Efficacy and safety of transcranial magnetic stimulation on cognition in mild cognitive impairment, Alzheimer's disease, Alzheimer's disease-related dementias, and other cognitive disorders: a systematic review and meta-analysis.

OBJECTIVE: We aim to analyze the efficacy and safety of TMS on cognition in mild cognitive impairment (MCI), Alzheimer's disease (AD), AD-related dementias, and nondementia conditions with comorbid cognitive impairment. DESIGN: Systematic review, Meta-Analysis. SETTING: We searched MEDLINE, Embase, Cochrane database, APA PsycINFO, Web of Science, and Scopus from January 1, 2000, to February 9, 2023. PARTICIPANTS AND INTERVENTIONS: RCTs, open-label, and case series studies reporting cognitive outcomes following TMS intervention were included. MEASUREMENT: Cognitive and safety outcomes were measured. Cochrane Risk of Bias for RCTs and MINORS (Methodological Index for Non-Randomized Studies) criteria were used to evaluate study quality. This study was registered with PROSPERO (CRD42022326423). RESULTS: The systematic review included 143 studies (n = 5,800 participants) worldwide, encompassing 94 RCTs, 43 open-label prospective, 3 open-label retrospective, and 3 case series. The meta-analysis included 25 RCTs in MCI and AD. Collectively, these studies provide evidence of improved global and specific cognitive measures with TMS across diagnostic groups. Only 2 studies (among 143) reported 4 adverse events of seizures: 3 were deemed TMS unrelated and another resolved with coil repositioning. Meta-analysis showed large effect sizes on global cognition (Mini-Mental State Examination (SMD = 0.80 [0.26, 1.33], p = 0.003), Montreal Cognitive Assessment (SMD = 0.85 [0.26, 1.44], p = 0.005), Alzheimer's Disease Assessment Scale-Cognitive Subscale (SMD = -0.96 [-1.32, -0.60], p < 0.001)) in MCI and AD, although with significant heterogeneity. CONCLUSION: The reviewed studies provide favorable evidence of improved cognition with TMS across all groups with cognitive impairment. TMS was safe and well tolerated with infrequent serious adverse events.

Use of Gabapentin for Alcohol Withdrawal Syndrome in the Hospital Setting: A Randomized Open-Label Controlled Trial.

Background/objectives: Patients hospitalized with alcohol withdrawal syndrome (AWS) are typically treated with CIWA-directed benzodiazepines to prevent complications, such as seizures and delirium tremens. Gabapentin is an evidence-based alternative to benzodiazepines in the outpatient setting, but there is limited data for hospitalized patients with AWS. This study compared fixed-dose gabapentin to CIWA-directed benzodiazepines for AWS in the hospital setting. Methods: This open-label, randomized controlled trial enrolled 88 adults from February 1, 2017 to August 16, 2020 with a risk of complicated alcohol withdrawal as defined by the Prediction of Alcohol Withdrawal Severity Scale (PAWSS) ≥4. Patients were randomized within 16 h of admission to either fixed-dose gabapentin taper or continued CIWA-directed benzodiazepine administration. The primary outcome was the length of stay (LOS). Secondary outcomes included seizure, delirium tremens, ICU transfer, and patient-reported symptoms (alcohol cravings, anxiety, sleepiness). Results: LOS was shorter, but not statistically different in the gabapentin group compared to the benzodiazepine group. Because benzodiazepines were received in both gabapentin and benzodiazepine groups before randomization, the mean amount of benzodiazepines received in each group was also not statistically different, although the amount received by the gabapentin group was less than half of that received by the benzodiazepine group (4.3 vs. 10.6 mg, p = 0.146 by per protocol analysis). There were no statistical differences in secondary measures. Conclusions: Fixed-dose gabapentin taper showed similar outcomes compared to CIWA-directed benzodiazepines for the treatment of hospitalized patients with mild/moderate AWS, but the interpretation of the results is limited due to under-enrollment and the use of benzodiazepines in both groups pre-enrollment.Clinical trial registration: NCT03012815.

Simulated Electroconvulsive Therapy: A Novel Approach to a Control Group in Clinical Trials.

OBJECTIVES: Agitation is the most common behavioral symptom of Alzheimer disease (AD) affecting approximately 40% to 60% of the AD population, yet there are no Food and Drug Administration-approved therapies for the myriad of behavioral or psychological symptoms of dementia. There is growing evidence from naturalistic studies that electroconvulsive therapy (ECT) is a safe and effective treatment for agitation in AD patients who are refractory to pharmacotherapy and behavioral interventions. Despite the existing evidence, ECT remains underused because of stigma, lack of education, and concerns regarding adverse cognitive effects. Randomized controlled clinical trials of ECT are an opportunity to provide high-quality evidence of ECT as a safe and efficacious treatment for agitation in the AD population. We describe the methods for the Electroconvulsive Therapy in Alzheimer's Dementia study, which uses a novel, simulated ECT (S-ECT) control group to conduct a single-blind efficacy study of ECT for the treatment of agitation and aggression in individuals with moderate to severe AD. METHODS: We discuss the rationale, study design, methodology, ethical and practical challenges, and management strategies in using an S-ECT group as the comparator arm in this randomized controlled trial of ECT in AD-related treatment refractory agitation and aggression. CONCLUSIONS: Validation of the safety and efficacy of ECT in patients with advanced AD with refractory agitation and aggression is necessary. This can be accomplished through creative formulation of S-ECT groups that effectively maintain the blind while providing scientific integrity.

A feasibility study of virtual group therapy to improve quality of life of cancer caregivers.

BACKGROUND: Cancer caregiving can negatively impact the quality of life (QOL) of the caregiver. In-person interventions for improving coping skills have been shown to be effective in improving QOL for caregivers. OBJECTIVES: This pilot project explored the feasibility and acceptability of a virtual group therapy intervention to improve short-term cancer caregiver QOL. METHODS: Caregivers of cancer patients were enrolled in a structured multidisciplinary intervention of eight virtual group therapy sessions provided over four weeks between September 9, 2013 and November 17, 2014. Group sessions were led by trained facilitators and included components of physical therapy, occupational therapy, psychosocial education, cognitive-behavioral intervention, supportive discussion, spiritual reflection, and mindfulness therapy. Feasibility was based on acceptable number of recruited participants per session; acceptability was defined using attendance and 80% QOL completion rates. QOL domains and symptom burden were assessed using validated single items. RESULTS: The 20 cancer caregivers who enrolled were mostly older (80% were ≥ 65 years), female (76.5%), married to the patient (88.2%), Caucasian (100%), and highly educated (100%). 60% attended one to five sessions, 15% attended six to eight sessions, and 25% attended no sessions. Thirty percent completed pre- and post- intervention ratings of QOL items. SIGNIFICANCE OF RESULTS: Findings suggested that a virtual group therapy intervention is feasible for the cancer caregivers in this study. Although not statistically significant, the caregivers reported higher QOL and less symptom burden in multiple domains after participating in the virtual group therapy intervention.

Effects of a multidisciplinary quality of life intervention on sleep quality in patients with advanced cancer receiving radiation therapy.

OBJECTIVES: Sleep disturbances are prevalent in cancer patients, especially those with advanced disease. There are few published intervention studies that address sleep issues in advanced cancer patients during the course of treatment. This study assesses the impact of a multidisciplinary quality of life (QOL) intervention on subjective sleep difficulties in patients with advanced cancer. METHOD: This randomized trial investigated the comparative effects of a multidisciplinary QOL intervention (n = 54) vs. standard care (n = 63) on sleep quality in patients with advanced cancer receiving radiation therapy as a secondary endpoint. The intervention group attended six intervention sessions, while the standard care group received informational material only. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS), administered at baseline and weeks 4 (post-intervention), 27, and 52. RESULTS: The intervention group had a statistically significant improvement in the PSQI total score and two components of sleep quality and daytime dysfunction than the control group at week 4. At week 27, although both groups showed improvements in sleep measures from baseline, there were no statistically significant differences between groups in any of the PSQI total and component scores, or ESS. At week 52, the intervention group used less sleep medication than control patients compared to baseline (p = 0.04) and had a lower ESS score (7.6 vs. 9.3, p = 0.03). SIGNIFICANCE OF RESULTS: A multidisciplinary intervention to improve QOL can also improve sleep quality of advanced cancer patients undergoing radiation therapy. Those patients who completed the intervention also reported the use of less sleep medication.

Effectiveness of Electroconvulsive Therapy in Patients With Major Depressive Disorder and Comorbid Borderline Personality Disorder.

OBJECTIVE: Previous research suggests that electroconvulsive therapy (ECT)-the criterion standard for the treatment of severe depression-is not as effective when the patient has comorbid borderline personality disorder (BPD). The ECT outcomes of patients with and without BPD were compared in a retrospective chart review to test this claim. METHODS: We enrolled 137 patients with a diagnosis of major depressive disorder who completed the McLean Screening Instrument for Borderline Personality Disorder. Twenty-nine patients had positive screening scores for BPD. The difference in Patient Health Questionnaire (PHQ-9) scores before and after ECT was compared between patients with and without BPD. Follow-up PHQ-9 scores determined after treatment were collected and analyzed. RESULTS: Electroconvulsive therapy equally improved symptoms of depression as measured by PHQ-9 score in both patients who screened positive and patients who screened negative for BPD. No difference in the increase in PHQ-9 scores between these 2 groups was noted 1 month after treatment (P = 0.19). CONCLUSIONS: These data showed that a positive BPD screen does not necessarily predict a poorer response to ECT, nor does it predict greater symptom recurrence after ECT. This does not suggest that ECT is necessarily an appropriate treatment for major depressive disorder in patients with a comorbid BPD, given the limitations of screening instruments.

Cancer caregiver quality of life: need for targeted intervention.

OBJECTIVES: Caregiving can negatively impact well-being. Cancer caregivers face unique challenges given the intense nature of cancer and treatment, which increases their risk for burden, poor quality of life (QOL), and burnout. Studies to reduce caregiver burden demonstrate QOL improvement and distress reduction in the short term. However, few studies exist to address long-term benefits. We assessed changes in various QOL domains after participation in a QOL intervention for caregivers of patients having newly diagnosed advanced cancer. METHODS: Our institutional review board-approved study randomized patient-caregiver dyads to either usual care or an in-person group intervention composed of six 90-min sessions of structured multidisciplinary QOL components delivered over 4 weeks, with 10 follow-up phone calls within 20 weeks. Caregivers attended four of the six sessions attended by patients. Sessions included physical therapy, coping and communication strategies, mental health education, spirituality, and social needs. Caregiver QOL (Caregiver Quality of Life Index-Cancer Scale [CQOLC] and Linear Analogue Self-Assessment [LASA]) and mood (Profile of Mood States-Brief [POMS-B]) were measured at baseline and 4, 27, and 52 weeks. Wilcoxon tests and effect sizes were used to compare the caregiver groups. RESULTS: Of the 131 caregivers (65 intervention and 66 usual care), 116 completed the study. Caregivers post-intervention (at 4 weeks) had improved scores on LASA Spiritual Well-being; POMS-B total score, Vigor/Activity, and Fatigue/Inertia; and CQOLC Adaptation. At long term (at 27 weeks), caregivers retained improvement in POMS-B Fatigue/Inertia and gained improvements in CQOLC Disruptiveness and Financial Concerns. CONCLUSIONS: Caregivers who received the intervention had higher QOL ratings for specific QOL domains but not for overall QOL. Although a comprehensive intervention was helpful, more specific, targeted interventions tailored for individual needs are recommended. Copyright © 2015 John Wiley & Sons, Ltd.

Effect of Age on Psychiatric Rehospitalization Rates After Electroconvulsive Therapy for Patients With Depression.

OBJECTIVES: The aims of this naturalistic study are to examine psychiatric rehospitalization rates in geriatric compared to nongeriatric patients who receive electroconvulsive therapy (ECT) and to characterize the sustained effectiveness of ECT for treatment of depression. METHODS: Retrospective review of electronic medical records at a tertiary care center for patients with major depressive disorder who received an acute course of ECT at an index psychiatric hospitalization over a 5-year period. Data for subsequent psychiatric and primary care encounters were ascertained by chart review. Outcomes of interest included between-group differences in rates of psychiatric rehospitalization, time to rehospitalization, rates of other types of clinical follow-up care, and effect of demographic variables on clinical outcome. RESULTS: Of 482 total patients, there were 210 (44%) geriatric patients (≥65 years). These patients experienced lower overall rates of psychiatric rehospitalization after ECT (6.2% vs 22%; P < 0.0001) compared to the nongeriatric group. Cox proportional hazard models indicated that older age, assessed both as a dichotomous and continuous variable, was associated with lower risk of rehospitalization. The majority (76.9%) of detected rehospitalizations among geriatric patients occurred within 6 months. In comparison, rates of outpatient primary care and psychiatric follow-up after ECT did not differ as a function of age. CONCLUSIONS: Our findings suggest that geriatric patients with major depression receive greater long-term benefit from an acute course of ECT than do nongeriatric patients. Much more research is needed on this topic to rigorously evaluate the long-term efficacy of ECT in geriatric populations.

An Open-Label, Pilot Study of Daily Right Unilateral Ultrabrief Pulse Electroconvulsive Therapy.

Right unilateral ultrabrief (RUL-UB) pulse width electroconvulsive therapy (ECT) has attracted much research attention recently due to its smaller effect on memory than is associated with other forms of ECT, such as bitemporal placement or unilateral standard pulse width. However, RUL-UB has demonstrated slower antidepressant efficacy in comparison to the other techniques. One method to enhance the speed of response to RUL-UB ECT is administration of 5 times a week (termed "daily") treatments as opposed to the more standard twice or thrice weekly schedule. In this open label study, we treated 20 depressed patients with daily RUL-UB treatments for up to 2 weeks (ie, 10 treatments) using standardized assessments of depression and retrograde amnesia. Response and remission rates were commensurate with those reported in other recent studies using this technique with twice or thrice weekly treatment frequencies, and there was no clinically significant effect on retrograde memory function. We conclude that daily administration of RUL-UB ECT may shorten the duration of the course of ECT treatments without compromising cognition. A randomized trial comparing this technique to a thrice weekly schedule of RUL-UB treatments is indicated.

Association between history of psychosis and cardiovascular disease in bipolar disorder.

OBJECTIVES: To determine whether clinical features of bipolar disorder, such as history of psychosis, and cardiovascular disease (CVD) risk factors contribute to a higher risk of CVD among patients with bipolar disorder. METHODS: This cross-sectional study included a sample of 988 patients with bipolar I or bipolar II disorder or schizoaffective bipolar type confirmed by the Structured Clinical Interview for DSM-IV-TR disorders (SCID). Medical comorbidity burden was quantified utilizing the Cumulative Illness Severity Rating Scale (CIRS). This 13-item organ-based scale includes cardiac disease severity quantification. Confirmed by medical record review, patients who scored 1 (current mild or past significant problem) or higher in the cardiac item were compared by logistic regression to patients who scored 0 (no impairment), adjusting for CVD risk factors that were selected using a backwards stepwise approach or were obtained from the literature. RESULTS: In a multivariate model, age [odds ratio (OR) = 3.03, 95% confidence interval (CI): 1.66-5.54, p < 0.0001], hypertension (OR = 2.43, 95% CI: 1.69-3.55, p < 0.0001), and history of psychosis (OR = 1.48, 95% CI: 1.03-2.13, p = 0.03) were associated with CVD. When CVD risk factors from the literature were added to the analysis, age (OR = 3.19, 95% CI: 1.67-6.10, p = 0.0005) and hypertension (OR = 2.46, 95% CI: 1.61-3.76, p < 0.01) remained significant, with psychosis being at the trend level (OR = 1.43, 95% CI: 0.96-2.13, p = 0.08). CONCLUSIONS: The phenotype of psychotic bipolar disorder may reflect higher illness severity with associated cardiac comorbidity. Further studies are encouraged to clarify the effect of the disease burden (i.e., depression), lifestyle, and treatment interventions (i.e., atypical antipsychotics) on this risk association.

Respecting the spiritual side of advanced cancer care: a systematic review.

Spirituality is among the resources that many turn to as they deal with a diagnosis of advanced cancer. Researchers have made much progress in exploring and understanding spirituality's complex and multifaceted role in the midst of metastatic disease. As a result, spirituality is seen as an important aspect of a holistic and respectful approach to clinical care for patients and their loved ones. In this article, we provide a systematic review of the literature related to the interface between spirituality and metastatic cancer. We included articles published from January 2013 to June 2014. Twenty-two articles were reviewed, consisting of clinical intervention trials, association studies, surveys, qualitative studies, and review articles. The articles discussed efforts to improve patients' spiritual well-being, with relevant measurement scales; the associations of spirituality and end of life treatment practices; and efforts to better understand and meet the spiritual needs of patients and caregivers.

Cancer Caregiver: Perceived Benefits of Technology.

BACKGROUND: The burden associated with caregiving has been well documented. Caregivers have multiple responsibilities, and technology may be accessible as a potential burden-alleviating resource. MATERIALS AND METHODS: We surveyed cancer caregivers regarding current technology use and willingness to use technology for easing burden or distress. Because age has been associated with technology use, responses were compared between geriatric (≥65 years old) and nongeriatric (18-64 years old) caregivers. RESULTS: We had 112 respondents. Based on nonmissing responses, 66% (n=71) were women, 95% (n=106) were white, and 84% (n=91) had post-high school education. Almost all caregivers reported having Internet (105 [94%]) and e-mail (102 [91%]) access. Nongeriatric caregivers indicated more willingness to access Internet-based tools that help caregivers (54 [93%] versus 41 [76%]; p=0.04) and were more frequent users of social media (37 [64%] versus 16 [30%]; p=0.01), smartphones (33 [57%] versus 16 [30%]; p=0.01), and other mobile wireless devices (42 [72%] versus 19 [35%]; p<0.001) than geriatric caregivers. They also more frequently expected technologies to improve their own quality of life (p=0.009), increase their feelings of being effective as a caregiver (p=0.02), and save time (p=0.003). Regardless of age, a majority of caregivers (67 [62%]) endorsed the potential benefit of caregiving technologies in preventing burnout. CONCLUSIONS: Most caregivers have high access to and use of technology. Geriatric and nongeriatric caregivers were receptive to technology-based tools to help with their caregiving roles. Although nongeriatric caregivers expected to derive more benefit from such tools, both groups believed that caregiving technologies could reduce burden.

The importance of code status discussions in the psychiatric hospital: results of a single site survey of psychiatrists.

OBJECTIVES: Documentation of code status is a requirement with hospital admission, yet this discussion may present unique challenges with psychiatric inpatients. Currently, no standards exist on conducting these discussions with psychiatric inpatients. The authors surveyed psychiatry trainees and faculty regarding their perceptions and practice to gain further insight into the types of approaches used. METHODS: The authors conducted an IRB-approved, Web-based survey of psychiatry faculty and trainees using a 25-item questionnaire of demographics and opinions about code status among psychiatric inpatients. RESULTS: The response rate was 36.1 % (n = 30; 15 faculty and 15 trainees). Respondents felt that it was important to discuss code status with each admission. Faculty placed a higher emphasis on assessing patients with a recent suicide attempt (p = 0.024). CONCLUSION: Psychiatric faculty and trainees endorsed the importance of assessing code status with each admission. The authors suggest that educational programs are needed on strategies to conduct code status discussions properly and effectively in psychiatric populations.

Identification of non-regulated aromatic amines of toxicological concern which can be cleaved from azo dyes used in clothing textiles.

Azo dyes in textiles may release aromatic amines after enzymatic cleavage by skin bacteria or after dermal absorption and metabolism in the human body. From the 896 azo dyes with known chemical structure in the available textile dyes database, 426 azo dyes (48%) can generate one or more of the 22 regulated aromatic amines in the European Union in Annex XVII of REACH. Another 470 azo dyes (52%) can be cleaved into exclusively non-regulated aromatic amines. In this study, a search for publicly available toxicity data on non-regulated aromatic amines was performed. For a considerable percentage of non-regulated aromatic amines, the toxicity database was found to be insufficient or non-existent. 62 non-regulated aromatic amines with available toxicity data were prioritized by expert judgment with objective criteria according to their potential for carcinogenicity, genotoxicity, and/or skin sensitization. To investigate the occurrence of azo dye cleavage products, 153 random samples of clothing textiles were taken from Swiss retail outlets and analyzed for 22 high priority non-regulated aromatic amines of toxicological concern. Eight of these 22 non-regulated aromatic amines of concern could be detected in 17% of the textile samples. In 9% of the samples, one or more of the aromatic amines of concern could be detected in concentrations >30 mg/kg, in 8% of the samples between 5 and 30 mg/kg. The highest measured concentration was 622 mg/kg textile. There is an obvious need to assess consumer health risks for these non-regulated aromatic amines and to fill this gap in the regulation of clothing textiles.

Treatment-resistant depression patients with baseline suicidal ideation required more treatments to achieve therapeutic response with ketamine/esketamine.

BACKGROUND: There is an urgent need to identify interventions to reduce suicidality. We investigated the antisuicidal effects of intravenous (IV) ketamine and intranasal (IN) esketamine among patients with treatment-resistant depression (TRD) in a historical cohort study. METHODS: The Quick Inventory of Depressive Symptomatology self-report (QIDS-SR) question 12 was used to measure suicidal ideation (SI). Cox proportional hazards models were used to evaluate associations between the number of treatments to response and baseline SI (yes, Q12 > 0 versus no, Q12 = 0), adjusting for covariates and modified baseline QIDS-SR score. We evaluated associations between the number of treatments to a 50 % reduction in SI score between IV and IN treatment. RESULTS: Fifty-two adults (62.5 % female, median age 49.1 years) received IV ketamine (71 %, n = 37) or IN esketamine (29 %, n = 15). Eighty-one percent of patients reported SI at baseline. Among those with baseline SI, 60 % had improved SI scores while 38 % did not change, and among those with no SI, 80 % did not change. After adjusting for covariates, the hazard ratios (HR) of response were significantly lower among those with baseline SI (HR = 0.36, 95 % CI, 0.14-0.92, p = 0.03). The number of treatments to achieve a 50 % reduction in SI score did not depend on group (IN esketamine vs. IV ketamine HR = 0.74 [95 % CI, 0.27-2.05]; p = 0.57). LIMITATIONS: Small sample size and lack of a placebo group. CONCLUSIONS: This study suggests that patients with baseline suicidal ideation require more treatments to achieve a response with ketamine or esketamine. The antisuicidal response seemed similar between IV ketamine and IN esketamine.