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Objective: To compare initiation of PTSD evidence-based psychotherapy (EBP) between Veterans with and without a co-occurring substance use disorder (SUD), and identify factors associated with EBP initiation among Veterans with PTSD-SUD. Method: A national sample of Veterans with PTSD (n = 301,872) and PTSD-SUD (n = 94,515) were identified from VA Electronic Health Record data. Treatment initiation was defined as having at least one mental health encounter associated with Cognitive Processing Therapy or Prolonged Exposure therapy. Generalized estimating equations were used to compare EBP initiation between Veterans with and without co-occurring SUD, and to identify patient- and facility characteristics associated with EBP initiation among Veterans with PTSD-SUD. Results: The majority of Veterans were 30 - 44 years old, male sex, and Non-Hispanic White. No significant differences were observed in EBP initiation between Veterans with and without a co-occurring SUD (OR=1.00, p=0.985). Among Veterans with PTSD-SUD, co-occurring bipolar disorder (OR=0.83, p=.000), co-occurring psychotic disorder (OR=0.69, p=.000), service connection (OR=0.94, p=.001), female sex (OR=0.87, p=.000), and being 60 years or older (OR=0.57, p=.000) were associated with a reduced likelihood of initiating a PTSD EBP. Having a co-occurring anxiety disorder (OR=1.06, p=.020), MST history (OR=1.95, p=.000), and high risk for suicide (OR=1.15, p=.000) were associated with an increased likelihood of initiating EBP. Discussion: These findings support VA provision of EBP for Veterans with PTSD regardless of the presence of co-occurring SUD. Identifying characteristics that increase or reduce the likelihood of EBP initiation may provide insight into treatment pathways and subgroups warranting augmented outreach.
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This article describes the reallocation of space and construction of a new adult shock trauma intensive care unit implementing methods to mitigate the environmental impact. The environmental burden was reduced through innovative reallocation of space and diversity of lighting sources. Circular economy principles were implemented which enabled much of the infrastructure materials to be reused. Collaboration among interdisciplinary health care teams, such as described in this article, helped to ensure expertise was shared so that the environmental impact was lessened. This article provides insight into innovative methods to mitigate the carbon footprint of a critical care renovation project.
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Rural populations rely on primary care services for depression care due to shortages and maldistributions of specialty mental health care favoring urban areas. Yet, it is unknown which primary care models are effective at reducing depressive symptoms and emergency department (ED) use for depression among rural populations. The purpose of this systematic review is to synthesize the effectiveness of primary care models on depressive symptoms and ED utilization for depression in rural populations. PubMed, PsycINFO, CINAHL, and reference lists of included studies were searched. Eligible articles focused on the impact of primary care models on depressive symptoms or ED utilization for depression among rural populations in the United States. Seventeen studies met the inclusion criteria. Three care models were identified in the studies, including collaborative care (i.e., team-based integrated care that tracks patient populations with a registry; n = 7), tele-psychotherapy (i.e., identification of patients in primary care and referral to virtual psychotherapy; n = 6), or self-management support (i.e., identification of patients in primary care and referral to community support for depression self-management; n = 4). These care models were associated with improved patient-reported depressive symptoms such as Patient-Health Questionnaire reported remission of depression (score < 5). No studies assessed depression ED utilization as an outcome. Collaborative care, tele-psychotherapy, and self-management support may be effective at reducing depressive symptoms, specifically in rural populations and should be implemented at the practice level. Research focused on primary care models and ED utilization for depression among rural populations is needed.
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To improve the translation of preclinical cancer research data to successful clinical effect, there is an increasing focus on the use of primary patient-derived cancer cells with limited growth in culture to reduce genetic and phenotype drift. However, these primary lines are less amenable to standardly used methods of exogenous DNA introduction. Adeno-associated viral (AAV) vectors display tropism for a wide range of human tissues, avidly infect primary cells and have a good safety profile. In the present study, we therefore used a next-generation sequencing (NGS) barcoded AAV screening method to assess transduction capability of a panel of 36 AAVs in primary cell lines representing high-grade glioma (HGG) brain tumours including glioblastoma (GBM) and diffuse intrinsic pontine glioma (DIPG)/diffuse midline glioma (DMG). As proof of principle, we created a reporter construct to analyse activity of the transcriptional co-activators yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ). Transcriptional activation was monitored by promoter-driven expression of the Timer fluorescent tag, a protein that fluoresces green immediately after transcription and transitions to red fluorescence over time. As expected, attempts to express the reporter in primary HGG cells from plasmid expression vectors were unsuccessful. Using the top candidate from the AAV screen, we demonstrate successful AAV-mediated transduction of HGG cells with the YAP/TAZ dynamic activity reporter. In summary, the NGS-screening approach facilitated screening of many potential AAVs, identifying vectors that can be used to study the biology of primary HGG cells.
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PURPOSE: Spaced repetition is superior to repeated study for learning and knowledge retention, but literature on the effect of different spaced repetition strategies is lacking. The authors evaluated the effects of different spaced repetition strategies on long-term knowledge retention and transfer. METHOD: This prospective cohort study, conducted from October 1, 2020, through July 20, 2023, used the American Board of Family Medicine Continuous Knowledge Self-Assessment (CKSA) to assess learning and knowledge transfer of diplomates and residents. Participants were randomized to a control group or 1 of 5 spaced repetition conditions during 5 calendar quarters (January 1, 2021, to March 31, 2022). Participants in the spaced repetition groups received 6 repeated questions once or twice. Incorrectly but confidently answered questions were prioritized for repetition, with decreasing priority for questions answered incorrectly with lesser confidence. All participants received 6 rewritten questions corresponding to their initial questions chosen for repetition in quarter 10 (second quarter of calendar year 2023). RESULTS: A total of 26,258 family physicians or residents who completed the CKSA in the baseline period were randomized. Spaced repetition was superior to no spaced repetition for learning at quarter 6 (58.03% vs 43.20%, P < .001, Cohen d = 0.62) and knowledge transfer at quarter 10 (58.33% vs 52.39%, P < .001, Cohen d = 0.26). Double-spaced repetitions were superior to single-spaced repetitions for learning (62.24% vs 51.83%, P < .001, Cohen d = 0.43) and transfer (60.08% vs 55.72%, P < .001, Cohen d = 0.20). There were no meaningful differences in learning or transfer between repetition strategy chosen in the single- or double-repetition groups. CONCLUSIONS: This study affirms the value of spaced repetition in improving learning and retention in medical education and ongoing professional development.
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BACKGROUND: Cosmetic tourism is an increasingly common phenomenon, both in Ireland and internationally. Complications associated with procedures performed abroad may manifest after the patient has traveled back to their home country with patients often presenting to local health services. Such complications can be infectious in nature requiring either antimicrobial therapy and/or source control in the form of wound debridement or radiologically guided interventional procedures. METHODS: Patients who had presented to a regional plastic surgery unit between September 2021 and December 2022 with complications related to aesthetic procedures performed outside Ireland were identified in this retrospective-prospective design. Medical records were reviewed to ascertain what procedures were performed, where the procedure had taken place, the nature of complications, and microbial culture and sensitivity results. RESULTS: Thirty patients were identified during the study timeframe, predominantly female (n = 28) with a mean age of 40.27 years (SD 10.6). Abdominoplasty was the most common procedure (n = 17), and Turkey was the most frequently cited destination (70%). Wound dehiscence accounted for the majority of complications (n = 18). Wound cultures were obtained in 80% (n = 24) of patients and a causative organism was isolated in 85% (n = 34) of cultures. Eighteen species of bacteria were identified and antimicrobial sensitivities were obtained for 16 of these. Antimicrobial resistance to commonly prescribed empiric antibiotics was noted in several isolates. CONCLUSION: Post-operative infections related to cosmetic tourism are a growing concern in plastic surgery. The bacterial etiology is varied, and antimicrobial resistance poses significant challenges, highlighting the need for early intervention and wound cultures to guide effective management.
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Mechanical ventilation stands as a life-saving intervention in the management of respiratory failure. However, it carries the risk of ventilator-induced lung injury. Despite the adoption of lung-protective ventilation strategies, including lower tidal volumes and pressure limitations, mortality rates remain high, leaving room for innovative approaches. The concept of mechanical power has emerged as a comprehensive metric encompassing key ventilator parameters associated with the genesis of ventilator-induced lung injury, including volume, pressure, flow, resistance, and respiratory rate. While numerous animal and human studies have linked mechanical power and ventilator-induced lung injury, its practical implementation at the bedside is hindered by calculation challenges, lack of equation consensus, and the absence of an optimal threshold. To overcome the constraints of measuring static respiratory parameters, dynamic mechanical power is proposed for all patients, regardless of their ventilation mode. However, establishing a causal relationship is crucial for its potential implementation, and requires further research. The objective of this review is to explore the role of mechanical power in ventilator-induced lung injury, its association with patient outcomes, and the challenges and potential benefits of implementing a ventilation strategy based on mechanical power.
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BACKGROUND: While total ankle arthroplasty (TAA) has evolved over the years with improved designs and enhanced bony fixation methods, it remains a technically demanding procedure with a risk of early postoperative complications. One of the most common complications associated with TAA is medial and lateral gutter ankle impingement, which can lead to issues such as increased pain and decreased range of motion (ROM). However, there is a paucity of information in the literature discussing the impact of certain risk factors on gutter impingement complications. METHODS: A retrospective analysis was conducted on a cohort of patients who underwent a TAA at a single institution from 2003 to 2019 with a minimum of 2-year follow-up. Patient were identified as having gutter impingement based on diagnostic imaging and/or clinical examination. Data collection included demographics, implant type, follow-up time, and co-morbidities. Multivariate odds ratios (OR) of experiencing gutter impingement were calculated for perioperative variables. RESULTS: The study included a total of 908 patients who underwent TAA with a minimum of 2 year follow up and 121 patients (13.3 %) who subsequently experienced gutter impingement. The average follow-up time was 5.84 + /- 3.07 years. There were 178 patients under 55 years old, 495 patients aged 55 to 70, and 235 patients over 70 years old. A higher rate of gutter impingement was observed in patients under 55 years of age compared to those aged 55 to 70 and over 70 (20.8 % vs. 13.5 % vs. 7.2 %; p < 0.01). Multivariable logistic regression revealed that patient age was significantly correlated with gutter impingement following TAA, with an OR of 0.94 (CI: 0.91-0.98; p < 0.01). CONCLUSION: This study demonstrated increased incidence of gutter impingement in younger patients who underwent TAA. Propensity for scar tissue formation may be higher in this population. Scar tissue deposition following TAA can cause narrowing of the medial and lateral clear spaces, potentially leading to gutter impingement. Additionally, younger patients may have increased activity demands, which subsequently may cause higher rates of symptomatic impingement. As increased impingement after TAA may require the need for additional debridement surgeries, it is important to understand the intricate relationship between age and gutter impingement for managing patient expectations following TAA. LEVEL OF EVIDENCE: Level III.
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PURPOSE: Finite courses of androgen deprivation therapy (ADT) are often utilized in men undergoing treatment for prostate cancer. Previous evidence suggests that timing of testosterone (T) recovery can be variable after ADT. Recently, an oral gonadotropin releasing-hormone (GnRH) antagonist, relugolix, has demonstrated more rapid T recovery than injectable GnRH agonists such as leuprolide. In this study, we sought to evaluate patient characteristics associated with T recovery in patients undergoing ADT of defined duration. MATERIALS AND METHODS: The Northwestern Enterprise Data Warehouse was queried for men with prostate cancer who completed a course of ADT and subsequently had a testosterone lab performed. Testosterone recovery was evaluated for levels that reached above castrate (T > 50 ng/dl), partial recovery (T > 150 ng/dl), and full recovery (T ≥ 300 ng/dl). RESULTS: 388 men who received finite courses of ADT were identified (348 receiving leuprolide, 36 receiving relugolix, and 4 receiving degarelix). In multivariable Cox regression analysis, men who were prescribed GnRH antagonists (HRâ¯=â¯3.74, CIâ¯=â¯2.53-5.53, P ≤ 0.001) and who were younger (HR for 1 year increase in ageâ¯=â¯0.96, CIâ¯=â¯0.95-0.98, P < 0.001) were more likely to achieve partial recovery. In a subgroup analysis, men who received extended ADT courses (>12 months) with a GnRH agonist had lower rates of partial T recovery (HRâ¯=â¯0.58, CIâ¯=â¯0.41-0.81, Pâ¯=â¯0.001). CONCLUSION: T recovery after ADT is variable with roughly one sixth of men remaining castrate. GnRH antagonist use and younger age are associated with higher rates of T recovery after ADT. Longer ADT courses were associated with worse T recovery rates.
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BACKGROUND: Patients with rare, pathogenic cardiomyopathy (CM) and arrhythmia variants can present with atrial fibrillation (AF). The efficacy of AF ablation in these patients is unknown. OBJECTIVE: This study tested the hypotheses that: 1) patients with a pathogenic variant in any CM or arrhythmia gene have increased recurrence following AF ablation; and 2) patients with a pathogenic variant associated with a specific gene group (arrhythmogenic left ventricular CM [ALVC], arrhythmogenic right ventricular CM, dilated CM, hypertrophic CM, or a channelopathy) have increased recurrence. METHODS: We performed a prospective, observational, cohort study of patients who underwent AF catheter ablation and whole exome sequencing. The primary outcome measure was ≥30 seconds of any atrial tachyarrhythmia that occurred after a 90-day blanking period. RESULTS: Among 1,366 participants, 109 (8.0%) had a pathogenic or likely pathogenic (P/LP) variant in a CM or arrhythmia gene. In multivariable analysis, the presence of a P/LP variant in any gene was not significantly associated with recurrence (HR 1.15; 95% CI 0.84-1.60; P = 0.53). P/LP variants in the ALVC gene group, predominantly LMNA, were associated with increased recurrence (n = 10; HR 3.75; 95% CI 1.84-7.63; P < 0.001), compared with those in the arrhythmogenic right ventricular CM, dilated CM, hypertrophic CM, and channelopathy gene groups. Participants with P/LP TTN variants (n = 46) had no difference in recurrence compared with genotype-negative-controls (HR 0.93; 95% CI 0.54-1.59; P = 0.78). CONCLUSIONS: Our results support the use of AF ablation for most patients with rare pathogenic CM or arrhythmia variants, including TTN. However, patients with ALVC variants, such as LMNA, may be at a significantly higher risk for arrhythmia recurrence.
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This paper presents a narrative review protocol to explore how the proportion of child-specific content of pre-registration programmes in universities impact upon newly qualified nurses' perceptions of preparedness to care for children, young people (CYP), and their families. The preparation and education to become a nurse who cares for children and young people differs from country to country. Providers of pre-registration nurse education offer routes into nursing from diploma to degree and in some countries post-graduate routes. The United Kingdom offers pre-registration programmes leading to qualifying as a children's nurse whereas programmes in countries such as the USA and Canada lead to a professional registration as a registered nurse with postgraduate study to specialize in areas such as pediatrics. The role of pre-registration nursing programmes is to facilitate preparedness for practice. Preparation for practice can include theoretical teaching and practice learning through simulation and face-to-face experience with countries requiring different numbers of practice hours to be completed. Although practice hours are central to nursing education, there is limited evidence on the impact and portion of child-specific content, including clinical learning in preparation of newly qualified nurses to care for CYP and their families. A preliminary search of Prospero, CINAHL, Medline and Cochrane Database indicates that there are no current or in progress reviews identified. The Population of interest, Exposure of interest, and Outcome framework were used to define the research question and inform the eligibility criteria. The review will consider different research designs if related to the research question. The search strategy will conform to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines for systematic reviews. Two independent reviewers will be involved in the screening progress to determine the final studies for inclusion. Eligible studies will be assessed for methodological quality using the Joanna Briggs Institute critical appraisal tools. Extraction of study characteristics and data related to the research question will be extracted into a predefined table. Data synthesis will be conducted using a descriptive analytical approach to summarize extracted data.
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Cutaneous manifestations of mixed neuroendocrine non-neuroendocrine neoplasms remain a diagnostic rarity. Predominantly identified within internal glandular organs, the digestive tract, and in the hepatobiliary system, this case report illustrates a unique occurrence of a mixed squamous cell and neuroendocrine tumor in the index finger of a justice-affected patient. We discuss the complexities of diagnosis and complications as well as emphasize the importance for hand surgeons to recognize presentations like this and the need for vigilant follow-up and improved care coordination.
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The 2-aminothiazole grouping is a significant feature of many series of biologically active molecules, including antibiotics, anticancer agents and NSAIDs. We have a longstanding interest in the synthesis and biological evaluation of thiazolides, viz. [2-hydroxyaroyl-N-(thiazol-2-yl)-amides] which have broad spectrum antiinfective, especially antiviral, properties. However, 2-amino-4-substituted thiazoles, especially 4-halo examples, are not easily available. We now report practical, efficient syntheses of this class from readily available pseudothiohydantoin, or 2-aminothiazol-4(5H)-one: the key intermediate was its Boc derivative, from which, under Appel-related conditions, Br, Cl and I could all be introduced at C(4). Whereas 2-amino-4-Br/4-Cl thiazoles gave low yields of mixed products on acylation, including a bis-acyl product, further acylation of the Boc intermediates, with a final mild deprotection step, afforded the desired thiazolides cleanly and in good yields. In contrast, even mild hydrolysis of 2-acetamido-4-chlorothiazole led to decomposition with fast reversion to 2-aminothiazol-4(5H)-one. We also present a correction of a claimed synthesis of 2-acetamido-4-chlorothiazole, which in fact produces its 5-chloro isomer.
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This article explores the ongoing debate about whether there is a workforce shortage in veterinary medicine. Despite numerous discussions, no consensus has been reached on whether the demand for veterinarians and their teams exceeds supply. The authors argue that current public discussions fail to address the core issues. The article explores the workforce issue from an economic perspective and provides a perspective on the way forward. Key aspects covered include recognizing the distinction between needs and wants, collecting better data, employing rigorous empirical analysis, differentiating market failures from high prices, and fostering cooperation.
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BACKGROUND: Concept analysis studies play major role in clarifying and operationalizing concepts. This approach has been used to clarify and advance knowledge about the concept of Family Centred Care (FCC). The concept of FCC has been studied by many nursing scholars using different methods. AIM: This review aimed to combine outcomes of concept analysis studies to assess the level of maturity of the concept of Family Centred Care. METHODS: Formal electronic databases (MEDLINE and CINAHL) and informal (Google Scholar) were searched using the terms "Family Centred Care" and "concept analysis". The Morse concept maturity evaluation approach was used to appraise the retrieved studies. RESULTS: 35studies were identified of which12 met the inclusion criteria and were included in the analysis. Three studies used Walker and Avant concept analysis methodology, three applied the Rodgers evolutionary model while six applied modified mixed/hybrid approaches. While a few provided a definition of FCC, none have been able to confirm the maturity of the concept. This review summarized the different trials to analyze the concept of FCC supporting the rethinking of the model and emergence of new models such as Child and Family Centred Care (CFCC). IMPLICATIONS: Concept analyses should be done periodically to assess the maturity of emerging concepts. Previously published FCC concept analyses manuscripts show the concept has evolved and gained significant recognition and acceptance over time. A clearer definition of FCC supports its positive impact on patient outcomes. A comprehensive FCC tool that can evaluate the effective delivery of FCC is needed.
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Perfusable hydrogels have garnered substantial attention in recent years for the fabrication of microphysiological systems. However, current methodologies to fabricate microchannels in hydrogel platforms involve sophisticated equipment and techniques, which hinder progress of the field. In this protocol, we present a cost-effective, simple, versatile and ultrafast method to create perfusable microchannels of complex shapes in photopolymerizable hydrogels. Our method uses one-step UV photocross-linking and a photomask printed on inexpensive transparent films, to photopattern both synthetic (PEG-norbornene) and natural (hyaluronic acid-norbornene) hydrogels in just 0.8 s. Moreover, these perfusable hydrogels are fully integrated into a custom-made microfluidic device that allows continuous fluid perfusion when connected to an external pump system. This methodology can be easily reproduced by professionals with basic laboratory skills and a fundamental knowledge of polymers and materials science. In this protocol, we demonstrate the functionality of our photopatterned hydrogels by seeding human endothelial cells into the microchannels, culturing them under dynamic conditions for 7 d, and exposing them to inflammatory stimuli to elicit cellular responses. This highlights the versatility of our platform in fabricating microphysiological systems and different microenvironments. The fabrication of perfusable channels within the hydrogels, including the fabrication of the microfluidic devices, requires ~3 d. The development of the cell-seeded microphysiological system, including the stimulation of cells, takes ~7 d. In conclusion, our approach provides a straightforward and widely applicable solution to simplify and reduce the cost of biofabrication techniques for developing functional in vitro models using perfusable three-dimensional hydrogels.
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Capitalizing the inherent strain energy within molecules, strain-release-driven reactions have been widely employed in organic synthesis. Small cycloalkanes like cyclopropanes and cyclobutanes, with their moderate ring strain, typically require dense functionalization to induce bias or distal activation of (hetero)aromatic rings via single-electron oxidation for relieving the tension. In this study, we present a pioneering direct activation of alkyl cyclopropanes/butanes through electrochemical oxidation. This approach not only showcases the potential for ring-opening of cyclopropane/butane under electrochemical conditions but also streamlines the synthesis of diverse oxazolines and oxazines. The applicability of our method is exemplified by its broad substrate scopes. Notably, the products derived from cyclobutanes undergo a formal ring contraction to cyclopropanes, introducing an intriguing aspect to our discoveries. These discoveries mark a significant advancement in strain-release-driven skeletal rearrangement reactions of moderately strained rings, offering sustainable and efficient synthetic pathways for future endeavours.