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This article is a clinical guide which discusses the “state-of-the-art” usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (more than 70 international expert endorsers), based on 6 decades of experience, for the recommendations herein exposited. They are based on empirical evidence and expert opinion—this guide is presented as a new specialist-consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to electroconvulsive therapy—while taking into account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some tricyclic antidepressants. It also illustrates the straightforward “bridging” methods that may be used to transition simply and safely from other antidepressants to MAOIs.
Disruptive behavior disorders (DBD) are heterogeneous at the clinical and the biological level. Therefore, the aims were to dissect the heterogeneous neurodevelopmental deviations of the affective brain circuitry and provide an integration of these differences across modalities.
We combined two novel approaches. First, normative modeling to map deviations from the typical age-related pattern at the level of the individual of (i) activity during emotion matching and (ii) of anatomical images derived from DBD cases (n = 77) and controls (n = 52) aged 8–18 years from the EU-funded Aggressotype and MATRICS consortia. Second, linked independent component analysis to integrate subject-specific deviations from both modalities.
While cases exhibited on average a higher activity than would be expected for their age during face processing in regions such as the amygdala when compared to controls these positive deviations were widespread at the individual level. A multimodal integration of all functional and anatomical deviations explained 23% of the variance in the clinical DBD phenotype. Most notably, the top marker, encompassing the default mode network (DMN) and subcortical regions such as the amygdala and the striatum, was related to aggression across the whole sample.
Overall increased age-related deviations in the amygdala in DBD suggest a maturational delay, which has to be further validated in future studies. Further, the integration of individual deviation patterns from multiple imaging modalities allowed to dissect some of the heterogeneity of DBD and identified the DMN, the striatum and the amygdala as neural signatures that were associated with aggression.
Clinically significant weight gain (CSWG) is associated with increased morbidity and mortality. This study describes CSWG and comorbidities observed in patients with bipolar I disorder (BD-I) and schizophrenia (SZ) after initiating select second-generation antipsychotics (SGAs).
Percent change in weight, CSWG (=7% weight increase), and incident comorbidities within 12 months of treatment were assessed among patients initiating oral SGAs of moderate-to-high weight gain risk using medical records/claims (OM1 Real-World Data Cloud; January 2013-February 2020). Oral SGAs included clozapine (SZ), iloperidone (SZ), paliperidone (SZ), olanzapine, olanzapine/fluoxetine (BD-I), quetiapine, and risperidone. Outcomes were stratified by baseline body mass index and reported descriptively.
Among patients with BD-I (N = 9142) and SZ (N = 8174), approximately three-quarters were overweight/obese at baseline. During treatment (mean duration = 30 weeks), average percent weight increase was 3.7% (BD-I) and 3.3% (SZ). Average percent weight increase was highest for underweight/normal weight patients (BD-I = 5.5%; SZ = 4.8%), followed by overweight (BD-I = 3.8%; SZ = 3.4%) and obese patients (BD-I = 2.7%; SZ = 2.3%). Within 3 months of treatment, 12% of all patients experienced CSWG. A total of 11.3% (BD-I) and 14.7% (SZ) of patients developed coronary artery disease, hypertension, dyslipidemia, or type 2 diabetes within 12 months of treatment; development of comorbidities was highest among overweight/obese patients and those with CSWG.
Patients who were underweight/normal weight at baseline had the greatest percent change in weight during treatment. Increased comorbidities were observed within 12 months of treatment, specifically among overweight/obese patients and those with CSWG. The magnitude of weight gain and development of comorbidities were similar for patients with BD-I and SZ.
This study evaluated: (1) apolipoprotein E (APOE) ϵ4 prevalence among Black, Latino, and White older adults, (2) associations of APOE ϵ4 status with baseline level and change over time of cognitive outcomes across groups, and (3) combined impact of APOE ϵ4 prevalence and magnitude of effect on cognitive decline within each racial/ethnic group.
Participants included 297 White, 138 Latino, and 149 Black individuals from the longitudinal UC Davis Diversity Cohort who had APOE genotyping and ≥2 cognitive assessments. Magnitude of associations of ϵ4 with cognitive baseline and change across racial/ethnic groups was tested with multilevel parallel process longitudinal analyses and multiple group models.
ϵ4 prevalence in Black (46%) and White participants (46%) was almost double that of Latino participants (24%). ϵ4 was associated with poorer baseline episodic memory only in White participants (p = .001), but had a moderately strong association with episodic memory change across all racial/ethnic groups (Blacks= −.061 SD/year, Latinos = −.055,Whites= −.055). ϵ4 association with semantic memory change was strongest in White participants (−.071), intermediate in Latino participants (−.041), and weakest in Black participants (−.022).
Calculated cognitive trajectories across racial/ethnic groups were influenced in an additive manner by ϵ4 prevalence and strength of association with cognitive decline within the group. Group differences in ϵ4 prevalences and associations of ϵ4 with cognition may suggest different pathways from APOE to cognitive decline, and, AD possibly having less salient impact on cognitive decline in non-White participants. Differential effects of APOE on episodic memory and non-memory cognition have important implications for understanding how APOE influences late life cognitive decline.
From 2014 to 2020, we compiled radiocarbon ages from the lower 48 states, creating a database of more than 100,000 archaeological, geological, and paleontological ages that will be freely available to researchers through the Canadian Archaeological Radiocarbon Database. Here, we discuss the process used to compile ages, general characteristics of the database, and lessons learned from this exercise in “big data” compilation.
We aimed to identify unmet treatment needs for improving social and occupational functioning in early schizophrenia using a data-driven causal discovery analysis.
Demographic, clinical, and psychosocial measures were obtained for 276 participants from the Recovery After an Initial Schizophrenia Episode Early Treatment Program (RAISE-ETP) trial at baseline and 6-months, along with measures of social and occupational functioning from the Quality of Life Scale. The Greedy Fast Causal Inference algorithm was used to learn a partial ancestral graph modeling causal relationships across baseline variables and 6-month functioning. Effect sizes were estimated using a structural equation model. Results were validated in an independent dataset (N = 187).
In the data-generated model, greater baseline socio-affective capacity was a cause of greater baseline motivation [Effect size (ES) = 0.77], and motivation was a cause of greater baseline social and occupational functioning (ES = 1.5 and 0.96, respectively), which in turn were causes of their own 6-month outcomes. Six-month motivation was also identified as a cause of occupational functioning (ES = 0.92). Cognitive impairment and duration of untreated psychosis were not direct causes of functioning at either timepoint. The graph for the validation dataset was less determinate, but otherwise supported the findings.
In our data-generated model, baseline socio-affective capacity and motivation are the most direct causes of occupational and social functioning 6 months after entering treatment in early schizophrenia. These findings indicate that socio-affective abilities and motivation are specific high-impact treatment needs that must be addressed in order to promote optimal social and occupational recovery.
One out of every twenty emergency department (ED) visits in the United States is due to a psychiatric issue. Providing a gateway between the community and the mental health system, psychiatry emergency clinicians are responsible for assessing and managing a wide array of clinical presentations and conditions. Among emergency mental health-related visits, substance-related disorders, mood disorders, anxiety disorders, psychosis, and suicide attempts are among the most prevalent presentations. Although urgent conditions are common, increasing numbers of patients who present to the emergency department seek treatment for routine or non-acute psychiatric symptoms. Some patients self-refer to the emergency department, while others may be referred by family, friends, outpatient treatment providers, public agencies, or representatives of the law enforcement system.
The Hawaiian archipelago was formerly home to one of the most species-rich land snail faunas (> 752 species), with levels of endemism > 99%. Many native Hawaiian land snail species are now extinct, and the remaining fauna is vulnerable. Unfortunately, lack of information on critical habitat requirements for Hawaiian land snails limits the development of effective conservation strategies. The purpose of this study was to examine the plant host preferences of native arboreal land snails in Puʻu Kukui Watershed, West Maui, Hawaiʻi, and compare these patterns to those from similar studies on the islands of Oʻahu and Hawaiʻi. Concordant with studies on other islands, we found that four species from three diverse families of snails in Puʻu Kukui Watershed had preferences for a few species of understorey plants. These were not the most abundant canopy or mid canopy species, indicating that forests without key understorey plants may not support the few remaining lineages of native snails. Preference for Broussaisia arguta among various island endemic snails across all studies indicates that this species is important for restoration to improve snail habitat. As studies examining host plant preferences are often incongruent with studies examining snail feeding, we suggest that we are in the infancy of defining what constitutes critical habitat for most Hawaiian arboreal snails. However, our results indicate that preserving diverse native plant assemblages, particularly understorey plant species, which facilitate key interactions, is critical to the goal of conserving the remaining threatened snail fauna.
Among patients with schizophrenia (SZ) and bipolar I disorder (BD-I) treated with second-generation antipsychotics (SGAs), clinically-significant weight gain (CSWG) and treatment interruptions (TIs) are challenges that may result in morbidity/mortality.
CSWG and TIs were assessed among patients who initiated oral SGAs of moderate-to-high weight gain risk (no exposure to index SGAs/first-generation antipsychotics for =12 months) using medical records/claims (OM1 Data Cloud; January 2013-February 2020). Outcomes included CSWG (=7% increase in baseline weight) and TIs (switches [to SGAs of low weight gain risk/long-acting injectables] or discontinuations [no SGAs for >30 days]). Descriptive analyses included proportions of patients with CSWG and TIs, and median time to these outcomes.
Approximately three-quarters of patients were overweight/obese at baseline (SZ: N=8,174; BD-I: N=9,142). Within 3 months of SGA initiation, 12% of all patients experienced CSWG. For patients on treatment with index SGAs for >6 months (SZ: 29%; BD-I: 27%), 28% (SZ) and 30% (BD-I) experienced CSWG during follow-up. Median time to CSWG was 14 weeks. CSWG results were numerically similar among patients with SZ and BD-I.
Over 96% of patients had TIs during follow-up (median time of 12 [SZ] and 13 [BD-I] weeks). Among patients with CSWG and subsequent TIs and weight measurements, 74% did not return to baseline weight after interrupting treatment; the remainder returned to baseline weight with median times of 38 (SZ) and 39 (BD-I) weeks. Results suggest that most patients with CSWG do not return to baseline weight after stopping treatment with oral SGAs of moderate-to-high weight gain risk.
Modern videography provides an ever-widening window into subsea echinoderm life with vast potential for new knowledge. Supported by video evidence throughout, this Element begins with time-lapse video made in 1983 on film, using an off-the-shelf camera, flash, and underwater housings. Although quality has now been significantly improved by digital imagery, films from over thirty years ago captured crinoid feeding behavior previously unknown and demonstrated a great potential to learn about many other aspects of their biology. This sequence is followed by several examples of recent digital videography from submersibles of deep-sea crinoids and remotely operated vehicles (ROVs) (stalked and unstalked), as well as close-up video of crinoids in aquaria. These recent studies enabled a new classification of crinoid arm postures, provided detailed views of food particle capture, and revealed a wide range of behaviors in taxa never before seen in life.
During the late nineteenth and early twentieth centuries, arsenic was used as an embalming agent in the United States. In 1996, Konefes and McGee brought the potential danger of arsenic poisoning during excavation to the attention of archaeologists. They developed methodology that was later refined by the present authors. This article discusses the history of arsenic as an embalming agent, explores socioeconomic and demographic factors that might suggest the presence of arsenic in certain burials, and presents methods for testing arsenic in archaeological contexts. We also discuss environmental impact mitigation considerations and review examples of arsenic testing in archaeological contexts.
Previous genetic association studies have failed to identify loci robustly associated with sepsis, and there have been no published genetic association studies or polygenic risk score analyses of patients with septic shock, despite evidence suggesting genetic factors may be involved. We systematically collected genotype and clinical outcome data in the context of a randomized controlled trial from patients with septic shock to enrich the presence of disease-associated genetic variants. We performed genomewide association studies of susceptibility and mortality in septic shock using 493 patients with septic shock and 2442 population controls, and polygenic risk score analysis to assess genetic overlap between septic shock risk/mortality with clinically relevant traits. One variant, rs9489328, located in AL589740.1 noncoding RNA, was significantly associated with septic shock (p = 1.05 × 10–10); however, it is likely a false-positive. We were unable to replicate variants previously reported to be associated (p < 1.00 × 10–6 in previous scans) with susceptibility to and mortality from sepsis. Polygenic risk scores for hematocrit and granulocyte count were negatively associated with 28-day mortality (p = 3.04 × 10–3; p = 2.29 × 10–3), and scores for C-reactive protein levels were positively associated with susceptibility to septic shock (p = 1.44 × 10–3). Results suggest that common variants of large effect do not influence septic shock susceptibility, mortality and resolution; however, genetic predispositions to clinically relevant traits are significantly associated with increased susceptibility and mortality in septic individuals.
Isolated aortic regurgitation and myocardial infarction are a rare congenital defect among neonatal patients. We present a case of a neonate with an unusual aortic valve morphology causing both regurgitation and obstruction of the left coronary artery ostium. Despite both non-invasive and invasive imaging modalities, accurate diagnosis of the valve morphology was only determined by direct visualisation at the time of surgical repair. To the knowledge of authors, this particular aortic valve morphology in neonatal population has not been previously reported in the literature.
In 2019, a 42-year-old African man who works as an Ebola virus disease (EVD) researcher traveled from the Democratic Republic of Congo (DRC), near an ongoing EVD epidemic, to Philadelphia and presented to the Hospital of the University of Pennsylvania Emergency Department with altered mental status, vomiting, diarrhea, and fever. He was classified as a “wet” person under investigation for EVD, and his arrival activated our hospital emergency management command center and bioresponse teams. He was found to be in septic shock with multisystem organ dysfunction, including circulatory dysfunction, encephalopathy, metabolic lactic acidosis, acute kidney injury, acute liver injury, and diffuse intravascular coagulation. Critical care was delivered within high-risk pathogen isolation in the ED and in our Special Treatment Unit until a diagnosis of severe cerebral malaria was confirmed and EVD was definitively excluded.
This report discusses our experience activating a longitudinal preparedness program designed for rare, resource-intensive events at hospitals physically remote from any active epidemic but serving a high-volume international air travel port-of-entry.