[Integrating psychotherapeutic treatment of severe mental illness: between desirability and clinical practice]

Psychiatric care for severe and persistent mentally ill individuals has considerably changed over the last three decades. Striving for improvement in services provision for these patients has led to the emergence of various specialized community services, suited housing and supported work offers. Moreover, community-based treatment is also offered during acute episodes of mental illness. At the same time a range of evidence-based psychotherapeutic approaches targeting treatment needs of people with severe mental illness were developed in a process independent of the rise of community psychiatry. At present, however, a sufficient level of coordination of psychiatric services and integration of evidence-based psychological treatment into psychiatric care has not been achieved. Thus, these issues represent important steps in the further development.This paper discusses recent developments in psychiatric care of people with severe mental illness and reviews the evidence-based psychotherapy approaches suited to fit the needs of patient-centered integrated care.

Determinants of timely management of acute bacterial meningitis in the ED

PURPOSE: The purpose was to study the emergency management of patients with suspected meningitis to identify potential areas for improvement. METHODS: All patients who underwent cerebrospinal fluid puncture at the emergency department of the University Hospital of Bern from January 31, 2004, to October 30, 2008, were included. A total of 396 patients were included in the study. For each patient, we analyzed the sequence and timing for the following management steps: first contact with medical staff, administration of the first antibiotic dose, lumbar puncture (LP), head imaging, and blood cultures. The results were analyzed in relation to clinical characteristics and the referral diagnosis on admission. RESULTS: Of the 396 patient analyzed, 15 (3.7%) had a discharge diagnosis of bacterial meningitis, 119 (30%) had nonbacterial meningitis, and 262 (66.3%) had no evidence of meningitis. Suspicion of meningitis led to earlier antibiotic therapy than suspicion of an acute cerebral event or nonacute cerebral event (P < .0001). In patients with bacterial meningitis, the average time to antibiotics was 136 minutes, with a range of 0 to 340 minutes. Most patients (60.1%) had brain imaging studies performed before LP. On the other hand, half of the patients with a referral diagnosis of meningitis (50%) received antibiotics before performance of an LP. CONCLUSIONS: Few patients with suspected meningitis received antimicrobial therapy within the first 30 minutes after arrival, but most patients with pneumococcal meningitis and typical symptoms were treated early; patients with bacterial meningitis who received treatment late had complex medical histories or atypical presentations.

Acute Encephalopathy with Unilateral Cortical-Subcortical Lesions in Two Unrelated Kindreds Treated with Glucocorticoids Prenatally for Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency: Established Facts and Novel Insight

Background: Prenatal glucocorticoid (GC) treatment of the female fetus with 21-hydroxylase deficiency (21-OHD) may prevent genital virilization and androgen effects on the brain, but prenatal GC therapy is controversial because of possible adverse effects on fetal programming, the cardiovascular system and the brain. Case Reports: We report 2 patients with congenital adrenal hyperplasia (CAH) due to 21-OHD who were treated prenatally with dexamethasone, suffered from an acute encephalopathy and showed focal and multifocal cortical and subcortical diffusion restrictions in early MRI and signs of permanent alterations in the follow-up neuroimaging studies. Both patients recovered from the acute episode. Whereas the first patient recovered without neurological sequelae the second patient showed hemianopsia and spastic hemiplegia in the neurological follow-up examination. Conclusion: These are 2 children with CAH, both treated prenatally with high doses of dexamethasone to prevent virilization. The question arises whether prenatal high-dose GC treatment in patients with CAH might represent a risk factor for brain lesions in later life. Adverse effects/events should be reported systematically in patients undergoing prenatal GC treatment and long-term follow-up studies involving risk factors for cerebrovascular disease should be performed.

Catheter-based treatment of ilio-femoral deep vein thrombosis - an update on current evidence

Ilio-femoral deep vein thrombosis (DVT) has a high rate of long-term morbidity in the form of the postthrombotic syndrome (PTS). Therefore, management of acute thrombosis should not only focus on the prevention of acute complications such as propagation or embolisation of the initial clot but also on preventing PTS and recurrent thrombosis. Contemporary catheter-based treatments of deep vein thrombosis have proven to be safe and effective in selected patients. Current guidelines recommend medical therapy with anticoagulation alone for all but the most severe, limb-threatening thrombosis. They additionally allow for consideration of catheter-based treatment in patients with acute DVT and low risk of bleeding complications to prevent PTS. Recent studies favoring interventional therapy have not been included in these guidelines. Data on long-term outcome is expected to be published soon, clarifying and very likely strengthening the role of catheter-based treatments in the management of acute ilio-femoral DVT.

Management of Patients Presenting with Acute Subdural Hematoma due to Ruptured Intracranial Aneurysm

Acute subdural hematoma is a rare presentation of ruptured aneurysms. The rarity of the disease makes it difficult to establish reliable clinical guidelines. Many patients present comatose and differential diagnosis is complicated due to aneurysm rupture results in or mimics traumatic brain injury. Fast decision-making is required to treat this life-threatening condition. Determining initial diagnostic studies, as well as making treatment decisions, can be complicated by rapid deterioration of the patient, and the mixture of symptoms due to the subarachnoid hemorrhage or mass effect of the hematoma. This paper reviews initial clinical and radiological findings, diagnostic approaches, treatment modalities, and outcome of patients presenting with aneurysmal subarachnoid hemorrhage complicated by acute subdural hematoma. Clinical strategies used by several authors over the past 20 years are discussed and summarized in a proposed treatment flowchart.

Oral prednisolone induced acute generalized exanthematous pustulosis due to corticosteroids of group A confirmed by epicutaneous testing and lymphocyte transformation tests

BACKGROUND: Acute generalized exanthematous pustulosis (AGEP) is a rare cutaneous eruption which is often provoked by drugs. CASE REPORT: We report 2 cases of AGEP which showed rapidly spreading pustular eruptions accompanied by malaise, fever and neutrophilia after the administration of systemic prednisolone (corticosteroid of group A, hydrocortisone type). The histological examination showing neutrophilic subcorneal spongiform pustules was consistent with the diagnosis of AGEP. In both cases the rash cleared within a week upon treatment with topical steroids (corticosteroid of group D1, betamethasonedipropionate type and corticosteroid of group D2, hydrocortisone-17-butyrate type). Three months after recovery, the sensitization to corticosteroids of group A was confirmed by epicutaneous testing and positive lymphocyte transformation tests. CONCLUSION: These cases show that systemic corticosteroids can induce AGEP and demonstrate that epicutaneous testing and lymphocyte transformation tests may be helpful in identifying the causative drug. Our data support previous reports indicating an important role for drug-specific T cells in inducing neutrophil inflammation in this disease.

Epidermal caspase-3 cleavage associated with interferon-gamma-expressing lymphocytes in acute atopic dermatitis lesions

Keratinocyte apoptosis mediated by Fas/Fas ligand molecular interactions and subsequent caspase activation is believed to play an important role in the pathogenesis of atopic dermatitis (AD), in particular for the formation of spongiosis. To estimate epidermal caspase activation in normal and AD skin under in vivo conditions, we analysed caspase-3 cleavage by immunohistology. In normal skin as well as non-lesional AD skin, we detected caspase-3 cleavage in single cells of the basal layer. In contrast, in acute lesional AD skin, we not only obtained evidence for increased expression of cleaved caspase-3 in keratinocytes of the basal layer but also observed caspase-3 cleavage in one or more layers of the spinous cell layer, in particular in spongiotic areas. Short-term topical treatment of the skin lesions with tacrolimus or pimecrolimus abolished the expression of cleaved caspase-3 in the spinous layer. Moreover, epidermal caspase-3 cleavage correlated with the numbers of dermal interferon-gamma (IFN-gamma)-expressing CD4+ and CD8+ lymphocytes in skin lesions of AD patients, supporting the view that IFN-gamma is important for the activation of proapoptotic pathways in keratinocytes. This is also confirmed by the observation of increased Fas expression on keratinocytes in acute AD lesions that was markedly reduced following topical calcineurin inhibitor treatment. These data suggest that caspase-3 cleavage in the spinous layer of the epidermis is a pathologic event contributing to spongiosis formation in AD, whereas cleavage of caspase-3 in basal cells might represent a physiologic mechanism within the process of epidermal renewal.

Vitamin E reduces antidepressant-related beta-adrenoceptor down-regulation in cultured cells. Comparable effects on St. John's wort and tricyclic antidepressant treatment

The mode of action of antidepressants is still a matter of debate. Acute inhibition of neurotransmitter reuptake in central neuronal synapses, followed by a down-regulation of central postsynaptic beta-adrenoceptor (beta-AR) numbers were consistently observed in vivo, while a reduction in surface beta-AR density was found in cell cultures. Effects of the tricyclic antidepressant desipramine (DMI) were abolished by vitamin E (alpha-TOC) in vitro as well as in vivo. Alpha-TOC interfered with antidepressant-induced changes of cellular plasma membrane properties and with recycling of beta-AR. St. John's wort (SJW) extract reduced beta-AR numbers in cultured cells to a similar extent as DMI or the selective serotonin re-uptake inhibitor fluoxetine. We chronically co-exposed cell cultures to SJW extract and to alpha-TOC. Receptor down-regulation following exposure to the plant extract was inhibited in the presence of alpha-TOC suggesting a mode of action of SJW extract comparable to that of synthetic antidepressants. Inhibition of cell proliferation by the plant extract was also significantly reduced by alpha-TOC.

Stent grafting of acute hepatic artery bleeding following pancreatic head resection

The purpose of this study was to report the potential of hepatic artery stent grafting in cases of acute hemorrhage of the gastroduodenal artery stump following pancreatic head resection. Five consecutive male patients were treated because of acute, life-threatening massive bleeding. Instead of re-operation, emergency angiography, with the potential of endovascular treatment, was performed. Because of bleeding from the hepatic artery, a stent graft (with the over-the-wire or monorail technique) was implanted to control the hemmorhage by preserving patency of the artery. The outcome was evaluated. In all cases, the hepatic artery stent grafting was successfully performed, and the bleeding was immediately stopped. Clinically, immediately after the procedure, there was an obvious improvement in the general patient condition. There were no immediate procedure-related complications. Completion angiography (n=5) demonstrated control of the hemorrhage and patency of the hepatic artery and the stent graft. Although all patients recovered hemodynamically, three individuals died 2 to 10 days after the procedure. The remaining two patients survived, without the need for re-operation. Transluminal stent graft placement in the hepatic artery is a safe and technically feasible solution to control life-threatening bleeding of the gastroduodenal artery stump.

Invasive sphenoidal aspergillosis: successful treatment with sphenoidotomy and voriconazole

Treatment of invasive sphenoidal aspergillosis is surgical, followed by antifungal therapy, mostly amphotericin B. To optimize the adjuvant antifungal treatment, which is often limited by severe side effects, the new triazole antifungal agent voriconazole with broad coverage of fungal pathogens including Aspergillus was investigated in a study of 4 patients with clinical, radiological and histological signs of invasive sphenoidal aspergillosis. They first underwent endoscopic sphenoidotomy with drainage and extraction of the fungal mass. Postoperatively, 2 patients were immediately treated with voriconazole. Two patients initially received amphotericin B; but this treatment had to be stopped because of acute renal toxicity. Finally, all patients were treated orally with 200 mg voriconazole twice a day for 12-14 weeks. After this combined treatment all patients were asymptomatic and there were no endoscopic or radiological signs of residual fungal disease. The only side effects were nausea in one and transient visual disturbances in 2 other patients. In the 4 patients presented and treated, voriconazole was shown to be effective and less toxic than amphotericin B in adjuvant treatment of invasive sphenoidal aspergillosis. Copyright (c) 2007 S. Karger AG, Basel.

Mechanical thrombectomy for acute ischemic stroke: thrombus-device interaction, efficiency, and complications in vivo

BACKGROUND AND PURPOSE: Mechanical thrombectomy is a promising new modality of interventional stroke treatment. The various devices differ with regard to where they apply force on the thrombus, taking a proximal approach such as aspiration devices or a distal approach such as basket-like devices. The study compares the in vivo effectiveness and thrombus-device interaction of these 2 approaches. METHODS: Angiography and embolization with a radioopaque whole blood thrombus was performed in 10 swine. Mechanical thrombectomy was performed in 20 cranial vessels using a proximal aspiration device (Vasco35) and a distal basket-like device (Catch) with and without proximal balloon occlusion. Fifty-six retrieval attempts were made. RESULTS: The proximal device allowed fast repeated application with a low risk of thromboembolic events (3%) and vasospasm, but it had a significantly lower success rate (39.4%) in retrieving thrombotic material than the distal device (DD) (82.6%; odds ratio, 7.3; 95% CI, 2.0 to 26.4). The compaction of the thrombus during retrieval with DD increased the risk of vessel wall irritation significantly (P<0.01) and complicated retrieval into the guiding catheter. The number of embolic events was significantly higher with DD (26%; odds ratio, 11.3; 95% CI, 1.35 to 101.6) unless proximal balloon occlusion was used. CONCLUSIONS: The proximal and the distal approaches to mechanical thrombectomy proved to be effective at achieving recanalization of cranial vessels. The proximal device is faster in application and allowed repeated attempts with a low complication rate. The DD is more successful at removing thrombotic material, but its method of application and attendant thrombus compaction increase the risk of thromboembolic events and vasospasms.

Time to admission in acute ischemic stroke and transient ischemic attack

BACKGROUND AND PURPOSE: The effect of thrombolysis depends on the time from stroke onset to treatment and therefore also on the time when patients come to the hospital. This study was designed to analyze the variables that influence the time from symptom onset to admission (TTA) to the stroke unit. METHODS: We evaluated the medical records of 615 consecutive stroke or transient ischemic attack (TIA) patients admitted to our neurological department within 48 hours after symptom onset. RESULTS: The median TTA was 180 minutes. Referral by emergency medical services (EMS; P<0.001), high National Institutes of Health Stroke Scale (NIHSS) scores (P<0.001), strokes in the carotid territory (P<0.001), and strokes not attributable to small vessel disease (P<0.001) were associated with shorter prehospital delays. The TTA was adjusted for travel times (adjTTA), and all these variables remained significantly associated with time to admission. In addition, patients with previous experience with stroke or TIA had longer adjTTA (P=0.028). Regression analysis confirmed the independent association between referral by EMS (P=0.010), high NIHSS scores (P<0.001), carotid territory stroke (P<0.001), and first-ever cerebrovascular event (P=0.022) with shorter adjTTA. CONCLUSIONS: Factors such as NIHSS scores and stroke location influence the time to admission but, unlike referral pathways, cannot be modified. Educational programs and stroke campaigns should therefore not only teach typical and less common stroke symptoms and signs but also that EMS provides the fastest means of transportation to a stroke unit and the best chances to get treatment early.

ATRA resolves the differentiation block in t(15;17) acute myeloid leukemia by restoring PU.1 expression

Tightly regulated expression of the transcription factor PU.1 is crucial for normal hematopoiesis. PU.1 knockdown mice develop acute myeloid leukemia (AML), and PU.1 mutations have been observed in some populations of patients with AML. Here we found that conditional expression of promyelocytic leukemia-retinoic acid receptor alpha (PML-RARA), the protein encoded by the t(15;17) translocation found in acute promyelocytic leukemia (APL), suppressed PU.1 expression, while treatment of APL cell lines and primary cells with all-trans retinoic acid (ATRA) restored PU.1 expression and induced neutrophil differentiation. ATRA-induced activation was mediated by a region in the PU.1 promoter to which CEBPB and OCT-1 binding were induced. Finally, conditional expression of PU.1 in human APL cells was sufficient to trigger neutrophil differentiation, whereas reduction of PU.1 by small interfering RNA (siRNA) blocked ATRA-induced neutrophil differentiation. This is the first report to show that PU.1 is suppressed in acute promyelocytic leukemia, and that ATRA restores PU.1 expression in cells harboring t(15;17).

Safety and outcome of patients with an acute ST-elevation myocardial infarction transferred for primary coronary intervention: the Neuchâtel experience

BACKGROUND: Transferring patients with ST-elevation myocardial infarction (STEMI) for primary percutaneous coronary intervention (PCI) from a community hospital to a PCI centre has been evaluated in randomised trials and shown to be safe and effective. A prolonged transfer time may restrict the benefit of this strategy. AIM: We sought to assess 1) safety of transfer from Neuchâtel to Berne, 2) time intervals of patients transferred either directly from on-site or after evaluation in the local emergency room, and 3) clinical long-term outcome. METHODS AND RESULTS: 42 patients with STEMI eligible for reperfusion therapy were prospectively included between January 2003 and June 2004. Twenty patients (48%, group 1) were directly transferred to the PCI centre from on-site. Twenty-two were transferred after initial treatment in the local emergency room: 11 patients (26%, group 2) presented spontaneously at the hospital and 11 patients (26%, group 3) were admitted by the rescue team. No major complication occurred during transport. Median transport time was 33 minutes. Median time from first healthcare contact to balloon consisted of 131 minutes in group 1, 158 minutes in group 2 and 174 minutes in group 3. The overall rate of Major Adverse Cardiac Events (MACE) at 6 months amounted to 9.5%. CONCLUSIONS: Transfer for primary PCI of our patients with acute STEMI was safe. Direct transfer from on-site to the PCI centre reduced the time of ischaemia. The overall MACE rate was low.

Alternate or additional findings to stone disease on unenhanced computerized tomography for acute flank pain can impact management

PURPOSE: We evaluated the incidence and clinical relevance of alternate or additional findings on unenhanced CT in patients with acute flank pain and suspected urinary calculi. MATERIALS AND METHODS: A consecutive series of 1,500 patients underwent unenhanced CT due to acute flank pain. The absence or presence of urinary tract calculi and their localization were recorded. Alternate or additional CT findings were classified according to whether they required immediate or deferred treatment, or were of little or no clinical importance. RESULTS: Of the 1,500 patients 1,035 (69%) had urinary tract calculi, including 309 (30%) with nephrolithiasis, 377 (36%) with ureterolithiasis and 349 (34%) with the 2 conditions. Urolithiasis alone was found in 331 of these patients (32%) and additional pathological conditions were noted in 704 (68%). Of all patients 1,064 (71%) had other or additional CT findings. Of all patients 207 (14%) had nonstone related CT findings requiring immediate or deferred treatment, 464 (31%) had pathological conditions of little clinical importance and 393 (26%) had pathological conditions of no clinical relevance. CT was normal in 105 of all patients (7%). CONCLUSIONS: Unenhanced CT in patients with acute flank pain allows the accurate diagnosis of urinary stone disease and it can also provide further important information leading to emergency or deferred treatment in a substantial number of patients.