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Medically unexplained symptoms otherwise referred to as persistent physical symptoms (PPS) are debilitating to patients. As many specific PPS syndromes share common behavioural, cognitive, and affective influences, transdiagnostic treatments might be effective for this patient group. We evaluated the clinical efficacy and cost-effectiveness of a therapist-delivered, transdiagnostic cognitive behavioural intervention (TDT-CBT) plus (+) standard medical care (SMC) v. SMC alone for the treatment of patients with PPS in secondary medical care.
A two-arm randomised controlled trial, with measurements taken at baseline and at 9, 20, 40- and 52-weeks post randomisation. The primary outcome measure was the Work and Social Adjustment Scale (WSAS) at 52 weeks. Secondary outcomes included mood (PHQ-9 and GAD-7), symptom severity (PHQ-15), global measure of change (CGI), and the Persistent Physical Symptoms Questionnaire (PPSQ).
We randomised 324 patients and 74% were followed up at 52 weeks. The difference between groups was not statistically significant for the primary outcome (WSAS at 52 weeks: estimated difference −1.48 points, 95% confidence interval from −3.44 to 0.48, p = 0.139). However, the results indicated that some secondary outcomes had a treatment effect in favour of TDT-CBT + SMC with three outcomes showing a statistically significant difference between groups. These were WSAS at 20 weeks (p = 0.016) at the end of treatment and the PHQ-15 (p = 0.013) and CGI at 52 weeks (p = 0.011).
We have preliminary evidence that TDT-CBT + SMC may be helpful for people with a range of PPS. However, further study is required to maximise or maintain effects seen at end of treatment.
Regionalizing pre-colonial Africa aids in the collection and interpretation of primary sources as data for further analysis. This article includes a map with six broad regions and 34 sub-regions, which form a controlled vocabulary within which researchers may geographically organize and classify disparate pieces of information related to Africa’s past. In computational terms, the proposed African regions serve as data containers in order to consolidate, link, and disseminate research among a growing trend in digital humanities projects related to the history of the African diasporas before c. 1900. Our naming of regions aims to avoid terminologies derived from European slave traders, colonialism, and modern-day countries.
Memory symptoms and objective impairment are common in HIV disease and are associated with disability. A paradoxical issue is that objective episodic memory failures can interfere with accurate recall of memory symptoms. The present study assessed whether responses on a self-report scale of memory symptoms demonstrate measurement invariance in persons with and without objective HIV-associated memory impairment.
In total, 505 persons with HIV completed the Prospective and Retrospective Memory Questionnaire (PRMQ). Objective memory impairment (n = 141) was determined using a 1-SD cutoff on clinical tests of episodic memory. PRMQ measurement invariance was assessed by confirmatory factor analyses examining a one-factor model with increasing cross-group equality constraints imposed on factor loadings and item thresholds (i.e., configural, weak, and strong invariance).
Configural model fit indicated that identical items measured a one-factor model for both groups. Comparison to the weak model indicated that factor loadings were equivalent across groups. However, there was evidence of partial strong invariance, with two PRMQ item thresholds differing across memory impairment groups. Post hoc analyses using a 1.5-SD memory impairment cutoff (n = 77) revealed both partial weak and partial strong invariance, such that PRMQ item loadings differed across memory groups for three items.
The PRMQ demonstrated a robust factor structure among persons with and without objective HIV-associated memory impairment. However, on select PRMQ items, individuals with memory impairment reported observed scores that were relatively higher than their latent score, while items were more strongly associated with the memory factor in a group with greater memory impairment.
Adolescent risk for self-injurious thoughts and behaviors (STBs) involves disturbance across multiple systems (e.g., affective valence, arousal regulatory, cognitive and social processes). However, research integrating information across these systems is lacking. Utilizing a multiple-levels-of-analysis approach, this person-centered study identified psychobiological stress response profiles and linked them to cognitive processes, interpersonal behaviors, and STBs. At baseline, adolescent girls (N = 241, Mage = 14.68 years, Range = 12–17) at risk for STBs completed the Trier Social Stress Test (TSST), questionnaires, and STB interviews. Positive affect (PA), negative affect (NA), and salivary cortisol (SC) were assessed before and after the TSST. STBs were assessed again during 3, 6, and 9 month follow-up interviews. Multitrajectory modeling of girls’ PA, NA, and SC revealed four profiles, which were compared on cognitive and behavioral correlates as well as STB outcomes. Relative to normative, girls in the affective distress, hyperresponsive, and hyporesponsive subgroups were more likely to report negative cognitive style (all three groups) and excessive reassurance seeking (hyporesponsive only) at baseline, as well as nonsuicidal self-injury (all three groups) and suicidal ideation and attempt (hyporesponsive only) at follow-up. Girls’ close friendship characteristics moderated several profile–STB links. A synthesis of the findings is presented alongside implications for person-centered tailoring of intervention efforts.
Systemic ventricular end-diastolic pressure is important in patients with single ventricle heart disease. Predictors of an elevated systemic ventricular end-diastolic pressure prior to bidirectional Glenn operation have been incompletely identified.
All patients who underwent bidirectional Glenn operation operation at our centre between January 2007 and March 2017 were retrospectively identified and patient variables were extracted. For patients who had undergone Fontan operation at the time of this study, post-Fontan patient variables were also extracted.
One-hundred patients were included with a median age at pre-bidirectional Glenn operation catheterisation of 4.5 months. In total, 71 (71%) patients had a systemic right ventricle. At the pre-bidirectional Glenn operation catheterisation, the mean systemic ventricular end-diastolic pressure was higher amongst those with systemic right ventricle compared to left ventricle (9.1 mmHg ± 2.1 versus 7.7 ± 2.7 mmHg, p < 0.01). On univariate analysis, pre-bidirectional Glenn operation systemic ventricular end-diastolic pressure was positively associated with the presence of a systemic right ventricle (p < 0.01), history of recoarctation (p = 0.03), history of Norwood operation (p = 0.04), and ventricular systolic pressure (p < 0.01). On multivariate analysis, systemic ventricular end-diastolic pressure was positively associated with the presence of a systemic right ventricle (p < 0.01) and ventricular systolic pressure (p < 0.01). Amongst those who had undergone Fontan operation at the time of study (n = 49), those with a higher pre-bidirectional Glenn operation systemic ventricular end-diastolic pressure were more likely to have experienced death, transplantation, or listed for transplantation (p = 0.02) and more likely to have had heart failure symptoms (p = 0.04) at a mean time from Fontan of 5.2 years ± 1.3.
In patients undergoing bidirectional Glenn operation operation, the volume-loaded, pre-bidirectional Glenn operation state may expose diastolic dysfunction that has prognostic value.
The occurrence of early childhood adversity is strongly linked to later self-harm, but there is poor understanding of how this distal risk factor might influence later behaviours. One possible mechanism is through an earlier onset of puberty in children exposed to adversity, since early puberty is associated with an increased risk of adolescent self-harm. We investigated whether early pubertal timing mediates the association between childhood adversity and later self-harm.
Participants were 6698 young people from a UK population-based birth cohort (ALSPAC). We measured exposure to nine types of adversity from 0 to 9 years old, and self-harm when participants were aged 16 and 21 years. Pubertal timing measures were age at peak height velocity (aPHV – males and females) and age at menarche (AAM). We used generalised structural equation modelling for analyses.
For every additional type of adversity; participants had an average 12–14% increased risk of self-harm by 16. Relative risk (RR) estimates were stronger for direct effects when outcomes were self-harm with suicidal intent. There was no evidence that earlier pubertal timing mediated the association between adversity and self-harm [indirect effect RR 1.00, 95% confidence interval (CI) 1.00–1.00 for aPHV and RR 1.00, 95% CI 1.00–1.01 for AAM].
A cumulative measure of exposure to multiple types of adversity does not confer an increased risk of self-harm via early pubertal timing, however both childhood adversity and early puberty are risk factors for later self-harm. Research identifying mechanisms underlying the link between childhood adversity and later self-harm is needed to inform interventions.
ABSTRACT IMPACT: The Independent Investigator Incubator program provides 1:1 mentoring from ‘super-mentors’ to enhance junior faculty careers in research. OBJECTIVES/GOALS: In 2014, the Indiana University School of Medicine (IUSM) in collaboration with the Indiana CTSI established the Independent Investigator Incubator (I3) Program. The I3 Program is designed to provide 1:1 mentoring for new research faculty during the crucial early years of their careers. Our goal is to provide an overview of the I3 design and 5-year data. METHODS/STUDY POPULATION: The I3 Program employs a resource-sharing, centralized design that provides concentrated 1:1 mentorship from a senior faculty ‘super mentor’ as well as other resources, such as grant writing support. Unlike many mentorship programs, I3 mentors closely interact with the mentees within the School and are compensated for their efforts (5% full-time equivalency per mentee, max of 15%). The number of ‘super mentors’ has grown from 6 to 15 faculty over 5 years, and mentors typically serve 4 to 5 mentees. Mentee applications are accepted on a rolling enrollment basis. The I3 mentees represent a diverse group based on sex, ethnicity, terminal degree, academic track, and discipline. Mentors and mentees have annual reviews through the program. RESULTS/ANTICIPATED RESULTS: In five years, 110 mentees have enrolled in the I3 program. Upon entering, 53% had no external funding, 28% had internal funding, 12% had K-awards, 7% had R03/R21 awards. Over the first five years, 75% have received extramural funding. The median funding was $340,000 with nearly a third of mentees securing grants > 1 million in direct costs. For mentees who joined the program in its first three years (n=59), the average time to a notable extramural grant (defined as a NIH or foundation grant >$300K direct costs) was 2.2 years (median - 2.6 years). Nearly all mentees were satisfied with their mentor pairing based on the mentor’s ‘availability’ and ‘valuable feedback,’ and all mentees wanted the mentoring relationship to continue DISCUSSION/SIGNIFICANCE OF FINDINGS: Since 2014, the I3 Program has had a positive impact on the careers of junior faculty at IUSM as determined by faculty satisfaction and funding metrics. Future focus areas will include developing criteria/models for graduating from the program to balance fiscal sustainability with mentee needs during their transition to mid-career.
It is uncertain if long-term levels of low-density lipoprotein-cholesterol (LDL-C) affect cognition in middle age. We examined the association of LDL-C levels over 25 years with cognitive function in a prospective cohort of black and white US adults.
Lipids were measured at baseline (1985–1986; age: 18–30 years) and at serial examinations conducted over 25 years. Time-averaged cumulative LDL-C was calculated using the area under the curve for 3,328 participants with ≥3 LDL-C measurements and a cognitive function assessment. Cognitive function was assessed at the Year 25 examination with the Digit Symbol Substitution Test [DSST], Rey Auditory Visual Learning Test [RAVLT], and Stroop Test. A brain magnetic resonance imaging (MRI) sub-study (N = 707) was also completed at Year 25 to assess abnormal white matter tissue volume (AWMV) and gray matter cerebral blood flow volume (GM-CBFV) as secondary outcomes.
There were 15.6%, 32.9%, 28.9%, and 22.6% participants with time-averaged cumulative LDL-C <100 mg/dL, 101–129 mg/dL, 130–159 mg/dL, and ≥160 mg/dL, respectively. Standardized differences in all cognitive function test scores ranged from 0.16 SD lower to 0.09 SD higher across time-averaged LDL-C categories in comparison to those with LDL-C < 100 mg/dL. After covariate adjustment, participants with higher versus lower time-averaged LDL-C had a lower RAVLT score (p-trend = 0.02) but no differences were present for DSST, Stroop Test, AWMV, or GM-CBFV.
Cumulative LDL-C was associated with small differences in memory, as assessed by RAVLT scores, but not other cognitive or brain MRI measures over 25 years of follow-up.
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.
The goal of this study was to assess the utility of participatory needs assessment processes for continuous improvement of developing clinical and translational research (CTR) networks. Our approach expanded on evaluation strategies for CTR networks, centers, and institutes, which often survey stakeholders to identify infrastructure or resource needs, using the case example of the Great Plains IDeA-CTR Network. Our 4-stage approach (i.e., pre-assessment, data collection, implementation of needs assessment derived actions, monitoring of action plan) included a member survey (n = 357) and five subsequent small group sessions (n = 75 participants) to better characterize needs identified in the survey and to provide actionable recommendations. This participatory, mixed-methods needs assessment and strategic action planning process yielded 11 inter-related recommendations. These recommendations were presented to the CTR steering committee as inputs to develop detailed, prioritized action plans. Preliminary evaluation shows progress towards improved program capacity and effectiveness of the network to respond to member needs. The participatory, mixed-methods needs assessment and strategic planning process allowed a wide range of stakeholders to contribute to the development of actionable recommendations for network improvement, in line with the principles of team science.
Host–microbial co-metabolism products are being increasingly recognised to play important roles in physiological processes. However, studies undertaking a comprehensive approach to consider host–microbial metabolic relationships remain scarce. Metabolomic analysis yielding detailed information regarding metabolites found in a given biological compartment holds promise for such an approach. This work aimed to explore the associations between host plasma metabolomic signatures and gut microbiota composition in healthy adults of the Milieu Intérieur study. For 846 subjects, gut microbiota composition was profiled through sequencing of the 16S rRNA gene in stools. Metabolomic signatures were generated through proton NMR analysis of plasma. The associations between metabolomic variables and α- and β-diversity indexes and relative taxa abundances were tested using multi-adjusted partial Spearman correlations, permutational ANOVA and multivariate associations with linear models, respectively. A multiple testing correction was applied (Benjamini–Hochberg, 10 % false discovery rate). Microbial richness was negatively associated with lipid-related signals and positively associated with amino acids, choline, creatinine, glucose and citrate (−0·133 ≤ Spearman’s ρ ≤ 0·126). Specific associations between metabolomic signals and abundances of taxa were detected (twenty-five at the genus level and nineteen at the species level): notably, numerous associations were observed for creatinine (positively associated with eleven species and negatively associated with Faecalibacterium prausnitzii). This large-scale population-based study highlights metabolites associated with gut microbial features and provides new insights into the understanding of complex host–gut microbiota metabolic relationships. In particular, our results support the implication of a ‘gut–kidney axis’. More studies providing a detailed exploration of these complex interactions and their implications for host health are needed.
The COVID-19 pandemic and mitigation measures are likely to have a marked effect on mental health. It is important to use longitudinal data to improve inferences.
To quantify the prevalence of depression, anxiety and mental well-being before and during the COVID-19 pandemic. Also, to identify groups at risk of depression and/or anxiety during the pandemic.
Data were from the Avon Longitudinal Study of Parents and Children (ALSPAC) index generation (n = 2850, mean age 28 years) and parent generation (n = 3720, mean age 59 years), and Generation Scotland (n = 4233, mean age 59 years). Depression was measured with the Short Mood and Feelings Questionnaire in ALSPAC and the Patient Health Questionnaire-9 in Generation Scotland. Anxiety and mental well-being were measured with the Generalised Anxiety Disorder Assessment-7 and the Short Warwick Edinburgh Mental Wellbeing Scale.
Depression during the pandemic was similar to pre-pandemic levels in the ALSPAC index generation, but those experiencing anxiety had almost doubled, at 24% (95% CI 23–26%) compared with a pre-pandemic level of 13% (95% CI 12–14%). In both studies, anxiety and depression during the pandemic was greater in younger members, women, those with pre-existing mental/physical health conditions and individuals in socioeconomic adversity, even when controlling for pre-pandemic anxiety and depression.
These results provide evidence for increased anxiety in young people that is coincident with the pandemic. Specific groups are at elevated risk of depression and anxiety during the COVID-19 pandemic. This is important for planning current mental health provisions and for long-term impact beyond this pandemic.
This work investigated the photophysical pathways for light absorption, charge generation, and charge separation in donor–acceptor nanoparticle blends of poly(3-hexylthiophene) and indene-C60-bisadduct. Optical modeling combined with steady-state and time-resolved optoelectronic characterization revealed that the nanoparticle blends experience a photocurrent limited to 60% of a bulk solution mixture. This discrepancy resulted from imperfect free charge generation inside the nanoparticles. High-resolution transmission electron microscopy and chemically resolved X-ray mapping showed that enhanced miscibility of materials did improve the donor–acceptor blending at the center of the nanoparticles; however, a residual shell of almost pure donor still restricted energy generation from these nanoparticles.
Background: Since 2015, the CDC has supported the development and implementation of healthcare-associated infection (HAI) surveillance in resource-limited settings through technical support of case definitions and methods that are feasible with existing surveillance capacity and integration with clinical care to maximize sustainability and data use for action. Methods: Surveillance initiatives included facility-level implementation programs in Kenya, Sierra Leone, Thailand, and Georgia; larger national or regional network-level projects in India and Vietnam were also supported. For assessment and planning, surveillance capacities were grouped into 3 domains: staff, informatics, and diagnostic capacities. Based on these capacities, simplified case definitions surveillance methodologies were devised to balance resources and effort with the anticipated value and use of findings. Results: There was broad understanding of the importance of HAI surveillance; however, the required resources and other challenges (eg, training, staffing, quality of available data) were underappreciated. Staff capacities were often influenced by a lack of dedicated surveillance staff and limited experience in systematic data collection and analysis. Informatics capacities were generally limited by the lack of digital data management, nonstandardized clinical data collection and storage, and the inability to assign and maintain unique patient identifiers. We found that capacity for diagnostics, a critical component of traditional HAI surveillance systems, was limited by its availability, frequency of use, and inconsistent rationale in clinical care. We found that successful surveillance strategies were generally simple, matched existing capacities, and targeted specific HAI priorities identified by clinical teams. For example, in Kenya and Sierra Leone, participating facilities established, with minimal external support, simplified SSI surveillance among post–caesarean-delivery patients. These initiatives improved integration of surveillance with clinical care through encouraging participation of the clinical team in surveillance and planning. Furthermore, these models directly linked surveillance activities to improved patient care (eg, combined clinical checklists with surveillance data collection forms). Discussion: In resource-limited settings, the local cost and effort required to establish and sustain the necessary infrastructure for HAI surveillance can be substantial. Establishing actionable and sustainable HAI surveillance can be achieved through simplifying HAI surveillance to match existing capacities and can result in valuable surveillance programs, even in very resource-limited settings.
Background: As of July 1, 2019, ~18% of all cases in the Ebola virus disease (EVD) outbreak in the Democratic Republic of Congo (DRC) were healthcare-associated (ie, nosocomial) infections (HAIs) and healthcare worker (HCW) infections. Although progress has been achieved, gaps remained in infection prevention and control (IPC), specifically, a need to reinforce standardized, evidence-based IPC practices to effectively address HAIs. The Ministry of Health (MOH), in collaboration with partners, developed an IPC tool kit consisting of >70 documents (ie, terms of reference, standard operating procedures, training modules, etc) to improve HCW IPC knowledge and practices at healthcare facilities among staff. The tool kit incorporated international IPC standards, DRC-specific experiences, and best practices. Thus, it serves as a technical and operational package, covering general guidance (standard precautions) and EVD specific issues. Methods: A decentralized rollout approach was used to disseminate the tool kit content at the various health-system levels over several months. Initially, national-level training of trainers was held, followed by subnational-level training of IPC supervisors and key IPC implementers, and lastly, training of healthcare facility (HCF) IPC focal persons. The 5-day training adhered to the MOH standard of 60% theory and 40% practice. Participants completed evaluations before and after training; changes in knowledge between the pre- and posttraining tests were analyzed and the results of the statistical tests were reported (P < .05 was considered statistically significant). Results: In total, 294 IPC supervisors were trained across 7 subnational commissions. Data were analyzed for 138 participants. Participants were 60.9% IPC supervisors, 8% WASH supervisors, and 31% others. MOH representation was 52.9% The average results before the test were 66% (19.8 of 30), the average posttest results were 72% (21.6 of 30)—a significant improvement. The worst-performing pretest IPC domain was IPC approach, and facility closure was the worst performing for posttest. As of November 11, 15.7% of all cases were HAIs. Conclusions: The IPC training program initiated during an outbreak can increase knowledge and potentially improve practices and confidence. An association with the downward HAI trend is yet to be validated. The MOH anticipates that this tool kit will be the go-to resource for future Ebola outbreaks and that it will be incorporated into the preservice medical curriculum to ensure a resilient heath system.
The dynamics of choice and self-selection are central features of politics but absent from most experimental designs. We show how designs that incorporate choice, by allowing some subjects the option to receive or avoid treatment, can be extended by randomizing conditional on subjects’ treatment choices to answer further questions of interest while preserving statistical power. We apply this design to study how the gender of messengers for the #MeToo social movement conditions who receives the movement’s message and how they respond. Our results, from both convenience and nationally representative samples, suggest that #MeToo movement’s message reaches a wide audience with the intended effect. The potential for backlash in response to the message appears limited but more likely when this message is delivered by a woman.
This article reviews the advancements and prospects of liquid cell transmission electron microscopy (TEM) imaging and analysis methods in understanding the nucleation, growth, etching, and assembly dynamics of nanocrystals. The bonding of atoms into nanoscale crystallites produces materials with nonadditive properties unique to their size and geometry. The recent application of in situ liquid cell TEM to nanocrystal development has initiated a paradigm shift, (1) from trial-and-error synthesis to a mechanistic understanding of the “synthetic reactions” responsible for the emergence of crystallites from a disordered soup of reactive species (e.g., ions, atoms, molecules) and shape-defined growth or etching; and (2) from post-processing characterization of the nanocrystals’ superlattice assemblies to in situ imaging and mapping of the fundamental interactions and energy landscape governing their collective phase behaviors. Imaging nanocrystal formation and assembly processes on the single-particle level in solution immediately impacts many existing fields, including materials science, nanochemistry, colloidal science, biology, environmental science, electrochemistry, mineralization, soft condensed-matter physics, and device fabrication.