Structural differences in the diaphragm of patients following controlled vs assisted and spontaneous mechanical ventilation.

PURPOSE: Ventilator-induced diaphragm dysfunction or damage (VIDD) is highly prevalent in patients under mechanical ventilation (MV), but its analysis is limited by the difficulty of obtaining histological samples. In this study we compared diaphragm histological characteristics in Maastricht III (MSIII) and brain-dead (BD) organ donors and in control subjects undergoing thoracic surgery (CTL) after a period of either controlled or spontaneous MV (CMV or SMV). METHODS: In this prospective study, biopsies were obtained from diaphragm and quadriceps. Demographic variables, comorbidities, severity on admission, treatment, and ventilatory variables were evaluated. Immunohistochemical analysis (fiber size and type percentages) and quantification of abnormal fibers (a surrogate of muscle damage) were performed. RESULTS: Muscle samples were obtained from 35 patients. MSIII (n = 16) had more hours on MV (either CMV or SMV) than BD (n = 14) and also spent more hours and a greater percentage of time with diaphragm stimuli (time in assisted and spontaneous modalities). Cross-sectional area (CSA) was significantly reduced in the diaphragm and quadriceps in both groups in comparison with CTL (n = 5). Quadriceps CSA was significantly decreased in MSIII compared to BD but there were no differences in the diaphragm CSA between the two groups. Those MSIII who spent 100 h or more without diaphragm stimuli presented reduced diaphragm CSA without changes in their quadriceps CSA. The proportion of internal nuclei in MSIII diaphragms tended to be higher than in BD diaphragms, and their proportion of lipofuscin deposits tended to be lower, though there were no differences in the quadriceps fiber evaluation. CONCLUSIONS: This study provides the first evidence in humans regarding the effects of different modes of MV (controlled, assisted, and spontaneous) on diaphragm myofiber damage, and shows that diaphragm inactivity during mechanical ventilation is associated with the development of VIDD.

Head movement measurement: An alternative method for posturography studies.

The present study evaluated the measurement of head movements as a valid method for postural emotional studies using the comparison of simultaneous recording of center of pressure (COP) sway as criterion. Thirty female students viewed a set of 12 pleasant, 12 unpleasant and 12 neutral pictures from the International Affective Picture System, repeated twice, using a block presentation procedure while standing on a force platform (AMTI AccuSway). Head movements were recorded using a webcam (©KPC139E) located in the ceiling in line with the force platform and a light-emitting diode (LED) placed on the top of the head. Open source software (CvMob 3.1) was used to process the data. High indices of correlation and coherence between head and COP sway were observed. In addition, pleasant pictures, compared with unpleasant pictures, elicited greater body sway in the anterior-posterior axis, suggesting an approach response to appetitive stimuli. Thus, the measurement of head movement can be an alternative or complementary method to recording COP for studying human postural changes.

Prognostic value of brachioradialis muscle oxygen saturation index and vascular occlusion test in septic shock patients / Valor pronóstico del índice de saturación de oxígeno y el test de oclusión vascular en el músculo braquiorradial de pacientes con shock séptico

OBJECTIVES: To compare rSO2 (muscle oxygen saturation index) static and dynamic variables obtained by NIRS (Near Infrared Spectroscopy) in brachioradialis muscle of septic shock patients and its prognostic implications. DESIGN: Prospective and observational study. SETTING: Intensive care unit. SUBJECTS: Septic shock patients and healthy volunteers. Interventions: The probe of a NIRS device (INVOS 5100) was placed on the brachioradialis muscle during a vascular occlusion test (VOT). VARIABLES: Baseline, minimum and maximum rSO2 values, deoxygenation rate (DeOx), reoxygenation slope (ReOx) and delta value. RESULTS: Septic shock patients (n = 35) had lower baseline rSO2 (63.8 ± 12.2 vs. 69.3 ± 3.3%, p < 0.05), slower DeOx (-(-0.54 ± 0.31 vs. -0.91 ± 0.35%/s, p = 0.001), slower ReOx (2.67 ± 2.17 vs. 9.46 ± 3.5%/s, p<0.001) and lower delta (3.25 ± 5.71 vs. 15.1 ± 3.9%, p < 0.001) when compared to healthy subjects (n=20). Among septic shock patients, non-survivors showed lower baseline rSO2 (57.0 ± 9.6 vs. 69.8 ± 11.3%, p = 0.001), lower minimum rSO2 (36.0 ± 12.8 vs. 51.3±14.8%, p < 0.01) and lower maximum rSO2 values (60.6 ± 10.6 vs. 73.3 ± 11.2%, p < 0.01). Baseline rSO2 was a good mortality predictor (AUC 0.79; 95% CI: 0.63-0.94, p < 0.01). Dynamic parameters obtained with VOT did not improve the results. CONCLUSION: Septic shock patients present an important alteration of microcirculation that can be evaluated by NIRS with prognostic implications. Monitoring microvascular reactivity in the brachioradialis muscle using VOT with our device does not seem to improve the prognostic value of baseline rSO2

OBJETIVO: Comparar las variables microcirculatorias estáticas y dinámicas obtenidas mediante espectroscopia cercana al infrarojo en el músculo braquiorradial de pacientes con shock séptico y sus implicaciones pronósticas. DISEÑO: Estudio prospectivo y observacional. ÁMBITO: Unidad de Cuidados Intensivos. PACIENTES: Pacientes con shock séptico y voluntarios sanos. Intervenciones: En el músculo braquioradial de todos los sujetos se realizaron mediciones NIRS (del inglés Near Infrared Spectroscopy) durante un test de oclusión vascular. Variables: Valores rSO2 basal, mínimo y máximo, pendiente de desoxigenación, pendiente de reoxigenación y valor delta. Resultados: Los pacientes con shock séptico (n = 35) presentaron unos valores basales de rSO2 más bajos (63,8 ± 12,2 frente a 69,3 ± 3,3%; p< 0,05), una pendiente de desoxigenación y reoxigenación más lenta (-0,54 ± 0,31 frente a -0,91 ± 0,35 %/s, p = 0,001; 2,67 ± 2,17 frente a 9,46 ± 3,5%/s, p < 0,001) y un delta menor (3,25±5,71 frente a 15,1 ± 3,9%; p < 0,001) en comparación con los sujetos sanos (n = 20). De los pacientes con shock séptico, los no supervivientes presentaron unos valores basales de rSO2 más bajos (57,0 ± 9,6 frente a 69,8 ± 11,3%; p = 0,001), de rSO2 mínimo y máximo igualmente inferiores (36,0 ± 12,8 frente a 51,3 ± 14,8%; p < 0,01; 60,6 ± 10,6 frente a 73,3 ± 11,2%; p < 0,01). El rSO2 basal fue un buen factor predictivo de mortalidad (AUC 0,79; IC del 95%: 0,63-0,94; p < 0,01). Los parámetros dinámicos obtenidos mediante la prueba de oclusión vascular no mejoraron los resultados. Conclusión: Los pacientes con shock séptico presentan una alteración importante de la microcirculación que se puede evaluar mediante la espectroscopia cercana al infrarrojo con implicaciones pronósticas. La monitorización de la reactividad microvascular en el músculo braquiorradial mediante el test de oclusión vascular con nuestro dispositivo no parece mejorar el valor pronóstico de la rSO2 basal

Prognostic value of brachioradialis muscle oxygen saturation index and vascular occlusion test in septic shock patients.

OBJECTIVES: To compare rSO2 (muscle oxygen saturation index) static and dynamic variables obtained by NIRS (Near Infrared Spectroscopy) in brachioradialis muscle of septic shock patients and its prognostic implications. DESIGN: Prospective and observational study. SETTING: Intensive care unit. SUBJECTS: Septic shock patients and healthy volunteers. INTERVENTIONS: The probe of a NIRS device (INVOS 5100) was placed on the brachioradialis muscle during a vascular occlusion test (VOT). VARIABLES: Baseline, minimum and maximum rSO2 values, deoxygenation rate (DeOx), reoxygenation slope (ReOx) and delta value. RESULTS: Septic shock patients (n=35) had lower baseline rSO2 (63.8±12.2 vs. 69.3±3.3%, p<0.05), slower DeOx (-0.54±0.31 vs. -0.91±0.35%/s, p=0.001), slower ReOx (2.67±2.17 vs. 9.46±3.5%/s, p<0.001) and lower delta (3.25±5.71 vs. 15.1±3.9%, p<0.001) when compared to healthy subjects (n=20). Among septic shock patients, non-survivors showed lower baseline rSO2 (57.0±9.6 vs. 69.8±11.3%, p=0.001), lower minimum rSO2 (36.0±12.8 vs. 51.3±14.8%, p<0.01) and lower maximum rSO2 values (60.6±10.6 vs. 73.3±11.2%, p<0.01). Baseline rSO2 was a good mortality predictor (AUC 0.79; 95%CI: 0.63-0.94, p<0.01). Dynamic parameters obtained with VOT did not improve the results. CONCLUSION: Septic shock patients present an important alteration of microcirculation that can be evaluated by NIRS with prognostic implications. Monitoring microvascular reactivity in the brachioradialis muscle using VOT with our device does not seem to improve the prognostic value of baseline rSO2.

Normativa SEPAR sobre disfunción muscular de los pacientes con enfermedad pulmonar obstructiva crónica / Guidelines for the evaluation and treatment of muscle dysfunction in patients with chronic obstructive pulmonary disease

La disfunción muscular de pacientes con enfermedad pulmonar obstructiva crónica (EPOC) constituye una de las comorbilidades más importantes, con repercusiones negativas en su capacidad de ejercicio y calidad de vida. En la presente normativa se ha resumido la literatura publicada más recientemente sobre los diferentes aspectos del tema y se ha utilizado también la escala Grading of Recommendations Assessment, Development, and Evaluation (GRADE) de recomendaciones sobre el grado de evidencia de las diferentes propuestas de la normativa. Respecto a una población control, se estima que en un tercio de los pacientes EPOC la fuerza del cuádriceps es un 25% inferior incluso en estadios precoces de su enfermedad. Aunque tanto los músculos respiratorios como los de las extremidades están alterados, estos últimos suelen verse mayormente afectados. Diversos factores y mecanismos biológicos están involucrados en la disfunción muscular de los pacientes. Se proponen diversas pruebas para evaluar y diagnosticar el grado de afectación de los músculos respiratorios y de las extremidades (periféricos), así como identificar la capacidad de esfuerzo de los pacientes (prueba de marcha de 6min y cicloergometría). Se describen también las posibles estrategias terapéuticas vigentes que incluyen las diversas modalidades de entrenamiento y de soporte farmacológico y nutricional.(AU)

In patients with chronic obstructive pulmonary disease (COPD), skeletal muscle dysfunction is a major comorbidity that negatively impacts their exercise capacity and quality of life. In the current guidelines, the most recent literature on the various aspects of COPD muscle dysfunction has been included. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) scale has been used to make evidence-based recommendations on the different features. Compared to a control population, one third of COPD patients exhibited a 25% decline in quadriceps muscle strength, even at early stages of their disease. Although both respiratory and limb muscles are altered, the latter are usually more severely affected. Numerous factors and biological mechanisms are involved in the etiology of COPD muscle dysfunction. Several tests are proposed in order to diagnose and evaluate the degree of muscle dysfunction of both respiratory and limb muscles (peripheral), as well as to identify the patients' exercise capacity (six-minute walking test and cycloergometry). Currently available therapeutic strategies including the different training modalities and pharmacological and nutritional support are also described.(AU)

Intensive care practices in brain death diagnosis and organ donation.

We conducted a multicentre study of 1844 patients from 42 Spanish intensive care units, and analysed the clinical characteristics of brain death, the use of ancillary testing, and the clinical decisions taken after the diagnosis of brain death. The main cause of brain death was intracerebral haemorrhage (769/1844, 42%), followed by traumatic brain injury (343/1844, 19%) and subarachnoid haemorrhage (257/1844, 14%). The diagnosis of brain death was made rapidly (50% in the first 24 h). Of those patients who went on to die, the Glasgow Coma Scale on admission was ≤ 8/15 in 1146/1261 (91%) of patients with intracerebral haemorrhage, traumatic brain injury or anoxic encephalopathy; the Hunt and Hess Scale was 4-5 in 207/251 (83%) of patients following subarachnoid haemorrhage; and the National Institutes of Health Stroke Scale was ≥ 15 in 114/129 (89%) of patients with strokes. Brain death was diagnosed exclusively by clinical examination in 92/1844 (5%) of cases. Electroencephalography was the most frequently used ancillary test (1303/1752, 70.7%), followed by transcranial Doppler (652/1752, 37%). Organ donation took place in 70% of patients (1291/1844), with medical unsuitability (267/553, 48%) and family refusal (244/553, 13%) the main reasons for loss of potential donors. All life-sustaining measures were withdrawn in 413/553 of non-donors (75%).

Regional oxygen saturation index (rSO2) in brachioradialis and deltoid muscle. Correlation and prognosis in patients with respiratory sepsis

Objective. To compare oxygen saturation index (rSO2) obtained simultaneously in two different brachial muscles. Design. Prospective and observational study. Setting. Intensive care unit. Patients. Critically ill patients with community-acquired pneumonia. Interventions. Two probes of NIRS device (INVOS 5100) were simultaneously placed on the brachioradialis (BR) and deltoid (D) muscles. Variables. rSO2 measurements were recorded at baseline (ICU admission) and at 24h. Demographic and clinical variables were registered. Pearson's correlation coefficient was used to assess the association between continuous variables. The consistency of the correlation was assessed using the intraclass correlation coefficient (ICC) and Bland–Altman plot. The predictive value of the rSO2 for mortality was calculated by ROC curve. Results. Nineteen patients were included with an ICU mortality of 21.1%. The rSO2 values at baseline and at 24h were significantly higher in D than in BR muscle. Values obtained simultaneously in both limbs showed a strong correlation and adequate consistency: BR (r=0.95; p<0.001; ICC=0.94; 95% CI: 0.90–0.96; p<0.001), D (r=0.88; p=0.01; ICC=0.88; 95% CI: 0.80–0.90; p>0.001) but a wide limit of agreement. Non-survivors had rSO2 values significantly lower than survivors at all times of the study. No patient with rSO2 >60% in BR died, and only 17.6% died with an rSO2 value >60% in D. Both muscles showed consistent discriminatory power for mortality. Conclusion. Both BR and D muscles were appropriate for measuring rSO2 (AU)

Objetivo. Comparar el índice de saturación tisular de oxígeno (rSO2) medido de forma simultánea en 2 diferentes músculos braquiales. Diseño. Estudio prospectivo, observacional. Ámbito. Servicio de Medicina Intensiva. Pacientes. Críticos con neumonía comunitaria. Intervenciones. Dos sensores con tecnología NIRS (INVOS™ 5100) fueron ubicados de forma simultánea en los músculos braquiorradial (BR) y deltoides (D). Variables. Las mediciones del rSO2 se efectuaron al ingreso (basal) y a las 24h. Se registraron los datos demográficos y clínicos. La correlación de Pearson se utilizó para estudiar la asociación entre variables continuas. La concordancia de la correlación fue valorada mediante el coeficiente de correlación intraclase (ICC) y el análisis de Bland-Altman. El valor predictivo de rSO2 para mortalidad fue calculado mediante curva ROC. Resultados. Se incluyeron 19 pacientes con una mortalidad de 21,1%. El valor basal y a las 24h de rSO2 fue significativamente mayor en D respecto del BR. Los valores obtenidos de forma simultánea en ambos miembros evidenciaron una buena correlación y una adecuada concordancia: BR (r=0,95; p<0,001. ICC=0,94; IC 95%: 0,90-0,96; p<0,001), D (r=0,88; p=0,01. ICC=0,88; IC 95%: 0,80-0,90; p<0,001), así como un amplio rango de concordancia. Los fallecidos presentaron valores de rSO2 significativamente menores que los supervivientes en todos los momentos del estudio. Ningún paciente con rSO2>60% en BR falleció, y solo el 17,6% fallecieron con un rSO2>60% en D. Ambos músculos evidenciaron un buen poder de discriminación para mortalidad. Conclusiones. Tanto el músculo BR como el D fueron apropiados para la medición del rSO2 (AU)

Regional oxygen saturation index (rSO2) in brachioradialis and deltoid muscle. Correlation and prognosis in patients with respiratory sepsis.

OBJECTIVE: To compare oxygen saturation index (rSO2) obtained simultaneously in two different brachial muscles. DESIGN: Prospective and observational study. SETTING: Intensive care unit. PATIENTS: Critically ill patients with community-acquired pneumonia. INTERVENTIONS: Two probes of NIRS device (INVOS 5100) were simultaneously placed on the brachioradialis (BR) and deltoid (D) muscles. VARIABLES: rSO2 measurements were recorded at baseline (ICU admission) and at 24h. Demographic and clinical variables were registered. Pearson's correlation coefficient was used to assess the association between continuous variables. The consistency of the correlation was assessed using the intraclass correlation coefficient (ICC) and Bland-Altman plot. The predictive value of the rSO2 for mortality was calculated by ROC curve. RESULTS: Nineteen patients were included with an ICU mortality of 21.1%. The rSO2 values at baseline and at 24h were significantly higher in D than in BR muscle. Values obtained simultaneously in both limbs showed a strong correlation and adequate consistency: BR (r=0.95; p<0.001; ICC=0.94; 95% CI: 0.90-0.96; p<0.001), D (r=0.88; p=0.01; ICC=0.88; 95% CI: 0.80-0.90; p>0.001) but a wide limit of agreement. Non-survivors had rSO2 values significantly lower than survivors at all times of the study. No patient with rSO2 >60% in BR died, and only 17.6% died with an rSO2 value >60% in D. Both muscles showed consistent discriminatory power for mortality. CONCLUSION: Both BR and D muscles were appropriate for measuring rSO2.

Acquired haemophilia A. First line treatment with calcineurin inhibitors and steroid pulses: a 10-year follow-up study.

Acquired haemophilia A (AH) is defined as the presence of autoantibodies or inhibitors against factor VIII (FVIII) with a clinical bleeding onset that can be life-threatening. Immunosuppressant therapy must be initiated rapidly to eradicate the inhibitor. Current treatments based on steroids plus cyclophosphamide or rituximab are quite effective, but with significant side-effects. Based on previous described AH cases treated with cyclosporine, with a good side-effect profile, we aimed at assessing prospectively a first-line calcineurin inhibitor based immunosuppressive therapy. We included a total of 11 patients affected with AH. Once diagnosed, pulse steroids and calcineurin inhibitors were started. Time to achieve sustained response (SR), defined as testing negative for inhibitor and with stable FVIII level >50%, immunosuppressant side-effects, and relapse of AH were evaluated. Eight patients received cyclosporine and three patients received tacrolimus. SR was achieved in 10 of 11 patients (90.9%) in a median time of 3 weeks (range 2-8 weeks), and none of them relapsed during a median follow-up time of 14 months (range 4-120). One major side-effect appeared (posterior encephalopathy) that forced to discontinue cyclosporine. Overall 5-year survival rate was 54.5%, with a total of five patients dying during the follow-up (mortality rate of 45.5%). These five patients had achieved SR and died because of complications of basal morbidities and/or senescence, not related to AH (bleeding) or to immunosuppressant's (infection) side-effects. Combination therapy of calcineurin inhibitors and pulse steroids seems clinically effective as a first-line treatment of AH.

Beta2-glycoprotein I gene polymorphisms Val247Leu and Trp316Ser in Spanish patients with primary antiphospholipid syndrome.

The significance of beta2-glycoprotein I (ß2GPI) polymorphisms in the production of anti-ß2GPI and other antiphospholipid autoantibodies (aPL) and in the pathogenesis of primary antiphospholipid syndrome (PAPS) is not well understood. We performed a study comparing the distribution of polymorphisms at codons 247 (Val247Leu) and 316 (Trp316Ser) of the ß2GPI gene in a Caucasian Spanish population of PAPS patients and healthy controls, and then making correlations with the development of anti-ß2GPI antibodies and other aPL and associated clinical manifestations. A total of 57 PAPS patients and 100 control subjects were included. In the analysis of Val247Leu polymorphism, alleles (V and L) and genotypes (V/V, V/L, L/L) were similarly distributed in PAPS patients and controls (P = 0.66 and P = 0.22, respectively). Regarding Trp316Ser polymorphism, we found a higher percentage of patients with respect to controls expressing S allele (11.4 vs. 5%, P = 0.02) and T/S genotype (22.8 vs. 10%, P = 0.02). However, when we compared T/T and T/S genotypes in PAPS patients, we found no differences regarding generation of anti-ß2GPI, other aPL and clinical manifestations favoring any genotype. Our findings suggest that among Spanish Caucasians, polymorphisms at codon 247 (Val247Leu) do not seem to influence PAPS pathogenesis. On the contrary, polymorphisms at codon 316 (Trp316Ser), by means of an increased S allele and T/S genotype presence in Spanish Caucasian patients, might play a role in the pathogenic development of PAPS, although mechanism would not involve an increased production of anti-ß2GPI and other aPL.

Evaluation of the respiratory muscles efficiency during an incremental flow respiratory test.

The aim of this study was to evaluate the respiratory muscles efficiency during a progressive incremental flow (IF) respiratory test in healthy and Chronic Obstructive Pulmonary Disease (COPD) subjects. To achieve this, the relationship between mouth Inspiratory Pressure (IP) increment, which is a measure of the force produced by respiratory muscles, and respiratory muscular activity increment, evaluated by means of Mechanomyografic (MMG) signals of the diaphragm muscle, was analyzed. Moreover, the correlation between the respiratory efficiency measure and the obstruction severity of the subjects was also examined. Data from two groups of subjects were analyzed. One group consisted of four female subjects (two healthy subjects and two moderate COPD patients) and the other consisted of ten male subjects (six severe and four very severe COPD patients). All subjects performed an easy IF respiratory test, in which small IP values were reached. We have found that there is an increase of amplitude and a displacement towards low frequencies in the MMG signals when the IP increases. Furthermore, it has also been found that respiratory muscles efficiency is lower when greater the obstructive severity of the patients is, and it is lower in women than in men. These results suggest that the information provided by MMG signals could be used to evaluate the muscular efficiency in healthy and COPD subjects.

Interpretation of the approximate entropy using fixed tolerance values as a measure of amplitude variations in biomedical signals.

A new method for the quantification of amplitude variations in biomedical signals through moving approximate entropy is presented. Unlike the usual method to calculate the approximate entropy (ApEn), in which the tolerance value (r) varies based on the standard deviation of each moving window, in this work ApEn has been computed using a fixed value of r. We called this method, moving approximate entropy with fixed tolerance values: ApEn(f). The obtained results indicate that ApEn(f) allows determining amplitude variations in biomedical data series. These amplitude variations are better determined when intermediate values of tolerance are used. The study performed in diaphragmatic mechanomyographic signals shows that the ApEn(f) curve is more correlated with the respiratory effort than the standard RMS amplitude parameter. Furthermore, it has been observed that the ApEn(f) parameter is less affected by the existence of impulsive, sinusoidal, constant and Gaussian noises in comparison with the RMS amplitude parameter.

Reference values of respiratory and peripheral muscle function in rats.

Skeletal muscle dysfunction is a common systemic manifestation in several prevalent diseases. Predictive values are useful tools for the diagnosis and prognosis of diseases. In experimental animals, no reference values of muscle function evaluation have been so far reported. The objective was to obtain predictive values of maximal inspiratory pressure (MIP) and grip strength measurements in healthy rats. In 70 healthy rats, MIP and grip strength were measured in vivo weekly for five consecutive weeks using non-invasive methodologies. Three ranges of rat body weights (250-299, 300-349 and 350-399 g) and lengths (37.0-41.0, 41.1-42.0 and 42.1-44.0 cm) were established. MIP and grip strength measurements falling within the ranges of weight 350-399 and 300-349 g and length 42.1-44.0 cm were significantly greater than values falling within 250-299 g and 37.0-41.0 cm ranges respectively. Specific weight- and length-percentile distributions for MIP and grip strength measurements were calculated. As significant direct correlations were observed between rat weights and lengths and either MIP or grip strength measurements, regression equations relating all these variables were also determined. Skeletal muscle dysfunction is frequently associated with highly prevalent conditions. The significant predictive equations described for both MIP and grip strength measurements will enable scientists to better estimate the respiratory and peripheral muscle dysfunctions of laboratory animals, especially when conducting follow-up and/or intervention investigations.

[Drug interaction caused by communication problems. Rhabdomyolysis due to a combination of itraconazole and simvastatin]. / Geneesmiddelinteractie door communicatieproblemen. Rabdomyolyse door de combinatie van itraconazol en simvastatine.

A 58-year-old man, who spoke very little Dutch, had various symptoms and used several drugs including simvastatin. He was prescribed itraconazole for onychomycosis. Simvastatin was concurrently replaced with pravastatin to prevent drug interactions. However, the interaction still occurred when the pravastatin ran out, and the patient resumed taking simvastatin on his own initiative. Myalgia and muscle weakness developed after one week. The general practitioner found a strongly elevated creatine kinase level in the blood. The patient required hospitalisation for severe rhabdomyolysis. He was treated with an infusion of an ample quantity of physiological saline solution and made a full recovery. Due to the elevated risk of toxic interactions, doctors should beware of communication problems in complex patients and avoid new prescriptions not strictly required.

Echocardiography at diagnosis of antiphospholipid syndrome provides prognostic information on valvular disease evolution and identifies two subtypes of patients.

The evolution of valvular disease in antiphospholipid syndrome (APS) is barely known. In order to evaluate whether the presence or absence of valvular disease at the time of diagnosis of APS, assessed by an initial echocardiogram, predicts its subsequent evolution, we performed a prospective cohort study. We included 53 patients with APS. An initial transthoracic echocardiogram was performed on patients at the time of diagnosis of APS. Serial echocardiograms were conducted along a 12-year follow-up. Final echocardiograms were used for comparative purposes. We started with 29 patients (54%) with and 24 (45%) without valvulopathy at initial echo. At the final echocardiogram, 27 of 29 patients with initial valvulopathy continued to have valvular disease (a 93% observed likelihood), and 22 of 24 patients without initial valvulopathy demonstrated an absence of valvular disease (a 91% observed likelihood). Patients with valvulopathy in comparison with those without presented more arterial thrombotic events (69% vs. 20%, P < 0.001), atherosclerotic risk factors (62% vs. 29%, P = 0.01), livedo (48% vs. 16%, P = 0.01) and migraine (41% vs. 12%, P = 0.02). We have identified two subtypes of APS patients with and without valvulopathy by defining differential clinical features and with little crossover in valvular involvement over a long follow-up period, giving a high prognostic value to the initial echocardiographic assessment.