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OBJECTIVE: We aimed to validate a food-frequency questionnaire (FFQ) for Dutch pregnant women, against three 24 h-recalls and blood concentrations of B-vitamins and fatty acids, using the method of triads. METHODS: We included 83 pregnant women from the general population of Rotterdam, the Netherlands, at a median gestational age of 15.6 weeks. Participants completed three non-consecutive 24 h-recalls, and subsequently filled out the 293-item FFQ. Participants provided blood samples from which we analyzed serum folate and vitamin B12, as well as red blood cell folate, linoleic acid, and total saturated, monounsaturated, and polyunsaturated fatty acids. RESULTS: Estimated energy intake did not differ between the FFQ and 24 h-recalls. Deattenuated Pearson's correlation coefficients, between energy-adjusted nutrient intake estimates from the FFQ and the 24 h-recalls, ranged from 0.41 (fat) to 0.88 (fiber) for macronutrients, and were around 0.6 for most micronutrients, except for vitamin E (0.27). Using the triad method, we obtained validity coefficients of 0.86 (95% Confidence Interval (CI) 0.36, 1.00) for serum folate, 0.86 (95% CI 0.18, 1.00) for red blood cell folate, and 1.00 (95% CI 0.42, 1.00) for vitamin B12. Validity coefficients for serum fatty acids ranged from 0.22 to 0.67. CONCLUSION: This FFQ is a reliable tool for estimating intake of energy, macronutrients, folate and vitamin B12 among women in mid-pregnancy.
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Encuestas sobre Dietas/métodos , Ingestión de Alimentos/fisiología , Evaluación Nutricional , Mujeres Embarazadas , Encuestas y Cuestionarios , Adulto , Ingestión de Energía , Ácidos Grasos/sangre , Femenino , Ácido Fólico/sangre , Humanos , Ácido Linoleico/sangre , Micronutrientes/administración & dosificación , Países Bajos , Nutrientes/administración & dosificación , Embarazo , Reproducibilidad de los Resultados , Vitamina B 12/sangreRESUMEN
BACKGROUND: Compared to men, women live longer but have more years with disability. We assessed the contribution of gender differences in mortality and disability, total and by cause, to women's excess unhealthy life years (ULYs). METHODS: We used mortality data for France 2008 from Eurostat, causes of death from the CépiDc-INSERM-database; and disability and chronic conditions data from the French Disability Health Survey 2008-09. ULYs were calculated by the Sullivan method. The contributions of mortality and disability differences to gender differences in ULY were based on decomposition analyses. RESULTS: Life expectancy of French women aged 50 was 36.3 years of which 19.0 were ULYs; life expectancy of men was 30.4 years of which 14.2 were ULYs. Of the 4.8 excess ULYs in women, 4.0 years were due to lower mortality. Of these 4.0 ULYs, 1.8 ULY originated from women's lower mortality from cancer, 0.8 ULY from heart disease and 0.3 ULY from accidents. The remaining 0.8 excess ULY in women were from higher disability prevalence, including higher disability from musculoskeletal diseases (+1.8 ULY) and anxiety-depression (+0.6 ULY) partly offset by lower disability from heart diseases (-0.8 ULY) and accidents (-0.3 ULY). CONCLUSION: Lower mortality and higher disability prevalence contributed to women's longer life expectancy with disability. Women's higher disability prevalence due to non-fatal disabling conditions was partly offset by lower disability from heart disease and accidents. Conditions differentially impact gender differences in ULY, depending on whether they are mainly life-threatening or disabling. The conclusions confirm the health-survival paradox.
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Estado de Salud , Esperanza de Vida , Mujeres , Factores de Edad , Anciano , Anciano de 80 o más Años , Causas de Muerte , Personas con Discapacidad/estadística & datos numéricos , Femenino , Francia/epidemiología , Encuestas Epidemiológicas , Humanos , Masculino , Persona de Mediana Edad , Mortalidad , Prevalencia , Factores SexualesRESUMEN
BACKGROUND: Chronic-active antibody mediated rejection (c-aABMR) is a major contributor to long-term kidney allograft loss. We conducted a retrospective analysis to establish the efficacy of treatment with intravenous immunoglobulins (IVIG) and pulse methylprednisolone (MP) of patients with c-aABMR. METHODS: Sixty-nine patients, in the period 2005-2017, with the diagnosis (suspicious for) c-aABMR that were treated with IVIG and MP were included. Patients were administered three doses of 1 g intravenous MP combined with a single dose of IVIG (1 g/kg body weight). Primary outcome was the decline in allograft function one year post treatment. Responders to IVIG-MP therapy were defined by an eGFR one year after treatment which was at least 25% above the projected allograft function. RESULTS: Patients showed an average decline in eGFR of 9.8 ml/min/1.73m2 the year prior to treatment. Following treatment, a significant reduction (p < 0.001) in eGFR decline was observed (6.3 ml/min/1.73m2). Furthermore, a significant improvement in proteinuria was observed upon treatment (p < 0.001). Sixty-two percent (n = 43) of the patients were considered a responder and showed considerable slowing of graft function deterioration in the year after treatment (p < 0.001). Three and 5-year graft survival was significantly superior in responders. CONCLUSIONS: More than 60% of patients with c-aABMR with a progressive decline in eGFR respond favorably to treatment with IVIG-MP resulting in a significant improvement of graft survival (Sablik, Am J Transplant 18, 2018).
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Supervivencia de Injerto/inmunología , Inmunoglobulinas Intravenosas/administración & dosificación , Fallo Renal Crónico , Metilprednisolona/administración & dosificación , Complicaciones Posoperatorias , Adulto , Tasa de Filtración Glomerular , Glucocorticoides/administración & dosificación , Humanos , Factores Inmunológicos/administración & dosificación , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Evaluación de Resultado en la Atención de Salud , Complicaciones Posoperatorias/inmunología , Complicaciones Posoperatorias/fisiopatología , Complicaciones Posoperatorias/terapiaRESUMEN
BACKGROUND: Socioeconomic inequalities in neonatal mortality are substantial in many developing countries. Little is known about how to address this problem. Trials in Asia and Africa have shown strong impacts on neonatal mortality of a participatory learning and action intervention with women's groups. Whether this intervention also reduces mortality inequalities remains unknown. We describe the equity impact of this women's groups intervention on the neonatal mortality rate (NMR) across socioeconomic strata. METHODS: We conducted a meta-analysis of all four participatory women's group interventions that were shown to be highly effective in cluster randomized trials in India, Nepal, Bangladesh and Malawi. We estimated intervention effects on NMR and health behaviours for lower and higher socioeconomic strata using random effects logistic regression analysis. Differences in effect between strata were tested. RESULTS: Analysis of 69120 live births and 2505 neonatal deaths shows that the intervention strongly reduced the NMR in lower (50-63% reduction depending on the measure of socioeconomic position used) and higher (35-44%) socioeconomic strata. The intervention did not show evidence of 'elite-capture': among the most marginalized populations, the NMR in intervention areas was 63% lower [95% confidence interval (CI) 48-74%] than in control areas, compared with 35% (95% CI: 15-50%) lower among the less marginalized in the last trial year (P-value for difference between most/less marginalized: 0.009). The intervention strongly improved home care practices, with no systematic socioeconomic differences in effect. CONCLUSIONS: Participatory women's groups with high population coverage benefit the survival chances of newborns from all socioeconomic strata, and perhaps especially those born into the most deprived households.
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Países en Desarrollo , Mortalidad Infantil , Atención Prenatal , Factores Socioeconómicos , Mujeres , Bangladesh , Participación de la Comunidad , Investigación Participativa Basada en la Comunidad , Femenino , Conductas Relacionadas con la Salud , Humanos , India , Lactante , Recién Nacido , Malaui , Nepal , Embarazo , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Background: Women report more disability than men perhaps due to gender differences in the prevalence of diseases and/or in their disabling impact. We compare the contribution of chronic diseases to disability in men and women in France, using a disability survey conducted in both private households and institutions, and we also examine the effect of excluding the institutionalized population. Methods: Data comprised 17 549 individuals age 50+, who participated in the 2008-09 French Disability Health Survey including people living in institutions. Disability was defined by limitations in activities people usually do due to health problems (global activity limitation indicator). Additive regression models were fitted separately by gender to estimate the contribution of conditions to disability taking into account multi-morbidity. Results: Musculoskeletal diseases caused most disability for both men (10.1%, CI: 8.1-12.0) and women (16.0%, CI 13.6-18.2). The second contributor for men was heart diseases (5.7%, CI: 4.5-6.9%), and for women anxiety-depression (4.0, CI 3.1-5.0%) closely followed by heart diseases (3.8%, CI 2.9-4.7%). Women's higher contribution of musculoskeletal diseases reflected their higher prevalence and disabling impact; women's higher contribution of anxiety-depression and lower contributions of heart diseases reflected gender differences in prevalence. Excluding the institutionalized population did not change the overall conclusions. Conclusions: The largest contributors to the higher disability of women than men are moderately disabling conditions with a high prevalence. Whereas traditional disabling conditions such as musculoskeletal diseases are more prevalent and disabling in women, fatal diseases such as cardiovascular disease are also important contributors in women and men.
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Enfermedad Crónica/psicología , Personas con Discapacidad/psicología , Personas con Discapacidad/estadística & datos numéricos , Encuestas Epidemiológicas , Anciano , Anciano de 80 o más Años , Femenino , Francia , Humanos , Masculino , Persona de Mediana Edad , Factores Sexuales , Encuestas y CuestionariosRESUMEN
Chronic-active antibody-mediated rejection (c-aABMR) is defined as histological evidence of chronic endothelial injury (cg), also known as transplant glomerulopathy, and either microvascular inflammation (MVI) or positivity for C4d. Importantly, the presence of donor-specific antibodies (DSA) is currently still mandatory for the diagnosis of c-aABMR. This retrospective study of 41 c-aABMR patients investigates whether cases suspicious for c-aABMR (DSA negative, n = 24) differ from cases of c-aABMR (DSA positive, n = 17) with respect to renal histology, allograft function and long-term graft survival. All included patients had progressive loss of allograft function and were diagnosed by for cause biopsy and scored according to the Banff '15 criteria. In all DSApos cases, DSA were de novo and the majority was directed against HLA-II being mostly anti-HLA-DQ antibodies. There were no statistically significant differences in clinical characteristics, decline in allograft function and renal allograft survival in cases with or without DSAs. All cases showed chronic histomorphological damage and inflammation, irrespective of the presence of DSA. Renal histology and clinical outcome of patients suspicious for c-aABMR (DSAneg) do not significantly differ from patients with a diagnosis of c-aABMR (DSApos). We believe that our study adds to the ongoing debate regarding the need for DSAs to be present for the diagnosis of c-aABMR.
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Rechazo de Injerto/inmunología , Rechazo de Injerto/patología , Trasplante de Riñón/efectos adversos , Riñón/patología , Anticuerpos/inmunología , Femenino , Supervivencia de Injerto , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosAsunto(s)
Prednisona/uso terapéutico , Sarcoidosis Pulmonar/terapia , Espirometría/métodos , Esteroides/uso terapéutico , Adulto , Femenino , Servicios de Atención de Salud a Domicilio , Humanos , Masculino , Persona de Mediana Edad , Monitoreo Ambulatorio , Estudios Prospectivos , Calidad de Vida , Pruebas de Función Respiratoria , Sarcoidosis Pulmonar/psicología , Capacidad VitalRESUMEN
OBJECTIVES: To investigate the kidney selection procedure before donation to maximize donor safety, we investigated whether ultrasonographic measurements of kidney volume are comparable with computed tomography measurements. Predonation volume and increases in kidney size may be important indicators of renal function after donation and subsequent loss of function. MATERIALS AND METHODS: Consecutive donors with predonation computed tomography scans were approached preoperatively for additional ultrasonographic examinations. Measurements were independently performed by 2 ultrasonographers and considered accurate when the mean differences between both examiners for length, width, and thickness of the kidneys were < 5 mm. Ultrasonographic volumes were calculated with the ellipsoid equation (length × width × thickness × π/6) and an adjusted equation (length × width × thickness × 0.674), and computed tomography volumes were calculated with the voxel count method, which is considered the criterion standard. RESULTS: For this study (Dutch Trial Register NTR3795), 100 kidneys were measured. The mean differences between examiner 1 and 2 for similar ultrasonography measurements were < 5 mm. The ellipsoid equation underestimated the volume for examiner 1 by 16.9% and for examiner 2 by 14.8%, whereas the adjusted equation overestimated the volume by 6.8% and 9.5% respectively. The correlation between computed tomography and ultrasonographic volume with the adjusted equation was strong for both examiner 1 (r = 0.76; P < .001) and examiner 2 (r = 0.80; P < .001). CONCLUSIONS: Ultrasonographic measurements of kidney volume are comparable with computed tomography measurements. Therefore, ultrasonography is a reliable modality for living kidney donor follow-up monitoring of kidney size adaption after donation.
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Selección de Donante/métodos , Trasplante de Riñón/métodos , Riñón/diagnóstico por imagen , Donadores Vivos , Ultrasonografía , Adaptación Fisiológica , Adulto , Anciano , Femenino , Humanos , Riñón/cirugía , Masculino , Persona de Mediana Edad , Tomografía Computarizada Multidetector , Nefrectomía , Países Bajos , Variaciones Dependientes del Observador , Tamaño de los Órganos , Valor Predictivo de las Pruebas , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Prednisone is used as first-line therapy for pulmonary sarcoidosis. What dosing strategy has the best balance between effect and side-effects is largely unknown. We analyzed change in forced vital capacity (FVC) and weight during different prednisone doses used in daily practice for treatment naïve pulmonary sarcoidosis patients. METHODS: Multilevel models were used to describe FVC and weight change over time. Correlations were calculated using linear regression models. RESULTS: Fifty-four patients were included. FVC changed over time (p < 0.001), with an average increase of 9.6% predicted (95% CI: 7.2 to 12.1) at 12 months. Weight changed significantly over time (p < 0.001), with an average increase of 4.3 kg (95% CI: 3.0 to 5.6) at 12 months. Although FVC and weight changed significantly over time, there was little correlation between prednisone dose and FVC change, while weight increase correlated significantly with cumulative prednisone dose at 24 months. In patients treated with a high cumulative prednisone dose, baseline FVC was on average lower (p = 0.001) compared to low dose treated patients, while no significant differences were observed in need for second/third-line therapy or number of exacerbations. A strategy leading to a low cumulative dose at 12 months was defined by rapid dose tapering to 10 mg/day within 3.5 months. CONCLUSIONS: These results suggest that prednisone therapy aimed at improving or preserving FVC in newly- treated pulmonary sarcoidosis can often be reduced in dose, using a treatment regimen that is characterized by early dose tapering.
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Glucocorticoides/administración & dosificación , Prednisona/administración & dosificación , Sarcoidosis Pulmonar/tratamiento farmacológico , Adulto , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Capacidad de Difusión Pulmonar , Estudios Retrospectivos , Sarcoidosis Pulmonar/fisiopatología , Capacidad Vital , Aumento de PesoRESUMEN
PURPOSE: Craniofacial microsomia (CFM) is a congenital malformation of structures derived from the first and second pharyngeal arches leading to underdevelopment of the face. However, besides the craniofacial underdevelopment, extracraniofacial anomalies including cardiac, renal and skeletal malformation have been described. The aim of this study is to analyse a large population of patients with regard to demographics, typical phenotypes including craniofacial and extracraniofacial anomalies, and the correlations between the different variables of this condition. MATERIAL AND METHODS: A retrospective study was conducted in patients diagnosed with CFM with available clinical and/or radiographic images. All charts were reviewed for information on demographic, radiographic and diagnostic criteria. The presence of cleft lip/palate and extracraniofacial anomalies were noted. Pearson correlation tests and principal component analysis was performed on the phenotypic variables. RESULTS: A total of 755 patients were included. The male-to-female ratio and right-to-left ratio were both 1.2:1. A correlation was found among Pruzansky-Kaban, orbit and soft tissue. Similar correlations were found between ear and nerve. There was no strong correlation between phenotype and extracraniofacial anomalies. Nevertheless, extracraniofacial anomalies were more frequently seen than in the 'normal' population. Patients with bilateral involvement had a more severe phenotype and a higher incidence of extracraniofacial and cleft lip/palate. CONCLUSION: Outcomes were similar to those of other smaller cohorts. Structures derived from the first pharyngeal arch and the second pharyngeal arch were correlated with degree of severity. Extracraniofacial anomalies were positively correlated with CFM. The findings show that bilaterally affected patients are more severely affected and should be approached more comprehensively.
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Anomalías Múltiples/etiología , Síndrome de Goldenhar/complicaciones , Anomalías Múltiples/diagnóstico , Anomalías Múltiples/epidemiología , Niño , Femenino , Humanos , Masculino , Estudios RetrospectivosRESUMEN
BACKGROUND: Children with the neurogenetic disorder neurofibromatosis type 1 (NF1) often have problems with learning and behaviour. In both parent reports and neuropsychological assessment, motor problems are reported in approximately one third to one half of the children with NF1. Studies using broad motor performance test batteries with relatively large groups of children with NF1 are limited. The aim of this cross-sectional observational study was to describe the severity of motor problems in children with NF1 and to explore the predictive value of demographics, intelligence, and behavioural problems. METHODS: From 2002 to 2014, 69 children with NF1, aged 4 to 16 years (age = 9.5 ± 2.8 years; 29 girls) had a motor, psychological, and neurological evaluation in an NF1 expertise centre. Data were collected about (1) motor performance (M-ABC: Movement Assessment Battery for Children), (2) intelligence, and (3) emotional and behavioural problems as rated by parents. RESULTS: Sixty-one percent of these children scored within the clinical range of the M-ABC. In ordinal logistic regression analyses, motor problems were associated with symptoms of attention-deficit/hyperactivity disorder (ADHD), symptoms of autism spectrum disorder (ASD), and externalising behavioural problems. Motor outcome was not predicted by age, intelligence, scoliosis, hypotonia, nor hypermobility. CONCLUSIONS: Motor problems are among the most common comorbid developmental problems in children with NF1, and these problems do not diminish with age. Because of their impact on daily functioning, motor problems need to be specifically addressed in diagnosis, follow-up, and treatment of NF1.
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Long-term follow-up data on the effects of screening are scarce, and debate exists on the relative contribution of screening versus treatment to breast cancer mortality reduction. Our aim was therefore to assess the long-term effect of screening by age and time of implementation. We obtained data on 69,630 breast cancer deaths between 1980 and 2010 by municipality (N = 431) and age of death (40-79) in the Netherlands. Breast cancer mortality trends were analyzed by defining the municipality-specific calendar year of introduction of screening as Year 0. Additionally, log-linear Poisson regression was used to estimate the turning point in the trend after Year 0, per municipality, and the annual percentage change (APC) before and after this point. Twenty years after introduction of screening breast cancer mortality was reduced by 30% in women aged 55-74 and by 34% in women aged 75-79, compared to Year 0. A similar and significant decrease was present in municipalities that started early (1987-1992) and late (1995-1997) with screening, despite the difference in availability of effective adjuvant treatment. In the age groups 55-74 and 75-79, the turning point in the trend in breast cancer mortality was estimated in Years 2 and 6 after the introduction of screening, respectively, after which mortality decreased significantly by 1.9% and 2.6% annually. These findings show that the implementation of mammography screening in Dutch municipalities is associated with a significant decline in breast cancer mortality in women aged 55-79, irrespective of time of implementation.
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Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/mortalidad , Mamografía/métodos , Tamizaje Masivo/métodos , Adulto , Distribución por Edad , Anciano , Detección Precoz del Cáncer , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Mortalidad/tendencias , Países Bajos/epidemiología , Análisis de RegresiónRESUMEN
The 'fundamental causes' theory stipulates that when new opportunities for lowering mortality arise, higher socioeconomic groups will benefit more because of their greater material and non-material resources. We tested this theory using harmonised mortality data by educational level for 22 causes of death and 20 European populations from the period 1980-2010. Across all causes and populations, mortality on average declined by 2.49 per cent (95%CI: 2.04-2.92), 1.83% (1.37-2.30) and 1.34% (0.89-1.78) per annum among the high, mid and low educated, respectively. In 69 per cent of cases of declining mortality, mortality declined faster among the high than among the low educated. However, when mortality increased, less increase among the high educated was found in only 46 per cent of cases. Faster mortality decline among the high educated was more manifest for causes of death amenable to intervention than for non-amenable causes. The difference in mortality decline between education groups was not larger when income inequalities were greater. While our results provide support for the fundamental causes theory, our results suggest that other mechanisms than the theory implies also play a role.
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Escolaridad , Mortalidad/tendencias , Factores Socioeconómicos , Adulto , Causas de Muerte , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos EstadísticosRESUMEN
OBJECTIVES: Improved life expectancy and reduced transmission probabilities due to ART may result in behavioural disinhibition - that is an increase in sexual risk behaviour in response to a perceived lower risk of HIV. We examined trends in sexual risk behaviour in the general population of sub-Saharan African countries 1999-2015. METHODS: We systematically reviewed scientific literature of sexual behaviour and reviewed trends in Demographic and Health Surveys. A meta-analysis on four indicators of sexual risk behaviour was performed: unprotected sex, multiple sexual partners, commercial sex and prevalence of sexually transmitted infections. RESULTS: Only two peer-reviewed studies met our inclusion criteria, while our review of DHS data spanned 18 countries and 16 years (1999-2015). We found conflicting trends in sexual risk behaviour. Reported unprotected sex decreased consistently across the 18 countries, for both sexes. In contrast, reporting multiple partners was decreasing over the period 1999 to the mid-2000s, yet has been consistently increasing thereafter. Similar trends were found for reported sexually transmitted infections and commercial sex (men only). CONCLUSIONS: In conclusion, we found no clear evidence of behavioural disinhibition due to expanded access to ART in sub-Saharan Africa. Substantial increases in condom use coincided with increases in reported multiple partners, commercial sex and sexually transmitted infections, especially during the period of ART scale-up. Further research is needed into how these changes might affect HIV transmission.
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Antirretrovirales/uso terapéutico , Actitud Frente a la Salud , Infecciones por VIH/prevención & control , Infecciones por VIH/psicología , Conducta Sexual/psicología , Conducta Sexual/estadística & datos numéricos , África del Sur del Sahara , Humanos , Asunción de Riesgos , Sexo Inseguro/psicología , Sexo Inseguro/estadística & datos numéricosRESUMEN
Population aging is accompanied by the burden of chronic diseases and disability. Chronic diseases are among the main causes of disability, which is associated with poor quality of life and high health care costs in the elderly. The identification of which chronic diseases contribute most to the disability prevalence is important to reduce the burden. Although longitudinal studies can be considered the gold standard to assess the causes of disability, they are costly and often with restricted sample size. Thus, the use of cross-sectional data under certain assumptions has become a popular alternative. Among the existing methods based on cross-sectional data, the attribution method, which was originally developed for binary disability outcomes, is an attractive option, as it enables the partition of disability into the additive contribution of chronic diseases, taking into account multimorbidity and that disability can be present even in the absence of disease. In this paper, we propose an extension of the attribution method to multinomial responses, since disability is often measured as a multicategory variable in most surveys, representing different severity levels. The R function constrOptim is used to maximize the multinomial log-likelihood function subject to a linear inequality constraint. Our simulation study indicates overall good performance of the model, without convergence problems. However, the model must be used with care for populations with low marginal disability probabilities and with high sum of conditional probabilities, especially with small sample size. For illustration, we apply the model to the data of the Belgian Health Interview Surveys.
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Personas con Discapacidad/estadística & datos numéricos , Modelos de Riesgos Proporcionales , Enfermedad Crónica , Estudios Transversales , Humanos , Calidad de Vida , Factores de RiesgoRESUMEN
Objective To compare the cumulative incidence of cervical cancer diagnosed within 72 months after a normal screening sample between conventional cytology and liquid based cytology tests SurePath and ThinPrep.Design Retrospective population based cohort study.Setting Nationwide network and registry of histo- and cytopathology in the Netherlands (PALGA), January 2000 to March 2013.Population Women with 5 924 474 normal screening samples (23 833 123 person years).Exposure Use of SurePath or ThinPrep versus conventional cytology as screening test.Main outcome measure 72 month cumulative incidence of invasive cervical cancer after a normal screening sample for each screening test. Cox regression analyses assessed the hazard ratios, adjusted for calendar time, age, screening history, and socioeconomic status and including laboratories as random effects.Results The 72 month cumulative cancer incidence was 58.5 (95% confidence interval 54.6 to 62.7) per 100 000 normal conventional cytology samples, compared with 66.8 (56.7 to 78.7) for ThinPrep and 44.6 (37.8 to 52.6) for SurePath. Compared with conventional cytology, the hazard of invasive cancer was 19% lower (hazard ratio 0.81, 95% confidence interval 0.66 to 0.99) for SurePath, mainly caused by a 27% lower hazard (0.73, 0.57 to 0.93) of a clinically detected cancer. For ThinPrep, the hazard was on average 15% higher (hazard ratio 1.15, 0.95 to 1.38), mainly caused by a 56% higher hazard of a screen detected cancer (1.56, 1.17 to 2.08).Conclusions These findings should provoke reconsideration of the assumed similarity in sensitivity to detect progressive cervical intraepithelial neoplasia between different types of liquid based cytology and conventional cytology.
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Citodiagnóstico , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Frotis Vaginal , Citodiagnóstico/métodos , Citodiagnóstico/estadística & datos numéricos , Progresión de la Enfermedad , Femenino , Humanos , Incidencia , Tamizaje Masivo/métodos , Países Bajos/epidemiología , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y Especificidad , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/epidemiología , Frotis Vaginal/métodos , Frotis Vaginal/estadística & datos numéricos , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/epidemiologíaRESUMEN
BACKGROUND: The role of DNA methylation in the regulation of the anti-donor-directed immune response after organ transplantation is unknown. Here, we studied the methylation of two mediators of the immune response: the pro-inflammatory cytokine interferon γ (IFNγ) and the inhibitory receptor programmed death 1 (PD1) in naïve and memory CD8+ T cell subsets in kidney transplant recipients receiving immunosuppressive medication. Both recipients experiencing an episode of acute allograft rejection (rejectors) as well as recipients without rejection (non-rejectors) were included. RESULTS: CpGs in the promoter regions of both IFNγ and PD1 were significantly (p < 0.001) higher methylated in the naïve CD8+ T cells compared to the memory T cell subsets. The methylation status of both IFNγ and PD1 inversely correlated with the percentage of IFNγ or PD1-producing cells. Before transplantation, the methylation status of both IFNγ and PD1 was not significantly different from healthy donors. At 3 months after transplantation, irrespective of rejection and subsequent anti-rejection therapy, the IFNy methylation was significantly higher in the differentiated effector memory CD45RA+ (EMRA) CD8+ T cells (p = 0.01) whereas the PD1 methylation was significantly higher in all memory CD8+ T cell subsets (CD27+ memory; p = 0.02: CD27- memory; p = 0.02: EMRA; p = 0.002). Comparing the increase in methylation in the first 3 months after transplantation between rejectors and non-rejectors demonstrated a significantly more prominent increase in the PD1 methylation in the CD27- memory CD8+ T cells in rejectors (increase in rejectors 14%, increase in non-rejectors 1.9%, p = 0.04). The increase in DNA methylation in the other memory CD8+ T cells was not significantly different between rejectors and non-rejectors. At 12 months after transplantation, the methylation of both IFNγ and PD1 returned to baseline levels. CONCLUSIONS: The DNA methylation of both IFNγ and PD1 increases the first 3 months after transplantation in memory CD8+ T cells in kidney transplant recipients. This increase was irrespective of a rejection episode indicating that general factors of the kidney transplantation procedure, including the use of immunosuppressive medication, contribute to these variations in DNA methylation.
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Linfocitos T CD8-positivos/metabolismo , Metilación de ADN , Rechazo de Injerto/genética , Interferón gamma/genética , Trasplante de Riñón , Receptor de Muerte Celular Programada 1/genética , Adulto , Anciano , Islas de CpG , Epigénesis Genética , Femenino , Rechazo de Injerto/sangre , Humanos , Interferón gamma/metabolismo , Masculino , Persona de Mediana Edad , Receptor de Muerte Celular Programada 1/metabolismoRESUMEN
BACKGROUND: Biologics are a safe and efficacious therapy for psoriasis. The drug survival of biologics may be disappointing, primarily due to loss of efficacy. Therefore, safe combination treatments are sought to improve their clinical response. OBJECTIVE: To assess the efficacy, safety and tolerability of the combination therapy of etanercept with fumarates versus etanercept monotherapy. METHODS: Thirty-three patients with psoriasis were randomized 1:1 to receive etanercept combined with fumarates or etanercept monotherapy. The primary outcome measure was the difference in PASI-75 response after 24 weeks; additionally, a longitudinal analysis was performed. An important secondary outcome measure was the proportion of patients with a Physician Global Assessment (PGA) of clear or almost clear. Adverse events were collected throughout the study. RESULTS: In the combination therapy group, 78% (14 out of 18 patients) reached PASI-75 at week 24 versus 57% (8 out of 14 patients) in the monotherapy group (p = 0.27). The longitudinal analysis showed a PASI reduction of 5.97% per week for the combination therapy group and of 4.76% for the monotherapy group (p = 0.11). In the combination therapy group, 94% (17 out of 18 patients) of patients had a PGA of clear/almost clear versus 64% (9 out of 14 patients) in the monotherapy group (p = 0.064). The incidence of mild gastrointestinal complaints was higher in the combination group than in the monotherapy group. CONCLUSION: Using the PGA, combination therapy showed a trend towards faster improvement in the first 24 weeks. The difference in the PASI score between the two groups was not statistically significant. Addition of fumarates to etanercept for 48 weeks appeared safe with an acceptable tolerability.
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Etanercept/administración & dosificación , Fumaratos/administración & dosificación , Psoriasis/tratamiento farmacológico , Adulto , Biopsia , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Inmunosupresores/administración & dosificación , Masculino , Persona de Mediana Edad , Psoriasis/diagnóstico , Índice de Severidad de la Enfermedad , Piel/patología , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVE: To investigate whether mammalian target of rapamycin complex 1 (mTORC1) inhibitors could reduce seizure frequency in children with tuberous sclerosis complex (TSC). METHODS: Due to slow inclusion rate, target inclusion of 30 children was not reached. Twenty-three children with TSC and intractable epilepsy (age 1.8-10.9 years) were randomly assigned (1:1) to open-label, add-on sirolimus treatment immediately or after 6 months. Sirolimus was titrated to trough levels of 5-10 ng/mL. Primary endpoint was seizure frequency change during the sixth month of sirolimus treatment. RESULTS: Intention-to-treat analysis showed sirolimus treatment resulted in 41% seizure frequency decrease (95% confidence interval [CI] -69% to +14%; p = 0.11) compared to the standard-care period. Per protocol analysis of 14 children who reached sirolimus target trough levels in the sixth sirolimus month showed a seizure frequency decrease of 61% (95% CI -86% to +6%; p = 0.06). Cognitive development did not change. All children had adverse events. Five children discontinued sirolimus prematurely. CONCLUSIONS: We describe a randomized controlled trial for a non-antiepileptic drug that directly targets a presumed causal mechanism of epileptogenesis in a genetic disorder. Although seizure frequency decreased, especially in children reaching target trough levels, we could not show a significant benefit. Larger trials or meta-analyses are needed to investigate if patients with TSC with seizures benefit from mTORC1 inhibition. This trial was registered at trialregister.nl (NTR3178) and supported by the Dutch Epilepsy Foundation. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that sirolimus does not significantly reduce seizure frequency in children with TSC and intractable epilepsy. The study lacked the precision to exclude a benefit from sirolimus.