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BACKGROUND: Doctors in German hospitals are critical of their working conditions. They complain about long working hours, inadequate remuneration for their work, poor training and development opportunities, and increasing time spent on administrative tasks. As these points of criticism are largely based on subjective perception, in the present study we documented in detail the workflows of physicians in a major regional hospital, determined the time taken for the workflows, and performed a statistical evaluation of the data. METHODS: Nine doctors from the specialties of internal medicine, surgery, and anesthesia/intensive care medicine were observed during their shifts for a total period of 216 hours at an urban hospital in Germany. All of the tasks performed by the doctors were recorded in an observation protocol. RESULTS: The time spent daily on documentation by doctors of all specialties was on average 93.1â±â23.4 minutes, accounting for 19.4â% of a doctor's working hours. The specialists who spent the longest period of time on documentation were internists (120.2â±â15.0 minutes; 25â%). During an eight-hour working day, computers were used on average for 123.5â±â44.4 minutes; surgeons spent the shortest period of time on computers (71.5â±â16.6 minutes). The direct patient-related work time (excluding the time spent on operations) was considerably lower (33.8â+â22.7 minutes; 7â%) than the time spent daily on documentation, increased to 80.7â±â62.9 minutes when the time expended on actual surgical tasks was taken into account, and was then similar to the time spent on documentation (93.1 minutes). DISCUSSION: This pilot study was the first to determine, in real time, the work processes of doctors from different specialties at a German hospital. We noted a disparity between administrative and patient-related tasks in the in-patient setting. Legal and economic requirements exert a negative impact on medical care. We need to develop strategies for effective utilization of medical resources and for ensuring a high standard of medical care.
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Documentación , Alemania , Humanos , Carga de Trabajo/legislación & jurisprudencia , Medicina Interna , Médicos/legislación & jurisprudencia , Flujo de TrabajoRESUMEN
Upper tract urothelial carcinoma (UTUC) accounts for 5-10% of all UCs. Immune checkpoint inhibitors (ICIs) have been established for UCs. The prognostic and predictive potential of programmed cell death ligand 1 (PD-L1) expression to stratify patients benefiting from ICIs is not fully understood, and additional markers influencing the impact of PD-L1-mediated ICI response are needed. Previously, the chemokine-like MARVEL transmembrane domain-containing protein 6 (CMTM6) was identified as a positive regulator of PD-L1. Our aim was to investigate the expression profiles and impact of PD-L1 and CMTM6 protein status on the prognostic parameters and survival of UTUC patients. In this retrospective study, the combined positive score (CPS), tumor proportion score (TPS), and immune cell score (ICS) for PD-L1 and CMTM6 were determined. High PD-L1 CPS, ICS, and TPS were found in 77.4%, 58.3%, and 45.2% of cases, and high CMTM6 CPS, ICS, and TPS were seen in 52.5%, 51.5%, and 55.5% of cases, respectively. The scores of both markers had a significant positive correlation. High PD-L1 and CMTM6 expression was coupled with higher pT status, WHO grade, necrosis, and metastasis (p < 0.05, respectively). In the univariate survival analysis, patients with a PD-L1 ICS high and higher degree of intratumoral inflammation showed significantly longer overall survival. Compared to other studies on UC, our study shows a substantially higher rate of PD-L1-positive tumors. CMTM6 was associated with more aggressive tumors.
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Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Humanos , Carcinoma de Células Transicionales/metabolismo , Antígeno B7-H1 , Pronóstico , Estudios Retrospectivos , Ligandos , Apoptosis , Biomarcadores , Quimiocinas , Proteínas con Dominio MARVEL/genéticaRESUMEN
BACKGROUND AND AIMS: Achieving Hepatitis B e antigen seroconversion (HBeAg SC) at an earlier age confers a better prognosis. We examined baseline and post-partum factors associated with HBeAg SC after pregnancy. We developed a tool, the SydPregScore, to estimate the likelihood of HBeAg SC in the years after pregnancy. METHODS: A retrospective analysis of an HBeAg-positive pregnant cohort was conducted. Variables including baseline age, parity, alanine aminotransferase level, HBV viral load, quantitative HBsAg, use of antiviral therapy and post-partum flare were collected. Univariate and multivariate Cox regression analyses to determine predictors of HBeAg SC and develop a predictor score were performed. RESULTS: We analysed HBeAg SC rates in 220 pregnancies to 149 HBeAg-positive women from 2006 to 2019. At baseline, their median age was 33 (IQR 29-37), ALT 23 U/L (IQR 17-33) and viral load 8 log10 IU/mL (IQR 6.3-8.2 log10 IU/mL). The majority (133/198, 67.2%) received short-course antiviral therapy to prevent mother-to-child transmission, and 109/192 (56.8%) had a post-partum flare. HBeAg SC occurred in 74/220 (33.6%) after pregnancy (median follow-up 814 days, IQR 405-1531). Multivariate analysis identified baseline viral load <8 log10 IU/mL (HR 2.426 [1.224-4.809], p = .011), baseline ALT ≥2 ULN (HR 2.726 [1.299-5.721], p = .008) and age <35 (HR 2.859 [1.255-6.513], p = .012) to be positive predictors of HBeAg SC. The 'SydPreg Score' estimated the probability of HBeAg SC at 2000 days as 10%, 30%, 70% and 80% for 0, 1, 2, and 3 predictors respectively. CONCLUSION: The SydPreg Score allows the prediction of HBeAg SC in the years after pregnancy. Even in those without elevated ALT, age <35 and viral load <8 log10 IU/mL can identify women with a good chance of subsequent HBeAg SC. Those without a chance may benefit from viral suppression.
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Antígenos e de la Hepatitis B , Hepatitis B Crónica , Embarazo , Humanos , Femenino , Adulto , Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/tratamiento farmacológico , Seroconversión , Estudios Retrospectivos , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Antígenos de Superficie de la Hepatitis B , ADN Viral , Antivirales/uso terapéutico , Virus de la Hepatitis B/genéticaRESUMEN
INTRODUCTION: The aim of this analysis is to determine whether regular physical activity is associated with less analgesic use in men and women suffering from headache disorders based on population-based cross-sectional data. METHODS: We used data from a random general population sample in Germany that comprised 2477 participants aged ≥ 14 years. A standardized questionnaire addressing headache and headache treatment was filled in during the face-to-face survey. RESULTS: Thirty-nine percent of the participants reported headache. Of these, 37.5% of men and 33.6% of women were physically active. Of the participants with headache, 43.3% reported taking analgesics on < 2 days a month, 40.7% on 2-5 days a month, 10.1% on 6-10 days a month, and 5.9% on > 10 days a month. Frequent headache, severe impact of headache on daily life, and depressive symptoms were associated with higher analgesic use in both men and women. For women, physical inactivity was associated with the frequency of analgesic use adjusted for sociodemographic and headache-related variables. For men, results did not suggest any association between physical inactivity and frequency of analgesic use. CONCLUSIONS: There are both sex-unspecific and sex-specific factors associated with analgesic use among men and women with headache. In women with increased analgesic use, promoting physical activity may reduce analgesic use. For men, education about the therapeutic effects of physical activity for headaches is an important resource.
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Following conventional i.v. hematopoietic stem cell transplantation (IV-HSCT), most of the hematopoietic stem cells get trapped in peripheral organs and do not reach the bone marrow niche. A promising approach to overcome this cell loss during the homing process seems to be the infusion of hematopoietic stem cells directly into the bone marrow cavity (intra-bone marrow [IBM]-HSCT). This study aimed to investigate the engraftment efficiency of IBM-HSCT compared with IV-HSCT following reduced-intensity conditioning in a canine HSCT model. Furthermore, the impact of 2 different graft infusion rates during IBM-HSCT on the engraftment was evaluated. Dogs received 4.5 Gy total body irradiation for conditioning at day -1 and 15 mg/kg cyclosporin A twice daily at days -1 to +35 as immunosuppression. The IV-HSCT group (n = 7) received unmodified bone marrow. The IBM-HSCT cohorts received buffy coat-enriched bone marrow that was applied into the humerus and femur simultaneously with an infusion time of either 10 minutes (IBM10; n = 8) or 60 minutes (IBM60; n = 7). Statistical analyses were performed using the Kruskal-Wallis test followed by the Mann-Whitney U test with Bonferroni correction for multiple comparisons. Statistical significance was declared at Bonferroni-adjusted P < .017. All dogs initially engrafted. One dog of the IBM10 cohort died at day +15 from infection. All 21 evaluable dogs developed a durable mixed donor chimerism over the course of 112 days. Engraftment kinetics did not differ significantly across the 3 groups. Leukocyte and platelet nadirs, as well as the durations of leukopenia and thrombocytopenia, were comparable in the 3 groups. Signs of toxicity for ingestion, body temperature, activity, and defecation did not show statistically significant differences among the 3 groups; only weight loss was greater in the IBM60 group compared with the IV group. IBM-HSCT following reduced-intensity conditioning resulted in an engraftment efficiency and hematopoietic recovery comparable to that seen with conventional IV-HSCT. In addition, modification of the graft infusion rate had no impact on engraftment and hematopoietic recovery in the canine IBM-HSCT model.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Animales , Médula Ósea , Perros , Antígenos HLA , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Acondicionamiento Pretrasplante/métodosRESUMEN
Coastal Carolina is a popular retirement destination. Ten individuals, previously interviewed regarding their decision to retire here, were re-interviewed after Hurricane Florence. This sample of eight women and two men, mean age 74.4 (range = 68-88), provided a unique opportunity to learn about their hurricane experiences and to compare their pre- and post-responses about their choice to move to the coast. Nine evacuated, including one to a local shelter. Respondents reported a lack of preparations, but neighbors played an important supportive role. Issues about the shelter and for single women were identified. Results have implications for future disaster preparations.
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Tormentas Ciclónicas , Planificación en Desastres , Anciano , Planificación en Desastres/métodos , Femenino , Humanos , Aprendizaje , Masculino , JubilaciónRESUMEN
BACKGROUND: Reduced temporal muscle thickness (TMT) has been discussed as a prognostic marker in IDH-wildtype glioblastoma. This retrospective multicenter study was designed to investigate whether TMT is an independent prognostic marker in newly diagnosed glioblastoma. METHODS: TMT was retrospectively measured in 335 patients with newly diagnosed glioblastoma between 1 January 2014 and 31 December 2019 at the University Hospitals of Leipzig and Rostock. The cohort was dichotomized by TMT and tested for association with overall survival (OS) after 12 months by multivariate proportional hazard calculation. RESULTS: TMT of 7.0 mm or more was associated with increased OS (46.3 ± 3.9% versus 36.6 ± 3.9%, p > 0.001). However, the sub-groups showed significant epidemiological differences. In multivariate proportional hazard calculation, patient age (HR 1.01; p = 0.004), MGMT promoter status (HR 0.76; p = 0.002), EOR (HR 0.61), adjuvant irradiation (HR 0.24) and adjuvant chemotherapy (HR 0.40; all p < 0.001) were independent prognostic markers for OS. However, KPS (HR 1.00, p = 0.31), BMI (HR 0.98, p = 0.11) and TMT (HR 1.06; p = 0.07) were not significantly associated with OS. CONCLUSION: TMT has not appeared as a statistically independent prognostic marker in this cohort of patients with newly diagnosed IDH-wildtype glioblastoma.
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Obesity is one of the most challenging diseases of the 21st century and is accompanied by behavioural disorders. Exercise, dietary adjustments, or time-restricted feeding are the only successful long-term treatments to date. Fibroblast growth factor 21 (FGF21) plays a key role in dietary regulation, but FGF21 resistance is prevalent in obesity. The aim of this study was to investigate in obese mice whether weight reduction leads to improved behaviour and whether these behavioural changes are associated with decreased plasma FGF21 levels. After establishing a model for diet-induced obesity, mice were subjected to three different interventions for weight reduction, namely dietary change, treadmill exercise, or time-restricted feeding. In this study, we demonstrated that only the combination of dietary change and treadmill exercise affected all parameters leading to a reduction in weight, fat, and FGF21, as well as less anxious behaviour, higher overall activity, and improved olfactory detection abilities. To investigate the interrelationship between FGF21 and behavioural parameters, feature selection algorithms were applied designating FGF21 and body weight as one of five highly weighted features. In conclusion, we concluded from the complementary methods that FGF21 can be considered as a potential biomarker for improved behaviour in obese mice after weight reduction.
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Factores de Crecimiento de Fibroblastos/sangre , Locomoción , Obesidad/sangre , Olfato , Pérdida de Peso , Animales , Biomarcadores/sangre , Dieta Alta en Grasa , Prueba de Laberinto Elevado , Ayuno , Femenino , Factores de Crecimiento de Fibroblastos/metabolismo , Humanos , Aprendizaje Automático , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Prueba de Campo Abierto , Condicionamiento Físico AnimalRESUMEN
OBJECTIVES: Transfemoral transcatheter aortic valve implantation (TF-TAVI) is an established therapy for patients with symptomatic aortic stenosis, which requires periprocedural anaesthesia care. In 2015, the German Federal Joint Committee released a directive on minimally invasive heart valve interventions which defines institutional infrastructural requirements in German heart centres. But still generally accepted expert consensus recommendations or national or international guidelines regarding periprocedural anaesthesia management for TF-TAVI are lacking. This nationwide cross-sectional study had two major objectives: first to assess the concordance with existing national regulations regarding infrastructural requirements and second to evaluate the status quo of periprocedural anaesthesia management for patients undergoing TF-TAVI in German heart centres. DESIGN: Multicentre cross-sectional online study to evaluate the periprocedural anaesthesia management. SETTING: In this nationwide cross-sectional study, electronic questionnaires were sent out to anaesthesia departments at TF-TAVI-performing centres in Germany in March 2019. PARTICIPANTS: 78 anaesthesia departments of German heart centres. RESULTS: 54 (69.2%) centres returned the questionnaire of which 94.4% stated to hold regular Heart Team meetings, 75.9% to have ready-to-use heart-lung machines available on-site, 77.8% to have cardiac surgeons and 66.7% to have perfusionists routinely attending throughout TF-TAVI procedures. Regarding periprocedural anaesthesia management, 41 (75.9%) of the participating centres reported to predominantly use 'monitored anaesthesia care' and 13 (24.1%) to favour general anaesthesia. 49 (90.7%) centres stated to use institutional standard operating procedures for anaesthesia. Five-lead ECG, central venous lines, capnometry and intraprocedural echocardiography were reported to be routine measures in 85.2%, 83.3%, 77.8% and 51.9% of the surveyed heart centres. CONCLUSIONS: The concordance with national regulations, anaesthesia management and in-house standards for TF-TAVI vary broadly among German heart centres. According to the opinion of the authors, international expert consensus recommendations and/or guidelines would be helpful to standardise peri interventional anaesthesia care.
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Estenosis de la Válvula Aórtica , Implantación de Prótesis de Válvulas Cardíacas , Reemplazo de la Válvula Aórtica Transcatéter , Anestesia General , Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/cirugía , Estudios Transversales , Humanos , Resultado del TratamientoRESUMEN
BACKGROUND: The development of presbyopia is correlated with increased lens stiffness. To reveal structural changes with age, ultrahigh field magnetic resonance imaging (UHF-MRI) was used to analyze water diffusion in differently aged human lenses ex vivo. METHODS: After enucleation lens extractions were performed. Lenses were photographed, weighed, and embedded in 0.5% agarose dissolved in culture medium. UHF-MRI was conducted to analyze anatomical characteristics of the lens using T2-weighted Turbo-RARE imaging and to obtain apparent diffusion coefficients (ADC) measurements. A Gaussian fit routine was used to examine the ADC histograms. RESULTS: An age-dependent increase in lens wet weight, lens thickness, and lens diameter was found (P<0.001). T2-weighted images revealed a hyperintense lens cortex and a gradually negative gradient in signal intensity towards the nucleus. ADC histograms of the lens showed bimodal distributions (lower ADC values mainly located in the nucleus and higher ADC values mainly located in the cortex), which did not change significantly with age [ßPeak1=1.96E-7 (-20E-7, 10E-7), P=0.804 or ßPeak2=15.4E-7 (-10E-7, 40E-7), P=0.276; respectively]. CONCLUSIONS: Clinically relevant age dependent lens hardening is probably not correlated with ADC changes within the nucleus, which could be confirmed by further measurements.
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Aim: We aimed to explore ceruloplasmin (CP) expression in clear cell renal cell carcinoma (ccRCC). Materials & methods: CP was analyzed in biofluid samples of 63 ccRCC patients, divided into three grading groups, and immunohistochemically, in 308 ccRCC. Results: Significant differences of mean plasma and urine CP levels in different grading groups were found. CP immunoreactivity was significantly linked to high-grade disease. Log rank tests showed a significant shorter overall survival rate in CP-positive cases (all p < 0.05). Conclusion: CP protein levels in biofluid samples confirmed differential CP expressions, depending on nuclear grade in ccRCC as previously seen in RNA expression analysis. CP expression was linked to high-grade disease and reduced survival rate in RCC.
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Carcinoma de Células RenalesRESUMEN
There exists a variety of interval estimators for the overall treatment effect in a random-effects meta-analysis. A recent literature review summarizing existing methods suggested that in most situations, the Hartung-Knapp/Sidik-Jonkman (HKSJ) method was preferable. However, a quantitative comparison of those methods in a common simulation study is still lacking. Thus, we conduct such a simulation study for continuous and binary outcomes, focusing on the medical field for application. Based on the literature review and some new theoretical considerations, a practicable number of interval estimators is selected for this comparison: the classical normal-approximation interval using the DerSimonian-Laird heterogeneity estimator, the HKSJ interval using either the Paule-Mandel or the Sidik-Jonkman heterogeneity estimator, the Skovgaard higher-order profile likelihood interval, a parametric bootstrap interval, and a Bayesian interval using different priors. We evaluate the performance measures (coverage and interval length) at specific points in the parameter space, that is, not averaging over a prior distribution. In this sense, our study is conducted from a frequentist point of view. We confirm the main finding of the literature review, the general recommendation of the HKSJ method (here with the Sidik-Jonkman heterogeneity estimator). For meta-analyses including only two studies, the high length of the HKSJ interval limits its practical usage. In this case, the Bayesian interval using a weakly informative prior for the heterogeneity may help. Our recommendations are illustrated using a real-world meta-analysis dealing with the efficacy of an intramyocardial bone marrow stem cell transplantation during coronary artery bypass grafting.
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Metaanálisis como Asunto , Proyectos de Investigación , Teorema de Bayes , Simulación por Computador , ProbabilidadRESUMEN
OBJECTIVES: The future state treaty on the admission of students to German medical schools calls for a variety of selection criteria among which at least two are required to be independent of school leaving grades. Against this background, the present study investigated achievement motivation and executive functions as predictors of academic success in medical school. MATERIAL AND METHODS: Second year medical students were assessed for executive functioning by using the Tower of London Test (ToL), a German version of the Controlled Oral Word Association Test (COWAT), the Trail Making Test (TMT-A) and for motivation by using the Achievement Motivation Inventory (AMI). Academic success was evaluated twofold, i) whether the first state exam (M1) was passed at the earliest possible, after completion of the second year and ii) via the grades obtained. RESULTS: 81 out of 226 students enrolled participated in our study. Passing the M1 was best explained by semantic fluency including task switching. Moreover, academically successful students achieved significantly higher levels in the AMI-facets "compensatory effort" and "engagement". All students scored above average in the TMT-A and average in the ToL. CONCLUSION: Alternating semantic fluency-requiring simultaneously inhibition, updating and task shifting-turned out highly predictive of academic success in medical school. Moreover, higher levels in "compensatory effort" and "engagement" suggested that both, increased energy expenditure as response to fear of failure and elevated readiness to exert effort also impacted positively on success.
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Éxito Académico , Función Ejecutiva , Pruebas de Inteligencia , Criterios de Admisión Escolar , Estudiantes de Medicina/psicología , Estudios Transversales , Femenino , Alemania , Humanos , Masculino , Facultades de Medicina/normas , Facultades de Medicina/estadística & datos numéricos , Semántica , Adulto JovenRESUMEN
BACKGROUND: Strong line of evidence suggests that the increased risk to develop AD may at least be partly mediated by cholesterol metabolism. A key regulator of cholesterol transport is the Apolipoprotein E4 (ApoE4), which plays a fundamental role in neuronal maintenance and repair. Impaired function of ApoE4 may contribute to altered cerebral metabolism leading to higher susceptibility to neurodegeneration. METHODS: To determine a possible link between ApoE function and alterations in AD in the brain of Apolipoprotein E-deficient mice (ApoE-/-) in a longitudinal manner metabolic and neurochemical parameters were analyzed. Cortical metabolism was measured by 2-deoxy-2-[18F]fluoroglucose ([18F]FDG)-PET/CT and proton magnetic resonance spectroscopy (1H-MRS) served to record neurochemical status. RESULTS: By using [18F]FDG-PET/CT, we showed that brain metabolism declined significantly stronger with age in ApoE-/- versus wild type (wt) mice. This difference was particularly evident at the age of 41 weeks in almost each analyzed brain region. In contrast, the 1H-MRS-measured N-acetylaspartate to creatine ratio, a marker of neuronal viability, did not decline with age and did not differ between ApoE-/- and wt mice. CONCLUSION: In summary, this longitudinal in vivo study shows for the first time that ApoE-/- mice depict cerebral hypometabolism without neurochemical alterations.
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Schistosomiasis represents one of the most devastating worm parasitosis in the world. Current diagnostic methods are insufficient to determine the infection grade and the disease related organ damage. We herein investigated whether discrimination of infection grade and its correlation to liver damage could be accurately performed by multimodal imaging in a mouse model of Schistosoma mansoni infection. Therefore, groups of uninfected and infected mice underwent MRI and [18F]FDG PET/CT imaging. Anatomical MRI images were used for liver volumetry and for quantification of hepatic granulomas. For PET/CT images a volume of interest based analyses were employed to calculate the [18F]FDG uptake in liver, portal vein, spleen and abdomen. Herein, we demonstrate that the combined use of [18F]FDG-PET/CT and MRI represents an appropriate diagnostic tool for Schistosoma mansoni infection, but fails to discriminate the infection grade and the linked organ damage. Only the splenic [18F]FDG uptake in the 25 cercariae group (5.68 ± 0.90%ID/cc) and 50 cercariae group (4.98 ± 1.43%ID/cc) was significantly higher compared to the control group (2.13 ± 0.69%ID/cc). Nevertheless, future multimodal imaging studies with new radiopharmaceuticals could build a highly sensitive and specific basis for the diagnosis and evaluation of organ damage of schistosomiasis.
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Imagen por Resonancia Magnética/métodos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Esquistosomiasis mansoni/diagnóstico por imagen , Animales , Modelos Animales de Enfermedad , Fluorodesoxiglucosa F18 , Hígado/parasitología , Ratones , Recuento de Huevos de Parásitos , Reproducibilidad de los Resultados , Esquistosomiasis mansoni/patologíaRESUMEN
The standard estimator for the log odds ratio (the unconditional maximum likelihood estimator) and the delta-method estimator for its standard error are not defined if the corresponding 2 × 2 table contains at least one "zero cell". This is also an issue when estimating the overall log odds ratio in a meta-analysis. It is well known that correcting for zero cells by adding a small increment should be avoided. Nevertheless, these zero-cell corrections continue to be used. With this Brief Method Note, we want to warn of a particularly bad zero-cell correction. For this, we conduct a simulation study comparing the following two zero-cell corrections under the ordinary random-effects model: (a) adding 1 2 to all cells of all the individual studies' 2 × 2 tables independently of any zero-cell occurrences and (b) adding 1 2 to all cells of only those 2 × 2 tables containing at least one zero cell. The main finding is that correction (a) performs worse than correction (b). Thus, we strongly discourage the use of correction (a).
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Interpretación Estadística de Datos , Metaanálisis como Asunto , Estadística como Asunto , Algoritmos , Ensayos Clínicos como Asunto , Simulación por Computador , Humanos , Funciones de Verosimilitud , Modelos Estadísticos , Oportunidad Relativa , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Crohn's disease (CD) is characterized by a multifactorial etiology and a significant impact of genetic traits. While NOD2 mutations represent well established risk factors of CD, the role of other genes is incompletely understood. AIM: To challenge the hypothesis that single nucleotide polymorphisms (SNPs) in the genes CLEC5A and CLEC7A, two members of the C-type lectin domain family of pattern recognition receptors, may be associated with CD. METHODS: SNPs in CLEC5A, CLEC7A and the known CD risk gene NOD2 were studied using real time PCR-based SNP assays. Therefore, DNA samples from 175 patients and 157 healthy donors were employed. Genotyping data were correlated with clinical characteristics of the patients and the results of gene expression data analyses. RESULTS: In accordance with previous studies, rs2066844 and rs2066847 in NOD2 were found to be significantly associated with CD (allelic P values = 0.0368 and 0.0474, respectively). Intriguingly, for genotype AA of rs1285933 in CLEC5A, a potential association with CD (recessive P = 0.0523; odds ratio = 1.90) was observed. There were no associations between CD and SNPs rs2078178 and rs16910631 in CLEC7A. Variants of rs1285933 had no impact on CLEC5A gene expression. In contrast, genotype-dependent differences of CXCL5 expression in peripheral blood mononuclear cells were observed. There is no statistical interaction between the tested SNPs of NOD2 and CLEC5A, suggesting of a novel pathway contributing to the disease. CONCLUSION: Our data encourage enlarged follow-up studies to further address an association of SNP rs1285933 in CLEC5A with CD. The C-type lectin domain family member also deserves attention regarding a potential role in the pathophysiology of CD.
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Enfermedad de Crohn/genética , Predisposición Genética a la Enfermedad , Lectinas Tipo C/genética , Receptores de Superficie Celular/genética , Adulto , Enfermedad de Crohn/sangre , Femenino , Técnicas de Genotipaje , Humanos , Lectinas Tipo C/metabolismo , Leucocitos Mononucleares/metabolismo , Masculino , Persona de Mediana Edad , Proteína Adaptadora de Señalización NOD2/genética , Polimorfismo de Nucleótido Simple , Receptores de Superficie Celular/metabolismoRESUMEN
BACKGROUND: Upper tract urothelial carcinoma (UTUC) may arise in the setting of hereditary non-polyposis colorectal cancer (Lynch syndrome [LS]) or sporadically. Variable frequencies of microsatellite instability (MSI) were found in UTUC. For advanced solid MSI tumors, targeted therapy with programmed death-ligand 1 inhibitors is available. Therefore, we aimed to determine the prevalence of mismatch repair (MMR) protein loss and MSI in UTUC using a tissue microarray approach and further molecular and correlation analysis. MATERIALS AND METHODS: We studied the immunohistochemical expression of MLH1, MSH2, MSH6, and PMS2 on tissue microarrays containing formalin-fixed, paraffin-embedded samples of 128 patients with UTUC. MSI analysis was performed in 79 cases with deficient MMR protein expression, and/or in patients aged 60 years and below, and/or other tumors possibly related to LS. RESULTS: Loss of MMR protein expression was seen in 24 (18.8%) of 128 cases. MSI analysis revealed MSI-high in 29, MSI-low in 7 cases. The Fisher exact test demonstrated significant differences between MSI and loss of MMR protein expression, clinically possible LS, tumor growth pattern, inverted growth pattern, and death (P < .001, P < .001, P = .002, P = .003, and P = .033, respectively). MSI does not appear to influence survival (overall and progression-free), but there was a significant shorter progression-free survival in MSI-high versus MSS patients who had received chemotherapy. CONCLUSION: The frequency of MSI in UTUC was 36 (28.1%) of 128 patients with a good accuracy of immunohistochemistry. In daily practice, MSI screening especially is recommended in patients with advanced UTUC and inverted papillary tumor growth pattern with the aim of screening patients for possible targeted therapy.
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Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Carcinoma de Células Transicionales/genética , Reparación de la Incompatibilidad de ADN/genética , Humanos , Inestabilidad de Microsatélites , Homólogo 1 de la Proteína MutL/genéticaRESUMEN
Parkinson's disease (PD) is the second-most common age-related neurodegenerative disorder. Despite recommendations for a palliative approach, little is known about what palliative needs are unmet by standard care. This study aims to (a) identify palliative needs of PD patients, (b) determine the relationship between palliative needs and health-related quality of life (HRQoL), and (c) probe into factors affecting HRQoL. PD patients and neurologists were recruited for a survey on palliative need; a subset of patients was interviewed. Significant differences between physicians and patients were found in Physical, Psychological, Social, Financial, and Spiritual domains. Physical and Psychological needs predicted HRQoL. Primary themes across interviews included (a) lack of healthcare education and (b) need for care coordination. Secondary themes included (a) the importance of support groups, (b) the role of spirituality/religion, and (c) the narrow perceived role of the neurologist. Findings highlight the importance of coordinated individualized care.
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Evaluación de Necesidades , Neurólogos/psicología , Cuidados Paliativos , Enfermedad de Parkinson/psicología , Pacientes/psicología , Calidad de Vida/psicología , Anciano , Continuidad de la Atención al Paciente , Femenino , Humanos , Masculino , Encuestas y CuestionariosRESUMEN
Data were collected at five elder cohousing neighborhoods to understand more about who lives in these communities, their reasons for moving, their satisfaction, and to explore the intersection between loneliness and sense of community. The average age of the predominantly white, female, and well-educated sample (n = 86, 56% response rate), was 68 ± 6.573 at move-in. Respondents moved in search of a sense of community and were generally satisfied with their experiences. Prevalence of loneliness was lower than the national average, but still affected 24% of the sample. Findings suggest that senior cohousing is delivering on the promise to promote sense of community.