Multiple sclerosis is linked to MAPKERK overactivity in microglia.

Reassessment of published observations in patients with multiple sclerosis (MS) suggests a microglial malfunction due to inappropriate (over)activity of the mitogen-activated protein kinase pathway ERK (MAPKERK). These observations regard biochemistry as well as epigenetics, and all indicate involvement of this pathway. Recent preclinical research on neurodegeneration already pointed towards a role of MAPK pathways, in particular MAPKERK. This is important as microglia with overactive MAPK have been identified to disturb local oligodendrocytes which can lead to locoregional demyelination, hallmark of MS. This constitutes a new concept on pathophysiology of MS, besides the prevailing view, i.e., autoimmunity. Acknowledged risk factors for MS, such as EBV infection, hypovitaminosis D, and smoking, all downregulate MAPKERK negative feedback phosphatases that normally regulate MAPKERK activity. Consequently, these factors may contribute to inappropriate MAPKERK overactivity, and thereby to neurodegeneration. Also, MAPKERK overactivity in microglia, as a factor in the pathophysiology of MS, could explain ongoing neurodegeneration in MS patients despite optimized immunosuppressive or immunomodulatory treatment. Currently, for these patients with progressive disease, no effective treatment exists. In such refractory MS, targeting the cause of overactive MAPKERK in microglia merits further investigation as this phenomenon may imply a novel treatment approach.

Validation of the Emergency Severity Index (ESI) in self-referred patients in a European emergency department.

OBJECTIVE: To validate the Emergency Severity Index (ESI) triage algorithm in predicting resource consumption and disposition by self-referred patients in a European emergency department. METHODS: This was a prospective, observational cohort study using a convenience sample of self-referred emergency department patients >14 years of age presenting to a busy urban teaching hospital during a 39-day period (27 May-4 July 2001). Observed resource use was compared with resource utilisation predicted by the ESI. Outpatient referrals after discharge and hospitalisations were also recorded. RESULTS: ESI levels were obtained in 1832/3703 (50%) self-referred patients, most of whom were in the less severe ESI-4 (n = 685, 37%) and ESI-5 (n = 983, 54%) categories. Use of resources was strongly associated with the triage level, rising from 15% in ESI-5 to 97% in ESI-2 patients. Specialty consultations and admissions also rose with increasing ESI severity. Only 5% of ESI-5 patients required consultation and <1% were admitted, whereas 85% of ESI-2 patients received a consultation and 56% were admitted, 26% to a critical care bed. Only 2% of the ESI-5 patients underwent blood tests, compared with 76% of the sicker ESI-2 patients. X rays were the most commonly used resource in patients triaged to ESI-4 and ESI-5. CONCLUSION: The ESI triage category reliably predicts the severity of a patient's condition, as reflected by resource utilisation, consultations and admissions in a population of self-referred patients in a European emergency department. It clearly identifies patients who require minimal resources, or at most an x ray, and those unlikely to require admission.

In-hospital resuscitation of the elderly: characteristics and outcome.

OBJECTIVES: To determine the characteristics of the geriatric patient population subjected to resuscitation attempts at a 1000-bed university hospital and to determine factors associated with mortality and outcome after in-hospital CPR. METHODS: Retrospective chart review. The hospital records from all patients >75 years subjected to in-hospital resuscitation attempts during 2000-2001 were reviewed. Data regarding patient characteristics, mode of arrest and outcome details were extracted. RESULTS: During the study period 151 resuscitation attempts were registered, and 53 (35%) of the patients were > or =75 years of age. The average age was 81 years; 29/53 (55%) patients were female. The admission diagnosis was "cardiac ischaemia" (angina pectoris, myocardial infarction) in 18/53 (34%) of the patients. PEA (pulseless electric activity) was the most common primary arrhythmia (17/53, 32%), and cardiac aetiology was the most common cause of arrest (41/53, 77%). The time of arrest was spread equally over the day. Most resuscitation attempts were performed at the general wards (28 patients, 53%). More then half-part of the patients died immediately (32/53, 60%); initially ROSC (return of spontaneous circulation) was established in 21/53 (40%) patients. A total of 9/53 (17%) patients were discharged home. 'Do not attempt resuscitation' (DNAR) orders or a statement that DNAR orders had been discussed with the patient was not documented in any of the patients resuscitated. CONCLUSION: Selected patients among the geriatric hospitalised patients may benefit a from a short resuscitation attempt. This includes especially those admitted for cardiac ischemia suffering a cardiac arrest with VT or VF as a primary arrhythmia or patients suffering a primary respiratory/hypoxic arrest. Patients who are unlikely to benefit from CPR should be identified on or during hospital admission and the possibility of DNAR orders should be discussed to avoid inappropriate treatment and potential patient suffering. There is a need for implementing routines for discussing the existence of advance-directives or DNAR orders upon admission.

Emergency department patient characteristics: Potential impact on emergency medicine residency programs in the Netherlands.

OBJECTIVES: We set out to study emergency department patient characteristics at a busy level-2 trauma center, to gain insight into the practise of emergency medicine, which is not yet recognized as a specialty in the Netherlands. METHODS: From May 27 to July 4 2001, the following data were recorded from the charts of all patients presenting to the emergency department: age, time and form of presentation, diagnostics, treatment, disposition and the single best diagnosis (International Classification of Disease-10 classification). RESULTS: The majority (84%) of the 5234 patients (134/day) patients seen were self-referred and treated by the emergency department physician. The remaining 16% were referred, usually by their general practitioner, directly to a specialty service, which saw them in the emergency department. Self-referred patients tended to be younger (average 33 years), with minor trauma, and infrequently required diagnostics (37%), treatment (49%) or admission (4%). The referred patients were older (average 50 years), with 41% needing admission. Only 16% of all patients were under 16 years of age. In all, there were five deaths (referred patients), 12 resuscitations, seven intubations, seven chest tube insertions and no lumbar punctures performed during the study period. CONCLUSION: The acuity of self-referred patients seen by the emergency physicians is low, with little diagnostic testing and few interventions and resuscitations, even in a busy center. This has both training and practise implications and it may be inappropriate to take an emergency medicine practise model or curriculum from another country based on its emergency department population.

A description of emergency department-related malpractice claims in The Netherlands: closed claims study 1993-2001.

BACKGROUND: The aim of this study was to assess the quality of care provided at emergency departments (ED) in the Netherlands by analysing medical liability insurance claims. METHODS: A retrospective study performed by reviewing records at MediRisk, presently the largest insurer for medical liability in the Netherlands. The following data were abstracted from the files available for analysis: medical discipline involved, physician involved (resident or consultant), nature and gravity of the complaint, and final claim disposition. RESULTS: Between 1993 and 2001 a total of 326 claims involving the ED were filed at MediRisk. Of these, 256 claims (79%) were closed and were available for analysis. Medical liability claims were filed primarily for alleged errors in diagnosis and treatment. The majority of claims involved minor surgical conditions: fractures, luxations (joint dislocations), wounds and tendon injuries (210/256, 82%). Residents were involved in 76% of the claims; resident supervision by a consultant was documented in only 15% of the medical records. Permanent patient disability resulting from improper ED treatment was alleged in 22% of the claims. Four per cent of the claims involved the death of a patient. Physicians accepted liability in 16% of the claims filed. Indemnity payments during the 8-year study period totalled Euros 504,000. CONCLUSION: The number of medical liability claims is low compared with the number of patients treated in ED in the Netherlands. Claims primarily concerned alleged mistakes in diagnosis and the treatment of minor trauma. Residents were involved in the majority of the claims. More resident supervision is needed, as are specific training programmes for emergency physicians.