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1.
Surg Endosc ; 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33398570

RESUMO

BACKGROUND: Hepatectomy, living donor liver transplantations and other major hepatic interventions rely on precise calculation of the total, remnant and graft liver volume. However, liver volume might differ between the pre- and intraoperative situation. To model liver volume changes and develop and validate such pre- and intraoperative assistance systems, exact information about the influence of lung ventilation and intraoperative surgical state on liver volume is essential. METHODS: This study assessed the effects of respiratory phase, pneumoperitoneum for laparoscopy, and laparotomy on liver volume in a live porcine model. Nine CT scans were conducted per pig (N = 10), each for all possible combinations of the three operative (native, pneumoperitoneum and laparotomy) and respiratory states (expiration, middle inspiration and deep inspiration). Manual segmentations of the liver were generated and converted to a mesh model, and the corresponding liver volumes were calculated. RESULTS: With pneumoperitoneum the liver volume decreased on average by 13.2% (112.7 ml ± 63.8 ml, p < 0.0001) and after laparotomy by 7.3% (62.0 ml ± 65.7 ml, p = 0.0001) compared to native state. From expiration to middle inspiration the liver volume increased on average by 4.1% (31.1 ml ± 55.8 ml, p = 0.166) and from expiration to deep inspiration by 7.2% (54.7 ml ± 51.8 ml, p = 0.007). CONCLUSIONS: Considerable changes in liver volume change were caused by pneumoperitoneum, laparotomy and respiration. These findings provide knowledge for the refinement of available preoperative simulation and operation planning and help to adjust preoperative imaging parameters to best suit the intraoperative situation.

2.
Cancer Epidemiol ; 70: 101873, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33360605

RESUMO

BACKGROUND AND OBJECTIVE: The potential existence of spatial clusters in childhood cancer incidence is a debated topic. Identification of such clusters may help to better understand etiology and develop preventive strategies. We evaluated widely used statistical approaches to cluster detection in this context. METHODS: Incidence of newly diagnosed childhood cancer (140/1,000,000 children under 15 years) and nephroblastoma (7/1,000,000) was simulated. Clusters of defined size (1-50) were randomly assembled on the district level in Germany. Each cluster was simulated with different relative risk levels (1-100). For each combination 2000 iterations were done. Simulated data was then analyzed by three local clustering tests: Besag-Newell method, spatial scan statistic and Bayesian Besag-York-Mollié with Integrated Nested Laplace Approximation approach. The operating characteristics (sensitivity, specificity, predictive values, power and correct classification) of all three methods were systematically described. RESULTS: Performance varied considerably within and between methods, depending on the simulated setting. Sensitivity of all methods was positively associated with increasing size, incidence and RR of the high-risk area. Besag-York-Mollié showed highest specificity for minimally increased RR in most scenarios. The performance of all methods was lower in the nephroblastoma scenario compared with the scenario including all cancer cases. CONCLUSION: This study illustrates the challenge to make reliable inferences on the existence of spatial clusters based on single statistical approaches in childhood cancer. Application of multiple methods, ideally with known operating characteristics, and a critical discussion of the joint evidence seems recommendable when aiming to identify high-risk clusters.

3.
Arthritis Rheumatol ; 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33142016

RESUMO

OBJECTIVE: In the SENSCIS trial in subjects with systemic sclerosis-associated ILD (SSc-ILD), nintedanib reduced the rate of decline in forced vital capacity (FVC) over 52 weeks by 44% versus placebo. We investigated the effects of nintedanib on categorical changes in FVC and other measures of ILD progression. METHODS: In post-hoc analyses, we assessed the proportions of subjects with categorical changes in FVC % predicted at week 52 and the time to absolute decline in FVC ≥5% predicted or death and absolute decline in FVC ≥10% predicted or death. RESULTS: A total of 288 subjects received nintedanib and 288 received placebo. At week 52, in subjects treated with nintedanib and placebo, respectively, 55.7% and 66.3% had any decline in FVC % predicted, 13.6% and 20.1% had an FVC decline >5%-≤10% predicted, and 3.5% and 5.2% had an FVC decline >10%-≤15% predicted; 34.5% and 43.8% had a decrease in FVC ≥3.3% predicted (proposed minimal clinically important difference [MCID] for worsening of FVC), while 23.0% and 14.9% had an increase in FVC ≥3.0% predicted (proposed MCID for improvement in FVC). Over 52 weeks, the hazard ratio for an absolute decline in FVC ≥5% predicted or death with nintedanib versus placebo was 0.83 (95% CI: 0.66, 1.06) (P=0.14) and the hazard ratio for an absolute decline in FVC ≥10% predicted was 0.64 (95% CI: 0.43, 0.95); P=0.029. CONCLUSION: These results suggest that nintedanib has a clinically relevant benefit on the progression of SSc-ILD.

4.
Clin Transl Gastroenterol ; 11(10): e00243, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33031193

RESUMO

INTRODUCTION: To quantify the association of self-reported lower gastrointestinal endoscopy use measured in 2004/05 with colorectal cancer (CRC) mortality changes over 2004-2015 in Europe. METHODS: An ecological analysis was performed using endoscopy utilization data from the Survey of Health, Aging, and Retirement in 11 European countries in 2004/05 and CRC mortality data from the World Health Organization Mortality Database over 2004-2015. Mortality trends were compared through annual mortality changes from joinpoint regression models. Cross-national variations in mortality trends with respect to endoscopy use were tested for statistical significance by negative binomial regression models. RESULTS: The proportion of respondents who reported having had an endoscopy within 10 years varied widely across countries, from 6.1% to 25.1%. Large disparities in CRC mortality trends were also observed, with annual mortality change ranging from a decline of 3.3% to an increase of 0.9% for men and from a decline of 3.3% to a decline of 0.6% for women. Endoscopy uptake was negatively associated with the magnitude of annual mortality change over 2004-2015 (rate ratio for a 10-year mortality change per 10% higher endoscopy use, 0.88; 95% confidence interval, 0.82-0.94). DISCUSSION: This analysis provides quantitative evidence on the contributions of endoscopy use to CRC mortality declines in European countries over the past decade. A considerable fraction of protection is likely to be delivered through endoscopic removal of adenomas and sessile serrated lesions. With many European countries having recently implemented CRC screening programs, an increase in endoscopy use and a subsequent reduction in CRC mortality would be expected.

5.
BMC Med Res Methodol ; 20(1): 257, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33059585

RESUMO

BACKGROUND: Projection of future cancer incidence is an important task in cancer epidemiology. The results are of interest also for biomedical research and public health policy. Age-Period-Cohort (APC) models, usually based on long-term cancer registry data (> 20 yrs), are established for such projections. In many countries (including Germany), however, nationwide long-term data are not yet available. General guidance on statistical approaches for projections using rather short-term data is challenging and software to enable researchers to easily compare approaches is lacking. METHODS: To enable a comparative analysis of the performance of statistical approaches to cancer incidence projection, we developed an R package (incAnalysis), supporting in particular Bayesian models fitted by Integrated Nested Laplace Approximations (INLA). Its use is demonstrated by an extensive empirical evaluation of operating characteristics (bias, coverage and precision) of potentially applicable models differing by complexity. Observed long-term data from three cancer registries (SEER-9, NORDCAN, Saarland) was used for benchmarking. RESULTS: Overall, coverage was high (mostly > 90%) for Bayesian APC models (BAPC), whereas less complex models showed differences in coverage dependent on projection-period. Intercept-only models yielded values below 20% for coverage. Bias increased and precision decreased for longer projection periods (> 15 years) for all except intercept-only models. Precision was lowest for complex models such as BAPC models, generalized additive models with multivariate smoothers and generalized linear models with age x period interaction effects. CONCLUSION: The incAnalysis R package allows a straightforward comparison of cancer incidence rate projection approaches. Further detailed and targeted investigations into model performance in addition to the presented empirical results are recommended to derive guidance on appropriate statistical projection methods in a given setting.

6.
Int J Chron Obstruct Pulmon Dis ; 15: 2601-2608, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33122898

RESUMO

Background: The Global Initiative for Chronic Obstructive Lung Disease 2020 report recommends that patients with chronic obstructive pulmonary disease (COPD) suffering from persistent dyspnea, despite long-acting ß2-agonist (LABA)/inhaled corticosteroid (ICS) maintenance therapy, are switched to either a long-acting muscarinic antagonist (LAMA)/LABA combination regimen or LAMA/LABA/ICS triple therapy. However, to date, no studies have investigated the direct switch from LABA/ICS to LAMA/LABA therapy-instead of switching to triple therapy-in a prospective, real-world, non-interventional setting. Methods: EVELUT® (NCT03954132) is an ongoing, prospective, open-label, multicenter, non-interventional study comparing the once-daily fixed-dose combination of tiotropium and olodaterol (tio/olo) versus any triple therapy (LAMA/LABA/ICS) in patients with COPD who are symptomatic despite LABA/ICS maintenance therapy. Patients with acute or frequent COPD exacerbations are excluded from the study. Participants will receive LABA/ICS maintenance treatment until Visit 1, followed by switching of treatment to tio/olo or LAMA/LABA/ICS. The primary endpoints are changes in modified Medical Research Council (mMRC) and COPD Assessment Test (CAT®) scores after approximately 12 weeks of treatment. Secondary endpoints are change in the patients' general condition according to the Physician's Global Evaluation score, the proportion of responders with a change in mMRC score of ≥1 and in CAT® score of ≥2, and patient satisfaction with the inhaler and therapy. The study is expected to enroll approximately 900 patients. Conclusion: EVELUT results are expected to add to the current real-world evidence informing therapeutic decisions for COPD in everyday clinical practice. Trial Registration: The European Union electronic Register of Post-authorisation Studies (EU PAS Register): EUPAS29784; the Federal Institute for Drugs and Medical Devices (BfArM): NIS Study No 7305; Clinicaltrials.gov: NCT03954132.

7.
Front Neurol ; 11: 573381, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33101182

RESUMO

Background: Widespread quick access to mechanical thrombectomy (MT) for acute ischemic stroke (AIS) is one of the main challenges in stroke care. It is unclear if newly established MT units are required 24 h/7 d. We explored the diurnal admission rate of patients with AIS potentially eligible for MT to provide a basis for discussion of daytime-adapted stroke care concepts. Methods: Data collected from the Baden-Württemberg Stroke Registry in Germany were assessed (2008-2012). We analyzed the admission rate of patients with AIS stratified by the National Institutes of Health Stroke Scale (NIHSS) score at admission in 3-h intervals. An NIHSS score ≥10 was considered a predictor of large vessel occlusion. The average annual admission number of patients with severe AIS were stratified by stroke service level and calculated for a three-shift model and working/non-working hours. Results: Of 91,864, 22,527 (21%) presented with an NIHSS score ≥10. The average admission rates per year for a hospital without Stroke Unit (SU), with a local SU, with a regional SU and a stroke center were 8, 52, 90 and 178, respectively. Approximately 61% were admitted during working hours, 54% in the early shift, 36% in the late shift and 10% in the night shift. Conclusions: A two-shift model, excluding the night shift, would cover 90% of the patients with severe AIS. A model with coverage during working hours would miss ~40% of the patients with severe AIS. To achieve a quick and area-wide MT, it seems preferable for newly implemented MT-units to offer MT in a two-shift model at a minimum.

8.
BMJ Open ; 10(10): e039747, 2020 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-33093036

RESUMO

BACKGROUND: Polypharmacy interventions are resource-intensive and should be targeted to those at risk of negative health outcomes. Our aim was to develop and internally validate prognostic models to predict health-related quality of life (HRQoL) and the combined outcome of falls, hospitalisation, institutionalisation and nursing care needs, in older patients with multimorbidity and polypharmacy in general practices. METHODS: Design: two independent data sets, one comprising health insurance claims data (n=592 456), the other data from the PRIoritising MUltimedication in Multimorbidity (PRIMUM) cluster randomised controlled trial (n=502). Population: ≥60 years, ≥5 drugs, ≥3 chronic diseases, excluding dementia. Outcomes: combined outcome of falls, hospitalisation, institutionalisation and nursing care needs (after 6, 9 and 24 months) (claims data); and HRQoL (after 6 and 9 months) (trial data). Predictor variables in both data sets: age, sex, morbidity-related variables (disease count), medication-related variables (European Union-Potentially Inappropriate Medication list (EU-PIM list)) and health service utilisation. Predictor variables exclusively in trial data: additional socio-demographics, morbidity-related variables (Cumulative Illness Rating Scale, depression), Medication Appropriateness Index (MAI), lifestyle, functional status and HRQoL (EuroQol EQ-5D-3L). Analysis: mixed regression models, combined with stepwise variable selection, 10-fold cross validation and sensitivity analyses. RESULTS: Most important predictors of EQ-5D-3L at 6 months in best model (Nagelkerke's R² 0.507) were depressive symptoms (-2.73 (95% CI: -3.56 to -1.91)), MAI (-0.39 (95% CI: -0.7 to -0.08)), baseline EQ-5D-3L (0.55 (95% CI: 0.47 to 0.64)). Models based on claims data and those predicting long-term outcomes based on both data sets produced low R² values. In claims data-based model with highest explanatory power (R²=0.16), previous falls/fall-related injuries, previous hospitalisations, age, number of involved physicians and disease count were most important predictor variables. CONCLUSIONS: Best trial data-based model predicted HRQoL after 6 months well and included parameters of well-being not found in claims. Performance of claims data-based models and models predicting long-term outcomes was relatively weak. For generalisability, future studies should refit models by considering parameters representing well-being and functional status.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32875386

RESUMO

Over the last two decades, the understanding of how dysregulated ion channels and transporters are involved in carcinogenesis and tumor growth and progression, including invasiveness and metastasis, has been increasing exponentially. The present review specifies virtually all ion channels and transporters whose faulty expression or regulation contributes to esophageal, hepatocellular, and colorectal cancer. The variety reaches from Ca2+, K+, Na+, and Cl- channels over divalent metal transporters, Na+ or Cl- coupled Ca2+, HCO3- and H+ exchangers to monocarboxylate carriers and organic anion and cation transporters. In several cases, the underlying mechanisms by which these ion channels/transporters are interwoven with malignancies have been fully or at least partially unveiled. Ca2+, Akt/NF-κB, and Ca2+- or pH-dependent Wnt/ß-catenin signaling emerge as cross points through which ion channels/transporters interfere with gene expression, modulate cell proliferation, trigger epithelial-to-mesenchymal transition, and promote cell motility and metastasis. Also miRs, lncRNAs, and DNA methylation represent potential links between the misexpression of genes encoding for ion channels/transporters, their malfunctioning, and cancer. The knowledge of all these molecular interactions has provided the basis for therapeutic strategies and approaches, some of which will be broached in this review.

11.
Depress Anxiety ; 37(9): 898-907, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32542951

RESUMO

BACKGROUND: Depression is common in patients with chronic heart failure (CHF) and is a predictor of rehospitalization and mortality. However, the complex bidirectional relationships between these two conditions are barely understood. We investigated the course of depression and markers of CHF (New York Heart Association [NYHA] functional class, N-terminal-prohormone B-type natriuretic peptide [NT-proBNP], and left ventricular ejection fraction [LVEF]) in a longitudinal study over a period of 2 years, using three assessment points. METHODS: Data of n = 446 patients with documented CHF were analyzed using structural equation modeling. Specifically, a Bayesian cross-lagged structural equation model was applied. RESULTS: Our study revealed that an aggravation of depression predicted an increase in NYHA functional class (significant cross-lagged effect γh = 0.103, 95% confidence interval [CI] [0.017; 0.194]), whereas an increase in NYHA functional class did not predict an aggravation of depression (γd = 0.002 95% CI [-0.057; 0.194]). This association was found only for NYHA functional class and depression-not for NT-proBNP and LVEF. CONCLUSIONS: Experiencing depression and associated symptoms, such as lack of energy and fatigue, may lead to a further decrease of functional capacity, and consequently to a higher NYHA functional class in CHF patients. As NYHA functional class is associated with higher mortality, this may be a critical development for affected patients. Further studies are required to investigate whether or not this association could be an essential key that explains the pathway from depression to increased mortality in heart failure patients.

12.
Cells ; 9(2)2020 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-32085585

RESUMO

Increased metabolic acid production and upregulation of net acid extrusion render pH homeostasis profoundly dysregulated in many cancers. Plasma membrane activity of vacuolar H+ ATPases (V-ATPases) has been implicated in acid extrusion and invasiveness of some cancers, yet often on the basis of unspecific inhibitors. Serving as a membrane anchor directing V-ATPase localization, the a subunit of the V0 domain of the V-ATPase (ATP6V0a1-4) is particularly interesting in this regard. Here, we map the regulation and roles of ATP6V0a3 in migration, invasion, and growth in pancreatic ductal adenocarcinoma (PDAC) cells. a3 mRNA and protein levels were upregulated in PDAC cell lines compared to non-cancer pancreatic epithelial cells. Under control conditions, a3 localization was mainly endo-/lysosomal, and its knockdown had no detectable effect on pHi regulation after acid loading. V-ATPase inhibition, but not a3 knockdown, increased HIF-1 expression and decreased proliferation and autophagic flux under both starved and non-starved conditions, and spheroid growth of PDAC cells was also unaffected by a3 knockdown. Strikingly, a3 knockdown increased migration and transwell invasion of Panc-1 and BxPC-3 PDAC cells, and increased gelatin degradation in BxPC-3 cells yet decreased it in Panc-1 cells. We conclude that in these PDAC cells, a3 is upregulated and negatively regulates migration and invasion, likely in part via effects on extracellular matrix degradation.

13.
Cancer Cell Int ; 19: 285, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31728131

RESUMO

Background: Both cell adhesion and matrix metalloproteinase (MMP) activity depend on pH at the cell surface. By regulating extracellular juxtamembrane pH, the Na+/H+ exchanger NHE1 plays a significant part in human melanoma (MV3) cell migration and invasion. Because NHE1, besides its pH-regulatory transport function, also serves as a structural element tying the cortical actin cytoskeleton to the plasma membrane, we investigated whether NHE1 affects cortical stiffness of MV3 cells, and how this makes an impact on their invasiveness. Methods: NHE1 overexpressing MV3 cells were compared to the corresponding mock-transfected control cells. NHE1 expression was verified by Western blotting, cariporide (HOE642) was used to inhibit NHE1 activity, cell stiffness was determined by atomic force microscopy, and F-actin was visualized by phalloidin-staining. Migration on, and invasion of, native and glutaraldehyde-fixed collagen I substrates were analyzed using time-lapse video microscopy and Boyden-chamber assays, respectively. MMP secretion and activity were detected by Western blot and zymography, respectively. MMP activity was inhibited with NNGH. Results: The cortical, but not the bulk stiffness, was significantly higher in NHE1 overexpressing cells. This increase in cortical stiffness was accompanied by a reorganization of the cortical cytoskeleton, i.e. a condensation of F-actin underneath and along the plasma membrane. However, it was not affected by NHE1 inhibition. Nevertheless, actin dynamics is required for cell invasion as demonstrated with the application of cytochalasin D. NHE1 overexpression was associated with an elevated MMP3 secretion and an increase in the invasion of a native matrix. This increase in invasiveness could be antagonized by the MMP inhibitor NNGH. Transmigration through a glutaraldehyde-fixed, indigestible substrate was not affected by NHE1 overexpression. Conclusion: NHE1, as a structural element and independently of its transport activity, contributes to the organization of the cortical F-actin meshwork and thus impacts cortical stiffness. Since NHE1 overexpression stimulates MMP3 secretion but does not change transmigration through a fixed substrate, MV3 cell invasion of a native substrate depends on MMP activity rather than on a modifiable cortical stiffness.

14.
Neurology ; 93(20): e1834-e1843, 2019 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-31653709

RESUMO

BACKGROUND: It is common practice to withhold IV thrombolysis (IVT) for acute ischemic stroke in patients with preexisting disabilities. To test the hypothesis of an association of IVT and good clinical outcome also in patients with preexisting disabilities without an increase in mortality, we analyzed data from 52,741 patients (15,317 treated with IVT) depending on prestroke Rankin Scale (pRS) score. METHODS: We performed an observational study based on a consecutive stroke registry covering 10.8 million inhabitants. The outcome at discharge of patients with stroke admitted in the time window of potential eligibility for IVT (<4.5 hours after stroke onset) was compared between patients treated and those not treated with thrombolysis, stratified by pRS score. Logistic regression analysis was used to estimate adjusted odds ratios (ORs) along with 95% confidence intervals (CIs) for favorable clinical outcome, defined as returning to the baseline pRS score or a score of 0 or 1 and mortality. Sensitivity analyses for subgroups of mildly and severely affected patients with stroke were performed, and the influence of treatment duration was assessed. RESULTS: Among included patients, IVT rates were 32% for patients with pRS scores of 0 to 1 and 20% for patients with pRS scores of 2 to 5. IVT in patients with pRS scores of 0 to 4 was associated with a higher chance of returning to the baseline pRS score (or a modified Rankin Scale score of 0/1), with ORs ranging between 1.42 (pRS score 2; 95% CI 1.16-1.73) and 1.73 (pRS score 0; 95% CI 1.61-1). The OR observed in patients with a pRS score of 5 was 0.65 (95% CI 0.25-1.70). Observed associations remained consistent in sensitivity analyses. Subgroup analyses revealed no evidence of bias due to potential floor and ceiling effects. No evidence of elevated in-hospital mortality of patients treated with thrombolysis was observed. CONCLUSIONS: Our study suggests that IVT can be effective even in patients with severe preexisting disabilities, provided that they were not bedridden before stroke onset. Withholding IVT on the sole ground of prestroke disabilities may not be justified.


Assuntos
Pessoas com Deficiência , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Acidente Vascular Cerebral/fisiopatologia , Resultado do Tratamento
15.
Prev Med ; 123: 333-340, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30946858

RESUMO

An increasing number of countries have recently introduced colorectal cancer (CRC) screening programs. Typically, one specific screening exam, such as fecal occult blood test (FOBT) or flexible sigmoidoscopy, is offered as a primary screening test. We aimed to assess trends in FOBT and colonoscopy use in Germany following the introduction of the offer of screening colonoscopy as an alternative to FOBT in 2002. We used data from 4052 control participants aged 50-79 years recruited during 2003-2016 for a population-based case-control study in Germany. Prevalence of FOBT and colonoscopy lifetime and recent use was analyzed and trends over time were examined. The percentage of all respondents who had ever undergone a colonoscopy (for either screening or diagnostic purpose) increased markedly over time from 44.6% in 2003-2005 to 57.5% in 2013-2016 (p < 0.0001). Large increases were also observed for colonoscopy use within 10 years (from 38.0% to 52.8%, p < 0.0001), whereas FOBT uptake within one to two years declined from 54.0% to 33.3%. By 2013-2016, 67.2% of respondents either had an FOBT within one to two years or a colonoscopy within 10 years, and this percentage had remained relatively stable over time. This study demonstrates a large increase in colonoscopy utilization since colonoscopy was included as an alternative primary screening test, which was accompanied by a substantial decline in FOBT use. Although the overall adherence to CRC screening recommendations remained stable, the substantial shift of share from FOBT to colonoscopy is expected to yield more protection against CRC incidence and mortality.


Assuntos
Colonoscopia/tendências , Neoplasias Colorretais/prevenção & controle , Detecção Precoce de Câncer/métodos , Sangue Oculto , Cooperação do Paciente/estatística & dados numéricos , Melhoria de Qualidade , Distribuição por Idade , Idoso , Estudos de Casos e Controles , Colonoscopia/métodos , Neoplasias Colorretais/diagnóstico , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Distribuição por Sexo
16.
BMC Infect Dis ; 19(1): 304, 2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30943917

RESUMO

BACKGROUND: Screening programmes for tuberculosis (TB) among immigrants rarely consider the heterogeneity of risk related to migrants' country of origin. We assess the performance of a large screening programme in asylum seekers by analysing (i) the difference in yield and numbers needed to screen (NNS) by country and WHO-reported TB burden, (ii) the possible impact of screening thresholds on sensitivity, and (iii) the value of WHO-estimated TB burden to improve the prediction accuracy of screening yield. METHODS: We combined individual data of 119,037 asylum seekers screened for TB in Germany (2002-2015) with TB estimates of the World Health Organization (WHO) (1990-2014) for their 81 countries of origin. Adjusted rate ratios (aRR) and 95% credible intervals (CrI) of the observed yield of screening were calculated in Bayesian Poisson regression models by categories of WHO-estimated TB incidence. We assessed changes in sensitivity depending on screening thresholds, used WHO TB estimates as prior information to predict TB in asylum seekers, and modelled country-specific probabilities of numbers needed to screen (NNS) conditional on different screening thresholds. RESULTS: The overall yield was 82 per 100,000 and the annual yield ranged from 44.1 to 279.7 per 100,000. Country-specific yields ranged from 10 (95%- CrI: 1-47) to 683 (95%-CrI: 306-1336) per 100,000 in Iraqi and Somali asylum seekers, respectively. The observed yield was higher in asylum seekers from countries with a WHO-estimated TB incidence > 50 relative to those from countries ≤50 per 100,000 (aRR: 4.17, 95%-CrI: 2.86-6.59). Introducing a threshold in the range of a WHO-estimated TB incidence of 50 and 100 per 100,000 resulted in the lowest "loss" in sensitivity. WHO's TB prevalence estimates improved prediction accuracy for eight of the 11 countries, and allowed modelling country-specific probabilities of NNS. CONCLUSIONS: WHO's TB data can inform the estimation of screening yield and thus be used to improve screening efficiency in asylum seekers. This may help to develop more targeted screening strategies by reducing uncertainty in estimates of expected country-specific yield, and identify thresholds with lowest loss in sensitivity. Further modelling studies are needed which combine clinical, diagnostic and country-specific parameters.


Assuntos
Emigrantes e Imigrantes/estatística & dados numéricos , Tuberculose/diagnóstico , Adolescente , Adulto , Idoso , Teorema de Bayes , Criança , Controle de Doenças Transmissíveis , Feminino , Alemanha , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Modelos Estatísticos , Prevalência , Saúde Pública , Refugiados , Tuberculose/epidemiologia , Organização Mundial da Saúde , Adulto Jovem
17.
Gerodontology ; 36(2): 171-179, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30821850

RESUMO

OBJECTIVE: To assess the validity of patient self-reported oral health measures as used in a large multi-country survey for populations aged 50+. BACKGROUND: Information on people's oral health status is important for assessing oral health needs within populations. However, clinical examination is not always possible. Patient self-reported measures may provide an alternative when time and other resources are scarce. MATERIALS AND METHODS: Using oral health items from the Survey of Health, Ageing and Retirement in Europe (SHARE), self-reported measures were collected from 186 patients receiving treatment at Heidelberg University Hospital. Self-reports were compared with subsequent clinical examinations. Analyses were conducted for patients of all age groups and separately for patients aged 50+ (analogous to the SHARE study population). Diagnostic accuracy, agreement and correlation of patient-reported information were examined using descriptive statistics and Bland-Altman plots. RESULTS: Patient-reported presence or absence of a full tooth count was closely related to clinical measurement, both for all age groups (sensitivity: 93%; specificity: 92%) and persons aged 50+ (sensitivity: 100% specificity: 94%). Bland-Altman plots indicate good agreement between patient- and clinical reports of the number of teeth at age 50+ (Concordance Correlation Coefficient = 0.95). Discriminatory power of patient-reporting was good regarding presence vs absence of artificial teeth, but less robust regarding partial vs full replacement of missing teeth. CONCLUSION: Patient self-evaluations provide reasonable estimates of clinical measures and appear sufficiently accurate for examining variations in the number of teeth, including among populations aged 50+. However, patient reports of the extent of replacement of missing teeth may not constitute reliable reflections of clinical conditions.


Assuntos
Saúde Bucal , Perda de Dente , Europa (Continente) , Humanos , Pessoa de Meia-Idade , Autorrelato , Inquéritos e Questionários
19.
Gastrointest Endosc ; 89(5): 1017-1025.e12, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30639539

RESUMO

BACKGROUND AND AIMS: Recent guidelines on colorectal cancer (CRC) screening recommend starting screening earlier than before. We performed a simulation study to examine and compare the optimal ages to have once-only screening colonoscopy and repeated colonoscopies. METHODS: A Markov model was set up using data from the German national screening colonoscopy registry to simulate the natural history of the adenoma-carcinoma process. CRC deaths and years of potential life lost (YPLL) for a hypothetical unscreened 50-year-old German population were estimated for a single screening colonoscopy or 2 or 3 screening colonoscopies with 10-year intervals at various ages. RESULTS: One single screening colonoscopy performed between 50 and 65 years of age was expected to reduce CRC death by 49% to 69% and YPLL by 51% to 68%. An inverted U-shaped association was found between screening age and proportion of CRC deaths or YPLL prevented. The optimal age for once-only colonoscopy that yielded the highest reductions in YPLL was around 54 years for men and 56 years for women. Estimates were approximately 6 to 8 years higher when proportions of CRC deaths prevented were examined. For 2 or 3 screening colonoscopies, the optimal starting age fell to around 50 years or even younger for both genders. CONCLUSIONS: Based on the YPLL estimates, in a high CRC incidence and high life expectancy country like Germany, the optimal age for once-only screening colonoscopy is around 55 years and possibly slightly younger for men than for women. When 2 or more screening colonoscopies are offered with 10-year intervals, screening should start at age 50 at the latest or possibly even younger for both genders.


Assuntos
Adenocarcinoma/diagnóstico , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/métodos , Cadeias de Markov , Adenocarcinoma/epidemiologia , Fatores Etários , Idoso , Neoplasias Colorretais/epidemiologia , Feminino , Alemanha , Humanos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Medição de Risco
20.
Front Physiol ; 10: 1566, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32009977

RESUMO

Na+/H+ exchangers (NHEs) are expressed in virtually all human tissues and organs. Two major tasks of those NHE isoforms that are located in plasma membranes are cell volume control by Na+-uptake and cellular pH regulation by H+-extrusion. Several NHEs, particularly NHE 1-4 and 8, are involved in the pathogenesis of diseases of the digestive system such as inflammatory bowel disease (ulcerative colitis, Crohn's disease) and gastric and colorectal tumorigenesis. In the present review, we describe the physiological purposes, possible malfunctions and pathophysiological effects of the different NHE isoforms along the alimentary canal from esophagus to colon, including pancreas, liver and gallbladder. Particular attention is paid to the functions of NHEs in injury repair and to the role of NHE1 in Barrett's esophagus. The impact of NHEs on gut microbiota and intestinal mucosal integrity is also dealt with. As the hitherto existing findings are not always consistent, sometimes even controversial, they are compared and critically discussed.

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