Adopting a Novel Approach to Prevent and Address Patient Mistreatment of Staff in a Community Mental Health Center.

Verbal mistreatment of staff by patients is common in health care settings. Experiencing or witnessing mistreatment can have harmful psychological impacts, affecting well-being and clinical practice. As part of an effort to become an antiracist organization, an academic community mental health center based in Connecticut developed an initiative to address verbal mistreatment. Training in the Expect, Recognize, Address, Support, Establish (ERASE) framework was provided to 140 staff members. This training and subsequent actions to enhance the culture of safety were perceived as helpful by staff. Further development of the initiative is proceeding as the center's primary performance improvement program.

High-throughput mass spectrometry analysis using immediate drop-on-demand technology coupled with an open port sampling interface.

RATIONALE: The sampling throughput of immediate drop-on-demand technology (I.DOT) coupled with an open port sampling interface (OPSI) is limited by software communication. To enable much-needed high-throughput mass spectrometry (MS) analysis capabilities, a novel software was developed that allows for flexible sample selection from a 96-well plate and for maximized analysis throughput using I.DOT/OPSI-MS coupling. METHODS: Wells of a 96-well I.DOT plate were filled with propranolol solution and were used to test maximum sampling throughput strategies to minimize analysis time. Demonstration of chemical reaction monitoring was done using acid-catalyzed ring closure of 2,3-diaminonaphthalene (DAN) with nitrite to form 2,3-naphthotriazole (NAT). Analytes were detected in positive electrospray ionization mode using selected reaction monitoring. RESULTS: A maximum throughput of 1.54 s/sample (7.41 min/96-well plate with three technical replicates) was achieved, and it was limited by the peak width of the MS signal resulting in an occasional slight overlap between the peaks. Relative standard deviation was 10 ± 1% with all tested sampling strategies. Chemical reaction monitoring of DAN to NAT using nitrite was successfully accomplished with 2 s/sample throughout showing almost complete transformation in 10 min with no signal overlap. CONCLUSIONS: This work illustrates the development of a noncontact, automated I.DOT/OPSI-MS system with improved throughput achieved through an optimized software interface. Its achievable analysis time and precision make it a viable approach for drug discovery and in situ reaction monitoring studies.

Rapid Droplet Sampling Interface for Low-Volume, High-Throughput Mass Spectrometry Analysis.

Here, we present a rapid droplet sampling interface (RDSI) electrospray ionization mass spectrometry (ESI-MS) system as a high-throughput, low-volume, noncontact, and minimal-carryover approach for characterization of liquids. Liquid characterization was achieved by combining droplet ejection with an open-face microflow capillary with a 2.5 µL/min continuous flow of carrier solvent. Through this implementation, single 0.3 nL droplets containing the analyte effectively mix with 4-8 nL of carrier solvent and create a combined electrospray plume. The carrier solvent continuously cleaned the system, eliminating carryover. A sampling rate of 5 Hz was achieved for droplets containing 1 µM propranolol or 5 µM leu-enkephalin with each droplet fully baseline-resolved (138 ± 32 ms baseline-to-baseline). Using a SCIEX API4000 mass spectrometer, a lower limit of quantification (LLOQ) of propranolol was 15 nM, corresponding to 1.16 fg of propranolol in the droplet, and was linear across 3 orders of magnitude. Quantitation could be achieved by adding an isotopically labeled internal standard, as done in conventional ESI. Signal transients were faster than the acquisition speed of the mass spectrometer, resulting in artificially high reproducibility of 15-30% RSD droplet-to-droplet. Analyte-solvent mixing ratios could be controlled by adjusting droplet positioning along the open-face capillary with an optimal position about 0.4 mm from the tip end. The range of analyte coverage was exemplified by measures of peptides and drugs in methanol, water, and buffer solutions. In a comparison to the Open Port Sampling Interface (OPSI) implemented on the same system, the RDSI had 78× greater sensitivity, 6× greater throughput and used significantly less carrier solvent.

Structure-Driven Liquid Microjunction Surface-Sampling Probe Mass Spectrometry.

The rhizosphere is the narrow region of soil surrounding the roots of plants that is influenced by root exudates, root secretions, and associated microbial communities. This region is crucial to plant growth and development and plays a critical role in nutrient uptake, disease resistance, and soil transformation. Understanding the function of exogenous compounds in the rhizosphere starts with determining the spatiotemporal distribution of these molecular components. Using liquid microjunction surface-sampling probe mass spectrometry (LMJ-SSP-MS) and microfluidic devices with attached microporous membranes enables in situ, nondisruptive, and nondestructive spatiotemporal measurement of exogenous compounds from plant roots. However, long imaging times (>2 h) can negatively affect plant heath and limit temporal studies. Here, we present a novel strategy to optimize the number and location of sampling sites on these microporous membrane-covered microfluidic devices. This novel, "structure-driven" sampling workflow takes into consideration the channel structure of the microfluidic device to maximize sampling from the channels and minimize acquisition time (∼4× less time in some cases while providing similar chemical image accuracy), thus reducing stress on plants during in situ LMJ-SSP-MS analysis.

High-Throughput Characterization and Optimization of Polyamide Hydrolase Activity Using Open Port Sampling Interface Mass Spectrometry.

Enzymatic biodegradation of polymers, such as polyamides (PA), has the potential to cost-effectively reduce plastic waste, but enhancements in degradation efficiency are needed. Engineering enzymes through directed evolution is one pathway toward identification of critical domains needed for improving activity. However, screening such enzymatic libraries (100s-to-1000s of samples) is time-consuming. Here we demonstrate the use of robotic autosampler (PAL) and immediate drop on demand technology (I.DOT) liquid handling systems coupled with open-port sampling interface-mass spectrometry (OPSI-MS) to screen for PA6 and PA66 hydrolysis by 6-aminohexanoate-oligomer endo-hydrolase (nylon hydrolase, NylC) in a high-throughput (8-20 s/sample) manner. The OPSI-MS technique required minimal sample preparation and was amenable to 96-well plate formats for automated processing. Enzymatic hydrolysis of PA characteristically produced soluble linear oligomer products that could be identified by OPSI-MS. Incubation temperatures and times were optimized for PA6 (65 °C, 24 h) and PA66 (75 °C, 24 h) over 108 experiments. In addition, the I.DOT/OPSI-MS quantified production of PA6 linear dimer (8.3 ± 1.6 µg/mL) and PA66 linear monomer (13.5 ± 1.5 µg/mL) by NylC with a lower limit of detection of 0.029 and 0.032 µg/mL, respectively. For PA6 and PA66, linear oligomer production corresponded to 0.096 ± 0.018% and 0.204 ± 0.028% conversion of dry pellet mass, respectively. The developed methodology is expected to be utilized to assess enzymatic hydrolysis of engineered enzyme libraries, comprising hundreds to thousands of individual samples.

Promoting the Success and Sustainability of Coordinated Specialty Care Teams in Ohio.

Recent COVID-19-related federal legislation has resulted in time-limited increases in Mental Health Block Grant (MHBG) set-aside dollars for coordinated specialty care (CSC) throughout the United States. The state of Ohio has opted to apply these funds to establish a learning health network of Ohio CSC teams, promote efforts to expand access to CSC, and quantify the operating costs and rates of reimbursement from private and public payers for these CSC teams. These efforts may provide other states with a model through which they can apply increased MHBG funds to support the success of their own CSC programs.

Integrating Ambulatory Addiction Consultation Service Into a Community Mental Health Center.

Despite the escalation in substance related overdose mortality-culminating in more than 100,000 deaths in each of the first 2 years of the COVID-19 pandemic-healthcare systems have not kept up with the demands for care among people who use drugs. There remains a significant gap in access to evidence-based treatment. The addiction consult services has served to address this gap, as a critical intervention that engages mostly hospitalized patients and initiate addiction treatment in acute settings, but little is known about addiction consult services in ambulatory settings. This model of care could potentially serve to scale up the care for people who use drugs in the community by embedding the limited number of addiction professionals within existing ambulatory systems, thus extending their reach. We describe here an innovative, yet simple and potentially replicable model for an ambulatory addiction consultation service in a large, advanced community mental health center.

Granular analysis of pathways to care and durations of untreated psychosis: A marginal delay model.

OBJECTIVE: An extensive international literature demonstrates that understanding pathways to care (PTC) is essential for efforts to reduce community Duration of Untreated Psychosis (DUP). However, knowledge from these studies is difficult to translate to new settings. We present a novel approach to characterize and analyze PTC and demonstrate its value for the design and implementation of early detection efforts. METHODS: Type and date of every encounter, or node, along the PTC were encoded for 156 participants enrolled in the clinic for Specialized Treatment Early in Psychosis (STEP), within the context of an early detection campaign. Marginal-delay, or the portion of overall delay attributable to a specific node, was computed as the number of days between the start dates of contiguous nodes on the PTC. Sources of delay within the network of care were quantified and patient characteristic (sex, age, race, income, insurance, living, education, employment, and function) influences on such delays were analyzed via bivariate and mixed model testing. RESULTS: The period from psychosis onset to antipsychotic prescription was significantly longer (52 vs. 20.5 days, [p = 0.004]), involved more interactions (3 vs. 1 nodes, [p<0.001]), and was predominated by encounters with non-clinical nodes while the period from antipsychotic to STEP enrollment was shorter and predominated by clinical nodes. Outpatient programs were the greatest contributor of marginal delays on both before antipsychotic prescription (median [IQR] of 36.5 [1.3-132.8] days) and (median [IQR] of 56 [15-210.5] days). Sharper functional declines in the year before enrollment correlated significantly with longer DUP (p<0.001), while those with higher functioning moved significantly faster through nodes (p<0.001). No other associations were found with patient characteristics and PTCs. CONCLUSIONS: The conceptual model and analytic approach outlined in this study give first episode services tools to measure, analyze, and inform strategies to reduce untreated psychosis.

Navigating the digital divide: providing services to people with serious mental illness in a community setting during COVID-19.

Community mental healthcare around the world has been strained as people need more help and experience more barriers to access due to COVID-19. The rapid shift to telehealth services necessitated by the pandemic has made these difficulties even more pronounced. While this transition presented challenges for nearly every healthcare system, it has proven especially difficult for low resource settings such as community health centers. This article is a critical observational study of the care transformation of a state-funded safety net psychiatric system responding to the clinical needs of patients during the COVID-19 pandemic. By discussing the challenges, opportunities, and creative solutions for staff and patients, the article highlights the new importance of technology and adaptability in clinical care and outlines clear recommendations to ensure vulnerable populations do not fall into the "digital divide."

In Situ Detection of Amino Acids from Bacterial Biofilms and Plant Root Exudates by Liquid Microjunction Surface-Sampling Probe Mass Spectrometry.

The plant rhizosphere is a complex and dynamic chemical environment where the exchange of molecular signals between plants, microbes, and fungi drives the development of the entire biological system. Exogenous compounds in the rhizosphere are known to affect plant-microbe organization, interactions between organisms, and ultimately, growth and survivability. The function of exogenous compounds in the rhizosphere is still under much investigation, specifically with respect to their roles in plant growth and development, the assembly of the associated microbial community, and the spatiotemporal distribution of molecular components. A major challenge for spatiotemporal measurements is developing a nondisruptive and nondestructive technique capable of analyzing the exogenous compounds contained within the environment. A methodology using liquid microjunction-surface sampling probe-mass spectrometry (LMJ-SSP-MS) and microfluidic devices with attached microporous membranes was developed for in situ, spatiotemporal measurement of amino acids (AAs) from bacterial biofilms and plant roots. Exuded arginine was measured from a living Pantoea YR343 biofilm, which resulted in a chemical image indicative of biofilm growth within the device. Spot sampling along the roots of Populus trichocarpa with the LMJ-SSP-MS resulted in the detection of 15 AAs. Variation in AA concentrations across the root system was observed, indicating that exudation is not homogeneous and may be linked to local rhizosphere architecture and different biological processes along the root.

Reducing Delay From Referral to Admission at a U.S. First-Episode Psychosis Service: A Quality Improvement Initiative.

Duration of untreated psychosis (DUP), the period between psychosis onset and entry into care, is a time of great vulnerability. Longer DUP predicts poorer outcomes, and delayed treatment access can limit the effectiveness of coordinated specialty care (CSC) services. This column details one component of a broader early detection campaign, a quality improvement intervention focusing on reducing the delay between confirmation of eligibility and admission to care within a benchmark period of 7 days. Median delay significantly fell (from 13.5 to 3 days), and the proportion of admissions that met the benchmark increased (from 33% to 71%) over 4 years. This intervention provides a sustainable model to reduce wait times at CSC services.

Risk of deaths due to injuries in travellers: a systematic review.

BACKGROUND: Annual global travel reached an all-time high of 1.4 billion international tourist visits in 2019. It is estimated that injury accounts for close to 25% of deaths in travellers, most of which are theoretically preventable. However, there are limited data available on injury occurrence and outcomes in travellers. Our objective was to better understand the relative risk of dying from injury that arises from the novel environments and behavioural changes associated with foreign travel. METHODS: A systematic literature review was conducted (PubMed, Embase and Scopus) according to PRISMA guidelines that included studies published in English since 1990 that reported injury deaths in tourists per 100 000-person years or as a proportion of total tourist deaths in comparison to a non-traveller population. We also included studies that reported data allowing calculation of these rates. Relative rates or proportions of overall injury mortality, mortality due to traffic accidents, drowning and homicide were summarized. RESULTS: In total, 1847 articles were identified, 105 underwent full-text review, and 10 articles were suitable for data extraction. There was great variability of relative risk reported, but overall, travellers appear to have a higher risk of injury mortality than domestic populations, with relative rates of injury death ranging from 1.04 to 16.7 and proportionate mortality ratios ranging from 1.43 to 3. CONCLUSIONS: Tourists should be aware of the increased risk of dying from road traffic hazards, drowning and homicide while traveling abroad. Specific geographies and activities associated with higher risk should be emphasized. Travel medicine practitioners and organizations that send people abroad should counsel travellers regarding these risks and seek ways to reduce them, including encouraging potential risk-mitigating behaviours. There is a need to improve systems of data collection and reporting on injury deaths in travellers and to study the impact of pre-travel and institutional interventions aimed at reducing this risk.

Reducing the Duration of Untreated Psychosis (DUP) in a US Community: A Quasi-Experimental Trial.

Objective: Duration of Untreated Psychosis (DUP) remains unacceptably long and limits effectiveness of care. To determine whether an early detection campaign ("Mindmap") can reduce DUP in a US community setting. Methods: In this nonrandomized controlled trial, Mindmap targeted the catchment of one specialty first-episode service or FES (STEP, Greater New Haven) from 2015 to 2019, while usual detection efforts continued at a control FES (PREP, Greater Boston). Mindmap targeted diverse sources of delay through mass & social media messaging, professional outreach & detailing, and rapid enrollment of referrals. Both FES recruited 16-35 years old with psychosis onset ≤3 years. Outcome measures included DUP-Total (onset of psychosis to FES enrollment), DUP-Demand (onset of psychosis to first antipsychotic medication), and DUP-Supply (first antipsychotic medication to FES enrollment). Results: 171 subjects were recruited at STEP and 75 at PREP. Mindmap was associated with an increase in the number of referrals and in efficiency of engagement at STEP. Pre-campaign DUP (2014-2015) was equivalent, while Mindmap was associated with DUP reductions at STEP but not PREP. DUP-Total fell significantly in both the first and the second quartile (11.5 and 58.5 days reduction per campaign year, respectively). DUP-Demand and DUP-Supply fell in the third quartiles only (46.3 and 70.3 days reduction per campaign year, respectively). No reductions were detectable across all quartiles at PREP, but between site comparisons were not significant. Conclusions: This is the first controlled demonstration of community DUP reduction in the US, and can inform future early detection efforts across diverse settings.

Taking the next step: Improving care transitions from a first-episode psychosis service.

AIMS: First-episode services (FES) improve outcomes in recent onset psychosis, but there is growing concern about how patients fare after discharge from these time-limited services. METHODS: A quality improvement approach (QI) was used to improve patient engagement in the discharge planning process (disposition), and successful engagement in care 3 months after discharge from the FES (transfer). Data from 144 consecutive discharges over 62 months are presented. A planning phase was followed by recurrent Plan-Do-Study-Act cycles (PDSA) that included the introduction of proactive efforts targeting disposition planning (with patients and families) and follow-up to facilitate transfer after discharge. Fisher's exact test was used to compare disposition and transfer outcomes across the QI phases. RESULTS: This QI approach was sustained through a three-fold escalation in discharge volume. Transfer status at 3 months was significantly different between the pre- and post PDSA phases (p = .02). A greater proportion were confirmed transfers post-PDSA (54.3 vs. 37%), but of those with known status at 3 months, similar proportions were successfully transferred (76, 73%). Patients discharged post-PDSA were less likely to have unknown treatment status (26 vs. 51%). Disposition outcomes were also significantly improved post-PDSA (p = .03). Patients were more likely to engage with discharge planning (69.7 vs. 48.6%) and less likely to be lost to follow-up (13.8 vs. 25.7%), or to refuse assistance (11.0 vs. 20.0%). CONCLUSION: This QI approach offers a feasible way to improve disposition and transfer after FES and can be built upon in efforts to sustain functional gains in onward pathways.

Hotspots of root-exuded amino acids are created within a rhizosphere-on-a-chip.

The rhizosphere is a challenging ecosystem to study from a systems biology perspective due to its diverse chemical, physical, and biological characteristics. In the past decade, microfluidic platforms (e.g. plant-on-a-chip) have created an alternative way to study whole rhizosphere organisms, like plants and microorganisms, under reduced-complexity conditions. However, in reducing the complexity of the environment, it is possible to inadvertently alter organism phenotype, which biases laboratory data compared to in situ experiments. To build back some of the complexity of the rhizosphere in a fully-defined, parameterized approach we have developed a rhizosphere-on-a-chip platform that mimics the physical structure of soil. We demonstrate, through computational simulation, how this synthetic soil structure can influence the emergence of molecular "hotspots" and "hotmoments" that arise naturally from the plant's exudation of labile carbon compounds. We establish the amenability of the rhizosphere-on-a-chip for long-term culture of Brachypodium distachyon, and experimentally validate the presence of exudate hotspots within the rhizosphere-on-a-chip pore spaces using liquid microjunction surface sampling probe mass spectrometry.

Quantitation of amiodarone and N-desethylamiodarone in single HepG2 cells by single-cell printing-liquid vortex capture-mass spectrometry.

Quantitative measure of a drug and its associated metabolite(s) with single-cell resolution is often limited by sampling throughput or other compromises that limit broad use. Here, we demonstrate the use of single-cell printing-liquid vortex capture-mass spectrometry (SCP-LVC-MS) to quantitatively measure the intracellular concentrations of amiodarone (AMIO) and its metabolite, N-desethylamiodarone (NDEA), from thousands of single cells across several AMIO incubation concentrations ranging from 0 to 10 µM. Concentrations obtained by SCP-LVC-MS were validated through comparison with average assays and traditional measurement of cells in bulk. Average of SCP-LVC-MS measurements and aggregate vial collection assay the concentrations differed by < 5%. Both AMIO and NDEA had clear log-normal distributions with similar standard deviation of concentrations in the cell population. The mean of both AMIO and NDEA intracellular concentrations were positively correlated with AMIO incubation concentration, increasing from 0.026 to 0.520 and 0.0055 to 0.048 mM for AMIO and NDEA, respectively. The standard deviation of AMIO and NDEA log-normal distribution fits were relatively similar in value across incubation concentrations, 0.15-0.19 log10 (mM), and exhibited a linear trend with respect to each other. The single cell-resolved conversion ratio of AMIO to NDEA increased with decreasing incubation concentration, 7 ± 2%, 18 ± 3%, and 20 ± 7% for 10.0, 1.0, and 0.1 µM AMIO incubation concentrations, respectively. Association with simultaneously measured lipids had several ions with statistically significant difference in intensity but no clear correlations with AMIO intracellular content was observed.

Integrated laser ablation-dropletProbe-mass spectrometry for absolute drug quantitation, metabolite detection, and distribution in tissue.

RATIONALE: Spatially resolved and accurate quantitation of drug-related compounds in tissue is a much-needed capability in drug discovery research. Here, application of an integrated laser ablation-dropletProbe-mass spectrometry surface sampling system (LADP-MS) is reported, which achieved absolute quantitation of propranolol measured from <500 × 500 µm thin tissue samples. METHODS: Mouse liver and kidney thin tissue sections were coated with parylene C and analyzed for propranolol by a laser ablation/liquid extraction workflow. Non-coated adjacent sections were microdissected for validation and processed using standard bulk tissue extraction protocols. High-performance liquid chromatography with positive ion mode electrospray ionization tandem mass spectrometry was applied to detect the drug and its metabolites. RESULTS: Absolute propranolol concentration in ~500 × 500 µm tissue regions measured by the two methods agreed within ±8% and had a relative standard deviation within ±17%. Quantitation down to ~400 × 400 µm tissue regions was shown, and this resolution was also used for automated mapping of propranolol and phase II hydroxypropranolol glucuronide metabolites in kidney tissue. CONCLUSIONS: This study exemplifies the capabilities of integrated laser ablation-dropletProbe-mass spectrometry (LADP-MS) for high resolution absolute drug quantitation analysis of thin tissue sections. This capability will be valuable for applications needing to quantitatively understand the spatial distribution of small molecules in tissue.

Establishing the Early Psychosis Intervention Clinic, New Orleans (EPIC-NOLA): Sustainability Challenges Threaten Clinical Success.

This paper describes the implementation of the first coordinated specialty care clinic for first episode psychosis in New Orleans, Louisiana (Early Psychosis Intervention Clinic-New Orleans), a historically underserved area. Successes, lessons, and challenges will be explored in the context of a mission to provide highest quality clinical care in the current insurance reimbursement systems.

Design and Evaluation of a Tethered, Open Port Sampling Interface for Liquid Extraction-Mass Spectrometry Chemical Analysis.

Presented is a tethered, liquid-extraction-sampling interface designed for the mass spectrometric surface sampling/analysis of 3D objects. The tethered, open port sampling interface (TOPSI) incorporates a vacuum line between the sampling probe and ionization source, which enables the ability for an extended, tethered sample transfer line. Herein, several designs of the hand-held TOPSI are presented and evaluated on the basis of the analytical metrics of analyte transport time, peak width, and analyte sensitivity. The best analytical metrics were obtained with capillary flow resistances arranged in a particular order and the vacuum region set at 6.2 kPa. This TOPSI design incorporated a transfer capillary 1 m in length, while retaining a fast analyte transport time (12 s), short signal peak width (5 s baseline-to-baseline), and high analyte signal at 90% of that obtained with a regular open port sampling interface (OPSI). The hand-held TOPSI was demonstrated for the characterization of extracted small molecules and metabolites from the surface of mint and rosemary leaves.

Spatially resolved absolute quantitation in thin tissue by mass spectrometry.

Mass spectrometry (MS) has become the de facto tool for routine quantitative analysis of biomolecules. MS is increasingly being used to reveal the spatial distribution of proteins, metabolites, and pharmaceuticals in tissue and interest in this area has led to a number of novel spatially resolved MS technologies. Most spatially resolved MS measurements are qualitative in nature due to a myriad of potential biases, such as sample heterogeneity, sampling artifacts, and ionization effects. As applications of spatially resolved MS in the pharmacological and clinical fields increase, demand has become high for quantitative MS imaging and profiling data. As a result, several varied technologies now exist that provide differing levels of spatial and quantitative information. This review provides an overview of MS profiling and imaging technologies that have demonstrated quantitative analysis from tissue. Focus is given on the fundamental processes affecting quantitative analysis in an array of MS imaging and profiling technologies and methods to address these biases.Graphical abstract.