).â¢Testing of multiple chemicals in mixtures combined with constituent specific analysis: Primary biodegradation kinetics of chemicals are determined in tests of multi-constituent mixtures or UVCBs using constituent specific analysis.
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INTRODUCTION: Parkinson's disease (PD) is a widespread neurodegenerative disorder characterised by wide range of symptoms. Freezing of gait (FoG), a transient feeling that the patient's feet are nailed to the floor, resulting in an inability to move, is a particularly distressful symptom. The assessment of FoG can be challenging. Often, clinicians are reliant on patients' subjective experiences and patient questionnaires such as the Freezing of Gait Questionnaire (FOGQ) and its updated version, the New FOGQ (NFOGQ).Until now, the NFOGQ has not been validated and piloted for use in Danish. Therefore, few attempts have been made to assess the prevalence and severity of FoG in Danish patients with PD. METHODS: This report describes a two-step process of adapting the NFOGQ into Danish and piloting its use among a cohort of patients with PD. A satisfactory translation (Danish NFOGQ) was produced and successfully piloted. RESULTS: The translation showed robust test-retest reliability after two weeks. Patients fully understood the questionnaire. Using the Danish NFOGQ in an online prevalence survey, we found that 35.7% of respondents had experienced FoG and that the prevalence correlated with disease duration. CONCLUSION: The Danish NFOGQ appears to be appropriate for assessing FoG in Danish patients with PD in both clinical and research settings. FUNDING: None. TRIAL REGISTRATION: Not relevant.
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Trastornos Neurológicos de la Marcha , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/epidemiología , Prevalencia , Trastornos Neurológicos de la Marcha/epidemiología , Trastornos Neurológicos de la Marcha/etiología , Reproducibilidad de los Resultados , Marcha , Dinamarca/epidemiologíaRESUMEN
INTRODUCTION: Allowing young drivers to gain experience while being supervised by an experienced driver is a widely used measure to try to reduce crash risk. On 1 January 2017, the Danish licensing system was updated to allow licensing at age 17 with post-license supervised driving until solo driving at age 18. METHOD: Based on data from the Danish Driving License register and Statistics Denmark, including the entire population, the purpose of this study is to determine if sociodemographic characteristics and a history of violations and crash involvement among youth predict licensing at age 17. A second purpose is to estimate the time period from licensing until the driver turns 18 and to explore changes in license demand in the context of Denmark's updated licensing system. RESULTS: An increasing proportion choose to license at the age of 17, but the proportion below 19 with a driver's license is unchanged. On average, the license is obtained 5.3â¯months before turning 18. Living in rural areas, with both parents, and in a family with several cars and higher income increases the likelihood of licensing at age 17. Young people with a history of involvement in non-traffic-related accidents or violations are more likely to license at age 17. CONCLUSION: Lowering the license age to allow supervised driving increases early licensing. The average time period from licensing until the driver turns 18 is less than six months. Sociodemographic characteristics predict early licensing. PRACTICAL IMPLICATIONS: Minimum requirements for the time period from licensing until the driver turns 18 are needed to support a safety benefit. Follow-up studies mapping supervised driving, crash involvement, and possible changes in crash risk associated with the change in the Danish licensing system are needed to specify the requirements.
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Accidentes de Tránsito , Conducción de Automóvil , Accidentes de Tránsito/prevención & control , Adolescente , Automóviles , Dinamarca , Humanos , Concesión de LicenciasRESUMEN
Background: The biomarker S100B is used for the rule-out of intracranial lesions in patients with mild traumatic brain injury (TBI) and is suggested for prehospital use in Europe. Early kinetics of S100B are not exhaustively investigated in human TBI. This post hoc descriptive study of the data from the PreTBI studies aimed to characterize the early temporal changes of S100B using two-sample timepoints. Materials and Methods: Two consecutive blood samples were taken prehospital and in-hospital after injury and assayed for S100B. The endpoint adjudication of the outcome intracranial lesion was done by the evaluation of electronic medical patient journals. The data were analyzed using descriptive statistics, scatterplots, and temporal changes estimated by the locally weighted scatterplot smoothing (LOWESS) regression line. Results: A total of 592 adult patients with TBI were included; 566 with Glasgow Coma Scale (GCS) 14-15, 20 with GCS 9-13, and 6 with GCS 3-8. Intracranial lesions were diagnosed in 44/566 (7.4%) of patients. In 90% of patients, S100B concentrations decreased from prehospital to in-hospital sampling. The mean decrease was-0.34 µg/L. S100B concentrations seem to decline already within 60 min. Patients sampled very close to trauma and patients suffering intracranial lesions may express a slight incline before this decline. Temporal changes of S100B did not differ in patients >65 years of age, in antiplatelet/-coagulant treatment, alcohol intoxicated, or suffering extra-cranial injuries. Conclusion: S100B concentrations may peak earlier than expected from previous studies of temporal changes in human TBI. Patterns of S100B stand robust to parameters stated as limiting factors to the use for early rule-out of intracranial lesions in the current guidelines. Further studies are needed to investigate the ultra-early temporal profiles of other novel TBI biomarkers to assess prehospital applicability and optimal diagnostic performance in TBI.
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PURPOSE: The relation between breast induration grade 2-3 at 3 years after radiation therapy and irradiated breast volume was investigated for patients in the Danish Breast Cancer Group (DBCG) Partial Breast Irradiation (PBI) trial. METHODS Treatment plan data was obtained from the Danish radiotherapy plan database. Dosimetric parameters for breast and organs at risk were determined. Breast induration data was obtained from the DBCG database. The volume of the whole breast (CTVp_breast) treated to various dose levels was determined for treatment plans in both arms. Logistic regression was used to assess the frequency of induration on breast volume irradiated to ≥40 Gy. RESULTS PBI and WBI was given to 433 and 432 patients, respectively. Median and interquartile ranges (IQR) for CTVp_breast were 710 mL (467-963 mL; PBI) and 666 mL (443-1012 mL; WBI) (p = 0.98). Median and IQR for CTVp_breast treated to ≥40 Gy was 24.9% (18.6-32.6%; PBI) and 59.8% (53.6-68.5%; WBI). Grade 2-3 induration was observed in 5% (PBI) and 10% (WBI) of the patients. A dose-response relationship was established between irradiated breast volume and frequency of breast induration. From the model, 5% and 10% risks of breast induration were observed for ≥40 Gy delivered to CTVp_breast volumes of 177 mL (95%CI, 94-260 mL) and 426 mL (95%CI, 286-567 mL), respectively. CONCLUSION The frequency of breast induration increased significantly with increasing irradiated breast volume, strongly favouring small volumes and PBI. Thus, treated breast volume - not the breast size itself - is the risk factor for induration. This is the first report directly linking the 40 Gy irradiated breast volume to breast induration.
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Neoplasias de la Mama , Femenino , Humanos , Mama/efectos de la radiación , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Dinamarca , Mastectomía Segmentaria , RadiometríaRESUMEN
Introduction: Gait difficulties are common in Parkinson's disease (PD) and cause significant disability. These symptoms are often resistant to treatment. Spinal cord stimulation (SCS) has been found to improve gait, including freezing of gait, in a small number of patients with PD. The mechanism of action is unclear, and some patients are non-responders. With this double-blind, placebo-controlled efficacy and feasibility clinical and imaging study, we aim to shed light on the mechanism of action of SCS and collect data to inform development of a scientifically sound clinical trial protocol. We also aim to identify clinical and imaging biomarkers at baseline that could be predictive of a favourable or a negative outcome of SCS and improve patient selection. Methods and analysis: A total of 14 patients will be assessed with clinical rating scales and gait evaluations at baseline, and at 6 and 12 months after SCS implantation. They will also receive serial 18F-deoxyglucose and 18FEOBV PET scans to assess the effects of SCS on cortical/subcortical activity and brain cholinergic function. The first two patients will be included in an open pilot study while the rest will be randomised to receive active treatment or placebo (no stimulation) for 6 months. From this point, the entire cohort will enter an open label active treatment phase for a subsequent 6 months. Ethics and dissemination: This study was reviewed and approved by the Committee on Health Research Ethics, Central Denmark RM. It is funded by the Danish Council for Independent Research. Independent of outcome, the results will be published in peer-reviewed journals and presented at national and international conferences. Trial registration number: NCT05110053; ClinicalTrials.gov Identifier.
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INTRODUCTION: In this study we explore the added value of bicycle crash descriptions from open text fields in hospital records from the Aarhus municipality in Denmark. We also explore how bicycle crash data from the hospital complements crash data registered by the police in the same area and time period. METHOD: The study includes 5,313 Danish bicycle crashes, of which 4,205 were registered at the hospital and 1,078 by the police. All crashes occurred from 2010 to 2015. We performed an in-depth analysis of the open text fields on hospital records to identify factors associated with each crash using four categories: bicyclist, road, bicycle, and the other party. We employed the chi-squared test to compare the distribution of variables between crashes registered at the hospital and by the police. A binary logit model was used to estimate the probability that a crash factor is identified, and that each crash factor is associated with a single-bicycle crash. RESULTS: The open-ended text fields in hospital records provide detailed information about crash factors not available in police records, including riding speed, inattention, clothing, specific road conditions, and bicycle defects. The factors alcohol and curb had the highest odds of being identified in relation to a single-bicycle crash. Crash data registered at the hospital included a larger number of bicycle crashes, particularly single-bicycle crashes and crashes with slight injuries only. CONCLUSION: Crash information registered at the hospital in Aarhus Municipality contributes to a better understanding of bicycle crashes due to detailed information about crash-associated factors as well as information about a larger number of bicycle crashes, particularly single-bicycle crashes. Practical implication: Efforts to improve access to detailed information about bicycle crashes are needed to provide a better basis for bicycle crash prevention.
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Accidentes de Tránsito/estadística & datos numéricos , Ciclismo/estadística & datos numéricos , Registros Médicos/estadística & datos numéricos , Accidentes de Tránsito/clasificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Distribución de Chi-Cuadrado , Niño , Preescolar , Dinamarca , Femenino , Hospitales , Humanos , Lactante , Recién Nacido , Modelos Logísticos , Masculino , Persona de Mediana Edad , Probabilidad , Adulto JovenRESUMEN
Road anger is an increasing problem that does not only lead to discomfort but is also associated with aggressive driving and an increased risk of crash involvement. Based on a cognitive-behavioural approach, we developed and tested a short group intervention (90 min) that aimed at decreasing road anger among drivers. We used a before-after control group design, surveying people who did (EG) and who did not (CG) participate in the group intervention. The sample (n = 126) consisted of 80 men and 46 women with a mean age of 54 years (SD = 13). In addition, a sub-sample (n = 37) participated in a driving simulator study before and after the intervention. To enrich the survey- and simulator-based findings, we conducted a focus group discussion about post-intervention experiences in traffic. Comparisons of pre and post survey results showed that constructive expression as measured by a slightly revised sub-scale of the Driving Anger Expression Inventory (DAX-short), increased significantly for EG participants but not within the CG. In addition, the involvement in milder forms of road anger (e.g., yelling) decreased significantly in the EG but not in the CG. In the simulator study, we observed that EG participants decreased the extent of aggressive driving, commenting and gesturing - however, none of these differences were statistically significant. EG participants self-assessed the intervention overall positive and 44 % reported that they had changed their way of thinking or reacting in traffic. Overall, results indicate a positive effect of the cognitive-behavioural group intervention. Study limitations, possibilities to improve the intervention and different areas of application are discussed.