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Sex-dependent differences in vulnerability to early risk factors for posttraumatic stress disorder: results from the AURORA study
- Stephanie Haering, Antonia V. Seligowski, Sarah D. Linnstaedt, Vasiliki Michopoulos, Stacey L. House, Francesca L. Beaudoin, Xinming An, Thomas C. Neylan, Gari D. Clifford, Laura T. Germine, Scott L. Rauch, John P. Haran, Alan B. Storrow, Christopher Lewandowski, Paul I. Musey, Jr., Phyllis L. Hendry, Sophia Sheikh, Christopher W. Jones, Brittany E. Punches, Robert A. Swor, Nina T. Gentile, Lauren A. Hudak, Jose L. Pascual, Mark J. Seamon, Claire Pearson, David A. Peak, Roland C. Merchant, Robert M. Domeier, Niels K. Rathlev, Brian J. O'Neil, Leon D. Sanchez, Steven E. Bruce, Steven E. Harte, Samuel A. McLean, Ronald C. Kessler, Karestan C. Koenen, Jennifer S. Stevens, Abigail Powers
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- Psychological Medicine , First View
- Published online by Cambridge University Press:
- 22 May 2024, pp. 1-11
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Background
Knowledge of sex differences in risk factors for posttraumatic stress disorder (PTSD) can contribute to the development of refined preventive interventions. Therefore, the aim of this study was to examine if women and men differ in their vulnerability to risk factors for PTSD.
MethodsAs part of the longitudinal AURORA study, 2924 patients seeking emergency department (ED) treatment in the acute aftermath of trauma provided self-report assessments of pre- peri- and post-traumatic risk factors, as well as 3-month PTSD severity. We systematically examined sex-dependent effects of 16 risk factors that have previously been hypothesized to show different associations with PTSD severity in women and men.
ResultsWomen reported higher PTSD severity at 3-months post-trauma. Z-score comparisons indicated that for five of the 16 examined risk factors the association with 3-month PTSD severity was stronger in men than in women. In multivariable models, interaction effects with sex were observed for pre-traumatic anxiety symptoms, and acute dissociative symptoms; both showed stronger associations with PTSD in men than in women. Subgroup analyses suggested trauma type-conditional effects.
ConclusionsOur findings indicate mechanisms to which men might be particularly vulnerable, demonstrating that known PTSD risk factors might behave differently in women and men. Analyses did not identify any risk factors to which women were more vulnerable than men, pointing toward further mechanisms to explain women's higher PTSD risk. Our study illustrates the need for a more systematic examination of sex differences in contributors to PTSD severity after trauma, which may inform refined preventive interventions.
The mediating role of health behaviors in the association between depression, anxiety and cancer incidence: an individual participant data meta-analysis
- Kuan-Yu Pan, Lonneke van Tuijl, Maartje Basten, Judith J. M. Rijnhart, Alexander de Graeff, Joost Dekker, Mirjam I. Geerlings, Adriaan Hoogendoorn, Adelita V. Ranchor, Roel Vermeulen, Lützen Portengen, Adri C. Voogd, Jessica Abell, Philip Awadalla, Aartjan T. F. Beekman, Ottar Bjerkeset, Andy Boyd, Yunsong Cui, Philipp Frank, Henrike Galenkamp, Bert Garssen, Sean Hellingman, Monika Hollander, Martijn Huisman, Anke Huss, Melanie R. Keats, Almar A. L. Kok, Steinar Krokstad, Flora E. van Leeuwen, Annemarie I. Luik, Nolwenn Noisel, Yves Payette, Brenda W. J. H. Penninx, Susan Picavet, Ina Rissanen, Annelieke M. Roest, Judith G. M. Rosmalen, Rikje Ruiter, Robert A. Schoevers, David Soave, Mandy Spaan, Andrew Steptoe, Karien Stronks, Erik R. Sund, Ellen Sweeney, Alison Teyhan, Emma L. Twait, Kimberly D. van der Willik, Femke Lamers
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- Psychological Medicine , First View
- Published online by Cambridge University Press:
- 29 April 2024, pp. 1-14
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Background
Although behavioral mechanisms in the association among depression, anxiety, and cancer are plausible, few studies have empirically studied mediation by health behaviors. We aimed to examine the mediating role of several health behaviors in the associations among depression, anxiety, and the incidence of various cancer types (overall, breast, prostate, lung, colorectal, smoking-related, and alcohol-related cancers).
MethodsTwo-stage individual participant data meta-analyses were performed based on 18 cohorts within the Psychosocial Factors and Cancer Incidence consortium that had a measure of depression or anxiety (N = 319 613, cancer incidence = 25 803). Health behaviors included smoking, physical inactivity, alcohol use, body mass index (BMI), sedentary behavior, and sleep duration and quality. In stage one, path-specific regression estimates were obtained in each cohort. In stage two, cohort-specific estimates were pooled using random-effects multivariate meta-analysis, and natural indirect effects (i.e. mediating effects) were calculated as hazard ratios (HRs).
ResultsSmoking (HRs range 1.04–1.10) and physical inactivity (HRs range 1.01–1.02) significantly mediated the associations among depression, anxiety, and lung cancer. Smoking was also a mediator for smoking-related cancers (HRs range 1.03–1.06). There was mediation by health behaviors, especially smoking, physical inactivity, alcohol use, and a higher BMI, in the associations among depression, anxiety, and overall cancer or other types of cancer, but effects were small (HRs generally below 1.01).
ConclusionsSmoking constitutes a mediating pathway linking depression and anxiety to lung cancer and smoking-related cancers. Our findings underline the importance of smoking cessation interventions for persons with depression or anxiety.
VaTEST III: Validation of eight potential super-earths from TESS data
- Priyashkumar Mistry, Aniket Prasad, Mousam Maity, Kamlesh Pathak, Sarvesh Gharat, Georgios Lekkas, Surendra Bhattarai, Dhruv Kumar, Jack J. Lissauer, Joseph D. Twicken, Abderahmane Soubkiou, Francisco J. Pozuelos, Jon Jenkins, Keith Horne, Steven Giacalone, Khalid Barkaoui, Mathilde Timmermans, Cristilyn N. Watkins, Ramotholo Sefako, Karen A. Collins, David R. Ciardi, Catherine A. Clark, Boris S. Safonov, Avi Shporer, Joshua E. Schlieder, Zouhair Benkhaldoun, Chris Stockdale, Carl Ziegler, Emily A. Gilbert, Jehin Emmanuël, Felipe Murgas, Ian J. M. Crossfield, Martin Paegert, Michael B. Lund, Norio Narita, Richard P. Schwarz, Robert F. Goeke, Sergio B. Fajardo-Acosta, Steve B. Howell, Thiam-Guan Tan, Thomas Barclay, Yugo Kawai
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- Publications of the Astronomical Society of Australia / Volume 41 / 2024
- Published online by Cambridge University Press:
- 11 April 2024, e030
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NASA’s all-sky survey mission, the Transiting Exoplanet Survey Satellite (TESS), is specifically engineered to detect exoplanets that transit bright stars. Thus far, TESS has successfully identified approximately 400 transiting exoplanets, in addition to roughly 6 000 candidate exoplanets pending confirmation. In this study, we present the results of our ongoing project, the Validation of Transiting Exoplanets using Statistical Tools (VaTEST). Our dedicated effort is focused on the confirmation and characterisation of new exoplanets through the application of statistical validation tools. Through a combination of ground-based telescope data, high-resolution imaging, and the utilisation of the statistical validation tool known as TRICERATOPS, we have successfully discovered eight potential super-Earths. These planets bear the designations: TOI-238b (1.61$^{+0.09} _{-0.10}$ R$_\oplus$), TOI-771b (1.42$^{+0.11} _{-0.09}$ R$_\oplus$), TOI-871b (1.66$^{+0.11} _{-0.11}$ R$_\oplus$), TOI-1467b (1.83$^{+0.16} _{-0.15}$ R$_\oplus$), TOI-1739b (1.69$^{+0.10} _{-0.08}$ R$_\oplus$), TOI-2068b (1.82$^{+0.16} _{-0.15}$ R$_\oplus$), TOI-4559b (1.42$^{+0.13} _{-0.11}$ R$_\oplus$), and TOI-5799b (1.62$^{+0.19} _{-0.13}$ R$_\oplus$). Among all these planets, six of them fall within the region known as ‘keystone planets’, which makes them particularly interesting for study. Based on the location of TOI-771b and TOI-4559b below the radius valley we characterised them as likely super-Earths, though radial velocity mass measurements for these planets will provide more details about their characterisation. It is noteworthy that planets within the size range investigated herein are absent from our own solar system, making their study crucial for gaining insights into the evolutionary stages between Earth and Neptune.
440 Muscle Protein Synthesis and Whole-Body Protein Balance Following Ingestion of Beef or a Soy Protein Based Meat Alternative
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- David D. Church, Katie R. Hirsch, Shiloah A. Kviatkovsky, Arny A. Ferrando, Gohar Azhar, Robert R Wolfe
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- Journal:
- Journal of Clinical and Translational Science / Volume 8 / Issue s1 / April 2024
- Published online by Cambridge University Press:
- 03 April 2024, pp. 130-131
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OBJECTIVES/GOALS: We endeavor to investigated the hypothesis that muscle protein synthesis (MPS) is stimulated more after consumption of a 4-ounce beef patty as compared to 4- and 8-ounces of a soy protein based meat alternative (SPBMA) and if a greater stimulation is related to differences in the responses of plasma essential amino acid (EAA) concentrations. METHODS/STUDY POPULATION: Participants were aged 18 to 40 years of age with a BMI between 20 and 32 kg/m2. Written informed consent was obtained from all participants, and approved by UAMS IRB. Participants were assigned to one of three intervention groups via a single-blinded permuted block randomization, stratified for sex: 4 oz beef patty; 4 oz SPBMA; 2 x 4 oz (8oz) SPBMA. The impossible burgerTM was selected as it is primarily soy protein, a high-quality plant protein, and specifically designed to mimic a beef burger. Stable isotope were infused to assess protein metabolism. Appropriate muscle and blood samples were obtained. Enrichment and plasma EAA concentrations were measured with mass spectrometry. ANOVA’s on the change from basal to postprandial were used to identify group difference, significance was accepted at p < 0.05. RESULTS/ANTICIPATED RESULTS: The MPS increase from basal to postprandial indicated a significant main effect of group (p = 0.026), with the beef group (0.020 ± 0.016%/hour) being significantly greater than the 4oz SPBMA (0.003 ± 0.010%/hour; p = 0.021) but not the 8oz PBMA group (0.013 ± 0.016%/hour; p = 0.454). Similar results were observed for whole-body protein synthesis, where the beef group (p = 0.042) and 8oz SPBMA (p = 0.033) were significantly greater than the 4oz SPBMA (p = 0.021). Whole-body protein balance was significantly greater in the 8oz SPBMA as compared to 4oz of beef and SPBMA. Lastly, we observed a significantly relationship (p = 0.046; r = 0.411) between the maximal plasma EAA concentration and change in MPS, indicating the greater rate of MPS following 4oz of beef is mediated by an higher increase in plasma EAA concentrations. DISCUSSION/SIGNIFICANCE: In conclusion, 4oz of beef stimulates muscle protein FSR more than 4oz of a SPBMA. A common SPBMA can stimulate increase in protein metabolism, however, greater amounts are required as compared to beef protein. Further, the change in the muscle protein FSR response was significantly correlated with the maximal EAA concentration.
High-Resolution Transmission Electron Microscopy and Electron Diffraction of Mixed-Layer Illite/Smectite: Experimental Results
- David R. Veblen, George D. Guthrie, Jr., Kenneth J. T. Livi, Robert C. Reynolds, Jr.
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- Clays and Clay Minerals / Volume 38 / Issue 1 / February 1990
- Published online by Cambridge University Press:
- 02 April 2024, pp. 1-13
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High-resolution transmission electron microscopy (HRTEM) and electron diffraction experiments have been performed on R1 and R> 1 illite/smectite (I/S) samples that from X-ray powder diffraction (XRD) experiments appear to contain well-ordered layer sequences. The HRTEM images confirmed earlier computer image simulations, which suggested that periodicities due to I/S ordering can be imaged in TEM instruments of moderate resolution. The experiments also confirmed that in instruments of this sort, the strongest contrast arising from the compositional difference between I and S layers occurs under rather unusual imaging conditions of strong overfocus. Some selected-area electron diffraction (SAD) patterns showed additional diffraction spots consistent with R1 and R3 ordering. SAD patterns and cross-fringes arising in HRTEM images from non-00l reciprocal lattice rows indicated that the stacking vectors of most adjacent 2:1 layers were not randomly oriented with respect to each other. Thus, the I/S was not fully turbostratic, but instead consisted of very thin, coherently stacked crystallites that extended across the fundamental particles postulated by Nadeau and coworkers.
S/(I + S) ratios were determined for about seventy HRTEM images obtained and interpreted by three different TEM operators. These ratios were consistent with those obtained from standard XRD procedures, suggesting that results obtained by XRD can be used to infer the initial structural state of mixed-layer I/S prior to treatment of samples for XRD experiments. The HRTEM experiments thus demonstrated that the two specimens examined consisted of ordered I/S existing as small crystals, most of which contained more layers than the fundamental particles of Nadeau and coworkers. The non-turbostratic stacking suggests an energetic interaction between the individual fundamental particles, leading to at least two alternative thermodynamic descriptions of these materials. Although the I/S crystals in the present experiments probably were disaggregated into fundamental particles during sample preparation for XRD, the I/S crystals appear to have separated only along the smectite interlayers. If the term “fundamental particle” is to be used for primary, untreated I/S, its original definition should be modified to include not only free particles, but also those that occur as layers within small crystals. It further should be recognized that these particles can interact thermodynamically and crystallographically with their neighbors.
Healthcare personnel with laboratory-confirmed mpox in California during the 2022 outbreak
- Allison E. Bailey, Shua J. Chai, Robert E. Snyder, David P. Bui, Linda S. Lewis, Kayla Saadeh, J. Bradford Bertumen, Erin Epson, Jane D. Siegel
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- Infection Control & Hospital Epidemiology , First View
- Published online by Cambridge University Press:
- 27 March 2024, pp. 1-3
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The California Department of Public Health (CDPH) reviewed 109 cases of healthcare personnel (HCP) with laboratory-confirmed mpox to understand transmission risk in healthcare settings. Overall, 90% of HCP with mpox had nonoccupational exposure risk factors. One occupationally acquired case was associated with sharps injury while unroofing a patient’s lesion for diagnostic testing.
Phosphates in Some Missouri Refractory Clays
- Robert B. Hall, Eugene E. Foord, David J. Keller, Walter D. Keller
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- Clays and Clay Minerals / Volume 45 / Issue 3 / June 1997
- Published online by Cambridge University Press:
- 28 February 2024, pp. 353-364
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This paper describes in detail phosphate minerals occurring in refractory clays of Missouri and their effect on the refractory degree of the clays. The minerals identified include carbonate-fluorapatite (francolite), crandallite, goyazite, wavellite, variscite and strengite. It is emphasized that these phosphates occur only in local isolated concentrations, and not generally in Missouri refractory clays.
The Missouri fireclay region comprises 2 districts, northern and southern, separated by the Missouri River. In this region, clay constitutes a major part of the Lower Pennsylvanian Cheltenham Formation. The original Cheltenham mud was an argillic residue derived from leaching and dissolution of pre-Pennsylvanian carbonates. The mud accumulated on a karstic erosion surface truncating the pre-Cheltenham rocks. Fireclays of the northern district consist mainly of poorly ordered kaolinite, with variable but minor amounts of illite, chlorite and fine-grained detrital quartz. Clays of the southern district were subjected to extreme leaching that produced well-ordered kaolinite flint clays. Local desilication formed pockets of diaspore, or more commonly, kaolinite, with oolite-like nubs or burls of diaspore (“burley” clay).
The phosphate-bearing materials have been studied by X-ray diffraction (XRD), scanning electron microscopy-energy dispersive spectral analysis (SEM-EDS) and chemical analysis. Calcian goyazite was identified in a sample of diaspore, and francolite in a sample of flint clay. A veinlet of wavellite occurs in flint clay at one locality, and a veinlet of variscite-strengite at another locality.
The Missouri flint-clay-hosted francolite could not have formed in the same manner as marine francolite. The evidence suggests that the Cheltenham francolite precipitated from ion complexes in pore water, nearly simultaneously with crystallization of kaolinite flint clay from an alumina-silica gel. Calcian goyazite is an early diagenetic addition to its diaspore host. The wavellite and variscite-strengite veinlets are secondary, precipitated from ion complexes in ground water percolating along cracks in the flint clay. The flint clay host of the variscite-strengite veinlet contains strontian crandallite. All of the phosphates contain significant amounts of strontium. The source of P, Ca and Sr was the marine carbonates. Dissolution of these carbonates produced the argillic residue that became the primordial Cheltenham paludal mud, which ultimately altered to fireclay.
Preliminary firing tests show that the presence of phosphates lowers fusion temperature. However, it is not clear whether poor refractoriness is due to the presence of phosphates, per se, or to Ca, Sr and other alkaline elements present in the phosphates.
9 Serum Neurofilament is Associated with Diffusion Kurtosis Imaging in Chronic Mild-Moderate Traumatic Brain Injury
- Erin R Trifilio, Robert D Claar, Aditi Venkatesh, Sarah Bottari, David Barton, Claudia S Robertson, Richard Rubenstein, Amy K Wagner, Kevin K W Wang, Damon G Lamb, John B Williamson
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, p. 121
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Objective:
To determine the association between blood markers of white matter injury (e.g., serum neurofilament light and phosphorylated neurofilament heavy) and a novel neuroimaging technique measuring microstructural white matter changes (e.g., diffusion kurtosis imaging) in regions (e.g., anterior thalamic radiation and uncinate fasciculus) known to be impacted in traumatic brain injury (TBI) and associated with symptoms common in those with chronic TBI (e.g., sleep disruption, cognitive and emotional disinhibition) in a heterogeneous sample of Veterans and non-Veterans with a history of remote TBI (i.e., >6 months).
Participants and Methods:Participants with complete imaging and blood data (N=24) were sampled from a larger multisite study of chronic mild-moderate TBI. Participants ranged in age from young to middle-aged (mean age = 34.17, SD age = 10.96, range = 19-58) and primarily male (66.7%). The number of distinct TBIs ranged from 1-5 and the time since most recent TBI ranged from 0-30 years. Scores on a cognitive screener (MoCA) ranged from 22-30 (mean = 26.75). We performed bivariate correlations with mean kurtosis (MK) in the anterior thalamic radiation (ATR; left, right) uncinate fasciculus (UF; left, right), and serum neurofilament light (NFL), and phosphorylated neurofilament heavy (pNFH). Both were log transformed for non-normality. Significance threshold was set at p<0.05.
Results:pNFH was significantly and negatively correlated to MK in the right (r=-0.446) and left (r=-0.599) UF and right (r=-0.531) and left (r=-0.469) ATR. NFL showed moderate associations with MK in the right (r=-0.345) and left (r=-0.361) UF and little to small association in the right (r=-0.063) and left (r=-0.215) ATR. In post-hoc analyses, MK in both the left (r=0.434) and right (r=0.514) UF was positively associated with performance on a frontally-mediated list-learning task (California Verbal Learning Test, 2nd Edition; Trials 1-5 total).
Conclusions:Results suggest that serum pNFH may be a more sensitive blood marker of microstructural complexity in white matter regions frequently impacted by TBI in a chronic mild-moderate TBI sample. Further, it suggests that even years after a mild-moderate TBI, levels of pNFH may be informative regarding white matter integrity in regions related to executive functioning and emotional disinhibition, both of which are common presenting problems when these patients are seen in a clinical setting.
4 Risk Factor and Biomarker Correlates of FLAIR White Matter Hyperintensities in Former American Football Players
- Monica T Ly, Fatima Tuz-Zahra, Yorghos Tripodis, Charles H Adler, Laura J Balcer, Charles Bernick, Elaine Peskind, Megan L Mariani, Rhoda Au, Sarah J Banks, William B Barr, Jennifer V Wethe, Mark W Bondi, Lisa Delano-Wood, Robert C Cantu, Michael J Coleman, David W Dodick, Michael D McClean, Jesse Mez, Joseph N Palmisano, Brett Martin, Kaitlin Hartlage, Alexander P Lin, Inga K Koerte, Jeffrey L Cummings, Eric M Reiman, Martha E Shenton, Robert A Stern, Sylvain Bouix, Michael L Alosco
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 608-610
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Objective:
White matter hyperintensity (WMH) burden is greater, has a frontal-temporal distribution, and is associated with proxies of exposure to repetitive head impacts (RHI) in former American football players. These findings suggest that in the context of RHI, WMH might have unique etiologies that extend beyond those of vascular risk factors and normal aging processes. The objective of this study was to evaluate the correlates of WMH in former elite American football players. We examined markers of amyloid, tau, neurodegeneration, inflammation, axonal injury, and vascular health and their relationships to WMH. A group of age-matched asymptomatic men without a history of RHI was included to determine the specificity of the relationships observed in the former football players.
Participants and Methods:240 male participants aged 45-74 (60 unexposed asymptomatic men, 60 male former college football players, 120 male former professional football players) underwent semi-structured clinical interviews, magnetic resonance imaging (structural T1, T2 FLAIR, and diffusion tensor imaging), and lumbar puncture to collect cerebrospinal fluid (CSF) biomarkers as part of the DIAGNOSE CTE Research Project. Total WMH lesion volumes (TLV) were estimated using the Lesion Prediction Algorithm from the Lesion Segmentation Toolbox. Structural equation modeling, using Full-Information Maximum Likelihood (FIML) to account for missing values, examined the associations between log-TLV and the following variables: total cortical thickness, whole-brain average fractional anisotropy (FA), CSF amyloid ß42, CSF p-tau181, CSF sTREM2 (a marker of microglial activation), CSF neurofilament light (NfL), and the modified Framingham stroke risk profile (rFSRP). Covariates included age, race, education, APOE z4 carrier status, and evaluation site. Bootstrapped 95% confidence intervals assessed statistical significance. Models were performed separately for football players (college and professional players pooled; n=180) and the unexposed men (n=60). Due to differences in sample size, estimates were compared and were considered different if the percent change in the estimates exceeded 10%.
Results:In the former football players (mean age=57.2, 34% Black, 29% APOE e4 carrier), reduced cortical thickness (B=-0.25, 95% CI [0.45, -0.08]), lower average FA (B=-0.27, 95% CI [-0.41, -.12]), higher p-tau181 (B=0.17, 95% CI [0.02, 0.43]), and higher rFSRP score (B=0.27, 95% CI [0.08, 0.42]) were associated with greater log-TLV. Compared to the unexposed men, substantial differences in estimates were observed for rFSRP (Bcontrol=0.02, Bfootball=0.27, 994% difference), average FA (Bcontrol=-0.03, Bfootball=-0.27, 802% difference), and p-tau181 (Bcontrol=-0.31, Bfootball=0.17, -155% difference). In the former football players, rFSRP showed a stronger positive association and average FA showed a stronger negative association with WMH compared to unexposed men. The effect of WMH on cortical thickness was similar between the two groups (Bcontrol=-0.27, Bfootball=-0.25, 7% difference).
Conclusions:These results suggest that the risk factor and biological correlates of WMH differ between former American football players and asymptomatic individuals unexposed to RHI. In addition to vascular risk factors, white matter integrity on DTI showed a stronger relationship with WMH burden in the former football players. FLAIR WMH serves as a promising measure to further investigate the late multifactorial pathologies of RHI.
36 Reactivity to Loss and Its Relationship to Clinical Symptoms of ADHD in Adults
- Lauren T. Olson, David A.S. Kaufman, Fred W. Sabb, Edythe D. London, Robert M. Bilder
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 643-644
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Objective:
Individuals with attention-deficit/hyperactivity disorder (ADHD) exhibit deficits in reward-based learning, which have important implications for behavioral regulation. Prior research has shown that these individuals show altered patterns of risky decision-making, which may be partially explained as a function of dysfunctional reactivity to rewards and punishments. However, research findings on the relationships between ADHD and punishment sensitivity have been mixed. The current study used the Balloon Analog Risk Task (BART) to examine risky decision-making in adults with and without ADHD, with a particular interest in characterizing the manner in which participants react to loss.
Participants and Methods:612 individuals (Mage = 31.04, SDage = 78.77; 329 females, 283 males) were recruited through the UCLA Consortium for Neuropsychiatric Phenomics (CNP). All participants were administered the Structured Clinical Interview for DSM-IV-TR (SCID-IV), which provided diagnoses used for group comparisons between adults with ADHD (n = 35) and healthy controls (n = 577). A computerized BART paradigm was used to examine impulsivity and risky decision-making, while participants also completed the Barratt Impulsiveness Scale (BIS-11), and ADHD participants completed the Adult Self-Report Scale-V1.1 (ASRS-V1.1). The BART presented two colors of balloons with differing probabilities of exploding, and participants were incentivized to pump the balloons as many times as possible without causing them to explode. The primary endpoint was "mean adjusted pumps", determined as mean across trials of the number of pumps on trials that did not end in explosion. An index of reactivity to loss was calculated as the difference between the mean adjusted pumps following an explosion and the mean adjusted pumps following trials in which the balloon did not explode.
Results:The ADHD and control groups did not differ on mean adjusted pumps across trials, but they did differ in their reactivity to explosion of balloons that followed the most pumps, incurring the greatest level of loss (F(1, 551) = 7.1, p < 0.01). Interestingly, ADHD participants showed a greater reactivity to loss on these balloons than controls (p < 0.05), indicating that they reduced their number of pumps following balloon explosions more than controls. For participants as a whole, there were small correlations between loss reactivity and scales of everyday impulsivity on the BIS-II (ps < 0.05). For ADHD participants, loss reactivity was unrelated to symptoms of inattention but was significantly correlated with symptoms of hyperactivity/impulsivity (p = 0.01) and total ADHD symptoms (p < 0.05) on the ASRS-V1.1.
Conclusions:In the context of a risky decision-making task, adults with ADHD showed greater reactivity to loss than controls, despite showing comparable patterns of overall performance during the BART. The magnitude of behavioral adjustment following loss was correlated with symptoms of hyperactivity/impulsivity in adults with ADHD, suggesting that loss sensitivity is clinically related to impulsive behavior in everyday life. These findings help to expand our understanding of motivational processing in ADHD and suggest new insight into the ways in which everyday symptoms of ADHD are related to sensitivity to losses and punishments.
62 Exploration of Sex Differences in Cannabis Use Patterns, Driving Performance, and Subjective Intoxication Effects
- Kyle F. Mastropietro, Jeffrey M. Rogers, Dafna Paltin, Anya Umlauf, David J. Grelotti, Robert L. Fitzgerald, Igor Grant, Thomas D. Marcotte
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 847-848
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Objective:
Although some animal research suggests possible sex differences in response to THC exposure (e.g., Cooper & Craft, 2018), there are limited human studies. One study found that among individuals rarely using cannabis, when given similar amounts of oral and vaporized THC females report greater subjective intoxication compared to males (Sholler et al., 2020). However, in a study of daily users, females reported indistinguishable levels of intoxication compared to males after smoking similar amounts (Cooper & Haney, 2014), while males and females using 1–4x/week showed similar levels of intoxication, despite females having lower blood THC and metabolite concentrations (Matheson et al., 2020). It is important to elucidate sex differences in biological indicators of cannabis intoxication given potential driving/workplace implications as states increasingly legalize use. The current study examined if when closely matching males and females on cannabis use variables there are predictable sex differences in residual whole blood THC and metabolite concentrations, and THC/metabolites, subjective appraisals of intoxication, and driving performance following acute cannabis consumption.
Participants and Methods:The current study was part of a randomized clinical trial (Marcotte et al., 2022). Participants smoked ad libitum THC cigarettes and then completed driving simulations, blood draws, and subjective measures of intoxication. The main outcomes were the change in Composite Drive Score (CDS; global measure of driving performance) from baseline, whole blood THC, 11-OH-THC, and THC-COOH levels (ng/mL), and subjective ratings of how “high” participants felt (0 = not at all, 100 = extremely). For this analysis of participants receiving active THC, males were matched to females on 1) estimated THC exposure (g) in the last 6 months (24M, 24F) or 2) whole blood THC concentrations immediately post-smoking (23M, 23F).
Results:When matched on THC exposure in the past 6 months (overall mean of 46 grams; p = .99), there were no sex differences in any cannabinoid/metabolite concentrations at baseline (all p > .83) or after cannabis administration (all p > .72). Nor were there differences in the change in CDS from pre-to-post-smoking (p = .26) or subjective “highness” ratings (p = .53). When matched on whole blood THC concentrations immediately after smoking (mean of 34 ng/mL for both sexes, p = .99), no differences were found in CDS change from pre-to-post smoking (p = .81), THC metabolite concentrations (all p > .25), or subjective “highness” ratings (p = .56). For both analyses, males and females did not differ in BMI (both p > .7).
Conclusions:When male/female cannabis users are well-matched on use history, we find no significant differences in cannabinoid concentrations following a mean of 5 days of abstinence, suggesting that there are no clear biological differences in carryover residual effects. We also find no significant sex differences following ad libitum smoking in driving performance, subjective ratings of “highness,” nor whole blood THC and metabolite concentrations, indicating that there are no biological differences in acute response to THC. This improves upon previous research by closely matching participants over a wider range of use intensity variables, although the small sample size precludes definitive conclusions.
Radiofrequency ice dielectric measurements at Summit Station, Greenland
- Juan Antonio Aguilar, Patrick Allison, Dave Besson, Abby Bishop, Olga Botner, Sjoerd Bouma, Stijn Buitink, Maddalena Cataldo, Brian A. Clark, Kenny Couberly, Zach Curtis-Ginsberg, Paramita Dasgupta, Simon de Kockere, Krijn D. de Vries, Cosmin Deaconu, Michael A. DuVernois, Anna Eimer, Christian Glaser, Allan Hallgren, Steffen Hallmann, Jordan Christian Hanson, Bryan Hendricks, Jakob Henrichs, Nils Heyer, Christian Hornhuber, Kaeli Hughes, Timo Karg, Albrecht Karle, John L. Kelley, Michael Korntheuer, Marek Kowalski, Ilya Kravchenko, Ryan Krebs, Robert Lahmann, Uzair Latif, Joseph Mammo, Matthew J. Marsee, Zachary S. Meyers, Kelli Michaels, Katharine Mulrey, Marco Muzio, Anna Nelles, Alexander Novikov, Alisa Nozdrina, Eric Oberla, Bob Oeyen, Ilse Plaisier, Noppadol Punsuebsay, Lilly Pyras, Dirk Ryckbosch, Olaf Scholten, David Seckel, Mohammad Ful Hossain Seikh, Daniel Smith, Jethro Stoffels, Daniel Southall, Karen Terveer, Simona Toscano, Delia Tosi, Dieder J. Van Den Broeck, Nick van Eijndhoven, Abigail G. Vieregg, Janna Z. Vischer, Christoph Welling, Dawn R. Williams, Stephanie Wissel, Robert Young, Adrian Zink
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- Journal:
- Journal of Glaciology , First View
- Published online by Cambridge University Press:
- 09 October 2023, pp. 1-12
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We recently reported on the radio-frequency attenuation length of cold polar ice at Summit Station, Greenland, based on bi-static radar measurements of radio-frequency bedrock echo strengths taken during the summer of 2021. Those data also allow studies of (a) the relative contributions of coherent (such as discrete internal conducting layers with sub-centimeter transverse scale) vs incoherent (e.g. bulk volumetric) scattering, (b) the magnitude of internal layer reflection coefficients, (c) limits on signal propagation velocity asymmetries (‘birefringence’) and (d) limits on signal dispersion in-ice over a bandwidth of ~100 MHz. We find that (1) attenuation lengths approach 1 km in our band, (2) after averaging 10 000 echo triggers, reflected signals observable over the thermal floor (to depths of ~1500 m) are consistent with being entirely coherent, (3) internal layer reflectivities are ≈–60$\to$–70 dB, (4) birefringent effects for vertically propagating signals are smaller by an order of magnitude relative to South Pole and (5) within our experimental limits, glacial ice is non-dispersive over the frequency band relevant for neutrino detection experiments.
Introduction to A Compendium of Strategies to Prevent Healthcare-Associated Infections In Acute-Care Hospitals: 2022 Updates
- Deborah S. Yokoe, Sonali D. Advani, Deverick J. Anderson, Hilary M. Babcock, Michael Bell, Sean M. Berenholtz, Kristina A. Bryant, Niccolò Buetti, Michael S. Calderwood, David P. Calfee, Valerie M. Deloney, Erik R. Dubberke, Katherine D. Ellingson, Neil O. Fishman, Dale N. Gerding, Janet Glowicz, Mary K. Hayden, Keith S. Kaye, Larry K. Kociolek, Emily Landon, Elaine L. Larson, Anurag N. Malani, Jonas Marschall, Jennifer Meddings, Leonard A. Mermel, Payal K. Patel, Trish M. Perl, Kyle J. Popovich, Joshua K. Schaffzin, Edward Septimus, Kavita K. Trivedi, Robert A. Weinstein, Lisa L. Maragakis
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- Journal:
- Infection Control & Hospital Epidemiology / Volume 44 / Issue 10 / October 2023
- Published online by Cambridge University Press:
- 19 October 2023, pp. 1533-1539
- Print publication:
- October 2023
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Since the initial publication of A Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals in 2008, the prevention of healthcare-associated infections (HAIs) has continued to be a national priority. Progress in healthcare epidemiology, infection prevention, antimicrobial stewardship, and implementation science research has led to improvements in our understanding of effective strategies for HAI prevention. Despite these advances, HAIs continue to affect ∼1 of every 31 hospitalized patients,1 leading to substantial morbidity, mortality, and excess healthcare expenditures,1 and persistent gaps remain between what is recommended and what is practiced.
The widespread impact of the coronavirus disease 2019 (COVID-19) pandemic on HAI outcomes2 in acute-care hospitals has further highlighted the essential role of infection prevention programs and the critical importance of prioritizing efforts that can be sustained even in the face of resource requirements from COVID-19 and future infectious diseases crises.3
The Compendium: 2022 Updates document provides acute-care hospitals with up-to-date, practical expert guidance to assist in prioritizing and implementing HAI prevention efforts. It is the product of a highly collaborative effort led by the Society for Healthcare Epidemiology of America (SHEA), the Infectious Disease Society of America (IDSA), the Association for Professionals in Infection Control and Epidemiology (APIC), the American Hospital Association (AHA), and The Joint Commission, with major contributions from representatives of organizations and societies with content expertise, including the Centers for Disease Control and Prevention (CDC), the Pediatric Infectious Disease Society (PIDS), the Society for Critical Care Medicine (SCCM), the Society for Hospital Medicine (SHM), the Surgical Infection Society (SIS), and others.
Advocacy at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery
- Bistra Zheleva, Amy Verstappen, David M. Overman, Farhan Ahmad, Sulafa K.M. Ali, Zohair Y. Al Halees, Joumana Ghandour Atallah, Isabella E. Badhwar, Carissa Baker-Smith, Maria Balestrini, Amy Basken, Jonah S. Bassuk, Lee Benson, Horacio Capelli, Santo Carollo, Devyani Chowdhury, M. Sertaç Çiçek, Mitchell I. Cohen, David S. Cooper, John E. Deanfield, Joseph Dearani, Blanca del Valle, Kathryn M. Dodds, Junbao Du, Frank Edwin, Ekanem Ekure, Nurun Nahar Fatema, Anu Gomanju, Babar Hasan, Lewis Henry, Christopher Hugo-Hamman, Krishna S. Iyer, Marcelo B. Jatene, Kathy J. Jenkins, Tara Karamlou, Tom R. Karl, James K. Kirklin, Christián Kreutzer, Raman Krishna Kumar, Keila N. Lopez, Alexis Palacios Macedo, Bradley S. Marino, Eva M. Marwali, Folkert J. Meijboom, Sandra S. Mattos, Hani Najm, Dan Newlin, William M. Novick, Sir Shakeel A. Qureshi, Budi Rahmat, Robert Raylman, Irfan Levent Saltik, Craig Sable, Nestor Sandoval, Anita Saxena, Emma Scanlan, Gary F. Sholler, Jodi Smith, James D. St Louis, Christo I. Tchervenkov, Koh Ghee Tiong, Vladimiro Vida, Susan Vosloo, Douglas J. “DJ” Weinstein, James L. Wilkinson, Liesl Zuhlke, Jeffrey P. Jacobs
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- Journal:
- Cardiology in the Young / Volume 33 / Issue 8 / August 2023
- Published online by Cambridge University Press:
- 24 August 2023, pp. 1277-1287
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The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery (WCPCCS) will be held in Washington DC, USA, from Saturday, 26 August, 2023 to Friday, 1 September, 2023, inclusive. The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery will be the largest and most comprehensive scientific meeting dedicated to paediatric and congenital cardiac care ever held. At the time of the writing of this manuscript, The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery has 5,037 registered attendees (and rising) from 117 countries, a truly diverse and international faculty of over 925 individuals from 89 countries, over 2,000 individual abstracts and poster presenters from 101 countries, and a Best Abstract Competition featuring 153 oral abstracts from 34 countries. For information about the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery, please visit the following website: [www.WCPCCS2023.org]. The purpose of this manuscript is to review the activities related to global health and advocacy that will occur at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery.
Acknowledging the need for urgent change, we wanted to take the opportunity to bring a common voice to the global community and issue the Washington DC WCPCCS Call to Action on Addressing the Global Burden of Pediatric and Congenital Heart Diseases. A copy of this Washington DC WCPCCS Call to Action is provided in the Appendix of this manuscript. This Washington DC WCPCCS Call to Action is an initiative aimed at increasing awareness of the global burden, promoting the development of sustainable care systems, and improving access to high quality and equitable healthcare for children with heart disease as well as adults with congenital heart disease worldwide.
Executive Summary: A Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute-Care Hospitals: 2022 Updates
- Deborah S. Yokoe, Sonali D. Advani, Deverick J. Anderson, Hilary M. Babcock, Michael Bell, Sean M. Berenholtz, Kristina A. Bryant, Niccolò Buetti, Michael S. Calderwood, David P. Calfee, Erik R. Dubberke, Katherine D. Ellingson, Neil O. Fishman, Dale N. Gerding, Janet Glowicz, Mary K. Hayden, Keith S. Kaye, Michael Klompas, Larry K. Kociolek, Emily Landon, Elaine L. Larson, Anurag N. Malani, Jonas Marschall, Jennifer Meddings, Leonard A. Mermel, Payal K. Patel, Trish M. Perl, Kyle J. Popovich, Joshua K. Schaffzin, Edward Septimus, Kavita K. Trivedi, Robert A. Weinstein, Lisa L. Maragakis
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- Journal:
- Infection Control & Hospital Epidemiology / Volume 44 / Issue 10 / October 2023
- Published online by Cambridge University Press:
- 22 August 2023, pp. 1540-1554
- Print publication:
- October 2023
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Agricultural Research Service Weed Science Research: Past, Present, and Future
- Stephen L. Young, James V. Anderson, Scott R. Baerson, Joanna Bajsa-Hirschel, Dana M. Blumenthal, Chad S. Boyd, Clyde D. Boyette, Eric B. Brennan, Charles L. Cantrell, Wun S. Chao, Joanne C. Chee-Sanford, Charlie D. Clements, F. Allen Dray, Stephen O. Duke, Kayla M. Eason, Reginald S. Fletcher, Michael R. Fulcher, John F. Gaskin, Brenda J. Grewell, Erik P. Hamerlynck, Robert E. Hoagland, David P. Horvath, Eugene P. Law, John D. Madsen, Daniel E. Martin, Clint Mattox, Steven B. Mirsky, William T. Molin, Patrick J. Moran, Rebecca C. Mueller, Vijay K. Nandula, Beth A. Newingham, Zhiqiang Pan, Lauren M. Porensky, Paul D. Pratt, Andrew J. Price, Brian G. Rector, Krishna N. Reddy, Roger L. Sheley, Lincoln Smith, Melissa C. Smith, Keirith A. Snyder, Matthew A. Tancos, Natalie M. West, Gregory S. Wheeler, Martin M. Williams, Julie Wolf, Carissa L. Wonkka, Alice A. Wright, Jing Xi, Lew H. Ziska
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- Journal:
- Weed Science / Volume 71 / Issue 4 / July 2023
- Published online by Cambridge University Press:
- 16 August 2023, pp. 312-327
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The U.S. Department of Agriculture–Agricultural Research Service (USDA-ARS) has been a leader in weed science research covering topics ranging from the development and use of integrated weed management (IWM) tactics to basic mechanistic studies, including biotic resistance of desirable plant communities and herbicide resistance. ARS weed scientists have worked in agricultural and natural ecosystems, including agronomic and horticultural crops, pastures, forests, wild lands, aquatic habitats, wetlands, and riparian areas. Through strong partnerships with academia, state agencies, private industry, and numerous federal programs, ARS weed scientists have made contributions to discoveries in the newest fields of robotics and genetics, as well as the traditional and fundamental subjects of weed–crop competition and physiology and integration of weed control tactics and practices. Weed science at ARS is often overshadowed by other research topics; thus, few are aware of the long history of ARS weed science and its important contributions. This review is the result of a symposium held at the Weed Science Society of America’s 62nd Annual Meeting in 2022 that included 10 separate presentations in a virtual Weed Science Webinar Series. The overarching themes of management tactics (IWM, biological control, and automation), basic mechanisms (competition, invasive plant genetics, and herbicide resistance), and ecosystem impacts (invasive plant spread, climate change, conservation, and restoration) represent core ARS weed science research that is dynamic and efficacious and has been a significant component of the agency’s national and international efforts. This review highlights current studies and future directions that exemplify the science and collaborative relationships both within and outside ARS. Given the constraints of weeds and invasive plants on all aspects of food, feed, and fiber systems, there is an acknowledged need to face new challenges, including agriculture and natural resources sustainability, economic resilience and reliability, and societal health and well-being.
Associations of alcohol and cannabis use with change in posttraumatic stress disorder and depression symptoms over time in recently trauma-exposed individuals
- Cecilia A. Hinojosa, Amanda Liew, Xinming An, Jennifer S. Stevens, Archana Basu, Sanne J. H. van Rooij, Stacey L. House, Francesca L. Beaudoin, Donglin Zeng, Thomas C. Neylan, Gari D. Clifford, Tanja Jovanovic, Sarah D. Linnstaedt, Laura T. Germine, Scott L. Rauch, John P. Haran, Alan B. Storrow, Christopher Lewandowski, Paul I. Musey, Phyllis L. Hendry, Sophia Sheikh, Christopher W. Jones, Brittany E. Punches, Michael C. Kurz, Robert A. Swor, Lauren A. Hudak, Jose L. Pascual, Mark J. Seamon, Elizabeth M. Datner, Anna M. Chang, Claire Pearson, David A. Peak, Roland C. Merchant, Robert M. Domeier, Niels K. Rathlev, Paulina Sergot, Leon D. Sanchez, Steven E. Bruce, Mark W. Miller, Robert H. Pietrzak, Jutta Joormann, Diego A. Pizzagalli, John F. Sheridan, Steven E. Harte, James M. Elliott, Ronald C. Kessler, Karestan C. Koenen, Samuel A. McLean, Kerry J. Ressler, Negar Fani
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- Journal:
- Psychological Medicine / Volume 54 / Issue 2 / January 2024
- Published online by Cambridge University Press:
- 13 June 2023, pp. 338-349
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Background
Several hypotheses may explain the association between substance use, posttraumatic stress disorder (PTSD), and depression. However, few studies have utilized a large multisite dataset to understand this complex relationship. Our study assessed the relationship between alcohol and cannabis use trajectories and PTSD and depression symptoms across 3 months in recently trauma-exposed civilians.
MethodsIn total, 1618 (1037 female) participants provided self-report data on past 30-day alcohol and cannabis use and PTSD and depression symptoms during their emergency department (baseline) visit. We reassessed participant's substance use and clinical symptoms 2, 8, and 12 weeks posttrauma. Latent class mixture modeling determined alcohol and cannabis use trajectories in the sample. Changes in PTSD and depression symptoms were assessed across alcohol and cannabis use trajectories via a mixed-model repeated-measures analysis of variance.
ResultsThree trajectory classes (low, high, increasing use) provided the best model fit for alcohol and cannabis use. The low alcohol use class exhibited lower PTSD symptoms at baseline than the high use class; the low cannabis use class exhibited lower PTSD and depression symptoms at baseline than the high and increasing use classes; these symptoms greatly increased at week 8 and declined at week 12. Participants who already use alcohol and cannabis exhibited greater PTSD and depression symptoms at baseline that increased at week 8 with a decrease in symptoms at week 12.
ConclusionsOur findings suggest that alcohol and cannabis use trajectories are associated with the intensity of posttrauma psychopathology. These findings could potentially inform the timing of therapeutic strategies.
Derivation and validation of risk prediction for posttraumatic stress symptoms following trauma exposure
- Raphael Kim, Tina Lin, Gehao Pang, Yufeng Liu, Andrew S. Tungate, Phyllis L. Hendry, Michael C. Kurz, David A. Peak, Jeffrey Jones, Niels K. Rathlev, Robert A. Swor, Robert Domeier, Marc-Anthony Velilla, Christopher Lewandowski, Elizabeth Datner, Claire Pearson, David Lee, Patricia M. Mitchell, Samuel A. McLean, Sarah D. Linnstaedt
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- Journal:
- Psychological Medicine / Volume 53 / Issue 11 / August 2023
- Published online by Cambridge University Press:
- 01 July 2022, pp. 4952-4961
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Background
Posttraumatic stress symptoms (PTSS) are common following traumatic stress exposure (TSE). Identification of individuals with PTSS risk in the early aftermath of TSE is important to enable targeted administration of preventive interventions. In this study, we used baseline survey data from two prospective cohort studies to identify the most influential predictors of substantial PTSS.
MethodsSelf-identifying black and white American women and men (n = 1546) presenting to one of 16 emergency departments (EDs) within 24 h of motor vehicle collision (MVC) TSE were enrolled. Individuals with substantial PTSS (⩾33, Impact of Events Scale – Revised) 6 months after MVC were identified via follow-up questionnaire. Sociodemographic, pain, general health, event, and psychological/cognitive characteristics were collected in the ED and used in prediction modeling. Ensemble learning methods and Monte Carlo cross-validation were used for feature selection and to determine prediction accuracy. External validation was performed on a hold-out sample (30% of total sample).
ResultsTwenty-five percent (n = 394) of individuals reported PTSS 6 months following MVC. Regularized linear regression was the top performing learning method. The top 30 factors together showed good reliability in predicting PTSS in the external sample (Area under the curve = 0.79 ± 0.002). Top predictors included acute pain severity, recovery expectations, socioeconomic status, self-reported race, and psychological symptoms.
ConclusionsThese analyses add to a growing literature indicating that influential predictors of PTSS can be identified and risk for future PTSS estimated from characteristics easily available/assessable at the time of ED presentation following TSE.
The Hierarchical Taxonomy of Psychopathology (HiTOP) in psychiatric practice and research
- Roman Kotov, David C. Cicero, Christopher C. Conway, Colin G. DeYoung, Alexandre Dombrovski, Nicholas R. Eaton, Michael B. First, Miriam K. Forbes, Steven E. Hyman, Katherine G. Jonas, Robert F. Krueger, Robert D. Latzman, James J. Li, Brady D. Nelson, Darrel A. Regier, Craig Rodriguez-Seijas, Camilo J. Ruggero, Leonard J. Simms, Andrew E. Skodol, Irwin D. Waldman, Monika A. Waszczuk, David Watson, Thomas A. Widiger, Sylia Wilson, Aidan G. C. Wright
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- Psychological Medicine / Volume 52 / Issue 9 / July 2022
- Published online by Cambridge University Press:
- 02 June 2022, pp. 1666-1678
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The Hierarchical Taxonomy of Psychopathology (HiTOP) has emerged out of the quantitative approach to psychiatric nosology. This approach identifies psychopathology constructs based on patterns of co-variation among signs and symptoms. The initial HiTOP model, which was published in 2017, is based on a large literature that spans decades of research. HiTOP is a living model that undergoes revision as new data become available. Here we discuss advantages and practical considerations of using this system in psychiatric practice and research. We especially highlight limitations of HiTOP and ongoing efforts to address them. We describe differences and similarities between HiTOP and existing diagnostic systems. Next, we review the types of evidence that informed development of HiTOP, including populations in which it has been studied and data on its validity. The paper also describes how HiTOP can facilitate research on genetic and environmental causes of psychopathology as well as the search for neurobiologic mechanisms and novel treatments. Furthermore, we consider implications for public health programs and prevention of mental disorders. We also review data on clinical utility and illustrate clinical application of HiTOP. Importantly, the model is based on measures and practices that are already used widely in clinical settings. HiTOP offers a way to organize and formalize these techniques. This model already can contribute to progress in psychiatry and complement traditional nosologies. Moreover, HiTOP seeks to facilitate research on linkages between phenotypes and biological processes, which may enable construction of a system that encompasses both biomarkers and precise clinical description.
Real-world clinical and cost-effectiveness of community clozapine initiation: mirror cohort study
- Emma Butler, Toby Pillinger, Kirsten Brown, Faith Borgan, Alice Bowen, Katherine Beck, Enrico D'Ambrosio, Lisa Donaldson, Sameer Jauhar, Stephen Kaar, Tiago Reis Marques, Robert A. McCutcheon, Maria Rogdaki, Fiona Gaughran, James MacCabe, Rosalind Ramsay, David Taylor, Paul McCrone, Alice Egerton, Oliver D. Howes
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- Journal:
- The British Journal of Psychiatry / Volume 221 / Issue 6 / December 2022
- Published online by Cambridge University Press:
- 19 April 2022, pp. 740-747
- Print publication:
- December 2022
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Background
Clozapine is the only drug licensed for treatment-resistant schizophrenia (TRS) but the real-world clinical and cost-effectiveness of community initiation of clozapine is unclear.
AimsThe aim was to assess the feasibility and cost-effectiveness of community initiation of clozapine.
MethodThis was a naturalistic study of community patients recommended for clozapine treatment.
ResultsOf 158 patients recommended for clozapine treatment, 88 (56%) patients agreed to clozapine initiation and, of these, 58 (66%) were successfully established on clozapine. The success rate for community initiation was 65.4%; which was not significantly different from that for in-patient initiation (58.82%, χ2(1,88) = 0.47, P = 0.49). Following clozapine initiation, there was a significant reduction in median out-patient visits over 1 year (from 24.00 (interquartile range (IQR) = 14.00–41.00) to 13.00 visits (IQR = 5.00–24.00), P < 0.001), and 2 years (from 47.50 visits (IQR = 24.75–71.00) to 22.00 (IQR = 11.00–42.00), P < 0.001), and a 74.71% decrease in psychiatric hospital bed days (z = −2.50, P = 0.01). Service-use costs decreased (1 year: –£963/patient (P < 0.001); 2 years: –£1598.10/patient (P < 0.001). Subanalyses for community-only initiation also showed significant cost reductions (1 year: –£827.40/patient (P < 0.001); 2 year: –£1668.50/patient (P < 0.001) relative to costs prior to starting clozapine. Relative to before initiation, symptom severity was improved in patients taking clozapine at discharge (median Positive and Negative Syndrome Scale total score: initial visit: 80 (IQR = 71.00–104.00); discharge visit 50.5 (IQR = 44.75–75.00), P < 0.001) and at 2 year follow-up (Health of Nation Outcome Scales total score median initial visit: 13.00 (IQR = 9.00–15.00); 2 year follow-up: 8.00 (IQR = 3.00–13.00), P = 0.023).
ConclusionsThese findings indicate that community initiation of clozapine is feasible and is associated with significant reductions in costs, service use and symptom severity.