Treatment-related changes in serum neutrophil gelatinase-associated lipocalin (NGAL) in psoriatic arthritis: results from the PIPA cohort study.

OBJECTIVES: Obesity and psoriatic arthritis (PsA) have a complicated relationship. While weight alone does not cause PsA, it is suspected to cause worse symptoms. Neutrophil gelatinase-associated lipocalin (NGAL) is secreted through various cell types. Our objective was to assess the changes and trajectories in serum NGAL and clinical outcomes in patients with PsA during 12 months of anti-inflammatory treatment. METHOD: This exploratory prospective cohort study enrolled PsA patients initiating conventional synthetic or biological disease-modifying anti-rheumatic drugs (csDMARDs/bDMARDs). Clinical, biomarker, and patient-reported outcome measures were retrieved at baseline, and 4 and 12 months. Control groups at baseline were psoriasis (PsO) patients and apparently healthy controls. The serum NGAL concentration was quantified by a high-performance singleplex immunoassay. RESULTS: In total, 117 PsA patients started a csDMARD or bDMARD, and were compared indirectly at baseline with a cross-sectional sample of 20 PsO patients and 20 healthy controls. The trajectory in NGAL related to anti-inflammatory treatment for all included PsA patients showed an overall change of -11% from baseline to 12 months. Trajectories in NGAL for patients with PsA, divided into treatment groups, showed no clear trend in clinically significant decrease or increase following anti-inflammatory treatment. NGAL concentrations in the PsA group at baseline corresponded to the levels in the control groups. No correlation was found between changes in NGAL and changes in PsA outcomes. CONCLUSION: Based on these results, serum NGAL does not add any value as a biomarker in patients with peripheral PsA, either for disease activity or for monitoring.

The interplay between the impact of household's and children's education on the risk of type 2 diabetes and death among older adults: a Danish register-based cohort study.

OBJECTIVES: This study aims to assess the association of household's and children's education on the risk of type 2 diabetes (T2D) and subsequent death. STUDY DESIGN: Danish register-based cohort study. METHODS: In total, 1,021,557 adults were included at their 65th birthday between 2000 and 2018. A multistate survival model was performed to estimate the association of household's and children's education on the transition between the three states: 1) 65th birthday; 2) diagnosis of T2D; and 3) all-cause death. RESULTS: The incidence rates per 1000 person-years were 9.1 for T2D, 18.4 for death without T2D, and 45.0 for death with T2D. Compared to long household's education and children's education, long household's education combined with either short-medium children's education or no children were associated with a 1.49- (95% confidence interval [CI]: 1.44; 1.54] and 1.69-times (95% CI: 1.61;1.78) higher hazard of T2D, respectively. Short-medium household's education combined with either long children's education or no children were associated with 0.64- (95% CI: 0.62; 0.66) and 0.77-times (95% CI: 0.74; 0.79) lower hazard of T2D, respectively. Compared to long household's education and children's education, any other combination of household's and children's education was associated with higher hazards of death both without and with T2D. CONCLUSION: Older adults living in households with long education with no children or children with short-medium education had higher hazards of T2D. Households with short-medium education and no children or children with long education were associated with lower hazards of T2D. Both household's and children's education were associated with higher hazard of death without and with T2D.

Immediate adverse reactions following COVID-19 vaccination among 16-65-year-old Danish citizens.

INTRODUCTION: There is sparse knowledge of immediate adverse reactions following COVID-19 vaccination. OBJECTIVE: This study aimed to estimate the frequency and number of immediate adverse reactions following COVID-19 vaccination in a Danish population. METHODS: The study used data from the Danish population-based cohort study BiCoVac. The frequencies of 20 self-reported adverse reactions were estimated for each vaccine dose stratified by sex, age, and vaccine type. Also, the distributions of number of adverse reactions following each dose were estimated stratified by sex, age, vaccine type, and prior COVID-19 infection. RESULTS: A total of 889,503 citizens were invited and 171,008 (19 %) vaccinated individuals were included in the analysis. The most frequently reported adverse reaction following the first dose of COVID-19 vaccine was redness and/or pain at the injection site (20 %) while following the second and third dose, tiredness was the most frequently reported adverse reaction (22 % and 14 %, respectively). Individuals aged 26-35 years, females, and those with a prior COVID-19 infection were more likely to report adverse reactions compared with older individuals, males, and those with no prior COVID-19 infection, respectively. Following the first dose, individuals vaccinated with ChAdOx1-2 (AstraZeneca) reported more adverse reactions compared with individuals vaccinated with other vaccine types. Individuals vaccinated with mRNA-1273 (Moderna) reported more adverse reactions following the second and third dose compared with individuals vaccinated with BNT162b2 (Pfizer-BioNTech). CONCLUSION: The frequency of immediate adverse reactions was highest among females and younger persons, however, most of the Danish citizens did not experience immediate adverse reactions following COVID-19 vaccination.

25-year trends in first-time hospitalizations for Parkinson's disease and subsequent mortality: A Danish nationwide cohort study.

BACKGROUND: In most countries, incidence and mortality for Parkinson's disease (PD) have not been monitored by surveillance registries, although it could demonstrate the need for primary and tertiary prevention. OBJECTIVE: To examine 25-year trends in first-time hospitalizations for PD in Denmark and subsequent short and long-term mortality. METHODS: In a nationwide population-based cohort we identified all 34,947 individuals with a first-time hospitalization for PD from 1995 through 2019. We calculated standardized incidence rates of PD and 1-year and 5-year mortality by sex. Mortality rates were compared with a reference cohort randomly selected from the background population matched on sex, age, and index date. RESULTS: The annual standardized incidence rate of PD was relatively stable during the study period in both men and women. The incidence of PD was higher in men than in women and with the highest incidence in those aged 70-79 years. One and 5-year mortality risk after first-time hospitalization for PD was similar for men and women, and decreased by around 30% and 20%, respectively, between 1995 and 2019. The matched reference cohort had a similar decline in mortality over time. CONCLUSION: The rate of first-time hospitalization for PD was relatively stable between 1995 and 2019, whereas subsequent short and long-term mortality declined during the period as in the reference cohort.

Increased prevalence of sleep disturbance in psoriatic arthritis is associated with inflammatory and non-inflammatory measures.

OBJECTIVES: To examine the prevalence of sleep disturbances, quantified by the Pittsburgh Sleep Quality Index (PSQI), in patients with psoriatic arthritis (PsA), psoriasis (PsO) and healthy controls (HCs), explore associations between PSQI and clinical and patient-reported outcomes, and evaluate the effect of treatment on PSQI. METHOD: Patients were included from the Parker Institute's PsA patient cohort to evaluate the prevalence of sleep disturbances. Univariate and multivariate regression analyses were used to explore associations between sleep disturbance and outcome measures. Treatment effect in PsA patients was assessed with a mixed-effect model for repeated measures. RESULTS: In total, 109 PsA patients, 20 PsO patients, and 20 HCs were included. Sleep disturbances were reported by 66.1% of PsA patients, 45.0% of PsO patients, and 15.0% of HCs. Univariate regression analyses revealed statistically significant associations (p < 0.001) between PSQI and Disease Activity Score (DAS28CRP), tender points, visual analogue scale (VAS) patient global and pain, Psoriatic Arthritis Impact of Disease fatigue, Health Assessment Questionnaire (HAQ), and painDETECT score. Multivariate regression analysis demonstrated VAS patient global, VAS pain, and tender points as being independently associated with PSQI. The mixed-effect model revealed no effect of treatment. CONCLUSION: More PsA patients than PsO patients and HCs reported sleep disturbances. Sleep disturbances were associated with inflammatory and non-inflammatory measures possibly explaining the limited effect of treatment. This demonstrates the need for interdisciplinary approaches to improve the management of sleep disturbance in PsA.Trial registration: ClinicalTrials.gov (NCT02572700).

La importancia de la geriatría transversal en la cirugía abdominal oncológica / The importance of cross-speciality geriatrics in abdominal oncologic surgery

Introducción. El paciente de edad avanzada es el usuario más frecuente en los centros sanitarios. La Geriatría transversal comparteel proceso asistencial con el cirujano atendiendo la esfera cognitiva, funcional y social del paciente, con el objetivo de optimizar loscuidados (tales como mantenimiento de la independencia funcional, nutrición, detección del deterioro cognitivo…) ofreciendo unacobertura integral y reduciendo complicaciones, costes y estancia hospitalaria de manera sobreañadida. El objetivo del trabajo esdar visibilidad a la contribución que el geriatra puede llevar acabo en los servicios de Cirugía General. Material y métodos. Seriede casos mediante estudio descriptivo retrospectivo en el que se analizaron los pacientes mayores de 75 años intervenidos de cáncerde colón durante el año 2021 en el Hospital Central de la Cruz Roja mediante cirugía programada y su evolución clínica posteriora los 6 meses. Resultados: 10 pacientes (80% mujeres), edad media 76,4 años (±3,2), Escala Cruz Roja Funcional media de 1/5(±0,9), con índice de Barthel modificado 80/100 (±15,2), Escala Cruz Roja Mental de 0/5 (±0,6). Índice de Charlson medio de 4,3puntos (±2,2) con 60% enfermedades cardiovasculares, 20% insuficiencia renal crónica y 20% neumopatías. Destacó la elevadapolifarmacia (100%) y desnutrición (60%) previo a la cirugía. El 50% presentó delirium y el 40% padeció insuficiencia cardiacadescompensada. Conclusiones. La Geriatría transversal ayuda a detectar necesidades silentes y debe participar en la atenciónmulticomponente tanto previa a la cirugía (prehabilitación) como en la hospitalización y seguimiento posterior, colaborando con el cirujano en la atención al paciente crónico complejo geriátrico. (AU)

Introduction. The older patient is the most frequent user in healthcare centers. Cross-speciality geriatrics shares the care processwith the surgeon attending the cognitive, functional and social sphere of the patient, with the aim of optimizing care (such asmaintenance of functional independence, nutrition, detection of cognitive deterioration...) offering a comprehensive coverage andreducing complications, costs and hospital stay in a superadded way. The aim of this study is to give visibility to the contributionthat geriatricians can make in general surgery services. Material and methods. Case series by retrospective descriptive study inwhich patients over 75 years of age operated on for colon cancer during the year 2021 in the Central Hospital of the Red Cross byscheduled surgery and their clinical evolution after 6 months were analyzed. Results: 10 patients (80% women), mean age 76.4years (±3.2), mean Functional Red Cross Scale of 1/5 (±0.9), with modified Barthel index 80/100 (±15.2), Mental Red Cross Scaleof 0/5 (±0.6). Mean Charlson index of 4.3 points (±2.2) with 60% cardiovascular disease, 20% chronic renal failure and 20% pneumopathies. The high polypharmacy (100%) and malnutrition (60%) prior to surgery stood out. Fifty percent presented deliriumand 40% suffered from decompensated heart failure. Conclusions. Cross-speciality geriatrics helps to detect silent needs and shouldparticipate in multicomponent care both prior to surgery, during hospitalization and subsequent follow-up, collaborating with thesurgeon in the care of the geriatric complex chronic patient. (AU)

La hernia umbilical en régimen de cirugía mayor ambulatoria: procedimiento seguro y de menor coste / Umbilical hernia in major outpatient surgery: safe and lower-cost procedure

Introducción: La cirugía mayor ambulatoria (CMA) constituye una estrategia coste-efectiva comparada con la cirugía tradicional, al resolver el procedimiento quirúrgico sin comprometer la calidad de la atención ni la seguridad del paciente. Objetivo: Demostrar que la cirugía abierta de la hernia umbilical en régimen de CMA es un procedimiento seguro y de menor coste. Para ello realizamos un estudio de los factores de riesgo de ingreso no previsto en pacientes intervenidos de hernia umbilical en nuestro servicio, durante cuatro años. Material y métodos: Estudio observacional retrospectivo de 478 pacientes consecutivos intervenidos durante los años 2015 a 2018. Se revisaron las historias electrónicas de los pacientes y se creó una base de datos para el estudio de los resultados. Se utilizó un modelo de regresión logística para analizar el factor de riesgo de ingreso no previsto por edad, sexo, antecedentes personales, índice de masa corporal, ASA del paciente, tipo de reparación, tamaño del defecto, utilización de prótesis, causa del ingreso no previsto y complicaciones. Resultados: Edad media 48,1 ± 13 años con un índice de hospitalización global del 8,8 %. Hombres 319 (66,7 %) y mujeres 159 (33,3 %) con una tasa de ingresos no previstos del 6,9 % y 12,6 %, respectivamente ( p = 0,039). El análisis estadístico demostró que no se incrementa el riesgo de ingreso no previsto con la edad (0,678). El riesgo de hospitalización fue 2,78 veces mayor en las mujeres que en los hombres ( p = 0,005). Los pacientes ASA II tienen un riesgo de hospitalización 6,49 veces superior a los pacientes con ASA I (0,021) (AU)

Introducción: La cirugía mayor ambulatoria (CMA) constituye una estrategia coste-efectiva comparada con la cirugía tradicional, al resolver el procedimiento quirúrgico sin comprometer la calidad de la atención ni la seguridad del paciente. Objetivo: Demostrar que la cirugía abierta de la hernia umbilical en régimen de CMA es un procedimiento seguro y de menor coste.To this end, we conducted a study of the risk factors for unforeseen admission in patients operated on for umbilical hernia in our service, for four years. Material and methods: Retrospective observational study of 478 consecutive patients operated on during the years 2015 to 2018. Electronic patient records were reviewed and a database was created for the study of outcomes. A logistic regression model was used to analyze the risk factor for unplanned admission by age, sex, personal history, body mass index, patient ASA, type of repair, defect size, use of prostheses, cause of unplanned admission and complications. Results: Mean age 48.1 ± 13 years with an overall hospitalization rate of 8.8 %. Males 319 (66.7%) and females 159 (33.3%) with an unforeseen income rate of 6.9% and 12.6%, respectively (p = 0.039). Statistical analysis showed that the risk of unplanned admission does not increase with age (0.678) The risk of hospitalization was 2.78 times higher in women than in men (p = 0.005). ASA II patients have a 6.49-fold higher risk of hospitalization than patients with ASA I (0.021). A greater number of admissions was found in patients operated on with general anesthesia and spinal anesthesia, compared to those operated with local anesthesia and sedation or with a laryngeal mask (p = 0.000). Major outpatient surgery was cheaper than surgery with admission, between 45-52%, with a statistically significant difference (p = 0.000) (AU)

Angiogenic potential is reduced in skeletal muscle of aged women.

KEY POINTS: The risk of cardiovascular disease and associated skeletal muscle microvascular rarefaction is enhanced in women after menopause, yet knowledge about the angiogenic potential in ageing women is generally sparse. Aged healthy and sedentary women were found to present a markedly impaired capacity for proliferation of skeletal muscle derived microvascular endothelial cells compared to young women. Vascular endothelial growth factor (VEGF) levels in skeletal muscle myocytes and release of VEGF from myocytes tended to be lower in aged compared to young women. The aged women did not show a detectable increase in skeletal muscle capillarization with 8 weeks of intense aerobic cycle training. Combined, the findings indicate that aged women have a reduced potential for capillary growth in skeletal muscle which, with ageing, may lead to age-induced microvascular rarefaction. ABSTRACT: Skeletal muscle angiogenic potential was examined in cell cultures derived from aged and young women, and the effect of 8 weeks of intense cycle training on muscle capillary growth was determined in the group of aged women. Basal muscle samples were obtained from healthy sedentary aged (n = 12; 64 ± 4.2 years) and young women (n = 5; 24 ± 3.2 years) for endothelial cell and skeletal muscle myocyte isolation and experiments. In addition, the aged women completed an 8-week training intervention. Peak oxygen uptake and muscle samples for histology and protein determination were obtained before and after the training period. Before training, muscle microdialysate was collected from the aged women at rest and during exercise. In Part 1 of the experiments, growth-supplement stimulated proliferation of endothelial cells was ∼75% lower in cells from aged compared to young women (P < 0.001). There was a tendency for a lower vascular endothelial growth factor (VEGF) concentration in muscle conditioned media (P = 0.0696) and for a lower VEGF content in the myocytes (P = 0.0705) from aged compared to young women. Endothelial proliferation was found to be highly dependent on mitochondrial function. Acute exercise resulted in a modest (1.3-fold; P = 0.0073) increase in muscle interstitial VEGF protein in the aged women. In Part 2, 8 weeks of intense training did not change muscle capillarization (P ≥ 0.1502) in the aged women, but led to an increased amount of muscle VEGF (P = 0.0339). In conclusion, aged women have impaired angiogenic potential, which is associated with a compromised response both at the skeletal muscle myocyte and microvascular endothelial cell level.

Factores predictivos de recurrencia tras la reparación abierta de la hernia umbilical en 551 pacientes consecutivos. Estudio observacional retrospectivo / Predictors for recurrence after open um-bilical hernia repair in 551 consecutive patients. Observactional retrospective study

INTRODUCCIÓN: La recurrencia tras la reparación abierta de la hernia umbilical, constituye un problema importante para el paciente, el sistema sanitario y para el equipo quirúrgico. Actualmente, no existe consenso entre las sociedades quirúrgicas sobre los factores de riesgo de recidiva. Determinar estos factores es fundamental para corregirlos, realizar el tratamiento más apropiado y disminuir la tasa de la misma. OBJETIVO: El propósito de este estudio es evaluar los factores predictivos de recidiva tras la reparación abierta de la hernia umbilical con y sin malla, en cado uno de los periodos del proceso quirúrgico (preoperatorio, intraoperatorio y postoperatorio), en los pacientes operados en nuestro servicio durante 4 años. Material y MÉTODOS: Estudio observacional retrospectivo de 551 pacientes consecutivos intervenidos durante los años 2015 a 2018. Se revisaron las historias electrónicas de los pacientes y se creó una base de datos para el estudio de los resultados. El modelo de la regresión de Cox univariable y multivariable se utilizó para analizar la supervivencia libre de recurrencia por edad, sexo, índice de masa corporal, ASA del paciente, tabaquismo, diabetes, broncopatía, tamaño del defecto, tipo de reparación, clase de prótesis y complicaciones. Las curvas de Kaplan-Meier se utilizaron para analizar la supervivencia libre de recurrencia para factores de riesgo preoperatorios, intraoperatorios y postoperatorios. RESULTADOS: Edad media de los pacientes, 49,9 ± 13,9 años con una tasa de recurrencia global del 6,5%. Hombres 367 (66,6%) y recidiva del 5,7%. Mujeres 184 (33,4%) y recaída del 8,2% (P = 0,276). Seguimiento medio de 14,6 (± 12,3) meses. La mayoría de los pacientes (96,4%), se clasificaron de bajo riesgo anestésico (ASA I y II), con una recurrencia del 6,3% y 20 pacientes ASA III (3,6%) con recidiva del 10% (P = 0,564). Respecto al peso, 124 pacientes (22,5%) tenían un IMC < 25 con una tasa de recidiva del 5,6%, 215 pacientes (39%) con IMC >25-30 con una recurrencia del 6,5% y 212 pacientes (38,5%) con IMC >30 (38,5%) y recidiva del 7,5%. Se contabilizaron 61 pacientes (11,1%) diabéticos con 4 recidivas (6,6%) (p = 0,994). Broncopatía en 64 pacientes (11,6%) con una recurrencia del 10,9% (p = 0,129). Tabaquismo en 132 pacientes (24,5%) con recurrencia del 6,3% y 74 herniorráfias (13,4%) con una recidiva del 8,1%. Hernioplástia con malla simple en 424 casos con una recurrencia del 6,6% y hernioplástia con malla compuesta en 53 casos con una recidiva del 3,8% (P=0,617). Tamaño medio del defecto 2,75 cm (0,5-4 cm). Complicaciones postoperatorias: seroma en 22 casos (4%) y tasa recidiva 22,7% (P=0,002), infección quirúrgica en 18 casos con recurrencia del22,2% (P = 0,006). El análisis estadístico demuestra que por cada año de edad, el riesgo de recurrencia aumenta un 3% (P = 0.068), que las mujeres tienen un 52% más riesgo de recidiva que los hombres (P = 0,277), que la obesidad presenta un 46% más riesgo de recaída (p = 0,313) y que la broncopatía tiene 3 veces más riesgo de recidiva (P = 0,030). La infección quirúrgica representa un 75% más riesgo de recurrencia (p = 0,608) y el seroma representa un riesgo 5 veces mayor de recurrencia, estadísticamente significativa (p = 0,004). CONCLUSIÓN: Nuestros resultados indican que a mayor edad, el sexo femenino, ASA III, alto índice de masa corporal, diabetes, broncopatía, tamaño del defecto herniario, tipo de reparación, infección quirúrgica y seroma fueron los factores asociados con un mayor riesgo de recurrencia después de la reparación abierta de la hernia umbilical

INTRODUCTION: Recurrence after open umbilical hernia repair constitutes an important problem for the patient, the health system and the surgical team. Currently, there is no consensus among surgical societies on the risk factors for hernia recurrence. Determining these factors is essential to correct them, carry out the most appropriate treatment and reduce the recurrence rate. OBJECTIVE: The purpose of this study is to evaluate the predictive factors of recurrence after open repair of umbilical hernia with and without mesh, in each of the periods of the surgical process (preoperative, intraoperative and postoperative), in patients operated on in our service for 4 years. MATERIAL AND METHODS: Retrospective observational study of 551 consecutive patients operated during the years 2015 to 2018. The electronic records of the patients were reviewed and a database was created to study the results. Univariate and multivariate Cox regression was used to analyze recurrence-free survival by age, sex, body mass index, ASA of the patient, smoking, diabetes, bronchopathy, size of the defect, type of repair, class of prosthesis, and complications. Kaplan-Meier curves were used to analyze recurrence-free survival for preoperative, intraoperative, and postoperative risk factors. RESULTS: Mean age of the patients, 49.9 ± 13.9 years. Men 367 (66.6%) and women 184 (33.4%) (P = 0.693). Global recurrence rate 6.5%. Recurrence in women, 8.2%. Recurrence in men 5.7% (P = 0.276). Mean follow-up of 14.6 (± 12.3) months. Most of the patients were classified as low anesthetic risk (ASA I and II), 531 patients (96.4%) with a recurrence of 6.3% and 20 ASA III patients (3.6%) with a recurrence of the 10% (P = 0.564). Regarding weight, 124 patients (22.5%) had a normal weight with a relapse of 5.6%, 215 patients (39%) were overweight with a relapse of 6.5% and 212 were obese (38.5% ) with a recurrence rate of 7.5%. There were 61 diabetic patients (11.1%) with 4 relapses (6.6%) (p = 0.994). Bronchopathy in 64 patients (11.6%) with a recurrence of 10.9% (p = 0.129). Smoking in 132 patients (24.5%) with a recurrence of 6.1% (P = 0.801). Regarding the technical aspects, 477 hernioplasties (86.6%) were performed with a recurrence rate of 6.3% and 74 herniorrhaphies (13.4%) with a recurrence of 8.1%. Simple mesh hernioplasty in 424 cases with a recurrence of 6.6% and hernioplasty with composite mesh in 53 cases with a recurrence of 3.8% (P = 0.617). Ave-rage default size 2.75 cm (0.5-4 cm). Postoperative complications: 22 patients (4%) presented seroma with a recurrence of 22.7% (P = 0.002) and 18 patients (3.3%) presented surgical infection with a recurrence rate of 22.2% (P = 0.006 ). After statistical analysis and when adjusting the selected variables, it was detected: that for each year of age, the risk of recurrence increases by 3% (P = 0.068), that women have a 52% higher risk of recurrence than men (P = 0.277), that obesity has a 46% higher risk of relapse (p = 0.313) and that bronchopathy has a 3 times higher risk of recurrence (P = 0.030). Surgical infection represents a 75% higher risk of recurrence (p = 0.608) and postoperative seroma represents a statistically significant 5 times higher risk of recurrence (p = 0.004). CONCLUSION: Our results indicate that at older age, female sex, ASA III, high body mass index, diabetes, bronchopathy, size of the hernial defect, type of repair, surgical infection and seroma were the factors associated with a higher risk of recurrence. after open umbilical hernia repair

The association between depressive mood and ischemic heart disease: a twin study.

OBJECTIVE: Individuals with mood disorders have increased risk of cardiovascular disease. The aims of this study were to evaluate if the risk of cardiovascular disease in individuals with mood disorder could be explained by shared genetic and early environmental factors. METHODS: We included 6714 Danish middle and old aged twins from two large population-based studies. Cox proportional hazards regression was used to perform individual-level and intra-pair analyses of the association between self-reported depression symptomatology scores and register-based diagnoses of ischemic heart disease. RESULTS: Higher depression symptomatology scores (both total, affective, and somatic) were associated with higher incidence of ischemic heart disease after multivariable adjustment in individual-level analyses. In intra-pair analyses, this association was similar but with slightly larger confidence intervals. There was no interaction with gender and no major differences between mono- or dizygotic twins. Within twin pairs, the twin scoring highest on depressive symptoms developed ischemic heart disease more often or earlier than the lower scoring twin. A sensitivity analysis including a 2-year time lag of depression symptomatology to limit the risk of reverse causality showed similar results. CONCLUSION: Genetic factors and early life environment do not seem to explain the association between depressive mood and ischemic heart disease.

Determinants for symptomatic gallstone disease readmissions - results from a cohort with screen-detected gallstone disease.

AIM OF THE STUDY: Selection of patients for cholecystectomy is hampered by lack of objective criteria. The objectives of this cohort study were to identify if patient, symptoms, or gallstone disease characteristics determined readmission in an unselected cohort with screen-detected gallstone disease and who had experienced a first admission with symptomatic gallstone disease. METHODS: Data from three random sampled population-based cohorts were used. At baseline, participants were screened with ultrasound and 664 had gallstones of which 84 had a first admission without cholecystectomy performed. A cohort study was performed with follow-up up for hospital readmissions beyond 30 days through central registers. Age adjusted Cox regression analyses were performed. RESULTS: Readmissions occurred in 60.8% and cholecystectomy was eventually performed in 47.7% of patients. Early readmissions were determined by abdominal pain in the epigastrium (Hazard ratio (HR) 3.63, 95% confidence interval (CI) [1.62;8.12]) and of moderate intensity (HR 2.71, 95% CI [1.20;6.16]). Late readmissions were determined by larger gallstone size, especially when above 10mm (HR 4.11, 95% CI [1.18;14.3]) and inversely determined by age (HR 0.97, 95% CI [0.95;0.998]). In patients with initially uncomplicated gallstone disease, cholecystectomy was inversely determined by age (HR 0.96, 95% CI [0.93;0.98]). CONCLUSION: Once gallstones have become symptomatic and caused hospital admission, a persisting high risk for future readmission exists and half of patients end up having cholecystectomy. Pain in the epigastrium, larger gallstones, and younger age determine readmission. These determinants should be tested in future clinical treatment algorithms for gallstone disease.

Biological treatment in ankylosing spondylitis in the Nordic countries during 2010-2016: a collaboration between five biological registries.

OBJECTIVES: Large-scale observational cohorts may be used to study the effectiveness and rare side effects of biological disease-modifying anti-rheumatic drugs (bDMARDs) in ankylosing spondylitis (AS), but may be hampered by differences in baseline characteristics and disease activity across countries. We aimed to explore the research infrastructure in the five Nordic countries regarding bDMARD treatment in AS. METHOD: This observational cohort study was based on data from biological registries in Denmark (DANBIO), Sweden (SRQ/ARTIS), Finland (ROB-FIN), Norway (NOR-DMARD), and Iceland (ICEBIO). Data were collected for the years 2010-2016. Registry coverage, registry inventory (patient characteristics, disease activity measures), and national guidelines for bDMARD prescription in AS were described per country. Incident (first line) and prevalent bDMARD use per capita, country, and year were calculated. In AS patients who started first line bDMARDs during 2010-2016 (n = 4392), baseline characteristics and disease activity measures were retrieved. RESULTS: Registry coverage of bDMARD-treated patients ranged from 60% to 95%. All registries included extensive prospectively collected data at patient level. Guidelines regarding choice of first line drug and prescription patterns varied across countries. During the period 2010-2016 prevalent bDMARD use increased (p < 0.001), whereas incident use tended to decrease (p for trend < 0.004), with large national variations (e.g. 2016 incidence: Iceland 10.7/100 000, Finland 1.7/100 000). Baseline characteristics were similar regarding C-reactive protein, but differed for other variables, including the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (range 3.5-6.3) and Ankylosing Spondylitis Disease Activity Score (ASDAS) (2.7-3.8) (both p < 0.0001). CONCLUSION: Collaboration across the five Nordic biological registries regarding bDMARD use in AS is feasible but national differences in coverage, prescription patterns, and patient characteristics must be taken into account depending on the scientific question.

Hyperthyroxinemia is positively associated with prevalent and incident type 2 diabetes mellitus in two population-based samples from Northeast Germany and Denmark.

BACKGROUND AND AIMS: A potential causal relationship between thyroid function and type 2 diabetes mellitus is currently under debate, but the current state of research is limited. Our aim was to investigate the association of thyroid hormone levels with prevalent and incident type 2 diabetes mellitus (T2DM) in two representative studies. METHODS AND RESULTS: Analyses are based on data from the Study of Health in Pomerania (SHIP), a German population based cohort with 4308 individuals at baseline and 3300 individuals at a five-year follow-up, and from INTER99, a Danish population-based randomized controlled trial with 6784 individuals at baseline and 4516 individuals at the five-year-follow-up. Serum thyroid-stimulating hormone (TSH) and free thyroxine (fT4) concentrations were measured in both studies, while free triiodothyronine was measured in SHIP only. T2DM was defined by self report or intake of anti-diabetic medication. Neither in SHIP nor in INTER99 we detected significant associations of serum TSH levels with prevalent or incident T2DM. Serum fT4 levels were significantly positively associated with prevalent T2DM in SHIP and INTER99. In longitudinal analyses baseline levels of fT4 were significantly positively associated with incident T2DM in SHIP (RR per pmol/L = 1.07; 95%-CI = 1.05-1.10), while this association barely missed statistical significance in INTER99 (RR per pmol/L = 1.03; 95%-CI = 0.99-1.06). In SHIP baseline fT3 levels were significantly associated with incident T2DM (RR per pmol/L = 1.21; 95%-CI = 1.16-1.27). CONCLUSION: We demonstrated positive associations of thyroid hormones with prevalent and incident type 2 diabetes mellitus suggesting that hyperthyroxinemia may contribute to the pathogenesis of this condition.

Wellbeing of gay fathers with children born through surrogacy: a comparison with lesbian-mother families and heterosexual IVF parent families.

STUDY QUESTION: Are there differences in levels of parental wellbeing (parental stress, psychological adjustment and partner relationship satisfaction) between gay-father families with infants born through surrogacy, lesbian-mother families with infants born through donor insemination, and heterosexual-parent families with infants born through IVF? SUMMARY ANSWER: There were no differences in parental wellbeing. WHAT IS KNOWN ALREADY: The only other study of parental wellbeing in gay-father families formed through surrogacy (mean age children: 4 years old) found no difference in couple relationship satisfaction between these families and lesbian-mother families formed through donor insemination and heterosexual-parent families formed without assisted reproductive technologies. STUDY DESIGN, SIZE, DURATION: This cross-sectional study is part of an international research project involving 38 gay-father families, 61 lesbian-mother families and 41 heterosexual-parent families with 4-month-olds. In each country (the UK, the Netherlands and France), participants were recruited through several sources, such as specialist lawyers with expertise in surrogacy (for the recruitment of gay fathers), lesbian and gay parenting support groups, fertility clinics (for the recruitment of lesbian and heterosexual parents), and/or online forums and magazines. PARTICIPANTS/MATERIALS, SETTING, METHODS: During a home visit when their infants were between 3.5 and 4.5 months old, participants completed standardized measures of parental stress, parental psychological adjustment (anxiety and depression) and partner relationship satisfaction. MAIN RESULTS AND THE ROLE OF CHANCE: All parents reported relatively low levels of parental stress, anxiety and depression, and were all relatively satisfied with their intimate relationships. After controlling for caregiver role (primary or secondary caregiver role), there were no significant family type differences in parental stress, P = 0.949, depression, P = 0.089, anxiety, P = 0.117, or relationship satisfaction, P = 0.354. LIMITATIONS, REASONS FOR CAUTION: The findings cannot be generalized to all first-time ART parents with infants because only families from relatively privileged backgrounds participated. WIDER IMPLICATIONS OF THE FINDINGS: Our findings may have implications for the development of policy and legislation in relation to these new family forms, as well as the regulation of surrogacy in the Netherlands and France. In addition, our findings might encourage professional organizations of obstetricians and gynecologists in these countries to recommend that requests for assisted reproduction should be considered regardless of the applicants' sexual orientation. STUDY FUNDING/COMPETING INTEREST(S): This research was supported, under the auspices of the Open Research Area (Application BO 3973/1-1; Principal Investigator, Michael E Lamb), by grants from the UK Economic and Social Research Council (ESRC; Grant ES/K006150/1; Principal Investigator, Michael E. Lamb), The Netherlands Organisation for Scientific Research (NWO; Grant NWO 464-11-001, Principal Investigator, Henny W.M. Bos) and the French Agence Nationale de Recherche (ANR; Grant ANR-12-ORAR-00005-01, Principal Investigator, Olivier Vecho) whose support is gratefully acknowledged. There were no competing interests.

Estimating the causal effect of body mass index on hay fever, asthma and lung function using Mendelian randomization.

BACKGROUND: Observational studies have shown that body mass index (BMI) is positively associated with asthma. However, observational data are prone to confounding and reverse causation. In Mendelian randomization, genetic variants are used as unconfounded markers of exposures to examine causal effects. We examined the causal effect of BMI on asthma, hay fever, allergic sensitization, serum total immunoglobulin E (IgE), forced expiratory volume in one-second (FEV1) and forced vital capacity (FVC). METHODS: We included 490 497 participants in the observational and 162 124 participants in the genetic analyses. A genetic risk score (GRS) was created using 26 BMI-associated single nucleotide polymorphisms (SNPs). Results were pooled in meta-analyses and expressed as odds ratios (ORs) or ß-estimates with 95% confidence interval (CI). RESULTS: The GRS was significantly associated with asthma (OR=1.009; 95% CI: 1.004, 1.013), but not with hay fever (OR= 0.998; 95% CI: 0.994, 1.002) or allergic sensitization (OR=0.999; 95% CI: 0.986, 1.012) per BMI-increasing allele. The GRS was significantly associated with decrease in FEV1: ß=-0.0012 (95% CI: -0.0019, -0.0006) and FVC: ß=-0.0022 (95% CI: -0.0031, -0.0014) per BMI-increasing allele. Effect sizes estimated by instrumental variable analyses were OR=1.07 (95% CI: 1.03, 1.10) for asthma, a 9 ml decrease in FEV1 (95% CI: 2.0-15 mL decrease) and a 16 ml decrease in FVC (95% CI: 7.0-24 mL decrease) per 1 kg/m2 higher BMI. CONCLUSIONS: The results support the conclusion that increasing BMI is causally related to higher prevalence of asthma and decreased lung function, but not with hay fever or biomarkers of allergy.

Evidence of opposing fitness effects of parental heterozygosity and relatedness in a critically endangered marine turtle?

How individual genetic variability relates to fitness is important in understanding evolution and the processes affecting populations of conservation concern. Heterozygosity-fitness correlations (HFCs) have been widely used to study this link in wild populations, where key parameters that affect both variability and fitness, such as inbreeding, can be difficult to measure. We used estimates of parental heterozygosity and genetic similarity ('relatedness') derived from 32 microsatellite markers to explore the relationship between genetic variability and fitness in a population of the critically endangered hawksbill turtle, Eretmochelys imbricata. We found no effect of maternal MLH (multilocus heterozygosity) on clutch size or egg success rate, and no single-locus effects. However, we found effects of paternal MLH and parental relatedness on egg success rate that interacted in a way that may result in both positive and negative effects of genetic variability. Multicollinearity in these tests was within safe limits, and null simulations suggested that the effect was not an artefact of using paternal genotypes reconstructed from large samples of offspring. Our results could imply a tension between inbreeding and outbreeding depression in this system, which is biologically feasible in turtles: female-biased natal philopatry may elevate inbreeding risk and local adaptation, and both processes may be disrupted by male-biased dispersal. Although this conclusion should be treated with caution due to a lack of significant identity disequilibrium, our study shows the importance of considering both positive and negative effects when assessing how variation in genetic variability affects fitness in wild systems.

Are incident gallstones associated to sex-dependent changes with age? A cohort study.

Age and female sex have repeatedly been identified as gallstone determinants but the underlying mechanisms are not clarified. The objectives of this study were to determine if changes with age in physiology, lifestyle, or reproductive hormones were associated with incident gallstones. A cohort study of a general population random sample (N = 2366) aged 30-60 years was performed. Participants were ultrasound screened for gallstones in 1982-84 and again in 1993-94. Lifestyle data and blood samples were obtained and re-analyzed in 2004. Changes with age in physiology (body mass index, blood pressure, blood lipids, self-rated health), lifestyle (smoking, alcohol and coffee consumption, dietary habits, physical activity level), and indices of reproductive function (number of births, oral contraceptive use, hormone replacement therapy, male reproductive hormones) were explored in females and males separately. Adjusted logistic regression analyses were performed. Incident gallstones (gallstones and cholecystectomy) at ultrasound examination in participants initially free of gallstones at baseline occurred in 9.9% of the study population. In females, increasing alcohol consumption (odds ratio (OR) 0.94, 95% confidence interval (CI) [0.90; 0.98]) and the cessation of hormone replacement therapy (OR 0.29, 95% CI [0.10; 0.83]) inversely determined incident gallstones. In males, increasing levels of SHBG (OR 0.97, 95% CI [0.94; 0.998]) inversely determined incident gallstones. Other changes with age in physiology, lifestyle, or reproductive hormones were not associated. High baseline free testosterone determined incident gallstones in males (OR 1.15, 95% CI [1.02; 1.30]). To conclude, changes with age in alcohol consumption in females and in reproductive hormones determined incident gallstones. Male reproductive hormones seem to have an impact on incident gallstones. Sex differences should be explored further in future studies.

Do high participation rates improve effects of population-based general health checks?

The aim is to investigate if the effect of a health check differs between areas with different participation rates. The Inter99 population-based randomized lifestyle intervention study covered 73 areas within the suburbs of Copenhagen, Denmark. Adults aged 30-60years were randomly drawn from a population and were randomized to intervention group (n=11,483) or control group (n=47,122). Participation rates in the health check varied considerably between areas (mean 52%; range 35-85%). In separate survival analyses, area participation rate was included both as a continuous exposure variable and as a categorical variable (tertiles; low: 35-49%, meddle: 50-54%, high: 55-84%). All persons in the intervention and control group were followed in registers for 10-year total mortality and combined events (ischemic heart disease, stroke, or both). In adjusted models (including sociodemographic variables, ethnicity, number of children and comorbidity), among men, there was no difference in risk of death between areas with varying participation rates. Surprisingly, among women living in high-participation areas a significantly higher risk of all-cause mortality (HR: 1.32 [1.03-1.69]) was found in the intervention group (ref=controls). For both men and women, in no areas there was any difference between intervention and control group in incident IHD/stroke. Higher participation rates in population based health checks is probably unlikely to improve the effects of these, and may in worst case be harmful in subgroups of the population. Further well-designed studies within non-participation research should have high priority and are required to establish link between health checks and risk of death in subgroups of the population.

Homozygous carriers of the TCF7L2 rs7903146 T-allele show altered postprandial response in triglycerides and triglyceride-rich lipoproteins.

The TCF7L2 rs7903146 T-allele shows the strongest association with type 2 diabetes (T2D) among common gene variants. The aim of this study was to assess circulating levels of metabolites following a meal test in individuals carrying the high risk rs790346 TT genotype (cases) and low-risk CC genotype (controls). Sixty-two men were recruited based on TCF7L2 genotype, 31 were TT carriers and 31 were age- and BMI-matched CC carriers. All participants consumed a test meal after 12 hours of fasting. Metabolites were measured using proton nuclear magnetic resonance (NMR) spectroscopy. Metabolomic profiling of TCF7L2 carriers were performed for 141 lipid estimates. TT carriers had lower fasting levels of L-VLDL-L (total lipids in large very low density lipoproteins, p = 0.045), L-VLDL-CE (cholesterol esters in large VLDL, p = 0.03), and L-VLDL-C (total cholesterol in large VLDL, p = 0.045) compared to CC carriers. Additionally, TT carriers had lower postprandial levels of total triglycerides (TG) (q = 0.03), VLDL-TG (q = 0.05, including medium, small and extra small, q = 0.048, q = 0.0009, q = 0.04, respectively), HDL-TG (triglycerides in high density lipoproteins q = 0.037) and S-HDL-TG (q = 0.00003). In conclusion, TT carriers show altered postprandial triglyceride response, mainly influencing VLDL and HDL subclasses suggesting a genotype-mediated effect on hepatic lipid regulation.

Clopidogrel-Paclitaxel Drug-Drug Interaction: A Pharmacoepidemiologic Study.

Paclitaxel is mainly eliminated by CYP2C8 in the liver. CYP2C8 is strongly inhibited by the clopidogrel metabolite acyl-ß-D-glucuronide. To determine if this interaction has clinical relevance, we identified 48 patients treated with clopidogrel and paclitaxel using databases and a prescription register. Peripheral sensory neuropathy was retrospectively evaluated from medical charts and compared to that of 88 age- and sex-matched controls treated with paclitaxel and low-dose aspirin. By a cumulative dose of 1,500 mg paclitaxel, 35% of the patients had developed severe neuropathy. The overall hazard ratio between clopidogrel use and severe paclitaxel neuropathy was 1.7 (95% confidence interval, 0.9-3.0). Among those receiving a high-dose paclitaxel regimen, the hazard ratio was 2.3 (95% confidence interval, 1.1-4.5). Our study indicates that clopidogrel is associated with a clinically relevant increased risk of neuropathy in patients treated with high-dose paclitaxel.