Hochang B. Lee

Restless legs syndrome/Willis-Ekbom disease diagnostic criteria: Updated International Restless Legs Syndrome Study Group (IRLSSG) consensus criteria - history, rationale, description, and significance

BACKGROUND In 2003, following a workshop at the National Institutes of Health, the International Restless Legs Syndrome Study Group (IRLSSG) developed updated diagnostic criteria for restless legs syndrome/Willis-Ekbom disease (RLS/WED). These criteria were integral to major advances in research, notably in epidemiology, biology, and treatment of RLS/WED. However, extensive review of accumulating literature based on the 2003 NIH/IRLSSG criteria led to efforts to improve the diagnostic criteria further. METHODS The clinical standards workshop, sponsored by the WED Foundation and IRLSSG in 2008, started a four-year process for updating the diagnostic criteria. That process included a rigorous review of research advances and input from clinical experts across multiple disciplines. After broad consensus was attained, the criteria were formally approved by the IRLSSG executive committee and membership. RESULTS Major changes are: (i) addition of a fifth essential criterion, differential diagnosis, to improve specificity by requiring that RLS/WED symptoms not be confused with similar symptoms from other conditions; (ii) addition of a specifier to delineate clinically significant RLS/WED; (iii) addition of course specifiers to classify RLS/WED as chronic-persistent or intermittent; and (iv) merging of the pediatric with the adult diagnostic criteria. Also discussed are supportive features and clinical aspects that are important in the diagnostic evaluation. CONCLUSIONS The IRLSSG consensus criteria for RLS/WED represent an international, interdisciplinary, and collaborative effort intended to improve clinical practice and promote further research.

Clinical significance of RLS.

While the restless legs syndrome (RLS) may have been known in antiquity, it has only recently come to medical attention. Individuals with RLS fall along a spectrum from mild, infrequent symptoms to those with severe daily life‐impairing discomforts and sleep disruption. These problems can cause impaired mood, daytime fatigue, cognitive difficulties, and inability to participate in a variety of quiet activities. This leads to a general reduction in quality of life similar to other significant psychiatric and medical disorders. Recent studies suggest that RLS may be a risk factor for developing both psychiatric disorders (such as major depression and anxiety) and somatic diseases (such as hypertension and cardiovascular disease). In dialysis patients, RLS has been found to be a risk factor for mortality. Therefore, those with RLS who have clinically significant symptoms suffer increased morbidity and are at risk for impaired long‐term medical outcomes.

The Epidemiology of Delirium: Challenges and Opportunities for Population Studies

Delirium is a serious and common acute neuropsychiatric syndrome that is associated with short- and long-term adverse health outcomes. However, relatively little delirium research has been conducted in unselected populations. Epidemiologic research in such populations has the potential to resolve several questions of clinical significance in delirium. Part 1 of this article explores the importance of population selection, case-ascertainment, attrition, and confounding. Part 2 examines a specific question in delirium epidemiology: What is the relationship between delirium and trajectories of cognitive decline? This section assesses previous work through two systematic reviews and proposes a design for investigating delirium in the context of longitudinal cohort studies. Such a design requires robust links between community and hospital settings. Practical considerations for case-ascertainment in the hospital, as well as the necessary quality control of these programs, are outlined. We argue that attention to these factors is important if delirium research is to benefit fully from a population perspective.

Circadian Rhythm Disruption in the Critically Ill: An Opportunity for Improving Outcomes.

Objectives:Circadian rhythms are severely disrupted among the critically ill. These circadian arrhythmias impair mentation, immunity, autonomic function, endocrine activity, hormonal signaling, and ultimately healing. In this review, we present a modern model of circadian disruption among the critically ill, discuss causes of these circadian arrhythmias, review observational and intervention studies of the effects of circadian-rhythm–restoring factors on medical outcomes, and identify needed key trials of circadian interventions in the critically ill. Data Sources:MEDLINE, EMBASE, PsychINFO, Google Scholar through December 2014. Study Selection:Articles relevant to circadian rhythms, melatonin, and light in the critically ill were selected. Data Extraction and Data Synthesis:Articles were synthesized for this review of circadian arrhythmia and the use of circadian-rhythm–restoring interventions among the critically ill. Conclusions:Circadian disruption often demonstrates serial degradation: initially, the amplitude attenuates along with delayed circadian phase. With increasing acuity of illness, circadian rhythmicity may be lost entirely. Causes of chronodisruption may be environmental or internal to the patient. In particular, inadequate daytime illumination and nocturnal light pollution disrupt healthy circadian periodicity. Internal causes of circadian arrhythmia include critical illness itself and subjective experience of distress and pain. Observational studies of windowed rooms and real-time ambient lighting have found that physiologic light-dark patterns may support recovery from critical illness. Studies of early morning bright light or evening melatonin agonists have found improved rates of delirium, enhanced sleep, and lower arrhythmia prevalence. The current evidence base emphasizes that lighting and melatoninergic interventions deserve to be tested in full-scale trials.

Non-pharmacological prevention of major depression among community-dwelling older adults: A systematic review of the efficacy of psychotherapy interventions

Depression is a major public health burden among the aging population. While older adults prefer non-pharmacological treatment, few options for psychotherapy are available in primary care settings, which is where older adults tend to receive mental health services. Indicated prevention is a cost-effective, public health approach to prevent major depressive disorder among people with depressive symptoms who do not yet meet standard criteria for major depression. We critically reviewed randomized controlled trials (RCTs) that assessed the efficacy of psychotherapy among community-dwelling older adults with subthreshold depression (depressive symptoms that do not meet standard criteria for major depression). We examined the intervention types, results, internal validity, and external validity of five studies. We used the United States Preventive Services Task Force (USPSTF) guidelines to rate the quality of the studies and to provide recommendations. Results suggest that psychotherapy is a safe and cost-effective method to reduce the public health burden of depression among older adults with subthreshold depression.

Intraoperative Infusion of Dexmedetomidine for Prevention of Postoperative Delirium and Cognitive Dysfunction in Elderly Patients Undergoing Major Elective Noncardiac Surgery: A Randomized Clinical Trial.

Importance Postoperative delirium occurs in 10% to 60% of elderly patients having major surgery and is associated with longer hospital stays, increased hospital costs, and 1-year mortality. Emerging literature suggests that dexmedetomidine sedation in critical care units is associated with reduced incidence of delirium. However, intraoperative use of dexmedetomidine for prevention of delirium has not been well studied. Objective To evaluate whether an intraoperative infusion of dexmedetomidine reduces postoperative delirium. Design, Setting, and Participants This study was a multicenter, double-blind, randomized, placebo-controlled trial that randomly assigned patients to dexmedetomidine or saline placebo infused during surgery and for 2 hours in the recovery room. Patients were assessed daily for postoperative delirium (primary outcome) and secondarily for postoperative cognitive decline. Participants were elderly (>68 years) patients undergoing major elective noncardiac surgery. The study dates were February 2008 to May 2014. Interventions Dexmedetomidine infusion (0.5 µg/kg/h) during surgery and up to 2 hours in the recovery room. Main Outcomes and Measures The primary hypothesis tested was that intraoperative dexmedetomidine administration would reduce postoperative delirium. Secondarily, the study examined the correlation between dexmedetomidine use and postoperative cognitive change. Results In total, 404 patients were randomized; 390 completed in-hospital delirium assessments (median [interquartile range] age, 74.0 [71.0-78.0] years; 51.3% [200 of 390] female). There was no difference in postoperative delirium between the dexmedetomidine and placebo groups (12.2% [23 of 189] vs 11.4% [23 of 201], P = .94). After adjustment for age and educational level, there was no difference in the postoperative cognitive performance between treatment groups at 3 months and 6 months. Adverse events were comparably distributed in the treatment groups. Conclusions and Relevance Intraoperative dexmedetomidine does not prevent postoperative delirium. The reduction in delirium previously demonstrated in numerous surgical intensive care unit studies was not observed, which underscores the importance of timing when administering the drug to prevent delirium. Trial Registration clinicaltrials.gov Identifier NCT00561678

Suicide in cancer patients within the first year of diagnosis

A diagnosis of cancer is associated with an increased suicide risk, and this risk is the highest within the first year of diagnosis. The aim of the present study was to determine risk factors of suicide occurring within the first year of cancer diagnosis (early suicide).

Lifetime manic spectrum episodes and all-cause mortality: 26-year follow-up of the NIMH Epidemiologic Catchment Area Study.

BACKGROUND While evidence suggests that depression is associated with medical morbidity and mortality, the potential role of mania has received less attention. This analysis evaluated the association between manic spectrum episodes and risk of all-cause mortality over a 26-year follow-up in a population-based study. METHODS Participants included 14,870 adults (mean age 48.2 ± 20.3; 58.2% female; 31.1% non-white) from four sites of the Epidemiologic Catchment Area Study who completed the Diagnostic Interview Schedule (DIS) mania assessment between 1980 and 1983 and had vital status data available through 2007. Participants were grouped into four mutually exclusive categories based on DIS mania assessment: (1) manic episode (n=46); (2) hypomanic episode (n=195); (3) sub-threshold manic symptoms (n=1041); and (4) no manic spectrum episodes (n=13,588). To determine vital status, participants were matched with the National Death Index. Participants with manic spectrum episodes were compared to those without such episodes with regard to mortality after 26 years. RESULTS After adjusting for major depressive symptoms and demographic differences, odds of mortality at follow-up for participants with lifetime manic spectrum episodes in the 30-44 and 45-64 year age cohorts at baseline were higher than those with no lifetime manic spectrum episodes in the same age cohorts (OR=1.39, 95% CI=[1.00, 1.93] and OR=1.41, 95% CI=[1.02, 1.95] respectively). CONCLUSIONS History of lifetime manic spectrum episodes in early to mid adulthood is associated with increased risk of all-cause mortality in mid to late life. LIMITATIONS Future studies of mania and mortality should evaluate specific causes of mortality.

Review of Severity Rating Scales for Restless Legs Syndrome: Critique and Recommendations

Over the last decade, research in restless legs syndrome (RLS; also known as Willis‐Ekbom disease) has increased dramatically. The International Parkinson and Movement Disorder Society commissioned a task force to formally evaluate the available evidence on severity rating scales in RLS. A literature search retrieved instruments specific to RLS. Each scale was evaluated by three criteria: (1) use in RLS; (2) use by research or clinical groups other than the group that developed the scale; and (3) formal validation and adequate clinimetric properties. Scales were then qualified as “recommended” when all three criteria were met, “suggested” when used for RLS but only one of the other criteria was met, and “listed” when only used in RLS. Details regarding the development, use, and psychometric properties of each instrument and the recommendations of the committee are summarized. The scale of the International Restless Legs Syndrome Study Group for rating the severity of RLS (International Restless Legs Scale or IRLS) and the Augmentation Severity Rating Scale fulfilled criteria for “recommended” instruments to assess severity. Future endeavors should include a validation of the Pediatric RLS Severity Scale, the only available instrument for evaluation of the severity of pediatric RLS, and a validation of a patient version of the IRLS that will not require the interface of a live interviewer.

Cognitive and functional status predictors of delirium and delirium severity after coronary artery bypass graft surgery: an interim analysis of the Neuropsychiatric Outcomes After Heart Surgery study.

BACKGROUND Cognitive and functional impairment increase risk for post-coronary artery bypass graft (CABG) surgery delirium (PCD), but how much impairment is necessary to increase PCD risk remains unclear. METHODS The Neuropsychiatric Outcomes After Heart Surgery (NOAHS) study is a prospective, observational cohort study of participants undergoing elective CABG surgery. Pre-operative cognitive and functional status based on Clinical Dementia Rating (CDR) scale and neuropsychological battery are assessed. We defined mild cognitive impairment (MCI) based on either (1) CDR global score 0.5 (CDR-MCI) or (2) performance 1.5 SD below population means on any cognitive domain on neurocognitive battery (MCI-NC). Delirium was assessed daily post-operative day 2 through discharge using the confusion assessment method (CAM) and delirium index (DI). We investigate whether MCI - either definition - predicts delirium or delirium severity. RESULTS So far we have assessed 102 participants (mean age 65.1 ± 9; male: 75%) for PCD. Twenty six participants (25%) have MCI-CDR; 38 (62% of those completing neurocognitive testing) met MCI-NC criteria. Fourteen participants (14%) developed PCD. After adjusting for age, sex, comorbidity, and education, MCI-CDR, MMSE, and Lawton IADL score predicted PCD on logistic regression (OR: 5.6, 0.6, and 1.5, respectively); MCI-NC did not (OR [95% CI]: 11.8 [0.9, 151.4]). Using similarly adjusted linear regression, MCI-CDR, MCI-NC, CDR sum of boxes, MMSE, and Lawton IADL score predicted delirium severity (adjusted R(2): 0.26, 0.13, 0.21, 0.18, and 0.32, respectively). CONCLUSIONS MCI predicts post-operative delirium and delirium severity, but MCI definition alters these relationships. Cognitive and functional impairment independently predict post-operative delirium and delirium severity.