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1.
Sci Rep ; 14(1): 310, 2024 01 03.
Artículo en Inglés | MEDLINE | ID: mdl-38172217

RESUMEN

The benefits of a telemedical support system for prehospital emergency medical services include high-level emergency medical support at the push of a button: delegation of drug administration, diagnostic assistance, initiation of therapeutic measures, or choice of hospital destination. At various European EMS sites telemedical routine systems are shortly before implementation. The aim of this study was to investigate the long-term effects of implementing a tele-EMS system on the structural and procedural quality indicators and therefore performance of an entire EMS system. This retrospective study included all EMS missions in Aachen city between 2015 and 2021. Regarding structural indicators of the EMS system, we investigated the overall number of emergency missions with tele-EMS and onsite EMS physicians. Furthermore, we analyzed the distribution of tracer diagnosis and process quality with respect to the time spans on the scene, time until teleconsultation, duration of teleconsultation, prehospital engagement time, and number of simultaneous teleconsultations. During the 7-year study period, 229,384 EMS missions were completed. From 2015 to 2021, the total number of EMS missions increased by 8.5%. A tele-EMS physician was consulted on 23,172 (10.1%) missions. The proportion of telemedicine missions increased from 8.6% in 2015 to 12.9% in 2021. Teleconsultations for missions with tracer diagnoses decreased during from 43.7% to 30.7%, and the proportion of non-tracer diagnoses increased from 56.3% to 69.3%. The call duration for teleconsultation decreased from 12.07 min in 2015 to 9.42 min in 2021. For every fourth mission, one or more simultaneous teleconsultations were conducted by the tele-EMS physician on duty. The implementation and routine use of a tele-EMS system increased the availability of onsite EMS physicians and enabled immediate onsite support for paramedics. Parallel teleconsultations, reduction in call duration, and increase in ambulatory onsite treatments over the years demonstrate the increasing experience of paramedics and tele-EMS physicians with the system in place. A prehospital tele-EMS system is important for mitigating the current challenges in the prehospital emergency care sector.


Asunto(s)
Servicios Médicos de Urgencia , Consulta Remota , Telemedicina , Indicadores de Calidad de la Atención de Salud , Estudios Retrospectivos , Telemedicina/métodos , Servicios Médicos de Urgencia/métodos , Consulta Remota/métodos
2.
Int J Mol Sci ; 24(13)2023 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-37445740

RESUMEN

Whooping cough is a severe childhood disease, caused by the bacterium Bordetella pertussis, which releases pertussis toxin (PT) as a major virulence factor. Previously, we identified the human antimicrobial peptides α-defensin-1 and -5 as inhibitors of PT and demonstrated their capacity to inhibit the activity of the PT enzyme subunit PTS1. Here, the underlying mechanism of toxin inhibition was investigated in more detail, which is essential for developing the therapeutic potential of these peptides. Flow cytometry and immunocytochemistry revealed that α-defensin-5 strongly reduced PT binding to, and uptake into cells, whereas α-defensin-1 caused only a mild reduction. Conversely, α-defensin-1, but not α-defensin-5 was taken up into different cell lines and interacted with PTS1 inside cells, based on proximity ligation assay. In-silico modeling revealed specific interaction interfaces for α-defensin-1 with PTS1 and vice versa, unlike α-defensin-5. Dot blot experiments showed that α-defensin-1 binds to PTS1 and even stronger to its substrate protein Gαi in vitro. NADase activity of PTS1 in vitro was not inhibited by α-defensin-1 in the absence of Gαi. Taken together, these results suggest that α-defensin-1 inhibits PT mainly by inhibiting enzyme activity of PTS1, whereas α-defensin-5 mainly inhibits cellular uptake of PT. These findings will pave the way for optimization of α-defensins as novel therapeutics against whooping cough.


Asunto(s)
Tos Ferina , Humanos , Niño , Toxina del Pertussis/farmacología , Tos Ferina/microbiología , Bordetella pertussis , Proteínas , Línea Celular
3.
Health Res Policy Syst ; 21(1): 42, 2023 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-37277868

RESUMEN

BACKGROUND: Systems thinking can be used as a participatory data collection and analysis tool to understand complex implementation contexts and their dynamics with interventions, and it can support the selection of tailored and effective implementation actions. A few previous studies have applied systems thinking methods, mainly causal loop diagrams, to prioritize interventions and to illustrate the respective implementation context. The present study aimed to explore how systems thinking methods can help decision-makers (1) understand locally specific causes and effects of a key issue and how they are interlinked, (2) identify the most relevant interventions and best fit in the system, and (3) prioritize potential interventions and contextually analyse the system and potential interventions. METHODS: A case study approach was adopted in a regional emergency medical services (EMS) system in Germany. We applied systems thinking methods following three steps: (1) a causal loop diagram (CLD) with causes and effects (variables) of the key issue "rising EMS demand" was developed together with local decision-makers; (2) targeted interventions addressing the key issue were determined, and impacts and delays were used to identify best intervention variables to determine the system's best fit for implementation; (3) based on steps 1 and 2, interventions were prioritized and, based on a pathway analysis related to a sample intervention, contextually analysed. RESULTS: Thirty-seven variables were identified in the CLD. All of them, except for the key issue, relate to one of five interlinked subsystems. Five variables were identified as best fit for implementing three potential interventions. Based on predicted implementation difficulty and effect, as well as delays and best intervention variables, interventions were prioritized. The pathway analysis on the example of implementing a standardized structured triage tool highlighted certain contextual factors (e.g. relevant stakeholders, organizations), delays and related feedback loops (e.g. staff resource finiteness) that help decision-makers to tailor the implementation. CONCLUSIONS: Systems thinking methods can be used by local decision-makers to understand their local implementation context and assess its influence and dynamic connections to the implementation of a particular intervention, allowing them to develop tailored implementation and monitoring strategies.


Asunto(s)
Servicios Médicos de Urgencia , Humanos , Toma de Decisiones , Análisis de Sistemas , Alemania
4.
Front Public Health ; 10: 841013, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35372226

RESUMEN

Background: In the Euregio-Meuse-Rhine (EMR), cross-border collaboration is essential for resource-saving and needs-based patient care within the emergency medical service (EMS) systems and interhospital transport (IHT). However, at the onset of the novel coronavirus SARS-COV-2 (COVID-19) pandemic, differing national measures highlighted the fragmentation within the European Union (EU) in its various approaches to combating the pandemic. To assess the consequences of the pandemic in the EMR border area, the aim of this study was to analyze the effects and "lessons learned" regarding cross-border collaboration in EMS and IHT. Method: A qualitative study with 22 semi-structured interviews was carried out. Experts from across the EMR area, including the City of Aachen, the City region of Aachen, the District of Heinsberg (Germany), South Limburg (The Netherlands), and the Province of Limburg, as well as Liège (Belgium), took part. The interviews were coded and analyzed according to changes in cross-border collaboration before and during the pandemic, as well as lessons learned and recommendations. Results: Each EU member country within the EMR area, addressed the pandemic individually with national measures. Cross-border collaboration between regional actors was hardly or not at all addressed at the national level during political decision- or policymaking. Previous direct communication at the personal level was replaced by national procedures, which made regular cross-border collaboration significantly more difficult. The cross-border transfer regulations of patients with COVID-19 proved to be complex and led, among other things, to patients being transported to hospitals far outside the border region. Collaboration continues to be seen as valuable and Euregional emergency services including hospitals work well together, albeit to different degrees. The information and data exchange should, however, be more transparent to use resources more efficiently. Conclusion: Effective Euregional collaboration of emergency services is imperative for public safety in a multi-border region with strong economic, cultural, and social cross-border links. Our findings indicate that existing (pre-pandemic) structures which included regular meetings of senior managerial staff in the region and a number of thematic working groups were helpful to deal with and to compensate for the disruptions during the crisis. Regional cross-border agreements that are currently based on mutual but more or less informal arrangements need to be formalized and better promoted and recognized also at the national and EU level to increase resilience. The continuous determination of synergies and good and best practices are further approaches to support cross-border collaboration especially in preparation for future crises.


Asunto(s)
COVID-19 , Servicios Médicos de Urgencia , COVID-19/epidemiología , Unión Europea , Testimonio de Experto , Humanos , SARS-CoV-2
5.
J Neural Transm (Vienna) ; 129(5-6): 649-659, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-34812928

RESUMEN

Major depression disorder (MDD) is characterized by cognitive control (CC) dysfunctions associated with increased attention toward negative information. The paced auditory serial addition task (PASAT) has been used as a targeted training of CC and studies show promising effects on depressive symptoms. However, neural mechanisms underlying its efficacy are still unclear. Based on previous findings of feedback-locked event-related potentials in healthy subjects, we investigated neural signatures during PASAT performance in 46 depressed patients. We found significantly larger amplitudes after negative than positive feedback for the P300 and late positive potential (LPP). However, this difference was not significant for the feedback-related negativity (FRN). Moreover, no associations of valence-specific ERPs and PASAT performance nor depressive symptoms were found. This indicates that depressed patients seem unable to use neural activation in late feedback processing stages (P300, LPP) to adapt accordingly. Moreover, lack of valence-specific neural reaction in early feedback processing stages (FRN) might point toward emotional indifference in depressed patients.Trial registration number: NCT03518749 Date of registration: May 8, 2018.


Asunto(s)
Trastorno Depresivo Mayor , Potenciales Evocados , Atención , Cognición , Electroencefalografía , Potenciales Evocados/fisiología , Humanos
7.
Neuropsychologia ; 156: 107850, 2021 06 18.
Artículo en Inglés | MEDLINE | ID: mdl-33812945

RESUMEN

BACKGROUND: Deficient cognitive control (CC) over emotional distraction is a central characteristic of borderline personality disorder (BPD). Reduced activation of the left dorsolateral prefrontal cortex (dlPFC) has been linked to this deficit. This study investigates whether it is possible to ameliorate CC deficits via anodal tDCS over the left dlPFC in BPD. Furthermore, we investigate whether the extent of CC impairment influences how well one responds to tDCS. METHODS: The effect of a single-session tDCS (1 mA for 20 min, reference electrode on the contralateral mastoid bone) to the left dlPFC (F3) on the CC of patients with BPD (N = 20) and healthy control participants (HCs, N = 20) was examined in a double-blinded, balanced randomized, sham-controlled crossover trial. A delayed response working memory task with negative, neutral and positive pictures presented during the delay period was conducted to assess CC. Stimulation was applied simultaneously with the task. RESULTS: Negative pictures caused prolonged response times as compared to a control condition in patients with BPD and HCs. Anodal tDCS to the left dlPFC did not significantly reduce this interference effect in the overall sample. Further analyses showed, however, that participants with impaired CC profited the most from anodal tDCS. In the subgroup of participants who actually showed an interference effect we found the expected significant amelioration of CC under tDCS. CONCLUSIONS: The present study demonstrates that anodal tDCS applied to the left dlPFC improves deficient CC. Thereby, base-level performance moderates tDCS effects. Hence, tDCS might be suitable to support behavioral trainings to enhance CC specifically in people whose impairments in CC are comparably high.


Asunto(s)
Trastorno de Personalidad Limítrofe , Estimulación Transcraneal de Corriente Directa , Trastorno de Personalidad Limítrofe/terapia , Método Doble Ciego , Emociones , Humanos , Memoria a Corto Plazo , Corteza Prefrontal
8.
Front Hum Neurosci ; 15: 630468, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33679350

RESUMEN

Research on cognitive control has sparked increasing interest in recent years, as it is an important prerequisite for goal oriented human behavior. The paced auditory serial addition task (PASAT) has been used to test and train cognitive control functions. This adaptive, challenging task includes continuous performance feedback. Therefore, additional cognitive control capacities are required to process this information along with the already high task-load. The underlying neural mechanisms, however, are still unclear. To explore the neural signatures of the PASAT and particularly the processing of distractive feedback information, feedback locked event-related potentials were derived from 24 healthy participants during an adaptive 2-back version of the PASAT. Larger neural activation after negative feedback was found for feedback related negativity (FRN), P300, and late positive potential (LPP). In early stages of feedback processing (i.e., FRN), a larger difference between positive and negative feedback responses was associated with poorer overall performance. This association was inverted in later stages (i.e., P300 and LPP). Together, our findings indicate stage-dependent associations between neural activation after negative information and cognitive functioning. Conceivably, increased early responses to negative feedback signify distraction, whereas higher activity at later stages reflects cognitive control processes to preserve ongoing performance.

9.
Sci Rep ; 10(1): 17982, 2020 10 22.
Artículo en Inglés | MEDLINE | ID: mdl-33093557

RESUMEN

In 2014, a telemedicine system was established in 24-h routine use in the emergency medical service (EMS) of the city of Aachen. This study tested whether the diagnostic concordance of the tele-EMS physician reaches the same diagnostic concordance as the on-site-EMS physician. The initial prehospital diagnoses were compared to the final hospital diagnoses. Data were recorded retrospectively from the physicians' protocols as well as from the hospital administration system and compared. Also, all diagnostic misconcordance were analysed and reviewed in terms of logical content by two experts. There were no significant differences between the groups in terms of demographic data, such as age and gender, as well as regarding the hospital length of stay and mortality. There was no significant difference between the diagnostic concordance of the systems, except the diagnosis "epileptic seizure". Instead, in these cases, "stroke" was the most frequently chosen diagnosis. The diagnostic misconcordance "stroke" is not associated with any risks to patients' safety. Reasons for diagnostic misconcordance could be the short contact time to the patient during the teleconsultation, the lack of personal examination of the patient by the tele-EMS physician, and reversible symptoms that can mask the correct diagnosis.


Asunto(s)
Errores Diagnósticos/estadística & datos numéricos , Servicios Médicos de Urgencia/métodos , Médicos/estadística & datos numéricos , Consulta Remota/métodos , Convulsiones/diagnóstico , Accidente Cerebrovascular/diagnóstico , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia
10.
J Med Internet Res ; 21(10): e14907, 2019 10 08.
Artículo en Inglés | MEDLINE | ID: mdl-31596244

RESUMEN

BACKGROUND: As a consequence of increasing emergency medical service (EMS) missions requiring an EMS physician on site, we had implemented a unique prehospital telemedical emergency service as a new structural component to the conventional physician-based EMS in Germany. OBJECTIVE: We sought to assess the utilization, safety, and technical performance of this telemedical emergency service. METHODS: We conducted a retrospective analysis of all primary emergency missions with telemedical consultation of an EMS physician in the City of Aachen (250,000 inhabitants) during the first 3 operational years of our tele-EMS system. Main outcome measures were the number of teleconsultations, number of complications, and number of transmission malfunctions during teleconsultations. RESULTS: The data of 6265 patients were analyzed. The number of teleconsultations increased during the run-in period of four quarters toward full routine operation from 152 to 420 missions per quarter. When fully operational, around the clock, and providing teleconsultations to 11 mobile ambulances, the number of teleconsultations further increased by 25.9 per quarter (95% CI 9.1-42.6; P=.009). Only 6 of 6265 patients (0.10%; 95% CI 0.04%-0.21%) experienced adverse events, all of them not inherent in the system of teleconsultations. Technical malfunctions of single transmission components occurred from as low as 0.3% (95% CI 0.2%-0.5%) during two-way voice communications to as high as 1.9% (95% CI 1.6%-2.3%) during real-time vital data transmissions. Complete system failures occurred in only 0.3% (95% CI 0.2%-0.6%) of all teleconsultations. CONCLUSIONS: The Aachen prehospital EMS is a frequently used, safe, and technically reliable system to provide medical care for emergency patients without an EMS physician physically present. Noninferiority of the tele-EMS physician compared with an on-site EMS physician needs to be demonstrated in a randomized trial.


Asunto(s)
Ambulancias/normas , Servicios Médicos de Urgencia/métodos , Calidad de la Atención de Salud/normas , Telemedicina , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
11.
Sci Rep ; 9(1): 6797, 2019 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-31043662

RESUMEN

Cognitive control of information processing is an essential prerequisite of human behavior. Particularly, focusing attention in the face of failure poses a common challenge. Previous work has demonstrated that transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (dlPFC) can improve cognitive control in a challenging and repeatedly frustrating task. In a randomized, sham-controlled, crossover design 22 healthy, male participants performed an adaptive 2-back version of the Paced Auditory Serial Addition Task (PASAT), parallel to anodal or sham tDCS over the left dlPFC and the return electrode on the right upper arm. Before and after the 2-back PASAT, the affective state was assessed by means of the Positive and Negative Affective Schedule (PANAS). We observed an interaction between stimulation condition and task performance driven by an increase in performance with anodal tDCS and no improvement with sham stimulation. In addition, after the 2-back PASAT we found a higher positive and a trend towards lower negative affect with anodal as compared to sham tDCS. Our data support and extend previous results showing improved processing speed under anodal stimulation associated with a reduced task-induced negative affect indicating an improvement of cognitive control. Further studies will investigate long-term effects and clinical applicability.


Asunto(s)
Atención/fisiología , Cognición/fisiología , Emociones/fisiología , Corteza Prefrontal/fisiología , Análisis y Desempeño de Tareas , Estimulación Transcraneal de Corriente Directa/métodos , Adolescente , Adulto , Voluntarios Sanos , Humanos , Masculino , Adulto Joven
12.
J Invest Dermatol ; 138(3): 527-533, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29045820

RESUMEN

For the treatment of superficial basal cell carcinoma, a prospective, noninferiority, randomized controlled multicenter trial with 601 patients showed that 5% imiquimod cream was superior and 5-fluorouracil cream not inferior to methyl aminolevulinate photodynamic therapy (MAL-PDT) at 1 and 3 years after treatment. No definite conclusion could be drawn regarding the superiority of imiquimod over 5-fluorouracil. We now present the 5-year follow-up results according to the intention-to-treat analysis. Five years after treatment, the probability of tumor-free survival was 62.7% for methyl aminolevulinate photodynamic therapy (95% confidence interval [CI] = 55.3-69.2), 80.5% for imiquimod (95% CI = 74.0-85.6), and 70.0% for 5-fluorouracil (95% CI = 62.9-76.0). The hazard ratio for treatment failure of imiquimod and 5-fluorouracil were 0.48 (95% CI = 0.32-0.71, P < 0.001) and 0.74 (95% CI = 0.53-1.05, P = 0.09), respectively, when compared with methyl aminolevulinate photodynamic therapy. Compared with 5-fluorouracil, imiquimod showed a hazard ratio of 0.65 (95% CI 0.43-0.98, P = 0.04). In conclusion, 5 years after treatment, the results of this trial show that 5% imiquimod cream is superior to both methyl aminolevulinate photodynamic therapy and 5-fluorouracil cream in terms of efficacy for superficial basal cell carcinoma. We therefore consider 5% imiquimod cream as the first choice for noninvasive treatment in most primary superficial basal cell carcinomas.


Asunto(s)
Carcinoma Basocelular/tratamiento farmacológico , Fluorouracilo/administración & dosificación , Imiquimod/administración & dosificación , Fotoquimioterapia , Neoplasias Cutáneas/tratamiento farmacológico , Administración Cutánea , Adulto , Anciano , Anciano de 80 o más Años , Ácido Aminolevulínico/administración & dosificación , Ácido Aminolevulínico/análogos & derivados , Carcinoma Basocelular/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pomadas , Neoplasias Cutáneas/mortalidad
13.
J Invest Dermatol ; 136(8): 1568-1574, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27113429

RESUMEN

A randomized controlled trial including 601 patients previously showed that the effectiveness of imiquimod and fluorouracil cream were not inferior to methyl aminolevulinate photodynamic therapy (MAL-PDT) in patients with superficial basal cell carcinoma after 1 year of follow-up. We now present the 3-year follow-up results. The probability of tumor-free survival at 3 years post-treatment was 58.0% for MAL-PDT (95% confidence interval [CI] = 47.8-66.9), 79.7% for imiquimod (95% CI = 71.6-85.7), and 68.2% for fluorouracil (95% CI = 58.1-76.3). The hazard ratio for treatment failure comparing imiquimod with MAL-PDT was 0.50 (95% CI = 0.33-0.76, P = 0.001). Comparison of fluorouracil with MAL-PDT and fluorouracil with imiquimod showed hazard ratios of 0.73 (95% CI = 0.51-1.05, P = 0.092) and 0.68 (95% CI = 0.44-1.06, P = 0.091), respectively. Subgroup analysis showed a higher probability of treatment success for imiquimod versus MAL-PDT in all subgroups with the exception of elderly patients with superficial basal cell carcinoma on the lower extremities. In this subgroup, the risk difference in tumor-free survival was 57.6% in favor of MAL-PDT. In conclusion, according to results at 3 years post-treatment, imiquimod is superior and fluorouracil not inferior to MAL-PDT in treatment of superficial basal cell carcinoma.


Asunto(s)
Aminoquinolinas/uso terapéutico , Carcinoma Basocelular/tratamiento farmacológico , Fluorouracilo/uso terapéutico , Fotoquimioterapia , Neoplasias Cutáneas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Biopsia , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Imiquimod , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Modelos de Riesgos Proporcionales , Método Simple Ciego , Resultado del Tratamiento
14.
J Phys Chem B ; 118(23): 6159-66, 2014 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-24827589

RESUMEN

Superparamagnetic iron oxide nanoparticles (SPIONs) with a mixed phase composition (γ-Fe2O3)(1-x)(Fe3O4)x and sizes between 9 and 20 nm were synthesized via coprecipitation and were either left uncoated or subsequently surface-stabilized with citrate or malate anions. The sizes, morphology, surface chemistry, and magnetic properties of the nanoparticles were characterized using transmission electron microscopy (TEM), Fourier transform infrared spectroscopy, and superconducting quantum interference device measurements, respectively. Cellular uptake and intracellular distribution in normal tissue and tumor cells were verified by TEM images. X-ray-induced changes of the oxidation state and site geometries of surface iron ions of uncoated and citrate-coated SPIONs were explored by collecting Fe K-edge X-ray absorption spectroscopy data. The potential applicability of citrate- and malate-coated SPIONs as an X-ray enhancer for radiation cancer therapy was substantiated by their drastic enhancement of the concentration of reactive oxygen species (ROS) in X-ray irradiated tumor cells.


Asunto(s)
Compuestos Férricos/química , Nanopartículas/química , Fármacos Sensibilizantes a Radiaciones/química , Radioterapia/métodos , Células 3T3 , Animales , Aniones/química , Células CACO-2 , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Ácido Cítrico/química , Compuestos Férricos/metabolismo , Compuestos Férricos/uso terapéutico , Humanos , Células MCF-7 , Fenómenos Magnéticos , Malatos/química , Ensayo de Materiales , Ratones , Nanopartículas/metabolismo , Nanopartículas/uso terapéutico , Oxidación-Reducción/efectos de la radiación , Tamaño de la Partícula , Fármacos Sensibilizantes a Radiaciones/metabolismo , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , Dosificación Radioterapéutica , Especies Reactivas de Oxígeno/metabolismo , Propiedades de Superficie , Rayos X
15.
Lancet Oncol ; 14(7): 647-54, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23683751

RESUMEN

BACKGROUND: Superficial basal-cell carcinoma is most commonly treated with topical non-surgical treatments, such as photodynamic therapy or topical creams. Photodynamic therapy is considered the preferable treatment, although this has not been previously tested in a randomised control trial. We assessed the effectiveness of photodynamic therapy compared with imiquimod or fluorouracil in patients with superficial basal-cell carcinoma. METHODS: In this single blind, non-inferiority, randomised controlled multicentre trial, we enrolled patients with a histologically proven superficial basal-cell carcinoma at seven hospitals in the Netherlands. Patients were randomly assigned to receive treatment with methylaminolevulinate photodynamic therapy (MAL-PDT; two sessions with an interval of 1 week), imiquimod cream (once daily, five times a week for 6 weeks), or fluorouracil cream (twice daily for 4 weeks). Follow-up was at 3 and 12 months post-treatment. Data were collected by one observer who was blinded to the assigned treatment. The primary outcome was the proportion of patients free of tumour at both 3 and 12 month follow up. A pre-specified non-inferiority margin of 10% was used and modified intention-to-treat analyses were done. This trial is registered as an International Standard Randomised controlled trial (ISRCTN 79701845). FINDINGS: 601 patients were randomised: 202 to receive MAL-PDT, 198 to receive imiquimod, and 201 to receive fluorouracil. A year after treatment, 52 of 196 patients treated with MAL-PDT, 31 of 189 treated with imiquimod, and 39 of 198 treated with fluorouracil had tumour residue or recurrence. The proportion of patients tumour-free at both 3 and 12 month follow-up was 72.8% (95% CI 66.8-79.4) for MAL-PDT, 83.4% (78.2-88.9) for imiquimod cream, and 80.1% (74.7-85.9) for fluorouracil cream. The difference between imiquimod and MAL-PDT was 10.6% (95% CI 1.5-19.5; p=0.021) and 7.3% (-1.9 to 16.5; p=0.120) between fluorouracil and MAL-PDT, and between fluorouracil and imiquimod was -3.3% (-11.6 to 5.0; p=0.435. For patients treated with MAL-PDT, moderate to severe pain and burning sensation were reported most often during the actual MAL-PDT session. For other local adverse reactions, local skin redness was most often reported as moderate or severe in all treatment groups. Patients treated with creams more often reported moderate to severe local swelling, erosion, crust formation, and itching of the skin than patients treated with MAL-PDT. In the MAL-PDT group no serious adverse events were reported. One patient treated with imiquimod and two patients treated with fluorouracil developed a local wound infection and needed additional treatment in the outpatient setting. INTERPRETATION: Topical fluorouracil was non-inferior and imiquimod was superior to MAL-PDT for treatment of superficial basal-cell carcinoma. On the basis of these findings, imiquimod can be considered the preferred treatment, but all aspects affecting treatment choice should be weighted to select the best treatment for patients. FUNDING: Grant of the Netherlands Organization for Scientific Research ZONMW (08-82310-98-08626).


Asunto(s)
Ácido Aminolevulínico/uso terapéutico , Aminoquinolinas/administración & dosificación , Carcinoma Basocelular/tratamiento farmacológico , Fluorouracilo/administración & dosificación , Fotoquimioterapia , Fármacos Fotosensibilizantes/uso terapéutico , Neoplasias Cutáneas/tratamiento farmacológico , Administración Tópica , Adulto , Anciano , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/administración & dosificación , Antineoplásicos/administración & dosificación , Carcinoma Basocelular/patología , Femenino , Estudios de Seguimiento , Humanos , Imiquimod , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Método Simple Ciego , Neoplasias Cutáneas/patología
16.
Biochem Biophys Res Commun ; 425(2): 393-7, 2012 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-22842461

RESUMEN

Internalization of citrate-coated and uncoated superparamagnetic iron oxide nanoparticles by human breast cancer (MCF-7) cells was verified by transmission electron microscopy imaging. Cytotoxicity studies employing metabolic and trypan blue assays manifested their excellent biocompatibility. The production of reactive oxygen species in iron oxide nanoparticle loaded MCF-7 cells was explained to originate from both, the release of iron ions and their catalytically active surfaces. Both initiate the Fenton and Haber-Weiss reaction. Additional oxidative stress caused by X-ray irradiation of MCF-7 cells was attributed to the increase of catalytically active iron oxide nanoparticle surfaces.


Asunto(s)
Compuestos Férricos/farmacología , Nanopartículas de Magnetita , Neoplasias/metabolismo , Fármacos Sensibilizantes a Radiaciones/farmacología , Especies Reactivas de Oxígeno/metabolismo , Línea Celular Tumoral , Compuestos Férricos/química , Compuestos Férricos/metabolismo , Humanos , Fármacos Sensibilizantes a Radiaciones/química , Fármacos Sensibilizantes a Radiaciones/metabolismo , Rayos X
17.
Ned Tijdschr Geneeskd ; 153: B99, 2009.
Artículo en Holandés | MEDLINE | ID: mdl-19818183

RESUMEN

Foam echosclerotherapy is increasingly being used for the treatment of trunk varicositas because of its minimally invasive character and its high success rate in the occlusion of varicose veins. To achieve a better understanding of treatment and to standardize it, a consensus meeting was organised by experts. Based on their clinical experiences and on data from the literature, a Dutch guideline was drawn up which offers guidance on the treatment of trunk varicositas with foam echosclerotherapy and an overview of this new technique for both specialists and general practitioners.


Asunto(s)
Soluciones Esclerosantes/uso terapéutico , Escleroterapia/métodos , Várices/terapia , Humanos , Resultado del Tratamiento , Ultrasonografía Doppler Dúplex , Várices/diagnóstico por imagen
19.
Int J Dermatol ; 47 Suppl 1: 13-7, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-18986478

RESUMEN

Difficulty in differentiation between a solitary basal cell carcinoma, which is known as a malign skin lesion and a benign trichoepithelioma, is a frequent problem in all day dermatologic practice. Clinically as well as histopathologically there are a lot of resemblances between these skin tumors. By means of two real life cases, we give here an overview of the possible problems and appliances in distinguishing these two entities; at the end we do some recommendation about the policy.


Asunto(s)
Carcinoma Basocelular/patología , Neoplasias Cutáneas/patología , Adulto , Anciano , Dorso , Biopsia , Diagnóstico Diferencial , Femenino , Humanos , Masculino
20.
Int J Dermatol ; 47 Suppl 1: 29-31, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-18986482

RESUMEN

Four days after foamsclerotherapy of an incompetent great saphenous vein of the left lower leg a 49-year-old woman developed a superficial thrombophlebitis of the venous dorsal arch. In the course of follow-up repeated color duplex sonography initially did not show involvement of the deep venous system and, hence, she was treated with non-steroidal anti-inflammatory drugs and compression hosiery. However, six weeks after foam treatment we diagnosed a deep venous thrombosis (DVT) of the popliteal vein and started an oral anticoagulant therapy. Although rarely observed, DVT is among the most serious complications of foamsclerotherapy Therefore, we suggest that the occurrence of a superficial thrombophlebitis that is not located in close vicinity of the vein treated should be an indication for regular follow-up examinations to prevent missing the occurrence of disease progression and a possible involvement of the deep venous system.


Asunto(s)
Pie/irrigación sanguínea , Escleroterapia/efectos adversos , Tromboflebitis/etiología , Várices/terapia , Trombosis de la Vena/etiología , Femenino , Humanos , Persona de Mediana Edad , Vena Poplítea
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