Effects of non-pharmacologic prevention on delirium in critically ill patients: A network meta-analysis.

BACKGROUND: Delirium is a common complication among patients in the intensive care unit (ICU). It is important to prevent the occurrence of delirium in critically ill patients. AIM: This review aimed to evaluate the efficacy of non-pharmacological interventions and determine what combination of these is effective in preventing delirium among Intensive Care Unit patients. STUDY DESIGN: A systematic review and meta-analysis. This review follows the guidelines of the Preferred Reporting Items for Systematic reviews and Meta Analysis statements for Network Meta-Analysis (PRISMA-NMA). Data sources included the Cumulative Index to Nursing & Allied Health Literature., MEDLINE, and Cochrane library databases. The integrated data were investigated with odds ratio (OR) and 95% confidence interval (95% CI), using the random-effects Mantel-Haenszel model. Data were considered significant when p < 0.05. Furthermore, to reveal what combination of care is effective, we performed a network meta-analysis estimated OR, 95% CI. RESULTS: We identified three randomized controlled trials and eight controlled before-after trials (11 in total, with 2549 participants). The pooled data from 11 trials of multicomponent intervention had a significant effect on delirium prevention (OR 0.58, 95% CI 0.44-0.76, p < 0.001). As a result of network meta-analysis, two bundles were effective compared to the control group in reducing the incidence of delirium: a) the combination of sleep promotion (SP), cognitive stimulation (CS), early mobilization (EM), pain control (PC), and assessment (AS) (OR 0.47, 95% CI 0.35-0.64, p < 0.002), and b) the combination of SP and CS (OR 0.46, 95% CI 0.28-0.75, p < 0.001). CONCLUSION: This study revealed that non-pharmacological interventions, particularly multicomponent interventions, helped to prevent delirium in critically ill patients. In the network meta-analysis, the most effective care combination for reducing incidence of delirium was found to be multicomponent intervention, which comprises SP-CS-EM-PC-AS, and SP-CS. RELEVANCE TO CLINICAL PRACTICE: These findings reveal an efficient combination of multicomponent interventions for preventing delirium, which may be a very important prerequisite in planning care programs in the future.

Changes in cortical, cardiac, and respiratory activities in relation to spontaneous rhythmic jaw movements in ketamine-anesthetized guinea pigs.

It has been reported that rhythmic jaw movements (RJMs) spontaneously occur in ketamine-anesthetized animals. The present study investigated the physiological processes that occur during the cortical, cardiac, and respiratory events which contribute to the genesis of RJMs in animals after supplemental ketamine injections. Fourteen guinea pigs were prepared to allow electroencephalographic, electrocardiographic, and electromyographic activities to be recorded from the digastric muscle, measurement of jaw movements, and nasal expiratory airflow under ketamine-xylazine anesthesia. Rhythmic jaw movements spontaneously occurred with rhythmic digastric muscle contractions, 23-29 minutes after injection of supplemental ketamine (12.5 and 25.0 mg kg-1 , intravenously). The cycle length of RJMs did not differ significantly between the two doses of ketamine (mean±SD: 12.5 mg kg-1 , 326.5 ± 60.0 ms; 25 mg kg-1 , 278.5 ± 45.1 ms). Following injection of ketamine, digastric muscle activity, heart and respiratory rates, and cortical beta power significantly decreased, while cortical delta and theta power significantly increased. These changes were significantly larger in animals given 25.0 mg kg-1 of ketamine than in those given 12.5 mg kg-1 . With the onset of RJMs, the levels of these variables returned to pre-injection levels, regardless of the dose of ketamine administered. These results suggest that, following supplemental ketamine injections, spontaneous RJMs occur during a specific period when the pharmacological effects of ketamine wear off, and that these RJMs are characterized by stereotypical changes in cardiac, respiratory, and cortical activities.

Upregulation of calcitonin gene-related peptide, neuronal nitric oxide synthase, and phosphorylated extracellular signal-regulated kinase 1/2 in the trigeminal ganglion after bright light stimulation of the eye in rats.

Bright light stimulation of the eye activates trigeminal subnucleus caudalis (Vc) neurons in rats. Sensory information is conveyed to the Vc via the trigeminal ganglion (TG). Thus, it is likely that TG neurons respond to photic stimulation and are involved in photic hypersensitivity. However, the mechanisms underlying this process are unclear. Therefore, the hypothesis in this study is bright light stimulation enhances the excitability of TG neurons involved in photic hypersensitivity. Expressions of calcitonin gene-related peptide (CGRP) and neuronal nitric oxide synthase (nNOS) were significantly higher in TG neurons from 5 min to 12 h after photic stimulation of the eye. Phosphorylation of extracellular signal-regulated kinase1/2 (pERK1/2) was enhanced in TG neurons within 5 min after photic stimulation, while pERK1/2 immunoreactivity in satellite glial cells (SGCs) persisted for more than 12 h after the stimulus. Activation of SGCs was observed from 5 min to 2 h. Expression of CGRP, nNOS, and pERK1/2 was observed in small and medium TG neurons, and activation of SGCs and pERK1/2-immunoreactive SGCs encircling large TG neurons was accelerated after stimulation. These results suggest that upregulation of CGRP, nNOS, and pERK1/2 within the TG is involved in photic hypersensitivity.

Measurement of Respiration Rate and Depth Through Difference in Temperature Between Skin Surface and Nostril by Using Thermal Image.

The purpose of the present study was to propose a method to measure a respiration rate (RR) and depth at once through difference in temperature between the skin surface and nostril by using a thermal image. Although there have been a lot of devices for contact RR monitoring, it was considered that the subjects could be inconvenienced by having the sensing device in contact with their body. Our algorithm enabled us to make a breathing periodic function (BPF) under the non-contact and non-invasive condition through temperature differences near the nostril during the breath. As a result, it was proved that our proposed method was able to classify differences in breathing pattern between normal, deep, and shallow breath (P < 0.001). These results lead us to conclude that the RR and depth is simultaneously measured by the proposed algorithm of BPF without any contact or invasive procedure.

Asymmetric synthesis of α-chiral hydroxyalkylphosphines by a catalytic enantioselective reduction of acylphosphines.

Enantioselective reduction of acylphosphines, after precomplexation with borane, proceeded smoothly in the presence of a chiral oxazaborolidine catalyst and catecholborane. α-Hydroxyalkylphosphine products were obtained as phosphine-borane complexes in good yield and enantioselectivity. One of the products of the enantioselective reduction was successfully applied as an optically active phosphine ligand for asymmetric catalysis after suitable derivatization.

Risk factors for left atrial thrombus from transesophageal echocardiography findings in ischemic stroke patients.

BACKGROUND: To identify the cause of cerebral embolism, we performed transesophageal echocardiography (TEE) in patients suspected of embolic brain infarction including transient ischemic attack (TIA). We analyzed TEE findings and investigated factors associated with left atrial thrombus (LAT) detected by TEE. METHODS: We enrolled 98 consecutive patients who underwent TEE and had acute brain infarction or TIA that was possibly due to embolism. We assessed age, sex, presence of atrial fibrillation (AF), days from admission to TEE and TEE findings, including the prevalence of LAT, spontaneous echo contrast (SEC), left atrial appendage (LAA) slow flow velocity, patent foramen ovale (PFO), atrial septal aneurysm and aortic plaque (ASA). RESULTS: LAT was detected with TEE in 20 patients (20%). The factors that were significantly associated with the presence of LAT were male sex (unadjusted odds ratio (OR), 3.94; 95% confidence interval (CI), 1.07-14.58; p=0.037), presence of AF (unadjusted OR, 9.58; 95% CI, 2.58-35.50; p< 0.001), SEC (unadjusted OR, 8.48; 95% CI, 2.57-28.00; p< 0.001) and LAA slow flow velocity (unadjusted OR, 5.18; 95% CI, 1.59-16.91; p=0.005). Multivariate logistic regression analysis revealed that male sex (adjusted OR, 5.30; 95% CI, 1.09-25.71; p=0.039), presence of AF (adjusted OR, 8.97; 95% CI, 1.10-73.20; p=0.041) and SEC (adjusted OR, 10.87; 95% CI, 1.001-118.0; p=0.049) were independently associated with LAT, but LAA slow flow velocity was not. CONCLUSION: SEC is an important risk factor associated with LAT in patients suspected of embolic brain infarction that is independent of AF.

Asymmetric Suzuki-Miyaura coupling in water with a chiral palladium catalyst supported on an amphiphilic resin.

You oughta use water: Broad functional-group (FG) tolerance was observed for the title coupling of aryl halides (X = Cl, Br, I) and aryl boronic acids to give biaryl compounds with up to 94% ee. The chiral imidazoindole phosphine-palladium catalyst supported on an amphiphilic polystyrene-poly(ethylene glycol) (PS-PEG) resin could be recycled readily.

Phosphorus-carbon bond formation by lewis Acid catalyzed/mediated addition of silylphosphines.

Triethylaluminum-catalyzed/mediated addition of a silylphosphine to aldehydes and epoxides is described. Organophosphines containing a silyloxy group at the alpha- or beta-position on the alkyl substituent are successfully prepared in good yields.

Regio- and stereoselective synthesis of alkenylphosphines: a rhodium-catalyzed hydrophosphination of alkynes using a silylphosphine.

A novel rhodium-catalyzed hydrophosphination of alkynes using a silylphosphine as a phosphino group source is described. A variety of alkynes, both terminal and internal ones with aryl, alkyl, and carboxyl groups, gave the corresponding alkenylphosphines in a highly regioselective and syn-selective manner. Alkenes with an electron-withdrawing group also gave the corresponding adducts in good yields.

[Two cases of top of the basilar syndrome with onset seizure].

We reported 2 patients with top of the basilar syndrome manifested by onset seizure. Patient 1 was a 76-year-old man. When he was sleeping, suddenly he gave a loud cry and went into convulsions. So he was brought to our hospital by ambulance. On admission, he had unconsciousness and left hemiplegia. Patient 2 was a 70-year-old man. When he was bathing, he lost his consciousness and brought to our hospital by ambulance. On admission, he had convulsion and tetraplegia. Both patients had convulsions and palsy when they had brain infarctions. Brain diffusion weighted MR image showed high intensity area in bilateral internal thalamus, brainstem and cerebellum and no high intensity area in cerebral cortex. We know well that Todd's palsy is palsy after convulsion, but vertebro-basilar occlusion also shows convulsion and palsy. Therefore attention should be paid in the case of the patients who had convulsion and palsy.

[Evaluation of neurosonography for a case of brainstem transient ischemic attack (TIA) due to proximal subclavian artery stenosis, with favorable outcome after axillo-axillary bypass grafting].

We report an 82-year-old man with crescendo brainstem TIA and left upper-limb ischemia due to the left proximal subclavian artery stenosis. Angiography revealed that the left proximal subclavian artery was stenotic. The right vertebral artery was considered to be aplastic or occlusive. Neurosonography, especially the echo-Doppler study of the left vertebral artery, showed that the subclavian artery steal phenomenon did not occur. This study has enabled us to opt for axillo-axillary bypass. We preferred to avoid percutaneous transluminal angioplasty in order to avoid the risk of embolization. The patient received the axillo-axillary bypass operation. He has been free of TIAs and the left upper-limb ischemia since the surgery. We have evaluated his blood circulation fully, by comparing his state before and after the axillo-axillary bypass grafting.

Intracranial invasive aspergillosis originating in the sphenoid sinus: a successful treatment with high-dose itraconazole in three cases.

We report three cases of intracranial aspergillosis originating in the sphenoid sinus in immunocompetent patients. The patients presented with an orbital apex syndrome in that a unilateral loss of vision and cranial nerve III palsy were seen in all cases and a contralateral involvement was also seen in one case. Despite the initial treatment with a conventional dose of itraconazole (ITCZ, 200 mg/day), the neurological deficits failed to improve and the granulomatous inflammation was not suppressed. Therefore, we treated with a combination of a high dose of ITCZ at 500-1000 mg/day (16-24 mg/kg/day) and amphotericin B (AMPH-B) at 0.5 mg/kg/day, in conjunction with a pulse dose of methylprednisolone at 1000 mg/day. Two cases responded favorably in that the ocular movements completely recovered, and their maximum serum concentrations of the hydroxy ITCZ were 7816 ng/ml and 5370 ng/ml. However, the other case worsened, despite ITCZ treatment at 16 mg/kg/day, and the serum concentration of the hydroxy ITCZ was 3863 ng/ml. The surgical decompression of the cavernous sinus via an extradural approach was performed, and the dose of ITCZ was increased to 24 mg/kg/day. The resulting serum concentration of the hydroxy ITCZ was 4753 ng/ml, and the outcome of this case has been favorable. These results suggest that a high blood level of the hydroxy ITCZ (more than 4500 ng/ml) is a prerequisite for the successful treatment of intracranial aspergillosis and that the combination treatment of ITCZ with AMPH-B would be preferred. The concomitant use of steroid and/or surgical decompression should be considered, if the invasiveness is not well-controlled in spite of intensive medical therapy.

[Dramatic but temporary improvements in a case of CNS intravascular malignant lymphomatosis].

A 54-year-old man with a past history of gastric malignant lymphoma treated by the total gastrectomy and the chemotherapy, developed bilateral sudden deafness one year later. Two years after the gastrectomy he became abruptly paraplegic with sensory impairments of the lower extremities and neurogenic bladder. Serum LDH and soluble IL-2 receptor were high in titers (552 U/l and 1,090 U/l, normal range 145-519). Although the imaging studies of the spinal cord were negative, the myelopathic symptoms resolved dramatically after a course of pulse dose methylprednisolone therapy. However, he soon developed an abnormal behavior and mental deterioration in 3 weeks. The MRIs of the brain revealed abnormal signals compatible with multiple cerebral infarctions. As intravascular malignant lymphomatosis (IML) was suspected because of the laboratory and MRI findings, biopsies of the skin, the bone marrow, the muscle and the lymph node were carried out, without evidence of lymphoma. The brain biopsy ultimately confirmed the presence of IML. The patient remarkably responded to biweekly CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) therapy in terms of regaining the mental alertness and improved hearing. However, the CHOP therapy was prematurely interrupted prior to completion because of infective arthritis. The relapse soon ensued, and he died 6 months after admission. This case was of interest because a solid gastric lymphoma appears to have transformed into the form of intravascular lymphomatosis without mass formations or leukemic changes. Although the neurological symptoms in association with IML are thought to be the results of ischemic events, this case illustrates a remarkable reversibility of the symptoms. This implies that the cerebral symptoms are not necessarily the results of typical ischemic infarction, but due to relative ischemia because of chiefly capillary-venous occlusion by lymphoma cells. The majority of the symptoms is thus attributable to the functional impairment. Therefore, the therapeutic intervention may dramatically improve the symptoms due to IML.

[A case of brain infarction with nephrotic syndrome].

A 47-year-old man lost his consciousness and brought to our hospital by ambulance. On admission, he had aphasia and upper right limb paresis. Diffusion weighted MR image of the brain on admission showed multiple high intensity areas in the left middle cerebral artery (MCA) territory. Brain angiography performed on the 2nd hospital day revealed the left MCA severe stenosis. We started intravenous antithrombotic therapy on the 1st day. The left carotid angiography on 12th day demonstrated that the left MCA stenosis was improved. He had medical history of hypertension, diabetes mellitus and gout. But he had only slight atherosclerosis, and had no arrhythmia and patent foramen ovale. Blood chemistry test showed marked hypoproteinemia and hyperlipidemia, and urine examination showed proteinuria. He was diagnosed as nephrotic syndrome for the first time. Nephrotic syndrome brought hypercoagulability, so we suspected that nephrotic syndrome concerned with brain infarction.

[A case of recurrent bacterial meningitis by delayed cerebrospinal fluid (CSF) leakage due to a head trauma].

A 42-year-old man was admitted due to recurrent bacterial meningitis, as he had been treated here for bacterial meningitis three years prior to the current event. He had a remote history of head injury that he had almost forgotten, and his laboratory data showed no immunodeficiency state. 111In-DTPA cisternography showed an abnormal radioactive accumulation in the frontal lobe adjacent to the left frontal sinus at 23 hours after intrathecal injection, and MPR CT images revealed the left frontal sinus bone fracture. These findings indicated that he had a head injury by which a delayed CSF fistula has been formed. He was surgically treated for a CSF leakage. Although a combination therapy of ABPC and CTRX was efficacious for this patient, this regimen may not be ideal, as meningitis by PRSP has been increasing in incidence. Pneumococcal meningitis, once not a difficult infection to treat, could be a difficult one, as resistant strains to ABPC and CTRX have been more common.

[Recurrent multiple cerebral hemorrhages complicated with polyarteritis nodosa].

In January 2001, a 72-year-old woman, who had been treated for polyarteritis nodosa, and vasculitic neuropathy, was admitted in somnolent state. She was monoparetic in her right leg, and disoriented. Neuroimaging studies revealed multiple superficial parenchymal hemorrhages in the bilateral hemispheres with dural Gd enhancement and parenchymal thickenings. No evidence of intracranial vasculitis was seen in visible arterial branches and veins by MRV and helical CTs. While in the hospital, intracerebral hemorrhage recurred three times. In April 2001, the third large intracerebral hemorrhage occurred, for which the removal of hematoma was carried out and brain biopsy was done. The specimens showed an evidence of cerebrovascular amyloidosis, but no inflammation. In view of the absence of angitis in the parenchymal and pial blood vessels, despite the presence of pachymeningitis, the cortical and bridging veins which drained into the venous sinuses, were likely involved in inflammation. Impaired venous drainage due to pachymeningitis might be a mechanism by which recurrent multiple cerebral hemorrhages have taken place in the presence of amyloid angiopathy.