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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.
Airway management is a controversial topic in modern Emergency Medical Services (EMS) systems. Among many concerns regarding endotracheal intubation (ETI), unrecognized esophageal intubation and observations of unfavorable neurologic outcomes in some studies raise the question of whether alternative airway techniques should be first-line in EMS airway management protocols. Supraglottic airway devices (SADs) are simpler to use, provide reliable oxygenation and ventilation, and may thus be an alternative first-line airway device for paramedics. In 2019, Alachua County Fire Rescue (ACFR; Alachua, Florida USA) introduced a novel protocol for advanced airway management emphasizing first-line use of a second-generation SAD (i-gel) for patients requiring medication-facilitated airway management (referred to as “rapid sequence airway” [RSA] protocol).
This was a one-year quality assurance review of care provided under the RSA protocol looking at compliance and first-pass success rate of first-line SAD use.
Records were obtained from the agency’s electronic medical record (EMR), searching for the use of the RSA protocol, advanced airway devices, or either ketamine or rocuronium. If available, hospital follow-up data regarding patient condition and emergency department (ED) airway exchange were obtained.
During the first year, 33 advanced airway attempts were made under the protocol by 23 paramedics. Overall, compliance with the airway device sequence as specified in the protocol was 72.7%. When ETI was non-compliantly used as first-line airway device, the first-pass success rate was 44.4% compared to 87.5% with adherence to first-line SAD use. All prehospital SADs were exchanged in the ED in a delayed fashion and almost exclusively per physician preference alone. In no case was the SAD exchanged for suspected dislodgement evidenced by lack of capnography.
First-line use of a SAD was associated with a high first-pass attempt success rate in a real-life cohort of prehospital advanced airway encounters. No SAD required emergent exchange upon hospital arrival.
OBJECTIVES/GOALS: We aim to determine whether non-neuronal, non-synaptic glutamate signaling mechanisms can be targeted to produce highly specific, narrow changes in brain function that would benefit CNS disorders. To do this, we investigated cognitive changes produced through manipulating the activity of the astrocytic glutamate release mechanism system xc-. METHODS/STUDY POPULATION: System xc- (Sxc) activity was eliminated by mutating the gene Slc7a11 through pronuclear injection of zinc-finger nucleases into Sprague Dawley rat embryos to create a line of rats lacking Sxc (MSxc rats). To confirm a lack of Sxc activity, we verified that tissue from MSxc rats had a complete lack of xCT, which is the regulatory subunit of Sxc that is encoded by Slc7a11. We also verified that astrocyte cultures generated from MSxc tissue lacked cystine-evoked glutamate release. Next, we measured development (body weight), CNS regulation of metabolism, and other indicators of generalized, non-specific brain function as well as behaviors that are reliant on executive function, such as cognitive flexibility, impulse control, decision-making, and response inhibition. RESULTS/ANTICIPATED RESULTS: Eliminating Sxc was not lethal and did not impair development or produce widespread changes in brain function as is commonly observed when deleting other glutamate mechanisms. MSxc rats did not differ from wildtype in growth rate, central regulation of metabolism as reflected by absolute or diurnal changes in core body temperature, locomotor activity in a familiar or novel environment, or simple forms of cognition such as novel object recognition, or operant responding (food and cocaine-reinforced). In contrast, behaviors that rely on executive function were impaired. MSxc rats displayed deficits in cocaine reinstatement and attentional set-shifting. We anticipate MSxc rats to also show impairments in decision-making in the rat gambling task and response inhibition in the stop-signal reaction time task. DISCUSSION/SIGNIFICANCE: Eliminating Sxc activity in rats produced deficits in behaviors reliant on executive function without impacting development or simple brain function. These results highlight the potential of targeting Sxc to enhance cognition without generating therapeutically limiting adverse effects resulting from non-specific changes in brain function.
The coronavirus disease 2019 (COVID-19) pandemic has significantly increased depression rates, particularly in emerging adults. The aim of this study was to examine longitudinal changes in depression risk before and during COVID-19 in a cohort of emerging adults in the U.S. and to determine whether prior drinking or sleep habits could predict the severity of depressive symptoms during the pandemic.
Participants were 525 emerging adults from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA), a five-site community sample including moderate-to-heavy drinkers. Poisson mixed-effect models evaluated changes in the Center for Epidemiological Studies Depression Scale (CES-D-10) from before to during COVID-19, also testing for sex and age interactions. Additional analyses examined whether alcohol use frequency or sleep duration measured in the last pre-COVID assessment predicted pandemic-related increase in depressive symptoms.
The prevalence of risk for clinical depression tripled due to a substantial and sustained increase in depressive symptoms during COVID-19 relative to pre-COVID years. Effects were strongest for younger women. Frequent alcohol use and short sleep duration during the closest pre-COVID visit predicted a greater increase in COVID-19 depressive symptoms.
The sharp increase in depression risk among emerging adults heralds a public health crisis with alarming implications for their social and emotional functioning as this generation matures. In addition to the heightened risk for younger women, the role of alcohol use and sleep behavior should be tracked through preventive care aiming to mitigate this looming mental health crisis.
Initial assessments of coronavirus disease 2019 (COVID-19) preparedness revealed resource shortages and variations in infection prevention policies across US hospitals. Our follow-up survey revealed improvement in resource availability, increase in testing capacity, and uniformity in infection prevention policies. Most importantly, the survey highlighted an increase in staffing shortages and use of travel nursing.
An early economic evaluation to inform the translation into clinical practice of a spectroscopic liquid biopsy for the detection of brain cancer. Two specific aims are (1) to update an existing economic model with results from a prospective study of diagnostic accuracy and (2) to explore the potential of brain tumor-type predictions to affect patient outcomes and healthcare costs.
A cost-effectiveness analysis from a UK NHS perspective of the use of spectroscopic liquid biopsy in primary and secondary care settings, as well as a cost–consequence analysis of the addition of tumor-type predictions was conducted. Decision tree models were constructed to represent simplified diagnostic pathways. Test diagnostic accuracy parameters were based on a prospective validation study. Four price points (GBP 50-200, EUR 57-228) for the test were considered.
In both settings, the use of liquid biopsy produced QALY gains. In primary care, at test costs below GBP 100 (EUR 114), testing was cost saving. At GBP 100 (EUR 114) per test, the ICER was GBP 13,279 (EUR 15,145), whereas at GBP 200 (EUR 228), the ICER was GBP 78,300 (EUR 89,301). In secondary care, the ICER ranged from GBP 11,360 (EUR 12,956) to GBP 43,870 (EUR 50,034) across the range of test costs.
The results demonstrate the potential for the technology to be cost-effective in both primary and secondary care settings. Additional studies of test use in routine primary care practice are needed to resolve the remaining issues of uncertainty—prevalence in this patient population and referral behavior.
Elective surgical patients routinely bathe with chlorhexidine gluconate (CHG) at home days prior to their procedures. However, the impact of home CHG bathing on surgical site CHG concentration is unclear. We examined 3 different methods of applying CHG and hypothesized that different application methods would impact resulting CHG skin concentration.
Smoking rates in people with depression and anxiety are twice as high as in the general population, even though people with depression and anxiety are motivated to stop smoking. Most healthcare professionals are aware that stopping smoking is one of the greatest changes that people can make to improve their health. However, smoking cessation can be a difficult topic to raise. Evidence suggests that smoking may cause some mental health problems, and that the tobacco withdrawal cycle partly contributes to worse mental health. By stopping smoking, a person's mental health may improve, and the size of this improvement might be equal to taking antidepressants. In this article we outline ways in which healthcare professionals can compassionately and respectfully raise the topic of smoking to encourage smoking cessation. We draw on evidence-based methods such as cognitive–behavioural therapy (CBT) and outline approaches that healthcare professionals can use to integrate these methods into routine care to help their patients stop smoking.
Impact craters are the dominant landform on Mercury and range from the largest basins to the smallest young craters. Peak-ring basins are especially prevalent on Mercury, although basins of all forms are far undersaturated, probably the result of the extensive volcanic emplacement of intercrater plains and younger smooth plains between about 4.1 and 3.5 Ga. This chapter describes the geology of the two largest well-preserved basins, Caloris and Rembrandt, and the three smaller Raditladi, Rachmaninoff, and Mozart basins. We describe analyses of crater size–frequency distributions and relate them to populations of asteroid impactors (Late Heavy Bombardment in early epochs and the near-Earth asteroid population observable today during most of Mercury’s history), to secondary cratering, and to exogenic and endogenic processes that degrade and erase craters. Secondary cratering is more important on Mercury than on other solar system bodies and shaped much of the surface on kilometer and smaller scales, compromising our ability to use craters for relative and absolute age-dating of smaller geological units. Failure to find “vulcanoids” and satellites of Mercury suggests that such bodies played a negligible role in cratering Mercury. We describe an absolute cratering chronology for Mercury’s geological evolution as well as its uncertainties.
Here we present the synthesis of porous platinum–palladium macrobeams templated from high aspect ratio Magnus’ salt needle derivatives. The combination of [PtCl4]2− and/or [PdCl4]2− with [Pt(NH3)4]2+ ions results in salt needles ranging from 15 to 300 µm in length. Electrochemical reduction of the salt templates results in porous macrobeams with a square cross-section. Porous side wall texture and elemental composition was controlled with initial platinum to palladium salt ratio. Macrobeam free-standing films exhibited a specific capacitance up to 11.73 F/g and a solvent accessible surface area of 26.6 m2/g. These salt-templated porous platinum–palladium macrobeams offer a promising material for fuel cell catalysis.
Gary P. Baker, Research Associate at the University of East Anglia, and a Researcher at the University of Groningen in the Netherlands.,
Craig L. Lambert, Lecturer in Maritime History at the University of Southampton.,
David Simpkin, Teacher of History at Birkenhead Sixth-Form College.,
J. J. N. Palmer
Given the contribution Andrew Ayton has made to the study of late medieval military history we hope he is not surprised by the production of a Festschrift in his honour. All the editors of this volume were supervised by Andrew for their doctoral studies, and all no doubt thrashed out the general outlines to their theses in one of the infamous ‘Ayton’ meetings that regularly ran into the late evening. Andrew's enthusiasm for his subject was infectious and it is to his credit that many of his former students have gone on to publish contributions on late medieval military and naval history. The papers featured in the present volume highlight the important international impact Andrew's work has had on his students and academic colleagues.
Andrew, a native of Dorset, is in his own words ‘a country dweller at heart’ but has spent much of his working life in the big city. He studied as an undergraduate at the University of Hull in the early 1980s, during which time he undertook several modules taught by Professor John Palmer. John's module on the Hundred Years’ War in particular seems to have kindled Andrew's interest in medieval military history and military communities; it certainly began a fruitful association between two like-minded scholars which was to span some three decades until John's retirement in 2002. Andrew often visited John's home to discuss their latest research and he will be pleased to know he is remembered with some affection by John's children.
After graduating, Andrew spent a brief spell in a ‘real’ job, before returning to Hull to study for his Ph.D. under John Palmer – ‘The Warhorse and Military Service under Edward III’ – and from 1985 to 1987 Andrew was employed, alongside Virginia Davis, on John's Domesday Project. This was a role for which Andrew was particularly well equipped. He had taken John Palmer's special subject on the Domesday Book as an undergraduate, which had provided him with the essential background plus the basic computing skills – in particular related to databases – needed for the research: rare qualifications in the mid-1980s. This period, of course, included the 900th anniversary of Domesday Book, which for Andrew and Virginia entailed a frenetic year, giving lectures and demonstrations around the UK while trying to keep to a research schedule and do some work on their own account.
Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
To describe the epidemiology of complex surgical site infection (SSI) following commonly performed surgical procedures in community hospitals and to characterize trends of SSI prevalence rates over time for MRSA and other common pathogens
We prospectively collected SSI data at 29 community hospitals in the southeastern United States from 2008 through 2012. We determined the overall prevalence rates of SSI for commonly performed procedures during this 5-year study period. For each year of the study, we then calculated prevalence rates of SSI stratified by causative organism. We created log-binomial regression models to analyze trends of SSI prevalence over time for all pathogens combined and specifically for MRSA.
A total of 3,988 complex SSIs occurred following 532,694 procedures (prevalence rate, 0.7 infections per 100 procedures). SSIs occurred most frequently after small bowel surgery, peripheral vascular bypass surgery, and colon surgery. Staphylococcus aureus was the most common pathogen. The prevalence rate of SSI decreased from 0.76 infections per 100 procedures in 2008 to 0.69 infections per 100 procedures in 2012 (prevalence rate ratio [PRR], 0.90; 95% confidence interval [CI], 0.82–1.00). A more substantial decrease in MRSA SSI (PRR, 0.69; 95% CI, 0.54–0.89) was largely responsible for this overall trend.
The prevalence of MRSA SSI decreased from 2008 to 2012 in our network of community hospitals. This decrease in MRSA SSI prevalence led to an overall decrease in SSI prevalence over the study period.
To determine the association (1) between shorter operative duration and surgical site infection (SSI) and (2) between surgeon median operative duration and SSI risk among first-time hip and knee arthroplasties.
Retrospective cohort study
A total of 43 community hospitals located in the southeastern United States.
Adults who developed SSIs according to National Healthcare Safety Network criteria within 365 days of first-time knee or hip arthroplasties performed between January 1, 2008 and December 31, 2012.
Log-binomial regression models estimated the association (1) between operative duration and SSI outcome and (2) between surgeon median operative duration and SSI outcome. Hip and knee arthroplasties were evaluated in separate models. Each model was adjusted for American Society of Anesthesiology score and patient age.
A total of 25,531 hip arthroplasties and 42,187 knee arthroplasties were included in the study. The risk of SSI in knee arthroplasties with an operative duration shorter than the 25th percentile was 0.40 times the risk of SSI in knee arthroplasties with an operative duration between the 25th and 75th percentile (risk ratio [RR], 0.40; 95% confidence interval [CI], 0.38–0.56; P<.01). Short operative duration did not demonstrate significant association with SSI for hip arthroplasties (RR, 1.04; 95% CI, 0.79–1.37; P=.36). Knee arthroplasty surgeons with shorter median operative durations had a lower risk of SSI than surgeons with typical median operative durations (RR, 0.52; 95% CI, 0.43–0.64; P<.01).
Short operative durations were not associated with a higher SSI risk for knee or hip arthroplasty procedures in our analysis.
Infect. Control Hosp. Epidemiol. 2015;36(12):1431–1436
A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.
Many species of marine sponges on tropical reefs host abundant and diverse symbiont communities capable of varied metabolic pathways. While such communities may confer a nutritional benefit to some hosts (termed High Microbial Abundance (HMA) sponges), other sympatric species host only sparse symbiont communities (termed Low Microbial Abundance (LMA) sponges) and obtain a majority of their C and N from local sources. Sponge communities are widespread across large latitudinal gradients, however, and recent evidence suggests that these symbioses may also extend beyond the tropics. We investigated the role that symbionts play in the ecology of sponges from the temperate, hard-bottom reefs of Gray's Reef National Marine Sanctuary by calculating the niche size (as standard ellipse area (SEAc)) and assessing the relative placement of five HMA and four LMA sponge species within bivariate (δ13C and δ15N) isotopic space. Although photosymbiont abundance was low across most of these species, sponges were widespread across isotopic niche space, implying that microbial metabolism confers an ecological benefit to temperate sponges by expanding host metabolic capability. To examine how these associations vary across a latitudinal gradient, we also compared the relative placement of temperate and tropical conspecifics within isotopic space. Surprisingly, shifts in sponge δ13C and δ15N values between these regions suggest a reduced reliance on symbiont-derived nutrients in temperate sponges compared with their tropical conspecifics. Despite this, symbiotic sponges in temperate systems likely have a competitive advantage, allowing them to grow and compete for space within these habitats.
In North America, terrestrial records of biodiversity and climate change that span Marine Oxygen Isotope Stage (MIS) 5 are rare. Where found, they provide insight into how the coupling of the ocean–atmosphere system is manifested in biotic and environmental records and how the biosphere responds to climate change. In 2010–2011, construction at Ziegler Reservoir near Snowmass Village, Colorado (USA) revealed a nearly continuous, lacustrine/wetland sedimentary sequence that preserved evidence of past plant communities between ~140 and 55 ka, including all of MIS 5. At an elevation of 2705 m, the Ziegler Reservoir fossil site also contained thousands of well-preserved bones of late Pleistocene megafauna, including mastodons, mammoths, ground sloths, horses, camels, deer, bison, black bear, coyotes, and bighorn sheep. In addition, the site contained more than 26,000 bones from at least 30 species of small animals including salamanders, otters, muskrats, minks, rabbits, beavers, frogs, lizards, snakes, fish, and birds. The combination of macro- and micro-vertebrates, invertebrates, terrestrial and aquatic plant macrofossils, a detailed pollen record, and a robust, directly dated stratigraphic framework shows that high-elevation ecosystems in the Rocky Mountains of Colorado are climatically sensitive and varied dramatically throughout MIS 5.