D-cycloserine augmentation of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders: a systematic review and meta-analysis of individual participant data

Importance: Whether and under which conditions D-cycloserine (DCS) augments the effects of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders is unclear. Objective: To clarify whether DCS is superior to placebo in augmenting the effects of cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders and to evaluate whether antidepressants interact with DCS and the effect of potential moderating variables. Data Sources: PubMed, EMBASE, and PsycINFO were searched from inception to February 10, 2016. Reference lists of previous reviews and meta-analyses and reports of randomized clinical trials were also checked. Study Selection: Studies were eligible for inclusion if they were (1) double-blind randomized clinical trials of DCS as an augmentation strategy for exposure-based cognitive behavior therapy and (2) conducted in humans diagnosed as having specific phobia, social anxiety disorder, panic disorder with or without agoraphobia, obsessive-compulsive disorder, or posttraumatic stress disorder. Data Extraction and Synthesis: Raw data were obtained from the authors and quality controlled. Data were ranked to ensure a consistent metric across studies (score range, 0-100). We used a 3-level multilevel model nesting repeated measures of outcomes within participants, who were nested within studies. Results: Individual participant data were obtained for 21 of 22 eligible trials, representing 1047 of 1073 eligible participants. When controlling for antidepressant use, participants receiving DCS showed greater improvement from pretreatment to posttreatment (mean difference, -3.62; 95% CI, -0.81 to -6.43; P = .01; d = -0.25) but not from pretreatment to midtreatment (mean difference, -1.66; 95% CI, -4.92 to 1.60; P = .32; d = -0.14) or from pretreatment to follow-up (mean difference, -2.98, 95% CI, -5.99 to 0.03; P = .05; d = -0.19). Additional analyses showed that participants assigned to DCS were associated with lower symptom severity than those assigned to placebo at posttreatment and at follow-up. Antidepressants did not moderate the effects of DCS. None of the prespecified patient-level or study-level moderators was associated with outcomes. Conclusions and Relevance: D-cycloserine is associated with a small augmentation effect on exposure-based therapy. This effect is not moderated by the concurrent use of antidepressants. Further research is needed to identify patient and/or therapy characteristics associated with DCS response.2018-05-0

Dendrochronological data from twelve countries proved definite growth response of black alder (Alnus glutinosa [L.] Gaertn.) to climate courses across its distribution range

Black alder (Alnus glutinosa [L.] Gaertn.) is an important component of riparian and wetland ecosystems in Europe. However, data on the growth of this significant broadleaved tree species is very limited. Presently, black alder currently suffers from the pathogen Phytophthora and is particularly threatened by climate change. The objective of this study was to focus on the impact of climatic variables (precipitation, temperature, extreme climatic events) on the radial growth of alder across its geographic range during the period 1975–2015. The study of alder stands aged 46–108 years was conducted on 24 research plots in a wide altitude range (85–1015 m) in 12 countries of Europe and Asia. The most significant months affecting alder radial growth were February and March, where air temperatures are more significant than precipitation. Heavy frost and extreme weather fluctuations in the first quarter of the year were the main limiting factors for diameter increment. Within the geographical setting, latitude had a higher effect on radial growth compared to longitude. However, the most important variable concerning growth parameters was altitude. The temperature’s effect on the increment was negative in the lowlands and yet turned to positive with increasing altitude. Moreover, growth sensitivity to precipitation significantly decreased with the increasing age of alder stands. In conclusion, the growth variability of alder and the number of negative pointer years increased with time, which was caused by the ongoing climate change and also a possible drop in the groundwater level. Riparian alder stands well supplied with water are better adapted to climatic extremes compared to plateau and marshy sites

Depression prevalence using the HADS-D compared to SCID major depression classification:An individual participant data meta-analysis

Objectives: Validated diagnostic interviews are required to classify depression status and estimate prevalence of disorder, but screening tools are often used instead. We used individual participant data meta-analysis to compare prevalence based on standard Hospital Anxiety and Depression Scale – depression subscale (HADS-D) cutoffs of ≥8 and ≥11 versus Structured Clinical Interview for DSM (SCID) major depression and determined if an alternative HADS-D cutoff could more accurately estimate prevalence. Methods: We searched Medline, Medline In-Process & Other Non-Indexed Citations via Ovid, PsycINFO, and Web of Science (inception-July 11, 2016) for studies comparing HADS-D scores to SCID major depression status. Pooled prevalence and pooled differences in prevalence for HADS-D cutoffs versus SCID major depression were estimated. Results: 6005 participants (689 SCID major depression cases) from 41 primary studies were included. Pooled prevalence was 24.5% (95% Confidence Interval (CI): 20.5%, 29.0%) for HADS-D ≥8, 10.7% (95% CI: 8.3%, 13.8%) for HADS-D ≥11, and 11.6% (95% CI: 9.2%, 14.6%) for SCID major depression. HADS-D ≥11 was closest to SCID major depression prevalence, but the 95% prediction interval for the difference that could be expected for HADS-D ≥11 versus SCID in a new study was −21.1% to 19.5%. Conclusions: HADS-D ≥8 substantially overestimates depression prevalence. Of all possible cutoff thresholds, HADS-D ≥11 was closest to the SCID, but there was substantial heterogeneity in the difference between HADS-D ≥11 and SCID-based estimates. HADS-D should not be used as a substitute for a validated diagnostic interview.This study was funded by the Canadian Institutes of Health Research (CIHR, KRS-144045 & PCG 155468). Ms. Neupane was supported by a G.R. Caverhill Fellowship from the Faculty of Medicine, McGill University. Drs. Levis and Wu were supported by Fonds de recherche du Québec - Santé (FRQS) Postdoctoral Training Fellowships. Mr. Bhandari was supported by a studentship from the Research Institute of the McGill University Health Centre. Ms. Rice was supported by a Vanier Canada Graduate Scholarship. Dr. Patten was supported by a Senior Health Scholar award from Alberta Innovates, Health Solutions. The primary study by Scott et al. was supported by the Cumming School of Medicine and Alberta Health Services through the Calgary Health Trust, and funding from the Hotchkiss Brain Institute. The primary study by Amoozegar et al. was supported by the Alberta Health Services, the University of Calgary Faculty of Medicine, and the Hotchkiss Brain Institute. The primary study by Cheung et al. was supported by the Waikato Clinical School, University of Auckland, the Waikato Medical Research Foundation and the Waikato Respiratory Research Fund. The primary study by Cukor et al. was supported in part by a Promoting Psychological Research and Training on Health-Disparities Issues at Ethnic Minority Serving Institutions Grants (ProDIGs) awarded to Dr. Cukor from the American Psychological Association. The primary study by De Souza et al. was supported by Birmingham and Solihull Mental Health Foundation Trust. The primary study by Honarmand et al. was supported by a grant from the Multiple Sclerosis Society of Canada. The primary study by Fischer et al. was supported as part of the RECODEHF study by the German Federal Ministry of Education and Research (01GY1150). The primary study by Gagnon et al. was supported by the Drummond Foundation and the Department of Psychiatry, University Health Network. The primary study by Akechi et al. was supported in part by a Grant-in-Aid for Cancer Research (11−2) from the Japanese Ministry of Health, Labour and Welfare and a Grant-in-Aid for Young Scientists (B) from the Japanese Ministry of Education, Culture, Sports, Science and Technology. The primary study by Kugaya et al. was supported in part by a Grant-in-Aid for Cancer Research (9–31) and the Second-Term Comprehensive 10-year Strategy for Cancer Control from the Japanese Ministry of Health, Labour and Welfare. The primary study Ryan et al. was supported by the Irish Cancer Society (Grant CRP08GAL). The primary study by Keller et al. was supported by the Medical Faculty of the University of Heidelberg (grant no. 175/2000). The primary study by Love et al. (2004) was supported by the Kathleen Cuningham Foundation (National Breast Cancer Foundation), the Cancer Council of Victoria and the National Health and Medical Research Council. The primary study by Love et al. (2002) was supported by a grant from the Bethlehem Griffiths Research Foundation. The primary study by Löwe et al. was supported by the medical faculty of the University of Heidelberg, Germany (Project 121/2000). The primary study by Navines et al. was supported in part by the Spanish grants from the Fondo de Investigación en Salud, Instituto de Salud Carlos III (EO PI08/90869 and PSIGEN-VHC Study: FIS-E08/00268) and the support of FEDER (one way to make Europe). The primary study by O'Rourke et al. was supported by the Scottish Home and Health Department, Stroke Association, and Medical Research Council. The primary study by Sanchez-Gistau et al. was supported by a grant from the Ministry of Health of Spain (PI040418) and in part by Catalonia Government, DURSI 2009SGR1119. The primary study by Gould et al. was supported by the Transport Accident Commission Grant. The primary study by Rooney et al. was supported by the NHS Lothian Neuro-Oncology Endowment Fund. The primary study by Schwarzbold et al. was supported by PRONEX Program (NENASC Project) and PPSUS Program of Fundaçao de Amparo a esquisa e Inovacao do Estado de Santa Catarina (FAPESC) and the National Science and Technology Institute for Translational Medicine (INCT-TM). The primary study by Simard et al. was supported by IDEA grants from the Canadian Prostate Cancer Research Initiative and the Canadian Breast Cancer Research Alliance, as well as a studentship from the Canadian Institutes of Health Research. The primary study by Singer et al. (2009) was supported by a grant from the German Federal Ministry for Education and Research (no. 01ZZ0106). The primary study by Singer et al. (2008) was supported by grants from the German Federal Ministry for Education and Research (# 7DZAIQTX) and of the University of Leipzig (# formel. 1–57). The primary study by Meyer et al. was supported by the Federal Ministry of Education and Research (BMBF). The primary study by Stone et al. was supported by the Medical Research Council, UK and Chest Heart and Stroke, Scotland. The primary study by Turner et al. was supported by a bequest from Jennie Thomas through Hunter Medical Research Institute. The primary study by Walterfang et al. was supported by Melbourne Health. Drs. Benedetti and Thombs were supported by FRQS researcher salary awards. No other authors reported funding for primary studies or for their work on this study. No funder had any role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication

Anxiety in Patients Treated with Hemodialysis.

Anxiety is a common yet frequently overlooked psychiatric symptom in patients with ESRD treated with hemodialysis (HD). Anxiety is characterized by disruptive feelings of uncertainty, dread, and fearfulness. A variety of common medical complaints may be manifestations of an anxiety disorder, including palpitations, tremors, indigestion, numbness/tingling, nervousness, shortness of breath, diaphoresis, and fear. It is essential for the clinician to rule out specific medical conditions, including cardiovascular, pulmonary, and neurologic diseases, before ascribing these symptoms to an anxiety disorder. In addition, there is considerable overlap between the symptoms of anxiety and those of depression and uremia. This psychiatric condition has a significant adverse impact on patients’ perception of quality of life. Little is known regarding the prevalence and impact of anxiety disorders in patients with ESRD treated with HD; however, many of the seemingly irrational behaviors of patients, or behaviors which place them in conflict with staff and physicians, such as behavioral noncompliance, may be the expression of an underlying anxiety disorder. In this review, we present three clinical vignettes, highlighting the impact of anxiety disorders in patients with ESRD treated with HD

Can Simulation Measure Differences in Task-Switching Ability Between Junior and Senior Emergency Medicine Residents?

Introduction: Work interruptions during patient care have been correlated with error. Task-switching is identified by the Accreditation Council for Graduate Medical Education (ACGME) as a core competency for emergency medicine (EM). Simulation has been suggested as a means of assessing EM core competencies. We assumed that senior EM residents had better task-switching abilities than junior EM residents. We hypothesized that this difference could be measured by observing the execution of patient care tasks in the simulation environment when a patient with a ST-elevation myocardial infarction (STEMI) interrupted the ongoing management of a septic shock case. Methods: This was a multi-site, prospective, observational, cohort study. The study population consisted of a convenience sample of EM residents in their first three years of training. Each subject performed a standardized simulated encounter by evaluating and treating a patient in septic shock. At a predetermined point in every sepsis case, the subject was given a STEMI electrocardiogram (ECG) for a separate chest pain patient in triage and required to verbalize an interpretation and action. We scored learner performance using a dichotomous checklist of critical actions covering sepsis care, ECG interpretation and triaging of the STEMI patient. Results: Ninety-one subjects participated (30 postgraduate year [PGY]1s, 32 PGY2s, and 29 PGY3s). Of those, 87 properly managed the patient with septic shock (90.0% PGY1s, 100% PGY2, 96.6% PGY 3s; p=0.22). Of the 87 who successfully managed the septic shock, 80 correctly identified STEMI on the simulated STEMI patient (86.7% PGY1s, 96.9% PGY2s, 93.1% PGY3s; p=0.35). Of the 80 who successfully managed the septic shock patient and correctly identified the STEMI, 79 provided appropriate interventions for the STEMI patient (73.3% PGY1s, 93.8% PGY2s, 93.8% PGY3s; p=0.07). Conclusion: When management of a septic shock patient was interrupted with a STEMI ECG in a simulated environment we were unable to measure a significant difference in the ability of EM residents to successfully task-switch when compared across PGY levels of training. This study may help refine the use of simulation to assess EM resident competencies