Exploring the Efficacy of an Online Training Programme to Introduce Mental Health Recovery to Carers.

Family carers often support people with mental ill-health, however, there is a dearth of research on the importance of recovery to mental health carers. This article describes the delivery and qualitative evaluation of an online training programme on recovery to a group of eleven carers. The participants considered their understanding of the meaning of recovery, differentiating between its personal and clinical nature. They highlighted the importance of carer involvement in the service users' professional support, alongside the need for carers to participate more widely in service development. Finally, the participants found the training useful in enabling them to recognise their own needs in a caring journey, particularly valuing its delivery by a service user and carer trainer. This study is limited by the small number of participants in this programme; however, this series of connected studies suggests its potential to be rolled out more widely, possibly embedded in Recovery Colleges.

Simultaneous inhibition assay for human and microbial kinases via MALDI-MS/MS.

Selective inhibition of one kinase over another is a critical issue in drug development. For antimicrobial development, it is particularly important to selectively inhibit bacterial kinases, which can phosphorylate antimicrobial compounds such as aminoglycosides, without affecting human kinases. Previous work from our group showed the development of a MALDI-MS/MS assay for the detection of small molecule modulators of the bacterial aminoglycoside kinase APH3'IIIa. Herein, we demonstrate the development of an enhanced kinase MALDI-MS/MS assay involving simultaneous assaying of two kinase reactions, one for APH3'IIIa, and the other for human protein kinase A (PKA), which leads to an output that provides direct information on selectivity and mechanism of action. Specificity of the respective enzyme substrates were verified, and the assay was validated through generation of Z'-factors of 0.55 for APH3'IIIa with kanamycin and 0.60 for PKA with kemptide. The assay was used to simultaneously screen a kinase-directed library of mixtures of ten compounds each against both enzymes, leading to the identification of selective inhibitors for each enzyme as well as one non-selective inhibitor following mixture deconvolution.

Comparing the Efficacy of Targeted and Blast Portal Messaging in Message Opening Rate and Anticoagulation Initiation in Patients With Atrial Fibrillation in the Preventing Preventable Strokes Study II: Prospective Cohort Study.

BACKGROUND: The gap in anticoagulation use among patients with atrial fibrillation (AF) is a major public health threat. Inadequate patient education contributes to this gap. Patient portal-based messaging linked to educational materials may help bridge this gap, but the most effective messaging approach is unknown. OBJECTIVE: This study aims to compare the responsiveness of patients with AF to an AF or anticoagulation educational message between 2 portal messaging approaches: sending messages targeted at patients with upcoming outpatient appointments 1 week before their scheduled appointment (targeted) versus sending messages to all eligible patients in 1 blast, regardless of appointment scheduling status (blast), at 2 different health systems: the University of Massachusetts Chan Medical School (UMass) and the University of Florida College of Medicine-Jacksonville (UFL). METHODS: Using the 2 approaches, we sent patient portal messages to patients with AF and grouped patients by high-risk patients on anticoagulation (group 1), high-risk patients off anticoagulation (group 2), and low-risk patients who may become eligible for anticoagulation in the future (group 3). Risk was classified based on the congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke, vascular disease, age between 65 and 74 years, and sex category (CHA2DS2-VASc) score. The messages contained a link to the Upbeat website of the Heart Rhythm Society, which displays print and video materials about AF and anticoagulation. We then tracked message opening, review of the website, anticoagulation use, and administered patient surveys across messaging approaches and sites using Epic Systems (Epic Systems Corporation) electronic health record data and Google website traffic analytics. We then conducted chi-square tests to compare potential differences in the proportion of patients opening messages and other evaluation metrics, adjusting for potential confounders. All statistical analyses were performed in SAS (version 9.4; SAS Institute). RESULTS: We sent 1686 targeted messages and 1450 blast messages. Message opening was significantly higher with the targeted approach for patients on anticoagulation (723/1156, 62.5% vs 382/668, 57.2%; P=.005) and trended the same in patients off anticoagulation; subsequent website reviews did not differ by messaging approach. More patients off anticoagulation at baseline started anticoagulation with the targeted approach than the blast approach (adjusted percentage 9.3% vs 2.1%; P<.001). CONCLUSIONS: Patients were more responsive in terms of message opening and subsequent anticoagulation initiation with the targeted approach.

Synthesis, characterization and pre-clinical evaluation of (99m) Tc-tricarbonyl complexes as potential myocardial perfusion imaging agents.

Myocardial perfusion imaging is an established Nuclear Medicine investigation. Current myocardial perfusion imaging agents sestamibi and tetrofosmin have number of drawbacks; low heart uptake coupled with uptake into the surrounding tissues leads to a poorer image quality. There is a need for continued research into designing and evaluating potentially superior myocardial imaging agents. Tri-carbonyl-technetium and rhenium complexes were prepared by combination with mono-dentate and bi-dentate ligands. Complexes were characterized by HPLC, MAS, nuclear magnetic resonance, infrared, single-crystal X-ray diffraction and partition coefficient determinations. (99m) Tc(CO)3 complexes were administered intravenously to Sprague Dawley rats, and tissue distribution studies were carried out at 15 min and 1 h p.i. Radiochemical purity was assessed as >90%. 1-10-phenanthroline, 2,2'-bipyridine and imidazole complexes gave the highest heart uptake. The percentage injected dose per gram (n = 3) at 1 h for 1-10-phenanthroline/imidazole was blood 0.21 ± 0.01, heart 1.12 ± 0.11, kidney 3.61 ± 1.13, liver 0.62 ± 0.06, lung 0.28 ± 0.12, spleen 0.24 ± 0.05, small intestine contents 1.87 ± 0.92; and for 2,2'-bipyridine /imidazole was blood 0.23 ± 0.02, heart 1.07 ± 0.18, kidney 3.31 ± 1.28, liver 0.56 ± 0.09, lung 0.14 ± 0.02, spleen 0.2 ± 0.1, small intestine content 1.05 ± 0.48. Further investigation to evaluate more complexes based on 1,10-phenanthroline, 2,2'-bipyridine and imidazole derivatives could potentially lead to agents with an increased heart uptake and faster clearance from the liver and gastrointestinal tract.

Periodontal health of palatally displaced canines treated with open or closed surgical technique: a multicenter, randomized controlled trial.

INTRODUCTION: The aim of this study was to investigate differences in the periodontal outcomes of palatally displaced canines (PDC) exposed with either an open or a closed surgical technique. METHODS: A multicenter, randomized controlled trial was undertaken in 3 hospitals in the United Kingdom, involving 2 parallel groups. Patients with unilateral PDC were randomly allocated to receive either an open or a closed surgical exposure. Periodontal health was assessed 3 months after removal of fixed appliances. Parameters measured included clinical attachment levels, recession, alveolar bone levels, and clinical crown height. RESULTS: Data from 62 participants (closed, 29; open, 33) were analyzed. There was no difference between PDC exposed with an open vs a closed surgical technique (mean difference, 0.1 mm; 95% confidence interval [CI], -0.2-0.5). There was, however, a statistical difference in mean attachment loss between the operated and unoperated (contralateral) canines (mean difference, 0.5 mm; 96% CI, 0.4-0.7; P <0.001). Twenty of the 62 subjects had some recession on the palatal aspect of the operated canine, whereas only 4 subjects had some visible root surface on the palatal aspect on the unoperated side (P = 0.001). CONCLUSIONS: There is a periodontal impact when a unilateral PDC is exposed and aligned. This impact is small and unlikely to have clinical relevance in the short term; however, the long-term significance is unknown. When the open and closed techniques were compared, no difference in periodontal health was found.

No difference in surgical outcomes between open and closed exposure of palatally displaced maxillary canines.

PURPOSE: To investigate differences in surgical outcomes between open and closed exposure for palatally displaced maxillary canines. MATERIALS AND METHODS: This multicenter randomized controlled trial involved 2 parallel groups. The settings were 1 dental teaching hospital in and 2 hospital units near Sheffield, UK. Participants were younger than 20 years, had a unilateral palatally displaced maxillary canine, and provided informed consent. They were randomly allocated to receive the open or the closed surgical procedure. The outcomes were time spent in the operating room and 10-day postoperative patient questionnaire findings. Statistical differences between the 2 techniques were tested using independent t tests for continuous variables and χ(2) tests for frequencies. RESULTS: The final study sample was composed of 71 participants (64% female). There were no differences in the gender ratios (open: 27 female, 13 male; closed; 25 female, 16 male) or mean ages (open: 14.3 yrs; standard deviation [SD], 1.3 yrs; closed: 14.1 yrs; SD, 1.6 yrs) of the 2 groups at the start. The mean operating times for the open and closed techniques were 34.3 minutes (SD, 11.2 min) and 34.3 minutes (SD, 11.9 min), respectively (P = .986). There were no statistically significant differences between the 2 treatment groups for any patient-assessed outcome (P > .05). CONCLUSIONS: There were no differences in the surgical outcomes investigated in this study between open and closed exposure for palatally displaced maxillary canines.

Impact of Established and Emerging Software Tools on the Metabolite Identification Landscape.

Scientists' ability to detect drug-related metabolites at trace concentrations has improved over recent decades. High-resolution instruments enable collection of large amounts of raw experimental data. In fact, the quantity of data produced has become a challenge due to effort required to convert raw data into useful insights. Various cheminformatics tools have been developed to address these metabolite identification challenges. This article describes the current state of these tools. They can be split into two categories: Pre-experimental metabolite generation and post-experimental data analysis. The former can be subdivided into rule-based, machine learning-based, and docking-based approaches. Post-experimental tools help scientists automatically perform chromatographic deconvolution of LC/MS data and identify metabolites. They can use pre-experimental predictions to improve metabolite identification, but they are not limited to these predictions: unexpected metabolites can also be discovered through fractional mass filtering. In addition to a review of available software tools, we present a description of pre-experimental and post-experimental metabolite structure generation using MetaSense. These software tools improve upon manual techniques, increasing scientist productivity and enabling efficient handling of large datasets. However, the trend of increasingly large datasets and highly data-driven workflows requires a more sophisticated informatics transition in metabolite identification labs. Experimental work has traditionally been separated from the information technology tools that handle our data. We argue that these IT tools can help scientists draw connections via data visualizations and preserve and share results via searchable centralized databases. In addition, data marshalling and homogenization techniques enable future data mining and machine learning.

Preventing preventable strokes: A study protocol to push guideline-driven atrial fibrillation patient education via patient portal.

Background: The main approach to preventing stroke in patients with atrial fibrillation (AF) is anticoagulation (AC), but only about 60% of at-risk individuals are on AC. Patient-facing electronic health record-based interventions have produced mixed results. Little is known about the impact of health portal-based messaging on AC use. Objective: The purpose of this study was describe a protocol we will use to measure the association between AC use and patient portal message opening. We also will measure patient attitudes toward education materials housed on a professional society Web site. Methods: We will send portal messages to patients aged ≥18 years with AF 1 week before an office/teleconference visit with a primary care or cardiology provider. The message will be customized for 3 groups of patients: those on AC; those at elevated risk but off AC; and those not currently at risk but may be at risk in the future. Within the message, we will embed a link to UpBeat.org, a Web site of the Heart Rhythm Society containing patient educational materials. We also will embed a link to a survey. Among other things, the survey will request patients to rate their attitude toward the Heart Rhythm Society Web pages. To measure the effectiveness of the intervention, we will track AC use and its association with message opening, adjusting for potential confounders. Conclusion: If we detect an increase in AC use correlates with message opening, we will be well positioned to conduct a future comparative effectiveness trial. If patients rate the UpBeat.org materials highly, patients from other institutions also may benefit from receiving these materials.

Heart Rhythm Society Atrial Fibrillation Centers of Excellence Study: A survey analysis of stakeholder practices, needs, and barriers.

BACKGROUND: An integrated, coordinated, and patient-centered approach to atrial fibrillation (AF) care delivery may improve outcomes and reduce cost. OBJECTIVE: The purpose of this study was to gain a better understanding from key stakeholder groups on current practices, needs, and potential barriers to implementing optimal integrated AF care. METHODS: A series of comprehensive questionnaires were designed by the Heart Rhythm Society Atrial Fibrillation Centers of Excellence (CoE) Task Force to conduct surveys with physicians, advanced practice professionals, patients, and hospital administrators. Data collected focused on the following areas: access to care, stroke prevention, education, AF quality improvement, and AF CoE needs and barriers. Survey responses were collated and analyzed by the Task Force. RESULTS: The surveys identified 5 major unmet needs: (1) Standardized protocols, order sets, or care pathways in the emergency department or inpatient setting were uncommon (36%-42%). (2) All stakeholders agreed stroke prevention was a top priority; however, prior bleeding or risk of bleeding was the most frequent barrier for initiation. (3) Patients indicated that education on modifiable causes, AF-related complications, and lowering stroke risk is most important. (4) Less than half (43%) of the health care systems track patients with AF or treatment status. Patients reported that stroke and heart failure prevention and access to procedures were priority areas for an AF CoE. The most common barriers to implementing AF CoE identified by clinicians were administrative support (69%) and cost (52%); administrators reported physical space (43%). CONCLUSION: On the basis of the findings of this study, the Task Force identified high priority areas to develop initiatives to aid the implementation of AF CoE.

Igniting Harmonized Digital Clinical Quality Measurement through Terminology, CQL, and FHIR.

BACKGROUND: Electronic clinical quality measures (eCQMs) seek to quantify the adherence of health care to evidence-based standards. This requires a high level of consistency to reduce the effort of data collection and ensure comparisons are valid. Yet, there is considerable variability in local data capture, in the use of data standards and in implemented documentation processes, so organizations struggle to implement quality measures and extract data reliably for comparison across patients, providers, and systems. OBJECTIVE: In this paper, we discuss opportunities for harmonization within and across eCQMs; specifically, at the level of the measure concept, the logical clauses or phrases, the data elements, and the codes and value sets. METHODS: The authors, experts in measure development, quality assurance, standards and implementation, reviewed measure structure and content to describe the state of the art for measure analysis and harmonization. Our review resulted in the identification of four measure component levels for harmonization. We provide examples for harmonization of each of the four measure components based on experience with current quality measurement programs including the Centers for Medicare and Medicaid Services eCQM programs. RESULTS: In general, there are significant issues with lack of harmonization across measure concepts, logical phrases, and data elements. This magnifies implementation problems, confuses users, and requires more elaborate data mapping and maintenance. CONCLUSION: Comparisons using semantically equivalent data are needed to accurately measure performance and reduce workflow interruptions with the aim of reducing evidence-based care gaps. It comes as no surprise that electronic health record designed for purposes other than quality improvement and used within a fragmented care delivery system would benefit greatly from common data representation, measure harmony, and consistency. We suggest that by enabling measure authors and implementers to deliver consistent electronic quality measure content in four key areas; the industry can improve quality measurement.

Shared decision-making for ICDs: a regional collaborative initiative.

The National Institute for Health and Care Excellence (NICE) and NHS England have shown a commitment to embedding shared decision-making (SDM) in clinical practice and developing decision aids based on clinical guidelines. Healthcare policy makers are keen to enhance the engagement of patients in SDM in the belief that it improves the benefits accrued from healthcare interventions. This may be important for interventions such as implantable cardioverter-defibrillator (ICD) implantation, where cost-effectiveness is under scrutiny. NHS England invited the ICD implanters in the north of England to participate in a regional commissioning quality incentive (CQUIN) project to improve decision- making around a primary prevention ICD implant. A collaborative project included the development of a specific SDM tool, the first of its kind in the UK, followed by training and education of the clinical teams. The project illustrates that this approach is practical and deliverable and could be applied and used in other regions, and considered in additional clinical areas.

Development of a bioactive paper sensor for detection of neurotoxins using piezoelectric inkjet printing of sol-gel-derived bioinks.

There is an increasing interest in new strategies to rapidly detect analytes of clinical and environmental interest without the need for sophisticated instrumentation. As an example, the detection of acetylcholinesterase (AChE) inhibitors such as neurotoxins and organophosphates has implications for neuroscience, drug assessment, pharmaceutical development, and environmental monitoring. Functionalization of surfaces with multiple reagents, including enzymes and chromogenic reagents, is a critical component for the effective development of "dipstick" or lateral flow biosensors. Herein, we describe a novel paper-based solid-phase biosensor that utilizes piezoelectric inkjet printing of biocompatible, enzyme-doped, sol-gel-based inks to create colorimetric sensor strips. For this purpose, polyvinylamine (PVAm, which captures anionic agents) was first printed and then AChE was overprinted by sandwiching the enzyme within two layers of biocompatible sol-gel-derived silica on paper. AChE inhibitors, including paraoxon and aflatoxin B1, were detected successfully using this sensor by measuring the residual activity of AChE on paper, using Ellman's colorimetric assay, with capture of the 5-thio-2-nitrobenzoate (TNB(-)) product on the PVAm layer. The assay provided good detection limits (paraoxon, approximately 100 nM; aflatoxin B1, approximately 30 nM) and rapid response times (<5 min). Detection could be achieved either by eye or using a digital camera and image analysis software, avoiding the need for expensive and sophisticated instrumentation. We demonstrate that the bioactive paper strip can be used either as a dipstick or a lateral flow-based biosensor. The use of sol-gel-based entrapment produced a sensor that retained enzyme activity and gave reproducible results after storage at 4 degrees C for at least 60 days, making the system suitable for storage and use in the field.

Evaluation of 99mTc(CO)5I as a potential lung perfusion agent.

INTRODUCTION: The use of (99m)Tc-macroggregated albumin for lung perfusion imaging is well established in nuclear medicine. However, there have been safety concerns over the use of blood-derived products because of potential contamination by infective agents, for example, Variant Creutzfeldt Jakob Disease. Preliminary work has indicated that Tc(CO)(5)I is primarily taken up in the lungs following intravenous administration. The aim of this study was to evaluate the biodistribution and pharmacokinetics of (99m)Tc(CO)(5)I and its potential as a lung perfusion agent. METHODS: (99m)Tc(CO)(5)I was synthesized by carbonylation of (99m)TcO(4-) at 160 atm of CO at 170 degrees C in the presence of HI for 40 min. Radiochemical purity was determined by HPLC using (99)Tc(CO)(5)I as a reference. (99m)Tc(CO)(5)I was administered by ear-vein injection to three chinchilla rabbits, and dynamic images were acquired using a gamma camera (Siemens E-cam) over 20 min. Imaging studies were also performed with (99m)Tc-labeled macroaggregated albumin ((99m)Tc-MAA) and (99m)TcO(4-) for comparison. (99m)Tc(CO)(5)I was administered intravenously to Sprague-Dawley rats, and tissue distribution studies were obtained at 15 min and 1 h postinjection. Comparative studies were performed using (99m)Tc-MAA. RESULTS: Radiochemical purity, assessed by HPLC, was 98%. The retention time was similar to that of (99)Tc(CO)(5)I. The dynamic images showed that 70% of (99m)Tc(CO)(5)I appeared promptly in the lungs and remained constant for at least 20 min. In contrast, (99m)TcO(4-) rapidly washed out of the lungs after administration. As expected (99m)Tc-MAA showed 90% lung accumulation. The percentage of injected dose per gram of organ +/-S.D. at 1 h for (99m)Tc(CO)(5)I was as follows: blood, 0.22+/-0.02; lung, 12.8+/-2.87; liver, 0.8+/-0.15; heart, 0.15+/-0.01; kidney, 0.47+/-0.08. The percentage of injected dose per organ +/-S.D. at 1 h was as follows: lung, 22.47+/-2.31; liver, 10.53+/-1.8; heart, 0.18+/-0.01; kidney, 1.2+/-0.17. Tissue distribution studies with (99m)Tc-MAA showed 100% lung uptake. CONCLUSION: (99m)Tc(CO)(5)I was synthesized with a high radiochemical purity and showed a high accumulation in the lungs. Further work on the mechanism and optimization of lung uptake of (99m)Tc-pentacarbonyl complexes is warranted.

The use of citric acid to prolong the in vivo gastro-retention of a floating dosage form in the fasted state.

Gastro-retentive dosage forms have the potential to improve local therapy and decrease the variation in bioavailability that is observed with a number of commercially available immediate and modified release preparations. In this study, a dosage form has been developed, utilising freeze-dried calcium alginate beads, designed to float on the surface of the stomach contents thus prolonging the retention time. The aim of the study was to also assess the in vivo behaviour of the radio-labelled calcium alginate beads when they were administered under fasting conditions with either water or an aqueous solution of citric acid, a potential gut transit delaying substance. The study was performed in healthy male volunteers who swallowed the radio-labelled calcium alginate beads after a 10h overnight fast. Gamma scintigraphy was selected as the method to monitor the movement of the calcium alginate beads. The volunteers consumed no further food or drink until gastric emptying of the calcium alginate beads was complete. The results indicated that prolonged gastric retention was achieved when the dosage form was administered with the citric acid solution when compared to retention in the absence of citric acid. Citric acid, therefore, has the potential to delay the gastric emptying of the calcium alginate beads when administered to fasted volunteers.