Impact of a series of measures for optimisation hospital code stroke care on door-to-needle times.

INTRODUCTION: Time continues to be a fundamental variable in reperfusion treatments for acute ischaemic stroke. Despite the recommendations made in clinical guidelines, only around one-third of these patients receive fibrinolysis within 60minutes. In this study, we describe our experience with the implementation of a specific protocol for patients with acute ischaemic stroke and evaluate its impact on door-to-needle times in our hospital. METHODS: Measures were gradually implemented in late 2015 to shorten stroke management times and optimise the care provided to patients with acute ischaemic stroke; these measures included the creation of a specific on-call neurovascular care team. We compare stroke management times before (2013-2015) and after (2017-2019) the introduction of the protocol. RESULTS: The study includes 182 patients attended before implementation of the protocol and 249 attended after. Once all measures were in effect, the overall median door-to-needle time was 45minutes (vs 74 minutes before, a 39% reduction; P<.001), with 73.5% of patients treated within 60minutes (a 47% increase; P<.001). Median overall time to treatment (onset-to-needle time) was reduced by 20minutes (P<.001). CONCLUSIONS: The measures included in our protocol achieved a significant, sustained reduction in door-to-needle times, although there remains room for improvement. The mechanisms established for monitoring outcomes and for continuous improvement will enable further advances in this regard.

Recommendations for vaccination in patients with multiple sclerosis who are eligible for immunosuppressive therapies: Spanish consensus statement. / Recomendaciones para la vacunación en pacientes con esclerosis múltiple candidatos a terapias inmunosupresoras: documento de consenso español.

BACKGROUND: The recent development of highly effective treatments for multiple sclerosis (MS) and the potential risk of infectious complications require the development of prevention and risk minimisation strategies. Vaccination is an essential element of the management of these patients. This consensus statement includes a series of recommendations and practical scenarios for the vaccination of adult patients with MS who are eligible for highly effective immunosuppressive treatments. METHODOLOGY: A formal consensus procedure was followed. Having defined the scope of the statement, we conducted a literature search on recommendations for the vaccination of patients with MS and specific vaccination guidelines for immunosuppressed patients receiving biological therapy for other conditions. The modified nominal group technique methodology was used to formulate the recommendations. DEVELOPMENT: Vaccination in patients who are candidates for immunosuppressive therapy should be considered before starting immunosuppressive treatment providing the patient's clinical situation allows. Vaccines included in the routine adult vaccination schedule, as well as some specific ones, are recommended depending on the pre-existing immunity status. If immunosuppressive treatment is already established, live attenuated vaccines are contraindicated. For vaccines with a correlate of protection, it is recommended to monitor the serological response in an optimal interval of 1-2 months from the last dose.

Impact of a series of measures for optimisation hospital code stroke care on door-to-needle times. / Impacto en los tiempos puerta-aguja de un conjunto de medidas para optimizar la atención hospitalaria del código ictus.

INTRODUCTION: Time continues to be a fundamental variable in reperfusion treatments for acute ischaemic stroke. Despite the recommendations made in clinical guidelines, only around one-third of these patients receive fibrinolysis within 60minutes. In this study, we describe our experience with the implementation of a specific protocol for patients with acute ischaemic stroke and evaluate its impact on door-to-needle times in our hospital. METHODS: Measures were gradually implemented in late 2015 to shorten stroke management times and optimise the care provided to patients with acute ischaemic stroke; these measures included the creation of a specific on-call neurovascular care team. We compare stroke management times before (2013-2015) and after (2017-2019) the introduction of the protocol. RESULTS: The study includes 182 patients attended before implementation of the protocol and 249 attended after. Once all measures were in effect, the overall median door-to-needle time was 45minutes (vs 74 minutes before, a 39% reduction; P<.001), with 73.5% of patients treated within 60minutes (a 47% increase; P<.001). Median overall time to treatment (onset-to-needle time) was reduced by 20minutes (P<.001). CONCLUSIONS: The measures included in our protocol achieved a significant, sustained reduction in door-to-needle times, although there remains room for improvement. The mechanisms established for monitoring outcomes and for continuous improvement will enable further advances in this regard.

Functional Evaluation of the Visual Pathway in Patients with Multiple Sclerosis Using a Multifunction Stimulator Monitor.

OBJECTIVES: To assess the capability of the vision monitor unit Monpack One of detecting visual function alterations in patients with multiple sclerosis (MS) and to evaluate the correlation between structural retinal parameters and functional measurements obtained with this device. METHODS: Forty-eight patients with MS and 46 healthy controls were included in a cross-sectional study. All participants underwent a complete functional evaluation of the visual pathway, which included low-contrast visual acuity (LCVA), contrast sensitivity vision (CSV), automated perimetry, multifocal visual evoked potentials (mfVEPs), and pattern electroretinogram (ERG). All tests were performed using the vision monitor unit Monpack One (Metrovision, France), a multifunction stimulator device. Retinal structural measurements were obtained in all subjects using Triton swept source optical coherence tomography (Topcon, Japan). RESULTS: Patients with MS presented reduced low-contrast VA (p < 0.001) and reduced CSV at medium (p=0.001, p=0.013) and low (p=0.001, p=0.002) spatial frequencies. All visual field parameters were found to be altered in MS patients compared with controls (≤0.001). Patients with MS presented lower amplitude of the P100 waveform of the mfVEP in areas corresponding to central (p < 0.001), inferonasal (p=0.001), and inferotemporal (p=0.003) retina. The pattern ERG did not show significant differences. Significant correlations were observed between structural retinal measurements and functional parameters, especially between the inner macular areas and measurements corresponding to contrast sensitivity and perimetry indexes. CONCLUSIONS: Patients with MS present visual dysfunction detectable with the vision monitor unit Monpack One. This device may be a fast and useful tool to provide a full evaluation of axonal damage in patients with multiple sclerosis.

Trends in stroke hospitalisation rates and in-hospital mortality in Aragon, 1998-2010. / Tendencia de las tasas de hospitalización y de letalidad hospitalaria de la enfermedad cerebrovascular aguda en Aragón en el periodo 1998-2010.

INTRODUCTION: Despite the impact of cerebrovascular disease (CVD) on global health, its morbidity and time trends in Spain are not precisely known. OBJECTIVE: The purpose of our study was to characterise the epidemiology and trends pertaining to stroke in Aragon over the period 1998-2010. METHODS: We conducted a retrospective, descriptive study using the data of the Spanish health system's Minimum Data Set and included all stroke patients admitted to acute care hospitals in Aragon between 1 January 1998 and 31 December 2010. We present data globally and broken down by stroke subtype, sex, and age group. RESULTS: The number of cases increased by 13% whereas age- and sex-adjusted hospitalisation rates showed a significant decrease for all types of stroke (mean annual decrease of 1.6%). Men and women in younger age groups showed opposite trends in hospitalisation rates for ischaemic stroke. Case fatality rate at 28 days (17.9%) was higher in patients with intracerebral haemorrhage (35.8%) than in those with subarachnoid haemorrhage (26.2%) or ischaemic stroke (13%). CVD case fatality showed a mean annual decline of 2.8%, at the expense of the fatality rate of ischaemic stroke, and it was more pronounced in men than in women. DISCUSSION: Understanding stroke epidemiology and trends at the regional level will help establish an efficient monitoring system and design appropriate strategies for health planning.

[Relationship between homocysteinaemia and sympathetic skin response in Parkinson's disease]. / Relacion entre homocisteinemia y respuesta simpaticocutanea en la enfermedad de Parkinson.

INTRODUCTION: High levels of homocysteine linked to treatment with levodopa have been observed in patients with Parkinsons disease (PD). Our aim was to assess the influence of serum homocysteine levels and other PD-related on the sympathetic skin response. PATIENTS AND METHODS: An observational, cross-sectional study was conducted that consecutively included patients with PD. We unilaterally assessed the sympathetic skin response in the upper limbs. We measured the influence of PD severity (measured by the Hoehn and Yahr and the Schwab and England scales, and the Unified Parkinson Disease Rating Scale) and blood homocysteine, vitamin B12 and folic acid levels on the latency and amplitude of the sympathetic skin response. RESULTS: A total of 78 patients were enrolled, and all achieved a sympathetic skin response. In the bivariate analysis, latency was significantly correlated with age, age at PD onset and homocysteinaemia levels. The presence of hyper-homocysteinemia was associated with a longer latency. The amplitude was only correlated with the score on the Schwab and England scale. In the multivariate analysis, age was the only variable that showed a significant association with the latency duration and homocysteine levels. CONCLUSION: A direct association could not be established between the increase in homocysteinaemia levels and sympathetic skin response dysfunction in PD. The results of the multivariate analysis suggest that latency prolongation in elderly patients could be due to the fact that these patients have higher blood levels of homocysteinaemia.

TITLE: Relacion entre homocisteinemia y respuesta simpaticocutanea en la enfermedad de Parkinson.Introduccion. En la enfermedad de Parkinson (EP) se han observado niveles elevados de homocisteina en relacion con el tratamiento con levodopa. Nuestro objetivo ha sido valorar su influencia y la de otras variables relacionadas con la propia EP sobre la respuesta simpaticocutanea. Pacientes y metodos. Estudio observacional, transversal, en el que se incluyo de forma consecutiva a pacientes con EP. Se valoro la respuesta simpaticocutanea de forma unilateral en los miembros superiores, y se determino la influencia de la gravedad de la EP segun la Unified Parkinson Disease Rating Scale, y las escalas de Hoehn y Yahr y de Schwab y England, y de los niveles sanguineos de homocisteina, vitamina B12 y acido folico sobre la latencia y amplitud de la respuesta simpaticocutanea. Resultados. Se incluyo a 78 pacientes. La respuesta simpaticocutanea se obtuvo en todos ellos. En el analisis bivariante, la latencia se correlaciono significativamente con la edad, con la edad de inicio de la EP y con los niveles de homocisteina. La presencia de hiperhomocisteinemia se relaciono con una latencia mas prolongada. La amplitud solo se correlaciono con la puntuacion en la escala de Schwab y England. En el analisis multivariante, la edad fue la unica variable que demostro una asociacion significativa tanto con la duracion de la latencia como con los niveles de homocisteina. Conclusion. No pudo establecerse una asociacion directa entre el aumento de homocisteinemia y la disfuncion de la respuesta simpaticocutanea. Los resultados del analisis multivariante sugieren que la prolongacion de la latencia en los pacientes de una mayor edad podria deberse a que estos presentan unos mayores niveles sanguineos de homocisteina.

Effect of optic neuritis on progressive axonal damage in multiple sclerosis patients.

OBJECTIVE: The objective of this research was to study the effect of optic neuritis (ON) on axonal damage in multiple sclerosis (MS) patients. Specifically, we compared changes over 2 years in the retinal nerve fibre layer (RNFL) between affected and contralateral eyes in MS patients with a prior history of ON. METHODS: Thirty-four patients with one unilateral definitive episode of ON were included and underwent a complete ophthalmic examination, optical coherence tomography (OCT), scanning laser polarimetry, visual evoked potentials (VEP) and pattern electroretinogram (pERG). All patients were re-evaluated at 12 and 24 months. Parameters were compared between ON-affected and contralateral eyes in an initial exploration and over the course of the follow-up. Correlations between parameter changes were analysed. RESULTS: RNFL thickness and functional parameters showed more affection in ON eyes (p ≤ 0.05), but changes in measurements during the study were similar between both groups of eyes. CONCLUSIONS: Progressive axonal loss can be detected in the optic nerve, but ON is not a risk factor for increased chronic damage in MS patients without ophthalmic relapses. Loss of the RNFL is caused by progressive degeneration associated with the disease.

[Effect of treatment in loss of retinal nerve fibre layer in multiple sclerosis patients]. / Influencia del tratamiento en la pérdida de fibras nerviosas de la retina en pacientes con esclerosis múltiple.

OBJECTIVE: To evaluate the effect of pathogenic treatments in the reduction of the retinal nerve fibre layer (RNFL) in patients with Multiple Sclerosis (MS) by means of ocular imaging technologies. MATERIAL AND METHODS: A total 155 eyes of 79 patients with MS were enrolled in this study. All patients underwent a complete ophthalmic examination including best corrected visual acuity using Snellen chart, colour vision using Ishihara pseudoisochromatic plates, visual field examination, optical coherence tomography (OCT), scanning laser polarimetry (GDx) and visual evoked potentials. The patients were re-evaluated after a one year period and changes were assessed in order to detect differences between treatments using the Anova statistical test. The patients were divided into four groups: 1) Patients without treatment, 2) Patients treated with interferon beta-1a, 3) Subjects who received interferon beta-1b, 4) Patients treated using glatiramer acetate. RESULTS: There were no statistically significant differences between patients with or without treatment and between the four groups (P>0.05, t test), but functional and structural parameters showed greater loss in RNFL thickness in non-treated patients. Temporal quadrant RNFL thickness measured by OCT was the parameter with the highest variation (reduction of 4.97µm in patients without treatment vs 1.08µm in treated patients). CONCLUSIONS: MS pathogenic treatment may be a protective factor in the RNFL loss that is associated to the disease progression. More studies are needed.

Correlation between functional and structural assessments of the optic nerve and retina in multiple sclerosis patients.

OBJECTIVE: The aim of this study was to evaluate the correlation between functional eye examinations (visual evoked potentials: VEPs; pattern electroretinogram: PERG) and structural measurements of the optic nerve (optical coherence tomography: OCT; scanning laser polarimetry: GDx) in patients with multiple sclerosis (MS). METHODS: Patients with definite MS and disease-free controls were enrolled in the study. VEPs and PERG were recorded in all subjetcs. Ophthalmologic examination, including visual acuity, visual field determination, OCT and GDx were performed. RESULTS: Nineteen MS patients and 19 age- and sex-matched controls were included in the study. Significant differences between both groups were observed with respect to VEP (P100 latency and amplitude), PERG (N95 amplitude and N95/P50 ratio) and OCT parameters (average, temporal and macular volume). There were a statistically significant correlation between VEP or PERG parameters and OCT or GDx results. CONCLUSIONS: In MS patients, axonal loss in ganglion cells can be detected with OCT and GDx. PERG is a useful complementary tool to identify this damage.

[Atrophy of the retinal nerve fibre layer in multiple sclerosis patients. Prospective study with two years follow-up]. / Atrofia de la capa de fibras nerviosas de la retina en pacientes con esclerosis múltiple. Estudio prospectivo con dos años de seguimiento.

OBJECTIVE: To evaluate the changes over two years in the retinal nerve fibre layer (RNFL) of patients with multiple sclerosis (MS). To compare the ability of optical coherence tomography (OCT), scanning laser polarimetry (GDx), visual evoked potentials (VEP) and visual field examination to detect axonal loss in these patients. MATERIAL AND METHODS: Fifty eyes of MS patients without episodes or optic neuritis during follow-up were enrolled in this study. All patients underwent a complete ophthalmic examination that included visual acuity (VA), colour vision, refractive evaluation, visual field examination, OCT, GDx and VEP. All the patients were re-evaluated over a period of 12 and 24 months. Correlations between parameters were analysed by Pearson's test. RESULTS: There were changes in the RNFL thickness in MS patients with a 12 and 24-month follow-up. Differences between baseline and 2-year evaluation were statistically significant (p ≤ 0.05, t test) in the mean, superior and inferior RNFL thickness and macular volume provided by OCT, while no significant differences were found using functional parameters (VA, colour vision, visual field and VEP) and GDx. The greater differences were obtained in the inferior RNFL thickness (113.67 frente a 105.39 µm, p < 0.001). Correlations were observed between structural parameters using GDx and TCO. CONCLUSIONS: Progressive axonal loss can be detected in the optic nerve of MS patients. Measurements provided by TCO are useful tools to evaluate structural abnormalities in the RNFL and changes in macular volume, however these changes were not detected using functional tests or GDx.

[Quality as management tool. Actions to improve efficiency in neurological care]. / La calidad como herramienta de gestión. Actuaciones para mejorar la eficiencia en la atención neurológica.

INTRODUCTION: Quality of care involves meeting the needs and expectations of patients with the lowest consumption of resources and in accordance with scientific knowledge. In this context it is important to know if the changes in medical care procedures based on scientific and technical aspects of the quality positively impacts both efficiency measures and perceived quality. METHODS: Prospective study carried out during the 2000-2006 period at the neurology department of a public hospital with has 1303 beds. Changes in medical care introduced: adequacy of a high resolution hospitalization zone, setting up of three care pathways (transient ischemic attach [TIA], multiple sclerosis exacerbation and first epileptic seizure) and practice guidelines for stroke, and implementation of neurological care at the emergency department. RESULTS: There has been an increase in the number of patients treated in the emergency department of the hospital (17%), although the number of admissions has stabilized. In the neurology department, the number of admissions has decreased by 20%, especially those arising from TIA (decrease by 47%), the average stay has been reduced by 30% (especially in demyelinating and vascular disease, which has fallen by 50%). Adjusted average length of stay has remained below 1 and the complexity index above 1. Satisfaction with the information and health care has undergone little change. CONCLUSIONS: The changes in clinical practice to improve the quality of care have been associated with improvements in the efficiency indicators but not in patient satisfaction. The improvement in the perceived quality probably requires specific actions.

[Pseudoballism secondary to spinal trauma]. / Seudobalismo secundario a traumatismo medular.

INTRODUCTION: Ballism is a rare movement disorder that presents with violent and wide amplitude flinging movements of the limbs, mainly caused by injury in the contralateral subthalamic nucleus or its afferent or efferent connections. CLINICAL CASE: We describe the case of a 50-year old male who had ballistic movements after a cervical trauma. He subsequently developed choreoathetoid movements and a distonic attitude in the left upper limb later. A C2-C3 sensory level and proprioceptive loss in this limb were the main findings in the examination. The cervical magnetic resonance showed a transverse linear spinal lesion at C1 level that affected most of its section. CONCLUSIONS: This case stands outs because of the wide abnormal movements spectrum secondary to spinal proprioceptive pathway injury: ballistic, choreoathetoid, and distonic movements. Choreoathetoid movements occurring in association with loss of propioception have been called pseudochoreoathetosis. We propose the term pseudoballism to define the movements that were observed during the acute phase in this patient.

[Importance and factors related to chronic fatigue in multiple sclerosis]. / Importancia y factores relacionados con la fatiga crónica en la esclerosis múltiple.

INTRODUCTION: The importance of fatigue in multiple sclerosis (MS) is determined by its high frequency and it is an important cause of disability. OBJECTIVE: To determine factors that are related to the presence of chronic fatigue in patients with MS. PATIENTS AND METHODS: The series comprises patients with MS, consecutively attended in the demyelinizating diseases unit, who met the following criteria: clinically definite MS (RR or SP), MS duration of more than two years, and no relapses during the previous month. Analyzed variables were as follows: chronic fatigue, demographic data, functional systems, EDSS, ISS, ESS, disease activity, Hamilton, depression scale GHQ-28, PSQI, and interferon. Statistical study: bivariate and multivariate analysis by logistic regression. RESULTS: A hundred patients were included, 72 female and 28 male. Mean age was 39.27 years. Of the 100 patients 88 had RR disease and 12 SP disease. MS mean duration was 11.2 years. Mean EDSS 2.54. Chronic fatigue was 53 %. The presence of depression increased the probability of chronic fatigue 3.6 fold, and every point in PSQI-7 increases it 3.5 fold. CONCLUSION: Depression and the PSQI-7 subscale (day sleep dysfunction) are the only variables independently related to chronic fatigue in patients with MS.

[Sleep disorders in multiple sclerosis]. / Trastornos del sueño en la esclerosis múltiple.

INTRODUCTION: To determine the frequency of sleep disorders in multiple sclerosis (MS) patients and their relation with other manifestations of the disease. METHODS: Selected patients had clinically definite MS (relapsing-remitting and secondary progressive forms) and duration of the disease over two years. They were serially evaluated at the unit of demyelinating diseases of a third level hospital. The following scales were applied: the Pittsburgh Sleep Quality Index, the Hamilton Depression Rating Scale, EDSS, ISS and ESS. Statistical analysis by means of non parametric test and logistic regression was carried out. RESULTS: One hundred patients were included (72% women and 28% males). Mean age was 39 years. Eighty eight were relapsing-remitting forms and the rest secondary progressive forms. Mean EDSS was: 2.5. Mean duration of evolution: 11.2 years. The prevalence of sleep disorders was 36%. Age, sex, evolutionary form, degree of disability and chronic fatigue did not relate with the sleep disorders in these patients. In the multivariant analysis by means of logistic regression, we found that every point more in Hamilton's scale multiplies the probability of presenting sleep disorders by 1.2. CONCLUSIONS: Depression is the only variable that independently relates, with the presence of sleep disorders in MS patients.

Corticosteroids, ibuprofen, and acetaminophen for IFNbeta-1a flu symptoms in MS: a randomized trial.

OBJECTIVE: To compare the efficacy of acetaminophen, ibuprofen, and prednisone in the treatment of interferon beta-1a (IFNbeta-1a) flu-like syndrome (FLS). METHODS: Patients with relapsing-remitting multiple sclerosis initiating treatment with IM IFNbeta-1a were randomized in a multicenter, randomized, double-blind, controlled trial to receive acetaminophen 500 mg before and 6 and 12 hours after each injection, ibuprofen 400 mg before and 6 and 12 hours after each injection, or prednisone 60 mg daily for 1 week, plus tapering. Patients were instructed to keep a daily diary of fever severity, myalgia, chills, headache, and asthenia for 27 days. The sum of the scores of individual symptoms was used to obtain a daily FLS index. The primary outcome was the FLS index area under the curve (AUC) corrected by the number of measurement days. RESULTS: Eighty-four patients were randomized at 11 hospitals: acetaminophen (n = 28), ibuprofen (n = 28), and corticosteroids (n = 28). No differences were detected between treatments in the mean AUC of the FLS index. With limitation of the analysis to the days of IM IFNbeta-1a injection, differences favoring ibuprofen were observed in the mean FLS index (p = 0.0007). CONCLUSIONS: No prophylactic treatment for flu-like syndrome seems to be superior to another in terms of overall well-being during the first month of IM IFNbeta-1a therapy. However, ibuprofen confers better control of symptoms immediately following IM IFNbeta-1a injection.

[Modifications of the lipid metabolism induced by interferon beta in multiple sclerosis patients and its relationship with the disease activity]. / Modificaciones del metabolismo lipídico inducidas por interferón beta en los pacientes con esclerosis múltiple y su relación con la actividad de la enfermedad.

INTRODUCTION: It has been recently suggested that total cholesterol and low density lipoproteins (LDL) levels can behave as biological markers of activity in demyelinating diseases. Thus, our aim has been to describe the modifications of the plasma levels of total cholesterol and triglyceride due to treatment with interferon-beta in multiple sclerosis (MS) patients and to determine their relationship with the disease activity. PATIENTS AND METHODS: Study of the follow-up of MS patients under treatment with interferon-beta. Clinical and analytical controls were performed before initiating treatment and than at 1, 3, 6, 12, 18 and 24 months of its initiation. RESULTS: Fifty six patients have been studied, 41 of them women. Mean age was 37.4 years. Fifty were relapsing- remitting forms and the rest secondary progressive forms. The mean plasma levels of triglyceride increased and total cholesterol levels diminished during the 24 months of treatment with interferon, mainly in the first 3 months. No statistically significant relationship was found between disease activity and mean plasma levels of triglyceride and total cholesterol before the beginning of the treatment and during the period of follow-up. CONCLUSIONS: Treatment with interferon-beta in the MS patients originates changes in the plasma lipid profile, but neither these changes nor the plasma lipid levels before the treatment behave as biological markers of disease activity.

[Predicting factors for depression in multiple sclerosis]. / Factores predictores de depresión en la esclerosis múltiple.

INTRODUCTION: We assess frequency and intensity of depression in multiple sclerosis (MS) patients, the degree at which it is detected and its relationship to the treatment with beta interferon and other clinical and paraclinical factors. METHODS: The series comprises MS patients, seen in the Demyelinating Disease Unit of a tertiary hospital, who fulfilled the following criteria: clinically defined MS (relapsing-remitting or secondary progressive), disease duration greater than two years and absence of relapses during the month prior to the study. The variables analyzed were detection and assessment of depression with the Hamilton Depression Scale, general demographic data, functional systems, EDSS, ISS, ESS, Pittsburgh Sleep Quality Index, interferon treatment, chronic fatigue and a series of analytical variables. Statistical study: both variate and multivariate analysis by logistic regression. RESULTS: 100 patients (72 female and 28 male). Mean age: 39.27 years. RR MS form, 88%, and SPMS form, 12 %. Mean evolution time, 11.2 years. Mean EDSS, 2.54. Depression was present in 44 % of the patients in our group and was not related to neurological degree of disability, disease evolution time, clinical form, interferon treatment, or to sleep disorders. However, depression was related to the presence of both chronic fatigue and ESS scores. CONCLUSIONS: Depression is common in MS patients and is associated with the presence of chronic fatigue and a worse social status.