Evaluation of Fourier transform-infrared spectroscopy (FT-IR) as a control measure for nosocomial outbreak investigations.

Whole-genome sequencing (WGS) provides greater resolution than other molecular epidemiology strategies and is emerging as a new gold standard approach for microbial strain typing. The Bruker IR Biotyper is designed as a screening tool to identify bacterial isolates that require WGS to establish accurate relationships, but its performance and utility in nosocomial outbreak investigations have not been thoroughly investigated. Here, we evaluated the IR Biotyper by retrospectively examining isolates tested by WGS during investigations of potential nosocomial transmission events or outbreaks. Ninety-eight clinical isolates from 14 different outbreak investigations were examined: three collections of Acinetobacter baumannii (n = 2, n = 9, n = 5 isolates in each collection), one of Escherichia coli (n = 16), two of Pseudomonas aeruginosa (n = 2 and n = 5), two of Serratia marcescens (n = 9 and n = 7), five of Staphylococcus aureus (n = 8, n = 4, n = 3, n = 3, n = 17), and one of Stenotrophomonas maltophilia (n = 8). Linear regression demonstrated a weak, positive correlation between the number of pairwise genome-wide single-nucleotide polymorphisms (SNPs) and IR Biotyper spectral distance values for Gram-positive (r = 0.43, P ≤ 0.0001), Gram-negative (r = 0.1554, P = 0.0639), and all organisms combined (r = 0.342, P ≤ 0.0001). Overall, the IR Biotyper had a positive predictive value (PPV) of 55.81% for identifying strains that were closely related by genomic identity, but a negative predictive value (NPV) of 86.79% for identifying unrelated isolates. When experimentally adjusted cut-offs were applied to A. baumannii, P. aeruginosa, and E. coli, the PPV was 62% for identifying strains that were closely related and the NPV was 100% for identifying unrelated isolates. Implementation of the IR Biotyper as a screening tool in this cohort would have reduced the number of Gram-negative isolates requiring further WGS analysis by 50% and would reduce the number of S. aureus isolates needing WGS resolution by 48%.

Report: A Pox Presenting Without Pox.

ABSTRACT: A man with virally suppressed human immunodeficiency virus (HIV) presented with an erythematous, morbilliform rash without pustules in the setting of fever, fatigue, and myalgias after recent travel to Mexico and Puerto Rico. He was diagnosed with nonvariola orthopoxvirus (monkeypox) infection. This case report highlights an atypical presentation in the 2022 outbreak.

Relationship between clinician-level attributes and implementation outcomes from the Pathways to Comorbidity Care training program.

BACKGROUND: The process of determining the best strategy for increasing the uptake of evidence-based practice might be improved through an understanding of relevant clinician-level factors. The Pathways to Comorbidity Care (PCC) training program (Louie E, et al., J Dual Diagnosis 17:304-12, 2021) aimed to facilitate integrated management of comorbid drug and alcohol and mental disorders amongst drug and alcohol clinicians. We hypothesised that uptake of integrated management of comorbidity following the implementation of the PCC program would be associated with clinician-level: (i) demographics (gender, education, experience), (ii) attitudes (evidence-based practice, therapist manuals, counselling self-efficacy), and (iii) organisational readiness to change. METHODS: Twenty clinicians participated in the 9-month PCC training program. Attitudes towards evidence-based practices and psychotherapist manuals, self-efficacy, and organisational readiness to change, along with demographics, were measured at baseline. At follow-up, change in Comorbidity Practice (CoP) scores related to integrated comorbidity management were obtained using a file audit checklist and categorised into high (at least 60% increase in CoP), medium or low (a decrease of - 20% or less in CoP). Clinician-level characteristics were examined across the implementation categories. RESULTS: There were no significant differences found between implementation groups on sociodemographic variables (p's > 0.30), attitudes to evidence-based practices, attitudes to therapist manuals, and self-efficacy (p's > 0.52). The high implementation group demonstrated significantly higher scores on leadership practices aspect of organisational readiness to change relative to the low and medium implementation group ((F(2, 16) = 3.63, p = 0.05; Cohen's d = .31) but not on the other subscales (p's > 0.07). CONCLUSIONS: Confidence that leadership will play a positive role in the implementation process may improve effectiveness of comorbidity training programs for drug and alcohol clinicians. On the other hand, contrary to our hypothesis, counselling self-efficacy, evidence-based practice attitudes, attitudes towards therapist manuals, gender, education and experience were not distinguishing factors.

Matrix metalloproteinases cleave membrane-bound PD-L1 on CD90+ (myo-)fibroblasts in Crohn's disease and regulate Th1/Th17 cell responses.

Increased T helper (Th)1/Th17 immune responses are a hallmark of Crohn's disease (CD) immunopathogenesis. CD90+ (myo-)fibroblasts (MFs) are abundant cells in the normal (N) intestinal mucosa contributing to mucosal tolerance via suppression of Th1 cell activity through cell surface membrane-bound PD-L1 (mPD-L1). CD-MFs have a decreased level of mPD-L1. Consequently, mPD-L1-mediated suppression of Th1 cells by CD-MFs is decreased, yet the mechanism responsible for the reduction in mPDL-1 is unknown. Increased expression of matrix metalloproteinases (MMPs) has been reported in CD. Herein we observed that when compared to N- and ulcerative colitis (UC)-MFs, CD-MFs increase in LPS-inducible levels of MMP-7 and -9 with a significant increase in both basal and inducible MMP-10. A similar pattern of MMP expression was observed in the CD-inflamed mucosa. Treatment of N-MFs with a combination of recombinant human MMP-7, -9 and -10 significantly decreased mPD-L1. In contrast, inhibition of MMP activity with MMP inhibitors or anti-MMP-10 neutralizing antibodies restores mPD-L1 on CD-MFs. CD-MFs demonstrated reduced capacity to suppress Th1 and Th17 responses from activated CD4+ T cells. By contrast, supplementation of the CD-MF:T-cell co-cultures with MMP inhibitors or anti-MMP neutralizing antibodies restored the CD-MF-mediated suppression. Our data suggest that (i) increased MMP-10 expression by CD-MFs and concomitant cleavage of PD-L1 from the surface of CD-MFs are likely to be one of the factors contributing to the decrease of mPD-L1-mediated suppression of Th1/Th17 cells in CD; and (ii) MMPs are likely to have a significant role in the intestinal mucosal immune responses.

Psychosocial Interventions for Reducing Suicidal Behaviour and Alcohol Consumption in Patients With Alcohol Problems: A Systematic Review of Randomized Controlled Trials.

OBJECTIVE: We aimed to provide a synthesis and evaluation of psychosocial interventions to prevent suicide and reduce self-harm, as well as alcohol intake, for patients with alcohol problems. METHODS: The systematic review was carried out according to the PRISMA guidelines and considered articles published in English from all countries. Terms relating to suicidality and alcohol problems were used to search Medline, EMBASE and PsycINFO databases. Randomized controlled trials of psychosocial interventions targeted for outpatient settings were included. RESULTS: Six studies with a total of 400 participants were included. Two investigated dialectic behavioural therapy (DBT), one internet-delivered DBT, one dynamic deconstructivist psychotherapy (DDP) and two integrated cognitive behavioural therapy (CBT). Face to face and online DBT was significantly associated with abstinence and reductions in consumption with only a trend for a reduction in suicide attempts in one study relative to treatment at usual (TAU). DDP yielded significant reductions in alcohol consumption and suicide attempts versus community care. CBT was significantly effective relative to TAU in reducing alcohol use and suicide attempts in one trial with adolescents but not in another trial in an adult population. CONCLUSION: Integrated CBT has promise for adolescents, DBT may be helpful for alcohol patients with borderline personality disorder and iDBT may be useful for the wider community with heavy alcohol use. However, given the paucity of studies and the exploratory nature of these trials, there is currently no strong evidence for an effective psychosocial intervention to reduce alcohol consumption and suicidal behaviour in adults with problematic alcohol use.

Implementation of a Multi-Modal Training Program for the Management of Comorbid Mental Disorders in Drug and Alcohol Settings: Pathways to Comorbidity Care (PCC).

OBJECTIVES: We aimed to evaluate the impact of the Pathways to Comorbidity Care (PCC) training program for alcohol and other drugs (AOD) clinicians to improve the management of comorbidity. METHODS: A controlled before-and-after study using PCC training was conducted across 6 matched sites in Australia including 35 clinicians. Controls received standard workplace training. PCC training included seminar presentations, workshops conducted by local "clinical champions," individual clinical supervision, and access to an online information portal. We examined (a) identification (screening, assessment) and treatment (treatment, referral) of comorbidity in practice (N = 10 clinical files per clinician), (b) self-efficacy, knowledge, and attitudes of clinicians. RESULTS: Significant improvements were observed in the PCC group but not the control sites with regards to the rate of clinical files showing identification of comorbidity (+50% v -12% change from baseline, respectively; [X2 (1, N = 340) = 35.29, p = .01] with only a trend for improvements in the rate of files demonstrating treatment of comorbidity [X2 (1, N = 340) = 10.45, p = .06]. There were significant improvements in the PCC relative to the control group for clinician self-efficacy, F(1,33) = 6.40, p = .02 and knowledge and attitudes of comorbidity monitoring, F(1,33) = 8.745, p = .01. CONCLUSIONS: The PCC training package may help improve identification of comorbidity, self-efficacy, and attitudes toward screening and monitoring of comorbidity in drug and alcohol settings.

Lactobacillus rhamnosus GG increases cyclooxygenase-2 expression and prostaglandin E2 secretion in colonic myofibroblasts via a MyD88-dependent mechanism during homeostasis.

Prostaglandin E2 (PGE2 ) plays a critical role in intestinal mucosal tolerance and barrier integrity. Cyclooxygenase-2 (COX-2)-dependent PGE2 production involves mobilisation of arachidonic acid. Lactobacillus rhamnosus GG (LbGG) is one of the most widely used probiotics reported to colonise the colonic mucosa. LbGG contributes to the protection of the small intestine against radiation injury through the repositioning of mucosal COX-2 expressing cells. However, it is unknown if LbGG modulates PGE2 production in the colonic mucosa under homeostasis and the major cellular elements involved in these processes. Colonic epithelial and CD90+ mesenchymal stromal cells, also known as (myo) fibroblasts (CMFs), are abundant innate immune cells in normal colonic mucosa able to produce PGE2 . Herein, we tested the hypothesis that under colonic mucosal homeostasis, LbGG modulates the eicosanoid pathway resulting in increased PGE2 production in both epithelial and stromal cells. Among the five tested human colonic epithelial cell lines, only exposure of Caco-2 to LbGG for 24 hr led to the mobilisation of arachidonic acid with concomitant increase in the components within the leukotriene and COX-2-dependent PGE2 pathways. By contrast, CMFs isolated from the normal human colonic mucosa responded to LbGG with increased expression of COX-2 and PGE2 in the prostaglandin pathway, but not 5-LO in the leukotriene pathway. Oral gavage of C57BL/6 mice for 5 days with LbGG (5 × 108 Colony-Forming Unit (CFU)/dose) increased COX-2 expression in the colonic mucosa. The majority of cells upregulating COX-2 protein expression were located in the colonic lamina propria and colocalised with α-SMA+ cells corresponding to the CMF phenotype. This process was myeloid differentiation factor-88-dependent, because silencing of myeloid differentiation factor-88 expression in CMFs abrogated LbGG-induced upregulation of COX-2 in culture and in vivo. Taken together, our data suggest that LbGG increases release of COX-2-mediated PGE2 , contributing to the maintenance of mucosal homeostasis in the colon and CMFs are among the major contributors to this process.

Translating Evidence-Based Practice for Managing Comorbid Substance Use and Mental Illness Using a Multimodal Training Package.

OBJECTIVE: Comorbid mental health and substance use problems are highly prevalent in substance use treatment settings and generally lead to poorer treatment outcomes. Pathways to Comorbidity Care (PCC) is a multimodal training program developed to encourage an integrated service approach to improve clinicians capacity to identify and manage comorbid substance use and mental health outcomes within public drug and alcohol treatment settings. METHODS: In this paper we describe the concepts underlying the PCC package and the use of implementation science to assess and overcome potential barriers, including clinicians preferences, knowledge about best practice, and professional culture. RESULTS: The training components include didactic seminars, group workshops run by a local clinical champion on relevant subjects such as motivational interviewing and cognitive behavioral therapy, individual clinical consultation, and feedback with a senior clinical psychologist. The PCC also includes an online portal containing comorbidity resources including manuals, guidelines, and booster webinars. Finally, we describe the evaluation of PCC implementation. CONCLUSIONS: Drug and alcohol services need to be equipped to treat the majority of comorbid mental health conditions in their clients. We anticipate that this multimodal training package, which applies the principles of implementation science, will facilitate effective and integrated care for these vulnerable clients.

Determinants and health outcomes of trajectories of social mobility in Australia.

Objectives: To investigate trajectories in socio-economic position (SEP) and the onset of a range of physical and mental health outcomes and commencement of treatment. Methods: The Household Income and Labour Dynamics Australia (HILDA) study, a nationally representative prospective cohort study over the period 2001 to 2020 was used to define trajectories of SEP. Trajectories of low, low-middle, upper-middle and high SEP and decreasing (low-middle to upper-middle SEP) or increasing (upper-middle to lower-middle SEP) SEP were identified using k-longitudinal means. Cox-regression was used to assess SEP trajectories and physical (arthritis or osteoporosis, any cancer, asthma, chronic bronchitis or emphysema, Type 1 diabetes, Type 2 diabetes, hypertension or high blood pressure, and coronary heart disease), and mental health (depression or anxiety) outcomes, and treatment commencement. Predictors of SEP trajectories were also investigated using multinomial logistic regression and random forests. Results: Decreasing SEP had a higher relative risk of new onset illness than increasing SEP for all health outcomes. Increasing SEP had relative risk estimates that were more consistent with upper-middle income groups and decreasing SEP had a relative risk consistent with lower-middle income groups. In contrast, there was no socio-economic gradient in treatment commencement for physical health outcomes, or depression or anxiety, with the exception of arthritis or osteoporosis. Conclusion: Decreasing SEP was associated with poor health outcomes, and increasing SEP with better health outcomes. A range of socio-demographic and psychosocial determinants of SEP trajectories were identified to inform policy responses that could modify trajectories of health inequalities in the Australian context.

Geographical variation in implementation of the Pathways to Comorbidity Care program in Australian drug and alcohol services.

AIM: Comorbid drug and alcohol and mental health disorders are highly prevalent. Significant gaps in service provision make this problem particularly difficult to address in regional Australia. The Pathways to Comorbidity Care (PCC) program was designed to improve management of comorbidity by outpatient drug and alcohol clinicians in New South Wales, Australia. This paper uses the Consolidated Framework for Implementation Research (CFIR) to evaluate variations in implementation outcomes across geographically diverse services. METHODS: Twenty clinicians across three drug and alcohol services from metropolitan, outer metropolitan and regional geographic locations were engaged at multiple levels of influence (directors, managers, clinicians) during the implementation of the multimodal PCC training package. The CFIR guided the development of self-report measures and semi-structured interviews evaluating implementation of the PCC training, and disparities in implementation barriers and facilitators were determined. RESULTS: Metropolitan clinicians identified less barriers than regional clinicians on several intervention characteristics (adaptability, complexity, design quality and packaging), as well as outer setting (peer pressure), inner setting (implementation climate, staff incentives, leadership engagement, available resources) and process (planning, opinion leaders, executing) domains. Regional clinicians evaluated the networks and communications construct more favourably. CONCLUSIONS: Specific barriers identified more strongly by regional clinicians included the importance of communication with local clinicians and leadership about the practicalities of incorporating the approach into routine practice (allocation of time, increased accessibility of implementation team). Metropolitan clinicians provided more favourable evaluations of the package design, implementation climate and specific implementation processes such as a clear and informative implementation plan.

Validation of a New High-Throughput BD COR System Using the BD CTGCTV2 Assay.

This study determined the precision and reproducibility of results for the BD CTGCTV2 (CTGCTV2) assay on the BD COR System (COR). The clinical performance of the CTGCTV2 assay conducted on COR was compared with its performance on the BD MAX System (MAX) for detecting Chlamydia trachomatis, Neisseria gonorrhoeae, or Trichomonas vaginalis. The multiday precision and multisite reproducibility studies were conducted using contrived panels of positive and negative urine and PreservCyt specimens. A total of 433 panel members, generated from remnant clinical specimens, were tested in the clinical comparison study. Each panel member was tested three times on MAX and three times on COR. The results in the same testing group were compared for agreement by target. The cycle threshold scores from MAX and COR were analyzed by paired t-test and Deming regression. The CTGCTV2 assay on COR showed high reproducibility in the multiday and multisite precision analysis. The point estimates of positive percent agreement and negative percent agreement in the clinical comparison study for all three targets were greater than 95%, with all corresponding lower bounds of two-sided 95% CIs greater than 90%. Cycle threshold score comparison showed no systematic difference between the two systems. The results of this study show equivalent performance of the CTGCTV2 assay on the MAX and COR systems.

Unpacking the design, implementation and uptake of community-integrated health care services: a critical realist synthesis.

INTRODUCTION: Community-integrated care initiatives are increasingly being used for social and health service delivery and show promising outcomes. Nevertheless, it is unclear what structures and underlining causal agents (generative mechanisms) are responsible for explaining how and why they work or not. METHODS AND ANALYSIS: Critical realist synthesis, a theory-driven approach to reviewing and synthesising literature based on the critical realist philosophy of science, underpinned the study. Two lenses guided our evidence synthesis, the community health system and the patient-focused perspective of integrated care. The realist synthesis was conducted through the following steps: (1) concept mining and framework formulation, (2) searching for and scrutinising the evidence, (3) extracting and synthesising the evidence (4) developing the narratives from causal explanatory theories, and (5) disseminate, implement and evaluate. RESULTS: Three programme theories, each aligning with three groups of stakeholders, were unearthed. At the systems level, three bundles of mechanisms were identified, that is, (1) commitment and motivation, (2) willingness to address integrated health concerns and (3) shared vision and goals. At the provider level, five bundles of mechanisms critical to the successful implementation of integrated care initiatives were abstracted, that is, (1) shared vision and buy-in, (2) shared learning and empowerment, (3) perceived usefulness, (4) trust and perceived support and (5) perceived role recognition and appreciation. At the user level, five bundles of mechanisms were identified, that is, (1) motivation, (2) perceived interpersonal trust, (3) user-empowerment, (4) perceived accessibility to required services and (5) self-efficacy and self-determination. CONCLUSION: We systematically captured mechanism-based explanatory models to inform practice communities on how and why community-integrated models work and under what health systems conditions. PROSPERO REGISTRATION NUMBER: CRD42020210442.

Smart Nanoparticles for Chemo-Based Combinational Therapy.

Cancer is a heterogeneous and complex disease. Traditional cancer therapy is associated with low therapeutic index, acquired resistance, and various adverse effects. With the increasing understanding of cancer biology and technology advancements, more strategies have been exploited to optimize the therapeutic outcomes. The rapid development and application of nanomedicine have motivated this progress. Combinational regimen, for instance, has become an indispensable approach for effective cancer treatment, including the combination of chemotherapeutic agents, chemo-energy, chemo-gene, chemo-small molecules, and chemo-immunology. Additionally, smart nanoplatforms that respond to external stimuli (such as light, temperature, ultrasound, and magnetic field), and/or to internal stimuli (such as changes in pH, enzymes, hypoxia, and redox) have been extensively investigated to improve precision therapy. Smart nanoplatforms for combinational therapy have demonstrated the potential to be the next generation cancer treatment regimen. This review aims to highlight the recent advances in smart combinational therapy.

Barriers and Facilitators to the Implementation of the Pathways to Comorbidity Care (PCC) Training Package for the Management of Comorbid Mental Disorders in Drug and Alcohol Settings.

Background: We have previously reported that the Pathways to Comorbidity Care (PCC) training program for alcohol and other drug (AOD) clinicians improved identification of comorbidity, self-efficacy, and attitudes toward screening and monitoring of comorbidity. We aimed to identify barriers and facilitators of implementation of the PCC training program in drug and alcohol settings. Methods: The PCC training program was implemented across 6 matched sites in Australia as per (1), and 20 clinicians received training. PCC training included seminar presentations, workshops conducted by local "clinical champions," individual clinical supervision, and access to an online information portal. We examined barriers and facilitators of implementation according to the Consolidated Framework for Implementation Research. Results: Barriers included inner setting (e.g., allocated time for learning) and characteristics of individuals (e.g., resistance). Facilitators included intervention characteristics (e.g., credible sources), inner setting (e.g., leadership), and outer setting domains (e.g., patient needs). Clinical champions were identified as an important component of the implementation process. Conclusions: Barriers included limited specific allocated time for learning. A credible clinical supervisor, strong leadership engagement and an active clinical champion were found to be facilitators of the PCC training program.

Impairment of Tissue-Resident Mesenchymal Stem Cells in Chronic Ulcerative Colitis and Crohn's Disease.

BACKGROUND AND AIMS: Little is known about the presence and function of tissue-resident mesenchymal stem cells [MtSCs] within the gastrointestinal mucosa in health and inflammatory bowel disease [IBD]. The contribution of MtSCs to the generation of inflammatory fibroblasts during IBD is also poorly understood. We hypothesized that IBD-MtSCs are impaired and contribute to the generation of the pathological myofibroblasts in IBD. METHODS: In a cohort of clinically and endoscopically active IBD patients and normal controls, we used quantitative RT-PCR and stem cell differentiation assays, as well as confocal microscopy, to characterize MtSCs. RESULTS: Expression of two stem cell markers, Oct4 and ALDH1A, was increased in the inflamed IBD colonic mucosa and correlated with an increase of the mesenchymal lineage marker Grem1 in ulcerative colitis [UC], but not Crohn's disease [CD]. Increased proliferation and aberrant differentiation of Oct4+Grem1+ MtSC-like cells was observed in UC, but not in CD colonic mucosa. In contrast to normal and UC-derived MtSCs, CD-MtSCs lose their clonogenic and most of their differentiation capacities. Our data also suggest that severe damage to these cells in CD may account for the pathological PD-L1low phenotype of CD myofibroblasts. In contrast, aberrant differentiation of MtSCs appears to be involved in the appearance of pathological partially differentiated PD-L1high myofibroblasts within the inflammed colonic mucosa in UC. CONCLUSION: Our data show, for the first time, that the progenitor functions of MtSCs are differentially impaired in CD vs UC, providing a scientific rationale for the use of allogeneic MSC therapy in IBD, and particularly in CD.

The role of clinical champions in facilitating the use of evidence-based practice in drug and alcohol and mental health settings: A systematic review.

Background: The dissemination and adoption of research into clinical practice in health care settings is a complex and challenging process. Clinical champions have been increasingly used in health care to facilitate the implementation and adoption of evidence-based practice and to overcome organizational barriers. In relation to substance use and mental health disorders, translation of new evidence into practice is an ongoing challenge. The utilization of a clinical champion to motivate staff to implement evidence-based practice in these settings may improve treatment quality and reduce the burden of disease. We thus aimed to conduct a systematic review to examine the role and efficacy of clinical champions in the drug and alcohol and mental health settings. Methods: We conducted a systematic literature search (1980-present) using the following databases: PubMed and PsycINFO. Additional studies were identified using reference searches of relevant reviews. Results: Thirteen separate studies were included in the final review. Clinical champions were typically selected rather than emergent, including clinical staff members engaging in a professional clinical role (e.g., physicians, psychologists, social workers). Training provided for these roles was often not stated. Clinical champions assisted with faster initiation and persistence in the application of novel interventions, facilitating overcoming system barriers, and enhanced staff engagement and motivation. Conclusions: In the substance use and mental health field, clinical champions appear to be an important component to facilitating practice changes. Future studies should provide specific details regarding attributes and training and also examine the relevant combination of personal characteristics and training sufficient to facilitate implementation of evidence-based practice in drug and alcohol and mental health settings. Plain language abstract: Treatment delivery in drug and alcohol and mental health settings may not always be based on best available evidence. Organizational context and individual factors are important in determining whether new practices will be adopted. Passive approaches such as websites or treatment manuals do not necessarily lead to change in practice. The clinical champion model has been shown to be effective in aiding implementation of evidence-based practice in health care settings. However, there is limited evidence evaluating its use in drug and alcohol and mental health settings. The current review aims to synthesize and evaluate the use of clinical champions in implementation research in drug and alcohol and mental health settings. We found that clinical champions were typically clinical staff members engaging in a professional clinical role. Training provided for these roles was often limited. Clinical champions may assist with faster initiation and persistence in the application of novel interventions, facilitating overcoming system barriers, and enhanced staff engagement and motivation.