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1.
Br J Haematol ; 2024 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-39442921

RESUMO

During a fatal disease, patients often request updated information on their prognosis. After patients have already survived a certain time, conditional survival captures their future survival probability. We investigated conditional overall and failure-free survival in 473 younger mantle cell lymphoma (MCL) patients from a randomized phase III trial comparing immunochemotherapies R-CHOP and alternating R-CHOP/R-DHAP before autologous transplantation. Using conditional Kaplan-Meier method and Cox regression, we estimated subsequent survival of patients who had survived 1-8 years, considering MIPI, Ki-67, and treatment failure status. Starting at a lower level, R-CHOP patients only showed increasing subsequent survival as they survived longer (5-year conditional survival: 72% and 81% after surviving 1 and 7 years), while R-CHOP/R-DHAP patients had stable future survival over time (77% and 78%). The prognostic value of MIPI diminished after 3 years in R-CHOP patients but remained unchanged after R-CHOP/R-DHAP. Patients with treatment failure had markedly inferior survival compared with those in ongoing remission, regardless of the time survived. The longer patients remained in remission, the longer they would stay free of treatment failures. Our results enable personalized counselling for younger MCL patients by offering dynamic prognosis and underscore the importance of highly effective first-line treatment to improve survival.

2.
Transplant Cell Ther ; 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39299503

RESUMO

BACKGROUND: Prophylactic antibiotics are still controversial during allogeneic hematopoietic stem cell transplantation (allo-HSCT). In our transplant center, we suspended antibiotic prophylaxis during allo-HSCT in 2017. OBJECTIVE: The main objective of this study was the detailed analysis of the potentially beneficial impact of omittance of standard antibiotic prophylaxis during allo-HSCT in survival and Graft-versus-Host disease (GvHD) development, especially with consideration of confounding factors and competing events. Secondary objectives were the evaluation of the risk of severe infections and transplant-related mortality without antibiotic prophylaxis, the detailed assessment of bacterial and viral infections including multiresistant pathogens as well as occurrence of relapse in both groups. This study aims to support the development of future antibiotic strategies in allo-HSCT. STUDY DESIGN: We retrospectively analyzed patient outcome in the time periods before (between December 2012 and February 2017) and after suspension (between March 2017 and June 2020) of antibiotic prophylaxis during allo-HSCT. Relevant clinical outcome parameters of the patients (n = 221) were collected by chart-review in the two groups (with antibiotic prophylaxis n = 101 versus without antibiotic prophylaxis n = 120). All patients were 18 years or older. Propensity score methods were used to adjust for potentially confounding patient characteristics. To address competing events, transitions between moderate/severe acute and chronic GvHD, relapse and death were analyzed using an inverse-propensity score weighted multistate modeling approach. RESULTS: While we observed a trend towards an improved outcome in the cohort without antibiotic prophylaxis, the inverse-propensity-score-weighted analyses did not show significant differences between the two groups in overall survival (OS) (P = .811) or development of acute GvHD (aGvHD) grade 3/4 (P = .158) and chronic moderate/severe GvHD (cGvHD) (P = .686). Multistate analysis respecting competing events revealed comparable estimated probabilities without antibiotic prophylaxis versus with antibiotic prophylaxis in OS (35.0% [95% CI: 28.2%-42.7%] versus 35.3% [95% CI: 27.8%-41.1%]) as well as development of aGvHD grade 3/4 (7.7% [95% CI: 5.9%-12.2%] vs. 10.6% [95% CI: 7.7%-15.7%]) and moderate/severe cGvHD (21.0% [95% CI: 17.7%-30.0%] vs. 23.8% [95% CI: 19.6%-31.4%]). Similar analyses showed also no significant differences in relapse rate, transplant-related mortality, relapse-related mortality, or GvHD-free/relapse-free survival between the two groups. An observed increase in severe infections without antibiotic prophylaxis did not lead to a significantly higher mortality rate. Viral reactivation and detection of multiresistant bacteria were comparable, yet a higher incidence of Clostridioides difficile infections was observed in patients receiving antibiotic prophylaxis. CONCLUSION: Our study supports previous reports of noninferiority of allo-HSCT without use of antibiotic prophylaxis with close monitoring and rapid intervention, if infection is suspected. The trend towards improved outcomes without antibiotic prophylaxis, however, might not only be due to the absence of antibiotic prophylaxis but also due to additional progresses in the field over the recent years. While the present study is too small to draw definite conclusions, these results strongly warrant further multicenter studies addressing the potential benefit of omitting antibiotic prophylaxis during allo-HSCT.

4.
Nephrol Dial Transplant ; 39(9): 1504-1513, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-38323492

RESUMO

INTRODUCTION: Mechanisms underlying kidney benefits with sodium-glucose cotransporter-2 (SGLT2) inhibition in heart failure and/or type 2 diabetes (T2D) with established cardiovascular disease are currently unclear. METHODS: We evaluated post hoc the factors mediating the effect of empagliflozin on a composite kidney outcome (first sustained estimated glomerular filtration rate ≥40% reduction from baseline, initiation of renal replacement therapy or death due to kidney disease) in EMPA-REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients). Variables, calculated as change from baseline or updated mean, were evaluated as time-dependent covariates and using a landmark approach (at Week 12) in Cox regression analyses. In multivariable analyses, variables with the greatest mediating effect were added using a step-up procedure. RESULTS: In univariable time-dependent updated mean covariate analyses, the strongest mediator was hematocrit (99.5% mediation). Hemoglobin, uric acid and urine albumin-to-creatinine ratio mediated 79.4%, 33.2% and 31.0%, respectively. Multivariable analyses were not performed due to the very strong mediation effect of hematocrit. In univariable Week 12 landmark change from baseline analyses, the strongest mediators included hematocrit (40.7%), glycated hemoglobin (28.3%), systolic blood pressure (16.8%) and free fatty acids (16.5%), which yielded a combined mediation of 78.9% in multivariable analysis. CONCLUSIONS: Changes in hematocrit and hemoglobin were the strongest mediators of empagliflozin's kidney benefits in EMPA-REG OUTCOME participants with T2D and cardiovascular disease.


Assuntos
Compostos Benzidrílicos , Diabetes Mellitus Tipo 2 , Taxa de Filtração Glomerular , Glucosídeos , Inibidores do Transportador 2 de Sódio-Glicose , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Benzidrílicos/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Seguimentos , Glucosídeos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Análise de Mediação , Prognóstico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
5.
Ann Hematol ; 103(5): 1613-1622, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38308707

RESUMO

Biomarkers in chronic lymphocytic leukemia (CLL) allow assessment of prognosis. However, the validity of current prognostic biomarkers based on a single assessment point remains unclear for patients who have survived one or more years. Conditional survival (CS) studies that address how prognosis may change over time, especially in prognostic subgroups, are still rare. We performed CS analyses to estimate 5-year survival in 1-year increments, stratified by baseline disease characteristics and known risk factors in two community-based cohorts of CLL patients (Freiburg University Hospital (n = 316) and Augsburg University Hospital (n = 564)) diagnosed between 1984 and 2021. We demonstrate that 5-year CS probability is stable (app. 75%) for the entire CLL patient cohort over 10 years. While age, sex, and stage have no significant impact on CS, patients with high-risk disease features such as non-mutated IGHV, deletion 17p, and high-risk CLL-IPI have a significantly worse prognosis at diagnosis, and 5-year CS steadily decreases with each additional year survived. Our results confirm that CLL patients have a stable survival probability with excess mortality and that the prognosis of high-risk CLL patients declines over time. We infer that CS-based prognostic information is relevant for disease management and counseling of CLL patients.


Assuntos
Leucemia Linfocítica Crônica de Células B , Humanos , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/terapia , Prognóstico , Biomarcadores , Análise de Sobrevida , Mutação
6.
Vasa ; 53(1): 68-76, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38047756

RESUMO

Background: Current evidence indicates that erectile dysfunction (ED) is an independent risk factor for future cardiovascular events. This study aimed to estimate the cost-effectiveness of screening and subsequent preventive treatment for cardiovascular risk factors among men newly diagnosed with ED from the Swiss healthcare system perspective. Methods: Based on known data on ED and cardiovascular disease (CVD) prevalence and incidence costs and effects of a screening intervention for cardiovascular risk including corresponding cardiovascular prevention in men with ED were calculated for the Swiss population over a period of 10 years. Results: Screening and cardiovascular prevention over a period of 10 years in Swiss men with ED of all seriousness degrees, moderate and severe ED only, or severe ED only can probably avoid 41,564, 35,627, or 21,206 acute CVD events, respectively. Number needed to screen (NNS) to prevent one acute CVD event is 30, 23, and 10, respectively. Costs for the screening intervention are expected to be covered at the seventh, the fifth, and the first year, respectively. Conclusion: Screening and intervention for cardiovascular risk factors in men suffering from ED is a cost-effective tool not only to strengthen prevention and early detection of cardiovascular diseases but also to avoid future cardiovascular events.


Assuntos
Doenças Cardiovasculares , Disfunção Erétil , Masculino , Humanos , Disfunção Erétil/diagnóstico , Disfunção Erétil/epidemiologia , Disfunção Erétil/terapia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Análise Custo-Benefício , Fatores de Risco , Suíça/epidemiologia , Fatores de Risco de Doenças Cardíacas
7.
CVIR Endovasc ; 6(1): 56, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37975993

RESUMO

BACKGROUND: Venous leak appears to be the most common cause of vasculogenic erectile dysfunction (ED), which can be treated with venous embolization. Traditionally, conventional cavernosography was used for the diagnosis and treatment planning of venous leak. Recently, computed tomography (CT) cavernosography was introduced as a novel cross-sectional imaging method proposed to be advantageous over conventional cavernosography. We created a novel management algorithm for diagnosing venous leak including CT cavernosography as an imaging modality. In order to provide a broader basis for our management algorithm, a systematic literature review was conducted. MAIN BODY: In this article we systematically review relevant literature on using CT cavernosography for the diagnosis and treatment planning in ED patients with venous leak following the PRISMA selection process. Nine full-text articles were included in the review and assigned a level of evidence grade (all grade II). Two studies (2/9) compared the results of conventional cavernosography with those of CT cavernosography which was superior for site-specific venous leak identification (19.4% vs. 100%, respectively). CT cavernosography is a more detailed imaging method that is faster to perform, exposes the patient to less radiation, and requires less contrast material. In one study (1/9), CT cavernosography was used for diagnostic purposes only. Eight studies (8/9) cover both, diagnostic imaging and treatment planning including embolization (1/9) and sclerotherapy (2/9) of venous leak in patients with venogenic ED. Three studies (3/9) describe anatomical venous leak classifications that were established based on CT cavernosography findings for accurate mapping of superficial and/or deep venous leak and identification of mixed or more complex forms of venous leak present in up to 84% of patients. In addition to treatment planning, one study (1/9) used CT cavernosography also for follow-up imaging post treatment. CONCLUSION: CT cavernosography is superior to conventional cavernosography for diagnosis and treatment planning in patients with ED caused by venous leak (grade II levels of evidence). Consequently, CT cavernosography should be included in management algorithms for ED patients with suspected venous leak.

8.
J Endovasc Ther ; : 15266028231183775, 2023 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-37365869

RESUMO

PURPOSE: Endovascular therapy of erection-related arteries was shown to be a promising treatment option for patients with severe erectile dysfunction. Purpose of this study was to assess the longer-term safety and clinical success rate of endovascular revascularization of erection-related arteries with the Angiolite BTK stent in patients with arteriogenic erectile dysfunction. MATERIALS AND METHODS: A total of 147 consecutive men (63.5±9.3 years) with erectile dysfunction due to 345 atherosclerotic lesions underwent endovascular revascularization. Patients received an International Index of Erectile Function (IIEF)-15 questionnaire at 30.3±7.2 months (follow-up [FU] period no less than 18 months) after stenting. An improvement by 4 points in the erectile function domain consisting of 6 questions (IIEF-6) was defined as minimal clinically important difference (MCID). RESULTS: Technical success was achieved in 99% of lesions. One major adverse event occurred after endovascular revascularization. Sixty-eight (46%) patients completed their latest FU at least 18 months following the last intervention. Minimal clinically important difference was achieved in 54% (37/68) of patients. CONCLUSIONS: In patients with arteriogenic erectile dysfunction not responding to phosphodiesterase-5-inhibitors (PDE-5-Is), endovascular therapy with a novel thin-strut sirolimus-eluting stent is a safe and effective treatment option during short- and longer-term FU. CLINICAL IMPACT: Patients with severe erectile dysfunction profit greatly from endovascular therapy of erection-related arteries. Stable clinical outcomes are seen beyond a 1-year timeframe. It is proven that, the drug-eluting stent therapy for atherosclerotic ED in patients who have not responded to PDE-5-I therapy is safe and effective during longer-term follow-up.

9.
J Pers Med ; 13(5)2023 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-37241007

RESUMO

The dexamethasone suppression test (DST) assesses the functionality of the HPA axis and can be regarded as the first potential biomarker in psychiatry. In 1981, a group of researchers at the University of Michigan published a groundbreaking paper regarding its use for diagnosing melancholic depression, reporting a diagnostic sensitivity of 67% and a specificity of 95%. While this study generated much enthusiasm and high expectations in the field of biological psychiatry, subsequent studies produced equivocal results, leading to the test being rejected by the American Psychiatric Association. The scientific reasons leading to the rise and fall of the DST are assessed in this review, suggestions are provided as to how the original test can be improved, and its potential applications in clinical psychiatry are discussed. An improved, standardized, and validated version of the DST would be a biologically meaningful and useful biomarker in psychiatry, providing a tool for clinicians caring for depressed patients in the areas of diagnosis, treatment, and prognosis, and predicting the risk of suicide. Additionally, such a test could be a crucial part in the generation of biologically homogenous patient cohorts, necessary for the successful development of new psychotropic medications.

11.
J Appl Stat ; 50(3): 535-554, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36819080

RESUMO

Covariates in regressions may be linked to each other on a network. Knowledge of the network structure can be incorporated into regularized regression settings via a network penalty term. However, when it is unknown whether the connection signs in the network are positive (connected covariates reinforce each other) or negative (connected covariates repress each other), the connection signs have to be estimated jointly with the covariate coefficients. This can be done with an algorithm iterating a connection sign estimation step and a covariate coefficient estimation step. We develop such an algorithm, called 3CoSE, and show detailed simulation results and an application forecasting event times. The algorithm performs well in a variety of settings. We also briefly describe the publicly available R-package developed for this purpose.

12.
Int J Epidemiol ; 52(3): 837-845, 2023 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-36413012

RESUMO

BACKGROUND: Even though the population-attributable fraction (PAF) is a well-established metric, it is often incorrectly estimated or interpreted not only in clinical application, but also in statistical research articles. The risk of bias is especially high in more complex time-to-event data settings. METHODS: We explain how the PAF can be defined, identified and estimated in time-to-event settings with competing risks and time-dependent exposures. By using multi-state methodology and inverse probability weighting, we demonstrate how to reduce or completely avoid severe types of biases including competing risks bias, immortal time bias and confounding due to both baseline and time-varying patient characteristics. RESULTS: The method is exemplarily applied to a real data set. Moreover, we estimate the number of deaths that were attributable to ventilator-associated pneumonia in France in the year 2016. The example demonstrates how, under certain simplifying assumptions, PAF estimates can be extrapolated to a target population of interest. CONCLUSIONS: Defining and estimating the PAF in advanced time-to-event settings within a framework that unifies causal and multi-state modelling enables to tackle common sources of bias and allows straightforward implementation with standard software packages.


Assuntos
Viés , Humanos , Probabilidade , Tempo , França
13.
Eur J Neurosci ; 57(2): 324-350, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36509461

RESUMO

Conducting constitutes a well-structured system of signs anticipating information concerning the rhythm and dynamic of a musical piece. Conductors communicate the musical tempo to the orchestra, unifying the individual instrumental voices to form an expressive musical Gestalt. In a functional magnetic resonance imaging (fMRI) experiment, 12 professional conductors and 16 instrumentalists conducted real-time novel pieces with diverse complexity in orchestration and rhythm. For control, participants either listened to the stimuli or performed beat patterns, setting the time of a metronome or complex rhythms played by a drum. Activation of the left superior temporal gyrus (STG), supplementary and premotor cortex and Broca's pars opercularis (F3op) was shared in both musician groups and separated conducting from the other conditions. Compared to instrumentalists, conductors activated Broca's pars triangularis (F3tri) and the STG, which differentiated conducting from time beating and reflected the increase in complexity during conducting. In comparison to conductors, instrumentalists activated F3op and F3tri when distinguishing complex rhythm processing from simple rhythm processing. Fibre selection from a normative human connectome database, constructed using a global tractography approach, showed that the F3op and STG are connected via the arcuate fasciculus, whereas the F3tri and STG are connected via the extreme capsule. Like language, the anatomical framework characterising conducting gestures is located in the left dorsal system centred on F3op. This system reflected the sensorimotor mapping for structuring gestures to musical tempo. The ventral system centred on F3Tri may reflect the art of conductors to set this musical tempo to the individual orchestra's voices in a global, holistic way.


Assuntos
Conectoma , Gestos , Humanos , Encéfalo , Imageamento por Ressonância Magnética , Idioma , Mapeamento Encefálico/métodos
14.
ESC Heart Fail ; 8(6): 4517-4527, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34605192

RESUMO

AIMS: In the EMPA-REG OUTCOME trial, empagliflozin reduced risk of death from heart failure (HF) or hospitalization for heart failure (HHF) versus placebo in patients with type 2 diabetes mellitus (T2DM) and established cardiovascular (CV) disease. We evaluated post hoc the degree to which covariates mediated the effects of empagliflozin on HHF or HF death. METHODS AND RESULTS: A mediator had to fulfil the following criteria: (i) affected by active treatment, (ii) associated with the outcome, and finally (iii) adjustment for it results in a reduced treatment effect compared with unadjusted analysis. Potential mediators were calculated as change from baseline or updated mean and evaluated in univariable analyses as time-dependent covariates in Cox regression of time to HHF or HF death; those with the largest mediating effects were then included in a multivariable analysis. Increases in heart rate, log urine albumin-to-creatinine ratio (UACR), waist circumference, and uric acid were associated with increased risk of HHF or HF death; increases in high-density lipoprotein cholesterol, estimated glomerular filtration rate, haematocrit, haemoglobin, and albumin were associated with reduced risk of HHF or HF death. In univariable analyses, change from baseline in haematocrit, haemoglobin, albumin, uric acid, and logUACR mediated 51%, 54%, 23%, 24%, and 27% of the risk reduction with empagliflozin versus placebo, respectively. Multivariable analysis including haemoglobin, logUACR, and uric acid mediated 85% of risk reduction with similar results when updated means were evaluated. CONCLUSIONS: Changes in haematocrit and haemoglobin were the most important mediators of the reduction in HHF and death from HF in patients with T2DM and established CV disease treated with empagliflozin. Albumin, uric acid, and logUACR had smaller mediating effects in this population.


Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Compostos Benzidrílicos/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Glucosídeos/uso terapêutico , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Humanos
15.
BMC Med Res Methodol ; 21(1): 182, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34465296

RESUMO

BACKGROUND: Healthcare decisions are ideally based on clinical trial results, published in study registries, as journal articles or summarized in secondary research articles. In this research project, we investigated the impact of academically and commercially sponsored clinical trials on medical practice by measuring the proportion of trials published and cited by systematic reviews and clinical guidelines. METHODS: We examined 691 multicenter, randomized controlled trials that started in 2005 or later and were completed by the end of 2016. To determine whether sponsorship/funding and place of conduct influence a trial's impact, we created four sub-cohorts of investigator initiated trials (IITs) and industry sponsored trials (ISTs): 120 IITs and 171 ISTs with German contribution compared to 200 IITs and 200 ISTs without German contribution. We balanced the groups for study phase and place of conduct. German IITs were funded by the German Research Foundation (DFG), the Federal Ministry of Education and Research (BMBF), or by another non-commercial research organization. All other trials were drawn from the German Clinical Trials Register or ClinicalTrials.gov. We investigated, to what extent study characteristics were associated with publication and impact using multivariable logistic regressions. RESULTS: For 80% of the 691 trials, results were published as result articles in a medical journal and/or study registry, 52% were cited by a systematic review, and 26% reached impact in a clinical guideline. Drug trials and larger trials were associated with a higher probability to be published and to have an impact than non-drug trials and smaller trials. Results of IITs were more often published as a journal article while results of ISTs were more often published in study registries. International ISTs less often gained impact by inclusion in systematic reviews or guidelines than IITs. CONCLUSION: An encouraging high proportion of the clinical trials were published, and a considerable proportion gained impact on clinical practice. However, there is still room for improvement. For publishing study results, study registries have become an alternative or complement to journal articles, especially for ISTs. IITs funded by governmental bodies in Germany reached an impact that is comparable to international IITs and ISTs.


Assuntos
Projetos de Pesquisa , Pesquisadores , Alemanha , Humanos , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Sistema de Registros
16.
BMC Med Res Methodol ; 21(1): 164, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376146

RESUMO

BACKGROUND: An essential aspect of preventing further COVID-19 outbreaks and to learn for future pandemics is the evaluation of different political strategies, which aim at reducing transmission of and mortality due to COVID-19. One important aspect in this context is the comparison of attributable mortality. METHODS: We give a comprehensive overview of six epidemiological measures that are used to quantify COVID-19 attributable mortality (p-score, standardized mortality ratio, absolute number of excess deaths, per capita rate, z-score and the population attributable fraction). RESULTS: By defining the six measures based on observed and expected deaths, we explain their relationship. Moreover, three publicly available data examples serve to illustrate the interpretational strengths and weaknesses of the various measures. Finally, we give recommendation which measures are suitable for an evaluation of public health strategies against COVID-19. The R code to reproduce the results is available as online supplementary material. CONCLUSION: The number of excess deaths should be always reported together with the population attributable fraction, the p-score or the standardized mortality ratio instead of a per capita rate. For a complete picture of COVID-19 attributable mortality, quantifying and communicating its relative burden also to a lay audience is of major importance.


Assuntos
COVID-19 , Surtos de Doenças , Humanos , Mortalidade , Pandemias , Saúde Pública , SARS-CoV-2
17.
Biom J ; 63(7): 1493-1506, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33949712

RESUMO

Oral mucositis is an inflammatory adverse event when treating head and neck cancer patients with radiation therapy (RT). The severity of its occurrence is believed to mainly depend on its site and the distribution of a cumulative radiation dose in the mouth area. The motivating study investigating differences in radiosensitivities (mucositis progression) at distinct sites where the severity of mucositis is assessed regularly at eight distinct sites on an ordinal scale results in multivariate longitudinal data and thus poses certain challenges. To deal with the multivariate longitudinal data in this particular setting, we take a time-to-event approach focusing on the first occurrence of severe mucositis at the distinct sites using the fact that the site-specific cumulative radiation dose thought to be the main driver of oral mucositis develops over time. Thereby, we may address multivariate longitudinal processes in a simpler and more compact fashion. In this article, to find out differences in mucositis progression at eight distinct sites we propose a shared frailty model for multivariate parallel processes within individuals. The shared frailty model directly incorporating 'process indicators' as covariates turns out to adequately explain the differences in the parallel processes (here, mucositis progressions at distinct sites) while taking individual effects into account. The parallel result with the one from the previous analysis based on the same data but conducted with an alternative statistical methodology shows adequacy of the proposed approach.


Assuntos
Fragilidade , Neoplasias de Cabeça e Pescoço , Estomatite , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Estomatite/epidemiologia , Estomatite/etiologia
19.
BMC Cancer ; 21(1): 173, 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33596881

RESUMO

BACKGROUND: The standard to ensure utmost cancer treatment is a prerequisite in national cancer plans for comprehensive cancer centers (CCCs) and ensured through multidisciplinary tumor boards (MTBs). Despite these being compulsory for CCCs, various analyses on MTBs have been performed, since MTBs are resource-intensive. Outcome measures in these prior analyses had been survival (OS), MTB-adherence and -satisfaction, inclusion of patients into clinical trials and better cancer care. MAIN BODY: A publication from Freytag et al. performed an analysis in multiple tumor entities and assessed the effect of number of MTBs. By matched-pair analysis, they compared response and OS of patients, whose cases were discussed in MTBs vs. those that were not. The analysis included 454 patients and 66 different tumor types. Only patients with > 3 MTBs showed a significantly better OS than patients with no MTB meeting. Response to treatment, relapse free survival and time to progression were not found to be better, nor was there any difference for a specific tumor entity with vs. without MTB discussions. An in-depth discussion of these results, with respect to the literature (PubMed search: "MTBs AND cancer") and within the author group, including statisticians specialized in data analysis of cancer patients and questions addressed in MTBs, was performed to interpret these findings. We conclude that the results by Freytag et al. are deceiving due to an "immortal time bias" that requires more careful data interpretation. CONCLUSIONS: The result of Freytag et al. of a seemingly positive impact of higher number of MTBs needs to be interpreted cautiously: their presumed better OS in patients with > 3 MTB discussions is misleading, due to an immortal time bias. Here patients need to survive long enough to be discussed more often. Therefore, these results should not lead to the conclusion that more MTBs will "automatically" increase cancer patients' OS, rather than that the insightful discussion, at best in MTBs and with statisticians, will generate meaningful advice, that is important for cancer patients.


Assuntos
Comunicação Interdisciplinar , Neoplasias/terapia , Avaliação de Resultados em Cuidados de Saúde/métodos , Equipe de Assistência ao Paciente/normas , Guias de Prática Clínica como Assunto/normas , Humanos
20.
Vasa ; 50(4): 306-311, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33615871

RESUMO

Background: The extent of arterial disease in patients with erectile dysfunction (ED) non-responsive to intracavernosal injection of Alprostadil is of importance for therapeutic options. However, published evidence, in particular angiographically validated is scarce. Here we investigated arterial lesion patterns in this specific patient cohort by selective angiography. Patients and methods: A cohort of 239 patients received a clinical and duplex-sonographic workup for ED of suspected vascular origin. Duplex ultrasound of the cavernosal arteries was performed after intracavernosal injection of 10 µg Alprostadil. Consequently, standardized workup included grading of the erectile and determination of peak systolic velocity (PSV) and end-diastolic velocity (EDV) in both cavernosal arteries. PSV-values below 30 cm/sec indicated reduced arterial flow, whereas EDV-values above 15 cm/sec indicated a venous leak of the pudendal veins. All patients with suspected arterial ED based on duplex sonography underwent contrast-enhanced computed tomography. Endovascular therapy was carried out in ED patients not responsive or with significant side effects to PDE-5-inhibitors or Alprostadil by selective angiographic depiction of erection-related arteries. Results: 54 patients with a mean age of 61.2 (±9.8) years underwent angioplasty of erectionr elated arteries. Out of these 48/54 (89%) patients presented with an erection considered insufficient for penetration (E0-E3) subsequent to intracavernous application of 10 µg Alprostadil. 14/48 (29%) patients had bilateral arterial obstructions and 34/48 (71%) had unilateral disease. Commonly affected was the internal pudendal artery (n = 31, 65%), followed closely by the common penile artery (n = 30, 64%). The least affected arteries were the dorsal penile (n = 6, 13%), hypogastric (n = 4, 8%), common iliac (n = 4, 8%), cavernosal (n = 4, 8%), and inferior gluteal (n = 1, 2%) arteries. Conclusions: Arterial obstructions amenable to endovascular revascularization are frequent in patients non-responsive to intracavernosal prostaglandin administration. Therapeutic strategies in ED patients non-responsive to conservative measures should therefore consider endovascular treatment opportunities.


Assuntos
Disfunção Erétil , Idoso , Alprostadil , Humanos , Masculino , Pessoa de Meia-Idade , Ereção Peniana , Pênis , Prostaglandinas
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