Analyzing Non-urgent Emergency Department Visits: Patterns, Demographics, Motivations, and Triage System Awareness in Al-Qassim.

OBJECTIVE: This cross-sectional descriptive study aimed to ascertain the prevalence of non-urgent cases, investigate gender and age preferences, and explore factors influencing individuals' selection of the emergency department (ED) for non-urgent cases in the Al-Qassim region of Saudi Arabia. METHODS: From July 15, 2022, to December 31, 2022, a structured online questionnaire via a Google Docs survey collected data. The study sampled 425 patients from two prominent Al-Qassim healthcare institutions: Buraydah King Fahad Specialized Hospital and Buraydah Central Hospital. Encompassing patients aged 20 to 80 admitted to the ED between 8:00 and 16:00, concurrent with primary healthcare center availability, the study categorized participants by urgency using the Canadian Triage and Acuity Scale (CTAS) criteria. Data analysis employed descriptive statistics, chi-square tests, and probit regression in R version 4.3.3, with a significance level of p < 0.05 for result interpretation. RESULTS: In Al-Qassim in 2022, 82.4% of ED visitors sought care for non-urgent cases, while 17.6% sought care for urgent cases. No statistically significant relationship was found between age and gender and urgent ED visits. Among those with non-urgent conditions, the top reasons for bypassing primary healthcare services were slow treatment (52.7%), lack of knowledge about primary healthcare (PHC) services (33.9%), and appointment unavailability (5.5%). Evaluation of awareness of the ED triage system showed a significant difference only among patients with excellent awareness. CONCLUSION: The investigation found a higher prevalence of non-urgent cases, especially among females. Challenges in appointment booking, accessibility, and the perception of urgency were key factors leading patients to choose the emergency department over PHC centers. The study emphasized the crucial role of ED triage system awareness and the impact of satisfaction with PHC services on healthcare-seeking behavior, with younger individuals less likely to visit the ED and males more inclined at specific satisfaction levels.

The Role of Interproximal Reduction (IPR) in Clear Aligner Therapy: A Critical Analysis of Indications, Techniques, and Outcomes.

Interproximal reduction (IPR) has become a standard practice in orthodontic treatment, particularly in the clear aligner therapy. It became an integral part of the digital plan when using clear aligners. Given the irreversible nature of IPR, precise planning and performance is essential. This article aims to analyze and summarize the existing literature on IPR in the context of clear aligners. The goal is to help clinicians to gain essential knowledge for safely and effectively navigating IPR. The review critically examines different perspectives found in the literature, covering indications, methods, and outcomes. Topics exploring the impact of IPR on treatment outcomes include space gaining, addressing tooth size discrepancies, tooth shape adjustments, resolving malocclusion, and enhancing aesthetics. Emphasizing precision of the procedure by the clinician and awareness of contraindications, the article also discusses the impact of IPR on patients. This includes considerations like increased pulp temperature, susceptibility to cavities due to changes in enamel roughness, effects on soft tissues, and post-IPR tooth sensitivity.

Efficacy and Safety of Esketamine Nasal Spray in Patients with Treatment-Resistant Depression Who Completed a Second Induction Period: Analysis of the Ongoing SUSTAIN-3 Study.

BACKGROUND: Treatment-resistant depression (TRD) is a chronic illness requiring long-term treatment. Esketamine nasal spray (ESK) has been studied in several long-term trials of patients with TRD, including SUSTAIN-1 (NCT02493868) and SUSTAIN-3 (NCT02782104). This subgroup analysis of SUSTAIN-3 evaluated patients with TRD who received a second induction (IND) and maintenance treatment with ESK plus oral antidepressant (AD) after a relapse in SUSTAIN-1. METHODS: Patients aged 18-64 years who achieved stable remission or response with ESK and subsequently relapsed after randomization to continue ESK or switch to placebo nasal spray (PBO) in SUSTAIN-1 and entered the IND phase of SUSTAIN-3 were included in this interim analysis. Response (≥50% improvement in total score from baseline for Montgomery-Åsberg Depression Rating Scale [MADRS] and Patient Health Questionnaire 9-item [PHQ-9]), remission (MADRS score ≤12; PHQ-9 total score <5), changes in depression rating scores (measured as mean change from baseline), and safety were evaluated (incidence of treatment-emergent and serious adverse events [AE]). RESULTS: Of the 96 eligible patients who entered IND in SUSTAIN-3, 32 (33.3%) were taking ESK+AD at the time of relapse in SUSTAIN-1 and 64 (66.7%) were taking AD+PBO. Substantial improvements in depressive symptoms were observed over the second IND phase in both groups and were maintained over the optimization/maintenance (OP/M) phase. MADRS response rates following a second IND were 71.9% and 73.4% for previously relapsed (PR) ESK+AD and PR-AD+PBO, respectively; remission rates were 62.5% and 60.9%, respectively. During the IND and OP/M phases, 58.3% and 83.3% of patients experienced a treatment-emergent AE, respectively. No patients discontinued due to an AE during the second IND. CONCLUSIONS: Patients with TRD benefitted from receiving a second IND and maintenance treatment with ESK and no new safety signals were identified.

Awareness, preconception, and fear of epidural analgesia among childbearing women in Saudi Arabia: An observational cross-sectional study.

Background: Labor pain is one of the most excruciatingly painful sensations a woman can have. A woman's attitude toward childbirth might be influenced by her lack of understanding of the birth process and the pain she experiences throughout labor and delivery. The control of pain is an important aspect of appropriate obstetrical care. Our study aims to measure the level of awareness, preconception, and fear of epidural analgesia (EDA) among childbearing women. Methods: An observational cross-sectional, hospital-based study was conducted using a self-administered questionnaire. The study included all pregnant women who were attending an obstetrical clinic for routine antenatal follow-up at King Khalid university hospital in Riyadh, Saudi Arabia, during the month of August 2022. They were asked about five main parts that tapped their awareness, preconception, and fear of EDA. Data were analyzed by SPSS version 26 using descriptive methods, including mean, frequency, and percentage, and also Pearson's correlation coefficient for regression analysis to find the correlation between socio-demographics and awareness and between awareness and fear. Results: Participants in our study included 202 childbearing women. Most women, about 113 (55.9%), participating in the study were aged between 25 and 34 years old. The majority of the participants of this study were Saudi, about 196 (97.0%). In terms of education, 120 (59.4%) of the participants graduated from university. One hundred and forty two (70.3%) of the participants had a monthly income of less than 10000. When it comes to parity, the majority of participants, about 102 (50.5%), have had more than two pregnancies. The average percentage of awareness among the participants showed 45.9%, with an insignificant very moderate correlation between parity and awareness (r = -0.088, P = 0.107); women's knowledge, income, and age were also insignificantly related to awareness. Also, the result showed a moderate level of fear with an average percentage of 44.6% among the participants, with a moderate correlation between awareness and fear with a value of (r = 0.184, P = 0.004). Conclusion: This study results demonstrate a good level of desirability toward using EDA for labor pain, yet there is a limited level of preconceptions and a low level of awareness and knowledge about EDA. In addition, the results showed that the average percentage of fear is 44.6%. Therefore, we suggest that more awareness, knowledge, and guidance about EDA should be provided to pregnant women through antenatal clinics. Furthermore, educational campaigns should be made to dispel misconceptions and fears about EDA.

Clinical, Radiological and Pathological Appraisal of Acute Appendicitis in Al Qassim, Saudi Arabia: A Single-Center Retrospective Analysis.

Background Acute appendicitis can occur at any age but is rare among people of extreme age; it is more common in teenagers and young adults. Traditionally diagnosis is made on clinical grounds. In recent times imaging techniques have been deployed to improve diagnosis and reduce negative appendicectomy rates. The aim of the study was to describe the common clinical features of acute appendicitis among our patients, highlight the role of medical imaging, and compare all these with the histological report of the excised appendix. Methods A 24-months retrospective review of all patients who underwent appendicectomy (July 1, 2019-June 30, 2021) for suspected acute appendicitis was performed. Medical records numbers of patients who had appendicectomies were retrieved from the operating room register. These numbers were used to access the hospital's electronic medical records database for the patients' records. These records were reviewed for biodata, clinical features, laboratory, medical imaging findings, and histological reports. Result In this hospital, 354 appendicectomies were performed. Only 336 had complete data set suitable for further review. There were more males (N=257; 76.5%) than females (N=79, 23.5%), yielding a male to female ratio of 4:1. There were also more Saudi citizens (n=266, 79.2%), with the predominant age group being 11-30 years. Abdominal pain was the predominant symptom (100%) and was localized to the right iliac region in 331 (98.7%) of patients. Other symptoms recorded were anorexia (n=247, 73.5%), vomiting (n=190, 56.5%), and nausea (n=93, 27.7%). Atypical symptoms included diarrhoea (n=27, 8%) and constipation (n=12, 3.6%). Acute appendicitis, complicated appendicitis, and no appendicitis were the reported histological disposition in 174 (51.8%), 124 (36.9%), and 38 (11.3%) cases respectively. Abdominal CT scan had a higher sensitivity (98.6% vs 70.5%), higher diagnostic odd ratio (2.5 vs 1.4) and a lower miss (false negative) rate (1.4% vs 29.5%) compared to ultrasonography. However, the CT scan, from this study, has a rather low specificity (3.4%) and high false positive rates (96.5%). Open (n=205; 61%) and laparoscopic (n=131;39%) approaches were used for the appendicectomies. In our study, 44 patients were diagnosed with the decision to operate based on clinical grounds; and of this, 42 (95.4%; n=44) had confirmatory histology reports of appendicitis. Also, 38 patients had negative appendicectomy; giving a negative appendicectomy rate of 11.3%. This high rate may be due to the lower specificity and high false positive rate observed in this study. The post-operative complication rate was 21.4%, and this was solely due to surgical site infection, and this was more common with the open approach (p=0.001). Conclusion Suspected acute appendicitis was the sole indication for our appendicectomies. A computerized tomography scan was a more reliable diagnostic tool than ultrasonography. Despite the fact that acute appendicitis is majorly a clinical diagnosis, and good clinical acumen is an excellent skill in the management of patients, we observed an overreliance on medical imaging for diagnosis. Open appendicectomies were more common, and surgical site infection was the sole complication of surgery. There was a relatively high negative appendicectomy rate for an image-assisted diagnosis.

Impact of COVID-19 pandemic quarantine on physical, nutritional, psychosocial life and work aspects in the Kingdom of Saudi Arabia.

Background: The coronavirus disease-2019 (COVID-19) is a global public health disaster imposing a nationwide lockdown. This study was undertaken to determine the impact of COVID-19 quarantine on physical, nutritional, psychosocial life, and work aspects on the population of Saudi Arabia. Methods: Data collection was based on the fear of COVID-19 Scale (FCV-19S) and was analyzed by the Likert-type scale. A total of 2828 individuals participated during their COVID-19 quarantine. The data were collected during June 10-17, 2020 using the psychosocial FCV-19S. Results: COVID-19 quarantine was negatively correlated with the physical, nutritional, psychosocial life and work aspects of the Saudi Arabia's population (P < 0.05). As a result of the correlation analysis, gender, sociodemographic status and having a family member dying of COVID-19, marital status (single), monthly income (<3000) and occupation (student), and lost a job or businesses were significantly associated with fear of COVID-19 (P < 0.05). Furthermore, the participants reported a reduction in their physical activity by 59%, whereas 26.5% of participants showed an increase of body weight. Moreover, 23% of participants lost their jobs during the pandemic. Conclusions: The lockdown period was associated with an increase in the COVID-19 fear score. The degree FCV-19S was varied in different categories in several aspects. Low levels of physical activity and weight gained were observed during the lockdown period.

Identification of an optimal dose of intravenous ketamine for late-life treatment-resistant depression: a Bayesian adaptive randomization trial.

Evidence supporting specific therapies for late-life treatment-resistant depression (LL-TRD) is necessary. This study used Bayesian adaptive randomization to determine the optimal dose for the probability of treatment response (≥50% improvement from baseline on the Montgomery-Åsberg Depression Rating Scale) 7 days after a 40 min intravenous (IV) infusion of ketamine 0.1 mg/kg (KET 0.1), 0.25 mg/kg (KET 0.25), or 0.5 mg/kg (KET 0.5), compared to midazolam 0.03 mg/kg (MID) as an active placebo. The goal of this study was to identify the best dose to carry forward into a larger clinical trial. Response durability at day 28, safety and tolerability, and effects on cortical excitation/inhibition (E/I) ratio using resting electroencephalography gamma and alpha power, were also determined. Thirty-three medication-free US military veterans (mean age 62; range: 55-72; 10 female) with LL-TRD were randomized double-blind. The trial was terminated when dose superiority was established. All interventions were safe and well-tolerated. Pre-specified decision rules terminated KET 0.1 (N = 4) and KET 0.25 (N = 5) for inferiority. Posterior probability was 0.89 that day-seven treatment response was superior for KET 0.5 (N = 11; response rate = 70%) compared to MID (N = 13; response rate = 46%). Persistent treatment response at day 28 was superior for KET 0.5 (response rate = 82%) compared to MID (response rate = 37%). KET 0.5 had high posterior probability of increased frontal gamma power (posterior probability = 0.99) and decreased posterior alpha power (0.89) during infusion, suggesting an acute increase in E/I ratio. These results suggest that 0.5 mg/kg is an effective initial IV ketamine dose in LL-TRD, although further studies in individuals older than 75 are required.

A study of expected lifetime of XLPE insulation cables working at elevated temperatures by applying accelerated thermal ageing.

Deterioration of cable insulation during its normal operation is a major concern. Usually, electric cables receive less periodic maintenance compared to the other electric components, although they are subjected to several environmental conditions during operation such as high temperature and oxidative atmospheres. In this study, a standardized accelerated thermal ageing technique was used, with the application of the Arrhenius model. This technique is commonly used in accelerated life testing to establish a lifetime-stress relationship and estimate cable lifetime. Two types of Cross-Linked Polyethylene (XLPE) material working at elevated temperatures between 95 and 105 °C were selected for testing. In such accelerated ageing processes, it is required for the insulation to reach a degradation level, which is considered the end of life for the material under evaluation. The end of life criteria (also called endpoint) is defined as a percentage reduction of elongation at break, which is considered in this study to be 50% retention of elongation at break. Thermal ageing was carried out according to the BS 7870-2 standard, while elongation at break was evaluated at several ageing stages. The uncertainty in the measurement was estimated. The short-term data points determined by ageing treatment is represented graphically in the Arrhenius plot. The extrapolation of such data was used to predict the long-term performance and estimate the cable lifetime. The lifetime for XLPE is expected to be between 40 and 60 years at 90 °C rated operating temperature. Experimental findings of this study show an estimated cable lifetime between 7 and 30 years for rated operating temperatures between 95 and 105 °C.

Sero-prevalence ABO and Rh blood groups and their associated Transfusion-Transmissible Infections among Blood Donors in the Central Region of Saudi Arabia.

BACKGROUND: Screening of blood products is considered a mandatory protocol implemented in health care facilities in order to reduce the onset of transfusion-transmitted infections (TTIs). This study was aimed to determine the sero-prevalence of ABO and Rh blood groups and their associated TTIs among blood donors in the Central Region of Saudi Arabia. METHODS: This was retrospective study performed on the blood donors' records from March 2017 to December 2018 at Buraidah Central Hospital Blood Bank. Study was conducted on a total of 4590 blood donors. ABO and Rh typing was performed.The blood samples were also screened serologically for hepatitis B surface antigen (HBsAg), anti-hepatitis B core total antibodies (anti-HBc total), hepatitis C virus (HCV), human immunodeficiency viruses (HIV), human T-lymphotrophic virus-1 (HTLV-1) and veneral disease research laboratory test(VDRL) for syphilis. RESULTS: Out of 4590 blood donors, O positive blood group was found to be highest (42%), followed by A positive (23.4%), B positive (20.9%), O negative (5.45%), AB positive (3.4%), A negative (2.8%), B negative (2.1%) and AB negative (0.5%). Moreover, total number of Rh-negative donors was significantly lowered as compared with Rh-positive. Seroreactive tests were found to be positive in only 1.002% of all studied donors and mainly found in male donors. Among TTI, anti-HBc total was the highest (0.784%), followed by HBsAg, HCV, VDRL and TPHA. Whereas all tested donors were found to be negative for HIV infections. CONCLUSIONS: The information collected for the frequency of ABO blood phenotypic groups has a vital significance in establishing a simple blood group database. This study clearly determined significantly lower rate of seropositive TTIs among the studied blood donors but still steps are needed to improve the knowledge and to prevent the seropositive occurrence of TTIs.

Attitude of medical students at King Saud Bin Abdulaziz University for Health Sciences toward family medicine as a future specialty.

BACKGROUND: Owing to the rising population of the Kingdom of Saudi Arabia, the need for family physicians is growing. The number of family physicians who would be available in the health service in future is dependent on the attitudes of medical students because their choice of specialty is a major factor in satisfying this demand. The aim of the study was to evaluate the attitudes of medical students to family medicine as a future career. MATERIALS AND METHODS: This cross-sectional study was conducted at King Saud Bin Abdulaziz University for Health Sciences. A total of 308 students were randomly selected from problem-based learning groups. Data were collected using a 25-item validated questionnaire, and Excel and SPSS were used for data entry and analysis. Mean and standard deviation were used to describe numerical data and frequencies and percentages to describe categorical data. P < 0.05 was considered statistically significant. RESULTS: A total of 308 medical students, 201 (65.3%) of whom were male, completed the questionnaire. Majority of the students (229 [74.3%]) agreed that family physicians make important contributions to medicine although family medicine was one of the least preferred specialties of the students. CONCLUSIONS: Most students were aware of the importance of family medicine; however, only a few of them chose this specialty. Further studies should be conducted to identify the factors that influence medical students' decisions in their choice of family medicine as a future career.

GERI-BD: A Randomized Double-Blind Controlled Trial of Lithium and Divalproex in the Treatment of Mania in Older Patients With Bipolar Disorder.

(Reprinted with permission from Am J Psychiatry 2017; 174:1086-1093).

Assessing bipolar disorder in the older adult: the GERI-BD toolbox.

INTRODUCTION: The evidence base regarding characteristics of older adults with bipolar disorder (BD) remains limited. The NIH-funded multicenter study Acute Pharmacotherapy of Late-Life Mania (GERI-BD) assessed various clinical domains before and during mood stabilizer treatment in older adults participating in a 9-week, double-blind randomized controlled trial. We describe the rationale for selecting these instruments. METHODS: Domains and instruments were selected on the basis of the study design and the participants. The investigators' experience in clinical trials involving young adults with BD or older adults with major depressive disorder, along with open studies of older adults with BD, contributed to the selection process. RESULTS: We identified domains and selected instruments that could be used to assess the participants given their diagnostic, treatment history, and medical and mood state characteristics. They were also intended to measure tolerability and efficacy and permit examination of potential moderating and mediating factors. CONCLUSIONS: Decisions regarding the assessment domains to be included in the clinical trial highlight the challenges facing researchers studying drug treatments for older adults with BD, or more generally, mood disorders. We suggest that the domains and instruments selected by GERI-BD investigators constitute a "toolbox" that can be customized for other investigators. Copyright © 2017 John Wiley & Sons, Ltd.

GERI-BD: A Randomized Double-Blind Controlled Trial of Lithium and Divalproex in the Treatment of Mania in Older Patients With Bipolar Disorder.

OBJECTIVE: Clinicians treating older patients with bipolar disorder with mood stabilizers need evidence from age-specific randomized controlled trials. The authors describe findings from a first such study of late-life mania. METHOD: The authors compared the tolerability and efficacy of lithium carbonate and divalproex in 224 inpatients and outpatients age 60 or older with bipolar I disorder who presented with a manic, hypomanic, or mixed episode. Participants were randomly assigned, under double-blind conditions, to treatment with lithium (target serum concentration, 0.80-0.99 mEq/L) or divalproex (target serum valproate concentration, 80-99 µg/mL) for 9 weeks. Participants with an inadequate response after 3 weeks received open adjunctive risperidone. The authors hypothesized that divalproex would be better tolerated and more efficacious than lithium. Tolerability was assessed based on a measure of sedation and on the proportions of participants achieving target concentrations. Efficacy was assessed with the Young Mania Rating Scale (YMRS). RESULTS: Attrition rates were similar for lithium and divalproex (14% and 18% at week 3 and 51% and 44% at week 9, respectively). The groups did not differ significantly in sedation. Participants in the lithium group tended to experience more tremor. Similar proportions of participants in the lithium and divalproex groups achieved target concentrations (57% and 56%, respectively). A longitudinal mixed model of improvement (change from baseline in YMRS score) favored lithium (change in score, 3.90; 97.5% CI=1.71, 6.09). Nine-week response rates did not differ significantly between the lithium and divalproex groups (79% and 73%, respectively). The need for adjunctive risperidone was low and similar between groups (17% and 14%, respectively). CONCLUSIONS: Both lithium and divalproex were adequately tolerated and efficacious; lithium was associated with a greater reduction in mania scores over 9 weeks.

A report on older-age bipolar disorder from the International Society for Bipolar Disorders Task Force.

OBJECTIVES: In the coming generation, older adults with bipolar disorder (BD) will increase in absolute numbers as well as proportion of the general population. This is the first report of the International Society for Bipolar Disorder (ISBD) Task Force on Older-Age Bipolar Disorder (OABD). METHODS: This task force report addresses the unique aspects of OABD including epidemiology and clinical features, neuropathology and biomarkers, physical health, cognition, and care approaches. RESULTS: The report describes an expert consensus summary on OABD that is intended to advance the care of patients, and shed light on issues of relevance to BD research across the lifespan. Although there is still a dearth of research and health efforts focused on older adults with BD, emerging data have brought some answers, innovative questions, and novel perspectives related to the notion of late onset, medical comorbidity, and the vexing issue of cognitive impairment and decline. CONCLUSIONS: Improving our understanding of the biological, clinical, and social underpinnings relevant to OABD is an indispensable step in building a complete map of BD across the lifespan.

Psychopharmacological Agents and Suicide Risk Reduction: Ketamine and Other Approaches.

Suicide is a major global public health problem and the leading cause of injury mortality in the USA. Suicide is a complex phenomenon involving several systems and neurobiological pathways, with interacting genetic and environmental mechanisms. The literature on the neurobiology and pharmacotherapy of suicide has been limited. To date, no medications have proven efficacious for treating acute suicidal crises. There is an emerging literature supporting a rapid anti-suicidal effect of ketamine, a non-competitive N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, among depressed patients with suicidal ideation. Potential ketamine's anti-suicidal effect mechanisms are linked to interruption of the kynurenine pathway and modulating pro-inflammatory cytokines exacerbation. However, available data are not sufficient for its routine integration in clinical practice, and larger and replicated randomized control studies are needed.

Cognitive function and suicide risk in Han Chinese inpatients with schizophrenia.

The lifetime risk of suicide in patients with schizophrenia is estimated to be 4.9-13%. While there are many known risk factors for suicide in schizophrenia, the relationship between cognitive function and suicide risk is unclear, particularly in non-Caucasian populations. In our cross-sectional study, we administered the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to 316 Han Chinese chronic inpatients with schizophrenia and compared the performance of those who had attempted suicide (n=25) to non-attempters (n=291). The lifetime suicide attempt data were collected from medical records and interviews with patients and their family members. We found a lifetime suicide attempt rate of 7.9%. Suicide attempters were more likely to be single, but showed no significant differences in other demographic factors such as age, gender, or living arrangements. Contrary to our hypothesis, there was no significant relationship between performance on the RBANS test and lifetime risk of suicide attempts in Han Chinese inpatients with schizophrenia. The literature remains mixed on this topic. Culturally influenced differences in suicidal behavior may have affected the outcome of this study and further investigation of this topic is necessary.

Effects of ketamine on explicit and implicit suicidal cognition: a randomized controlled trial in treatment-resistant depression.

BACKGROUND: Preliminary evidence suggests intravenous ketamine has rapid effects on suicidal cognition, making it an attractive candidate for depressed patients at imminent risk of suicide. In the first randomized controlled trial of ketamine using an anesthetic control condition, we tested ketamine's acute effects on explicit suicidal cognition and a performance-based index of implicit suicidal cognition (Implicit Association Test; IAT) previously linked to suicidal behavior. METHOD: Symptomatic patients with treatment-resistant unipolar major depression (inadequate response to ≥3 antidepressants) were assessed using a composite index of explicit suicidal ideation (Beck Scale for Suicidal Ideation, Montgomery-Asberg Rating Scale suicide item, Quick Inventory of Depressive Symptoms suicide item) and the IAT to assess suicidality implicitly. Measures were taken at baseline and 24 hr following a single subanesthetic dose of ketamine (n = 36) or midazolam (n = 21), a psychoactive placebo agent selected for its similar, rapid anesthetic effects. Twenty four hours postinfusion, explicit suicidal cognition was significantly reduced in the ketamine but not the midazolam group. RESULTS: Fifty three percent of ketamine-treated patients scored zero on all three explicit suicide measures at 24 hr, compared with 24% of the midazolam group (χ(2) = 4.6; P = .03). Implicit associations between self- and escape-related words were reduced following ketamine (P = .01; d = .58) but not midazolam (P = .68; d = .09). Ketamine-specific decreases in explicit suicidal cognition were largest in patients with elevated suicidal cognition at baseline, and were mediated by decreases in nonsuicide-related depressive symptoms. CONCLUSIONS: Intravenous ketamine produces rapid reductions in suicidal cognition over and above active placebo. Further study is warranted to test ketamine's antisuicidal effects in higher-risk samples.

Social support in late life mania: GERI-BD.

OBJECTIVE: Using the database of the National Institute of Mental Health-sponsored acute treatment of late life mania study (GERI-BD), we assessed the role of social support in the presentation of late life bipolar mania. METHODS: In the first 100 subjects randomized in geriatric BD, we explored the demographic, clinical, and social support characteristics (assessed using the Duke Social Support Index) and aspects of manic presentation. We selected two dependent variables: symptom severity, as determined by the Young Mania Rating Scale (YMRS) at baseline, and duration of episode. We selected nine potential independent variables on the basis of Pearson correlation coefficients. We derived two final models using multiple regression analysis employing an iterative process. RESULTS: In our severity model, being married was associated with a higher YMRS score (p = 0.05), whereas higher social interaction scores with non-family members were associated with a lower YMRS score (p = 0.011). In the episode duration model, longer duration was associated with a higher Hamilton Depression Rating Scale score (p = 0.03) and higher social interaction scores with non-family members (p = 0.0003), younger age (p = 0.04), higher number of persons in one's family social network (p = 0.017), and higher instrumental support scores (p = 0.0062). CONCLUSIONS: In late life mania, more social interaction with one's community appears to be associated with less severe symptoms at presentation for treatment, however, it can also be associated with slightly longer the duration of episode. Two aspects of the Duke Social Support Index are associated with a shorter episode duration prior to seeking treatment: being part of a larger family network and a having a higher level of instrumental support prior to treatment. The Instrumental Support Subscale measures the degree of assistance that is available for the respondent in performing daily tasks. These findings suggest that in older adults with BD, close social interactions and support are important in limiting the length of the illness episode prior to treatment. Social interactions involving non-family members may be less important in moderating the intensity of the symptoms at presentation.

Correlates of disability in depressed older adults with bipolar disorder.

Aims To identify clinical factors associated with disability in depressed older adults with bipolar disorder (BPD) receiving lamotrigine. Methods Secondary analysis of a multi-site, 12-week, open-label, uncontrolled study of addon lamotrigine in 57 adults 60 years and older with BD I or II depression. Measures included the Montgomery Asberg Depression Rating Scale (MADRS), Young Mania Rating Scale (YMRS), Cumulative Illness Rating Scale for Geriatrics (CIRS-G), Dementia Rating Scale (DRS), and WHO-Disability Assessment Scale II (WHO-DAS II). Results Medical comorbidiy in this group of elders was substantial, with roughly 60% of subjects having disorders of the vascular, musculoskeletal/integument, and endodrine/metabolic/breast systems. We found significant relationships among mood (MADRS), medical comorbidity (CIRS-G), cognition (DRS), and disability (WHO-DAS II). More severe BPD depression, more medical comorbidity and more impaired cognition were all associated with lower functioning in BPD elders. Conclusions Our findings fit the paradigm shift that has been occurring in BPD, supporting the notion that BPD is not solely an illness of mood but that it affects multiple domains impacting overall functioning.

Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial.

OBJECTIVE: Ketamine, a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist, has shown rapid antidepressant effects, but small study groups and inadequate control conditions in prior studies have precluded a definitive conclusion. The authors evaluated the rapid antidepressant efficacy of ketamine in a large group of patients with treatment-resistant major depression. METHOD: This was a two-site, parallel-arm, randomized controlled trial of a single infusion of ketamine compared to an active placebo control condition, the anesthetic midazolam. Patients with treatment-resistant major depression experiencing a major depressive episode were randomly assigned under double-blind conditions to receive a single intravenous infusion of ketamine or midazolam in a 2:1 ratio (N=73). The primary outcome was change in depression severity 24 hours after drug administration, as assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS). RESULTS: The ketamine group had greater improvement in the MADRS score than the midazolam group 24 hours after treatment. After adjustment for baseline scores and site, the MADRS score was lower in the ketamine group than in the midazolam group by 7.95 points (95% confidence interval [CI], 3.20 to 12.71). The likelihood of response at 24 hours was greater with ketamine than with midazolam (odds ratio, 2.18; 95% CI, 1.21 to 4.14), with response rates of 64% and 28%, respectively. CONCLUSIONS: Ketamine demonstrated rapid antidepressant effects in an optimized study design, further supporting NMDA receptor modulation as a novel mechanism for accelerated improvement in severe and chronic forms of depression. More information on response durability and safety is required before implementation in clinical practice.