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BACKGROUND: Third ventricular colloid cysts are benign but may cause acute hydrocephalus, raised intracranial pressure, decreased consciousness level, and sudden death. These ventricular colloid cysts associated with stunned myocardium are rarely reported in the literature. This study reported a case of a third ventricular colloid cyst presented as acute hydrocephalus complicated with severe neurogenic pulmonary edema, stunned myocardium, and heart failure, which survived at the end. CASE PRESENTATION: A 29-year-old woman presented to the emergency department with one day history of headache, vomiting, and altered consciousness level. Early brain imaging showed a cyst in the third ventricle. The patient rapidly deteriorated neurologically and developed severe pulmonary edema and heart failure requiring immediate external ventricular drain and heart failure management. Once stabilized, she underwent endoscopic excision of the ventricular cyst. Histopathology confirmed the diagnosis of colloidal cyst. She survived all these acute life-threatening events, improved, and stabilized, and was discharged home. She was followed up in outpatient clinics after 6 months of discharge with no symptoms or neurological deficit. CONCLUSION: A third ventricular colloid cyst can cause acute hydrocephalus leading to stunned myocardium requiring immediate surgical intervention, advanced hemodynamic monitoring, and acute heart failure management.
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OBJECTIVES: The primary aim of the study was to assess the convergent validity of the Surgical Fear Questionnaire (SFQ) with other self-report instruments and biological indices of stress. Secondary aims were the examination of predictors of the level and time course of fear and preferences for fear treatment. METHODS: In a prospective observational cohort study SFQ short-term (SFQ-s) and long-term (SFQ-l) scores were assessed one week, one day, and the morning before cataract surgery, together with salivary cortisol and alpha-amylase (sAA) levels, and numeric rating scale (NRS) fear score. SFQ-scores were also assessed before second eye surgery. Expected pain and recovery, and sociodemographic and medico-psychological predictors of fear were assessed at baseline. RESULTS: Data of 98 patients were analyzed. Scores of both SFQ-subscales (range 0-40) were generally low, all mean ≤ 9.0. SFQ-s and SFQ-l correlated significantly with the other self-report instruments: NRS fear .83 and .89, expected pain .49 and .54, expected recovery -.27 and -.44. No association was found between SFQ-scores and cortisol or sAA level. Predictors of the level of fear were baseline pain and stress. Additional effects of time were found for subgroups based on educational level, antidepressant use, and presurgical stress (SFQ-l). SFQ-scores were significantly lower before the second cataract surgery than before the first, and higher in patients who would have appreciated treatment of fear. DISCUSSION: Convergent validity of the SFQ with other self-report measures is shown. The sensitivity of the SFQ permits the detection of small variations in fear caused by time or other factors.
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Extracción de Catarata/psicología , Miedo/psicología , Dolor Postoperatorio/psicología , Reoperación/psicología , Autoinforme , Estrés Psicológico/psicología , Anciano , Extracción de Catarata/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Dolor Postoperatorio/diagnóstico , Dolor Postoperatorio/etiología , Periodo Posoperatorio , Estudios Prospectivos , Psicometría , Reoperación/efectos adversos , Sensibilidad y Especificidad , Estrés Psicológico/diagnóstico , Estrés Psicológico/etiología , Factores de TiempoRESUMEN
[This corrects the article DOI: 10.1371/journal.pone.0100225.].
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Chronic postsurgical pain (CPSP) is 1 important aspect of surgical recovery. To improve perioperative care and postoperative recovery knowledge on predictors of impaired recovery is essential. The aim of this study is to assess predictors and epidemiological data of CPSP, physical functioning (SF-36PF, 0-100), and global surgical recovery (global surgical recovery index, 0-100%) 3 and 12 months after hysterectomy for benign indication.A prospective multicenter cohort study was performed. Sociodemographic, somatic, and psychosocial data were assessed in the week before surgery, postoperatively up to day 4, and at 3- and 12-month follow-up. Generalized linear model (CPSP) and linear-mixed model analyses (SF-36PF and global surgical recovery index) were used. Baseline data of 468 patients were collected, 412 (88%) patients provided data for 3-month evaluation and 376 (80%) patients for 12-month evaluation.After 3 and 12 months, prevalence of CPSP (numeric rating scale ≥ 4, scale 0-10) was 10.2% and 9.0%, respectively, SF-36PF means (SD) were 83.5 (20.0) and 85.9 (20.2), global surgical recovery index 88.1% (15.6) and 93.3% (13.4). Neuropathic pain was reported by 20 (5.0%) patients at 3 months and 14 (3.9%) patients at 12 months. Preoperative pain, surgery-related worries, acute postsurgical pain on day 4, and surgery-related infection were significant predictors of CPSP. Baseline level, participating center, general psychological robustness, indication, acute postsurgical pain, and surgery-related infection were significant predictors of SF-36PF. Predictors of global surgical recovery were baseline expectations, surgery-related worries, American Society of Anesthesiologists classification, type of anesthesia, acute postsurgical pain, and surgery-related infection.Several predictors were identified for CPSP, physical functioning, and global surgical recovery. Some of the identified factors are modifiable and optimization of patients' preoperative pain status and psychological condition as well as reduction of acute postsurgical pain and surgery-related infection may lead to improvement of outcome.
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Dolor Crónico/epidemiología , Histerectomía , Dolor Postoperatorio/epidemiología , Dolor Crónico/etiología , Estudios de Cohortes , Femenino , Humanos , Histerectomía/efectos adversos , Persona de Mediana Edad , Dolor Postoperatorio/etiología , Pronóstico , Estudios Prospectivos , Recuperación de la Función , Factores de TiempoRESUMEN
Outpatient knee arthroscopy is one of the most commonly performed surgical procedures. Previous research has demonstrated that chronic postsurgical pain (CPSP) after outpatient surgery is prevalent. Our objective was to determine the prevalence and predictive factors of CPSP and Global Surgical Recovery (GSR) 1 year after knee arthroscopy.A prospective longitudinal cohort study was performed. Patients were included during an 18-month period. Data were collected by using 3 questionnaires: at 1 week preoperatively, 4 days postoperatively, and 1 year postoperatively. A value of >3 on an 11-point numeric rating scale (NRS) was defined as moderate to severe pain. A score of ≤80% on the Global Surgical Recovery Index was defined as poor GSR. Stepwise logistic regression analysis was performed to determine which variables were predictors for CPSP and poor GSR.The prevalence of moderate to severe preoperative pain in patients undergoing knee arthroscopy (nâ=â104) was 71.2%, of acute postsurgical pain 37.5%, and of CPSP 32.7%. Risk factors for CPSP were the presence of preoperative pain and preoperative analgesic use, with odds ratios of 6.31 (1.25-31.74) and 4.36 (1.58-12.07), respectively. The prevalence of poor GSR 1 year after outpatient knee arthrosocpy was 50.0%. Poor GSR 4 days after the surgery was a risk factor with an odds ratio of 8.38 (0.92-76.58) and quality of life 4 days after surgery was a protective factor with and odds ratio of 0.10 (0.02-0.64).Both CPSP and poor GSR are common 1 year after knee arthroscopy. Patients at risk for CPSP can be identified during the preoperative phase. Prediction of poor GSR 1 year after surgery is mainly related to early postoperative recovery.
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Artroscopía/efectos adversos , Artroscopía/métodos , Articulación de la Rodilla , Osteoartritis de la Rodilla/cirugía , Dolor Postoperatorio/epidemiología , Adulto , Factores de Edad , Dolor Crónico , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Pacientes Ambulatorios , Dimensión del Dolor , Prevalencia , Estudios Prospectivos , Calidad de Vida , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores Sexuales , Factores SocioeconómicosRESUMEN
BACKGROUND: Neurogenic pulmonary edema (NPE) is a clinical syndrome usually defined as an acute pulmonary edema occurring shortly after a central neurologic insult. NPE was identified 100 years ago, but it is still underappreciated in the clinical setup. NPE usually appears within minutes to hours after the injury. It has a high mortality rate if not recognized early and treated appropriately. Similarly, neurogenic shock is a known complication of spinal cord injury reported incidence is more than 20% in isolated upper cervical spinal injury. But NPE is rare to occur, and stunned myocardium (SM) is not reported in spinal arteriovenous malformation (AVM) rupture. SM is a reversible cardiomyopathy resulting in transient left ventricular dysfunction which has been described to occur in the setting of catecholamine release during situations of physiologic stress. We report a case of high spinal AVM rupture presenting as SM, NPE, and neurogenic shock. CASE DESCRIPTION: A 32-year-old male who presented with sudden onset of pain and weakness in upper limbs. Imaging studies showed AVM rupture by imaging techniques. Initially, the patient had severe hypertension, respiratory distress requiring intubation and ventilation, then he developed hypotension, bradycardia, and asystole, which required immediate cardiopulmonary resuscitation and atropine. He remained with quadriplegia and suffered from frequent episodes of bradycardia and asystole. CONCLUSIONS: Spinal AVM rupture can present as neurogenic shock, stunned myocardium, and pulmonary edema. Early recognition of AVM rupture and prompt surgical intervention, as well as aggressive treatment of shock, may enhance recovery and decrease the long-term morbidity.
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OBJECTIVES: To prospectively describe the prevalence and predictive factors of chronic postsurgical pain (CPSP) and poor global recovery in a large outpatient population at a university hospital, 1 year after outpatient surgery. MATERIALS AND METHODS: A prospective longitudinal cohort study was performed. During 18 months, patients presenting for preoperative assessment were invited to participate. Outcome parameters were measured by using questionnaires at 3 timepoints: 1 week preoperatively, 4 days postoperatively, and 1 year postoperatively. A value of >3 on an 11-point numeric rating scale was considered to indicate moderate to severe pain. A score of ≤80% on the Global Surgical Recovery Index was defined as poor global recovery. RESULTS: A total of 908 patients were included. The prevalence of moderate to severe preoperative pain was 37.7%, acute postsurgical pain 26.7%, and CPSP 15.3%. Risk factors for the development of CPSP were surgical specialty, preoperative pain, preoperative analgesic use, acute postoperative pain, surgical fear, lack of optimism, and poor preoperative quality of life. The prevalence of poor global recovery was 22.3%. Risk factors for poor global recovery were recurrent surgery because of the same pathology, preoperative pain, preoperative analgesic use, surgical fear, lack of optimism, poor preoperative and acute postoperative quality of life, and follow-up surgery during the first postoperative year. DISCUSSION: Moderate to severe CPSP after outpatient surgery is common, and should not be underestimated. Patients at risk for developing CPSP can be identified during the preoperative phase.
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Pacientes Ambulatorios , Dolor Postoperatorio/epidemiología , Dolor Postoperatorio/fisiopatología , Recuperación de la Función/fisiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Dolor Crónico/epidemiología , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Valor Predictivo de las Pruebas , Estadística como Asunto , Encuestas y Cuestionarios , Adulto JovenRESUMEN
OBJECTIVES: Because existing instruments for assessing surgical fear seem either too general or too limited, the Surgical Fear Questionnaire (SFQ) was developed. The aim of this study is to assess the validity and reliability of the SFQ. METHODS: Based on existing literature and expert consultation the ten-item SFQ was composed. Data on the SFQ were obtained from 5 prospective studies (Nâ=â3233) in inpatient or day surgery patients. These data were used for exploratory factor analysis (EFA), confirmatory factor analysis (CFA), reliability analysis and validity analysis. RESULTS: EFA in Study 1 and 2 revealed a two-factor structure with one factor associated with fear of the short-term consequences of surgery (SFQ-s, item 1-4) and the other factor with fear of the long-term consequences of surgery (SFQ-l, item 5-10). However, in both studies two items of the SFQ-l had low factor loadings. Therefore in Study 3 and 4 the 2-factor structure was tested and confirmed by CFA in an eight-item version of the SFQ. Across all studies significant correlations of the SFQ with pain catastrophizing, state anxiety, and preoperative pain intensity indicated good convergent validity. Internal consistency (Cronbach's alpha) was between 0.765-0.920 (SFQ-total), 0.766-0.877 (SFQ-s), and 0.628-0.899 (SFQ-l). The SFQ proved to be sensitive to detect differences based on age, sex, education level, employment status and preoperative pain intensity. DISCUSSION: The SFQ is a valid and reliable eight-item index of surgical fear consisting of two subscales: fear of the short-term consequences of surgery and fear of the long-term consequences.
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Miedo/psicología , Procedimientos Quirúrgicos Operativos/psicología , Adulto , Anciano , Anciano de 80 o más Años , Análisis Factorial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Psicometría , Reproducibilidad de los Resultados , Factores de Riesgo , Autoinforme , Encuestas y CuestionariosRESUMEN
In analyzing time-locked event-related potentials (ERPs), many studies have focused on specific peaks and their differences between experimental conditions. In theory, each latency point after a stimulus contains potentially meaningful information, regardless of whether it is peak-related. Based on this assumption, we introduce a new concept which allows for flexible investigation of the whole epoch and does not primarily focus on peaks and their corresponding latencies. For each trial, the entire epoch is partitioned into event-related fixed-interval areas under the curve (ERFIAs). These ERFIAs, obtained at single trial level, act as dependent variables in a multilevel random regression analysis. The ERFIA multilevel method was tested in an existing ERP dataset of 85 healthy subjects, who underwent a rating paradigm of 150 painful and non-painful somatosensory electrical stimuli. We modeled the variability of each consecutive ERFIA with a set of predictor variables among which were stimulus intensity and stimulus number. Furthermore, we corrected for latency variations of the P2 (260 ms). With respect to known relationships between stimulus intensity, habituation, and pain-related somatosensory ERP, the ERFIA method generated highly comparable results to those of commonly used methods. Notably, effects on stimulus intensity and habituation were also observed in non-peak-related latency ranges. Further, cortical processing of actual stimulus intensity depended on the intensity of the previous stimulus, which may reflect pain-memory processing. In conclusion, the ERFIA multilevel method is a promising tool that can be used to study event-related cortical processing.
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Potenciales Evocados/fisiología , Adolescente , Adulto , Anciano , Electroencefalografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Pre-analytical variables interact with standard coagulation parameters. How these variables affect the platelet function analysis is not completely known. How collection site and puncture method affect multiple electrode aggregometry (MEA) and platelet function analyzer (PFA-100®) was compared regarding contact activation. First, volunteers scheduled for elective cardiac surgery had blood collected from four lines: venous, arterial, central venous and by venipuncture. MEA and PFA-100® were analysed blinded for site origin. Second, two samples (citrate, Corn Trypsin Inhibitor, CTI) were collected in syringe or vacuum tubes. Thrombin generation (TG) was determined. MEA was triggered by adenosine diphosphate (ADP, 6.4 µM), arachidonic acid (ASPI, 0.5 mM), collagen (Col, 3.2 µg/ml), ristocetin (Risto, 0.2 mg/ml) and thrombin receptor-activating peptide (TRAP, 32 µM). PFA-100® was triggered by collagen/epinephrine and collagen/ADP. TG was assessed in platelet-poor plasma with 1 pM tissue factor and 4 µM phospholipids and without trigger. Data were analysed using a two-way mixed-effects model for the intraclass correlation (ICC) and by the Mann-Whitney U-test. MEA and PFA-100® revealed good correlation (ICC) between the sites. CTI inhibited TG significantly more effective than citrate. Contact activation was independent of the collection method. Only the MEA ASPI test revealed significant differences between the two collection methods. Blood sampling from all lines for MEA and PFA-100® assays is justified. Contact activation is always present. Apparently this does not influence platelet function test results. Collection methods do not seem relevant, although, one should always consider using a standardized method.
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Plaquetas/fisiología , Recolección de Muestras de Sangre , Anciano , Recolección de Muestras de Sangre/instrumentación , Recolección de Muestras de Sangre/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas de Función PlaquetariaRESUMEN
After the first description of platelets more than a century ago, the knowledge about their origin and function grew continuously. The development of the impedance method as a completely automated assay allowed integrating mean platelet volume (MPV) measurement as a routine parameter of the complete blood count. This enabled us to focus more on the association of platelet function and size. Since then, many authors described MPV as a marker of platelet reactivity and risk factor for cardiovascular diseases. Hence, the preanalytical variability of this parameter is known from its introduction as standard laboratory value. Unfortunately no preanalytical standards have been implemented. This review shows the high variability in the literature with MPV as a risk factor for cardiovascular disease. After a brief description of the biology of platelets, we provide an in-depth survey of the measurement methods and their drawbacks. Finally, we propose a possible approach to standardization.
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Plaquetas/metabolismo , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/diagnóstico , Biomarcadores/sangre , Recuento de Células Sanguíneas/métodos , Recuento de Células Sanguíneas/normas , Plaquetas/patología , Humanos , Factores de RiesgoRESUMEN
BACKGROUND: Observational data sets can be used for population pharmacokinetic (PK) modeling. However, these data sets are generally less precisely recorded than experimental data sets. This article aims to investigate the influence of erroneous records on population PK modeling and individual maximum a posteriori Bayesian (MAPB) estimation. METHODS: A total of 1123 patient records of neonates who were administered vancomycin were used for population PK modeling by iterative 2-stage Bayesian (ITSB) analysis. Cut-off values for weighted residuals were tested for exclusion of records from the analysis. A simulation study was performed to assess the influence of erroneous records on population modeling and individual MAPB estimation. Also the cut-off values for weighted residuals were tested in the simulation study. RESULTS: Errors in registration have limited the influence on outcomes of population PK modeling but can have detrimental effects on individual MAPB estimation. A population PK model created from a data set with many registration errors has little influence on subsequent MAPB estimates for precisely recorded data. A weighted residual value of 2 for concentration measurements has good discriminative power for identification of erroneous records. CONCLUSIONS: ITSB analysis and its individual estimates are hardly affected by most registration errors. Large registration errors can be detected by weighted residuals of concentration.
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Teorema de Bayes , Registros de Salud Personal , Modelos Biológicos , Farmacocinética , Antibacterianos/administración & dosificación , Antibacterianos/farmacocinética , Bases de Datos como Asunto , Femenino , Humanos , Recién Nacido , Masculino , Registros Médicos , Población , Sistema de Registros , Proyectos de Investigación , Vancomicina/administración & dosificación , Vancomicina/farmacocinéticaAsunto(s)
Administración Intranasal , Analgésicos Opioides/administración & dosificación , Dolor Irruptivo/tratamiento farmacológico , Fentanilo/administración & dosificación , Satisfacción del Paciente , Adolescente , Adulto , Anciano , Analgésicos Opioides/uso terapéutico , Femenino , Fentanilo/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Encuestas y Cuestionarios , Adulto JovenRESUMEN
UNLABELLED: Thromboelastometry (ROTEM) is a popular point-of-care test. It generates results quickly and may benefit individualised guided haemostatic therapy. However, processing of specimens by non-technicians might decrease the quality and reproducibility of results. Centralised laboratory equipment receiving specimens through a pneumatic tube system (PTS) could avoid this. This study aimed to evaluate the influence of PTS transport on ROTEM results and its contribution to contact activation assessed by thrombin generation (TG). METHODS: Specimens from 44 patients were drawn immediately after arterial puncture. Two were anticoagulated by citrate and two by citrate/corn trypsin inhibitor, a Factor XIIa pathway inhibitor. Both types of samples were transported by walking and PTS. Subsequently, analysis was performed: ROTEM on citrated blood, and TG on citrated and corn trypsin inhibitor (CTI) blood using either 0 or 1 pM tissue factor (TF). RESULTS: In ROTEM analysis the NATEM assay showed significant differences. The EXTEM assay revealed small significant differences for clot formation time: 65 seconds (SD ± 20) versus 67 seconds (SD ± 17), and alpha angle 79° (SD ± 3) versus 77° (SD ± 3). The results remained within reference range. TG was not significantly affected by the type of tube transport, independent of the amount of TF. CONCLUSION: PTS for ROTEM analysis is feasible except for NATEM assays. The amount of contact activation via Factor XIIa in terms of TG is independent of transport type. However, due to the different characteristics of pneumatic systems, hospitals should check its impact on the results before introducing this route of transport.
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Artefactos , Reología/instrumentación , Tromboelastografía/instrumentación , Tiempo de Trombina , Anciano , Diseño de Equipo , Análisis de Falla de Equipo , Femenino , Humanos , Masculino , Presión , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Intranasal (IN) midazolam is a potential alternative to rectal diazepam for the acute treatment of epileptic seizures. OBJECTIVE: The purpose of this pilot study was to investigate the pharmacokinetics and tolerability of IN midazolam (50 mg/mL) compared with intravenous (IV) midazolam (2.5 mg) in healthy adult volunteers. METHODS: In this single-dose, randomized-sequence, open-label, 2-period crossover pilot study subjects were randomly assigned to receive IN or IV midazolam, with a washout period of at least 5 days between treatments. The 50-mg/mL IN midazolam formulation consisted of 5 mg midazolam base per 0.1 mL (1 spray) and was administered once in 1 nostril. The IV midazolam solution (2.5 mg) was infused over 10 seconds. Blood samples were taken before and at regular intervals up to 240 minutes after dosing. Pharmacokinetic data (ie, C(max), T(max), t(½), and AUC) were analyzed using a 2-compartment model. RESULTS: Of 9 volunteers screened and enrolled, 7 completed the study (mean age 34.1 [9.0] years; mean weight, 68.6 [10.4] kg, range 53-89 kg; 6 men, 3 women; all white). The mean C(max) of 78 (40) ng/mL was reached 44 minutes after IN administration, whereas the mean C(max) was 51 (5) ng/mL after IV administration. The mean estimated C(t=5 min) was 31.4 (28.1) ng/mL after IN administration. The elimination t(½) was 1.9 (0.41) hours for IN midazolam and 2.3 (0.19) hours for IV midazolam. The bioavailability of IN midazolam was 82%. There were few adverse events, with a local burning feeling in the nose being the most reported event (6 of 7 subjects). CONCLUSIONS: In this select group of healthy volunteers, concentrations of midazolam >30 ng/mL were reached within 5 minutes of IN administration at a dose of 5 mg/0.1 mL. A burning feeling in the nostril was the main adverse effect. Additional research is needed to evaluate the safety profile, convenience, satisfaction, and efficacy of nasal midazolam in the treatment of adults with seizures. This trial is registered at www.isrctn.org, No. ISRCTN79059168.
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Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/farmacocinética , Midazolam/administración & dosificación , Midazolam/farmacocinética , Administración Intranasal , Adulto , Anticonvulsivantes/efectos adversos , Estudios Cruzados , Femenino , Humanos , Infusiones Intravenosas , Masculino , Midazolam/efectos adversos , Persona de Mediana Edad , Rociadores Nasales , Países Bajos , Proyectos PilotoRESUMEN
PURPOSE OF REVIEW: This review intends to give an overview of developments in anaesthesia residency training. RECENT FINDINGS: Healthcare institutions are stimulated to improve residency training programmes by worldwide quality assurance movements. Research and literature has increased the comprehension of which factors are needed to stimulate effective learning. Recent studies promote the use of (electronic) portfolios that stimulate and monitor the learning process, simulation for training and assessment purposes, and quality assurance with a focus on the role of the clinical teacher and the learning environment. SUMMARY: Innovations in the field of educational studies have provided us with tools to improve the training of our residents. Portfolio, simulation and quality assurance are among the most prominent developments aimed at creating successful residency programmes. Financial implications of the implementation of educational innovations should, however, be considered.
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Anestesiología/educación , Competencia Clínica/normas , Internado y Residencia/métodos , Internado y Residencia/normas , Documentación , Humanos , Simulación de PacienteRESUMEN
Neuropathic pain is currently being treated by a range of therapeutic interventions that above all act to lower neuronal activity in the somatosensory system (e.g. using local anesthetics, calcium channel blockers, and opioids). The present review highlights novel and often still largely experimental treatment approaches based on insights into pathological mechanisms, which impact on the spinal nociceptive network, thereby opening the 'gate' to higher brain centers involved in the perception of pain. Cellular and molecular mechanisms such as ectopia, sensitization of nociceptors, phenotypic switching, structural plasticity, disinhibition, and neuroinflammation are discussed in relation to their involvement in pain hypersensitivity following either peripheral neuropathies or spinal cord injury. A mechanism-based treatment approach may prove to be successful in effective treatment of neuropathic pain, but requires more detailed insights into the persistence of cellular and molecular pain mechanisms which renders neuropathic pain unremitting. Subsequently, identification of the therapeutic window-of-opportunities for each specific intervention in the particular peripheral and/or central neuropathy is essential for successful clinical trials. Most of the cellular and molecular pain mechanisms described in the present review suggest pharmacological interference for neuropathic pain management. However, also more invasive treatment approaches belong to current and/or future options such as neuromodulatory interventions (including spinal cord stimulation) and cell or gene therapies, respectively.
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Hiperalgesia/tratamiento farmacológico , Hiperalgesia/patología , Nociceptores/patología , Enfermedades del Sistema Nervioso Periférico/tratamiento farmacológico , Enfermedades del Sistema Nervioso Periférico/patología , Animales , Ensayos Clínicos como Asunto/métodos , Humanos , Hiperalgesia/etiología , Nociceptores/efectos de los fármacos , Umbral del Dolor/efectos de los fármacos , Umbral del Dolor/fisiología , Enfermedades del Sistema Nervioso Periférico/complicacionesRESUMEN
Maximum a posteriori Bayesian (MAPB) pharmacokinetic parameter estimation is an accurate and flexible method of estimating individual pharmacokinetic parameters using individual blood concentrations and prior information. In the past decade, many studies have developed optimal sampling strategies to estimate pharmacokinetic parameters as accurately as possible using either multiple regression analysis or MAPB estimation. This has been done for many drugs, especially immunosuppressants and anticancer agents. Methods of development for optimal sampling strategies (OSS) are diverse and heterogeneous. This review provides a comprehensive overview of OSS development methodology using MAPB pharmacokinetic parameter estimation, determines the transferability of published OSSs, and compares sampling strategies determined by MAPB estimation and multiple regression analysis. OSS development has the following components: 1) prior distributions; 2) reference value determination; 3) optimal sampling time identification; and 4) validation of the OSS. Published OSSs often lack all data necessary for the OSS to be clinically transferable. MAPB estimation is similar to multiple regression analysis in terms of predictive performance but superior in flexibility.
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Antineoplásicos/farmacocinética , Teorema de Bayes , Inmunosupresores/farmacocinética , Proyectos de Investigación , Humanos , Reproducibilidad de los ResultadosRESUMEN
Monitoring the course of platelet function in HELLP (haemolysis, elevated liver-enzymes and low platelets) syndrome is important for clinical decision-making. We present a primigravid woman developing HELLP syndrome at 29 weeks and 6 days. Platelet function was monitored by multiple electrode aggregometry (MEA), platelet function analyzer (PFA-100®), platelet count and mean platelet volume (MPV) over an 11-day period. MPV and PFA-100® seem better predictors for platelet function than platelet levels.