Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 18 de 18
Filtrar
1.
N Engl J Med ; 2021 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-34459570

RESUMO

BACKGROUND: Myocardial infarction is a frequent cause of out-of-hospital cardiac arrest. However, the benefits of early coronary angiography and revascularization in resuscitated patients without electrocardiographic evidence of ST-segment elevation are unclear. METHODS: In this multicenter trial, we randomly assigned 554 patients with successfully resuscitated out-of-hospital cardiac arrest of possible coronary origin to undergo either immediate coronary angiography (immediate-angiography group) or initial intensive care assessment with delayed or selective angiography (delayed-angiography group). All the patients had no evidence of ST-segment elevation on postresuscitation electrocardiography. The primary end point was death from any cause at 30 days. Secondary end points included a composite of death from any cause or severe neurologic deficit at 30 days. RESULTS: A total of 530 of 554 patients (95.7%) were included in the primary analysis. At 30 days, 143 of 265 patients (54.0%) in the immediate-angiography group and 122 of 265 patients (46.0%) in the delayed-angiography group had died (hazard ratio, 1.28; 95% confidence interval [CI], 1.00 to 1.63; P = 0.06). The composite of death or severe neurologic deficit occurred more frequently in the immediate-angiography group (in 164 of 255 patients [64.3%]) than in the delayed-angiography group (in 138 of 248 patients [55.6%]), for a relative risk of 1.16 (95% CI, 1.00 to 1.34). Values for peak troponin release and for the incidence of moderate or severe bleeding, stroke, and renal-replacement therapy were similar in the two groups. CONCLUSIONS: Among patients with resuscitated out-of-hospital cardiac arrest without ST-segment elevation, a strategy of performing immediate angiography provided no benefit over a delayed or selective strategy with respect to the 30-day risk of death from any cause. (Funded by the German Center for Cardiovascular Research; TOMAHAWK ClinicalTrials.gov number, NCT02750462.).

2.
BMC Cancer ; 21(1): 386, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33836671

RESUMO

BACKGROUND: Gliomas are often associated with symptoms including seizures. Most patients with high-grade gliomas are treated with radiotherapy or radio-chemotherapy. Since irradiation causes inflammation, it may initially aggravate symptoms. Studies focusing on seizure activity during radiotherapy for gliomas are not available. Such knowledge may improve patient monitoring and anti-epileptic treatment. This study evaluates seizure activity during radiotherapy for high-grade gliomas. METHODS: The primary objective this prospective interventional study is the evaluation of seizure activity during a course of radiotherapy for high-grade gliomas. Progression of seizure activity is defined as increased frequency of seizures by > 50%, increased severity of seizures, or initiation/increase by ≥25% of anti-epileptic medication. Seizure frequency up to 6 weeks following radiotherapy and electroencephalography activity typical for epilepsy will also be evaluated. Patients keep a seizure diary during and up to 6 weeks following radiotherapy. Every day, they will document number (and type) of seizures and anti-epileptic medication. Once a week, the findings of the diary are checked and discussed with a neurologist to initiate or adjust anti-epileptic medication, if necessary. Patients complete a questionnaire regarding their satisfaction with the seizure diary. If the dissatisfaction rate is > 40%, the seizure diary will be considered not suitable for the investigated indication. Thirty-five patients (32 patients plus drop-outs) should be enrolled. With this sample size, a one-sample binomial test with a one-sided significance level of 2.5% has a power of 80% to yield statistical significance, if the rate of patients with progression of seizure activity is 30% (rate under the alternative hypothesis), assuming a 'natural' background progression-rate of 10% without radiotherapy (null hypothesis). DISCUSSION: If an increase in seizure activity during a course of radiotherapy for high-grade glioma occurs, the findings of this study may pave the way for a larger prospective trial and will likely lead to closer patient monitoring and better anti-epileptic treatment. TRIAL REGISTRATION: clinicaltrials.gov ( NCT04552756 ); registered on 16th of September, 2020.


Assuntos
Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/patologia , Irradiação Craniana/efeitos adversos , Glioma/complicações , Glioma/patologia , Convulsões/diagnóstico , Convulsões/etiologia , Anticonvulsivantes/uso terapêutico , Neoplasias Encefálicas/radioterapia , Quimiorradioterapia , Irradiação Craniana/métodos , Gerenciamento Clínico , Suscetibilidade a Doenças , Eletroencefalografia , Feminino , Glioma/radioterapia , Humanos , Masculino , Gradação de Tumores , Estadiamento de Neoplasias , Convulsões/terapia , Avaliação de Sintomas , Resultado do Tratamento
3.
Clin Transl Radiat Oncol ; 28: 90-96, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33912695

RESUMO

Background: Several recent randomized therapeutic exploratory trials demonstrated improvement of progression-free survival and in some even overall survival using stereotactic body radiotherapy in patients with oligometastatic disease. However, only very few patients enrolled in these trials had breast cancer, and results from confirmatory trials are lacking. Methods/design: The OLIGOMA-trial is a randomized controlled multi-national multi-center therapeutic confirmatory trial studying the role of local ablative radiotherapy as an additive treatment in patients with oligometastatic breast cancer receiving standard systemic therapy. Patients will be randomized 1:1 to standard systemic therapy according to national guidelines with or without radiotherapy to all metastatic sites. Randomization will be stratified according to type and line of systemic therapy, which has to be determined by a multidisciplinary tumor board before enrollment. Patients with up to five metastatic lesions are eligible, including patients with up to three brain metastases (only in case of extracranial disease) and with locoregional recurrence (only in case of additional metastatic lesions). In the standard arm, palliative radiotherapy to symptomatic metastases is permitted if at least one lesion remains untreated. The co-primary endpoints are progression-free survival and quality of life. The primary hypothesis is that progression-free survival in the experimental arm will be superior to the standard arm while simultaneously demonstrating non-inferiority of quality of life at 12 weeks after randomization. Secondary endpoints are feasibility, overall survival, toxicity, quality of life and patient satisfaction. A translational sub-study with collection of ctDNA will be conducted. Discussion: The OLIGOMA-trial will provide high level evidence on the use of and benefit from local ablative radiotherapy for patients with oligometastatic breast cancer. Trial registration: The OLIGOMA-trial is registered at clinicialtrials.gov under the identification NCT04495309. The related information was first posted on July 31st 2020.

4.
Strahlenther Onkol ; 197(9): 802-811, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33320286

RESUMO

PURPOSE: Hypofractionated radiotherapy is the standard of care for adjuvant whole breast radiotherapy (RT). However, adoption has been slow. The indication for regional nodal irradiation has been expanded to include patients with 0-3 involved lymph nodes. We investigated the impact of the publication of the updated German S3 guidelines in 2017 on adoption of hypofractionation and enrollment of patients with lymph node involvement within a randomized controlled phase III trial. METHODS: In the experimental arm of the HYPOSIB trial (NCT02474641), hypofractionated RT with simultaneous integrated boost (SIB) was used. In the standard arm, RT could be given as hypofractionated RT with sequential boost (HFseq), normofractionated RT with sequential boost (NFseq), or normofractionated RT with SIB (NFSIB). The cutoff date for the updated German S3 guidelines was December 17, 2017. Temporal trends were analyzed by generalized linear regression models. Multiple logistic regression models were used to investigate the influence of time (prior to/after guideline) and setting (university hospital/other institutions) on the fractionation patterns. RESULTS: Enrollment of patients with involved lymph nodes was low throughout the trial. Adoption of HFseq increased over time and when using the guideline publication date as cutoff. Results of the multiple logistic regressions showed an interaction between time and setting. Furthermore, the use of HFseq was significantly more common in university hospitals. CONCLUSION: The use of HFseq in the standard arm increased over the course of the HYPOSIB trial and after publication of the S3 guideline update. This was primarily driven by patients treated in university hospitals. Enrolment of patients with lymph node involvement was low throughout the trial.

5.
BMC Cancer ; 20(1): 785, 2020 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-32819311

RESUMO

BACKGROUND: Pneumonitis is a possible side effect of radiotherapy for lung cancer. Since it can occur up to several months following treatment, symptoms may not be associated with previous radiotherapy, and pneumonitis can become severe before diagnosed. This study aimed to develop a symptom-based scoring system to contribute to earlier detection of radiation pneumonitis requiring medical intervention (grade ≥ 2). METHODS: Patients irradiated for lung cancer complete a paper-based questionnaire (symptom-based score) during and up to 24 weeks following radiotherapy. Patients rate symptoms potentially associated with pneumonitis, and scoring points are assigned to severity of these symptoms. Sum scores are used to identify radiation pneumonitis. If radiation pneumonitis is suspected, patients undergo standard diagnostic procedures. If grade ≥ 2 pneumonitis is confirmed, medical intervention is indicated. The discriminative power of the score will be assessed by calculating the area under the receiver operating characteristic curve (AUC). If statistical significance of the AUC is reached, the optimal sum score to predict radiation pneumonitis will be established, which is defined as a cut-off value with sensitivity ≥90% and specificity ≥80%. Assuming a ratio between patients without and with pneumonitis of 3.63, a sample size of 93 patients is required in the full analysis set to yield statistical significance at the level of 5% with a power of 90% if the AUC under the alternative hypothesis is at least 0.9. Considering potential drop-outs, 98 patients should be recruited. If > 20% of patients are not satisfied with the score, modification is required. If the dissatisfaction rate is > 40%, the score is considered not useful. In 10 patients, functionality of a mobile application will be tested in addition to the paper-based questionnaire. DISCUSSION: If an optimal cut-off score resulting in sufficiently high sensitivity and specificity can be identified and the development of a symptom-based scoring system is successful, this tool will contribute to better identification of patients experiencing pneumonitis after radiotherapy for lung cancer. TRIAL REGISTRATION: Clinicaltrials.gov ( NCT04335409 ); registered on 2nd of April, 2020.


Assuntos
Neoplasias Pulmonares/radioterapia , Pneumonite por Radiação/diagnóstico , Índice de Gravidade de Doença , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Aplicativos Móveis , Curva ROC , Pneumonite por Radiação/etiologia , Adulto Jovem
6.
Trials ; 21(1): 424, 2020 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-32450921

RESUMO

BACKGROUND: Radiotherapy of head-and-neck cancer can be associated with significant toxicities including dermatitis and oral mucositis. Severe toxicities may require interruptions of the radiation treatment associated with impairment of the patients' prognoses. This study will investigate whether the addition of a reminder app to standard care can reduce dermatitis and oral mucositis rates during radiotherapy in these patients. METHODS: This randomized trial compares standard care supported by a reminder app (Arm A) to standard care alone (Arm B) with respect to grade ≥ 2 radiation dermatitis and oral mucositis at 60 Gy of radiotherapy, the minimum planned dose for patients receiving definitive or adjuvant radiotherapy for locally advanced head- and-neck cancer. Moreover, radiation-induced dermatitis and oral mucositis grade ≥ 3 at 60 Gy and both grade ≥ 2 and grade ≥ 3 at the end of radiation treatment (EOT) will be evaluated, as well as quality of life and pain. According to sample size calculations, 80 patients are required per arm within the full analysis set. Taking into account that 5% of patients will not qualify for full analysis set, 168 patients should be randomized. The impact of the reminder app will be considered clinically relevant, if the rates of grade ≥ 2 radiation dermatitis (primary endpoint) and oral mucositis (secondary endpoint) can be reduced by 20%. DISCUSSION: If the addition of a reminder app to standard care will lead to a significant reduction of radiation dermatitis and oral mucositis, it could become a helpful tool for patients with head-and-neck cancer during radiotherapy. TRIAL REGISTRATION: clinicaltrials.gov (NCT04110977). Registered on September 27, 2019. First patient is planned to be included in December 2019.


Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Aplicativos Móveis , Radiodermatite/prevenção & controle , Higiene da Pele/métodos , Estomatite/prevenção & controle , Humanos , Qualidade de Vida , Radiodermatite/etiologia , Radioterapia/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estomatite/etiologia
7.
Clin Res Cardiol ; 109(11): 1319-1332, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32306083

RESUMO

BACKGROUND: Single-session high-dose stereotactic radiotherapy (radiosurgery) is a new treatment option for otherwise untreatable patients suffering from refractory ventricular tachycardia (VT). In the initial single-center case studies and feasibility trials, cardiac radiosurgery has led to significant reductions of VT burden with limited toxicities. However, the full safety profile remains largely unknown. METHODS/DESIGN: In this multi-center, multi-platform clinical feasibility trial which we plan is to assess the initial safety profile of radiosurgery for ventricular tachycardia (RAVENTA). High-precision image-guided single-session radiosurgery with 25 Gy will be delivered to the VT substrate determined by high-definition endocardial electrophysiological mapping. The primary endpoint is safety in terms of successful dose delivery without severe treatment-related side effects in the first 30 days after radiosurgery. Secondary endpoints are the assessment of VT burden, reduction of implantable cardioverter defibrillator (ICD) interventions [shock, anti-tachycardia pacing (ATP)], mid-term side effects and quality-of-life (QoL) in the first year after radiosurgery. The planned sample size is 20 patients with the goal of demonstrating safety and feasibility of cardiac radiosurgery in ≥ 70% of the patients. Quality assurance is provided by initial contouring and planning benchmark studies, joint multi-center treatment decisions, sequential patient safety evaluations, interim analyses, independent monitoring, and a dedicated data and safety monitoring board. DISCUSSION: RAVENTA will be the first study to provide the initial robust multi-center multi-platform prospective data on the therapeutic value of cardiac radiosurgery for ventricular tachycardia. TRIAL REGISTRATION NUMBER: NCT03867747 (clinicaltrials.gov). Registered March 8, 2019. The study was initiated on November 18th, 2019, and is currently recruiting patients.


Assuntos
Ablação por Cateter/métodos , Qualidade de Vida , Radiocirurgia/métodos , Taquicardia Ventricular/terapia , Estudos de Viabilidade , Feminino , Alemanha , Humanos , Masculino , Estudos Prospectivos , Taquicardia Ventricular/fisiopatologia , Resultado do Tratamento
8.
Int J Radiat Oncol Biol Phys ; 106(4): 780-789, 2020 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-31812719

RESUMO

OBJECTIVE: To investigate precision radiation therapy for metastatic spinal cord compression and compare it to conventional radiation therapy. METHODS AND MATERIALS: In a multicenter phase 2 study, 40 patients received 5 Gy × 5 fractions of precision radiation therapy (38 volume modulated arc therapy, 2 intensity modulated radiation therapy) for metastatic spinal cord compression and were evaluated for local progression-free survival (LPFS), motor function, ambulatory status, sensory function, sphincter dysfunction, pain, distress, overall survival (OS), and toxicity. Maximum spinal cord dose was 101.5% (myelopathy risk, <0.03%) of the prescription dose. Patients were compared with a historical control group conventionally irradiated with 4 Gy × 5 fractions (propensity score analysis). The equivalent dose in 2 Gy-fractions of 5 Gy × 5 fractions is similar to 3 Gy × 10 fractions, which results in better LPFS than 4 Gy × 5 fractions. It was assumed that 5 Gy × 5 fractions is also superior to 4 Gy × 5 fractions for LPFS. (ClinicalTrials.gov-identifier: NCT03070431) RESULTS: Six-month rates of LPFS and OS were 95.0% and 42.6%, respectively. Improvement of motor function occurred in 24 patients (60%). Thirty-three patients (82.5%) were ambulatory after radiation therapy. Eight of 16 patients (50.0%) with sensory deficits improved. Pain and distress relief were reported by 61.9% and 54.2% of patients 1 month after radiation therapy. Grade 3 toxicities occurred in 1 patient and grade 2 toxicities in another 3 patients. Of the control group, 664 patients qualified for the propensity score analysis; 5 Gy × 5 fractions was significantly superior to 4 Gy × 5 fractions with regard to LPFS (P = .026) but not motor function (P = .51) or OS (P = .82). CONCLUSIONS: Precision radiation therapy with 5 Gy × 5 fractions was well tolerated and effective and appeared superior to 4 Gy × 5 fractions in terms of LPFS. The retrospective nature of the historic control group, which might have led to a hidden selection bias, needs to be considered when interpreting the results.


Assuntos
Medicina de Precisão , Compressão da Medula Espinal/radioterapia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Resultado do Tratamento
9.
BMC Cancer ; 19(1): 1163, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31783816

RESUMO

BACKGROUND: Patients with metastatic spinal cord compression (MSCC) and favorable survival prognoses can benefit from radiation doses greater than 30Gy in 10 fractions in terms of improved local progression-free survival (LPFS) and overall survival (OS). METHODS/DESIGN: This prospective study mainly investigates LPFS after precision radiotherapy (volumetric modulated arc therapy or stereotactic body radiotherapy) with 18 × 2.33Gy in 3.5 weeks. LPFS is defined as freedom from progression of motor deficits during radiotherapy and an in-field recurrence of MSCC following radiotherapy. The maximum relative dose allowed to the spinal cord is 101.5% of the prescribed dose, resulting in an equivalent dose in 2Gy-fractions (EQD2) for radiation myelopathy is 45.5Gy, which is below the tolerance dose of 50Gy according to the Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC). The EQD2 of this regimen for tumor cell kill is 43.1Gy, which is 33% higher than for 30Gy in 10 fractions (EQD2 = 32.5Gy). Primary endpoint is LPFS at 12 months after radiotherapy. Secondary endpoints include the effect of 18 × 2.33Gy on motor function, ambulatory status, sensory function, sphincter dysfunction, LPFS at other follow-up times, overall survival, pain relief, relief of distress and toxicity. Follow-up visits for all endpoints will be performed directly and at 1, 3, 6, 9 and 12 months after radiotherapy. A total of 65 patients are required for the prospective part of the study. These patients will be compared to a historical control group of at least 235 patients receiving conventional radiotherapy with 10x3Gy in 2 weeks. DISCUSSION: If precision radiotherapy with 18 × 2.33Gy results in significantly better LPFS than 10x3Gy of conventional radiotherapy, this regimen should be strongly considered for patients with MSCC and favorable survival prognoses. TRIAL REGISTRATION: Clinicaltrials.gov NCT04043156. Registered 30-07-2019.


Assuntos
Fracionamento da Dose de Radiação , Compressão da Medula Espinal/radioterapia , Neoplasias da Coluna Vertebral/radioterapia , Neoplasias da Coluna Vertebral/secundário , Ensaios Clínicos como Assunto , Relação Dose-Resposta à Radiação , Humanos , Lesões por Radiação , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Compressão da Medula Espinal/patologia , Análise de Sobrevida
10.
Radiother Oncol ; 139: 79-82, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31431372

RESUMO

Mepitel® Film (MEP) and standard care (STD) were compared for radiation dermatitis in SCCHN patients. This trial was stopped prematurely since13/28 patients did not tolerate MEP. Grade ≥2 dermatitis: 34.8% (MEP) vs. 35.7% (STD) at 50 Gy, 65.2% vs. 59.3% at 60 Gy. MEP was unsatisfactorily tolerated and appeared not superior (NCT03047174).


Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Radiodermatite/prevenção & controle , Silicones/uso terapêutico , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Silicones/efeitos adversos
12.
Am Heart J ; 209: 20-28, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30639610

RESUMO

Patients experiencing out-of-hospital cardiac arrest (OHCA) without ST-segment elevation are a heterogenic group with a variety of underlying causes. Up to one-third of patients display a significant coronary lesion compatible with myocardial infarction as OHCA trigger. There are no randomized data on patient selection and timing of invasive coronary angiography after admission. METHODS AND RESULTS: The TOMAHAWK trial randomly assigns 558 patients with return of spontaneous circulation after OHCA with no obvious extracardiac origin of cardiac arrest and no ST-segment elevation/left bundle-branch block on postresuscitation electrocardiogram to either immediate coronary angiography or initial intensive care assessment with delayed/selective angiography in a 1:1 ratio. The primary end point is 30-day all-cause mortality. Secondary analyses will be performed with respect to initial rhythm, electrocardiographic patterns, myocardial infarction as underlying cause, neurological outcome, as well as clinical and laboratory markers. Clinical follow-up will be performed at 6 and 12 months. Safety end points include bleeding and stroke. CONCLUSION: The TOMAHAWK trial will address the unresolved issue of timing and general indication of angiography after OHCA without ST-segment elevation.


Assuntos
Reanimação Cardiopulmonar/métodos , Angiografia Coronária/métodos , Eletrocardiografia , Parada Cardíaca Extra-Hospitalar/diagnóstico , Tempo para o Tratamento , Triagem/métodos , Causas de Morte/tendências , Europa (Continente)/epidemiologia , Seguimentos , Humanos , Parada Cardíaca Extra-Hospitalar/mortalidade , Parada Cardíaca Extra-Hospitalar/terapia , Estudos Prospectivos , Taxa de Sobrevida/tendências , Fatores de Tempo
13.
Dtsch Med Wochenschr ; 144(2): e12-e20, 2019 01.
Artigo em Alemão | MEDLINE | ID: mdl-30428493

RESUMO

BACKGROUND: The efficacy of the German disease management programs (DMP) asthma and chronic obstructive pulmonary disease (COPD) cannot be shown with the legally bound documentations. Studies with control groups are rare. Aim of this work was to investigate in a cross-sectional study whether the disease control differs in participants (DMP+) and non-participants (DMP-) of the DMPs asthma and COPD. METHODS: The study was a prospective multicenter cross-sectional study. Primary endpoints were the Asthma Control Test™ (ACT) in the asthma part of the study and the COPD Assessment Test™ (CAT) for the COPD part. RESULTS: A total of 1038 asthma patients and 846 COPD patients were included, of whom about 70 % participated in the corresponding DMP. The ACT total score was higher in asthma DMP+ patients than in DMP- patients (mean difference 0.86; 95 %CI:0.29 - 1.43;p = 0.003), but not clinically relevant. For COPD there was no clinically relevant difference in COPD disease impact (0.52; 95 %CI:-0.71 - 1.75;p = 0.405). Although DMP patients had to be enrolled in the respective DMP for at least one year, only 60 % of these patients had participated in a structured education. We did not observe a difference in disease control in DMP patients who respectively participated and did not participate in a structured education. DISCUSSION: There was no clinically relevant difference in disease control between DMP+ and DMP- patients. The efficacy of DMPs has been demonstrated internationally in randomized controlled trials. Randomized controlled trials should be conducted in Germany for demonstrating efficacy of DMPs asthma and COPD. REGISTRATION: drks.de, DRKS00007664, Registration date: Jan 15, 2015.


Assuntos
Asma , Doença Pulmonar Obstrutiva Crônica , Asma/diagnóstico , Asma/terapia , Estudos Transversais , Humanos , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/terapia
14.
Neurol Res Pract ; 1: 31, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-33324897

RESUMO

Background: This study focuses on genetically stratified subgroups of Parkinson's disease patients (PD) with an enrichment of risk variants in mitochondrial genes,who might benefit from treatment with the "mitochondrial enhancer" coenzyme Q10 (156 mg coenzyme Q10/d [QuinoMit Q10® Fluid] over six months). The study will be performed in a double-blind, randomized, and placebo-controlled parallel group manner. Methods: PD patients will be specifically identified and assigned to treatment groups stratified by their genetic "mitochondrial risk burden" and consequently expected mitochondrial dysfunction and treatment response to coenzyme Q10 (homozygous or compound heterozygous Parkin/PINK1 mutation carriers [P++], heterozygous Parkin/PINK1 mutation carriers [P+], "omics" positive [omics+], and "omics" negative PD patients [omics-]). The primary endpoint is the change in motor symptoms over six months (as measured by the change in the motor subscore of the MDS-UPDRS). Secondary clinical endpoints include motor fluctuations, non-motor symptoms, results of magnetic resonance imaging of brain energy metabolism (31P-magnetic resonance spectroscopy imaging), and changes in structural and functional brain anatomy (MRI). Perspective: This study may be a first step towards a successful prediction of treatment response based on the genetic status of PD patients and translate progress in molecular genetics into personalized patient care. Further, magnetic resonance spectroscopy imaging may help quantify increased energy supply objectively and within a brief time after the start of treatment. Therefore, the potential of MRSI also for other studies addressing brain energy metabolism may will be assessed. Trial registration: This study was registered at the German Clinical Trial Registry (DRKS, DRKS00015880) on November 15th, 2018.

15.
BMC Cancer ; 18(1): 197, 2018 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-29454311

RESUMO

BACKGROUND: The aim of the present trial is to investigate a new option of skin protection in order to reduce the rate of grade ≥ 2 skin toxicity in patients receiving radiotherapy alone or radiochemotherapy for locally advanced squamous cell carcinoma of the head-and-neck (SCCHN). METHODS / DESIGN: This is a randomized, active-controlled, parallel-group multi-center trial that compares the following treatments of radiation dermatitis in patients with head-and-neck cancer: Mepitel® Film (Arm A) vs. standard care (Arm B). The primary aim of this trial is to investigate the rate of patients experiencing grade ≥ 2 radiation dermatitis (according to Common Toxicity Criteria for Adverse Events (CTCAE) Version 4.03) until 50 Gy of radiotherapy. Evaluation until 50 Gy of radiotherapy has been selected as the primary endpoint, since up to 50 Gy, the irradiated volume includes the primary tumor and the bilateral cervical and supraclavicular lymph nodes, and, therefore, is similar in all patients. After 50 Gy, irradiated volumes are very individual, depending on location and size of the primary tumor, involvement of lymph nodes, and the treatment approach (definitive vs. adjuvant). In addition, the following endpoints will be evaluated: Time to grade 2 radiation dermatitis until 50 Gy of radiotherapy, rate of patients experiencing grade ≥ 2 radiation dermatitis during radio(chemo)therapy, rate of patients experiencing grade ≥ 3 skin toxicity during radio(chemo)therapy, adverse events, quality of life, and dermatitis-related pain. Administration of Mepitel® Film will be considered to be clinically relevant, if the rate of grade ≥ 2 radiation dermatitis can be reduced from 85% to 65%. DISCUSSION: If administration of Mepitel® Film instead of standard care will be able to significantly reduce the rate of grade ≥ 2 radiation dermatitis, it could become the new standard of skin care in patients irradiated for SCCHN. TRIAL REGISTRATION: clinicaltrials.gov NCT03047174 . Registered on 26th of January, 2017. First patient included on 9th of May, 2017.


Assuntos
Neoplasias de Cabeça e Pescoço/complicações , Radiodermatite/etiologia , Radiodermatite/terapia , Radioterapia/efeitos adversos , Quimiorradioterapia/efeitos adversos , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Masculino , Metástase Neoplásica , Estadiamento de Neoplasias , Radiodermatite/diagnóstico , Radioterapia/métodos , Dosagem Radioterapêutica , Índice de Gravidade de Doença
16.
BMC Cancer ; 17(1): 818, 2017 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-29202720

RESUMO

BACKGROUND: For metastatic spinal cord compression (MSCC), conventional radiotherapy with 10 × 3 Gy in 2 weeks results in better local progression-free survival (LPFS) than 5 × 4 Gy in 1 week. Since patients with MSCC are often significantly impaired, an overall treatment time of 1 week would be preferable if resulting in similar outcomes as longer programs. This may be achieved with 5 × 5 Gy in 1 week, since the biologically effective dose is similar to 10 × 3 Gy. It can be expected that 5 × 5 Gy (like 10 × 3) Gy results in better LPFS than 5 × 4 Gy in 1 week. METHODS/DESIGN: This phase 2 study investigates LPFS after high-precision RT with 5 × 5 Gy in 1 week. LPFS is defined as freedom from both progression of motor deficits during RT and new or progressive motor deficits dur to an in-field recurrence of MSCC following RT. Considering the tolerance dose of the spinal cord, 5 × 5 Gy can be safely administered with high-precision radiotherapy such as volumetric modulated arc therapy (VMAT) or stereotactic body radiotherapy (SBRT). Maximum dose to the spinal cord should not exceed 101.5% of the prescribed dose to keep the risk of radiation myelopathy below 0.03%. Primary endpoint is LPFS at 6 months following radiotherapy; secondary endpoints include motor function/ability to walk, sensory function, sphincter dysfunction, LPFS directly and 1 and 3 months following radiotherapy, overall survival, pain relief, quality of life and toxicity. Follow-up visits will be performed directly and at 1, 3 and 6 months following radiotherapy. After completion of this phase 2 study, patients will be compared to a historical control group receiving conventional radiotherapy with 5 × 4 Gy in 1 week. Forty-four patients will be included assuming 5 × 5 Gy will provide the same benefit in LPFS when compared to 5 × 4 Gy as reported for 10 × 3 Gy. DISCUSSION: If superiority regarding LPFS is shown for high-precision radiotherapy with 5 × 5 Gy when compared to conventional radiotherapy with 5 × 4 Gy, patients with MSCC would benefit from 5 × 5 Gy, since high LPFS rates could be achieved with 1 week of radiotherapy instead of 2 weeks (10 × 3 Gy). TRIAL REGISTRATION: clinicaltrials.gov NCT03070431 . Registered 27 February 2017.


Assuntos
Transtornos Motores/terapia , Compressão da Medula Espinal/radioterapia , Neoplasias da Coluna Vertebral/radioterapia , Ensaios Clínicos Fase II como Assunto , Intervalo Livre de Doença , Fracionamento da Dose de Radiação , Humanos , Transtornos Motores/etiologia , Estudos Multicêntricos como Assunto , Planejamento da Radioterapia Assistida por Computador , Compressão da Medula Espinal/complicações , Neoplasias da Coluna Vertebral/secundário
17.
Exp Gerontol ; 47(7): 527-33, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22580060

RESUMO

BACKGROUND AND OBJECTIVE: The cortisol awakening response (CAR) is a useful endocrine marker for the hypothalamic-pituitary-adrenal axis activity. Recent studies suggest that the cortisol level influences the expression of the hPER1 clock gene which is involved in the generation of biological rhythms. This study aimed to analyze the relationship between CAR and hPER1 gene expression with respect to human aging. SUBJECTS AND METHODS: Salivary cortisol levels were determined in 20 older women (mean age ± SD, 67.9 ± 5.12 yrs) and 30 young women (24.4 ± 2.13 yrs) at awakening (T0) and at 15 min, 30 min, 45 min, and 60 min after awakening (T15, T30, T45, T60) by enzyme linked immunosorbent assay. CAR was calculated as difference of the cortisol levels at T0 and T30. The expression of the hPER1 gene at 0800 h was determined from oral mucosa cells by relative quantification using h36B4 as house-keeping gene. Additional variables, which may affect the CAR, were assessed by questionnaire. Relationships between CAR and other variables were analyzed by correlation and regression analyses. RESULTS: Older women showed significantly lower mean cortisol levels than young women at all five time points (P < 0.05 to P < 0.01). The cortisol levels at T30, T45, and T60 correlated positively and significantly with hPER1 gene expression in older women (each, P < 0.01), but not in young women. In both older and young women, the CAR correlated positively with the hPER1 gene expression. This relationship was very strong in older women (r = -0.90, P<0.001) and non-significant in young women (r = 0.33, P = 0.390). Regression analysis showed that hPER1 gene expression was the only significant predictor of CAR (r² = 0.798, SEM = 0.07, P < 0.001) in older women. CONCLUSIONS: The present study documents the influence of cortisol secretion on hPER1 gene expression in older women. The morning cortisol increase as indicated by CAR correlated positively and significantly with hPER1 gene expression in older women suggesting that hPER1 expression increases in response to the morning cortisol increase in older women. The higher hPER1 response to cortisol increase in older women could be due to the finding that the hPER1 response to cortisol increase seems to be sensitive only at low cortisol levels, but not at higher cortisol levels. This would explain why the older women with low cortisol levels showed an increase of hPER1 expression with increasing cortisol level, whereas young women with higher cortisol levels did not.


Assuntos
Envelhecimento/metabolismo , Ritmo Circadiano/fisiologia , Hidrocortisona/metabolismo , Proteínas Circadianas Period/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Feminino , Regulação da Expressão Gênica/fisiologia , Humanos , Mucosa Bucal/metabolismo , Proteínas Circadianas Period/genética , Saliva/metabolismo , Sono/fisiologia , Adulto Jovem
18.
Chronobiol Int ; 28(8): 681-9, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21929299

RESUMO

Melatonin concentration and core body temperature (CBT) follow endogenous circadian biological rhythms. In the evening, melatonin level increases and CBT decreases. These changes are involved in the regulation of the sleep-wake cycle. Therefore, the authors hypothesized that age-related changes in these rhythms affect sleep quality in older people. In a cross-sectional study design, 11 older poor-sleeping women (aged 62-72 yrs) and 9 older good-sleeping women (60-82 yrs) were compared with 10 younger good-sleeping women (23-28 yrs). The older groups were matched by age and body mass index. Sleep quality was assessed by the Pittsburgh Sleep Quality Index questionnaire. As an indicator of CBT, oral temperature was measured at 1-h intervals from 17:00 to 24:00 h. At the same time points, saliva samples were collected for determining melatonin levels by enzyme-linked immunosorbent assay (ELISA). The dim light melatonin onset (DLMO), characterizing the onset of melatonin production, was calculated. Evening changes in melatonin and CBT levels were tested by the Friedman test. Group comparisons were performed with independent samples tests. Predictors of sleep-onset latency (SOL) were assessed by regression analysis. Results show that the mean CBT decreased in the evening from 17:00 to 24:00 h in both young women (from 36.57°C to 36.25°C, p < .001) and older women (from 36.58°C to 35.88°C, p < .001), being lowest in the older poor sleepers (p < .05). During the same time period, mean melatonin levels increased in young women (from 16.2 to 54.1 pg/mL, p < .001) and older women (from 10.0 to 23.5 pg/mL, p < .001), being lowest among the older poor sleepers (from 20:00 to 24:00 h, p < .05 vs. young women). Older poor sleepers also showed a smaller increase in melatonin level from 17:00 to 24:00 h than older good sleepers (mean ± SD: 7.0 ± 9.63 pg/mL vs. 15.6 ± 24.1 pg/mL, p = .013). Accordingly, the DLMO occurred at similar times in young (20:10 h) and older (19:57 h) good-sleeping women, but was delayed ∼50 min in older poor-sleeping women (20:47 h). Older poor sleepers showed a shorter phase angle between DLMO and sleep onset, but a longer phase angle between CBT peak and sleep onset than young good sleepers, whereas older good sleepers had intermediate phase angles (insignificant). Regression analysis showed that the DLMO was a significant predictor of SOL in the older women (R(2) = 0.64, p < .001), but not in the younger women. This indicates that melatonin production started later in those older women who needed more time to fall asleep. In conclusion, changes in melatonin level and CBT were intact in older poor sleepers in that evening melatonin increased and CBT decreased. However, poor sleepers showed a weaker evening increase in melatonin level, and their DLMO was delayed compared with good sleepers, suggesting that it is not primarily the absolute level of endogenous melatonin, but rather the timing of the circadian rhythm in evening melatonin secretion that might be related to disturbances in the sleep-wake cycle in older people.


Assuntos
Temperatura Corporal/fisiologia , Melatonina/biossíntese , Transtornos do Sono-Vigília/metabolismo , Sono/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Ritmo Circadiano , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Vigília
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...