text:
Assessment Methods > Health Services
The Assessment and Management of Agitation and Delirium in the General Hospital
Theodore A. Stern, MD; Christopher M. Celano, MD; Anne F. Gross, MD; Jeff C. Huffman, MD; Oliver Freudenreich, MD; Nicholas Kontos, MD; Shamim H. Nejad, MD; Jennifer Repper-DeLisi, PMHCNS-BC, APN; and B. Taylor Thompson, MD
The Psychiatric Consultation Service at Massachusetts General Hospital (MGH) sees medical and surgical inpatients with comorbid psychiatric symptoms and conditions. Such consultations require the integration of medical and psychiatric knowledge. During their twice-weekly rounds, Dr Stern and other members of the Consultation Service discuss the diagnosis and management of conditions confronted. These discussions have given rise to rounds reports that will prove useful for clinicians practicing at the interface of medicine and psychiatry.
Dr Stern is chief of the Psychiatric Consultation Service at MGH and is a professor of psychiatry at Harvard Medical School (HMS); Drs Celano and Gross are clinical fellows in psychiatry at HMS and fellows in adult psychiatry at MGH and McLean Hospital; Dr Huffman is director of Inpatient Psychiatry Services at MGH; Drs Freudenreich, Kontos, and Nejad are attending physicians on the Psychiatric Consultation Service at MGH; Ms Repper-DeLisi is a psychiatric nurse clinician on the Nursing Consultation Service at MGH; Dr Thompson is director of the Medical Intensive Care Unit at MGH and an associate professor of medicine at HMS.
Dr Stern is an employee of the Academy of Psychosomatic Medicine; has served on the speaker's board of Reed Elsevier; is a stock shareholder in WiFiMed (Tablet MD); and has received royalties from Mosby/Elsevier and McGraw Hill. Dr Freudenreich has served as a consultant to Beacon Health Strategies and has received grant/research support from Pfizer and honoraria from Reed Medical Education.
Drs Celano, Gross, Huffman, Kontos, Nejad, and Thompson and Ms Repper-DeLisi report no financial or other affiliations relevant to the subject of this article.
Corresponding author: Anne F. Gross, MD, Department of Psychiatry, Massachusetts General Hospital, Warren 6 275 Charles St, Boston, MA 02114 (afgross@partners.org).
Prim Care Companion J Clin Psychiatry 2010;12(1):e1-e11
Published online: February 25, 2010 (doi:10.4088/PCC.09r00938yel)
Theodore A. Stern, MD; Christopher M. Celano, MD;
Anne F. Gross, MD; Jeff C. Huffman, MD;
Oliver Freudenreich, MD; Nicholas Kontos, MD;
Shamim H. Nejad, MD;
Jennifer Repper-DeLisi, PMHCNS-BC, APN;
and B. Taylor Thompson, MD
Have you ever wondered what is responsible for a patient's agitation and confusion? Have you debated about what the workup of agitation should involve? Have you been uncertain about how best to manage agitation? If so, then the following case vignette and discussion should provide the forum for answers to these and other questions related to the differential diagnosis, the assessment, and the treatment of agitation in the medically ill.
CASE VIGNETTE
Mr A, a 60-year-old man, had an unwitnessed fall from approximately 15 ft while painting his house. He was found some time later by passers-by, who called emergency medical services. At the scene, he was combative and moving all 4 extremities. He was electively intubated and brought to the hospital for further care.
Upon arrival at the emergency department, his Glasgow Coma Scale was 10. His vital signs were a heart rate of 88 beats/min, a blood pressure of 117/80 mm Hg, a respiratory rate of 14 breaths/min, an oxygen saturation of 98% on Fio2 100%, and a temperature of 98°F. He was 6 ft tall, weighed 258 lb, and had a body mass index of 35. A neurologic examination was nonfocal; Mr A's eyes were midline and his extraocular muscles showed full range.
His laboratory studies were significant for a white blood cell count of 20,000 with 90% neutrophils. A comprehensive metabolic panel, liver function tests, urinalysis, urine toxicology screen, and serum toxicology screens were all unremarkable. A noncontrast computerized tomography scan of the head revealed multiple, small hemorrhagic contusions within the right parietal and bilateral inferior frontal lobes with minimal surrounding edema, scattered subarachnoid hemorrhages, and a nondepressed right parietal lobe fracture. C-spine imaging revealed a ventral epidural hematoma with no significant cord compression and a left alar ligamentous avulsive injury but no fracture. His chest x-ray showed a right-sided sixth rib fracture and bilateral upper and lower lobe airspace opacities, consistent with aspiration pneumonia.
Mr A's medical history included hypertension, obstructive sleep apnea (for which he received continuous positive airway pressure), and thyroid nodules (for which he had undergone a thyroidectomy). His psychiatric history was unremarkable.
Treatment of his head injuries involved use of nimodipine for bleeding prophylaxis and levetiracetam for seizure prophylaxis; for his neck injury, he was maintained in an Aspen collar; for his pneumonia, he was started on antibiotics (vancomycin and cefepime). Mr A was transferred to the surgical intensive care unit (ICU) for further treatment.
In the surgical ICU, he remained intubated and was sedated with a propofol drip (initially at 300 mg/h, then titrated to a Richmond Agitation Sedation Scale score of −1 to +1; he received intravenous [IV] hydromorphone 0.25-0.5 mg q 3 hours prn for pain; he received 1.25 mg on hospital day 2 and 1.25 mg on hospital day 3). His respiratory status slowly improved; on hospital day 5, his sedation was weaned, and he was extubated. When sputum cultures revealed abundant methicillin-sensitive staphylococcus aureus, his antibiotic regimen was changed to ampicillin. Although his respiratory status was improving, his cognition remained impaired. He had periods of relative clarity and incoherent speech, as well as periods of oversedation and agitation, especially at night. He frequently pulled at his IV lines, and he removed his Foley catheter 3 times before he was adequately restrained with 2-point soft restraints. On hospital day 6, he received 1 dose of haloperidol (10 mg IV) for agitation; this was modestly effective, but his QTc lengthened (from 459 ms to 584 ms). Haloperidol was discontinued. When he became agitated later that day, he received olanzapine (5 mg); its use was not associated with QTc prolongation (his QTc ranged between 420 ms and 450 ms); olanzapine decreased his agitation. The psychiatry department was then consulted for further recommendations regarding management of his agitation.
The psychiatric consultant found Mr A sleeping in 2-point restraints. He was easily arousable and intermittently confused. He was unable to state his location or to recount the events that led to his hospitalization; he identified his location as a hospital when provided with choices. His speech was soft and slurred, and it was fluent with normal prosody (emotional melody and tone of language); however, he made frequent paraphasic (substitution of an inappropriate word) errors. He had no abnormal movements, but he frequently pulled at his nasogastric tube. He said his mood was "happy," and he appeared inappropriately bright. He responded appropriately to some direct questions but at times would respond with answers unrelated to the questions asked. He did not appear to be preoccupied. He was oriented to person but not to the month or year; he registered 3 words but recalled none at 5 minutes; with prompts, he could provide the days of the week forward but not backward. He perseverated at times (persistently giving the days of the week even after he had completed the task).
On physical examination, Mr A's temperature maximum was 101.5°F. There was wide variability in his heart rate and blood pressure; his heart rate ranged from 36 to 96 beats/min and his systolic blood pressure ranged from 100 to 190 mm Hg. His oxygen saturation was 99% while receiving 4 L via nasal cannulae. Mr A's neck was supple, and he was not diaphoretic.
On neurologic examination, cranial nerves II-X were intact. There was no evidence of hemineglect. No snout, palmomental, or glabellar reflexes were elicited. Grip strength was 5/5 bilaterally, and Mr A was able to move his toes on command. His upper extremities revealed no rigidity, cogwheeling, or tremor.
Laboratory studies revealed a calcium level of 9.1 mEq/L, a magnesium level of 1.9 mEq/L, and a potassium level of 3.6 mEq/L. Serum glucose levels were within normal limits. A complete blood count revealed a mild normocytic anemia and a borderline elevated white blood cell count. His thyroid-stimulating hormone level was 0.43. Rapid plasma reagin and human immunodeficiency virus tests had been negative the year before; they were not repeated.
A diagnosis of delirium was made. Contributing factors were thought to include hypoxia, pneumonia, and traumatic brain injury. Recommendations included the following: to continue to optimize his respiratory status, to treat his infection, and to perform frequent neurologic checks observing for signs of increased intracranial pressure. Pharmacologic interventions for agitation included use of olanzapine (2.5 mg/2.5 mg/5 mg) and valproic acid (125 mg/125 mg/500 mg); olanzapine and haloperidol were also available on a prn basis. Recommendations for an alternative antibiotic were made, as ampicillin can prolong the QTc. Repletion of electrolytes and a check of a daily electrocardiogram (EKG) were recommended to reduce the risk of torsades de pointes.
Over the next several days, Mr A's olanzapine was increased (to 10 mg po tid), valproic acid was increased (to 1,000 mg po bid), and haloperidol was tapered. On this regimen, his cognition improved slowly. Although he was suffering from a Wernicke's aphasia, his attention and orientation improved (to where he could state the year, month, and name of the hospital). Olanzapine was tapered slowly, and valproic acid was continued (due to its antiepileptic properties and its ability to decrease impulsivity).
On hospital day 14, he was transferred to a rehabilitation center that specializes in the care of patients with an acute brain injury.
WHAT IS DELIRIUM?
Broadly defined, delirium designates a disturbance of brain or mental function characterized by a clouded consciousness and confusion, a disturbance that is usually acute and transient (ie, potentially reversible) and with a restitutio ad integrum if the underlying etiology can be treated. The etymology of delirium is also informative. Delirium is derived from the Latin terms de, meaning down or away from, and lira, meaning a furrow or track in the fields; that is, to be off the track. In the case of a delirious person, his or her brain is off track. Other equally descriptive terms include acute brain failure, acute confusional state, or encephalopathy.
According to Chédru and Geschwind1 and Mesulam and associates,2 inattention is the sine qua non of delirium, with difficulties sustaining, focusing, or shifting attention. Table 1 contrasts the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision3 and the International Classification of Diseases, Tenth Revision4 operationalized diagnostic criteria. Both classification systems identify inattention and a disturbance in consciousness as the hallmarks of delirium. Ancillary cognitive features that can overshadow these core features include perceptual disturbances and psychosis (eg, illusions, visual hallucinations, or persecutory ideation that tends to be fleeting and poorly formed), language problems (eg, rambling speech or perseveration), or problems with memory and orientation. Fluctuation in symptomatology over the course of the day is characteristic, as is a disturbance in the sleep-wake cycle.5 A patient can be agitated or apathetic.6 In an extreme case, a patient is agitated and awake at night, while barely arousable during the day. Affective changes ranging from euphoria to abulia can also be observed. Not all features of the syndrome must be present; this accounts for why delirious patients look different from one another.
In a widely used algorithm that aids in the recognition of delirium, the Confusion Assessment Method inquires about the presence of a common alteration in mental status (one involving both an acute nature and a fluctuating course and characterized by inattentiveness) in addition to either disorganized thinking or an altered level of consciousness (defined as anything but alert).7
WHAT CONDITIONS LOOK LIKE DELIRIUM?
One of the conditions most commonly confused with delirium is dementia, a condition considered to have an irreversible and progressive alteration in brain function, typically with an insidious onset and without fluctuations. In general, patients with dementia are alert and fail to exhibit clouded mentation. However, dementia is a risk factor for delirium; the 2 diagnoses are not mutually exclusive, and they may be very difficult to separate from one another.8 Several other psychiatric syndromes can be confused with delirium, eg, Bell's mania (also called delirious mania),9 a category of acute and transient psychotic disorder,10 chronic psychosis, depression, and catatonia.11 A more complete differential diagnosis is provided in Table 2.
WHAT IS RESPONSIBLE FOR DELIRIUM?
The medical causes of delirium are legion. An organized approach may be facilitated by use of the mnemonic "WHHHIMP," indicating 7 potentially fatal etiologies: Wernicke's encephalopathy, hypoxemia, hypoglycemia, hypertensive crisis, intracranial bleeding, meningitis/encephalitis, and poisoning.12 Table 3 provides a more extensive list of etiologies and expands on the original WHHHIMP mnemonic.13
HOW SHOULD DELIRIUM BE ASSESSED?
Awareness of several principles may reduce the likelihood of diagnostic errors while dealing with delirium.
Delirium "always" has a medical cause. Since delirium, by definition, always has a medical cause, the identification of such a cause (including a rare cause of delirium, eg, paraneoplastic syndrome) must be aggressively pursued. In a minority of cases of delirium, no etiology can be identified. If delirium is overlooked, a patient's symptoms are often falsely attributed to a psychiatric syndrome and medical treatments are foregone.
Delirium is often multifactorial. In many cases, more than 1 factor is responsible for the development of delirium. Failing to understand this may lead to premature closure and to the overlooking of potentially reversible causes of delirium.
Delirium has no etiologic specificity. Unfortunately, delirium is a rather nonspecific response pattern of the brain. While many authors, most prominent among them the German psychiatrist Karl Bonhoeffer (the father of the theologian Dietrich Bonhoeffer),14 have attempted to delineate etiology-specific deliria, the clinical phenomenology does not provide enough guidance as to help with the etiology.
Delirium is potentially life threatening. Delirium should be suspected in anyone with an alteration in mental status; when detected, a workup should be initiated urgently.
Delirium can be subtle. In milder, subsyndromal cases or in cases with lucid periods, delirium can be missed and misdiagnosed.15 The delirium-specific aspects of the mental state (ie, inattention and impaired consciousness) can be subtle or overshadowed by more striking psychopathology (such as psychosis or oppositional behavior), leading to the inappropriate application of psychiatric diagnoses. In 1 case series of consecutively referred inpatients with delirium, 43% of patients were psychotic.16
Our patient, Mr A, fell off a ladder and developed delirium (characterized by an acute onset and by prominent problems with attention and consciousness). At least 1 of the etiologies was obvious: his head trauma. However, since delirium is often multifactorial, other causes (eg, hypoxemia due to aspiration pneumonia) were appropriately considered.
HOW SHOULD AGITATION AND DELIRIUM BE ASSESSED?
Since the core principles in the treatment of delirium are to identify and to correct the etiologic factor(s) that contribute to the patient's symptoms, a careful review of the patient's medical history and information from collateral sources may provide the necessary clues and information, especially when the patient is an unreliable historian or when his or her underlying medical condition (eg, intubation) prevents a clinician from obtaining an extensive or accurate history. One should also be cynical and consider why Mr A fell off the ladder. Was he intoxicated? Might he have been experiencing delirium as a consequence of substance withdrawal? In addition, laboratory and radiologic data may also shed light on contributing factors to the patient's problems.
As use of, and withdrawal from, pharmacologic agents are among the most common iatrogenic causes of delirium, a review of current and past medications should always be conducted. Delirium may occur when certain drugs and substances associated with physiologic dependence are discontinued abruptly or when central nervous system-active drugs reach supratherapeutic levels (with resultant neurotoxicity). Pharmacokinetic and pharmacodynamic drug interactions may further exacerbate delirium; however, management generally entails discontinuing or reducing the dose of the offending drug(s) whenever possible. If necessary, administration of the necessary antidote(s), eg, naloxone, flumazenil, or physostigmine, may be required.
WHICH DRUGS CAN PRECIPITATE DELIRIUM WHEN ABRUPTLY WITHDRAWN?
Drug withdrawal syndromes are common in general hospital settings.17 Moreover, emergent medical and surgical admissions may result in the sudden discontinuation of abused drugs, and a history of chronic drug use may be difficult to establish in an intubated patient. In addition, the physical signs of withdrawal are nonspecific (eg, increased temperature, tachycardia, or diaphoresis) and may mimic the signs of medical illness. Furthermore, while certain laboratory results (such as elevated liver enzymes and mean corpuscular volume) may indicate heavy alcohol use, no laboratory test can confirm the diagnosis.
Alcohol. Alcohol withdrawal may also be accompanied by agitation and psychosis. Its treatment often consists of the administration of increasing doses of benzodiazepines to achieve autonomic system control and to prevent alcohol withdrawal seizures. In certain cases, adjunctive treatment with neuroleptics or α2 agonists is required, especially for cases of delirium tremens manifest by an altered mental status and by agitation.18,19
Sedative-hypnotic withdrawal. Sedative hypnotics, like alcohol, also result in γ-aminobutyric acid (GABA) receptor withdrawal, and, thus, their withdrawal presents in a fashion similar to that of alcohol withdrawal. Symptom onset is a function of the half-life of the agent in question; the shorter the half-life, the quicker the onset of withdrawal. Withdrawal symptoms are generally more intense with agents (such as lorazepam, oxazepam, and alprazolam) associated with a half-life of 10-20 hours. Treatment of withdrawal from these agents consists of using a drug from the same class, but with a longer half-life, such as diazepam or chlordiazepoxide.17
Narcotic withdrawal. Delirium tends to be a rare complication of opioid withdrawal; such patients are usually able to provide an accurate history of their drug use, which prompts replacement therapy. The major clinical dilemma arises when differentiating symptoms associated with narcotic withdrawal from those due to an underlying medical illness. The syndrome is generally mild (with abdominal cramping, nausea, emesis, diarrhea, rhinorrhea, and general discomfort). Treatment involves use of a longer half-life agent, such as methadone, which can be tapered during the hospital course. Use of clonidine may also help to reduce noradrenergic signs of withdrawal; antiemetics may mitigate nausea and emesis.
HOW CAN AGITATION AND DELIRIUM BE MANAGED?
The management of patients with delirium must take into account several overarching goals: to ensure the safety of the patient and staff, to identify and treat the underlying causes, and to improve the patient's level of function.
Cognitive dysfunction, behavioral dyscontrol, and other behavioral changes associated with delirium often endanger the patient or medical staff.20 The psychiatric consultant should always assess for the risk of suicide, for self-harm, and for violence; then, a plan to minimize these risks should be implemented. Self-destructive or suicidal acts may result from underlying cognitive dysfunction (along with sensory and perceptual impairment, hallucinations, or delusions). In addition, a patient may be impulsive and attempt to get out of bed, to wander, and to fall (which may lead to further injury or death) and attempt to remove IV lines, tubes, or catheters.21
Removal of potentially dangerous items from the room and the surrounding area, institution of sitters to provide greater supervision, utilization of physical restraints, and initiation of pharmacologic treatment are often necessary.
WHICH PHARMACOLOGIC AGENTS EFFECTIVELY TREAT AGITATION AND DELIRIUM?
Although the best treatment of delirium is one that treats the problem specifically, the symptoms of delirium often decrease with use of pharmacologic agents. Antipsychotics are most frequently used for control of agitation, paranoia, and psychosis associated with delirium. In addition, depending on the etiology of the agitation, use of benzodiazepines, narcotics, and other sedatives may also be employed.
Haloperidol. Haloperidol, administered intravenously, is the preferred treatment for agitated delirious patients (as described by the guidelines of the American Psychiatric Association22) despite the fact that this route of administration has not been approved by the US Food and Drug Administration and that it now carries a "black box warning" associated with the risk of ventricular arrhythmia, including torsades de pointes.
Haloperidol has strong dopamine D2 receptor-binding affinity; this may explain its efficacy in the treatment of delirious patients. It has minimal anticholinergic activity and has few active metabolites. The effects of haloperidol on blood pressure, pulmonary artery pressure, heart rate, and respiration are mild when compared to those of IV benzodiazepines and other neuroleptics. In addition, it has little effect on respiratory drive. Intravenous administration of haloperidol is preferable to intramuscular administration since drug absorption after intramuscular administration may be inconsistent, especially in critically ill patients with hemodynamic instability. In addition, painful intramuscular injections can exacerbate paranoia, agitation, and treatment noncompliance. Moreover, use of IV haloperidol is less likely to produce extrapyramidal symptoms (EPS) than is intramuscular or even oral haloperidol.12
IV haloperidol has a mean distribution time of 11 minutes, with tranquilizing effects generally seen in 10-20 minutes. The mean half-life of haloperidol when given intravenously is approximately 24 hours. Generally, the dose of haloperidol is titrated to the severity of the underlying agitation. If agitation is mild, it is reasonable to start with 0.5-2.5 mg of IV haloperidol, if it is moderate, 5-10 mg IV is given, and if severe, 10 mg IV is given at the outset. The clinician should adjust the dose to the clinical course, and IV doses can be repeated every 15-30 minutes until calm is achieved. If marked agitation persists, the previous dose can be doubled after 30 minutes. Successive doublings may follow, as the goal of ameliorating the agitation is sought. Although rarely needed, for persistent agitation, continuous infusions of 5-10 mg/h can be initiated.12
Other typical antipsychotics. IV droperidol may also reduce agitation in delirious patients. Droperidol is more sedating than haloperidol, and, thus, care should be taken when used in patients with underlying respiratory compromise. In addition, it is a more potent α1-adrenergic receptor antagonist and thus is more likely to cause hypotension.12
Other neuroleptics that are occasionally administered parenterally for agitation include perphenazine and chlorpromazine; however, they are more often associated with hypotension, arrhythmias, and anticholinergic effects than is haloperidol.12
Atypical antipsychotics. Atypical antipsychotics (including risperidone, olanzapine, quetiapine, aripiprizole, ziprasidone, and clozapine) have also been used for the treatment of delirium. While the number of studies is limited, there does not seem to be any significant difference with regard to the efficacy of atypical antipsychotics, and none has shown a greater efficacy or an improved safety profile when compared to the use of IV haloperidol among delirious patients.23-25
Benzodiazepines. There have been few controlled studies of the efficacy of benzodiazepines as monotherapy for the treatment of delirium. The limited data available suggest that benzodiazepine monotherapy is generally ineffective as a treatment for most cases of delirium, ie, delirium that is not associated with alcohol or GABA receptor withdrawal syndromes.26,27 However, adding a benzodiazepine as an adjunctive agent to haloperidol in the management of a severely agitated patient can be helpful, as benzodiazepines may reduce the EPS (especially akathisia) of haloperidol.28 In addition, in several open studies, the combination of IV lorazepam with IV haloperidol has resulted in greater efficacy and a shorter duration of the delirium when compared with use of haloperidol alone.29,30 Of the benzodiazepines, lorazepam is most commonly used, as it has no active metabolites and is least likely to cause respiratory depression.
Narcotics. When pain may be an aggravating factor or a cause of delirium, narcotics may be useful. Morphine is the most commonly used agent in the medical setting. Morphine has very weak anticholinergic effects; however, its antihistaminergic activity may cause hypotension. Hydromorphone, a more potent narcotic, is also well tolerated in appropriate doses. Fentanyl and meperidine should be avoided in patients with an altered mental status; each has anticholinergic effects, and the accumulation of normeperidine, an active metabolite of meperidine, may cause neurotoxicity and worsening delirium.31 Methadone, with a long half-life, is also often used for pain control, and it helps to provide stable therapeutic levels of pain relief. In addition, it has been associated with N-methyl-d-aspartate receptor antagonism and decreased mesolimbic dopamine release that may help explain the lower rates of altered mental status changes seen.32,33 Respiratory depression and hypotension are side effects of all narcotics, and these should be monitored closely.
Valproate. The addition of IV valproate may be considered in the management of severe agitation when conventional therapy is inadequate or when problematic side effects emerge from the use of antipsychotics.34 Its use may be particularly helpful in patients who exhibit symptoms of disinhibition or impulsivity during episodes of agitation.35
Propofol. When agitation fails to respond to more traditional medications, IV sedation may be required. Propofol is a short-acting, IV-administered hypnotic agent. It is used for the induction and maintenance of general anesthesia, for sedation of mechanically ventilated adults, and for procedural sedation.36 Clinically, propofol is not considered an analgesic, so opioids (such as fentanyl) are often combined with propofol to help alleviate pain in critically injured patients. It has several mechanisms of action, both through potentiation of GABA-A receptor activity and also acting as a sodium channel blocker.37 Recent research has also suggested the endocannabinoid system may contribute significantly to propofol's anesthetic action and to its unique properties.38
Dexmedetomidine. Dexmedetomidine is a highly selective α2-adrenoreceptor agonist that has been shown to have both sedative and analgesic effects. Compared with clonidine, an α2-agonist used for the treatment of hypertension, dexmedetomidine has an α2 : α1-adrenoreceptor ratio of approximately 1,600 : 1 (7 to 8 times higher than clonidine), making it primarily a sedative-anxiolytic like propofol.39 It has no GABAergic activity or any anticholinergic activity, and a recent study in cardiac surgery patients has shown low rates of postoperative delirium following its administration.40 Case reports have also highlighted its usefulness in the treatment of alcohol withdrawal delirium.41,42
WHAT ARE THE COMMON SIDE EFFECTS OF
THE ANTIPSYCHOTICS USED TO TREAT DELIRIUM?
Antipsychotics used for the treatment of delirium are associated with a variety of adverse effects. These include anticholinergic effects, EPS, neuroleptic malignant syndrome (NMS), orthostatic hypotension, and, perhaps most importantly, the risk of QT interval prolongation and torsades de pointes ventricular arrhythmia.
Anticholinergic side effects (including dry mouth, urinary retention, constipation, tachycardia, and confusion) result from blockade of muscarinic cholinergic receptors. They are most often found with use of low-potency typical antipsychotics and clozapine; these agents are infrequently used to treat delirium. Among the antipsychotics typically used to treat delirium (eg, haloperidol and most atypical antipsychotics), anticholinergic side effects are rare. However, higher doses of the atypical antipsychotics olanzapine and quetiapine can result in anticholinergic effects, and one must monitor patients for these side effects when using these medications at high doses.
EPS—dystonia, akathisia, and parkinsonism—occur most often with antipsychotics that are potent D2 receptor blockers. Among agents most frequently used to treat delirium, these include haloperidol, risperidone, and, at higher doses, olanzapine. Interestingly, however, EPS are much less common with use of IV administration of haloperidol43,44; such rates are seen much less often when haloperidol is given via the IV route than orally or intramuscularly. The reason that EPS occur at markedly lower rates via the IV route is not known, though presumably this phenomenon is related to the avoidance of first-pass metabolism through the gut and the liver with IV administration.
NMS is a syndrome associated with the administration of antipsychotics. Symptoms of NMS include confusion, fever, autonomic instability, and a lead-pipe rigidity; substantially elevated levels of creatine phosphokinase (CPK) are very common. Though it is more commonly considered in patients who have primary psychotic illnesses, NMS has been observed in patients who receive antipsychotics for the treatment of delirium.45 Risk factors for NMS appear to include the type of antipsychotic used (NMS appears to occur more commonly with agents associated with EPS such as oral haloperidol) and appears to occur more frequently when these agents are given at higher doses.45,46 There is some question about whether treatment with atypical antipsychotics causes an "incomplete" form of NMS, with fewer motor symptoms and less of an elevation of CPK, but the existing literature suggests that such a syndrome appears to be associated with clozapine but not the atypicals (such as risperidone) that do have significant D2 receptor activity.47,48
Orthostatic hypotension, a significant drop in blood pressure upon sitting or standing, is related to blockade of α1 receptors. Among antipsychotics commonly used to treat delirium, orthostatic hypotension is most common among patients receiving quetiapine or risperidone. This is an important effect since patients with delirium—who have ongoing medical issues and are often deconditioned—are already at substantial risk of falls.12
One final and important adverse effect associated with antipsychotics is prolongation of the corrected QT interval (QTc). The QT interval is measured on the EKG from the beginning of the QRS complex to the end of the T wave, and it represents ventricular depolarization and repolarization within the heart. The QT interval has a characteristic length of 400-450 ms when corrected for heart rate; when the QTc is over 500 ms, it is considered as clearly prolonged. When the QTc prolongs, it serves as a substantial risk factor for torsades de pointes, a malignant polymorphic ventricular arrhythmia that may result in sudden death.12
It appears that all antipsychotics can cause QTc prolongation. Though there has not been a systematic study of the comparative QTc prolongation caused by antipsychotics in delirious patients, a study of antipsychotic administration in healthy volunteers found differential QTc prolongation depending on the agent.49 In that study, olanzapine and (oral) haloperidol appeared to cause the least prolongation of the QTc. Though haloperidol appears to be associated with limited prolongation of the QTc when given orally, IV haloperidol has been associated with QTc prolongation and with over 2 dozen cases of torsades de pointes; therefore, clinicians should be aware of significant QTc changes when this agent is used to treat patients with delirium.12
HOW DOES ONE MANAGE THE RISK OF Torsades de Pointes IN A PATIENT RECEIVING ANTIPSYCHOTICS FOR DELIRIUM?
First, it is important to monitor the QTc interval before and after administration of antipsychotics. Fortunately, the vast majority of patients admitted to medical or surgical units have had a baseline EKG from admission. If the patient's baseline QTc is > 500 ms, or if the QTc prolongs to that length or increases by an absolute value of 60 ms with administration of an antipsychotic, alternatives should be considered.
In addition to simply monitoring the QTc, measures should be taken to reduce the risk of QTc prolongation. When antipsychotics (and especially IV haloperidol) are used, other QT-prolonging medications (such as macrolide antibiotics, fluoroquinolones, tricyclic antidepressants, or amiodarone) (Table 4)50,51 should be avoided when other alternatives are available. Low potassium and low magnesium are associated with both QTc prolongation and torsades de pointes, and, where possible, levels of potassium and magnesium should be repleted to high-normal levels.
If the QTc interval becomes prolonged, several alternatives are available, depending on the clinical situation and the extent of the QTc prolongation. If the QTc interval has increased to slightly over 500 ms and the patient clearly would benefit from use of an antipsychotic, using a low dose of an antipsychotic that may have a lesser propensity for QT prolongation (eg, olanzapine) is an option. If the QTc has been substantially prolonged or rather high doses of an agent are needed, benzodiazepines can be used urgently for more immediate sedation and treatment of agitation. Finally, if agitation or confusion are mild and can be managed temporarily with nonpharmacologic methods, it is often the case that with time and repletion of potassium or magnesium, the QTc will normalize and antipsychotics can be restarted.50,51
WHAT SIDE EFFECTS ARE ASSOCIATED WITH OTHER PHARMACOLOGIC AGENTS USED TO TREAT DELIRIUM?
A number of other agents (including benzodiazepines, propofol, and narcotic analgesics) are sometimes given to patients with delirium. These treatments are not typically associated with anticholinergic effects, orthostatic hypotension, EPS, or QTc prolongation. However, these agents can generate side effects (eg, oversedation, respiratory depression, and gait disturbance and with benzodiazepines, risk of paradoxical disinhibition) that limit their use among patients with delirium. Furthermore, these agents frequently worsen confusion (indeed, they are common causes of delirium), and for this reason, they are much less commonly used to treat delirium.
Finally, the selective α2 agonist dexmedetomidine is generally well tolerated; the most common side effect of treatment appears to be bradycardia.52,53 At this stage, its use is more limited by reduced availability and experience (especially outside of ICUs) than by its side effect profile.
HOW COSTLY IS DELIRIUM?
Remarkably, the care of delirious patients accounts for approximately 1% of the annual US gross domestic product54 and is associated with increased length of stay, complications, and poor outcomes (including increased mortality).55-59 In a prospective study of 224 consecutive mechanically ventilated medical ICU patients (without coma), costs were significantly higher (1.6 times higher) for those with at least 1 episode of delirium versus those without delirium, after adjustment for age, comorbidity, severity of illness, degree of organ dysfunction, nosocomial infections, hospital mortality, and other potential confounders. Given that delirium developed in the majority of mechanically ventilated medical ICU patients,60 the cost savings and reduction of suffering would be substantial if the course of delirium could be shortened or, better yet, prevented.
CAN WE PREVENT DELIRIUM?
Given the high prevalence of delirium in the general hospital, its occurrence seems inevitable. Those who are elderly or who get sick enough are prone to mental status changes. While for some, the proverbial "horse has already left the barn" by the time of hospital admission, the majority of cases of delirium develop after admission.61
To prevent delirium, one must start with an analysis of risk factors. Risk factors for delirium can be divided into 3 overlapping categories: modifiable risk factors, nonmodifiable risk factors, and risks that may not be risks at all. Modifiable risk factors include sleep deprivation, impairments of vision and/or hearing, dehydration, iatrogenic and other complications of being an inpatient (most notably, having an infection), and polypharmacy62; depressive illness is also a risk for delirium.63 While it is a correctable condition, it may not be a correctable risk factor; aside from elective surgery, there are few inpatient circumstances wherein it can be addressed before delirium onset. Nonmodifiable risk factors include advanced age, acute and chronic illness, and so-called "organic" brain diseases (most notably the dementias),62 especially when executive dysfunction is present.63 Our patient, Mr A, will forever be considered at high risk for delirium because of his traumatic brain injury. Finally, we come to risks that may not be risks at all (eg, restraints and Foley catheters).64 The implementation of these measures often conveys that a mental status change or a deliriogenic condition is already afoot.
It is also crucial to ask what we seek to prevent. Delirium is not, strictly speaking, a disease; rather, it is a cluster of symptoms that is shared by a vast number of other diseases and conditions. Therefore, when delirium prevention is sought (eg, by paying proactive attention to the risk for alcohol withdrawal), is this delirium prevention or the prevention of illnesses that themselves may or may not subsequently trigger delirium? The distinction may not really matter. Conversely, surrogate terms for delirium such as confusion or agitation only capture a component of a broader syndrome. If these symptoms are prevented, is delirium actually being prevented or just ameliorated?
Keeping the above points in mind, prevention strategies can be divided into positive ("doing something") and negative ("not doing something") categories. Among the positive strategies are some old standbys (eg, providing frequent active and passive orientation cues that include displays of calendars, use of note boards, nursing reminders, and lengthy family visitations). In what is perhaps the best-known study of delirium prevention, Inouye and colleagues65 implemented either usual care or an extensive array of orientation, mobilization, sleep correction, sensory optimization, and hydration protocols among 852 geriatric patients admitted to either a regular or a specialized unit. Delirium incidence (as measured by the Confusion Assessment Method) decreased significantly by these means, though severity and recurrence rates were unaffected.65
Other positive interventions include proactive geriatrics consultation that may decrease delirium incidence66 and prophylactic low-dose haloperidol (~1.5 mg/d) that may reduce the severity and duration of delirium; however, the latter was not shown to be strictly preventative.67 Data from a large, randomized, double-blind, placebo-controlled study of olanzapine and placebo in elderly joint replacement patients68 revealed that 10 mg of olanzapine administered perioperatively reduced the incidence of postoperative delirium (from 40% to 14%) and increased the likelihood of discharge to home (versus a rehabilitation facility). A similar strategy using risperidone reduced the incidence of delirium.69 Negative prevention measures include avoidance of medications associated with the onset of delirium (eg, benzodiazepines and those agents with anticholinergic properties). While the delirium prevention literature is sparse, it is not surprising that little attention has been paid to negative strategies; in fact, it has been shown conclusively (albeit inadvertently) that benzodiazepines reliably worsen delirium27; nonetheless, this class of medications is still prescribed frequently for the "sedation" of the agitated and delirious patient.
Obstacles to delirium prevention include a small and shaky evidence base, hindered by suboptimal study designs70 and difficulty implementing nonpharmacologic strategies (as they are highly labor and training intensive). The latter issue was demonstrated by Inouye et al71 in the very hospital wherein they conducted the partially successful prevention trial. This problem may reflect an underemphasis in practice on nonpharmacologic techniques for delirium prevention or mitigation at the same time that there is a philosophical overemphasis on the idea that environment is the dominant factor in deliriogenesis. This can lead to a paradoxical situation in which there is a strong push to pharmacologically "sedate" a patient, while the pathophysiologic workup for mental status change is stalled since the patient is thought to suffer from an entity such as the so-called "ICU psychosis" (in which the ICU itself is mistakenly held to be the etiologic culprit). Whether we mitigate or prevent delirium and whether we prevent its primary causes or its secondary manifestation may not matter from a patient-suffering point of view, but it does matter in terms of how staff and family members are affected by the delirious patient.
Delirium is a common and dread complication associated with myriad conditions and medications. Early recognition and timely treatment can reduce morbidity, hospital length of stay, health care costs, and mortality. Educational efforts directed at the prevention, the diagnosis, and the effective resolution of the syndrome are sorely needed.
1. Chédru F, Geschwind N. Disorders of higher cortical functions in acute confusional states. Cortex. 1972;8(4):395-411. PubMed
2. Mesulam MM, Waxman SG, Geschwind N, et al. Acute confusional states with right middle cerebral artery infarctions. J Neurol Neurosurg Psychiatry. 1976;39(1):84-89. doi:10.1136/jnnp.39.1.84 PubMed
3. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington, DC: American Psychiatric Association; 2000.
4. World Health Organization. The ICD-10 Classification of Mental and Behavioural Disorders: Diagnostic Criteria for Research. Geneva, Switzerland: World Health Organization; 1993.
5. Meagher DJ, Moran M, Raju B, et al. Phenomenology of delirium. Assessment of 100 adult cases using standardised measures. Br J Psychiatry. 2007;190(2):135-141. doi:10.1192/bjp.bp.106.023911 PubMed
6. Meagher D. Motor subtypes of delirium: past, present and future. Int Rev Psychiatry. 2009;21(1):59-73. doi:10.1080/09540260802675460 PubMed
7. Inouye SK, van Dyck CH, Alessi CA, et al. Clarifying confusion: the confusion assessment method. A new method for detection of delirium. Ann Intern Med. 1990;113(12):941-948. PubMed
8. Meagher D, Trzepacz PT. Phenomenological distinctions needed in DSM-V: delirium, subsyndromal delirium, and dementias. J Neuropsychiatry Clin Neurosci. 2007;19(4):468-470. PubMed
9. Karmacharya R, England ML, Ongür D. Delirious mania: clinical features and treatment response. J Affect Disord. 2008;109(3):312-316. doi:10.1016/j.jad.2007.12.001 PubMed
10. Marneros A, Pillmann F, Haring A, et al. Features of acute and transient psychotic disorders. Eur Arch Psychiatry Clin Neurosci. 2003;253(4):167-174. doi:10.1007/s00406-003-0420-y PubMed
11. Swartz C, Francis A, Malur C. Delirium or catatonic disorder due to a general medical condition. J ECT. 2002;18(3):167-168, author reply 168. doi:10.1097/00124509-200209000-00012 PubMed
12. Cassem NH, Murray GB, Lafayette JM, et al. Delirious patients. In: Stern TA, Fricchione GL, Cassem NH, et al, eds. Massachusetts General Hospital Handbook of General Hospital Psychiatry. Fifth edition. Philadelphia, PA: Mosby/Elsevier; 2004;119-134. doi:10.1016/B978-0-323-02767-0.50016-4
13. Caplan JP, Cassem NH, Murray GB, et al. Delirium. In: Stern TA, Rosenbaum JF, Fava M, et al, eds. Massachusetts General Hospital Comprehensive Clinical Psychiatry. Philadelphia, PA: Mosby/Elsevier; 2008:217-229.
14. Ströhle A, Wrase J, Malach H, et al. Karl Bonhoeffer (1868-1948). Am J Psychiatry. 2008;165(5):575-576. doi:10.1176/appi.ajp.2008.07061031 PubMed
15. Meagher DJ, Maclullich AM, Laurila JV. Defining delirium for the International Classification of Diseases, 11th Revision. J Psychosom Res. 2008;65(3):207-214. doi:10.1016/j.jpsychores.2008.05.015 PubMed
16. Webster R, Holroyd S. Prevalence of psychotic symptoms in delirium. Psychosomatics. 2000;41(6):519-522. doi:10.1176/appi.psy.41.6.519 PubMed
17. Kosten TR, O' Connor PG. Management of drug and alcohol withdrawal. N Engl J Med. 2003;348(18):1786-1795. doi:10.1056/NEJMra020617 PubMed
18. Palestine ML, Alatorre E. Control of acute alcoholic withdrawal symptoms: a comparative study of haloperidol and chlordiazepoxide. Curr Ther Res Clin Exp. 1976;20(3):289-299. PubMed
19. Crippen D, Ermakov S. Continuous infusions of haloperidol in critically ill patients. Crit Care Med. 1995;23(1):214-215. doi:10.1097/00003246-199501000-00041 PubMed
20. Breitbart W, Payne DK. Pain. In: Holland J, ed. Psycho-oncology. New York, NY: Oxford University Press; 1998:450-467.
21. Lakatos BE, Capasso V, Mitchell MT, et al. Falls in the general hospital: association with delirium, advanced age, and specific surgical procedures. Psychosomatics. 2009;50(3):218-226. doi:10.1176/appi.psy.50.3.218 PubMed
22. American Psychiatric Association. Practice Guidelines for the Treatment of Psychiatric Disorders: Compendium 2006. Washington, DC: American Psychiatric Publishing; 2006.
23. Han CS, Kim YK. A double-blind trial of risperidone and haloperidol for the treatment of delirium. Psychosomatics. 2004;45(4):297-301. PubMed
24. Lacasse H, Perreault MM, Williamson DR. Systematic review of antipsychotics for the treatment of hospital-associated delirium in medically or surgically ill patients. Ann Pharmacother. 2006;40(11):1966-1973. doi:10.1345/aph.1H241 PubMed
25. Lonergan E, Britton AM, Luxenberg J, et al. Antipsychotics for delirium. Cochrane Database Syst Rev. 2007;(2):CD005594. PubMed
26. Lonergan E, Luxenberg J, Areosa Sastre A, et al. Benzodiazepines for delirium. Cochrane Database Syst Rev. 2009;(1)CD006379.
27. Breitbart W, Marotta R, Platt MM, et al. A double-blind trial of haloperidol, chlorpromazine, and lorazepam in the treatment of delirium in hospitalized AIDS patients. Am J Psychiatry. 1996;153(2):231-237. PubMed
28. Menza MA, Murray GB, Holmes VF, et al. Controlled study of extrapyramidal reactions in the management of delirious, medically ill patients: intravenous haloperidol versus intravenous haloperidol plus benzodiazepines. Heart Lung. 1988;17(3):238-241. PubMed
29. Fernandez F, Levy JK, Mansell PW. Management of delirium in terminally ill AIDS patients. Int J Psychiatry Med. 1989;19(2):165-172. PubMed
30. Adams F, Fernandez F, Andersson BS. Emergency pharmacotherapy of delirium in the critically ill cancer patient. Psychosomatics. 1986;27(suppl):33-38. PubMed
31. Fogarty T, Murray GB. Psychiatric presentation of meperidine toxicity. J Clin Psychopharmacol. 1987;7(2):116-117. PubMed
32. Choi DW, Viseskul V. Opioids and non-opioid enantiomers selectively attenuate N-methyl-d-aspartate neurotoxicity on cortical neurons. Eur J Pharmacol. 1988;155(1-2):27-35. doi:10.1016/0014-2999(88)90399-8 PubMed
33. Smith MT. Neuroexcitatory effects of morphine and hydromorphone: evidence implicating the 3-glucuronide metabolites. Clin Exp Pharmacol Physiol. 2000;27(7):524-528. doi:10.1046/j.1440-1681.2000.03290.x PubMed
34. Bourgeois JA, Koike AK, Simmons JE, et al. Adjunctive valproic acid for delirium and/or agitation on a consultation-liaison service: a report of six cases. J Neuropsychiatry Clin Neurosci. 2005;17(2):232-238. PubMed
35. Lindenmayer JP, Kotsaftis A. Use of sodium valproate in violent and aggressive behaviors: a critical review. J Clin Psychiatry. 2000;61(2):123-128. PubMed
36. Siegel MD. Management of agitation in the intensive care unit. Clin Chest Med. 2003;24(4):713-725. doi:10.1016/S0272-5231(03)00104-7 PubMed
37. Kotani Y, Shimazawa M, Yoshimura S, et al. The experimental and clinical pharmacology of propofol, an anesthetic agent with neuroprotective properties. CNS Neurosci Ther. 2008;14(2):95-106. doi:10.1111/j.1527-3458.2008.00043.x PubMed
38. Guindon J, LoVerme J, Piomelli D, et al. The antinociceptive effects of local injections of propofol in rats are mediated in part by cannabinoid CB1 and CB2 receptors. Anesth Analg. 2007;104(6):1563-1569.doi:10.1213/01.ane.0000263278.05423.a3 PubMed
39. Carollo DS, Nossaman BD, Ramadhyani U. Dexmedetomidine: a review of clinical applications. Curr Opin Anaesthesiol. 2008;21(4):457-461. doi:10.1097/ACO.0b013e328305e3ef PubMed
40. Maldonado JR, Wysong A, van der Starre PJ, et al. Dexmedetomidine and the reduction of postoperative delirium after cardiac surgery. Psychosomatics. 2009;50(3):206-217. doi:10.1176/appi.psy.50.3.206 PubMed
41. Darrouj J, Puri N, Prince E, et al. Dexmedetomidine infusion as adjunctive therapy to benzodiazepines for acute alcohol withdrawal. Ann Pharmacother. 2008;42(11):1703-1705. doi:10.1345/aph.1K678 PubMed
42. Rovasalo A, Tohmo H, Aantaa R, et al. Dexmedetomidine as an adjuvant in the treatment of alcohol withdrawal delirium: a case report. Gen Hosp Psychiatry. 2006;28(4):362-363. doi:10.1016/j.genhosppsych.2006.03.002 PubMed
43. Fricchione GL, Nejad SH, Esses JA, et al. Postoperative delirium. Am J Psychiatry. 2008;165(7):803-812. doi:10.1176/appi.ajp.2008.08020181 PubMed
44. Tesar GE, Murray GB, Cassem NH. Use of high-dose intravenous haloperidol in the treatment of agitated cardiac patients. J Clin Psychopharmacol. 1985;5(6):344-347. PubMed
45. Seitz DP, Gill SS. Neuroleptic malignant syndrome complicating antipsychotic treatment of delirium or agitation in medical and surgical patients: case reports and a review of the literature. Psychosomatics. 2009;50(1):8-15. doi:10.1176/appi.psy.50.1.8 PubMed
46. Caroff SN, Mann SC. Neuroleptic malignant syndrome. Med Clin North Am. 1993;77(1):185-202. PubMed
47. Trollor JN, Chen X, Sachdev PS. Neuroleptic malignant syndrome associated with atypical antipsychotic drugs. CNS Drugs. 2009;23(6):477-492. doi:10.2165/00023210-200923060-00003 PubMed
48. Ananth J, Parameswaran S, Gunatilake S, et al. Neuroleptic malignant syndrome and atypical antipsychotic drugs. J Clin Psychiatry. 2004;65(4):464-470. PubMed
49. US Food and Drug Administration. Center for Drug Evaluation and Research Psychopharmacological Drugs Advisory Committee. Meeting transcript (for the approval of Zeldox [ziprasidone]); Bethesda, MD; July 19, 2000. Available at: www.fda.gov/ohrms/dockets/ac/00/transcripts/3619t1a.pdf .
50. Haddad PM, Anderson IM. Antipsychotic-related QTc prolongation, torsade de pointes and sudden death. Drugs. 2002;62(11):1649-1671. doi:10.2165/00003495-200262110-00006 PubMed
51. Gupta A, Lawrence AT, Krishnan K, et al. Current concepts in the mechanisms and management of drug-induced QT prolongation and torsade de pointes. Am Heart J. 2007;153(6):891-899. doi:10.1016/j.ahj.2007.01.040 PubMed
52. Riker RR, Shehabi Y, Bokesch PM. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA. 2009;301(5):489-499. PubMed doi:10.1001/jama.2009.56
53. Pandharipande PP, Pun BY, Herr DL. Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial. JAMA. 2007;298(22):2644-2653. PubMed doi:10.1001/jama.298.22.2644
54. Socioeconomic Status and Health Chartbook. US Department of Health and Human Services publication PHS 98-1232. Hyattsville, MD: US Department of Health and Human Services; 1998.
55. Ely EW, Margolin R, Francis J, et al. Evaluation of delirium in critically ill patients: validation of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Crit Care Med. 2001;29(7):1370-1379. doi:10.1097/00003246-200107000-00012 PubMed
56. Ely EW, Siegel MD, Inouye SK. Delirium in the intensive care unit: an under-recognized syndrome of organ dysfunction. Semin Respir Crit Care Med. 2001;22(2):115-126. PubMed doi:10.1055/s-2001-13826
57. Ely EW, Inouye SK, Bernard GR, et al. Delirium in mechanically ventilated patients: validity and reliability of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). JAMA. 2001;286(21):2703-2710. doi:10.1001/jama.286.21.2703 PubMed
58. Ely EW, Gautam S, Margolin R, et al. The impact of delirium in the intensive care unit on hospital length of stay. Intensive Care Med. 2001;27(12):1892-1900. doi:10.1007/s00134-001-1132-2 PubMed
59. Ely EW, Shintani A, Bernard G, et al. Delirium in the IU is associated with prolonged length of stay in the hospital and higher mortality [abstract]. Am J Respir Crit Care Med. 2002;165:A23.
60. Milbrandt EB, Deppen S, Harrison PL, et al. Costs associated with delirium in mechanically ventilated patients. Crit Care Med. 2004;32(4):955-962. doi:10.1097/01.CCM.0000119429.16055.92 PubMed
61. Levkoff SE, Evans DA, Liptzin B, et al. Delirium: the occurrence and persistence of symptoms among elderly hospitalized patients. Arch Intern Med. 1992;152(2):334-340. doi:10.1001/archinte.152.2.334 PubMed
62. O' Keefe S. The prevention of delirium. In: Lindesay J, Rockwood K, Macdonald A, eds. Delirium in Old Age. New York, NY: Oxford University Press; 2002.
63. Greene NH, Attix DK, Weldon BC, et al. Measures of executive function and depression identify patients at risk for postoperative delirium. Anesthesiology. 2009;110(4):788-795. doi:10.1097/ALN.0b013e31819b5ba6 PubMed
64. Inouye SK, Charpentier PA. Precipitating factors for delirium in hospitalized elderly persons: predictive model and interrelationship with baseline vulnerability. JAMA. 1996;275(11):852-857. doi:10.1001/jama.275.11.852 PubMed
65. Inouye SK, Bogardus ST Jr, Charpentier PA, et al. A multicomponent intervention to prevent delirium in hospitalized older patients. N Engl J Med. 1999;340(9):669-676. doi:10.1056/NEJM199903043400901 PubMed
66. Marcantonio ER, Flacker JM, Wright RJ, et al. Reducing delirium after hip fracture: a randomized trial. J Am Geriatr Soc. 2001;49(5):516-522. doi:10.1046/j.1532-5415.2001.49108.x PubMed
67. Kalisvaart KJ, de Jonghe JFM, Bogaards MJ, et al. Haloperidol prophylaxis for elderly hip surgery patients at risk for delirium: a randomized placebo-controlled study. J Am Geriatr Soc. 2005;53(10):1658-1666. doi:10.1111/j.1532-5415.2005.53503.x PubMed
68. Larsen KA, Kelly SE, Stern TA, et al. Administration of olanzapine to prevent postoperative delirium in elderly joint replacement patients: a randomized controlled study. Psychosomatics. In press.
69. Prakanrattana U, Prapaitrakool S. Efficacy of risperidone for prevention of postoperative delirium in cardiac surgery. Anaesth Intensive Care. 2007;35(5):714-719. PubMed
70. Siddiqi N, Stockdale R, Britton AM, et al. Interventions for preventing delirium in hospitalised patients. Cochrane Database Syst Rev. 2007;2(2):CD005563. PubMed
71. Inouye SK, Bogardus ST, Williams CS, et al. The role of adherence on the effectiveness of nonpharmacologic interventions: evidence from the delirium prevention trial. Arch Intern Med. 2003;163(8):958-964. doi:10.1001/archinte.163.8.958
Quick Links: Assessment Methods , Health Services


What devices do the Razer Hammerhead USB-C work with?
Please remove any attached silicon tips. Then take a soft cloth that is lightly saturated with warm water and carefully wipe down the ear buds. Be careful not to allow liquid to penetrate the actual speaker. The silicone tips and cords can be cleaned the same way and allowed to dry before re-installing.
First confirm the issue is with the headset itself and not your audio source. ( To do this you can simply try the headset using a different source and see if the issue is still there.) Because earbuds come in direct contact with your ears, wax can sometimes build up and cause issues with the audio quality and output levels. To clean your earbuds remove any silicone tips that are installed and follow the directions below.
Take a soft cloth that is lightly saturated with warm water and carefully wipe down the ear buds. Be careful not to allow liquid to penetrate the actual speaker. If desired the silicone tips can also be cleaned in the same manner.
The Razer Hammerhead USB-C's silicon ear-tips are designed to fit snugly into your ear to keep music in your ear and at the same time keeping external sound out. Included in the packaging are ear-tips in three(3) different sizes to ensure that you have the perfect fit for you Razer Hammerhead USB-C earphones.
Does the omnidirectional microphone on the Hammerhead USB-C have any controls?
Yes, you can control volume and pick up calls with the Razer Hammerhead USB-C in-line control.
Can I use the Razer Hammerhead USB-C on my PC?
Yes, you can, if your PC has a USB-C port.
What accessories are included with the Razer Hammerhead USB-C?
The Razer Hammerhead USB-C comes out of the box with a carrying pouch, small, medium and large eartips and a pair of bi-flanges.
If you're unable to find an FAQ article that helps resolve the issue, please contact our Customer Support team here. User guides and product manuals are also available on the Razer Support page.


text:
Australia retain Ashes after victory at Old Trafford
England, who resumed the day on 18-2, were bowled out for 197 on the final day, with Australia seamer Pat Cummins taking four wickets. Australia have taken a 2-1 lead in the series and cannot lose the Ashes urn now.
By: Reuters | Manchester | Updated: September 9, 2019 12:09:50 am
Australia players react as the last England wicket falls (after a DRS review) in the 4th Ashes Test in Manchester on Sunday (Reuters Photo)
Australia retained the Ashes after beating England by 185 runs at Old Trafford on Sunday to take a 2-1 lead in the series with just one Test remaining.
Our Aussies come out on top in another gripping #Ashes contest! The urn has been retained, but a series win remains up for grabs at The Oval! #CmonAussie pic.twitter.com/XL9uP4xybV
— Cricket Australia (@CricketAus) September 8, 2019
England, who resumed on 18-2, were bowled out for 197 on the final day with Australia seamer Pat Cummins taking four for 43.
Australia's victory, with 81 balls remaining, was a convincing one but England's spirit cannot be criticised as they fought until the final hour in their attempt to save the test and keep the series alive.
The tourists lead 2-1 going into next week's final test at The Oval where they hope to become the first Australian team to win an Ashes series in England since 2001.
Steve Smith, whose magnificent double century and then second innings 82 were the key factors in this win and whose batting throughout the series has ensured the Ashes remain in Australian hands, was delighted.
"It feels amazing to know the urn is coming home. I've been here a few times when things haven't gone our way. This was always one to tick off my bucket list. It's extremely satisfying," he said.
The main early resistance from England came from Joe Denly who made 53 from 123 balls and Jos Buttler, who lasted 111 balls for his 34.
England's hopes of an unlikely escape-act rose when Jack Leach and Craig Overton batted for over an hour giving the crowd belief over a second 'miracle' after the comeback win at Headingley.
But part-time leg spinner Marnus Labuschagne finally removed Leach, with a ball that turned sharply in the rough and was gloved to Matthew Wade at short leg.
Overton batted with sense, stoicism and a strong technique, but he was trapped lbw by Josh Hazlewood to set off the Australian celebrations.
"I didn't think it would be this emotional," said Australia captain Tim Paine.
"The amount of work that's gone in to retain the Ashes has been enormous and I'm really proud of this group and how we bounced back from Headingley," he added.
England captain Joe Root told the BBC: "I'm bitterly disappointed. I thought the way we fought today, the character we showed, every single one of them can be proud of that today.
"To come so close to taking it to The Oval is hard to take. We've still got to look forward and make sure we level the series."
England will look back on the second day of this test as the turning point when they simply could find no way to remove Smith and Australia's 497-8 declared gave them an advantage that they were unable to seriously challenge.
The final day was never going to be a run-chase of Headingley vintage, given the target of 383, with England's task simply to survive until the close.
That challenge was made all the more difficult after they lost Jason Roy and Ben Stokes before lunch.
Roy was well set before the impressive Cummins bowled him for 31 with a beautiful delivery that cut back off the seam to leave England at 66-3.
The crowd rose to welcome Stokes, the hero of England's last day triumph at Headingley, but there was to be no repeat performance from the all-rounder.
Another fine delivery from Cummins clipped the inside edge of Stokes's bat and was well taken by wicketkeeper Paine, the England batsman not waiting for the umpire's verdict as he walked off.
Denly had been the pick of England's batsmen before he was outdone by sharp turn and bounce from spinner Nathan Lyon, the ball striking his glove and being snaffled up by Labuschagne at short leg.
Jonny Bairstow (25) was lbw to Mitchell Starc before Overton came in to join Buttler, in what was probably England's last realistic chance of a big partnership.
But Buttler misjudged a delivery from Hazlewood which he left only to see it cut back sharply and clatter into his off-stump.
Australia keep the Ashes, which they won on home turf last year and it is the first time they have retained the urn since the end of their long period of domination in 2002.
There is though plenty left to play for when the teams meet again at The Oval on Thursday — England could level the series while Australia will be desperate to ensure they go home as winners.
For all the latest Sports News, download Indian Express App
SportsMohun Bagan look to make most of emotional derby
India blow away Australia as Virat Kohli's men level series with a 36-run win in Rajkot
Virat Kohli named ICC's ODI, Test captain of 2019; Rohit Sharma bags 'ODI cricketer of the year'
David Warner-Aaron Finch's record partnership guides Australia to 10-wicket win over India in 1st ODI
India go through paces for Australian white-ball trouble in Mumbai
BCCI Annual awards: Jasprit Bumrah, Poonam Yadav receive top awards

redpajama_set_name: RedPajamaCommonCrawl


I didn't do an empties post last month because I didn't have very many products, but between then and now I finished up/decluttered a ton of things that I can't wait to share! I'm reaching a point in my makeup collection where I'm trying not to buy as much simply because I'm running out of room to store it all! Lipsticks especially are getting overwhelming, which is why I'm decluttering so many in this post.
Also I mentioned in my Going Cruelty Free post, I am making the transition to no longer buying makeup that is sold in mainland China (and is subjected to animal testing there) so a lot of things that I would have repurchased are no longer options for me. I will be honest about whether or not I liked a product, but I put a Not CF label next to non-cruelty free items as an explanation as to why I won't repurchase it. And with that, let's get on with the empties!
A boring, standard empty--I'm pretty sure I've included a tube of this in every empties post I've done--I wear this every night before going to bed so that I don't wake up with dry lips. Already repurchased!
I bought this on a whim from TJ Maxx, mostly because of the packaging. It is shaped like an old-fashioned milk bottle. It doesn't smell amazing, unfortunately, but it produces some major bubbles. I might consider repurchasing and mixing in with a bath product that has a nicer scent.
I bought this to use as an alternative to Batiste dry shampoo, which leaves a white cast, while this one doesn't. However, I don't think that it absorbs oil quite as well as the Batiste ones and I will not be repurchasing.
I loved this concealer and it lasted me a very long time! This was in my Project Pan for 2017 so I'm happy to be done with it. It blended nicely, had a good medium coverage, and felt hydrating and brightening under the eye. I haven't actually seen this in the drugstore in a long time so it may have been discontinued, either way I will not be repurchasing.
This was one of my favorite mascaras back in the day so I decided to repurchase it and see if I still liked it. It's good for lengthening, but overall it's no longer one of my favorites.
Another Project Pan product, I'm glad to finally be done with this one. By the end I was just using it to finish it if that makes sense! This Chubby Stick leaves a subtle pink tint that you could get with any tinted lip balm, therefore I don't recommend it and I won't repurchase it. However, the Chubby Stick Intenses are much more pigmented and still hydrating, so if you're curious about these I would recommend the Intenses instead!
This is one of my favorite foundations from the drugstore. It has high coverage, doesn't emphasize texture, and there is a shade that matches me perfectly in the winter. It's very affordable though I would have been willing to pay an extra dollar or two for a pump! It has a subtle luminous finish, somewhere between satin and glowy for my skin.
Most of the things I've decided to declutter from my collection are either very old, things that I never use, or both!
I've had this bright Barbie pink tinted lip balm for years and though I like the formula, the shade isn't very flattering on me.
This is the first liquid lipstick that I ever bought based on a pretty Instagram post from several years ago. I wore it a lot at first so that I could do a review of it, but since then I haven't worn it once. The formula is amazing but this color makes my teeth look so yellow! I think if you have a deeper skin tone and/or really white teeth you may love this for summer, but I just don't want it anymore.
I truly don't know why I bought this? A few years ago I had decided to get really tan one summer, so I over-estimated how dark I would get and bought this tinted moisturizer. I used to mix this with foundations in the summer, but it is just too dark for me and it's definitely getting old. I can't even tell you how it performs because I never wore it on it's own!
This looks amazingly metallic in the pan, but the moment I brought it home and swatched it....no. It's just glitter. Even with a wet brush I can't get it to look nice on the eyes. I'm sure my sister will like it, so I'll pass it on now rather than let it take up space in my drawers.
I've had these for so long, they are definitely expired by now. Raspberry used to be one of my favorites. All of the shades are quite pretty, but they are getting lost in my collection. They are pretty standard lipsticks in my opinion. Raspberry and Rose Taffy both have some shimmer/glitter to them, while Plum Brandy is a typical creme finish.
Same as the Clinique ones, I've had these for many years and it's time to get rid of them. Both of these are gorgeous colors. I would consider them both satin finishes.
9 comments on "June Empties and Declutter"
It's unbelievable how many brands are not cruelty free, isn't it? And with the recent news that Nars are launching in China and will be testing their products on animals, what can I say?? It's a shame!
such a shame about that stila eyeshadow. It looks so beautiful in the pan!
I need to try more from Stila I've only ever used their lip gloss, but I've heard so many good things about them. I feel the same way about the Carmex lip balm, it's in every empties post I've done.
Is it hard when you know some of your favorite products (like this Rimmel foundation) is not CF and you just decided to go CF?


Often, the automation of the production process for logistical labels is critical. Just printing isn't enough, automatically applying labels on boxes and pallets saves time and money and reduces errors.
Our printers and applicators ensure that labels are printed correctly and applied fully automatically - with or without contact - on the product, the packaging or the pallet. Without interfering with your logistical process, even in the most complex circumstances.
Below is a video with the CAB Hermes C for printing and automatically applying labels.
Other suppliers of applicators are a.o. Toshiba Tec (video) and Eticoncept (video).
This automatic print & apply solution can be seamlessly combined with a LabelEasy all-in-one formula: from the design of the technical set-up, the installation and operation, the maintenance, up to the software support and the complete integration, all this we offer as an all-in-one solution.
Choose LabelEasy for an OPEX formula that allows you a carefree management of your labelling without prior investment.
A Print & Apply module to label the front, back or side.
These functionalities are standard in the labelling machine.
The machine is designed to apply labels of different sizes without major adjustments.
This module is meant to apply labels to a stationary or moving product which moves at a higher speed.
Choice of print resolution of 200 or 300 dpi and also available in 4 and 6 inch.
The Print & Apply module guarantees reliable, qualitative labeling of products on automated production lines.
The possibility to develop a custom-made device.


Today, we want to show you a convenient way to keep track of commits and releases happening in a Github repository using feediary.
Let's say we want to get informed about new releases of eleventy, the static site generator used for this blog.
As a first step we open feediary and navigate to Add new feed. There we can enter the URL of the Github repository (in this case https://github.com/11ty/eleventy) and click "Add feed".
You will get to a new page where you could choose between two available feeds. One will notify you about all new commits in the repository (the one starting with Commits -) and the other will notify you about all new releases.
For our example, we choose Releases as we want to know if there is a new release, want to see what changed since the last version, if there is anything we should be aware of before updating and get informed if there is a security update. This all helps us to decide if we want or may even need to update our version for this blog.
For developers it is really useful to keep up-to-date with Github repositories and by using feediary this is pretty easy.
If you become a PRO member you can also create a new list and add all your Github feeds there, making it even more convenient to stay up-to-date.
If you are not using feediary by now, why not give it a try and Sign up. Get started for free and become a PRO member later any time.


text:
Highlight Little Free Library Creative Services 03/28/2014 - 3:16pm
Press Item Live from Lincoln Center "Danny Elfman's Music from the Films of Tim Burton" Kristin Tutino 09/15/2015 - 3:00pm
Highlight LIVE FROM LINCOLN CENTER: New York Philharmonic New Year's Eve: La Vie Parisienne Gretchen Spittler Arts and Culture, Music, WXXI-TV 12/14/2015 - 2:13pm
Press Item Live from Temple B'rith Kodesh: A Rosh Hashanah Celebration Kristin Tutino 08/14/2019 - 8:21am
Imported Story Local organizers prepare for a statewide call to march for education justice feedbot 02/09/2017 - 5:45pm
Highlight Louisa May Alcott: American Masters Kristin Tutino WXXI-TV 12/08/2009 - 2:27pm
Imported Story Main and Gibbs Streets get a new look feedbot 06/24/2019 - 12:00pm
Highlight Marathon: ATK Celebration Kristin Tutino WXXI Create 12/11/2019 - 1:51pm
Highlight Marathon: Cook's Country Cravings Kristin Tutino WXXI Create 11/06/2019 - 1:55pm
Highlight MASTERPIECE CLASSIC: Mr. Selfridge Gretchen Spittler Arts and Culture, WXXI-TV, BritFest 03/04/2013 - 3:28pm
Highlight Masterpiece Mystery! Inspector Lewis "Your Sudden Death Question" on WXXI-TV Gretchen Spittler 08/31/2010 - 8:55am
Rotator item Masterpiece Mystery's "Zen" series Kristin Tutino 07/13/2011 - 4:16pm
Highlight MASTERPIECE: MYSTERY! "Endeavour: Fugue" Gretchen Spittler WXXI-TV, BritFest 06/26/2013 - 2:41pm
Imported Story Mayor Warren Emerges From NY Mayor Summit Optimistic feedbot 09/28/2015 - 5:30pm
Rotator item Meet Dr. Gregory Vincent, the new Kristin Tutino 07/18/2017 - 1:55pm
Highlight MOTOWN: BIG HITS AND MORE (MY MUSIC) Gretchen Spittler Arts and Culture, Music, WXXI-TV 11/12/2012 - 4:12pm
Imported Story Movie Fans Anticipate "The Force Awakens" feedbot 12/14/2015 - 12:15pm
Highlight NATURE: American Eagle Gretchen Spittler Go Green, Science & Nature, WXXI-TV 12/10/2010 - 3:38pm
Highlight NATURE: Braving Iraq on WXXI-TV Gretchen Spittler 10/26/2010 - 12:53pm
Highlight NATURE: Kalahari: The Great Thirstland Gretchen Spittler WXXI World, Science & Nature 08/09/2012 - 2:46pm
Highlight NATURE: Wild Balkans on WXXI-TV Gretchen Spittler Go Green 06/03/2011 - 8:43am
Highlight Neil Simon Film Fest Kristin Tutino Arts and Culture 02/26/2014 - 5:00pm
Imported Story New York leaders react with dismay to ACA repeal feedbot 05/04/2017 - 4:00pm
Imported Story New York's Presidential Primary Takes The Political Spotlight feedbot 04/19/2016 - 10:00am
Press Item Norm & Company: Naomi Silver Kristin Tutino 02/15/2017 - 12:00pm


TIP! Clean up long titles in the permalink. For instance, if you have a long phrase in a URL, that can seem very long.
WordPress can be a little complicated. If this platform is new to you, you may benefit from some helpful tips. The more you know about WordPress, the larger your potential as a blogger. This article will give you tips on how to do just that.
TIP! Familiarize yourself with the options and tools available on WordPress. You will get more choices when you do this.
Choose a website design that is individualized for your WordPress site. You may be tempted to do this because it's a time saver, but your site will just look run of the mill. It's essential to create a website that shows your business' individuality.
TIP! It can happen where you have made changes to your blog on WordPress, only to think that the changes weren't saved. That is usually not the case.
If your post has a lengthy title, make sure to adjust the permalink. Excessively long titles make for cumbersome, clumsy URLs. Instead, try making the permalink "tips-parents-uncontrollable-children" or something comparable based on the SEO keywords.
TIP! Do you get many comments on your posts? If so, it can be hard to weed through all of these comments. Use a plugin that adds pages to your blog comments.
Make sure you use Alt and Title. text whenever you upload pictures. This area is going to let you put in some great SEO keywords within your content, and they also let viewers see what you have on the site when they can't access images.
TIP! Your search engine ranking can be improved by taking a few moments to enhance your pictures when you upload them. Make sure that your title tags are clearly indicated.
Make a schedule for posting to your blog. If you are aware of your posting time, your motivation will increase. You can make your posts all at once and schedule them to upload at a specified time.
TIP! Ensure that your readers can send content to an e-mail as they please. This is crucial for sharing purposes.
Clean up the content and comments that do not add any value to your website. Your website will be user-friendly for the people who view it. Akismet is one of the better plugins for filtering out spam.
TIP! Do not make something such as "admin" your own username. Your blog is more vulnerable to attack by bots if you choose this as your username.
Blog post URLs should not have special characters in them. They make it difficult for search engine spiders to "crawl" around your pages. It is also a good idea to shorten URLs to keywords.
TIP! Make sure your plugins remain updated. WordPress plugins are great for adding versatility to your site.
Do you have lots of comments? You may not want to sort through all of the comments. Add a plugin that will add page numbers to this section. Navigation will be significantly easier, and the site itself will appear far more organized.
TIP! Don't install more plugins than you need. Sure plugins are fun and cool, but every one you add increases the load time of your website.
Create a suitable greeting and heading at the very top of your home page on your site. That makes for a better connection with visitors, since you will be able to personalize a message. A possible plugin to use is WP Greet Box; using this will make the things feel less robotic.
TIP! Using the most current version of WordPress is very important. Updates contain security patches that eliminate vulnerabilities.
Ensure that your readers can send content to an e-mail as they please. This is crucial for the purpose of sharing also, since many users might not have access to Twitter or Facebook at their job but may want to share with their friends your articles. A WP Email plugin can make this possible.
TIP! Always back up your blog. This is an important step in ensuring that you don't lose your entire blog.
Security is essential for WordPress users, so make your password is kept confidential. Additionally, only use reputable sites when downloading plugins. If your site is hit with malware or by hackers, you can lose everything you worked on.
TIP! Use the scheduler tool to schedule the publishing of your blog posts. Have the articles posted at times when you are unable to post them.
Always organize your media library. It may be tempting to just upload images directly into the library, but things can become chaotic really quick. Organize your folders into different themes if necessary. It will make images easier to find when you need them.
TIP! Is it hard for you to post during the times you intend to or when you plan to? Write something well ahead of the scheduled time, but set the posting at the chosen time and date. When you open a page for a new posting, you have the option to time the publication.
Only install WordPress plugins you will actually use. The more you have, the more time it will take for your site to load. This means that the site will run slower for both you and your readers, and worse, it can make an negative impact on your search engine ranking. Slow websites do not rank very well in the search engines when compared to sites that are optimized to load quickly.
TIP! As you search for plugins, make certain to read reviews. Remember, anyone who can program is able to create a plugin.
Using WordPress is not so simple, which is particularly the case if you have little familiarity with it. Of course just making the choice to read this article is a great initial step. Use this information to improve the quality of your WordPress site.


text:
package ezvcard.property;

import java.util.EnumSet;
import java.util.Set;

import lombok.EqualsAndHashCode;
import lombok.ToString;
import org.w3c.dom.Document;
import org.w3c.dom.Element;
import org.w3c.dom.Node;
import org.xml.sax.SAXException;

import ezvcard.VCardVersion;
import ezvcard.util.XmlUtils;

/**
 *

 * Contains an XML element that was not recognized when parsing an xCard
 * (XML-formatted vCard).
 *

 *
 *

 * Code sample
 *

 *
 *

 * VCard vcard = new VCard();
 *
 * Xml xml = new Xml("<b>Some xml</b>");
 * vcard.addXml(xml);
 *

 *
 *

 * Property name: {@code XML}
 *

 *

 * Supported versions: {@code 4.0}
 *

 * @author Michael Angstadt
 */
@EqualsAndHashCode(callSuper = true)
@ToString(callSuper = true)
public class Xml extends SimpleProperty<Document> implements HasAltId {
	/**
	 * Creates an XML property.
	 * @param xml the XML to use as the property's value
	 * @throws SAXException if the XML cannot be parsed
	 */
	public Xml(String xml) throws SAXException {
		this(XmlUtils.toDocument(xml));
	}

	/**
	 * Creates an XML property.
	 * @param element the XML element to use as the property's value (the
	 * element is imported into an empty {@link Document} object)
	 */
	public Xml(Element element) {
		this(detachElement(element));
	}

	/**
	 * Creates an XML property.
	 * @param document the XML document to use as the property's value
	 */
	public Xml(Document document) {
		super(document);
	}

	@Override
	public Set<VCardVersion> _supportedVersions() {
		return EnumSet.of(VCardVersion.V4_0);
	}

	//@Override
	public String getAltId() {
		return parameters.getAltId();
	}

	//@Override
	public void setAltId(String altId) {
		parameters.setAltId(altId);
	}

	private static Document detachElement(Element element) {
		Document document = XmlUtils.createDocument();
		Node imported = document.importNode(element, true);
		document.appendChild(imported);
		return document;
	}
}

redpajama_set_name: RedPajamaGithub


text:
Q: NSPopUpButton not updating selectItem I have a NSPopUpButton where I'm preselecting item in the menu and is been selected but is not showing as selected. Here is my code:
[self.categoryMenu selectItemWithTitle:@"cineRush"];

Here is how is showing:

But here is how show if I click on the NSPopUpButton:

But it show "cineRush" as selected item.
Any of you knows why this is happening or how can this fix?

redpajama_set_name: RedPajamaStackExchange


Your daily newsletter containing the most important news & research in the Internet of Things.
It's nearly impossible to stay on top of all the important developments in the IoT industry that are impacting your company, your bottom line, your career, and even your future.
In the exploding world of IoT technology, not a day goes by without another development that could change everything you currently know on the topic.
If you want to succeed at ANY aspect of the Internet of Things, you've simply got to know what's happening all around you. But it's easily a full-time job just to follow the news...and an even bigger job to try to make sense of it.
No one else attends the conferences, digs into technical journals, analyzes the reports, and brings it all to you in a simple, easy-to-understand format like our IoT Briefing, the new daily newsletter from Business Insider Intelligence.
With our IoT Briefing, you'll know the newest and hottest technologies, the breaking deals, the important trends and the shifting landscape.
Our IoT Briefing gives you the context around critical developments in IoT technology so that you can run your business more efficiently, more profitably and more successfully. We strive to uncover the most important trends and insights to help you plan for the future.
The IoT will change the way all businesses, governments, and consumers interact with the physical world. It doesn't matter what your industry is, nothing will be left untouched by the IoT revolution.
Our IoT Briefing will help you stay ahead of the curve and get ahead of the competition.
The Internet of Things is revolutionizing industries and changing the face of our world.
To take a single example, the ability to bring internet connection to nearly every type of consumer device will have huge implications for the insurance industry over the next five years. Insurers looking to cut costs, improve business practices, and better assess clients' risk levels, will increasingly invest in the Internet of Things.
Some auto and health insurers are already offering a new type of insurance — usage–based insurance (UBI) that uses IoT devices to track clients' activity and offer discounts or rewards for healthy and safe behavior. We expect 17 million people will have tried UBI auto insurance by the end of this year.
It's the same all over — the IoT is the cutting edge and where you need the most help in staying on top of all the fast-moving developments.
Our IoT Briefing gives you the news and insights you need in clear, no-BS format. If we ever use industry jargon, it's because it's necessary.
Our IoT Briefing has no agenda beyond helping you understand the digital world better. We don't do sponsored research or "pay to play" deals like some of our competitors. We're not trying to sell you a product, pitch you a stock or make you a true believer of any worldview.
When you read our IoT Briefing, you know the most important news and events that happened in the IoT ecosystem in the last 24 hours. Not just news about deals, but data-driven insights that provide context and explain why things are happening now... and what's going to happen next.
But no matter how great we tell you our IoT Briefing is, the only way for you to see for yourself how valuable it can be is to try it.
We know that there's a lot of hype in the world of emerging technology, and you may be disposed to be wary of buying something that disappoints you, so we back up our promise about the benefits of our IoT Briefing with our satisfaction guarantee.
Just try our IoT Briefing for 14 days to see if it is as good as we say it is.
Keep everything you've received— all the issues, all the intelligence—with our thanks for giving our IoT Briefing a try.
Business Insider Intelligence analyzes the developing role of blockchain in the IoT ecosystem. First, the report looks at how blockchain works, both generally and as part of an IoT solution. It then identifies the areas most suited to use blockchain as part of larger IoT projects, specifically looking into the supply chain, asset tracking and monitoring, and health care. Finally, the report discuss the challenges companies looking into blockchain solutions for IoT programs will face, and explores what the future holds for blockchain in the IoT.
Business Insider Intelligence examines the benefits drone delivery can provide as an e-commerce fulfillment method, and explains the different approaches companies are taking as they experiment with the nascent technology. In addition, the report details the key players working in the space and discusses the challenges drone delivery faces in reaching mainstream adoption.
Are you 100% certain that you're on top of the fast-moving IoT ecosystem?
IoT isn't slowing down — it's speeding up.
P.S. Remember, you risk nothing by giving our IoT Briefing a risk-free try. You receive a full refund if you cancel in the first 14 days. With nothing to lose and so much to gain, sign up today!