Physical activity in rheumatoid arthritis: relationship to cardiovascular risk factors, subclinical atherosclerosis, and disease activity.

Objective: To investigate associations between physical activity and risk factors for cardiovascular disease (CVD), subclinical atherosclerosis, and disease activity in patients with early and long-standing rheumatoid arthritis (RA).Method: This cross-sectional study included 84 patients with early and 37 with long-standing RA (disease duration, mean ± sd: 1.4 ± 0.4 and 16.3 ± 2.3 years, respectively). Physical activity was measured using a combined accelerometer and heart-rate monitor. Further assessments were disease activity (erythrocyte sedimentation rate, Disease Activity Score in 28 joints), functional ability (Health Assessment Questionnaire), risk factors for CVD (blood lipids, i.e. triglycerides, high-density lipoprotein, low-density lipoprotein; blood glucose, blood pressure, sleeping heart rate, waist circumference, body mass index, and body fat), and subclinical atherosclerosis (pulse-wave velocity, augmentation index, and carotid intima-media thickness).Results: Physical activity variables did not differ between patients with early and long-standing RA. However, 37% of the patients with early and 43% of those with long-standing RA did not reach the World Health Organization's recommended levels of moderate to vigorous physical activity (MVPA). In a final multiple regression model, adjusted for age, gender, disease duration, and activity monitor wear time, higher total physical activity was associated with lower body fat and higher functional ability. With the same adjustments, more time spent in MVPA was associated with lower high-density lipoprotein and lower sleeping heart rate.Conclusions: Physical activity was associated with more favourable risk factors for CVD. However, many patients were physically inactive, stressing the importance of promoting physical activity in RA.

Superselective endovascular tissue access using trans-vessel wall technique: feasibility study for treatment applications in heart, pancreas and kidney in swine.

OBJECTIVES: With the emergence of targeted cell transplantation and gene therapy, there is a need for minimally invasive tissue access to facilitate delivery of therapeutic substrate. The objective of this study was to demonstrate the suitability of an endovascular device which is able to directly access tissue and deliver therapeutic agent to the heart, kidney and pancreas without need to seal the penetration site. METHODS: In vivo experiments were performed in 30 swine, including subgroups with follow-up to evaluate complications. The previously described trans-vessel wall (VW) device was modified to be sharper and not require tip detachment to seal the VW. Injections into targets in the heart (n = 13, 24-h follow-up n = 5, 72-h follow-up n = 3), kidney (n = 8, 14-day follow-up n = 3) and pancreas (n = 5) were performed. Some animals were used for multiple organ injections. Follow-up consisted of clinical monitoring, angiography and necropsy. Transvenous (in heart) and transarterial approaches (in heart, kidney and pancreas) were used. Injections were targeted towards the subepicardium, endomyocardium, pancreas head and tail, and kidney subcapsular space and cortex. RESULTS: Injections were successful in target organs, visualized by intraparenchymal contrast on fluoroscopy and by necropsy. No serious complications (defined as heart failure or persistent arrhythmia, haemorrhage requiring treatment or acute kidney injury) were encountered over a total of 157 injections. CONCLUSIONS: The trans-VW device can achieve superselective injections to the heart, pancreas and kidney for delivery of therapeutic substances without tip detachment. All parts of these organs including the subepicardium, pancreas tail and renal subcapsular space can be efficiently reached.

Handling underlying discrete variables with bivariate mixed hidden Markov models in NONMEM.

Non-linear mixed effects models typically deal with stochasticity in observed processes but models accounting for only observed processes may not be the most appropriate for all data. Hidden Markov models (HMMs) characterize the relationship between observed and hidden variables where the hidden variables can represent an underlying and unmeasurable disease status for example. Adding stochasticity to HMMs results in mixed HMMs (MHMMs) which potentially allow for the characterization of variability in unobservable processes. Further, HMMs can be extended to include more than one observation source and are then multivariate HMMs. In this work MHMMs were developed and applied in a chronic obstructive pulmonary disease example. The two hidden states included in the model were remission and exacerbation and two observation sources were considered, patient reported outcomes (PROs) and forced expiratory volume (FEV1). Estimation properties in the software NONMEM of model parameters were investigated with and without random and covariate effect parameters. The influence of including random and covariate effects of varying magnitudes on the parameters in the model was quantified and a power analysis was performed to compare the power of a single bivariate MHMM with two separate univariate MHMMs. A bivariate MHMM was developed for simulating and analysing hypothetical COPD data consisting of PRO and FEV1 measurements collected every week for 60 weeks. Parameter precision was high for all parameters with the exception of the variance of the transition rate dictating the transition from remission to exacerbation (relative root mean squared error [RRMSE] > 150%). Parameter precision was better with higher magnitudes of the transition probability parameters. A drug effect was included on the transition rate probability and the precision of the drug effect parameter improved with increasing magnitude of the parameter. The power to detect the drug effect was improved by utilizing a bivariate MHMM model over the univariate MHMM models where the number of subject required for 80% power was 25 with the bivariate MHMM model versus 63 in the univariate MHMM FEV1 model and > 100 in the univariate MHMM PRO model. The results advocates for the use of bivariate MHMM models when implementation is possible.

Reduced and optimized trial designs for drugs described by a target mediated drug disposition model.

Monoclonal antibodies against soluble targets are often rich and include the sampling of multiple analytes over a lengthy period of time. Predictive models built on data obtained in such studies can be useful in all drug development phases. If adequate model predictions can be maintained with a reduced design (e.g. fewer samples or shorter duration) the use of such designs may be advocated. The effect of reducing and optimizing a rich design based on a published study for Omalizumab (OMA) was evaluated as an example. OMA pharmacokinetics were characterized using a target-mediated drug disposition model considering the binding of OMA to free IgE and the subsequent formation of an OMA-IgE complex. The performance of the reduced and optimized designs was evaluated with respect to: efficiency, parameter uncertainty and predictions of free target. It was possible to reduce the number of samples in the study by 30% while still maintaining an efficiency of almost 90%. A reduction in sampling duration by two-thirds resulted in an efficiency of 75%. Omission of any analyte measurement or a reduction of the number of dose levels was detrimental to the efficiency of the designs (efficiency ≤ 51%). However, other metrics were, in some cases, relatively unaffected, showing that multiple metrics may be needed to obtain balanced assessments of design performance.

EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update.

Patients with rheumatoid arthritis (RA) and other inflammatory joint disorders (IJD) have increased cardiovascular disease (CVD) risk compared with the general population. In 2009, the European League Against Rheumatism (EULAR) taskforce recommended screening, identification of CVD risk factors and CVD risk management largely based on expert opinion. In view of substantial new evidence, an update was conducted with the aim of producing CVD risk management recommendations for patients with IJD that now incorporates an increasing evidence base. A multidisciplinary steering committee (representing 13 European countries) comprised 26 members including patient representatives, rheumatologists, cardiologists, internists, epidemiologists, a health professional and fellows. Systematic literature searches were performed and evidence was categorised according to standard guidelines. The evidence was discussed and summarised by the experts in the course of a consensus finding and voting process. Three overarching principles were defined. First, there is a higher risk for CVD in patients with RA, and this may also apply to ankylosing spondylitis and psoriatic arthritis. Second, the rheumatologist is responsible for CVD risk management in patients with IJD. Third, the use of non-steroidal anti-inflammatory drugs and corticosteroids should be in accordance with treatment-specific recommendations from EULAR and Assessment of Spondyloarthritis International Society. Ten recommendations were defined, of which one is new and six were changed compared with the 2009 recommendations. Each designated an appropriate evidence support level. The present update extends on the evidence that CVD risk in the whole spectrum of IJD is increased. This underscores the need for CVD risk management in these patients. These recommendations are defined to provide assistance in CVD risk management in IJD, based on expert opinion and scientific evidence.

A rare missense mutation in CHRNA4 associates with smoking behavior and its consequences.

Using Icelandic whole-genome sequence data and an imputation approach we searched for rare sequence variants in CHRNA4 and tested them for association with nicotine dependence. We show that carriers of a rare missense variant (allele frequency=0.24%) within CHRNA4, encoding an R336C substitution, have greater risk of nicotine addiction than non-carriers as assessed by the Fagerstrom Test for Nicotine Dependence (P=1.2 × 10(-4)). The variant also confers risk of several serious smoking-related diseases previously shown to be associated with the D398N substitution in CHRNA5. We observed odds ratios (ORs) of 1.7-2.3 for lung cancer (LC; P=4.0 × 10(-4)), chronic obstructive pulmonary disease (COPD; P=9.3 × 10(-4)), peripheral artery disease (PAD; P=0.090) and abdominal aortic aneurysms (AAAs; P=0.12), and the variant associates strongly with the early-onset forms of LC (OR=4.49, P=2.2 × 10(-4)), COPD (OR=3.22, P=2.9 × 10(-4)), PAD (OR=3.47, P=9.2 × 10(-3)) and AAA (OR=6.44, P=6.3 × 10(-3)). Joint analysis of the four smoking-related diseases reveals significant association (P=6.8 × 10(-5)), particularly for early-onset cases (P=2.1 × 10(-7)). Our results are in agreement with functional studies showing that the human α4ß2 isoform of the channel containing R336C has less sensitivity for its agonists than the wild-type form following nicotine incubation.

Lobectomy for non-small cell lung carcinoma: a nationwide study of short- and long-term survival.

INTRODUCTION: Lobectomy is the standard curative treatment for non-small cell carcinoma (NSCLC) of the lung. Most studies on lobectomy have focused on short-term outcome and 30-day mortality. The aim of this study was to determine both short-term and long-term surgical outcome in all patients who underwent lobectomy for NSCLC in Iceland over a 24-year period. MATERIAL AND METHODS: The study involved 489 consecutive patients with NSCLC who underwent lobectomy with curative intent in Iceland, 1991-2014. Patient demographics, pTNM stage, rate of perioperative complications, and 30-day mortality were registered. Overall survival was analyzed with the Kaplan?Meier method. The Cox proportional hazards model was used to evaluate factors that were prognostic of overall mortality. To study trends in survival, the study period was divided into six 4-year periods. The median follow-up time was 42 months and no patients were lost to follow-up. RESULTS: The average age of the patients was 67 years and 53.8% were female. The pTNM disease stage was IA in 148 patients (30.0%), IB in 125 patients (25.4%), IIA in 96 patients (19.5%), and IIB in 50 patients (10.1%), but 74 (15.0%) were found to be stage IIIA, most often diagnosed perioperatively. The total rate of major complications was 4.7%. Thirty-day mortality was 0.6% (three patients). One- and 5-year overall survival was 85.0% and 49.2%, respectively, with 3-year survival improving from 48.3% to 72.8% between the periods 1991-1994 and 2011-2014 (p = .0004). Advanced TNM stage and age were independent negative prognostic factors for all-cause mortality, and later calendar year and free surgical margins were independent predictors of improved survival. CONCLUSIONS: The short-term outcome of lobectomy for NSCLC in this population-based study was excellent, as reflected in the low 30-day mortality and low rate of major complications. The long-term survival was acceptable and the overall 3-year survival had improved significantly during the study period.

Endovascular method for transplantation of insulin-producing cells to the pancreas parenchyma in swine.

Insulin-producing cells are transplanted by portal vein injection as an alternative to pancreas transplantation in both clinical and preclinical trials. Two of the main limitations of portal vein transplantation are the prompt activation of the innate immunity and concomitant loss of islets and a small but significant risk of portal vein thrombosis. Furthermore, to mimic physiological release, the insulin-producing cells should instead be located in the pancreas. The trans-vessel wall approach is an endovascular method for penetrating the vessel wall from the inside. In essence, a working channel is established to the parenchyma of organs that are difficult to access by percutaneous technique. In this experiment, we accessed the extra-vascular pancreatic parenchyma in swine by microendovascular technique and injected methylene blue, contrast fluids and insulin-producing cells without acute adverse events. Further, we evaluated the procedure itself by a 1-year angiographical follow-up, without adverse events. This study shows that the novel approach utilizing endovascular minimal invasiveness coupled to accurate trans-vessel wall placement of an injection in the pancreatic parenchyma with insulin-producing cells is possible. In clinical practice, the potential benefits compared to portal vein cell transplantation should significantly improve endocrine function of the graft and potentially reduce adverse events.

Mental health indicators and quality of life among individuals with musculoskeletal chronic pain: a nationwide study in Iceland.

OBJECTIVES: Musculoskeletal chronic pain is a costly public health threat. The aim of our study was to investigate mental health indicators, including self-reported symptoms of depression, sleep disruption, stress, well-being, and quality of life (QoL), among men and women with musculoskeletal chronic pain in a general population. METHOD: This was a cross-sectional study; a postal questionnaire was mailed to a stratified random sample of 9807 eligible Icelanders retrieved from a national registry, of whom 5906 responded (response rate = 60.2%). Chronic pain conditions included reports of current chronic back pain, chronic neck symptoms, and/or fibromyalgia. Gender-stratified associations of chronic pain conditions with mental health indicators were estimated with logistic regression analyses adjusting for age, income, body mass index (BMI), smoking, education, and residence. RESULTS: We observed higher odds of low satisfaction with life [adjusted odds ratio (OR(adj)) women 2.0, 95% confidence interval (CI) 1.5-2.6; OR(adj) men 2.3, 95% CI 1.7-3.1], higher levels of perceived stress (OR(adj) women 1.7, 95% CI 1.3-2.2; OR(adj) men = 1.5, 95% CI 1.1-2.1), depressive symptoms (OR(adj) women 2.4, 95% CI 1.9-3.0; OR(adj) men 2.8, 95% CI 2.1-3.7), and sleep disruption (OR(adj) women 2.8, 95% CI 2.2-3.5; OR(adj) men 2.2, 95% CI 1.5-3.1), and diminished QoL (OR(adj) women 1.6, 95% CI 1.2-2.1; OR(adj) men 1.5, 95% CI 1.0-2.1) among individuals with chronic pain compared with those without the condition. CONCLUSIONS: Our data indicate that individuals with musculoskeletal chronic pain have increased risk of poor mental health and diminished QoL. Further studies are needed on treatment and preventative measures of a decline in mental health among individuals with chronic pain.

The apoB/apoA1 ratio predicts future cardiovascular events in patients with rheumatoid arthritis.

OBJECTIVES: Patients with rheumatoid arthritis (RA) have increased mortality and morbidity due to cardiovascular disease (CVD). A high apolipoprotein (apo)B/apoA1 ratio is known to predict cardiovascular events (CVEs) in the population. apoA1 has, besides anti-atherogenic effects, anti-inflammatory properties. The importance of apolipoproteins in the development of CVEs, in the context of lipids, haemostatic factors, and inflammation, was evaluated over 18 years in patients with RA. METHOD: Seventy-four patients with inflammatory active RA (61 females/13 males, mean age 63.6 years, disease duration 22.1 years) had been previously investigated in a study of haemostatic factors [tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI)-1, von Willebrand factor (vWF)], lipids (cholesterol and triglycerides), apolipoproteins (apoA1 and apoB), lipoprotein(a) [Lp(a)], and markers of inflammation [erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and haptoglobin]. After 18 years, the first CVE during follow-up and the presence of traditional CV risk factors, extra-articular disease, and pharmacological treatment were registered. Cox proportional hazards regression was used to identify predictors of a new CVE. RESULTS: A new CVE (n = 34) was predicted by the apoB/apoA1 ratio (p < 0.01), the triglyceride level (p < 0.01), PAI-1 (p < 0.01) and tPA (p < 0.01) activities, vWF (p < 0.001), ESR (< 0.001), CRP (< 0.05), and haptoglobin (p < 0.05). apoA1 (p = 0.056) and apoB (p < 0.05) correlated weakly and inversely with haptoglobin and CRP, respectively. In a multiple Cox regression model, adjusted for gender and previous CVD, the apoB/apoA1 ratio significantly predicted a new CVE, as did vWF, PAI-1, and ESR. CONCLUSIONS: The apoB/apoA1 ratio was a good predictor of CVE during 18 years of follow-up in patients with active RA. Apolipoproteins correlated negatively with inflammation.

Circulating plasma levels of cathepsin S and L are not associated with disease severity in patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is characterized by chronic synovitis and articular cartilage destruction. Increased activities of cathepsin S and cathepsin L, two potent cysteine proteases, are thought to play a role in the pathogenesis of the irreversible articular cartilage destruction. Nevertheless, data regarding the potential importance of the cathepsins as circulating biomarkers in RA patients are limited. METHOD: Subjects enrolled in this study are part of a larger study where patients from the three northern counties of Sweden diagnosed with early RA are followed in an ongoing prospective study. In total, 71 patients were included, along with 44 age- and sex-matched control subjects. Plasma levels of cathepsin S and L were analysed. Disease severity was assessed using the 28-joint count Disease Activity Score (DAS28). RESULTS: Plasma levels of cathepsin S and L were significantly increased in patients with RA compared to healthy controls (p < 0.05 for both). However, in the patients with RA, no association between the cathepsins and the severity of the disease, as characterized by DAS28, was observed (p > 0.51). CONCLUSIONS: Although circulating levels of cathepsin S and L were significantly increased in patients with recently diagnosed RA, our data do not support the notion that circulating levels of cathepsins are relevant biomarkers for disease severity.

The Basic Erosive Wear Examination (BEWE) applied retrospectively to two studies.

OBJECTIVES: A scoring method for tooth erosion is needed to enable community-based assessments. The aim of this study was to evaluate the Basic Erosive Wear Examination (BEWE) scoring method, using data previously collected from two studies. MATERIALS AND METHODS: In a national survey of erosion in children and adolescents, a representative, 20 % nationwide sample of 2,251 children, aged 6, 12 and 15 years, was examined. Erosion, recorded for all surfaces of permanent teeth, was converted to a BEWE score. For a group of referred patients, erosion was scored for 351 patients and then converted to a BEWE score. RESULTS: From the national survey, no erosion was seen in permanent teeth of 6 years old, but was present in 12 years old (19.9 % boys, mean BEWE of 0.22; 11.0 % girls, mean BEWE of 0.079; p < 0.001). Among 15 years old, erosion was seen in 30.7 % of subjects (38.3 % boys, mean BEWE of 1.00; 22.7 % girls, mean BEWE of 0.42; p < 0.001). For the referred patients, the BEWE score was 9.4 for subjects with gastric reflux symptoms but 6.0 for those without symptoms (p < 0.001). CONCLUSIONS: The value of scoring with the BEWE methodology was clearly demonstrated, showing increasing severity of erosion between 12 and 15 years and gender differences in erosion severity. Intrinsic acid erosion clearly caused an increased BEWE score. CLINICAL RELEVANCE: The BEWE scoring methodology appears valuable for assessing erosion in populations.

Observations of growth and postspawning survival of lumpfish Cyclopterus lumpus from mark-recapture studies.

Growth and postspawning survival of lumpfish Cyclopterus lumpus are described by mark-recapture experiments using juveniles in offshore areas in the north-east Atlantic Ocean and spawning adults in coastal Norway and Iceland. A female fish tagged as a juvenile and recaptured as an adult matured in a period of 18 months, providing the first observation on development in a wild C. lumpus. The von Bertalanffy growth function, fitted to data from recaptured fish, was used to estimate K and L∞ and recaptured fish spawning after a year at liberty indicated a postspawning survival of c. 10% in Iceland.

Functional limitations and physical symptoms of individuals with chronic pain.

OBJECTIVES: Chronic pain is a debilitating condition that may cause additional symptoms affecting the sufferers' working capacity and quality of life. Studying the prevalence and consequences of chronic pain in various populations remains important for a complete picture of the global burden imposed by chronic pain conditions. METHODS: We investigated the prevalence of self-reported chronic pain conditions in Iceland in addition to symptoms and functional limitations within the group, using a population-based random sample. A questionnaire was mailed to 9807 Icelanders aged 18-79 years and, of these, 5906 participated in the study. Chronic pain was considered manifest in people reporting chronic low back pain, chronic neck symptoms, and/or fibromyalgia. Prevalence calculations were weighted with respect to gender, age, and residential area to represent the underlying population. Associations of chronic pain conditions with symptoms and functional limitations were measured with adjusted logistic regression models, contrasting symptoms in individuals reporting any of the three pain conditions with those who did not. RESULTS: The population-estimated prevalence of chronic pain condition was 19.9% with distinct gender differences (men = 15.2%, women = 24.7%). Several symptoms and functional limitations in daily life were strongly associated with chronic pain, including deficient energy and muscular discomfort, physical mobility limitations, lifting groceries, climbing stairs, and stooping. Women, but not men, with chronic pain tended to refrain from physical activity. CONCLUSIONS: Chronic pain is a prevalent condition and those who report chronic pain generally suffer from ill health and limitations in their daily life compared to individuals not suffering from the condition.

Gamma spectrometric measurement of uranium isotopic composition and mass in sintered UO2 pellets using the efficiency transfer method.

Gamma spectrometric measurements to determine the isotopic composition and total uranium mass in UO2 pellets (D = 7.5 mm; H = 3.5 mm, ρ = 10 g/cm3) were carried out. The required efficiency curve was obtained by applying the efficiency transfer method from a calibration standard (D = 65 mm; H = 20 mm) of a slightly acidified water solution. The average isotopic composition of ten UO2 pellets was consistent with values of natural uranium given by IUPAC. The average relative bias for the 235U/238U amount ratio was -0.73% using the 1001 keV gamma line for 238U and 0.50% using the 63 keV gamma line (186 keV was always used for 235U). For the total uranium mass, the mean deviation as compared to mass determinations using a balance was 5.5% using the 1001 keV gamma line for 238U and 4.3% using the 63 keV gamma line.

Tradeoffs and synergies in wetland multifunctionality: A scaling issue.

Wetland area in agricultural landscapes has been heavily reduced to gain land for crop production, but in recent years there is increased societal recognition of the negative consequences from wetland loss on nutrient retention, biodiversity and a range of other benefits to humans. The current trend is therefore to re-establish wetlands, often with an aim to achieve the simultaneous delivery of multiple ecosystem services, i.e., multifunctionality. Here we review the literature on key objectives used to motivate wetland re-establishment in temperate agricultural landscapes (provision of flow regulation, nutrient retention, climate mitigation, biodiversity conservation and cultural ecosystem services), and their relationships to environmental properties, in order to identify potential for tradeoffs and synergies concerning the development of multifunctional wetlands. Through this process, we find that there is a need for a change in scale from a focus on single wetlands to wetlandscapes (multiple neighboring wetlands including their catchments and surrounding landscape features) if multiple societal and environmental goals are to be achieved. Finally, we discuss the key factors to be considered when planning for re-establishment of wetlands that can support achievement of a wide range of objectives at the landscape scale.

A population-based investigation of the autoantibody profile in mothers of children with atrioventricular block.

The objective of the study was to investigate the antigen specificity and occurrence of individual autoantibodies in mothers of children diagnosed with atrioventricular (AV) block in a nation-wide setting. Patients with AV block detected before 15 years of age were identified using national quality registries as well as a network of pediatric and adult cardiologists and rheumatologists at the six university hospitals in Sweden. Patients with gross heart malformations, surgically or infectiously induced blocks were excluded. Blood samples were obtained from the mothers and maternal autoantibody profile, including the occurrence of antibodies against Ro52, Ro60, La, SmB, SmD, RNP-70k, RNP-A, RNP-C, CENP-C, Scl-70, Jo-1, ribosomal RNP and histones was investigated in 193 mothers of children with AV block by immunoblotting and ELISA. Autoantibody reactivity was detected in 48% (93/193) of the mothers of children with AV block. In autoantibody-positive mothers, the vast majority, 95% (88/93), had antibodies against Ro52, while 63% (59/93) had autoantibodies to Ro60 and 58% (54/93) had autoantibodies to La. In addition, 13% (12/93) of the autoantibody-positive mothers had antibodies to other investigated antigens besides Ro52, Ro60 and La, and of these anti-histone antibodies were most commonly represented, detected in 8% (7/93) of the mothers. In conclusion, this Swedish population-based study confirms that maternal autoantibodies may associate with heart block in the child. Further, our data demonstrate a dominant role of Ro52 antibodies in association with AV block.

Alpha spectrometry and liquid scintillation counting for the measurement of 238Pu, 239Pu, 240Pu, 241Pu, 242Pu and age.

A method for the measurement of the isotopic composition and time since last chemical separation (age) of plutonium is presented. The method includes alpha spectrometric measurement of 238Pu, 239Pu and 240Pu where the ratio of 239Pu and 240Pu was determined using spectral deconvolution, and liquid scintillation counting of 241Pu, after chemical separation of plutonium and americium. For the age determination, the 241Pu determined using liquid scintillation counting was combined with alpha spectrometric measurement of 241Am. The results of the isotopic composition were compared with certified reference materials with known isotopic composition, and the results of the age determination were compared with literature values of the separation dates.

Timing of paediatric orchidopexy in universal healthcare systems: international administrative data cohort study.

BACKGROUND: International guidelines in 2008 recommended orchidopexy for undescended testis at 6-12 months of age to reduce the risk of testicular cancer and infertility. Using administrative data from England, Finland, Ontario (Canada), Scotland and Sweden (with data from Victoria (Australia) and Iceland in supplementary analyses), the aim of this study was to investigate compliance with these guidelines and identify potential socioeconomic inequities in the timing of surgery before 1 and 3 years. METHODS: All boys born in 2003-2011 with a diagnosis code of undescended testis and procedure codes indicating orchidopexy before their fifth birthday were identified from administrative health records. Trends in the proportion of orchidopexies performed before 1 and 3 years of age were investigated, as were socioeconomic inequities in adherence to the guidelines. RESULTS: Across all jurisdictions, the proportion of orchidopexies occurring before the first birthday increased over the study period. By 2011, from 7·6 per cent (Sweden) to 27·9 per cent (Scotland) of boys had undergone orchidopexy by their first birthday and 71·5 per cent (Sweden) to 90·4 per cent (Scotland) by 3 years of age. There was limited evidence of socioeconomic inequities for orchidopexy before the introduction of guidelines (2008). Across all jurisdictions for boys born after 2008, there was consistent evidence of inequities in orchidopexy by the first birthday, favouring higher socioeconomic position. Absolute differences in these proportions between the highest and lowest socioeconomic groups ranged from 2·5 to 5·9 per cent across jurisdictions. CONCLUSION: Consistent lack of adherence to the guidelines across jurisdictions questions whether the guidelines are appropriate.

ANTECEDENTES: En el 2008, las guías internacionales recomendaban efectuar una orquidopexia para los testículos no descendidos entre los seis y los 12 meses de edad para reducir los riesgos de cáncer testicular e infertilidad. Utilizando datos administrativos de Inglaterra, Finlandia, Ontario (Canadá), Escocia y Suecia (con datos de Victoria, Australia e Islandia para análisis complementarios), el objetivo de este estudio fue investigar el cumplimiento de estas guías y la identificación de posibles desigualdades socioeconómicas con relación al momento de la cirugía antes de 1 y 3 años de edad. MÉTODOS: A partir de los registros administrativos de salud, se identificaron todos los niños nacidos entre 2003 y 2011 con código diagnóstico de testículos no descendidos y con código de procedimiento correspondiente a orquidopexia antes de cumplir 5 años. Se investigaron las tendencias en la proporción de orquidopexias realizadas antes de 1 y 3 años de edad, respectivamente, al igual que las desigualdades socioeconómicas en el cumplimiento de las directrices de las guías. RESULTADOS: En todas las jurisdicciones, la proporción de orquidopexias realizadas antes del primer año de vida aumentó durante el periodo de estudio. En 2011, del 7,6% (Suecia) al 27,9% (Escocia) de los niños habían sido sometidos a orquidopexia en su primer año de vida y del 71,5% (Suecia) al 90,4% (Escocia) a los 3 años de edad. Hubo evidencia limitada de las inequidades socioeconómicas para la orquidopexia antes de la introducción de las guías (2008). En todas las jurisdicciones para los niños nacidos después de 2008, hubo evidencia consistente de inequidades para la práctica de una orquidopexia en el primer año de vida en favor de una posición socioeconómica más alta (socioeconomic position, SEP). Las diferencias absolutas en estas proporciones entre los grupos SEP más altos y más bajos oscilaron entre el 2,5% y el 5,9% en todas las jurisdicciones. CONCLUSIÓN: La falta de adherencia a las guías observada consistentemente en todas las jurisdicciones cuestiona si las guías son apropiadas.