Efficacy and safety of a 4-week course of repeated subcutaneous ketamine injections for treatment-resistant depression (KADS study): randomised double-blind active-controlled trial.

BACKGROUND: Prior trials suggest that intravenous racemic ketamine is a highly effective for treatment-resistant depression (TRD), but phase 3 trials of racemic ketamine are needed. AIMS: To assess the acute efficacy and safety of a 4-week course of subcutaneous racemic ketamine in participants with TRD. Trial registration: ACTRN12616001096448 at www.anzctr.org.au. METHOD: This phase 3, double-blind, randomised, active-controlled multicentre trial was conducted at seven mood disorders centres in Australia and New Zealand. Participants received twice-weekly subcutaneous racemic ketamine or midazolam for 4 weeks. Initially, the trial tested fixed-dose ketamine 0.5 mg/kg versus midazolam 0.025 mg/kg (cohort 1). Dosing was revised, after a Data Safety Monitoring Board recommendation, to flexible-dose ketamine 0.5-0.9 mg/kg or midazolam 0.025-0.045 mg/kg, with response-guided dosing increments (cohort 2). The primary outcome was remission (Montgomery-Åsberg Rating Scale for Depression score ≤10) at the end of week 4. RESULTS: The final analysis (those who received at least one treatment) comprised 68 in cohort 1 (fixed-dose), 106 in cohort 2 (flexible-dose). Ketamine was more efficacious than midazolam in cohort 2 (remission rate 19.6% v. 2.0%; OR = 12.1, 95% CI 2.1-69.2, P = 0.005), but not different in cohort 1 (remission rate 6.3% v. 8.8%; OR = 1.3, 95% CI 0.2-8.2, P = 0.76). Ketamine was well tolerated. Acute adverse effects (psychotomimetic, blood pressure increases) resolved within 2 h. CONCLUSIONS: Adequately dosed subcutaneous racemic ketamine was efficacious and safe in treating TRD over a 4-week treatment period. The subcutaneous route is practical and feasible.

Differences in clinical presentations of patients seeking care for treatment-resistant depression across sexual orientations and gender identities.

BACKGROUND: Sexual and/or gender minority (SGM) individuals experience higher rates and greater severity of depressive disorders than non-SGM persons. SGM individuals are more likely than non-SGM individuals to seek mental health treatment and to present to treatment with unique characteristics that should be accounted for when considering treatment recommendations. Patients seeking care for treatment-resistant depression (TRD) are offered a variety of evidence-based interventions ranging in modality and invasiveness (eg, psychotherapy and neuromodulation). METHODS: The current study used data from a TRD clinical research program to examine whether SGM (N = 52) and non-SGM (N = 202) patients differed in their clinical presentations and the treatment recommendations offered to them. RESULTS: We found that SGM patients were younger, had a more severe history of childhood trauma, and reported greater current suicidality than non-SGM patients. There were no significant differences in treatment recommendations between groups. CONCLUSIONS: This study adds to nascent literature investigating clinical characteristics of SGM populations seeking mental health care and provides foundational evidence for the unique treatment considerations necessary for SGM individuals seeking treatment for TRD. Research into whether treatment outcomes differ for SGM and non-SGM individuals with TRD is encouraged, given clinical differences in trauma history and suicidality.

Psychometric Properties of the Chinese Version of the ElectroConvulsive Therapy Cognitive Assessment: An Electroconvulsive Therapy-Specific Cognitive Screening Tool.

OBJECTIVES: Electroconvulsive therapy (ECT) is an effective somatic treatment, but it may be limited by cognitive adverse effects. The existing cognitive screening instruments often lack specificity to ECT-associated cognitive deficits. The ElectroConvulsive Therapy Cognitive Assessment was developed and validated in a clinical setting, but the reliability and validity of the Chinese version of ElectroConvulsive Therapy Cognitive Assessment (ECCA-C) have not been studied in a large clinical sample. METHODS: The ECCA-C and the Montreal Cognitive Assessment (MoCA) were administered to patients with major depressive disorder (MDD) undergoing ECT at 3 time points: pretreatment (baseline), before the fifth treatment, and 1 week posttreatment. The instruments were also administered to a sample of healthy subjects. RESULTS: Sixty-five patients with MDD and 50 age- and sex-matched healthy controls were recruited in this study. Overall, the patient group had statistically significantly lower MoCA and ECCA-C scores than the control group (both P values <0.001). The Cronbach α of the ECCA-C was 0.88 at baseline. Statistically significant decreases over time were observed in ECCA-C: pre-ECT (23.9 ± 4.0) > mid-ECT (21.3 ± 3.4) > post-ECT (18.7 ± 4.8) (all P values <0.001), whereas no statistically significant changes in MoCA scores were found at these 3 time points (F = 1.86, P = 0.165). A cutoff score of 26.5 on the ECCA-C was found to best differentiate between MDD patients and healthy controls. CONCLUSIONS: The ECCA-C showed satisfactory psychometric properties and may be a more sensitive instrument than the MoCA to assess cognitive impairment associated with ECT.

The use of ketamine infusion to dramatically reduce opioid requirements in a patient whose high-dose intrathecal opioid pump was inadvertently cut during surgery.

BACKGROUND: Chronic opioid therapy may lead to high level tolerance development, hyperalgesia, and central sensitization, which further complicates long-term therapeutic management of chronic pain patients. In this case, we encounter a patient who was receiving over 15,000 morphine milligram equivalents through their intrathecal pain pump. Unfortunately, the intrathecal pump was inadvertently cut during a spinal surgery. It was deemed unsafe to delivery IV equivalent opioid therapy in this case; instead, the patient was admitted to the ICU and given a four-day ketamine infusion. METHOD: The patient was started on a ketamine infusion at a rate of 0.5mg/kg/h, which was continued for three days. On the fourth day, the infusion rate was tapered over 12 h before being completely stopped. No coinciding opioid therapy was given during this time, which was only restarted in the outpatient setting. RESULTS: Despite chronic high levels of opioid therapy immediately prior to the ketamine infusion, the patient did not experience florid withdrawals during the infusion period. Additionally, the patient experienced remarkable improvement in their subjective pain rating, which decreased from 9 to 3-4 on an 11-point Number Rating Scale, while simultaneously being managed on an MME <100. These results were sustained through a 6-month follow-up period. CONCLUSION: Ketamine may play an important role in attenuating not only tolerance but also acute withdrawal in a setting where rapid or instant weaning from high dose chronic opioid therapy is needed.

Cardiovascular Effects of High-Frequency Magnetic Seizure Therapy Compared With Electroconvulsive Therapy.

BACKGROUND: Magnetic seizure therapy (MST) is a novel convulsive therapy that has been shown to have antidepressant efficacy comparable to electroconvulsive therapy (ECT) with fewer cognitive side effects. However, the cardiovascular (CVS) effects of high frequency MST in comparison to ECT have not been investigated. MATERIALS AND METHODS: Forty-five patients with depression received 6 treatment sessions of 100 Hz MST versus 6 bifrontal ECT treatments in a nonrandomized comparative clinical design. Data on CVS function including heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and rate pressure product (RPP) were collected at baseline (T0), after the induction of anesthesia but before the electrical stimulation (T1), during convulsion (T2), 2 minutes after cessation of motor seizure (T3), 5 minutes after cessation of motor seizure (T4), and 10 minutes after cessation of motor seizure (T5). Comparisons were made with baseline data and between MST and ECT groups. RESULTS: There were statistically significant elevations in the maximum HR, SBP, DBP, and RPP in patients receiving ECT compared with MST both in the initial and sixth treatments (all P < 0.05). Particularly, at T2, the ECT group had significantly higher HR, SBP, DBP, and RPP than those in MST group both in initial and sixth treatment (all P < 0.001). At the sixth treatment, the ECT group had significantly higher SBP, DBP, and RPP during the treatment than in the MST group (all P < 0.001). LIMITATIONS: The anesthetic choices for this study may limit the generalizability of our findings. The sample size was relatively small. CONCLUSIONS: Compared with ECT, high-frequency MST has fewer CVS side effects and may be a safer option for depression patients with CVS disorders.

National Network of Depression Centers' Recommendations on Harmonizing Clinical Documentation of Electroconvulsive Therapy.

ABSTRACT: Electroconvulsive therapy (ECT) is a highly therapeutic and cost-effective treatment for severe and/or treatment-resistant major depression. However, because of the varied clinical practices, there is a great deal of heterogeneity in how ECT is delivered and documented. This represents both an opportunity to study how differences in implementation influence clinical outcomes and a challenge for carrying out coordinated quality improvement and research efforts across multiple ECT centers. The National Network of Depression Centers, a consortium of 26+ US academic medical centers of excellence providing care for patients with mood disorders, formed a task group with the goals of promoting best clinical practices for the delivery of ECT and to facilitate large-scale, multisite quality improvement and research to advance more effective and safe use of this treatment modality. The National Network of Depression Centers Task Group on ECT set out to define best practices for harmonizing the clinical documentation of ECT across treatment centers to promote clinical interoperability and facilitate a nationwide collaboration that would enable multisite quality improvement and longitudinal research in real-world settings. This article reports on the work of this effort. It focuses on the use of ECT for major depressive disorder, which accounts for the majority of ECT referrals in most countries. However, most of the recommendations on clinical documentation proposed herein will be applicable to the use of ECT for any of its indications.

Defining focal brain stimulation targets for PTSD using neuroimaging.

INTRODUCTION: Focal brain stimulation has potential as a treatment for posttraumatic stress disorder (PTSD). In this review, we aim to inform selection of focal brain stimulation targets for treating PTSD by examining studies of the functional neuroanatomy of PTSD and treatment response. We first briefly review data on brain stimulation interventions for PTSD. Although published data suggest good efficacy overall, the neurobiological rationale for each stimulation target is not always clear. METHODS: Therefore, we assess pre- and post-treatment (predominantly psychotherapy) functional neuroimaging studies in PTSD to determine which brain changes seem critical to treatment response. Results of these studies are presented within a previously proposed functional neural systems model of PTSD. RESULTS: While not completely consistent, research suggests that downregulating the fear learning and threat and salience detection circuits (i.e., amygdala, dorsal anterior cingulate cortex and insula) and upregulating the emotion regulation and executive function and contextual processing circuits (i.e., prefrontal cortical regions and hippocampus) may mediate PTSD treatment response. CONCLUSION: This literature review provides some justification for current focal brain stimulation targets. However, the examination of treatment effects on neural networks is limited, and studies that include the stimulation targets are lacking. Further, additional targets, such as the cingulate, medial prefrontal cortex, and inferior parietal lobe, may also be worth investigation, especially when considering how to achieve network level changes. Additional research combining PTSD treatment with functional neuroimaging will help move the field forward by identifying and validating novel targets, providing better rationale for specific treatment parameters and personalizing treatment for PTSD.

Altered Mental Status as a Novel Initial Clinical Presentation for COVID-19 Infection in the Elderly.

The coronavirus disease of 2019 or COVID-19 was first identified in Hubei Province in China in November of 2019 and quickly spread to become a global pandemic. The virus, SARS-Coronavirus-2, is particularly virulent in the elderly who can develop symptoms and become mortally ill within days of contracting the virus. The virus is easily transmitted by droplets (e.g., sneezing and coughing) and communal living settings such as personal care homes can be vulnerable to the spread of the virus. Identifying patients early in the disease process is important to providing appropriate medical interventions. To date, most of the medical literature, including Center for Disease Control guidelines, has relied on three necessary symptoms in making the diagnosis of COVID-19: fever, cough, and shortness of breath. We present four cases of elderly patients who developed altered mental status as their presenting symptom without associated fever or respiratory symptoms.

Efficacy and Safety of ECT for Behavioral and Psychological Symptoms of Dementia (BPSD): A Retrospective Chart Review.

OBJECTIVE: Much of the functional disturbance in patients with dementia reflects the presence of noncognitive behavioral and psychological symptoms of dementia (BPSD). Agitation is among the most distressing symptoms for patients, clinicians, and caregivers. Currently no pharmacotherapy has clearly been shown to be of value for this condition. This study used a chart review method to examine the safety and efficacy of electroconvulsive therapy (ECT) for patients with dementia receiving ECT for agitation. METHODS: A retrospective chart review was conducted of patients with dementia presenting with symptoms of aggression or agitation and who received ECT treatments. Aggression and agitation were measured by pre- and post-ECT Pittsburg Agitation Scale (PAS) scores. Detailed history of the use of psychotropic medications as well as other clinically relevant variables was analyzed. FINDINGS: Sixty elderly patients (45 women and 15 men, 75% female, mean age 77.5 ± 8.0 years) were included in the analysis. Most patients were treatment resistant to multiple psychotropic medications prior to ECT (mean number 6.1±1.5). The baseline PAS total was 9.3 ± 3.7 and it decreased significantly after three (2.5±2.8) and six (1.5±2.3) ECT treatments. No significant ECT-related medical complications were observed except transient confusion. A decrease in the number of psychotropics prescribed along with an increase in the GAF score was observed after the ECT treatment course. CONCLUSION: ECT was safe in this sample of patients who had co-morbid medical conditions. ECT was associated with the following observations: 1) a reduction in agitation; 2) a reduction in psychotropic polypharmacy; and 3) an improvement in global functioning level. Further research evaluating the effects of ECT in the setting of dementia is warranted.

A Review of PTSD Augmentation Strategies for Older Adults and Case of rTMS-Augmented Prolonged Exposure.

Evidence-based psychotherapies such as prolonged exposure therapy (PE) are recommended by clinical practice guidelines as first-line treatments for post-traumatic stress disorder (PTSD) and are safe and acceptable for use with older adults. One third to one half of all patients do not achieve a clinically meaningful response to standard outpatient PE and recent research suggests that older adults in particular may experience barriers to full engagement and response. Standard treatment may be challenging in older adults due to cognitive, medical, and psychosocial barriers. This article reviews the current state of the evidence on adjunctive and second-tier interventions that show promise for increasing response and/or engagement in evidence-based psychotherapy for PTSD, including medications such as d-cycloserine and 3,4-methylenedioxy-methamphetamine, neuromodulation techniques such as repetitive transcranial magnetic stimulation, and augmentations to the structure and content of psychotherapy, such as intensive outpatient formats. A case illustration of successful application of multiple augmentations to PE with an initially nonresponsive older adult patient is presented. A creative interdisciplinary approach based in available research may be beneficial for older adults who do not respond to first-line treatments.

Neurocognitive effects of transcranial direct current stimulation (tDCS) in unipolar and bipolar depression: Findings from an international randomized controlled trial.

OBJECTIVE: Transcranial direct current stimulation (tDCS) has been found to have antidepressant effects and may have beneficial neurocognitive effects. However, prior research has produced an unclear understanding of the neurocognitive effects of repeated exposure to tDCS. The study's aim was to determine the neurocognitive effects following tDCS treatment in participants with unipolar or bipolar depression. METHOD: The study was a triple-masked, randomized, controlled clinical trial across six international academic medical centers. Participants were randomized to high dose (2.5 mA for 30 min) or low dose (0.034 mA, for 30 min) tDCS for 20 sessions over 4 weeks, followed by an optional 4 weeks of open-label high dose treatment. The tDCS anode was centered over the left dorsolateral prefrontal cortex at F3 (10/20 EEG system) and the cathode over F8. Participants completed clinical and neurocognitive assessments before and after tDCS. Genotype (BDNF Val66Met and catechol-o-methyltransferase [COMT] Val158Met polymorphisms) were explored as potential moderators of neurocognitive effects. RESULTS: The study randomized 130 participants. Across the participants, tDCS treatment (high and low dose) resulted in improvements in verbal learning and recall, selective attention, information processing speed, and working memory, which were independent of mood effects. Similar improvements were observed in the subsample of participants with bipolar disorder. There was no observed significant effect of tDCS dose. However, BDNF Val66Met and COMT Val158Met polymorphisms interacted with tDCS dose and affected verbal memory and verbal fluency outcomes, respectively. CONCLUSIONS: These findings suggest that tDCS could have positive neurocognitive effects in unipolar and bipolar depression. Thus, tDCS stimulation parameters may interact with interindividual differences in BDNF and COMT polymorphisms to affect neurocognitive outcomes, which warrants further investigation.

Social media recruitment for mental health research: A systematic review.

BACKGROUND: Social media holds exciting promise for advancing mental health research recruitment, however, the extent and efficacy to which these platforms are currently in use are underexplored. OBJECTIVE: A systematic review was conducted to characterize the current use and efficacy of social media in recruiting participants for mental health research. METHOD: A literature review was performed using MEDLINE, EMBASE, and PsychINFO. Only non-duplicative manuscripts written in the English language and published between 1/1/2004-3/31/2019 were selected for further screening. Data extracted included study type and design, participant inclusion criteria, social media platform, advertising strategy, final recruited sample size, recruitment location, year, monetary incentives, comparison to other recruitment methods if performed, and final cost per participant. RESULTS: A total of 176 unique studies that used social media for mental health research recruitment were reviewed. The majority of studies were cross-sectional (62.5%) in design and recruited adults. Facebook was overwhelmingly the recruitment platform of choice (92.6%), with the use of paid advertisements being the predominant strategy (60.8%). Of the reviewed studies, substance abuse (43.8%) and mood disorders (15.3%) were the primary subjects of investigation. In 68.3% of studies, social media recruitment performed as well as or better than traditional recruitment methods in the number and cost of final enrolled participants. The majority of studies used Facebook for recruitment at a median cost per final recruited study participant of $19.47. In 55.6% of the studies, social media recruitment was the more cost-effective recruitment method when compared to traditional methods (e.g., referrals, mailing). CONCLUSION: Social media appears to be an effective and economical recruitment tool for mental health research. The platform raises methodological and privacy concerns not covered in current research regulations that warrant additional consideration.

Neurocognitive Effects of Repetitive Transcranial Magnetic Stimulation With a 2-Coil Device in Treatment-Resistant Major Depressive Disorder.

BACKGROUND: Neurocognitive dysfunction is an understudied and undertreated aspect of psychiatric research and treatment. There is emerging evidence to suggest that repetitive transcranial magnetic stimulation (rTMS) may possess neurocognition-enhancing capabilities. METHODS: This study examined the neurocognitive data from a randomized, double-blind, sham-controlled trial of an investigational 2-coil rTMS device in antidepressant treatment or treatment-intolerant major depressive disorder patients. This device has the potential to stimulate deeper areas of the brain than the Food and Drug Administration-approved TMS devices, which primarily stimulate cortical brain areas and may therefore have different neurocognitive adverse effects. Patients received 20 daily rTMS treatments (10-Hz stimulation; either active or sham) with coil centers positioned over the left dorsolateral prefrontal cortex and dorsomedial prefrontal cortex. Neurocognitive safety was evaluated at baseline and within 72 hours of final treatment session with a computerized battery assessing aspects of attention and memory in 84 participants. RESULTS: There were no observed negative neurocognitive effects of the 2-coil rTMS device. A significant effect of active rTMS was observed on the quality of episodic memory. There were no observed effects for attention or working memory. Baseline quality of episodic memory predicted depression treatment response and remission, in that lower baseline episodic memory was associated with greater likelihood of depression response/remission. This was observed in logistic regression analyses controlling for treatment and baseline depressive symptoms. CONCLUSIONS: The 2-coil rTMS device is a cognitively safe treatment for treatment-resistant depression that may possess episodic memory-enhancing capabilities. Furthermore, baseline episodic memory may reflect an important predictor of subsequent depression treatment response/remission to rTMS.

Psychiatric associations of adult-onset focal dystonia phenotypes.

BACKGROUND: Depression and anxiety frequently accompany the motor manifestations of isolated adult-onset focal dystonias. Whether the body region affected when this type of dystonia first presents is associated with the severity of these neuropsychiatric symptoms is unknown. OBJECTIVES: The aim of this study was to determine whether depression, anxiety and social anxiety vary by dystonia onset site and evaluate whether pain and dystonia severity account for any differences. METHODS: Patients with isolated focal dystonia evaluated within 5 years from symptom onset, enrolled in the Natural History Project of the Dystonia Coalition, were included in the analysis. Individual onset sites were grouped into five body regions: cervical, laryngeal, limb, lower cranial and upper cranial. Neuropsychiatric symptoms were rated using the Beck Depression Inventory, Hospital Anxiety and Depression Scale and Liebowitz Social Anxiety Scale. Pain was estimated using the 36-Item Short Form Survey. RESULTS: Four hundred and seventy-eight subjects met our inclusion criteria. High levels of depression, anxiety and social anxiety occurred in all groups; however, the severity of anxiety and social anxiety symptoms varied by onset site group. The most pronounced differences were higher anxiety in cervical and laryngeal, lower anxiety in upper cranial and higher social anxiety in laryngeal. Increases in pain were associated with worse neuropsychiatric symptom scores within all groups. Higher anxiety and social anxiety in laryngeal and lower anxiety in upper cranial persisted after correcting for pain and dystonia severity. CONCLUSION: Anxiety and social anxiety severity vary by onset site of focal dystonia, and this variation is not explained by differences in pain and dystonia severity.

Neuromodulation Treatments for Geriatric Mood and Cognitive Disorders.

There is increasing evidence for the efficacy of neuromodulation in the treatment of resistant mood disorders and emerging data supporting the use of neuromodulation in cognitive disorders. A significant minority of depressed elders do not respond to pharmacotherapy and/or psychotherapy. This has led clinicians to recommend the increasing use of electroconvulsive therapy (ECT) in the treatment of medication-resistant or life-threatening geriatric depression. Multiple studies have supported the safety and efficacy of ECT in the elderly, yet ECT is associated with side effects including cardiovascular and cognitive side effects. Neuromodulation therapies have the potential for providing effective treatment for treatment-resistant older adults with reduced side effects and this review will outline the risks and benefits of neuromodulation treatment in geriatric psychiatry. There is also emerging evidence of the efficacy of neuromodulation devices in the treatment of cognitive disorders. Pharmacotherapy has been largely ineffective in changing the course of neurodegenerative diseases causing dementia and other treatments are clearly needed. This review will outline the available evidence for neuromodulation in the treatment of mood and cognitive disorders in the elderly.

Accelerated TMS - moving quickly into the future of depression treatment.

Accelerated TMS is an emerging application of Transcranial Magnetic Stimulation (TMS) aimed to reduce treatment length and improve response time. Extant literature generally shows similar efficacy and safety profiles compared to the FDA-cleared protocols for TMS to treat major depressive disorder (MDD), yet accelerated TMS research remains at a very early stage in development. The few applied protocols have not been standardized and vary significantly across a set of core elements. In this review, we consider nine elements that include treatment parameters (i.e., frequency and inter-stimulation interval), cumulative exposure (i.e., number of treatment days, sessions per day, and pulses per session), individualized parameters (i.e., treatment target and dose), and brain state (i.e., context and concurrent treatments). Precisely which of these elements is critical and what parameters are most optimal for the treatment of MDD remains unclear. Other important considerations for accelerated TMS include durability of effect, safety profiles as doses increase over time, the possibility and advantage of individualized functional neuronavigation, use of biological readouts, and accessibility for patients most in need of the treatment. Overall, accelerated TMS appears to hold promise to reduce treatment time and achieve rapid reduction in depressive symptoms, but at this time significant work remains to be done. Rigorous clinical trials combining clinical outcomes and neuroscientific measures such as electroencephalogram, magnetic resonance imaging and e-field modeling are needed to define the future of accelerated TMS for MDD.

High-Intensity Care for Nursing Home Residents with Severe Dementia Hospitalized at the End of Life: A Mixed Methods Study.

OBJECTIVE: For nursing home residents with severe dementia, high-intensity medical treatment offers little possibility of benefit but has the potential to cause significant distress. Nevertheless, mechanical ventilation and intensive care unit (ICU) transfers have increased in this population. We sought to understand how and why such care is occurring. DESIGN: Mixed methods study, with retrospective collection of qualitative and quantitative data. SETTING: Department of Veterans Affairs (VA) hospitals. METHODS: Using the Minimum Data Set, we identified veterans aged ≥65 years who had severe dementia, lived in nursing homes, and died in 2013. We selected those who underwent mechanical ventilation or ICU transfer in the last 30 days of life. We restricted our sample to patients receiving care at VA hospitals because these hospitals share an electronic medical record, from which we collected structured information and constructed detailed narratives of how medical decisions were made. We used qualitative content analysis to identify distinct paths to high-intensity treatment in these narratives. RESULTS: Among 163 veterans, 41 (25.2%) underwent mechanical ventilation or ICU transfer. Their median age was 85 (IQR, 80-94), 97.6% were male, and 67.5% were non-Hispanic white. More than a quarter had living wills declining some or all treatment. There were 5 paths to high-intensity care. The most common (18 of 41 patients) involved families who struggled with decisions. Other patients (15 of 41) received high-intensity care reflexively, before discussion with a surrogate. Four patients had families who advocated repeatedly for aggressive treatment, against clinical recommendations. In 2 cases, information about the patient's preferences was erroneous or unavailable. In 2 cases, there was difficulty identifying a surrogate. CONCLUSIONS AND IMPLICATIONS: Our findings highlight the role of surrogates' difficulty with decision making and of health system-level factors in end-of-life ICU transfers and mechanical ventilation among nursing home residents with severe dementia.