Ketamine versus ECT for Nonpsychotic Treatment-Resistant Major Depression.

BACKGROUND: Electroconvulsive therapy (ECT) and subanesthetic intravenous ketamine are both currently used for treatment-resistant major depression, but the comparative effectiveness of the two treatments remains uncertain. METHODS: We conducted an open-label, randomized, noninferiority trial involving patients referred to ECT clinics for treatment-resistant major depression. Patients with treatment-resistant major depression without psychosis were recruited and assigned in a 1:1 ratio to receive ketamine or ECT. During an initial 3-week treatment phase, patients received either ECT three times per week or ketamine (0.5 mg per kilogram of body weight over 40 minutes) twice per week. The primary outcome was a response to treatment (i.e., a decrease of ≥50% from baseline in the score on the 16-item Quick Inventory of Depressive Symptomatology-Self-Report; scores range from 0 to 27, with higher scores indicating greater depression). The noninferiority margin was -10 percentage points. Secondary outcomes included scores on memory tests and patient-reported quality of life. After the initial treatment phase, the patients who had a response were followed over a 6-month period. RESULTS: A total of 403 patients underwent randomization at five clinical sites; 200 patients were assigned to the ketamine group and 203 to the ECT group. After 38 patients had withdrawn before initiation of the assigned treatment, ketamine was administered to 195 patients and ECT to 170 patients. A total of 55.4% of the patients in the ketamine group and 41.2% of those in the ECT group had a response (difference, 14.2 percentage points; 95% confidence interval, 3.9 to 24.2; P<0.001 for the noninferiority of ketamine to ECT). ECT appeared to be associated with a decrease in memory recall after 3 weeks of treatment (mean [±SE] decrease in the T-score for delayed recall on the Hopkins Verbal Learning Test-Revised, -0.9±1.1 in the ketamine group vs. -9.7±1.2 in the ECT group; scores range from -300 to 200, with higher scores indicating better function) with gradual recovery during follow-up. Improvement in patient-reported quality-of-life was similar in the two trial groups. ECT was associated with musculoskeletal adverse effects, whereas ketamine was associated with dissociation. CONCLUSIONS: Ketamine was noninferior to ECT as therapy for treatment-resistant major depression without psychosis. (Funded by the Patient-Centered Outcomes Research Institute; ELEKT-D ClinicalTrials.gov number, NCT03113968.).

Quantitative diffusion imaging and genotype-by-sex interactions in a rat model of Alexander disease.

PURPOSE: The clinical diagnosis and classification of Alexander disease (AxD) relies in part on qualitative neuroimaging biomarkers; however, these biomarkers fail to distinguish and discriminate different subtypes of AxD, especially in the presence of overlap in clinical symptoms. To address this gap in knowledge, we applied neurite orientation dispersion and density imaging (NODDI) to an innovative CRISPR-Cas9 rat genetic model of AxD to gain quantitative insights into the neural substrates and brain microstructural changes seen in AxD and to potentially identify novel quantitative NODDI biomarkers of AxD. METHODS: Multi-shell DWI of age- and sex-matched AxD and wild-type Sprague Dawley rats (n = 6 per sex per genotype) was performed and DTI and NODDI measures calculated. A 3 × 2 × 2 analysis of variance model was used to determine the effect of genotype, biological sex, and laterality on quantitative measures of DTI and NODDI across regions of interest implicated in AxD. RESULTS: There is a significant effect of genotype in the amygdala, hippocampus, neocortex, and thalamus in measures of both DTI and NODDI brain microstructure. A genotype by biological sex interaction was identified in DTI and NODDI measures in the corpus callosum, hippocampus, and neocortex. CONCLUSION: We present the first application of NODDI to the study of AxD using a rat genetic model of AxD. Our analysis identifies alterations in NODDI and DTI measures to large white matter tracts and subcortical gray nuclei. We further identified genotype by sex interactions, suggesting a possible role for biological sex in the neuropathogenesis of AxD.

Preexisting Psychiatric Conditions as Risk Factors for Diagnosed Long COVID-19 Syndrome Within Aggregated Electronic Health Record Data.

OBJECTIVE: This study aimed to investigate the frequency of long COVID diagnosis among patients infected with severe acute respiratory syndrome coronavirus 2 with preexisting psychiatric conditions versus those without preexisting psychiatric conditions. METHODS: The TriNetX Analytics platform, an aggregated electronic health record research network containing the deidentified electronic health record data of more than 90 million patients, was queried for patients who were diagnosed with COVID-19 infection based on International Classifications of Disease, Tenth Revision codes. Patients were stratified based on their preexisting psychiatric conditions, and new diagnoses of long COVID were recorded and reported as the primary outcome. RESULTS: Among 1,180,948 patients previously diagnosed with COVID-19, 17,990 patients (1.52%) were diagnosed with long COVID based on the newly implemented International Classifications of Disease, Tenth Revision code "U09: post-COVID-19 condition." After propensity score matching, patients with any preexisting psychiatric diagnosis had a 1.52 (95% confidence interval [CI] = 1.47-1.58) times greater prevalence of diagnosed long COVID within 180 days of infection than patients without preexisting psychiatric diagnoses. Patients with diagnosed anxiety disorders (relative risk [RR] = 1.64; 95% CI = 1.57-1.71), mood disorders (RR = 1.65; 95% CI = 1.57-1.72), bipolar disorder (RR = 1.37; 95% CI = 1.21-1.54), major depressive disorder (RR = 1.69; 95% CI = 1.56-1.83), psychotic disorders (RR = 1.23; 95% CI = 1.06-1.44), and substance use disorders (RR = 1.28; 95% CI = 1.22-1.36) had higher risks for long COVID diagnoses when compared with patients without preexisting psychiatric illness at the time of diagnosis. CONCLUSIONS: Multiple preexisting psychiatric diagnoses are associated with an increased risk of being diagnosed with long COVID after COVID-19 infection.

Methamphetamine-associated catatonia: Case series and systematic review of the literature from 1943-2020.

BACKGROUND: Catatonia due to a general medical condition may result from a variety of causes, including substance intoxication and withdrawal. Stimulants are occasionally associated with catatonia, though there has been little investigation of methamphetamine's relationship to catatonia. Here we present 5 cases of catatonia associated with methamphetamine use and a systematic review of the associated literature from 1943 to 2020. METHODS: We performed a systematic review of the literature and present 5 cases of catatonia evaluated using the Bush-Francis Catatonia Rating Scale and KANNER catatonia rating scale. RESULTS: Methamphetamine use was associated with catatonia in a small number of cases in the literature. However, some of these reports included other possible etiologies. The patients in our case series met DSM-5 criteria for catatonia due to a general medical condition, with all reporting recent methamphetamine use and testing positive for amphetamines on urine drug screen. CONCLUSIONS: Given the ongoing rise in methamphetamine use in the United States, it is important that clinicians understand that methamphetamine use can be associated with catatonia. Patients with methamphetamine-associated catatonia may respond favorably to lorazepam and require shorter hospital stays than other catatonic patients. Lastly, methamphetamine-associated catatonia highlights how alteration in dopamine function and projections may be a critical neural mechanism underlying catatonia in general.

Clinical translational neuroimaging of the antioxidant effect of N-acetylcysteine on neural microstructure.

PURPOSE: Oxidative stress and downstream effectors have emerged as important pathological processes that drive psychiatric illness, suggesting that antioxidants may have a therapeutic role in psychiatric disease. However, no imaging biomarkers are currently available to track therapeutic response. The purpose of this study was to examine whether advanced DWI techniques are able to sensitively detect the potential therapeutic effects of the antioxidant N-acetylcysteine (NAC) in a Disc1 svΔ2 preclinical rat model of psychiatric illness. METHODS: Male and female Disc1 svΔ2 rats and age-matched, sex-matched Sprague-Dawley wild-type controls were treated with a saline vehicle or NAC before ex vivo MRI acquisition at P50. Imaging data were fit to DTI and neurite orientation dispersion and density imaging models and analyzed for region-specific changes in quantitative diffusion metrics. Brains were further processed for cellular quantification of microglial density and morphology. All experiments were repeated for Disc1 svΔ2 rats exposed to chronic early-life stress to test how gene-environment interactions might alter effectiveness of NAC therapy. RESULTS: The DTI and neurite orientation dispersion and density imaging analyses demonstrated amelioration of early-life, sex-specific neural microstructural deficits with concomitant differences in microglial morphology across multiple brain regions relevant to neuropsychiatric illness with NAC treatment, but only in male Disc1 svΔ2 rats. Addition of chronic early-life stress reduced the ability of NAC to restore microstructural deficits. CONCLUSION: These findings provide evidence for a treatment pathway targeting endogenous antioxidant capacity, and the clinical translational utility of neurite orientation dispersion and density imaging microstructural imaging to sensitively detect microstructural alterations resulting from antioxidant treatment.

The perceptions of cancer health-care practitioners in New Zealand and the USA toward psychedelic-assisted therapy with cancer patients: A cross-sectional survey.

OBJECTIVES: A resurgence of research investigating the administration of psychedelic compounds alongside psychotherapy suggests that this treatment is a promising intervention for anxiety, depression, and existential distress in people with cancer. However, psychedelic treatment that induces a mind-altering experience potentially poses barriers to vulnerable cancer patients, and health-care practitioners may have concerns about referring their patients to trials investigating this approach. The aim of the current study was to investigate the perceptions of cancer health-care practitioners based in New Zealand and the USA related to psychedelic-assisted therapy. METHODS: This study utilized a cross-sectional survey of cancer health-care practitioners in New Zealand and the USA via convenience sampling to identify their perceptions about the concept of conducting psychedelic-assisted therapy with cancer patients. RESULTS: Participants perceived that (1) psychedelic-assisted therapy has the potential to provide benefit for cancer patients, (2) research in this area across a variety of domains is important, (3) work should consider spiritual and indigenous perspectives of health, and (4) there was willingness to refer patients to trials in this area, especially patients with advanced disease who were no longer going through curative treatment. Participants in the USA had greater awareness of psychedelics than the New Zealand sample; however, New Zealand participants more strongly believed that spiritual/indigenous factors should be considered in psychedelic-assisted therapy. SIGNIFICANCE OF RESULTS: Cancer health-care practitioners in our sample considered research investigating the potential for psychedelic-assisted therapies to be important and may be more open to studies that start in palliative and end-of-life contexts.

Before Li Ion Batteries.

This Review covers a sequence of key discoveries and technical achievements that eventually led to the birth of the lithium-ion battery. In doing so, it not only sheds light on the history with the advantage of contemporary hindsight but also provides insight and inspiration to aid in the ongoing quest for better batteries of the future. A detailed retrospective on ingenious designs, accidental discoveries, intentional breakthroughs, and deceiving misconceptions is given: from the discovery of the element lithium to its electrochemical synthesis; from intercalation host material development to the concept of dual-intercalation electrodes; and from the misunderstanding of intercalation behavior into graphite to the comprehension of interphases. The onerous demands of bringing all critical components (anode, cathode, electrolyte, solid-electrolyte interphases), each of which possess unique chemistries, into a sophisticated electrochemical device reveal that the challenge of interfacing these originally incongruent components often outweighs the individual merits and limits in their own properties. These important lessons are likely to remain true for the more aggressive battery chemistries of future generations, ranging from a revisited Li-metal anode, to conversion-reaction type chemistries such as Li/sulfur, Li/oxygen, and metal fluorides, and to bivalent cation intercalations.

A Survey of American Psychiatrists Concerning Medication Prior Authorization Requirements.

This study examined opinions of American psychiatrists regarding prior authorization (PA) requirements for third-party payer coverage of medications and quantified perceived impact of these requirements on clinical practice. One thousand selected psychiatrist members of the American Psychiatric Association were invited to participate in a survey. Response rate was 33.1%. Respondents predominantly believed the obligation to obtain PA reduces job satisfaction and negatively impacts patient care. A total of 59.9% of respondents reported employing either diagnosis modification or falsification of previous medication trials at least occasionally in order to obtain PA. A total of 66.6% refrained at least occasionally from prescribing preferred medications due to PA requirement or expectation of one. On multivariate analysis, risk factors for refraining at higher frequency included seeing 300 or more patients in the previous 3 months, engaging more frequently in diagnosis modification, and reporting increased perception that obtaining PA reduces time for patient care.

Risk factors for readmission among a cohort of psychiatric inpatients in Lilongwe, Malawi.

Objectives: Inpatient psychiatric capacity is limited in Malawi and no published studies have assessed psychiatric readmissions there. Information about factors associated with readmission may help guide strategies to reduce readmission rates and keep patients stabilised in the community. Our goal was to determine factors associated with readmission among a cohort of psychiatric inpatients in Lilongwe, Malawi.Methods: We conducted a retrospective chart review of all patients admitted to an inpatient psychiatric unit in Lilongwe, Malawi from January 1 to December 31, 2011. We used logistic regression to test for associations between readmissions during the study period and patient variables.Results: 419 patients were hospitalised during the study period. Twenty-nine patients (6.9%) were readmitted at least once during the study period. Readmission was associated only with intentional medication non-adherence at home (aOR: 3.33, p = 0.02).Conclusions: Intentional medication non-adherence is a potentially modifiable behaviour associated with psychiatric readmission. Efforts to improve medication adherence among patients following hospital discharge may help decrease the risk of readmission.KEY POINTSThe prevalence of readmission among psychiatric inpatients in Lilongwe, Malawi was 6.9% during the 1-year study period.Readmission was associated with intentional medication non-adherence at home.Future research efforts in Malawi should focus on improving medication adherence among psychiatric patients in the community to help decrease rates of readmission.

Factors associated with long length of stay in an inpatient psychiatric unit in Lilongwe, Malawi.

PURPOSE: Studies of factors affecting length of stay during psychiatric hospitalization in sub-Saharan Africa are sparse. A better understanding of such factors may lead to interventions resulting in quicker patient stabilization and discharge, freeing up needed psychiatric beds and reducing health care system expenditures. Therefore, we sought to identify factors associated with long length of stay in Malawi. METHODS: We reviewed the charts of 417 patients hospitalized at Kamuzu Central Hospital's Bwaila Psychiatric Unit in Lilongwe, Malawi from January 1 to December 31, 2011. Multivariate logistic regression analysis was employed to test for associations between patient factors and long length of stay (defined as more than 28 days). RESULTS: Mean length of stay was 22.08 ± 27.70 days (range 0-243). 21.82% (91/417) of patients stayed longer than 28 days. Long length of stay was associated with living outside of Lilongwe district [aOR: 3.65 (1.66-8.01), p = 0.001] and treatment for antipsychotic extrapyramidal side effects (EPS) during hospitalization [aOR: 3.45 (1.32-9.03), p = 0.012]. Patients who had more interactions with medical providers for this episode of illness prior to presentation at the unit were less likely to have a long length of stay [aOR: 0.35 (0.16-0.76), p = 0.008]. CONCLUSIONS: Our findings demonstrate areas of possible intervention to reduce length of stay, including securing means for patient transport home, rapid identification and treatment of EPS, and reducing the risk of EPS by decreased use of high potency first-generation antipsychotics.

Rapid transition from methadone to buprenorphine using naltrexone-induced withdrawal: A case report.

Background: Patients taking methadone for opioid use disorder may desire transition to buprenorphine for a number of reasons. However, the current recommended approach for this transition generally takes weeks to months as an outpatient, causing considerable discomfort to the patient and a heightened risk of relapse during the transition period. Case: We describe the case of a patient on methadone maintenance who was rapidly transitioned to buprenorphine because of her desire to not return to her methadone clinic. In order to rapidly transition the patient from methadone to buprenorphine, naltrexone was administered to precipitate acute opioid withdrawal, which was followed soon after by buprenorphine induction. Discussion: Rapid transition from methadone maintenance to buprenorphine can be accomplished in inpatients by precipitating acute withdrawal with naltrexone, providing an effective alternative for patients who cannot tolerate the typical protracted methadone taper required prior to buprenorphine induction as an outpatient.

A Survey of American Psychiatrists' Attitudes Toward Classic Hallucinogens.

Recent years have seen renewed interest and research about the use of hallucinogens as possible agents in the treatment of psychiatric disorders. However, we are unaware of studies assessing the current attitudes of American psychiatrists regarding hallucinogens. Therefore, we e-mailed surveys to 1000 members of the American Psychiatric Association-250 resident-fellows and 750 attending psychiatrists. The response rate was 32.4%. Respondents tended to perceive hallucinogens as potentially hazardous and appropriately illegal for recreational purposes. However, a large minority expressed optimism about the potential use of hallucinogens for psychiatric treatment. Male and trainee respondents, as compared with female and attending respondents, reported less concern about the risks of hallucinogens and greater optimism about their therapeutic potential. Younger psychiatrists also seemed more optimistic. Optimism among trainees and younger psychiatrists may possibly reflect greater exposure to recent positive publications about hallucinogens and less awareness of more negative past reports.

Muscle adaptations following 21 consecutive days of strength test familiarization compared with traditional training.

INTRODUCTION: Large increases in 1-repetition maximum (1RM) strength have been demonstrated from repeated testing, but it is unknown whether these increases can be augmented by resistance training. METHODS: Five trained individuals performed a 1RM test and maximal voluntary isometric contraction (MVC) for unilateral elbow flexion exercise on 1 arm (testing arm), while the other arm performed a 1RM test and MVC, in addition to 3 sets of exercise (70% 1RM) (training arm), for 21 straight days. RESULTS: Although only the training arm had increased muscle thickness [mean 0.28 cm, 95% confidence interval (CI) 0.22-0.33 cm], 1RM strength increased similarly in the training (2.2 kg, 95% CI 0.9-3.4 kg; P = 0.008) and testing (1.9 kg, 95% CI 0.5-3.2 kg; P = 0.019) arms. CONCLUSION: Increases in 1RM strength from resistance training are related to the specificity of exercise and are likely driven by mechanisms other than muscle growth. Muscle Nerve 56: 307-314, 2017.

Delay in initiation of adjuvant trastuzumab therapy leads to decreased overall survival and relapse-free survival in patients with HER2-positive non-metastatic breast cancer.

Trastuzumab reduces the risk of relapse in women with HER2-positive non-metastatic breast cancer, but little information exists on the timing of trastuzumab initiation. The study investigated the impact of delaying the initiation of adjuvant trastuzumab therapy for >6 months after the breast cancer diagnosis on time to relapse, overall survival (OS), and relapse-free survival (RFS) among patients with non-metastatic breast cancer. Adult women with non-metastatic breast cancer who initiated trastuzumab adjuvant therapy without receiving any neoadjuvant therapy were selected from the US Department of Defense health claims database from 01/2003 to 12/2012. Two study cohorts were defined based on the time from breast cancer diagnosis to trastuzumab initiation: >6 months and ≤6 months. The impact of delaying trastuzumab initiation on time to relapse, OS, and RFS was estimated using Cox regression models adjusted for potential confounders. Of 2749 women in the study sample, 79.9 % initiated adjuvant trastuzumab within ≤6 months of diagnosis and 20.1 % initiated adjuvant trastuzumab >6 months after diagnosis. After adjusting for confounders, patients who initiated trastuzumab >6 months after the breast cancer diagnosis had a higher risk of relapse, death, or relapse/death than those who initiated trastuzumab within ≤6 months of diagnosis (hazard ratios [95 % CIs]: 1.51 [1.22-1.87], 1.54 [1.12-2.12], and 1.43 [1.16-1.75]; respectively). The results of this population-based study suggest that delays of >6 months in the initiation of trastuzumab among HER2-positive non-metastatic breast cancer patients are associated with a higher risk of relapse and shorter OS and RFS.

Influence of relative blood flow restriction pressure on muscle activation and muscle adaptation.

INTRODUCTION: The aim of this study was to investigate the acute and chronic skeletal muscle response to differing levels of blood flow restriction (BFR) pressure. METHODS: Fourteen participants completed elbow flexion exercise with pressures from 40% to 90% of arterial occlusion. Pre/post torque measurements and electromyographic (EMG) amplitude of each set were quantified for each condition. This was followed by a separate 8-week training study of the effect of high (90% arterial occlusion) and low (40% arterial occlusion) pressure on muscle size and function. RESULTS: For the acute study, decreases in torque were similar between pressures [-15.5 (5.9) Nm, P = 0.344]. For amplitude of the first 3 and last 3 reps there was a time effect. After training, increases in muscle size (10%), peak isotonic strength (18%), peak isokinetic torque (180°/s = 23%, 60°/s = 11%), and muscular endurance (62%) changed similarly between pressures. CONCLUSION: We suggest that higher relative pressures may not be necessary when exercising under BFR.

Assessment of potential adjuvanticity of Cry proteins.

Genetically modified (GM) crops have achieved success in the marketplace and their benefits extend beyond the overall increase in harvest yields to include lowered use of insecticides and decreased carbon dioxide emissions. The most widely grown GM crops contain gene/s for targeted insect protection, herbicide tolerance, or both. Plant expression of Bacillus thuringiensis (Bt) crystal (Cry) insecticidal proteins have been the primary way to impart insect resistance in GM crops. Although deemed safe by regulatory agencies globally, previous studies have been the basis for discussions around the potential immuno-adjuvant effects of Cry proteins. These studies had limitations in study design. The studies used animal models with extremely high doses of Cry proteins, which when given using the ig route were co-administered with an adjuvant. Although the presumption exists that Cry proteins may have immunostimulatory activity and therefore an adjuvanticity risk, the evidence shows that Cry proteins are expressed at very low levels in GM crops and are unlikely to function as adjuvants. This conclusion is based on critical review of the published literature on the effects of immunomodulation by Cry proteins, the history of safe use of Cry proteins in foods, safety of the Bt donor organisms, and pre-market weight-of-evidence-based safety assessments for GM crops.