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Multicenter clinical trials are essential for evaluating interventions but often face significant challenges in study design, site coordination, participant recruitment, and regulatory compliance. To address these issues, the National Institutes of Health’s National Center for Advancing Translational Sciences established the Trial Innovation Network (TIN). The TIN offers a scientific consultation process, providing access to clinical trial and disease experts who provide input and recommendations throughout the trial’s duration, at no cost to investigators. This approach aims to improve trial design, accelerate implementation, foster interdisciplinary teamwork, and spur innovations that enhance multicenter trial quality and efficiency. The TIN leverages resources of the Clinical and Translational Science Awards (CTSA) program, complementing local capabilities at the investigator’s institution. The Initial Consultation process focuses on the study’s scientific premise, design, site development, recruitment and retention strategies, funding feasibility, and other support areas. As of 6/1/2024, the TIN has provided 431 Initial Consultations to increase efficiency and accelerate trial implementation by delivering customized support and tailored recommendations. Across a range of clinical trials, the TIN has developed standardized, streamlined, and adaptable processes. We describe these processes, provide operational metrics, and include a set of lessons learned for consideration by other trial support and innovation networks.
Electronic health records (EHRs), increasingly available in low- and middle-income countries (LMICs), provide an opportunity to study transdiagnostic features of serious mental illness (SMI) and its trajectories.
Aims
Characterise transdiagnostic features and diagnostic trajectories of SMI using an EHR database in an LMIC institution.
Method
We conducted a retrospective cohort study using EHRs from 2005–2022 at Clínica San Juan de Dios Manizales, a specialised mental health facility in Colombia, including 22 447 patients with schizophrenia (SCZ), bipolar disorder (BPD) or severe/recurrent major depressive disorder (MDD). Using diagnostic codes and clinical notes, we analysed the frequency of suicidality and psychosis across diagnoses, patterns of diagnostic switching and the accumulation of comorbidities. Mixed-effect logistic regression was used to identify factors influencing diagnostic stability.
Results
High frequencies of suicidality and psychosis were observed across diagnoses of SCZ, BPD and MDD. Most patients (64%) received multiple diagnoses over time, including switches between primary SMI diagnoses (19%), diagnostic comorbidities (30%) or both (15%). Predictors of diagnostic switching included mentions of delusions (odds ratio = 1.47, 95% CI 1.34–1.61), prior diagnostic switching (odds ratio = 4.01, 95% CI 3.7–4.34) and time in treatment, independent of age (log of visit number; odds ratio = 0.57, 95% CI 0.54–0.61). Over 80% of patients reached diagnostic stability within 6 years of their first record.
Conclusions
Integrating structured and unstructured EHR data reveals transdiagnostic patterns in SMI and predictors of disease trajectories, highlighting the potential of EHR-based tools for research and precision psychiatry in LMICs.
To evaluate the impact of a mobile-app-based central line-associated bloodstream infection (CLABSI) prevention program in oncology clinic patients with peripherally inserted central catheters (PICCs).
Design:
Pre-post prospective cohort study with baseline (July 2015–December 2016), phase-in (January 2017–April 2017), and intervention (May 2017–November 2018). Generalized linear mixed models compared intervention with baseline frequency of localized inflammation/infection and dressing peeling. Cox proportional hazards models compared days-to-removal of lines with localized inflammation/infection. Chi-square test compared bacteremia rates before and after intervention.
Setting:
Oncology clinic at a large medical center.
Patients:
Oncology clinic adult patients with PICCs.
Intervention:
CLABSI prevention program consisting of an actionable scoring system for identifying insertion site infection/inflammation coupled with a mobile-app enabling photo-assessments and automated physician alerting for remote response.
Results:
We completed 5,343 assessments of 569 PICCs in 401 patients (baseline: 2,924 assessments, 300 PICCs, 216 patients; intervention: 2,419 assessments, 269 PICCs, 185 patients). The intervention was associated with a 92% lower likelihood of having a dressing with peeling (OR 0.08, 95%CI 0.04-0.17, P < 0.001), 53% lower local inflammation/infection (OR 0.47, 95%CI 0.27-0.84, P < 0.011), and 24% (non-significant) lower CLABSI rates (P = .63). Physician mobile-app alerting and response enabled 80% lower risk of lines remaining in place after inflammation/infection was identified (HR 0.20, 95%CI:0.14-0.30, P < 0.001) and 85% faster removal of infected lines from mean (SD) 11.1 (9.7) to 1.7 (2.4) days.
Conclusions:
A mobile-app-based CLABSI prevention program decreased frequency of inflamed/infected central line insertion sites and increased speed of removal when inflammation/infection was found.
Interprofessional teams in the pediatric cardiac ICU consolidate their management plans in pre-family meeting huddles, a process that affects the course of family meetings but often lacks optimal communication and teamwork.
Methods:
Cardiac ICU clinicians participated in an interprofessional intervention to improve how they prepared for and conducted family meetings. We conducted a pretest–posttest study with clinicians participating in huddles before family meetings. We assessed feasibility of clinician enrollment, assessed clinician perception of acceptability of the intervention via questionnaire and semi-structured interviews, and impact on team performance using a validated tool. Wilcoxon rank sum test assessed intervention impact on team performance at meeting level comparing pre- and post-intervention data.
Results:
Totally, 24 clinicians enrolled in the intervention (92% retention) with 100% completion of training. All participants recommend cardiac ICU Teams and Loved ones Communicating to others and 96% believe it improved their participation in family meetings. We exceeded an acceptable level of protocol fidelity (>75%). Team performance was significantly (p < 0.001) higher in post-intervention huddles (n = 30) than in pre-intervention (n = 28) in all domains. Median comparisons: Team structure [2 vs. 5], Leadership [3 vs. 5], Situation Monitoring [3 vs. 5], Mutual Support [ 3 vs. 5], and Communication [3 vs. 5].
Conclusion:
Implementing an interprofessional team intervention to improve team performance in pre-family meeting huddles is feasible, acceptable, and improves team function. Future research should further assess impact on clinicians, patients, and families.
Improving functioning in adults with major depressive disorder (MDD) and bipolar disorder (BD) is a priority therapeutic objective.
Methods
This retrospective post hoc secondary analysis evaluated 108 patients with MDD or BD receiving the antidepressants vortioxetine, ketamine, or infliximab. The analysis aimed to determine if changes in objective or subjective cognitive function mediated the relationship between depression symptom severity and workplace outcomes. Cognitive function was measured by the Perceived Deficits Questionnaire (PDQ-5), the Digit Symbol Substitution Test (DSST), and the Trail Making Test Part B (TMT-B). Depression symptom severity was measured by the Montgomery–Åsberg Depression Rating Scale (MADRS). Workplace function was measured by the Sheehan Disability Scale (SDS) work–school item.
Results
When co-varying for BMI, age, and sex, the association between MADRS and SDS work scores was partially mediated by PDQ-5 total scores and DSST total scores, but not DSST error scores and TMT-B time.
Limitations
This study was insufficiently powered to perform sub-group analyses to identify distinctions between MDD and BD populations as well as between antidepressant agents.
Conclusions
These findings suggest that cognitive impairment in adults with MDD and BD is a critical mediator of workplace function and reinforces its importance as a therapeutic target.
Poisonous birds are rare but on New Guinea, including Indonesia’s easternmost provinces, no less than nine poisonous species, eight pitohuis and one species of ifrita, are found. Pitohuis when handled can cause sneezing with numbness and burning of nasal tissue and nausea in humans. In the bird markets of western Indonesia novelty birds are traded at a premium and overexploitation of popular songbirds leads traders to find replacement species to meet demand. We conducted over 800 surveys in the bird markets of Sumatra, Java, Bali, Lombok, and Sulawesi between 1994 and 2023 and from 2015 onwards we assessed the online trade in pitohuis and Blue-capped Ifrit Ifrita kowaldi. We identified the species, recorded their prices and location, and the date when the birds were offered for sale. We analysed temporal trends, volumes, prices, and geographical origin of the sellers. Between 1994 and 2014 we did not encounter a single pitohui in the Indonesian bird markets. In the following years we recorded 113 pitohuis in 12 bird markets and we recorded 199 pitohuis for sale online; 248 were variable pitohuis and 54 were Hooded Pitohui Pitohui dichrous. No ifritas were recorded. Most pitohuis were recorded in eastern Java and Bali. Prices differed between eastern Java (mean of US$93) and western Java and Bali (US$185), possibly suggesting pitohuis arrive from West Papua in eastern Java and from there make their way to the outer markets. Pitohuis are marketed as “Papuan Straw-headed Bulbuls”; the Straw-headed Bulbul Pycnonotus zeylanicus is a very popular and expensive songbird from Southeast Asia, including western Indonesia, that has become rare both in the wild and in the markets due to overexploitation. Discussions about pitohuis on online forums rarely mention “poisonous” but when it is mentioned traders dismiss this as something not to worry about and they claim it to be dietary-dependent. Poisonous pitohuis are novelty, as well as master, birds in Indonesia, where they are marketed for their song ignoring any negative side-effects of them being poisonous. The trade in novelty species, when detected early, does allow for the authorities to intervene in a timely manner to ensure that this trade does not impede their conservation.
Head and neck squamous cell carcinomas (HNSCCs) are aggressive tumours lacking a standardised timeline for treatment initiation post-diagnosis. Delays beyond 60 days are linked to poorer outcomes and higher recurrence risk.
Methods:
A retrospective review was conducted on patients over 18 with HNSCC treated with (chemo)radiation at a rural tertiary care centre (September 2020–2022). Data on patient demographics, oncologic characteristics, treatment details and delay causes were analysed using SPSS.
Results:
Out of 93 patients, 35.5% experienced treatment initiation delays (TTIs) over 60 days. Median TTI was 73 days for delayed cases, compared to 41.5 days otherwise. No significant differences in demographics or cancer characteristics were observed between groups. The primary reasons for the delay were care coordination (69.7%) and patient factors (18.2%). AJCC cancer stage showed a trend towards longer delays in advanced stages.
Conclusion:
One-third of patients faced delayed TTI, primarily due to care coordination and lack of social support. These findings highlight the need for improved multidisciplinary communication and patient support mechanisms, suggesting potential areas for quality improvement in HNSCC treatment management.
The reward positivity (RewP) is an event-related potential that indexes reinforcement learning and reward system activation. The RewP has been shown to increase across adolescence; however, most studies have examined the RewP across two assessments, and no studies have examined within-person changes across adolescence into young adulthood. Moreover, the RewP has been identified as a neurobiological risk factor for adolescent-onset depression, but it is unclear whether childhood psychosocial risk factors might predict RewP development across adolescence. In a sample of 317 8- to 14-year-old girls (Mage = 12.4, SD = 1.8), the present study examined self-report measures of depression symptoms and stressful life events at baseline and the ΔRewP during the doors guessing task across three timepoints. Growth modeling indicated that, across all participants, the ΔRewP did not demonstrate linear change across adolescence. However, baseline anhedonia symptoms predicted within-person changes in the ΔRewP, such that individuals with low anhedonia symptoms demonstrated a linear increase in the ΔRewP, but individuals with high anhedonia symptoms had no change in the ΔRewP across adolescence. Similar patterns were observed for stressful life events. The present study suggests that childhood risk factors impact the development of reward-related brain activity, which might subsequently increase risk for psychopathology.
This Element represents the first systematic study of the risks borne by those who produced, commissioned, and purchased art, across Renaissance Europe. It employs a new methodology, built around concepts from risk analysis and decision theory. The Element classifies scores of documented examples of losses into 'production risks', which arise from the conception of a work of art until its final placement, and 'reception risks', when a patron, a buyer, or viewer finds a work displeasing, inappropriate, or offensive. Significant risks must be tamed before players undertake transactions. The Element discusses risk-taming mechanisms operating society-wide: extensive communication flows, social capital, and trust, and the measures individual participants took to reduce the likelihood and consequences of losses. Those mechanisms were employed in both the patronage-based system and the modern open markets, which predominated respectively in Southern and Northern Europe.
Spinal muscular atrophy (SMA) is a leading genetic cause of infant death and represents a significant burden of care. An improved understanding of the epidemiology of SMA in Canada may help inform strategies to improve the standard of care for individuals living with SMA.
Methods:
We employed a multisource approach to estimate the minimal incidence and prevalence of 5q SMA and to gain greater insight into recent clinical practices and treatment trends for the Canadian SMA population. Data sources included the Canadian Paediatric Surveillance Program (CPSP), Canadian Neuromuscular Disease Registry (CNDR), and molecular genetics laboratories in Canada.
Results:
The estimated annual minimum incidence of 5q SMA was 4.38, 3.44, and 7.99 cases per 100,000 live births in 2020 and 2021, based on CPSP, CNDR, and molecular genetics laboratories data, respectively, representing approximately 1 in 21,472 births (range 12,516–29,070) in Canada. SMA prevalence was estimated to be 0.85 per 100,000 persons aged 0–79 years. Delay in diagnosis exists across all SMA subtypes. Most common presenting symptoms were delayed milestones, hypotonia, and muscle weakness. Nusinersen was the most common disease-modifying treatment received. Most patients utilized multidisciplinary clinics for management of SMA.
Conclusion:
This study provides data on the annual minimum incidence of pediatric 5q SMA in Canada. Recent therapeutic advances and newborn screening have the potential to drastically alter the natural history of SMA. Findings underline the importance of ongoing surveillance of the epidemiology and long-term health outcomes of SMA in the Canadian population.
Spotted-wing drosophila, Drosophila suzukii, is a global pest of soft fruits that is capable of reproducing on a wide range of cultivated and wild plant species. In Canada, D. suzukii was first reported in British Columbia in 2009 and is now widespread across the country. Understanding the genetic structure of D. suzukii populations could be important for pest management if there are phenotypic differences between genetically distinct populations. For example, insect pest populations could respond differently to directional selection imposed by insecticides, differ in their host plant preferences, and vary in their susceptibility to biological control agents. Here, we used double-digest restriction site–associated DNA sequencing to examine large- and fine-scale patterns of the genetic structure of D. suzukii reared from fruit hosts in Canada. We found that this species has a large-scale spatial genetic structure; the flies collected formed two distinct genetic clusters, one of which was distinct to western Canada and the other to eastern Canada. At the local scale, D. suzukii populations showed no evidence of host-associated structuring in British Columbia, suggesting that pest management tactics may be best applied at the landscape level. Our results highlight the need to investigate phenotypic differences between western and eastern D. suzukii populations in Canada.
Circadian rhythms have a period of approximately 24 hours and are set to precisely 24 hours by various zeitgebers (time givers), light being the most prominent zeitgeber. The central pacemakers for mammalian circadian rhythms are the suprachiasmatic nuclei (SCN) in the anterior hypothalamus. Humoral and neural signals from the SCN help synchronize circadian clocks throughout the body. At the molecular level, cellular circadian rhythms are formed from interlocking transcriptional-translational feedback loops (TTFL) of circadian clock genes that drive spontaneous oscillations of gene and protein expression with an approximately 24-hour period. Remarkably, the molecular clock components are expressed rhythmically in nearly every cell of the body and are entrained by signals from the SCN. Disruption of clock genes either through genes or environment can impair optimal biological function. Circadian rhythms regulate myriad homeostatic systems including the cardiac, immune, metabolic, and central nervous systems. Circadian regulation of physiological and behavioral functions can be disrupted by several factors including the timing of light exposure and food intake. This chapter reviews circadian disruptors to set up the remainder of the book.
Life on earth has evolved under a consistent cycle of light and darkness caused by the earth's rotation around its axis. This has led to a 24-hour circadian system in most organisms, ranging all the way from fungi to humans. With the advent of electric light in the 19th century, cycles of light and darkness have drastically changed. Shift workers and others exposed to high levels of light at night are at increased risk of health problems, including metabolic syndrome, depression, sleep disorders, dementia, heart disease, and cancer. This book will describe how the circadian system regulates physiology and behavior and consider the important health repercussions of chronic disruption of the circadian system in our increasingly lit world. The research summarized here will interest students in psychology, biology, neuroscience, immunology, medicine, and ecology.
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.