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Comprehensive cognitive remediation improves cognitive and functional outcomes in people with serious mental illness, but the specific components required for effective programs are uncertain. The most common methods to improve cognition are facilitated computerized cognitive training with coaching and teaching cognitive self-management strategies. We compared these methods by dismantling the Thinking Skills for Work program, a comprehensive, validated cognitive remediation program that incorporates both strategies.
Methods
In a randomized controlled trial we assigned 203 unemployed people with serious mental illness in supported employment programs at two mental health agencies to receive either the full Thinking Skills for Work (TSW) program, which included computerized cognitive training (based on Cogpack software), or the program with cognitive self-management (CSM) but no computer training. Outcomes included employment, cognition, and mental health over 2 years. To benchmark outcomes, we also examined competitive work outcomes in a similar prior trial comparing the TSW program with supported employment only.
Results
The TSW and CSM groups improved significantly on all outcomes, but there were no differences between the groups. Competitive work outcomes for both groups resembled those of the TSW program in a prior trial and were better than the supported employment-only group in that study, suggesting that participants in both groups benefited from cognitive remediation.
Conclusions
Providing facilitated computerized cognitive training improved neither employment nor cognitive outcomes beyond teaching cognitive self-management strategies in people receiving supported employment. Computerized cognitive training may not be necessary for cognitive remediation programs to improve cognitive and functional outcomes.
Single ventricle patients undergoing comprehensive stage II palliation have higher incidence of severe acute kidney injury compared to the bidirectional Glenn palliation; however, the optimal method for early detection remains unknown. Several urinary biomarkers are increased in other patient populations with postoperative kidney injury. We explored the kinetics of these biomarkers in this high-risk population.
We conducted prospective, observational study of 20 patients with single ventricle physiology who underwent second stage palliation (July 2019–December 2021). Acute kidney injury was defined by Kidney Diseases Improving Global Guidelines, based on peak serum creatinine value and urine output. Urine samples were collected pre-operatively and at 1-, 6-, and 24-hours post-surgery. Urinary biomarkers neutrophil gelatinase-associated lipocalin, interleukin-18, liver fatty acid-binding protein, kidney injury molecule-1, and cystatin C were quantified by enzyme linked immunosorbent assay, normalised to urinary creatinine, and shown as median [interquartile range].
Four patients (50%) undergoing comprehensive stage II and 1 patient (8%) undergoing bidirectional Glenn palliation developed stage ≥ 2 acute kidney injury. Comprehensive stage II compared to bidirectional Glenn group had higher median neutrophil gelatinase-associated lipocalin (1769 [1309–1961] versus 91[18–1120] ng/mg) and liver fatty acid-binding protein (12,836 [5016–19798] versus 1272 [220–5172] ng/mg) that peaked 1-hour post-surgery. Kidney injury molecule-1 was significantly greater at 1-, 6-, and 24-hours (greatest) post-surgery in comprehensive stage II than bidirectional Glenn (24h: 11[9–23]) versus 2 [1–6] ng/mg).
Elevated urinary neutrophil gelatinase-associated lipocalin, liver fatty acid-binding protein, and kidney injury molecule-1 may be useful biomarkers for early detection of acute kidney injury in children following comprehensive stage II palliation.
Following the recent report of strongyloidiasis caused by Strongyloides fuelleborni within a semi-captive colony of baboons in a UK safari park, we investigated the genetic relationships of this isolate with other Strongyloides isolates across the world. Whole-genome sequencing data were generated with later phylogenetic analysis of mitochondrial (mt) cytochrome oxidase subunit 1 (cox1) and nuclear ribosomal 18S sequences against 300 published Strongyloides reference genotypes. The putative African origin of the UK S. fuelleborni was confirmed and full-length mt genome sequences were assembled to facilitate a more detailed phylogenetic analysis of 14 mt coding regions against all available Strongyloides species. Our analyses demonstrated that the UK isolate represented a novel African lineage not previously described. Additional complete mt genomes were assembled for several individual UK safari park worms to reveal a slightly altered mt genome gene arrangement, allowing clear separation from Asian S. fuelleborni. Furthermore, these UK worms possessed expanded intergenic regions of unknown function that increase their mt genome size to approximately 24 kilobases (kb) as compared with some 16 kb for Asian S. fuelleborni; this may have arisen from unique populational founder and genetic drift effects set within the peculiar mixed species baboon and drill ancestry of this semi-captive primate colony. A maximum likelihood phylogeny constructed from 14 mt coding regions also supported an evolutionary distinction between Asian and African S. fuelleborni.
The Department of Veterans Affairs (VA) does not have system-wide standardized policies or procedures for ultraviolet-C (UV-C) use. Qualitative researchers performed content analysis of VAV UV-C guidance documents. We observed that lack of specificity and uniformity across guidance documents is a potential barrier to UV-C implementation and future quality control.
In many areas experiencing severe impacts from climate change, it is not the state, but rather rebel groups who wield authority over populations. Rebels are often engaged in responding and adapting to the risks and impacts of climate change as part of their local governance efforts; however, a systematic consideration of the activities and implications has been lacking. This Element looks at a set of behaviors we call “rebel environmental governance” (REG+). This refers to rebel actions aimed at protecting or managing the natural environment to affect civilian welfare amidst increasing pressures of climate change. A framework is advanced for understanding why rebels engage in environmental governance and the implications for security and climate governance. The Element brings rebel organizations into the conversation on climate change, highlighting their role in areas where state power is contested, weak, or absent. This title is also available as Open Access on Cambridge Core.
Nick Cunningham of Oil Price.com has written a timely article summarizing the World Cup's gargantuan energy consumption and carbon footprint. The World Cup soccer competition underway in Brazil is held quadrennially, and is apparently the most watched sporting event of all. This year's games are to culminate in the July 17 finale in Rio de Janeiro. The games appear likely to set both a viewing record as well as a record for energy consumption and carbon emissions. An estimated 900 million watched the opening ceremonies of London's 2012 Olympics. But the World Cup governing body FIFA's research suggests 909.6 million viewers watched at least a minute of the 2010 World Cup, and Cunningham tells us there may be as many as 3 billion viewers for this event in 2014. Moreover, broadcasting's technical innovations are proceeding apace. Ultra-high definition broadcasts (expected to become standard in 2017) are being used for three of this year's matches, taking advantage of the event's eyeball-dense economics. The official match ball is the Adidas Brazuca, one of which has its own twitter account and micro-cameras studding its surface.
At first glance, the handful of Tokyo rightists who created a furor about a graphic scene of the Nanjing Massacre in two September issues of the popular manga magazine Young Jump Weekly are a surprisingly tolerant lot. They restricted their complaint to technical issues in “My Country is Burning” (Kuni ga moeru!) by Motomiya Hiroshi, the only remotely educational series in a popular weekly comic book, and ignored 400 pages of gratuitous sex, violence, scatology and gore that dominates this illustrated publication with a reported circulation of 2 million.
Clashing views about Thailand's future are being played out on the streets of Bangkok, taking the form of forceful demonstrations, contentious commemorations and populist grandstanding by red shirted and yellow shirted rivals. Behind the searing rhetoric and policy clashes are battles of personality, in which patron-client links coalesce, regroup and solidify, rewarding loyalty with a top-down sharing of power and spoils.
What follows is an account of a return visit to Tiananmen Square in commemoration of the 25th anniversary of the peaceful demonstrations and violent crackdown that I witnessed in Beijing in 1989.
Initially I had planned to go to Hong Kong, as I had been invited to join the well-publicized commemoration in Victoria Park where the people of Hong Kong have held a candlelight vigil for the lost souls and lost dreams of 1989 on an annual basis for a quarter of a century now. In past years I have marched with the conscientious objectors of Hong Kong, lit candles in the warm tropical air and drawn strength from the distant but principled and persistent expression of solidarity with the uprising at Tiananmen.
The sniper shooting of Seh Daeng, Maj. Gen. Khattiya Sawasdipol, on May 13, 2010 by an unknown assailant while chatting with foreign reporters has brought to rupture the standoff between Reds and Yellows in the heart of Bangkok and signals a new stage in the movement and its repression. Seh Daeng, whose nickname means “red commander”, was the reddest of the red shirts. His daughter, who sat at his bedside in the hospital until he succumbed to his grievous wounds on May 17, 2010, has been a staunch supporter of the yellow shirts, illustrative of the convoluted politics of the era. To better put in context the convoluted color-coded politics of the present day, and to identify some of the key heroes and villains and historic reference points being talked about on both sides of the barricades in Bangkok, a brief review of Thai political activism over the years will follow.
“Ladies and gentlemen, your attention please. We have just experienced an earthquake. Please move away from the buildings to an open area…We will provide more detailed information as soon as possible…”
The polite but authoritative “we” was the voice of the Tokyo DisneySea theme park in this instance, but similar, oddly reassuring warnings of peril were being echoed across Japan, mostly following the lead of television broadcaster NHK.
Objectives/Goals: One in 14 individuals have a substance use disorder (SUD). We suggest that a trait of poor impulse control, or high impulsivity, may predict relapse risk. We explore how changes in brain structure linked to decision-making and reward might drive high impulsivity, helping create a “biosignature” to identify those most at risk and guide treatment choices. Methods/Study Population: Male rats were phenotyped as high impulsive (HI) or low impulsive (LI) based on premature responses on the one-choice serial reaction time (1-CSRT) task. Rats then received an intracranial infusion of a retrograde virus (AAVr2) in the nucleus accumbens (NAc) to trace corticoaccumbens neurons back to the medial prefrontal cortex (mPFC). After impulsivity phenotyping (ITI8), another cohort of animals performed cocaine self-administration followed by 30 days of abstinence. Cue reactivity, a measure of relapse-like behaviors, was performed on abstinence day 30. Analyses of microtubule-associated protein 2 (MAP2), a cytoskeletal marker of dendrites, spines, and somas was performed with western blotting and fluorescent images of brain slices after phenotyping and cocaine abstinence. Results/Anticipated Results: HI rats made greater premature responses, a marker of impulsive action vs. LI rats at baseline (p Discussion/Significance of Impact: Poor inherent impulse control and drug cues heighten relapse risk. We found high impulsivity linked to brain structure differences and lower protein markers of synaptic (units supporting signaling) strengthening. Future investigations into brain-behavior links with impulsivity may further identify a SUD relapse vulnerability biosignature.
Objectives/Goals: The gut microbiome and its metabolites, such as short-chain fatty acids (SCFA), are dysregulated in rheumatoid arthritis (RA); however, the significance of this observation and its implications in pathogenesis and therapeutics is unclear. Here, we explore the role of the SCFA, butyrate, in treatment efficacy in new-onset rheumatoid arthritis. Methods/Study Population: We designed a proof-of-principle study to determine the effects of butyrate supplementation in new-onset RA (NORA) patients that fulfilled 2010 ACR/EULAR RA criteria. We evaluated the effects of methotrexate (MTX) plus butyrate in NORA (n = 17; 1 gm butyrate, 3 times daily) compared to MTX alone (n = 19) over 4 months. MTX responders were defined by a change in disease activity score (DAS)-28 ESR of > 1.8 at 4 months. Fecal samples were collected at baseline and followed up for 16s rRNA sequencing and metabolite quantification by 1H NMR spectroscopy. Unpaired-t, paired-t, Wilcox and Fisher’s exact test were performed as appropriate. Results/Anticipated Results: MTX responders in the MTX-only group had a higher concentration of fecal butyrate than nonresponders at baseline (p = 0.045). Fecal butyrate concentration decreased over time in treatment responders in MTX group (p = 0.05), whereas butyrate concentration remained similar in MTX/butyrate group. Prior to treatment, both MTX and MTX/butyrate groups demonstrated similar levels of gut bacterial alpha diversity (Shannon index), yet only the MTX/butyrate group demonstrated a significant increase in alpha diversity by 4 months (p = 0.022). LefSe analysis demonstrated increased abundances of Bacteroides, Clostridium, and Phascolarctobacterium in responders in the MTX/butyrate group by 4 months. Ten (52.6%) patients in MTX and 11 (64.7%) in MTX/butyrate group were considered MTX responders by 4 months (p = 0.516). Discussion/Significance of Impact: Butyrate supplementation increased gut microbial diversity in patients and led to increased abundance of Bacteroides, which has been implicated in efficacy of methotrexate, a first line medication in rheumatoid arthritis. Butyrate may have implications for the maximization of therapeutic effectiveness in rheumatoid arthritis.
Patients with Opioid Use Disorder (OUD) are prone to Multidrug-Resistant Organism (MDRO) colonization and infections, thus at risk for worse outcomes during critical illness. Understanding the prevalence and predictors of MDRO infections is essential to optimize interventions and treatments.
Design:
Retrospective cohort study.
Methods:
The study evaluated the prevalence of MDRO isolation among adults with OUD admitted to an intensive care unit (ICU) between January 1, 2018, and July 31, 2023. It included adults admitted to an ICU with bacterial infections and positive cultures obtained within 48 hours of admission. Demographics, clinical traits, and MDRO isolation rates were analyzed using descriptive statistics, univariate methods, and Least Absolute Shrinkage and Selection Operator (LASSO) regression.
Results:
MDRO isolation occurred in 178 of 790 patients (22.5%), with methicillin-resistant Staphylococcus aureus as the most frequently isolated organism. LASSO regression identified housing insecurity (OR: 1.79, 95% CI 1.09–2.93, P = .022), no receipt of medications for OUD treatment (OR: 1.56, 95% CI 1.06–2.29, P = .023), positive hepatitis C virus (HCV) status (OR: 2.19, 95% CI 1.19–4.03, P = .012), and intravenous antibiotic use in the prior 90 days (OR: 1.04 per 24 h, 95% CI 1.01–1.07, P = .007) as significant predictors of MDRO isolation.
Conclusions:
The study highlights a high prevalence of MDRO isolation in critically ill OUD patients admitted for infection-related issues with positive cultures obtained within 48 hours of admission, influenced by factors like housing insecurity, no receipt of medications for OUD treatment, HCV status, and prior antibiotic use.
The aim of this policy article is twofold: (i) to provide a summary and update of recent important policy developments, in particular relevant guidance on the use of real-world data/real-world evidence (RWD/RWE) by health technology assessment (HTA) bodies and (ii) to set out our policy recommendations on how the different elements of an “RWE framework” we have previously developed could support, further enhance and facilitate the use of RWE for HTA purposes and by HTA bodies and payers.
Methods
We undertook a targeted review and analysis of recent important policy developments. The aim was to build on our recommendations from previous work on the “RWE Framework,” and consider how the relevant tools from our Framework can further enhance and facilitate the use of RWE for HTA purposes and by HTA bodies/payers.
Results
We provide eight conditions that we argue would, in combination, constitute the optimal use and acceptance of RWD/RWE for HTA. We believe that, should the eight conditions hold, RWD/RWE would enable more efficient access to medicines and healthcare technologies for patients.
Conclusions
High-quality, fit-for-purpose RWD/RWE can and should be used more frequently in HTA. Multi-stakeholder and cross-geography collaborative partnerships are needed to align on best practices to optimize the evidence that needs to be generated to satisfy all stakeholders’ needs.
Humankind came to substances early. Poppy pods have been found with Neanderthal burials and spiritual and other group practices, still seen today but with millennia behind them, bear witness to the role of induced experiential change in human social evolution. Despite generations of history, the knowledge to unlock what mind-altering substances might do and the substrates through which they do it has only started to reveal itself within living memory through development of innovative investigative methods and an expanding cast of centrally acting compounds with clinical and laboratory potential.
A widening, if somewhat artificial, distinction has emerged where those who seek to modify brain systems with patients are considered psychopharmacologists, while those seeking to unravel mechanisms are considered neuropharmacologists. Expertise may differ, but the quest of clinician and basic scientist is the same, each benefitting from knowledge of the other.
A retrospective tour of the haunts and hideouts of the 1989 Tiananmen student uprising would not be complete without a visit to Beijing University, known simply as Beida. Arguably the most prestigious university in China, Beida has long been home to creative thinkers and intellectual ferment ever since the days a young Mao Zedong worked in its associated library and literati such as Hu Shih and Lu Xun graced its grounds.
In 1989 Beida was the fount of discussion and discontent that spread to other campuses. Among Beijing colleges, it was the most distant from Tiananmen, but the Beida contingent always seemed to show up first.