Medication error with methotrexate. / Feildosering av metotreksat.

Background: A woman in her seventies presented to the accident and emergency department (A&E) with shortness of breath that had increased over a period of three weeks. She had a history of COPD, hypertension and polymyalgia rheumatica. A medication error involving methotrexate, used for autoimmune diseases, was discovered during her medical history review. Case presentation: The patient arrived with stable vital signs, including 94 % oxygen saturation and a respiratory rate of 20 breaths/min. She had been taking 2.5 mg of methotrexate daily for the past three weeks instead of the prescribed weekly dose of 15 mg. Other examinations revealed no alarming findings, except for a slightly elevated D-dimer level. Interpretation: Considering her medical history and exclusion of other differential diagnoses, methotrexate toxicity was suspected. The patient was admitted to the hospital and intravenous folinic acid was initiated as an antidote treatment. Five days later, the patient was discharged with an improvement in the shortness of breath. This case underscores the importance of effective communication in health care, particularly in complex cases like this, where understanding dosages and administration is crucial. Medical history, clinical examinations and medication reviews, often involving clinical pharmacists, are vital in the A&E to reveal medication errors.

Patients' pathways to the emergency department: a scoping review.

BACKGROUND: Emergency department (ED) crowding is a common healthcare issue with multiple causes. One important knowledge area is understanding where patients arrived from and what care they received prior to ED admission. This information could be used to inform strategies to provide care for low acuity patients outside of the hospital and reduce unnecessary ED admissions. The aim of this scoping review was to provide a comprehensive overview of global published research examining the acute care trajectory of all ED patients. METHODS: The scoping review was performed according to the JBI Manual for Evidence Synthesis and the PRISMA-SCR checklist. A comprehensive literature search was performed to identify studies describing where patients arrived from and/or whose pathway of care was before an ED visit. The search was conducted in MEDLINE, Embase, and the Cochrane Library from inception through December 5th, 2022. Two reviewers independently screened the records. RESULTS: Out of the 6,465 records screened, 14 studies from Australia, Canada, Haiti, Norway, Sweden, Switzerland, Belgium, Indonesia, and the UK met the inclusion criteria. Four studies reported on where patients physically arrived from, ten reported how patients were transported, six reported who referred them, and six reported whether medical care or advice was sought prior to visiting an ED. CONCLUSION: This scoping review revealed a lack of studies describing patients' pathways to the ED. However, studies from some countries indicate that a relatively large proportion of patients first seek care or guidance from a primary care physician (PCP) before visiting an ED. However, further research and published data are needed. To improve the situation, we recommend the development and implementation of a template for the uniform reporting of factors outside the ED, including where the patient journey began, which healthcare facilities they visited, who referred them to the ED, and how they arrived.

Current postgraduate training in emergency medicine in the Nordic countries.

BACKGROUND: Emergency Medicine (EM) is an independent specialty in all five Nordic countries. This study aims to evaluate the structure of post-graduate EM training in the area. METHODS: A leading hospital or hospitals in EM training in each country were identified. An e-survey was sent to each hospital to gather data on patient volume and physician staffing, curriculum, trainee supervision, and monitoring of progression in training. RESULTS: Data were collected from one center in Iceland and Norway, two in Finland and Sweden, and four centers in Denmark. The data from each country in Denmark, Finland, and Sweden, were pooled to represent that country. The percentage of consultants with EM specialist recognition ranged from 49-100% of all consultants working in the participating departments. The number of patients seen annually per each full time EM consultant was almost three times higher in Finland than in Sweden. In Iceland, Denmark, and Sweden a consultant was present 24/7 in the ED but not in all centers in the other countries. The level of trainee autonomy in clinical practice varied between countries. Requirements for completing standardized courses, completing final exams, scientific and quality improvement projects, and evaluation of trainee progression, varied between the countries. CONCLUSIONS: All Nordic countries have established EM training programs. Despite cultural similarities, there are significant differences in how the EM training is structured between the countries. Writing and implementing a standardized training curriculum and assessment system for EM training in the Nordic countries should be considered.

Patient characteristics in sepsis-related deaths: prevalence of advanced frailty, comorbidity, and age in a Norwegian hospital trust.

OBJECTIVE: To examine the prevalence of advanced frailty, comorbidity, and age among sepsis-related deaths in an adult hospital population. METHODS: Retrospective chart reviews of deceased adults within a Norwegian hospital trust, with a diagnosis of infection, over 2 years (2018-2019). The likelihood of sepsis-related death was evaluated by clinicians as sepsis-related, possibly sepsis-related, or not sepsis-related. RESULTS: Of 633 hospital deaths, 179 (28%) were sepsis-related, and 136 (21%) were possibly sepsis-related. Among these 315 patients whose deaths were sepsis-related or possibly sepsis-related, close to three in four patients (73%) were either 85 years or older, living with severe frailty (Clinical Frailty Scale, CFS, score of 7 or more), or an end-stage condition prior to the admission. Among the remaining 27%, 15% were either 80-84 years old, living with frailty corresponding to a CFS score of 6, or severe comorbidity, defined as 5 points or more on the Charlson Comorbidity Index (CCI). The last 12% constituted the presumably healthiest cluster, but in this group as well, the majority died with limitations of care due to their premorbid functional status and/ or comorbidity. Findings remained stable if the population was limited to sepsis-related deaths on clinicians' reviews or those fulfilling the Sepsis-3 criteria. CONCLUSIONS: Advanced frailty, comorbidity, and age were predominant in hospital fatalities where infection contributed to death, with or without sepsis. This is of importance when considering sepsis-related mortality in similar populations, the applicability of study results to everyday clinical work, and future study designs.

Low-voltage electrical accidents, immediate reactions and acute health care associated with self-reported general health 4 years later.

BACKGROUND AND AIMS: Electricians frequently experience low-voltage electrical accidents. Some such accidents involve long-term negative health consequences. Early identification of victims at risk for long-term injury may improve acute medical treatment and long-term follow-up. This study aimed to determine acute exposure, health effects and treatment associated with general health ≥ 2 years after low-voltage electrical accidents. METHODS: In a cross-sectional study, 89 male electricians who had experienced an electrical accident between 1994 and 2001 participated in a 2003 follow-up health examination. They were identified from a registry of low-voltage electrical accidents and included in the study. Based on exposure descriptions in the original accident reports, they were stratified into the following three groups: a current arc accident group (N = 34, mean age 38.8 years [standard deviation, SD = 12.2, range = 21-59]) and two groups with the passage of current through the body, either fixed to the current source ("no-let-go" group; N = 35, mean age 34.0 years [SD = 10.5, range = 21-57]) or not ("let-go" group; N = 20, mean age = 38.7 years [SD = 10.3, range = 21-63]). They retrospectively described acute reactions and assessed their current general health at the health examination. Multivariate linear regression, ordinal logistic regression and Fisher's exact test were used to compare acute reactions with health at follow-up in each exposure group. RESULTS: The multivariate analysis indicated that after accidents with the passage of current through the body, severe acute headache (ß = - 0.56, p = 0.013), years since the accident (ß = - 0.16, p = 0.017) and the accident being perceived as frightening (ß = - 0.48, p = 0.040) were negatively associated with general health ≥ 2 years later (R2 = 0.25, p = 0.002). If the exposure included a no-let-go experience, then acute severe body numbness (ß = - 0.53, p = 0.029) was also negatively associated with general health (R2 = 0.38, p = 0.002). Without such experience, only acute confusion (ß = - 0.90, p = 0.029) was negatively associated with the health at follow-up (R2 = 0.24, p = 0.029). In univariate analyses, after the passage of current through the body, acute dizziness (p = 0.029), apathy (p = 0.028), confusion (p = 0.007) and irregular heartbeat (p ≤ 0.05) were associated with poor long-term general health. The no-let-go group, more often than the let-go group, reported panic (p = 0.001), fear of death (p = 0.029), confusion (p = 0.014), exhaustion (p = 0.009), bodily numbness (p = 0.013) and immediate unconsciousness (p = 0.019). Acute symptoms beyond the first day after a current arc accident were associated with poor long-term general health (p = 0.015). DISCUSSION AND CONCLUSIONS: The acute reactions negatively associated with general health ≥ 2 years after low-voltage electrical accidents should alert the clinician in the acute phase after an electrical accident to the risk of developing negative long-term health effects. Future studies should specify long-term health beyond the concept of general health.

Clinical Characteristics and Management of Patients with a Suspected COVID-19 Infection in Emergency Departments: A European Retrospective Multicenter Study.

Background: Our aim is to describe and compare the profile and outcome of patients attending the ED with a confirmed COVID-19 infection with patients with a suspected COVID-19 infection. Methods: We conducted a multicentric retrospective study including adults who were seen in 21 European emergency departments (ED) with suspected COVID-19 between 9 March and 8 April 2020. Patients with either a clinical suspicion of COVID-19 or confirmed COVID-19, detected using either a RT-PCR or a chest CT scan, formed the C+ group. Patients with non-confirmed COVID-19 (C− group) were defined as patients with a clinical presentation in the ED suggestive of COVID-19, but if tests were performed, they showed a negative RT-PCR and/or a negative chest CT scan. Results: A total of 7432 patients were included in the analysis: 1764 (23.7%) in the C+ group and 5668 (76.3%) in the C− group. The population was older (63.8 y.o. ±17.5 vs. 51.8 y.o. +/− 21.1, p < 0.01), with more males (54.6% vs. 46.1%, p < 0.01) in the C+ group. Patients in the C+ group had more chronic diseases. Half of the patients (n = 998, 56.6%) in the C+ group needed oxygen, compared to only 15% in the C− group (n = 877). Two-thirds of patients from the C+ group were hospitalized in ward (n = 1128, 63.9%), whereas two-thirds of patients in the C− group were discharged after their ED visit (n = 3883, 68.5%). Conclusion: Our study was the first in Europe to examine the emergency department's perspective on the management of patients with a suspected COVID-19 infection. We showed an overall more critical clinical situation group of patients with a confirmed COVID-19 infection.

Observational study on chest pain during the Covid-19 pandemic: changes and characteristics of visits to a Norwegian emergency department during the lockdown.

BACKGROUND: Following the spread of the Covid-19 pandemic in 2020, reports emerged on decreasing emergency department (ED) visits in many countries. Patients experiencing chest pain was no exception. The aim of the current study was to describe how the Covid-19 pandemic and the subsequential lockdown impacted the chest pain population in a Norwegian ED. METHODS: All patients presenting to the ED with chest pain during the study period were included. Data were collected retrospectively from the time period January 6th to August 30th, 2020, and compared to the corresponding period in 2019, assessing variations in the number of ED visits, severity, gender, and age. RESULTS: Fewer patients with chest pain were seen in the ED following the national lockdown in Norway, compared to the corresponding 2019 period (week 13: 38% fewer; weeks 11-27: 16% fewer). By week 28, the rate normalized compared to 2019 levels. There was a relative increase in lower acuity patients among these patients, while fewer moderate acuity patients were seen. During the initial period following lockdown, the median age was lower compared to the corresponding 2019 period (58 years (IQR 25) vs 62 years (IQR 24), respectively). Admissions due to acute coronary syndromes (ACS) remained proportionally stable. CONCLUSIONS: Succeeding the Covid-19 outbreak and the subsequent national lockdown in Norway, fewer chest pain patients presented to the ED. Paradoxically, the patients seemed to be less severely ill and were on average younger compared to 2019 data. However, the proportion of patients admitted with ACS was stable during this period. This could imply that some patients may have failed to seek medical advice despite experiencing a myocardial infarction.

Low-voltage electric shock - proposed new recommendations. / Strømgjennomgang fra lavspenning ­ forslag til nye anbefalinger.

We propose new recommendations for the emergency treatment of low-voltage electric injuries (<1 000 volts). A large proportion of these patients can be treated as outpatients.

Patients with low-voltage electric shock referred to an Emergency Department. / Pasienter med strømgjennomgang fra lavspenning henvist til et akuttmottak.

BACKGROUND: Patients exposed to electricity are often referred to the Emergency Department, but guidelines differ as to how they should be managed. In this article, we describe patients with low-voltage electric shock in the Emergency Department at St Olav's Hospital, Trondheim University Hospital. MATERIAL AND METHOD: Retrospective data from patients referred to the Emergency Department following low-voltage electric shock (< 1,000 V) in the period 1.1.2012-31.12.2017 (N = 210) were included. RESULTS: The median age was 26 years and 186/210 (89 %) were men. Out of the 210 patients, 165 (79 %) had symptoms following electric shock. Localised pain and chest discomfort occurred in 84/165 (51 %) and 57/165 (35 %) of patients respectively. ECG findings were normal in 168/209 (80 %), and no patients had arrhythmias requiring treatment or elevated troponin T or creatine kinase. No patients had serious complications or died. INTERPRETATION: Low-voltage electric shock did not cause serious arrhythmias or elevated levels of troponin T or creatine kinase. It should be possible to manage asymptomatic patients with normal findings on clinical examination and ECG in a prehospital setting without reducing patient safety.

Prehospital Stressors: A Cross-sectional Study of Norwegian Helicopter Emergency Medical Physicians.

OBJECTIVE: Personnel working in helicopter emergency medical services (HEMS) and search and rescue (SAR) are exposed to environmental stressors, which may impair performance. The aim of this survey was to study the extent HEMS and SAR physicians report the influence of specific danger-based and non-danger-based stressors. METHODS: The study was performed as a cross-sectional, anonymous, Web-based (Questback AS, Bogstadveien 54, 0366 Oslo, Norway) survey of Norwegian HEMS and SAR physicians between December 2, 2019, and February 25, 2020. RESULTS: Of the recipients, 119 (79.3%) responded. In helicopter operations, 33.6% (n = 40) reported involvement in a minor accident and 44.5% (n = 53) a near accident. In the rapid response car, 26.1% (n = 31) reported near accidents, whereas 26.9% (32) reported this in an ambulance. Of physicians, 20.2% (n = 24) received verbal abuse or threats during the last 12 months. When on call, 50.4% (n = 60) of physicians reported sometimes or often being influenced by fatigue. CONCLUSION: This study shows that Norwegian HEMS and SAR physicians are exposed to several stressors of both a danger-based and non-danger-based nature, especially regarding accidents, threatening patient behavior, and fatigue. Very serious incidents appear to be seldom, and job satisfaction is high.

Prehospital naloxone administration - what influences choice of dose and route of administration?

BACKGROUND: Amidst the ongoing opioid crisis there are debates regarding the optimal route of administration and dosages of naloxone. This applies both for lay people administration and emergency medical services, and in the development of new naloxone products. We examined the characteristics of naloxone administration, including predictors of dosages and multiple doses during patient treatment by emergency medical service staff in order to enlighten this debate. METHODS: This was a prospective observational study of patients administered naloxone by the Oslo City Center emergency medical service, Norway (2014-2018). Cases were linked to The National Cause of Death Registry. We investigated the route of administration and dosage of naloxone, clinical and demographic variables relating to initial naloxone dose and use of multiple naloxone doses and one-week mortality. RESULTS: Overall, 2215 cases were included, and the majority (91.9%) were administered intramuscular naloxone. Initial doses were 0.4 or 0.8 mg, and 15% of patients received multiple dosages. Unconscious patients or those in respiratory arrest were more likely to be treated with 0.8 mg naloxone and to receive multiple doses. The one-week mortality from drug-related deaths was 4.1 per 1000 episodes, with no deaths due to rebound opioid toxicity. CONCLUSIONS: Intramuscular naloxone doses of 0.4 and 0.8 mg were effective and safe in the treatment of opioid overdose in the prehospital setting. Emergency medical staff appear to titrate naloxone based on clinical presentation.

Patient visits to an emergency department in anticipation of the COVID-19 pandemic. / Pasienttilstrømming i et akuttmottak i påvente av covid-19-pandemien.

BACKGROUND: The Emergency Department in Trondheim has prepared for a large influx of patients infected with the SARS-CoV-2 virus. We conducted a study comparing patients in the Emergency Department in the first weeks of the pandemic in Norway (weeks 11 and 12) with the average number of patient visits. MATERIAL AND METHOD: Data from patients at the Emergency Department of St Olav's Hospital in the period 6 January 2020-22 March 2020 were retrieved from the Emergency Department's database. Logistical patient data concerning patient numbers, chief complaints, length of stay in the Emergency Department, acuity level, isolation status, and treatment level were analysed. RESULTS: In week 12, 331 patients were referred to the Emergency Department, a reduction of 39 % compared with the average of 541 patients in weeks 2-10. There was a general reduction in all patient groups, but particularly those discharged from the Emergency Department. In week 12 there were 56 more patients isolated with suspected/potentially infectious disease (187 %) compared with the average for weeks 2-10, and these patients spent almost two hours longer in the Emergency Department than other patients. INTERPRETATION: There was a reduction in patient visits to the Emergency Department in the first weeks of the pandemic. The percentage of patients isolated for infection control increased, and the time spent in the Emergency Department for these patients was greater than for other patients. The reduction in the inflow of patients is expected to be temporary, and the Emergency Department at St Olav's Hospital expects a large influx of patients with suspected COVID-19 disease.

Description of chest pain patients in a Norwegian emergency department.

OBJECTIVES: Chest pain is one of the most frequent chief complaints in patients admitted to the emergency department (ED). No study has evaluated this patient population in Norway. The aim of the present study was to describe the diagnoses and logistics of chest pain patients admitted to the ED at a Norwegian university hospital. DESIGN: Data were collected from all patients referred to the ED at St. Olav's Hospital-Trondheim University Hospital in 2015. Patients presenting at the ED with a chief complaint of chest pain based on the Rapid Emergency Triage and Treatment System were included in this study. RESULTS: In the study period, 22,403 patients were admitted to the ED. Chest pain was the second most common chief complaint (11%), only exceeded by acute abdominal pain (18%). Among the chest pain patients, 12% had acute coronary syndrome (ACS) and 37% were diagnosed with non-specific chest pain. Gastrointestinal, musculoskeletal, and pulmonary conditions were less common, affecting 6%, 4%, and 4% of the patients, respectively. In total, 90% of the ED chest pain patients were handled by the Clinic of Cardiology. CONCLUSIONS: Chest pain was the second most common chief complaint among patients admitted to the ED, and most patients were handled by the Clinic of Cardiology. More than one-third of the patients received a cardiac diagnosis, but the largest group of patients was discharged with a diagnosis of non-specific chest pain. Other conditions managed by non-cardiac medical specialties were less common.

Compliance With a National Standard by Norwegian Helicopter Emergency Physicians.

OBJECTIVE: The "National Standard Requirements for Helicopter Emergency Medicine Services Physicians" gives recommendations on medical requirements for flight physicians. This study describes the level of formal competence, experience, and guideline compliance of Norwegian helicopter emergency medical service (HEMS) physicians. METHODS: In May 2013, all HEMS physicians with full-time engagement at Norwegian HEMS bases were invited to participate in a cross-sectional survey using a structured, Web-based questionnaire. RESULTS: A total of 108 (79%) of 136 physicians replied to the survey, and all bases were represented. The majority (89%) had specialist training, and more than 60% had longer than 6 years of experience as a flight physician. Over 60% had attended trauma, pediatric, and incubator courses, and all physicians worked regularly in an anesthesia department. Most physicians were participating in simulation and procedure training. CONCLUSION: Many of the basic requirements of the guidelines were met by HEMS physicians, but room exists for improvements. Norwegian HEMS physicians are experienced, but a need exists for a more structured curriculum in emergency medicine for HEMS physicians based on the broad spectrum of presented medical conditions to ensure optimal quality of care and safety for all patients in Norway.

Poor performance of quick-SOFA (qSOFA) score in predicting severe sepsis and mortality - a prospective study of patients admitted with infection to the emergency department.

BACKGROUND: We aimed to evaluate the clinical usefulness of qSOFA as a risk stratification tool for patients admitted with infection compared to traditional SIRS criteria or our triage system; the Rapid Emergency Triage and Treatment System (RETTS). METHODS: The study was an observational cohort study performed at one Emergency Department (ED) in an urban university teaching hospital in Norway, with approximately 20,000 visits per year. All patients >16 years presenting with symptoms or clinical signs suggesting an infection (n = 1535) were prospectively included in the study from January 1 to December 31, 2012. At arrival in the ED, vital signs were recorded and all patients were triaged according to RETTS vital signs, presenting infection, and sepsis symptoms. These admission data were also used to calculate qSOFA and SIRS. Treatment outcome was later retrieved from the patients' electronic records (EPR) and mortality data from the Norwegian population registry. RESULTS: Of the 1535 admitted patients, 108 (7.0%) fulfilled the Sepsis2 criteria for severe sepsis. The qSOFA score ≥2 identified only 33 (sensitivity 0.32, specificity 0.98) of the patients with severe sepsis, whilst the RETTS-alert ≥ orange identified 92 patients (sensitivity 0.85, specificity 0.55). Twenty-six patients died within 7 days of admission; four (15.4%) of them had a qSOFA ≥2, and 16 (61.5%) had RETTS ≥ orange alert. Of the 68 patients that died within 30 days, only eight (11.9%) scored ≥2 on the qSOFA, and 45 (66.1%) had a RETTS ≥ orange alert. DISCUSSION: In order to achieve timely treatment for sepsis, a sensitive screening tool is more important than a specific one. Our study is the fourth study were qSOFA finds few of the sepsis cases in prehospital or at arrival to the ED. We add information on the RETTS triage system, the two highest acuity levels together had a high sensitivity (85%) for identifying sepsis at arrival to the ED - and thus, RETTS should not be replaced by qSOFA as a screening and trigger tool for sepsis at arrival. CONCLUSION: In this observational cohort study, qSOFA failed to identify two thirds of the patients admitted to an ED with severe sepsis. Further, qSOFA failed to be a risk stratification tool as the sensitivity to predict 7-day and 30-day mortality was low. The sensitivity was poorer than the other warning scores already in use at the study site, RETTS-triage and the SIRS criteria.

Assessment of pain in a Norwegian Emergency Department.

BACKGROUND: Although pain management is a fundamental aspect of care in emergency departments (EDs), inadequate treatment of pain is unfortunately common. There are multiple local protocols for pain assessment in the ED. This study evaluated whether the initial assessment and treatment of pain in the ED are in accordance with the in-hospital protocol of the ED at a Norwegian University Hospital. MATERIALS AND METHODS: Prospective data on pain assessment and initial treatment in the ED were collected from nursing and physician documentation. The patients' perceptions of subjective pain were recorded using a numerical rating scale (NRS) that ranged from 0 to 10. RESULTS: Seventy-seven percent of the 764 enrolled patients were evaluated for pain at arrival. Female patients had a higher probability of not being asked about pain, but there was no difference in the percentage of patients asked about pain with respect to age. Additionally, patients with low oxygen saturation and systolic blood pressure were less likely to be asked about pain. Of those with moderate and severe pain (58 %), only 14 % received pain relief. DISCUSSION: Assessment and treatment of pain in the ED are inadequate and not in line with the local protocols. A focus on strategies to improve pain treatment in the ED is a necessary aspect of developing optimal acute patient care in Norway in the future.

The GLT-1 (EAAT2; slc1a2) glutamate transporter is essential for glutamate homeostasis in the neocortex of the mouse.

Glutamate is the major excitatory neurotransmitter, and is inactivated by cellular uptake catalyzed mostly by the glutamate transporter subtypes GLT-1 (EAAT2) and GLAST (EAAT1). Astrocytes express both GLT-1 and GLAST, while axon terminals in the neocortex only express GLT-1. To evaluate the role of GLT-1 in glutamate homeostasis, we injected GLT-1 knockout (KO) mice and wild-type littermates with [1-(13)C]glucose and [1,2-(13)C]acetate 15 min before euthanization. Metabolite levels were analyzed in extracts from neocortex and cerebellum and (13)C labeling in neocortex. Whereas the cerebellum in GLT-1-deficient mice had normal levels of glutamate, glutamine, and (13)C labeling of metabolites, glutamate level was decreased but labeling from [1-(13)C] glucose was unchanged in the neocortex. The contribution from pyruvate carboxylation toward labeling of these metabolites was unchanged. Labeling from [1,2-(13)C] acetate, originating in astrocytes, was decreased in glutamate and glutamine in the neocortex indicating reduced mitochondrial metabolism in astrocytes. The decreased amount of glutamate in the cortex indicates that glutamine transport into neurons is not sufficient to replenish glutamate lost because of neurotransmission and that GLT-1 plays a role in glutamate homeostasis in the cortex. Glutamate is the major excitatory neurotransmitter, and is inactivated by uptake via GLT-1 (EAAT2) and GLAST (EAAT1) transporters, while axon terminals in the neocortex only express GLT-1. To evaluate the role of GLT-1 in glutamate homeostasis, we used [1-(13)C]glucose and [1,2-(13)C]acetate injection and NMR spectroscopy. The results indicate that glutamine transport into neurons is not sufficient to replenish glutamate lost because of neurotransmission and that GLT-1 plays a role in glutamate homeostasis in the neocortex.