Aspirin non-responder status and early neurological deterioration: a prospective study

Objectives

In acute ischemic stroke, early neurological deterioration (END) has a severe impact on patient outcome. We tested the hypothesis that initial biological aspirin non-responder status (ANRS) helps predict END.

Methods

A total of 85 patients with acute ischemic stroke on 160 mg aspirin daily were prospectively included. END was defined as an increase in the National Institutes of Health Stroke Scale (NIHSS) ≥4 points in the first 72 h after admission. Platelet responsiveness to aspirin was assessed using the PFA-100 system, and ANRS was defined as a collagen/epinephrine closure time <165 ms.

Results

END was observed in 10 patients (11.8%). The presumed reasons for END were progressive stroke (40%), recurrent cerebral ischemia (30%), malignant middle cerebral artery infarction (20%) and secondary acute hydrocephalus (10%). Patients with END had a non-significant worse neurological status on the NIHSS at hospital admission (8.4 vs. 4.2; p = 0.15). Initial impaired consciousness (30% vs. 3%), visual disturbance (60% vs. 23%) and ANRS (60% vs. 20%) were observed more frequently in patients with END. In multivariate analysis, impaired consciousness (OR: 17.3; 95% CI: 2.0-149.5; p = 0.01) and ANRS (OR: 6.4; 95% CI: 1.4-29.6; p = 0.017) were found to be independently associated with END.

Conclusion

ANRS is common in acute ischemic stroke patients and is predictive of END. The clinical significance of these findings requires further evaluation in larger longitudinal studies.     

Time interval between stroke onset and hospital arrival in acute ischemic stroke patients in Shanghai, China

Objective

To observe the time interval between stroke onset and hospital arrival (time-to-hospital) in acute ischemic stroke patients and analyze its putatively associated factors.

Methods

During the period from November 1, 2006 to August 31, 2008, patients with acute ischemic stroke admitted consecutively to the Department of Neurology, Ninth Hospital, Shanghai, were enrolled in the study. Information of the patients was registered including the time-to-hospital, demographic data, history of stroke, season at attack, neurological symptom at onset, etc. Characteristics of the patients were analyzed and logistic regression analyses were conducted to identify factors associated with the time-to-hospital.

Results

There were 536 patients in the study, 290 (54.1%) males and 246 (45.9%) females. The median time-to-hospital was 8 h (ranged from 0.1 to 300 h) for all patients. Within 3 h after the onset of stroke, 162 patients (30.2%) arrived at our hospital; and within 6 h, 278 patients (51.9%). Patients with a history of stroke, unconsciousness at onset, or a high NIHSS score at admission had significantly less time-to-hospital.

Conclusion

The time interval between stroke onset and hospital arrival was <6 h for around half of our patients with acute cerebral ischemic stroke. A history of stroke and severe symptoms at onset were significantly associated with shorter time-to-hospital. The results might indicate that the knowledge of stroke and understanding the importance of seeking immediate medical help after stroke onset of patients and their relatives could significantly influence their actions.     

Quality of life in 1931 adult patients with epilepsy: seizures do not tell the whole story

Objective

The aim of the work described here was to characterize quality of life (QOL) and its determinants in a large cohort of adult patients with epilepsy.

Methods

Validated measures reflecting disease severity and psychosocial functioning were electronically collected on all outpatients seen during 2009. Multivariate regression adjusting for repeated measures identified determinants of QOL, as defined by the Quality of Life in Epilepsy Questionnaire-10 (QOLIE-10).

Results

Seven thousand seven hundred eighty-four visits from patients with epilepsy were identified. The questionnaire completion rate was 77%, yielding 5960 records corresponding to 1931 individual patients for analysis. Following multivariate modeling, the two most clinically significant QOL predictors were seizure severity (mean QOLIE-10 score = 28.8 if LSSS > 40 vs 19.2 otherwise) and depression (mean QOLIE-10 score = 31.7 if PHQ-9 ≥ 10 vs 19.3 otherwise).

Conclusions

Optimizing quality of life in patients with epilepsy requires an approach that extends beyond controlling seizures. Collection of validated health status measures improving patient management is possible within the setting of routine clinical care.     

Cost of acute ischemic and hemorrhagic stroke in Turkey

Objective

The aim of this study is to examine the direct medical costs and outcomes of patients with stroke.

Material and methods

The records of the patients admitted with ischemic and hemorrhagic stroke to the University of Trakya, School of Medicine, Department of Neurology were reviewed retrospectively in year 2007. Direct medical costs (total costs, radiological, laboratory, medicine, and other) were calculated, additionally cost per life saved and per life-year saved were calculated for stroke patients.

Results

The study group consisted of 328 patients (169 male/159 female) and mean age was 66.5 ± 12.4 years. Length of hospital stay was 10.7 ± 7.5 days. Mortality rate was 20.4% and the mRS score of the patients was 3.2 ± 2.1. The average cost of stroke was US$ 1677 ± 2964 (29.9% medicine, 19.9% laboratory, 12.8% neuroimaging, and 38% beds and staff). Cost per life saved and per life-year saved were US$ 2108 and US$ 1070, respectively.

Conclusion

This is the first study in order to determine direct medical cost of stroke in Turkey, therefore, it may be guideline for disease-cost management of stroke.     

Alteration in surface muscle electrical anisotropy in the rat SOD1 model of amyotrophic lateral sclerosis

Objective

To evaluate the effects of progressive neurogenic change on surface-measured anisotropy via study in the rat superoxide dismutase 1 (SOD1) G93A amyotrophic lateral sclerosis (ALS) model.

Methods

Eight male ALS rats were studied over a period of 10 weeks. In each, the 20 kHz to 1 MHz electrical impedance of the gastrocnemius-soleus complex was measured with electrodes placed at 0° and at 90° relative to the major muscle fiber direction. The major outcome measure, the anisotropy difference (AD) for each of the resistance, reactance, and phase, was calculated as 90-0° values.

Results

All three parameters showed substantial alterations with disease progression. However, the phase AD demonstrated the most substantial change, increasing from 1.8 ± 1.58° to 10.2 ± 2.13° (mean ± standard error) comparing the first and last set of measurements (p = 0.028).

Conclusions

Anisotropy increases substantially with disease progression in the ALS rat.

Significance

Measurement of surface electrical anisotropy offers a non-invasive means for quantifying neurogenic change in muscle.     

Delay in seeking treatment by patients with stroke: who decides, where they go, and how long it takes

Objectives

To find out about stroke patients: who decides to seek medical help, where they go, how long it takes to contact the health system and to arrive at the ED.

Methods

Prospective study of patients admitted in our hospital for transient or established stroke.

Results

Among 388 stroke patients (mean NIHSS of 7.8 (±7.4), there were 37 intracerebral hemorrhage, 70 TIA, and 281 cerebral infarction. 39.2% arrived at the ED in less than 3 h. The decision to seek medical help was taken by patients in 20.4% of the episodes. First contact was with primary care in 48.3% of the cases and with Emergency Medical Services in 18.2%. The median time of decision was 60 min [P25:15; P75:323]. Considering the event as serious, recognizing the stroke, not going to a primary care physician, having a TIA and onset away from home significantly decreased delay. Age, sex and previous stroke were not associated with less delay in decision nor with an earlier arrival to the ED.

Conclusions

In order to improve stroke treatment it is necessary to harness the use of the 112 emergency line and include primary care in the stroke assistance chain.     

Lutein enhances survival and reduces neuronal damage in a mouse model of ischemic stroke

Introduction

Stroke is one of the leading causes of death worldwide. Protective agents that could diminish the injuries induced by cerebral ischemia/reperfusion (I/R) are crucial to alleviate the detrimental outcome of stroke. The aim of this study is to investigate the protective roles of lutein in cerebral I/R injury.

Methods

Two-hour cerebral ischemia was induced by unilateral middle cerebral artery occlusion (MCAo) in mice. Either lutein (0.2 mg/kg) or vehicle was given to mice intraperitoneally 1 h after MCAo and 1 h after reperfusion. Neurological deficits were evaluated at 22 h after reperfusion while survival rate was assessed daily until 7 days after reperfusion. Brains were cut into 2 mm-thick coronal slices and stained with 2% 2,3,5-triphenyltetrazolium chloride to determine the infarct size after MCAo. Paraffin-embedded brain sections were prepared for TUNEL assay and immunohistochemistry. Protein lysate was collected for Western blotting experiments.

Results

Higher survival rate, better neurological scores, smaller infarct area and smaller infarct volume were noted in the lutein-treated group. Immunohistochemistry data showed a decrease of immunoreactivity of nitrotyrosine, poly(ADP-ribose) and NFκB in the lutein-treated brains. Western blotting data showed decreased levels of Cox-2, pERK, and pIκB, but increased levels of Bcl-2, heat shock protein 70 and pAkt in the lutein-treated brains.

Conclusions

Post-treatment of lutein protected the brain from I/R injury, probably by its anti-apoptotic, anti-oxidative and anti-inflammatory properties. These suggest that lutein could diminish the deleterious outcomes of cerebral I/R and may be used as a potential treatment for stroke patients.     

Characteristics of first ever ischemic stroke in the very elderly: profile of vascular risk factors and clinical outcome

Purpose

Age is the most significant non-modifiable risk factor for ischemic stroke (IS). With increasing expectancy of life, the majority of IS patients will be elderly subjects. We studied the epidemiological, clinical and rehabilitation features of patients aged ≥85 years with first-ever IS.

Methods

Demographic data, prevalence of risk factors, etiology of stroke, severity of neurological deficit, major complications and mortality rates were collected from a hospital-based stroke registry and compared between patients at the age of 65-84 and ≥85. Clinical assessment was performed by means of the National Institutes of Health Stroke Scale (NIHSS) and Modified Rankin Scale (mRS).

Results

Among 216 patients aged ≥85 years there was significantly higher proportion of a history of atrial fibrillation than in 128 patients at the age of 65-84 years and lower prevalence of hypertension, diabetes mellitus, hyperlipidemia and smoking. Large artery atherosclerosis was more frequently identified in the older patients (49% vs. 32%, p = 0.002). Although NIHSS scores on admission were lower in the older patients they were more disabled at discharge.

Conclusions

With respect to the patients aged <85 years very old IS patients showed different vascular risk factors profile, clinical and rehabilitation course. These findings suggest specializing stroke care in the very elderly.     

Decreased serum BDNF levels in major depressive patients

Background

Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal plasticity. The aim of the present study was to measure serum BDNF levels in depression and to analyze the relationship between BDNF levels and severity of depression.

Methods

Thirty patients meeting the DSM-IV criteria for major depressive disorder and 40 normal control subjects were recruited for this study. Patients had not used psychotropic drugs. The severity of depression was assessed by the Hamilton Rating of Depression Scale (HAM-D). Serum BDNF levels were determined by using ELISA.

Results

HAM-D scores were 17.09 ± 4.96 in depressed patients. We determined that the serum BDNF levels of the depression patients were lower than those of the healthy control group (respectively, 1453.42 ± 144.51 pg/ml, 1632.23 ± 252.93 pg/ml, t = 3.467, p = 0.001, independent t test). No correlation was found between the patients’ serum BDNF levels and HAM-D scores (p > 0.05, Pearson correlation analysis).

Conclusions

Our results suggest that serum BDNF levels are low in depression. However it was not found association between serum BDNF levels and the severity of depression.     

Effects of microbubbles on transcranial Doppler ultrasound-assisted intracranial urokinase thrombolysis

Introduction

To evaluate the efficacy of microbubbles in transcranial Doppler ultrasound (TCD)-assisted urokinase thrombolysis.

Materials and Methods

Male New Zealand white rabbits (N = 32) were randomly divided into 2 groups, a urokinase group and a combined urokinase plus microbubble group. The middle cerebral artery (MCA) was occluded by injecting autologous blood clots through the carotid artery. In the urokinase plus microbubble group, sulfur hexafluoride (SonoVue) microbubbles were injected intravenously immediately after intravenous injection of urokinase. The 2 groups were monitored by TCD from before until 2 h after thrombolysis, and the hemodynamic changes and infarct size were recorded.

Results

The urokinase alone group had 1 case of complete recanalization and 4 cases of partial recanalization (recanalization rate, 31.3%). The urokinase plus microbubble group had 3 cases of complete recanalization and 6 cases of partial recanalization (recanalization rate, 56.3%). The average size of the infarction foci was 13.9% in the urokinase group and 9.1% in the urokinase plus microbubble group (P = 0.025). Pathological examination revealed no cerebral hemorrhage in either group.

Conclusions

The addition of microbubbles enhanced the effects of transcranial Doppler ultrasound-assisted urokinase thrombolysis.     

Suicidality in temporal lobe epilepsy: measuring the weight of impulsivity and depression

Objective

The aim of the work described here was to measure the role of psychopathological features, specifically impulsivity and depression, in suicidality in patients with temporal lobe epilepsy (TLE).

Methods

Neuropsychiatric evaluation of 66 outpatients with TLE was performed with the following instruments: a structured clinical interview (Mini International Neuropsychiatric Interview Plus), the Barratt Impulsiveness Scale, the Hamilton Anxiety Scale, the Beck Depression Inventory, and the Brief Psychiatric Rating Scale.

Results

A current Axis I psychiatric diagnosis, mainly mood and anxiety disorders, was assigned to 37 subjects (56.1%) Presence of suicide risk was identified in 19 patients (28.8%), and 14 (21.2%) had attempted suicide. Frequency of seizures (P = 0.012), current major depression (P = 0.001), and motor impulsivity (P = 0.005) were associated with suicide risk on univariate analysis. Logistic regression stressed the main relevance of major depression (OR = 12.82, 95% CI = 2.58-63.76, P = 0.002) and motor impulsivity (OR = 1.21, 95% CI = 1.06-1.38, P = 0.005) to suicide risk.

Conclusion

Depression has a major influence on suicidality in epilepsy. Motor impulsivity is also relevant and may be an important component of depression in TLE associated with suicide risk.     

Depression and cognitive deficits in geriatric schizophrenia

Objective

Past reports have found patients with comorbid depression and schizophrenia spectrum disorders exhibit greater deficits in memory and attention compared to schizophrenia spectrum disorder patients without depressive symptoms. However, in contrast to younger schizophrenia patients, the few past studies using cognitive screens to examine the relationship between depression and cognition in inpatient geriatric schizophrenia have found that depressive symptomatology was associated with relatively enhanced cognitive performance. In the current study we examined the relationship between depressive symptoms and cognitive deficits in geriatric schizophrenia spectrum disorder patients (n = 71; mean age = 63.7) on an acute psychiatric inpatient service.

Method

Patients completed a battery of cognitive tests assessing memory, attention and global cognition. Symptom severity was assessed via the PANSS and Calgary Depression Scale for Schizophrenia.

Results

Results revealed that geriatric patients' depression severity predicted enhancement of their attentional and verbal memory performance. Patients' global cognitive functioning and adaptive functioning were not associated with their depression severity.

Conclusion

Contrary to patterns typically seen in younger patients and non-patient groups, increasing depression severity is associated with enhancement of memory and attention in geriatric schizophrenia spectrum disorder patients. Also, diverging from younger samples, depression severity was unassociated with patients adaptive and global cognitive functioning.     

Outcome in delusional depression comparing trimipramine monotherapy with a combination of amitriptyline and haloperidol - A double-blind multicenter trial

Background

Patients with delusional depression are difficult to treat. The atypical antidepressant trimipramine was effective in a previous 4-week open label pilot study in patients with this disorder. The major neurobiological effect of trimipramine is the inhibition of the hypothalamic-pituitary-adrenocortical (HPA) system. In delusional depression HPA overactivity is more distinct than in other subtypes of depression. HPA suppression is thought to contribute to the action of trimipramine.

Methods

In a double-blind, randomized, placebo controlled multicenter trial we compared the effects of trimipramine monotherapy versus a combination of amitriptyline and haloperidol. Dosage was increased stepwise from 100 mg up to 400 mg trimipramine and from 100 mg up to 200 mg amitriptyline combined with 2 mg up to 7.5 mg haloperidol. The average dose of trimipramine was higher than that of amitriptyline throughout the trial. During sixth week mean dosage (±standard deviation) were 356.1 ± 61.2 mg trimipramine, 184.0 ± 23.6 mg amitriptyline and 6.3 ± 1.8 mg haloperidol. During six weeks psychometric assessments were performed weekly. For HPA monitoring a dexamethasone/corticotropin-releasing hormone (Dex/CRH) test was performed before active medication and at the end of treatment. Additionally tolerability was monitored by ECG, EEG assessment of extrapyramidal symptoms and akathisia, clinical laboratory routine and recording of blood pressure and heart rate. Adverse events were documented.

Results

94 patients were enclosed into the study. The per protocol sample consisted of 33 patients of the trimipramine group and of 24 patients of the amitriptyline/haloperidol group. The decrease of the Hamilton depression (HAMD) score (24 items) showed non-inferiority of trimipramine compared to amitriptyline/haloperidol. Twenty-eight patients (84.84%) in the trimipramine arm and 17 patients (70.83%) in the amitriptyline/haloperidol arm were responders (HAMD ? 50%). Remission (HAMD < 8) was found in 18 (54.55%) patients after trimipramine and in 11 (45.83%) patients after amitriptyline/haloperidol. No significant differences were found concerning response and remission. The cortisol and ACTH response in the Dex/CRH test decreased between days 1 and 42 in both groups. Serious side effects were not reported.

Conclusion

In all, trimipramine monotherapy appears to be an effective treatment in delusional depression.     

Acute ischemic stroke in the very elderly Chinese: risk factors, hospital management and one-year outcome

Background

Little information is available on Asian patients over 80 years with stroke. We aimed to investigate characteristics of the very elderly ischemic stroke hospitalized patients in China.

Methods

We prospectively enrolled consecutive patients with acute ischemic stroke from March, 2002 to October, 2008 into the analysis. Patients were divided into two groups: <80 years versus ≥80 years and risk factors, hospital management and one-year outcome were compared.

Results

Of the 2619 cases included, 302 (11.5%) patients were 80 years or older. Compared with patients <80 years, patients over 80 years old had higher rates of hypertension (66.2% versus 56.1%, p = 0.001), atrial fibrillation (23.5% versus 14.5%, p = 0.000), and coronary heart disease (13.6% versus 5.7%, p = 0.000). In addition, they were less likely to have received transthoracic echocardiography (45.4% versus 55.4%, p = 0.001), color Doppler of extracranial vessels (54.0% versus 61.2%, p = 0.015), antiplatelet agents (80.8% versus 86.8%, p = 0.004), or anticoagulants (4.0% versus 9.0%, p = 0.003). After adjusting for sex and stroke severity on admission, the very elderly patients had higher case-fatality and disability rates at one year (33.8% versus 13.2%, p = 0.000; 37.8% versus 20.9%, p = 0.000; respectively).

Conclusions

In China, the proportion of the very elderly in hospitalized stroke population is lower than that in western countries whereas the most common risk factors seem similar. The hospital management for these patients is relatively insufficient and the long-term outcome is generally unfavorable compared with patients under 80 years old.     

Undiagnosed depression and its correlates in a predominantly immigrant Hispanic neurology clinic

Objective

Previous studies have reported a high incidence of depression in neurology clinics, however areas where there are predominantly underserved immigrants have not been studied.

Methods

Retrospective cohort study in an academic outpatient neurology clinic in Los Angeles, California. Newly referred patients (N = 318) were assessed consecutively for depression using a PHQ-9 questionnaire, accompanied by review of the assessment of the depressive disorder.

Results

The patient cohort consisted of 190 females (59%) and 130 males (41%), primarily of Hispanic descent (72%), with 8% Asian 11% white, and 5% African-American. Sixty-eight percent (68%) had depression, with 40% exhibiting moderate to severe depression. Patients who had moderate to severe depression (based on PHQ-9) were more likely to be unemployed (75.2% vs. 60.7%, p = 0.008), dependent on government income (29.5% vs. 20.4%, p = 0.06), and have headache or pain as the reason for referral (42.4% vs. 28.5%, p = 0.03). Severity of depression also significantly correlated with current treatment by psychiatrist, current antidepressant use, and less independent living. Patients with moderate to severe depression were more likely to have made ER visits in the last 12 months (0.9 vs. 0.7, p = 0.01) and were taking more medications (3.3 vs. 2.5, p = 0.03), compared to patient with mild or no depression.

Conclusion

The presence of moderate to severe depression significantly correlated with socioeconomic status, use of emergency room, and presence of headache/pain. Neurology clinics with predominantly underserved immigrant patients have a disproportionate amount of depression, which may be related to socioeconomic factors resulting in overutilization of scarce healthcare resources.     

The relationship between plasma and placental tissue factor, and tissue factor pathway inhibitors in severe pre-eclampsia patients

Objective

To investigate the mechanism underlying the hypercoagulable state in severe pre-eclampsia.

Methods

Plasma tissue factor (TF) and tissue factor pathway inhibitor (TFPI) expression from pre-eclampsia patients and healthy pregnant controls were determined by ELISA. Placental TF and TFPI gene and protein expression were detected by quantitative RT-PCR, immunohistochemistry, and Western analysis.

Results

The plasma TF level in the pre-eclampsia group was significantly higher than the control group (p < 0.01), and surprisingly, the plasma TFPI-1 and TFPI-2 in the pre-eclampsia group were significantly lower (p < 0.01). Placental TF gene and protein expression levels in the pre-eclampsia group was significantly higher than the control group, while TFPI-1 and TFPI-2 levels were significantly lower (p < 0.05). Lastly, a significant correlation was found between plasma and placental TF protein levels in the pre-eclampsia group (p < 0.01).

Conclusion

Higher expression and/or release of TF from the placenta may contribute towards a pathological hypercoagulable state in pre-eclampsia patients.     

Recovery of submaximal upper limb force production is correlated with better arm position control and motor impairment early after a stroke

Objective

This study determined whether recovery of upper limb position control using submaximal force production correlates with an improvement in functional arm impairment during early recovery from stroke.

Methods

Ten consecutive inpatients were recruited from a stroke unit. Each patient was in early recovery (<8 weeks post-lesion) from their first ever stroke. Evaluations of submaximal continuous force production and position control, maximal force production at the shoulder and a clinical outcome measure of motor impairment (Fugl-Meyer score; FM) were performed 20 days post-stroke as a baseline and then once a week for the following four weeks.

Results

Submaximal force production and its modulation during a position-holding task improved in early recovery after stroke, whereas maximal force production did not. Better modulation of submaximal force production enabled improved arm position control which was significantly correlated to the changes in FM score of motor impairment during recovery.

Conclusions

This study demonstrated that improvement in submaximal force modulation can operate as a mechanism enabling better motor behaviour such as arm position control during early recovery from a stroke.

Significance

Future rehabilitation strategies may benefit from adding submaximal force development and modulation to early interventions after stroke.     

Differences in findings of nocturnal polysomnography and multiple sleep latency test between narcolepsy and idiopathic hypersomnia

Objectives

To compare differences in nocturnal and daytime polysomnographic findings between narcolepsy (NA) with and without cataplexy (CA) and idiopathic hypersomnia without long sleep time (IHS w/o LST).

Methods

Nocturnal polysomnography (n-PSG) and multiple sleep latency test (MSLT) findings were compared among subjects with NA with CA (n = 52), NA without CA (n = 62), and IHS w/o LST (n = 50).

Results

The NA with CA group had significantly more disrupted and shallower nocturnal sleep than the other groups. On MSLT, the IHS w/o LST group had significantly longer sleep latency (SL) compared with the two NA groups. The latter two groups did not show statistical differences in diurnal variation of SL.

Conclusions

The IHS w/o LST group had milder objective daytime sleepiness compared with the NA groups. In patients with NA, nocturnal sleep disturbances appeared only in cases with CA, despite a similar trend in diurnal changes in sleep propensity between the two NA groups.

Significance

Objective nocturnal sleep disturbances are specific to NA patients with CA, whereas diurnal variations of sleep propensity are observed irrespective of the presence of CA among NA patients. These findings could be helpful for choosing optimal treatment plans for patients with these disorders.     

Coagulation factor XIII activation peptide and subunit levels in patients with acute ischaemic stroke: A pilot study

Introduction

We have recently shown that FXIII activation peptide (AP-FXIII) can be measured in plasma. The objective of this pilot study was to investigate for the first time if AP-FXIII can be detected in plasma from patients with acute ischaemic stroke.

Materials and methods

We included 66 patients with acute ischaemic stroke admitted between 1 and 7 hours after the onset of clinical symptoms. We collected plasma samples upon admission and on the two following days and measured AP-FXIII and subunit levels by ELISA. Clinical stroke severity was assessed by NIHSS stroke score.

Results

AP-FXIII could be detected in 34 patients upon admission (range 0.2-26.3 ng/ml), on day 1 in 15 patients (0.2-10.4 ng/ml), and on day 2 in 11 patients (0.1-15.1 ng/ml. AP-FXIII was higher in patients with severe stroke. Lower AP-FXIII levels upon admission were associated with clinical improvement. FXIII-A and FXIII-B subunit levels decreased significantly from day 0 to day 1.

Conclusions

For the first time, we detected AP-FXIII in patients upon an acute thrombotic event. The decrease in FXIII subunit levels during acute ischaemic stroke is evidence for ongoing coagulation activity and FXIII consumption. Our results suggest that FXIII activation and concomitant AP-FXIII release might be associated with an unfavourable short-term clinical outcome. Larger studies are needed to further investigate whether AP-FXIII might serve as a diagnostic and/or prognostic marker for acute thrombotic diseases.     

Is switching antidepressants following early nonresponse more beneficial in acute-phase treatment of depression?: a randomized open-label trial

Rationale

Treatment guidelines for major depressive disorder (MDD) recommend a continuous use of antidepressants for several weeks, while recent meta-analyses indicate that antidepressant efficacy starts to appear within 2 weeks and early treatment nonresponse is a predictor of subsequent nonresponse.

Objectives

We prospectively compared 8-week outcomes between switching antidepressants and maintaining the same antidepressant in early nonresponders, to generate a hypothesis on possible benefits of early switching strategy.

Method

Patients with MDD without any treatment history for the current episode were included. When subjects failed to show an early response (i.e., ≥ 20% improvement in the Montgomery-Åsberg Depression Rating Scale (MADRS)) to the initial treatment with sertraline 50 mg at week 2, they were randomly divided into two groups; in the Continuing group, sertraline was titrated at 50-100 mg, whereas sertraline was switched to paroxetine 20-40 mg in the Switching group. A primary outcome measure was a response rate (i.e., ≥ 50% improvement in the MADRS) at week 8.

Results

Among 132 subjects, 41 subjects showed early nonresponse. The Switching group (n = 20) showed a higher rate of responders than the Continuing group (n = 21) (75% vs. 19%: p = 0.002). Further, the Switching group was also superior in the rate of remitters (total score of ≤ 10 in the MADRS) (60% vs. 14%: p = 0.004) and continuous changes in the MADRS (19.0 vs. 7.5: p < 0.001).

Conclusions

Our preliminary findings suggest that patients with MDD who fail to show early response to an initial antidepressant may derive benefits from the early switching antidepressants in the acute-phase treatment of depression.