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The impact of chronic pain and opioid use on cognitive decline and mild cognitive impairment (MCI) is unclear. We investigated these associations in early older adulthood, considering different definitions of chronic pain.
Methods:
Men in the Vietnam Era Twin Study of Aging (VETSA; n = 1,042) underwent cognitive testing and medical history interviews at average ages 56, 62, and 68. Chronic pain was defined using pain intensity and interference ratings from the SF-36 over 2 or 3 waves (categorized as mild versus moderate-to-severe). Opioid use was determined by self-reported medication use. Amnestic and non-amnestic MCI were assessed using the Jak-Bondi approach. Mixed models and Cox proportional hazards models were used to assess associations of pain and opioid use with cognitive decline and risk for MCI.
Results:
Moderate-to-severe, but not mild, chronic pain intensity (β = −.10) and interference (β = −.23) were associated with greater declines in executive function. Moderate-to-severe chronic pain intensity (HR = 1.75) and interference (HR = 3.31) were associated with a higher risk of non-amnestic MCI. Opioid use was associated with a faster decline in verbal fluency (β = −.18) and a higher risk of amnestic MCI (HR = 1.99). There were no significant interactions between chronic pain and opioid use on cognitive decline or MCI risk (all p-values > .05).
Discussion:
Moderate-to-severe chronic pain intensity and interference related to executive function decline and greater risk of non-amnestic MCI; while opioid use related to verbal fluency decline and greater risk of amnestic MCI. Lowering chronic pain severity while reducing opioid exposure may help clinicians mitigate later cognitive decline and dementia risk.
Integrating scientific research across multiple disciplines to advance breakthroughs is at the heart of clinical-translational science (CTS); among competencies that have been identified as essential for progress, skillful communication is critical. Few tools are available to address the social dynamics of the multidimensional diversity characteristics of CTS. We created the “Building a Diverse Biomedical Workforce Through Communication Across Difference (CAD)” workshop intervention. Based on principles of intercultural communication, CAD taught novel situationally-based communication skills to dyads of near-peer mentors and their undergraduate mentees. This study reports on the effectiveness of the operative mechanisms employed in CAD workshops for helping participants navigate highly diverse research environments.
Methods:
Participant data were collected from multiple sources, including workshop artifacts as well as focus groups conducted post-workshop. Data were organized, individually coded, and then iteratively and collectively into pre-defined and emergent themes.
Results:
Responses indicated that the content and activities resonated strongly with participants and illuminated their understanding of challenges (both their own and others’) related to belonging, confidence, and connectedness to the research environment; several participants shared that they planned to use or had successfully used the skills. Focus group comments revealed that participants recognized the potential of the skills to include significant opportunities for non-instrumental interaction, contributing to a psychologically healthier workplace.
Conclusion:
A brief intervention to develop communication skills across a variety of differences characteristic of clinical-translational settings improves communication between mentors and mentees and with peers and increases sense of belonging in the workplace, with potential benefits to wellbeing.
The efficacy and safety of aripiprazole once-monthly 400 mg (AOM 400) as maintenance monotherapy treatment for bipolar I disorder (BP-I) were demonstrated in a double-blind, placebo-controlled, 52-week randomized withdrawal trial (NCT01567527). This post hoc analysis of data from NCT01567527 evaluated the efficacy of AOM 400 in the earlier BP-I population.
Methods
Patients within the first quartile of the dataset according to age (18–32 years: AOM 400, n=36; placebo, n=34) or disease duration (≤4.6 years: AOM 400, n=33; placebo, n=34) were considered to be in the earlier stages of BP-I, and were included. The primary outcome was time from randomization to recurrence of any mood episode, defined as meeting any one of several predetermined criteria, including Young Mania Rating Scale (YMRS) total score ≥15 or clinical worsening.
Results
Time to recurrence of any mood episode was significantly delayed with AOM 400 versus placebo in patients aged 18–32 years (hazard ratio [HR]: 2.462 [95% confidence interval (CI): 1.092, 5.547]; p<0.05) and in patients with a disease duration ≤4.6 years (HR: 3.207 [95% CI: 1.346, 7.645]; p<0.01). Further analysis suggested that the benefit of AOM 400 versus placebo was driven by a significantly lower proportion of patients experiencing a YMRS total score ≥15 (18–32 years: 5.60% versus 44.10%, p<0.001; disease duration ≤4.6 years: 6.10% versus 41.20%, p<0.01) or clinical worsening (18–32 years: 8.30% versus 38.20%, p<0.01; disease duration ≤4.6 years: 6.10% versus 38.20%, p<0.01).
Conclusion
The efficacy of AOM 400 was demonstrated in the earlier BP-I population.
Study registration number: NCT01567527 (ClinicalTrials.gov)
The data in this poster were originally presented at Psych Congress, held on 6–10th September 2023 in Nashville, TN, USA.
Funding
Otsuka Pharmaceutical Development & Commercialization Inc. (Princeton, NJ, USA) and Lundbeck LLC (Deerfield, IL, USA).
To characterize the relationship between chlorhexidine gluconate (CHG) skin concentration and skin microbial colonization.
Design:
Serial cross-sectional study.
Setting/participants:
Adult patients in medical intensive care units (ICUs) from 7 hospitals; from 1 hospital, additional patients colonized with carbapenemase-producing Enterobacterales (CPE) from both ICU and non-ICU settings. All hospitals performed routine CHG bathing in the ICU.
Methods:
Skin swab samples were collected from adjacent areas of the neck, axilla, and inguinal region for microbial culture and CHG skin concentration measurement using a semiquantitative colorimetric assay. We used linear mixed effects multilevel models to analyze the relationship between CHG concentration and microbial detection. We explored threshold effects using additional models.
Results:
We collected samples from 736 of 759 (97%) eligible ICU patients and 68 patients colonized with CPE. On skin, gram-positive bacteria were cultured most frequently (93% of patients), followed by Candida species (26%) and gram-negative bacteria (20%). The adjusted odds of microbial recovery for every twofold increase in CHG skin concentration were 0.84 (95% CI, 0.80–0.87; P < .001) for gram-positive bacteria, 0.93 (95% CI, 0.89–0.98; P = .008) for Candida species, 0.96 (95% CI, 0.91–1.02; P = .17) for gram-negative bacteria, and 0.94 (95% CI, 0.84–1.06; P = .33) for CPE. A threshold CHG skin concentration for reduced microbial detection was not observed.
Conclusions:
On a cross-sectional basis, higher CHG skin concentrations were associated with less detection of gram-positive bacteria and Candida species on the skin, but not gram-negative bacteria, including CPE. For infection prevention, targeting higher CHG skin concentrations may improve control of certain pathogens.
To assess whether measurement and feedback of chlorhexidine gluconate (CHG) skin concentrations can improve CHG bathing practice across multiple intensive care units (ICUs).
Design:
A before-and-after quality improvement study measuring patient CHG skin concentrations during 6 point-prevalence surveys (3 surveys each during baseline and intervention periods).
Setting:
The study was conducted across 7 geographically diverse ICUs with routine CHG bathing.
Participants:
Adult patients in the medical ICU.
Methods:
CHG skin concentrations were measured at the neck, axilla, and inguinal region using a semiquantitative colorimetric assay. Aggregate unit-level CHG skin concentration measurements from the baseline period and each intervention period survey were reported back to ICU leadership, which then used routine education and quality improvement activities to improve CHG bathing practice. We used multilevel linear models to assess the impact of intervention on CHG skin concentrations.
Results:
We enrolled 681 (93%) of 736 eligible patients; 92% received a CHG bath prior to survey. At baseline, CHG skin concentrations were lowest on the neck, compared to axillary or inguinal regions (P < .001). CHG was not detected on 33% of necks, 19% of axillae, and 18% of inguinal regions (P < .001 for differences in body sites). During the intervention period, ICUs that used CHG-impregnated cloths had a 3-fold increase in patient CHG skin concentrations as compared to baseline (P < .001).
Conclusions:
Routine CHG bathing performance in the ICU varied across multiple hospitals. Measurement and feedback of CHG skin concentrations can be an important tool to improve CHG bathing practice.
Abnormal tau, a hallmark Alzheimer’s disease (AD) pathology, may appear in the locus coeruleus (LC) decades before AD symptom onset. Reports of subjective cognitive decline are also often present prior to formal diagnosis. Yet, the relationship between LC structural integrity and subjective cognitive decline has remained unexplored. Here, we aimed to explore these potential associations.
Methods:
We examined 381 community-dwelling men (mean age = 67.58; SD = 2.62) in the Vietnam Era Twin Study of Aging who underwent LC-sensitive magnetic resonance imaging and completed the Everyday Cognition scale to measure subjective cognitive decline along with their selected informants. Mixed models examined the associations between rostral-middle and caudal LC integrity and subjective cognitive decline after adjusting for depressive symptoms, physical morbidities, and family. Models also adjusted for current objective cognitive performance and objective cognitive decline to explore attenuation.
Results:
For participant ratings, lower rostral-middle LC contrast to noise ratio (LCCNR) was associated with significantly greater subjective decline in memory, executive function, and visuospatial abilities. For informant ratings, lower rostral-middle LCCNR was associated with significantly greater subjective decline in memory only. Associations remained after adjusting for current objective cognition and objective cognitive decline in respective domains.
Conclusions:
Lower rostral-middle LC integrity is associated with greater subjective cognitive decline. Although not explained by objective cognitive performance, such a relationship may explain increased AD risk in people with subjective cognitive decline as the LC is an important neural substrate important for higher order cognitive processing, attention, and arousal and one of the first sites of AD pathology.
Background:Candida auris is an emerging multidrug-resistant yeast that is transmitted in healthcare facilities and is associated with substantial morbidity and mortality. Environmental contamination is suspected to play an important role in transmission but additional information is needed to inform environmental cleaning recommendations to prevent spread. Methods: We conducted a multiregional (Chicago, IL; Irvine, CA) prospective study of environmental contamination associated with C. auris colonization of patients and residents of 4 long-term care facilities and 1 acute-care hospital. Participants were identified by screening or clinical cultures. Samples were collected from participants’ body sites (eg, nares, axillae, inguinal creases, palms and fingertips, and perianal skin) and their environment before room cleaning. Daily room cleaning and disinfection by facility environmental service workers was followed by targeted cleaning of high-touch surfaces by research staff using hydrogen peroxide wipes (see EPA-approved product for C. auris, List P). Samples were collected immediately after cleaning from high-touch surfaces and repeated at 4-hour intervals up to 12 hours. A pilot phase (n = 12 patients) was conducted to identify the value of testing specific high-touch surfaces to assess environmental contamination. High-yield surfaces were included in the full evaluation phase (n = 20 patients) (Fig. 1). Samples were submitted for semiquantitative culture of C. auris and other multidrug-resistant organisms (MDROs) including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), extended-spectrum β-lactamase–producing Enterobacterales (ESBLs), and carbapenem-resistant Enterobacterales (CRE). Times to room surface contamination with C. auris and other MDROs after effective cleaning were analyzed. Results:Candida auris colonization was most frequently detected in the nares (72%) and palms and fingertips (72%). Cocolonization of body sites with other MDROs was common (Fig. 2). Surfaces located close to the patient were commonly recontaminated with C. auris by 4 hours after cleaning, including the overbed table (24%), bed handrail (24%), and TV remote or call button (19%). Environmental cocontamination was more common with resistant gram-positive organisms (MRSA and, VRE) than resistant gram-negative organisms (Fig. 3). C. auris was rarely detected on surfaces located outside a patient’s room (1 of 120 swabs; <1%). Conclusions: Environmental surfaces near C. auris–colonized patients were rapidly recontaminated after cleaning and disinfection. Cocolonization of skin and environment with other MDROs was common, with resistant gram-positive organisms predominating over gram-negative organisms on environmental surfaces. Limitations include lack of organism sequencing or typing to confirm environmental contamination was from the room resident. Rapid recontamination of environmental surfaces after manual cleaning and disinfection suggests that alternate mitigation strategies should be evaluated.
Background: Bathing ICU patients with chlorhexidine gluconate (CHG) decreases bloodstream infections and multidrug-resistant organism transmission. The efficacy of CHG bathing on skin microorganism reduction may be influenced by patient-level clinical factors. We assessed the impact of clinical factors on the recovery of microorganisms from the skin of patients admitted to an ICU who were receiving routine CHG bathing. Methods: We analyzed data obtained from 6 single-day point-prevalence surveys of adult ICU patients between January and October 2018 at 1 medical ICU, in the context of a CHG bathing quality initiative. Demographics and covariates were collected at the bedside and by chart review. Skin swabs were collected from neck, axilla, and inguinal regions and were plated to selective and nonselective media. Standard microbiologic methods were used for species identification and susceptibilities. Multivariable models included patients who received a CHG bath and accounted for clustering of body sites within patients. Results: Across all time points, 144 patients participated, yielding 429 skin swab samples. Mean age was 57 years (SD, 17); 49% were male; 44% had a central venous catheter; and 15% had a tracheostomy Also, 140 patients (97%) had >1 CHG bath prior to skin swab collection, with a median of 9 hours since their last CHG bath (IQR, 6–13 hours). Gram-positive bacteria were more commonly recovered than gram-negative or Candida spp across all skin sites (Table 1). Variation by body site was detected only for gram-positive bacteria, with recovery more common from the neck compared to axilla or groin sites. On multivariate logistic regression (Table 2), presence of central venous catheter was associated with lower odds of gram-positive bacteria recovery among those who received a CHG bath. Presence of tracheostomy was associated with a significantly higher odds of gram-negative bacteria detection on skin. No clinical factors were independently associated with recovery of Candida spp. Conclusions: Central venous catheter presence was associated with lower odds of gram-positive bacteria detection on skin, suggesting the possibility of higher quality CHG bathing among such patients. Tracheostomy presence was associated with greater odds of gram-negative bacteria detection, suggesting that it may be a potential reservoir for skin contamination or colonization. Indwelling medical devices may influence CHG bathing effectiveness in reducing microorganism burden on skin.
Despite global deterioration of coral reef health, not all reef-associated organisms are in decline. Bioeroding sponges are thought to be largely resistant to the factors that stress and kill corals, and are increasing in abundance on many reefs. However, there is a paucity of information on how environmental factors influence spatial variation in the distribution of these sponges, and how they might be affected by different stressors. We aimed to identify the factors that explained differences in bioeroding sponge abundance and assemblage composition, and to determine whether bioeroding sponges benefit from the same environmental conditions that can contribute towards coral mortality. Abundance surveys were conducted in the Wakatobi region of Indonesia on reefs characterized by different biotic and abiotic conditions. Bioeroding sponges occupied an average of 8.9% of available dead substrate and variation in abundance and assemblage composition was primarily attributed to differences in the availability of dead substrate. Our results imply that if dead substrate availability increases as a consequence of coral mortality, bioeroding sponge abundance is also likely to increase. However, bioeroding sponge abundance was lowest on a sedimented reef, despite abundant dead substrate. This suggests that not all forms of coral mortality will benefit all bioeroding sponge species, and sediment-degraded reefs are likely to be dominated by a few resilient bioeroding sponge species. Overall, we demonstrate the importance of understanding the drivers of bioeroding sponge abundance and assemblage composition in order to predict possible impacts of different stressors on reefs communities.
This article considers the relationship between constitutions and political settlements and locates the special issue articles within this wider discussion. The article points to the apparently paradoxical connection between disillusionment with internationalised state-building techniques on one hand, and increased international faith in constitution-making as a state-building tool on the other. Using understandings of the relationship of the constitution to political settlement which draws on conventional constitutional theory, it argues that the current context of negotiated transitions requires constitution-making to be approached with an eye to the distinctive dilemmas of statecraft that pertain in contemporary transitions. The most central dilemma concerns how power-balances between political/military elites can be broadened to ensure the constitution’s capacity to fulfil its normative role in restraining power and delivering broader social inclusion. The pieces which make up this special issue draw together development and legal discourses. This article suggests how constitutional theory provides a resource for those seeking to promote constitutionalism as a tool for reaching political settlements capable of resolving conflict. It also argues that those who seek to rely on constitutions for conflict resolution need to understand this enterprise as just as political and fraught as all other institution-building efforts.
In this short piece, I open a conversation over how the Colombian Final Peace Accord provides evidence of, and a contribution to, a more general lex pacificatoria or “law of the peacemakers” (lex pax for short). In light of the Accord’s recent ballot defeat, I integrate into this assessment the merits of using a referendum to approve (in Colombia’s case “affirm or deny”) the Agreement as a whole. Throughout, I draw on a peace agreement database which has coded over one thousand four hundred peace agreements since 1990 for comparative insight.
Twin pairs discordant for disease may help elucidate the epigenetic mechanisms and causal environmental factors in disease development and progression. To obtain the numbers of pairs, especially monozygotic (MZ) twin pairs, necessary for in-depth studies while also allowing for replication, twin studies worldwide need to pool their resources. The Discordant Twin (DISCOTWIN) consortium was established for this goal. Here, we describe the DISCOTWIN Consortium and present an analysis of type 2 diabetes (T2D) data in nearly 35,000 twin pairs. Seven twin cohorts from Europe (Denmark, Finland, Norway, the Netherlands, Spain, Sweden, and the United Kingdom) and one from Australia investigated the rate of discordance for T2D in same-sex twin pairs aged 45 years and older. Data were available for 34,166 same-sex twin pairs, of which 13,970 were MZ, with T2D diagnosis based on self-reported diagnosis and medication use, fasting glucose and insulin measures, or medical records. The prevalence of T2D ranged from 2.6% to 12.3% across the cohorts depending on age, body mass index (BMI), and national diabetes prevalence. T2D discordance rate was lower for MZ (5.1%, range 2.9–11.2%) than for same-sex dizygotic (DZ) (8.0%, range 4.9–13.5%) pairs. Across DISCOTWIN, 720 discordant MZ pairs were identified. Except for the oldest of the Danish cohorts (mean age 79), heritability estimates based on contingency tables were moderate to high (0.47–0.77). From a meta-analysis of all data, the heritability was estimated at 72% (95% confidence interval 61–78%). This study demonstrated high T2D prevalence and high heritability for T2D liability across twin cohorts. Therefore, the number of discordant MZ pairs for T2D is limited. By combining national resources, the DISCOTWIN Consortium maximizes the number of discordant MZ pairs needed for in-depth genotyping, multi-omics, and phenotyping studies, which may provide unique insights into the pathways linking genes to the development of many diseases.
Fruit and vegetable (F&V) intake is influenced by behavioural and environmental factors, but these have rarely been assessed simultaneously. We aimed to quantify the relative influence of supermarket availability, perceptions of the food environment and shopping behaviour on F&V intake.
Design
A cross-sectional study.
Setting
Eight counties in South Carolina, USA, with verified locations of all supermarkets.
Subjects
A telephone survey of 831 household food shoppers ascertained F&V intake with a seventeen-item screener, primary food store location, shopping frequency and perceptions of healthy food availability, and supermarket availability was calculated with a geographic information system. Path analysis was conducted. We report standardized beta coefficients on paths significant at the 0·05 level.
Results
Frequency of grocery shopping at primary food store (β = 0·11) was the only factor exerting an independent, statistically significant direct effect on F&V intake. Supermarket availability was significantly associated with distance to utilized food store (β = −0·24) and shopping frequency (β = 0·10). Increased supermarket availability was significantly and positively related to perceived healthy food availability in the neighbourhood (β = 0·18) and ease of shopping access (β = 0·09). Collectively considering all model paths linked to perceived availability of healthy foods, this measure was the only other factor to have a significant total effect on F&V intake.
Conclusions
While the majority of the literature to date has suggested an independent and important role of supermarket availability for F&V intake, our study found only indirect effects of supermarket availability and suggests that food shopping frequency and perceptions of healthy food availability are two integral components of a network of influences on F&V intake.
The present study compared the effects of feeding uncooked pea fractions (embryo v. seed coat) on glucose homeostasis in glucose-intolerant rats and examined potential mechanisms influencing glucose homeostasis. Rats were made glucose intolerant by high-fat feeding, after which diets containing both high-fat and pea fractions were fed for 4 weeks. Rats fed diets containing uncooked pea seed coats low (non-coloured seed coat; NSC) or high (coloured seed coat; CSC) in proanthocyanidins but not embryos had improved oral glucose tolerance (P < 0·05). NSC also lowered fasting and glucose-stimulated insulin secretion (P < 0·05), decreased β-cell mass by 50 % (P < 0·05) and lowered levels of malondialdehyde, a marker of oxidative stress. Furthermore, NSC decreased the mucosal thickness of the colon by 25 % (P < 0·05), which might affect fibre fermentation and other gut functions. Small but statistically significant (P < 0·05) effects consistent with enhanced glucose transport or metabolism were observed in the skeletal muscle of rats fed NSC or CSC, for example, increased levels of AMP-dependent kinase or akt. We conclude that pea seed coats are the fraction exerting beneficial effects on glucose tolerance. Most of the changes were small in amplitude, suggesting that additive effects on multiple tissues may be important. NSC content appeared to have the most beneficial effects in improving glucose homeostasis but our ability to detect the effect of flavonoids may have been limited by their low concentration in the diet.